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11.3 Disorders of Acid-Base Homeostasis

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11.3 Disorders of Acid-Base Homeostasis 674 Chapter 11. Fluids and electrolytes ( H. Sap´akov´a, D. Maasov´a) apparatus is very acidic (pH < 5.0). On the con- trary, 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. Maasov´a, S.ˇ Navarˇc´ıkov´a) 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. Sap´akov´a, D. Maasov´a) • 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 distur- bances depends on the speed of the respiratory dis- order 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).
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