Acid Base Balance II Seminar No. 10 - Chapter 21, II. part - Three ways of CO[2] transport in blood (scheme, p. 121) * cca 85 % in the form of HCO[3]^- it is formed in ery by the action of carbonic anhydrase, then is transported to plasma, exchange for chloride is needed to maintain electroneutrality in ery * cca 10 % in the form of unstable carbamates [* ] cca 5 % of physically dissolved CO[2 ] Q. How is CO[2] formed in tissues? The production of CO[2] in tissues * CO[2] is produced in decarboxylation reactions * oxidative decarboxylation of pyruvate (r) acetyl-CoA * two decarboxylations in CAC (isocitrate, 2-oxoglutarate) * decarboxylation of aminoacids (r) biogenous amines * non-enzymatic decarboxylation of acetoacetate (r) aceton * catabolism of pyrimidine bases (cytosine, uracil (r) CO[2] + NH[3] + b-alanine) * catabolism of glycine (r) CO[2] + NH[3] + methylen-THF Q. Write the reaction of carbamate formation. A. Kidney functions in acid-base balance * kidneys excrete acid species: ammonium cation NH[4]^+ dihydrogenphosphate anion H[2]PO[4]^- (uric acid and some other ...) * kidneys resorb basic species: the main buffer base = hydrogencarbonate anion HCO[3]^- Q. How is NH[4]^+ formed in the kidney? Glutaminase catalyses the hydrolysis of amide group in glutamine Glutamine deamination in tubular cells occurs stepwise Q. What is pH range of urine? A. the pH of urine usual range: 5 -- 6 extremes: 4.5 -- 8.0 Q. What are the three main acid species in urine? A. Q. What is the ratio of HPO[4]^2- / H[2]PO[4]^- in urine with pH = 4.8? A. Calculation from H.-H. equation 4.8 = 6.8 + log x log x = -2 x = 10^-2 = 0.01 TH [HPO[4]^2-] : [H[2]PO[4]^-] = 1 : 100 under normal conditions (in mild acidic urine) the essentially prevailing species is dihydrogenphosphate Q. What is the consequence of the reversed ratio? HPO[4]^2- / H[2]PO[4]^- > 1 A. formation of urine concrements calcium hydrogenphosphate CaHPO[4] is insoluble Solubility of calcium phosphates Liver functions maintaining acid base balance two ways of ammonia detoxication occur in liver: * synthesis of urea TH proton-productive process * synthesis of glutamine TH proton-neutral process Synthesis of urea Synthesis of glutamine Liver functions maintaining acid base balance * in acidosis, liver preferably makes glutamine instead of urea * glutamine is transported by blood to kidneys, where it is hydrolyzed (glutaminase) - NH[4]^+ cation is released into urine * glutamate can be further deaminated and NH[4]^+ cation is again released into urine Parameters of acid base balance Measured in arterial blood * pH = 7.40 +/- 0.04 = 7.36 -- 7.44 * pCO[2] = 4.8 -- 5.8 kPa * supporting data: pO[2], tHb, sO[2], HbO[2], COHb, MetHb Calculated * [HCO[3]^-] = 24 +/- 3 mmol/l (from H.-H. eq.) * BE = 0 +/- 3 mmol/l (from S.-A. nomogram, see physilogy) * NBB[p] = 42 +/- 3 mmol/l * NBB[b] = 48 +/- 3 mmol/l Q. Which buffer bases are in the plasma? Buffer bases in (arterial) plasma Q. Compare NBB[p] with NBB[b] and explain the difference. A. NBB[p] = 42 +/- 3 mmol/l NBB[b] = 48 +/- 3 mmol/l hemoglobin in erythrocytes increases NBB[b] by 6-8 mmol/l Four types of acid-base disorders Maintanance of constant pH in body Causes of metabolic acidosis * Hypoxia of tissues -- insufficient supply of O[2] TH anaerobic glycolysis: glucose (r) 2 lactate * elevated AG -- lactoacidosis * Starvation, diabetes * TAG (r) FA (b-oxidation in liver)(r) acetyl-CoA (excess, over the capacity of CAC) TH KB production * elevated AG - ketoacidosis Ketone bodies Q. Explain why chronic alcoholism leads to lactoacidosis. Metabolic oxidation of ethanol leads to excess of NADH Metabolic consequences of EtOH biotransformation Q. Explain why methanol intoxication leads to metabolic acidosis. Metabolic oxidation of methanol provides a rather strong formic acid Compare two acids ethanol acetic acid pK[A] = 4.75 K[A] = 1.8 ´ 10^-5 methanol formic acid pK[A] = 3.75 K[A] = 1.8 ´ 10^-4 Q. Explain why ethylene glycol poisoning leads to metabolic acidosis. Intoxication by ethylene glycol Q. Excessive infusions of isotonic solution lead to metabolic acidosis. Explain. Excessive infusions of NaCl isotonic solution lead to metabolic acidosis Q. Explain lactoacidosis in thiamine deficit. A. * thiamine is the cofactor of aerobic decarboxylation of pyruvate * thiamine deficit TH pyruvate cannot be converted to acetyl-CoA * therefore pyruvate is hydrogenated to lactate * even in aerobic conditions: glucose (r) lactate * increased plasma lactate TH elevated AG TH lactoacidosis Q. In chronic acidosis Ca^2+ ions are released from bones and plasma proteins and pass into urine. Explain. A. Metabolic acidosis Causes of metabolic alkalosis * Repeated vomiting -- the loss of chloride (Cl^-) anion TH hypochloremic alkalosis * Direct administration of buffer base HCO[3]^- per os: baking soda, some mineral waters intravenous infusions of sodium bicarbonate * Hypoalbuminemia severe malnutrition liver damage, kidney damage Q. What is baking soda? A. NaHCO[3 ] sodium hydrogencarbonate (sodium bicarbonate) sold in pharmacy Q. How is SID changed in alkalosis? SID corresponds to buffer bases of plasma Q. What is the acid-base status of a patient if: pCO[2] = 5.5 kPa [HCO[3]^-] = 39 mmol/l pH = 7.6 Which parameter will be changed after compensation? A. Q. What is the effect of the following infusions (alkalizing / acidifying) ? * NaCl * KHCO[3 ]* NH[4]Cl * NaHCO[3 ]* sodium lactate Metabolic alkalosis