11.3 Disorders of Acid-Base Homeostasis

674 Chapter 11. Fluids and electrolytes ( H. Sapáková, D. Maasová)

apparatus is very acidic (pH < 5.0). On the contrary, mitochondrial compartment is slightly more 11.3 Disorders of acid-base basic than the cytosole (pH 6.7–7.2). It is diﬃcult to measure the intracellular pH. As a consequence, homeostasis only measurements of pH of ECF(blood or plasma) are used in clinical praxis.

11.3.1.1 Sources of hydrogen ions 11.3.1 Regulation mechanisms of There are two main sources of hydrogen ions in hu- acid-base homeostasis man body: 1. the metabolism of proteins and phospholipids One of the conditions to maintain the stability of inner environment is the isohydria, i.e. the stabil- and the incomplete metabolism of fatty acids and carbohydrates. Formed acids (so called non- ity of hydrogen ion concentration in the organism. volatile acids) are no further dissociated, and Since the concentration of hydrogen ions in body flu- they must be eliminated by kidneys, ids represents a very small number (e.g. in the blood 0.00004meq/l), it is commonly expressed as pH. The 2. the complete metabolism of fatty acids and pH is defined as the negative decadic logarithm of the carbohydrates, whereby CO2 is formed. Even molar H+ concentration: pH = − log H+. The pH in though CO2 is not an acid, in the solution it is biological systems has a specific significance. The hydrated to carbonic acid which is the source of electrochemical potential of ions is proportional not + → → + − H :CO2 +H2O H2CO3 H +HCO3 . to their concentration but to its logarithm. For this Carbonic acid is called volatile acid because this reason the responses of the sensors or receptors in reaction is reversible, and the acid can be elim- the body are more likely to be proportional to pH inated by expiration in form of CO2. than to concentration. The concentration of H+ is the main determinant 11.3.1.2 Transport and neutralisation of hy- of many physiological and biochemical processes. Al- drogen ion ready in physiological pH range, the activity of en- zymes varies due to the changes in protein charge Approximately 40 mmol of nonvolatile acids and and conformation. The influence of pH values on 20 000 mmol of CO2 are daily formed in the cells proteins leads further to consequent changes in mem- and delivered into the circulation. To maintain a brane transport systems activity for metabolites and normal value of H+ concentration (40 nmol/l), the ions. The dissociation of many physiologically and hydrogen ions in body fluids have to be promptly pharmacologically important weak acids and bases and sufficiently neutralised. There are efficient ex- depends on the value of pH. Changes of their dis- tracellular (plasma) and intracellular (erythrocytes) sociation can lead to alterations in their distribution buffers acting in the blood. The main intracellular in compartments separated by lipid membrane. That buffer is haemoglobin. The main buffer of plasma is is why the pathological changes in pH disturb many bicarbonate-carbonic acid buffer system followed by important functions of organism. other, less important systems (phosphates, plasma Hydrogen ions are components of chemical - proteins). Protein system plays an important role in anatomical structures, and their activity in individ- keeping the pH of tissue cells. Phosphate system is ual compartments varies. The physiological pH value involved in maintaining the pH of tissue cells, ery- of arterial blood is 7.40, the pH of venous blood and throcytes, and tubular urine. Bicarbonate-carbonic interstitial fluid is 7.35 due to increased amount of acid buffer system, consisting of weak carbonic acid carbon dioxide. Intracellular pH depends on the type and its strong natrium salt, plays an important role of cells and their metabolism, it usually reaches the in keeping the pH of extracellular fluid. value of 6.9. Subcellular organelles also maintain the Henderson–Hasselbalch’s equation derives the value of pH on the level necessary for their optimal blood pH from the equation: − function. The inner space of lysosomes and Golgi pH = pK + log[HCO3 ]/[H2CO3] 11.3. Disorders of acid-base homeostasis (D. Maasová, S.ˇ Navarˇc´ıková) 675

Since H2CO3 is in equilibrium with dissolved CO2, ion accompanying bicarbonate, phosphate, sul- and CO2 is in equilibrium with pCO2, we can use the phate anions, and the anions of other nonvolatile term pCO2 instead of H2CO3. From the equation acids in the urine. follows that the pH of extracellular fluid depends on − Immensely important for the excretion of H+ is the reciprocal relation between [HCO3 ] and pCO2 and not on their absolute amounts. Bicarbonate- ammoniagenesis. It takes place primarily in the carbonic acid buffer system is very efficient one be- proximal tubular cells. Since the excretion of hy- cause of its greatest amount in extracellular fluid, drogen ions is limited by tubular fluid acidity (limit and mainly because it is an ”open system” i.e. – both of pH 4.5), natrium ion, in excess of strong acid‘s salts in the urine, is exchanged for H+ after its con- its components are regulated by lungs and kidneys + according to the demands of organism. nection with NH3 to NH4 . This reaction helps to Except the introduced physical-chemical buffers avoid the rise of strong acids in urine, and excretion also others, so called biological buffers, operate in of hydrogen ions is not restricted. the organism, e.g. metabolic reactions consuming or producing hydrogen ion, if they, as an response to 11.3.2 Classification of acid-base pH shift, change their speed in order to maintain disturbances homeostasis. Another mechanism is the transport of protons by proton pumps through the lipid mem- The acid-base disturbances arise as a result of dis- branes. They maintain the pH of intracellular com- balance in production, buffering and final excretion partments (cytosole, mitochondria, lysosomes, Golgi of hydrogen ions. apparatus) on a level unresponding to passive dis- Increased activity of H+ (pH < 7.36) is called aci- tribution according to the electrochemical gradient. dosis. The most important proton pumps act in the mito- Decreased activity of H+ (pH > 7.44) is called al- chondrial and lysosomal membrane. kalosis. The values of pH that are suitable for living or- 11.3.1.3 Excretion of hydrogen ion ganisms are 7.0 to 7.8. Very important is the speed of development of the disorder. Acute disorders are Two basic mechanisms are responsible for definite worsely tolerated. excretion of hydrogen ions : − Using the equation pH = pK+log[HCO3 ]/[CO2], it is obvious that the shift in pH is due not to the 1. Removal of CO by lungs. The quantity of 2 absolute amount, but due to the disturbance in re- ventilation is regulated by respiratory centre in ciprocal ratio of these two components in the extra- medulla oblongata, responding to changes in − cellular fluid. HCO3 is the metabolic part of the pCO2 and pH. Under physiological condition, buffer, and pCO2 the respiratory part. Therefore the pCO2 is kept on the value 5.3 kPa. − the states with primary change in [HCO3 ] are called 2. Excretion of hydrogen ion by tubular cells of metabolic disturbances, and the states with primary + kidneys. The H is formed in the tubular cells change in pCO2 are respiratory disturbances. From of proximal and distal tubule by the dissociation this point of view, we can define four basic acid-base of carbonic acid. Carbonic acid is formed in the disturbances: reaction of CO and H O catalyzed by carbon 2 2 • metabolic acidosis (shift in pH to the acidic side anhydrase. The amount and activity of carbon due to primary decrease in [HCO−] without a anhydrase is one of the factors determining the 3 change in pCO ) speed of H+ production in the tubular cells. It 2 − is necessary to realise that also HCO3 is formed • respiratory acidosis (shift in pH to the acidic by the dissociation of carbonic acid. Simultane- side due to primary increase in pCO2 without a ously with hydrogen ion elimination to the tubu- − − change in [HCO3 ]) lar fluid, HCO3 returns to the blood (therefore expression ”kidney eliminates H+”meansthe • metabolic alkalosis (shift in pH to the alkalic − same as ”kidney saves bicarbonate”). The elim- side due to primary increase in [HCO3 ] without inated hydrogen ion is exchanged for natrium a change in pCO2) 676 Chapter 11. Fluids and electrolytes ( H. Sapáková, D. Maasová)

• respiratory alkalosis (shift in pH to the alkalic 11.3.3.2 Participation of kidneys in compen- side due to primary decrease in pCO2 without a satory processes change in [HCO−]). 3 The degree of compensation in respiratory disturbances depends on the speed of the respiratory disorder development. 11.3.3 Compensation of acid-base In acute respiratory disorders (lasting about 6 ho- disturbances urs) only immediately reacting chemical buffers of extracellular fluid help to correct pH. These non- The organism reacts by compensatory processes to bicarbonate buffers (plasma proteins, haemoglobin, changes in metabolic or respiratory component of the phosphates, sulphates) bind or release H+,thatis buffer system. The purpose of compensatory pro- − demonstrated by an unimportant change in HCO3 cess is the appropriate shift of the other, originally concentration. Relatively weak total activity of these unchanged component so that pH returns closer to buffers is the cause of uncomplete compensation of normal value. This process leads to compensation of acute respiratory disorders. the disorder. But even maximal compensatory effort In chronic respiratory disorders, kidneys take part can not return pH on the physiological value (ex- in the compensation. The compensatory activity of cept chronic respiratory alkalosis that can be com- kidneys is held by increased or decreased secretion of pensated by kidneys to physiological pH). H+ and, simultaneously, by increased and decreased reabsorption of bicarbonate. In this way, the level of bicarbonate adjusts to the changed value of pCO , 11.3.3.1 Participation of respiratory system 2 and pH returns toward the normal standard. Regu- in compensatory processes lation processes need enzyme reconstruction of tubu- Pathological changes in pH, caused by primary lar cells (carbon anhydrase). The maximal compen- − satory effort of kidneys is then achieved after 5 days, change in HCO3 concentration in extracellular fluid (metabolic acidosis and alkalosis), are compensated and it remains for the same time after the removal by the change in depth and frequency of respira- of a disorder. Compensation of chronic respiratory tion. In this way, the primary change in bicar- disorders by healthy kidneys is very effective. bonate concentration induces a respiratory response To understand the typical shifts of several other ions that will be mentioned in individual acid-base which changes plasma CO2 in the same direction. Metabolic acidosis is compensated by hyperventila- disturbances, it is necessary to remember: tion, metabolic alkalosis, on the contrary, by hy- 1. Hydrogen ions in surplus remove potassium ions poventilation. However, respiratory compensation from the cells to the extracellular fluid. This for metabolic alkalosis is relatively weak because its shift (sc. distributive hyperkalemia) often ac- limitation by hypoxemic hypoxia. Respiratory cen- companies metabolic acidosis. On the other tre, regulating the process, is sensitive to changes in hand, in alkalosis potassium enters the cells, but pCO2 and pH. In the compensatory process, the res- this effect is short lasting. If the alkalosis lasts piratory centre reacts only to the pH shift caused by − longer, increased loss of potassium by kidneys the change in HCO3 concentration, because in pri- occurs, which leads to mild deficiency of potas- mary metabolic disturbances the value of pCO2 does sium in the organism. Typical relationships are not change. Bicarbonate anion is slowly diffusible – acidosis – hyperkalemy, alkalosis – hypokalemy. the equilibration of its changed level between blood These relationships are not always present, it de- and liquor is slow. Therefore, the compensatory pro- pends on underlying cause of the disorder and cess starts 1 hour after the rise of the disorder and is other circumstances of it’s development. developed to it’s maximum in 12 to 24 hours. On the contrary, sudden and total therapeutical correction 2. To maintain the electroneutrality, the number of of bicarbonate plasma level in compensated patient cations has to be equal to the number of anions. causes dangerous shift of pH to the other side, be- The major plasma cation is Na+, while other cause of compensatory process sustaining for longer cations (K+,Mg2+,Ca2+) form the nonessen- period of time. tial part of the cationic pool. The major plasma 11.3. Disorders of acid-base homeostasis (D. Maasová, S.ˇ Navarˇc´ıková) 677

− − anions are HCO3 and Cl ,andtherearealso This close relation is not present in acidosis anions of nonvolatile acids in the pool. We can caused by accumulation of organic acids. + − − express basic relationship: Na =HCO3 +Cl (+ anions of nonvolatile acids). Therefore, in • Administration of ammonium chloride and ly- primary change of chloride concentration, ap- sine or arginine hydrochloride. The cations of − propriate amount of HCO3 originates or disap- these drugs enter the metabolism, while chloride pears. This reaction is accompanied with pH anions cause the extinction of adequate amount change. On the other hand, primary change of bicarbonate anions in order to maintain elec- in bicarbonate will be accompanied with the troneutrality. retention or excretion of chloride (hyper- and hypochloremy in some metabolic acid-base dis- Increased production of nonvolatile acids turbances). 3. Plasma sodium plays an important role in keep- Ketoacidosis: ing pH as well as in maintaining the volume of • Diabetic ketoacidosis: In diabetes mellitus, due body fluids. Maintaining the stable volume of to altered carbohydrate and lipid metabolism, body fluids is vitally important, and it has pref- ketoacids are produced more rapidly than they erence in the kidneys before regulation of pH. can be metabolised. Formed nonvolatile ke- This fact is the direct cause of some pH distur- toacids are the source of H+ which binds with bances owing to decrease of body fluid volume HCO−. Simultaneously, hydrogen shifts potas- (see metabolic alkalosis). 3 sium out from the cells into the blood and dis- 4. The activity of H+ is one of the factors influ- tributive hyperkalemia occurs. In patients with encing the ionisation of plasma calcium.De- uncontrolled diabetes, blood glucose can over- crease in H+ activity lowers the ionisation of shoot the renal threshold and osmotic diuresis plasma calcium (tetany in severe alkalosis); in- arises. During osmotic diuresis, normal reab- crease in H+ activity increases the ionisation of sorption of potassium is impossible because of calcium (in acidosis with hypocalcemia, symp- rapid flow of tubular fluid. Primary distributive toms of tetany are ”masked”, until the moment hyperkalemia can be gradually decreased what when acidosis is therapeutically repaired). represents, however, total potassium depletion. Drugs, used in treatment of diabetic ketoaci- 11.3.4 Metabolic acidosis dosis (insulin, glucose) cause shift of potassium from extra- to intracellular space and therefore Metabolic acidosis is characterized by decrease of pH sudden, life-threatening hypokalemia can arise. below 7.35 due to primary decrease in plasma bicarbonate below 22 mmol/l. • Starvation (i.e. long-lasting fever with anorexia) The main reasons of metabolic acidosis: may cause mild ketoacidosis. Reduced carbohydrate intake leads to low insulin and high + Intake of substances producing H glucagon levels. These hormonal changes favour • Intoxication by salicylates: salicylates create a glycolysis and ketogenesis. metabolic block, which leads to production of • a mixture of endogenous organic acids. At the Alcoholic ketoacidosis: The main causes of ke- same time, salicylates have the additional effect toacidosis are prolonged restriction of food in- of direct respiratory centre stimulation, which take, vomiting and alcohol intake. leads to independent respiratory alkalosis. Lactic acidosis: It arises most often in severe cir- • Intoxication by inorganic acids: resulting acido- culatory or respiratory failure as a result of hypoxia sis is characterised by close relation between the due to hypoperfusion of peripheral tissues. During decrease in pH and degree of hyperkalemia (de- the insufficiency of peripheral circulation, certain decrease of pH by 0.1 causes the increase of potas- gree of acidosis is advantageous since haemoglobin, sium in extracellular fluid by cca 0.8 mmol/l). at lower pH, easier releases oxygen to hypoperfused 678 Chapter 11. Fluids and electrolytes ( H. Sapáková, D. Maasová) tissues. Another cause of lactic acidosis may be se- moderate acidosis by increasing bicarbonate loss vere anaemia because of diminished blood oxygen- in the urine. carrying capacity, and intoxication by drugs (ethy- lene glycol, paraldehyde) which are metabolised into Clinical pattern in metabolic acidosis is due to un- lactate. Overproduction of lactate by neoplastic tis- derlying disorder. Acidosis per se has a negative sue is probably the cause of lactic acidosis associated inotropic effect on the heart that is, hovewer, hid- with tumours. den by increased production and excretion of kate- cholamines. It also causes the constriction of veins Reduced excretion of H+ that results in increased venous return with the risk of pulmonary edema. When pH is lowered to 7.0, • Renal failure: It seems that the main defect depression of CNS ranging from fatigue to confusion is the failure of amoniagenesis, decreased renal and coma is present. The compensation of acido- proton secretion and decreased number of func- sis is hyperventilation. In acute metabolic acidosis, tional nephrons. For this reason the excretion hyperventilation may be very intensive (Kussmaul’s of phosphates, important acceptors of hydrogen respiration). in tubular urine, fails. In these, usually chronic conditions, the plasma bicarbonate rarely falls 11.3.5 Metabolic alkalosis below 10 mmol/l because the formed acids are partially buffered by phosphate and carbonate Metabolic alkalosis is characterized by increased pH from bones. above the value 7.45 due to primary increase in plasma bicarbonate above 26 mmol/l. – The basic reasons of metabolic alkalosis: Increased losses of HCO3 • Severe diarrhea or intestinal malabsorption cau- Increased supply or production of bicarbonate se loss of bicarbonate, potassium, sodium and water by the stool. Hyperchloremic, hy- • Metabolic alkalosis can originate in long-term pokalemic acidosis and volume depletion result. parenteral application of substances containing Dehydration is very dangerous especially in new- organic anions (natrium lactate, natrium cit- born and infants. rate). The organic anions are metabolised, and remaining cations are the reason of correspond- • Chronic vomiting, in which there is a loss of ing increase of bicarbonate to maintain the elec- gastric contents accompanied by a loss of alka- − troneutrality. Transfusion of larger amount lic duodenal contents. If the loss of HCO3 is of conserved blood, that contains natrium cit- higher than the loss of acids (e.g. during hypo- rate, ammonium and potassium, can lead to or anacidity of gastric juice), and there is almost metabolic alkalosis. Therapeutical correction of no food intake, acidosis, usually accompanied by metabolic acidosis or an overdose of bicarbonate dehydration, arises. and other alkalising substances can lead to the development of metabolic alkalosis. • Renal tubular acidosis is the term used to de- scribe metabolic acidosis which is caused by a Chloride depletion disorder of the renal tubules. It is due to decreased ability of tubular cells to secrete H+ and • Loss of hydrochloric acid in gastric contents by therefore to reabsorb an appropriate amount of vomiting (e.g. patients with increased gastric the filtered bicarbonate. Sodium is in increased acid secretion or pyloric stenosis),or by gastric amounts exchanged for potassium, and potas- aspirate, leads to increased concentration of bi- sium depletion results. Typical clinical finding is carbonate to maintain the electroneutrality. hyperchloremic metabolic acidosis and increased − • urinary HCO excretion. Low intake of chlorides in patients with restric- 3 tion of NaCl in the diet. The kidneys, in order • Carbon anhydrase inhibitors, such as acetazo- to maintain the volume of ECF reabsorb sodium lamide, have similar effect. They cause mild to in increased amounts. If only small amount of 11.3. Disorders of acid-base homeostasis (D. Maasová, S.ˇ Navarˇc´ıková) 679

sodium in form of NaCl is available, its reabsorp- in most cases the symptoms of underlying disorder tion is increased by exchanging for H+,what are dominating. however leads to increased reabsorption of bicarbonate and to the shift of pH to alkalic values. 11.3.6 Respiratoryacidosis • An overdose of diuretics that primarily sup- Respiratory acidosis is characterized by decrease in presses the reabsorption of chlorides (”loop” di- pH below 7.36 due to primary increase in pCO (hy- uretics). Kidneys, that cannot reabsorb sodium 2 percapnia) over 5.8 kPa. in form of NaCl in sufficient amounts, compen- sate its reabsorption by exchange for H+ that There is no disorder known characterized by over- leads to increase in blood bicarbonate. production of CO2. Thus, all causes of respiratory acidosis have in common a defect in the excretion of • Metabolic alkalosis is most often formed as a re- CO2. sult of extracellular volume depletion. During Central depression of respiration. The causes of volume depletion, renal conservation of sodium decreased activity of respiratory centre may be: takes priority over the other homeostatic mechanisms. Kidneys maximally increase the reab- • drugs (hypnotics, sedatives, morphium) supress- sorption of sodium in the form of NaCl, by ex- ing the activity of respiratory centre change for H+ and by exchange for K+ influ- • enced by aldosterone. local damage of the respiratory centre by inflammation, tumour, trauma, as well as by is- - Reduced elimination of HCO3 chemia during embolisation or during thrombo- sis of a. vertebralis • Primary hyperaldosteronism. Aldosterone stimulates the reversed reabsorption of Na+ in the Impaired respiratory mechanics: deformities of tubular cells by stimulating the secretion of K+, thorax, high position of diaphragm, morbus Bech- H+,Mg2+, and ammonium ions. Pathological terev, pain after chest traumas etc. graduation of this mechanism leads to minimal Pulmonary disorders. The most common cause or moderate hypokalemic alkalosis. Patients are of chronic respiratory acidosis is chronic obstructive not volume- or chloride-deficient. lung disease (chronic bronchitis and emphysema), in which ventilation and perfusion are mismatched • Primary potassium depletion causes increased and effective alveolar ventilation is decreased. Other loss of H+ by kidneys. It seems that there is diseases (pneumonia, pulmonary edema, bronchial a relation between the elimination of K+ and asthma, pneumothorax, haemothorax, atelectasis, H+ that compete for common transport mecha- chronic pulmonary fibrosis) usually cause respira- nism. It means that the deficit of one cation tory alkalosis. In these conditions, hypoxia stimu- leads to increased elimination of another one. lates ventilation and since CO is much more dif- Hypokalemia is the reason for increased secre- 2 fusible than oxygen, excretion of CO is enhanced tion of H+. However, only chronic and severe 2 (hypocapnia). Respiratory acidosis occurs only with hypokalemia may generate metabolic alkalosis. respiratory fatigue in advanced stages of the above Clinical pattern. Metabolic alkalosis directly en- mentioned disease. hances neuromuscular irritability. This effect, rather Neuromuscular disorders:musculardystrophy, than the decrease in ionized plasma calcium induced myasthenia, poliomyelitis, botulism etc. by alkalosis, is the major cause of tetany. Alkalosis Clinical manifestations of respiratory acidosis de- may cause slight increase of myocardial contractil- pend on the speed of it’s development. In acute dis- ity as well as increased sensibility of myocardium to orders dominate confusion up to loss of conscious- heart glycosides. Severe alkalemia has been associ- ness. If the respiratory acidosis develops more slowly, ated with cardiac arrhytmias. The relationship be- it is characterized by symptoms that are typical for tween alkalosis and potassium depletion is complex, cerebral vasodilation caused by hypercapnia: somno- and it is still not sufficiently explained. Symptoms lence, headache, papilledema, dilatation of conjunc- of metabolic alkalosis are generally inexpressive, and tival and superficial facial blood vessels. Influence of 680 Chapter 11. Fluids and electrolytes ( H. Sapáková, D. Maasová) acidemia on cardiovascular system was described in hypocapnia causes constriction of small vessels in the part considering metabolic acidosis. the brain. This condition is clinically manifested by Acute respiratory acidosis is nearly always accom- headache, dizziness and light-headedness. Severe res- panied by hypoxemia, i.e. cardiopulmonary arrest is piratory alkalosis may cause confusion or loss of con- a combination of respiratory acidosis and metabolic sciousness. Alkalosis, in combination with hypocap- lactic acidosis. nia, enhances neuromuscular excitability that is typ- ically manifested by paresthesias around mouth and 11.3.7 Respiratoryalkalosis on the fingers. In some cases, severe symptoms of CNS irritation may occur. Irritation is manifested Respiratory alkalosis is characterised by increase in e.g. as extreme nervousness or convulsions (in epilep- pH over 7.44 due to primary decrease of pCO2 tics purposely performed hyperventilation may in- (hypocapnia) under 4.8 kPa. duce seizures that are clinically used to determine The basic reasons of respiratory alkalosis: the degree of seizure emergency). Disorders of CNS • Cerebrovascular incidents with hypoxia in the 11.3.8 Therapeutical principles of surroudings of the respiratory centre. Local de- acid-base disturbances crease of pH in the area of respiratory centre causes hyperventilation and consequent decrease Disorders of acid-base balance may accompany var- of pCO2 in the blood ious diseases and they are not detectable by clinical observation alone. It is necessary, especially • Trauma, tumour and inflammation of CNS in acutely ill patients, to determine the value of when causing an irritation of respiratory centre pH, pCO2, and bicarbonate in capillary blood. • Drugs (salicylates, progesterone) cause hyper- Analysators of blood gases measure pH and pCO2 ventilation by direct stimulation of medullary directly by specific electrodes. The equipment auto- respiratory centre matically calculates the concentration of bicarbonate using Henderson-Hasselbalch equation. The value • Extreme anxiety and hysterical fit. Strong hy- is usually expressed as ”standard bicarbonate” that perventilation is conditioned by the sensation of represents the theoretical concentration of bicarbon- air shortage, and it may be as intensive as to ate in the blood saturated with oxygen, at pCO2 cause the tetanic spasm. 5.3 kPa and temperature of 37oC. After applying Diseases of lungs with the failure of alveolo- the obtained value to nomogram, we can determine capillar oxygen transfer or with reduced respiratory the concentration of ”actual bicarbonate”, the con- surface area. Decrease of pO2 causes irritation of the centration at actual pH, pO2,pCO2,andtempera- chemoreceptors, leading to hyperventilation. Respi- ture of patient’s blood. This determination, in clin- ratory alkalosis occurs during initial stages of the dis- ical practice, is sufficient for accurate and relatively eases, e.g. during mild pulmonary embolism, pneu- rapid classification of pure or combined acid-base dis- monia, mild pulmonary edema or asthma. If the disturbances. order causes failure of CO2 exhalation, respiratory The appropriate therapy is choosed considering acidosis with hypoxia arises. the type and the stage of the disorder. As discussed Irritation of the respiratory centre from the pe- above, acid-base disturbance is in almost all cases ripheral receptors during localized pulmonary and secondary one. Therefore, the optimal therapy is the pleural diseases. elimination of the underlying disorder. If it is not Mountain sickness.LowerpO2 in the inhaled air possible and patient’s health requires a rapid correc- stimulates the medullar respiratory centre. During tion of pH, the application of substances normalising hyperventilation, highly diffusible carbon dioxide es- the surplus of acids or bases is justified. capes in greater amounts and hypocapnia occurs. Immediate and rapid arrangement of acidosis is Clinical manifestations of respiratory alkalosis de- indicated only in acute intoxication. Alkalisation pend on its severity and acuteness. Hyperventila- of extracellular fluid, and hence of urine, simulta- tion may or may not be clinically apparent. Acute neously helps to eliminate the acids more quickly. 11.3. Disorders of acid-base homeostasis (D. Maasová, S.ˇ Navarˇc´ıková) 681

Intravenous application of sodium bicarbonate is rec- To correct the alkalosis, ammonium chloride per ommended if pH falls below 7.2, or plasma bicarbon- os can be used. After the resorption into the blood, ate falls below 10 mmol/l. Intravenous application of the NH4 is metabolised to urea in the liver. This bicarbonate requires considerable attention because reaction releases HCl that immediately reacts with it changes the pH very strongly and suddenly. We the buffers of extracellular fluid and shifts pH to the apply only one third or one half of calculated amount acidic side. Intravenous application of ammonium over the period of 24 hours, and we lean on the ac- chloride is dangerous because of its toxicity. An- tivity of compensatory mechanisms of the body. other substance commonly used, is monohydrochlo- For slowlier neutralisation of acid surplus in aci- rid lysine. During acidifying therapy, enhancement dosis, a larger amount of sodium bicarbonate per os of diuresis for the elimination of bicarbonate is re- can be applied. After absorption from GIT to the quired. blood, pH is shifted to the alkalic side. In therapeutical approach of acid-base distur- For slow alkalisation of body fluids, substances bance, it is necessary to regulate other components metabolised in the body (sodium lactate or sodium of body fluids simultaneously (potassium, calcium, gluconate) can be used. Lactate or gluconate part of sodium, chlorides). It is important to think of the the molecule is metabolised, and sodium remains in outlast of compensatory processes and to eliminate the extracellular fluid as sodium bicarbonate. the underlying disorder to maximal possible extent.