The Ministry of Health of Ukraine Ukrainian Medical Stomatological Academy

Approved at the Department of Propaedeutics to Internal Medicine with Care of Patients meeting on 11 09 2018 Protocol No2 The Head of the Department Professor Yu. Kazakov

METHODICAL INSTRUCTION FOR STUDENTS’ SELF-PREPARATION WORK

Educational discipline Propaedeutics to Internal Medicine Module No 2 Enclosure module No 6 Topic Mitral valvular diseases: the main symptoms and syndromes based on clinical and instrumental methods of examination Year 3 Faculty medical

Poltava - 2018

1. The topic basis: mital valvular diseases take first place among acquired heart valvular diseases. It causes topicality of problem that is studied. 2. The specific aims:  To explain etiology of mitral regurgitation and mitral stenosis.  To explain disorders of hemodynamics in case of mitral regurgitation and mitral stenosis.  To analyze results of examination of patients with mitral regurgitation and mitral stenosis.  To interpret results of examination of patients with mitral regurgitation and mitral stenosis. 3. Basic knowledge, experience, skills necessary for studying the topic in connection with other subjects (interdisciplinary integration) : Previous disciplines Obtained skills 1. Anatomy To know human anatomy, cardiovascular system organs particularly. 2. Physiology To know physiology of cardiovascular system. 3. Medical psychology To be able to observe principles of ethics and deontology in medical practice. 4. Pathological morphology To know pathologic-morphological picture of mitral regurgitation and mitral stenosis. 5. Latin and medical To know terminology (in Latin transcription): terminology mitral regurgitation, mitral stenosis, systemic circulation, pulmonary circulation.

4. Tasks for self-work during preparation to the class. 4.1 List of the main terms, parameters, characteristics, which should be mastered during preparation to the class: Term Definition 1. Mitral regurgitation It is heart valvular disease which develops due to incomplete closure of the left atrioventricular orifice during systole. As a result, the blood is regurgitated from the left ventricle to the left atrium. 2. Mitral stenosis It is heart valvular disease which develops due to narrowing of left atrioventricular orifice.

4.2. Theoretical questions to be answered before class: 1. Tell about ethiology of mitral regurgitation. 2. Describe disorders of hemodynamics in case of mitral regurgitation. 3. What are potential results of questioning, inspection, palpation and auscultation of patients with mitral regurgitation? 4. What instrumental methods are used for diagnostics of mitral regurgitation? 5. What complications of mitral regurgitation do you know? 6. Tell about ethiology of mitral stenosis. 7. Describe disorders of hemodynamics in case of mitral stenosis 8. What are potential results of questioning, inspection, palpation and auscultation of patients with mitral stenosis? 9. What change of pulse can be marked in the patients with aortic stenosis? 10. What complications of mitral stenosis do you know? 11. What instrumental methods are used for diagnostics of mitral stenosis?

4.3. Practical work (tasks), which should be performed during class: 1. To carry out examination of patients with mitral regurgitation and mitral stenosis. 2. To interpret obtained results. 3. To interpret results of laboratory and instrumental methods examination of patients with mitral regurgitation and mitral stenosis.

The contents of topic: Text MITRAL REGURGITATION Mitral regurgitation (insufficientia valvae atrioventricularis sinistra; syn.: mitral incompetence) occurs when left atrioventricular valve doesn’t close atrioventricular opening completely during systole of the left ventricle and inverted blood flow (regurgitation) from ventricle into atrium occurs. Mitral regurgitation can be organic, relative and functional. Organic regurgitation occurs mainly as result of rheumatic endocarditis. Due to this pathology connective tissue is formed in cusps of mitral valve. In the future connective tissue is wrinkled and results shortening of valve’s cusps and tendinous fibers, directed to cusps. As result of these changes valve’s edges don’t close up completely during systole, forming fissure. Part of blood flows back into the left atrium through this fissure. In case of relative regurgitation mitral valve isn’t changed, but orifice, which must be closed by valve, is increased and valve’s cusps don’t close it completely. Relative mitral regurgitation can be developed due to dilatation of the left ventricle in myocarditis, myocardiodystrophy, cardiosclerosis, when circular muscle fibers, forming muscular ring around atrio-ventricular opening, weaken, and in case of lesion of papillary muscles also. Functional regurgitation is caused by dysfunction of muscular apparatus, securing closing of valve. It can be observed also in mitral valve prolapse as in this case blood regurgitation from left ventricle into left atrium is possible also.

Hemodynamics In case of incomplete closure of mitral valve’s cusps during systole - part of blood returns into the left atrium. Filling of atrium by blood is increased, as part of blood returned from left ventricle, is added to usual blood volume, going from pulmonary veins. Pressure in left atrium is elevated, atrium is dilated and hypertrophied. During diastole more than normal amount of blood passes from overfilled left atrium into left ventricle. It results to its overfilling and distension. Left ventricle must work with increased load. Due to this factor its hypertrophy arises. Increased work of the left ventricle compensates available mitral regurgitation during protracted period (Fig. 1.).

Fig. 1. Intracardiac hemodynamics in norm (a) and in mitral regurgitation (b). Hypertrophied parts of the heart are marked with red color. Pointers direct the following: red straight - normal blood flow, red wavy - inverse blood flow from the left ventricle into the left atrium, dark short - contraction of cardiac muscle.

In case of weakening of contractile ability of left ventricular myocardium - diastolic pressure is elevated in it. This process leads to elevation of pressure in left atrium. Elevation of pressure in left atrium results to elevation of pressure in pulmonary veins. Last one due to irritation of baroceptors causes reflex constriction of pulmonary circulation’s arterioles (Kitayev’s reflex). Spasm of arterioles elevates pressure in pulmonary artery significantly. In connection with it right ventricle load increases. Last one should be contracted with more strength for blood expulsion into pulmonary trunk. That is why in expressed mitral regurgitation during long period right ventricle can be hypertrophied also.

Clinical picture Majority of patients with mitral regurgitation, insignificantly or moderately expressed, don’t present any problems and don’t differ in appearance from healthy persons. Only in case of development of congestive signs in pulmonary circulation such symptoms as dyspnea, cyanosis and other occur. Duirng palpation of heart region displacement of apex beat to the left (sometimes - downwards also) is diagnosed; beat becomes diffuse, forced, and resistant, it reflects left ventricular hypertrophy. During percussion of the heart displacement of its borders upwards and to the left due to enlargement of the left atrium and left ventricle is revealed.

Fig.2. PCG in mitral regurgitation, registered at the heart apex. Diminishing of the I sound’s amplitude and systolic murmur, occupied whole pause between I and II sounds.

Configuration of the heart becomes mitral with flat waist. In case of right ventricular hypertrophy cardiac borders are displaced to the right also. During auscultation weakening of the I sound at heart apex is heard (as period of closed valves is absent). In the same place systolic murmur is heard; it is the major sign of mitral regurgitation. It occurs in blood regurgitation during systole from left ventricle into left atrium. Systolic murmur is mixed with I sound. In case of elevated pressure in pulmonary circulation accent of the II sound over pulmonary trunk appears. Results of auscultation are confirmed and become more exactly by means of phonocardiography (Fig. 2). Pulse and blood pressure in case of compensated mitral regurgitation aren’t changed. During X-ray study enlargement of the left atrium and left ventricle, typical for this heart valvular disease, is diagnosed. It is revealed by enlargement of heart shadow to the left, upwards and back. In case of elevation of blood pressure in pulmonary circulation dilatation of aortic arch is revealed. On ECG also it is possible to find reflection of left atrial and left ventricular hypertrophy: ECG becomes “of left type”, P waves in I and II standard leads are increased. During echocardiography dilation of left atrial and left ventricular cavities is revealed, diverse-directed movement of mitral valve’s cusps, their thickening and absence of closure during systole are marked. Heart valvular disease during long period can be compensated. But in case of long mitral regurgitation and weakening of left atrial and left ventricular contractility venous congestion in pulmonary circulation is developed. In future weakening of right ventricular contractile ability with development of venous congestion in systemic circulation can be added. MITRAL STENOSIS Mitral stenosis (stenosis ostii atrioventriculari sinistri) occurs, as a rule, due to rheumatic endocarditis, taking its long course; it can be congenital or occur as a result of bacterial endocarditis very rarely. Mitral stenosis occurs in case of adhesion of mitral valve’s cusps, their consolidation and thickening and also in shortening and thickening of tendinous fibers. As a result of these changes valve becomes like funnel or diaphragm with opening (fissure) in the middle. Cicatrical- inflammatory stricture of valvular ring has less importance for genesis of stenosis. Lime can be precipitated in tissue of affected valve in long being of heart valvular disease. Hemodynamics In mitral stenosis hemodynamics is disturbed essentially in case of significant constriction of atrio-ventricular opening when its transverse section decreased from 4-6 cm2 (normally) to 1,5 cm2 and less. During diastole blood isn’t in time for transfer from the left atrium into the left ventricle. Some amount of blood remains in atrium. This blood is added with blood flow from pulmonary veins. Overfilling of the left atrium and elevation of blood pressure in it occurs. At the beginning they are compensated by means of intensified contraction of atrium and its hypertrophy. But myocardium of the left atrium is very weak for long compensation of expressive mitral stenosis; that is why its contractile ability is decreased rather quickly, atrium is dilated more, pressure in it becomes higher. It results elevation of pressure in pulmonary veins, reflectory spasm of pulmonary circulation’s arterioles and elevation of pressure in pulmonary artery, which needs greater work of the right ventricle. Eventually right ventricle is hypertrophied (Fig.3). Left ventricle in mitral stenosis obtains not much blood, carries out less then normal work, that is why its sizes are some diminished.

Fig. 3. Intracardiac hemodynamics in norm (a) and in mitral stenosis (b). Hypertrophied parts of the heart are marked with red color. Pointers direct the following: red straight - normal blood flow, red wavy - difficult blood flow from the left atrium into the left ventricle, dark short -relaxation of cardiac muscle.

Clinical picture In case of presence of congestive signs in pulmonary circulation dyspnea, palpitation on physical exertion, sometimes - pains in heart region, cough and hemoptysis appear in patients. During inspection acrocyanosis is marked often; it is typical ruddiness touched with cyanotic (facies mitralis). If heart valvular disease is developed during childhood, physical developmental lagging, infantilism (“mitral nanism”) is observed often. During inspection of heart region heart beat due to dilatation and hypertrophy of the right ventricle is marked often. Apex beat isn’t intensified; during palpation in its region so called dyastolic “cat’s purr” (presystolic trembling) is revealed, that is to say low-frequent dyastolic murmur is diagnosed. By means of percussion dilatation of zone of cardiac dullness upwards and to the right due to hypertrophy of the left atrium and right ventricle is revealed. Configuration of the heart becomes mitral. During auscultation of the heart changes, very typical for mitral stenosis, are diagnosed. As little amount of blood gets into the left ventricle and its contraction occurs swiftly, the I sound at the heart apex becomes loud, snapping. In the same place after the II sound it is possible to hear additional sound - sound of opening of the mitral valve. Loud I sound, II sound and sound of opening of the mitral valve form typical for mitral stenosis melody, called “quail rhythm”. In case of elevation of pressure in pulmonary circulation accent of the II sound over pulmonary trunk appears. Dyastolic murmur is typical for mitral stenosis, as constriction on the way of blood flow from left atrium to ventricle during diastole is present. This murmur can occur at once after sound of opening of the mitral valves as blood circulation will be higher during beginning of diastole due to difference of pressure in atrium and ventricle; as equalization of pressure murmur will decrease. Often murmur appears at the end of diastole, closely before systole - presystolic murmur. It occurs in acceleration of blood flow during the end of ventricular diastole due to systole of atria, which begins. Diastolic murmur in mitral stenosis can be heard during whole diastole. Murmur is intensified before systole and directly is mixed with snapping I sound. Pulse in case of mitral stenosis can be different on the right and left hands. As in significant left atrial hypertrophy left subclavicular artery is pressed, filling of pulse to the left is diminished (pulsus differens). In case of decrease of left ventricular filling and decrease of stroke volume pulse becomes small - pulsus parvus. Mitral stenosis often is complicated by cardiac fibrillation; in these cases pulse is arrhythmic. Blood pressure usually is normal, sometimes slightly systolic pressure is decreased and diastolic one is increased.

Fig. 4. X-ray film in mitral stenosis. a - mitral configuration of the heart; b - declining of contrasted esophagus by arc of little radius in the right anterior oblique view.

X-ray study reveals enlargement of the left atrium, typical for this heart valvular disease. This enlargement results to disappearing of heart “waist” and forming of mitral configuration of the heart (Fig.4,a). First oblique view of the film reveals enlargement of the left atrium by its declining of esophagus. Last one well visible in case of barium swallow by patient (Fig.4,b). In case of pressure elevation in pulmonary circulation X-ray study reveals bulging of arch of pulmonary artery and right ventricular hypertrophy. Sometimes during X-ray study mitral valve calcification is diagnosed. In long hypertension of pulmonary circulation’s vessels pneumosclerosis is developed. It also can be revealed during X-ray study.

Fig. 5. PCG in mitral stenosis, registered at the heart apex. Increase of the I sound’s amplitude, diastolic (presistolic) murmur and sound of opening of the mitral valve are marked.

ECG in mitral stenosis reflects hypertrophy of left atrium and right ventricle; amplitude and wide of P-wave, in I and II standard leads particularly, is increased, electrical axis of the heart is declined to the right, high R-wave in right chest leads and expressed S-wave in left chest leads appear. On PCG, registered at the heart apex, high amplitude of the I sound is marked, sound of opening of the mitral valve and diastolic murmur are revealed after II sound; amplitude of the II sound is increased over pulmonary artery in comparison with aorta (Fig. 5.). In case of synchronous recording of PCG and ECG it is necessary to pay one’s attention to length of Q-I sound interval (from beginning of Q-wave on ECG to I sound on PCG) and II sound - QS interval: more expressed stenosis, more length of Q-I sound interval and less length of II sound- QS interval. Echo-CG in mitral stenosis obtains number of typical peculiarities: 1. Pick A, reflected maximal opening of mitral valve’s cusps during atrial systole, is decreased significantly or disappears. 2. Velocity of diastolic closing of anterior cusp of the valve is decreased; it results to diminishing of E-f interval inclination. 3. Movement of valve’s cusps is changed. If normally during diastole cusps are diverged to opposite sides (anterior cusp - to anterior wall, posterior cusp - to posterior wall), in case of stenosis their movements become one-directed as due to adhesion of comissures more massive anterior cusp pulls posterior cusp. Movement of cusps on EchoCG acquired П-type configuration. Besides that, by means of EchoCG it is possible to reveal enlargement of the left atrium, change of valve’s cusps (fibrosis, calcinosis). In case of mitral stenosis congestion in pulmonary circulation occurs early. It requires increased work of the right ventricle. That is why decrease of contractile ability of the right ventricle and venous congestion in systemic circulation is developed in mitral stenosis earlier and more often, than in mitral regurgitation. Weakening of right ventricular myocardium and its dilatation sometimes is accompanied by appearance of relative tricuspid insufficiency. Besides, prolong venous congestion in pulmonary circulation in mitral stanosis eventually results to vascular sclerosis and overgrowth of connective tissue in the lungs. Second, pulmonary, barrier for passage of the blood along vessels of pulmonary circulation is formed. It makes more difficult work of the right ventricle.

A. Test tasks to be done: - with a single selective answer - I-st level: 1. What hemodynamic changes are basis for complaints of cough, dyspnea, hemoptysis in patients with mitral stenosis? a) decrease of systemic blood pressure; b) increase of pressure in pulmonary circulation; c) congestion of blood in the liver; d) enlargement of the left atrium and pressing of organs of mediastinum; e) decrease of cardiac output (from left ventricle). 2. What complaints of patients with mitral stenosis are caused by decreasing of minute blood volume? a) cough, dyspnea, hemoptysis; b) elevation of body temperature, joint pains; general weakness; c) pains in heart area, cardiac intermissions, palpitation; d) edema of the lower extremities, feeling of heaviness in right hypochondrium; e) headache, dizziness, general weakness, undue fatiguability. 3. What forced position can be in patients with mitral stenosis? a) knee-elbow position; b) “bedouin, which is prayed”; c) ortopnea; d) opisthotonus; e) “hound position”. 4. What is the face of the patient with mitral stenosis? a) puffy, cyanotic; b) puffy, pale with enophtalmos; c) “face of wax doll”; d) puffy, pale with edemas around eyes ; e) pale with bluish, localized on the cheeks, cyanotic color of the tip of nose, ears, chin.

5. What are the resuts of palpation of heart region in the patient with mitral stenosis? a) changes are absent; b) apex beat is displaced to the left, resistant; c) increased pulsation in the 2nd interspace to the left of sternum edge is marked; d) amplified epigastric pulsation, increased during deep inspiration is marked; e) systolic “cat’s purr” in the 2nd interspace to the right of sternum is marked. 6. There are following data of palpation of heart area in patient with mitral stenosis: a) changes are absent; b) apex beat is displaced to the left, resistant; c) increased pulsation in the 2nd interspace to the left of sternum edge is marked; d) diastolic “cat’s purr” at the heart apex or over Botkin-Erb point is marked; e) systolic “cat’s purr” in the 2nd interspace to the left edge is revealed. 7. Data of percussion of the heart in patient with mitral stenosis are the following: a) displacement of the left heart border to the left; b) dilatation of the vascular bundle due to aorta; c) dilatation of the vascular bundle due to pulmonary artery and aorta; d) displacement of the upper heart border upwards; e) displacement of the right and left heart border. 8. Data of auscultation of the heart in patient with mitral stenosis are the following: a) decreased I sound at the heart apex; b) increased snapping I sound; c) accent of the II sound over the aorta; d) splitting of the I sound at the heart apex; e) decreasing in loudness (decrescendo) systolic murmur at the heart apex.

9. What are the data of auscultation of the heart in the patient with mitral stenosis? a) decreased I sound at the heart apex; b) triple rhythm (quail rhythm); c) protodiastolic gallop rhythm; d) presystolic gallop rhythm; e) decreasing in loudness (decrescendo) systolic murmur at the heart apex. 10. What are the data of auscultation of the heart in the patient with mitral stenosis? a) decreased I sound at the heart apex; b) accent of the II sound over the aorta; c) protodiastolic gallop rhythm; d) presystolic gallop rhythm; e) presystolic increasing in loudness (crescendo) murmur at the heart apex or over Botkin-Erb point.

11. What important PCG-sign of mitral stenosis do you know? a) increase of the I sound duration; b) decrease of the I sound duration; c) increase of Q-I sound interval duration; d) diminishing of the I sound amplitude; e) decrease of the Q-I sound intervalduration. 12. What functional heart valvular disease is potential as result of appearance of disturbances of intracardiac hemodynamics in the patient with mitral stenosis? a) relative mitral valve incompetence; b) relative aortic ostium stenosis; c) relative aortic valves incompetence; d) relative tricuspid valve incompetence; e) relative tricuspid stenosis. 13. Quail rhythm is: a) increased, snapping I sound; b) increased, snapping I sound, accent of the II sound over pulmonary artery, mitral valve opening sound; c) mitral valve opening sound; d) sound as result of distension of weakened left ventricle; e) sound as result of increased systole of the left atrium. 14. What functional murmur is potential in mitral stenosis? a) Grehem-Still murmur; b) Coombs murmur; c) Flint’s murmur; d) Vinogradov-Durozier murmur; e) top murmur. - with the selective group of right answers - II - nd level: 1. What are complaints of the patients with mitral regurgitation when congestion in the pulmonary circulation occurs? a) cough; b) dyspnea; c) pain in the right hypochondrium; d) palpitation; e) fatigue; f) edemas; g) pain in the heart region. 2. What are potential results of general inspection of patients with mitral regurgitation (in late stage)? a) passive position in a bed; b) forced position in a bed - orthopnea; c) acrocyanosis; d) pale skin; e) yellow skin; f) diffuse apex beat; g) facies feverish. 3. What are potential results of examination of cardiovascular system in patients with mitral regurgitation? a) diffuse apex beat, displaced to the left; b) intensified apex beat; c) resistant apex beat; d) apex beat is of normal location, area, height and strength; e) displacement of the upper border of relative cardiac dullness upward; f) displacement of the upper border of relative cardiac dullness downward; g) displacement of the left border of relative cardiac dullness to the left; h) “aortic” configuration with pronounced waist of the heart. 4. What are potential results of X-ray examination of patients with mitral regurgitation? a) smoothed of the left border; b) marked heart waist; c) moderate enlarging of the pulmonary trunk; d) protrusion of the left low arch; e) post-stenotic dilatation of ascending aorta; f) narrowing of the retrocardial space in the second oblique position; g) declining of the esophagus on the radius. 5. What are potential results of Echo-CG of patients with mitral regurgitation? a) narrowing of the orifice of the left atrioventricular valve; b) change of flow character through the mitral orifice in diastole (a turbulent stream); c) dilatation of the left parts of heart; d) reduced rate of diastolic filling; e) excursion of the atrioventricular partition and back wall of the left ventricle; f) different direction of the diastolic motion of mitral valve, unclosing them during systole; g) reduced valve area. 6. What are specific complaints of the patients with mitral stenosis? a) vomiting; b) exertional and nocturnal dyspnea; c) cough; d) palpitation; e) edemas; f) pain in the heart; g) pain in right hypochondrium.

7. What are potential results of heart auscultation in patients with mitral stenosis? a) loud and snapping first sound at the heart apex; b) sound of opening of the mitral valve; c) decreased first sound at the heart apex; d) second heart sound is accentuated over aorta; e) second heart sound is accentuated over pulmonary trunk; f) systolic murmur at the heart apex; g) diastolic murmur at the heart apex. 8. What are potential complications of miral stenosis? a) atrial fibrillation, flutter; b) arterial or venous emboli; c) acute pulmonary edema; d) sudden cardiac death; e) chronic left atrial heart failure; f) hypertensive crisis; g) right ventricle heart failure.

B. Tasks to be done: Task 1. In patient R. during palpation diastolic trembling of the chest at the heart apex was revealed. The borders of relative cardiac dullness are the following: left - 0,5 cm medially of the left midclavicular line, right - 3 cm laterally of the right edge of sternum, upper - along upper edge of the 2nd rib. In patient it can be: a) Mitral valve insufficiency; b) Mitral stenosis; c) Aortic stenosis; d) Aortic valve insufficiency; e) Tricuspid valve insufficiency.

Task 2. In patient S. triple rhythm at the heart apex is marked; here the I sound is loud (snapping) and it is louder than II sound significantly. Presystolic murmur is heard at the heat apex. In the 2nd intercosltal space to the left of sternum the II sound is louder than I sound. In patient it can be: a) Mitral valve insufficiency; b) Mitral stenosis; c) Aortic valve insufficiency; d) Aortic stenosis; e) Tricuspid valve insufficiency.

Task 3. During inspection of the chest of patient D. pathological changes aren’t revealed. The borders of relative cardiac dullness are the following: left - along midclavicular line, right - along right edge of the sternum, upper - along 3rd intercostal space. Results of heart auscultation: diminishing of the I sound at the heart apex and slight systolic decrescendo murmur, occupying 2/3 of systole and radiated to left axillar fossa. In patient it can be: a) Mitral valve insufficiency; b) Mitral stenosis; c) Aortic valve insufficiency; d) Aortic stenosis; e) Tricuspid valve insufficiency.

Task 4. Patient N. complains of dyspnea on little exertion. The lips are cyanotic. The blush is observed on cheekbones. Ears and tip of nose are cyanotic slightly. Expressed pulsation of jugular veins is visible on the neck. Diastolic vibration of the chest is revealed at the heart apex. Apex beat is in the 5th intercostal space 1 cm medially of the left midclavicular line, it isn’t increased. Triple rhythm is heard at the heart apex. The I sound is loud. The II sound is increased in the 2nd intercostal space to the left of sternum. Diastolic decrescendo murmur is heard at the heat apex. Murmur is heard during whole diastolic period and has presystolic increasing. For which heart valvular disease such symptomatology is typical? a) Mitral stenosis; b) Mitral valve insufficiency; c) Aortic stenosis; d) Aortic valve insufficiency; e) Tricuspid valve insufficiency.

Task 5. Woman, 34 years old, came to the out-patient department with purpose of prophylactic examination. Complains of weakness, rapid fatigability, dyspnea on exertion are marked. Edemas on the dorsal surface of feet appear in the evening. From results of anamnesis: first rheumatic attack, taking its course with lesion of joints and endocarditis, she had when she was in 14 years old. General condition is satisfactory. Skin covers are clear, pale. The I sound is diminished. Rough pansystolic murmur with epicenter in the first point of auscultation is heard. What conclusion is correct? a) Mitral regurgitation; b) Mitral stenosis; c) Aortic stenosis; d) Aortic regurgitation; e) Tricuspid stenosis.

Task 6. Patient A., 21 years old, is a student. He complains of dyspnea, palpitation. Inspection. He is lean. Cyanosis of the face, marked on cheekbones, lips and tip of the nose particularly, is observed. Palpation. Vibration of the chest at the heart apex is marked. Percussion. Borders of relative cardiac dullness: left- 0,5 cm medially of the left midclavicular line, upper - along upper edge of the 2nd rib, right - 3 cm laterally of the right edge of sternum. Borders of absolute cardiac dullness: left- 1,5 cm medially of the left midclavicular line, upper - along upper edge of the 3rd rib, right - 2 cm laterally of the right edge of sternum Auscultation. Heart sounds are rhythmic. Heart rate is 108 per minute. Triple rhythm is marked at the heart apex; here the I sound is slapping and it is louder than II sound significantly. In the 2nd intercostal space to the left of sternum the II sound is louder than the I sound. Questions to the task 6: 1. What heart valvular disease is in this patient? a) Mitral regurgitation. b) Mitral stenosis. c) Aortic stenosis. d) Aortic regurgitation. e) Tricuspid insufficiency. 2. What objective symptoms are in this patient revealed? a) Acrocyanosis. b) Bradycardia. c) Tachycardia. d) “Quail” rythm. e) “Cat’s purr”. 3. What are potential ECG-results in this patient? a) Hypertrophy of the right ventricle; b) Hypertrophy of the left ventricle; c) Hypertrophy of the right atrium; d) Hypertrophy of the left atrium[ e) Sinus tachycardia.

Task 7. Patient K., 34 years old, was admitted to the hospital with complaints of dyspnea, edemas, and weakness. He has dyspnea about 6 years. He began feel appearance of edemas on the legs to the end of the day at first two years before admitting to the hospital. About rheumatism in past he didn’t remember. Acrocyanosis is marked at the admitting. Feet and shins are edematic. Significant enlargement of cardiac dullness (to the right particularly) is revealed by means of percussion. Accent of the I sound at the heart apex is observed. Presystolic murmur is heard in this point. Heart rate is 100. Blood pressure is 110/75 mm Hg. Venous pressure is 200 mm . Enlargement of the cardiac shadow to the right, enlargement of the left atrium, bulging of the pulmonary artery, expressed congestive lung pattern are revealed by means of X-ray. Right type of ECG, enlargement of P-wave in II and III standard leads are marked on ECG; RavF > 20 mm, Rv1 = 23 mm, Sv5 = 12 mm. What conclusion is correct? a) Mitral regurgitation. b) Mitral stenosis. c) Aortic stenosis. d) Aortic regurgitation. e) Tricuspid insufficiency.

Task 8. Patient A., 30 years old. Complaints. Dyspnea on moderate exertion is marked. Anamnesis morbi. In 12 years old he was ill with disease of joints, which didn’t trouble him later. From 26 years old he began to feel dyspnea on exertion. During last 2 years dyspnea became more expressed and it is marked on moderate exertion even. Little edemas on the legs appear to the end of the day rarely. Inspection. He is lean. The face is cyanotic slightly. Bluish on cheekbones is marked. Legs are edematic. Palpation. Diastolic thrill of the chest is revealed at the heart apex. Percussion. Borders of relative cardiac dullness: left - along left midclavicular line, upper - along the 2nd rib, right - 2 cm laterally of the right edge of sternum. Auscultation. Heart rhythm is regular, triple due to slapping sound at once after the II sound. Such rhythm is heard better at the heart apex. Here in short interval after this sound decrescendo murmur is heard. Before sound this murmur increases and coincides with it, ending by loud slapping sound. Loudness of the II sound is more than one of the I sound over the pulmonary artery. The II sound here is louder than over aorta. ECG. Displacement of electrical axis to the right is marked. PCG. Sound recording is in accordance with auscultative data. Interval PQ=0,08 sec. What conclusion is correct? a) Mitral regurgitation. b) Mitral stenosis. c) Aortic stenosis. d) Aortic regurgitation. e) Tricuspid insufficiency.

1 - b 6 - d 11- c 2 - e 7 - d 12- d 3 - c 8 - b 13- b 4 - e 9 - b 14- a 5 - a 10- e

Answers for test tasks of the II-nd level: 1 - a , b , d , e 6 - b , c , d , f 2 - b , c 7 - a , b , e , g 3 - a , b , c , e , g 8 - a , b , c , e , g 4 - a , c , d , f , g 5 - c , e , f

Standards of right answer for tasks: 1) - b 2) - b 3) - a 4) - a 5) - a 6) 1 - b 2 – a, c, d, e 3 – a, d, e 7) - b 8) – b

Literature recommended: Main Sources:

1. Propedeutics to Internal Medicine : textbook for English learning students of higher medical schools. Pt. 1. Diagnosis / O. N. Kovalyova, T. Ashcheulova. - 2nd ed. - Vinnytsya : Nova Knyha Publ., 2011. - 424 p.

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3. Propaedeutics of Internal Medicine: a textbook / Y.I.Detsyk, O.H. Jaworski, R.J. Dutka et al., Ed. prof. O.H. Jaworski. 3rd ed., Correct. and reported. - K. VSV "Medicine", 2013. - 552 p. 4. Basics of Internal Medicine.: Propedeutics of internal diseases / Detsyk Y.I., Jaworski E.G., Dutka R.J., Ed. O.H. Jaworski. - K.: Health 2004.-500 p.

5. Grebenev A.L. Propedeutics Internal Medicine: A Textbook AL Grebenev, 5th ed. pererab.i ext. - Moscow: Meditsina, 2002. - 585 p.

6. Study Guide "Computer tests of propedeutics of internal diseases" (by V.V. Korotkyj, A.B. Novosad). Kyiv: Health 2001 – 148p.

7. Introduction to the Course of Internal Diseases. Book 1. Diagnosis / Zh. D. Semidotska, O. S. Bilchenko [et al.] ; ed. by Zh. D. Semidotska. - 2nd ed., revised and supplememted. - Kharkiv : Tornado, 2006. - 314 p.

8. General thesis about organization and conduction of complex practically oriented state examination from internal medicine, professional and infectious diseases : manual for out-class work with English-medium graduates / KhNMU ; comp. O. Babak [et al.]. - Kharkov : KhNMU, 2012. - 40 p. - англ.

Electronic resources:

7. Англо-русский тематический словарь по пропедевтике внутренних болезней и общему уходу за больными : справочное издание / Витебский государственный медицинский университет, Кафедра пропедевтики внутренних болезней; сост. Л.М. Немцов; под ред. Г.И. Юпатова. - Витебск : ВГМУ, 2005. - 153 с. URI: http://elib.vsmu.by/handle/123/11343 8. Special propedeutics of internal diseases : lecture course / Vitebsk State Medical University, Dep. of Propedeutics of Internal Diseases ; comp. by L. M. Nemtsov. - 2-е изд. - Vitebsk : VSMU, 2016. - 318 p. URI: http://elib.vsmu.by/handle/123/9837 9. General propedeutics of internal diseases : lecture course / Vitebsk State Medical University ; compiled by L. M. Nemtsov. - Vitebsk : VSMU, 2006. - 175 p. http://elib.vsmu.by/handle/123/268

Additional ones:

1. McCombs R.P. Fundamentals of Internal Medicine. A physiologic and clinical approach to disease. - 1971. - 860 p. 2. Гребенев А.Л. Пропедевтика внутренних болезней: Учебник – 5-е изд., перераб. и доп.- М.: Медицина, 2001.- 592 с. 3. Ивашкин В.Т., Султанов В.К. Пропедевтика внутренних болезней: практикум. 2-е изд.- СПб.: Питер, 2003.-544 с.

Methodical instruction is composed by lecturer Ye.Ye. Petrov.

20__/20__ academic year. Methodical instruction is revised and approved again At the Chair of Propaedeutics of Internal Medicine with care of patients meeting On “____”______20__р. Protocol №_____ The Head of Chair, professor Yu.M.Kazakov

The Ministry of Health of Ukraine Ukrainian Medical Stomatological Academy

Approved at the Department of Propaedeutics to Internal Medicine with Care of Patients meeting on 11 09 2018 Protocol No2 The Head of the Department Professor Yu. Kazakov

METHODICAL INSTRUCTION FOR STUDENTS’ SELF-PREPARATION WORK

Educational discipline Propaedeutics to Internal Medicine Module No 2 Enclosure module No 6 Topic Aortic valvular diseases: the main symptoms and syndromes based on clinical and instrumental methods of examination Year 3 Faculty medical

Poltava - 2018 1. The topic basis: Aortic valvular diseases on frequency take the second place after mitral ones and they are combined with them very frequently. Mistakes during diagnostics of aortal defects on 50% are caused by expectation of presence of all signs of these diseases. All signs of aortal defects occur only in 20% patients. 2. The specific aims:  To explain etiology of aortic regurgitation and aortic stenosis.  To explain disorders of hemodynamics in case of aortic regurgitation and aortic stenosis.  To analyze results of examination of patients with aortic regurgitation and aortic stenosis.  To interpret results of examination of patients with aortic regurgitation and aortic stenosis. 3. Basic knowledge, experience, skills necessary for studying the topic in connection with other subjects (interdisciplinary integration) : Previous disciplines Obtained skills 1. Anatomy To know human anatomy, cardio-vascular system organs particularly. 2. Physiology To know physiology of cardio-vascular system. 3. Medical psychology To be able to observe principles of ethics and deontology in medical practice. 4. Pathological morphology To know pathologic-morphological picture of aortic regurgitation and aortic stenosis. 5. Latin and medical To know terminology (in Latin transcription): terminology aortic regurgitation, aortic stenosis, systemic circulation, pulmonary circulation.

4. Tasks for self-work during preparation to the class. 4.1 List of the main terms, parameters, characteristics, which should be mastered during preparation to the class: Term Definition 1.Aortic regurgitation It is defined as incomplete closing of aortic valve during diastole that lead to retrograde blood flow from aorta into the left ventricle

2.Aortic stenosis It is heart valvular disease which develops due to the narrowing of the aortic orifice resulted from different origin.

4.2. Theoretical questions to be answered before class: 1. Tell about ethiology of aortic regurgitation. 2. Describe disorders of hemodynamics in case of aortic regurgitation. 3. What are potential results of questioning, inspection, palpation and auscultation of patients with aortic regurgitation? 4. What are changes of pulse and blood pressure in the patients with aortic regurgitation? 5. What instrumental methods are used for diagnostics of aortic regurgitation? 6. What complications of aortic regurgitation do you know? 7. Tell about ethiology of aortic stenosis. 8. Describe disorders of hemodynamics in case of aortic stenosis. 9. What are potential results of questioning, inspection, palpation and auscultation of patients with aortic stenosis? 10. What are changes of pulse and blood pressure in the patients with aortic stenosis? 11. What complications of aortic stenosis do you know?

4.3. Practical work (tasks), which should be performed during class: 1. To carry out examination of patients with aortic regurgitation and aortic stenosis. 2. To interpret obtained results. 3. To interpret results of laboratory and instrumental methods examination of patients with aortic regurgitation and aortic stenosis.

The contents of topic: Text

AORTIC REGURGITATION Aortic regurgitation (insufficientia valvae aortae; syn.:aortic insufficiency) - heart valvular disease, when semilunar valves don’t close completely aortic orifice and during diastole reverse blood flow from aorta into the left ventricle occurs. The most often aortic regurgitation is developed as a result of rheumatic endocarditis, more rarely - due to bacterial endocarditis, syphilitic lesion of aorta, atherosclerosis. Anatomical changes of valve depend on etiology of heart valvular disease. In case of rheumatic endocarditis - inflammatory-sclerotic process on basis of valve’s cusps results to their shrinkage and shortening. In syphilis and atherosclerosis patological process can affect only aorta, causing its dilation and taking up of valve’s cusps without their lesion, or cicatricial process spreads to valve’s cusps and deforms them. In case of sepsis ulcerous endocarditis results to destruction of valve’s parts, forming of defects in cusps and following their cicatrization and shortening.

Hemodynamics During diastole blood doesn’t passes into the left ventricle from left atrium only, but from aorta also due to reverse blood flow. It results to overfilling and distension of the left ventricle during diastole. During systole left ventricle must contract with greater force for output of increased stroke blood volume into aorta. Intensified work of the left ventricle results to its hypertrophy, and increase of systolic blood volume in aorta causes its dilatation (Fig. 6).

Fig. 6. Intacardiac hemodynamics in norm (a) and in aortic regurgitation. Hypertrophied parts of the heart are marked with red color, pointers direct the following: red straight-normal blood flow, red wavy - inverse blood flow from aorta, dark short-relaxation of cardiac muscle.

For aortic regurgitation it is typical sharp fluctuation of blood pressure in aorta during systole and diastole. Blood volume in aorta, which is increased in comparison with normal one, causes elevation of systolic pressure during systole. As part of blood returns into ventricle during period of diastole, the diastolic pressure falls quickly.

Clinical picture Patients with aortic regurgitation can feel well during long period, as this heart valvular disease is compensated by means of increased work of the left ventricle. Eventually pains in heart area like ones in case of angina pectoris appear. They are caused by relative coronary insufficiency due to acute hypertrophy of myocardium and impairment of coronary arteries’ filling by the blood at low diastolic pressure in aorta. Sometimes dizziness as result of cerebral impairment is observed. It also is connected with low diastolic pressure. In weakening of left ventricular myocardial contractility congestion in pulmonary circulation is developed and dyspnea, palpitation, weakness, etc. appears. During patients’ inspection skin paleness, caused by small filling by blood of arterial system during diastole, is marked. Sharp fluctuation of the blood in arterial system during systole and diastole causes number of symptoms: pulsation of peripheral arteries - carotid (“dancing of carotids”), subclavicular, brachial, temporal and others, rhythmical movement of the head synchronous with the pulse (de Musset’s sign), rhythmical change in the color of the nail bed under a slight pressure on the nail end, so-called capillary pulse - Quincke’s pulse, rhythmical reddening of the skin after rubbing and others. During inspection of the heart region enlarged and displaced to the left and downwards apex beat is almost always visible. Sometimes side by side with apex beat it is marked slight retraction in area of neighboring interspaces.

Fig.7. PCG in aortic regurgitation, registered over aorta. Decrease of amplitude of sounds and decrescendo diastolic murmur are marked.

During palpation apex beat is revealed in the sixth and sometimes seventh intercostal space, laterally of midclavicular line. It is diffuse, intense, rising like a dome. It testifies about significant enlargement of the left ventricle due to its hypertrophy and dilatation of cavity. During percussion displacement of the borders of cardiac dullness to the left is reveled. Heart configuration becomes “aortic” (with pronounced waist of the heart). During auscultation weakening of the I sound at the heart apex is revealed, as the period when the valves are closed during left ventricular systole is absent. The II sound over aorta is weakened also and in case of significant destruction of valve’s cusps it can’t be heard absolutely. In case of syphilitic and atherosclerotic lesion of aorta the II sound can be relatively sonorous. It is typical dyastolic murmur, heard over aorta and at the Botkin-Erb’s point. Usually it is soft, blowing protodiastolic murmur; murmur decreases to the end of diastole in proportion with falling of blood pressure in aorta and slowing-down of blood flow (decrescendo murmur). Marked changes of sounds and murmurs are well reveled on PCG (Fig.7). In aortic regurgitation at the heart apex it is possible to hear murmurs of functional origin. So, in case of great dilatation of the left ventricle relative mitral insufficiency occurs and systolic murmur appears at the heart apex. Rarely it is possible to hear diastolic (presystolic) murmur - Flint’s murmur. It arises due to an intense regurgitation of the blood that moves aside the mitral valve’s cusps and forms the functional mitral stenosis. Sometimes in this heart valvular disease two sounds (double Traube’s tone) and double Vinogradov-Duroziez’s murmur are heard over the femoral artery.

Fig. 8. X-ray film in aortic regurgitation. Aortic configuration of the heart; hypertrophy of the left ventricle and dilatation of ascending aorta are marked.

It is typical change of pulse, which becomes fast, high, large (pulsus celer, altus, magnus). It is caused by large pulse pressure and increased stroke blood volume, passing into aorta during systole. Blood pressure is changed always: systolic is increased, diastolic is decreased, that is why pulse blood pressure is high. X-ray study reveals enlargement of the left ventricle with marked heart waist (Fig.8), dilation of aorta. Intensified its pulsation is marked. On ECG signs of hypertrophy of the left ventricle appear also (Fig.9). They are: deviation of the electrical axis to the left, deep S-waves in the right chest leads and high amplitude of R-waves in left chest leads, often combined with signs of left ventricular overstrain and relative coronary insufficiency (change of final part of ventricular complex, depression of ST-interval, inverted T-wave). On EchoCG of the patients with aortic regurgitation it is revealed flutter of anterior cusp of mitral valve during diastole due to impact of stream during blood regurgitation from aorta into ventricle. During recording of two-dimensional EchoCG it is possible to reveal dilatation of root of aorta and calcinosis of valve’s cusps; during Doppler-echoCG diastolic flow of regurgitation from aorta into ventricle is revealed.

Fig. 9. ECG in aortic regurgitation.

Aortic regurgitation during long period can be compensated by means of intensive work of hypertrophied strong left ventricle. In weakening of its contractile ability congestive signs in pulmonary circulation are developed. In aortic regurgitation acute weakness of the left ventricle occurs sometimes. It is manifested clinically by attack of cardiac asthma. Dilatation of the left ventricle at weakening of its myocardium can result to relative mitral insufficiency. It increases venous congestion in pulmonary circulation, connected with decompensation, and makes additional load for the right ventricle. It is called “mitralization of aortic regurgitation”. Last one can become reason of venous congestion in systemic circulation.

AORTIC STENOSIS Aortic stenosis (stenosis ostii aortae) forms obstruction for blood flow into aorta during contraction of the left ventricle. Rheumatic endocarditis is the most often reason of aortic stenosis, more rarely stenosis is developed as result of bacterial endocarditis, atherosclerosis or it has congenital origin. Stenosis occurs in adhesion of aortic valve’s cusps or appears due to cicatricial constriction of aortic orifice.

Hemodynamics Little constriction of aortic orifice doesn’t cause essential circulatory disturbance. At the expressed narrowing of aortic orifice when its area decreases from 3 cm2 (normally) to 1,0-0,5 cm2 during systole left ventricle doesn’t empty completely as all blood doesn’t have time to pass into aorta through constricted orifice. During diastole normal amount of blood from left atrium is added to this blood, remained in ventricle. It leads to overfilling of ventricle and elevation of pressure in it. This disorder of intracardiac hemodynamics is compensated by the intensified work of the left ventricle and causes its hypertrophy (Fig.10).

Fig. 10. Intracardiac hemodynamics in norm (a) and in aortic stenosis. Hypertrophied parts of the heart are marked with red color, pointers direct the following: red straight-normal blood flow, red wavy -difficult blood flow from left ventricle into aorta, dark short-contraction of cardiac muscle.

Clinical picture During many years aortic stenosis can be compensated heart valvular disease and doesn’t cause in patients any unpleasant subjective fillings even on large physical activity. In expressed stenosis of aortic orifice insufficient blood output into arterial system results to blood supply disturbance of hypertrophied myocardium. In this connection pains in heart region like in case of angina pectoris appear in patients. Cerebral impairment results to dizziness, headaches, propensity to syncope. These signs like pains in heart region more often occur during physical work, emotional stress. During patients’ inspection skin paleness, connected with little blood filling of arterial system, is marked. Apex beat is displaced to the left, more rarely- downwards; it is diffuse, high, and resistant. During palpation systolic thrill (“cat’s purr”) can be revealed over the aorta. During percussion displacement of the left border to the left and aortic configuration of the heart are revealed. It is caused by left ventricular hypertrophy. During heart auscultation at the heart apex it is possible to mark weakening of the I sound, connected with overfilling of the left ventricle and prolongation of its systole. The II sound is weakened over aorta; when aortic cusps adhere and are immobile, the second sound can be inaudible. Rough systolic murmur over aorta is typical. This murmur is generated by the blood flow through the narrowed orifice. It is conducted by the blood on the a.carotis and can sometimes be heard in the interscapular space. The pulse is small, slow and rare (pulsus parvus, tardus et rarus), as the blood passes into aorta slowly and its volume is decreased. Systolic pressure is usually diminished, while diastolic one remains normal or it is increased, that is why pulse pressure is diminished. X-ray in aortic stenosis reveals left ventricular hypertrophy, and aortic configuration of the heart, dilatation of ascending aorta (poststenotic dilatation); often calcification of aortic valve’s cusps is revealed. ECG reveals signs of left ventricular hypertrophy and often - of coronary insufficiency. PCG reflects changes of heart sounds, typical for this heart valvular disease: diminishing of amplitude of the I sound at the heart apex and amplitude of the II sound - over aorta. Crescendo -decrescendo systolic murmur, registered over aorta, is typical for aortic stenosis. Recorder of its oscillation has like-rhomb form (Fig.11). Sphigmography helps in diagnostics of aortic stenosis. Slowing down of elevation and lowering of pulse wave (slow pulse), little amplitude of pulse waves and their notched tops (sphigmogram as “cock’s comb”, reflecting fluctuations, connected with conducting of systolic murmur to the cervical vessels) are marked on sphigmogram. On EchoCG sharp decrease of opening degree of aortic cusps during systole is registered. Echo-signal from cusps becomes more intensive, signs of left ventricular hypertrophy are revealed.

Fig. 11 . PCG and sphigmogram in aortic stenosis, registered over aorta. Crescendo - decrescendo systolic (like-rhomb) murmur is marked; top of sphigmogram is notched as cock’s comb.

Aortic stenosis during long period is compensated heart valvular disease. Circulatory insufficiency is developed in weakening of contractile ability of left ventricle and is manifested like aortic regurgitation.

A. Test tasks to be done: - with a single selective answer - I-st level: 1. In which stenosis of aortic ostium is the appearance of haemodynamic disturbances and clinical picture of aortic stenosis observed? a) to 10-20 %; b) to 25-30 %; c) to 35-40 %; d) to 40-45 %; e) more than 50 %. 2. In which stenosis of aortic ostium does the decrease of minute blood volume appear? a) to 10-20 %; b) to 25-40 %; c) to 45-50 %; d) to 50-70 %; e) more than 75 %.

3. Mechanism of hemodynamic compensation in aortic stenosis is the following: a) shortening of systole; b) decrease pressure in the left atrium; c) bradycardia; d) increase of systolic arterial pressure in aorta; e) increase of pressure in the left ventricle. 4. In which heart valvular disease is the maximal degree of hypertrophy of the left ventricle? a) mitral insufficiency; b) mitral stenosis; c) aortic stenosis; d) aortic insufficiency; e) combined mitral valvular disease.

5. What are complaints of the patient with aortic stenosis caused by? a) by increase pressure in pulmonary artery; b) by absence of adequate increase minute blood volume on physical exertion; c) by stagnation of blood in systemic circulation; d) by compression of mediastinum organs; e) by sharp elevation and fast decrease of arterial pressure in aorta during systole and diastole of the left ventricle. 6. Data of palpation of precardic area in aortic stenosis are the following: a) diastolic “cat’s purr” in the 2nd intercostal space to the right; b) systolic “cat’s purr” in the 2nd intercostal space to the right; c) diastolic “cat’s purr” at the heart apex; d) systolic “cat’s purr” at the heart apex; e) systolic “cat’s purr” in the 2nd intercostal space to the left.

7. Data of auscultation in aortic stenosis are the following: a) increasing of the I sound at the heart apex; b) accent of the II sound over the aorta; c) presystolic gallop rhythm; d) soft, blowing, decrescendo systolic murmur on an aorta; e) rough, loud crescendo-decrescendo systolic murmur on an aorta. 8. Systolic murmur in aortic stenosis is radiated: a) into the heart apex and Botkin’s point; b) into the left axillary area; c) into the 2nd left intercostals space; d) into the xiphoid process area; e) into carotids, subcavicular arteries.

9. In basis of disturbances of hemodynamic in aortic insufficiency is the following: a) difficulty of flow of the blood from the left ventricle into aorta; b) fast systolic flow of great blood mass from the left ventricle into aorta and fast diastolic regurgitation of great blood amount from aorta into the left ventricle; c) increasing of pressure in the left ventricle; d) blood stagnation in pulmonary circulation; e) blood stagnation in systemic circulation. 10. Volume of regurgitated blood from aorta into the left ventricle in aortic insufficiency mostly depends on: a) area of defect of aortic valves; b) degree of mitralization of this heart valvular disease; c) degree of hypertrophy of the left ventricle; d) degree of dilatation of the left ventricle; e) degree of pressure increasing in pulmonary circulation.

11. In which limits can the regurgitation of blood from aorta into the left ventricle in aortic insufficiency be observed? a) 10-20 %; b) 20-70 %; c) 5-50 %; d) 20-40 %; e) 30-80 %. 12. What can maximal value of cardiac output in aortic insufficiency be? a) 70-100 ml; b) 80-120 ml; c) 100-150 ml; d) 180-200 ml; e) 200-230 ml.

13. What is compensatory mechanism in aortic insufficiency? a) hypertrophy of the left ventricle; b) dilatation of the left ventricle; c) increasing of pressure in arteries of systemic circulation; d) development of bradycardia, lengthening of systole; e) increasing of pressure in pulmonary circulation as result of mitralization of this defect. 14. Main complaints in aortic insufficiency are caused by: a) sharp output of great blood amount from the left ventricle and significant returning of blood from aorta into the left ventricle; b) development of arrhythmia; c) dilatation of the left ventricle; d) increasing of pressure in pulmonary circulation; e) blood stagnation in systemic circulation.

15. What can be revealed during examination of the patient with aortic insufficiency? a) swelling and pulsation of cervical veins; b) “dancing of carotids” c) “face of wax doll”; d) “Corvisart’s face”; e) enlargement of the left pupil (anisocoria). 16. Positive Quince’s symptom in aortic insufficiency is: a) rhythmic movements of the head, synchronous with pulse; b) positive capillary (arteriolar) pulse, manifested by reddening and turning pale of nail bed, synchronous with pulse; c) pulsating pupils; d) enlargement of the left pupil (anisocoria). e) different pulse on radial arteries according to filling ( decreasing of filling of the left radial artery).

17. Data of auscultation in aortic insufficiency are the following: a) increasing of I sound at the heart apex; b) increasing of II sound over aorta; c) increasing of II sound over pulmonary trunk; d) rough, loud crescendo-decrescendo systolic murmur on an aorta; e) soft, blowing diastolic murmur on an aorta, transmitted to the Botkin-Erb point. 18. What functional murmur can be heard in patients with aortic insufficiency? a) systolic hydremic; b) systolic hemodynamic; c) Flint’s murmur; d) Coomb’s murmur; e) Grehem-still murmur.

19. As result of which causes does diastolic Flint‘s murmur in aortic insufficiency occur? a) relative mitral valve insufficiency; b) relative mitral stenosis; c) relative aortic stenosis; d) relative tricuspid valve insufficiency; e) relative pulmonary artery ostium stenosis. 20. What is pulse in aortic insufficiency? a) tense, irregular; b) large, tense; c) small, soft, slow; d) large, swift, rapid; e) different filling on both radial arteries.

- with the selective group of right answers - II - nd level: 1. Aortic stenosis can be caused by: a) sepsis; b) syphilis; c) chronic rheumatic disease of heart; d) rheumatoid arthritis; e) atherosclerosis; f) myocardial infarction; g) anemia. 2. What complaints are caused by aortic stenosis? a) dyspnea on physical exertion; b) intermissions; c) vomiting; d) pain in the heart area; e) palpitation; f) syncope; g) general weakness. 3. What are the data of palpation of heart area in case of aortic stenosis? a) displacement of heart beat to the left and downwards; b) displacement of apex beat to the left and downwards; c) displacement of apex beat upwards; d) diastholic thrill of the chest in the 2nd intercostal space to the right of sternum; e) diastholic thrill of the chest in the 2nd intercostal space to the left of sternum; f) systolic thrill of the chest in the 2nd intercostal space to the left of sternum; g) systolic thrill of the chest in the 2nd intercostal space to the right of sternum. 4. What are the data of percussion of the heart in aortic stenosis? a) left border of relative cardiac dullness is displaced to the left; b) right border of relative cardiac dullness is displaced laterally; c) waist of the heart is smoothed; d) waist of the heart is evident; e) aortal configuration; f) mitral configuration; g) normal configuration.

5. What are main complaints of patients with aortic insufficiency? a) feeling of air deficit; b) palpitation; c) intermissions; d) edemas; e) pain in the heart; f) feeling of pulsation in the head; g) headache; h) asphyxia attacks. 6. What murmur, except diastolic over aorta and in Botkin-Erb point can be heard, in case of aortic insufficiency? a) systolic murmur at xiphoid process; b) anemic murmur over the aorta; c) muscular murmur at the heart apex; d) Coomb’s murmur; e) systolic murmur at the heart apex (murmur of relative mitral valve insufficiency); f) functional presystolic Flint’s murmur at the heart apex; g) functional Grehem-Still murmur over the 2nd intercostal space to the left. 7. What is the pulse in aortic insufficiency? a) “pulsus celer”; b) “pulsus tardus”; c) “pulsus difference”; d) “pulsus altus” e) “pulsus magnus”; f) “pulsus frequens”; g) “pulsus parvus”. 8. What are potential complications in patients with aortic regurgitation? a) cardiac asthma; b) hypertensive crisis; c) pulmonary edema; d) chronic heart failure due to its “mitralization”; e) atrial fibrillation; f) vascular failure .

A. Tasks to be done:

Task 1. In patient R., 35 years old, during palpation systolic trembling in the II intercostal space to the right of sternum was revealed. Left border of relative cardiac dullness (by percussion) is 1,5 cm laterally of the left midclavicular line. Apex beat is forced. In patient it can be: a) Mitral stenosis; b) Mitral valve insufficiency; c) Aortic stenosis; d) Aortic valve insufficiency; e) Tricuspid valve insufficiency.

Task 2. In patient S. during auscultation moderate weakening of the I sound at the heart apex was revealed. Loud systolic murmur is heard on the level of the II intercostal space to the right of sternum. This murmur is radiated to all sides, but mainly - upwards, to the area of neck. In patient it can be: a) Mitral valve insufficiency; b) Mitral stenosis; c) Aortic valve insufficiency; d) Aortic stenosis; e) Tricuspid valve insufficiency.

Task 3. Patient N. complains of dyspnea on little exertion. The skin is pale. Expressed pulsation of carotids is visible on the neck. Apex beat is palpated in the VI intercostal space 2 cm laterally of the left midclavicular line. It is diffuse, forced. Diastolic murmur decrescendo, beginning at once after the II sound and occupying 2/3 of diastole, is heard in the II intercostal space to the rigth of sternum. Radiation of the murmur to the 5th point area and farther - to the apex heart is marked. The II sound is weakened in the II intercostal space to the right of sternum. For which heart valvular disease is such symptomatology typical? a) Mitral stenosis; b) Mitral valve insufficiency; c) Aortic stenosis; d) Aortic valve insufficiency; e) Tricuspid valve insufficiency.

Answers for test tasks of the I-st level: 1 - d 6 - b 1 1 - c 16- b 2 - d 7 - e 1 2 - d 17- e 3 - e 8 - e 1 3 - b 18- c 4 - c 9 - b 14- a 19- d 5 - b 1 0 - a 15- b 2 0 - d

Answers for test tasks of the II-nd level: 1 - c , e 5 - a,b,e,f,g,h 2 - a , d , f, g 6 - e , f 3 - b , g 7 - a , d , e , f 4 - a , d , e 8 - a , c , d

Standards of right answer for tasks: 1) - c 2) - d 3) – d Literature recommended: Main Sources: 1. Propedeutics to Internal Medicine : textbook for English learning students of higher medical schools. Pt. 1. Diagnosis / O. N. Kovalyova, T. Ashcheulova. - 2nd ed. - Vinnytsya : Nova Knyha Publ., 2011. - 424 p. 2. Propaedeutics to Internal Medicine: Syndromes; textbook for English learning Students of higher medical schools; Pt 2. / O.N. Kovalyova, S. Shapovalova – Vinnytsya: Nova Knyha publishers, 2011. – 424 p. 3. Propaedeutics of Internal Medicine: a textbook / Y.I.Detsyk, O.H. Jaworski, R.J. Dutka et al., Ed. prof. O.H. Jaworski. 3rd ed., Correct. and reported. - K. VSV "Medicine", 2013. - 552 p. 4. Basics of Internal Medicine.: Propedeutics of internal diseases / Detsyk Y.I., Jaworski E.G., Dutka R.J., Ed. O.H. Jaworski. - K.: Health 2004.-500 p. 5. Grebenev A.L. Propedeutics Internal Medicine: A Textbook AL Grebenev, 5th ed. pererab.i ext. - Moscow: Meditsina, 2002. - 585 p. 6. Study Guide "Computer tests of propedeutics of internal diseases" (by V.V. Korotkyj, A.B. Novosad). Kyiv: Health 2001 – 148p. 7. Introduction to the Course of Internal Diseases. Book 1. Diagnosis / Zh. D. Semidotska, O. S. Bilchenko [et al.] ; ed. by Zh. D. Semidotska. - 2nd ed., revised and supplememted. - Kharkiv : Tornado, 2006. - 314 p. 8. General thesis about organization and conduction of complex practically oriented state examination from internal medicine, professional and infectious diseases : manual for out-class work with English-medium graduates / KhNMU ; comp. O. Babak [et al.]. - Kharkov : KhNMU, 2012. - 40 p. - англ.

4. Propaedeutics as an Introduction to the Clinic of Internal Medicine Propaedeutics M. Yabluchansky L. Bogun, L.Martymianova, O. Bychkova, N. Lysenko, N. Makienko, E. Golubkina V.N. Karazin National University Medical School’ Internal Medicine Dept. http://dspace.univer.kharkov.ua/bitstream/123456789/10966/2/Lecture%20PI M_22.06.2015.pdf 5. ИИ Мистюкевич. Theses of lectures on propedeutics of internal diseases. www.gsmu.by/file/biblio/uchlit/tezisyprop.doc 6. Internal diseases propedeutics [Электронный ресурс] / Ivashkin V.T., Okhlobystin A.V. - М. : ГЭОТАР-Медиа, 2014. http://www.medcollegelib.ru/book/ISBN9785970430378.html 7. Англо-русский тематический словарь по пропедевтике внутренних болезней и общему уходу за больными : справочное издание / Витебский государственный медицинский университет, Кафедра пропедевтики внутренних болезней; сост. Л.М. Немцов; под ред. Г.И. Юпатова. - Витебск : ВГМУ, 2005. - 153 с. URI: http://elib.vsmu.by/handle/123/11343 8. Special propedeutics of internal diseases : lecture course / Vitebsk State Medical University, Dep. of Propedeutics of Internal Diseases ; comp. by L. M. Nemtsov. - 2-е изд. - Vitebsk : VSMU, 2016. - 318 p. URI: http://elib.vsmu.by/handle/123/9837 9. General propedeutics of internal diseases : lecture course / Vitebsk State Medical University ; compiled by L. M. Nemtsov. - Vitebsk : VSMU, 2006. - 175 p. http://elib.vsmu.by/handle/123/268

Additional ones:

Methodical instruction is composed by lecturer Ye.Ye. Petrov.

Approved at the Department of Propaedeutics to Internal Medicine with Care of Patients meeting on 11 09 2018 Protocol No2 The Head of the Department Professor Yu. Kazakov

METHODICAL INSTRUCTION FOR STUDENTS’ SELF-PREPARATION WORK

Educational discipline Propaedeutics to Internal Medicine Module No 2 Enclosure module No 6 Topic The main symptoms and syndromes on arterial hypertension and symptomatic arterial hypertension. Hypertensive crisis

Year 3 Faculty medical

Poltava - 2018

1. The topic basis: Epidemiological researches, carried out during last 20 years, show that arterial hypertension is one of the widespread disease. According to data of 2000, in Russia part of diseases, accompanied by elevated blood pressure (BP), in structure of all circulatory diseases morbidity was 27 %. Increase of arterial hypertension morbidity proportionally to age is marked. Arterial hypertension comes to light in 28% of the population of the USA and 44% of the population of the countries of the Europe according to the modern epidemiological researches. Approximately 45 million Americans have elevated BP or receiving treatment.

2. The specific aims:  To explain risk factors of arterial hypertension.  To explain stratification of risk accordance with diagnostic criteria.  To classify essential hypertension (WHO, 1962) and arterial hypertension (WHO and International Society of Hypertension, 1999).  To explain measurement of blood pressure for correct diagnostics.  To explain pathogenesis of essential hypertension.  To analyze potential lesion of “target-organs” in arterial hypertension.  To analyze results of examination of patients with arterial hypertension  To interpret results of examination of patients with arterial hypertension.  To explain principles of arterial hypertension treatment without drugs and with drugs.

3. Basic knowledge, experience, skills necessary for studying the topic in connection with other subjects (interdisciplinary integration) :

Previous disciplines Obtained skills 1. Anatomy To know human anatomy, cardio-vascular system organs particularly. 2. Physiology To know physiology of cardio-vascular system. 3. Pathological physiology To know pathogenesis of essential arterial hypertension 3. Medical psychology To be able to observe principles of ethics and deontology in medical practice. 4. Pathological morphology To know potential lesion of “target-organs” (heart, vessels, brain, kidneys) in case of arterial hypertension.

4. Tasks for self-work during preparation to the class. 4.1 List of the main terms, parameters, characteristics, which should be mastered during preparation to the class:

Term Definition 1. Arterial hypertension It is elevation of blood pressure (BP), i.e. diastolic one is more than 90 mm Hg, systolic is more than 140 mm Hg (as result of repeated BP measurements, carried out in different time in comfortable for patient situation; besides patient doesn’t intake medicaments both hypertensive and antihypertensive). 2. Primary (essential, idiopathic) arterial It is name of arterial hypertension in case of absence of frank reason. hypertension 3. Secondary (symptomatic) arterial It is arterial hypertension when its reasons are revealed. hypertension

4. Isolated systolic arterial It is arterial hypertension when only systolic BP is elevated (more than hypertension. 140 mm Hg).

5. Malignant (pale) It is arterial hypertension with expressed constant elevation of BP (of hypertension diastolic one - more than 120 mm Hg), which isn’t decreased during day, at night even.

6. Dipper It is type of change BP according to data of BP daily monitoring with normal reduction of BP at night.

7. Non-dipper It is type of change BP according to data of BP daily monitoring without normal reduction of BP at night.

8. Night-peaker It is type of change BP according to data of BP daily monitoring with night elevation of BP.

9. “Hypertension of white It is elevation of BP in presence of physician only. smock”

10. Hypertensive crisis It is fast, additional, significant elevation of BP.

4.2. Theoretical questions to be answered before class: 1. What does term “arterial hypertension” mean? 2. Tell about the main and additional risk-factors of arterial hypertension. 3. Tell about risk stratification accordance with diagnostic criteria. 4. What classifications of essential hypertension and arterial hypertension are used in Ukraine mainly? 5. Tell about pathogenesis of essential hypertension. 6. Tell about classification of arterial hypertension. 7. Describe lesions of target-organs in arterial hypertension. 8. Tell about complaints and anamnesis of patients with arterial hypertension. 9. What can potential results of objective examination of patients with arterial hypertension be? 10. What laboratory and instrumental methods are used for diagnostics of arterial hypertension and their potential results? 11. What does term “hypertensive crisis” mean? 12. What are purposes of examination of patients with arterial hypertension? 13. Tell about methods of BP decrease without drugs. 14. Tell about principles of arterial hypertension pharmacotherapy. 15. Tell about essence of the following symptomatic arterial hypertensions: in case of coarctation of aorta, pheochromacytoma, primary aldosteronism, Cushing’s syndrome, diseases of kidneys. 4.3. Practical work (tasks), which should be performed during class: 1. To carry out examination of patients with arterial hypertension. 2. To interpret obtained results. 3. To interpret results of laboratory and instrumental methods examination of patients with arterial hypertension.

The contents of topic: Text ARTERIAL HYPERTENSION Arterial hypertension is elevation of blood pressure (BP), i.e. diastolic one is more than 90 mm Hg, systolic is more than 140 mm Hg (as result of repeated BP measurements, carried out in different time in comfortable for patient situation; besides patient doesn’t intake medicaments both hypertensive and antihypertensive). Arterial hypertensive can be primary and secondary. Arterial hypertension is called primary (essential, idiopathic, in Ukraine - hypertensive disease, morbus hypertonicus) in case of absence of frank reason. If reasons of arterial hypertension are revealed, it is named secondary (symptomatic). If only systolic BP is elevated (more than 140 mm Hg), it is named isolated systolic arterial hypertension. Malignant (pale) hypertension is characterized by expressed constant elevation of BP (of diastolic one - more than 120 mm Hg), which isn’t decreased during day, at night even. Expressed changes of eye grounds with disk of optic nerve edema, eye grounds haemorrhages, and signs of progressive lesion of the heart, brain, and kidneys are typical for it usually. Significant fluctuations of BP, occurring under influencing of emotional and physical overstrain, are marked in the same person. Lower indices of the pressure are recorded at night, and maximal ones - at the end of day. Rarely BP can reach high indices, but in health persons pressure becomes normal at rest in some minutes. Arterial hypertension and risk of cardio-vascular complications Constant increase of risk of cardiovascular diseases and steady increase of mortality became evident in proportion with accumulation of epidemiological data about natural course of arterial hypertension. Besides, it is very difficult to mark distinct border between normal and pathological BP, as frequency of complications is increased even in case of its elevation within normal limits. And what is more - absolute majority of cardiovascular complications is registered in persons with insignificant elevation of BP, and their part exceeds number of patients with high BP essentially. Risk factors Prognosis in patients with arterial hypertension doesn’t depend on level of BP only. Risk factors have great importance. They are subdivided into the main and additional. The main risk factors  Male sex and menopause in women;  Smoking;  Cholesterol more than 6,5 mmol/l;  Early cardiovascular diseases (in women - less than 65 years old, in men - less than 55 years old) in family history. Additional risk factors  Decrease of cholesterol of high-density lipoproteins contents;  Increase of cholesterol of low-density lipoproteins contents;  Diabetes mellitus;  Disorder of glucose tolerance;  Obesity;  Sedentary life-style;  Increase of fibrinogen level;  Endogenous tissue-type plasminogen activator;  Hyperhomocysteinemia;  Increase of C-reactive protein level;  Estrogens deficit;  Certain social-economic status;  Ethnic factor. During estimation of risk, first of all, the main risk factors is used usually, from additional ones - cholesterol fractions, obesity, disorder of glucose tolerance;

Risk stratification Presence of accompanying risk factors, degree of involving of target organs, and accompanying pathologic conditions don’t have less importance than degree of BP elevation. In this connection stratification of the patients depending on risk degree is introduced into modern classification.  Stratification of the patients according to risk degree (Table 1, 2) is based on traditional estimation of lesion of target-organs and cardiovascular complications. It allows to estimate individual forecast qualitatively (risk is higher, forecast is worse) and to choose groups for social-medical supporting. Clinical manifestations of cardiovascular diseases and lesions of target-organs are more valuable prognostic factors in comparison with traditional risk factors.  Special value of this approach is in the following: level of BP loss dominant role during choice of treatment tactics. It is very important, taking into account big variability of BP, particularly in patients without regular treatment, and inevitable difficulties, if the patient belongs to any risk-group only on the basis of BP results. So, dividing of the patients according to risk degree has been introduced. It allows to take into account essentially greater amount of objective parameters, facilitates estimation of individual prognosis and simples choose of treatment tactics. Spectrum of risk factors is refilled constantly. Side by side with traditional risk factors now new additional risk factors are discussed. Their importance and methods of quantitative estimation must be defined more exactly in future.

Table 1 Criteria of risk stratification Risk factors Lesion of target-organs Associated clinical conditions Men more than 55 Hypertrophy of the left Cerebrovascular diseases years old ventricle (ECG, EchoCG  Ischemic stroke Women more than or X-ray study)  Hemorrhagic stroke 65 years old Proteinuria and/or blood  Transitory ischemic attack Smoking creatinine 1,2-2,0 mg% Heart diseases Cholesterol Ultrasound or X-ray  Myocardial infarction content more than signs of atherosclerotic  Angina pectoris 6,5 mmol/l plaque  Coronary revascularization Family anamnesis Generalized of focal  Congestive heart failure of early constriction of retinal Renal diseases cardiovascular arteries  Diabetic nephropathy diseases (in women less than  Renal failure (blood creatinine is more 65 years old and than 2 mg% men less than 55 Vascular diseases years old)  Dissecting aortic aneurysm  Lesion of peripheral arteries, accompanied by corresponding signs Hypertensive retinopathy  Haemorrhages or exudates  Edema of optic papilla Diabetes mellitus

Table 2 Risk stratification in accordance with criteria Risk category Diagnostic criteria Low risk I degree of arterial hypertension; risk factors, lesions of target-organs, (risk 1) cardiovascular diseases and associated diseases are absent Moderate risk II-III degree of arterial hypertension, risk factors, lesions of target-organs, (risk 2) cardiovascular diseases and associated diseases are absent I-III degree of arterial hypertension, one and more risk factors are present, lesions of target-organs, cardiovascular diseases and associated diseases are absent

High risk I-III degree of arterial hypertension, lesions of target-organs and (not always) (risk 3) other risk factors are present, associated diseases are absent

Very high risk I-III degree of arterial hypertension and (not always) diabetes mellitus and (not (risk 4) always) other risk factors, associated diseases are present

Effective population strategy, directed to prevention of BP elevation proportionally to age and decrease of mean level of BP, can reduce general cardiovascular morbidity and mortality not less than treatment of patients with arterial hypertension. The main criterion for prescription of drug therapy is belonging to certain risk group (degree of BP elevation isn’t the main criterion). In case of high risk the drug therapy must be began immediately. In case of low and moderate risk the non-drug programme of reduce of BP with length from 3 to 12 months must precede to it. Modern recommendations direct that systolic BP side by side with diastolic one is criterion of diagnostics, severity of the course and effectiveness of antihypertensive therapy. It is connected with the following: close, independent from age, association of systolic BP with risk of development of coronary, cerebral and renal complications (more strong than in case of diastolic BP) was established during long term prospective study. Decrease of systolic BP results to distinct diminishing of this risk. So, in elderly persons systolic BP allows to prognosticate risk of complications better than diastolic one. Recently it was established that elevated pulse BP has more importance.

Classifications In connection with great attention to estimation of risk of cardiovascular complications in patients with arterial hypertension, deviation from classification, based on determining of stage and transfer to determining degree of BP elevation with simultaneous diagnostics of risk ( low, moderate, high, very high) are outlined. This approach was formulated in recommendations of experts of WHO and International Society of Hypertension and supposed in Report of Russian experts on arterial hypertension (RAH-1). Classifications, used now in Ukraine and Russia, are shown below. Until now classification of essential hypertension of WHO (1962) is the most widespread (Table 3). Table 3 Clasification of essential hypertension, WHO, 1962 Stage I Elevation of BP more than 160/95 mm Hg without organic changes of cardiovascular system Stage II Elevation of BP more than 160/95 mm Hg in combination with changes of target-organs (heart, kidneys, brain, vessels of eye grounds), caused by arterial hypertension, but without their dysfunction. Stage III Arterial hypertension, combined with lesion of target-organs (heart, kidneys, brain, eye grounds) with their dysfunctions.

In 1999 WHO and International Society of Hypertension propose the following classification of arterial hypertension by BP level (Table 4). Table 4 Classification of arterial hypertension WHO and International Society of Hypertension Category Systolic BP, Diastolic BP, mm Hg mm Hg Optimal <120 <80 Normal <130 <85 High normal 130-139 85-89 I degree (mild) 140-159 90-99 subgroup: border 140-149 90-94 II degree (moderate) 160-179 100-109 III degree (expressed) > 180 > 110 Isolated systolic 140-149 <90 subgroup: 140-149 <90 border

In case of little elevation of BP it is necessary to estimate spectre of risk-factors completely and to begin non-medication (without drug) programme of the treatment; in case of more expressed elevation of BP tactics of patients’ treatment is decided by physician according to concrete clinical situation.

Measurement of blood pressure Level of BP is estimated on the basis of average indices of not less than two measurements at two medical examinations (minimally) with interval 2 months after first revealing of elevated BP. In case of BP measurement at home it is possible to estimate it in different days in patients’ everyday conditions. It eliminates “effect of white smock” (elevation of BP at physician’s presence only). Self-control of BP disciplines patient and improves his/her adherence to the treatment. In case of first revealed arterial hypertension it is necessary to measure BP on both hands and in young persons - on the legs also. Besides, serious reasons of BP elevation as aortoarteritis, coarctation of aorta can be excluded easily. Non-invasive automatic apparatuses for long BP registration in the outpatient settings become now widespread. Recommended daily monitoring programme proposes BP registration with 15-minutes intervals during wakeful state period and 30-minutes intervals during sleep period. Approximate limits of normal BP in the day-time and at night are 135/85 and 120/70 mm Hg, accordingly; degree of BP decrease at night is 10-20%. It is known numerous data about more close correlation between degree of target-organs’ lesion in arterial hypertension (hypertrophy of the left ventricle, severity of retinopathy, microalbuminuria, level of serum creatinine) and results of daily monitoring of BP in comparison with single measurement. According to data of BP daily monitoring there are three types of changes during 24 hours: with normal reduction of BP at night - dipper, without BP reduction at night - non-dipper, with night elevation of BP - night-peaker. Monitoring also reveales patients, in which BP is elevated in presence of physician only (“hypertension of white smock”).

Pathogenesis Notions about origin of essential hypertension were formulated by G.F.Lang and A.L. Myasnikov. They attached much importance to mental stress, negative emotions, dysfunction of cerebral hemisphere cortex and hypothalamus. These notions weren’t confirmed completely during future researches. Number of other pathogenetic mechanisms of arterial hypertension was established. Factors, influencing to level of BP include vasoactive substances, changing general peripheral vascular resistance (GPVR) (their production is connected with sympathetic nervous system activity, particularly), value of cardiac output, volume of extracellular fluid, functioning of kidneys and genetic factors.  Cardiac output and GPVR are two the main factors. Elevation of BP can be connected with increase of minute blood volume and /or increase of GPVR. In this connection hyperkinetic (increased minute volume), eukinetic (normal cardiac output, normal GPVR) and hypokinetic (low cardiac output, high GPVR) types of circulation are distinguished. Elevation of BP can occur in any of these types. In case of eukinetic circulation, in spite of normal values of minute volume and GPVR, disparity of one to another take place (with dominance of GPVR). It directs to significance of regulatory factors, changing both function of the heart, and peripheral vessels.  Changes of kidneys’ function and vasopressor hormones play important role in pathogenesis of arterial hypertension. Vasopressor hormones include renin, angiotensin I, vasopressin, endothelin. Natriuretic peptides, kallikrein-kinin system, adrenomedullin, nitrogen oxide, prostaglandins (preostaglandin I2, prostacyclin) are vasopressors. Change of sodium excretion can promote to increase of extracellular fluid amount and, consequently, to elevation of BP. Besides, kidneys produce number of vasoative substances, and what’s more - not only vasoconstrictive, but vasodilating (prostaglandins) also, which change blood flow locally. Action of all these renal and extrarenal factors is interconnected in any event and disorders of different links of this connection result to elevation of BP.  Close attention of researchers during last years is absorbed to inherited mechanisms of arterial hypertension. They suppose that in case of arterial hypertension disorder of BP regulation occurs as result of different genetic defects, determining functional response of circulation to external and internal influences. Genes, mutations of which promote to development of arterial hypertension, are estimated. They are: mutation of angiotensin gene, mutations, resulting to expression of enzyme aldosteronesinthetase, mutation of β-subunits of amyloridesensitive sodium canals of renal epithelium. Genetic defects can influence to disorder of transmembranous cellular transfer of sodium and calcium ions with accumulation of last ones inside of cells. It plays peculiar role in change of condition of smooth muscular cells of little vessels and in increasing of their propensity to contraction and occurrence of vascular spasm.  Mechanical constriction of arteriolar lumen as result of their edema has importance also. It promotes to increase of sensitivity to pressor stimuli. Epidemiological researches reveal factors, confirming importance of foregoing pathogenetic mechanisms greatly. These the most widespread risk-factors of essential hypertension includes surplus dietary salt intake (20/25 g/day), frequent and intensive psycho- emotional stresses, diabetes mellitus, presence of essential hypertension in patient’s relatives. It is necessary to emphasize that alcohol abuse promotes to development of arterial hypertension essentially, in men particularly. Lesion of target-organs Arterial hypertension, existing long period particularly, results to lesion of internal organs, called as target-organs, - of the heart, vessels, brain and kidneys. Lesion of the heart Lesion of the heart in arterial hypertension can be manifested by left ventricular hypertrophy and lesion of coronary vessels with development of angina pectoris, myocardial infarction, and sudden cardiac death. In case of progressing of heart lesion heart failure is developed. It can occur without left ventricular dilatation also, as result of disorder of diastolic filling (restriction). Myocardial ischemia can’t occur due to lesion of coronary arteries (of their epicardial parts) only, but due to relative coronary insufficiency (inability of unchanged coronary arteries to supply hypertrophied myocardium with blood) also and due to microvasculopathy. Lesion of vessels Vessels, taking part directly in supporting of high BP due to GPVR, are one of target- organ. Vascular lesion is characterized by involving of ocular retina vessels, carotids and aorta (aneurism) in process and also by lesion of smaller vessels: lesion of little arteries of the brain (occlusions or microaneurisms) can lead to occurrence of strokes, of renal arteries - to renal dysfunctions. Research of eye ground (ophthalmoscopy) give possibility to the physician to estimate vascular changes directly. In case of arterial hypertension vessels are constricted, than - are subjected to sclerosis. It is accompanied by forming of microaneurysms, microhemorrhages, and ischemic lesion of blood supplied organs. All these changes step by step can be visible on the eye ground of the patient with arterial hypertension. Lesion of brain Lesion of brain is characterized by thromboses and haemorrhages, hypertensive encephalopathy and forming of lacunas in tissues of the brain. Lesion of cerebral vessels can lead to changes of their walls (atherosclerosis). During different stages of disease these changes can be complicated by acute cerebral circulatory insufficiency due to thrombosis or rupture of cerebral arteries with haemorrhage. Lesion of kidneys Already by the early stage of disease tendency to change of renal vessels is present. It is characterized by some increase of glomerular filtration at the beginning, and then - by decrease of glomerular filtration. Long course of arterial hypertension results to nephroangiosclerosis with significant decrease of kidney’s functions and development of chronic renal failure. Changes of glomerular filtration rate (GFR) reflect kidney’s functions. During initial stages of arterial hypertension GFR isn’t decreased usually, but during later stages (or in case of malignant arterial hypertension) GFR is decreased progressively. Besides, blood creatinine content and protein concentration in urine (occurrence of microalbuminuria is typical) are indexes of kidneys’ involving in pathological process in arterial hypertension. Presence of microalbuminuria reflects progressing lesion of bloodstream generally.

Clinical manifestations Clinical picture depends, first of all, on degree of target-organs’ lesion. Complaints and anamnesis In many patients uncomplicated arterial hypertension is taking its latent course, and doesn’t cause deterioration of feeling; often it is diagnosed casually. Signs of neurosis, headaches, in the morning particularly, nausea, flashing of “spots” in front of eyes, pains in heart area, palpitation, rapid fatigability, nasal bleedings, hyperexcitability, irritability, sleep disturbance are possible. During later stages it is possible occurrence of angina pectoris attacks. Severity of these signs, of headaches particularly, isn’t always corresponding to degree of BP elevation. During analysis of anamnesis it is necessary to obtain information concerning to family anamnesis of arterial hypertension and other conditions, aggravating prognosis in its presence, - of diabetes mellitus, dyslipidemia, IHD, cerebral stroke. Information about length and degree of BP elevation, effectiveness of previous drug treatment and treatment without drugs are important also. It is necessary to ascertain peculiarities of patient’s life stile, including diets (fats, dietary salt, alcohol), smoking, physical activity, presence of excessive body weight or obesity. Inspection, physical and instrumental examination During inspection it is necessary to pay one’s attention to excessive body weight. It is marked both hyperaemia of the face and paleness of skin covers due to spasm of peripheral arterioles. During research of the heart signs of the main syndrome in arterial hypertension - of the left ventricular hypertrophy (displacement of the apex beat to the left) are revealed; it is confirmed by results of ECG, X-ray and Echo-CG- studies. In elevated BP increase of pulse tension is very typical; by degree of last one it is possible to think approximately about BP level. Besides, elevation of BP is characterized by appearance of accent of the II sound over aorta. Initially ECG changes are characterized by lowering of T wave in the left chest leads (reversible process). Hypertrophy of the left ventricle is manifested by high R wave with sloping lowering (depression) of ST segment in leads V4-6. Left bundle-branch block can occur. During Echo-CG hypertrophy of interventricuar septum of the posterior wall of the left ventricle is diagnosed. Sometimes these changes are accompanied by dilatation, increase of final systolic and diastolic sizes of the left ventricle. Appearance of hypokinesia areas and even dyskinesia areas in myocardium is sign of decreased contractive ability of the left ventricle. During last years different metabolic disorders are marked in arterial hypertension. They are hyperinsulinemia, decrease of glucose tolerance, (in number of cases - type II diabetes mellitus), dyslipidemia (it is characterized by increase of content of low-density lipoproteins in the blood and by decrease of high-density lipoproteins content - obesity). Hypertensive crisis The course of arterial hypertension can be complicated by hypertensive crisis. It is fast, additional, significant elevation of BP. It can be provoked by different physical and psychical stress, salt, fluid, alcohol intake in quantity, cessation of therapy. Besides, very high BP (diastolic BP can exceed 130-140 mm Hg) is revealed in patient. In majority cases cerebral symptomatology (nausea, vomiting, vision impairment) appears on the background of such BP elevation. Other manifestations and complications of arterial hypertension can be intensified simultaneously or some later. They are: exacerbation of IHD, development of acute left- ventricular failure, acute cerebral circulatory insufficiency. In case of severe crisis - haemorrhages, disk of optic nerve edema can occur on eye ground. Lesion of kidneys During late period of arterial hypertension symptoms of kidneys’ lesion, caused development of arteriosclerosis, appear. They are: decrease of kidneys’ concentration ability, decrease of specific gravity of urine, appearance of protein and erythrocytes in urine, during late stage - retention of nitrogenous slags. Signs of eye ground’s lesion are developed simultaneously. They are: increased constriction and crimpiness of retinal arteries, particularly in comparison with veins, dilation of veins; it is possible eye ground haemorrhages, and later - degenerative foci in retina. Lesion of central nervous system Lesion of CNS causes various symptoms, connected with expressiveness and localization of vascular disorders. Constriction of vessels (as result of their spasm) results to development of ischemia of cerebrum’s part with its partial dysfunction and in more severe cases is accompanied by cerebral haemorrhages. In case of sharp elevation of BP ruptures of arterial wall with massive haemorrhage are possible.

Purposes of examination of patients with arterial hypertension During examination of patients with arterial hypertension it is necessary:  to confirm stability of BP elevation;  to exclude secondary arterial hypertension;  to establish eliminated and non-eliminated risk factors of cardiovascular diseases;  to estimate presence of target-organs’ lesions, cardiovascular and other accompanying diseases;  to estimate individual risk degree of IHD and cardiovascular complications.

Symptomatic arterial hypertension Coarctation of aorta It is necessary to think about coarctation of aorta in case of arterial hypertension in young persons, in its casual revealing particularly. For confirming of diagnosis it is necessary to measure BP both on hands, and legs, besides on the legs pressure is normal or reduced. Pheochromacytoma Pheochromacytoma is tumour of medullar layer of adrenal glands, producing catecholamines. Paroxysms of arterial hypertension are typical for this disease, but almost in half of patients elevation of BP is stable. Complaints of hyperhydrosis, palpitation with tachycardia occur often. It is impotrant for diagnosis revealing of high level of catecholamines in blood, during attack particularly. For diagnostics it is necessary to study daily urine for catecholamines and visualization of tumour (computed tomogram, magnetic resonance image and ultrasound study as less effective diagnostic method).

Primary aldosteronism Primary aldosteronism (Conn’s syndrome) is caused by tumour of adrenal glands cortex with increased secretion of aldosterone. Apart from BP elevation, it is typical attacks of weakness, paresthesia and paralysis, hypokaliemia, dysfunction of kidneys with polyuria. For making diagnosis, apart from hypokaliemia, increase of aldosterone excretion with urine, revealed radioimmunne method, has importance. Besides, renin activity in plasma is low. Radiation methods of tumour visualization are analogous to ones in case of pheochromacytoma.

Cushing’s syndrome Cushing’s syndrome is developed as result of increase of glucocorticoids secretion by adrenal glands cortex. Apart from high BP, obesity with specific like-moon face, strias on lateral parts of trunk are typical for it. Cushing’s syndrome (apart from hypercortisonisms) can be developed as result of presence of tumours, producing adrenocorticotropic hormone and substances like it, and tumours of adrenal glands and other organs. Analogous manifestations occur in case of long therapy with glucocorticoids.

Diseases of kidneys Renoparenchymatous arterial hypertension occurs in renal diseases of diffuse character: glomerulonephritis, tubulointerstitial nephritis, pyelonephritis, renal amyloidosis (more rarely). Vasorenal arterial hypertension can be caused by:  atherosclerotic lesion of renal artery with forming of plaque;  fibromuscular dysplasia of renal artery (hyperplasia of renal artery wall due to its connective-tissue and muscular elements);  vessel occlusion by thrombus or embolus (for example, by cholesterol crystals). In case of chronic course of disease stenotic murmur over renal arteries can be revealed during auscultation. Reliable evidence of vascular lumen’s constriction can be obtained by means of aortography and renal arteriography. This pathology can be recovered radically by means of angioplasty or balloon dilatation of renal artery.

A. Test tasks to be done: -with a single selective answer – I-st level; 1. What factor is determinant for forming of blood arterial pressure level? a) minute blood volume; b) blood viscosity; c) volume of blood circulation; d) heart rate; e) venous bloodstream capacity. 2. What factor is determinant for forming of blood arterial pressure level? a) blood viscosity; b) heart rate; c) peripheral arterial resistance; d) volume of blood circulation; e) venous bloodstream capacity. 3. Degree of peripheral resistance depends mainly on the following: a) intravascular volume of fluid, caused by volume of blood circulation; b) arterial vessels patency, caused by tone of resistive vessels; c) distribution of extracellular fluid between its vascular and interstitial sectors; d) blood viscosity; e) blood velocity. 4. Where are the most active baroreceptors and chemoreceptors apparatuses regulating arterial blood pressure located? a) in vessels of capacity type; b) in aortic arch and synocarotid sinus; c) in medullar layer of adrenal glands; d) in juxtaglomerular apparatus of the kidneys; e) in cortical layer of adrenal glands. 5. Angiotensin-I: a) regulates sodium balance in organism; b) increases resistive vessels tone; c) activates secretion of catecholamines by medullar layer of adrenal glands; d) regulates intrarenal circulation; e) excites juxtaglomerular apparatus of the kidneys; 6. Angiotensin-II: a) activates secretion of catecholamines by adrenal cortex; b) regulates sodium balance in organism; c) is strong constrictor of arterioles; d) regulates intrarenal circulation; e) influences on adrenergic structures of central nervous system; 7. The main physiological effect of aldosterone is the following: a) increase of absorption of sodium and water by renal tubules; b) stimulation of renin production; c) influence on correlation of intra- and extracellular fluid volumes; d) change of calcium content in walls of arterial vessels; e) increase of resistive vessels tone. 8. What humoral factor does the most expressed pressure action have? a) aldosterone; b) renin; c) angiotensin-I; d) angiotensin-II; e) adrenaline. 9. What clinical data testify about the II stage of hypertensive disease? a) presence of cerebral stroke; b) myocardial infarction; c) eye grounds change; d) absence of urine changes; e) absence of hypertrophy of the left ventricle; 10. What is the most important criterion of differentiation of the II stage of hypertensive disease and the I stage? a) level of blood pressure more than 170/100 mm Hg; b) hypercreatinemia; c) myocardial infarction; d) cerebral stroke; e) hypertrophy of the left ventricle. 11. What clinical data testify about the III stage of hypertensive disease? a) chronic renal failure; b) hypertrophy of the left ventricle; c) eye grounds changes; d) changes of urine (persistent albuminuria); e) edema of the lower extremities. 12. What auscultative feature of change of the II sound over cardiac base is pathognomic for hypertensive disease? a) weakening of the I sound over aorta; b) accent of the II sound over aorta; c) accent of the II sound over pulmonary artery; d) reduplication of the II sound over aorta; e) splitting of the II sound over aorta.

13. Hypokinetic (hypodynamic) type of hypertensive disease occurs when: a) minute blood volume increases; b) minute blood volume and peripheral vascular resistance increases; c) peripheral vascular resistance increases; d) blood circulation increases; e) blood circulation and peripheral vascular resistance increases. 14. For hypertensive disease the following pulse is typical: a) tense (hard) pulse; b) full pulse; c) pulsus magnus; d) abrupt pulse (pulsus celer); e) rapid pulse (pulsus frequens). 15. For carrying out of daily monitoring of arterial pressure the patients should not receive the hypotensive preparations during previous: a) 1-2 days; b) 3-4 days; c) 5-7 days; d) 7-10 days; e) 1 month. 16. In case of absence of frank reason arterial hypertension last one is called: a) secondary; b) malignant; c) isolated systolic; d) primary; e) diastolic. 17. What are signs of essential hypertension, II stage (according to Clasification of essential hypertension, WHO, 1962)? a) elevation of BP more than 160/95 mm Hg; b) arterial hypertension, combined with lesion of target-organs (heart, kidneys, brain, eye grounds) with their dysfunctions; c) elevation of BP more than 160/95 mm Hg in combination with changes of target-organs, caused by arterial hypertension, but without their dysfunction; d) elevation of BP more than 180/110 mm Hg; e) arterial pressure doesn’t exceed 140/90 mm Hg. 18. I degree (mild) of arterial hypertension (according to classification of arterial hypertension WHO and International Society of Hypertension, 1999) is characterized by the following: a) systolic BP - 160-179 mm Hg, diastolic BP-100-109 mm Hg; b) systolic BP - 160-179mm Hg, diastolic BP-100-109 mm Hg; c) systolic BP - 140-159 mm Hg, diastolic BP- 90-99 mm Hg; d) systolic BP - 140-159 mm Hg, diastolic BP- 90-99 mm Hg; e) systolic BP - 130-139 mm Hg, diastolic BP-85-89 mm Hg.

-with the selective group of right answers – the II-nd level; 1. What are the main complaints of the patients with hypertensive disease? a) headache; b) ear noise; c) edema; d) decrease of vision; e) pain in the heart; f) palpitation, intermissions in the heart, in the morning after waking up mainly. g) heartburn; h) fever. 2. Corrective risk-factors of hypertensive disease development include: a) deficiency of physical activity; b) superfluous consumption of table salt; c) genetic factors; d) the sex; e) the age; f) abusing of alcohol, smoking; g) hormonal contraception in women; h) intercurrentive diseases in past; 3. What are potential results of X-ray examination in patients with hypertensive disease? a) dilatation of borders of heart to the right; b) dilatation of borders of heart to the left; c) aortic configuration of the heart; d) mitral configuration of the heart; e) aorta is prolonged, condensed and dilated; f) pulmonary artery is prolonged, condensed and dilated; g) trapezium configuration of the heart; h) cor bovinum. 4. The following indexes can be used as criterions of hypertrophy of the left ventricle by electrocardiogram: a) prothrombin index; b) Sokolov-Lajon’s index; c) Stang’s index; d) Tiffenean index; e) Kornel voltage index; f) Coombs index; g) Thoracic index. 5. The following is concerns to obligatory laboratory-instrumental methods of examination in hypertensive crises: a) hemoglobin of blood and hematocrit; b) phonocardiography; c) echocardiography; d) glucose of blood; e) potassium and sodium in plasma of blood; f) creatinine of plasma of blood; g) erythrocytes, leukocytes and protein in urine; h) electrocardiography; i) research of eye grounds. 6. Traditionally hypertensive crises are classified: a) by the clinic of the development; b) by the functional classes; c) by the principal lesion of target-organs; d) by a condition of the central hemodynamics; e) by the promptness of rendering of medical aid; f) by the age of the patients; g) by sex of the patient. 7. The additional risk factors of arterial hypertension include the following: a) smoking; b) decrease of cholesterol of high-density lipoproteins contents; c) increase of cholesterol of low-density lipoproteins contents; d) disorder of glucose tolerance; e) male sex and menopause in women; f) endogenous tissue-type plasminogen activator; g) ethnic factor. h) cholesterol more than 6,5 mmol/l. 8. What are diagnostic criteria of low risk of arterial hypertension? a) II-III degree of arterial hypertension; b) risk factors, lesions of target-organs are absent; c) cardiovascular diseases and associated diseases are absent; d) I degree of arterial hypertension; e) one and more risk factors are present; f) I-III degree of arterial hypertension; g) associated diseases are present; h) diabetes mellitus is present. 9. According to data of BP daily monitoring there are following types of changes during 24 hours: a) dipper; b) systolic; c) diastolic; d) non-dipper; e) night-peaker; f) latent; g) malignant. 10. Lesions of which internal organs (called as “target-organs”) occur in arterial hypertension, existing long period particularly: a) heart; b) spleen; c) pancreas; d) vessels; e) brain; f) liver; g) kidneys. 11. Symptomatic arterial hypertensions can occur in following diseases: a) coarctation of aorta; b) pheochromacytoma; c) primary aldosteronism; d) anemia; e) Cushing’s syndrome; f) glomerulonephritis; g) pyelonephritis; h) peptic ulcer.

B. Tasks to be done: Task 1. Patient M., 49 years old, teacher, admitted to the department with complaints of severe headache, which is intensified in the evening and accompanied by nausea; dizziness; “flashing of spots in front of eyes”; piercing and pressing pain in heart area. Pain increases in the evening and doesn’t stop after use of nitroglycerine. Anamnesis: 2 years ago headache, dizziness, nausea and vomiting were appeared at first. She was hospitalized to the therapeutic department. After discharging from a hospital her state was satisfactory during 4-5 months, but then headache again appeared, more often to the end of working day. She had out-patient treatment. She marked impairment of feeling during last week, when above described complaints appeared. Examination: Position is active. Hyperaemia of the face is observed. Cyanosis and peripheral oedemas are absent. Examination of arterial pulse: pulse is symmetric, rhythmical, a pulse rate is 82 per minute, it is tense (pulsus durus), satisfactory filling. What is the most probable syndrome in this patient?

Task 2. During prophylactic medical examination of the patient S. blood pressure was 135/87 mm Hg. Such level of BP is: a) optimal; b) normal; c) high normal; d) border arterial hypertension. Answers for test tasks of the I-st level: 1 - a 5 - b 9 - c 14- a 2 - c 6 - c 1 0 - e 15- d 3 - b 7 - a 1 1 - a 16- d 4 - b 8 - d 1 2 - b 17- c 1 3 - c 18- c

Answers for test tasks of the II-nd level: 1 - a , b , d , e , f 7 - b , c , d , f , g 2 - a , b , f , g , h 8 - b , c , d 3 - b , c , e 9 - a , d , e 4 - b , e 10- a , d , e , g 5 - a,d,e,f,g,h,i 1 1 - a,b,c,e,f,g 6 - a , c , d , e

Standards of right answer for tasks: 1) syndrome of arterial hypertension 2) c.

4. Propaedeutics as an Introduction to the Clinic of Internal Medicine Propaedeutics M. Yabluchansky L. Bogun, L.Martymianova, O. Bychkova, N. Lysenko, N. Makienko, E. Golubkina V.N. Karazin National University Medical School’ Internal Medicine Dept. http://dspace.univer.kharkov.ua/bitstream/123456789/10966/2/Lecture%20PIM_22.06.2015. pdf 5. ИИ Мистюкевич. Theses of lectures on propedeutics of internal diseases. www.gsmu.by/file/biblio/uchlit/tezisyprop.doc 6. Internal diseases propedeutics [Электронный ресурс] / Ivashkin V.T., Okhlobystin A.V. - М. : ГЭОТАР-Медиа, 2014. http://www.medcollegelib.ru/book/ISBN9785970430378.html 7. Англо-русский тематический словарь по пропедевтике внутренних болезней и общему уходу за больными : справочное издание / Витебский государственный медицинский университет, Кафедра пропедевтики внутренних болезней; сост. Л.М. Немцов; под ред. Г.И. Юпатова. - Витебск : ВГМУ, 2005. - 153 с. URI: http://elib.vsmu.by/handle/123/11343 8. Special propedeutics of internal diseases : lecture course / Vitebsk State Medical University, Dep. of Propedeutics of Internal Diseases ; comp. by L. M. Nemtsov. - 2-е изд. - Vitebsk : VSMU, 2016. - 318 p. URI: http://elib.vsmu.by/handle/123/9837 9. General propedeutics of internal diseases : lecture course / Vitebsk State Medical University ; compiled by L. M. Nemtsov. - Vitebsk : VSMU, 2006. - 175 p. http://elib.vsmu.by/handle/123/268

Additional ones: 1. McCombs R.P. Fundamentals of Internal Medicine. A physiologic and clinical approach to disease. - 1971. - 860 p. 2. Гребенев А.Л. Пропедевтика внутренних болезней: Учебник – 5-е изд., перераб. и доп.- М.: Медицина, 2001.- 592 с. 3. Ивашкин В.Т., Султанов В.К. Пропедевтика внутренних болезней: практикум. 2-е изд.- СПб.: Питер, 2003.-544 с

Methodical instruction is composed by lecturer Ye.Ye. Petrov.

Approved at the Department of Propaedeutics to Internal Medicine with Care of Patients meeting on 11 09 2018 Protocol No2 The Head of the Department Professor Yu. Kazakov

METHODICAL INSTRUCTION FOR STUDENTS’ SELF-PREPARATION WORK

Educational discipline Propaedeutics to Internal Medicine Module No 2 Enclosure module No 6 Topic Ischemic heart disease: the main symptoms and syndromes on angina pectoris and myocardial infarction

Year 3 Faculty medical

Poltava - 2018 1. The topic basis: ischemic heart disease (IHD) is the commonest cause of cardiovascular disability and death in the USA. Men are more often affected than women by an overall ratio of 4:1, but before age 40 the ratio is 8:1, and beyond are 70 it is 1:1. In men, the peak incidence of clinical manifestations is at age 50-60; in women, at age 60-70. Angina pectoris (stenocardia) is usually due to ischemic heart disease and occurs very often. Myocardial infarction results form prolonged myocardial ischemia, precipitated in most cases by an occlusive coronary thrombus at the site of a preexisting (though not necessarily severe) atherosclerotic plaque. More rarely, infarction may result from prolonged vasospasm, inadequate myocardial blood flow (e.g. hypotension), or excessive metabolic demand. 2. The specific aims:  To explain etiology and pathogenesis of ischemic heart disease.  To classify ischemic heart disease.  To analyze results of examination of patients with angina pectoris (stable and unstable) and myocardial infarction.  To interpret results of examination of patients with angina pectoris and myocardial infarction.  To explain principles of angina pectoris and myocardial infarction treatment. 3. Basic knowledge, experience, skills necessary for studying the topic in connection with other subjects (interdisciplinary integration) : Previous disciplines Obtained skills 1. Anatomy To know human anatomy, cardio-vascular system organs particularly. 2. Physiology To know physiology of cardio-vascular system. 3. Medical psychology To be able to observe principles of ethics and deontology in medical practice. 4. Pathological morphology To know pathologic-morphological picture of atherosclerosis of coronary arteries.

4. Tasks for self-work during preparation to the class. 4.1 List of the main terms, parameters, characteristics, which should be mastered during preparation to the class: Term Definition 1. Atherosclerosis It is pathological process, characterized by blood lipids deposits in arterial wall, that is accompanied by forming of fibrous (atherosclerotic) plaque, constricting vascular lumen. 2. Ischemic heart disease It is defined as acute and chronic heart damage, caused due to diminishing or stopping blood delivery to myocardium. Disease of the coronary arteries is almost always due to atheroma and its complications, particularly thrombosis.

3. Stable angina It is clinical syndrome characterized by discomfort in the chest or adjacent areas caused by myocardial ischemia typically aggravated by exertion or emotional stress and relieved by rest or by nitroglycerin. Patients often describe their symptom as discomfort rather than pain. 4. Unstable angina It is variant of angina when accelerating or “crescendo” pattern of pain in cases where previously stable angina occurs with less exertion or at rest, lasts longer, and is less responsive to medication. 5. Acute coronary syndrome It is includes both unstable angina and non-Q-wave myocardial infarction.

6. Myocardial infarction It is necrosis of cardiac muscle due to acute disparity between oxygen myocardium necessity and delivery of oxygen.

4.2. Theoretical questions to be answered before class: 1. Etiology, risk factors and pathogenesis of atherosclerosis. 2. What clinical manifestations of atherosclerosis do you know? 3. Tell about etiology and pathogenesis of ischemic heart disease. 4. Tell about classification of ischemic heart disease. 5. What are clinical features of stable angina? 6. Tell Canadian cardiovascular Society classification of stable angina. 7. What can be the potential results of objective examination of patients with stable angina? 8. What laboratory and instrumental methods are used for diagnostics of stable angina? 9. What does term “unstable angina pectoris” mean? 10. What can be the potential results of examination of patients with unstable angina? 11. What are clinical features of acute coronary syndrome? 12. What can be the potential results of objective examination of patients with acute coronary syndrome? 13. What laboratory and instrumental methods are used for making more precise of acute coronary syndrome? 14. Etioligy and pathogenesis of myocardial infarction. 15. Classification of myocardial infarction. 16. Clinical manifestations of myocardial infarction. 17. ECG-changes in patients with myocardial infarction (depending on stage and localisation). 18. Laboratory changes in patients with myocardial infarction. 19. What complications of myocardial infarction do you know? 20. Principles of treatment of patients with myocardial infarction. 21. Tell about hibernated (“sleeping”) and “deafened” myocardium.

4.3. Practical work (tasks), which should be performed during class: 1. To carry out examination of patients with angina pectoris and myocardial infarction. 2. To interpret obtained results. 3. To interpret results of laboratory and instrumental methods examination of patients with angina pectoris and myocardial infarction.

The contents of topic: Text

ISCHEMIC (CORONARY) HEART DISEASE Ischemic heart disease is disease, caused by disparity between oxygen necessity of organism and delivery of oxygen, it is characterized by constriction of coronary arteries’ lumen (due to atherosclerosis mainly). Besides atherosclerotic constriction of coronary arteries, forming of thrombocitic aggregates in these vessels and tendency to their spastic contraction have importance. Principally important condition - disparity between oxygen necessities of myocardial cells and nutritious substances and their delivery thought coronary arteries. So called “risk factors” (see parts “Arterial hypertension”, “Atherosclerosis”) promote to development of IHD. These factors don’t promote to progressing of atherosclerosis and IHD only, but they can lead to other dysfunctions of vascular wall also. There are five main clinical variants of IHD: 1. Angina pectoris. 2. Myocardial infarction. 3. Heart failure. 4. Cardiac arrhythmia. 5. Sudden cardiac death.

ANGINA PECTORIS Angina pectoris (stenocardia) - variant of IHD, characterized by typical retrosternal (anginous) pain attacks. Disease was described at first by William Heberden in 1768. There are several forms of angina: stable exertional angina, unstable angina and variant angina (Prinzmetal’s angina). In case of angina pectoris retrosternal pain occur in situations, accompanied by increase of heart’s work, usually on exertion and emotional overstrain (and after plentiful food intake and coming out of the warm room to cold also). Mechanism of development and clinical manifestations of anginal pains were described in topic “Inquiring of the patients with cardiovascular diseases”. Only patient’s questioning in detail allows to make peculiarities of this pain attack. Typical variants of angina pectoris attacks occur more often in men, exposed to effect of different risk-factors (of smoking and obesity, first of all). Presence of such risk-factors as arterial hypertension, obesity, diabetes mellitus, hyperlipidemia in patients with typical angina pectoris make diagnosis of stenosing atherosclerosis of coronary arteries as indisputable practically. In many patients presence of last one can be confirmed by myocardial infarction in past (anamnestically).

Stable exertional angina pectoris It is the most typical form of angina pectoris. On exertion patient feels retrosternal pain with irradiation to the left hand and left shoulder mainly. Pain is pressing, constricting, attack lasts during 1-3 minutes and can disappear after stop of exertion without medicaments intake. Nitroglycerine intake sublingually stops pain in 1-2 minutes. Longer interval between nitroglycerine intake and stop of the pain must excite doubt in relation to nitroglycerine effectiveness (in case of frequent using of nitrates - tolerancy is developed to them) or to correctness of diagnosis even. Apart from typical irradiation of pain to the left hand and shoulder, it can irradiate to the right shoulder, back, upper part of abdomen, lower jaw. Besides, sometimes pain can be localized in its irradiation zone only. Sometimes pain can be indistinct and characterized by feeling of tightness or heaviness behind sternum. Typical exertional angina, as a rule, is revealed in persons with constriction of coronary arteries more than 50%. Intensity and rate of angina attacks increase proportionally to degree of constriction (it is diagnosed by means of coronarography). During inquiring of the patient with angina pectoris it is necessary to estimate severity of its course (by amount of nitroglycerine tablets, used every day). Besides, it is important to estimate patient’s physical activity tolerance. Canadian classification of angina pectoris (1976) is the most widespread in clinical practice (Tabl. 5). Table 5 Canadian Cardiovascular Society classification of stable angina Class Severity of exertional stress including angina Limitation ordinary activity I Strenuous rapid or prolonged exertion at work or recreation None II Walking or climbing stairs rapidly, walking uphill, walking Slight or stair climbing III Walking one to two blocks on the level and climbing one Marked flight of stairs in normal condition and at a normal pace IV Symptoms may be present at rest Discomfort in all activity performed

Vasospastic angina pectoris This type of angina is called also “variant angina” or “Prinzmetal’s angina”. In typical cases angina attack occur at rest, at night and can be very intense. Expressed atherosclerotic constriction of coronary arteries isn’t revealed in these patients often, that is why physical activity tolerance varies to a great extent and sometimes it can be very high. Role of coronary arteries’ spasm in origin of such attacks was demonstrated. Usually spasm occurs in great coronary artery and results to ischemia of subendocardial area. Role of intravascular thrombocitic aggregation isn’t excluded also.

Unstable angina pectoris Term “unstable angina pectoris” includes the following types:  First arisen exertional angina;  Progressing exertional angina (angina attack occur more often, on less physical exertion, their length is increased);  First arisen rest angina. Base of unstable angina is capsular rupture of atherosclerotic plaque in coronary artery that causes thrombus forming with incomplete closure of vascular lumen. Every patient with unstable angina must be hospitalized, as future development of disease is unpredictable (myocardial infarction, arrhythmias, sudden cardiac death). First arisen angina pectoris It is characterized by appearance of clinical signs of angina de novo within limits of last month. Such patients need special supervision in connection with possibility of progressing of coronary insufficiency’s symptoms and development of myocardial infarction. Progressing exertional angina pectoris Patients mark increasing in frequency of exerional angina attacks with increase of nitroglycerine intake during day in 1,5-2 times and more; second form - change of pain attack’s stereotype (become more intense, longer,etc.). Physical activity tolerance becomes worse; increase of exertional angina’s class occurs. Subjective condition is aggravated. All these signs testify about exacerbation of IHD and need active treatment. Though patient’s inquiring in detail, which allows to reveal angina pectoris, is necessary for diagnostics of IHD first of all, often pain attacks have atypical signs. It requires confirming diagnosis by means of special research methods.

Instrumental research methods Electrocardiography Changes of ST segment and T wave in the left chest leads - ST segment displacement or lowering (loss) of T wave amplitude are revealed on ECG approximately in 50% of cases in presence of stenosing coronary atherosclerosis. It is important that in typical cases these changes occur during attack. Repeated research, on the background of clinical state’s aggravation peculiarly (ECG analysis in dynamics) has great diagnostic importance. Typical signs of vasospastic angina - significant elevation of ST segment. Monitor recording of ECG during day or several hours is very informative. It allows revealing changes on exercise stress, described before. Exercise stress tests - veloergometry, treadmill-test have great importance for revealing of stenosing sclerosis of coronary arteries. Transesophageal electric atrial pacing (stimulation) with “forcing” of cardiac rhythm to 100 per minute and its acceleration during following minutes can be used instead of exercise stress tests. Besides ST depression (lowering) during pacing period directs to presence of coronary blood flow disorders. Echocardiograpgy Apart from some enlargement of the left ventricle’s size - both final systolic and diastolic - zones of hypokinesia, akinesia and dyskinesia can be reveled. Sometimes these changes are marked only during angina attacks, but often they are constant. In these cases it helps to make diagnosis of IHD. During last years stress-echocardiography becomes popular. This method reveals local changes of myocardial contractility (circulatory insufficiency in lesion of one vessel) at conditions of tachycardia (dobutamine introduction). Radionuclide scintigraphy Myocardial perfusion is estimated by means of radioactive thallium introduction (201Tl). Scintigraphy, carried out at once after physical activity, is more informative. It reveals foci of isotope accumulation disorders and, consequently, of myocardial ischemia. Angiocardiography Angiocardiography is the most effective method to make more precise degree of coronary arteries’ stenosis and its localization. Using of this method is necessary for solution of question about possibility of operative treatment (aortocoronary bypass, balloon dilatation).

Laboratory research methods Laboratory results have subsidiary value for diagnostics of angina pectoris as they only help to reveal dyslipidemia, accompanying diseases and number of risk factors (diabetes mellitus) or to exclude other reasons of pain syndrome (inflammatory diseases, blood diseases, thyroid gland diseases). Estimation of blood lipid content, presence of hypercholesterolemia more than 5,2 mmol/l (200 mg%) particularly, has peculiar importance. It is important also increase of low- density lipoproteins contents in the blood more than 3,1 mmol/l, decrease of high-density lipoproteins less than 1 mmol/l and increase of triglycerides contents more than 2 mmol/l. Presence at least of one from foregoing indexes - typical manifestation of atherosclerotic process.

Treatment In case of IHD treatment is, first of all, in revealing (if it is possible) and elimination of risk factors (see “Atherosclerosis. Treatment”). In stable angina pectoris graduated tolerant exercise is important method of rehabilitation and treatment. In connection with it, it is indicated exercise therapy for these patients under supervision of specialist. Prescription of pharmacotherapy is indicated in majority of cases.  In case of angina attack nitroglycerine tablets or capsules are taken sublingually. This drug causes systemic dilation of veins and arteries, therefore it diminishes heart load and decreases its oxygen necessity and improves coronary circulation. Prolonged drugs, containing nitroglycerine (including oinments, plasters) and other nitrates are used for prevention of attacks.  β- adrenoceptor antagonists are effective for treatment of IHD with angina pectoris attacks. Their effect is caused by diminishing of myocardial oxygen necessity. Propronalol and selective β- adrenoceptor antagonists, for example, atenolol, metaprolol are used.  Acetylsalicylic acid is prescribed as antiaggregant. Operation aortocoronary bypass and/or balloon dilatation of coronary arteries is indicated to the patients with confirmed diagnosis of coronary arteries stenosis. These operations improve patients’ life quality and increase life span.

MYOCARDIAL INFARCTION Myocardial infarction is necrosis of cardiac muscle due to acute disparity between oxygen myocardium necessity and delivery of oxygen. MI is developed, as a rule, in coronary atherosclerosis, often accompanied by thrombosis of coronary arteries. Infarction occurs in men more often, mainly more than 50 years old, which have risk factors of coronary atherosclerosis (arterial hypertension, excess body weigh, diabetes mellitus, smoking, etc.). Stable angina proceeds to development of MI in half of patients approximately. Significant physical and emotional overstrain can be provoking factors, but sometimes MI occurs at rest and during sleep even. Presence of unstable angina testifies about high risk of MI development.

Etiology and pathogenesis MI occurs due to thrombosis of coronary artery on the background of its atherosclerotic lesion (95-97% of all cases).Disorder of integrity of atherosclerotic plaque’s capsule with release of its content (lipid nucleus) is in basis of MI. Besides, different mediators are released, activation of thrombocytes and coagulation blood system occurs. It leads to thrombus forming. More rarely MI can occur as result of other reasons (spasm of coronary artery, embolism, coronary artery wall dissection, anomalies of arteries). It is possible forming of transitory aggregate of thrombocytes in area of coronary artery’s plaque (prolonged spasm of vessels can promotes to it). Increase of oxygen myocardial necessity in case of stress or significant physical activity has less importance for development of MI. Development of irreversible lesion of myocardium occurs in 15-20 minutes after coming of ischemia; necrosis in corresponding zone is developed in 4 hours after stop of blood flow. Localization of myocardial infarction Anatomy of coronary arteries is shown in the fig. 12.  In usual type of myocardial blood supply thrombosis of anterior interventricular branch of the left coronary artery results to infarction of anterior wall of the left ventricle.  Occlusion of circumflex branch of the left coronary artery is accompanied by infarction of anterolateral wall of the heart.  Thrombosis of right coronary artery results to infarction of posterior wall of the heart, sometimes with involving of right ventricle.

Fig. 12. Location of coronary arteries: a-along anterior wall of the heart:1-aorta, 2- pulmonary veins, 3-left coronary artery, 4-circumflex branch of the left coronary artery, 5- interventricular branch of the left coronary artery, 6-right coronary artery; b-along posterior wall of the heart: 1-aorta, 2-pulmonary veins, 3-rigth coronary artery, 4-posterior interventricular branch of the right coronary artery, 5-circumflex branch of the left coronary artery. (From: Мясников А.Л. Пропедевтика внутренних болезней. М.: Медгиз, 1956)

Classification Before myocardial infarction was subdivided into transmural (necrosis of whole thickness of myocardium) and non-transmural (subendocardial usually). In first case necrosis, spreading to whole thickness of ventricular wall is developed. It is manifested by appearance of deep and wide Q wave in leads, reflected electric activity of affected heart part. Non-transmural (small- focal) infarction is limited usually by subendocardial zone and is manifested on ECG by changes of ST segment and T wave only. Now terms “myocardial infarction with Q wave” and “myocardial infarction without Q wave” are used more often. Such division was caused by clinical indications for carrying out of thrombolytic therapy (in myocardial infarction with Q wave introduction of thrombolytic agents for liquidation of thrombus in lumen of coronary artery is indicated).

Clinical manifestations Myocardial infarction due to thrombosis of great coronary artery was described by Kiev clinicians V.P. Obraztsov and N.D. Strazhesko in 1908. V.A. Kryzhanovsky quotes memoirs of N.D. Strazhesko in connexion with that: “Patient with intense retrosternal pains admitted to the second barrack of Alexandrovsk hospital of Kiev (described case is related to december, 1899.- Note V.K.). Pains lasted two days. Patient’s condition was grave: he was almost without consciousness, almost without pulse. Professor Obraztsov had the following habit: coming to Alexandrovsk hospital, he asked in intern, first of all, how many new patients, what are their diseases, and immediately does to them for examination, prescription of the treatment. He came to this patient, set on tabouret near him, became to observe, research, hear him. Then he asked in intern: “What disease is in this patient, according to your opinion?” Last one slapped (said): “Rheumatism of sternum”. Obraztsov screwed up left eye (it was his habit) and continue to set near the patient silently. Scepsis on his face was seen clearly. I stand here like other residents and also think what disease could be present in this patient. As to oneself I commented: “It can be coronary arteries occlusion, can’t it?” Obraztsov turned, saw astonishedly and said: “He is right, probably”. In day patient died. During postmortem examination really coronary arteries occlusion with following infarction was revealed. Here I note, before this case nobody diagnosed myocardial infarction life-timely. It was postmortem diagnosis”. The main syndromes of myocardial infarction were represented by V.P. Obraztsov and N.D. Strazhesko.  Pain syndrome - status anginosus.  Shock - status algidus cyanotics.  Heart failure with pulmonary edema - status asthmaticus.  Later such manifestations as expressed arrhythmias, occurring in case of this disease often, were described. Most often myocardial infarction occurs during period from 6 o’clock to 12 o’clock. It is caused by increase of sympatic nervous system activity during this time. Clinical manifestations and the main syndromes of myocardial infarction with Q wave or without Q wave are identical. But intensity of these manifestations in myocardial infarction without Q wave usually is less significantly. So, pain is shorter usually, lasts 20-30 minutes and is less intensive. Development of heart failure in patients with myocardial infarction without Q wave occurs only on the background of expressed sclerosis of coronary arteries, peculiarly in persons with myocardial infarction in past. Pain syndrome The most typical manifestation of myocardial infarction is pain like one in exertional angina pectoris, but more intensive. Clinical diagnostic criterion of myocardial infarction is pain syndrome with length more 15 minutes, which isn’t arrested by nitroglycerine intake.  Pain usually is retrosternal. It increases quickly and often it is like-wave. Usually it is constricting, pressing, cutting, very intense, isn’t stop after nitroglycerine intake and often - after introduction of narcotic analgetics also.  Length of pain attack is more than 30 minutes and sometimes it lasts during several hours.  Pain can be accompanied by symptoms of gastroduodenal dysfunction, by nausea, vomiting, meteorism, particularly. Part of the patients can have pain of epigastric localization mainly. In part of the patient with myocardial infarction pain syndrome is absent. This so called “painless form of myocardial infarction” occurs in elderly patients, in presence of chronic heart failure, in diabetes mellitus, in persons with alcohol intoxication and in case of myocardial infarction, occurred during operation, carried out under general narcosis (anesthesia). Physical examination Patients are anxious. During initial period of myocardial infarction elevation of blood pressure (in connection with psychic excitement of the patient) is marked. Later blood pressure is decreased. During auscultation it is possible to reveal weakening of the I sound (due to decrease of myocardial contractility), additional III sound (“gallop rhythm”), soft mesodiastolic murmur due to dysfunction of papillary muscles, pleural friction sound. In development of pulmonary edema - tachypnoe occurs, and moist fine bubbling rales are heard in lower parts of the lungs.

Cardiogenic shock Cardiogenic shock in myocardial infarction is frequent form of circulatory insufficiency. Usually it is developed in case of involving of more than 40% myocardial mass and occurs in 5- 20% patients with myocardial infarction. Sudden decrease of cardiac output is the main reason of shock development. Besides, decrease of minute cardiac volume can be compensated by means of increase of general peripheral vascular resistance and decrease of bloodstream capacity. It primarily supports relatively high level of blood pressure. In future, at depositing of circulation blood’s part in little vessels - going out of fluid from bloodstream and progressing of shock condition with development of its irreversible phase occurs. Shift of metabolism from aerobic to anaerobic with development of intracellular acidosis occurs in connection with insufficient oxygen maintenance of organs and tissues. Clinical picture of cardiogenic shock consists of triad symptoms:  Decrease of systolic blood pressure to 80 mm Hg, pulse blood pressure - less than 30 mm Hg. Patient’s pulse is thready, often it isn’t palpated.  Disorder of peripheral perfusion: - of central nervous system - psychical disturbances, flaccidity, lethargy; - of the kidneys - acute renal failure occurs as result of perfusion decrease , urinary excretion decreased to 20 ml/hour and less (oliguria or anuria); - of the skin - paleness, hyperhydrosis, coldness and cyanosis of skin cover.  Pulmonary edema - see part “Heart failure”.

Electrocardiography Myocardial infarction is accompanied by specific ECG-changes and, first of all, in those leads, which best of all reflect electrical activity of affected part of the heart. Besides, in leads, reflecting activity of myocardial parts, located opposite of affected ones (for example, posterior wall of the left ventricle is opposite to its anterior wall), it is observed inverse changes, first of all, of ST segment. These changes are called “reciprocal” - in elevation of ST segment in one leads, in opposite leads its depression occurs. During dynamical observing of process - graduate return of ST segment to isoelectric line with typical dynamics of QRS complex is marked.  In case of myocardial infarction with Q wave - ECG changes are in decrease of R wave amplitude, appearance of wide and deep Q wave and elevation of ST segment, taking the shape of arch with protuberance upwards. In further displacement of ST segment downwards and forming of negative T wave occurs.  In case of myocardial infarction without Q wave - changes of QRS are absent. ECG signs are limited only by appearance of negative T wave, which can occur in many other myocardial diseases also. That is why for making of diagnosis “myocardial infarction without Q wave” apart from clinical manifestations it is important to see for changes of leukocytic formula, ESR and contents of cardiospecific enzymes. It is necessary to remember that normal ECG doesn’t exclude presence of myocardial infarction. Stages of myocardial infarction Myocardial infarction with Q wave is taking its course with four stages (by ECG): the most acute, acute, subacute and cicatricial (scarry) (Fig.13).  Most acute (first hours) - monophase curve (expressed elevation of ST segment, interfluent with increased T wave.  Acute stage (2-3 weeks) is characterized by appearance of pathological Q wave and decrease of R wave amplitude (often it dysappears completely - QS wave is formed). Monophase curve is kept.  Subacute stage (to 4-8th week from beginning of disease) - ST segment returns to isoelectric line, pathologic Q wave (or QS) is kept, T wave is negative.  Cicatricial stage is characterized by forming of cicatrix (postrinfarction cardiosclerosis); on ECG pathological Q waves, low-amplitude R wave, negative T waves can be kept.

Fig. 13. Stages of myocardial infarction without Q-wave and with Q-wave. Explanation is in text. Localization Myocardial infarction of different localization is characterized by ECG changes in fully definite leads (Fig. 14). ECG in myocardial infarction of septum and antero-lateral wall of the left ventricle is represented on the Fig. 15. and Fig. 16., accordingly.

Fig. 14. Localization of myocardial infarction (MI) and leads, in which typical changes occur. Explanation is in text.

Fig. 15. ECG in anterolateral myocardial infarction: a-in 1 hour after beginning of pain attack; b-in 1 day; c-in 10 days. Extensive transmural infarction. Appearance of pathological Q -wave in lead V2 directs to lesion of interventricular septum, V4 - lesion of apex, V6 -lesion of lateral wall. Recording rate -25 mm/sec.

Fig. 16. ECG in myocardial infarction of posterior wall of the left ventricle: a-in 1 hour after beginning of pain attack; b-in 1 day; c-in 2 week. Pathological Q-wave in leads II, III, aVF directs to localization of infarction along lower wall of the left ventricle. Recording rate -25 mm/sec. ECG mapping Sometimes in case of clinical manifestations, with suspicion myocardial infarction, ECG in the main 12 leads is unchanged. In these cases for making more exact diagnosis it is reasonably using of so called “mapping” - recording of ECG in 35 precardiac leads (electrodes are applied along the same vertical lines, but in all interspaces). Besides, only sometimes it is possible to reveal signs, typical for myocardial infarction in 2-3 leads. Other changes Arrhythmias and disorders of cardiac conductivity are marked during monitoring almost in all patients with myocardial infarction. They occur as result of electrical instability of myocardium; besides some its areas have different electrophysiological activity. Ventricular premature beats, sinus tachycardia, paroxysms of atrial fibrillation, paroxysmal supraventricular and ventricular tachycardia are observed most often. From disorders of conductivity atrioventricular block down to III degree occurs most often.

Myocardial scintigraphy Myocardial scintigraphy with using of radioisotope technetium (99Tc) allows to reveal areas of “fresh” myocardial infarction in 6-12 hours after pain attack beginning. Changes are kept during 6-14 days. Scintigraphy has particular importance in case of suspicion to myocardial infarction in patients with disorder of intraventricular conductivity in absence of convincing picture of focal changes on ECG.

Laboratory changes Forming of necrotic focus in myocardium usually is accompanied by elevation of body temperature 2nd -3rd day of disease; temperature is normalized to 5th -7th day of disease. 2nd day of disease neutrophilic leukocytosis (10,2-12•109/l with neutrophilic shift to the left), decrease of eosinophils contents or total disappearance of eosinophils from peripheral blood occurs. Later 3rd -4th day of myocardial infarction acceleration of ESR occurs; it is kept during 3-4 weeks in case of myocardial infarction with Q wave. “Crossing” at the end of 1st week of disease, when leukocytes contents decreases and ESR increases, has diagnostic importance. Other signs of inflammation are observed also during acute period of disease: C-reactive protein positive reaction and increase of fibrinogen contents in the blood. Biochemical markers of myocardial infarction Forming of necrotic focus in myocardium is accompanied by entering of intracellular enzymes and other substances into the blood.  Creatine phosphokinase (CPK), its MB-fraction particularly, is increased in the blood in 3-6 hours and reaches maximum to the end of the first day and in 3-4 days it is normalized. Increase of total creatine phosphokinase content in 2-3 times can occur as result of any lesion of muscular tissue (for example, intramuscular injection). Determination of MB-CPK content is more specific.  Increase of myoglobin content in blood and urine occurs simultaneously. It is sensitive, but non specific markers of myocardial necrosis.  Troponin I and troponin T are proteins of cardiac muscle. They appear in blood only in case of cardiac muscles necrosis. These indexes are one of the most sensitive and early signs of myocardial infarction. Troponins content begin to increase in 3-12 hours after myocardial infarction, reaching maximum in 12-48 hours, and is normalized in 5-14 days.  Hyperglycemia due to transient insulin deficiency (as a result of pancreas’ hypoperfusion) is observed.  Increase activity of blood transaminases: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) occurs in 6-12 hours after attack beginning; activity of transaminases reverts to norm in 3-5 days. Activity of lactate dehydrogenase (LDG) is increased some later (in 1-2 days) and kept more than week. For myocardial infarction increase of isoenzyme LDG-1 activity is typical. Changes of transaminases and LDG activity is possible in case of many other states, that is why now it isn’t recommended to orient to these laboratory criteria. Dynamics of laboratory indexes in myocardial infarction is represented on Fig. 17.

Fig. 17. Dynamics of activity of cardiospecific enzymes in the blood in patient after myocardial infarction. CPK - creatine phosphokinase, MB-CPK- MB-fraction of CPK, AST - aspartate aminotransferase, LDG-lactate dehydrogenase.

Hyperfermentemia (hyperenzymemia), even transitory, has determinant importance for diagnostics of myocardial infarction without Q wave on ECG. Described changes are revealed in myocardial infarction with Q wave. In myocardial infarction without Q wave these changes are less expressed. That is why after pain attack in past it’s advisable to estimate all foregoing indexes in dynamics.

Complications of myocardial infarction The following states are the most often complications of myocardial infarction:  Cardiac aneurysm - acute and chronic. Chronic aneurysm is characterized by presence of “freezing” (“stiffening”) picture of myocardial infarction on ECG.  Cardiac rupture to 4-11th day - exertional cardiac rupture with development of hemopericardium, rupture of interventricular septum, papillary muscle rupture with development of acute valvular insufficiency.  Postinfarction Dressler’s syndrome with development of pleurisy, pericarditis, pneumonia, lesion of joints, muscles.  Thromboembolisms - of the lungs, central nerwous system, extremities.  Gastrointestinal bleeding. Such manifestations, as pulmonary edema, shock, arrhythmias also can be considered as early complications of myocardial infarction. But, taking into account, that myocardial infarction can be taking its course without pain syndrome also, these signs often are considered as main manifestations of disease instead of complications.

ACUTE CORONARY SYNDROME The main manifestations of IHD exacerbation are unstable angina pectoris, myocardial infarction without Q wave and myocardial infarction with Q wave. During initial stage clinical manifestations and ECG-signs of these states can be extremely similar. Particularly, pain syndrome can be prolonged both in infarction (with Q wave and without it) and in unstable angina pectoris. Its duration sometimes is more than 30 minutes. Besides, ECG-changes, typical for infarction with Q wave (as elevation of ST segment), and increase of cardiospecific enzymes content in the blood can occur later also. That is why during early stage of disease, when diagnosis isn’t clear yet, it is reasonable to mark coronary genesis of disease by means of term “acute coronary syndrome”. Besides, apart from character of pains (retrosternal, constricting or pressing), it is necessary to take into account coronary disorders in past (angina pectoris, myocardial infarction) and presence of risk factors especially (arterial hypertension, diabetes mellitus, unfavorable heredity, etc.). In several hours (sometimes in day and more) during monitoring of ECG and cardiospecific markers (blood enzymes, myoglobin and troponins particularly) diagnosis becomes more exactly. Appearance of Q wave, displacement of ST segment upwards allows to diagnose large-focal infarction. In case of absence of these changes - increase of enzymes MB-CPK, troponins (more than two norms) usually allows to diagnose myocardial infarction without Q wave. Absence of all these changes is estimated as unstable angina pectoris. It is necessary to take into account also that pain in the chest can’t be connected with coronary disorders only, but with many other reasons also, nervous-muscle lesions particularly.

A. Test tasks to be done: -with a single selective answer – I-st level: 1. During which stage of atherosclerosis do the attacks of angina pectoris (stenocardia) occur? a) during stage of increase of blood cholesterol level; b) during pre-clinical stage; c) during ischemic stage (neurometabolic); d) during thrombonecrotic stage (organic); e) during fibrinous stage. 2. Who described clinical picture of angina pectoris first? a) Corvisar; b) Laënnec; c) Heberden; d) V.P. Obraztsov and N.D. Strazhesko; e) S.P. Botkin. 3. What is character of the pain during attack of angina pectoris? a) the pain lasts hours, days, it is burning; b) the pain is dull, extended along whole heart area, irradiates into the left hand; c) the pain is constricting, burning, irradiates into the left hand, doesn’t stop after Validol or Nitroglycerin intake; d) retrosternal burning pain, irradiates into the left hand, relief begins after Validol or Nitroglycerin intake; e) aching, dull pain in one point of heart area without irradiation. 4. Pain attack in angina pectoris lasts during: a) 1-2 minutes; b) 5-10 minutes; c) 10-30 minutes; d) from some seconds to 20-30 minutes; e) hours, days. 5. What is patient’s behaviour during angina pectoris attack? a) he/she tosses, try to occupy comfortable position; b) anxiety, motor and talkative excitement is marked; c) he/she occupies orthopnea position; d) he/she occupies position of “bedouin, which prays”; e) he/she is “rooted to the stop”. 6. Stable angina of the II functional class: a) appears during performance of insignificant physical activities, such as usual walking on small distance (100-200 m) on horizontal district, thus there are rare attacks of a stenocardia of rest; b) appears during performance of the inordinate, extraordinary for concrete patient physical activities, which are fast or long; c) appears during performance of the habitual physical activities for the patient such as fast walking, rise on the 1st floor. d) appears during the periods of the minimal physical activities and at rest. 7. Stable angina of the III functional class: a) appears during performance of insignificant physical activities, such as usual walking on small distance (100-200 m) on horizontal district, thus there are rare attacks of a stenocardia of rest; b) appears during performance of the inordinate, extraordinary for concrete patient physical activities, which are fast or long; c) appears during performance of the habitual physical activities for the patient such as fast walking, rise on the 1st floor. d) appears during the periods of the minimal physical activities and at rest. 8. How many functional classes of the stable angina are according to criterions of Canadian society of cardiovascular pathology? a) one; b) two; c) three; d) four; e) five. 8. The following is marked on ECG in the patients with variant angina: a) ST segment isoelectric; b) ST segment elevation; c) ST segment depression; d) deep Q wave; e) inverted symmetrical T wave. 9. The “gold” standard of diagnostics of IHD is: a) ECG; b) PCG; c) Echo-CG; d) coronarography; e) blood analysis. 10. What term is used during the first hours after development of a painful attack on an ECG when it is not possible to define if it is an unstable angina pectoris or a myocardial infarction of the uncertain size? a) the primary stop of blood circulation; b) variant angina pectoris (Prinzmetal’s angina pectoris); c) acute coronary syndrome; d) microfocal myocardial infarction; e) heart disease. 11. An acute or chronic dysfunction of a myocardium owing to relative or absolute reduction of supply of a myocardium by the arterial blood, more often connected with pathological process in system of coronary arteries is called: a) stenocardia; b) myocardial infarction; c) chronic rheumatic heart disease; d) ischemic heart disease; e) hypertensive disease. 12. During which stage of atherosclerosis does myocardial infarction occur? a) during stage of increase of blood cholesterol level; b) during pre-clinical stage; c) during ischemic stage (neurometabolic); d) during thrombonecrotic stage (organic); e) during fibrinous stage. 13. Who described clinical picture of myocardial infarction first? a) Corvisar; b) Laënnec; c) Heberden; d) V.P. Obraztsov and N.D. Strazhesko; e) S.P. Botkin. 14. What is character of the pains in case of myocardial infarction? a) they are dull (aching) over whole heart area, irradiate into the left hand, shoulder, don’t stop after nitroglycerine intake; b) they are constricting, burning over whole heart area, irradiate widely, last more than 30 minutes, don’t stop after nitroglycerine intake; c) they are constricting retrosternal, irradiate into the left hand, under the left scapula, last from some seconds to 20-30 minutes; d) they are acute, constricting, burning, irradiate widely, lasts during hours, days, stop by means of analgetics; e) they are aching together with feeling of heaviness in the heart area, position of “bedouin who prays”. 15. Asthmatic variant of myocardial infarction is manifested by: a) asphyxia, cough, distant rales; b) sudden asphyxia attack with difficult expiration and cough with viscous sputum during the end of attack; c) dyspnea, asphyxia, bubbling in the chest, cyanosis; d) asphyxia, cough, swelling of cervical veins, emphysematous form of the chest; e) expiratory dyspnea, asphyxia, as they stop- the cough with expectoration of little amount of viscous sputum. 16. Potential data of auscultation in case of myocardial infarction are: a) increasing of the I sound; b) triple rhythm; c) muffled heard sounds; d) systolic murmur at the heart apex; e) diastolic murmur over the aorta. 17. Potential data of auscultation in case of myocardial infarction are: a) increasing of the I sound; b) triple rhythm; c) protodiastolic gallop rhythm; d) systolic murmur over aorta; e) diastolic murmur over aorta. 18. Potential data of auscultation during subacute period of myocardial infarction are: a) increasing of the I sound; b) triple rhythm; c) pericardial friction sound; d) systolic murmur over aorta; e) diastolic murmur over aorta. 19. Data of leukogramm in the patient with myocardial infarction are: a) leukopenia; b) eosinophilia; c) neutrophilic leukocytosis till 12-14 days of the disease; d) lymphocytosis; e) basophilic-eosinophilic association. 20. During which day of myocardial infarction does ESR begin to increase? a) during 1-2 day; b) during 3-4 day; c) during 5-6 day; d) during 7-10 day; e) during 12-14 day. 21. Which enzymes, appeared in the blood, testify about necrosis of myocardium? a) alkaline phosphatase; b) creatine phosphokinase; c) diastase; d) choline esterase; e) amylase. 22. How long cicatrization of uncomplicated myocardial infarction occur? a) till 1 month; b) 1-3 month; c) 2-5 months d) 3-6 months; e) 6-12 months. 23. What is “myocardial infarction”? a) ischemia of part of cardiac muscle due to sudden total stop of its blood supply; b) ischemic lesion of part of cardiac muscle due to sudden total stop of its blood supply; c) dystrophy of part of cardiac muscle due to sudden total stop of its blood supply; d) necrosis of part of cardiac muscle due to sudden total stop of its blood supply; e) it is functional disease of the heart. 24. Presence of injury zone on ECG in case of myocardial infarction is manifested by: a) inverted T wave; b) deep and wide Q wave; c) ST segment elevation; d) high R wave; e) deep and wide S wave. 25. Presence of necrosis in case of myocardial infarction is manifested by: a) inverted T wave; b) deep and wide Q wave; c) ST segment elevation; d) high R wave; e) deep and wide S wave. 26. Monophase curve on ECG in case of myocardial infarction is called: a) Botkin’s curve; b) Mobitz curve; c) Samilov-Wenchenbach curve; d) Pardie curve; e) Strazhesko’ curve. 27. When is postinfarction cardiosclerosis diagnosed (from beginning of myocardial infarction)? a) in 1 week; b) in 2 week; c) in 1 month; d) in 2 month; e) in 1 year. 28. By the size myocardial infarction is small if necrosis is: a) 10-30% of weight of the left ventricle; b) < 10% of weight of the left ventricle; c) > 30% of weight of the left ventricle; d) focal; e) < 30% of weight of the left ventricle. 29. By the size myocardial infarction is big if necrosis is: a) > 10% of weight of the left ventricle; b) > 20% of weight of the left ventricle; c) > 30% of weight of the left ventricle; d) > 40% of weight of the left ventricle; e) > 50% of weight of the left ventricle. 30. The course of myocardial infarction is acute if duration is: a) 1-2 hours; b) 2-4 hours; c) 4 hours - 14 days; d) 6 hours - 7 days; e) 1 - 28 days. 31. When does creatine kinase appear? a) in case of destruction of 0,1 gram of a myocardium; b) in case of destruction of 0,01 gram of a myocardium; c) in case of destruction of 1 gram of a myocardium; d) in case of destruction of 5 gram of a myocardium; e) in case of destruction of 10 gram of a myocardium. 32. Specific appearance of hemogram during dynamics (leukocytes and ESR) in the patient with myocardial infarction is sometimes called: a) symptom “of scissors”; b) “mirror” sign; c) niche sign; d) shaking’s sign; e) symptom of “comb”.

-with the selective group of right answers – the II-nd level; 1. Forms of Ischemic heart disease (according to classification of IHD, which had been offered by the commission of experts of WHO in 1979) include the following: a) the primary stop of blood circulation (sudden cardiac death); b) angina pectoris (or stenocardia); c) arterial hypertension; d) chronic rheumatic disease of the heart; e) myocardial infarction; f) heart failure; g) arrhythmia. 2. Exertional angina includes the following forms: a) for the first time arisen; b) stable; c) progressing; d) rest angina; e) Prinzmetal’s angina; f) the primary stop of blood circulation; g) myocardial infarction. 3. In typical cases of the stable stenocardia the pain irradiates to: a) the left hand; b) the left scapula; c) the right hand; d) the right shoulder; e) the left shoulder; f) the lower jaw. 4. The following objective signs can be observed in patient with angina pectoris: a) pallor of integuments; b) cold sweat; c) emotional excitation on a background of muscular braking; d) ventral decubitus; e) left lateral decubitus; f) the patient stiffens in that position, in which he/she is overtaken by a pain; g) the patient tosses in its bed; h) the oppression of mental condition. 5. The unstable angina pectoris includes the following types: a) the primary stop of blood circulation; b) for the first time arisen; c) progressing; d) myocardial infarction; e) heart failure; f) stable stenocardia. 6. There are the following peculiarities of Variant angina (Prinzmetal’s angina): a) appears at rest in early morning hours outside of connection with physical activity; b) appears on exertion; c) it is less intensive and long, than usual (stable) stenocardia; d) it is more intensive and long, than usual stenocardia; e) it can have cyclic character, arising in one and too time of day or night; f) disappears spontaneously or under influence of certain medicines; g) in the subsequent it can not repeat, however in some cases it can be subsequent development of myocardial infarction, dangerous arrhythmia. 7. Diagnosis of the stable angina pectoris is confirmed by means of: a) echocardiography; b) pneumotachography; c) Doppler cardiometry; d) veloergometry; e) plain film; f) coronarography. 8. The following potential results of the blood analysis can be marked in patients with angina pectoris: a) decreased level of troponin K; b) increased level of troponin K; c) the activity of creatine phosphokinase (CPK) and MB-CPK is in norm or is decreased slightly; d) the activity of creatine phosphokinase (CPK) and MB-CPK is in norm or is increased slightly; e) sometimes little leukocytosis, C-reactive protein (C-RP) and increasing of a level of fibrinogen; f) sometimes little leukopenia and decreasing of a level of fibrinogen; g) considerable elevation of ESR. 9. There are following forms (variants) of myocardial infarction: a) painful; b) asthmatic; c) hypertensive; d) arrhythmic; e) cerebral; f) rheumatic; g) gastralgic. 10. Diagnostic ECG-signs of myocardial infarction include the following: h) increased R wave amplitude in the leads facing the necrotic myocardium; i) deep and wide Q wave, deeper than ¼ of the R wave amplitude, and wider than 0.03 second; j) deep and wide S wave, deeper than ¼ of the R wave amplitude, and wider than 0.03 second; k) pathological T wave - high ischemic or inverted; l) decreased R wave amplitude or its absence in the leads facing the necrotic myocardium; m) ST segment changes; n) discordance of ST segment and T wave in opposite leads; o) the M-shaped QRS complex in leads V1, V2, (rare in leads III, avF). 11. Posterior - diaphragmatic (inferior) infarction is manifested in the following standard and augmented leads: a) I ; b) III; c) avL; d) avF; e) avR; f) II. 12. Septal infarction is manifested in the following leads: a) V1; b) V2; c) V3; d) V4; e) V5; f) V6; g) III. 13. Lateral infarction is manifested in the following leads: a) V1; b) V2; c) V3; d) V4; e) V5; f) V6; g) III. 14. ECG-signs of subacute stage of myocardial infarction include the following: a) deep Q wave; b) elevated ST segment; c) ST segment isoelectric; d) T wave returning to normal; e) T wave normal; f) inverted symmetrical T wave; g) deep S wave.

15. ECG-signs of recovery stage of myocardial infarction include the following: a) deep Q wave; b) elevated ST segment; c) ST segment isoelectric; d) T wave returning to normal (not always); e) T wave normal; f) inverted symmetrical T wave; g) high R wave. 16. Increase of which enzymes (of blood serum) activity testifies about necrosis of myocardium? a) creatine kinase, MB-isoenzyme; b) lactate dehydrogenase, isoenzymes LDH1,2; c) alanine aminotransferase; d) aspartate aminotransferase; e) alkaline phosphatase; f) acid phosphatase; g) amylase.

17. Specific markers of destruction of cardiomyocytes include the following: a) creatine kinase; b) creatine kinase -MB; c) lactate dehydrogenase - 1; d) lactate dehydrogenase; e) aspartate aminotransferase; f) glycogenphosphorylase; g) cardiotroponins T and G; h) myoglobin. 18. In 3-6 hours from the beginning of disease the following markers of acute myocardial infarction appear in blood: a) lactate dehydrogenase - 1; b) myoglobin; c) troponins; d) aspartate aminotransferase; e) myosin; f) glycogenphosphorylase.

B. Tasks to be done: Task 1. ECG-conclusion includes information about presence of myocardial ischemia in area of anterior wall of the left ventricle. What changes can be basis for such conclusion? a) Displacement of ST-segment upwards in leads I, avL, V4-5. b) Displacement of ST-segment downwards in leads I, avL, V4-5 c) Displacement of ST-segment upwards in leads III, avF, V6-7. d) Displacement of ST-segment downwards in leads III, avF, V6-7. e) Appearance of deep and wide Q-wave in leads I, avL, V4-5. f) Appearance of deep and wide Q-wave in leads III, avF, V6-7. Task 2. ECG-conclusion includes information about presence of acute phase of transmural myocardial infarction in area of anterior wall of the left ventricle. What changes can be basis for such conclusion? a) Displacement of ST-segment upwards in leads I, avL, V4-5. b) Displacement of ST-segment downwards in leads I, avL, V4-5 c) Displacement of ST-segment upwards in leads III, avF, V6-7. d) Displacement of ST-segment downwards in leads III, avF, V6-7. e) Appearance of deep and wide Q-wave in leads I, avL, V4-5. f) Appearance of deep and wide Q-wave in leads III, avF, V6-7.

Task 3. Patient F., 63 years old, was admitted to the cardiological clinic for the treatment. He complains of pressing, sometimes - burning pains in area of the lower third part of the sternum, which irradiated to the left shoulder and interscapular area. Pains appear during fast walking or other exercise stress, disappear in 3-5 minutes after stop of exercise stress. A patient also complains of dispnea, which appears even during moderate physical stress. Sometimes (rarely) he feels intermissions in heart area, during exercise stress mainly. Little edemas of feet and lower third part of shins appear to the evening. They disappear to the morning. Besides, patient complains frequent headaches, which is accompanied by dizziness and noise in ears sometimes. He became irritable, sleep worsened; often he wakens with headache. Anamnesis morbi. According to his opinion, disease began 10 years ago. At the beginning he marked only periodical headaches. He consulted district doctor, which revealed elevation of blood pressure - 160/95 mm Hg, prescribed treatment, and registered. Patient constantly uses antihypertensive drugs, blood pressure was within normal limits, and headaches disappeared. But periodically elevations of blood pressure were marked. During last ones patient didn’t complain of headaches only, but-dizziness and noise in ears also. During last two years he became to mark foregoing chest pains, which at the beginning appeared on significant physical stress, long walking. On ECG any changes weren’t diagnosed. Additional drugs were prescribed. Condition became better, retrosternal pains became rare. About 10 days retrosternal pains became to appear more often- to 10-15 times a day, on littler physical stress (after walking 200- 300 m with speed, usual for him). Dyspnea on exertion appeared. Sometimes he feels intermissions in heart work. On ECG, recorded at rest, any changes weren’t reveled. But on ECG, recorded on the background of dosing physical stress, depression of S-T segment was revealed. Anamnesis vitae. Father died from myocardial infarction in the age of 54 years old. Mother has arterial hypertension and diabetes mellitus. Diseases in past. Until 7 years old age he had diseases often, was sickly children. During school age sometimes he had “catarrhal” diseases. He goes in for sport. During adult age he doesn’t have diseases, but from 40 years old expressed body weight is marked. Living conditions. Family consists of 5 members (wife and three adult children). Three person works. He lives in private house; central water-supply and heating are present. Feeding is various. Animal course he uses every days. He likes sweat courses, pies, cakes and others. He uses salted foods, spices often. Harmful habits. He smokes from 16 years old age. During last years - 1 pack of cigarettes a day. Alcohol - 1-2 times a week. He never uses narcotics. Allergological anamnesis. He has allergological rhinitis during 23 years. Intake of sulfonamides (he treated tonsillitis) in 12-years old age was complicated by itching skin rash. Prescription of mildronate before admission to the clinics also was complicated by skin rash. General inspection Consciousness is clear, ratiocination. He comes into contact without difficulties. He answers the questions distinctly. Patient’s position is active. Constitution is hypersthenic. Height is 176 cm, body weight is 95 kg. Skin and mucous membrane has normal color. Xanthelasms are near nasal corner, little skin rash is on abdomen. Subcutaneous fat is excessively developed. Left submandibular lymph nodes are enlarged to size of haricot bean. Little edemas are on feet and lower third part of shins. Musculoskeletal system. Tone and development of the muscles are good. Tenderness of cervical part of spinal column is marked during palpation. Respiratory organs. The chest is like cone, wide. Painful parts are absent. Percussion sound is clear, in subscapular areas is increased. Lower borders of the lungs are the following: along midclavicular line - 7 rib, along midaxillar line - upper edge of the 9 rib, along scapular line - 10 intercostal space. Auscultation. Breathing is vesicular, some weakened. Simple dry rales are heard in middle and lower parts of the lungs. After cough they don’t disappear, but their timbre is changed. Respiratory rate is 22 per minute.

Circulatory organs Inspection of neck. Pulsation and filling of veins are usual; pulsation of the right carotid is decreased slightly. Inspection of heart region. Deformation and pathological pulsations are absent. Apex beat is amplified. Palpation. Apex beat is in the 5th interspace 1 cm laterally of midclavicular line, forced. Pathological thrill of the chest is absent. Pulsation on radial and dorsal arteries of feet is present. Pulsation of the right common carotid artery to the right is more intensive then left one. Percussion. Borders of relative cardiac dullness: Upper - 3rd interspace, left-1 cm laterally of midclavicular line, right - 1 cm laterally of the right edge of sternum. Heart configuration is normal. Auscultation. Cardiac rhythm is correct. Loudness of sounds at the heart apex is weakened, in the 2nd interspace - intensification of the II sound. Slight systolic murmur without irradiation is heard is this point. Change of loudness of murmur depending on changing of body’s position isn’t observed. It slightly increased after physical activity. Slight systolic murmur is heard over carotid artery. Blood pressure is 170/105 mm Hg. Digestive apparatus. Abdomen is soft, painless. Liver’s sizes according to Kurlov is 16- 10-8 cm. Spleen isn’t enlarged. Urinary organs. Kidneys aren’t palpated. Pasternatsky’ sign is negative. Disuric signs aren’t present.

Laboratory-instrumental researches: ECG. Heart rate is 96 per minute, P-Q - 0,23 sec, QRS-0,08 sec, Q-T- 0,52 sec, rhythm is sinus, left ventricular premature beats. S-T segment is displaced downwards from isoelectric line in leads V4-5. T-wave is smoothed in leads I, avL, V5-6. Echocardiography. Left ventricular weight is 185g (normally it is 135 g). Thickness of posterior wall of the left ventricle during diastole is 1,2 mm (normally it is to 11 mm). Ejection fraction is 25% (normally it is 50-60%). Final diastolic size of left ventricular cavity is 70 mm3 (normally it is 46-57 mm3 ). Area of hypokinesia with sizes 22-36 mm is present in the region of lateral wall of the left ventricle, closer to heart apex. Doppler echography of the cervical vessels. Mean linear blood circulation along right common carotid artery is 16 cm/sec (normally it is 21,9+5,03 cm/sec), along left one - 21,5 cm/sec (normally it is 21,9+5,03 cm/sec), along right iliac artery - 23,5 cm/sec (normally it is 23,5+6,08 cm/sec), along left one - 22,8 cm/sec (normally it is 23,5+6,08 cm/sec). General blood analysis. Hb - 145 g/l, erythrocytes - 4,8•109/l, leukocytes -11,4•109/l, ESR - 8 mm/hour. General urinalysis. Color - yellowish saturated. Transparence - total. Sediment is absent. Specific gravity - 1,024. Protein - 0,02 g/l. In sediments - simple erythrocytes, erythrocytes - 0-1 in v.f., simple cells of pavement epithelium. Biochemical research of blood. Total cholesterol - 6,8 mmol/l, low-density lipoproteins - 4,7 mmol/l, high-density lipoproteins - 0,7 mmol/l, triglycerides -2,1 mmol/l, blood sugar- 5,2 mmol/l. Questions to the task 3: 1. For which disease pains of this patient is typical? 2. What stages of heart failure according to Strazhesko-Vasilenko are patient’s complaints corresponded to? 3. About which diseases it is possible to think according to patient’s complaints of headaches, dizziness, noise in ears? 4. What concrete disease is it necessary to connect headaches, dizziness, noise in ears, taking into account results of anamnesis morbi? 5. What diagnostic estimation it is necessary to give to acceleration of retrosternal pains, their appearance on less physical activity? 6. What is reason of appearance of dyspnea during last 10 days? 7. On ECG, registered at rest, any abnormality weren’t marked. Does it contradict to your provisional diagnosis? 8. Why on ECG, registered on the background of physical exertion, abnormalities were appeared. 9. What diagnosis does depression of S-T segment on ECG (it is lower than isoelectric line), observed on physical activity, correspond to? 10. What conclusion can be made on the basis of list of diseases, which were present in parents of this patient? 11. What environment risk factors of development of IHD and essential hypertension were marked in life history of this patient? 12. To development of which other diseases does essential hypertension promote? 13. What diagnostic importance must be given to presence of xanthelasms in the patient? 14. What diagnostic importance must be given to presence of little-point skin rashes in the patient? 15. What is diagnostic importance of edemas, revealed in patients on feet and lower third of shins? 16. Little displacement of lower lung borders downwards is revealed in patient, during auscultation weakening of vesicular breathing and presence of periodical dry rales are marked. What can be reason of these symptoms? 17. Weakening of pulsation on common carotid artery was revealed during examination. What is reason of this weakening? 18. What is reason of appearance of systolic murmur on common carotid artery? 19. What signs of IHD was revealed on ECG, recorded in clinic? 20. What disorder of conductivity was revealed on this ECG? 21. What sign of disorder of excitability was revealed on this ECG? 22. What typical sign of IHD was revealed on Echo-CG? 23. What signs of heart failure were revealed on this echocardiogram? 24. What conclusion can be made by results of Doppler echography of the cervical vessels? 25. Give diagnostic estimation of cholesterol content. 26. Give diagnostic estimation of low-density lipoproteins content. 27. Give diagnostic estimation of high-density lipoproteins content. 28. Give diagnostic estimation of triglycerides content. 29. Give general diagnostic estimation of indexes of lipid metabolism. 30. Do you continue to think about essential hypertension as reason of headaches, dizziness and noise in the head? 31. What diagnosis can be made on the basis of results of all researches? Literature recommended: Main Sources: 1. Davidson’s principles and practice of medicine. Edited by Chrostopher Haslett, Edwin R. Chilvers, John A. Hunter, Nicholas A. Boon. - 18th ed. - 1999. - 1175 p. 2. Harrison’s principles of internal medicine /Dennis L. Kasper et al. - 16th ed.- Vol. II, 2005. - 2608 p. 3. Ivashkin V.T., Okhlobystin A.V. Internal diseases propedeutics.- M.: GEOTAR- MEDIA, 2005.- 176 p. 4. Kovalyova O.M., Ashcheulova T.V. Propedeutics to Internal Medicine. - Vinnytsya: NOVA KNYHA, 2006. - 424 p. 5. Kovalyova O.M., Shapovalova S.O., Nizhegorodtseva O.O. Propedeutics to Internal Medicine. Part 2. - Vinnytsya: NOVA KNYHA, 2007. - 264 p.

Additional ones: 1. Гребенев А.Л. Пропедевтика внутренних болезней: Учебник – 5-е изд., перераб. и доп.- М.: Медицина, 2001.- 592 с. 2. Мухин Н.А., Моисеев В.С. Пропедевтика внутренних болезней: Учебник – 2-е изд., перераб. и доп.- М.: ГЭОТАР-Медиа, 2007.-848 с. 3. Основи внутрішньої медицини: Пропедевтика внутрішніх хвороб/Децик Ю.І., Яворський О.Г., Нейко Є.М. та ін.;За ред. О.Г. Яворського.-К.: Здоров’я, 2004.- 500 с.

Answers for test tasks of the I-st level: 1 - c 7 - a 13- d 19- c 25- b 30- d 2 - c 8 - b 14- b 20- b 26- d 31- c 3 - d 9 - d 15- c 21- b 27- d 32- a 4 - d 10- c 16- c 22- b 28- b 5 - e 11- d 17- c 23- d 29- c 6 - c 12- d 18- c 24- c

Answers for test tasks of the II-nd level: 1 - a , b , e , f , g 7 - d , f 13- e , f 2 - a , b , c 8 - b , d , e 14- a , c , f 3 - a , b , e , f 9 - a , b , d , e , g 15- a , c , d 4 - a , b , c , f , h 10- b , d , e , f , g 16- a , b , d 5 - b , c 11- b , d , f 17- b , c , g 6 - a,d,e,f,g 12- a , b 18- b , c

Standards of right answer for tasks: 1) b. 2) a, d , e 3) 1. For IHD - angina pectoris (stenocardia). 2. 2 stage. 3. Such complaints can occur in hypertensive disease. But they occur in patients with cerebral circulatory insufficiency on the basis of cerebral arteries atherosclerosis. 4. With hypertensive disease. 5. Stable course of disease stop, it become to progress. Taking into account, that according to character pains correspond to angina pectoris, it is necessary to say about transformation of stable angina into more severe and dangerous its variant - unstable angina. 6. During last days progressing of angina is observed. Blood supply of myocardium became worse and as a result - contractile function of myocardium became worse. 7. It doesn’t contradict. Absence of changes on ECG, registered at rest, out of pain attacks, mean that in this situation blod supply of myocardium weren’t critical yet. It corresponded to minimal needs in conditions of rest. 8. During physical exertion needs of myocardium in blood supply increased. Amount of blood, passing through vessels, narrowed due to arthrosclerosis, stop to correspond to increased needs. 9. To diagnosis of angina pectoris. 10. Conclusion about presence of hereditary predisposition to these diseases in this patient. Patient has hereditary risk-factors of development of hypertensive disease and IHD. In case of presence of other environment risk-factors probability of development of disease becomes larger. 11. Presence of surplus body weight, increase of dietary salt and refined carbohydrates intake. Smoking is also important risk-factors. 12. Hypertensive disease is strong factor, promoting to development of atherosclerosis in all vascular areas with following development of IHD, cerebral vascular failure, intermittent claudication (Dejerine’s syndrome) etc. Development of contracted (granular) kidney and retinopathy is connected with elevated blood pressure also. 13. Skin xanthelasms are places of intracutaneous accumulations of cholesterol. They appear in case of long hypercholesterolemia, most often - in hereditary predisposition. 14. They appeared on the background of mildronate intake and, probably, are allergic reaction to this medicament. Patient, according to anamnesis vitae, has predisposition to allergic reactions. 15. They direct to presence of heart failure, like dyspnea, which troubles patient during last days. 16. The patient smokes during long period. Slightly expressed bronchitis of smoker with initial manifestations of pulmonary emphysema is present in the patient, probably. 17. Atherosclerotic constriction of artery below place of pulsation weakening. 18. Atherosclerotic constriction of artery in area of auscultation of systolic murmur. 19. Depression of S-T segment below isoelectric line and elongation of Q-T interval. 20. Disorder of atrio-ventricular conductivity, I degree. 21. Presence of ventricular ectopic beats (ventricular extrasystoles). 22. Presence of hypokinesia area in the wall of the left ventricle. 23. Significant decrease of ejection fraction and dilation of left-ventricular cavity. 24. Decrease of blood circulation is sign of constriction of carotid artery. 25. Total cholesterol content in the blood is increased. 26. Low-density lipoproteins content in the blood is increased. 27. High-density lipoproteins content in the blood is decreased. 28. Triglycerides content in the blood is normal. 29. Such changes of lipid blood spectrum are favourable for atherosclerosis development. 30. No, I don’t continue to think so. Weakening of pulsation of total carotid artery to the right, appearance of systolic murmur in this area and decrease of blood circulation in this place allow to say about constriction of total carotid artery (by atherosclerotic plaque, probably) and impairment of cerebral circulation. Observed chronic cerebrovascular insufficiency can be cause of dizziness and noise in the head. 31. Diagnosis: hypertensive disease II stage. IHD: unstable angina pectoris, disorder of atrioventricular conductivity, ventricular premature beats, heart failure II stage, III functional class. Atherosclerotic constriction of total right carotid artery, chronic cerebrovascular insufficiency.

4. Propaedeutics as an Introduction to the Clinic of Internal Medicine Propaedeutics M. Yabluchansky L. Bogun, L.Martymianova, O. Bychkova, N. Lysenko, N. Makienko, E. Golubkina V.N. Karazin National University Medical School’ Internal Medicine Dept. http://dspace.univer.kharkov.ua/bitstream/123456789/10966/2/Lecture%20PIM_22.06.2015. pdf 5. ИИ Мистюкевич. Theses of lectures on propedeutics of internal diseases. www.gsmu.by/file/biblio/uchlit/tezisyprop.doc 6. Англо-русский тематический словарь по пропедевтике внутренних болезней и общему уходу за больными : справочное издание / Витебский государственный медицинский университет, Кафедра пропедевтики внутренних болезней; сост. Л.М. Немцов; под ред. Г.И. Юпатова. - Витебск : ВГМУ, 2005. - 153 с. URI: http://elib.vsmu.by/handle/123/11343 7. Special propedeutics of internal diseases : lecture course / Vitebsk State Medical University, Dep. of Propedeutics of Internal Diseases ; comp. by L. M. Nemtsov. - 2-е изд. - Vitebsk : VSMU, 2016. - 318 p. URI: http://elib.vsmu.by/handle/123/9837 8. General propedeutics of internal diseases : lecture course / Vitebsk State Medical University ; compiled by L. M. Nemtsov. - Vitebsk : VSMU, 2006. - 175 p. http://elib.vsmu.by/handle/123/268

Methodical instruction is composed by lecturer Ye.Ye. Petrov.

Approved at the Department of Propaedeutics to Internal Medicine with Care of Patients meeting on 11 09 2018 Protocol No2 The Head of the Department Professor Yu. Kazakov

METHODICAL INSTRUCTION FOR STUDENTS’ SELF-PREPARATION WORK

Educational discipline Propaedeutics to Internal Medicine Module No 2 Enclosure module No 7 Topic The basic clinical features on bronchitis and bronchial asthma. Chronic obstructive pulmonary disease. Syndrome of increased airiness of pulmonary tissue. Year 3 Faculty medical

Poltava - 2018 1. The topic basis: syndrome of bronchial obstruction and syndrome of increasing of airiness of the pulmonary tissue and pathology, basis of which they form (bronchitis, pulmonary emphysema, and bronchial asthma) are very widespread. That is why knowledge of these questions is necessary for future physicians. 2. The specific aims:  To explain the main signs of syndrome of bronchial obstruction and syndrome of increasing airiness of the pulmonary tissue.  To explain etiology and pathogenesis of bronchitis (acute and chronic), bronchial asthma, pulmonary emphysema.  To explain essence of term “Chronic obstructive pulmonary disease”.  To analyze results of examination of patients with bronchitis, bronchial asthma, pulmonary emphysema.  To interpret results of examination of patients with bronchitis, bronchial asthma, pulmonary emphysema.  3. Basic knowledge, experience, skills necessary for studying the topic in connection with other subjects (interdisciplinary integration) : Previous disciplines Obtained skills 1. Anatomy To know human anatomy, respiratory system organs particularly. 2. Physiology To know physiology of respiratory system. 3. Medical psychology To be able to observe principles of ethics and deontology in medical practice. 4. Pathological morphology To know pathologic-morphological picture of bronchitis, bronchial asthma, pulmonary emphysema. 5. Latin and medical terminology To know terminology (in Latin transcription): bronchial asthma, asthmatic state, pulmonary emphysema.

2.Chronic obstructive It is defined as a disease state, characterized by the presence of airflow pulmonary disease obstruction due to chronic bronchitis or emphysema; the airflow obstruction is generally progressive, may be accompanied by airway hyperreactivity, and may be partially reversible.

3. Chronic bronchitis Disease, which is characterized by excessive secretion of bronchial mucus and is manifested by productive cough for 3 months or more in at least 2 consecutive years in the absence of any other disease that might account for this symptom.

4. Pulmonary emphysema It denotes abnormal, permanent enlargement of air spaces distal to terminal bronchiole, with destruction of their walls and without obvious fibrosis.

5. Bronchial asthma It is chronic disease, the basis of which is inflammatory process in respiratory tracts with participation of various cellular elements, mast cells and eosinophils particularly. In predisposed persons this inflammation leads to repetitive episodes of wheezes, dyspnea, sense of heaviness in thorax and cough, especially at night or in the early morning. These symptoms are accompanied by widespread and diverse obstruction of bronchial tree, which at last partially spontaneously reversible, or due to medical treatment. Inflammation also causes concord increase of response respiratory tracts to different stimuli. 6. Status asthmaticus It is prolonged attack of bronchial asthma, resistant to administered therapy and characterized by evident or acutely progressing respiratory failure due to block of respiratory tracts under resistance to adrenomimetic drugs.

4.2. Theoretical questions to be answered before class: 1. Tell about etiology and pathogenesis of bronchitis (acute and chronic). 2. Tell about classification of bronchitis. 3. Tell about clinical picture of acute bronchitis. 4. What does term “Chronic obstructive pulmonary disease” mean? 5. What are potential results of questioning, inspection, palpation, percussion and auscultation of patients with chronic bronchitis? 6. What laboratory and instrumental methods are used for diagnostics of chronic bronchitis? 7. Tell about etiology and pathogenesis of pulmonary emphysema. 8. Tell about classification and clinical picture of pulmonary emphysema. 9. What are potential results of instrumental methods examination of patients with pulmonary emphysema? 10. Tell about etiology and pathogenesis of bronchial asthma. 11. What are potential results of questioning, inspection, palpation, percussion and auscultation of patients with bronchial asthma? 12. What laboratory and instrumental methods are used for diagnostics of bronchial asthma? 13. Tell about classification of bronchial asthma. 4.3. Practical work (tasks), which should be performed during class: 1. To carry out examination of patients with chronic obstructive pulmonary disease (chronic bronchitis, pulmonary emphysema) and bronchial asthma. 2. To interpret obtained results. 3. To interpret results of laboratory and instrumental methods examination of patients with chronic obstructive pulmonary disease (chronic bronchitis, pulmonary emphysema) and bronchial asthma.

The contents of topic: Text SYNDROME OF BRONCHIAL OBSTRUCTION Syndrome of bronchial obstruction is characteristic for those pulmonary diseases, in case of which passage air through bronchi become difficult (bronchitis, bronchospasm, bronchial asthma, stenosis or compression of trachea or large bronchi, etc.). Owing to difficulty of the respiration during expiration phase, the lungs are dilated, amount of air in them is increased, and their respiratory excursion is decreased. The chest and the lungs are in constant inspiratory state. The form of the chest became barrel. Diaphragm is low, intercostal spaces become wide, respiratory movements - limited. Vocal fremitus can be weakened. During percussion of the lungs band box sound is heard. Lower lung borders are lowered, their excursion is diminished. Owing to emphysema diminishing of absolute cardiac dullness can be observed. During lung auscultation weakened or harsh respiration is revealed. In case of chronic bronchitis and during bronchial asthma attack great quantity of dry rales mainly appears. During X-examination wide intercostal spaces, their little excursion, low position of diaphragm are marked. Lung field became clearer. Degree of bronchial obstruction is revealed by means of research of external respiration (spirography, pneumotachometry, analysis of loop “flow-volume”, got at apparatus of type “Pneumoscrin”)

SYMDROME OF INCREASING OF AIRINESS OF THE PULMONARY TISSUE Syndrome of increasing airiness of the pulmonary tissue appears in those diseases, which are accompanied by prolong violent cough. These diseases include chronic and acute bronchitis, bronchial asthma, some forms of lung inflammation, chronic interstitial inflammation particularly. Owing to these causes and substitution of pulmonary parenchyma by connective tissue (pneumosclerosis) elasticity of pulmonary tissue is decreased. Elasticity of all tissues, including the lungs, is decreased in persons of elderly age. Smoking promotes decreasing of elasticity of pulmonary tissue to great extent. Owing to decreasing of elasticity of the lungs expiration becomes difficult as it is realized strictly thanks to elasticity of pulmonary tissue. Changed lungs are all time as if at inspiration phase. Alveolar septa are destructed. One and all results to increasing of airiness of the lungs. Described syndrome is typical for pulmonary emphysema. In patients dyspnea is marked. At the beginning it has expiratory character, but later when heart failure is developed, it has inspiratory character also (that is to say mixed character). During examination characteristic barrel (emphysematous) chest, cyanosis of lips, face, extremities (acrocyanosis) is marked. During palpation increasing of chest resistance, weakening of vocal fremitus are revealed. During comparative percussion band box sound is revealed. Lower lung borders are lowered on one-two intercostal spaces, excursion of the lower lung borders is diminished or it isn’t revealed absolutely. During auscultation weakened vesicular breathing is heard. Bronchophonia isn’t changed, sometimes it is weakened. During X- examination particularly clear lung field, lowering of lower borders of the lungs and limitation of excursion of diaphragm are revealed.

BRONCHITIS Bronchitis is disease, characterized by development of inflammatory process in bronchi. Ethiology and pathogenesis. In etiology of bronchitis infection (virus, pneumococcus, streptococcus, staphylococcus, etc.) plays important role. Toxic substances, affected mucous membrane of bronchi, smoking, and also physical and meteorological factors (dusty working room, low temperature) influence on development of bronchitis. Classification. Bronchitis can be primary and secondary. Development of primary bronchitis is characterized by isolated lesion of bronchi. Secondary bronchitis appears as complication of other diseases (influenza, tuberculosis, measles, pertussis, chronic non - specific pulmonary diseases, heart diseases, etc.). It can be defined as tracheobronchitis (lesion of trachea and large bronchi), bronchitis (inflammatory process in bronchi of medium and small caliber) and bronchiolitis (it appears more often in little children in case of lesion of bronchioli). According to clinical course bronchitis is subdivided into acute and chronic. ACUTE BRONCHITIS Clinical pictire. Acute bronchitis (bronchitis acuta) begins suddenly, on the background of catarrh of upper airways. Patient complains of dry cough (sometimes it is barking), difficult discharge of sputum. Later on the cough became productive, mucous or muco-purulent sputum begins be discharged. Amount of sputum depends on course of disease. Feeling of pressing in the chest, in upper part of the sternum particularly (trachea), is typical also. Due to frequent, violent cough the patient feels the pain in muscles of neck and chest. Elevation of temperature to 38-40° C is observed often, but temperature can be normal and subfebrile also. In case of acute bronchitis auscultation of the lung has main importance. Harsh breathing and diffuse dry rales of different character (from whistling to buzzing) are heard usually. Later on non-sonorous moist rales of different caliber can appear. Data of palpation of the chest, percussion and bronchophony are without changes. During X-ray study some increased bronchial pattern is marked. Course and complications. Acute bronchitis lasts usually 10-14 days and is finished, as a rule, by recovery usually. In debilitated patients with accompanying diseases of cardiovascular system disease can have prolonged course, lasting to the month and more. Adding of bronchopneumonia (in diagnostics of which important role belongs to X-ray examination) is the most frequent complication of acute bronchitis. Treatment of acute bronchitis must be complex, etiologically and pathogenetically substantiated. The main actions come to fight against infections, recovery of bronchial patency, and removal of harmful industrial and living factors. With this purpose antibacterial remedy with consideration sensitivity of microflora to them in combination with ascorbic acid, vitamins of groups B are prescript. For liquidation of bronchospasm bronchial spasmolythics are prescript. Expectorant remedies are used. Antipyretics, hot lime-flower tea with raspberry juice, warm milk with alkaline mineral water (1:1) or ½ tea spoon of sodium hydrocarbonatis for 1 glass of milk are used. Inhalations of sodium hydrocarbonatis, etc. are used also. Hot compresses, mustard plasters on the chest, cupping-glasses, mustard bathes for legs, physiotherapeutic procedures, massage of the chest, exercise therapy help. In case of dry troublesome cough for diminishing of cough reflex libexine, codeine, dionine, etc. are prescript. Prophylaxis of acute bronchitis comes to liquidation of systematic irritation of mucous membrane of bronchi by different substances (struggle against dustiness of industrial rooms, smoking), timely sanation of infection foci (of nasopharynx in the first place).

CHRONIC BRONCHITIS Chronic bronchitis (bronchitis chronica) is characterized by excessive secretion of bronchial mucus and is manifested by productive cough for 3 months or more in at least 2 consecutive years in the absence of any other disease that might account for this symptom. Etiology and pathogenesis.Chronic bronchitis is developed often after repeated acute bronchitis, in presence of chronic infections of nasal part of pharynx, in case of inhalation of dust and constant influence of unfavourable factors (low temperature of environment, smoking, etc.), chronic diseases of lungs and heart. Classification. According to character of inflammatory exudate chronic bronchitis is subdivided into catarrhal and purulent. Depending on presence of change of expiratory respiration function obstructive and non-obstructive types of disease are divided. Besides, chronic bronchitis like to almost any chronic disease can have exacerbation and remission stages. Clinical picture. Constant symptoms of chronic bronchitis are dyspnea, cough, which is accompanied by discharging of muco-purulent (of yellow colour) or purulent (green) sputum. Violent cough and bigger amount of the sputum appear in the morning more often. During examination of the patient in late stage cyanosis (acrocyanosis) of the face, neck, extremities can be revealed. During carrying out of physical examination of patients with chronic bronchitis harsh breathing and diffuse dry rales (buzzing in case of lesion of large and medium bronchi, and whistling in case of lesion of small bronchi) can be revealed. In presence of pulmonary emphysema, it is revealed band box sound. During exacerbation of process moist non-sonorous fine bubbling and medium bubbling rales can be heard also. In case of development of pneumosclerosis very sonorous fine bubbling rales, caused by adhesion and separation of small with sticky secret bronchi which lose their elasticity, are heard constantly. Chronic bronchitis is treated difficulty. Continuing during many years, it results to significant changes from side of the lungs - pneumosclerosis, bronchiectases, and pulmonary emphysema. Chronic bronchitis, complicated by pneumosclerosis and emphysema, results to development of pulmo-cardial failure (cor pulmonale is developed). Sometimes chronic bronchitis can mask tuberculosis of the lungs. X -examination of the lungs and sputum examination on presence of tuberculous bacilli help to make more precise diagnosis usually. Treatment of chronic bronchitis is carried out by means of expectorant, bronchial spasmolytic preparations, exercise therapy, massage of the chest, aerosol therapy, physiotherapy, climatotherapy. In case of exacerbation of disease antibiotics, sulfanilamide preparations, bronchial spasmolytics, antitussive and expectorant preparations, mustard plasters on the area of the chest are prescript. It is necessary to exclude hazard factors, promoted to development of bronchitis (smoking, dust, overcooling). Rehabilitation must be carried out in conditions of stationary and sanatoriums of pulmonological profile.

CHRONIC OBSTRUCTIVE PULMONARY DISEASE Chronic obstructive pulmonary disease (COPD) is defined as a disease state characterized by the presence of airflow obstruction due to chronic bronchitis or emphysema; the airflow obstruction is generally progressive, may be accompanied by airway hyperreactivity, and may be partially reversible. Although emphysema and chronic bronchitis must be diagnosed and treated as specific diseases, most patients with COPD have features of both conditions. The death rate from COPD is increasing rapidly, especially among elderly men. A characteristic of chronic bronchitis was given above, therefore stop in detail on pulmonary emphysema.

PULMONARY EMPHYSEMA Pulmonary emphysema denotes abnormal, permanent enlargement of air spaces distal to terminal bronchiole, with destruction of their walls and without obvious fibrosis. It is distinguished primary pulmonary emphysema, which is independent disease, and secondary pulmonary emphysema, which is complication of other diseases of respiratory organs. Etiology and pathogenesis. In appearance of primary pulmonary emphysema important role belongs to hereditary caused factors, specifically to deficiency of α 1-antitrypsin, leaded to accumulation of proteolytic enzymes and following degradation of thin structures of pulmonary tissue. The main cause of development of secondary pulmonary emphysema is chronic bronchitis and bronchial asthma, when as result of bronchial obstruction keep of air in alveoli and their superdistension occurs. Important factor, predisposing to appearance of pulmonary emphysema, is smoking (in smokers pulmonary emphysema occurs in 15 times more frequently than in nonsmokers). Certain etiologic role belongs to some professions, accompanied by systematic elevation of pressure in bronchi and alveoli (blow glass workers, musicians, played on wind- instruments, etc.). Classification. Besides mentioned already pathogenetic forms (primary and secondary pulmonary emphysema), diffuse and localized pulmonary emphysema are differed. Depends on morphological peculiarities panacinar or panlobular emphysema (with lesion of all acinus), centeracinar or centerlobular (with lesion of central part of acinus), periacinar, irregular (pericicatricial) and bullous are differed. Clinical picture. In patients with pulmonary emphysema the main complaint is dyspnea, arising on physical activity at first, but then - at rest also. Dyspnea has expiratory character and patients (with primary pulmonary emphysema particularly) made expiration with closed lips, inflating cheeks (“pant”).In patients with secondary pulmonary emphysema dyspnea, as a rule, connected to the cough, which was during many years in these patients. During inspection of these patients puffiness of the face, cyanosis, swelling of cervical veins is revealed. In patients with pulmonary emphysema barrel form of the chest with dilated intercostal spaces, smoothness and bulging of subclavicular and supraclavicular fosses, participation of additional respiratory muscles in respiratory act are marked. Diminishing of maximal respiratory excursion of the chest, weakening of vocal fremitus is revealed. During percussion band box sound, diminishing of excursion of the lower lung borders and lowering of the lower lung borders, diminishing of sizes of absolute cardiac dullness are revealed. During auscultation proportionally weakened vesicular breathing is heard. During X-examination particularly clear lung fields, decreased lung pattern, lower position and little mobility of diaphragm are revealed. During examination of function of external breathing diminishing of indices of VC, MLV, decreasing of the expiratory reserve volume and increasing of residual volume are marked. In connection with developing disturbances of gaseous composition of the blood (hypoxemia, hypercapnia) different hemodynamic changes, leading to tachycardia, secondary erythrocytosis, and pulmonary hypertension occur. Course and complications. Pulmonary emphysema is characterized by slowly progressive course. As result of increasing load on right parts of the heart and development dystrophic changes in myocardium is gradual augmenting of symptoms of chronic right- ventricular failure, addition of edema, ascites, and enlargement of liver. Treatment. Different methods of symptomatic therapy are used in treatment of the patients with pulmonary emphysema. For improvement of bronchial patency euphylline (aminophylline) is prescript. In disturbance of gaseous composition of the blood oxygenotherapy is indicated, in case of development of chronic right-ventricular failure diuretics are prescript. In high secondary erythrocytosis bloodlettings give good effect. Great role in complex treatment belongs to exercise therapy (respiratory gymnastics). Prophylaxis of pulmonary emphysema includes early diagnostics and timely treatment of the patients with chronic bronchitis, struggle against smoking and dustiness of atmospheric air, exercises.

BRONCHIAL ASTHMA Bronchial asthma (asthma bronchiale) is allergic disease, the main sign of which are periodical attacks of disturbance of bronchial patency as suffocation. This disease is very widespread. Approximately about 5% peoples in world have bronchial asthma. Ethiology and pathogenesis. High reactivity (hyperreactivity) of respiratory airways to mediators of immediate allergy and many non-specific (non-allergic) irritators is the cause of asthma. In patients with bronchial asthma mediators of allergic inflammation (histamine, serotonin, bradykinin, etc.) are discharged as result of connection of antigens with specific antibodies, which are fixed on labrocytes (mast cells), plasmocytes and lymphocytes. As a result vessels in mucous membrane are dilated, capillary permeability is increased; interstitial edema, bronchorrhea, bronchospasm appear. Now the most substantial from established risk factors of bronchial asthma is atopy - hereditary genetic readiness to allergic reactions. Risk factors, which can lead to asthma, include common allergens (mycelial fungi, house dust mite protein, allergens of animals, wool), organic and non-organic solvents, some foodstuffs (eggs, fish), flower pollen, etc. These risk factors can cause bronchial asthma attack, that is to say they can be triggers. Every patient can have his own triggers, about which they must know for prevention of attack. Internal risk factors can be helminthic invasion, chronic infections, and mycoses. Clinical picture is characterized by appearance of suffocation attack, which can be prolonged to 1 day and more (status asthmaticus). Dyspnea of expiratory character is typical. The patient takes forced position sitting (orthopnoe). Sometimes he leans by hands against armchair in order to include additional muscles for making expiration easy. Whistling rales are heard at distance from patient, during expiration particularly (distance rales). Cyanosis of lips, swelling of cervical veins, anxious face is observed. Supraclavicular fosses and jugular fossa are retracted (stretched out) markedly during inspiration. The cough with difficult discharge of viscous sputum appears. During physical examination changes same ones in case of pulmonary emphysema with bronchitis are marked. Vocal fremitus is weakened; during percussion band box sound is revealed, lower borders of lungs are lowered, excursion of lower lung borders is limited. During auscultation of the lungs diffuse dry rales, during expiration particularly, are revealed on the background of weakened breathing. Sometimes in case of severe asthma attack or in case of status asthmaticus in connection with obstruction of respiratory airways respiratory sounds can not be heard at all. The attack is finished by more easy discharge of viscous at the beginning, and then - liquid sputum. Breathing gradually becomes freer. In the lungs vesicular breathing is better heard, amount of dry whistling rales is decreased, but moist fine bubbling and medium bubbling non-sonorous rales appear; they disappeared in some time later. Changes can’t be revealed sometimes out of attack by means of physical methods examination. Nasal speech, which shows to presence of allergic rhinosinusopathy, can testify to recent attack. During blood examination in patients with bronchial asthma eosinophilia is observed. By means of microscopic research of the sputum during attack or after it many acidophilic granulocytes, often - Kurschman’s spirals and Charcot-Leiden crystals are revealed. During X-examination particularly clear lung fields and limitation of excursion of the diaphragm are revealed. The course of bronchial asthma depends on rate of suffocation attacks, addition of chronic bronchitis, pneumosclerosis and emphysema. In severe cases signs of pulmo-cardial failure, which can be the cause of patient’s death, are revealed. According to gravity of the course of disease four degree of bronchial asthma are differed. For determining of degrees of gravity frequency of appearance of attacks of whistling breathing, choking cough in the morning or at night, cough on exertion, and cough, whistling breathing or feeling of pressing in the chest after air allergens (triggers) also are taken into account. The 1-st degree of bronchial asthma - intermitting bronchial asthma is characterized by appearance of foregoing symptoms rarer than one time a week, night symptoms of asthma twice a month or more rarely. The 2-nd degree - long-lasting bronchial asthma of mild course manifested by appearance of symptoms of bronchospasm from one time a week to one time a day, night suffocation attacks one time a 1-2 week. The 3-rd degree - long-lasting bronchial asthma of moderate severity course is characterized by daily symptoms of bronchial asthma, disturbance of general state, physical activity and sleep. Night suffocation attacks occur more often than once a week. The patients are forced use inhalations of bronchial spasmolytics every day. For 4 -th degree of bronchial asthma - long-lasting bronchial asthma of severe course - constant symptoms of disease, frequent night suffocation attacks, considerable physical activity limitation is typical. Complete classification of bronchial asthma is given below:

Classification of bronchial asthma (according to international Consensus, 1992) 1. Intermitting asthma: - brief symptoms, appearing less than 1 or 2 per week; - nightly symptoms, appearing less than 1 or 2 per month; - symptoms are absent in a period between exacerbations; - FEV1 and PEFR make 80 % of predicted value. 2. Mild persisting (long-lasting) asthma: - brief symptoms appear more than 1-2 times per week; - nightly symptoms, appear more than 2 times per month; - exacerbations could violate sleep; - chronic symptoms require β2-agonists almost daily; - FEV1 and PEFR are of 60-80 % of norm. 3. Severe persisting (long-lasting) course: - frequent exacerbations; - permanent symptoms; - frequent nightly symptoms; - FEV1 and PEFR less than 60 % of predicted value. 4. Persisting (long-lasting) course of medium severity: its parameters are between mild and severe courses. Exacerbation stages of Bronchial asthma Symptoms Mild Medium Severe Risk of respiratory standstill Movement Patients walk Talk, try to seat Immobile, can Immobile activity and can lie hardly walk Speech Sentences Phrases Words Words Consciousness Possible Usually excitation Usually Confusion excitation excitation Breathing Frequent, exceeds 30 per minute Action of Absent Participate Participate Paradoxical thoracic- additional abdominal breathing muscles Whistling Moderate, Loud Whistling rales are breathing usually at the absent end of expiration Heartbeat rate <100 100-120 >120 Bradycardia Paradoxical No No No Absent due to pulse muscle overstrain PEFR after use >80 % 60-80 % <60 % of broncholytics

PO2 mm Hg Normal >60 >60 PCO2 mm Hg <45 <45 >45 Sa O2, % >90 91-95 <60

Treatment of bronchial asthma. There is therapy, directed to stop of suffocation attack, and to prolonged maintenance (supportive) treatment. During suffocation attack first of all it is necessary to provide of the patients by clear air, isolating his/her from influence of triggers, to give small amount of warm drinking, to reassure him/her. From medicaments it is used inhaled and in tablets short- acting β2- agonists (albuterol, metaproterenol, bitolterol, terbutaline, pirbuterol), anticholinergics (ipratropium bromide, oxytropium bromide), xanthins (theophylline, euphyline, aminophylline), sympathomimetics (adrenaline hydrochloride). In grave cases, in case of status asthmaticus, corticosteroids (prednisolone, hydrocortisone) are given intravenously. For prolonged maintaining therapy inhaled corticosteroids (beclomethasone, budesonide, flunisolide, fluticasone, triamcinolone), cromones (cromolyn sodium, nedocromil sodium), long- acting β2-agonists (salmeterol, formoterol), long-acting xanthins (theophylline-retard, theitard, aphonilume CP), leukotriene receptor antagonists (singular, zafirlukast, acolate), leucotriene synthesis inhibitors (zileuton, ziflou), antihistamine remedies (ketotifen) are used. In grave cases corticosteroids of systemic action (prednisolone, methylprednisolone) are used. In medical complex climatotherapy, speleotherapy, physiotherapy, reflexotherapy are used. Prophylaxis of bronchial asthma includes liquidation of potential allergens from environment, struggle against professional hazards, and smoking, careful sanation of foci of chronic infections (in nasopharynx particularly).

A. Test tasks to be done: - with a single selective answer - I-st level: 1. What breathing is heard during bronchial asthma attack? a) bronchial; b) interrupted; c) at the beginning of attack - harsh vesicular with long expiration, and at the hight of attack - significant weakened vesicular; d) at the beginning of attack - harsh vesicular with long expiration, and at the hight of attack - bronchial; e) amphoric respiration. 2.What auscultative phenomenon appears at the beginning of acute bronchitis? a) bronchial breathing; b) amphoric respiration; c) harsh vesicular breathing; d) weakened vesicular breathing; e) metal breath. 3. What adventitious respiratory sounds are auscultated in case of liquefaction of sputum in the patient with acute bronchitis? a) dry buzzing rales; b) dry whistling sounds; c) moist sonorous fine bubbling rales; d) moist non-sonorous bubbling rales; e) crepitation. 4. When bronchial asthma attacks occur most often? a) in the morning; b) in the afternoon; c) at night, in before-morning hours peculiarly; d) after breakfast; e) after supper. 5. What can be revealed during comparative percussion of the lungs in patient during bronchial asthma attack? a) tympanic percussion sound; b) band box percussion sound; c) dull sound; d) clear lung sound; e) dull-tympanic sound. 6. Syndrome of increasing airiness of the pulmonary tissue is typical for: a) focal pneumonia; b) croupous pneumonia; c) acute bronchitis; d) pulmonary emphysema; e) tuberculosis of the lungs. 7. Chronic bronchitis is characterized by: a) excessive secretion of bronchial mucus and is manifested by productive cough for 2 months or more in at least 2 consecutive years in the absence of any other disease that might account for this symptom; b) excessive secretion of bronchial mucus and is manifested by productive cough for 2 months or more in at least 3 consecutive years in the absence of any other disease that might account for this symptom; c) excessive secretion of bronchial mucus and is manifested by productive cough for 3 months or more in at least 2 consecutive years in the absence of any other disease that might account for this symptom; d) excessive secretion of bronchial mucus and is manifested by productive cough for 3 months or more in at least 3 consecutive years in the absence of any other disease that might account for this symptom; e) excessive secretion of bronchial mucus and is manifested by productive cough for 1 months or more in at least 2 consecutive years in the absence of any other disease that might account for this symptom. 8. The main complaint of patients with pulmonary emphysema is: a) cough; b) chest pain; c) suffocation; d) hemoptysis; e) dyspnea. 9. In world bronchial asthma occurs approximately in: a) 1 % people; b) 2 % people; c) 5 % people; d) 10 % people; e) 15 % people. 10. The 2-nd degree of bronchial asthma is: a) long-lasting bronchial asthma of mild course; b) intermitting bronchial asthma; c) long-lasting bronchial asthma of severe course; d) long-lasting bronchial asthma of moderate severity course; e) status asthmaticus.

- with the selective group of right answers - II - nd level: 1. What data of chest examination and palpation of the chest are typical for syndrome of increasing of airiness of the pulmonary tissue? a) flat chest; b) funnel chest; c) phthinoid chest; d) barrel chest; e) intensifying of vocal fremitus; f) weakening of vocal fremitus; g) vocal fremitus isn’t changed. 2. What data of percussion and auscultation are typical for syndrome of increasing of airiness of the pulmonary tissue? a) dull percussion sound; b) band box percussion sound; c) elevation of the lower lung borders; d) lowering of the lower lung borders; e) diminishing of excursion of the lower lung borders; f) bronchial breathing; g) weakened vesicular breathing. 3. What data of percussion and auscultation are typical for bronchial asthma attack? a) dull pescussion sound; b) band box percussion sound; c) lowering of the lower lung borders; d) diminishing of excursion of the lower lung borders; e) elevation of the lower lung borders; f) harsh vesicular breathing, in severe cases - significant weakened vesicular breathing; g) bronchial breathing; h) many dry whistling and buzzing rales. 4. What data of chest examination and its palpation are typical for acute bronchitis? a) barrel chest; b) funnel chest; c) form of the chest isn’t changed; d) weakened vocal fremitus; e) intensified vocal fremitus; f) vocal fremitus isn’t changed; g) increased rigidity of the chest. 5. What processes occur in bronchi during bronchial asthma attack? a) edema of mucous membrane; b) bronchospasm; c) dilation of bronchi; d) increasing of secretion of liquid secret by goblet cells; e) decreasing of secretion of liquid secret by goblet cells; f) decreasing of secretion of viscous secret by goblet cells; g) increasing of secretion of viscous secret by goblet cells. 6. What pathophysiologic processes play role in development of bronchial asthma attack? a) connection of antigens with specific antibodies, which are fixed on labrocytes (mast cells), plasmocytes and lymphocytes; b) discharge of mediators of allergic inflammation (histamine, serotonin, bradykinin); c) bronchospasm; d) dilation of bronchi; e) substitution of pulmonary parenchyma by connective tissue; f) edema of the mucous membrane of bronchi; g) bronchorrhea. 7. How bronchial asthma attack is manifested? a) frequent violent non-productive cough (with impossibility of coughing of viscous sputum); b) constant moist violent cough; c) difficulty of inspiration; d) difficulty of expiration; e) ortopnoe position with using of hands for support; f) lying position; g) crepitation. 8. How bronchial asthma attack is manifested? a) participation of intercostals muscles, jugular’s fossa in respiratory act; b) pale face; c) significant acrocyanosis; d) distance rales; e) moist rales; f) crepitation; g) bronchial breathing. 9. What is auscultative picture of the lungs in patient during bronchial asthma attack? a) bronchial breathing; b) interrupted breathing; c) weakened vesicular or harsh breathing; d) long inspiration; e) long expiration; f) many moist rales; g) many dry whistling rales. 10.During X-examination in case of syndrome of bronchial obstruction are marked the following: a) wide intercostal spaces; b) narrow intercostal spaces; c) little excursion of intercostal spaces; d) high position of diaphragm; e) low position of diaphragm; f) becoming clearer of the lung field. 11.Degree of bronchial obstruction is revealed by means: a) bronchography; b) spirography; c) bronchoscopy; d) pneumotachometry; e) roentgenography of the lungs; f) tomography; g) analysis of loop “flow-volume”, got at apparatus of type “Pneumoscrin”. 12.Continuing during many years, chronic bronchitis can result to: a) pneumonia; b) pulmonary emphysema; c) tuberculosis of the lungs; d) dry pleurisy; e) exudative pleurisy; f) pneumoconiosis; g) bronchiectases. 13.The main causes of development of secondary pulmonary emphysema are: h) chronic obstructive bronchitis; i) focal pneumonia; j) croupous pneumonia; k) pneumosclerosis; l) bronchial asthma; m) exudative pleurisy; n) tuberculosis of the lungs. 14.During examination of function of external breathing in patients with pulmonary emphysema following is marked: o) diminishing of indices of VC, MLV; p) increasing of indices of VC, MLV; q) decreasing of the expiratory reserve volume; r) increasing of the expiratory reserve volume; s) increasing of residual volume; t) decreasing of residual volume. 15. By means of microscopic research of the sputum during bronchial asthma attack or after following are revealed: a) many acidophilic granulocytes; b) many siderophages; c) Kurschman’s spirals; d) Dittrich’s plugs; e) Charcot-Leiden crystals; f) alveolar epithelium cells in large amount; u) columnar ciliated epithelium in large amount. 16. The 2-nd degree - long-lasting bronchial asthma of mild course is manifested by the following: a) symptoms of bronchospasm rarer than one time a week; b) night symptoms of asthma twice a month or more rarely; c) daily symptoms of bronchial asthma; d) disturbance of general state, physical activity and sleep; e) night suffocation attacks occur more often than once a week; f) the patients are forced use inhalations of bronchial spasmolytics every day; g) symptoms of bronchospasm from one time a week to one time a day; h) night suffocation attacks one time a 1-2 week. B. Tasks to be done: Task 1. Patient C., 49 years old, accounted, admitted to the department, complains of suffocation attack, which appears 2 hours ago at home, cough with little amount of viscous sputum. Objectively: general state is grave. Position is forced: patient is sitting in a bed, to resting on it by hands. The chest is emphysematous. Respiratory rate is 30 per minute, expiration is very difficult. Significant diffuse cyanosis, swelling of cervical veins is marked. What is the most probable case of dyspnea? Task 2. Patient H., 56 years old, worker, admitted to the department complains of dyspnea, which appears on exertion (rise on steps, fast walk). Other complaints are absent. Dyspnea troubles patient during 5-6 years. Objectively: general state is satisfactory. Position is active. The chest is emphysematous. Breathing is weakened vesicular from both halves. What is the most probable case of dyspnea?

Task 3. Some results of examination of patient F.: Inspecton: the chest is barrel. Obtuse epigastric angle, horizontal position of the ribs is revealed. Supra- and subscapular fosses are smoothed. Palpation: vocal fremitus is conducted same from both sides, it is some weakened. Percussion: band box percussion sound. The lower lung borders are lowered, upper ones - displaced upwards. Auscultation: Same weakened vesicular breathing is heard above both lungs. Adventitious respiratory sounds are absent. What pathology is in patient?

Task 4. Patient G., 70 years old, pensioner, admitted to the department, complains of significant dyspnea at rest. The patient is sitting in a bed. Considerable diffuse cyanosis is revealed. Breathing is heard on distance. Inspiration and expiration are difficult. Breathing is stertorous. What is the most probable case of dyspnea?

Answers for test tasks of the I-st level: 1 - c 7 - c 2 - c 8 - e 3 - d 9 - c 4 - c 10- a 5 - b 6 - d

Answers for test tasks of the II-nd level: 1 - d , f 6 - a , b , c , f , g 11- b , d , g 2 - b , d , e , g 7 - a , d , e 12- b , g 3 - b , c , d , f , h 8 - a , c , d 13- a , e 4 - c , f 9 - c , e , g 14- a , c , e 5 - a , b , g 10- a , c , e , f 15- a , c , e 16- g , h

Standards of right answer for tasks: 1) - Spasm of small bronchi. 2) - Decreasing of elasticity of the lungs due to pulmonary emphysema. 3) - Pulmonary emphysema. 4) - Mechanical obstruction in area of pharynx, trachea or large bronchi.

Electronic resources:

1. David Hui. Approach to Internal Medicine: A Resource Book for Clinical Practice http://file.zums.ac.ir/ebook/056-Approach%20to%20Internal%20Medicine%20- %20A%20Resource%20Book%20for%20Clinical%20Practice,%203rd%20Edition- David%20Hui-.pdf 2. The subject “Internal medicine propedeutics” as an introduction into the clinics of internal medicine. Main methods of examination of patients. Anamnesis as a part of a case history. Inspection of a patient and its value in diagnostic process. http://intranet.tdmu.edu.ua/data/kafedra/internal/propedeutic_vn_des/lectures_stud/en/med/lik/ ptn/Internal%20Medicine%20Propedeutics/3/01_Introduction.htm 3. Internal Medicine. Propaedeutics as an introduction to the clinic of internal medicine. http://im.medicine.karazin.ua/downloads/presentations/Lecture_Internal_Medicine_Propaed eutics_Basic%20concepts.pdf 4. Propaedeutics as an Introduction to the Clinic of Internal Medicine Propaedeutics M. Yabluchansky L. Bogun, L.Martymianova, O. Bychkova, N. Lysenko, N. Makienko, E. Golubkina V.N. Karazin National University Medical School’ Internal Medicine Dept. http://dspace.univer.kharkov.ua/bitstream/123456789/10966/2/Lecture%20PIM_22.06.2015. pdf 5. ИИ Мистюкевич. Theses of lectures on propedeutics of internal diseases. www.gsmu.by/file/biblio/uchlit/tezisyprop.doc 6. Англо-русский тематический словарь по пропедевтике внутренних болезней и общему уходу за больными : справочное издание / Витебский государственный медицинский университет, Кафедра пропедевтики внутренних болезней; сост. Л.М. Немцов; под ред. Г.И. Юпатова. - Витебск : ВГМУ, 2005. - 153 с. URI: http://elib.vsmu.by/handle/123/11343 7. Special propedeutics of internal diseases : lecture course / Vitebsk State Medical University, Dep. of Propedeutics of Internal Diseases ; comp. by L. M. Nemtsov. - 2-е изд. - Vitebsk : VSMU, 2016. - 318 p. URI: http://elib.vsmu.by/handle/123/9837 8. General propedeutics of internal diseases : lecture course / Vitebsk State Medical University ; compiled by L. M. Nemtsov. - Vitebsk : VSMU, 2006. - 175 p. http://elib.vsmu.by/handle/123/268

Methodical instruction is composed by lecturer Ye.Ye. Petrov.

Approved at the Department of Propaedeutics to Internal Medicine with Care of Patients meeting on 11 09 2018 Protocol No2 The Head of the Department Professor Yu. Kazakov

METHODICAL INSTRUCTION FOR STUDENTS’ SELF-PREPARATION WORK

Educational discipline Propaedeutics to Internal Medicine Module No 2 Enclosure module No7 Topic Pneumonias: the symptoms and syndromes grounds on the clinical, instrumental and laboratory methods of examination. Pneumosclerosis. Pulmonary cancer. Syndrome of compression of pulmonary tissue and respiratory failure in pathology of the broncho-pulmonary system Year 3 Faculty medical

Poltava - 2018 1. The topic basis: syndrome of focal consolidation of the pulmonary tissue and pathology, basis of which it forms (pneumonia, pneumosclerosis, pulmonary cancer particularly) are very widespread. For example, pneumonias are now on the 4th place among the causes of death after cardiovascular diseases, malignant neoplasm, traumas and poisoning. For last 30 years lethality from pneumonia has increased from 1 to 9 % and in the high-gravity complicated forms reaches to 40-50 %. Pulmonary cancer became the leading cause of death of the men from malignant neoplasm more than in 35 economically developed countries. The annual increase of a morbidity makes 3,8 %. For the last 50 years the frequency of lung cancer has become in 14 times higher. That is why knowledge of these questions is necessary for future physicians.

2. The specific aims:  To explain the main signs of syndrome of focal consolidation of the pulmonary tissue.  To explain etiology and pathogenesis of pneumonias (croupous and focal), pneumosclerosis and pulmonary cancer.  To analyze results of examination of patients with pneumonia, pneumosclerosis and pulmonary cancer.  To interpret results of examination of patients with pneumonia, pneumosclerosis and pulmonary cancer.  3. Basic knowledge, experience, skills necessary for studying the topic in connection with other subjects (interdisciplinary integration) :

Previous disciplines Obtained skills 1. Anatomy To know human anatomy, respiratory system organs particularly. 2. Physiology To know physiology of respiratory system. 3. Medical psychology To be able to observe principles of ethics and deontology in medical practice. 4. Pathological morphology To know pathologic-morphological picture of pneumonias, pneumosclerosis and pulmonary cancer. 5. Latin and medical terminology To know terminology (in Latin transcription): croupous pneumonia, focal pneumonia.

4. Tasks for self-work during preparation to the class. 4.1 List of the main terms, parameters, characteristics, which should be mastered during preparation to the class:

Term Definition 1. Pneumonia It is a local polyetiological infectious-inflammatory disease of lungs with involvement into pathological process of their respiratory parts and the necessary availability of intraalveolar inflammatory exudation.

1. Pneumosclerosis It is collective term. Expanding of connective tissue in the lungs as result of different diseases is called by this term.

4.2. Theoretical questions to be answered before class: 1. Tell about etiology and pathogenesis of pneumonias (croupous and focal). 2. Tell about classification of pneumonias. 3. What are potential results of questioning, inspection, palpation, percussion and auscultation of patients with croupous pneumonia (depending on stage)? 4. What are potential results of questioning, inspection, palpation, percussion and auscultation of patients with focal pneumonia? 5. What instrumental methods are used for diagnostics of pneumonia? 6. What are potential results of laboratory methods examination of patients with pneumonia? 7. Tell about course and potential complications of croupous pneumonia. 8. Tell about etiology and pathogenesis of pneumosclerosis. 9. Tell about classification and clinical picture of pneumosclerosis. 10. Tell about etiology and pathogenesis of pulmonary cancer. 11. What are potential results of questioning, inspection, palpation, percussion and auscultation of patients with pulmonary cancer? 1. What instrumental methods are used for diagnostics of pulmonary cancer? 2. What are potential results of laboratory methods examination of patients with pulmonary cancer?

4.3. Practical work (tasks), which should be performed during class: 1. To carry out examination of patients with pneumonia, pneumosclerosis and pulmonary cancer. 2. To interpret obtained results. 3. To interpret results of laboratory and instrumental methods examination of patients with pneumonia, pneumosclerosis and pulmonary cancer.

The contents of topic: Text

SYNDROME OF FOCAL CONSOLIDATION OF THE PULMONARY TISSUE Syndrome of focal consolidation of the pulmonary tissue is caused by filling of alveoli by exudates and fibrin (in pneumonia), blood (in pulmonary infarction), growing of lobe of the lung by connective tissue (pneumosclerosis, carnification) due to prolonged course of inflammation of the lung or by tumorous tissue. Complaint of dyspnea is usual; during examination lagging of affected half of the chest during respiration is marked; vocal fremitus in zone of consolidation is intensified; during percussion deadened or dull percussion sound (it depends on degree of consolidation of pulmonary tissue) is marked above area of lung consolidation; during auscultation – bronchial respiration, intensification of bronchophonia, and in case of presence of liquid secretion in small bronchi- sonorous rales. X-ray examination reveals focus of shadowing (so called decreased clear lung field) in pulmonary tissue, its size and shape are depend on character of disease, its stage and some other factors.

ACUTE PNEUMONIA Pneumonias – is group of inflammatory diseases of the lungs, which are differ one from another by etiology, pathogenesis and morphological characteristics. They are ones of the most widespread diseases of internal organs. Importance of pneumonias is conditioned else by that fact they often is direct case of death of the patients with oncology diseases, patents with severe cardiac insufficiency, impairment of cerebral circulation and middle-aged persons generally. Pneumonia, caused protozoa (Pneumocystis carnii) is one of the main direct causes of death of the patients with AIDS. Classification. Now classification of pneumonias according to etiology, pathogenesis, clinical-morphological characteristics is the most used. Depend on ethological factors, bacterial (pneumococcal, staphylococcal etc.), viruses, mycoplasmal and other pneumonias are differing. Accordance to pathogenesis primary pneumonias, appearing and taking their course as independent disease, and secondary pneumonias, complicating course of other diseases, are differ. Secondary pneumonias include, for example, hypostatic pneumonias due to blood stagnation in pulmonary circulation (during prolonged forced staying of the patients on confinement to bed (bed rest)), aspiration pneumonias, connected with hitting of alimentary particles, vomit and other substances in the respiratory tract (for example, in persons in unconsciousness state), postoperative, traumatic, infarct pneumonias (as result of embolism of little branches of pulmonary artery) and others. At last, according to clinical-morphological characteristics, parenchymatous (croupous and focal) and interstitial pneumonias are differ. Interstitial pneumonia (in this case inflammatory reaction is localized in interstitial tissue mainly) occurs relatively rarely (for example, in mycoplasmal infection). According to modern representations all pneumonias are subdivided into four types:  Community-acquired;  Hospital-acquired (nosocomial) - pneumonia occurring more than 48 hours after admission to the hospital;  Aspiration;  Pneumonia in patients with serious defects of immune system. Such classification allows conducting rational therapy even before obtaining the results of bacteriological research of a sputum and bronchial secret.

Croupous pneumonia Croupous pneumonia (pneumonia cruposa) is characterized by hyperergic type of inflammatory reaction, which is manifested by acuity and cyclicness of the disease, affection of lobe of the lung or segment of the lung, obligatory drawing into involving of pleura in process, severe disturbance of vassal penetrability and high content of fibrin in exudate. These peculiarities of croupous pneumonia found their reflecting in often used synonyms of this form of pneumonia: lobar, segmental, fibrinous, pleuropneumonia and others. Now part of croupous pneumonia in general structure of acute pneumonias is 12-24%. Etiology and pathogenesis. Croupous pneumonia is caused by pneumococcus (I and III types mainly) mainly, more rarely – by Fridlender’s diplobacteria, staphylococcus and other microorganisms. Predisposing to development of diseases factors can be congenital and acquired changes, impeded for timely removal of infectious agents: disturbance of mucociliary clirens, defects of surfactant system of the lungs, insufficient phagocytic activity of neutrophils and alveolar macrophages, changes of general and local immunity, overcooling of organism, irritation of respiratory tract by gas and dust, inebriation etc. In respiratory parts of the lungs microorganisms get by bronchogenic way manly. Pneumococcus, getting in alveoli directly, causes serous edema, which for them is good culture medium for reproduction and fast following getting in neighbouring alveoli. Clinical picture. During croupous pneumonia we can distinguish three stages. Initial stage (the stage of beginning of diseases) is expressed very distinctly usually. Disease begins sharply. Rigor appears suddenly, elevation of the body temperature to 39-40 0 C is marked. Shooting pain in the chest, headache, little dry cough, general weakness are added swiftly. In case of affection of diaphragmatic pleura, pain can irradiated to different abdominal parts, imitating picture of acute appendicitis, acute cholecystitis, perforated ulcer of stomach or acute pancreatitis (“thoraco – abdominal syndrome”). To the end of the first day of diseases or during second day the cough is intensified, the sputum with blood (rusty sputum) appears. General states of the patients become severe. During examination blush on cheeks, more marked on the affected side, is revealed, herpetic rush on the lips and nasal area, participation of wings of nose in respiration, cyanosis of naso-labial triangle are seen. Breathing becomes shallow, its rate increases to 30-40 per minute, tachycardia to 100- 120 per minute is revealed. Lagging of affected half of the chest during breathing, intensification of vocal fremitus and appearance of dull-tympanic percussion sound over affected lobe or segment are revealed. During auscultation weakened vesicular respiration is heard over inflammatory zone (with bronchial shade often), initial crepitation (crepitatio indux) and pleural friction sound are revealed. In stage of high level of disease due to consolidation of pulmonary tissue and disappearance of air in alveoli (hepatization phase) dull sound over affected lobe is revealed during percussion, sharp strengthening of vocal fremitus is revealed during palpation. During auscultation disappearance of crepitation is revealed, bronchial respiration, strengthening bronchophony are heard, pleural friction sound is preserved. At last, in stage of resolution, when gradual resolving of exudate occurs and air begins to get into alveoli again, during percussion over affected lobe dull-tympanic sound appears again. Strengthening of vocal fremitus and bronchophony become less evident. Recurrent (relapsing) crepitation (crepitation redux) is revealed during auscultation. In case of discharge of sufficient quantity of liquid sputum moist sonorous rales are heard. Before wide using of antibiotics feverish period in croupous pneumonia was during 9-11 days and, what’s more, temperature falling could be both critic and lytic. Now in cases of timely prescription of antibiotic therapy duration of feverish period can be reduced significantly, in individual cases to 2-4 days. In connection with it described staging of course of croupous pneumonia can’t be marked clearly. In blood analysis in croupous pneumonia we can see leucocytosis within 15-30 •10 9/L (15 000- 30 000 in 1mcl) with deviation of the differential count to the left (that is to say with increasing of relative contents of stab neutrophils to 6-30% and appearance of juvenile forms), uneosinophilia, elevation of the erythrocyte sedimentation rate (ESR) to 40-50 mm/hour. In urine analysis proteinuria and microhematuria sometimes are revealed. Sputum in croupous pneumonia can be different depending on stage of disease. During stage of red hepatization many erythrocytes, high fibrin are revealed in it. During stage of gray hepatization the sputum becomes mucous-purulent, many leucocytes appears in it. During stage of resolution detritus, which is destroyed leucocytes, and large amount of macrophages are revealed. In the sputum different microorganisms, at first pneumococcus, are revealed often. Roentgenological (X-ray) picture of croupous pneumonia depends on stage of course of disease. During first day only increased lung pattern can be revealed often. Then shadow patches, gradually occupying segment or lobe of the lung wholly appear. It tallies the stage of infiltrative changes. In the future, in 2-3 weeks, as pneumonia resolving, restoration of clear lung tissue occurs. Course and complications. In uncomplicated cases croupous pneumonia ended in full recovery in term till 4 weeks. Lethal outcome, which achieved to 20-25% in 30-th years of the 20–th century, now is decreased as result of use of antibiotics. But it is fairly high in elderly patients (to 17%) and in children of first life year (to 5%) and now. In case of severe course of croupous pneumonia different complications can appear. It is acute cardiovascular insufficiency first of all. Manifestation of acute cardiovascular insufficiency can be toxico-infective shock, connected with influence of microorganism’s toxins on walls of small vessels and following impairment of pulmonary circulation, cerebral circulation, renal circulation and manifested by loss of consciousness, cyanosis, cold limbs, rapid and small pulse, oliguria. In some patients stable arterial hypertension, caused by change of vascular tone in conditions of hyperergy, is observed. In croupous pneumonia pulmonary edema can appear also as result of both direct influence of toxins on pulmonary capillaries and development of acute left heart ventricle insufficiency. If croupous pneumonia appears on background of existing chronic obstructive bronchitis or pulmonary emphysema, acute right ventricular insufficiency, manifested by swelling of cervical veins, fast increasing of stagnation in systemic circulation is developed sometimes. Acute tachycardia and other arrhythmias can be manifestation of myocarditis. Acute lung failure as result of exception of large part of pulmonary tissue from respiration can appears in croupous pneumonia also. In 10-15% patients course of croupous pneumonia can be complicated by development of exudative pleurisy, which arises during peak of disease (parapneumonic) or after its resolution (metapneumonic). In 2,5-4% patients with croupous pneumonia formation of abscess occurs. In some patients, with chronic alcoholism specifically, acute psychoses can occur during high level of diseases. They manifested by delirium, hallucinations, disturbance of sleep. Such complications as pericarditis, mediastinitis, septic endocarditis, purulent meningitis and meningoencephalitis, toxic affections of liver, joints, kidneys, syndrome of disseminated intravascular coagulation (DIC) and others occur rarerly. In those cases, when total resolution of pneumonia doesn’t occur, exudate grow by connective tissue and postpneumonic pneumosclerosis is formed. Treatment. Bed rest is prescribed to the patients, during fever period in case of absence of heart failure signs - plentiful drinking, if it is necessary - oxygen inhalation. Right after making of disease’s diagnosis antibacterial therapy begins. In case of mild or moderate severity course of pneumonia preference is given to preparations of penicillin group (benzylpenicillin sodium or potassium salt intramuscularly in 3-4 hours to 3 000 000-6 000 000 Units a day, in their intolerance - macrolids are used (oleandomycin phosphate, erythromycin). In pneumonias with severe course aminoglycosides (gentamycin sulfate, amycacin sulfate), semisynthetic penicillines (oxacillinum sodium salt), cephalosporins (cephaloridin, or ceporin, to 6 g a day, cephazolin, of kefzol, to 3-4 g a day, cephotaxim, or claphoran, to 6 g a day), semisynthetic penicillins with anti-β-lactamase activity, derivates of quinoleincarbonic acid (ophloxacin, or tarivid) are used. During using of antibiotics physisian must be oriented to results of sputum inoculation for microorganisms to antibacterial preparations susceptibility. Disintoxication therapy (drop introduction of hemodez, 5% solution of glucose) is carried out, preparations, improving state of cardiovascular system (camphor, cordiamin, cardiac glycosides) are prescribed. In case of diminishing of intoxication signs with purpose of improvement of resorption respiratory gymnastics and physiotherapeutic treatment are used. Prophylaxis of pneumonias comes to carrying out of general sanitary-hygienic actions (struggle against dustiness), tempering, excluding of overcooling, stop of smoking, sanation of foci of chronic infection.

FOCAL PNEUMONIA In case of focal pneumonia (pneumonia focalis, sin. catarrhalis) crossing of inflammatory process from bronchial mucous membrane to pulmonary tissue is marked more often and focus of inflammation, which is formed, is limited by one or some lobules usually. These particularities of focal pneumonia are reflected in such its synonyms as lobular, catarrhal pneumonia, bronchopneumonia. Etiology and pathogenesis. In development of focal pneumonia great role belongs to pneumococcus (II type mainly), Gram-negative Pfeiffer’s bacillus, intestinal bacillus, proteus. Microorganisms penetrate into alveoli by bronchogenic tract. Besides great importance belongs to obstruction of bronchioles by mucus, which promotes to development of atelectases. Hematogenic and lymphogenic way of infection is possible in patient with secondary pneumonias, which occur, for example, in sepsis, after operations. Predisposing factors of focal pneumonia are overcooling, overstrain, virus infection, chronic diseases of respiratory organs (chronic bronchitis, bronchiectatic disease). Clinical picture. In some cases focal pneumonia can begin suddenly, but it develops on the background of acute respiratory (including virus) infections or tracheobronchitis more often. The main symptom of acute focal pneumonia is cough with muco-purulent sputum. In many patients subfebrile or moderate high fever is marked. But it can disappear in first 1-2 days of disease even, if antibacterial therapy was begun early. Pains in the chest, which is intensified during cough and deep inspiration, are observed in case of focal localization near pleura only. Dyspnea in focal pneumonia is marked relatively rarely, in elderly patients mainly. In case of deep localization of inflammatory focus and its little sizes, data of objective examination of the patients can not differ from same in acute bronchitis. In case of large pneumonic focus, situated superficially particularly, we can reveal strengthening of vocal fremitus during palpation, dull sound - during percussion, bronchovesicular breathing, strengthening of bronchophonia and moist sonorous rales, localized on certain area - during auscultation. Approximately in half of patients with focal pneumonia moderate neutrophilia to 10-15• 109 /L (10 000-15 000 in 1 mcL), elevation of ESR are revealed during blood examination. In other patients amount of leucocytes in blood can be normal, and in some patients (for example in virus pneumonia) leucopenia is revealed sometimes even. Sputum of the patients contains many leucocytes, macrophages, columnar epithelium and different bacterial flora also. During roentgenological (X-ray) study we can reveal foci of inflammatory infiltration of pulmonary tissue (in those cases when diameter of these foci isn’t less than 1-1,5cm), change of lung pattern in affected segment. In cases of little sizes of inflammatory foci typical roentgenological signs of focal pneumonia can be absent. Course and complications. Complications, typical for croupous pneumonia, in patients with focal pneumonia occur rarer. At the same time long course of disease is formed in focal pneumonia more often. Resistance of microorganisms cultures to using antibiotics, unpunctual beginning of treatment, weakening of host defenses (for example, in chronic alcoholism) etc. can promote to this process. Treatment. Patients with focal pneumonia are treated according to the same plan, that patients with croupous pneumonia.

PNEUMOSCLEROSIS Pneumosclerosis is collective term. Expanding of connective tissue in the lungs as result of different diseases is called by this term. Etiology and pathogenesis. Pneumosclerosis can be outcome of inflammatory and destructive lung diseases (pneumonia, abscess), diseases of specific nature (tuberculosis), professional diseases with affection of the lungs (pneumoconiosis), fibrosing alveolitis (Hamman-Rich syndrome), traumatic damages of lung tissue, radial affection, etc. During his/her practice therapeutist often found pneumosclerosis, which is developed in patients with heart failure due to prolonged stagnation of the blood in pulmonary circulation. Classification. Apart from pathomorphological estimation (diffuse or focal pneumosclerosis), physicians use classification of pneumosclerosis according to etiology (for example, infectious, posttraumatic, cardiovascular etc.) and pathogenetic mechanisms (postpneumonic, atelectatic and others). Clinical picture. Pneumosclerosis doesn’t have typical clinical signs. Symptoms of those diseases, which caused pneumosclerosis (pneumonia, bronchiectatic disease and others), can be on foreground in clinical picture. At the same time in pneumosclerosis, its diffuse forms particularly, ventilation function of the lungs is disturbed often (according to obstructive and restrictive type). Clinically it manifested by dyspnea (at first on exertion, but then at rest also) and cyanosis. During examination of function of external breathing in these patients decrease of indices of vital capacity of the lungs and maximal lung ventilation is registered. During roentgenological (X-ray) examination increased lung pattern and deformation of lung pattern, decreasing of clear lung fields are seen. During more late stages large patches of shadow, appropriate to fields of severe fibrosis, appear. Course. Pneumosclerosis is characterized by gradually progressive course, development of hypoxemia, pulmonary hypertension, marked lung failure and heart (right-ventricular) insufficiency. Treatment. Specific methods of pneumosclerosis treatment are absent. Treatment of diseases, causing its development, is carried out. Symptomatic therapeutic methods (oxygenotherapy, cardiac glycosides, diuretics) are used in case of adding of respiratory or heart failure signs. Prophylaxis of pneumosclerosis is in prevention and careful treatment of acute and chronic diseases of respiratory organs.

PULMONARY CANCER Pulmonary cancer, gaining first place among all malignant growth, is tumor, consisting of immature epithelial cells. Pulmonary cancer can arise from integumentary epithelium of bronchi or from epithelium of mucous glands of bronchial walls – such tumor is named bronchiogenic cancer. Tumor can arise from epithelium of alveoli and bronchioles also; in this case physicians say about “properly pulmonary (bronchiolar-alveolar) cancer”. Besides that, so called “secondary”, or metastatic cancer is made out. Besides, cancerous cells of primary tumor, which is localized in other organ, is brought in the lungs by current of the blood or lymph and they begin to multiply in the lungs. Etiology and pathogenesis. Etiology of cancer isn’t studied completely yet. But clinical and sanitary- hygienic observations denote to indirect connection of cancer etiology with the following exogenic factors: 1) with smoking, as pulmonary cancer in smokers occurs in several times often than in nonsmokers; 2) with pollution of atmospheric air (arsenic, radium, 3,4- benzpyrenum); 3) with influence of other professional harms, which occur in mines, fruitful in cobalt and arsenic, in gassy industry, at industrial works according to production of asbestos and others. Activity of exogenic carcinogenic substances is manifested in certain conditions only. Among these conditions important role belongs to hereditary predisposition and weakening of immunity, chronic inflammatory processes in bronchi and lungs – chronic bronchitis, bronchiectatic diseases, pneumosclerosis with slowly proceeding chronic interstitial pneumonia. In foci of chronic inflammation, to all appearances, under the influence, perhaps, carcinogenic or unknown yet factors disturbance of normal regeneration occurs, cellular methaplasia with following growth of malignant cells appears. Clinical picture. Clinical picture of pulmonary cancer depends on stage of tumor development, its localization, on appearance of intrapulmonary complications (pneumonia, abscess, hemorrhage and others), spreading and location of metastases. In case of localization of tumor in large bronchi (I, II, and III order) clinical symptoms appear early; in its localization in little peripheral bronchi the course of disease can be without any symptoms during prolonged period. The most typical signs of pulmonary cancer are cough, hemoptysis and chest pain. Cough is the most early and constant symptom. At the beginning it is dry, whistling, often as coughing fit appears at night. Then cough becomes troublesome, with suffocation attack. In case of disturbance of bronchial drainage function as result of constriction of bronchial lumen by tumor and addition of inflammation of bronchial wall, cough can be accompanied by sputum expectoration. At first sputum is crudum, hyaline, then – mucopurulent and purulent, odorless more often. In case of resolution of the tumor in the bronchial lumen and ulceration of the tumor, hemoptysis is added; in destruction of large blood vessel pulmonary hemorrhage is possible. Peculiar diagnostic importance belongs to hemoptysis, first appeared in patient without pulmonary disease at past. Dyspnea is early sign of pulmonary cancer also. At first it is seen during movement and talking. Then as growth of the tumor and connection of atelectasis, dyspnea appears in small movement or becomes constant. During beginning of resolution of the tumor and improvement of lung ventilation it can decrease temporarily, but then as growth of the tumor and repeated obstruction of the lumen - increase again. Chest pain is important, but later symptom of pulmonary cancer. According to character it can be dull, boring or piercing, rarer – pressing and tightening. The pain is intensified in cases of deep breathing, cough or movement of shoulder girdle and incline of body to the right or to the left. Localization of the pain depends on location of pathological process. In case of expansion of peripherally situated tumor or metastases into pleura, pain (as in dry pleurisy) is localized in affected half of the chest on wide space. In case of appearance of metastases in ribs the pain can be limited, strictly localized according to location of metastasis. Palpation of limited part of the rib is painful. Location of the tumor in apex of the lung can be accompanied by constant severe pains in shoulder girdle, appropriate half of the chest and hand (as result of pressure on shoulder plexus). The pain in case of pulmonary cancer, as rule, is constant and isn’t always relieved by analgesics or narcotics even. But in definite position it can now diminish, now intensify. As for general symptoms, causeless weakness, fatigue, perverted taste, suppressing or absence of appetite, and in later period of the course of disease – emaciation can be observed. Important symptom of pulmonary cancer is fever. At the beginning of disease it is marked in 35% patients, it can be subfebrile and changeable. Its cause is local secondary inflammation of the bronchial wall more often. In case of perifocal and hypoventilation pneumonia fever can be high and remittent, but in case of resolution of the tumor and formation of abscess of the lung – hectic. During general examination at the beginning of disease objective signs can absent. During later stage of the course skin becomes pale touched with yellow; visible mucous membranes become cyanotic; in case of pressing of superior cava vena by tumor edema of the neck can be seen; development of subcutaneous fat is reduced often (emaciation). Firm cervical, supraclavicular or axillary lymph nodes, from side of affected lung more often, can be revealed by palpation. Small cervical lymph node, having the size millet grain or pea, above left or right supraclavicular area can be palpated during rather early stages often. In case of localization of tumor in superior primary bronchus or in apex of the lung - more marked retraction of supraclavicular fossa and in expressed atelectasis – decrease of size affected half of the chest and lagging of movements of scapula of this half in comparison with “healthy” half in respiration are observed. In case of localization of tumor in core zone, above place of localization of tumor can be heard dull-tympanic sound during percussion; but in case of obstruction of lumen of the bronchus and formation of atelectasis – dull sound. But vocal fremitus above dull sound area will be sharply weaken, as strength and amplitude of oscillation of sound waves, which are spreading along bronchi and got into other environment (tumor), are changed. During auscultation change of breathing character depends on place of localization of the tumor, its size and degree of disturbance of bronchial patency. In case of localization of the tumor in primary bronchus and its significant constriction breathing can be stenotic, in total obstruction of lumen of the bronchus and formation of atelectasis – sharply weaken. In case of development of bronchitis, pneumonia or abscess, auscultation picture becomes typical for these diseases. In diagnostics of pulmonary cancer the main role belongs to roentgenological study and bronchoscopy with biopsy. During roentgenological examination, picture can be different depending on localization of the tumor. In case of location of the tumor in primary bronchus (central pulmonary cancer) enlarged root of the lung and nonhomogeneous shadowing along its periphery, and in case of atelectasis - shadowing of lung tissue, higher position of the diaphragm in comparison with “healthy” lung are occur. During the deep inspiration displacement of mediastinum to the side of affected lung (Goltskneht-Jakobsohn’s symptom) occurs. During tomographic examination in case of such tumour’s localization we can reveal partial local bronchial obstruction. In case of peripheral pulmonary cancer, tumour on X-ray film is revealed as homogeneous shadow with uneven and poorly defined outlines along periphery. In case of resolution of this tumour, in its centre oval clarification with fluid level often can appear. Affections of the heart can be manifested by myocardial dystrophy and weakening of the I sound at the apex. In case of compression of superior cava vein by tumour swelling of veins of upper body half and neck can occur. During blood examination elevation of the erythrocyte sedimentation rate is revealed early, periodical leucocytosis is possible. Treatment depends mainly on early diagnostic of pulmonary cancer, cellular type (small cell, large cell) and its localization. In case of timely revealing of tumor and its localization in bronchi II and III degree or on periphery surgical treatment (lobectomy, pulmonectomy) is indicated. It can be radical in case of absence of metastasis. Radiation therapy and chemotherapy (thiophosphamid, dopan, colloid gold and others) can give temporary therapeutic effect. Last ones often are combined with surgical treatment by developed indication. Prescription of antibiotics is indicated in case of complication of pulmonary cancer by inflammatory process. Prophylaxis of pulmonary cancer includes struggle against smoking, atmosphere of cities recovery, prevention of professional hazards, and regular medical check-up of patients with chronic pulmonary diseases.

A. Test tasks to be done: - with a single selective answer - I-st level:

1. Croupous pneumonia is caused mainly by: a) staphylococcus; b) Fridlender’s diplobacteria; c) virus; d) intestinal bacillus; e) pneumococcus. 2. How many stages can we distinguish during croupous pneumonia? a) 2; b) 3; c) 4; d) 5; e) 6. 3. When can we hear crepitatio redux (in case of croupous pneumonia)? a) during initial stage; b) during stage of high level of disease; c) during stage of resolution; d) during stage of exacerbation; e) during active stage. 4. What is heard in case of discharge of sufficient quantity of liquid sputum (during stage of resolution of croupous pneumonia)? a) dry rales; b) moist non-sonorous rales; c) moist sonorous rales; d) pleural friction sound; e) bronchial breathing. 5. In which disease is crossing of inflammatory process from bronchial mucous membrane to pulmonary tissue marked more often and focus of inflammation, which is formed, is limited by one or some lobules usually? a) pneumosclerosis; b) focal pneumonia; c) pulmonary cancer; d) croupous pneumonia; e) bronchiectatic disease. 6. Expanding of connective tissue in the lungs as result of different diseases means: a) focal pneumonia; b) croupous pneumonia; c) tuberculosis of the lungs; d) pneumosclerosis; e) pulmonary emphysema. 7. Pneumosclerosis: a) have typical clinical signs; b) doesn’t have typical clinical signs; c) have typical clinical signs in some its types only. 8. The most early and constant symptom of pulmonary cancer is: a) dyspnea; b) suffocation; c) pain in the chest; d) headache; e) cough. 9. In blood investigation of patient with pulmonary cancer is revealed early: a) elevation of the erythrocyte sedimentation rate ; b) decreasing of the erythrocyte sedimentation rate; c) raised number of erythrocytes; d) low number of leucocytes; e) deviation of the differential count to the right.

- with the selective group of right answers - II - nd level: 1. Syndrome of focal consolidation of the pulmonary tissue is caused by: a) filling of alveoli by exudates and fibrin; b) filling of alveoli by blood; c) accumulation of fluid in pleural cavity; d) presence of cavern in the lung; e) growing of lobe of the lung by connective tissue or by tumorous tissue; f) trauma of the chest. 2. Signs of syndrome of focal consolidation of the pulmonary tissue are: a) suffocation attack; b) lagging of affected half of the chest during respiration; c) weakening of vocal fremitus in zone of consolidation; d) strengthening of vocal fremitus in zone of consolidation; e) deadened or dull percussion sound above area of lung consolidation; f) tympanic percussion sound above area of lung consolidation. 3. Croupous pneumonia is sometimes called also: a) lobar; b) lobular; c) catarrhal; d) pleuropneumonia; e) bronchopneumonia; f) segmental. 4. Signs of beginning of croupous pneumonia (first day): a) rigor; b) elevation of the body temperature to 37-37,50 C; c) shooting pain in the chest; d) headache; e) cough of pus; f) little dry cough; g) general weakness. 5. Signs of initial stage of croupous pneumonia: a) lagging of affected half of the chest during breathing; b) weakening of vocal fremitus; c) dull percussion sound over affected lobe or segment; d) dull-tympanic percussion sound over affected lobe or segment; e) weakening vesicular respiration over inflammatory zone (with bronchial shade often); f) harsh respiration; g) crepitation. 6. Signs of croupous pneumonia in stage of high level of disease: a) dull - tympanic percussion sound over affected lobe; b) dull percussion sound over affected lobe; c) bronchial respiration; d) weakening of vesicular respiration; e) strengthening bronchophony; f) weakening bronchophony; g) harsh respiration. 7. In blood analysis in patient with croupous pneumonia we can see: a) leucocytosis; b) leucopenia; c) deviation of the differential count to the right; d) deviation of the differential count to the left; e) uneosinophilia; f) elevation of the erythrocyte sedimentation rate; g) low number of erythrocytes. 8. In stage of red hepatization of croupous pneumonia sputum of the patient contains: a) large amount of macrophages; b) many erythrocytes; c) high fibrin; d) many leucocytes; e) detritus; f) Charcot-Leiden crystals; g) Kurschman’s spirals. 9. Focal pneumonia is sometimes called as: a) lobular; b) lobar; c) catarrhal; d) pleuropneumonia; e) bronchopneumonia; f) segmental. 10. In case of large pneumonic focus, situated superficially particularly, we can reveal: a) strengthening of vocal fremitus; b) weakening of vocal fremitus; c) dull-tympanic percussion sound; d) dull percussion sound; e) strengthening of bronchophonia; f) harsh breathing; g) bronchovesicular breathing. 11. Pneumosclerosis can be outcome of: a) pneumonia; b) pulmonary abscess; c) tracheitis; d) dry pleurisy; e) tuberculosis; f) pneumoconiosis; g) bronchial foreign body. 12. According to pathomorphological estimation, pneumosclerosis is classified as: a) infectious; b) posttraumatic; c) diffuse; d) postpneumonic; e) atelectatic; f) focal; g) cardiovascular. 13. Pneumosclerosis is characterized by: a) gradually progressive course; b) development of hyperoxia; c) development of hypoxemia; d) development of arterial hypertension; e) development of marked lung failure; f) development of cardiac (right-ventricular) insufficiency; g) development of cardiac (left -ventricular) insufficiency. 14. Clinical and sanitary - hygienic observations denote to indirect connection of cancer etiology with the following exogenic factors: a) with smoking; b) with pollution of atmospheric air; c) with drinking hard; d) with hypodynamia; e) with influence of professional harms, which occur in mines, fruitful in cobalt and arsenic, in gassy industry; f) with hypovitaminosis; g) with overcooling. 15. In diagnostics of pulmonary cancer the main role belongs to: a) roentgenological study; b) spirography; c) pneumotachometry; d) bronchoscopy with biopsy; e) thoracoscopy; f) spirometry.

B. Tasks to be done: Task 1. Patient B., 45 years old, complains of cough with rusty sputum, rigor, shooting pain in the chest, headache, general weakness. Elevation of the body temperature to 39-40 0 C is marked. Objectively: blush on cheeks, more marked on the right, herpetic rush on the lips and nasal area, participation of wings of nose in respiration, cyanosis of naso-labial triangle are seen. Breathing shallow, its rate increases to 30-40 per minute, tachycardia to 100-120 per is revealed. Weakened vesicular respiration is heard on the right; crepitation and pleural friction sound are revealed. What disease does this patient have? What additional methods of diagnostics must be used?

Task 2. Patient L., 62 years old, complains of cough with muco-purulent sputum, subfebrile fever, dyspnea on moderate physical exertion. Acute respiratory infection was marked some days before. Objectively: little lagging of the right half of the chest in respiration. Vocal fremitus is intensified on the right. Percussion sound became duller on the right. Mixed respiration, fine bubbling and medium bubbling sonorous rales and strengthening bronchophony are heard on the right. What is previous diagnosis? What additional methods of diagnostics must be used and their potential results?

Task 3. Patient A., 34 years old, official of district administration, complains of chilling, cough during whole day with expectoration about 30-50ml of mucous sputum. The cough is intensified in the evening before sleep. He marks little dyspnea also. Anamnesis morbi. He is ill during 5 days. Disease began after overcooling from little chilling and weakness. Soon dry cough appears. Body temperature increased to 37,3º C. Patient used tablets “coldrex” (advertised by TV set as drug against flu) and continues to go to work. But in 3 days patient’s state aggravated, cough increased, sputum was appeared, he became to fill dyspnea. Body temperature increased to 38,7º C. District doctor, examined patient, after physical examination directs he to the clinic for stationary treatment. Anamnesis vitae. He grew healthy. He went in for sport. He had flu rarely. He doesn’t smoke, doesn’t use alcohol. He is married, has 2 children. They are healthy. Inspection. Constitution is normosthenic. Skin covers are moist, hot, body temperature is 39,1 º C. Face is hyperemic. Lips are cyanotic slightly. Respiratory organs. Respiratory rate is 30 per minute. The chest is conic. The left side lags during breathing. During palpation intensifying of vocal fremitus is marked to the left on the level of 5-6 intercostal spaces. Percussion sound over this area is weakened. Over other areas of the chest percussion sound is clear. During auscultation dry rales are heard over all areas of the lungs, and in lower lateral parts to the left - sonorous fine-bubbling rales. In the same area crepitation is heard. After hacking and discharge of sputum amount of dry rales becomes less, their timbre is changed, and moist rales aren’t heard temporarily, but crepitation is kept. Circulatory organs. Heart rate and pulse is 105 per minute. Heart sounds are clear, rhythmic. Blood pressure is 105/60 mm Hg. Organs of abdominal cavity. Abnormalities aren’t revealed. Results of laboratory-instrumental researches. Clinical blood analysis: erythrocytes - 4,5•1012/l, Hb-143 g/l, Leucocytes - 12,5•109/l, leucocyte formula: eosinophils -2%, basophils-1%, juvenile-4%, stab-10%, segmented-48%, lymphocytes-24%, monocytes-11%, ESR-34 mm/h. Clinical urinalysis: specific gravity - 1,022, protein-0,08 g/l, leucocytes-4 in v.f., erythrocytes-0-1 in v.f. Biochemical blood examination: C-reactive protein - reaction is very positive (++++), fibrinogen - 5,2 g/l, thymol test-7 units. Sputum examination: muco-purulent, viscous, contains many neutrophilic leucocytes, macrophages, cylinder epithelium, simple alveolar macrophages. X-ray study: moderate dilation of shadows of the lung root, to the left mainly, indistinct like-cloud shadowing 4x6 cm in the area of lower lobe of the left lung. Spirography: RV- 120%, VC - 65%, FEVC-75%, FEV1-83%, FEV1/VC-80%, momentary expiratory flow (MEF)25 -75%, MEF50 -70%, MEF75 -82%, midexpiratory flow 25-75 - 85%. Questions to the task 3: 1. What organ’s do diseases patient’s complaints direct to? 2. What is the cause of chilling? 3. What does presence of dyspnea in patients with foregoing complaints testify about? 4. Is patient’s disease acute or chronic? 5. What does lagging of the left half of the chest during breathing testify about? 6. What is diagnostic importance of intensifying of vocal fremitus to the left and laterally? 7. What is diagnostic importance of weakening of percussion sound on the area of 5-6 interspaces between posterior axillary and midaxillary lines? 8. What is the cause of appearance of the dry rales? 9. What is diagnostic importance of fine-bubbling rales during patient’s auscultation? 10. What is cause of sonorous timber of the moist rales? 11. What is diagnostic importance of crepitation over limited lung’s area during auscultation? 12. What does the frequent breathing in patient with respiratory disease testify about? 13. Patient has tachycardia. What is its cause? What is its diagnostic importance? 14. What clinical signs of respiratory failure are in the patient? 15. What abnormalities are in results of clinical blood analysis? 16. What is diagnostic importance of seen abnormalities in results of general blood analysis? 17. Proteinuria was revealed in the patient. What is diagnostic importance of this symptom? 18. What abnormalities are in biochemical indexes of the blood? 19. What is potential cause of seen abnormalities in biochemical indexes in this patient? 20. X-ray study of the lung reveals dilation of roots, to the left mainly. What can be cause of these changes? 21. What are abnormalities in indexes of spirogram? 22. What conclusion can be made according to data of spirography? 23. List all signs of respiratory failure, revealed by you. 24. What is your diagnosis? 25. On the basis of which results you diagnose degree of respiratory failure?

Answers for test tasks of the I-st level: 1 - e 6 - d 2 - b 7 - b 3 - c 8 - e 4 - c 9 - a 5 - b

Answers for test tasks of the II-nd level: 1 - a , b , e 6 - b , c , e 11- a , b , e , f 2 - b , d , e 7 - a , d , e , f 12- c , f 3 - a , d , f 8 - b , c 13- a , c , e , f 4 - a , c , d , f , g 9 - a , c , e 14- a , b , e 5 - a , d , e , g 10- a , d , e , g 1 5 - a , d

Standards of right answer for tasks: 1) - Croupous (lobar) pneumonia, initial stage. General blood analysis, examination of sputum, roentgenography of the lungs. 2) - Focal pneumonia. General blood analysis (moderate neutrophilia to 10-15 • 10 9/L, but it isn’t always. Amount of leucocytes in blood can be normal, and in some patient leucopenia is revealed sometimes even; elevation ESR), examination of sputum (it contains many leucocytes, macrophages, columnar epithelium and different bacterial flora also), roentgenography of the lungs (on the right-focus of inflammatory infiltration of pulmonary tissue, change of lung pattern in affected segment). 3) 1. To the lung disease. 2. Reaction of nervous system to elevation of body temperature. 3. About presence of respiratory failure. 4. It is acute. Disease began only 5 days ago. 5. About localization of pathological process in the left half of the chest. It can be in large- focal pneumonia, tuberculosis, pleurisy. 6. Presence in the lung of foci of consolidation of pulmonary tissue (pneumonia, tuberculous infiltrate, pulmonary infarction) is the cause of intensifying of vocal fremitus. Taking into account acute beginning of disease, it is possible to think about presence of pneumonic foci in the left lung in lower lateral area under area, where intensifying of vocal fremitus is revealed. 7. Weakening or dullness of percussion sound directs to localization of airless area (pneumonias, pulmonary infarction, obturator athelectasis under this part, fluid in pleural cavity). Pneumonic area in lateral part of lower lobe of the left lung is, probably, in this patient with acute inflamamtory process. 8. Dry rales are formed in bronchi in case of presence of viscous secret in their lumen or constriction of their lumen due to spasm or edema. In this patient it is necessary to think about presence of viscous secret, as discharge of muco-purulent sputum with cough is marked. After cough, which results to shift of sputum, timber of these rales is changed. Auscultation of these rales over all parts of the lungs testifies about presence of inflammatory process in all bronchi that is typical for acute bronchitis. 9. Moist rales are formed as result of passage of the air through liquid secret, filling bronchial lumen completely. Fine-bubbling rales are formed in fine bronchi. Localization of their auscultation directs to localization of bronchial part, filling with fluid secret. 10. Moist rales, which forms in bronchi with peribronchial consolidation, is sonorous, consonating. It can be pneumonic or tuberculous infiltration around bronchi. In case of localization of such rales in lower parts it is necessary to think about presence of bronchopneumonia. In case of localization over upper parts of the lungs - about tuberculous infiltrarion. 11. Crepitation occurs in presence of little amount of exudate in alveoli. Exudate promotes to sticking of alveolar walls during expiration. During inspiration their outsticking with fluctuation of alveolar walls occurs; it leads to appearance of sound wave. These sounds have specific timbre and they are named crepitation. Location of area of crepitation’ s auscultation directs to localness of pathological process (pneumonia, tuberculosis, pulmonary infarction). Appearance of local crepitation in patient with acute course of pulmonary process is connected with presence of pneumonia more often. 12. About respiratory failure. 13. In elevation of body temperature occurs becoming more frequent of cardiac contractions’ amount. Elevation of body temperature on 1º C is accompanied by becoming more frequent of cardiac contractions on 10 beats per minute. There is other reason also - respiratory failure, which is accompanied by tachypnoe and tachycardia simultaneously. 14. Tachypnoe, tachycardia, cyanosis of lips. 15. Leucocytosis, shift of leucocyte formula to the left, acceleration of ESR. 16. They are typical for acute inflammatory process. 17. Proteinuria is sign of renal diseases. But in a number of cases proteinuria appears also in other situations in patients without renal disease.In this patient fever, high body temperature can be cause of proteinuria. 18. Positive CRP, increase of fibrinogen level and positive thymol test. 19. Abnormalities in biochemical indexes in this patient directs to presence of inflamamtory process in organism. That is why these changes are in accordance with diagnosis of acute pneumonia, supposed by other symptoms. 20. Enlargement of lymph nodes, nearest to focus of inflamamtion, and inflammatory process in bronchi. 21. Increase of RV, decrease of VC, FEVC and FEV1, MEF50, MEF75. 22. Restrictive respiratory failure is in patient mainly (decrease of VC mainly).Besides, little decrease of bronchial patency along large and medium bronchi is observed (decrease of FEVC, MVR and mean expiratory flow, MEF50 and MEF25 particularly). 23. Complaint of dyspnea, tachypnoe, tachycardia, cyanosis of lips, increase of RV, decrease of VC. 24. Acute bronchopneumonia. Acute bronchitis. Respiratory failure, restrictive mainly, 3 degree. 25. Degree (severity) of respiratory failure is diagnosed by index of partial tension of carbonic acid and oxygen in blood more exactly.These reseres weren’t carried out. But clinical manifestations also allow to make degree of severity ofacute respiratory failure. Dyspnea and cyanosis of lips, tachypnoe, tachycardia, observed at rest, are signs of 3rd dergee severity of respiratory failure.

Electronic resources:

Methodical instruction is composed by lecturer Ye.Ye. Petrov.

The Ministry of Health of Ukraine Ukrainian Medical Stomatological Academy

Approved at the Department of Propaedeutics to Internal Medicine with Care of Patients meeting on 11 09 2018 Protocol No2 The Head of the Department Professor Yu. Kazakov

METHODICAL INSTRUCTION FOR STUDENTS’ SELF-PREPARATION WORK

Educational discipline Propaedeutics to Internal Medicine Module No 2 Enclosure module No 7 Topic Pleuritis dry and exudative: symptoms and syndromes based on clinical and instrumental and laboratory methods of investigation. Syndromes of fluid and air accumulation in the pleural cavity with pathology of the broncho-pulmonary system Year 3 Faculty medical

Poltava - 2018

1. The topic basis: syndrome of air accumulation in pleural cavity and syndrome of fluid accumulation in pleural cavity and pathology, basis of which they form (pneumothorax and pleurisy particularly) are extremely widespread. So, pleurisy, which is secondary pathology, complicates nearly 80 diseases. Between 1996 and 2001 pleurisy share in pulmonologic departments make 10 % and grew in 1,7 times. In the USA yearly pleural exudates of different etiology is revealed in 1000 000 of patients. As for syndrome of respiratory failure, it appears during development of many acute and chronic pulmonary diseases. That is why knowledge of these questions is necessary for future physicians. 2. The specific aims:  To explain the main signs of syndrome of fluid accumulation in pleural cavity and syndrome of air accumulation in pleural cavity.  To explain etiology and pathogenesis of pleurisies.  To explain classification of pleurisies.  To explain reasons and pathogenesis of respiratory failure.  To explain peculiarities of different types of respiratory failure.  To analyze results of examination of patients with pleurisy (dry or exudative) and respiratory failure.  To interpret results of examination of patients with pleurisy (dry or exudative) and respiratory failure. .

3. Basic knowledge, experience, skills necessary for studying the topic in connection with other subjects (interdisciplinary integration) : Previous disciplines Obtained skills 1. Anatomy To know human anatomy, respiratory system organs particularly. 2. Physiology To know physiology of respiratory system. 3. Medical psychology To be able to observe principles of ethics and deontology in medical practice. 4. Pathological morphology To know pathologic-morphological picture of pleurisies (dry and exudative). 5. Latin and medical terminology To know terminology (in Latin transcription): dry pleurisy, exudative pleurisy.

4. Tasks for self-work during preparation to the class. 4.1 List of the main terms, parameters, characteristics, which should be mastered during preparation to the class: Term Definition 1. Pleurisy It is inflammation of pleural layers, accompanied by accumulation of effusion in pleural cavity (exudative pleurisy) or sedimentation of fibrin on inflamed surface of pleura (dry or fibrinous pleurisy).

2.Respiratory failure It is organism’s state when supporting of normal gaseous blood composition isn’t provided or it takes place due to more intensive work of external breathing apparatus and heart, that results to decrease of functional possibilities of organism. 3. Cor pulmonale It denotes right ventricular hypertrophy and eventual failure resulting from pulmonary disease and attendant hypoxia.

4.2. Theoretical questions to be answered before class: 1. Tell about etiology and pathogenesis of pleurisies (dry and exudative). 2. Tell about classification of pleurisies. 3. Tell about clinical picture of dry pleurisy. 4. What are potential results of questioning, inspection, palpation and auscultation of patients with exudative pleurisy? 5. What laboratory and instrumental methods are used for diagnostics of exudative pleurisy? 6. Where are Garland’s triangle and Grokko-Rauhfous’ triangle placed? 7. What are potential results of physical metods examination over Garland’s triangle and Grokko-Rauhfous’ triangle? 8. Tell about reasons and mechanism of development of respiratory failure. 9. How many types of respiratory failure depending on causes and mechanism of occurrence do you know? 10. Tell about clinical manifestations of respiratory failure. 11. Describe features of different types of respiratory failure. 12. Tell about degrees and stages of respiratory failure.

4.3. Practical work (tasks), which should be performed during class: 1. To carry out examination of patients with pleurisies (dry and exudative) and respiratory failure. 2. To interpret obtained results. 3. To interpret results of laboratory and instrumental methods examination of patients with pleurisies (dry and exudative) and respiratory failure.

The contents of topic: Text SYNDROME OF AIR ACCUMULATION IN PLEURAL CAVITY Syndrome of air accumulation in pleural cavity occurs in communication of bronchi with pleural cavity (in case of subpleural localization of tuberculous cavern, abscess), in trauma of the chest or spontaneous pneumothorax. In this syndrome asymmetry of the chest due to enlargement of affected half (in which accumulation of air occurs), limitation of its participation in respiratory act are revealed. Over area of accumulation of air significantly weakened vocal fremitus or its absence is revealed during palpation; during percussion tympanic sound is revealed; during auscultation breathing and bronchophony are significantly weakened and aren’t conducted to the surface of the chest. During X-ray examination light lung field without lung pattern and near root - shadow of collapsed lung are revealed.

SYNDROME OF FLUID ACCUMULATION IN PLEURAL CAVITY Syndrome of fluid accumulation in pleural cavity is observed in hydrothorax (accumulation of noninflammatory fluid - transsudate, for example, in cardiac insufficiency) or in exudative pleurisy (inflammation of pleura). Its typical signs are dyspnea, which occurs as result of respiratory failure, caused by pressing of the lung and by diminishing of respiratory surface; asymmetry of the chest due to enlargement of that its half, in pleural cavity of which accumulation of fluid occurs; lagging of affected half of the chest in respiratory act. Over area of accumulation of fluid vocal fremitus is weakened significantly or absent, dull sound is revealed during percussion, breathing and bronchophony are weakened significantly or absent. X-ray examination reveals shadowing in zone of accumulation of the fluid, in lower part of the chest more often (in hydrothorax - bilateral often). Upper border of shadowing is well defined besides. In accumulation of transsudate in pleural cavity it is situated more horizontally, in accumulation of exudate (effusion) - obliquely, coinciding with Damoiseau’s line, which is revealed during percussion (look to “Exudative pleurisy”).

PLEURISY Pleurisy (pleuritis) is inflammation of pleural layers, accompanied by accumulation of effusion in pleural cavity (exudative pleurisy, pleuritis exudativa) or sedimentation of fibrin on inflamed surface of pleura (dry or fibrinous pleurisy, pleuritis sicca). In practice of therapeutist, surgeon, TB doctor pleurisy occurs often. Etiology and pathogenesis. Pleurisy isn’t independent disease. It is, as a rule, manifestation or complication of other diseases. Previously 70-90% of pleurisy was caused by tuberculosis, now - 13-20%. Now pleurisy is complication of pneumonia most often (in 18-70% cases). Besides, inflammatory changes of pleura can be marked in diffuse diseases of connective tissue (rheumatism, systemic lupus erythematosus and others). In 15-22% patients pleurisy is result of carcinomatous (primary or methastatic more often) lesion of pleura in oncologic diseases (pulmonary cancer, pleural mesothelioma, mammary gland cancer). Pleurisy can occur also in trauma of the chest, pulmonary artery embolism (due to pulmonary infarction and infarction-pneumonia), parositogenic diseases (echinococcosis, amebiasis). Sometimes pleurisy is complication of acute pancreatitis. In a number of cases pleurisy occurs in late period of myocardial infarction (in Dressler’s syndrome). Pathogenesis of different pleurisy has peculiarities, caused by character of the main disease. So, in infectious pleurisy it can be direct infection of pleura, lymphogenic or (rare) hematogenic permeation of causative agent into pleura. In tuberculosis pleurisy preceding sensitization of organism with following hyperergic reaction takes great place. Such pleurisy is infectious-allergic accordance to its origin. Pathogenesis of pleurisy in collagenous diseases is connected with systemic affection of the vessels and change of general reactivity of organism. In moderate quantity of exudate and presence of outflow liquid part of exudate is sucked and only layer of fibrin is remained on the pleural surface. Just so dry (fibrinous) pleurisy is formed. In those cases when rate of exudation exceeds possibility of outflow, liquid exudate begins to accumulate in pleural cavity, leading to appearance of exudative pleurisy. Classification. Depending on the main disease, leaded to rise of pleurisy, para- and metapneumonic pleurisy, tuberculous, rheumatic, carcinomatous and other pleurisy is differed. According to character of exudate fibrinous, serofibrinous, serous, purulent, hemorrhagic pleurisy is differed. So, serous and serofibrinous pleurisy occurs in tuberculosis and rheumatism, hemorrhagic - in pleural carcinomatosis, pulmonary infarction, purulent - in pleural empyema. Depending on presence or absent of limitation of pleural exudate diffuse and encysted pleurisy is distinguished. Encysted pleurisy can be apical, parietal, basalis (diaphragmalis), paramediastinalis, interlobar.

Dry pleurisy Clinical picture. Symptoms of dry pleurisy can add to clinical manifestations of the main disease (for example, of pneumonia) or go out on the foreground. Patients complain of piercing pain in the chest, intensified during respiratory movements, cough and diminished in limited mobility of the chest (forced position on the affected side). In case of diaphragmatic dry pleurisy pain can radiate in area of anterior wall of the abdomen. During inspection of the patient we can reveal shallow breathing, lagging of one (affected) half of the chest during respiration; during percussion only some diminishing of excursion of the lower border of the lungs on the affected side is revealed (if other symptoms, connected with main disease, are absent). Leading and one objective sign of dry pleurisy sometimes is pleural friction sound. It is heard on the background of some weakened breathing over zone of fibrinous sedimentations. During X-ray examination high position of dome of the diaphragm, limitation of its excursion on the affected side can be revealed. Course of dry pleurisy is determined by main disease. In many patients symptoms of pleurisy disappear in 2-3 weeks. Course of dry pleurisy of tuberculous etiology is more prolonged. In number of cases transition of dry pleurisy into exudative is marked.

Exudative pleurisy Clinical picture. Peculiarities of clinical manifestations of exudative pleurisy depend on character of the main disease in many respects. Thus, in tuberculous pleurisy attendant symptoms, connected with affection of apices of the lungs are observed often. In exudative pleurisy, caused by bronchogenic cancer, constant hemoptysis can be marked. If pleurisy arises in patients with systemic lupus erythematous, symptoms of pericarditis, affections of joints or kidneys are predominant sometimes. At the same time, in patients with exudative pleurisy general symptoms, connected with accumulation of exudates in pleural cavity are marked also. Patients complain of heaviness (dull pain) in the side, dyspnea, little dry cough. In purulent pleurisy (pleural empyema) high fever with chill, signs of intoxication are marked. Pleurisy, caused by tumorous affection of pleura and characterized by gradual accumulation of exudates in pleural cavity, can proceed with few symptoms. During inspection of the patient with exudative pleurisy asymmetry of the chest with bulging of costal interspaces on the affected side, lagging of this half of the chest during respiration are marked.

Fig. 18 Data of percussion and auscultation in exudative pleurisy. During percussion zone of dull sound is revealed; during auscultation respiratory sounds aren’t heard. 1 - exudate; 2 - Damoiseau’s line.

By means of physical examination methods accumulation of fluid in pleural cavity can be revealed only in that case, if its quantity is more than 400-500 ml. During percussion (Fig. 18) zone of dull sound with arched upper border (Damoiseau’s line), upper point of which is along posterior axillary line, is marked. Formation of this line (Fig. 19) is explained by easy accumulation of pleural exudate in area of costodiaphramatic recess in exudative pleurisy. Zone of dullness, formed in left-side pleurisy, leads to disappearance of tympanic sound of Traube’ space (semilunar space). It is well-known, if border of dull sound passes in front along level of the 4th rib, then 1000-1500 ml of fluid is accumulated in pleural cavity. Following displacement of the border of dull sound to one rib correspond with increase of fluid quantity to 500 ml.

Fig.19. Data of percussion and auscultation and location of exudate in left- side exudative pleurisy. a - front view; b - back view; 1 - exudate; 2 - Damoiseau’s line; 3 - Garland’s triangle; 4 - Grokko-Rauhfous’ triangle.

Besides Damoiseau’s line, in exudative pleurisy two triangles, characterized by peculiarities of obtained over them percussion sound, are differed. Garland’s triangle is placed on the affected side higher than fluid level. It is between Damoiseau’s line and spinal column. It is place of the lung, pressed by exudate. During percussion over it dull-tympanic sound is marked. Projection of the second triangle, Grokko-Rauhfous’ triangle, is on the health side. It is zone of dull sound. Its appearance is connected with displacement of mediastinum to the health side. Cathouses of Grokko-Rauhfous’ triangle are diaphragm and spinal column, and its hypotenuses is conventional prolongation of Damoiseau’s line. Signs of displacement of mediastinum and appearance of triangles, described above, are observed usually in accumulation in pleural cavity 1000 ml or more fluid. During auscultation vesicular breathing in exudate zone significantly weakened or absent. Higher than border of exudates (in Garland’s triangle area) intensified vocal fremitus and bronchophony, bronchial shade of breathing are revealed. It is caused by consolidation of pulmonary tissue due to pressed lung. In case of significant accumulation of fluid in pleural cavity tachycardia, low urine flow can be marked in patients. During X-ray examination homogeneous shadowing with oblique location of the upper border is revealed (Fig. 20). In case of little quantity of effusion shadowing is marked in costodiaphragmatic recess only. In massive effusion shadow of fluid can occupy whole lung field and shadow of mediastinum is displaced to the health side. X-ray study allows to reveal encysted pleurisy (as parietal shadowing), interlobular pleurisy (shadowing as spindle or triangle along interlobular sulcus), diaphragmatic pleurisy.

Fig. 20. X-ray film. Left-side exudative pleurisy. Changes, revealed in exudative pleurisy in blood analysis, depend on etiology of disease. Thus, in parapneumonic pleurisy moderate leukocytosis with neutrophilous deviation, elevation of ESR is marked. In case of purulent pleurisy leukocytosis becomes high and sudden deviation of the differential count to the left appears. In tuberculosis pleurisy high leukocytosis, as a rule, is absent, but relative lymphocytosis is revealed. Pleural puncture (technique of its carrying out is given below) with following careful laboratory analysis of punctate, cytological investigation, culture on special medium etc. allow to ascertain etiology of pleurisy more exactly. According to indication thoracoscopy and biopsy of pleura are used. Course of exudative pleurisy depends on its aetiology. Thus, rheumatic pleurisy is resolved in 2-3 weeks in case of performing of necessary therapy. Pleurisy of tuberculous etiology is characterized by more prolong and persistent course. Pleurisy in oncologic diseases is distinguished by progressive course and bad (unfavourable) prognosis. Prognosis in purulent pleurisy is serious also. Commissures in pleural cavity, limiting excursion of diaphragm on the affected side, remain after past exudative pleurisy often. They are manifested by rough pleural friction sound, which is heard during many years. Treatment. Treatment of exudative pleurisy depends on its etiology. In case of para- and metapneumonic pleurisies antibacterial therapy is carried out, in rheumatic pleurisies nonsteroid anti-inflammatory medicaments are used, according to indications - glucocorticoids. In case of tuberculous pleurisy therapy with isoniazids, rifampycin and streptomycin is carried out during some months. Analgesics, cardiovascular remedies and diuretics are used with symptomatic purposes, and during resorption period - physiotherapeutic methods, exercise therapy (in case of contraindications’ absence). When exudate is resolved slowly and its amount is large - pleural puncture is carried out. Besides, it isn’t recommended to remove more then 1000-1500 ml of fluid during one procedure in order to avoid potential collapse. In case of purulent pleurisy pleural cavity is syringed by antiseptic solutions with following introduction of antibiotics, in number of cases - constant draining of pleural cavity is used. Prophylaxis of pleurisies includes prevention and timely treatment of diseases, which can result to their development (of rheumatism, tuberculosis, acute pneumonias and others) and carrying out of actions for general improving of organizm.

Pleural puncture Pleural puncture (thoracocentesis) is performed to obtain pleural fluid for analysis, to remove pleural fluid, or to instill medication. Specimens are examined for gross appearance, consistency, glucose, protein content, cellular composition. Specimens are also examined cytologically for malignant cells and cultured for pathogens. During puncture the patient with crossed on the chest hands sits on the chair front its back (if unable to sit, the patient is placed on the unaffected side). Before puncture treatment of supposed place of puncture by iodine solution and local anesthesia are given. Puncture is performed along posterior axillary line in zone of maximum dullness of percussion sound, which is determined by percussion preliminary. It is usually in 7th or 8th costal interspace, along upper border of lower-lying rib as along lower border intercostal vessels pass. (Fig. 21).

Fig. 21. Pleural puncture. 1. Damoiseau’s line. 2. Garland’s triangle. 3. Grokko- Rauhfous’ triangle. 4. lower border of the lung.

For experimental puncture physician uses syringe having the capacity of 10 ml with pined on it rather thick and long needle, but for removal of much quantity of fluid – Potten’s apparatus or electrical ejector. Feeling of “free space” appears in case of hit of the needle in the pleural cavity; sometimes during puncture barrier is observed, it is connected with thickening of the pleura usually. 50-150 ml of fluid is taken for diagnostic purpose and sent for physical-chemical, cytological and bacteriological examination. In case of accumulation of considerable quantity of fluid in pleural cavity, 800-1200 ml is removed with medicinal purpose. Removal of lager quantity of fluid from pleural cavity leads to fast displacement of organs of mediastinum to affected side and can be accompanied by collapse. After extraction of the needle - place of puncture is smeared by 5% spirituous iodine solution.

RESPIRATORY FAILURE Function of external breathing apparatus is directed to provision of organism by oxygen and removing of carbon oxide (IV), formed during metabolic processes. This function is realized, firstly, by ventilation, i.e. gas exchange between external and alveolar air, providing necessary pressure of oxygen and carbon oxide (IV) in alveoli (intrapulmonary distribution of inspired air is important moment); secondly, by diffusion of oxygen and carbon oxide (IV) through wall of alveoli and pulmonary capillaries. This diffusion is realized into inverted directions (oxygen passes into the blood from alveoli, and carbon oxide (IV) diffuse into alveoli from the blood). Many acute and chronic diseases of bronchi and lungs leads to development of respiratory failure (this term was introduced by Wintreich in 1854), besides degree of morphological changes in the lungs doesn’t correlate (correspond) with degree of their dysfunction always. According to modern representations, respiratory failure is organism’s state when supporting of normal gaseous blood composition isn’t provided or it takes place due to more intensive work of external breathing apparatus and heart, that results to decrease of functional possibilities of organism. It is necessary to bear in mind, that external breathing apparatus function is connected closely with function of circulatory system; in case of external breathing dysfunction increase work of the heart is one of important elements of its compensation. Respiratory failure is manifested clinically by dyspnea, cyanosis, and during later stage - in case of adding of heart failure - by edemas also. In case of respiratory failure in patients with respiratory organs diseases organism uses the same compensatory reserve mechanisms that in healthy person during performing of hard physical work. But these mechanisms start to work more early and in such load when their necessity in healthy person doesn’t occur (for example, dyspnea and tachypnoe in patients with pulmonary emphysema can occur during slowly walking). Inadequate changes of ventilation (becoming of breathing more frequent and deeper) on relatively little for healthy person physical activity is one of the first sign of respiratory failure; minute volume (MV) of breathing is increased. In some cases (bronchial asthma, pulmonary emphysema, etc.) compensation of respiratory failure is realized mainly due to increased work of respiratory musculature, i.e. change of respiratory mechanics. So, in patients with respiratory system pathology supporting of external breathing function on necessary level is realized due to adding of compensatory mechanisms, i.e. at the cost of more efforts than in healthy persons and limitation of respiratory reserves: maximal lung ventilation (MLV) is decreased, oxygen consumption coefficient (CO2C) is diminished. Engaging of various compensatory mechanisms in the struggle with progressing respiratory failure is realized gradually, adequately to its degree. At the beginning, during early stages of respiratory failure function of external breathing apparatus is realized by usual way. Compensatory mechanisms connected up only during patient’s physical activity; therefore, only decreasing of reserve possibilities of external breathing apparatus takes place. In the future tachypnoe, tachycardia are observed also on little exertion and then at rest, signs of intensified work of respiratory musculature during inspiration and expiration, participation of additional muscular groups in respiratory act are revealed. During later stages of respiratory failure, when organism exhausts compensatory resources, arterial hypoxemia and hypercapnia are revealed. Signs of “latent” oxygen deficiency, accumulation of unoxidized products (lactic acid and others) in the blood and tissues are observed also parallely with increasing of “frank” arterial hypoxemia. In future heart (right-ventricular) failure due to development of hypertension in pulmonary circulation, accompanied by increased right-ventricular load, and arising dystrophic changes in myocardium due to its constant overload and insufficient oxygen supply are added to the lung failure. Hypertension of vessels of pulmonary circulation in diffuse pulmonary lesions occurs as reflex answer to insufficient lung ventilation, alveolar hypoxia (Eiler-Lilyestrand’s reflex); in case of focal pulmonary lesions this reflex mechanism plays important adaptive role, limiting blood supply of insufficiently ventilated alveoli). In future in chronic inflammatory pulmonary diseases blood passing along vessels of pulmonary circulation becomes more difficult due to cicatricial-sclerotic processes (and lesion of vascular pulmonary net). Increased right-ventricular myocardium load results to its insufficiency gradually. Last one is manifested by congestive signs in systemic circulation (so called “cor pulmonale”). There are three types of ventilation lung dysfunction: obstructive, restrictive and mixed depending on causes and mechanism of respiratory failure occurrence. Obstructive type is characterized by difficult passage of air through the bronchi (due to bronchitis - bronchial inflammation, bronchospasm, constriction or compression of trachea or large bronchi by a tumor, for example, etc.). During spirography expressed decrease of MLV, forced vital capacity (FVC) and insignificant decrease of vital capacity (VC) are revealed. Barrier to air jet passage makes increased demands to respiratory musculature, ability of respiratory apparatus to perform additional functional load disorders (capability of fast inspiration and expiration (particularly), sharp acceleration of breathing disturbs, specifically). Restrictive type of ventilation disorder is observed in case of limited ability of the lungs to expand and to collapse: in pneumosclerosis, hydro- and pneumothorax, massive pleural adhesions, kyphoscoliosis, ossification of costal cartilages, limited mobility of the ribs, etc. These conditions are in the first instance attended by a limited depth of the maximum of possible inspiration, i.e. VC (and MLV) decreases, but obstacle for dynamics of respiratory act (i.e. for rate of usual inspiratory depth, and when it is necessary - for significant increasing in frequency of breathing also) doesn’t arise. Mixed (combined) type includes the signs of two previous types, often with prevalence of one of them; this type of disorder occurs in long-termed diseases of the lungs and the heart. Dysfunction of external breathing occurs also in case of increase of so called “anatomical dead space” (in large cavities in the lung, caverns, abscesses, and multiple large bronchiectases). Respiratory failure due to circulatory disorders (for example, in case of thromboembolism and others) is closely to this type. In this case part of the lung doesn’t take part in gas exchange (at keeping of any ventilation degree). At last, respiratory failure occurs in unequal distribution of air in the lungs (“distributive disorders”) down to excluding of lung’s parts from ventilation (pneumonia, athelectasis), when their blood supply is kept. Owing to it part of venous blood without oxigenation gets into pulmonary veins and left part of the heart. Cases of so called “vascular shunt” (from right to left) , when part venous blood from pulmonary artery system gets into pulmonary veins directly (by-pass) of capillary bloodstream and is mixed with oxygenized arterial blood are close by pathogenesis to this type of respiratory failure. In last cases blood oxygenation in the lungs disturbs, but hypercapnia can be absent due to compensatory increase of ventilation in healthy parts of the lung. This is partial respiratory failure as contrast of total, “parenchymatous” one, when both hypoxemia, and hypercapnia are observed. So called “diffuse respiratory failure” is characterized by disorder of gas exchange through alveolar-capillary membrane of the lungs and can be observed in its thickening, causing disorder of diffusion of gases throught it (so called “pneumonoses”, alveolar-capillary block) and usually isn’t accompanied by hypocapnia as diffusion rate of carbon oxide (IV) in 20 times is more than oxygen. This type of respiratory failure first is manifested by arterial hypoxemia and cyanosis. Ventilation is intensified. Respiratory failure in toxic depression of respiratory center, anemia, oxygen deficiency in inspired air isn’t connected with lung pathology directly. There are acute (for example, in bronchial asthma attack, croupous pneumonia, spontaneous pneumothorax) and chronic respiratory failure. There are three degree and three stages of respiratory failure. Degrees of respiratory failure reflect its severity during this moment of disease. In the I degree of the respiratory failure patients complain of dyspnea, which becomes evident only on moderate or significant physical exertion. The respiratory rate at rest is normal, after moderate physical exercise it increases by 10-15 respirations. Spirography reveals changes in the lung ventilation intensity and lung volume indices. VC and (or) FVC decrease by 21-40% in comparison with proper values. In the II degree, the dyspnea develops during a light exercise, cyanosis is revealed on examination. In addition, spirography reveals disorder of the ventilation efficiency (CO2C and oxygen usage coefficient (CO2U)), VC and (or) FVC decrease by 41-60% of proper values. In the III degree dyspnea and cyanosis are revealed at rest. On examination the participation of the additional muscles in respiratory act (nose wings, intercostal muscles) is observed. The signs of heart failure (edema, the liver increase, accelerated pulse) are revealed. VC and (or) FVC decrease by more than 60% of proper ones. Stages of respiratory failure in chronic pulmonary diseases reflect its dynamics during progressing of disease. Usually the following stages are distinguished: latent pulmonary, expressed pulmonary and pulmo-cardiac failure. Treatment. In respiratory failure it includes the following actions: 1) treatment of the main disease, causing it (pneumonia, exudative pleurisy, chronic inflammatory processes in bronchi and pulmonary tissue, etc.); 2) relief of bronchospasm and improvement of pulmonary ventilation (using of bronchial spasmolytics, exercise therapy and others); 3) oxygenotherapy; 4) in case of “cor pulmonale” - using of diuretics; 5) in case of congestive signs in systemic circulation and symptomatic erythrocytosis bloodletting is carried out additionally.

ADULT RESPIRATORY DISTRESS SYNDROME Adult respiratory distress syndrome – severe respiratory failure, suddenly occurred, with expressed hypoxemia, which is caused by edema of pulmonary interstitium and alveoli of noncardiogenous origin (other name of syndrome – syndrome of moist lungs). Etiology and pathogenesis. Basis of its pathogenesis – fast accumulation of fluid in pulmonary tissue without signs of pulmonary hypertension or congestive heart failure (pulmonary artery wedge pressure is less then 18 mm Hg), but with significant increase of alveolar-capillary membranes’ permeability with following filling of air spaces by fluid, plasmatic proteins, destructed cells on the background of significant surfactant system’s insufficiency and intrapulmonary blood shunting. These processes are provocated by action of toxins and other agents, including cytokine and activated neutrophiles, affecting membranes. Development of syndrome is associated with: sepsis (caused by gram-negative bacteria particularly), trauma (multiple, craniocerebral particularly), fat embolism, aspiration of gastric contents, drowning, acute pancreatitis, toxic action of narcotics (heroin), uremia, some medicaments, hemotransfusion. Clinical manifestations. Fast development of respiratory failure, manifesting by dyspnea, including of additional muscles for the work, is typical. Noncardiogenic pulmonary edema with moist rales of different caliber (during auscultation) is developed. During X-ray study – signs of interstitial and alveolar edema (diffuse infiltrative changes) are revealed. Hypoxia and hypercapnia increase, fatal heart failure, DIC syndrome, infection are added. It makes extreme unfavorable prognosis for a disease.

A. Test tasks to be done: - with a single selective answer - I-st level: 1. The obstructive type of respiratory failure appears due to: a) disturbance of alveolar ventilation as result of decreasing of respiratory surface of alveoli and limitation of their smoothing out during inspiration; b) hard physical activity; c) disturbance of patency of airways; d) thick thoracic wall; e) thin thoracic wall. 2. The restrictive type of respiratory failure appears due to: a) disturbance of alveolar ventilation as result of decreasing of respiratory surface of alveoli and limitation of their smoothing out during inspiration; b) hard physical activity; c) disturbance of patency of airways; d) thick thoracic wall; e) thin thoracic wall. 3. How many degrees of respiratory failure are distinguished? a) 2; b) 3; c) 4; d) 5; e) 10. 4. What is data of comparative percussion of the lungs in patient with dry pleurisy: a) band box percussion sound; b) tympanic percussion sound; c) dull percussion sound; d) clear lung sound; e) dull-tympanic sound. 5. What data can be revealed by means of dynamic examination of the chest of the patients with exudative pleurisy? a) lagging of affected half of the chest during respiratory movements; b) slow breathing; c) Biot’s respiration; d) Cheyne-Stokes respiration; e) bronchial breathing. 6. What changes in area of pleural exudate can be revealed during percussion of the chest? a) tympanic percussion sound; b) band box percussion sound; c) clear lung percussion sound; d) dull or deadened percussion sound; e) dull-tympanic percussion sound. 7. Triangle, which is placed on the affected side higher than fluid level between Damoiseau’s line and spinal column and is placed in the lung, pressed by exudate, is named: a) Lieutaud’s triangle; b) Grokko-Rauhfous’ triangle; c) Emphysematous triangle; d) Garland’s triangle; e) Strazhesko’ triangle. 8. Triangle, projection of which is on the health side and appearance of which is connected with displacement of mediastinum to the health side (its cathouses are diaphragm and spinal column, and its hypotenuses is conventional prolongation of Damoiseau’s line) is named: a) Lieutaud’s triangle; b) Grokko-Rauhfous’ triangle; c) Emphysematous triangle; d) Garland’s triangle; e) Strazhesko’ triangle. 9. Maximal point of Damoiseau’s line is situated along: a) midclavicular line; b) anterior axillary line; c) midaxillary line; d) posterior axillary line; e) scapular line. 10. During lung auscultation in the area of Garland’s triangle we can hear: a) vesicular breathing; b) pathological bronchial breathing; c) harsh breathing; d) amphoric respiration; e) interrupted respiration. 11. During lung auscultation in the area of Grokko-Rauhfous’ triangle we can hear: a) pathological bronchial breathing; b) vesicular breathing; c) intensified vesicular breathing; d) harsh breathing; e) weakened vesicular breathing or respiratory sounds aren’t heard.

- with the selective group of right answers - II - nd level: 1. Signs of syndrome of respiratory failure include: a) cough; b) dyspnea; c) cyanosis; d) pain in the chest; e) tachycardia; f) edemas (in late stage, after adding of heart failure); g) headache. 2. What are the cases of appearance of syndrome of respiratory failure? a) respiratory airway obstruction; b) decreasing of elasticity of pulmonary tissue; c) hard physical activity; d) decreasing of area of respiratory surface; e) using strong tea and coffee; f) thoracodiaphragmatic pathology (myasthenia, kyphoscoliosis, trauma of the chest); g) low ambient temperature. 3. What are the causes of obstructive respiratory failure? a) inflammatory processes in the lungs; b) stagnation in the lungs; c) bronchial foreign body; d) bronchospasm; e) decreasing of elasticity of the lungs; f) pneumothorax; g) edema of mucous membrane of bronchi and larynx, their organic narrowing. 4. What are the causes of restrictive respiratory failure? a) inflammatory processes in the lungs; b) bronchospasm; c) compression atelectasis; d) pneumothorax; e) hydrothorax; f) laryngospasm; g) thoracodiaphragmal pathology. 5. What results of percussion and auscultation are typical for syndrome of accumulation of air in pleural cavity? a) tympanic percussion sound over affected half of the chest; b) band box sound over affected half of the chest; c) dull sound over affected half of the chest; d) intensification of vesicular respiration; e) significant weakening of vesicular respiration or its absence; f) strengthening bronchophony; g) weakening bronchophony or its absence. 6. What are basic subjective symptoms of dry pleurisy? a) moist cough; b) dry cough; c) suffocation; d) dyspnea; e) hemoptysis; f) palpitation; g) pain in the chest, in lateral parts mainly. 7. In parapneumonic pleurisy following results of blood analysis are marked: a) high leukocytosis; b) moderate leukocytosis; c) elevation of ESR; d) anemia; e) thrombocytopenia; f) deviation of the differential count to the right; g) lymphocytosis. 8. We can distinguish following pleurisy depending on presence or absent of limitation of pleural exudate: a) fibrinous; b) encysted; c) serofibrinous; d) serous; e) purulent; f) diffuse; g) hemorrhagic. 9. We can distinguish following pleurisy according to character of exudate: a) fibrinous; b) encysted; c) serofibrinous; d) serous; e) purulent; f) diffuse; g) hemorrhagic. 10. Encysted pleurisy can be: a) apical; b) parietal; c) diffuse; d) interlobar; e) basalis (diaphragmalis); f) paramediastinalis; g) dry. B. Tasks to be done: Task 1. Patient B., 45 years old, complains of piercing pain in right half of the chest, intensified during respiratory movements, cough and diminished in position on the right side. Objectively: shallow breathing, lagging of right half of the chest during respiration; during percussion - some diminishing of excursion of the lower border of the lungs on the right is revealed. 1. What pathology do you can suppose? 2. What are potential results of lung auscultation can be in this case?

Task 2. Patient L., 52 years old, complains of significant dyspnea, which appeared suddenly after acute pain in the left half of the chest (trauma of the chest was before this) Objectively: asymmetry of the chest, enlargement of left half of the chest, limitation of its participation in respiratory act. Over left half of the chest absence of vocal fremitus is revealed during palpation; during percussion tympanic sound is revealed; during auscultation absence of respiratory sounds and bronchophony is revealed. 1. What syndrome do you can suppose in this patient? 2. What are potential results of X-examination can be in this case?

Task 3. Spirography of the patient H., complaining of dyspnea, cough and expectoration of moderate amount of sputum revealed the following results: RV-120%, VC-90%, FVC-85%, FVC1-83%, FVC/VC-90%, momentary expiratory flow (MEF)25 -75%, MEF50 -50%, MEF75 - 40%, midexpiratory flow 25-75 - 35%. 1. For which type of respiratory failure these results are typical? a) obstructive respiratory failure with lesion of medium and large bronchi; b) obstructive respiratory failure with lesion of fine bronchi; c) mixed respiratory failure; d) restrictive respiratory failure.

Answers for test tasks of the I-st level: 1 - c 7 - d 2 - a 8 - b 3 - b 9 - d 4 - d 1 0 - b 5 - a 1 1 - e 6 - d

Answers for test tasks of the II-nd level: 1 - a , b , c , f 6 - b , g 2 - a , b , d , f 7 - b , c 3 - c , d , g 8 - b , f 4 - a , c , d , e , g 9 - a , c , d , e , g 5 - a , e , g 10- a , b , d , e , f

Standards of right answer for tasks: 1) 1. Right-side dry pleurisy. 2. On the right - pleural friction sound, that is heard on the background of some weakened breathing.

2) 1. Syndrome of accumulation of air in pleural cavity.. 2. During X-ray examination light lung field without lung pattern and near root - shadow of collapsed lung can be revealed on the left. 3) b

Literature recommended: Main Sources: 1. Propedeutics to Internal Medicine : textbook for English learning students of higher medical schools. Pt. 1. Diagnosis / O. N. Kovalyova, T. Ashcheulova. - 2nd ed. - Vinnytsya : Nova Knyha Publ., 2011. - 424 p. 2. Propaedeutics to Internal Medicine: Syndromes; textbook for English learning Students of higher medical schools; Pt 2. / O.N. Kovalyova, S. Shapovalova – Vinnytsya: Nova Knyha publishers, 2011. – 424 p. 3. Propaedeutics of Internal Medicine: a textbook / Y.I.Detsyk, O.H. Jaworski, R.J. Dutka et al., Ed. prof. O.H. Jaworski. 3rd ed., Correct. and reported. - K. VSV "Medicine", 2013. - 552 p. 4. Basics of Internal Medicine.: Propedeutics of internal diseases / Detsyk Y.I., Jaworski E.G., Dutka R.J., Ed. O.H. Jaworski. - K.: Health 2004.-500 p. 5. Grebenev A.L. Propedeutics Internal Medicine: A Textbook AL Grebenev, 5th ed. pererab.i ext. - Moscow: Meditsina, 2002. - 585 p. 6. Study Guide "Computer tests of propedeutics of internal diseases" (by V.V. Korotkyj, A.B. Novosad). Kyiv: Health 2001 – 148p. 7. Introduction to the Course of Internal Diseases. Book 1. Diagnosis / Zh. D. Semidotska, O. S. Bilchenko [et al.] ; ed. by Zh. D. Semidotska. - 2nd ed., revised and supplememted. - Kharkiv : Tornado, 2006. - 314 p. 8. General thesis about organization and conduction of complex practically oriented state examination from internal medicine, professional and infectious diseases : manual for out- class work with English-medium graduates / KhNMU ; comp. O. Babak [et al.]. - Kharkov : KhNMU, 2012. - 40 p. - англ. Electronic resources: 1. David Hui. Approach to Internal Medicine: A Resource Book for Clinical Practice http://file.zums.ac.ir/ebook/056-Approach%20to%20Internal%20Medicine%20- %20A%20Resource%20Book%20for%20Clinical%20Practice,%203rd%20Edition- David%20Hui-.pdf 2. The subject “Internal medicine propedeutics” as an introduction into the clinics of internal medicine. Main methods of examination of patients. Anamnesis as a part of a case history. Inspection of a patient and its value in diagnostic process. http://intranet.tdmu.edu.ua/data/kafedra/internal/propedeutic_vn_des/lectures_stud/en/med/lik/ ptn/Internal%20Medicine%20Propedeutics/3/01_Introduction.htm 3. Internal Medicine. Propaedeutics as an introduction to the clinic of internal medicine. http://im.medicine.karazin.ua/downloads/presentations/Lecture_Internal_Medicine_Propaed eutics_Basic%20concepts.pdf 4. Propaedeutics as an Introduction to the Clinic of Internal Medicine Propaedeutics M. Yabluchansky L. Bogun, L.Martymianova, O. Bychkova, N. Lysenko, N. Makienko, E. Golubkina V.N. Karazin National University Medical School’ Internal Medicine Dept. http://dspace.univer.kharkov.ua/bitstream/123456789/10966/2/Lecture%20PIM_22.06.2015. pdf 5. ИИ Мистюкевич. Theses of lectures on propedeutics of internal diseases. www.gsmu.by/file/biblio/uchlit/tezisyprop.doc 6. Англо-русский тематический словарь по пропедевтике внутренних болезней и общему уходу за больными : справочное издание / Витебский государственный медицинский университет, Кафедра пропедевтики внутренних болезней; сост. Л.М. Немцов; под ред. Г.И. Юпатова. - Витебск : ВГМУ, 2005. - 153 с. URI: http://elib.vsmu.by/handle/123/11343 7. Special propedeutics of internal diseases : lecture course / Vitebsk State Medical University, Dep. of Propedeutics of Internal Diseases ; comp. by L. M. Nemtsov. - 2-е изд. - Vitebsk : VSMU, 2016. - 318 p. URI: http://elib.vsmu.by/handle/123/9837 8. General propedeutics of internal diseases : lecture course / Vitebsk State Medical University ; compiled by L. M. Nemtsov. - Vitebsk : VSMU, 2006. - 175 p. http://elib.vsmu.by/handle/123/268

Methodical instruction is composed by lecturer Ye.Ye. Petrov.

Approved at the Department of Propaedeutics to Internal Medicine with Care of Patients meeting on 11 09 2018 Protocol No2 The Head of the Department Professor Yu. Kazakov

METHODICAL INSTRUCTION FOR STUDENTS’ SELF-PREPARATION WORK

Educational discipline Propaedeutics to Internal Medicine Module No 2 Enclosure module No 8 Topic Clinical, instrumental and laboratory examination of the patient with chronic gastritis, peptic ulcer disease and intestine pathology. The main symptoms and syndromes Year 3 Faculty medical

Poltava - 2018 1. The topic basis: The topicality of studied questions is caused first of all by a wide spreading of chronic gastritis among a human population. According to data of numerous works various its forms are revealed in 50-80% of all adult population. Peptic ulcer is one of the most widespread diseases of digestive apparatus. Now its prevalence among adult population is 7-10%. Men have this disease more often in comparison with women. Duodenal ulcers are revealed in 4 times more often then gastric ones. Among bowels diseases inflammatory diseases (enteritis, colitis), functional changes (dyskinesias) of large intestine and tumors occur mainly. 2. The specific aims:  To explain etiology and pathogenesis of chronic gastritis.  To classify types of chronic gastritis.  To analyze results of examination of patients with chronic gastritis.  To interpret results of examination of patients with chronic gastritis.  To explain etiology and pathogenesis of peptic ulcer disease, chronic enteritis, chronic colitis, dyskinesia of large intestine.  To classify types of peptic ulcer disease.  To analyze results of examination of patients with peptic ulcer disease, chronic enteritis, chronic colitis, dyskinesia of large intestine.  To interpret results of examination of patients with peptic ulcer disease, chronic enteritis, chronic colitis, dyskinesia of large intestine.

3. Basic knowledge, experience, skills necessary for studying the topic in connection with other subjects (interdisciplinary integration) :

Previous disciplines Obtained skills 1. Anatomy To know human anatomy, structure of organs of gastrointestinal tract particularly. 2. Physiology To know physiology of the gastrointestinal tract. 3. Medical psychology To be able to observe principles of ethics and deontology in medical practice 4. Biochemistry To know biochemical process, occurring during gastric digestion. 5. Pathological morphology To know pathologic-morphological picture of chronic gastritis and peculiarities of its different types. 6. Latin and medical terminology To know terminology (in Latin transcription): chronic gastritis, body of stomach, fundus of stomach, cardial part of the stomach, pyloric part of the stomach.

4. Tasks for self-work during preparation to the class. 4.1 List of the main terms, parameters, characteristics, which should be mastered during preparation to the class:

Term Definition

1. Chronic gastritis It is chronic inflammatory-dystrophic process in mucous membrane of the stomach, accompanying by disturbance of processes of cellular regeneration and progressing atrophy of glandular epithelium.

2. Peptic ulcer disease It is pathologic process based on stomach or duodenum mucous membrane inflammation with its local erosive damage due to infectious or non-infectious mechanism as response to impaired endogenous balance between local factors “aggression” and “prevention”

3. Chronic enteritis It is disease, taking its long course, when inflammatory and dystrophic changes of mucous membrane of small intestine are observed.

4.Chronic colitis It is disease, taking its long course, when inflammatory and dystrophic changes are developed in mucous membrane of large intestine mainly.

4.2. Theoretical questions to be answered before class: 1. Tell about ethiology and pathogenesis of chronic gastritis. 2. Classification of chronic gastritis. 3. What are potential results of questioning, inspection and palpation of abdomen in patients with chronic gastritis? 4. What laboratory and instrumental methods are used for diagnostics of chronic gastritis? 5. The course of chronic gastritis. 6. Tell about ethiology and pathogenesis of peptic ulcer disease. 7. Classification of peptic ulcer disease. 8. What are potential results of questioning, inspection and palpation of abdomen in patients with peptic ulcer disease? 9. What laboratory and instrumental methods are used for diagnostics of peptic ulcer disease? 10. The course and complications of peptic ulcer disease. 11. What are the main signs of malabsorption syndrome? 12. Tell about ethiology and pathogenesis of chronic enterits. 13. What are potential results of questioning, inspection and palpation of abdomen in patients with chronic enteriits? 14. What laboratory and instrumental methods are used for diagnostics of chronic enteritis? 15. Tell about ethiology and pathogenesis of dyskinesia of large intestine. 16. What are potential results of questioning, inspection and palpation of abdomen in patients with dyskinesia of large intestine? 17. What laboratory and instrumental methods are used for diagnostics of dyskinesia of large intestine? 18. Tell about ethiology and pathogenesis of chronic colitis. 19. What are potential results of questioning, inspection and palpation of abdomen in patients with chronic colitis? 20. What laboratory and instrumental methods are used for diagnostics of chronic colitis?

4.3. Practical work (tasks), which should be performed during class: 1. To carry out examination of patients with chronic gastritis. 2. To interpret obtained results. 3. To interpret results of laboratory and instrumental methods examination of patients with chronic gastritis. 4. To carry out examination of patients with peptic ulcer disease, chronic enteritis, dyskinesia of large intestine and chronic colitis. 5. To interpret obtained results. 6. To interpret results of laboratory and instrumental methods examination of patients with peptic ulcer disease, chronic enteritis, dyskinesia of large intestine and chronic colitis.

The contents of topic: Text SYNDROME OF DYSPEPSIA Syndrome of dyspepsia is characterized by presence of pains or feeling of discomfort in combination with heartburn, eructation and regurgitation in epigastrium. Pains in epigastrium can be various. They can be moderately expressed, dull, aching or intense, sharp, cramp-like. Sometimes pains occur at once or during 30 minutes after food intake, sometimes - in 1,5-2 hours after food intake, and in some patients - fasting mainly, sometimes at night. Often unpleasant sensations in epigastrium aren’t appreciated by patients as pain, but - as feeling of discomfort (of heaviness, overfilling). Directed manifestations are marked often in case of presence of distinct pains in epigastrium also. It is typical feeling of early saturation during meal regardless of amount of food. Heartburn is feeling of burning in epigastrium and behind sternum in its lower port. It is caused by reflux of sour gastric contents into esophagus. Eructation is sudden output of gastric contents into oral cavity. Air eructation or sour eructation occurs mainly. Reflux of bile from duodenum into stomach can cause bitter eructation. Food eructation into oral cavity is called regurgitation. In pathogenesis of symptoms of dyspepsia leading role belongs to the following mechanisms: increased sensitivity of receptor apparatus of gastric wall to distension (visceral afferent hypersensitivity), disturbance of the stomach ability to relax as answer to food intake (disorder of gastric accommodation), arrhythmia of gastric peristalsis, decrease of motor activity of antral portion with slowing down of gastric emptying, antroduodenal discoordination. Dyspepsia is subdivided into organic and functional (“non-ulcer”). In case of organic dyspepsia patient has disease or pathological states, which cause dyspeptic manifestations. First of all they are disease of gastrointestinal tract: peptic ulcer disease, carcinoma of the stomach, gastroesophageal reflux disease, gastric atony (gastroparesis), chronic pancreatitis, tumor of pancreas, chronic cholecystitis, lactose intolerance, lambliasis, helminthic invasion. Besides, organic dyspepsia can be caused by diseases of other systems and organs (diabetes mellitus, pathology of thyroid gland, ischemic heart disease, systemic vasculitis), pregnancy, alcohol abuse, drug therapy (aspirin and other nonsteroidal anti- inflammatory drugs, some antibacterial preparations, glucocorticoids, digoxin, theophillin, caffeine) and others. At the same time, researches of the last years point to absence of distinct connection between presence of morphological signs of chronic gastritis in the patient and symptoms of dyspepsia. Often chronic gastritis is taking its latent course. In patients with functional dyspepsia any reasons (from foregoing), which can cause its clinical manifestations, absent. Besides, it is can to say really and competently about syndrome of functional dyspepsia only in those cases when dyspeptic disorders are observed during more than 3 months. Functional dyspepsia occurs in two times more often than organic one. It is supposed that essential role in its occurrence belongs to stressor factors (of psychosocial character, particularly), for example, cessation of work, exchange (transfer) to less prestigious or less paid work, family troubles, etc. side by side with foregoing pathogenetic mechanisms (visceral afferent hypersensitivity, slowing down of gastric emptying, disorder of gastric accommodation). Signs of depression are revealed in patients often. It is typical presence of varied complaints of disorders of other systems of organism (side by side with ones of digestive system) in patients with “non-ulcer” dyspepsia. But these disorders aren’t confirmed by revealing of organic pathology during carrying out of physical, laboratory and instrumental examination. First physician’s task for patient with dyspeptic disorders is carrying out of differential diagnostics with aim to differ organic dyspepsia from functional. Besides, it is necessary to bear in mind, that even such most often type of organic dyspepsia as peptic ulcer disease can’t be differed exactly from “non-ulcer” dyspepsia according to character of dyspeptic manifestations. At the same time it is necessary to think about organic character of dyspepsia if dyspeptic disorders appears at first in persons of more than 45 years old, particularly in case of presence of the following accompanying signs: uncaused loss of body weigh, enlargement of organs of abdominal cavity or sizes of abdomen, persisting vomiting, blood admixture in vomit masses, melena, fever, anorexia, anemia. Revealing of these symptoms in patients with dyspepsia is indication for urgent carrying out of endoscopic, ultrasound, X-ray and other necessary researches.

CHRONIC GASTRITIS Chronic gastritis (gastritis chronica) is the most widespread disease of digestive apparatus. According to data of numerous works various its forms are revealed in 50-80% of all adult population. Etiology and pathogenesis. Now etiology and pathogenesis of chronic gastritis are studied insufficiently yet. According to modern conception, there are two main mechanisms of development of chronic gastritis. Appearance of chronic gastritis A is caused by production of specific autoantibodies to parietal cells of gastric mucous membrane, resulting to its atrophy, in fundal part first of all. Reasons of production of these autoantibodies aren’t ascertained completely yet: in number of patients they, possible, are caused by genetic factors. In majority patients appearance of chronic gastritis, named chronic gastritis B, isn’t connected with autoimmune mechanisms. Alimentary errors, smoking and alcohol abuse, duodenogastral reflux of bile, disorder of nervous and humor regulation of functions of the stomach in different diseases of internal organs usually are considered as factors, predisposing to its development. Concrete participation of foregoing factors in appearance of chronic gastritis isn’t revealed as yet finally. During last years important role in development and progressing of chronic gastritis B is given to microorganisms Helicobacter pylori (HP), which are revealed in such patients under parietal mucus on the surface of epithelial cells in area of intercellular junctions. That is why chronic gastritis B now is called “chronic gastritis, associated with HP”. Classification According to one of last classifications of the chronic gastritis, adopted in Houston (USA, 1996) there are following types of gastritis: I. Chronic gastritis: 1) nonatrophical (Helicobacterial, superficial diffuse, chronic antral gastritis, gastritis of type В); 2) atrophical (autoimmunal, multifocal, diffuse gastritis of the stomach body, gastritis of type А.); 3) special forms of gastritis (eosinophilic, granulomatous, lymphocytic, reactive - reflux gastritis). II. According to topography of lesion: antral gastritis, fundal gastritis, pangastritis, III. According to activity of process: acute, chronic, IV. According to type of metaplasia of mucous membrane: intestinal and/or pyloric.

Clinical picture. Chronic gastritis doesn’t have any typical clinical picture. Often disease is taking its latent course and is revealed only during endoscopy. At the same time, different complaints, which can be determined by morphological forms of chronic gastritis and level of gastric acid production, usually are revealed in many patients, during exacerbation period particularly. In patients with chronic gastritis with normal or increased acid-secretory function of the stomach, usually of young age, like-ulcer symptoms are marked often. They include “hunger”, night and late pains after food intake, heartburn, sour eructation, constipation. In patients with chronic gastritis with secretory insufficiency, which occurs among mean and elderly age patients mainly, feeling of heaviness, overfilling and dull pains in epigastrium, suppressed appetite, air eructation, meteorism and borborygmus are observed more often. Unstable stool is marked often (diarrhea mainly). In some patients with chronic achylic gastritis long disorder of digestion and malabsorption can lead to loss of body weigh, appearance of signs of hypovitaminosis (angular stomatitis, skin desquamation, nails fragility) During objective examination of the patients with chronic gastritis any changes aren’t revealed often. Insignificant tenderness in epigastrium during palpation is revealed in little number of patients only.

Syndromes, occurring in chronic gastritis*: (depending on its type)  Pain syndrome;  Dyspeptic syndrome:

Syndrome of gastric dyspepsia; Syndrome of intestinal dyspepsia;

 Malabsorption syndrome;

 Syndrome of acidism (acid dyspepsia);

 Dumping syndrome;

 Syndrome of cardiovascular disturbances;

 Asthenoneurotic syndrome.

* Syndromes are analyzed in detail during lecture course

Research of acid- and pepsin-secretory function of the stomach, carried by means of fractionary gastric intubation or intragastral pH-metry, is used for diagnostics of chronic gastritis and more precise definition of its type. Progressing of atrophic changes in mucous membrane of fundal part of the stomach is accompanied by decreasing of secretion of hydrochloric acid and diminishing of production of pepsin. Radiological study of the stomach isn’t the main method of revealing of chronic gastritis, but gives possibility to reveal changes of relief of mucous membrane (smoothing or, contrary, hypertrophy of folds) sometimes. It can reveal also different motor disorders of the stomach, occurring often in the patients with chronic gastritis. Leading role in diagnostics of chronic gastritis belongs to endoscopic research, particularly with combination with biopsy of mucous membrane of fundal and antral part of the stomach and following histological study of biopsy material. During diagnostics of chronic gastritis it is necessary to bear in mind that symptoms, typical for this disease, can occur also in other diseases of the stomach (peptic ulcer disease, gastric carcinoma), pancreas (pancreatitis), gall bladder (cholecystitis), intestines (enteritis, colitis). Besides, chronic gastritis often is combined with foregoing diseases of digestive apparatus. Directed circumstances require carrying out of multifold examination of the patients with chronic gastritis and complaining of pains and dyspeptic signs. Course. Chronic gastritis is characterized by protracted, long term course, often with alternation of exacerbation periods and remission and slow progressing of structural changes. Chronic atrophic gastritis, accompanied by decreasing of secretion of hydrochloric acid down to development of gastric achilia, particularly if it is combined with expressed dysplasia of epithelium, belongs to preneoplastic diseases. Patients with such pathology need regular medical check-up with carrying out regular endoscopic control. Treatment. Great role in treatment of chronic gastritis belongs to diet. During exacerbation period it is necessary to exclude products, which need long digestion and irritate mucous membrane of the stomach (rich meat soups, spices, fried meat, refractory fats and others). Patients with normal and increased secretion of hydrochloric acid in presence of pain syndrome need prescription of antisecretory agents, antacids and gastric mucosa protectant. In case of revealing of HP it is necessary to carry out antihelicobacter treatment. It is recommended long intake of substitutive agents (tablets of acidin-pepsin, abomin and others) to the patients with chronic gastritis with secretory insufficiency. Sanatorium-and-spa treatment is indicated during remission period. Prophylaxis of appearance and progressing of chronic gastritis foresees observance of correct eating pattern, struggle against smoking and alcohol intake, carrying out timely oral cavity sanation, revealing and treatment of other diseases of digestive apparatus.

PEPTIC ULCER DISEASE Peptic ulcer disease (morbus ulcerosus) is pathologic process based on stomach or duodenum mucous membrane inflammation with its local erosive damage due to infectious or non-infectious mechanism as response to impaired endogenous balance between local factors “aggression” and “prevention”. Etiology and pathogenesis. Now etiology and pathogenesis of peptic ulcer disease are studied insufficiently yet. Disturbance of regimen and character of feeding ( long breaks between food intakes, dry food, propensity to rough and piper food and others), nervous- psychical overstrains and physical overworks, smoking and alcohol abuse, constitutional and genetic factors (asthenic type of constitution, hereditary predisposition to peptic ulcer disease, 0 (I) blood group etc.), intake of medicines with ulcerogenous properties (salicylates, glucocorticoids and others) are factors, promoting to development of appearance of this disease. During last years connection of disease development with microorganisms Helicobacter pylori was proved: these bacteria are revealed in 90-95% of patients with duodenal ulcers and in 70% of patients with gastric ulcers. Pathogenesis of peptic ulcer disease is complex. In a few words it comes to imbalance between aggressive properties of gastric juice and protective resources of mucous membrane of the stomach and duodenum. Aggressive factors of ulcer formation include the following: hypersecretion of hydrochloric acid and pepsin, motor disorders of the stomach and duodenum (acceleration of evacuation from the stomach or, contrary, delay of acid content in its antral portion, duodeno-gastral reflux of bile). Intensification of factors of acid-peptic aggression play dominant role in development of peptic ulcer disease with localization of defect in bulb of duodenum. Decrease of resistance of mucous membrane of the stomach and duodenum occurs in case of diminishing of gastric mucus production and disorder of its qualitative composition, diminishing of pancreatic bicarbonates production, disorder of regenerative process of epithelial cells of mucous membrane of the stomach and duodenum, impairment of its blood supply. Decrease of protective properties of mucous membrane has the main importance in development of peptic ulcer disease with localization of defect in the stomach. Hormonal factors (sexual hormones, hormones of cortical layer of adrenal glands, gastrointestinal peptides), prostaglandins, biogenic amines (catecholamines, histamine, serotonin), immune mechanisms can take part in pathogenesis of peptic ulcer disease.

CLINICAL CLASSIFICATION OF THE PEPTIC ULCER DISEASE

1. Localization of peptic ulcer:  gastric ulcer ;  duodenal ulcer (bulbar, postbulbar);  combined gastric and duodenal ulcers;  gastrojejunal ulcer (ulcer of anastomosis), 2. Etiology:  Нр - positive ulcer;  Нр - negative ulcer;  medicinal;  stressful;  in endocrinopathologic diseases (Zollinger-Ellison syndrome, hyperparathyroidism);

 in Crohn’s disease, lymphoma or sarcoidosis;  in diseases of internal organs (cardiac failure, heaptocirrhosis, chronic non-specific pulmonary diseases);  idiopathic;

 mixed (Нр + other determined etiological factor); 3. Stages of ulcer process:  active (acute);  cicatrizing;  cicatrix stage;  indolent ulcer. 4. Accompanying morphofunctional changes:  Localization and activity of a gastritis and duodenitis;  Presence and degree of expressiveness of atrophy of mucous membrane;  Presence intestinal metaplasia;  Presence of erosions, polyps;  Presence gastroesophageal or duodenogastralis refluxes;  The characteristic of secretory and motor functions. 5. Complications (bleeding, perforation, penetration, stenosis, malignization).

Clinical picture. Pains which are localized in left part of epigastrium (in ulcers of stomach body) or right part of epigastrium (in pyloric ulcers or duodenal bulb ulcers) are the main symptoms of exacerbation of peptic ulcer disease. In ulcers of subcardial portion of the stomach pains can be localized in area of xiphoid process, in extrabulbar ulcers (ulcers of postbulbar part of duodenum) - in right hypochondrium. Pains often irradiate into left half of thorax, thoracic or lumbar part of spinal column. During exacerbation of peptic ulcer disease pains usually is connected distinctly with food intake. In ulcers of subcardial portion of the stomach they often occur right after food intake, in ulcers of body stomach - in 30 minutes-1 hour after food intake. In case of ulcers of pylorus and bulb of duodenum late pains, appearing in 2-3 hours after food intake, hunger and night pains occur most often. It is typically, that pains in peptic ulcer is relieved usually after intake of antacids, antisecretory preparation or applying of the hot-water bag. During exacerbations of peptic ulcer disease, which have seasonal character often (in autumn and in spring), dyspeptic signs are marked often also. In many patients acid gastric content vomiting, resulting to relief, occurs at the height of the pains. Therefore patients can provoke it artificially. Complaints of heartburn, nausea, eructation constipation occur often also. Loss of body weigh is observed during exacerbation often because of patients in spite of normal or increased appetite limit themselves in the food, fearing of pains increasing (sitophobia). But described typical clinical picture of peptic ulcer disease exacerbation isn’t marked in all patients. In some patients (with symptomatic ulcers particularly) pain syndrome can be absent and disease is manifested suddenly by means of their complications (bleeding and perforation). During palpation of the abdomen local tenderness and moderate resistance of muscles of anterior abdominal wall can be marked in patients with exacerbation of peptic ulcer disease. Sometimes limited area of percussion tenderness (Mendel symptom) is revealed in the same places (in epigastrium or pylorobulbar area).

Syndromes, occurring in peptic ulcer disease*:

 Pain syndrome  Dyspeptic syndrome  Asthenovegetative. * Syndromes are analyzed in detail during lecture course

Clinical blood analysis is unchanged in majority of patients. Only in some patients increasing of hemoglobin and erythrocytes content in the blood is marked. Anemia is revealed more often; it is sign of frank or occult bleedings. Occult blood feces analysis has certain diagnostic importance. Recurrent positive Gregersen or Veber reactions can direct to exacerbation of disease at condition of their correct performing and excluding of other hemorrhage origins. Research of acid-forming function of the stomach play certain pole for diagnostics. In duodenal ulcers increased indices of basal and stimulated secretion of hydrochrolic acid is revealed, in ulcers of subcardial portion and body stomach -normal or decreased. Revealing of histamine-stable achlorhydria usually excludes diagnosis of duodenal ulcer and force to doubt in benign character of gastric ulcer. Leading place in diagnostics of peptic ulcer disease belongs to X-ray and endoscopic methods of research. They often supplement each other. During X-ray study direct sign of ulcer - niche on circuit (Haudek’s niche) or relief of mucous membrane of the stomach and duodenum is revealed and different indirect symptoms of disease is reveled. They are: local circular spasm of smooth-muscular fibers as “pointing finger” on gastric wall, opposite to ulcer; convergence of mucous membrane folds to niche; cicatricial-ulcerous deformity of the stomach and duodenum; hypersecretion of gastric juice fasting, disorders of gastro-duodenal motor activity. During endoscopic research presence of ulcer is confirmed, its localization, form, depth and sizes become more exactly, condition of fundus and brims of the ulcer is analyzed, character of accompanying changes of mucous membrane of the stomach and duodenum is made clear. Presence of Helicobacter pylori infection is examined necessary in revealing of peptic gastric or duodenal ulcer. In case of revealing of ulceration in the stomach it is necessary to perform differential diagnostics between benign ulcers and infiltrative-ulcerous (primary-ulcerous) type of gastric carcinoma, which during initial stages can be taking its course as benign lesion. Its large sizes (in young persons particularly), ESR elevation and histamine-resistance achlorhydria testify about malignant genesis of ulcer. During X-ray study and endoscopy infiltrative-ulcerous type of gastric carcinoma is characterized by incorrect form of ulceration with irregular and tuberous edges, rigidity of gastric wall in this part. Final conclusion about character of lesion is made after repeat histological study of ulcerous biopsy material. Course and complications. Strict periodicity of the course is typical, as a rule, for uncomplicated cases of peptic ulcer disease. Periods of disease exacerbation (with length from 3- 4 to 6-8 weeks and more) alternate with more or loss long (from some months to some years) periods when patient feels well. In case of diet keeping, organization of correct day regimen, carrying out systematic prophylactic antirecurrent treatment remission of peptic ulcer disease can be persistent and exacerbations of disease occur rarely. On the contrary, it is possible development of various complications under influence of various unfavorable factors (athletic over exertion, alcohol abuse). Ulcerous bleeding occurs in 15-20% of the patients (in patients with symptomatic gastric ulcers particularly) and manifested by coffee-grounds vomiting or dark tarry stool (melena) and number of general symptoms (weakness, dizziness, tachycardia, decrease of blood pressure, loss of consciousness. Perforation - forming of total defect in the gastric wall on the place of its ulcerous lesion is marked in 5-15% of the patients, in men more often. Clinically perforation is manifested by intensive (knife-like) pains in epigastrium, development of collapse. During palpation of abdomen full-blown tenderness in epigastrium and expressive wooden muscular tension of anterior abdominal wall, symptoms of perineum irritation (Blumberg sign) are revealed. In further picture of diffuse peritonitis is developed. Permeation of gastric or duodenal ulcer into surrounding tissues (pancreas, lesser omentum etc.) is named penetration. Occurrence of ulcerous penetration is characterized by appearance of constant pains (for example, in lumbar region in penetration of ulcer into pancreas), loss of past interaction of pains with food intake, elevation of body temperature to mild pyrexia, elevation of ESR. Presence of ulcerous penetration is confirmed during X-ray and endoscopic research. When development of commissural process between stomach and duodenum and neighboring organs (pancreas, liver, gall bladder, etc.) occurs, it is accepted to say about perivisceritis (perigastritis, periduodenitis). In case of appearance of perivisceritis more intensive pains occur; they become more intensive after plentiful meal, on physical exertion, at the change of body position. During X-ray and endoscopy expressive deformation of stomach and duodenum with limitation of their motor activity is marked. Scarring of ulcers of pylorus and initial portion of duodenum and operation perforated ulcer closure in this region can result to development of cicatricial-ulcerous pyloric stenosis. Feeling of heaviness and overfilling in epigasrtium after food intake are first signs of pyloric stenosis. In development of pyloric stenosis foul-smelling eructation and vomiting by food eaten the day before are added to foregoing complaints. During examination of the patients late splashing sound (Vasilenko symptom) is revealed often in epigastrium. Disorder of evacuatory function of the stomach is diagnosed during X-ray study more exactly. Malignization of benign gastric ulcer is considered before as relatively often complication of disease. Now it is ascertained that probability of malignization of gastric ulcers is exaggerated largely. Until now cases of infiltrative-ulcerous type of gastric carcinoma is taken as malignization of ulcer often. Diagnostics of this complication of peptic ulcer disease is sometimes very difficult. In some cases it is possible to reveal change of initial course of peptic ulcer disease, loss of periodicity of exacerbations, connection of appearance of the pains with food intake, particularly. Final conclusion about presence of ulcer malignization (and absence of primary-ulcerous type of gastric carcinoma) can be made only after histological research of whole ulcer, that it is possible only after operative intervention. Treatment. Patients with uncomplicated course of peptic ulcer disease are treated by conservative treatment. It carried out by means of certain principle. During exacerbation of disease it is reasonable hospitalization of patients in therapeutic or gastroenterological department with following transfer to rehabilitation department or continuation of ambulant therapy. Complex antiulcerous therapy includes diet, based on principles of mechanical, chemical and thermal sparing of mucous membrane of the stomach, prescription of medicaments (antacids, proton pomp inhibitors, H2 receptors antagonists). In revealing of H. pylory- obligatory H. pylori eradication therapy must be carried out. After stop of symptoms of exacerbation and scarring of the ulcer patients must be under regular medical check-up. During period of potential exacerbation of disease (in spring and in autumn) courses of prophylactic antirecurrent treatment with length 1,5-2 months, allowing to diminish frequency and length of following exacerbation, must be carried out. Absolute indications to surgical treatment: perforation of ulcer, malignization, cicatricial- ulcerous pyloric stenosis. Relative indications: penetrative and recurrently bleeding ulcers, and severe course of peptic ulcer disease with frequent recurrences when conservative therapy is effective insufficiently. Now organ-preserving operations are preferable. They have less of postgastroresection disorders. Prophylaxis of peptic ulcer disease includes organization of correct eating pattern, day regimen, struggle against smoking and alcohol abuse, revealing and treatment of persons, which have increased risk of peptic ulcer disease development (with hereditary predisposition, functional gastric hypersecretion, gastroduodenitis with increased acid production).

MALABSORPTION SYNDROME Malabsorption syndrome - symptom complex, appearing due to disorder of absorption processes in small intestine. It is combined often with maldigestion syndrome. Etiology and pathogenesis. There are primary and secondary malabsorption syndromes. A primary malabsorption syndrome is developed as result of inherited disorders of thin structure of mucous membrane of intestinal wall and intestinal enzymopathy, determined genetically. A secondary malabsorption syndrome is developed due to acquired structural changes of mucous membrane of small intestine (acute and chronic enteritis, suddenly accelerated passage of small intestine’s contents, resection of small intestine and others). In case of acute or subacute states disorders of intraintestinal digestion of food and accelerated passage of contents along bowels (when time of contact of contents, passing from stomach, with absorpting surface of bowels is decreased) have the main importance; in chronic ones - dystrophic, atrophic and sclerotic changes of epithelium and proper layer of mucous membrane of intestinal wall, shortening and flattening of villi and crypts, metaplasia of prismatic intestinal epithelium (which has absorption ability) into one, secreting mucus, sudden diminishing of microvilli amount, development of fibrous tissue in intestinal wall with disorders of blood circulation and lymph circulation and processes of parietal digestion in it. Foregoing changes result to insufficient entering of protein hydrolysis products, fat hydrolysis products, carbohydrates hydrolysis products, mineral salts and vitamins through intestinal wall into organism and to development of alimentary dystrophy. Malabsorption of food promotes to intensive generalization of microflora in small intestine (intestinal dysbacteriosis), that make worse intestinal digestion and absorption, disturbs intestinal peristalsis. Clinical picture. Gradual cachexia of the patient is typical. Symptoms of metabolic imbalance (of protein, lipid, vitamins, water-salt), dystrophic changes of internal organs with their dysfunction, arising gradually, and diarrhea, steatorrhea, creatorrhea and amylorrhea are observed. Hypoproteinemia due to decrease of albumins contents in blood serum mainly, hypercholesterolemia, hypocalcaemia, moderate hypoglycemia are developed. Hypoproteinemic edemas occur in case of hypoproteinemia less than 4-5g%. Symptoms of polyhypovitaminosis, osteoporosis, anemia (hypochromic - in malabsorption of iron mainly and hyperchromic - in malabsorption of vitamin B12), trophic changes of the skin, nails, progressing muscular atrophy, signs of endocrine glands insufficiency, general weakness, in severe cases - acidosis, cachexia are typical. Laboratory methods allow to reveal hypoproteinemia and other disorders, which are result of malabsorption in intestine. During stool tests increased excretion of indigested alimentary substances and products of their degradation are revealed. Enterobiopsy allows to reveal atrophic changes of mucous membrane of proximal parts of small intestine. Various special methods are used for research of absorption processes. They are: iodine-potassium test, D-xylose test, galactose test, iron absorption test and others. During last time methods with using of radiolabeled albumin, oleic acid, methionine, vitamin B12, folic acid and other substances are carried out. Their principle is based on determining of their concentration, time of appearance in the blood, their excretion with urine and residual radioactivity of feces (last one give possibility to judge about amount of unabsorbed substances). Method of jejunoperfusion is used also. Course depends on character of the main disease and possibility of curability. In severe incurable cases prognosis is unfavorable. Treatment. 1. Treatment of the main disease. 2. Replacement therapy (with purpose to compensate malabsorption of products of enzymatic intestinal lysis of alimentary substances and vitamins, ions and trace elements) by means of pareneteral nutrition. It includes introduction of vitamins, plasma, protein hydrolyzates, glucose solution, correction of electrolytic metabolic imbalance. Prophylaxis of disease is in prevention and timely treatment of intestinal diseases, which is taking its course with malabsorption syndrome.

CHRONIC ENTERITIS Chronic enteritis (enteritis chronica) is disease, taking its long course, when inflammatory and dystrophic changes of mucous membrane of small intestine are observed. Etiology and pathogenesis. Chronic enteritis can be developed after acute infectious disease (cholera, salmonelosis) in past, in case of excess (luxury) bacterial growth syndrome, in long alcohol abuse, alimentary allergy, after ionizing radiation exposure, in hereditary enzymopathies (glutenic enteropathy, lactase deficiency), in some other diseases (thyrotoxicosis, collagenous diseases, diseases of stomach, liver and pancreas). Clinical picture. Feces disorders are leading clinical manifestations of chronic enteritis. Usually diarrhea is observed in patients (to 4-6 times a day), besides feces amount is increased and liquid stool, containing non-digested food debris, becomes green-yellow. Constipation or unstable stool with alternation of constipation and diarrhea are marked more rarely. Other complaints can be marked also; they are: pains in paraumbilical area, borborygmus, weight loss, weakness and fatigability. Signs of proteins, fats, carbohydrates, trace elements, vitamins malabsorption (malabsorption syndrome) are revealed objectively. Xerosis, nails fragility, loss of hair, angular stomatitis, signs of glossitis, etc. are marked. Expressed rumble is revealed during palpation of different parts of bowels. Anemia, hypoalbuminemia, hypercholesterolemia, are marked in blood analysis. Neutral fat and fatty acids, muscle fibers, non-digested cellular tissue is revealed in stool tests. During X-ray examination irregularity of small intestine filling by barium meal, change of mucous membrane relief and small intestine motor disorders are revealed. Diagnosis is confirmed during endoscopic examination (intestinoscopy) with morphological research of biopsy material of mucous membrane of small intestine. Course and complications. The course of chronic enteritis is recurrent (with alternation of exacerbation periods and remission periods) mainly. Prognosis for a disease is favorable in majority cases. Only in case of severe course, cachexia, anemia, signs of hypovitaminosis are developed as result of expressed maldigestion and malabsorption. Treatment. Treatment of patients with chronic enteritis includes diet (No 4), intake of enzymatic drugs (festal, panzynorm and others), vitamins and, according to indications, - antibacterial agents, restoration of normal composition of gut organisms (by means of bificol, colibacterin, etc.), sanatorium-and-spa treatment. Prophylaxis of chronic enteritis includes first of all timely and effective treatment of acute enteritis (first of all of infectious etiology), well-balanced diet, struggle against alcohol intake, systematic treatment of other diseases of digestive apparatus. DYSKINESIAS OF LARGE INTESTINE Dyskinesias of large intestine (irritable bowel syndrome) is related to group of functional diseases. They are caused by disorder of large intestine motility regulation. Dyskinesia of large intestine occurs often, but until now incorrect diagnosis is made to such patients frequently. Etiology and pathogenesis. Primary dyskinesias of large intestine are caused by psychogenic factors mainly and occur in persons with increased emotional lability. Other frequent reason is irregular feeding with intake of insufficient amount of plant cellular tissue and sedentary life style also. Secondary dysknesias occur in diseases of other digestive organs (for example, in peptic ulcer disease, chronic cholecystitis), diseases of urinary and endocrine systems. In case of dyskinesias motility function of large intestine suffers and spastic or atonic changes of motor activity of its different parts appear. Clinical picture. Feces disorders (diarrhea, constipation or alternation of diarrhea and constipation), aching or cramp-like pains along large intestine, meteorism, borborygmus - leading manifestations of dyskinesia of large intestine. It is typically, that in many patients with dyskinesia of large intestine directed complaints often are caused by emotional moments and combined with different vegetative disturbances (hyperhidrosis, palpitation, psychogenic dyspnea, face reddening, etc.). General condition of the patients with dyskinesia of large intestine usually isn’t changed. During palpation of abdomen it is possible to reveal spastically contracted and slightly painful different parts of large intestine, rambling. In stool tests essential changes, as a rule, aren’t revealed. Diagnosis of dyskinesia of large intestine is made after excluding of its organic diseases. During proctosigmoidoscopy normal mucous membrane of rectum and sigmoid is revealed in these patients, during irrigoscopy - only large intestine motor disorders (spastic contractions, interrupted filling, etc.) without changes of relief of its mucous membrane. Course and complications. The course of dyskinesia of large intestine during long period can be favorable. Sometimes in time organic changes of large intestine (signs of chronic colitis more often) can be added. Treatment. Treatment of the patients with dyskinesia of large intestine consists, first of all, in organization of rational diet and correct life-style with alternation of work and active rest. Intake of sedative drugs can be effective. According to indications drugs, normalizing motility of large intestine (for example, spasmolytics or prokinetics) are used. Prophylaxis of functional diseases of large intestine comes to strengthening of nervous system, correct feeding, systematic going in for sport and physical culture. It is necessary timely diagnostics and adequate treatment of accompanying diseases of digestive apparatus. CHRONIC COLITIS Chronic colitis (colitis chronica) is disease, taking its long course, when inflammatory and dystrophic changes are developed in mucous membrane of large intestine mainly. Etiology and pathogenesis. Reasons, promoting to appearance of chronic gastritis, are varied. In number of cases this disease is result of acute colitis (of infectious origin most often - in bacillary dysentery, amebiasis, salmonellosis) in past. Parasitic diseases (for example, helminthiasis), long heavy metals intoxication, some other diseases when toxic substances discharge by mucous membrane of large intestine (chronic renal failure, particularly) occurs, can lead to development of chronic colitis also. Maldevelopment of large intestine (dolichosigmoid, megacolon), atherosclerotic lesions of intestinal vessels (ischemic colitis), irradiation (radiation colitis), alcohol abuse, alimentary allergy, long intake of some drugs can be also predisposing factors. Maldigestion and malabsorption in small intestine, occurred in case of enteritis, result to entering of insufficiently digested contents into large intestine. It can cause development of inflammatory changes in mucous membrane. In these cases term “enterocolitis” is used often. Secondary (symptomatic) colitis occurs in other diseases of digestive system (chronic cholecystitis, hepatitis and others). Clinical picture. Pains along large intestine, usually decreased after defecation and passage of gases, feces disorders (constipation, diarrhea or their alternation), meteorism, borborygmus, tenesmus (in involving of mucous membrane of rectum into process), general complaints (increased irritability, poor spirits and others) are the most often complaints. In chronic colitis general condition of the patient isn’t changed essentially and significant loss of body weigh doesn’t occur usually (in contrast to condition in case of chronic enteritis). During palpation of abdomen tenderness and spastic contractions of different parts of large intestine are marked. During stool tests mucus, erythrocytes, leukocytes, sometimes - eggs of helminthes and cysts of protozoa are revealed. Disbacteriosis is revealed often in inoculation of medium (of intestinal contents). During irrigoscopy change of mucous membrane relief, asymmetrical haustrations, different motor disorders are marked in patients with chronic colitis. More exact diagnostics of chronic gastritis (revealing of edema and hyperemia of mucous membrane of large intestine, petechial hemorrhages, atrophic changes) is possible during endoscopic examination (proctosigmoidoscopy and colonoscopy). Course and complications. The course of chronic colitis, as a rule, is relatively favorable and characterized usually by alternation of exacerbation periods and remission periods. Complications of chronic colitis is connected with adding of accompanying lesions of other organs of digestive apparatus, appearance of commissural process in abdominal cavity (pericolitis) in case of long course, bleeding and perforation of intestinal wall in ulcerative types of lesion. Treatment. It must be complex. It includes diet, prescription of astringents and “coating” drugs, drugs, normalizing function of large intestine, physiotherapeutic procedures. According to indications antibacterial and antihelminthic preparations are used. Sanatorium-and-spa treatment is recommended during remission period. Prophylaxis of chronic colitis comes to prevention and timely treatment of acute intestinal infection, revealing and liquidation of helminthes - carrying, well-balanced diet.

A. Test tasks to be done: 1 block -with a single selective answer – I-st level: 1. Long time for neutralization of increased acid content, which passes into duodenum, and for reflectory open of pylorus in the patients with syndrome of increased secretory function of the stomach is the cause of: a) diarrhea; b) eructation; c) constipation; d) nausea; e) vomiting. 2. What is the cause of foul-smelling eructation in the patients with syndrome of decreased secretory function of the stomach? a) long time for neutralization of increased acid content, which passes into duodenum; b) pyloric opening (gaping); c) increased of antibacterial action of gastric juice; d) decreased of antibacterial action of gastric juice; e) putrefaction and putrefactive fermentation in the stomach. 3. How many hours is the food mixed in the stomach normally? a) 0,5-1 hour; b) 1-2 hours; c) 2-3 hours; d) 3-10 hours; e) 5-12 hours. 4. What food is evacuated from the stomach most swiftly? a) protein; b) lipid; c) carbohydrate; d) without any difference. 5. Which type of chronic gastritis is caused by Нelicobacter руlori (H.p.) and characterized by inflammation of a mucous membrane of pylorus at first: a) type A gastritis; b) type B gastritis; c) reactive gastritis; d) granulomatous gastritis; e) eosinophilic gastritis. 6.How is the reflux - gastritis called now? a) type A gastritis; b) type B gastritis; c) reactive gastritis; d) granulomatous gastritis; e) eosinophilic gastritis. 7. What syndrome is caused by secretory insufficiency of the stomach and secondary depression of secretion of pancreas and intestine, depression of cholecystokinetic reflex? a) pain syndrome; b) syndrome of gastric dyspepsia; c) syndrome of intestinal dyspepsia; d) syndrome of asidism; e) dumping syndrome. 8. For which type of chronic gastritis is the syndrome of acidism (acid dyspepsia) typical: a) type A gastritis; b) type B gastritis; c) reactive gastritis; d) granulomatous gastritis; e) eosinophilic gastritis. 9. Hypotension, cardialgia, and arrhythmia are manifestations of the following syndrome: a) asthenoneurotic syndrome; b) syndrome of cardiovascular disturbances; c) dumping syndrome; d) syndrome of gastric dyspepsia; e) syndrome of asidism. 10. In patients with chronic gastritis tongue is usually: a) furred; b) fissured; c) clear; d) black hairy ; e) brightly red. 11. What semiology can be developed in case of increase of gastric secretion in patients with gastritis caused by Helicobacter pylori? a) like-esophagitis; b) like-ulcer; c) like-cancer of the stomach; d) like -cholecystitis; e) like- pancreatitis. 12. The gold standard of diagnostics of chronic gastritis is: a) X-ray examination of the gastrointestinal tract; b) ultrasound research; c) fibrogastroduodenoscopy (FGDS); d) fibrogastroduodenoscopy (FGDS), in combination with multiple biopsy especially; e) study of gastric secretion by means of fractional method. 13. How many bits of biopsy material should be taken from the stomach for verification of gastritis optimally? a) not less than 2; b) not less than 3; c) not less than 4; d) not less than 5; e) not less than 10.

Block 2. -with a single selective answer – I-st level; 1. What is the main symptom in peptic ulcer disease? a) diarrhea; b) eructation; c) pain; d) constipation; e) palpitation. 2. Early pain in epigastrium is typical for: a) peptic ulcer disease of the stomach; b) peptic ulcer disease of duodenum; c) chronic gastroduodenitis; d) chronic duodenitis; e) chronic esophagitis. 3. What is early pain in epigastrium? a) occurring 2-5 min after meals; b) occurring 30-40 min after meals; c) occurring 40-60 min after meals; a) occurring 90-120 min after meals; b) which is abated after taking food. 4. Late, nocturnal and hunger pain is typical for: a) chronic gastritis type A; b) peptic ulcer disease of the stomach; c) peptic ulcer disease of duodenum; d) chronic reactive gastritis; e) chronic pancreatiits. 5. What is late pain in epigastrium? a) occurring 4-6 hours after meals; b) occurring 30-40 min after meals; c) occurring 40-60 min after meals; d) occurring 90-120 min after meals; a) pain after vomiting. 6. Is constant pain in epigastrium for non-complicated peptic ulcer disease typical? a) yes, it is; b) no, it isn’t; c) it is typical only for gastric ulcers; d) it is typical only for duodenal ulcers; a) it is typical only for depth ulcers. 7. Great role in etiology of peptic ulcer disease belongs to: a) viral infection; b) Helicobacter pylori; c) Staphylococcus; d) Streptococcus; e) Koch’s bacillus. 8.Clinical urine analysis in patients with peptic ulcer disease (without accompanying pathology) has the following result: a) leukocyturia; b) erythrocyturia; c) proteinuria; d) glucosuria; e) without pathology. 9. There is the following direct sign of ulcer during X-ray study: a) local circular spasm of smooth-muscular fibers as “pointing finger” on gastric wall, opposite to ulcer; b) convergence of mucous membrane folds to niche; c) niche on circuit (Haudek’s niche) or relief of mucous membrane of the stomach and duodenum; d) cicatricial-ulcerous deformity of the stomach and duodenum; e) hypersecretion of gastric juice fasting. 10. What is abdomen in patient with ulcer perforation? a) frog-like abdomen; b) pendulous abdomen; c) wooden abdomen; d) scaphoid abdomen; e) tympanic abdomen. 11. Diagnosis of chronic enteritis is confirmed by means of: a) irrigoscopy; b) proctosigmoidoscopy; c) colonoscopy; d) intestinoscopy; e) ultrasound examination. 12. Dyskinesia of large intestine is called also: a) chronic enteritis; b) chronic colitis; c) irritable bowel syndrome; d) Crohn’s disease; e) nonspecific ulcerative colitis. 13. The following sign is revealed during irrigoscopy in patients with irritable bowel syndrome: a) motor disorders of large intestine; b) change of mucous membrane relief; c) asymmetrical haustrations; d) edema and hyperemia of mucous membrane; e) petechial hemorrhages.

Block 3 -with the selective group of right answers – the II-nd level; 1. What symptoms are typical for syndrome of increased secretory function of the stomach (hypersecretion)? a) heartburn; b) acid eructation; c) suppressed appetite; d) diarrhea; e) constipation; f) increased appetite often; g) sometimes spastic pain in pyloroduodenal area; h) feeling of heaviness in epigastric area. 2. What changes of laboratory indexes of fraction research of gastric content is revealed in the patients with syndrome of increased secretory function of the stomach? a) increased level of free HCl in gastric juice; b) level of free HCl in basal secretion is more than 40 T.U. (titrametric units); c) level of free HCl in basal secretion is more than 10 T.U.; d) level of free HCl in basal secretion is less than 20 T.U.; e) free HCl discharge (output) in basal secretion is less than 1,4 mmol/h; f) free HCl discharge (output) of basal secretion is more than 2,7 mmol/h; g) stimulated secretion of free acid(according to Leporsky) is more than 45T.U.; h) stimulated secretion of free acid according to Leporsky is less than 20T.U.; i) stimulated (according to Leporsky) free HCl discharge (output) is more than 4,4 mmol/h. 3. What symptoms are typical for syndrome of decreased secretory function of the stomach (hyposecretion)? a) suppressed appetite; b) feeling of heaviness in epigastric area; c) acid eructation; d) heartburn; e) diarrhea often; f) foul-smelling eructation; g) sometimes spastic pain in pyloroduodenal area; h) feeling of heaviness in epigastric area. 4. What are the main causes of diarrhea in the patients with decreased secretory function of the stomach? a) long time for neutralization of increased acid content, which passes into duodenum; b) long time for reflectory open of pylorus; c) pyloric opening (gaping); d) increased of antibacterial action of gastric juice; e) decreased of antibacterial action of gastric juice; f) chalasia of cardiac opening; g) putrefaction and putrefactive fermentation in the stomach. 5. What do influences on motor function of the stomach? a) irritation of vagus nerve; b) glucagon; c) gastrin, cholecystokinin, motilin; d) somatostatin; e) character of food; f) insulin; g) irritation of phrenic nerve; h) irritation of vertebral nerve. 6. What are the main clinical signs of syndrome of accelerated evacuation of the food from the stomach? a) feeling of hunger right after food intake; b) diarrhea; c) constipation; d) abdominal distension; e) reflux-gastritis; f) foul-smelling eructation; g) hypovitaminosis; h) decrease of protein provision of organism; i) feeling of spasms in epigastrium. 7. What factors reduce evacuation from the stomach? a) irritation of mechanical receptors of duodenum; b) pH of duodenum more than 5,5; c) pH of duodenum less than 5,5; d) products of fat hydrolysis; e) irritation of vagus nerve; f) glucose; g) cholecystokinin. 8. What are the main clinical manifestations of stomach hypertonia syndrome? a) feeling of spasms in epigastrium; b) overfilling of stomach sensation; c) fast satiation after some spoon of food; d) heartburn; e) regurgitation of food; f) spastic pain in epigastrium of various intensity (in case of gastritis or peptic ulcer); g) subjective feeling of splash in epigastrium. 9. By means of which methods is the stomach hypertonia syndrome diagnosed? a) endoscopy; b) X-ray examination of gastrointestinal tract; c) electrogastrography; d) ultrasound examination; e) endogastric pH-metry; f) computed tomography; g) magnetic resonance imaging. 10. What are X-ray signs of hypertonia stomach syndrome? a) little stomach; b) stomach as hook; c) big gastric air bubble; d) stomach as sac; e) stomach is filled by barium suspension bottom-up; f) hourglass stomach. 11.There are the following types of chronic gastritis according to Houston (USA, 1996) classification: a) nonatrophical (type B); b) hyperacidic gastritis; c) atrophical (type A); d) hypoacidic gastritis; e) anacidic gastritis; f) special forms of gastritis. 12. Nonatrophical gastritis is also called: a) autoimmunal gastritis; b) multifocal gastritis; c) helicobacterial gastritis; d) chronic antral gastritis; e) gastritis of type В; f) gastritis of type A; g) eosinophilic gastritis; h) reactive gastritis. 13. There are following types of chronic gastritis according to topography of lesion: a)antral gastritis; b) erosive gastritis; c)corrosive gastritis; d) fundal gastritis; e)pangastritis; f) superficial gastritis; g) phlegmanous gastritis. 14. What are peculiarities of pain syndrome in the case of chronic gastritis of type A? a) pains are intensive, cramping; b) pains are localized behind sternum, in epigastrium, pyloroduodenal zone; c) pains have dull, aching character; d) pains are accompanied by feeling of heaviness, pressing in epigastrium or behind sternum; e) late character of the pains; f) pains appear shortly after meal; g) pains are monotonic, long, without irradiation; h) high effectiveness of cholinergic antagonists, spasmolytics and antacids; i) diminishing of the pains after use of coating drugs. 15.Decrease of secretory and acid-forming function of the stomach is manifested by syndromes of: a) gastric dyspepsia; b) syndrome of acidism; c) dumping syndrome; d) intestinal dyspepsia; e) syndrome of cardiovascular disturbances; f) asthenoneurotic syndrome. 16.Syndrome of gastric dyspepsia is manifested by: a) feeling of distension, causing to burst in abdomen; b) decrease of appetite; c) unpleasant taste in the mouth; d) eructation; e) borborygmus, gurgle in abdomen; f) migrate pains in paraumbilicus area; g) diarrhea. 17.Malabsorbtion syndrome is manifested by: a) decrease of appetite; b) unpleasant taste in the mouth; c) weight loss; d) feeling of distension; e) hypovitaminosis; f) hypoproteinemia; g) migrate pains in paraumbilicus area h) anemia and electrolytic disturbances. 18.Syndrome of asidism (acid dyspepsia) is manifested by: a) constant sour taste in the mouth; b) decrease of appetite; c) feeling of distension; d) migrate pains in paraumbilicus area e) acid eructation; f) heartburn; g) vomiting of acid masses; h) spastic constipation often. 19.What signs of hypovitaminosis is it possible to reveal in chronic autoimmune gastritis with syndrome of insufficiency of digestion and absorption (maldigestion and malabsorption): a) angular fissures; b) heartburn; c) gingival hemorrhage; d) fragility of nails; e) vomiting; f) hyperkeratosis; g) premature loss of hair; h) acrocyanosis. 20.Invasive methods of diagnostics of Helicobacter pylori include the following: j) histological; k) breath test with urea. l) fast ureasis test; m) bacteriological; n) serological; o) pH-metry; p) inspection.

Block 4. with the selective group of right answers – the II-nd level; 1. What are characteristics of the pain in peptic ulcer disease? a) it has periodical character; b) its close connection with food intake is observed; c) its close connection with physical exertion is observed; d) it is accompanied always by vomiting; e) often it has increased character; f) stop or diminishes after vomiting, intake of sodium hydrocarbonatis, using of heat, cholinolytics; g) stop or diminishes after nitroglycerine intake; h) seasonal character is marked. i) it doesn’t have seasonal character. 2. What is first aid for stopping of nocturnal pain in patients with duodenal peptic ulcer? a) food intaking; b) drinking of isotonic solution; c) drinking of sodium hydrocarbonatis solution; d) nitroglycerine intaking; e) applying of ice bag; f) applying of mustard plasters; g) occupying ortopnoe position. 3. Appearance of constant pain in epigastrium in patient with ulcerous anamnesis can testify about: a) development of perivisceritis; b) development of penetration; c) reflux esophagitis; d) development of ulcer malignization; e) development of accompanying gastroduodenitis; f) scarring of ulcer; g) incorrect diagnosis in past and absence of peptic ulcer disease. 1. There are following factors, promoting to appearance of peptic ulcer disease: a) disturbance of regimen and character of feeding; b) nervous-psychical overstrains and physical overworks; c) overcooling; d) smoking and alcohol abuse; e) contact with persons with viral infection; f) constitutional and genetic factors; g) intake of medicines with ulcerogenous properties; h) “sitting” profession. 2. Aggressive factors of ulcer formation include the following: a) hyperproduction of hydrochloric acid and pepsin; b) H. pylori bacterium; c) active cellular regeneration; d) traumatization of mucosa of gastroduodenal zone; e) generated cytoprotective substances, such as prostaglandins, fucosa, N-acetylneuraminic acid; f) motor disorders of the stomach and duodenum; g) superficial epitelium and mucous-bicarbonatic barrier; h) number of immune mechanisms of protection. 6. In order to describe the pain in patients with peptic ulcer disease it is necessary the detail description: a) location of the pain; b) duration of the pain; c) character of the pain; d) its connection with meals; e) its connection with profession of the patient; f) radiation of the pain; g) relieving factors; h) possible connection between pain and physical strain; 7. In superficial tentative oriental palpation and percussion of abdomen (in patient with peptic ulcer disease) the following can be distinguished: a) pain in epigastrium and umbilical regions; b) local muscular resistance; c) positive diastesis recti symptom; d) positive fluctuation symptom; e) negative diastesis recti symptom; f) negative fluctuation symptom; g) diffuse muscular resistance. 8. What complications of peptic ulcer disease do you know? a) bleeding; b) reflux-esophagitis; c) punching (perforation); d) penetration; e) pyloroduodenal stenosis; f) chronic pancreatitis; g) malignization; h) resection. 9. There the following signs of gastrointestinal bleeding: a) anemia; b) sudden intensive knee-like pain in epigastrium area; c) melena; d) accelerated ESR; e) sensation of the stomach overflow; f) vomiting by “coffee grounds”; g) mild pyrexia. 10. Signs of punching (perforation) include the following: a) melena; b) sudden intensive knee-like pain in epigastrium area; c) heartburn; d) collapse; e) muscular resistance of the anterior abdominal wall; f) vomiting by “coffee grounds”; g) delay of gases; h) positive Blumberg sign. 11. Signs of penetration include the following: a) intensive, constant pain in abdomen; b) sudden intensive knee-like pain in epigastrium area; c) vomiting by food; d) moderated leukocytosis; e) accelerated ESR; f) eructation sour; g) mild pyrexia; h) bradycardia. 12. Signs of pyloroduodenal stenosis include the following: a) sudden intensive knee-like pain in epigastrium area; b) sensation of the stomach overflow; c) heartburn; d) melena; e) eructation sour; f) postive Blumberg sign; g) vomiting by food. 13. During endoscopic research of the patient with peptic ulcer disease: a) presence of ulcer is confirmed; b) direct sign of ulcer - niche on circuit (Haudek’s niche) or relief of mucous membrane of the stomach and duodenum is revealed; c) localization, form, depth and sizes of ulcer become more exactly; d) condition of fundus and brims of the ulcer is analyzed; e) character of accompanying changes of mucous membrane of the stomach and duodenum is made clear; f) stomach acid secretory function is researched. 14. Chronic enteritis can be developed: a) after acute infectious disease in past; b) in persons with increased emotional lability; c) in case of excess (luxury) bacterial growth syndrome; d) in long alcohol abuse; e) in alimentary allergy; f) after ionizing radiation exposure; g) in case of irregular feeding with intake of insufficient amount of plant cellular tissue; h) in hereditary enzymopathies; i) in diseases of stomach. 15. The following complaints can be signs of chronic enteritis: a) diarrhea; b) constipation; c) alternation of constipation and diarrhea; d) pains in paraumbilical area; e) pains in epigastrium; f) borborygmus; g) nausea; h) weigh loss. 16. Potential results of blood analysis and feces analysis in patient with chronic enteritis: a) hyperalbuminemia; b) hypoalbuminemia; c) hypercholesterolemia; d) anemia; e) positive Gregersen test; f) erythrocytes in stool tests; g) neutral fat and fatty acids in stool tests; h) muscle fibers in stool tests; i) non-digested cellular tissue in stool tests. 17. The following complaints are typical for chronic colitis: a) pains along large intestine; b) constipation, diarrhea or their alternation; c) nausea; d) meteorism; e) vomiting; f) borborygmus; g) tenesmus; h) heartburn. 18. More exact diagnostics of chronic colitis is possible by means of: a) proctosigmoidoscopy; b) ultrasound examination; c) colonoscopy; d) intestinoscopy; e) gastroduodenoscopy; f) blood analysis; g) urine analysis.

B. Tasks to be done: 1st Block Task 1. Patient F., 52 years old complains of vomiting, which more often is observed in the morning on empty stomach. Vomit mass are sour, light, contain large amount of mucus. They don’t have food debris, eaten the day before. For which disease such vomiting is typical? a) Peptic ulcer disease; b) Atrophic gastritis; c) Neurosis of the stomach; d) Alcohol gastritis; e) Carcinoma of the stomach. Task 2. Coprological research was carried out to the patient S., which complains of mild pains and feeling of heviness in epigastrium after food intake. Macroscopically feces is porridge-like, brown, with putrefactive odor, pH-8,4. Microscopy: little lumps of connective tissues, many muscle fibers with transversal banding. In case of which disease such results are the most probable? a) Diseases of the liver and biliary tract with deficiency of bile; b) Chronic atrophic gastritis; c) Chronic enteritis; d) Chronic pancreatitis; e) Chronic spastic colitis. Task 3. Patient H. complains of constant pains in epigastrium, intensified after food intake. Questions to task 3: 1. What can be reason of appearamce of constant pains in epigastrium? 2. Explain the cause of intensifying of constant pains after food intake. 3. For which diseases constant pains in epigastrium are the most typical?

2nd Block

Task 1. Patient R. complains of pains in epigastrium, appearing in 15-20 minutes after food intake. The pains become more intensive after hearty food and salt and sour products intake. He complains of air eructation and more rarely - sour eructation also. Anamnesis morbi. He is ill about 1 year. During beginning of disease the pain occurs only after sour and salt products intake and it was short and stop by means of spasmolitycs intake. In time the pain became more intensive and longer. Usual duration of the pains is 1,5-2 hours. It is necessary to apply hot-water bag on epigastrium, to use spasmolytic or to provoke vomiting artificially for its stop. Anamnesis vitae. He was born and developed as healthy person. He devoted oneself to sport. Catarrhal diseases were rare. Family consists of 5 persons. They live on one’s father. Income for 1 member of family is less than living wage. One year ago he entered the university. He studies well. He is punctual. He smokes. Alcohol abuse isn’t marked. He lives in a boarding house. Feeding is irregular, mainly - tea with sandwiches, chips with any spices. The patient consulted a physician of out-patient department. Recommendations on feeding were given and medicaments were prescribed. The patient follows recommendations and used medicaments about 15 days. Condition became better. The treatment was stop. He didn’t consult a physician once more. Status praesens objectivus General condition is satisfactory. Consciousness is clear, he is active. Height is 178 cm, body weigh is 68 kg. Musculature is well developed. Subcutaneous fat is developed poorly. Lymph nodes aren’t enlarged. Respiratory organs. The chest has correct form. It takes part in breathing equal. Percussion sound is clear pulmonary. Borders of the lungs aren’t displaced. Breathing is vesicular, 18 per minute. Circulatory organs. Apex beat is in 5th interspace 1 cm medially of left midclavicular line. Heart sounds are clear, rhythmical. Heart rate is 72 per minute. Blood pressure is 110/75 mm Hg. Digestive organs. Configuration of the abdomen is usual. During palpation the abdomen is painful in upper part of epigastrium. Palpation of the intestine is painless. In area of caecum spastic part is palpated. Edge of the liver is on the level of costal margin, it is elastic, painless. The size of the liver along midclavicular line is 9 cm. Urinary organs. Kidneys aren’t palpated. Pasternatsky’ sign is negative. Disuria isn’t observed. Analysis of the gastric juice Fast: amount is 45 ml, total HCL-25 T.U., free HCl - 15 T.U. Basal: amount - 70 ml, total HCL-50 T.U., free HCl - 35 T.U. Submaximal histamine stimulation: amount - 120 ml, total HCL-85 T.U., free HCl - 75 T.U. Maximal histamine stimulation: amount - 120 ml, total HCL-120 T.U., free HCl - 110 T.U. Gastroscopy Gastrofibroscope is introduced easily. Esophageal mucous membrane is smooth, pink slightly. Cardia of the stomach is closed up. Gastric mucous membrane is hyperemic, edematic slightly, vessels are injected. Folds of the mucous membrane have normal sickness, relief is normal. Two ulcers (with diameter 6mm and 4 mm) are in the upper part of posterior wall of body stomach. Depth of ulcerous defects is 2mm, fundus is clear. Questions to task 1: 1. Are the pains, marked in epigastrium, early, hunger or nigh? 2. What is appearance of pains in epigastrium in 15-20 minutes after food intake caused by? 3. What can cause appearance of more intensive pains after hearty food and salt and sour products intake? 4. What does cause appearance of eructation? 5. How can you explain independent disappearance of the pains in 1,5-2 hours after food intake? 6. How can you explain relief of the pain after vomiting? 7. What risk-factors are in this patient? 8. Is the treatment, prescribed to the patient, correct? Why? 9. What causes can be in the patients for stop of prescribed treatment and for ignoring of visit to physician again at new exacerbation of the disease? 10. What diagnostic value can localization of the pain in upper part of epigastrium have? 11. Is fast acidity of gastric juice according to this analysis normal, decreased, increased? What is norm? 12. Is acidity of basal gastric juice normal, decreased or increased? 13. In acidity of gastric juice during submaximal stimulation normal, decreased or increased? What is norm? 14. Did you reveal indication for study of gastric secretion by means its maximal stimulation by histamine in this patient? 15. In which diseases such results of gastric juice are the most probable? 16. What conclusion can be made according to data of gastroscopy? 17. How can you explain hyperemic and edematic gastric mucous membrane and injected vessels in it? 18. Cardia of the stomach is closed up after passing of fibergastroscope. Is it normally? 19. What necessary procedure isn’t carried out by endoscopist?

Task 2. Patient N., 32 years old, complains of pains in epigastrium, appearing in 1,5-2,0 after food intake, heartburn in this area and behind sternum, sour eructation, constipation. He wakes up from pains and heartburn at night often. Intake of little amount of baking soda or mild food relieves pain. Anamnesis morbi. He is ill about 4 years. During beginning of disease the pain occurs only after sour and salt products intake and it was short and stop by means of spasmolitycs intake. In time the pain became more intensive and longer. Usual duration of the pains is 1,5-2 hours and more. Baking soda intake quickly relieves pain for short time. It was marked the pain and heartburn occur for 1-2 months in spring and autumn. During other time he feels normally, though feeding and life-stile isn’t changed. The patient many times appealed for medical aid, but isn’t carried out systematic treatment. Anamnesis vitae. He was born and developed as healthy person. Catarrhal diseases were rare. Family consists of 5 persons. He is commercial manager. Income for 1 member of family is more than living wage in 10 times. He goes on business trip often. Feeding is irregular. He likes piper and salt food. He smokes 2 packs of cigarettes in a day. Alcohol uses almost every day, from 50 to 300 ml of vodka. The patient consulted a physician, was treated irregularly. He was renounced of hospitalization. Status praesens objectivus General condition is satisfactory. Height is 188 cm, body weigh is 75 kg. Musculature is poor developed. Lymph nodes aren’t enlarged. Respiratory organs. The chest has correct form. It takes part in breathing equal. Percussion sound is clear pulmonary. Borders of the lungs aren’t displaced. Breathing is vesicular, 18 per minute. Circulatory organs. Apex beat is in 5th interspace 1 cm medially of left midclavicular line. Heart sounds are clear, rhythmical. Heart rate is 72 per minute. Blood pressure is 110/75 mm Hg. Digestive organs. Configuration of the abdomen is usual. During palpation the abdomen is painful in lower part of epigastrium and some to the right of median line. Palpation of the intestine is painful moderately. Edge of the liver is on the level of costal margin, it is painless. Urinary organs. Kidneys aren’t palpated. Pasternatsky’ sign is negative. Disuria isn’t observed. Analysis of the gastric juice Fast: amount is 75 ml, total HCL-55 T.U., free HCl - 25 T.U. Basal: amount - 130 ml, total HCL-10 T.U., free HCl - 95 T.U. Submaximal histamine stimulation: amount - 180 ml, total HCL-145 T.U., free HCl - 135 T.U. Gastroscopy Gastrofibroscope is introduced easily. Esophageal mucous membrane is hyperemic. Cardia of the stomach isn’t closed up fully. Gastric mucous membrane is hyperemic, edematic slightly, vessels are injected. Folds of the mucous membrane became sick, relief is normal. There are two little scars, narrowing lumen of duodenum slightly, at opening into bulb of duodemun. Ulcerative defect with diameter 0,6 mm is revealed in bulb of duodenum. Depth of ulcer is 3 mm. Edges became sick. 6 biopsies are taken from edges of fundus of ulcer. Questions to task 2: 1. Are the pains, marked in epigastrium, early, later, hunger or night? 2. What are the causes of these pains? 3. What is disappearance of the pains after soda or mild food intake caused by? 4. For which diseases of digestive organs is exacerbation in autumn and spring typical? 5. What risk-factors does this patient have? 6. What diagnostic value of localization of the pain is in this patient? 7. Is fast acidity of gastric juice in this patient normal, increased or decreased? 8. Is basal acidity of gastric juice normal, increased or decreased? 9. Is acidity of gastric juice during submaximal stimulation normal, increased or decreased? 10. When are such indexes of gastric juice the most probable? 11. What conclusion can be made according to results of gastroscopy? 12. How can you explain hyperemic and edematic gastric mucous membrane and injected vessels in it? 13. Cardia of the stomach isn’t closed up fully. Did it reflect on self-filling of the patient?

Task 3. Patient D. complains of watery, semi-liquid (doughy) feces twice during day, bloating and constant abdominal pains, expressed general weakness, undue fatigability, decrease of ability to work, irritability, suppressed appetite, impairment of memory, nails fragility, falling of hair. Anamnesis morbi. Disease began 3 year ago from appearance of watery feces to 5-6 times during day. Besides elevation of temperature was marked, diffuse periodical abdominal pain and expressed general weakness were observed. Acute intestinal infection was diagnosed, campylobacter was revealed in feces. Antibacterial therapy was carried out. During repeated bacteriological researches of feces campylobacter wasn’t revealed. After performed treatment temperature became normal, he felt better. But bloating, borborygmus, pains around umbilicus mainly became to trouble him. Feces became unstable, sometimes 2-3 times during day. Fecal masses were light-yellow, foamy with sour odor. At the beginning abdominal pains were appeared after food intake and were relieved after defecation of spasmolytics intake. Often abdominal pains occurred in bloating (abdominal distension) and were relieved after defecation or passage of gases (flatus). In one year they became constant and slightly increased after food intake. After sweet courses intake condition became worse markedly. Gradually weight loss occurs. General weakness became to increase. Nails became fragile; hair falls, convulsions of hands and legs trouble him often. The skin became faded, rough; pigment spots on the face were appeared. The patient was directed for examination and treatment to clinic because of increased deterioration of condition. Anamnesis vitae. During childhood he had catarrhal diseases often. Eggs of helminthes were revealed in feces often during examination. He got treatment. Financial and living conditions are unsatisfactory. Carbohydrate used mainly. Status praesens objectivus. Patient’s condition is moderate severity. Consciousness is clear. Subcutaneous fat is developed poorly. Height is 175 cm, body weight is 58 kg. Skin covers are dry, rough, sallow complexion; brown spots are on the face, neck and trunk. Tongue is crimson-red, with fissures and marks of teeth along edges, papillae are atrophied. Respiratory organs. The chest has normosthenic form. It takes part in breathing equal. Percussion sound is clear pulmonary. Lower borders of the lungs aren’t displaced, along midclavicular line - in the VI intercostal space, along midaxillary line - in the VII intercostal space. Breathing is vesicular, 18 per minute. Rales are absent. Circulatory organs. Heart area is without changes. Apex beat is in 5th interspace 1 cm medially of left midclavicular line. Heart sounds are clear, rhythmical. Heart rate is 86 per minute. Blood pressure is 90/50 mm Hg. Digestive organs. Abdomen is enlarged. During percussion diffuse tympanitis is revealed. During palpation the abdomen is painful in paraumbilical area and right ileac area. After passage of gases caecum is palpated in right ileac area; painful lynph nodes is palpated medially of caecum. Liver isn’t enlarged, is painless. Its sizes according to Kurlov are 11x8x6 cm. Spleen isn’t palpated. Its persussin sizes are 8x5 cm. Urinary organs. Kidneys aren’t palpated. Pasternatsky’ sign is negative. Disuria isn’t observed. Laboratory-instrumental researches General blood analysis Hemoglobin — 100 g/L Erythrocyte — 4,1 x 1012/L Color index — 0,73 Leucocytes — 4,1 x 109/L Leucocyte formula: Eosinophils — 2% Basophils — 1% Juvenile — 0% Stab — 2% Segmented — 48% Lymphocytes — 32% Monocytes — 15% ESR — 12 mm/h Reticulocytes - 0,2 % Thrombocytes - 315 x 109/L Hypochromia ++ Microcytosis + Anisocytosis + Poikilocytosis +

General urine analysis Amount - 400 ml Color - light-yellow Transparence - full Specific gravity — 1010 pH - 7,2 Protein - marks Microscopy of urine sediment: Squamous epithelium — 2-5 in f.v. Leucocytes —0-1-2 in f. v. Erythrocytes - unchanged 0-1 in f.v. Casts - absent Salts - absent

Analysis of feces Consistence — ointment-like Color — light-yellow pH — acidic Mucus - Pus - Blood - Helminthes aren’t revealed Chemical research Gregersen test - Pyrimidin test - Stercobilin ++ Microscopic research Muscle fibres: with transverse banding - ++ without transverse banding - ++ plant cellular tissue - ++ Starch - +++ Connective tissue - + Neutral fat - + Fat acids - +++ Leucocytes -3-5 in f. v. Erythrocytes - 1-2 in f.v. Eggs of helminthes - aren’t revealed Protozoa -aren’t revealed

Biochemical blood analysis. Total protein - 65 g/L (65-85); albumins - 25 g/L (36-50); fibrinogen - 4,5 g/L; cholesterol - 3,1 mmol/L (3,2-5,1);α - lipoproteins- 2,2 g/L (2,6-4,1); β - lipoproteins- 2,1 g/L (2,3-3,7), glucose - 3,3 (3,6-6,1); iron - 7,5 mcmol/L (9,0-31,3), calcium - 1,8 mmol/L (2,2-2,6), sodium - 132 mmol/L (135-150 mmol/L); D-xylose content in 60 minutes after its peroral intake - 0,9 g/L (0,1-0,16 g/L); potassium iodine test - 16 minutes (6-12 minutes). Footnote. Normative are given in brackets. Questions to task 3: 1. What complaints of the patient direct to presence of digestive organs disease? 2. Is it possible to think about presence of chronic campylobacillar infection in the patient on the basis of anamnesis? 3. What signs of intestinal dyspepsia are in this patient? 4. Is intestinal dyspepsia in this patient fermentative or putrefactive? 5. What can be the cause of increase of abdominal distension and abdominal pains in this patient after sweat products intake? 6. What process is in the base of syndrome of intestinal dyspepsia? 7. What term is for designation of disturbance of normal intestinal microflora used? 8. What is base of dysbacteriosis develoment in this patient? 9. Dysbacteriosis, appearing after antibiotics intake, stop independently in majority people. What promotes to chronic course development and intensification of dysbacteriosis in this patient? 10. What was character of the pain in beginning of the disease? 11. How can you explain disappearance of the pains in this patient after defecation or passage of gases? 12. In time in this patient abdominal pains loss their periodicity and became constant. What can it be caused by? 13. To disease of what digestive organ localization of pains around umbilicus directs most often during palpation of abdomen? 14. Why weight loss of the patient occurs? 15. What can the cause of skin changes in this patient be? 16. What can the cause of crimson-red tongue with atrophied papillae in this patient be? 17. In patient abdomen is enlarged. How can the reason be diagnosed? 18. What deviations are in general blood analyses? 19. What diagnosis can be made on the base of general blood analysis? 20. What form of feces is in healthy men? 21. What is the cause of appearance of ointment-like consistence feces with light-yellow color? 22. What does revealing of food debris in the feces testify about? 23. Stercobilin is revealed in the faeces of the patient. Is it normal sign or directs to pathology? 24. What is the reason of appearance of muscle fibres in the feces? 25. What is the reason of appearance of connective tissue in the feces? 26. What is the reason of appearance of fat acids in the feces? 27. What researches were carried out for study of absorption function of patient’s small intestine? 28. Does D-xylose test direct to malabsorption in the patient. What is norm? 29. Does potassium iodine test testify about intestinal malabsorption? 30. Is a content of albumins in the blood normal, decreased, or increased? What is norm? 31. What can be a reason of such level of albumins? 32. Is content of cholesterol in the blood normal, decreased or increased? What is norm? 33. Is content of lipids in the blood normal, decreased, or increased? What is norm? 34. What can be a reason of decrease of level of blood lipids in this patient? 35. Is content of iron and calcium in the patient’s blood normal, increased, or decreased? What is norm? 36. What factors could lead to decrease of iron level in blood serum of this patient? 37. What clinical signs in this patient can be connected with decrease of iron content in organism? 38. What clinical signs in this patient can be connected with decrease of calcium content in organism? 39. Is content of sodium in blood serum normal, decreased, or increased? What is norm?

Task 4. Patient P. complains of acid eructation. It accompanies by the pain and burning in epigastrium and behind sternum. Such eructation occurs in 2-3 hours after food intake more often. Questions to task 4: 1. For which disease such eructation is the most typical? 2. What does such eructation testify about? 3. What can be reason of the pain and burning behind sternum during eructation in this patient?

Task 5. Patient D. complains of periodical pains in epigastrium, which appear in 1,5-2 hours after food intake. Pains are more intensive after meat broth intake and also after intake of strong, salt and smoke-dried products. They stop or decreased by means of vomiting and food or baking soda intake. Positive effect also occurs after use of spasmolytics and applying of hot-water bag.

Questions to task 5: 1. What are pains, appearing in 1,5-2 hours after food intake (early, late, hunger, night) ? 2. What is the reason of periodicity of occurrence of the pains? 3. Why were more intensive pains after strong, salt and smoke-dried products intake observed? 4. Why were pains after vomiting decreased? 5. What is the reason of stop of the pain after baking soda intake? 6. What is the reason of stop of the pain after food intake? 7. Why does pain stop after use of spasmolytics? 8. What is reason of positive influence of hot-water bag on the pain? 9. For which disease are complaints of this patient the most typical?

1st Block

Answers for test tasks of the I-st level: 1 - c 5 - b 9 - b 2 - e 6 - c 10- a 3 - d 7 - c 11- b 4 - c 8 - b 12- d 13- d

Answers for test tasks of the II-nd level: 1 - a , b , e , f , g 8 - a , f 14- c , d , f , g , i 2 - a , b , f, g , i 9 - b , c 15- a , d 3 - a , b , e , f , h 10- a , b , f 16- b , c , d 4 - c , e 1 1 - a , c , f 17- c , e , f, h 5 - a , c , d , e . 1 2 - c , d , e 18- a , e , f, g , h 6 - a,b,d,e,g,h 1 3 - a , d , e 19- a , c , d , f, g 7 - a , c , d , f 20- a , c , d

Standards of right answer for tasks: (1st Block) 1) d. 2) b. 3) 1. Constant pains can be in case of constant influence of causative factor. Inflammatory process is such factor more often. But such pain can be in carcinoma of the stomach also. 2. Food intake is accompanied by activation of motor and secretor action of the stomach. They play role of additional factors of irritation of nervous receptors of mucous membrane. Besides, chemical composition of food can play role of irritative factor also. 3. For chronic gastritis and carcinoma of the stomach.

(2nd Block) Answers for test tasks of the I-st level: 1 - c 6 - b 11- d 2 - a 7 - b 12- c 3 - b 8 - e 13- a 4 - c 9 - c 5 - d 10- c

Answers for test tasks of the II-nd level: 1 - a , b , e , f , h 7 - a , b , e , f . 13- a , c , d , e 2 - a , c 8 - a , c , e , g 14 a,c,d,e,f,h,i 3 - a , b , d 9 - a , c , f 15- a,b,c,d,f,h 4 - a , b , d , f , g 10- b , d , e , g , h 16- b,c,d,g,h,i 5 - a , b , d , f 11- a , d , e , g 17- a , b , d , f , g 6 - a,c,d,f,g,h 12- b , c , e , g 18- a , c

Standards of right answer for tasks: (2nd Block) 1) 1. The pains are early. 2. Appearance of pains in epigastrium in 15-20 minutes after food intake is caused by irritation of ulceration and inflammation parts, located in fundus and body of the stomach and by spasm of musculature of the stomach due to this process. 3. It can be caused by more intensive irritation of nervous receptors by such food and by stronger spasm of gastric musculature. 4. Appearance of eructation is caused by gastric motor disorders, increase of motion activity as result of irritation of nerve endings of nerve vagus. 5. It can be explained by natural evacuation of food in intestine, weakening and disappearance of irritative effect of food to nerve receptors. 6. It can be explained by release of the stomach from food mass, irritating nerve receptors and causing spasm of musculature. 7. Irregular and low-quality feeding. 8. Treatment is correct as it was effective. 9. Punctual character of the patient is marked. The cause can’t be in usual undisciplined behavior of the patient. The most probably, it was economical causes. Observance of diet, proper feeding and purchase of medicines need certain expenses. Financial position of the family was unsatisfactory. 10. Such localization of pain area can be caused by localization of pathologic process in body of the stomach or fundus of the stomach. 11. It is normal. In healthy persons fast total acidity of gastric juice can vary from 0 to 40 T.U., and free HCl - to 20 T.U. 12. It is normal. 13. It is normal. In healthy persons – total acidity-80-100 T.U., free HCl – 60-85 T.U. 14. Such indications are absent. Maximal stimulation of gastric secretion must be carried out if clinical data and indexes of preceding researches give grounds for supposition of sharp decrease of acidity or presence of achlorhydria. 15. Indexes of gastric juice in this patient are within norm. Such results can be in some patients with chronic gastritis and peptic ulcer with localization defect in body of the stomach and fundus of the stomach. 16. Patient has peptic ulcer of the stomach. 17. It can be related with accompanying gastritis. 18. It is normally and testifies about normal tone of gastric sphincters. 19. Biopsy isn’t carried out. During gastroscopy it is necessary to take tissue from border of ulcerative defect for histological research. 2) 1. They are later, hunger and night. 2. Appearance of later, hunger and nigh pains is observed in increased acidity of gastric juice. In 1,5-2,0 hours after food intake and at night food is absent in the stomach and gastric juice with increased acidity irritates nerve endings significantly and causes strong spasm of musculature of the stomach. 3. It is caused by decrease of acidity of gastric juice. 4. For peptic ulcer of pylorus or duodenum. 5. Irregular feeding, piper course intake often, smoking, alcohol abuse. 6. Such localization of the pains is the most typical for peptic ulcer of duodenal bulb or pyloric part of the stomach. 7. It is increased. In healthy persons total acidity of fast gastric juice can fluctuates within limits from 0 to 40 T.U., free HCl - to 20 T.U. 8. It is increased. 9. It is increased. 10. Such indexes of gastric secretion are the most typical for peptic ulcer of pylorus and duodenal bulb. They can be observed in patients with hyperacidic gastritis also. 11. Patient has peptic ulcer of the stomach and duodemun. 12. It can be connected with accompanying gastritis. 13. When cardia isn’t closed up fully, conditions for reflux (regurgitation) of gastric content into esophagus is formed. Development of esophagitis and feeling of burn behind sternum can be as result of this process.

3) 1. Abdominal distension and abdominal pains, doughy frequent faeces. 2. It isn’t possible. Repeated bacteriological researches didn’t reveal these bacteria in feces. 3. Abdominal distension and abdominal pains, changes of faecal masses. 4. Intestinal dyspepsia in this patient is fermentative. Evident meteorism and foamy ointment-like light-yellow feces with gas bubbles and acid reaction directs to it. 5. Indemnification of fermentative processes. They are supported by carbohydrates food, sweat courses particularly. 6. Change of intestinal microflora. Disturbance of different microorganisms ratio. 7. Dysbacteriosis. 8. Intensive antibacterial therapy, carried out during acute intestinal infection three years ago. 9. Unbalanced feeding, carbohydrates intake mainly. 10. Pain had spastic character. Disappearance of them after spasmolytics intake directs to it. 11. Gases and acid fecal masses irritate intestine and cause its spasms. Irritative factor, causing spasm of intestine, is decreased after passage of gases and defecation. These factors cause pain due to distension of intestine. After passage of gases and defecation this mechanism of appearance of the pains stops to act also. 12. It can be caused by extension of inflammatory process into deeper layers of intestine and by involving of nearest mesenteric lymph nodes in pathological process. 13. It directs to disease of small intestine. 14. Due to malabsorption in small intestine. 15. Deficiency of vitamins of B-group due to intestinal malabsorption. 16. Deficiency of vitamins of B-group due to intestinal malabsorption. 17. By means of percussion. Presence of tympanic percussion sound in this patient directs that enlargement of the abdomen is caused by meteorism. 18. Decrease of haemoglobin level, color index, acceleration of ESR, hypochromia of erythrocytes, microcytosis. 19. Iron-deficiency anemia. 20. Sausage-like. 21. Accelerated passage of alimentary compound along intestines. Feces didn’t have time to form. 22. It testifies about accelerated passage of alimentary compound along intestines. Food didn’t have time to digest fully. Potential deficiency of alimentary enzymes promotes to it. 23. It is normal sign. Stercobilin is bilirubin’s metabolite, which get with bile into intestines (bowels) and is transformed by intestinal bacteria. In case of evident diarrhoeas bilirubin appears in native form in feces and gives green-yellow color to the feces. 24. Muscle fibres are digested in small intestine under influence of tripsin, produced by pancreas. It is possible decrease of excretory function of pancreas. But the main cause - accelerated passage of alimentary compound along intestines. The food didn’t have time to digest fully. 25. Accelerated passage of the food along intestines. It is possible decrease of excretory function of pancreas also. 26. Accelerated passage of the food along intestines. Fat acids didn’t have time to digest in intestines due to this reason and due to malabsorption of small intestine. 27. D-xylose test and potassium iodine test. 28. Yes, it does. D-xylose content in the blood is less, than it must be in case of normal absorption. Normally - 1,8 g in 5 hours after its peroral introduction. 29. Yes, it does. Time of appearance of potassium iodine in the saliva after its peroral introduction is reduced. Normally it is 6-12 minutes. 30. It is slightly decreased. Normally it is 36-59 g/L. 31. Its malabsorption in small intestine. 32. It is decreased. Normally it is 3,2-5,1 mmol/L. 33. It is slightly decreased. Normally content of α-lipoproteins in the blood is 2,6-4,1 g/L, β- lipoproteins - 2,3-3,7 g/L. 34. Decrease of their absorption in the intestines. Loss of body weight promotes to this process also. 35. It is decreased. Normally content of iron in the blood serum is 9,0-31,3 mcmol/L, calcium - 2,23-2,57 mmol/L. 36. Decrease of iron absorption in bowels. Deficiency of iron in the food (in carbohydrates character of feeding) is possible also. 37. Dryness and roughness of the skin, fragility of nails and falling of hair. 38. Appearance of convulsions. 39. It is decreased. Normally it is 135-145 mmol/L. 4) 1. For peptic ulcer of the stomach and duodenum. 2. About reflux of acid contents of the stomach into oral cavity in increased acidity of gastric juice. 3. Irritation of mucous membrane of esophagus by gastric juice with increased acidity. 5) 1. They are late pains and simultaneously they are hunger, as stop by means of food intake. 2. Periodicity of the pains is connected with periodicity of influence of causative factor. Spasm of musculature of the stomach (of pylorus more often) under influence of irritation of nerve vagus in increased acidity of gastric juice is such periodically appearing factor. 3. These products are stronger stimulators of gastric secretion. Therefore, they are also stronger irritants of nerve vagus, which starts reflex of spasm of gastric musculature. 4. During vomiting stomach is released acid content, which is cause of irritation of nerve vagus and appearance of the pains. 5. Baking soda neutralizes HCL of gastric juice, which irritates nerve vagus and results to painful reaction. 6. Food bonds acid ions of HCL and decreases acidity of gastric content and temporarily removes reason of pain appearance. 7. Spasmolytics relief spasm, which is reason of pains’ appearance in the patients with increased acidity of gastric juice. 8. Influence of heart relief spasm, which is reason of pains’ appearance in the patients with increased acidity of gastric juice. 9. For peptic ulcer of the stomach and duodenum.

Methodical instruction is composed by lecturer Ye.Ye. Petrov.

Approved at the Department of Propaedeutics to Internal Medicine with Care of Patients meeting on 11 09 2018 Protocol No2 The Head of the Department Professor Yu. Kazakov

METHODICAL INSTRUCTION FOR STUDENTS’ SELF-PREPARATION WORK

Educational discipline Propaedeutics to Internal Medicine Module No 2 Enclosure module No 8 Topic The main symptoms and syndromes in diseases of the hepato-biliary system: chronic cholecystitis, cholangitis, cholelithiasis; main clinical and laboratory manifestations of chronic hepatitis and liver cirrhosis Year 3 Faculty medical

Poltava – 2018

1. The topic basis: The topicality of studied questions is caused first of all by a wide spreading of a studied pathology among a human population (its growth observed in last years), rather late diagnostics in many cases, and also the appearing problems with therapy in connection with significant growth of bacterial stability to used antibiotics. Hepatocirrhosis is a serious and irreversible disease and is the eleventh leading cause of death in the USA, with an age-adjusted death rate of 9,2 per 100,00 per year. 2. The specific aims:  To explain essence of jaundice syndrome and mechanisms of different types of jaundice development.  To analyze results of examination of patients with biliary pathology: cholelythiasis, cholecystitis, cholangitis.  To explain mechanism of development of cholelythiasis, cholecystitis, cholangitis.  To interpret results of examination of patients with biliary pathology: cholelythiasis, cholecystitis, cholangitis.  To draw painful points and areas of skin hypersthesia in cholelythiasis and cholecystitis.  To explain essence of portal hypertension syndrome, hepatolienal syndrome and hepatic failure and mechanisms of their development.  To analyze results of examination of patients with chronic hepatitis and hepatocirrhosis.  To explain mechanism of development of chronic heptitis and hepatocirrhosis.  To classify types of chronic hepatitis and hepatocirrhosis.  To interpret results of examination of patients with liver pathology: chronic hepatitis, hepatocirrhosis.  To compose plane of emergency in attack of biliary colic. To classify types of bile stones.

3. Basic knowledge, experience, skills necessary for studying the topic in connection with other subjects (interdisciplinary integration) : Previous disciplines Obtained skills 1. Anatomy To know human anatomy, structure of organs of gastrointestinal tract particularly. 2. Physiology To know physiology of the gastrointestinal tract. 3. Medical psychology To be able to observe principles of ethics and deontology in medical practice 4. Biochemistry To know metabolism, lipid and pigment particularly 5. Pathological morphology To know pathologic-morphological picture of cholelythiasis, acute and chronic cholecystitis. 6. Latin and medical terminology To know terminology (in Latin transcription): jaundice, acute cholecystitis, chronic cholecystitis, common bile duct, common hepatic duct, cystic duct, gall bladder.

4. Tasks for self-work during preparation to the class. 4.1 List of the main terms, parameters, characteristics, which should be mastered during preparation to the class: Term Definition 1. Jaundice It is icteric colouring of the skin and mucous membranes, caused by increased content of bilirubin in tissues and blood. 2. Cholelythiasis It is disease, which is characterized by formation of stones in gall bladder or, rare, in biliary ducts. 3. Cholecystitis It is inflammation of gall bladder. 4. Cholangitis It is inflammation of bile ducts 5. Chronic hepatitis It is the diffuse inflammatory process in a liver, caused by the primary lesioncells of hepatic cells, which was not ended during 6 months and potentially can be transformed in a hepatocirrhosis.

6. Hepatocirrhosis It is the making progress diffuse chronic polyetiologic disease of liver, which is characterized by the considerable decreasing of mass of functioning hepatocytes, by expressed fibrosis with violation of structure of hepatic lobule and bloodstream of liver.

4.2. Theoretical questions to be answered before class: 1. What does term “jaundice” mean? 2. Classification of different types of jaundice. 3. Peculiarities of hemolytic jaundice 4. Peculiarities of hepatocellular jaundice. 5. Peculiarities of obstructive jaundice 6. Tell about ethiology and pathogenesis of cholelythiasis. 7. Describe hepatic colic in case of cholelythiasis. 8. What medicaments must be introduced for stop of hepatic colic attack? 9. What signs accompany pains in hepatic colic? 10. What are potential results of inspection and palpation of abdomen in patients with cholelythiasis? 11. Describe painful points and areas of skin hypersthesia in cholelythiasis. 12. What laboratory and instrumental methods are used for diagnostics of cholelythiasis? 13. Tell about different variants of course of cholelythiasis. 14. What complications of cholelythiasis do you know? 15. What factors have the greatest importance in occurrence of cholecystitis? 16. Describe clinical picture of acute cholecystitis. 17. What are course and potential complications of acute cholecystitis? 18. Describe complaints and potential results of inspection of patients with chronic cholecystitis. 19. What are potential results of palpation of abdomen in patients with chronic cholecystitis? 20. What laboratory and instrumental methods are used for diagnostics of chronic cholecystitis? What are their potential results? 21. Tell about prophylaxis of cholelythiasis and cholecystitis. 22. What does term “portal hypertension” mean? 23. What the main manifestations of portal hypertension syndrome do you know? 24. Describe hepatolienal syndrome. 25. Tell about causes and clinical picture of hepatic failure and hepatic coma. 26. Tell about ethiology and pathogenesis of chronic hepatitis. 27. Clinical picture and diagnostics of chronic persistent (benign) hepatits, chronic active hepatitis and chronic cholestetic hepatitis. 28. Etiology and pathogenesis of hepatocirrhosis. 29. What are potential results of questioning, inspection and palpation of abdomen in patients with hepatocirrhosis? 30. What laboratory and instrumental methods are used for diagnostics of hepatocirrhosis? 31. Tell about different variants of hepatocirhrosis 32. What complications of hepatocirhrosis do you know? 33. What Child’s criteria for hepatic functional reserve do you know?

4.3. Practical work (tasks), which should be performed during class: 1. To carry out examination of patients with cholelythiasis, cholecystitis and cholangitis. 2. To interpret obtained results. 3. To interpret results of laboratory and instrumental methods examination of patients with cholelythiasis, cholecystitis and cholangitis. 4. To carry out examination of patients with chronic hepatitis and hepatocirrhosis. 5. To interpret obtained results. 6. To interpret results of laboratory and instrumental methods examination of patients with chronic hepatitis and hepatocirhrosis.

The contents of topic: Text JAUNDICE SYNDROME Jaundice (icterus) is icteric colouring of the skin and mucous membranes, caused by increased content of bilirubin in tissues and blood. Blood serum, taken for research in the patient with true jaundice, also has more or less saturated yellow colour. Changes of urine colour (it become yellow or brown like bear) and feces colour (in one cases it become light-coloured, in others - become dark-brown) accompany and sometimes precede to jaundice. Jaundice can occurs quickly, during 1-2 days, reaching significant degree of intensity, or gradually and be slight (subicteriousness). Often patients (or surrounding persons) mark appearance of icteric skin colour; it causes to consult a physician. Sometimes jaundice can be accompanied by intensive skin itch, skin haemorrhages, nasal and intestinal bleedings. Jaundice can occur in many liver diseases, biliary tracts diseases, blood diseases and in diseases of other organs and systems when bilirubin metabolism is disturbed secondarily. Clinical symptoms, accompanying jaundice, allow to a certain degree to suppose its type and reason of occurrence in every case of disease. Exact diagnostics of different types of jaundice is possible by means of special laboratory examination methods. True jaundice can occur as result of three main reasons: 1) excessive destruction of erythrocytes and increased production of bilirubin (hemolytic jaundice); 2) disturbance of catch of unconjugated bilirubin by hepatic cells and its binding with glucuronic acid (parenchymatous jaundice); 3) presence of obstruction for bilirubin excretion with bile into intestine and return absorption of bilirubin into the blood (mechanical jaundice). Hemolytic jaundice is developed as result of intensive destruction of erythrocytes in cells of reticuloendotelial system (spleen, liver, bone marrow) and forming of unconjugated bilirubin from hemohlobin in quantity, which can’t be “processed” by the liver. As result - bilirubin is accumulated in the blood and causes appearance of jaundice. Hemolytic jaundice is the main symptom of hemolytic anaemia or one of the many symptoms of other diseases: B 12, folic acid deficiency anemia, malaria, subacute bacterial endocarditis and others. In case of hemolytic anemia skin usually is lemon-yellow; skin itch is absent. Unconjugated blood bilirubin content with indirect Van den Berg reaction is increased moderately (in 1,5-3 times). Bilirubin in urine is absent, but urine is pigmented significantly due to increased excretion of stercobilinogen (in 5-10 times) and, partly, urobilinogen. Feces has saturated dark colour due to significant content of stercobilin. Parenchymatous (hepatocellular) jaundice is developed as result of lesion of hepatic parenchyma cells (hepatocytes). Their ability to catch bilirubin from the blood, to bind with glucuronic acid (natural process of disintoxication of number of substances by the liver) and to excrete it into biliary tracts as bilirubinglucuronid (conjugated bilirubin) is decreased. Unconjugated and conjugated blood bilirubin content is increased in 4-10 times, rarely - more (unconjugated bilrubin is increased due to insufficient effectiveness of hepatocytes function, conjugated - as result of return diffusion of bilirubinglucuronid into blood capillaries from bile capillaries in dystrophy of hepatic cells). Conjugated bilirubin (bilirubinglucuronid, which is water soluble and pass through capillary membranes slightly, in contrast to unconjugated bilirubin) and bile acid appear in urine, its amount is increased gradually. Excretion of stercobilin with feces is decreased (as less amount of bilirubin is excreted into intestine by liver), but total its discolouring is observed rarely. Infection (viral hepatitis, leptospirosis and others) and toxic lesions of the liver (mycetismus, phosphorus compounds poisoning, arsenic compounds poisoning and others; medicament intolerance) have the greatest importance in origin of this type of jaundice. But parenchymatous jaundice can occurs in hepatocirrhosis also. Skin cover in case of this type of jaundice is saffron-yellow touched with red. Skin itch occurs much rarely than in mechanical jaundice, as in parenchymatous jaundice synthesis of bile acids by affected hepatic cells is disturbed. Symptoms of expressed hepatic failure can occur in the case of severe course of disease. There is also a group of inherited pigmentary hepatosis, when liver isn’t affected pathologically, functional liver tests aren’t changed, but some stages of binding of bilirubin with glucuronic acid is disturbed (Gilbert’s syndrome, Rotor’s syndrome and others). It is accompanied by constant or intermitting jaundice, expressed often, which is marked from birth. Mechanical (obstructive) jaundice is developed due to partial or total obstruction of common bile duct, caused by its pressing outside or tumour invasion more often (usually cancer of head of pancreas, cancer of major duodenal papilla and others) or stone obstruction, leading to bile stagnation over obstruction and elevation of the pressure in the ducts at continuing choleresis. As result -interlobular bile capillaries are distended and bile diffuses into hepatic cells, where dystrophic processes are developed, and enters into lymphatic spaces and blood. Besides, connection of little capillaries with lymphatic fissures occurs on the periphery of lobules (as result of pressure elevation in these capillaries). It results to bile entering into general blood flow. Skin and mucous membranes in mechanical jaundice become yellow, and then - green and dark-olive-coloured (due to oxidation of bilirubin into biliverdin). Conjugated blood bilirubin content (with direct Van den Berg reaction) becomes high (250-340 mkmol/l, or 15-20 mg%, and more). In case of long jaundice unconjugated bilirubin content is some increased also (in connection with dysfunction of the liver). Conjugated bilirubin appears in urine (bile pigments are revealed in general urinalysis). Urine becomes brown with bright-yellow foam. Feces becomes light-coloured either periodically (in case of incomplete obstruction, by stone more often), or during long term (in case of duct compression by tumour). In this case jaundice intensifies, colour of the skin and mucous membranes becomes green-brown (sallow complexion), patient’s emaciation grows more serious. In case of total biliary tracts obstruction feces is light-coloured, stercobilin in feces is absent. In this type of jaundice plenty of bile acids, produced by hepatocytes, enter into the blood also (cholemia). It results some symptoms, caused by intoxication: intensive skin itch, becoming more intensive at night, bradicardia (bile acids leads to increase of nerve vagus tonus).Disturbance of nervous system action is manifested by the following symptoms: rapid fatigability, general weakness, adynamia, irritability, headache and sleeplessness. If it is impossible to eliminate reason, causing common bile duct obstruction (stone or tumour removal), liver is affected gradually, symptoms of its functional insufficiency are added.

CHOLELYTHIASIS Cholelythiasis is characterized by formation of stones in gall bladder or, rare, in biliary ducts. It is widespread disease. According to materials of autopsy, stones in gall bladder are revealed in every ten person, died due to different reasons. At the same time, clinical manifestations of disease occur only in 10 % of carrier of stones, mainly in women 30-55 years old. Ethiology and pathogenesis. Metabolic imbalance, first of all, of lipids (cholesterol) and calcium, bilirubin also is in basis of disease. Formation of stones is result of these disturbances. Infection and stagnation of bile have importance also. Derangement of cholesterol metabolism with hypercholesterolemia and increase on cholesterol content in bile is the main mechanism, as cholesterol is in majority of stones. The following fact confirms foregone: cholelythiasis often is combined with atherosclerosis, diabetes mellitus, obesity and other states, which is accompanied by hypercholesterolemia. Often formation of pigment stones in increased level of bilirubin in bile in case of hemolytic anemia (hemolytic jaundice) is explained analogously. At the same time increased cholesterol content in blood isn’t in all patients; parallelism between cholesterol level in blood and bile absent also. It is known, the main elements, forming stones, -cholesterol, bilirubin and calcium - are in bile as unstable colloidal solution. Dissolved state of cholesterol in bile is cased by biliary acids mainly. In normal bile ratio cholates and cholesterol is 15:1, and in cholelythiasis it decreases to 6:1. So, determinant value in formation of stones belongs to disturbances of physicochemical composition of bile. Functional insufficiency of hepatic cells can be one of the reasons of dyscholia. As its result - formation of all biliary acids (or some of them) is decreased. Value of infectious factor is in following: in inflammation of gall bladder exudate, rich for proteins, disturbs colloidal and chemical composition of bile. Due to this process precipitation of cholesterol, bilirubin, calcium and formation of mixed stones, typical for infectious lesion of gall bladder, occurs. Bile stagnation in gall bladder forms premises to stone formation as promotes to its larger concentrating and increase of cholesterol and bilrubin concentration in it (in10-12 times); gradual absorption of biliary acids leads to decrease of their content in bile. Besides, stagnation of bile can be favourable basis for infective episode. Atony of gall bladder and ducts, anatomical changes of biliary tracts (flexures, commissures, scars), different reasons, disturbing gall bladder emptying: elevation of intraabdominal pressure (during pregnancy and others), splanchnoptosis, constant constipation, sedentary life-stile, rare food intake and others are essential factors, resulting to bile stagnation. Hereditary predisposition has indisputable value: often bile stones are marked in some generations of one family, in the female line particularly. Surplus intaking of food, rich for fat, increased caloric content of food leads to hypercholesterolemia and promotes to biliary stones formation also. Clinical picture. Attack of pains in right hypochondrium -so called “hepatic colic” is the most typical sign for cholelythiasis. Attacks of colic usually are caused by little stones during their transition in area of neck of gall bladder, ostium or directly in cystic duct. Spastic contractions of gall bladder and ducts are the cause of painful feelings. These contractions occur due to suddenly distension of gall bladder and increase pressure in it owing to mechanical obstruction to bile outflow, and due to irritation of nervous elements (as reflex) of receptors or cystic duct by stones. Appearance of biliary colic attack can be provoked by long nervous and physical exertion, jolty driving, plentiful fat food intake. Biliary colic begins suddenly. At the beginning of attack pains are diffuse and occupy whole right hypochondrium, then - they concentrated in area of gall bladder or epigastrium. Pains are very severe, cutting and can be so terrible that need use of different analgesics. Patients moan, toss in their bed, and don’t find comfortable position. Pains have typical irradiation upwards, to the right and backwards, to the right shoulder, neck, jaw, and under right scapula. Sometimes pains irradiate to heart area, provoking attack of stenocardia. Pain attack can lasts from some minutes to some hours and days even, and what’s more - pains now abate, now intensify. Increased contractions of gall bladder promote to further motion of stone (with diameter not more than 1-1,5 cm) from neck or duct of gall bladder into common bile duct; sometimes after relaxation of spasm stone slips back into gallbladder bottom. In both cases attack ends suddenly, same to the beginning, and patient’s condition is improved quickly. Often attack stop by means of warm and spasmolytics (intramuscular introduction of baralgin -5 ml of 0,1% solution, papaverin hydrochloride -2 ml of 2% solution and others). It is also important differential-diagnostic sign (in acute cholecystitis pains don’t stop after intaking of these medicaments, and warm, for example, hot-water bottle on area of liver isn’t indicated as increases blood flow and inflammatory process). If attack of colic is prolonged, jaundice (mechanical) can occur at the end of it. Jaundice is result of long spasm of common bile duct. Jaundice usually isn’t intensive and short-term (to 2-3 days). Biliary colic usually accompanied by nausea and recurrent vomiting. Fever (which often accompanies attack and stop after end of attack) is caused by reflex mechanism also. If fever is longer, it is connected with inflammatory process, complicated course of cholelythiasis. It is confirmed by increasing leukocytosis, acceleration of ESR and sudden disturbance of patient’s general condiiton. During patient’s inspection sometimes it is possible to mark obesity and xanthomas palpebrarum (cholesterol deposits), more rarely - xanthomas on other skin areas. Abdominal distension is marked; during superficial palpation tension of anterior abdominal wall, in right hypochondrium particularly, and sharp tenderness in this area are revealed. After relief of the pains, when muscle tension disappears, it is possible to palpate painful edge of liver and sometimes - gall bladder also as round or pear-shaped elastic body. Often it is possible to determine painful points and areas of skin hypersthesia according to Zakharin - Head’s zones. They are: 1) in area of projection of gall bladder; 2) in epigastrium; 3) in pancreato-cholecystic point; 4) in humeral zone; 5) in point of angle of scapula; 6) in paravertebral points to the right from VIII thoracic vertebra to XI thoracic vertebra: 7) in point of phrenic nerve - pain on pressure between the pedicles of m. sternocleidomastoideus (postive phrenicus-symptom or Mussy-Georgievsky symptom) In asymptomatic cholelythiasis number of laboratory and instrumental researches allow to suspect and reveal this disease. Blood examination reveals increased content of cholesterol. In duodenal intubation (performed out of attack) smallest concrements (microlithes) and many crystals of cholesterol are revealed sometimes. Sometimes during usual X-ray study, which is carried out in connexion with other disease, radiologist reveals radiopaque shadows; it allows to suspect presence of gallstones, containing salt of calcium. But the most essential value in diagnostics of cholelythiasis belongs to contrast X-ray study (cholecystography or cholegraphy) and ultrasound study of gall bladder (echography). It is possible to reveal even relatively small stones in gall bladder and biliary ducts by means of these methods. Course and complications. Cholelythiasis is taking its variously course. Uncomplicated cholelythiasis rare can be manifested as only one attack of biliary colic. More often recurrent attacks occur, one of which succeed other in little time, or attacks are repeated 1-2 times in year and rare. It is known rare cases of spontaneous recovery, when biliary colic ends with going out of stone into intestinal lumen. In long course of cholelythiasis infection is added usually. It complicates the course of the main disease by symptoms of cholecystitis or cholangitis. One of the comlication of disease is obstruction of gall bladder neck, which can result to its hydrops (hydrops vesicae fellae). Hydrops is manifested by very sharp painful attack, after which (in some weeks) it is possible to palpate significantly enlarged, elastic, unstable, painless gall bladder. In case of absence of adhesion with neighbouring organs (as result of pericholecystitis) it is displacing together with liver at deep breathing or during palpation easily. In case of gall bladder hydrops its slightly yellow or pale fluid, so called white bile, is its content. It is formed due to absorption of bile elements by gall bladder wall and discharge of serous exudate by its mucous membrane. If infection is added, gallbladder empyema occurs, and condition of the patient sudden impairs: chill and high temperature appears, pains in right hypochondrium renews. Neutrophile leukocytosis is observed in the blood, ESR is accelerated. In case of total obstruction of enter into gall bladder by stone, it can be shrunk gradually, sclerosis of its walls occurs. Obstruction of common bile duct occurs when stones from gall bladder pass into common bile duct (as a rule, stones are delayed in front of sphincter of hepato-pancreatic ampulla); besides mechanical jaundice is developed a little later after decreasing of pains. Total obstruction of common bile duct occurs when, side by side with presence of stone, spasm and inflammatory edema of mucous membrane of duct (cholangitis) are expressed. Past ones hinder bile outflow. Gall bladder, as a rule, isn’t enlarged in spite of stagnation, as its walls often can be changed due to accompanying inflammatory process and loss ability to be stretched (Courvoisier-Terrier’s symptom negative). At the moving of stones from more narrow to more wide part of common bile duct, their delaying in this part (so called valvular stones) or at temporary relaxation of their walls conditions for bile outflow into duodenum are formed; in these cases intensity of jaundice periodically now increased, now decreased; color of excrements is changed, accordingly. Perforation of gall bladder (rarer - of common bile duct) with development of external or internal vesico-intestinal tracts and sometimes - bile peritonitis is complication also. Long presence of stones in bile duct can result to cancer of gall bladder; in case of long obstruction of common bile duct, accompanied by bile stagnation and infection of biliary tract, biliary (cholestatic) liver cirrhosis is developed often. Treatment. Conservative treatment is directed to making conditions for better bile outflow and diminishing of propensity to further stone formation: it is recommended healthy life- style, often food intake with limitation of products, containing cholesterol. In presence of insignificant painful sensation different antispasmodic and analgesic agents are prescribed (heat, atropine preparations, papaverin and others). In acute attack of bile colic these preparations are introduced parenterally, if it is necessary - in 20-30 minutes repeatedly. In case of prolonged attack, which doesn’t stop after repeat injection of spasmolytics and baralginum (narcotic analgesics are contraindicated!); patient must be hospitalized in surgical department. Cholecystectomy by means of usual method, i.e. with laparotomy, or laparoscopic cholecystectomy is carried out. Urgent surgical treatment of cholelithiasis is carried out in case of such complications as hydrops of gall bladder, obstruction of common bile duct with mechanical jaundice , perforation of gall bladder with development of fistulas or bile peritonitis, or in frequent attacks of bile colic without effect from conservative treatment. During last years possibility of medicinal dissolution of little (to 8-10 mm) cholesterol stones, even multiple, appears. For this purpose preparations of cheno- and ursodeoxycholic acids are prescribed during long term. In case of larger cholesterol stones (with diameter to 30 mm) their lithotripsy is carried out. Prophylaxis is in liquidation of cases, causing bile stagnation and metabolic imbalance: it is recommended regular food intake, gymnastics, healthy life-style, diet, liquidation of constipation.

CHOLECYSTITIS

Cholecystitis is inflammation of gall bladder. This disease is widespread, occurs in women more often. Ethiology and pathogenesis. Different infections, autolytic lesion of mucous membrane of gall bladder (in case of reflux of pancreatic juice in it), helminthic invasion (ascarids) have the greatest value in occurrence of cholecystitis. Possibility of viral (viruses of hepatitis) ethiology of cholecystitis confirms during for some time past. Cholecystitis of toxic and allergic origin occurs also. Ethiological value of infection for occurrence of cholecystitis is confirmed by means of bacteriological research of microflora of cystic bile, got during operation or during duodenal intubation. Infection can penetrate into gall bladder enterogenously (from bowels), hematogenously (from distant foci of infection - tonsils, carious teeth and others) and lymphogenously. Ethiological value of lambliasis in development of cholecystitis is disputable. Congestion of bile in gall bladder predisposes to occurrence of cholecystitis. There are the following reasons of bile congestion: biliary stones, biliary dyskinesia (under influence of different psycho-emotional moments, dysfunction of endocrine and vegetative nervous system, numerous nervous reflexes from the side of pathologically changed organs of digestive system and others), anatomical peculiarities of structure of gall bladder and biliary tracts, splanchnoptosis, pregnancy, sedentary life-style, rare food intakes, habitual constipation and others. Cholecystitis is subdivided into acute and chronic.

Acute cholecystitis

Clinical picture. Acute cholecystitis begins suddenly: sharp pains in right hypochondrium appear; they spread along whole upper half of abdomen, irradiate into right half of thorax, neck and heart area sometimes. They can look like biliary colic, but usually they are less intensive and last during some days or (without treatment) - more prolonged period. Often pains are accompanied by nausea and vomiting with little amount of bile. Pains occur as result of inflammatory lesion of wall and mucous membrane of gall bladder and distension of peritoneum, covering it. Usually elevation of body temperature (to 38º C and even to 40º C) and chill are marked. Sometimes slight jaundice as result of inflammatory oedema of mucous membrane of common biliary tract and difficulty of bile outflow occurs. The tongue is dry, furred (by white deposit). Abdominal distension is marked, mobility of anterior wall is limited or it doesn’t take part in breathing. During superficial palpation tension of abdominal wall (at first - local, than - diffuse), sharp tenderness in right hypochondrium are marked. Besides, in case of acute cholecystitis it is possible to reveal number of symptoms: Zakharin’s symptom (sharp pain during tapping or pressing in area of projection of gall bladder), Vasilenko’ symptom (sharp pain during tapping in area of projection of gall bladder at the height of inspiration), Obraztsov-Murphy’s symptom (sharp pain during introduction of manus in area of right hypochondrium at the height of inspiration), Ortner’s symptom (pain on tapping with the edge of the manus on the right costal margin). Positive Blumberg’s symptom is revealed in spread of inflammatory process into peritoneum; in this case in gangrenous cholecystitis dangerous sign of potential perforation of gall bladder’s wall - peritoneal murmur in place of its projection on abdominal wall- appears. Sometimes in moderate tension of abdominal muscles (in purulent cholecystitis, particularly) it is possible to palpate enlarged and sharply painful gall bladder. Liver, as a rule, isn’t enlarged, but sometimes its painful edge is palpated. Positive Mussy-Georgievsky symptom (pain on pressure between the pedicles of m. sternocleidomastoideus) is revealed often; zones of skin hypesthesia (Zakharin - Head’s zones) - under lower angle of right scapula and in area of IX-XI intercostal space - can be observed. Lekocytosis with shift to the left, ESR acceleration are marked in the blood. During duodenal intubation (which can be carried out only during period of absolute dying down of inflammatory process) it isn’t possible to get B-bile often. There are many leukocytes, mucus, and cells of desquamated epithelium in bile. In bile inoculation appropriate microflora is revealed. Course and complications. In case of catarrhal cholecystitis recovery occurs relatively quickly, but transmission to chronic form is possible. Acute purulent cholecystitis is taking its more severe course, with signs of intoxication, signs of peritoneal irritation, high neutrophilic leukocytosis and significant acceleration of ESR. In gangrene of gall bladder signs of general intoxication are more evident, and in perforation of its wall symptoms of biliary peritonitis are added. Treatment. Hospitalization is necessary. In purulent and gangrenous forms of acute cholecystitis cholecystectomy is indicated. For patients with catarrhal cholecystitis the following is prescribed: bed rest, fast during first 2 days after attack, in further - diet No5 (according to Pevzner) with food intake by means of little portions 5-6 times in a day, broad-spectrum antibiotics (for example, claforan 1g or cephasolin 250-500 mg 2-3 times in a day intramuscularly during 5-7 days) and spasmolytics (papaverinum hydrochloride 2 ml 2% solution 3 times in a day subcutaneously, no spa and others).

Chronic cholecystitis

Chronic cholecystitis can occur after acute one, but more often it develops independently and gradually. Clinical picture. Patients feel dull pains in right hypochondrium, which usually occur in 1-3 hours after plentiful, fat food intake and fried courses. Pains irradiate upwards, into area of right shoulder, neck, scapula. In combination of cholecystitis with cholelithiasis sharp pains like biliary colic can appear. Side by side with pains number of dyspeptic signs occurs: feeling of bitter taste and metallic taste in the mouth, air eructation, nausea, abdominal distension, alternation of constipation and diarrhea. Sometimes disease is taking its course without pains, feeling of heaviness in epigastrium or right hypochondrium and dyspeptic signs are marked. Mild pyrexia is observed often. Patients’ appearance and degree of nourishment aren’t changed, sometimes moderate obesity is marked. During inspection of abdomen its distension (proportional or in upper half mainly) can be marked. During superficial palpation of abdomen sensitivity or significant tenderness in area of gall bladder’s projection is revealed. Muscular resistance of abdominal wall is absent usually. Positive Mussy-Georgievsky symptom, Ortner’s symptom, Obraztsov-Murphy’s symptom, Vasilenko’ symptom are marked. Liver, as a rule, isn’t enlarged, but in case of such complications as hepatitis, cholangitis can be some enlarged, its edge is firm and painful during palpation. Gall bladder is palpated rarely.

Syndromes, occurring in chronic cholecystitis*:

 Pain syndrome  Dyspeptic syndrome  Syndrome of vegetative dystonia  Right-side reactive syndrome  Syndrome of premenstrual tension  Cholecystocardial syndrome  Solar syndrome  Neurotic syndrome  Allergic syndrome * Syndromes are analyzed in detail during lecture course

Changes of the blood (out of exacerbation phase) aren’t typical or they are manifested by moderate leukocytosis and insignificant acceleration of ESR. In B-bile of duodenal contents signs of inflammation (mucus, leukocytes, desquamated epithelium) can be revealed. If inflammatory process is in biliary tracts also (cholangitis), the same changed are revealed in C-bile also. Sometimes it is impossible to get cystic reflex (B-bile) during reiterated intubation even. It testifies about disturbance of contractive function of gall bladder, typical for chronic cholecystitis. Bacteriological examination of cystic bile reveals type of microflora. Ultrasound examination of gall bladder can reveal signs, typical for its chronic inflammation. They are: deformation due to formation of commissures with neighbouring organs, sickness of the wall. During cholecystography changed form and indistinct image of gall bladder are observed. They testify about disturbance of concentration ability of its mucous membrane. After intaking of alimentary stimulator (it is two egg yolks usually) or parenteral introduction of stimulator (pancreozymin-cholecystokinin) insufficient contraction of gall bladder is marked. Course and complications. Alternation of exacerbation periods and remission periods is typical mainly. Malnutrition (fat, fried food abuse, smoke-dried food abuse, spice abuse, alcohol drinks abuse and others), acute intestinal infections and others can be reason of exacerbations. Process lasts during many years or decades. Cholecystitis often is complicated by inflammation of biliary tracts (cholangitis) or pancreas (pancreatitis). Treatment. During exacerbation period of chronic cholecystitis treatment must be carried out in in-patient department (like in acute cholecystitis). During remission period carrying out of anti-recurrent courses of treatment 1-2 times during year is effective. It includes the following: periodical duodenal intubation or “tubeless intubation” (with mineral water), use of choleretics (for example, allochol 1-3 tablets 3 times a day after meal; 10-20 g of choleretic preparation as tincture - 200 ml, 1/2 of glass 3 times a day 30 minutes before meal and others) during 3-4 weeks (as course); sanatorium-and-spa treatment is indicated. Prophylaxis of disease and prevention of recurrent exacerbations foresee measures, preventing to bile stagnation in gall bladder (gymnastics, airings, regular and frequent food intake with certain limitation), and treatment of foci of infection.

CHOLANGITIS

Cholangitis may be acute or chronic, and symptoms result from inflammation, which usually requires at least partial obstruction to the flow of bile. Bacteria are present on bile culture in approximately 75 % of patients with acute cholangitis early in the symptomatic course. The characteristic presentation of acute cholangitis involves biliary pain, jaundice, and spikling fevers with chills (Charcot’s triad). Blood cultures are frequently positive, and leukocytosis is typical. Nonsuppurative acute cholangitis is the most common and may respond relatively rapidly to supportive measures and to treatment with antibiotics. In suppurative acute cholangitis, however, the presence of pus under pressure in a completely obstructed ductal system led to symptoms of severe toxity-mental confusion, bacteriemia, and septic shock. Response to antibiotics alone in this setting is relatively poor, multiple hepatic abscesses are often present, and the mortality rate approaches 100 % unless prompt endoscopic or surgical relief of the obstruction and drainage of infected bile are carried out. Endoscopic management of bacterial cholangitis is as effective as surgical intervention. Endoscopic retrograde cholangiopancreatogram with endoscopic sphincterotom is safe and the preferred innitial procedure for both establishing a definitive diagnosis and providing effective therapy.

THE MAIN CLINICAL SYNDROMES

PORTAL HYPERTENSION

Portal hypertension is characterized by constant elevation of blood pressure in portal vein and manifested by dilatation of portocaval anastamoses, ascites and enlargement of the spleen. Portal hypertension occurs due to blood outflow disturbance from portal vein as result of its constriction from outside (by tumor, enlarged lymph nodi of the liver entry in metastases of cancer and others) or obliteration of its part of intrahepatic braches in chronic lesions of liver parenchyma (in cirrhosis), or thrombosis of portal vein or its branches. In hepatocirrhosis expanding and following scarring of connective tissue on the place of death hepatic cells lead to constriction or total obliteration of part of hepatic sinusoids and intrahepatic vessels. As result - obstruction of blood flow occurs, portal pressure is elevated, blood outflow from organs of abdominal cavity is disturbed. In these conditions transsudation of fluid from bloodstream into abdominal cavity is increased and ascites is formed. Decrease of oncotic pressure of plasma as result of disorder of synthesis of albumines in the liver plays role in development of ascites in hepatocirrhosis also; delay of sodium and water as result of increased production of aldosterone by adrenal glands (secondary hyperaldosteronism) and its insufficient inactivation in the liver (together with vasopressin) has value. Term of appearance of ascites depends on degree of development of collateral circulation - on amount of portocaval anastomoses. During long period disorders of portal circulation can be compensated by means of passing of the blood from portal vein into superior vena cava and inferior vena cava by anastomoses (they are normally). In case of portal hypertension these anastomoses are very developed. There are three groups of natural portocaval anastomoses: 1) in zone of hemorrhoidal venous plexuses - anastomoses between inferior mesenteric vein (portal vein system) and hemorrhoidal veins, flowing into inferior vena cava; in portal hypertension hemorrhoidal nodi is developed, their rupture often results hemorhroidal bleeding; 2) in zone of esophago-gastric plexuses - roundabout fashion (way) along left gastric vein, esophageal plexus and hemiazygos vein into superior vena cava. In case of significant portal hypertension large varicose venous “nodi” are formed in upper part of esophagus. In case of their trauma (for example, by firm food) bleeding as hematemesis (it is severe complication of diseases with portal hypertension, it is reason of patients’ death often) can occur; 3) in system of paraumbilical veins, anastomosing with veins of abdominal wall and diaphragm, carrying blood into superior vena cava and inferior vena cava. In portal hypertension dilated diverged into different sides veins around umbilicus form original picture, named as “Medusa head” (caput Medusae). Degree of increase of the pressure in system of portal vein can be revealed by measuring of the pressure in the spleen by means of special needle and liquid manometer (splenomanometry) or in dilated esophageal veins (by means of special needle, introduced through esophagoscope). It is considered that the pressure in the spleen is equal to one in the trunk of portal vein. Normally it is 70-150 mm water pole, in case of portal hypertension it reaches 400-600 mm water pole and more. If it is necessary to make more precise level of disorder of portal vein patency, physician must use special X-ray contrast methods: splenoportography, or (more rarely) transumbilical portohepatography. Some enlargement of the spleen as result of venous stagnation is marked in portal hypertension also. Treatment. In the patients with this syndrome anastomoses between poral vein system and inferior vena cava is formed by means of surgical method with purpose of elimination of portal hypertension (which is dangerous first of all by esophago-gastric and hemorrhoidal bleeding).

HEPATOLIENAL SYNDROME

Hepatolienal syndrome is characterized by simultaneous enlargement of the liver and spleen in primary lesion of one of these organs. Common participation of these organs in pathological processes (liver diseases, blood diseases, some infections, intoxications) is explained by presence of reticuloendothelial tissue in them. Sometimes (for example, in thrombosis of hepatic veins) simultaneous enlargement of liver and spleen is caused by venous stagnation in them. Palpation, ultrasound study, scanning allows to reveal hepatolienal syndrome. Significant enlargement of the spleen usually is accompanied by intensification of its function (hypersplenism). It is manifested by anemia, leukopenia, and thrombocytopenia; last one can lead to development of hemorrhagic complications. These changes are explained by the following: inhibition bone marrow hematosis occurs as result of very active function of the spleen; destruction of blood cells in the spleen and forming of antierythrocitic, antileukocytic and antithrombocytic autoantibodies are intensified.

HEPATIC FAILURE. HEPATIC COMA

Syndrome of hepatic failure (insufficientia hepatis) - is traditional for clinicians name of liver dysfunction of different degree severity. Severe acute and chronic liver diseases due to expressed dystrophy and death of hepatocytes ( in spite of significant compensatory possibility of the liver) are accompanied by severe disorders of its numerous functions, which are very important for organism. There are acute and chronic hepatic failure and its three stages: initial, compensated; expressed, decompensated; and terminal, dystrophic, which is finished by coma and patient’s death. Acute hepatic failure occurs in severe types of viral hepatitis (Botkin’ disease), poisoning by hepatotropic poisons: industrial, vegetable, some medicines and others. Acute hepatic failure is developed quickly- during some hours or days. Chronic hepatic failure occurs in many chronic liver diseases (cirrhosis, tumorous lesions and others) and characterized by slow, gradual development. Expressed dystrophy and necrobiosis of hepatocites, accompanied by significant decrease of all function of the liver and forming of numerous collaterals between poral vein system and superior and inferior vena cava (arising in difficulty of blood passing from portal vein in any liver lesions) are in the basis of hepatic failure development. By collaterals great amount of the blood, containing toxic substances, absorpted in intestine, get into systemic circulation passing past liver. Manifestations of hepatic failure are explained by complex disorders of different metabolic processes with liver’s participation, by disturbance of cholipoiesis, by disorder of antitoxic function of the liver. Hepatic coma (coma hepatica) is extreme degree of hepatic failure. Pathogenesis of hepatic coma comes to severe self-poisoning of organism due to almost total stop of liver action. Poisoning is caused by undeactivated products of intestinal (bacterial) protein destruction, final products of metabolism, ammonia particularly. Phenols are toxic substances also. In hepatic failure other toxic substances are accumulated in the blood also, electrolyte metabolism is disturbed, in severe cases hypokaliemia and alkalosis occur. The following factors can make worse hepatic failure and provoke appearance of hepatic coma:  alcohol, barbiturates, narcotic analgesics (morphine, promedole) intake;  excessive protein intake by patients with liver diseases (it results to intensification of putrefaction processes in intestine, increased formation of toxic products and their absorption in the blood);  massive bleedings from vessels of alimentary tract, often complicating hepatocirrhosis with syndrome of portal hypertension;  large doses diuretics intake;  single-stage removal of plenty ascitic fluid;  severe diarrhea;  accompanied severe infectious diseases.

Clinical manifestations of hepatic failure and hepatic coma

They usually are accompanied with symptoms of liver’s disease, which led to its dysfunction. Stages of symptoms increasing are seen very well in progressing of chronic hepatic failure (in patients with hepatocirrhosis, tumorous lesions of the liver and other diseases). During initial (compensated) stage clinical symptoms of hepatic failure are absent, but decrease alcohol and other toxic influences tolerance of organism is marked, indexes of laboratory liver function tests are changed. During second (expressed, or decompensated) stage clinical manifestations of hepatic failure appear: at first - slight, then - expressed weakness, undue fatigability during physical work, usual for patient, suppressed appetite, often-dyspeptic signs (poor fat food tolerance, meteorism, borborygmus and abdominal pains, feces disturbance, which are explained by cholepoiesis disturbance and intestinal digestion processes disorder. Signs of polyhypovinaminosis are explained by malabsorption of vitamins. Fever, observed often in hepatic failure, can be caused by the main disease and disorder of inactivation of some pyrogenic protein substances by the liver. Jaundice and hyperbilirubinemia with accumulation of unconjugated bilirubin in the blood are often signs of hepatic failure. Simultaneously conjugated bilirubin can be accumulated in the patients’ blood due to disorganization of the liver’s structure and cholestasis. Hypoproteinemic edema can appear and often existent ascitis (in the patients with chronic liver diseases) can grow more serious due to albumin synthesis disorder in the liver and expressed hypoalbuminemia. Synthesis disorder of some factors of coagulation blood system (fibrinogen, prothrombin, proconvertin and others) and decrease amount of thrombocytes in the blood (due to hypersplenism, accompanying to many chronic liver lesions) lead to occurrence of hemorrhagic diathesis - appearance of skin hemorrhages, nasal bleedings and others. Insufficient inactivation of estrogenic hormones by affected liver in its chronic diseases results to onset of endocrine disorders (gynecomastia in men, menstrual cycle disorder in women and others). During second stage of hepatic failure laboratory liver functional tests reveal significant changes. Decrease of substances, produced by the liver: albumin, cholesterol, fibrinogen and others is typical. Significant liver dysfunction is revealed by hepatobiliary scintigraphy also. Third, final (terminal, or dystrophic), stage of hepatic failure is characterized by more severe metabolic imbalance in organism, dystrophic changes in the liver and other organs; in the patients with chronic liver diseases emaciation is developed. Nervous-psychical disorders, presage of coma occurs. They are decrease of intellect, sluggish mentality, some euphoria, sometimes depression and apathy. Instable mood - irritability, changed by melancholy attacks, is observed often; sleep is disturbed. In the future disorders of consciousness with increase (with spatial and time disorientation), spotty memory defects, dysphasia, hallucinations, sleepiness occur. Side by side with large muscular tremor of upper and lower extremities typical little tremor is marked. Precoma period can lasts from some hours till some days and weeks even. After it patients sometimes can get out of this state completely, but coma occurs more often. Clinical picture of hepatic coma is characterized by excitement at first, but then - by general depression (stupor) and progressing impairment of consciousness (sopor) to total its loss (coma). Curve of electroencephalogram is flattened. Hyporeflex occurs, but sometimes - hyperreflex and appearance of pathologic reflexes (grasp, sucking and others) are marked. Motor anxiety, clonic convulsions, caused by hypokaliemia, muscular tremor, tremor of extremities (rhythmic and arrhythmic tremor of fingers and toes) are typical. Breathing rhythm is disturbed: Kussmaul respiration (more rarely - Cheyne-Stokes respirarion) occurs. Enuresis and encopresis (fecal incontinence) occurs. Fetor hepaticus is revealed in these patients. It is caused by excretion of methylmercaptane, which is formed as result of methionine metabolism disorder. Often during inspection signs of hemorrhagic diathesis (nasal, gingival, skin hemorrhages) are observed. Patient’s body temperature during terminal period is less than normal. Liver can be enlarged or becomes smaller. Jaundice is increased. Laboratory researches reveal moderate anemia, leukocytosis, elevated ESR, decreased amount of thrombocytes, fibrinogen, elongation of prothrombin time, severe disorder of liver functional tests, increase of bilirubin level; content of rest nitrogen and ammonia in blood serum is increased. It testifies about secondary lesion of the kidneys (hepato-renal syndrome). Hyponatriemia, hypokaliemia, metabolic acidosis are developed. Hepatic coma, as a rule, is finished by death. But sometimes it is possible recovery. Treatment. In case of acute hepatic failure treatment is directed to maintaining of patient’s life during critical period (some days, taking into account significant regenerative ability of the liver) by means of intensive medical actions: plasma transfusions, polyglucine transfusions, glutamic acid (which binds ammonia) solution infusions, oxygenotherapy, correction of water-salt disorders and others. In case of chronic liver lesions, apart from treatment of the main disease, it is necessary to suppress complicating factors (esophago-gastric bleedings, accompanying infectious disease), diet with poor protein content is prescribed; antibiotics are prescribed for suppressing of putrefactive processes in intestine and decrease of absorption of protein degradation products. Correction of electrolytic disorders and struggle against hemorrhagic signs are carried out. Now liver transplantation, hemosorption, plasmapheresis are used as methods of treatment.

HEPATITIS

Hepatitis - general name of inflammatory and inflammatory-dystrophic diffuse or focal diseases of the liver. There are acute hepatitis (taking its course within 3 months), lingering hepatitis (till 6-8 months) and chronic hepatitis. Besides, there is acute recurrent hepatitis when signs of inflammatory lesion of the liver is observed again during some period 2-4 months later after acute hepatitis (viral mainly) in past. CHRONIC HEPATITIS

Chronic hepatitis (hepatitis chronica) is chronic inflammatory diffuse and focal lesion of the liver. Etiology and pathogenesis. There are the following main groups of chronic hepatitis: 1) infectious (as result of viral hepatitis, in brucellosis, tuberculosis, syphilis and others) and parasitogenic; 2) toxic - in industrial, medicinal, food, everyday chronic hepatotropic venoms poisonings (chloroform, lead compounds, aminazine, trinitrotoluol and others); 3) toxico- allegical, caused by direct toxic effect of some medicinal and other hepatotropic chemical substances and by hypersensitization of hepatic cells and whole organism to them (drug-induced hepatitis, in collogenouse diseases); 4) metabolic due to metabolic derangements in the liver, caused by vitamin deficiency, in fatty degeneration and amyloidosis. In 40-70 % cases chronic hepatitis is result of acute viral hepatitis, caused by hepatitis B and C viruses. Hepatitis is diffuse mainly; focal inflammatory lesions of the liver can occur in tuberculosis (tuberculous granuloma, caseous abscess - tuberculoma), syphilis (gumma), some protozoal diseases (amebic abscess), fungous, bacterial lesions (abscess mainly) and others. Pathogenesis is caused by etiology of disease in great degree. In viral hepatitis it is probable prolong persisting of virus in hepatic cells with progressive cytopathic effect of virus. It leads to death of hepatocytes and following inflammatory reaction of connective tissue. In case of long action of toxic hepatotropic substances the main value belongs to their direct damaging effect to hepatocytes down to their necrobiosis, and secondary inflammatory reaction of hepatic mesenchyma. Often first place belongs to autoimmune processes, appearing as answer to primary lesion of hepatic tissue by any etiological factors. In pathogenesis of so called “cholestatic hepatitis” decisive value belongs to obstruction for bile flow, bile stagnation, appearance of cholangitis and cholangiolitis with following spread of inflammatory process to hepatic tissue and some medicinal intoxication (isoniazid and its derivatives and others). Clinical picture. The following symptoms are typical for chronic hepatitis: 1) dyspeptic signs; 2) jaundice (it doesn’t occur always); 3) moderate enlargement and consolidation of the liver and spleen; 4) dysfunction of the liver, revealed by laboratory methods and quantitative hepatobiliary scintigraphy. But clinical picture and course of every clinico-morphological form of hepatitis has some peculiarities.

Syndromes, occurring in chronic hepatitis*:  Asthenic syndrome  Abdominal-painful syndrome  Dyspeptic syndrome  Cholestatical syndrome  Syndrome of vegetative dystonia  Edematous-ascitic syndrome  Encephalopathical syndrome  Articular syndrome  Feverish syndrome  Hemorrhagic syndrome * Syndromes are analyzed in detail during lecture course

Chronic persistent (benign) hepatitis is characterized by indeterminate clinical picture. Patients complain of feeling of heaviness or dull pains in right hypochondrium, decrease of appetite, bitter taste in mouth, nausea, eructation. Jaundice, as a rule, doesn’t occur or it is insignificant. During objective examination little enlargement of the liver is revealed; its surface is smooth, during palpation it is revealed its moderately firm and slightly painful edge. The spleen is little enlarged. Laboratory researches reveal the following changes: bilirubin content in blood serum isn’t increased more often, but in case of jaundice it is increased approximately to 17-50 mkmol/l (1-3 mg%); insignificant hyperglobulinemia is present, activity of enzymes is changed little or it is normal, protrombin content is normal or some decreased, bromsulfalein test is slightly positive. Chronic active hepatitis is characterized by expressive complaints and objective signs. Patients complain of weakness, loss of weight, fever, pains in right hypochondrium, loss of appetite, nausea, eructation, meteorism, skin itch, jaundice, often - basal bleeding. The liver is enlarged, firm, with sharp edge. The spleen is enlarged. Laboratory researches often reveal anemia, leukopenia and thrombocytopenia (as manifestation of hypersplenism) and elevated ESR. Liver function tests are changes significantly: hyperbilirubinemia, hyperproteinemia, hypergammaglobulinemia are observed, protein-sedimentary tests are positive, activity of transaminases, aldolase and alkaline phosphatase is increased, activity of choline esterase is decreased. Serum iron content is increased, protrombin index is decreased significantly, delay of bromsulfalein excretion is observed. In patients with chronic viral hepatitis type B HBsAg and HBeAg are revealed in the blood, in patients with chronic viral hepatitis type C - virus hepatitis C antibodies (so called anti- HCV). For some time past polymerase chain reaction, revealing DNA of hepatitis B virus and RNA of hepatitis C is used often. Puncture biopsy of the liver and (in case of indications) laparoscopy allow to identify peculiarities of histological and macroscopic changes of the liver, typical for these forms, and to carry our differential diagnostics with other its diseases (cirrhosis, amyloidosis and others). It is necessary to mark that sometimes hystological and hystochemical research of biopsy materials reveal initial morphological changes of the liver, which precede to appearance of clinical and laboratory signs of chronic hepatitis. For chronic cholestatic hepatitis syndrome of cholestasis is typical first of all. Its signs are jaundice (mechanical), intensive skin itch (due to delay of excretion and increase of bile acids concentration in the blood), hyperbilirubinemia, increase of activity of alkaline phosphatase in the blood, increase of blood cholesterol; constant mild pyrexia is observed often; elevation of ESR is typical. Course. It can be very long -till 20 years - in case of benign (persistant) chronic hepatitis; exacerbation occur rarely and only under influence of strong provocation factors. Development of cirrhosis is observed rarely. In number of cases, under influence of therapy particularly, it is possible total clinical recovery with restoration of morphological structure of the liver. Active hepatitis is characterized by recurrences, their frequency can be various. Frequent recurrences lead to intensification of dystrophic and inflammatory-cicatricial changes of the liver and development of hepatocirrhosis. Prognosis in case of this type of hepatitis is more severe. The course and prognosis in cholestatic hepatitis depend on its etiology, the possibility of elimination of obstruction of bile flow particularly (in compression of common biliary duct by tumor, its cicatricial-inflammatory stenosis and others). Treatment. The main task during treatment of chronic hepatitis is elimination of reasons, caused disease (it is necessary to exclude alcohol intake and possibility of further contact with different toxic substances completely and others). During exacerbation of disease treatment must be directed to maximal protection of the liver and increase of ability of liver to regenerate: bed rest, diet, by indication - antiviral preparations (interferon, lamivudin, ribavirin and others).

HEPATOCIRRHOSIS

Hepatocirrhosis (cirrhosis hepatis) is chronic progressive disease, characterized by increasing hepatic failure in connection with dystrophy of hepatic cells, shrinkage and structural change of the liver. Etiology and pathogenesis. Hepatocirrhosis is polyetiological disease. The following factors have the greatest value for its appearance: 1) infection (hepatitis B virus and hepatitis C virus mainly); 2) alcoholism; 3) deficiency in proteins and vitamins intake; 4) toxico-allergic factor; 5) cholestasis. In Ukraine leading role in developing of disease belongs to viral hepatitis. This type of cirrhrosis, probably, is caused by long persisting of virus in hepatic cells. Prolong alcoholic intoxication has great value also. It results to malabsorption of vitamins and proteins, promoting to development of hepatocirrhosis, and directly specifically influences to metabolism of hepatic cells. Alimentary factor - undernutrition, deficiency of proteins and vitamins mainly, is the cause of hepatocirrhosis in some regions. Malnutrition factor has endogenous origin mainly; in this case malabsorption of proteins and vitamins occurs (in severe chronic diseases of gastrointestinal tract, after total gastrectomy, in chronic pancreatitis, enteritis and in other cases). Toxic hepatocirrhosis occurs relatively rarely, it appears in recurrent and long four-chloride carbon, phosphor compounds, arsenic compounds and others exposures, in poisoning (by toadstools, for example). Toxico-allergic cirrhosis includes lesions, connected with hypersensitivity (autoallergy) to different medicaments (aminazin, some antibiotics, sulfonamides and others); its result is dystrophy and necrosis of parenchyma of the liver. Obturation of intra- and extrahepatic biliary ducts, their inflammation, leading to bile stagnation - cholestasis has value in occurrence of biliary hepatocirrhosis. Etiological factor doesn’t determine ways of development of hepatocirrhosis always. The same cause of liver’s lesion can lead to forming of different morphological variants of cirrhosis (portal, postnecrotic, and biliary), and different etiological factors - to the same morphological changes. Questions of pathogenesis are connected with morphogenesis closely. Recurrent necroses of hepatic cells, appearing under influence of different etiological factors have greatest value in mechanism of hepatocirrhosis development. They result collapse of reticuline framework of the liver, forming of scars and blood supply disturbance in bordering areas of unchanged parenchyma. Undamaged hepatocytes or fragments of lobules begin to regenerate intensively under influence of substances (from necrotic focus), stimulating growth. Formed large “nodes- regenerators” press surrounding tissues with vessels, located in it; hepatic veins are pressed the most intensively. Disturbance of blood outflow occurs. It promotes to development of portal hypertension and forming of collaterals between branches of portal and hepatic veins, facilitating intrahepatic circulation. The blood goes along them bypassing unchanged hepatic parenchyma; it worsens its blood supply suddenly and can lead to new ischemic necroses, to growing more serious of cirrhosis at absence of action of primary etiological factor even. Growing of collagenous connective tissue occurs simultaneously; connective-tissue septa grow into parenchyma from periportal areas and fragment hepatic lobules. Formed “false” lobules can be source of nodular regeneration in the future. Long or recurrent direct toxic influence of some dangerous hepatotropic substances, autoimmune and some other mechanisms has value in pathogenesis of separate types of cirrhosis. Clinical picture. Portal hepatocirrhosis occurs mainly among persons of 40-60 years old, besides in men in 2 time more often, than in women. Postnecrotic and biliary hepatocirrhosis occur among more young persons, in women more often. Clinical manifestations of hepatocirrhosis depends on degree of lesion of hepatic cells and functional insufficiency of the liver and portal hypertension (as result of lesion), on stage of disease (compensated or decompensated) and degree of activity of pathological process in the liver. The following symptoms of disease are typical for majority of the patients with different variant of hepatocirrhosis. Pains in area of the liver, epigastrium or diffuse along whole abdomen are usually dull. They become more intensive after food intake, fatty particularly, plentiful drinking, and physical work. Pains usually are caused by enlargement of the liver and distension of capsule or by appearance of necrotic foci, located closely to capsule, by signs of perihepatitis, and by accompanying lesion of biliary tracts, inflammatory process. Dyspeptic signs: decrease of appetite to anorexia, heaviness in epigastrium after food intake, nausea, vomiting, meteorism and disorder of stool (after fatty food intake particularly) are caused by bile secretion disturbance and by maldigestion as result of this process. Besides, dyspeptic signs can be caused by accompanying biliary dyskinesia or alcoholic gastroenteritis. Decrease of working ability, general weakness, rapid fatigability and sleeplessness are observed in hepatocirrhosis often. Fever, more often wrong or wavy sometimes, accompanies postnecrotic hepatocirrhosis and is explained by destruction of hepatic cells in necrosis. Fever is expressive during period of activity of cirrhotic process and in case of infectious origin of cirrhosis. Hemorrhagic syndrome is observed in half of patients with hepatocirrhosis. Massive hemorrhage from dilated esophageal and gastric veins often can be one of the initial sign of portal hepatocirhrosis; their reason is elevated pressure in esophageal and gastric veins and proteolytic action of active gastric juice to mucous membrane of distal part of esophagus in gastro-esophageal reflux. In other types of cirrhosis nasal, gingival, uterine bleeding, skin hemorrhages occur in case of evident decompensation of cirrhosis and they are caused by decreasing of blood coagulation in connection with dysfunction of the liver. During inspection the following signs of cirrhosis are marked. Cachexia is typical for patients with portal hepatocirrhosis particularly. In case of long severe disease subcutaneous fat doesn’t disappear only, but muscular atrophy is developed also (of shoulder girdle particularly). The following general appearance is typical for such patients: emaciated face with grey or subicteric skin color, bright lips and tongue, erythema of cheekbone area, thin extremities, and large abdomen (due to ascites, enlargement of liver and spleen), dilation of subcutaneous veins of abdominal wall, edema of the legs. Malnutrition of the patients is caused by disorder of gastrointestinal digestion and uptake and synthesis of protein in affected liver. Jaundice, except cases of biliary cirrhosis, is manifestation of hepatocellular failure, connected with necrosis of hepatic cells. Affected hepatocytes lose ability to catch bilirubin from the blood and to connect it with glucuronic acid partly; excretion of conjugated bilirubun into bile is disturbed also. Due to this processes content of unconjugated and conjugated bilirubin in the blood serum is increased. Partly light-colored feces and presence of bile in duodenal content is usually typical for jaundice. Often jaundice is accompanied by skin itch. In case of biliary hepatocirrhosis jaundice is mechanical, excruciating skin itch is marked. Intensity of jaundice is various: from slight subinteritiousness to evident icteritiousness depending on degree of obstruction of biliary ducts. In case of prolong common biliary duct obstruction skin becomes greenish. Last sign depends on oxidation of bilirubin in the skin and forming of biliverdin. Besides, brown pigmentation of skin cover, depending on accumulation of melanin can be observed. During inspection of the patient it is possible to reveal “small” signs of cirrhosis also. They include the following: 1) vascular “stars”- like-star teleangiectasias (they can appear some years before expressed symptoms of this disease); increase of their number and very bright color are marked in exacerbation of disease; 2) erythema of palms (“hepatic palms”); 3) red shiny lips, red color of oral mucous membrane, red “lustrous” tongue; 4) gynecomastia (enlargement of mammary glands in men) and other like-women sexual signs, which are developed in men (decrease of hair growth of the beard, on the chest, abdomen, and alopecia also); 5) xanthomas on the skin (they are observed in the patients with biliary hepatocirrhosis); 6) clubbed (drumstick) fingers with skin hyperemia near nail beds. Inspection of the skin can reveal dilated veins, visible through thin skin of abdominal wall (caput Medusae). Collateral venous network can be visible on the chest also; dilation of hemorrhoidal veins occurs often. Ascites is one of the typical sign of portal cirrhosis. Ascitic fluid can be accumulated slowly, but often ascites is huge, in this case dyspnea appears. Sometimes edema occurs, and in number of cases - hydrothorax also. In other variants of cirrhosis ascites is developed during late stage of disease. During palpation enlargement of the liver is revealed in 50-75 % of the patients with hepatocirrhosis. Degree of its enlargement can be various: from insignificant, revealed by percussion only to huge, when liver occupies whole right and part of the left half of abdomen; liver is firm, its surface is irregular , lower edge is acute. Enlargement of the spleen often is accompanied by intensifying of its action (hypersplenism); it leads to rise of leukocytopenia, thrombocytopenia and anemia.

Syndromes, occurring in hepatocirrhosis*:  Asthenic  Dyspeptic  Abdominal-painful  Vegetodystonic  Cholestatic  Feverish  Articular  Syndrome of portal hypertension  Hepatolienal  Hepatorenal  Hepatic failure  Hemorrhagic syndrome * Syndromes are analyzed in detail during lecture course

Laboratory results during period of activity of cirrhotic process reveal anemia, leukopenia, thrombocytopenia and elevated ESR. Anemia can be result of hypersplenism and gastro-intestinal hemorrhage, hepatocellular hailure, and often - increased hemolysis, which is accompanied by reticulocytosis of peripheral blood. Level of blood serum bilirubin reaches significant degree only during final stage of disease. At the same time, we can judge about changes of excretory function of the liver by content of conjugated bilirubin. Last one often is elevated in increased and normal quantity of total bilirubin. Besides, content of unconjugated bilirubin in blood serum is increased also as result of disturbance of bilirubun conjugation in hepatic cells and hemolysis. In biliary hepatocirhhosis level of serum bilirubun fluctuates within wide limits - 26-340 mkmol/l (1,5-20 mg%), due to conjugated bilirubin mainly. Urobilin is revealed in urine in quantity. It is important index of hepatic insufficiency. In presence of expressive jaundice, when small quantity bilirubin enters into intestine, urobilin amount in urine and stercobilin amount in feces is decreased. In case jaundice bilirubin also is revealed in urine. Disturbance of excretory function of the liver is revealed by delay of bromsulfalein and vofaverdin (indocyan) in the blood after intavenous introduction of them (now these tests are used rarely), and by hepatobiliary scintigraphy and liver scanning also. Lesions of hepatic cells are manifested by typical changes of protein indexes: by decreasing of concentration of serum albumins and hypergammaglobulinemia, it leads to decrease albumin-globulin coefficient. In case of activity of inflammatory process in the liver α2- globulins content is increased, in case of jaundice - β- globulins content is increased. During remission period all these changes are less evident. In case of biliary cirrhosis level of lipids and cholesterol of the blood is increased significantly also. Decrease of activity of serum cholesterase is sensitive index of dysfunction of the liver. In exacerbation of cirrhosis activity of transaminases is increased, and in case of biliary cirrhosis- alkiline phosphatase also. Decrease of protrombin content (its synthesis is realized by hepatic cells), increase of antitrombin serum activity and decrease of general coagulation serum activity have great importance for origin of hemorrhagic diathesis. Laparoscopy and biopsy of the liver, particularly, give possibility to reveal morphological signs, typical for every variant of hepatocirrhosis. Dilated esophageal veins are revealed by means of X-ray study. Though clinical and laboratory-instrumental examination methods don’t allow to differentiate different variant of hepatocirrhosis always, however, comparing of foregoing signs, it is possible to mark that in case of portal hepatocirrhosis symptoms of portal hypertension often is revealed significantly before functional insufficiency of the liver. This insufficiency is developed during late stage of disease only. But in case of postnecrotic hepatocirrhosis signs of hepatic insufficiency is developed early and determinate whole clinical picture of disease significantly. Chronic mechanical jaundice (at satisfactory condition of the patient) with skin itch, sometimes - fever, accompanied by chill, is on the first place in clinical picture of biliary cirrhosis; content of alkaline phosphatase, cholesterol in the blood is increased. Transdermal cholangiography is carried out for more precise description of causes of cholestasis (according to indications). In case of compensated hepatocirrhosis patients’ complaints can be insignificant: sometimes disease is revealed casually during examination, when enlargement of the liver and spleen is revealed. Remission can be long (during years). Decompensated, active hepatocirrhosisis characterized by expressed symptoms of disease and rapid progressive course. Course and complications. The course is progressive, as a rule. Total length of disease usually is 3-5 years, rarely - to 10 years and more (more often it is observed in biliary hepatocirrhosis). Terminal period of disease, regardless of type of hepatocirrhosis is characterized by gastrointestinal bleeding and developing of signs of functional hepatic insufficiency with end as hepatic coma. This is two most often occurring direct reasons of death of patients with hepatocirrhosis. Gastro-intestinal hemorrhage as hematemesis and melena occur as result of varicose nodes rupture in lower third part of esophagus or, rarer, in stomach. Physical exertion or local damage of mucous membrane (by rough food, for example) is direct reason of varicose hemorrhage. Massive hemorrhages (if they aren’t cause of patient’s death) can lead to anemia with following becoming worse of function of hepatic cells and hasten development of hepatic coma. Liver carcinoma can occur on the background of cirrhosis (in case of adding of hepatitis D virus, particularly). Treatment. During compensation stage of hepatocirrhosis treatment is directed to prevention of further its lesion by alcohol, toxic substances and others, and to rational management of work regimen. Besides, it is necessary to provide caloric feeding with sufficient content of proteins and vitamins. During period of decompensation treatment must be carried out in in-patient department necessary. In case of presence of varicose-dilated veins prophylaxis of hemorrhage must be carried out (β-antagonists, sclerotherapy and others).Diet with restriction of salt consumption and periodical diuretics intake must be prescribed to the patients with ascites. In case of ascites, which doesn’t corrected by diuretics, paracentesis must be carried out. In case of primary biliary (Hanot’s) cirrhosis ursodeoxycholic acid is used for diminishing of cholestasis and for elimination of skin itch. In severe cases and late stages transplantation of the liver must be carried. In case of secondary biliary hepatocirrhosis, for example in obstruction of bile duct by stone, surgical treatment is indicated.

Table 6 Child’s criteria for hepatic functional reserve (Modified, with permission, from Child CG) A B C Minimal Maximal Advanced Serum bilirubin < 2,0 2,0 - 3,0 > 3,0 (mg/dL) Serum albimin > 3,5 3,0 - 3,5 < 3,0 (g/dL) Ascites None Easily controlled Poorly controlled Neurologic disorder None Minimal Advanced, “coma” Nutrition Excellent Good Poor, “wasting

A. Test tasks to be done:

Block 1 -with a single selective answer – I-st level; 1. What substance causes normal golden-yellow and dark-brown color of bile? a) undirected bilirubin; b) biliary acids; c) direct bilirubin; d) cholesterol; e) sterkobilin. 2. How much bile does liver produce during day (account to 1 kg body weight)? a) 20 ml; b) 30 ml; c) 10 ml; d) 5 ml; e) 50 ml. 3. What is specific gravity of A-bile? a) 1,016-1,034; b) 1,007-1,015; c) 1,007-1,010; d) 1,040-1,050; e) 1,003-1,006. 4. What is specific gravity of B-bile? a) 1,016-1,034; b) 1,007-1,015; c) 1,007-1,010; d) 1,040-1,050; e) 1,003-1,006. 5. How many times is bile concentrated in gall bladder in? a) in 20 times; b) in 10 times; c) in 2 times; d) in 4 times; e) in 30 times. 6. What is colour of feces in mechanical jaundice? a) black; b) dark-brown; c) light-colored feces; d) grey; e) brown. 7. Why does bile in patients with chronic cholecystitis its “classical” dark-blown color loss? a) due to increase of conjugated bilirubin; b) due to presence of urobilin; c) due to presence of chronic inflammatory process in gall bladder; d) due to presence of stercobilin; e) due to presence of unconjugated bilirubin. 8. What is the sign of chronic inflammatory process in gall bladder? a) decrease of bilirubin content in bile of gall bladder; b) decrease of erythrocytes; c) decrease of casts; d) increase of biliverdin; e) increase of urobilin. 9. What is the sign of chronic inflammatory process in gall bladder? a) presence of leukocytes in I phase of chromatic fraction duodenal intubation; b) decrease of leukocytes in II phase of duodenal intubation; c) increase of number of leukocytes in bile A; d) increase of number of leukocytes in bile B; e) increase of number of leukocytes in bile C; 10. What is the sign of chronic inflammatory process in bile ducts? a) presence of leukocytes in I phase of chromatic fraction duodenal intubation; b) decrease of leukocytes in II phase of duodenal intubation; c) increase of number of leukocytes in bile A; d) increase of number of leukocytes in bile B; e) increase of number of leukocytes in bile C. 11. What is the main factor, predisposing to development of cholecystitis? a) bile congestion; b) esophagitis; c) erosive gastritis; d) esophageal diverticulum; e) hiatal hernia. 12. What is type of jaundice in cholelythiasis? a) hemolytic; b) parenchymatous; c) mechanical; d) jaundice is absent; e) parenchymatous and mechanical jaundice can be present. 13. What symptom is typical for chronic cholecystitis? a) Kehr’s symptom; b) Blumberg’s symptom; c) tenderness in Shoffar’s zone; d) tenderness in Dejarden’s point; e) Mendel’s symptom. 14. What is pH of bile normally? a) 3,3-4,0; b) 4,3-5,0; c) 5,3-6,0; d) 6,3-7,0; e) 7,3-8,0. 15. What is cholangitis? a) stagnation of the bile; b) inflammation of the liver; c) inflammation of gall bladder; d) inflammation of biliary ducts; e) dyskinesia of biliary tracts. 16. What does “vesica fellea” mean (according to Latin)? a) gall bladder; b) biliary tract; c) common hepatic duct; d) acute cholecystitis; e) cholelythisis.

Block 1 - with the selective group of right answers – the II-nd level; 1. What is revealed during microscopic examination of bile? a) color; b) crystals of cholesterol, bilirubinate of calcium, fat acids, microlits, salts of calcium; c) epithelial cells, simple leukocytes, mucus; d) transparency; e) presence of sediment; f) lamblia, eggs of helminth or helminth. g) ratio biliary acids : cholesterol. 2. When B-bile isn’t possible to collect? a) in case of pathological process in gall bladder, which result to disturbance of its contractive function and absence of reflex of gall bladder; b) sometimes in dyskinesia of gall bladder; c) in chronic hepatitis; d) in case of pathological process in intrahepatic biliary ducts; e) sometimes in significant spasm of sphincter of hepato-pancreatic ampoule; f) in congestive processes in gall bladder. 3. What diseases can be cause of appearance of chronic cholangitis? a) acute cholangitis; b) chronic cholecystitis; c) chronic hepatitis; d) cholelythiasis; e) tumours of pancreatoduodenal area; f) stenosis of biliary tracts; g) dyskinesia of gall bladder. 4. Chronic cholangitis is dangerous for appearance of: a) sepsis; b) hepatic failure; c) heart failure; d) chronic gastritis e) renal failure; f) anemia; g) arterial hypertension. 5. What can provoke appearance of biliary colic attack? a) long nervous and physical exertion; b) strong tea abuse; c) coffee intake; d) jolty driving; e) plentiful fat food intake; f) plentiful salt food intake; g) smoking; 6. What can stop biliary colic attack? a) warm; b) cold; c) intramuscular introduction of benadryl; d) intramiscular introduction of adrenaline; e) intramuscular introduction of baralgin; f) intramuscular introduction of papaverin hydrochloride; g) rest. 7. What instrumental methods have the most essential value in diagnostics of cholelythiasis? a) contrast X-ray study (cholecystography or cholegraphy); b) endoscopy; c) duodenal intubation; d) ultrasound study of gall bladder; e) plan radiography; f) rheography; g) pH-metry. 8. What are reasons of bile congestion in gall bladder? a) biliary stones; b) biliary dyskinesia; c) diarrhoea; d) anatomical peculiarities of structure of gall bladder and biliary ducts; e) often food intakes; f) splanchnoptosis; g) pregnancy; h) sedentary life-style. 9. What are complaints of patients with cholelythiasis? a) abdominal pains; b) chill; c) diarrhoea; d) nausea; e) vomiting; f) heartburn; g) heart intermissions. 10. What dyspeptic signs can occur side by side with pains in patients with chronic cholecystitis? a) feeling of bitter taste and metallic taste in the mouth; b) air eructation; c) heartburn; d) nausea; e) perverted appetite; f) abdominal distension; g) alternation of constipation and diarrhea.

Block 1 B. Tasks to be done: Task 1. Patient K. complains of severe cramp-like pains in right hypochondrium, which appeared suddenly on the background of normal feeling soon after dinner. At first pains were only in right hypochondrium, but gradually were radiated along whole abdomen and upwards to area of right scapula and shoulder. He also complains of long dull pains in this area, which sometimes become more intensive after fried and fat food intake. He marks also poor, often bitter taste in the mouth, eructation. Body weight is increased. Body weight index is 38. Insignificant tenderness during palpation of the liver is marked. Sizes of the liver by Kurlov are 12-9-7 cm. For which disease are these results the most typical?

Task 2. Patient S. complains of severe constant feeling of heaviness in right hypochondrium and pains in this area after fat food intake. Sometimes pains become very intensive and spread upwards to area of right scapula and shoulder. He marks poor, often bitter taste in the mouth, eructation. He is ill about 3 years, beginning of disease is gradual. Body weight is increased. Body weight index is 36. Insignificant tenderness during palpation in right hypochondrium is marked. Sizes of the liver by Kurlov are 12-10-9 cm. For which disease are these results the most typical?

Task 3. Results of study of duodenal contents in patient R.:

Stimulating agent - 33% sol. MgSO4 Additional stimulating agent - 40% sorbitol sol.

Phases of the probing Time in min Amount of the bile in ml Portion “A” 10 20 Phase of the Oddi sphincter 10 contracting Portion “A-1” 4 18 Portion “B” 15 25 Portion “C” 30 45 Additional bile

Types of examination Portion “A” Portion “B” Portion “C” Macroscopy Color Yellow Dark-brown Yellow Transparency Cloudiness Cloudiness Cloudiness Mucus + ++ +++ Microscopy Leucocytes in f.v. 20-30 20-30 30-40 Epithelium in f.v. 15-20 15-20 30-50 Cholesterol crystals ++ +++ ++ Calcium bilirubinate ++ +++ ++ Lamblia - + +

What is your conclusion?

Block 2 -with a single selective answer – I-st level; 1. How are hepatocytes in lobules of liver situated? a) as concentric circles around vein; b) in the middle of lobule; c) along external circle of lobule; d) along internal circle of lobule; e) radially from the centre of the lobule to its periphery. 2. How many great venous vessels carrying blood into portal vein are there? a) two; b) three; c) four; d) five; e) six. 3. What is the main pathogenic process in hepatocirrhosis? a) substitution of lobules for pseudolobules; b) obturation of bile ducts; c) congestion of the blood in intralobular hepatic veins; d) congestion of lymph in hepatic lobules; e) inflammation of hepatic lobules. 4. How many systems of portacaval (postcaval) shunts can be developed in portal hypertension? a) one; b) two; c) three; d) four; e) five. 5. Synthesis of urea from ammonia in liver occurs by means of: a) oxidation; b) reduction; c) methylation; d) acetylation; e) conjugation with other substances. 6. Normal pressure in portal vein is: a) 0 - 4 mm Hg; b) 5 - 10 mm Hg; c) 11 - 15 mm Hg; d) 16 - 20 mm Hg; e) 0 - 2 mm Hg. 7. Normal bound bilirubin content in blood serum is: a) 6,3 - 15,4 mkmol/l; b) 2,2 - 5,1 mkmol/l; c) 8,5 - 20,5 mkmol/l; d) 0,1 - 0,68 mkmol/l; e) 0,1 - 0,45 mkmol/l; 8. Normal unbound bilirubin content in blood serum is: a) 6,3 - 15,4 mkmol/l; b) 2,2 - 5,1 mkmol/l; c) 8,5 - 20,5 mkmol/l; d) 0,1 - 0,45 mkmol/l; e) 0,1 - 0,68 mkmol/l; 9. Aspartate aminotransferases (AST) normal level is: a) 0,1 - 0,45 mmol/h x l; b) 0,1 - 0,68 mmol/h x l; c) 0,09 - 0,57 mmol/h x l; d) 0,5 - 1,3 mmol/h x l; e) 160 - 340 mmol/h x l; 10. What is the sign of chronic inflammatory process in bile ducts? a) presence of leukocytes in I phase of chromatic fraction duodenal intubation; b) decrease of leukocytes in II phase of duodenal intubation; c) increase of number of leukocytes in bile A; d) increase of number of leukocytes in bile B; e) increase of number of leukocytes in bile C. 11. What macroscopic sign is typical for alcohol (portal) hepatocirrhosis? a) micronodular surface of the liver; b) macronodular surface of the liver; c) dilation of bile tructs; d) wide fibrous areas between nodes; e) smooth surface of the liver. 12. Enlargement of which organ (apart from liver) in case of hepatocirrhosis occurs? a) heart; b) kidneys; c) pancreas; d) stomach; e) spleen. 13. What is peculiarity of extremities in hepatocirrhosis? a) acrocyanosis; b) hyperemia of palms, soles; drum-stick fingers; c) transverse lines on the nails, acrocyanosis; d) edema, deformation of joints; e) koilonychia, spoon-shaped nails. 14. What is mechanism of ascites forming in hepatocirrhosis? a) increased hydrophilia of tissues; b) hypoproteinemia; c) cardiovascular collapse; d) inflammation of peritoneum; e) olyguria. 15. What changes of proteinogram is typical for chronic hepatitis? a) normoalbuminemia; b) hypoalbuminemia; c) hyperalbuminemia; d) hypoglobulinemia; e) normoglobulinemia. 16. What changes occur in coagulation blood system in hepatocirrhosis? a) decrease of general coagulation activity of plasma; b) increase of general coagulation activity of plasma; c) increase of protrombin content; d) decrease of antitrombin plasma activity; e) increase of fibrinogen content. 17. The following is typical in urine in hepatocirhrosis: a) bile pigments; b) protein; c) sugar; d) acetone; e) erythrocytes. 18. What sign, typical for hepatocirrhosis, can be revealed during inspection of abdomen? a) enlargement of abdomen with outpouching of the right hypochondrium; b) limitation of mobility during respiratory act; c) presence of intestinal peristalsis; d) pulsation in epigastrium; e) pale color of skin of abdomen. 19. Hepatic jaundice is caused by: a) obstruction of biliary tracts by stone, tumor; b) hemolysis of erythrocytes; c) inflammation of hepatic tissue; d) spasm of biliary tracts; e) decrease of resistance of erythrocytes. 20. By means of which clinical syndrome is it possible to differ acute and chronic hepatitis from hepatocirrhosis for the most part? a) hemorrhagic syndrome; b) hepato-renal syndrome; c) hepato-cerebral syndrome; d) portal hypertension syndrome; e) hepato-cardial syndrome. 21. How is virus of A hepatitis marked? a) HAAg; b) anti-HAV; c) HBsAg; d) HAV; e) anti-HAV, IgM. 22. How is virus of B hepatitis marked? a) HBsAg; b) HBV; c) anti-HBs; d) HBeAg; e) anti-HBc. 23. How is virus of D hepatitis marked? a) HDV; b) HDAg; c) anti-HDV; d) anti-HDV-IgM. 24. How is virus of E hepatitis marked? a) anti-HEV; b) anti-HBs; c) HEV; d) anti-HBc. 25. How is virus of A hepatitis antibody marked? a) anti-HAV; b) HAAg; c) anti-HAV, anti-HBV; d) HBeAg. 26. How is virus of A hepatitis antibody during acute phase of infection marked? a) anti-HAV; b) HAAg; c) anti-HAV, IgM; d) HBeAg. 27. How is virus of C hepatitis antibody marked? a) HCV; b) HCAg; c) anti-HCV; d) HCV-RNA. 28. How is virus of D hepatitis antibody during acute phase of infectious process marked? a) HDV; b) HDVAg; c) анти-HDV; IgG; d) анти-HDV; IgM.

Block 2 -with the selective group of right answers – the II-nd level; 1. Position of the liver is caused by: a) intraabdominal pressure; b) sex of patient; c) position of diaphragm; d) body constitution; e) position of the heart; f) position of pancreas; g) position of the stomach. 2. What changes in the blood, urine and faeces are revealed in patient with parenchymatous jaundice? a) level of unconjugated and unconjugated bilirubin in the blood is increased (in 4-10 times); b) brown color of urine with bright-yellow foam due to presence of bilirubin in it; c) dark color of urine due to excretion of conjugated bilirubin and urobilin; d) light -yellow (sometimes - light-colored )faeces due to decrease of stercobilinogen excretion; e) light-colored faeces due to absence of stercobilinogen in it; f) level of conjugated bilirubin only is increased significantly; g) level of unconjugated bilirubin only is increased significantly. 3. What are the main clinical manifestations of chronic hepatitis? a) dyspeptic signs; b) enlargement of liver and pancreas; c) jaundice (not always); d) moderate enlargement and consolidation of liver and spleen; e) great enlargement and consolidation of liver and spleen; f) pale of the skin; g) dysfunction of the liver and disorder of liver’s structure, which are revealed by means of laboratory methods and radiohepatography. 4. What are the main etiological factors of occurrence of hepatocirrhosis? a) infection; b) alcoholism; c) deficiency of proteins and vitamins in feeding; d) deficiency of lipids and carbohydrates in feeding; e) stress; f) toxico-allergic factor; g) cholestasis; h) venous stagnation. 5. What main groups of chronic hepatitis (according to etiology) do you know? a) infectious; b) focal c) toxic; d) latent; e) toxico-allegical; f) metabolic; g) diffuse; h) acute. 6. Signs of chronic persistent (benign) hepatitis include the following: a) feeling of heaviness or dull pains in right hypochondrium; b) decrease of appetite; c) loss of weight; d) insignificant jaundice or it is absent; e) skin itch; f) evident jaundice; g) often-nasal bleeding; h) nausea. 7. Changes of liver function tests in case of active hepatitis include the following: a) hyperbilirubinemia; b) hypergammaglobulinemia; c) hypogammaglobulinemia; d) decreased activity of transaminases, aldolase and alkaline phosphatase; e) positive protein-sedimentary tests; f) increased activity of transaminases, aldolase and alkaline phosphatase; g) decreased activity of choline esterase; h) delay of bromsulfalein excretion. 8. Signs of chronic cholestatic hepatitis include the following: a) mechanical jaundice; b) hemolytic jaundice; c) intensive skin itch; d) hyperbilirubinemia; e) increase of activity of alkaline phosphatase in the blood; f) decrease of activity of alkaline phosphatase in the blood; g) decrease of blood cholesterol. h) increase of blood cholesterol. 9. Laboratory results during period of activity of cirrhotic process reveal the following: a) anemia; b) leukopenia; c) leukocytosis; d) thrombocytopenia; e) elevated ESR; f) increased level of conjugated bilirubin; g) increased level of unconjugated bilirubin; h) hypogammaglobulinemia.

Block 2 B. Tasks to be done: Task 1. Patient K. complains of feeling of heaviness in right hypochondrium and epigastrium, become more intensive after food intake, poor appetite, loss of body weigh, abdominal distension and borborygmus, unstable stool, eructation. Patient is thin. Body weight index is 17,5. Skin cover is like dirty, petechias and fruises are observed. Teleangioectasias with diameter to 5 mm are visible on the skin of face, neck and shoulder. Palms and soles are hyperemic. The tongue is crimson-red, smooth. Insignificant tenderness in the right hypochondrium is marked during palpation. Liver’s edge is firm, acute. Liver’s sizes according to Kurlov are 11-8-6. For which disease are these results the most typical? Block 1 Answers for test tasks of the I-st level: 1 - a 7 - c 12- c 2 - c 8 - a 13- a 3 - b 9 - d 14- e 4 - a 10- e 15- d 5 - b 11- a 16- a 6 - c

Block 1 Answers for test tasks of the II-nd level: 1 - b , c , f 5 - a , d , e 8 - a,b,d,f,g,h 2 - a , b , e 6 - a , e , f 9 - a , b , d , e 3 - a , b , d , e , f 7 - a , d 10- a , b , d , f , g 4 - a , b , e

Block 1 Standards of right answer for tasks: 1) For cholelythiasis. 2) For chronic cholecystitis. 3) Conclusion: prolongation of the phase of the Oddi sphincter contracting indicates hypertone of the Oddi sphincter; decreasing of the portion “B” time and its amount indicates hypermotor dysfunction of the gall bladder: cloudiness “B” and “C” bile with large amount of leukocytes, mucus and epithelium, mainly in “C” portion, presence of lamblia indicate inflammation of bile ducts due to parasite invasion - lamblious cholangitis; presence of large amount cholesterol crystals and calcium bilibubinate is typical for cholelithiasis. Block 2 Answers for test tasks of the I-st level: 1 - e 7 - b 12- e 17- a 23- a 2 - c 8 - a 13- b 18- a 24- c 3 - a 9 - a 14- b 19- c 25- a 4 - c 10- e 15- b 20- d 26- c 5 - e 11- a 16- a 21- d 27- c 6 - b 22- b 28- d

Block 2 Answers for test tasks of the II-nd level: 1 - a , c , d 5 - a , c , e , f 8 - a,c , d , e , h 2 - a , c , d 6 - a , b , d , h 9 - a,b,d,e,f,g 3 - a , c , d , g 7 - a,b,e,f,g,h 4 - a,b,c,f,g,h

Block 2 Standards of right answer for tasks: 1) For hepatocirrhosis.

Methodical instruction is composed by lecturer Ye.Ye. Petrov.

The Ministry of Health of Ukraine Ukrainian Medical Stomatological Academy

Approved at the Department of Propaedeutics to Internal Medicine with Care of Patients meeting on 11 09 2018 Protocol No2 The Head of the Department Professor Yu. Kazakov

METHODICAL INSTRUCTION FOR STUDENTS’ SELF-PREPARATION WORK

Educational discipline Propaedeutics to Internal Medicine Module No 2 Enclosure module No 8 Topic The main symptoms and syndromes in kidney diseases - acute and chronic glomerulonephritis and pyelonephritis. Chronic kidney disease. Clinical urine analysis Year 3 Faculty medical

Poltava - 2018 1. The topic basis: Renal pathology takes one of the leading places among diseases of organs, which are of special importance for life. These diseases often result to persistent invalidism and fast death even. That is why every future physician must know the main symptoms and syndromes of urinary system pathology, glomerulonephritis and pyelonephritis particularly. 2. The specific aims:  To explain mechanisms of development of the main syndromes, occurring in case of urinary diseases.  To classify glomerulonephritis and pyelonephritis.  To explain etiology and pathogenesis of acute and chronic glomerulonephritis and pyelonephritis.  To analyze results of examination of patients with acute and chronic glomerulonephritis and pyelonephritis.  To interpret results of examination of patients with acute and chronic glomerulonephritis and pyelonephritis.

3. Basic knowledge, experience, skills necessary for studying the topic in connection with other subjects (interdisciplinary integration) : Previous disciplines Obtained skills 1. Anatomy To know human anatomy, structure of urinary organs particularly 2. Physiology To know physiology of urinary system 3. Medical psychology To be able to observe principles of ethics and deontology in medical practice 4. Biochemistry To know role of kidneys in metabolic processes 5. Pathological morphology To know pathologic-morphological picture of acute and chronic glomerulonephritis and pyelonephritis 6. Latin and medical terminology To know terminology (in Latin transcription): acute glomerulonephritis, chronic glomerulonephritis, acute pyelonephritis, chronic pyelonephritis, acute renal failure, chronic renal failure

4. Tasks for self-work during preparation to the class. 4.1 List of the main terms, parameters, characteristics, which should be mastered during preparation to the class: Term Definition 1.Urinary syndrome It is syndrome, including changes detecting during chemical study of urine - proteinuria and in microscopic study - microhematuria, leukocyturia and cylindruria.

2. Nephrotic syndrome The main manifestations of nephrotic syndrome are massive proteinuria, hypoproteinemia, hyperlipidemia and oncotic (hypoproteinemic) edema.

3. Syndrome of nephritis It reflects clinical-laboratory changes, observed in inflammatory lesion of renal glomerules. It includes edema, arterial hypertension and characteristic changes of urine.

4. Acute renal failure It is syndrome, caused by sudden and quickly developing (during several hours or days) of stopping of urinary excretion function of kidneys as a result of severe disturbance of renal blood flow, glomerular filtration and tubular reabsorption.

5. Chronic renal failure It is syndrome that occurs due to the significant decrease of nephrones quantity and quality that leads to the impaired secretory and excretory renal function, homeostasis disbalance, disturbances of all substances exchange, acid-alkaline disorder and abnormal all organs and systems work.

6. Diffuse It is general infectious-allergic disease with lesion of renal glomerular glomerulonephritis vessels mainly.

7. Pyelonephritis It is inflamamtory renal disease with obligatory renal parenchyma and pelvis injury.

4.2. Theoretical questions to be answered before class: 1. What are the main signs of urinary syndrome? 2. What are the main signs of nephrotic syndrome? 3. What are reasons of nephrogenous arterial hypertension and its peculiarities? 4. What are the main signs of syndrome of nephritis? 5. What types and periods of acute renal failures do you know? 6. Describe clinical peculiarities of chronic renal failure according to its stages. 7. Tell about ethiology and pathogenesis of acute and chronic glomerulonephritis. 8. Classification of glomerulonephritis. 9. What are potential results of questioning, inspection and palpation, percusison and auscultation in patients with acute and chronic diffuse glomerulonephritis? 10. What laboratory and instrumental methods are used for diagnostics of acute and chronic glomerulonephritis? 11. The course and complications of acute and chronic glomerulonephritis.. 12. Tell about ethiology and pathogenesis of acute and chronic pyelonephritis. 13. What are potential results of questioning, inspection, palpation and auscultation in patients with acute and chronic pyelonephritis? 14. What laboratory and instrumental methods are used for diagnostics of acute and chronic pyelonephritis?

4.3. Practical work (tasks), which should be performed during class: 1. To carry out examination of patients with acute and chronic glomerulonephritis and pyelonephritis. 2. To interpret obtained results. 3. To interpret results of laboratory and instrumental methods examination of patients with acute and chronic glomerulonephritis and pyelonephritis.

Urinary syndrome Term “urinary syndrome” characterizes changes, revealed during urine examination. This syndrome can be isolated, when it isn’t accompanied by other clinical manifestations of disease or it is component of clinical picture of disease, which is marked together with edematic syndrome, hypertensive syndrome, syndrome of chronic renal failure etc. “Urinary syndrome” includes moderate proteinuria (from 100 mg to 3,5 g during the day), erythrocyturia (more than 1•106/L during the day), leukocyturia (more than 4 •106/L during the day), cylindruria, bacteriuria, excretion of salts and their crystals, renal and transitional epithelium and other elements of pathological urinary sediment with urine. There are the following most common causes of urinary syndrome development: acute and chronic glomerulonephritis; acute and chronic pyelonephritis, renal amyloidosis; nephropathy of pregnancy; toxic, medicamentous, inherited and congenital nephropathies; renal lesions, occurring on the background of systemic diseases of connective tissue, systemic vasculitis, diabetes mellitus, chronic heart failure, multiple myeloma, gout, development of renal and urinary tracts tumors etc. Pathogenesis of the main symptoms of urinary syndrome is complex and various. Proteinuria is one of the most common signs of renal lesions; it can have prerenal, renal (glomerular and tubular-intersticial) and postrenal origin, but such subdividing has conventional character. Prerenal proteinuria can be marked in healthy persons. It is massive never. Besides, proteins with low specific gravity (albumins, β2-microglobulin, lysozyme etc.) pass through unaffected renal filter. Then they partly or totally reabsorbed by epithelium of renal tubules. Development of glomerular mechanism of proteiuria mainly is caused by pathological permeability of glomerular filter or its functional changes on the level of electrostatic and enzymatic changes in cellular membranes. Glomerular proteinuria can be selective and nonselective and occurs in case of acute and chronic glomerulonephritis, nephropathies, developing on the background of systemic diseases of connective tissue (systemic lupus erythematosus, systemic scleroderma, periarteritis nodosa, purpura rheumatica, etc.), renal amyloidosis, diabetic glomerulosclerosis, nephropathy of pregnancy, hypertensive disease, etc. Development of tubular mechanism of proteinuria is caused by disturbance of ability of proximal tubules to reabsorb low molecular weight proteins, which are filtrated through renal glomerules. Besides, proteinuria doesn’t exceed 2 g a day; protein, which is filtrated, is low molecular fraction mainly. This type of proteinuria occurs in case of tubulointerstitial lesions of kidneys: acute and chronic pyelonephritis, interstitial nephritis, congenital tubular lesions, etc. Other mechanisms of proteinuria development are possible also. Orthostatic proteinuria can occur in teenagers and youths, particularly, if they have nephroptosis. It can occur also in case of long standing or walking and doesn’t exceed 1 g a day. It is supposed that mechanism of its development is in kinking of renal blood vessels, which occurs due to nephroptosis and results to disorders of venous blood outflow from kidneys. Congestive proteinuria (“cardiac kidney”) is developed due to blood circulation disturbance of II B - Ш stage that is caused by congestive hyperaemia of kidneys and their dystrophy. Feverish proteinuria is marked during development of feverish state; its appearance can be caused by toxic lesion of glomerular filter. Erythrocyturia can have renal or extrareanal origin and it is one of the most often symptoms of lesion of kidney and urinary tracts. Erythrocyturia can be dominant in urinary syndrome in case of development of urolithiasis, urinary acid diathesis, renal tumors, glomerulonephritis, with hematuria mainly, hemorrhagic diathesis (thrombocytopenia, thrombocytopathy, teleangiectasia, anticoagulants and preparations with thrombolythic action overdosage etc.). The following signs are demonstrative ones for renal erythrocyturia: domination of altered erythrocytes over unaltered; presence of erythrocytes casts; combination of macro- or microhematuria with proteiuria, which is above 1 g a day. Renoparenchymatous glomerular erythrocyturia occurs when erythrocytes, changing one’s form under influence of capillary pressure and change of electric charge gradient between erythrocyte surface, glomerular basal membrane and intercellular space of renal glomerule, and also due to becoming thin glomerular membrane, increase of pores in it, pass from cavity of glomerular capillary into cavity of Bowman’s capsule. Glomerular erythrocyturia is typical for different morphological types of glomerulonephritis, nephropathies, which are developed during course of systemic diseases of connective tissue, diabetic glomerulosclerosis, more rare it occurs in case of amyloidosis and some other diseases. Renoparenchymatous tubulointerstitial erythrocyturia occurs as result of permeation of erythrocytes through damaged wall of blood capillary, adjoining to wall of renal tubule. This type of erythrocyturia occurs in case of acute and chronic pyelonephritis, interstitial nephritis, polycystic renal disease and other diseases. The following signs are typical for extrarenal erythrocyturia: presence of unaltered erythrocytes in urine, absence of erythrocytes casts and relatively low accompanied proteinuria - less than 1 g a day even at the presence of macrohematuria. Urolithiasis, urinary acid diathesis, renal tumors, traumas of urinary tracts, their anomalies and inflammatory diseases (in case of last ones erythrocyturia is associated with leukocyturia) are the most often causes of extrarenal erythrocyturia development. Leukocyturia is excretion of leukocytes with urine; amount of leukocytes is more than normal (in case of 40-times repeated increase of microscope objective, urinary sediment contains 0-2 leukocytes in v.f. in healthy men and 0-6 leukocytes in v.f. - in healthy women). During quantitative research of urinary sediment according to Nechiporenko in healthy persons leukocyturia usually doesn’t exceed 2•106/L, sometimes reaching 4 •106/L. Expressed leukocyturia -pyuria (presence of pus admixtures in urine) - is marked visually: urine is cloudiness with sediment, which doesn’t disappear after adding of 10% acetic acid solution. Leukocyturia is the main symptom of infectious lesion of kidneys and urinary tracts - non-specific (acute and chronic pyelonephritis, cystitis, prostatitis, uretritis) and specific (tuberculosis, gonorrheal urethritis). Leukocyturia, which accompanies development of infectious diseases, as a rule, is accompanied by bacteriuria. Moderate leukocyturia (to 30-40 leukocytes in v.f.) can have non-infectious origin and occurs, for example, in patients with interstitial nephritis, and in combination with erythrocyturia and proteinuria - in patients with glomerulonephritis with interstitial component. Bacteriuria in these cases is absent. Qualitative difference between leukocytes is used as method of differentiation of leukocytes origin (tubules, renal calyces, ureters, urinary bladder, urethra). In case of pyelonephritis and infectious lesion of urinary tracts neutrophils are dominant in urine, but in pyelonephritis many leukocytes are osmotically active or are Shternhaimer-Malbin’s cells. Osmotically active leukocytes are pale, their size is increased, brownian movement of granules is marked in their cytoplasm. They are revealed in native sediment of urine after adding of distilled water and methylene blue or safranin. Active leukocytes - Shternhaimer-Malbin’s cells - are formed in urine with low specific gravity from swelled “alive” granulocytes. These cells aren’t pathognomonic for pyelonephritis as in condition of hyperosmolarity (for example, in presence of chronic renal failure or during polyuric stage of acute renal failure) they can be observed in case of inflammation of urinary tracts also. In case of development of immune-mediated inflammatory renal disease, particularly, of ones, occurring on the background of systemic diseases of connective tissue, primary majority of leukocytes are lymphocytes. Different types of urinary syndrome are typical for different renal diseases. For example, for glomerulonephritis combination of proteinuria, erythrocyturia and cylindeuria is typical, for pyelonephritis - leukocyturia and bacteriuria, for urolithiasis - erythrocyturia and presence of salts in urine. In case of renal amyloidosis proteinuria, insignificant cylindruria are the main symptoms, periodical erythrocyturia is possible also. Three-glasses Thompson’s test is used for determining of erythrocytes’ and leukocytes’ origin. Its essence is in the following: patient divides urination act into three portions: begins urinary excretion into first glass (10-25 ml), than - into second glass (the main part of urine), and finishes urinary excretion (15-20 ml) into third one. Presence of erythrocytes (leukocytes) only in first portion is sign of their origin from urethra, only in third - from urinary bladder. Equal distribution of them in all portions directs to their renal origin.

Edematic and nephrotic syndromes Edema is surplus accumulation of water in intercellular space. Presence of edema is typical for diffuse lesions of kidneys. The cause of edema for the most part of renal diseases is water and electrolyte imbalance with retention of sodium and water in bloodstream and following their diffusion in intersticium as a result of insufficient renal excretion. Great role in pathogenesis of renal edema belongs to hormonal shifts. They are surplus production of renin, angiotensin, aldosterone and antidiuretic hormone. Such hormonal imbalance results to retention of sodium and water in organism. In acute glomerulonephritis certain value in origin of edema belongs to capillary hyperpermeability, increasing of hydrophilia of intercellular matrix and increasing of intracapillary hydrostatic pressure due to arterial hypertension and heart failure also. Clinical peculiarities of renal edema include its sudden appearance (on the background of “absolute health”) and fast growth. During early stage of disease edema appear first in that places where the most pasty fat is, particularly, on the face (on eyelids peculiarly), and what’s more - in the morning after sleep. Besides the face becomes puffy, pale; eyelids - swelled, palpebral fissures - narrow; in the morning eyes open with difficulty. In the future edema of the lower extremities, hands, loin appears. Sometimes edema becomes generalized - it spread equally along whole body (anasarca) and is accompanied by accumulation of fluid in internal organs and serous cavities - edema of cavities (hydropericardium, hydrothorax, ascites). The skin above edema is pale due to vascular embarrassment by interstitial fluid. At pressing of the skin fossa is formed easily and it is smoothed out quickly. Renal edema distinguishes by motility and it is displaced to the lower-lying part of the body quickly. McClure-Oldrich’s test is used for revealing of latent edema: after intradermal introduction of 0,2 ml physiologic saline in area of internal surface of forearm wheal is formed. Normally it resolves during 1 hour, but in edema - longer essentially. In evident edematic syndrome repeated measuring of abdominal circumference and circumference of extremities at the same level, determining of level of fluid in pleural cavities help to observe dynamics of edema. Besides, regular weighing of the patient and control of diurnal diuresis in comparison with quantity of drunken fluid must be carried out. Positive fluid balance testifies about accumulation of fluid, negative - about fading away of edema. Special type of edema occurs in nephrotic syndrome. It is characterized by protein, lipid, and water-salt imbalances. The main manifestations of nephrotic syndrome are massive proteinuria, hypoproteinemia, hyperlipidemia and oncotic (hypoproteinemic) edema. In nephrotic syndrome capillary permeability of renal glomerules for protein is increased. It leads to significant and prolong proteinuria. Nephrotic syndrome occurs in glomerulonephritis, diabetic nephropathy, renal amyloidosis, poisoning of nephrotoxical venom (mercury and bismuth compounds, cadmium, lithium), medicinal nephropathy (treatment by gold preparations, D-penicillamin, antiepileptics, antibiotics), renal venous thrombosis, systemic lupus erythematous, generalized vasculitis (periarteritis nodosa), paraneoplastic reactions in patients with malignant neoplasms of internal organs. Chief link of patogenesis of nephrotic syndrome is significant loss of protein, albumin particularly, with urine. It exceeds protein-synthesis possibilities of the liver. Certain value belongs to disturbance of reabsorption of protein molecules by affected tubular epithelium. Massive proteinuria leads to hypoproteinemia (hypoalbuminemia mainly). It causes decrease of oncotic (colloid-osmotic) pressure of blood plasma and passage of part of fluid from bloodstream into intersticial space. Lipid metabolic imbalance is marked in majority patients with nephrotic syndrome due to significant disturbance of protein blood content and decreasing of lipid metabolism in kidneys. It is manifested by hyperlipidemia, increasing of cholesterol contents in blood serum first of all. The main clinical sign of nephrotic syndrome is diffuse edema of subcutaneous fat reaching degree of anasarca sometimes and accompanied by edema of cavities often. In expressive hydropericardium and hydrothorax heart and respiratory failure, accordingly, can appear. Constant massive proteinuria (more than 3 g/l) with large amount of waxy, granular and epithelial casts often is marked in analyses of urine. Sometimes double refracting fatty substances - so called “malta crosses” and drops of neutral fat are revealed in urine. It is decreased contents of total blood protein (to 40 g/l and less) and serum albumins (less than 30 g/l). Level of blood cholesterol and triglycerids sometimes is increased. It is necessary to bear in mind that other pathologic processes can be cause of generalize oncotic edema also, specifically, alimentary dystrophy (starvation), liver cirrhosis and malabsorption syndrome. Besides, it is necessary to take into account that evident edema of the face and eyelids can be revealed in Quincke’s edema, sting, myxedema, scleroderma systematica.

Kidneys and arterial hypertension

Kidneys, as it is known, play important role in regulation of arterial pressure. So, kidneys control content of sodium and water and, consequently, - volume of fluid circulation in bloodstream. Besides, kidneys realize secretion of renin in the blood. Renin is catalyst of process of angiotensin forming. Last one is one of the strongest vasoconstrictors; besides it simulates production of mineralocorticoid aldosterone by adrenal glands. Pressure mechanism of renin- angiotensine-aldosterone system is connected with functioning of so called juxtaglomerular apparatus of kidneys. It is accumulation of special cells near vascular pole of glomerules in place where afferent arteriole adjoins to initial part of distal tubule. Depressor substations, formed by cells of renal intersticium, prostaglandins and products of kallikrein-kinin system activation, particularly, set off against action of pressor factors. So, in case of renal diseases elevation of blood pressure can be realized by three main mechanisms: retention of sodium and water, activation of renin-angiotensin-aldosterone system, decrease of depressor factors production. Hypertensive syndrome in renal diseases can be caused by lesion of renal parenchyma and renal vascular occlusion (constriction). They are, correspondingly, renoparenchymatous and renovascular arterial hypertension. Reasons of nephrogenous arterial hypertension are shown in table 7. Table 7 Reasons of nephrogenous arterial hypertension

Causative factors Nosology Diseases of renal parenchyma (renoparenchymatous hypertension) a) inflammatory Lesion of kidneys in case of diffuse diseases of connective tissue processes (systemic lupus erythematosus) and generalized vasculitis (periarteritis nodosa), chronic pyelonephritis, renal tuberculosis

Diabetic nephropathy, nephropathy of pregnancy, polycystic renal b) degenerative diseases, hydronephrosis, renal amyloidosis, congenital renal hypoplasia lesions Hypernephroma, nephroblastoma (Wilms’ tumor) c) tumors

Constriction of renal arteries (renovascular Atherosclerosis of renal arteries, nonspecific aortoarteriis (Takayasu’s hypertension) disease), thromboembolism in case of infective endocarditis, hyperplasia a) stenosis fibro-muscularis

Retroperitoneal tumor, pararenal hematoma, retroperitoneal fibrosis b) compression from Compression of renal artery by ureter, its kinking in case of nephroptosis outside and floating kidney; atresia, hypoplasia, aneurysm of renal artery c) maldevelopment

Leading role in development of renal arterial hypertension plays renin-angiotensin- aldosterone system. Activation of juxtaglomerular apparatus with following increase of renin production by cells of middle coat of afferent arteriole and its release in bloodstream occurs as result of fall of perfusion pressure in arterial renal system and development of ischemia of renal tissue. Renin by enzymatic way degrades angiotensin precursor, produced by liver and circulating in the blood constantly, and transforms it into angiotensin. Angiotensin causes systemic spasm of arterioles and increase of general peripheral resistance and results, in this way, to elevation of arterial pressure. Besides, angiotensin stimulates production of aldosterone by glomerular zone of adrenal glands cortex, leading to secondary hyperaldosteronism and, accordingly, to intensifying of sodium reabsorption in renal tubules. Retention of sodium in organism is accompanied by its accumulation in vascular wall that results to edema of intima and constriction of lumen of arterioles and to significant increase of sensitivity of its unstriated-muscular cells to pressor influence of angiotensine, catecholamines and other vasoconstrictors. Besides, retention of sodium leads to increase of blood plasma osmolarity; it stimulates production of antidiuretic hormone by hypophysis. This hormone causes retention of water in organism and promotes, in this way, to increase of volume of fluid circulation. In case of glomerulonephritis important role in development of arterial hypertension belongs to increase of volume of fluid circulation, caused by diminishing of sodium and water excretion due to lesion of glomerular capillaries and decrease of glomerular filtration. Decreased production of depressor substantions by cells of intersticium of affected renal parenchyma can make certain contribution to arterial hypertension development. It occurs, particularly, in case of connective tissue overgrowth into medullar layer (nephrosclerosis) as result of any chronic renal disease. Clinical picture of arterial hypertension of renal origin is determined by degree of blood pressure elevation and expressiveness of lesion of the heart and vessels. Patients complains of headache in occipital area, dizziness, walking unsteadily, ear noise, “spots” in front of eyes, sleep disturbance, piercing or aching heart pains. Nausea, vomiting, inspiratory dyspnea and palpitation on exertion, visual impairment can be observed in case of significant elevation of blood pressure. Objective examination reveals increase of filling and tension of pulse (pulsus durus), retrosternal pulsation, accent of the II sound over aorta. Constant elevation of blood pressure results to appearance of physical signs of left ventricular hypertrophy (displaced laterally forced apex beat, displacement of the left border of relative cardiac dullness to the left), which is confirmed by results of ultrasound, X-ray and ECG-examination. Inspection of eye grounds reveales hypertonic angiopathy. More expressed degree of diastolic pressure elevation in comparison with increase of systolic one is peculiarity of renal arterial hypertension. Besides, in patients with renovascular hypertension high level of blood pressure is marked constantly. On the background of this high blood pressure any subjective manifestations are absent often until complications occurrs. Effect of antihypertensive drugs is insignificant usually, and tendency to rapid progressive and malignant course is observed. Malignant course of hypertensive syndrome is characterized by constant high level of diastolic pressure, exceeding 120 mm Hg, that quickly results to lesion of the heart (heart failure, myocardial infarction), hypertensive encephalopathy (temporary impairments of cerebral circulation or stroke) and expressed retinopathy (foci of retinal hemorrhages, retinal dystrophy, retinal detachment, disk of optic nerve edema) with sudden vision impairment down to blindness. Sometimes arterial hypertension syndrome is on the foreground in clinical picture of renal disease, making difficult its diagnostics and, at the same time, determining course of disease and clinical outcome. So, in case of fast and significant elevation of blood pressure in patients with acute glomerulonephritis left ventricle doesn’t compensate always suddenly increased load, it can lead to rise of acute left-ventricular failure as cardiac asthma. Edema in these cases can be localized on lower extremities mainly, as patient occupies forced position ortopnoe. That is why patient’s state can be apprehend erroneously as complication of hypertensive crisis in patient with hypertensive disease. On the other hand, in severe cases cardiac asthma can lead to pulmonary edema, which can be cause of patient’s death. Differential diagnosis of renal hypertension and essential hypertension in number of cases can be made only by means of renal biopsy and following morphological research of biopsy material.

Syndrome of nephritis (Nephritic syndrome) Syndrome of nephritis reflects clinical-laboratory changes, observed in inflammatory lesion of renal glomerules. It includes edema, arterial hypertension and characteristic changes of urine. This syndrome is typical first of all for acute stage of glomerulonephritis and also for periods of exacerbation of chronic glomerulonephritis, secondary nephritis in patients with infective endocarditis, systemic lupus erythematosus, periarteritis nodosa, etc. In nephritic syndrome typical “renal” edema is observed. It appears at first on the face, particularly, on eyelids, and increases quickly, spreading to lower and upper extremities. Edema is soft (fossa as result pressing disappears quickly), motility (it is shifted easily at change of body position), the skin above edema is pale. Disease can be complicated by addition of nephrotic syndrome when spreading of edema on body (anasarca) and serous cavities (hydrothorax, hydropericardium, ascites) is observed due to hypoproneinemia and decrease of oncotic pressure of blood serum. Arterial hypertension in syndrome of nephritis usually appears and increases simultaneously with edema. It is typical first elevation of diastolic pressure and relative resistance of hypertension to hypotensive therapy. In case of significant hypertension patients complain of headache in occipital area, dizziness, flashing of “spots” in front of eyes, deterioration of visual acuity, sleep disturbances. Development of nephritic syndrome often is accompanied by appearance of dull, aching or constricting pains in both halves of lumbar area, which have constant or intermittent character. These pains are caused by increase of intrarenal pressure and distension of renal capsule due to inflammatory edema and swelling of renal parenchyma. A change of urine in syndrome of nephritis is characterized by combination of proteinuria, cylindruria, and erythrocyturia. Sometimes increased numbers of leukocytes is revealed in urine also, but their amount is always significantly less than amount of erythrocytes. In evident hematuria urine has color of “meat slops”. In case of addition of nephrotic syndrome massive proteinuria (more than 3 g/l) , waxy, granular, and epithelial casts are revealed in urine, and in the blood - hypoproteinemia, hypoalbuminemia and hypercholesterolemia. Combination of arterial hypertension and significant increase of volume of blood circulation, caused by retention of sodium and water in organism, can lead to development of acute left-ventricular failure with clinical picture of cardiac asthma and pulmonary edema. Other complication, caused by arterial hypertension and retention of fluid in organism also, can be convulsive fits as renal eclampsia. The course of nephritic syndrome can be complicated by acute renal failure in a number of cases. Combination of arterial hypertension with changed urinary sediment always reduces to presupposition about presence of nephritic syndrome.

Renal failure Renal failure is pathological state when excretion with urine of products of protein metabolism (nitrous residues) decreases or stops completely, acid-base disturbance and water and electrolytic imbalance occurs. Renal failure appears in that case, if not less than ¾ nephrons stop functioning as a result of pathologic process. Acute and chronic renal failures are distinguished. Acute renal failure is syndrome, caused by sudden and quickly developing (during several hours or days) of stopping of urinary excretion function of kidneys as a result of severe disturbance of renal blood flow, glomerular filtration and tubular reabsorption. Depending on etiologic factor, acute renal failure is divided into three types. They are prerenal (suprarenal), renal and postrenal (subrenal) failure (table 8).

Table 8 Reasons of acute renal failure Type of acute Nosology renal failure Prerenal Different kinds of shock (cardiogenic, burn, anaphylactic, infectious-toxic, traumatic, posthemorrhagic), expressed dehydration of organism due to loss of fluid in quantity in case of intractable vomiting, profuse diarrhea, diuretics overdosage Renal Acute glomerulonephritis, renal lesion in diffuse diseases of connective tissue (systemic lupus erythematosus) and generalized vasculitis (periarteritis nodosa), viral hemorrhagic fevers with renal syndrome, leptospirosis, nephrotoxic influence of salts of heavy metals (of mercury, lead, bismuth, gold, cadmium, chrome),organic compounds (tetrachloric carbon, dichlorethane, ethylene glycole, methyl alcohol, acetic acid), poisonous fungi, medicaments (antibiotics, amynoglycosides particularly, sulfonamides, nonsteroidal anti-inflammatory medicines), radiopaque substances, crush (compression, Bywaters’) syndrome; massive intravascular hemolysis in case of hemolytic anemias and transfusion of incompatible blood, thrombosis of renal arteries and veins, severe trauma of both kidneys, nephrectomy of unique kidney Postrenal Occlusion of both ureters by stones, blood clots, detritus; tumors of urinary bladder, prostate and urethra, inflammatory edema or obturation of neck of urinary bladder by stone, dysfunctions of urinary bladder (atony) in diseases of spinal cord or long using of ganglionic blockers.

Prerenal acute failure (shock kidney) is connected with insufficient blood supply of kidneys due to sudden and fast fall of blood pressure at decrease of cardiac output, pronounced vasodilatation and decrease of volume of blood circulation. Renal acute failure is caused by lesion of renal parenchyma, particularly, in renal diseases of infectious, immune-inflammatory or toxic genesis, occlusion of glomerules and tubules by hemolysis and tissue destruction products and others. Postrenal (obstructive) acute failure is caused by obstacle to urine outflow, which can be at any level - from renal pelvis to urethra, and by sharp atony of urinary bladder also. Leading link of pathogenesis of acute renal failure is lesion of tubules, mechanism of which has its peculiarities depending on etiologic factor. So, in “shock kidney”, disturbance of hemodynamics and decrease of volume of blood circulation cause sharp fall of renal perfusion pressure. It results to disturbance of glomerular filtration and to spasm of preglomerular arterioles. Ischemic lesion of epithelium of tubules, which get blood from postglomerular arterioles, occurs. Lumen of tubules is filled by rejected epithelial cells and casts. Lesion of tubular epithelium in primary and secondary glomerulonephritis has ischemic character mainly also: inflammatory affection of glomerules leads to disturbance of blood flow in them. In case of affection of kidneys by nephrotoxic poisons direct lesion of tubular epithelium during resorption or excretion of toxins and obturation of tubular lumen by necrotic masses, crystals of toxic substances or their conglomerates with Tamm-Horsfall’s mucoprotein is observed. In case of intravascular hemolysis and crush syndrome obstruction of tubular lumen by hemoglobin or myoglobin, accordingly, occurs. In acute occlusion of urinary tract lesion of tubular epithelium is caused by sharp elevation of intrarenal pressure. Additional factor of occurrence of acute renal failure is interstitial edema, caused by passive diffusion of glomerular filtrate (primary urine) through affected wall of tubules. Edema leads to pinching of renal parenchyma in capsule, with pressing of tubules, venules and lymphatic tracts. Certain value belongs also to disturbances of renal hemodynamics, caused by biologically-active substances (prostaglandins, histamine, serotonin), to thrombosis of arterioles due to intravascular coagulation and redistribution of renal blood flow through arteriovenous shunts. From clinical point of view course of acute renal failure is subdivided into 4 periods. They are initial, period of oligoanuria, period of diuresis restoration, and recovery period. Initial period lasts during 1-3 days after beginning of action of etiologic factor. Besides, clinical symptomatology is manifestation of the main disease, caused acute renal failure. Period of oligoanuria lasts 5-15 days. It is characterized first of all by sharp decrease of diurnal diuresis to 200 ml and less, down to anuria. Besides urine has dark color, contents protein, erythrocytes and casts. Progressive increase of content of nitrous residues in the blood (azotemia), particularly, of urea, creatinine, oligopeptide products of natural destruction of tissue proteins occurs. Metabolic acidosis, extracellular hyperhydration and electrolyte imbalance (the greatest value belongs to increase of content of serum potassium) appear. In case of high level of azotemia sings of intoxication as general weakness, undue fatiguability, nausea, vomiting, anorexia, suppression of consciousness appear; cramps, comatose state can occur. Significant acidosis causes appearance of Kussmaul respiration. Extracellular hyperhydration results to increase of body weigh and in significant cases - to edema of cavities, pulmonary edema and brain edema. Hyperkaliemia (high level of serum potassium) more than 7mmol/l can cause cardiac arrest (high sharp-pointed T-wave with narrow base and prolongation of Q-T interval on ECG indicate to threat of cardiac arrest). If oliguria kept more than 2 weeks, it is, as a rule, testifies about irreversible (necrotic) changes of tubular epithelium and high probability of lethal outcome. Period of diuresis restoration lasts during 3-4 week and is manifested by increase of urine excretion, gradual decrease of azotemia to normal level, normalization of indices of water- electrolyte metabolism and acid-base balance. Quickly increase of diurnal diuresis is marked. In 3-5 days it is more than 2 l. Besides, specific gravity of urine is low as tubules are defective functionally and concentration capacity of kidneys is insufficient. Hazard of this period is in large loss of fluid and electrolytes, particularly, potassium with urine. As a result sharp dehydration of organism and hypokaliemia (low level of potassium), can occur. Last one can lead to severe cardiac rhythm disturbances and myocardiodystrophy. Moreover, addition of infection of urinary tracts is observed often. Recovery period begins after disappearance of azotemia and lasts from 6-12 months to 2 years. During this period pathological changes in kidneys disappear completely, but restoration of their functional capacity occurs more slowly. Chronic renal failure is pathological condition, which is final stage of any chronic progressing renal lesion; it occurs due to gradual death of nephrons and has one morphological equivalent - nephrosclerosis- in its basis. Constellation of clinical and laboratory signs, observed in case of chronic renal failure, is named uremia (from Greece - uron - urine, haima - blood). Chronic glomerulonephritis, diabetic nephropathy lead to chronic renal failure most frequently. Pyelonephritis, urolythiasis, polycystic renal disease, renal amyloidosis, atherosclerosis of renal arteries, malignant arterial hypertension, diffuse diseases of connective tissue (systemic lupus erythematous), generalized vasculitis (periarteritis nodosa) and others are more rare causes of chronic renal failure. Significant diminishing of amount of functioning nephrons and structural-functional inferiority of retaining nephrons in patients with chronic renal failure result to gradual increasing of nitrous slags content in the blood. They cause intoxication of organism. Leading role in development of uremic intoxication belongs to “mean molecules”. Accumulation of urea, creatinine, uric acid, aromatic nitgrogenous compounds and others in the blood has certain toxic influence also. Change of water-electrolyte balance during initial stage is characterized by decreasing of concentration ability of kidney with increase of amount of excretory urine with low specific gravity and hypokaliemia, caused by this process, during later stage, on the contrary, - by oliguria, hyperkaliemia. In significant uremia increase of magnesium, sulfates, phosphates content in the blood and decrease of sodium, calcium, chlorides concentration is observed. Besides, disorder of ions hydrogens excretion by kidneys and of reabsorption of bicarbonates results to occurrence and gradual increase of metabolic acidosis. Production of erythropoietin by kidneys is decreased. During early (initial) stage of chronic renal failure clinical and laboratory symptomatology depend on expressiveness of manifestations of basic renal disease mainly. Urinary syndromes, corresponding to character of renal pathology, are observed, as a rule. Dysfunction of kidneys is revealed by means of functional methods of examination mainly. So, Zimtitsky’s test allows to reveal signs of decreasing of concentration ability of kidney: polyuria, nicturia, and isohyposthenuria when specific gravity of urine constantly is within limits 1,008- 1,012 and comes nearer to gravity of ultrafiltrate of plasma (of primary urine). Results of Reberg’s test give possibility to reveal initial disorders of glomerular filtration and tubular reabsorption. Hypokaliemia, typical for early stage of uremia, is manifested first of all by changes of ECG as ventricular premature beats, flattening or inversion T wave, depression of ST segment. Symptoms of myocardial dystrophy and weakness of skeletal musculature can appear in case of expressive hypokaliemia. Full-scale clinical picture of chronic renal failure consists of signs, caused by compensatory elimination of nitrous slags through skin, mucous and serous membranes and symptoms of lesion of central nervous system and internal organs, caused by uremic intoxication, disorder of electrolyte balance and metabolic acidosis. Lesion of central nervous system (uremic encephalopathy) is characterized by general weakness, undue fatiguability, irritability, headache, impairment of memory, sleep disturbance. Apathy and sleepiness increase gradually; mental disturbances appear; inhibition of consciousness occurs. Skin changes are manifested by its paleness touched with yellow-green (due to anemia and accumulation of urochroms), xerosis, decrease of turgor. Skin as if powdered oneself a little (is covered by “hoarfrost”) due to presence of urea crystals on its surface. Marks of scratching, caused by excruciating skin itch, are observed often. During examination of oral cavity dryness of mucous membrane, aphthous stomatitis, smell of ammonia in expired air are revealed. Forming of ammonia is caused by decomposition of urea, which is excreted through mucous membranes, by urease of resident microflora. Hemorrhages on the skin and mucous membranes can be observed. In relation to cardiovascular system, arterial hypertension and signs of myocardial dystrophy of toxic genesis are marked. They are: pains in heart region, palpitation, tachycardia, displacement of apex beat and dilatation of borders to the left, diminishing of the I sound and systolic murmur at the heart apex, arrhythmias are possible. During examination of respiratory system signs of elimination bronchitis are revealed: cough, harsh breathing, dry rales, sometimes - symptoms of dry (fibrinous) pleurisy (pains in thorax during breathing, pleural friction sound). Changes of gastrointestinal tract are connected with elimination erosive-ulcerous gastritis and enterocolitis - abdominal pains, dyspeptic disorders, nausea, vomiting, suppressed appetite, abdominal distension, feces disorders. Gastric and intestinal bleedings can occur. Toxic affection of the liver is manifested by metallic taste in mouth, hepatomegaly, subicteritiousness of sclera or evident jaundice. Lesions of muskuloskeletal system in uremia can be caused by disturbances of phosphorus-calcium metabolism (osteoporosis) and retention of uric acid in organism (artralgia and arthritis as manifestations of secondary “uremic” gout). Hyporegeneratory anemia due to diminishing of erythropoietin production by kidneys is revealed in peripheral blood. Besides, neutrophilic leukocytosis with shift of leukocyte formula to the left and toxic granulosity of neutrophils, and thrombocytopenia are observed often. In serum blood urea, creatinine, uric acid and “mean molecules” content is increased; acidosis, hyperkaliemia are revealed. During examination of urine sudden diminishing of daily diuresis (oliguria), low specific gravity of urine (isohyposthenuria), expressed proteinuria, erythrocyturia and cylindruria are diagnosed. For terminal (final) stage of uremia increasing heart failure, caused by myocardiodysthrophy, arterial hypertension and anemia, is typical. Left-ventricular insufficiency with increased capillary permeability and hyperhydration cause appearance of stagnant signs in pulmonary circulation down to development of pulmonary edema. Besides, the following signs, unfavorable for forecast, appear: gallop rhythm, alternating pulse, and dry (fibrinous) pericarditis. The last one is manifested by retrosternal pain, dyspnea, and pericardium friction sound, which is called allegorically in these cases “knell”. High level of kaliemia can lead to severe disorders of cardiac function down to cardiac arrest. In patient neurological symptomatology increases, it is manifested by local convulsions or development of generalized convulsions. Manifestations of uremic encephalopathy are increased. At first periods of lethargy alternate with episodes of excitement, hallucinations. Then severe suppression of consciousness down to development of uremic coma occurs. Besides, Kussmaul’s respiration appears, more rarely Cheyne-Stokes (tidal) respiration is observed. For confirming of diagnosis of chronic renal failure and determining of its cause the following laboratory and instrumental research methods are used: examination of urine (clinical analysis, culture for microflora), functional Zimnitsky’s test and Reberg’s test, biochemical blood examination (urea, creatinine, “mean molecules”, acid-base state, potassium), ultrasonic examination of kidneys, intravenous (excretory) urography, special methods of urological examination (chromocystoscopy, retrograde ureteropyelography), biopsy of kidneys. During last decades forecast of patients with acute and chronic renal failure become better significantly due to broad using of hemodialysis (“artifical kidney”), peritoneal lavage and transplantation of kidneys.

DIFFUSE GLOMERULONEFRITIS

Diffuse glomerulonephritis (glomerulonephritis diffusa) is general infectious-allergic disease with lesion of renal glomerular vessels mainly. There are acute and chronic glomerulonephritis. Acute glomerulonephritis

Etiology. Acute (diffuse) glomerulonephritis occurs usually soon after acute infectious diseases: tonsillitis, scarlet fever, pneumonia, otitis. Diseases, caused by hemolytic streptococcus A (of 12 type more often), have peculiar importance. But glomerulonephritis can occur also after infectious diseases, caused by other bacteria, for example, by pneumococcus, staphylococcus. In number of cases acute glomerulonephritis occurs after severe supercooling, at influence of moist air, particularly. Cases of occurrence of acute glomerulonephritis after vaccination are described. Pathogenesis. It is typically, that acute glomerulonephritis isn’t developed during infectious disease, but occurs after a while, usually 2-3 weeks, and what’s more it isn’t possible to reveal streptococci in renal tissue. So, beginning of acute glomerulonephritis usually coincides with period of antibodies to streptococcus production. These results testify about following: acute glomerulonephritis isn’t only infectious disease, but - infectious-allergic one. It is supposed that bacterial antigens, passing into the blood during infection, affect renal tissue. Its proteins, changed due this process, acting as antigen, stimulate production of corresponding antibodies in reticuloendotelial system. Complex antigen-antibody is fixed on epithelial and endothelial cells of renal glomerules and on basal membrane of glomerular capillaries, resulting to their lesion. In case of acute glomerulonephritis both kidneys are affected always and all glomerules are affected equally. It distinguishes this disease from focal glomerulonephritis and confirms its allergic genesis. It is necessary to emphasize also that in case of acute glomerulonephritis capillaries of renal glomerules aren’t affected only, but vessels of other organs and tissues also. So, glomerulonephritis is total vascular lesion. It is described, for example, cases of this disease when in evident clinical picture of disease (edemas, hypertension) urinary symptoms were insignificant or were absent even. But in majority cases in acute glomerulonephritis renal glomerular apparatus is affected. It is explained by specific peculiarities function of kidneys as excretory organ. Clinical picture. Manifestations of acute glomerulonephritis are rather typical and characterized by three main syndromes. They are edemas, hypertension and changes of urine (hematuria, proteinuria). Most often patient complains of edemas, which appear at first on the face, under eyes; then they spread to trunk and extremities; their appearance is explained by disorder of capillary permeability first of all and by increased production of aldosterone by cortex of adrenal glands. Headache and feeling of heaviness in the head are often symptoms. They are caused by elevation of blood pressure and intracranial pressure in number of cases also. Vision can be disturbed due to spasms of vessels of retina and retinal hemorrhages. Many patients complain of general weakness, reduction of working ability. In case of expressed edematic syndrome and massive pleural effusion and also in overload of the heart due to significant increase of arterial pressure in patients with acute glomerulonephritis severe dyspnea is developed, sometimes asphyxia attacks occurs (of cardiac asthma type). In case of acute glomerulonephritis patients often complains of dull pains in the loin. More expressed oliguria, disease is more severe. Urinary excretion is decreased, but frequent vesical tenesmus can be marked also. Sometimes total anuria occurs. In case of expressed hematuria color of urine become like “meat slops”. During inspection patient’s appearance is typical: pale skin, edematic face, swollen and edematic eyelids, edemas on the trunk. Some patients are forced to occupy semi-sitting position due to expressed dyspnea. In severe cases renal eclampsia attacks are observed. Before attack blood pressure is elevated, headache is increased suddenly. Palpation allows to make more precise expansion and character of edema, and to study patient’s pulse also. For acute glomerulonephritis tense pulse and often pulsus rarus is typical. Apex beat usually is displaced to the left and forced due to hypertrophy of myocardium, appearing early on the background of arterial hypertension. Percussion of the chest in case of hydrosarca allows to reveal free fluid (transudate) in pleural cavities and congestion in area of roots of the lungs (deadened-tympanic sound). Left cardiac border is laterally left midclavicular line. During auscultation of the lung vesicular or harsh breathing is heard, in case of significant stagnation dry and moist congestive rales are revealed. During auscultation of the heart bradycardia is revealed (due to reflex, transmitted from aorta to vagus nerve in elevation of pressure in aorta), the I sound is weakened at the heart apex often; in case of significant overuse of cardiac muscle gallop rhythm is heard. Blowing systolic murmur (in case of significant dilatation of the left ventricle and expansion of fibrous ring of valves) can be heard at the heart apex. Accent of the II sound over aorta due to elevation of blood pressure usually is revealed. X-ray examination of the chest allows to confirm presence of transsudate in pleural cavities and congestion in roots of the lungs. Dilatation and hypertrophy of the left ventricle (its apex becomes round) is marked distinctly. Sphygmomanometry, allowing to reveal one of the main symptoms of acute glomerulonephritis - arterial hypertension, helps to make diagnosis. Systolic pressure is elevated to 200-220 mm Hg, but sometimes it is less high. Almost always elevation of diastolic pressure to 100-120 mm Hg is marked. ECG-examination allows to reveal signs of hypertrophy and left ventricular myocardium overload. In case of evident edemas of the trunk amplitude of ECG- waves is decreased. At last, for acute glomerulonephritis the urinary syndrome is typical. During period of edemas increasing - urinary excretion is diminished usually, oliguria is observed. Urine of the patient with acute glomerulonephritis usually contains many protein and erytrocytes (due to increase of renal capillaries porosity). In case of significant hematuria urine can become red- brown (color of “meat slops”). Cylinders, hyaline mainly, cells of renal epithelium are revealed during microscopic examination of urine sediment. Nitrogen-excretive function of kidneys in acute glomerulonephritis usually isn’t changed. Only in very severe cases, taking its course with anuria, nitrous residues can be accumulated in patient’s blood. Renal clearance tests diagnose more or less significant decrease of glomerular filtration. Infectious-allergic genesis of acute glomerulonephritis is confirmed by immunological shifts: during acute period of disease increase of α2- and γ-globulins content in blood serum is observed. Course and complications. Now acute glomerulonephritis is taking its mild course with trivial symptomatology often. It makes difficult its diagnostics and carrying out of treatment, accordingly. At the same time these variants of disease, same as variants with classic clinical picture, in absence of necessary treatment can begin chronic glimerulonephritis. The most severe complication of acute glomerulonephritis is renal eclampsia, which occurs in 4-10 % patients, more often in children and women. Severe contusions and ribs fractures can be result of eclampsia attack; cases of patients’ death due to cerebral circulation impairment or pulmonary edema are described, but it occurs rarely. More often attacks pass leaving no trace. In number of cases appearance of eclampsia is trigger to fast regression of disease’s symptoms and recovery. Acute glomerulonephritis doesn’t last more than some weeks or months in majority cases. Disappearance of edemas is first sign of beginning recovery, in further blood pressure is decreased. Insignificant hematuria and proteinuria can be during some months after disappearance of clinical symptoms of disease. In part of the patients full recovery doesn’t occur and disease transforms into chronic type. Treatment. Patients with acute glomerulonephritis are at bed rest. It is important presence of dry, warm air in the room, absence of draughts. Dietary salt intake is limited significantly (to 0,5-1,5 g a day), it promotes to liquidation of edemas and arterial hypertension. Protein intake is some limited (by means of diminishing of meat intake mainly). Prednisolone and other corticosteroids, having anti-allergic and anti-inflammatory properties, are effective drugs of pathogenetic therapy. Antihypertensive drugs are prescribed for struggle against arterial hypertension, for fast liquidation of edemas - furosemide and other diuretics. In case of renal eclampsia bloodletting is carried out or 10 ml of 25 % solution of sulfuric magnesia is introduced. But spinal puncture has the best effect: after releasing of part of cerebrospinal fluid intracranial pressure is decreased and eclampsia attack stops at moment. Prophylaxis of acute glomerulonephritis is in tempering and careful sanation of infectious foci (carious teeth, chronic tonsillitis, maxillary sinusitis, etc.).

Chronic glomerulonephritis

Etiology and pathogenesis. Chronic (diffuse) glomerulonephritis is relatively widespread disease. Sometimes acute types of glomerulonephritis, particularly in patients without timely and effective treatment in past, can transform into chronic glomerulonephritis. In other patients disease is diagnosed casually without acute glomerulonephritis in past in anamnesis. But it is possible to think, that in these cases acute glomerulonephritis was in past also, but it was taking its latent course without pronounced symptoms and consequently it was undetected. Chronic diffuse glomerulonephritis in number of cases can be result of unhealed nephropathy of pregnancy. Chronic glomerulonephritis is one of three classic variants of Bright’s disease. During last time great importance in pathogenesis of chronic glomerulonephritis is attached to autoimmune mechanism. In patients with chronic glomerulonephritis, to all appearance, apart from formation of antibodies to streptococcus, their formation to changed proteins of renal tissue occurs. It supports inflammatory process in kidneys and is reason of its chronic progressive course. Clinical picture. There are two distinct periods during disease. They are: first, when nitrogen-secretory function of kidneys isn’t disturbed essentially yet (stage of renal compensation) and second, when this function suffers appreciably (stage of renal decompensation). During first period (stage of renal compensation) disease is manifested by the same symptoms, such in case of acute glomerulonephritis. Patients can complain of weakness, more or less intractable headache and dizziness, edema. But severity of these symptoms usually is marked less than in case of acute glomerulonephritis. Often disease is taking its latent course and is revealed casually during pertaining to the prophylaxis examination. Elevation of blood pressure and hypertrophy of the left ventricle are diagnosed by means of objective methods examination. During examination of urine proteinuria and cylindruria are diagnosed; revealing of waxy casts (cylinders) is important for diagnostics particularly. Little amount (more rarely - significant amount) of altered erythrocytes is revealed, as a rule, in urine sediment. Blood cholesterol content is increased. More or less significant hypoproteinemia is observed due to constant proteinuria. Signs of the second, final period of disease are added gradually due to progressing nephroscrelosis. Low indices of renal clearance tests, with inulin particularly, testify about diminishing of functioning renal tissue. Filtration function during long period is normal and decreased only during period of exacerbation. Concentrating ability of kidneys is diminishing gradually; specific gravity of urine is decreased. Excretion of nitrous residues from organism during this period is supported due to excretion of large amount of fluid from organism - polyuria. Nocturnal diuresis is increased as compensation also (it exceeds 2/3-1/2 of daily one). Then, in case of more disorder of concentrating ability of kidneys, specific gravity of urine becomes low and monotonous - 1,009-1,011 and isn’t changed during day and under influence of dry eating (isohyposthenuria). During this period - content of nitrous residues in the blood (urea, creatinine, indican) increases. In further signs of uremia appears: weakness, flaccidity, and headache are increased, nausea, skin itch, bad ammonia fetor oris are marked, vision becomes worse. Patients lapse into uremic coma shortly before their death. Course. Chronic glomelunephritis usually lasts from 2-3 to 10-15 years. First period of disease (stage of renal compensation) is long, second one (stage of renal decompansation) - shorter. During the course of disease often more or less long exacerbation periods (usually they are provoked by overcooling or adding of infectious disease), and remission periods are observed. According to character of disease’s course and predominance of certain symptoms, some clinical types of chronic glomerulonephritis are distinguished. For nephrotic type edematic and urinary syndromes and relatively rapid course are typical. Hypertensive type, relatively benign, is characterized by hypertensive syndrome and insignificant changes of urine. In case of mixed type edemas, urinary and hypertensive syndromes are observed. This type of glomerulonephritis has the most severe and relatively quick course (2-3 years), results to expressed renal failure. At last, latent type is taking its latent course, without edemas and expressed hypertension, with insignificant changes of urine; renal failure is developed late, often after 10-15 years and more. In all cases death of the patients occurs as result of renal failure. Treatment. During period of symptoms exacerbation bed rest, milk-vegetable diet with restriction of salt consumption (to 1,5-2,5 g a day) and moderate protein content - 1 g and less /1kg of patient’s body weigh are prescribed; in case of nephrotic type and hypoproteinemia protein content in daily ration should be increased. Sanation of chronic infection foci (treatment of carious teeth, tonsillectomy) is carried out. For liquidation of infectious foci antibiotics are prescribed. During exacerbation of glomerulonephritis, in absence of acute arterial hypertension and azotemia, good effect is marked after long using of chloroquine. Symptomatic therapy in hypertensive and edematic types of chronic glomerulonephritis comes to prescription of antihypertensive drugs and diuretics (hydrochlorothiazide, furosemide and others). In patients with hypertensive and nephrotic types of chronic glomerulonephritis with compensated renal function significant improvement can be attained due to sanatorium-and-spa treatment. In case uremia the great attention must be given to struggle against azotemia. Intake of animal protein is limited (to 18-30 g a day), due to meat mainly. Course of broad spectrum antibiotics and sour-milk products (for example, kefir) are prescribed for suppressing of putrefaction in bowels. Plentiful drinking is healthy in case of absence of propensity to edemas. Large amount of B group vitamins, ascorbic acid, and glucose is introduced into organism for struggle against intoxication; recurrent blood transfusions, gastric lavage and enemas with solution of sodium hydrogen carbonate are prescribed. Peritoneal dialysis and hemodialysis (artificial kidney) are more effective methods of struggle against uremic intoxication. But these methods don’t eliminate reason of uremia’s appearnce; they only allow to prolong patients’ life. Renal transplantation, which is carried out in specialized surgical departments, open the debate in treatment of severe cases of chronic glomerulonephritis. Prophylaxis is in prevention and timely treatment of acute and chronic focal infection (tonsillitis, maxillary sinusitis, caries of teeth, parodontosis and others). Patients with chronic glomerulonephritis need regular medical check-up.

PYELONEPHRITIS Acute pyelonephritis Etiology and pathogenesis. Acute pyelonephritis (pyelonephritis acuta) occurs due to expansion of infection from renal pelvis to renal tissue in acute pyelitis or as result of entering of infection in kidney and its pelvis by hematogenous way. Last one occurs in case of presence of infectious focus in organism (chronic tonsillitis and others) or during acute infectious diseases (acute tonsillitis, sepsis, typhoid fever and others). But permeation of bacteria into kidney and pelvis doesn’t result to appearance of acute glomerulonephritis and focal glomerulonephritis always: bacteriuria without signs of renal tissue’s lesion is observed often. Difficulty of urine outflow from kidney (stone, ureter torsion and others) promotes to appearance of pyelonephritis. Clinical picture. Disease is manifested by severe general condition of patients, high fever of incorrect type, chill, dull pains in loin. In case of inflammation spreading to urinary bladder and urethra painful vesical tenesmus and severe colic during urination occur. Examination of urine reveals pyuria and bacteriuria, but in case of total obstruction of ureter and unilateral lesion changes in urine can be unrevealed. Latent (indistinct) type of acute pyelonephritis can be observed also (usually on the background of general severe diseases; in these cases renal lesion can be suspected on the base of results of urinalysis only. Tretment. Antibiotics, sulfonamides, nitrofuranes, fluoroquinolones are used.

Chronic pyelonephritis Etiology and pathogenesis. Chronic pyelonephritis (pyelonephritis chronica) often occurs in patients with chronic pyelitis due to spread of inflamamtory process from renal pelvis to renal tissue. Urolithiasis predisposes to fixation of infection in renal pelvis and its spread to renal tissue. Chronic pyelonephritis is caused by conditional - pathogenic microflora mainly - by colibacillus, more rarely - by enterococcus, proteus or other infection. In case of infection spread from renal pelvis to renal parenchyma papillae are affected at first, then - medullar and cortical layers of kidney. In case of chronic pyelonephritis process is unilateral often, and if it affects both kidneys, it is unequal. Clinical picture. Involving of renal tissue into process changes picture of pyelitis, bringing closer to one in case of chronic glomerulonephritis: arterial hypertension appears, disorders of concentrating and nitrogenous-excretion renal function are revealed gradually, then uremia appears. But, unilateral or asymmetrical renal lesion is typical for pyelonephritis (in contrast to chronic glomerulonephritis). It is diagnosed during ultrasound examination, intravenous and retrograde pyelography, separate examination of urine from right and left kidneys, obtained during catheterization of ureters, and separate examination of renal excretion of some substances - determining of renal clearance indexes (first of all, renal excretion of phenol-red, coefficient of PAG excretion is decreased, i.e. signs of distal tubules lesion are revealed relatively early). Rarer, according to indications, radioisotope examination - renography and scanning are used for these purposes. The following signs of renal pelvises inflammation are typical for chronic pyelonephritis: presence of bacteriuria, leukocyturia (revealing of “active leukocytes” - Shteinheimer-Malbin’s cells, particularly). Great importance belongs to bacteriological examination of urine: inoculation of mediums, determining of bacteria’s antibiotic susceptibility. It is necessary to remember that urine for examination, in women particularly, must be taken by means of urinary bladder catheterization only. Puncture biopsy of kidneys facilitates differential diagnosis also. During final period of disease all functional renal tests is disturbed significantly due to involving of great amount of tissue of both kidneys and development of nephrosclerosis. Patients’ death occurs as result of uremia mainly. Treatment. It includes influence to infection (antibiotics, nitrofuranes, fluoroquinolones), symptomatic therapy, directed to struggle against arterial hypertension and azotemia (during final period of disease).

A. Test tasks to be done: -with a single selective answer – I-st level; 1. Edema, high proteinuria, hypoproteinemia, dysproteinemia, hypercholesterolemia are typical for: a) syndrome of renal arterial hypertension; b) nephritic syndrome; c) nephrotic syndrome; d) syndrome of acute renal failure; e) syndrome of chronic renal failure. 2. What clinical symptom is typical for chronic nephrotic syndrome? a) dyspnea; b) evident constant edema; c) edema in the evening; d) pain in lumbar area; e) headache. 3. From clinical point of view course of acute renal failure is subdivided into: a) 2 periods; b) 3 periods; c) 4 periods; d) 5 periods; e) it isn’t subdivided. 4. Depending on etiologic factor, acute renal failure is divided into: a) 2 types; b) 3 types; c) 4 types; d) 5 types; e) It isn’t divided. 5. Which acute renal failure is caused by obstacle to urine outflow? a) prerenal acute failure; b) postrenal acute failure; c) acute renal failure during period of oligoanuria; d) latent renal failure; e) constant renal failure. 6. Initial period of acute renal failure lasts: a) 1-3 days; b) 7-8 days; c) 5-15 days; d) 3-4 week; e) 2-4 hours. 7. Where is primary urine formed? a) in glomerules; b) in proximal part of tubules; c) in distal part of tubules; d) in Henle’s loop; e) in glomerules and proximal part of tubules. 8. For which disease is leukocyturia the most typical? a) pyelonephritis; b) paranephritis; c) acute glomerulonephritis; d) renal amiloidosis; e) cystic cancer. 9. What urine changes are typical for chronic pyelonephritis? a) hematuria and cylindruria; b) leukocyturia, proteinuria; c) cylindruria; d) hematuria and bacteriuria; e) erythrocyturia, cylindruria, proteinuria. 10. Specific gravity of urine is depends on: a) quantity of using meal; b) character of feeding; c) quantity of salts in urine; d) quantity excreted urine and quantity dense substances in urine; e) body temperature. 11. What mechanisms of formation of urine occur at the level of glomerules? a) filtration and reabsorption; b) filtration; c) secretion; d) filtration and secretion; e) secretion and reabsorption. 12. Edemas in patients with acute nephritis are characterized by the following: a) appear in the evening; b) at first appear on the lower extremities; c) at first appear on the upper extremities; d) appear on the face in the morning; e) at once anasarca appear. 13. What syndrome is characterized by the following signs: edemas, high proteinuria, hypoproteinemia, dysproteinemia, and hypercholesterolemia? a) urinary; b) nephrotic; c) hypertensive; d) mixed; e) hypertensive and urinary. 14. Forming of “fresh” erythrocytes (unaltered erythrocytes) in urine is typical for: a) pyelonephritis; b) nephrotic syndrome; c) glomerulonephritis; d) uretritis. 15. Altered erythrocytes in sediment of the urine occur in case of: a) urolithiasis; b) cystitis; c) pyelonephritis; d) glomerulonephritis. 16. Content of rest nitrogen in blood of the healthy person is: a) 3,2-8,3 mmol/l; b) 14,28-28,56 mmol/l; c) 0,088-0,176 mmol/l; d) 28,56-57,12 mmol/l. 17. State of consciousness in terminal stage of uraemia is: a) sopor; b) stupor; c) coma; d) clear consciousness. 18. For which disease is long polyuria with high specific gravity of urine typical? a) heart failure; b) renal failure; c) diabetes mellitus; d) pyelonephritis; e) poisoning of nephrotoxic substances. 19. Kussmaul’s respiration is typical for: a) renal colic; b) pyelonephritis; c) uraemia; d) nephrotic syndrome. 20. The following triad of symptoms is typical for glomerulonephritis: a) pollakisuria, leucocyturia, polyuria; b) erythrocyturia, edemas, hypertension; c) leukocyturia, oliguria, pollakiuria; d) leukocyturia, nicturia, edemas. 21. The following triad of symptoms is typical for pyelonephritis: a) fever, erythrocyturia, hypertension; b) fever, low back pain, leukocyturia; c) hyposthenuria, azotemia, sopor; d) pollakiuria, erythrocyturia, dysuria. 22. For which disease is syndrome of renal colic typical? a) pyelonephritis; b) diabetes mellitus; c) urolithiasis; d) renal tuberculosis. 23. Concentration of blood creatinine in healthy persons is: a) 1,107-2,096 mmol/l; b) 0,176-0,297 mmol/l; c) 0,088-0,176 mmol/l; d) 0,044-0,088 mmol/l. 24. What indices of specific gravity of urine are typical for uraemia? a) 1,030-1,040; b) 1,009-1,011; c) 1,015-1,020; d) 1,020-1,030. 25. Concentration function of the kidneys is investigated by means of: a) Nechiporenko’ test; b) Zimnitsky’s test; c) Amburzhe’ test; d) Addis-Kakovsky’ test. 26. Nocturia is typical for: a) glomerulonephritis; b) pyelonephritis; c) cardiac decompensation; d) diabetes mellitus. 27. Which type of chronic glomerulonephritis takes its course without evident edemas, with normal arterial blood pressure and periodical insignificant changes in urine? a) nephrotic; b) hypertensive; c) mixed; d) latent; e) acute. 28. In case of which type of chronic glomerulonephritis does the most significant disturbance of protein metabolism occur? a) in nephrotic; b) in hypertensive; c) in mixed; d) in latent; e) it never occurs in chronic glomerulonephritis. 29. The following results of blood analysis are typical for acute pyelonephritis: a) anemia; b) leukopenia; c) leukocytosis and acceleration of ESR; d) thrombocytopenia; e) lymphocytosis.

-with the selective group of right answers – the II-nd level; 1. What most typical changes of urine are revealed in patients with chronic nephrotic syndrome? a) constant, significant proteinuria; b) hematuria; c) leucocyturia; d) large amount of hyaline, granular, waxy casts and renal epithelium cells; e) urobilinogenuria; f) bilirubinuria; g) periodical proteinuria. 2. What changes of urine are revealed in “frank” period of chronic renal failure? a) oliguria; b) isohyposthenuria; c) proneinuria; d) hematuria; e) urobilinogenuria; f) bilirubinuria; g) leukocyturia. 3. Symptoms and signs of uraemia, which concern to skin, include the following: a) hyperhydrosis; b) pruritus; c) easy bruisability; d) cyanosis; e) pallor; f) ecchymoses; g) edema; h) excoriations. 4. Symptoms and signs of uraemia, which concern to pulmonary system, include the following: a) dyspnea; b) bronchial brething; c) arterial hypertension; d) interrupted breathing; e) uruinous breath; f) crepitation; g) rales; h) pleural effusion. 5. Symptoms and signs of uraemia, which concern to digestive system, include the following: a) epistaxis; b) bitter taste in mouth; c) anorexia; d) nausea; e) perverted appetite; f) vomiting; g) bulimia. 6. In “frank” period of chronic renal failure during laboratory research the following can be revealed: a) anemia; b) elevation of blood urea nitrogen and serum creatinine; c) hypokalemia; d) decrease of blood urea nitrogen and serum creatinine; e) hyperkalemia; f) thrombocytosis. 7. “Urinary syndrome” includes the following signs: a) moderate proteinuria (from 100 mg to 3,5 g during the day); b) massive proteinuria (more than 3,5 g during the day); c) erythrocyturia (more than 1•106/L during the day); d) leukocyturia (more than 4 •106/L during the day); e) pains in loin area; f) cylindruria; g) oliguria; h) renal and transitional epithelium in urine. 8. The following signs are demonstrative for renal erythrocyturia: a) domination of altered erythrocytes over unaltered; b) domination of unaltered erythrocytes over altered; c) presence of erythrocytes casts; d) presence of waxy casts; e) combination of macro- or microhematuria with proteiuria, which is above 1 g a day; f) combination of macro- or microhematuria with proteiuria, which is less than 1 g a day; g) poikilocytosis. 9. Renoparenchymatous tubulointerstitial erythrocyturia occurs in case of: a) acute pyelonephritis; b) chronic pyelonephritis; c) urolithiasis; d) urinary acid diathesis; e) renal tumors; f) different morphological types of glomerulonephritis; g) interstitial nephritis; h) polycystic renal disease. 10.There are the following most often causes of extrarenal erythrocyturia development: a) tumors; b) acute pyelonephritis; c) chronic pyelonephritis; d) acute glomerulonephritis; e) urolithiasis; f) urinary acid diathesis; g) traumas of urinary tracts; h) chronic glomerulonephritis. 11. In case of renal diseases elevation of blood pressure can be realized by following mechanisms: a) retention of sodium and water; b) significant loss of protein, albumin particularly, with urine; c) activation of renin-angiotensin-aldosterone system; d) decrease of depressor factors production; e) disturbance of reabsorption of protein molecules by affected tubular epithelium; f) increase of depressor factor production; g) increase of capillary permeability. 12. Syndrome of nephritis is typical for: a) acute stage of glomerulonephritis; b) acute pyelonephritis; c) periods of exacerbation of chronic glomerulonephritis; d) secondary nephritis in patients with infective endocarditis; e) chronic pyelonephritis; f) secondary nephritis in patients with systemic lupus erythematosus; g) renal tumor. 13. The following signs are typical for oligoanuria period of acute renal failure: a) it lasts 5-15 days; b) it lasts 3-4 weeks; c) increase of urine excretion; d) normalization of indices of water-electrolyte metabolism and acid-base balance; e) gradual decrease of azotemia to normal level; f) sharp decrease of daily diuresis to 200 ml and less, down to anuria; g) diuresis is more than 2 l. h) urine has dark color, contents protein, erythrocytes and casts. 14. There are the following potential results of laboratory and instrumental examiantion in case of early (initial) stage of chronic renal failure: a) polyuria, nicturia (by means of Zimnitsky’s test); b) isohypersthenuria (by means of Zimnitsky’s test); c) isohyposthenuria (by means of Zimnitsky’s test); d) disorders of glomerular filtration and tubular reabsorption (by means of Reberg’s test); e) ventricular premature beats, flattening or inversion T wave; depression of ST segment; f) hypokaliemia; g) hyperkaliemia. 15. There are the following signs of the second, final period of chronic glomerulonephritis: a) low indices of renal clearance tests; b) high indices of renal clearance tests; c) pollakiuria; d) isohyposthenuria; e) increased content of nitrous residues in the blood (urea, creatinine, indican); f) increased nocturnal diuresis; g) decreased nocturnal diuresis. 16. There the following subjective signs of acute pyelonephritis: a) high fever; b) chill; c) intensive pains in inguinal areas; d) dull pains in loin; e) vomiting; f) oliguria; g) anuria.

B. Tasks to be done:

Task 1. Patient R., 17 years old, student of medical university, consulted a district doctor (doctor in charge of a section in a city area). He complains of dyspnea, diffuse edema, headache, impairment of vision, diminishing of urine amount and change of its color (it becomes brown-red). Anamnesis morbi. He observed moderate edemas of the face yesterday in the morning during washing. Little heaviness in the head was felt. In the evening headache began, edemas of the face become more intensive, they appeared on the legs also. Edemas become diffuse and headache - more intensive to the next morning. He observed impairment of vision and appearance of dyspnea at rest. Anamnesis vitae. Nobody has renal disease in his family. Living conditions are good. He was ill with tonsillitis several times during childhood. Three weeks before this disease he also was ill with acute tonsillitis. He was relieved from lessons. He was treated. In 4-5 days manifestations of tonsillitis disappeared completely. Inspection. Physical development is good, height is 176 cm, body weigh is 86 kg, before disease it was 68 kg. Skin is pale. Face is edematic. Eyelids are swollen; edemas of legs and trunk are marked. After pressing by finger on edematic areas depth fossa is marked. Lymph nodes aren’t enlarged. Respiratory organs. During inspection dyspnea is marked, breathing is deep, 24 per minute. Percussion sound is little weakened over all parts of the chest. Lower borders of both lungs are on the same level: along midclavicular line - 5 rib, along midaxillary line - 4th intercostal space, along posterior axillary line - 4th intercostal space, along scapular line - 8th intercostal space. Breathing in lower parts of the lungs is weakened, in subclavicular and axillary areas- rough breath sounds. In lower parts of the lungs diffuse dry and fine-bubbled rales are heard bilaterally. Circulatory organs. Heart region is without changes. Apex beat isn’t visible, during palpation is reveled in 5th interspace along midclavicular line. During percussion: left border of relative cardiac dullness - 0,5 cm laterally midclavicular line, upper - along 3rd interspace, right - 1 cm laterally right edge of sternum. During auscultation: gallop rhythm, the I sound at the heart apex is little decreased, accent of the II sound over aorta. Pulse rate is 106 per minute, rhythmical. Blood pressure is 210/140 mm Hg. Digestive organs. Mucous membrane of oral cavity is little pale, edematic.Tonsils aren’t enlarged, their color is usual, patch is absent. Swallowing is without difficulty, painless. Abdomen is enlarged, during palpation is painless, abdominal wall is edematic. Lower border of the liver is palpated 5 cm below costal margin along midclavicular line. The size of the liver along midclavicular line during percussion is 17 cm. Urinary organs. Kidneys aren’t palpated. Pasternatsky’ sign is slightly positive bilaterally. Urinary bladder isn’t palpated, isn’t determined during percussion. Questions to task 1: 1. For which disease is fast development of edematic syndrome and elevation of blood pressure typical? 2. What signs of heart failure are in the patient? 3. What is the cause of dyspnea in this patient? 4. What is the cause of dry and moist rales appearance in this patient? 5. What is the cause of displacement of the left border of relative cardiac dullness? 6. What is reason of heart failure in this patient? 7. What diagnosis should be made for this patient, according to your opinion? 8. What is the reason of headache? 9. What mechanisms can be involved in pathogenesis of arterial hypertension in this patient? 10. What mechanisms can be involved in pathogenesis of edemas in this patient? 11. How is it possible to explain diminishing of urine amount? 12. What is the cause of impairment of vision? 13. How is it possible to explain displacement of lower border of the lungs upwards? 14. What is the cause of rough breath sounds?

Task 2. Patient A., 26 years old, is treated in nephrologic department. She complains of weakness, headaches, dizziness, and edemas. Anamnesis morbi. At first headaches and dizziness occurred during pregnancy 4 years ago. After labor edemas are disappeared, headache occurred rarely. Two years ago after overcooling and infection of upper respiratory tract in past edemas appeared, headaches become almost constant. Vision becomes worse. Anamnesis vitae. She catches cold often. She had maxillary sinusitis. Living conditions are good. She works in room; work isn’t connected with influence of physical and chemical unfavorable factors. Inspection. Consciousness is clear. Position in a bed is active. She is normosthenic. The face is swollen, palpebral fissure is narrow. Skin is pale touched with waxen. Edemas are on the legs and loin, deep fossa is formed after pressing. Respiratory organs. The chest has correct form, breathing is without difficulty. Palpation, percussion and auscultation didn’t reveal abnormality. Circulatory organs. Left border of relative cardiac dullness is displaced 2cm laterally, upper and right ones - normal. Heart sounds are clear, rhythmical. The II sound is accented over aorta. Pulse rate is 68 per minute, tense. Blood pressure is 160/120 mm Hg. Digestive organs. Oral cavity is without changes. Swallowing is without difficulty. Configuration of the abdomen is usual; the liver is enlarged on 3cm along midaxillary line. Urinary organs. Kidneys aren’t palpated. Pasternatsky’ sign is negative. Disuria isn’t observed. Laboratory tests General urine analysis Amount - 400 ml Color - light-yellow Transparence - isn’t full pH - 6,5 Protein - 5,7 g/l Specific gravity — 1013 Microscopy of urine sediment: Renal epithelium — 5-6 in f.v. Leucocytes - 6-7 in f. v. Erythrocytes: altered - 15-18 in f.v. unaltered - 5-7 in f.v. Casts: hyaline - 7-8 in f.v. granular - 2-3 in f.v. Urinary sediment examination according to Kakovsky-Addis: Leukocytes - 1 500 000 Erythocytes - 12 000 000 Casts - 48 000 Urinary sediment examination according to Nechiporenko: Leukocytes - 2 000 Erythocytes - 18 000 Casts - 840 Zimnitsky’s test: Portion Volume Specific gravity of urine 1 240 1015 2 300 1018 3 360 1015 4 240 1010 5 200 1012 6 180 1018 7 150 1017 8 170 1019

Reberg’s test (by means of endogenous creatinine) Glomerular filtration - 60 ml/min Reabsorption - 98,5 %

Biochemical blood examination Cholesterol - 9,6 mmol/l Total lipids - 7 g/l Urea - 10,5 mmol/l Creatinine - 0,245 mkmol/l

Questions to task 2: 1. For which renal disease are complaints of edemas, headaches, dizziness the most typical? 2. What is the main reason of headaches and dizziness in case of renal diseases? 3. Is occurrence of headaches and dizziness in case of cardiovascular pathology possible? 4. Is the disease of this patient acute or chronic according to anamnesis information? 5. What risk-factors of renal diseases are in this patient? 6. For which renal diseases are edemas of the face typical? 7. For which renal diseases is pale, like wax, skin typical? 8. Is pale, like wax skin, typical for patients with cardiovascular pathology? 9. How can the displacement of the left border of cardiac dullness in this patient be explained? 10. Does this patient have proteinuria? 11. Does this patient have hyposthenuria? 12. Does this patient have nocturia? 13. Does this patient have isuria? 1. Does this patient have isosthenuria? 2. Does this patient have erythrocyturia? 3. What amount of erythrocytes can be present in urine of healthy person in general analysis, examination according to Kakovsky-Addis, Nechiporenko? 4. What amount of leukocytes can be present in urine of healthy person in geenral analysis, examination according to Kakovsky-Addis, Nechiporenko? 5. What amount of casts can be present in urine of healthy person in geenral analysis, examination according to Kakovsky-Addis, Nechiporenko? 6. Is decreasing of concentrating function of kidneys in this patient observed? 7. Is decreasing of glomerular filtration in this patient observed? 8. Are changes of urine in this patient typical for pyelonephritis? 9. Are changes of urine in this patient typical for glomerulonephritis? 10. What indexes of analyses direct to renal difunction? 11. What are normal indexes of total lipids and cholesterol in blood serum? 12. What are normal indexes of urea and creatinine in blood serum? 13. What clinical and laboratory signs of nephrotic syndrome are observed in this patient? 14. What is diagnosis of this patient, according to your opinion?

Answers for test tasks of the I-st level: 1 - c 8 - a 15- d 2 1 - b 2 - b 9 - b 16- b 2 2 - c 3 - c 10- d 17- c 23- c 4 - b 1 1 - b 18- c 24- b 5 - b 1 2 - d 19- b 25- b 6 - a 1 3 - b 2 0 - b 26- c 7 - a 14- d 27- d 28- a 29- b

Answers for test tasks of the II-nd level: 1 - a , d 5 - a , c , d , f 9 - a , b , g , h 13- a , f , h 2 - a , b , c , d 6 - a , b , e 10- a , e , f, g 14- a , c , d , e , f 3 - b,c,e,f,g,h 7 - a , c , d , f , h 11- a , c , d 15- a , d , e , f 4 - a , e , g , h 8 - a , c , e 12- a , c , f 16- a , b , d

Standards of right answer for tasks: 1) 1. For acute glomerulonephritis. 2. Dyspnea, tachycardia, gallop rhrythm. 3. Dyspnea is manifestaton of heart failure. 4. Swelling of bronchi and filtration of fluid in bronchi in conditions of expressed edematic syndrome and heart failure. 5. Dilation of chambers of heart, appearing in case of severe heart failure. 6. Fast development of arterial hypertension and very high level of blood pressure. 7. Acute glomerulonephritis. 8. Arterial hypertension. Edematic syndrome promotes to appearance of headaches also (elevation of intracranial pressure). 9. Development of inflammatory process in glomerules results to decrease of pressure in efferent artery. It activates juxtaglomerular apparatus. Secretion of renin is increased and activation of renin-angiotensin-aldosterone system (RAAS), playing greatest role in development of arterial hypertension, begins. 10. Activation of RAAS and increase of antidiuretic hormone (ADH) with following increasing of sodium and water reabsorption in renal tubules, increase of capillary permeability. Increase of capillary permeability promotes to development of edemas also. 11. By retention of fluid in organism. 12. Edema of retina and spasm of its vessels. 13. By accumulation of edematic (congestive) fluid in pleural cavities (transsudate). 14. Edema of alveolar walls.

2) 1. For glomerulonephritis. 2. Development of arterial hypertension. 3. Yes, they can be. They are observed in patients with hypertensive disease most often. 4. Chronic disease. 5. Focus of chronic infection - maxillary sinusitis, often catarrhal diseases. 6. For glomerulonephritis and amyloidosis. 7. For glomerulonephritis and amyloidosis. 8. No, it isn’t. 9. By hypertrophy of the left ventricle, observed in case of long arterial hypertension. 10. Yes, she has. Normally it is possible appearance of protein “marks” only (<0,03 g/l). 11. Yes, she has. Specific gravity of urine in all portions was less than 1020. 12. Yes, she has. Ratio of daily diuresis to nocturnal one wasn’t more than 2:1. 13. Yes, she has. Difference of volume of three-hour portions of urine during examination according Zimnitsky was significant. 14. No, she doesn’t have. Specific gravity of urine is more than specific gravity of blood plasma. 15. Yes, she has significant erythrocyturia. Normally 0-1-2 erythrocytes can be present in f.v. 16. In urine of healthy person it is possible to reveal 0-1-2 erythrocytes during carrying out of general urinalysis, during examination according to Kakovsky-Addis - to 1000 000, according to Nechiporenko - to 1000. 17. In urine of healthy person it is possible to reveal 0-1-2 leukocytes in f.v.( in women - to 5-10 in f.v) during carrying out of general urinalysis, during examination according to Kakovsky-Addis - to 2000 000, according to Nechiporenko - to 4000. 18. In urine of healthy person it is possible to reveal 0-1casts during carrying out of general urinalysis, during examination according to Kakovsky-Addis - to 20 000, according to Nechiporenko - to 220. 19. Little decreasing of concentrating function of kidneys is observed in this patient. 20. Yes, it is. Glomerular filtration in this patient was 60 ml/min. Normally it is 65-125 ml/min. 21. No, they aren’t. 22. Yes, they are (great proteinuria, great amount of erythrocytes, altered particularly). 23. Hyposthenuria, decrease of glomerular filtration, increase of urea and creatinine content in the blood. 24. Total lipids - 3400-6000 g/l, total cholesterol - 3,9-5,2 mmol/l. 25. Urea - 3,23-6,46 mmol/l, creatinine - 88-176 mkmol/l. 26. Edemas, proteinuria, hyperlipidemia. 27. Exacerbation of chronic glomerulonephritis, mixed type, chronic renal failure (CRF) 1.

Methodical instruction is composed by lecturer Ye.Ye. Petrov.

Approved at the Department of Propaedeutics to Internal Medicine with Care of Patients meeting on 11 09 2018 Protocol No2 The Head of the Department Professor Yu. Kazakov

METHODICAL INSTRUCTION FOR STUDENTS’ SELF-PREPARATION WORK

Educational discipline Propaedeutics to Internal Medicine Module No 2 Enclosure module No 9 Topic The main symptoms and syndromes on anemia. Clinical blood analysis Year 3 Faculty medical

Poltava - 2018 1. The topic basis: The topicality of studied questions is caused first of all by a wide spreading of a studied pathology among a human population; as many as 30 % of the world’s population may be affected at some time. In the former USSR about 13,5 % of people suffered anemia. Laboratory methods of diagnostics play great role in diagnostics of pathology of blood system on the whole and anemia specifically. The complete blood count (CBC) is an important part of routine screening and hospital admission. It involves several tests, each of which assesses the three major cells formed in the bone marrow. The CBC detects many disorders of the hematologic system and provides data for the diagnosis and evaluation of disorders in other body systems.

2. The specific aims:  To explain term “general blood analysis” and describe its results normally.  To explain how blood results of general analysis can be changed in physiological and pathological conditions.  To explain ethiology and pathogeny of different types of anaemia.  To compose plane of examination of the patients for determining type of anemia.  To analyze results of laboratory methods examination of the patient for determining type of anemia.  To interpret potential results of the patients with different types of anemia.

3. Basic knowledge, experience, skills necessary for studying the topic in connection with other subjects (interdisciplinary integration) :

Previous disciplines Obtained skills 1. Anatomy To know human anatomy, structure of hemopoietic organs. 2. Physiology To know physiology of the blood system. 3. Medical psychology To be able to observe principles of ethics and deontology in medical practice 4. Latin and medical terminology To know terminology (in Latin transcription): anaemia haemolytic, anaemia aplastic, B12 (folic acid) deficiency anaemia, iron deficiency anaemia, posthemorrhagic anaemia

4. Tasks for self-work during preparation to the class. 4.1 List of the main terms, parameters, characteristics, which should be mastered during preparation to the class: Term Definition 1.Erythremia It is increased erythrocyte count. 2. Erythropenia It is decreased erythrocyte count. 3. Anisocytosis It is excessive variation in the size of erythrocytes. 4. Microcytosis It is prevalence of smaller erythrocytes. 5.Macrocytosis It is prevalence of larger erythrocytes. 6. Poikilocytosis It is the change in the shape of erythrocytes. 7. Howell-Jolly bodies These are small, well-defined, round, densely staining basophilic inclusion bodies about 1μm, which usually occur singly but sometimes in multiples. They contain DNA and may be chromosomal remnants or nuclear fragments. 8. Cabot rings These are blue-staining, threadlike inclusions in the red cells in severe anemia. They may appear as rings, figures-of-eight, or twisted and convoluted in a variety of shapes. It has been postulated that they are remnants of the mitotic spindle, but other have found that they contain histone and iron. 9. Hemoglobin It is the oxygen-carrying pigment, the main component of red blood cells having a great affinity for oxygen. 10. Hematocrit It is compares the volume of red blood cells to the volume of plasma and is measured as a percentage of the total blood volume. 11. Color index It is a conventional value derived from the ration of hemoglobin to the number of erythrocytes. 12.Reticulocytes They are juvenile polychromatophilic cells. Their number in the blood is a measure of the activity of the bone marrow. 13. Blood shift to the left It is rejuvenation of the neutrophils composition, if the quantity of stab neutrophils increases and juvenile neutrophils and even myelocytes appear. 14. Leukaemoid reactions They are the pathologic reactions with high leukocytosis and occurrence of immature leukocytes in the blood, which are similar to those in leukemias, but are temporary and convertible. 15. Hiatus leucaemicus It is presence only youngest and most mature cells without intermediate forms in the peripheral blood. 16. Anemia It is clinico-hematologic syndrome, which is characterized by decrease of hemoglobin content in unit of blood volume (less then 130 h/L in men and less then 120 g/L in women), at simultaneous decrease of amount of erythrocytes (less then 4x1012/L). 4.2. Theoretical questions to be answered before class: 1. Tell about general blood analysis and its results normally. 2. How can the results of general blood analysis be changed in physiological and pathological conditions? 3. What does term “anemia” mean? 4. What are the factors for development of anemia? 5. What are the main compensatory mechanisms of organism as reply to anemia? 6. What is hemoglobin level in mild, moderate and severe degree of anemia? 7. What are the signs (subjective and objective) general for all types of anemia? 8. Tell about classification of anemias. 9. What main hematologic criteria of different forms of anemia do you know? 10. Causes, clinical picture and diagnostics of iron deficiency anemia. 11. Causes, clinical picture and diagnostics of megaloblastic anemia (pernicious or malignant anemia, Addison-Biermer disease). 12. Causes, clinical picture and diagnostics of haemolytic anemia. 13. Causes, clinical picture and diagnostics of acute posthemorrhagic anemia. 14. Causes, clinical picture and diagnostics of hypoplastic anemia. 4.3. Practical work (tasks), which should be performed during class: 1. To carry out questioning, physical examination of the patients with anemia. 2. To interpret obtained results. 3. To interpret results of blood analysis from case history. 4. To work in laboratory.

The contents of topic: Text

EXAMINATION OF BLOOD The complete blood count (CBC) is an important part of routine screening and hospital admission. It involves several tests, each of which assesses the three major cells formed in the bone marrow. The CBC detects many disorders of the hematologic system and provides data for the diagnosis and evaluation of disorders in other body systems. A CBC includes red and white cell counts, hematocrit, hemoglobin, erythrocyte indices, differential white cell count. For tests which require only a very small amount of blood, a sufficient amount may be obtained by puncturing the edge of the tip of a finger. In this method the skin is cleaned, and a quick stab is made with a sharp needle. The blood is collected in a pipette as it oozes from this puncture. The main elements of the blood are erythrocytes, leucocytes and thrombocytes. Normal the red blood cell count or erythrocyte count in women is 3,9-4,7xl012/L and in men — 4,0-5,0xl012/L of blood. Increased the red-cell count is called polycytemia or erythremia. It occurs in dehydration, at high altitudes and with hypoxia caused by cardiac or respiratory disorders. Temporary increase occurs with strong emotions or a cold shower. Decreased erythrocyte count is called erythropenia. It is present in almost all the anemia, leukemia and hypothyroidism. The size, shape, color and cell inclusions should be assessed. Excessive variation in the size of erythrocytes is called anisocytosis. Prevalence of smaller erythrocytes (microcytosis) occurs in iron deficiency anemia. Macrocytosis develops in hemopoietic dysfunction of the liver. Megalocytes appear in the blood of patients with vitamin B12 deficiency anemia. The change in the shape of erythrocytes is called poikilocytosis. In addition to round erythrocytes blood contains also erythrocytes of oval, pear-shaped and other configurations. During maturation of erythrocytes in pathological conditions nuclear remnants, known as Jolly bodies and Cabot rings (thread-like rings or convolutions) may be preserved. They are believed to be the remnants of the nuclear envelopes, and occur mostly in vitamin B12 deficiency anemia. The red blood cell count is not in itself always sufficient to determine the adequacy of red cell function, so it is frequently considered in conjunction with hemoglobin, hematocrit, and red cell indices. Hemoglobin is the oxygen-carrying pigment, the main component of red blood cells having a great affinity for oxygen. Concentration of hemoglobin in healthy people varies from 120-140 g/L in women and from 135-180 g/L in men. Increased hemoglobin is present in chronic obstructive pulmonary disease, high altitudes and polycytemia. A decrease of hemoglobin indicates anemia, severe hemorrhage. Hematocrit compares the volume of red blood cells to the volume of plasma and is measured as a percentage of the total blood volume. Normal hematocrit in women is 37-42%, in men — 38-44%. It increases in severe burns, shock, severe dehydration, polycytemia vera. Decreased hematocrit is present in severe blood loss and leukemia. Once the quantity of erythrocytes and hemoglobin in a given blood specimen is known, it is possible to calculate the hemoglobin content of each erythrocyte. A conventional value derived from the ration of hemoglobin to the number of erythrocytes is called red cell indices or color index (CI). This value is found by dividing a tripled quantity of hemoglobin in grams by the first three figures expressing the quantity of erythrocytes. For example:

Er 3,49xl012/L CI = 140 x 3 = 1,2 Hb 140 g/L 349

Normal color index varies from 0,85 to 1,15. The indices are valuable in the diagnosis of various anemias. If erythrocytes are undersaturated with hemoglobin (color index less than 0,85) they are poorly stained to become hypochromic (iron deficiency anemia); in folic acid deficiency, vitamin B12 deficiency anemia, liver cirrhosis erythrocytes are colored intensely, i. e. hypechromic (color index higher than 1,15). Juvenile polychromatophilic cells are called reticulocytes. The number of reticulocytes in the blood is a measure of the activity of the bone marrow. Normal reticulocytes count is 2-10 per 1000 erythrocytes (2-10%) or 0,2-1 per 100 erythrocytes (0,2-1%). Erythropoiesis is activated in blood loss and hemolysis, and the number of reticulocytes in normal bone marrow and peripheral blood increases. The absence of the reticulocytes increase indicates decreased function of the bone marrow (hypoplastic and aplastic anemia). The platelets or thrombocytes are the smallest formed elements in the blood, with a diameter of less than one half that of a red blood cell. Their chief function is related to blood clotting, which is aided by the agglutination of platelets. The normal number of thrombocytes (platelets) is 180-320xl09/L of blood. If the number of thrombocytes decreases significantly (thrombocytopenia), a tendency to hemorrhages develops. Decreased platelet counts occur with acute leukemia, thrombocytopenic purpura, and aplastic anemia. Trombocytosis (increased platelets) is found in essential thrompocytosis, hemorrhage, polycytemia and malignant lymphoma. Leucocytes (white blood cells) protect the body against disease. They are classified into granulocytes and agranulocytes depending on the presence or absence of granules in their cytoplasm. The granulocytes are further classified into neutrophils, basophils, and eosinophils depending on their ability to take up stain. The normal leukocyte count is 4,0-9,0x109/L of blood. Leucocytes respond quickly to various environmental factors and changes inside the body. The increased number of leucocytes (leucocytosis) is the result of activation of leucopoiesis. It can be in inflammatory process in the organism usually of bacterial origin infectious diseases, in trauma, surgery or in presence of tumor, or leukemia. The decreased number of leucocytes (leucopenia) depends on inhibition of the hemopoietic organs, their exhaustion, increased decomposition of leucocytes under the effect of antileucocytic antibodies. It can be in aplastic anemia, agranulocytosis and leukemia. The leukocyte count may not be increased if the individual is offering little or no resistance to the disease or if the infection is of little importance. For clear diagnostics of the pathological processes it is necessary to know the leycocyte formula. The leucocyte formula is the percentage of separate forms of the leucocytes. An increase in the percentage of one type of cell is accompanied by a decrease in another type of cell, because the common count of all types of cells is 100%. Neutrophils (stab (bands) and segmented) are the most changeable group of leucocytes. In norm the stab count is 1-6%, the segmented count is 47-72%. Increased neutrophils are found with a number of bacterial infections, inflammatory but non infectious diseases (collagen disorders, rheumatic fever, pancreatitis), and with malignancies; also increased with burns, crushing injuries, diabetic acidosis, and infarctions. Increased stabs are found with severe stress on bone marrow or severe bacterial disease. Neutropoiesis is characterized not only by increased total number of neutrophiles but also by the appearance in the blood of immature cells. If the quantity of stab neutrophils increases and juvenile neutrophils and even myelocytes appear that rejuvenation of the neutrophil composition is called the blood shift to the left. Regenerative and degenerative "shifts to the left" are distinguished. In the regenerative shift to the left the number of stab neutrophils increases in the presence of leucocytosis. It indicates active protective response of the body. The protective role of neutrophils consists in phagocytosis, bactericidal action and production of proteolytic enzymes promoting resolution of necrotized tissue and healing of wounds. In the degenerative shift to the left the number of stab neutrophilis only increases along with the degenerative changes in neutrophilis in the absence of leucocytosis. It indicates the absence of the body protective response. The regenerative shift to the left occurs most frequently in the presence of an inflammatory or necrotic focus. An especially marked shift to the left to promyelocytes and even myeloblasts in the presence of significant leucocytosis to 30-40x109/L is called leucaemoid reaction. It can be in pronounced infectious process (sepsis, acute infectious diseases). It must be differentiated with acute or chronic leucosis (leukemia). If only youngest and most mature cells without intermediate forms (hiatus leucaemicus) are revealed in the peripheral blood, it indicates acute leukemia. In chronic leukemia intermediate forms (together or without blasts) always are present in the peripheral blood. Neutrophils count decreases (neutropenia) in the presence of the inhibiting action of toxins, microbes, viruses, ionizing radiation. Eosinophils are present in the blood in relatively small quantity (0,5-5%). Eosinophils count increases (eosinophylia) in allergic processes, in helminthiasis or other parasitic disorders and itching dermatitis. Decreased eosinophils count (eosinopenia) occurs in sepsis, tuberculosis, typhus and poisoning. Basophils are carried of important mediators of tissue metabolism. In norm its count is 0-1%. Increased basophils count (basophylia) is found in allergic processes, myelofibrosis. Normal lymphocytes count is 19-37%. They control the immunological processes in our organism. Increased lymphocytes count (lymphocytosis) occurs during recovery in acute infectious diseases, in thyrotoxicosis. Marked increase in lymphocytes occurs in lympholeukemia. Lymphopenia (decreased lymphocytes count) occurs with radiation sickness, lymphogranulomatosis (Hodgkin's disease), with lupus erythematosus. Normal monocytes count is 3—11%. Increased monocytes count (monocytosis) indicates development of the immune processes. Monocytosis occurs in some chronic disease (chroniosepis, tuberculosis, malaria, syphilis). Monocytopenia (decreased monocytes count) occurs in severe septic forms and other infections. Erythrocyte sedimentation rate (ESR) is a common, although nonspecific, screening procedure that measures the rate at which red blood cells settle out in well-mixed venous blood. Red cell volume, surface area, density and surface chance affect aggregation. Plasma proteins, especially fibrinogen and globulin, encourage aggregation. Normal ESR for men is 2-10 mm/h and for women is 2-15 mm/h. Acceleration of erythrocyte sedimentation rate occurs in most inflammatory processes, infections, malignant tumours, collagenoses, tissue decomposition, anemia, leukemia. The sedimentation rate is a nonspecific test which may be altered by a large number of disease processes, much like the body temperature. It is of special value in following the activity of certain chronic diseases such as rheumatic fever, tuberculosis, and arthritis. ANEMIA Anemia - clinico-hematologic syndrome, which is characterized by decrease of hemoglobin content in unit of blood volume (less then 130 g/L in men and less then 120 g/L in women), at simultaneous decrease of amount of erythrocytes (less then 4x1012/L). Anemia has, as a rule, secondary character and is syndrome of any main disease. The following factors result to development of anemia: a) loss of blood (acute and chronic posthemorrhagic anemia); b) decrease of erythrocytes production (anemia, caused by disturbance of hemopoieseis due to iron, B12 or folic acid deficiency and also hypoplastic anemia, caused by influence of various exo- and endogenous pathogenic factors); c) increase rate of destruction of erythrocytes (congenital and acquired anemia); d) combination of directed factors. Anemia causes appearance of hypoxia of organs and tissues, it results development of dystrophic changes in them. Besides, brain and cardiac muscle suffer particularly. In case of severe anemia predisposition to acidosis due to accumulation of unoxidized products of metabolism is marked. It worsens tropics of tissues. The main compensatory mechanisms of organism as reply to anemia include stimulation of erythropoietic function of bone marrow, increase of stroke volume and cardiac rate. Severity of the course of anemia depends on rate of its development, level of hemoglobin, age of patient and functional possibilities of cardio-vascular system. In mild degree of anemia hemoglobin content decreases to 100 g/L, in anemia of moderate degree of severity - to 100-80 g/L, in severe degree of anemia -less then 80 g/L. The same clinical symptoms, caused by hypoxia of brain, cardiac muscle and other internal organs, are typical for all types of anemia, regardless of their origin. Patients complain of general weakness, rapid fatigability, sleepiness, irritability, headache, ear noise, “spots” ahead of eyes, dizziness, predispositions to syncope, piercing pains in heart region, palpitation, dyspnea on physical exertion. During objective examination paleness of skin and mucous membranes, tachycardia is marked, during auscultation functional systolic murmur, caused by disturbances of rheologic properties of the blood, is revealed at the heart apex. In evident anemia continuous blowing “humming-top murmur” can be heard over jugular veins, on the right more often. Blood pressure is decreased more often. In case of development of myocardial dystrophy signs of left ventricle’s enlargement (displacement of the heart apex laterally and dilation of the left cardiac border), diminishing of the I sound at the heart apex, appearance of pathologic III and IV sound are reveled; on ECG flattening or inversion of T-wave in all leads is marked. Apart from directed general symptoms every form of anemia is characterized by specific for it clinical and hematologic signs. Such forms of anemia as iron-deficiency, megaloblastic, hemolytic, acute posthemorrhagic and hypoplastic have the most importance in clinical practice. Before description peculiarities of directed forms of anemia, it is necessary to remind classification according to degree of saturation of erythrocytes by hemoglobin, based on color index (normally it is 0,85-1,1) and according to regenerator activity of bone marrow, which is estimated by amount reticulocytes in peripheral blood (normally it is 0,5-1,5%). It has great value in differential diagnostics. In accordance with this classification there are hypo-, normo-, and hyperchromic anemia. Anemia can be characterized also as hypo-, normo-, and hyperregeneratory. Comparative characteristic of changes of the main hematologic indexes in different types of anemia is represented in table 9. Table. 9. The main hematologic criteria of different forms of anemia Hematologic criteria Type of anemia Color index Content of reticulocytes Sizes of erythrocytes Iron-deficiency is decreased isn’t changed or is Microcytosis (hypochromia) increased moderately Megaloblastic is increased isn’t changed or is Macrocytosis (hyperchromia) decreased moderately Hemolytic is normal is increased significantly In norm (normochromia) Acute is normal is increased In norm posthemorrhagic (normochromia) Hypoplastic is normal is decreased sharply In norm (normochromia)

Iron-deficiency anemia can be caused by chronic loss of blood of different genesis (uterine, esophageal, gastro-intestinal, nasal, hemorrhoidal bleeding), disturbance of iron entering into organism (insufficient content of iron in food, malabsorption after gastrectomy and enterectomy, malabsorption syndrome), increased consumption of iron (during pregnancy and lactation), inherited defect of iron transport. Decrease of iron content in organism doesn’t lead to disturbance of hemoglobin synthesis and formation of erythrocytes only, but - to decrease activity of iron-bearing tissue respiratory enzymes also. It results to dystrophy of organs and tissues. In connection with directed reasons clinical picture of iron-deficiency anemia side by side with signs of disease, caused it, and anemic syndrome, is manifested by signs of sideropenic syndrome also. They are trophic changes of the skin and its derivates, and atrophy of mucous membranes also. Complaints of decrease of appetite, burning or pain in tongue, appearing spontaneously or after meal, sensation of difficulty of swallowing of dry and solid food (dysphagy), rapid satiation, heaviness or dull aching pains in epigastrium after meal, eructation are typical for sideropenic syndrome. Dysgeusia as desire to eat chalk, tooth powder, lime, burned matches, coal, clay and other inedible substances is marked often (pica chlorotica). Liking to unusual smells, for example, acetone, benzene, kerosene, naphthaline, pigments, shoe polish and others can be observed also. During patient’s inspection dry desquamating skin looks after oneself. Nails loss shine, they are fragile, with dissection, longitudinal and transverse banding; their surface can be flatten, become twist or pressed in like spoon (spoon nail or koilonychia). The hairs are dull, dry; their ends are fragile. Fissures in angles of the mouth can be observed (angular stomatitis). Signs of atrophic glossitis- shiny smooth raspberry tongue with atrophied papillae - are revealed during inspection of oral cavity often. Iron deficiency is accompanied by evident bluish color of sclera sometimes. In peripheral blood of the patient with iron-deficiency anemia poikilocytosis and anisocytosis with predominance of microcytes are revealed apart from decrease of amount and hypochromia of erythrocytes. Price-Jones curve (it is graph of erythrocytes’ distribution according to their diameter) is shifted to the left. Erythroid hyperplasia with delay hemohlobinization of erythrocytes and their maturation at the stage of polychromatophiles are revealed in punctate of bone marrow; amount of normoblasts is increased; amount of sideroblasts (erythrokaryocytes with granules of iron) is decreased significantly. Biochemical research of blood serum reveals decrease of iron content, increase iron - binding ability and low level of ferritin. It is necessary to bear in mind that hypochromic and microcytar anemia are observed also in heredity hemolytic anemia, caused by pathology of hemoglobin, for example, in thalassemia. At the same time, in directed pathologic conditions decrease of iron level in blood serum is absent. Hypochromic anemia in combination with decrease of serum iron level can be observed in chronic hemolytic anemia with intravascular hemolysis and periodic hemolytic crisis, accompanied by hemohlobinuria, which results to loss of blood with urine. Moreover, hypochromic microcytar anemia sometimes is revealed in infectious and immunopathologic inflammatory processes. Besides, decrease of iron content and iron - binding ability of blood serum is marked, but level of ferritin is within norm. Megaloblastic anemia (pernicious or malignant anemia, Addison-Biermer disease) occurs in deficiency of vitamin B12 or folic acid in organism. These substances as coenzymes take part in processes of synthesis of nucleic acids, deoxyribonucleic acid first of all, which is necessary for growth and cellular differentiation. Vitamin B12 (external Castl’s factor) gets into organism with animal origin products (meat, liver, kidneys, eggs, milk, and cheese). After binding with special glycoprotein, secreted by parietal cells of fundal glands of stomach (internal Castl’s factor), vitamin B12 is absorbed in distal portion of ileum and gets into bone marrow, liver, nervous system cells, gastrointestinal tract. Liver is the main depot of vitamin B12 in organism. There are the following causes of occurrence of vitamin B12 deficiency in organism: a) limited getting of vitamin B12 with food (purposive vegetarianism, low financial prosperity); b) absence or decrease of internal Castl’s factor production (type A gastritis, caused by autoimmune lesion of parietal cells of the stomach, condition after gasrectomy); c) competitor consumption of plenty of vitamin B12 by Diphylobotrium latum (in diphyllobothriasis) or in syndrome of surplus bacterial growth (in multiple diverticulosis of small intestine, syndrome of “blind” loop after application of small-intestinal anastomosis); d) vitamin B12 malabsorption in lesion of small intestine; e) defect of transport mechanism of vitamin B12 in organism. It is necessary to mark vitamin B12 resources in organism are so much, that in action of any directed pathogenetic factors appearance of first signs of megaloblastic anemia occurs not earlier than in 3 years. Vitamin B12 deficiency occurs in elderly persons most often. Folic acid is in all products practically and it is absorbed in small intestine well. But during cooking (boiling) the greatest part of vitamin, which is in food, is destructed. Reserve of folic acid in organism is little and is emaciated during 3-4 months. Folic acid deficiency occurs more often in women and children as result of its malabsorption (for example, in syndrome of malabsorption), and what’s more combinative deficiency of vitamin B12 and folic acid is observed more often. Absorption of folic acid is disturbed in persons, which during prolonged period used anticonvulsants (diphenylhydantoin, phenobarbital), contraceptive agents, some antituberculous drugs (cycloseril), in regular alcohol abuse. Disturbance of thymidine synthesis, which is component of DNA, is in the basis of pathogenesis of megaloblastic anemia. It is caused by the following: vitamin B12 takes part in enzymatic catalysis of transfer of folic acid’s inactive form into active one. Last one is part of enzyme, taking part in thymidine synthesis directly. As result of DNA deficiency processes of growth and differentiation of erythroblasts are disturbed, erythropoiesis is realized by means of primitive megaloblastic way. Besides, leuco- and thrombopoiesis are disturbed as result of DNA synthesis disorder; moreover tissues with rapid temp of cellular renewal, epithelium of gastro-intestinal tract particularly, suffer. Vitamin B12 also takes part in synthesis of special fatty substance of nervous tissue - myelin; that is why degenerative changes of posterior and lateral columns of spinal cord (funicular myelosis) occur in vitamin B12 deficiency. A number of typical clinical peculiarities, caused by atrophy of mucous membrane of digestive tract and lesion of nervous system as funicular myelosis, are revealed in megaloblastic anemia side by side with signs of anemic syndrome. The patients complain of burning or pain in tongue, decrease of appetite, heaviness in epigastric area. Changes of tongue are typical: it is light-red, shiny, smooth as polished due to evident atrophy of papillae, sometimes with places of inflammation and erosions along edges and on the tip (Hunter’s glossitis). Funicular myelosis is manifested by complaints of pricking in the skin, sensation of “creeps” on it (paresthesia), pains in legs, sensation of numbness in them (“wadded legs”), muscular weakness, uncertainty and unsteady during walking. During neurological examination disturbance of pain, temperature, vibration, and proprioceptive sensitivity, decrease of reflexes, uncoordinating (ataxic) gait are marked. Neurological changes have symmetrical character and are expressed on lower extremities mainly. Moderate increase content of unconjugated bilirubin in the blood occurs due to increased propensity of megaloblasts to hemolysis, and subicteritiousness of sclera can be observed. As a rule, spleen and liver are enlarged. In peripheral blood of the patients with megaloblastic anemia hyperchromic normo- or hyporegeneratory anemia, poikilocytosis and anisocytosis of erythrocytes with predominance of macrocytes (having oval form mainly) are revealed. Price-Jones curve is shifted to the right. Basophylic granulosity and also remains of nuclei as Jolly bodies and Cabot rings are revealed in erythrocytes often. Increase of ESR, moderate thrombocytopenia and leucopenia with decrease of neutrophils’ content mainly can be observed; besides cells, nuclei of which have 5-6 and more segments (hypersegmentation of neutrophils), are predominant. Sternal puncture is indicated in all cases of megaloblastic anemia. It must be performed before beginning of treatment by means of vitamin B12 and folic acid. Erythroid hyperplasia with significant increase of megaloblasts’ amount is revealed in punctate of bone marrow. It is necessary to bear in mind that megaloblasts in bone marrow can be revealed in acute leukemia, erythromyelosis, myelodysplastic syndrome, and also in treatment by means of cytostatic drugs (methotrexate, cytosar), disturbing synthesis of DNA. Hemolytic anemia is observed in inherited and acquired pathological conditions. Increased disintegration (hemolysis) of erythrocytes and, accordingly, decrease of their life span is their general sign. Hemolysis of erythrocytes can be intracellular (in macrophages of the spleen mainly) or occurs in bloodstream. Hemolysis of erythrocytes is accompanied by increased production of erythroid line cells in bone marrow and entering of plenty young cells into peripheral blood. The signs of anemia appear when increased hemolysis isn’t compensated by increased production of erythrocytes, accordingly. In pathogenesis of inherited hemolytic anemia the following factors can be determinants: a) disturbance of membrane of erythrocytes (membranopathy) - microspherocytosis, ovalocytosis, stomacytosis; b) anomalies of hemoglobin structure and disturbance of its synthesis (hemoglobinopathy) - sickle-cell anemia, thalassemia; c) deficiency of some erythrocytic enzymes (enzymopathy) - glucose- 6-phosphate dehydrogenase, pyruvate kinase. Intracellular hemolysis, basis of which is capture of defective erythrocytes by macrophages of the spleen, is observed mainly in all inherited anemia. Inherited hemolytic anemia, caused by enzymopathy of erythrocytes and taking its course as repeated hemolytic crisis, is exception. Acquired hemolytic anemia with intravascular hemolysis mainly can be acute and chronic. Acute intravascular hemolysis occurs in influence of hemolytic venoms, chemical, biological, physical and other agents to erythrocytes, incompatible blood transfusion, fetal erythroblastosis, and chronic one - in malaria, paroxysmal nocturnal hemoglobinuria, cold and march hemolytic anemia. Acquired hemolytic anemia with intracellular hemolysis mainly, as a rule, is characterized by chronic course and is caused by immune-pathologic disturbances, by appearance of antibodies to erythrocytes. Hemolytic anemia can be idiopathic disease or one of syndromes of basic disease, for example, in systemic lupus erythematosus or chronic lymphatic leukemia. Clinical picture. Increase of unconjugated (indirect reacting) bilirubin content in the blood, caused by hemolysis, is typical for all hemolytic anemias, regardless of their type. As result - jaundice appears and excretion of urobilinoids with urine increases. Jaundice in case of hemolytic anemia has lemon tint, as it is combined with skin paleness. In intracellular hemolysis, as a rule, enlargement of the spleen is marked. Sickle-cell anemia with small spleen, shrinked (wrinkled) due to fibrosis after multiply, recurrent its infarctions, is exception. Hemolytic anemia with intravascular hemolysis mainly usually has its course as recurrent hemolytic crises. Hemolytic crisis is characterized by sudden appearance of acute weakness, fever, jaundice, pains in abdomen and loin, splenomegaly; sometimes transient acute renal failure appears. Entering of large amount of unconjugated bilirubin into hepatocytes leads to increase conjugated bilirubin concentration in bile; it is accompanied often by formation of pigment stones in gallbladder and appearance of clinical picture of cholelithiasis as recurrence of biliary colic. In patients with some forms of inherited hemolytic anemia (spherocytosis, thalassemia, sickle-cell anemia) it is possible other congenital anomalies (so called “stigmata”), for example, disproportional stature, “tower” skull, high Gothic palate, changes of teeth and others. Trophic crus ulcers, unclosed prolong period can be observed in sickle-cell anemia and microspherocytic anemia. Laboratory diagnostics. Normochromia, poikilocytosis and anisocytosis of erythrocytes are typical for hemolytic anemia. Hyperregeneratory character of anemia (significant increase of reticulocytes amount, which can reaches 30-40% and more in hemolytic crisis) is very important sign of this type anemia. Polychromatophylia of erythrocytes (they contains remains of RNA in cytoplasm) and appearance of nuclear forms of erythrocytes (of erythrokaryocytes) testify about intensification of erythropoiesis. Typical changes of erythrocytes forms: spherocytes, ovalocytes, stomatocytes, acantocytes, like-target cells and like sickle cells and others are revealed in inherited hemolytic anemia. Hypochromic mycrocytar anemia and normal or increased iron serum content is typical for thalassemia. Decrease of osmotic resistance of erythrocytes is marked in many types of hemolytic anemia. Positive Coombs’ test, directing to presence of autoantibodies to erythrocytes, is marked in patients with acquired immune hemolytic anemia. Leukocytosis and increase of ESR are typical for hemolytic crises. Expressed hyperplasia of erytroid sprout is marked in punctate of bone marrow. In all patients with hemolytic anemia content of indirect reacting bilirubin in blood is elevated and content of urobilinoids in urine is very increased. Increase of free hemoglobin in the blood, hemoglobinuria and hemosiderinuria is observed in intravascular hemolysis. Acute posthemorrhgic anemia occurs as result of fast loss of plenty blood. Acute loss of blood most often is caused by traumas and wounds with lesion of large vessels, and also by internal organs diseases, complicated by massive hemorrhage from digestive tract, lungs, or uterus, for example, in disintegrating malignant neoplasm, esophageal or rectal varicose veins dilatation in hepatocirrhosis with portal hypertension, erosive- ulcerative lesions of mucous membrane of gastrointestinal tract, postpartum uterine bleeding, hemorrhagic diatheses and others. Besides, acute posthemorrhgic anemia occurs in intraperitoneal bleedings due to liver or splenic rupture, caused by closed abdominal injury. Decrease of blood volume (of plasma and circulating erythrocytes) with sharp falling of blood pressure down to collapse is developed quickly in the patient as a result of expressed hemorrhage. Clinical picture. Patients complains of weakness, sudden appeared, dizziness, ear noise, blackout, dryness in mouth, nausea, retching, palpitation. Expressed paleness of the skin and mucous membranes is marked; skin is covered by drops of cold, clammy sweat. Pulse is rapid, weak, thread-like often. During ausculatation of the heart it is possible to mark weakening of the I sound and systolic murmur at the heart apex. Systolic and diastolic blood pressure is decreased. Normochromic normocytar anemia with increased reticulocytes content and presence of nuclear forms of erythrocytes (erythrokariocytes) is revealed in peripheral blood of the patients with acute posthemorrhagic anemia. Besides, moderate neutrophilic leukocytosis and trombocytosis are marked. Picture of bone marrow isn’t changed. Hypoplastic anemia is caused by strong inhibition of erythroid or all three sprouts of hematosis. The following can be reasons of aplastic anemia: ionizing radiation (radiation sickness), intoxication by chemical substances (benzene and its derivatives, inorganic arsenic compounds), medicines intake (cytostatics, chloramphenicol, sulfonamides, mercazolile, butadione, cimetidine, gold preparations), chronic renal diseases, uremia, leukemia, limphoproliferative diseases, myelodysplasia, substitution of bone marrow by metastases of malignant tumor. As result of influence of directed factors proliferation and normal functioning of bone marrow’ cells is disturbed. It results to hypoplasia of red bone marrow with inhibition of eryhtrocytes’ formation, and often - of granulocytes and thrombocytes (pancytopenia). Clinical peculiarities of hypoplastic anemia are caused by leukopenia (granulocytopenia) and thrombocytopenia, accompanying to it. Side by side with anemic syndrome, adding of infectious complications (necrotic tonsillitis, pneumonia, otitis, pyelitis, paraproctitis, abscesses in places of injections) and thrombocytopenic hemorrhagic syndrome is characteristic. Last one is manifested by skin spotted hemorrhages, gingival hemorrhage, nasal and uterine hemorrhages. Normochromic hyporegenerator anemia, poikilocytosis and anisocytosis of erythrocytes, appearance of their nuclear forms are observed in peripheral blood in hypoplastic anemia. Leucopenia, granulocytopenia with presence of early granulocytar precursors (metamyelocytes, myelocytes, promyelocytes), and thrombocytopenia are marked in pancytopenia. Punctate of bone marrow is poor for cellular elements (“empty” bone marrow), content of cells of erythroid type or all sprouts of hemopoiesis, young forms particularly, is decreased.

Self-control material: A. Test tasks to be done: -with a single selective answer – I-st level:

1. Who is the leading therapeutist-hematologist? a) Ye.M. Tokarev; b) V.H. Vasilenko; c) I.A. Kasirsky; d) A.I. Nesterov. 2. Who proposed special needle for sternal puncture? a) I.A. Kasirsky; b) M.I. Arinkin; c) M.P. Konchalovsky; d) G.F. Lang; e) A.I. Vorobyov. 3. Icteritiousness of the skin is typical for: a) iron-deficiency anemia; b) acute leukemia; c) chronic lymphatic leukemia; d) hemolytic anemia; e) multiple myeloma. 4. Burning of tongue in patient is typical for: a) Addison-Biermer anemia; b) chronic lymphatic leukemia; c) lymphogranulomatosis; d) chronic myeloleukemia; e) thrombocytopenia. 5. Tongue as if it is polished is typical for: a) iron-deficiency anemia; b) B12 , folic acid deficiency anemia; c) Werlhof’s disease; d) hemophilia; e) thrombocytopenia. 6. Colicky pains in right hypochondrium can occur in patients with: a) hemolytic anemia; b) iron-deficiency anemia; c) hemophilia; d) B12 , folic acid deficiency anemia; e) thrombocytopenia. 7. What factors are the most important in blood diseases? a) overcooling; b) dietary pattern disturbance; c) emotional stress; d) exposure to rays (irradiation); e) seasonal influences. 8. What organ of the abdominal cavity is often enlarged in case of blood diseases? a) pancreas; b) spleen; c) stomach; d) left kidney; e) right kidney. 9. Erythrocytes are produced in: a) bone marrow; b) liver; c) spleen; d) lymph nodes; e) pancreas. 10. Thrombocytes are produced in: a) bone marrow; b) liver; c) spleen; d) lymph nodes; e) kidneys. 11. Concentration of hemoglobin in health persons is: a) 120-160 g/l; b) 100-120 g/l; c) 160-190 g/l; d) 80-100 g/l; e) 50 g/l. 12. Normal values of erythrocytes count in adult are: a) 2,0-3,0 x 1012 /l; b) 3,9-5,0 x 1012 /l; c) 5,0-6,0 x 1012 /l; d) 3,0-3,9 x 1012 /l; e) 10,0 x 1012 /l. 13. What does term “leukocyte formula” mean? a) increased number of leukocytes in peripheral blood; b) increased number of lymphocytes in peripheral blood; c) increased stabs and appearance of juvenile neutrophils in perypheral blood; d) the percentage of separate forms of leukocytes in peripheral blood; e) decreased number of leukocytes in peripheral blood. 14. What does term “shift of leukocyte formula to the left” mean? a) increased number of leukocytes in peripheral blood; b) increased number of lymphocytes in peripheral blood; c) decreased number of leukocytes in peripheral blood; d) increased number of stabs and appearance of juvenile neutrophils (in percentage) in peripheral blood; e) decreased number of lymphocytes in peripheral blood. 15. What color index is normal? a) 0,5-0,6; b) 0,85-1,1; c) 1,1-1,5; d) 0,7-0,8; e) 0,6-0,7. 16. Normal osmotic resistance of erythrocytes (in percents) is: a) 0,46-0,30; b) 0,70-0,46; c) 0,10-0,20; d) 0,85-0,70; e) 0,30-0,20. 17. The following sign is typical for hemolysis: a) increased number of leukocytes in peripheral blood; b) increased bilirubin amount in the blood; c) decreased number of leukocytes in peripheral blood; d) acceleration of ESR(erythrocyte sedimentation rate); e) increased number of basophiles in peripheral blood. 18. The sign of hemolytic anemia is: a) increase of unconjugated bilirubin level in the blood; b) increase of conjugated bilirubin level in the blood; c) leukocytosis; d) acceleration of ESR; e) decrease of unconjugated bilirubin level in the blood; 19. The following sign is typical for hemolysis: a) leukocytosis; b) leukopenia; c) acceleration of ESR; d) reticulocytosis; e) eosinophilia. 20. Reticulocytosis in peripheral blood can testify about: a) lymphogranulomatosis; b) hemophilia; c) hemolytic anemia; d) Werlhof’s disease (thrombocytopenic purpura); e) multiple myeloma. 21. Clinical picture of Addison-Biermer anemia is connected with: a) syndrome of lesion of cardiovascular system; b) syndrome of general intoxication; c) anemic syndrome; d) lesion of peripheral arteries; e) toxic lesion of the liver. 22. Clinical picture of Addison-Biermer anemia is connected with: a) syndrome of lesion of organs of digestive system; b) syndrome of lesion of cardiovascular system; c) toxic lesion of the liver. d) syndrome of general intoxication; e) syndrome of accumulation of fluid in pleural cavity. 23. What is test for revealing of free antierythrocytar autoantibodies (it has importance during diagnostic of autoimmune haemolytic anemia) called? a) Wassermann test; b) Pirquet’s test; c) Coombs’ test; d) Mantoux test; e) Bordet-Gengou test.

-with the selective group of right answers – the II-nd level; 1. What organs are hematopoietic? a) bone marrow; b) brain; c) heart; d) thymus; e) spleen; f) lymph nodi; g) lung. 2. What factors decrease ESR? a) increase of globulins concentration; b) increase of fibrinogen concentration; c) decrease of albumins concentration; d) erythrocytosis; e) microcytosis; f) anemia; g) acidosis; h) cholemia; i) increase of blood viscosity. 3. When does leucopenia of functional origin occur? a) in case of aplasia of bone marrow; b) in emaciated persons; c) in case of depressive influence of some toxins to maturation and passage of leukocytes from hemopoietic organs; d) in case of depressive influence of medicines to hemopoietic organs; e) in case of replacement of bone marrow by fat tissue; f) in case of allergic diseases and syndromes; g) in case of iron deficiency anemia. 4. What are the reasons of leucopenia of organic origin? a) aplasia of bone marrow; b) emaciated persons; c) depressive influence of some toxins to maturation and passage of leukocytes from hemopoietic organs; d) depressive influence of medicines to hemopoietic organs; e) replacement of bone marrow by fat tissue; f) allergic diseases and syndromes; g) iron deficiency anemia. 5. When does increased red-cell (erythrocyte) count occur? a) in dehydration; b) in almost all the anemia; c) in leukemia; d) at high altitudes; e) in hypoxia caused by cardiac or respiratory disorders; f) in hypothyroidism; g) in allergic processes. 6. When does decreased erythrocyte count (erythropenia) occur? a) in dehydration; b) in almost all the anemia; c) in leukemia; d) at high altitudes; e) in hypoxia caused by cardiac or respiratory disorders; f) in hypothyroidism; g) in allergic processes. 7. Increased hemoglobin is present in: a) anemia; b) chronic obstructive pulmonary disease; c) high altitudes; d) severe hemorrhage; e) polycytemia; f) allergic diseases; g) leukemia. 8. Decrease of hemoglobin indicates: a) chronic obstructive pulmonary disease; b) polycytemia; c) anemia; d) allergic diseases; e) severe hemorrhage; f) parasitic disorders. 9. Hematocrit increases in: a) severe blood loss; b) severe burns; c) shock; d) severe dehydration; e) leukemia; f) polycytemia vera; g) allergic diseases. 10. Hematocrit decreases in: a) severe blood loss; b) severe burns; c) shock; d) severe dehydration; e) leukemia; f) polycytemia vera; g) allergic diseases. 11. Leucocytosis can be in: a) aplastic anemia; b) inflammatory process in the organism, usually of bacterial origin infectious diseases; c) trauma; d) agranulocytosis; e) leukemia; f) presence of tumor. 12. There are following types of “blood shifts to the left”: a) regenerative; b) laucaemoid; c) degenerative; d) mixed; e) obstructive; f) restrictive; g) general. 13. Eosinopenia occurs in: a) allergic processes; b) sepsis; c) helminthiasis or other parasitic disorders; d) tuberculosis; e) itching dermatitis; f) typhus; g) poisoning. 14. Lymphopenia occurs in: a) radiation sickness; b) lymphogranulomatosis; c) acute infectious diseases during recovery; d) in thyrotoxicosis; e) lupus erythematosus; f) iron deficiency anemia; g) vitamin B12 deficiency anemia. 15. Signs of anemic syndrome include the following: a) general weakness, undue fatiguability; b) fragility of hair; c) cough; d) fragility of nails; e) nausea; f) palpitation; g) dyspnea; h) paleness of the skin and mucous membranes. 16.What complaints (except manifestations of anemic syndrome) occur often in patients with iron deficiency anemia (anaemia sideropriva)? a) excessive appetite; b) suppressed appetite; c) constipation often; d) perverted taste; e) nausea; f) heaviness in epigastium; g) eructation; h) diarrhea often. 17. What signs can be revealed during auscultation of patient with iron deficiency anemia? a) diastolic murmur at the heart apex; b) systolic murmur at the heart apex; c) systolic murmur over aorta; d) diastolic murmur over aorta; e) “top murmur” over right jugular vein; f) “top murmur” over left jugular vein; g) systolic murmur near xiphoid process. 18. What clinical signs (except manifestations of anemic syndrome) are typical for vitamin B12 (folic acid) deficiency anemia? a) burning of the tongue; b) pain in the sternum and other flat bones; c) manifestations of funicular myelosis; d) manifestations of leukemic myelosis; e) heaviness in left hypochondrium; f) heaviness in right hypochondrium; g) perverted taste. 19. What are the signs of funicular myelosis? a) paresthesia; b) staggering gait due to pyramidal paraparesis; c) disappearance of knee reflex; d) disappearance of corneal reflex; e) dysfunction of urinary bladder and rectum can be observed; f) wadding (goose) gait due to pyramidal paraparesis; g) burning of the tongue. 20. What factors play the main role in development of haemolytic anaemia? a) autoimmune processes; b) acute bleeding; c) deficit of enzymes in erythrocytes; d) chronic bleeding; e) deficit of folic acid; f) traumatic lesion of erythrocytes; g) decrease of secretion of gastromucoprotein. 21. What changes of laboratory values can be revealed in patients with haemolytic anemia? a) hyperchromic anemia; b) normochromic anemia; c) hypochromic anemia; d) reticulocytosis; e) accelerated ESR; f) increase of unconjugated bilirubin level in the blood; g) increase of conjugated bilirubin level in the blood; h) anisocytosis. 22. What changes of laboratory values can be revealed in patients with haemolytic anemia? a) increase of unconjugated bilirubin level in the blood; b) decrease of unconjugated bilirubin level in the blood; c) increase of conjugated bilirubin level in the blood; d) decrease of urobilin contents in urine; e) increase of urobilin content in urine; f) increase of stercobilin content in faces; g) decrease of stercobilin contents in faces. B. Tasks to be done: Task 1. Results of analyses of the blood in patient T.: Hemoglobin — 86 g/L Erythrocyte — 3,1 x 1012/L Reticulocytes — 0,5% Color index — 0,75 Thrombocytes — 190 x 109/L Leucocytes — 8 x 109/L Eosinophils — 1% Basophils — 0% Stab — 6% Segmented — 63% Lymphocytes — 29% Monocytes — 1% ESR — 25 mm/h Microcytosis, poikilocytosis

What is your conclusion?

Task 2. Results of analyses of the blood in patient P.: Hemoglobin — 96 g/L Erythrocyte — 3,2 x 1012/L Reticulocytes — 1,2% Color index — 0,88 Thrombocytes — 180 x 109/L Leucocytes — 6,2 x 109/L Eosinophils — 2% Basophils— 1% Stab — 6% Segmented — 64% Lymphocytes — 26% Monocytes — 1 % ESR — 24 mm/h

What is your conclusion? Task 3. Result of analyses of the blood in patient S.: Hemoglobin — 116 g/L Erythrocyte — 2,9 x 1012/L Reticulocytes — 0,5% Color index — 1,25 Thrombocytes — 170 x 109/L Leucocytes — 10 x 109/L Eosinophils — 1% Basophils — 0% Stab — 6% Segmented — 63% Lymphocytes — 29% Monocytes— 1% ESR—15 mm/h Macrocytosis, megalocytosis, poikilocytosis, Jolly bodies and Cabot rings. What is your conclusion?

Task 4. Patient S. complains of general weakness, fatigability, slight icterus. The same symptoms were marked in past periodically. During physical examination slight expressed hepatolienal syndrome was revealed. Changes of other organs and systems aren’t revealed. General blood analysis, which reveals presence of anemia, was carried out. Presence of hemolytic anemia is supposed. For confirmation of supposing diagnosis it is necessary to research: a) reticulocytes amount; b) thrombocytes amount; c) osmotic resistance of erythrocytes; d) mean Hb contents in 1 erythrocyte; e) bilirubin level in blood serum.

Answers for test tasks of the I-st level: 1- c 15- b 2- a 16- a 3- d 17- b 4- a 18- a 5- b 19- d 6- a 20- c 7- d 21- c 8- b 22- a 9- a 23- c 10- a 11- a 12- b 13- d 14- d

Answers for test tasks of the II-nd level: 1- a,d,e,f 8- c,e 15 -a,b,d,f,g,h 22- b,d,e,f 2- d,e,g,h,i 9- b,c,d,f 16- b,d,e,g,h 23- a,e,f 3- b,c,d 10- a,e 17- b,e 4- a,e 11- b,c,e,f 18- a,b,c,e 5- a,d,e 12- a,c 20- a,b,c,e 6- b,c,f 13- b,d,f,g 21- a,c,f 7- b,c,e 14- a,b,e

Standards of right answer for tasks: 1) Conclusion: decreased hemoglobin and erythrocytes count indicate anemia, presence of decreased color index, microcytosis, poikilocytosis are typical for hypochromic iron deficiency anemia. 2) Conclusion: decreased hemoglobin and erythrocytes count indicate anemia, presence of normal color index is typical for normochromic anemia, which can be after acute hemorrhage. 3) Conclusion: decreased hemoglobin and erythrocytes count indicate anemia, presence of increased color index, macrocytosis, poikilocytosis, Jolly bodies arid Cabot rings are typical for hyperchromic B12 deficiency anemia.

4) - a,c,e.

Electronic resources: 1. David Hui. Approach to Internal Medicine: A Resource Book for Clinical Practice http://file.zums.ac.ir/ebook/056-Approach%20to%20Internal%20Medicine%20- %20A%20Resource%20Book%20for%20Clinical%20Practice,%203rd%20Edition- David%20Hui-.pdf 2. The subject “Internal medicine propedeutics” as an introduction into the clinics of internal medicine. Main methods of examination of patients. Anamnesis as a part of a case history. Inspection of a patient and its value in diagnostic process. http://intranet.tdmu.edu.ua/data/kafedra/internal/propedeutic_vn_des/lectures_stud/en/med/lik/ ptn/Internal%20Medicine%20Propedeutics/3/01_Introduction.htm 3. Internal Medicine. Propaedeutics as an introduction to the clinic of internal medicine. http://im.medicine.karazin.ua/downloads/presentations/Lecture_Internal_Medicine_Propaed eutics_Basic%20concepts.pdf 4. Propaedeutics as an Introduction to the Clinic of Internal Medicine Propaedeutics M. Yabluchansky L. Bogun, L.Martymianova, O. Bychkova, N. Lysenko, N. Makienko, E. Golubkina V.N. Karazin National University Medical School’ Internal Medicine Dept. http://dspace.univer.kharkov.ua/bitstream/123456789/10966/2/Lecture%20PIM_22.06.2015. pdf 5. ИИ Мистюкевич. Theses of lectures on propedeutics of internal diseases. www.gsmu.by/file/biblio/uchlit/tezisyprop.doc 6. Англо-русский тематический словарь по пропедевтике внутренних болезней и общему уходу за больными : справочное издание / Витебский государственный медицинский университет, Кафедра пропедевтики внутренних болезней; сост. Л.М. Немцов; под ред. Г.И. Юпатова. - Витебск : ВГМУ, 2005. - 153 с. URI: http://elib.vsmu.by/handle/123/11343 7. Special propedeutics of internal diseases : lecture course / Vitebsk State Medical University, Dep. of Propedeutics of Internal Diseases ; comp. by L. M. Nemtsov. - 2-е изд. - Vitebsk : VSMU, 2016. - 318 p. URI: http://elib.vsmu.by/handle/123/9837 8. General propedeutics of internal diseases : lecture course / Vitebsk State Medical University ; compiled by L. M. Nemtsov. - Vitebsk : VSMU, 2006. - 175 p. http://elib.vsmu.by/handle/123/268

Methodical instruction is composed by lecturer Ye.Ye. Petrov.