1. 1 Acid-Base Balance Seminar No. 11

2. 2 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) BB s = 42 ± 3 mmol/l BB b = 48 ± 3 mmol/l

3. 3 Q. 1

4. 4 Buffer bases in (arterial) plasma Buffer basemmol/l HCO 3 - Protein-His HPO 4 2- ---------- Total 24 17* 1 ------------- 42 * Molarity of negative charge  binding sites for H +

5. 5 Q. 2

6. 6 A. 2 BB s = 42 ± 3 mmol/l BB b = 48 ± 3 mmol/l hemoglobin in erythrocytes increases BB b by 6-8 mmol/l

7. 7 Q. 3

8. 8 Abr.NameReference values sO 2 tHb COHb MetHb HbA 1c Oxygen parameters and hemoglobin derivatives

9. 9 Abr.NameReference values sO 2 saturation of Hb by oxygen 94 – 99 % tHbtotal Hb 2.15 – 2.65 mmol/l (tetramer) 120-175 g/l (diff. males × females) COHbcarbonylHb1-2 % (nonsmokers) MetHbmethemoglobin0.5 – 1.5 % HbA 1c glycated Hb2.8 - 4 % Oxygen parameters and hemoglobin derivatives Tissue hypoxia of any origin leads to lactic acidosis

10. 10 Q. 4

11. 11 A. 4 7.4 = 6.1 + log [HCO 3 - ] / 0.22 × 5.3 1.3 = log [HCO 3 - ] / 1.2 10 1.3 = [HCO 3 - ] / 1.2 20 = [HCO 3 - ] / 1.2 [HCO 3 - ] = 24 mmol/l

12. 12 Four types of acid-base disorders pH = 6.1 + log Changes in [HCO 3 - ]  metabolic acidosis  metabolic alkalosis Changes in pCO 2  respiratory alkalosis  respiratory acidosis

13. 13 Maintanance of constant pH in body System / OrganWhat is altered?How quickly? Buffers in ECF/ICFpHsec / min LungspCO 2 hours Liverway of NH 3 detoxicationdays Kidney NH 4 + / H 2 PO 4 - excretion HCO 3 - resorption days

14. 14 Responses to acute change compensation correction

15. 15 Q. 6

16. 16 A. 6 FeaturePlasmaICF Main cation Main anion Protein content Main buffer base Na + Cl -  HCO 3 - K + HPO 4 2-    HPO 4 2-

17. 17 Metabolic acidosis is the most common condition Metabolic alkalosis is the most dangerous condition

18. 18 Q. 8

19. 19 Na + Cl - HCO 3 - AG K+K+ normal status hyperchloremic MAC normochloremic MAC

20. 20 Na + Cl - HCO 3 - AG K+K+ Cl -  HCO 3 - ↓ AG no change Cl - no change HCO 3 - ↓ AG  normal status hyperchloremic MAC normochloremic MAC See Q. 11 NaCl infusions

21. 21 Q. 9

22. 22 A. 9 Excessive infusions of NaCl isotonic solution lead to metabolic acidosis Blood plasma (mmol/l)Isotonic solution (mmol/l) Na + Cl - Na + Cl - 133-15097-108154 Ratio ~ 1 : 0.7Ratio 1 : 1 Isotonic solution of NaCl has elevated concentration of Cl - compared to plasma Blood plasma is diluted by infusion solution  [HCO 3 - ] decreases pCO 2 in alveolar air is the same the ratio [A - ] / [HA] in H.-H. equation decreases  pH < 7.40 (acidosis)

23. 23 Q. 10

24. 24 Hyperchloremic MAc excessive infusions of NaCl solution the loss of HCO 3 - + Na + + water (diarrhoea, renal disorders)  relative higher concentration of chlorides in plasma

25. 25 Q. 11 How is AG calculated?

26. 26 AG Na + Cl - HCO 3 - AG K+K+ AG composition = HPO 4 2- + Prot - + SO 4 2- + OA AG calculation = [Na + ] + [K + ] - [Cl - ] - [HCO 3 - ]

27. 27 A. 11 MAc with increased AG Hypoxia of tissues – insufficient supply of O 2  anaerobic glycolysis: glucose  2 lactate elevated AG – lactoacidosis Starvation, diabetes TAG  FA (β-oxidation in liver)  acetyl-CoA (excess, over the capacity of CAC)  KB production elevated AG - ketoacidosis Renal insufficiency – elevated phosphates, sulfates Various intoxications

28. 28 Q. 12

29. 29 A. 12 AG – normal values SID – buffer bases (mainly HCO 3 - ) – decreased compare Q. 8a)

30. 30 Q. 13 Metabolic acidosis ParameterPhysiol. st.Ac. changeCompensationCorrection [HCO 3 - ]24 mmol/l  N pCO 2 5.3 kPaN  [A - ] / [HA]20 : 1< 20 : 1 pH7.40 ± 0.04< 7.36 Systemlungskidney Processhyperventilation  HCO 3 - resorption  NH 4 + / H 2 PO 4 - excr.

31. 31 Q. 15 Methanol intoxication

32. 32 Metabolic oxidation of methanol provides a rather strong formic acid Consequences: formate in plasma  elevated AG  acidosis excess of NADH  lactoacidosis

33. 33 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 K A (formic ac.) : K A (acetic ac.) = 10 : 1 formic acid is 10  stronger than acetic acid

34. 34 ethylene glycol intoxication

35. 35 Intoxication by ethylene glycol Consequences: oxalic acid is rather strong acid (pK A1 = 1.25, pK A2 = 4.29) oxalate in plasma  elevated AG  acidosis excess of NADH  lactoacidosis in urine  calcium oxalate concrements

36. 36 Calcium oxalate is insoluble chelate Draw formula

37. 37 Calcium oxalate is insoluble chelate

38. 38 Why MAc occurs in anemia?

39. 39 Not enough hemoglobin  insufficient supply of O 2  hypoxia  anaerobic glycolysis to lactate elevated AG – lactoacidosis

40. 40 Q. 16

41. 41 Metabolic oxidation of ethanol leads to excess of NADH acetaldehyde dehydrogenase alcohol dehydrogenase (ADH) acetaldehyde acetaldehyde hydrate acetic acid - NADH+H +

42. 42 Metabolic consequences of EtOH biotransformation Ethanol ADH MEOS acetaldehyde part. soluble in membrane PL toxic efects on CNS adducts with proteins, NA, biog. amines acetate acetyl-CoA FA synthesis liver steatosis ADH the excess of NADH in cytosol is reoxidized by pyruvate to lactate lactoacidosis various products causing hangover

43. 43 Q. 17

44. 44 thiamine is the cofactor of aerobic decarboxylation of pyruvate thiamine deficit  pyruvate cannot be converted to acetyl-CoA therefore pyruvate is hydrogenated to lactate even in aerobic conditions: glucose  lactate increased plasma lactate  elevated AG  lactoacidosis CH 3 -CO-COOH + CoA-SH + NAD +  CO 2 + CH 3 -CO-S-CoA + NADH+H + 1.Thiamin diphosphate 2.Lipoate 3.Coenzym A 4.FAD 5.NAD +

45. 45 Q. 18

46. 46 A. 18 calcium cations make electrostatic interactions with carboxylate anions in side chains of glutamate and aspartate (in various proteins) increased [H + ] (= decreased pH) of plasma leads to a partial cation exchange one calcium ion is liberated and replaced by two protons

47. 47 Causes of metabolic alkalosis Repeated vomiting – the loss of chloride (Cl - ) anion  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

48. 48 What is baking soda?

49. 49 A. NaHCO 3 sodium hydrogen carbonate (sodium bicarbonate) sold in pharmacy

50. 50 Q. 19 How is SID calculated?

51. 51 Na + Cl - SID K+K+ SID composition = HCO 3 - + HPO 4 2- + Prot - SID corresponds to buffer bases of plasma In MAlk  SID increases SID calculation = [Na + ] + [K + ] - [Cl - ]

52. 52 Q. 20

53. 53 Na + Cl - HCO 3 - AG K+K+ Cl -  HCO 3 - ↑ AG no change Cl - no change HCO 3 - ↑ AG  normal status hypochloremic MAlk normochloremic MAlk vomitinghypoalbuminemia

54. 54 Q. 21 Metabolic alkalosis ParameterPhysiol. st.Ac. changeCompensationCorrection [HCO 3 - ]24 mmol/l  N pCO 2 5.3 kPaN  [A - ] / [HA]20 : 1> 20 : 1 pH7.40 ± 0.04> 7.44 Systemlungskidney Processhypoventilation  HCO 3 - excretion

55. 55 Q. 23

56. 56 A. 23 pCO 2 = 5.5 kPa.......................... OK [HCO 3 - ] = 39 mmol/l..................  elevated pH = 7.6.....................................  elevated status: metabolic alkalosis pCO 2 will increase during compensation (hypoventilation)

57. 57 SolutionEffectExplanation NaCl KHCO 3 NH 4 Cl NaHCO 3 Na lactate Q. 25

58. 58 SolutionEffectExplanation NaClacid. plasma dilution  [HCO 3 - ]  while pCO 2 is constant KHCO 3 alkal.direct addition of the main buffer base NH 4 Clacid. NH 4 + excreted by urine, Cl - remains in plasma  [HCO 3 - ]  NaHCO 3 alkal.direct addition of the main buffer base Na lactatealkal. lactate anion goes from plasma to liver (gluconeogenesis), Na + remains in plasma  its pos. charge is balanced by extra HCO 3 - (similar effect like in vegetarian diet)

59. 59 Q. 26 Respiratory acidosis ParameterPhysiol. st.Ac. changeCompensationCorrection [HCO 3 - ]24 mmol/l N,  - pCO 2 5.3 kPa  N [A - ] / [HA]20 : 1 pH7.40 ± 0.04 Systemkidneylungs Process HCO 3 - resorption NH 4 + / H 2 PO 4 - excr. hyperventilation

60. 60 Q. 27 Describe the scheme on p. 5

61. 61 Excess of CO 2 in the body produces more H 2 CO 3 in blood Carbonic acid in buffering reaction with proteins gives HCO 3 - ion Hydrogen carbonate ion is driven to ICF Therefore the level of HCO 3 - in ECF is normal or slightly elevated

62. 62 Q. 29

63. 63 A. 29 pH 7.32........................................  pCO 2 9.3 kPa.............................  [HCO 3 - ] = 39 mmol/l..................  [Na + ] = 136 mmol/l......................OK [K + ] = 4.5 mmol/l.........................OK [Cl - ] = 92 mmol/l..........................  AG = 136 + 4.5 - 39 – 92 = 9.5 mmol/l.......   no MAc Conclusion: compensated RAc

64. 64 Q. 30 Respiratory alkalosis ParameterPhysiol. st.Ac. changeCompensationCorrection [HCO 3 - ]24 mmol/l N,  - pCO 2 5.3 kPa  - NN [A - ] / [HA]20 : 1 pH7.40 ± 0.04 Systemkidneylungs ProcessExcretion of HCO 3 - hypoventilation (if possible)

65. 65 Combined disorders Q. 33

66. 66 A. 33 pH 7. 4............................. OK pCO 2 5.13 kPa.......................OK BE 1 mmol/l............................OK  HCO 3 - = 25 mmol/l....... OK Na + 140 mmol/l......................OK K + 4.6 mmol/l........................OK Cl - 89 mmol/l.........................  AG = 140 + 4.6 – 25 – 89 = 30.6 mmol/l...............  SID = 140 + 4.6 – 89 = 55.6 mmol/l.......................  Conclusion: MAc + MAlk

67. 67 Q. 34

68. 68 A. 34 Q.Explanation a)MAc - lactoacidosis (alcohol) + loss of Cl - (vomiting) - MAlk b) MAc - ketoacidosis (starvation) + loss of Cl - (vomiting after overeating) - MAlk c) RAlk (stimulation of resp. centre) + MAc (salicylate – AG  ) d)MAc (ketoacidosis) + RAc (heart failure – circulation insuff.)