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Home , Bronchophony, Parasitic pneumonia

Restrictive and obstructive respiratory disorders. . Respiratory insuficiency

Institute of Pathophysiology Faculty of Medicine Comenius University Respirator insuficiency

• Definition: ▪ inability of the to ensure adequate gas exchange ▪ result: , or both

• Basic criterion: ▪ assessment of gases Respiratory inuficiency

Hypoxemia +/- hypercapnia • Normal levels of blood gases

▪ PaO2 = 10 – 13,3 kPa (75 – 100 mmHg) ▪ PaCO2 = 4,8 – 6,1 kPa (36 - 46 mmHg)

• Definition

▪ PaO2 < 8,0 kPa (hypoxemia) s / bez PaCO2 > 6,5 kPa (hypercapnia)

• Classification (according to blood gases levels) ▪ partial (type I, hypoxemic) – hypoxemia

▪ global (type II, hypercapnic) – hypoxemia, hypercapnia + according to ph value: compensated (normal ph value) / decompensated (↓ ph value) • Classification

1. partial / gobal

compensated / decompensated

2. acute /chronic / chronic – acutely exacerbated

3. latent / manifest Partial (type I, hypoxemic) Global (type II, hypercapnic) hypoxemia hypoxemia + hypercapnia respiratory alkalosis respiratory acidosis→ compensated / decompensated global RI acute cases chronic cases

V-P imbalance, intrapulmonary shunt ↓ minute ventilation / ↑ dead space Acute RI

➢Etiology: dramatic asphyxic conditions, acute CNS poisoning, acute , pulmonary inflammation, ARDS

➢CP: symptoms of basic disease + symptoms of RI: central , convulsions, ph <7,2 = disturbances of consciousness, ph <7 = unconsciousness

➢Therapy: urgent treatment of the underlying disease, airways release, reanimation, artificial respiration, therapy, ABB treatment Chronic RI • pulmonary causes: ➢chronic obstrction of URT and LRT (tumors, foreign bodies), COPD (80% of cases), pulmonary parenchymal diseases (pulmonary fibroses, pulmonary emphysema), cardiovascular diseases, chronic pleural diseases, pleural effusions

➢direct consequences of RI: pulmonary arterioles muscularization and right ventricular hypertrophy

➢complications: , cor pulmonale

➢CP: hypoxia =fatigue, weakness, restlessness, ↑ irritability, depression, speech and vision disorders; hypercapnia = sleepiness through the day, night restless sleep and dreadful dreams, attenuation of the CNS → coma

➢physical findings: central cyanosis, ↑ neuromuscular irritation (tremor, muscle swelling), signs of hyperkinetic circulation, pulmonary hypertension and cor pulmonale (warm wet skin, raised veins, swelling of the face, passive hyperaemia, increased scleral gloss), increased jugular vein filling, enlarged liver Chronic RI • extrapulmonary causes: ▪ CNS diseases and damage (infection, trauma, vascular disorders), PNS damage ▪ myopathies, chest wall damage, kyphoscoliosis, obesity, surgical procedures

• chronic hypoxia → adaptive changes: ➢↑ of increase of 2,3-diphosphoglycerate with the shift of the hemoglobin dissociation curve to the right, polyglobulia (↑ Htc and blood viscosity, ↑ concentration of Hb in erythrocytes) ➢↑ pressure in arteria pulmonalis→ muscularization of pulmonary arterioles, pulmonary hypertension → cor pulmonale ➢severe hypoxemia → lactic acidosis ➢hypercapnia → sequential adjustment of ph value and respiratory acidosis compensation Chronic – acutely exacerbated RI • chronic RI + intercurrent infection / oxygen therapy / sedation / cardiac weakness

Latent RI Manifest RI Summary: Etiology: • pulmonary failure – diseases of , alveoli, alveolocapillary membrane or pulmonary vascular system • extrapulmonary failure– disorders of center / prolonged spnal cord / respiratory muscles or their inervation, disorders of chest wall

Clinical picture: • tachypnoea, dyspnoea, ortopnoea (involvement of the auxiliary respiratory muscles) • – weakening / dysappearance of breathing sounds • cyanosis • anxiety, agitation, quantitative disturbance of consciousness

Investigation: • ABB and blood gases • history - circumstances of dyspnoea, intoxication, infections, state of consciousness • physical findings - pulmonary sound phenomena, cyanosis • RTG, CT • spirometry, ECG, ECHO Pathophysiology of RI

Oxygen-hemoglobin dissociation curve Respiration = 4 processes: ventilation diffusion perfusion breathing control diffusion disorders V-P disproportion R-L pulmonary shunt

compensation of hypoventilated alveolus - DLC RI vasoconstriction

functional, anatomical and physiological pulmonary shunt Effect of hypercapnia on the organism = acidosis and its effects on the CNS

1. hypercapnia = acidification of internal enviroment → vicious cycle = deepening of hypercapnia 2. hyperkapnia = vasodilatation (hot skin, risk of edema of the brain - headache, ↑ intracranial pressure, optic nerve papillae edema, ↓ mental performance, trauma, purposeless twitch movements, lazy speech, mood swings, somnolencia to coma)

3. alveolar hypoventilation → alveolar hypercapnia + alveolar hypoxia Effects of on the organism

• = alkalisation of the inner environment - ↓ degree of ionized calcium = from ↑ neuromuscular irritability to generalized convulsions

• = vasoconstriction of the cerebral vessels → symptoms of inadequate oxygen supply of the brain = headache, dizziness The relationship of neuromuscular irritability and concentrations of each ions

Na+ K+ Ca2+ Mg2+ H+ Pneumonia Defensive mechanisms of respiratory tract • Anatomical barriers of respiratory tract ▪ mucous membrane traps mucociliary apparatus removes particles / MO cleansing is aided by coughing

• Overcoming anatomical barrier ▪ in sleep – aspiration of oropharyngeal secretion ▪ change in viscosity of the secretion / in performance of the ciliary apparatus is involved in the removal of pathogens

• Alveoli ▪ do not contain mucociliary apparatus or muciparous cells → cleaning of these spaces by phagocytes and humoral factors in the surfactant Defensive mechanisms of respiratory tract

Pneumonia in otherwise healthy people???

→ occurs when several mechanisms are broken (anatomical barriers, cellular and humoral mechanisms in alveoli): ▪ changed consciousness ▪ impaired defensive reflexes (, disorder of mucociliary apparatus) ▪ bronchial obstruction ▪ impaired function of alveolar macrophages Inflammatory response

AM pathogen inflammatory response

leukotriene B4, C3a a C5a, components of the kinin system

chemotactic factors for PMNL + ↑ vascular permeability = massive supply of PMNL (infiltration)

IL-1, cachectin = Proteolytic fever, chills, enzymes malaise, myalgia Pneumonia

• inflammation distally from bronchioli terminales (respiratory bronchioli, alveoli, interstitium)

• transmission paths: ▪ aspiration from oral cavity / nasopharynx (most often) ▪ inhalation from air ▪ hematogenous ▪ penetration from the neighborhood

• especially children and elderly Pathophysiology

Immediate functional consequences of inflammation: • ↓ compliance of tissue • extension of the diffusion path for the breathing gases • R-L pulmonary shunt

→ hypoxemia, without accumulation of CO2, cyanosis, dyspnoea, ARDS, abscess, empyema, , organization Classification

• according to the course ▪ according to the place of acquisition ▪ acute ▪ community ▪ chronic (˃ 3 months) ▪ nosocomial ▪ recurrent (repeatedly in the same location) • according to X-ray imaging ▪ migrating (infiltrates migrate) ▪ alar, lobar,

• according to the etiology • according to the clinical picture ▪ infectious ▪ typical ▪ noninfectious = ▪ atypical (aspiration, inhalation, radiation, drugs, allergy) Etiology: the most common are bacterial: ▪ community: 90%, the agents: Str. pneumoniae, Str. pyogenes, St. aureus, Mycoplasma pneumoniae, HI, ▪ nosocomial: acquired from 48 hours to 4 days after hospitalization, the agents: Pseudomonas aeruginosa, Klebsiella pneumoniae, E. coli, Acinetobacter

Main symptoms of pneumonia: ▪ cough, fever, production, and dyspnoea (tachypnoea)

Physical examination: ▪ auscultation: tubular breathing ▪ : silenced ▪ bronchophony: strengthened ▪ pectoralis: enhanced Pneumococcal pneumonia

• Str. pneumoniae (pneumococcus) - the most common cause of community-acquired pneumonia • by inhalation / aspiration • usually – infections of the upper RT are prior

• 4 stages: 1. hyperaemia / congestion: inflammation begins in alveoli, exsudate formation, hyperaemia, pneumococcal reproduction 2. red hepatization: exudate fills alveoli, accumulation of PMNL, erythrocytes enter alveoli 3. gray hepatization: fibrin formation, accumulation of leucocytes, erythrocyte breakdown 4. resolution: resorption of exudate

• fever, painful breathing, cough (dry, later purulent / ), expectoration, dyspnea, tachypnoea (20-45 / min), high temperature (38.5-40.5 °C), takychardia (100-140 / min) • bacteraemia, possible extrapulmonary infections • Haemophilus influenzae ▪ 2nd most frequent agent ▪ the most virulent are the Hib strains, pleural exudate occurs in half of the patients

• Staphylococcal pneumonia ▪ nosocomial pneumonia; infants, elderly people, addicts (using i.v. drugs) ▪ CP as in pneumococcal, fever

• Pneumonia caused by Klebsiella and other G- bacteria ▪ most often in the weakened persons, the elderly and infants, nosocomial

• Peudomonas aeruginosa ▪ severe nosocomial pathogen, acute toxic disease, abscesses, pleural effusion / empyema, ARDS and septic shock • Mycoplasma pneumoniae ▪ in children, M. pneumoniae adheres to a ciliated epithelium, which is destroyed → interstitial pneumonia, and bronchiolitis ▪ leukocyte infiltration of peribronchial spaces, the disease is similar to flu, progression → mucopurulent sputum ▪ mild course, but if severe: hemolytic anemia, polyarthritis, thromboembolic complications, meningoencephalitis, peripheral neuropathy and cerebral ataxia

• Chlamydia pneumoniae ▪ , bronchitis, pneumonitis, CP as with mycoplasma

• ▪ viruses into bronchiolar epithelium → bronchiolitis, infection into interstitium → image of pneumonia, alveoli contain fibrin, mononuclear leukocytes and neutrophils, possible formation of hyaline membranes Typickal vs. atypical pneumonia

• S. pneumoniae, H. infuenzae • Mycoplasma, Chlamydia • sudden beginning • sequential beginning • high fever • subfebrile temperature • productive cough • dry cough • phys. finding: characteristic • phys. finding: insipid • lab. finding: FW, leukocytosis • lab. finding: FW, leukocytosis • RTG: unilateral, lobar • RTG: bilateral, diffuse Mycotic and parasitic pneumonia • Mycotic pneumonia ▪ most often as a complication of AIDS (Pneumocystis carinii) ▪ CP: fever, dyspnoea, dry non-productive cough, RTG bilateral perihilous infiltrates

▪ primary: obligatory pathogenic (histoplasmosis, blastomycosis) – disease also in immunocompetent patients ▪ secondary: opportunistic pathogenic - saprophytic fungi (candidiasis, aspergillosis, cryptococcosis, nokardiosis) - opportunistic infections in immunocompromised

• Parasitic ▪ protozoa: amoeba, toxoplasma ▪ helminths: echinococcus, ascaris, toxocara Noninfectious pneumonia • • most often – aspirating of stomach content • CP: dyspnoea, tachypnoea, tachycardia, cyanosis, bronchospasm, fever, coughing up of pink sputum, ARDS, RTG - diffuse infiltration, , most commonly in the lower right lobe • Inhalation pneumonia • irritant gases (thermal and toxic damage)

• SO2, NO2, O3, chlorine, ammonia, phosgene, formaldehyde, CO2, CO, radon, asbestos • Radiation pneumonitis • acute pneumonitis 2-3 months after actinoterapia – may be influenced by corticoids, after 6 months - - steroids without effect • Hypersensitive pneumonia see slide n. 79 • exogenous allergic alveolitis (type III allergic reaction) • etiology: multiple Ag, can be a professional illness • Pulmonary eosinophilia • eosinophilic pulmonary infiltrates and blood eosinophilia, probably as an allergic reaction to a parasitic disease Complications of pneumonia

Pulmonary abscess

• in the destroyed part of the - pus with necrotic tissue wrapped in the (so called) pyogenic membrane

• CP: chest pain with fever, occasional hemoptoea and dyspnoea, productive cough, rotting odor of sputum and breath, intermittent fever, weight loss, anorexia Revision

• What is the physiological in the respiratory tract?

• How can be pneumonia classificased?

• What are the most common pneumonia causing pathogens?

• What is the atypical pneumonia?

• What is the noninfectious pneumonia? Spirometry The measured parameters are divided into:

• static - alveolar space size → inform about possible restriction disorders

• dynamic – record of airflow in RT → inform about possible obstruction disorders Static volumes • Vt – breath volume • IRV – inspiratory reserve volume • ERV – exspiratory reserve volume • VC – vital capacity • TLC – total lung capacity • FRC – functional residual capacity

Dynamic volumes

• FEV1 - forced expiratory volume in the first second • PEF – peak exspiratory flow • MV – minute ventilation

• Tiffeneau index (FEV1 / VC)

Spirometry can not measure: • RV – residual volume • Vd – dead volume Restrictive and obstructive respiratory disorders • Obstructive diseases ➢obstruction in RT→ limited airflow

• Restrictive diseases ➢↓ pulmonary compliance → ↓ TLC Obstructive diseases • chronic bronchitis COPD VC: normal / slightly ↓ • emphysema FEV1: markedly ↓↓ • •

Tiffeneau ↓ ratio FEV1/VC index Restrictive diseases VC: ↓ • affection of the chest wall beside normal lungs FEV : normal / proport. ↓ • acute / chronic interstitial lung diseases 1

normal ratio FEV1/VC

Obstructive respiratory disorders COPD (Chronic obstructive pulmonary disease) • group of respiratory diseases, common sign - parmanent ↓ FEV1 + smoking is RF • cause - ↑ resistance of RT, ↓ elasticity of lung parenchyma

• constriction of RT: caused by chronic inflammation - typical for chron. bronchitis ▪ muciparous glands hypertrophy, mucus hypersecretion, change of epithelial lining to multilayer (metaplasia of cylindrical epithelium), edema and alternatively peribronchial fibrosis, collapse when their walls are damaged

• ↓ elasticity of lung tissue: due to loss of elastic component of its connective tissue - typical for emphysema

chronic bronchitis and emphysema – forms of COPD COPD Examination of breathing functions - stages of COPD:

▪ stage I – light, FEV1/FVC ˂ 70%, FEV1 je 80% ▪ stage II – intermediate, FEV1 50-79% ▪ stage III – severe, FEV1 30-49% ▪ stage IV – very severe, FEV1 ˂30% / present is RI or cor pulmonale

X-ray examination: • emphysema, depression of the diaphragm, enlargement of retrosternal space

Physical examination: • wheezing, dyspnoea, prolonged exspirium, signs of hypoxia Complication of COPD – COR PULMONALE

Alveolar hypoxia vasoconstriction of pulmonary arterioles + their structural modification pulmonary HT COR PULMONALE

Chronic ↑ work of respiratory muscles alveolar hypoventilation global RI (hypercapnia + respiratory acidosis) limited physical activity

Cyanosis, total edema COPD CP - 2 types: Chronic bronchitis

• Def: mucus hypersecretion with chronic cough lasting at least 3 months in a year in two following years • Etiopathogenesis: ▪ smoking cigarettes ▪ chronic bronchial inflammation with acute exacerbations ▪ inflammation → accumulation of inflammatory cells → the source of proteolytic enzymes (elastase, gelatinase, collagenase) - damaging RT and surrounding parenchyma ▪ → loss of epithelial ribs of affected bronchi and bronchioli, hyperplasia of glands, Goblet‘s cells and mucus hypersecretion

• chronic inflammation + structural changes of parenchyma = ventilation- perfusion imbalance → arterial hypoxemia, cyanosis, pulmonary HT

• functional abnormalities: ↑ RV, ↓ FEV1, ABB disorders Chronic bronchitis

• Etiology (RF): ▪ exogenous (tobacco, professional influences - dust, chemicals, polluted air, repeated respiratory infections - HI, pneumococcus) ▪ endogenous (RT hyperactivity - asthma, genetic factors - α1-antitrypsin deficiency, hypo- / dysagamaglobulinemia)

• CP: ▪ main symptom - dyspnoea, productive cough, advanced stage - weight loss Chronic bronchitis

• Physical examination ▪ , pouting the lips in the exspiration ▪ percussion - signs of emphysema (hyperresonant percussion), depressed position and movement of the diaphragm ▪ auscultation - prolonged exspirium, dry rales (whistling, rasping)

• Complications: • , ↑ risk (physical inactivity and cor pulmonale) Emphysema

• change of lung parenchyma- loss of part of alveolar walls inside pulmonary acini alveolar ducts and alveoli merge into larger air formations that are no longer supplied by pulmonary capillaries (which disappear with septa)

• pathological-anatomical def. ➢irreversible, progressing destruction of RT distal to terminal bronchioles ➢result of alveolar and bronchial septal damage – formation of cysts filled with air (greater than 1 cm) = bulls (bullous emphysema) Emphysema

• types: ▪ panacinar - congenital α1-antitrypsin defect ▪ centrolobular (cantroacinar) type - smoking ▪ distal acinar type

• manifest by dyspnoea, progressive irreversible expiratory obstruction, arterial hypoxemia and hypercapnia of varying degrees Emphysema - pathophysiology

• 1. loss of pulmonary acinus septa

↓ diffuse lung capacity

elastase, oxygen • 2. loss of elastic fibers α1- radicals, matrix antitrypsin metalloproteinase ↓ elasticity of pulmonary parenchyma

ventilation is ineffective in the exchanging of blood gases ventilation > perfusion Functional consequences of emphysema • mechanics of pulmonary ventilation is more affected during the expiration • ventilation is shifted to area of IRV, because FRC and RV are increasing • ventilation in area of IRV needs more extensive pressure changes for realisation of insipration = ↑ work of respiratory muscles during the inspiration • ↑ resistance of airways during the expiration because of premature narrowing / closing of bronchioles

• loss of septa = ↓ total diffuse lung capacity • FRC, RV, TLC ↑

• barrel-chest, prolonged expiration + pouting the lips in the expiration • more moderate hypoxaemia then in CHB → also less frequent cyanosis, hypercapnia • pulmonary HT – less singnificant then in CHB • CHB and pulmonary emphysema occurs very common together in patients – both are caused by smoking

• 10-15% of smokers has some form of COPD

• COPD affects ˃ 10% of adult population of USA • COPD is 4th leading cause of death in USA Chronic bronchitis

Emphysema

• monogenic disease, disorder of respiratory, digestive, urogenital system and skin • mutation of the gene for protein CFTR – canal for anion Cl- • disorder of the transport Na+ and Cl- (their ↑ resorption) → accompanied by ↑ resorption of water = secretions in airways are denser, more viscous

• cough, accumulation of secretion = failed natural purification capacity of airways → frequent infection → chronic infection with periods of remission and exacerbation • frequent infectious agents – Staphylococcus aureus, Pseudomonas aeruginosa

• damaged little bronchioles = ↑ expiratory resistance = ↑ RV and RV/TLC, ↓ FEV1 = signs, which allocate CF into group of obstructive pulmonary diseases • CF gradually results in chronic RI Asthma bronchiale

• chronic inflammatory disease of airways • AB is characterised by reversible bronchoconstrition with expiratory dyspnoea, with cough and loud breathing with wheezing

• prevalence in Europe - 5 %, in 63 % occurs before 5th year of age

Basic characterisctics of AB: • inflammatory process of the walls of airways • hyperreactivity of airways • obstruction of airways ▪ at the beginning reversible, gradually becomes permanent ▪ bronchoconstriction + edema of mucous membrane + hypersecretion of viscous mucus + hypertrophy of smooth muscle cells • T-lymphocytes + allergen → cytokines → production of IgE by B- lymphocytes → sensibilization of mast cells • allergen reexposure → mast cells release mediators symptoms of athma

• repeated contact with allergen → anaphylactic reaction • anaphylaxis ▪ reaction of early type of hypersensitivity ▪ by the binding of allergen to IgE, that are bound to receptors on the surface of mast cells and basophils → release mediators of anaphylaxis, histamin

▪ phase of sensibilization ▪ phase of activacion – very fast, in patients with atopy even faster 2 phases of anaphylactic reaction • early asthmatic response = EAR ➢within minutes, mediators are released from the mast cells→ bronchospazmus ➢main mediator: histamin, leukotrienes LTC4, LTD4, LTE4, prostaglandin D2 a PAF

• late asthmatic response = LAR ➢few hours after EAR, lasts several hours / days ➢symptoms – much more significant ➢inflammatory cells, eosinophils, basophils and T-lymphocytes, macrophages, epithelial cells produce substances → maintenance and promotion of inflammation with bronchoconstriction, ↑ capillary permeability, vascular congestion and edema formation, mucus production and impaired mucociliary transport ➢chemotactic substances – arrival of eosinophils, thrombocytes and PMNL to the place of mast cells stimulation • Functional consequences of asthmatic attack: ▪ ↑ work of respiratory muscles, dyspnoea, ↑ RV and FRC (inspiratory position of the chest and breathing in area of IRV), arterial hypoxemia

▪ classic asthmatic attack – only a slight hypercapnia

▪ during the asthmatic attack ↓ FEV1, PEF, can be ↑ FRC, RV, TLC, ↓ STK during the inspiration and ↓ pulse wave size (pulsus paradoxsus)

▪ mucus plugs

• Severe asthma attack (status asthmaticus) ▪ generalized bronchoconstriction - long-term, insufficient response to classical treatment, causes global RI ▪ life-threatening condition Clinical symptomatology

• always constant triad: dyspnoea, cough, wheezing • seizures often at night

• during seizure – prolonged exspirium, tachypnoea, tachycardia, hypoxia, hypocapnia, respiratory alkalosis, unproductive cough • Retained air in the lungs → ↑ intrathoracic pressure → difficult breathing, patient is restless, cyanosis (in later stages), ↑ jugular vein filling

• retention of CO2, tachycardia and tachypnoea are predictive hypercapnia = significant obstruction

• end of seizure – coughing up of fibrous sputum (Curschmann spirals, eosinophils, Charcot-Leyden crystals) • If cough is ineffective – mucus obstructs bronchiols → • rare complication – spontaneous pneumothorax Etiology + triggers

• genetic factors • trigger factors: ➢atopy ➢GER (especially during sleeping), ➢family history infections of airways, environmental and dietary problems (allergens), stressful state • environmental factors ➢physical stress, hyperosmolarity ➢allergens ➢infections (mainly viral) ➢professional expositions ➢smoking ➢air pollution Types of asthma

Extrinsic (atopic, allergic) asthma: Intrinsic (nonallergic) asthma: o participation of the immune system o greater importance is attributed to VNS o cause: reaction, o cause: trigger is emotional stress, cold, dry trigger is a substance from the air, physical stress, aspirin, viral infection environment (evidence of allergen) (lack of evidence of allergen) o ↑IgE in serum o normal IgE in serum Classification of asthma according to the severity of the manifestations, degree of and its variability 1. intermittent ▪ seizures: maximum once a week, nightly maximum twice a month ▪ between seizures: normal functions, PEF <20%, without limitation of physical activity

2. persistent light ▪ several times a week ▪ PEF 20-30%, spirometry at rest> 80%, sleep disturbance and disturbance of daily activities

3. persistent medium ▪ daily seizures ▪ PEF> 30%, spirometry values at rest 60-80%

4. persistent severe asthma ▪ persistent symptoms, significant activity limitation, nocturnal difficulties ▪ PEF often undetectable, spirometry values at rest <60% (state of permanent obstruction) Bronchiectasis

• irreversible anatomical dilation of one or more bronchi

• cause: chronic inflammation process → destruction of the elastic - muscular wall of the

• before the era of ATB - they were incurable diseases • Etiology + dividing: • disorders of the mucociliary • infections with bronchial wall apparatus (primary ciliary destruction dyskinesia = Kartagener syndrome) • cystic fibrosis • long lasting coughing • immunodeficiency states (agammaglobulinaemia) • after necrotizing pneumonia, aspergillosis

predispositions to infection • post-stenotic form of bronchiectasis

• cirrhotic form (fibrosing TB, diffuse pumonary fibrosis, )

congenital bronchiectasis obtained bronchiectasis • Etiopathogenesis: • beginning - an infectious / chemical pathogen is always present → subsequent development of inflammation

• disability of bronchi in the middle part of the tracheobronchial tree →peripheral parts are badly ventilated

• Radiologically - 3 types according to shape: ▪ cylindric ▪ varicose (fuziform, spindle) ▪ saccular / cystic

• saccular - a cavity filled with pus, it reaches the periphery of the lungs Clinical picture

• 90% of patients - ↑ expectoration in the morning after waking up • 50% of patients - hemoptoe

• disorder of respiratory functions - depending on the anatomical type and range • in advanced stages - dyspnoea, in extensive stages - hypoxemia without hypercapnia • complications - pulmonary hypertension and cor pulmonale • diagnosis is confirmed by X-ray of tracheobronchial tree, bronchography, CT • cultivation of sputum → targeted ATB treatment Restrictive respiratory disorders • heterogenous group of disorders • chronic bilateral involvement of connective tissue – of alveolar wall interstitium

• Etiology? Pathogenesis? • Similarities! ▪ signs, symptoms, radiological alterations, pathophysiological changes ▪ ↓ compliance of the lung tissue → ↑ work of respiratory muscles + dyspnoea ▪ V-P → hypoxia (RI) → pulmonary HT, cor pulmonale ▪ X-ray: small knots, irregular lines, “cut glass“ shades Fibrotizing diseases

• idiopathic pulmonary fibrosis unknown cause • sarcoidosis

• lung fibrosis in systemic diseases • interstitial lung diseases caused by dust inhalation known cause • hypersensitivity pneumonitis • drug and radiation-induced lung diseases Fibrotizing diseases

• ↑ fibrosis in the lung parenchyma = ↓ compliance against pressure changes = ↑ work of respiratory muscles

• the cause of fibrotic process – interstitial chronic inflammation and alveolitis • known causes of inflammation (, hypersensitivity pneumonitis, irradiation of lungs by ionizing radiation, acute lung damage by smoke and toxic gases, aspiration pneumonia, ARDS) • idiopathic lung fibrosis, sarcoidosis

• 1. clinical manifestation – exertional (later even resting) dyspnoea, crepitations, fisrtly latent RI (later manifest, in final stages even type II)

• typical restriction disease = ↓ TLC, VC, FEV1, RV, at normal FEV1/FVC, ↓ diffusion capacity by more than 30% Idiopathic pulmonary fibrosis

= diffuse interstitial lung fibrosis • etiology: unknown

• ↑ content of fibrotic tissue in the pulmonary parenchyma → ↓ compliance with pressure changes

• consequence: severe hypoxia + cyanosis

• CP: non-productive cough + progressive dyspnoea, later - cor pulmonale

• Prognosis: 2-4 years despite of intensive treatment Pathogenesis

• unknown Ag → stimulates T-ly → cytokines

• CIC → macrophages activation of macrophages

IL, leukotrienes TGFβ + PDGF

PMNL→ proteases mesenchymal cell proliferation

destruction of the alveolar epithelium interstitial fibrosis and interstitium Sarcoidosis

Def: • multisystemic disease • non-necrotizing granulomas (giant multinucleated cells, macrophages, epithelial cells, T-ly, B-ly, plasmatic cells, PMNL, fibroblasts, collagen, Ig and C3 component of complement)

Cause: unknown Sarcoidosis - CP • depends on the location of the granulomas ▪ lungs (80%), skin, LU, brain, eye, myocardium, reticuloendothelial system, muscles and joints ▪ granulomas degrade, penetrate, compress and distort tissues

• clinical triage in children: arthritis, uveitis, dermatitis • initial symptoms: anorexia, weight loss, lethargy, weakness, malaise, fever, nausea, headache, dry cough, dyspnoea, chest pain, tachypnoea and wheezing

• alveolitis and fibrosis (x-ray image - honeycomb) → cor pulmonale • extracorporal manifestation: • hepatosplenomegaly, lymphadenopathy, maculopapular lesions of the skin, affection of eye (even amaurosis), lacrimal and salivary glands, cardiac arrhythmias, cardiomyopathy, myocarditis, pericardial effusions, nervous affection of system (image of aseptic meningitis, encephalitis, peripheral neuritis), muscles, endocrine glands, bones, kidney disease (urethral obstruction / glomerulonephritis) sarcoidosis ▪ Löfgren sy. – erythema nodosum, hilar adenopathy, iritis, arthropathy and fever ▪ Mikulicz sy. – ccular disorder with bilateral edema of lacrimal and salivary glands variants / ▪ Sjögren sy. – keratoconjunctivitis with enlarged glandula parotis and lacrimal glands imitate sarcoidosis Sarcoidosis

Prognosis: • 50-60% spontaneous remission • 30-50% cured after corticotherapy • 10-20% disease persists – chronic fatigue, chronic RI, progressive dyspnoea • 2-5% mortality Lung fibrosis in systemic diseases

• rheumatoid arthritis - changes in the lungs in 25% of patients, possibly due to RA therapy (methotrexate)

• SLE – CIK deposition into alveolar wall → alveolitis

• Goodpasture syndrome • pulmonary haemorrhage, glomerulonephritis • Ig against alveolar BM and BM glomeruli

• idiopathic pulmonary hemosiderosis - alveolar haemorrhage, sideropenic anemia, lung infiltration Interstitial lung diseases caused by dust inhalation

Inhalation of inorganic dusts = Pneumoconiosis ▪ parcitles of inorganic dust damage the lung parenchyma → inflammatory response → disappearance of the alveolocapillary unit

Inhalation of organic dusts ▪ image of hypersensitivity pneumonitis (extrinsic allergic alveolitis) occurs, after repeating of episodes, an image of interstitial lung disease may develop Anorganic dust

• • anthracosis o pulmonary fibrosis, more frequent malignities RT o carbon behaves inertly (does not cause and pleura fibroproduction but pigmentation – soot), in o after 10 year exposure to asbestos dust miners after 20 years of exposure o macrophages phagocyt particles → macrophage o coal dust + smoking = very adverse membrane disruption → lysosomal enzymes → • anthracosilicosis lung parenchyma damage → fibrotizing changes = acinar obliteration = typical bee honeycomb image o Carbon particles and crystalline SiO2 in the inhaled aerosol o 80% of mesotheliomas are related to asbestosis o ↓↓ diffuse lung capacity, premature mortality o Caplan sy. – miners in coal mines, seropositive • rheumatoid arthritis + progressive fibrosis of the lungs o SiO2 particles (in quartz processing) o after 10 months of exposure, it may be fatal at <2 • beryliosis years o acute pneumonitis / chronic interstitial pneumonitis o biopsy - granulomatous formations Organic dust

• is the cause of hypersensitivity pneumonitis (exogenic allergic alveolitis) • it participates in the pathogenesis of asthma

• farmer's lungs ▪ usually an acute condition, begins after a 4-8-hour exposure ▪ CP: fever, cough, dyspnoea without wheezing ▪ form of hypersensitivity pneumonitis, workers in agriculture – plants with occurrence of thermophilic actinomycetes (in steamy hay)