1. 酸碱平衡及紊乱 Acid – Base Balance and Disturbances

2. Acid-Base Balance Maintenance of the H + concentration in body fluid in a normal range H + mol/L pH Extracellular fluid Arterial blood 4.0 x 10 -8 7.40 ± 0.05 Venous blood 4.5 x 10 -8 7.35 Interstitial fluid 4.5 x 10 -8 7.35 Intracellular fluid 1.0 x 10 -6 6.0 to 4.0 x 10 -8 7.4 pH = - lg  H + 

3. Why is the acid - base balance important for life ?

4. Acid generation Volatile acid CO 2 + H 2 O  H 2 CO 3  H + + HCO 3 - H + 15 –20 mol /d Fixed acids phosphoric, sulfuric, lactic, ketone bodies etc. H + < 0.05 –0.10 mol /d

5. Regulation of acid – base balance Buffering Buffer system can bind and release H + Dissociated buffer + H +  H undissociated buffer Principal buffers in blood: in Plasma in RBC H 2 CO 3 / HCO 3 - 35% 18% HHb / Hb - 35% HProt / Prot - 7% H 2 PO 4 - / HPO 4 2- 5%

6. Bicarbonate buffer system determines the pH of blood plasma CO 2 + H 2 O  H 2 CO 3 H + + HCO 3 - Handerson-Hasselbalch Equation + pH = pK + lg HCO 3 - / H 2 CO 3 Na + = 6.1 + lg HCO 3 - / 0.03 x PCO 2 = 6.1 + lg 24 / 1.2 = 7.4 Bicarbonate-carbonic acid system is the major extracellular buffer 53% H 2 CO 3 can be regulated by lung HCO 3 - can be regulated by kidney

7. Respiratory regulation  PaCO 2,  pH  Chemorecertor   Pulmonary ventilation   PaCO 2 pH 7.0  V A increases by 4-5 times  pH  V A decreases less

8. Renal regulation  Plasma pH  HCO 3 -  H + Reabsorption & Excretion Regeneration  Plasma pH Renal H + excretion = fixed acid production = 1mmol/kg/d

9. Reabsorption of HCO 3 - in different segments of renal tubule

10. Reabsorption of HCO 3 - coupled with H + excretion in proximal tubules CA Na +

11. RegenerationRegeneration Regeneration of HCO 3 - coupled with the buffering of secreted H + by filtered Na 2 HPO 4 in distal tubules Cl - ATP

12. Regeneration of HCO 3 - coupled with buffering of H + by NH 3 in proximal tubular cells Glutamine Tubular lumen glutaminase NH 3 NH 3  -keto glutaric acid NH 4 + NH 4 + H 2 CO 3 Na + Na + HCO 3 - H + H + ATP

13. Regeneration of HCO 3 - coupled with buffering of H + by NH 3 in collecting tubular cells Cl-

14. Net acid excretion by kidney = NH 4 + excretion + urinary titratable acid – bicarbonate excretion = nonvolatile acid production In acidosis, a net addition of HCO 3 - back to blood as more NH 4 + and urinary titratable acid are excreted In alkalosis, titratable acid and NH 4 + excretion drop to 0, whereas HCO 3 - excretion increases (No new bicarbonate is generated)

15. Parameters of acid – base balance 1.pH = 6.1 + lg HCO 3 - / H 2 CO 3 Normal value of pH in arterial blood 7.4±0.05 pH normal, may be 1) acid-base balance 2) compensatory acid-base disorder 3) mixed acid-base disorder

16. 2. PaCO 2 x 0.03 = H 2 CO 3 Normal PaCO 2 40 ± 6 mmHg determined by the rate of CO 2 elimination (alveolar ventilation), not by its production. --- Respiratory parameter 3. Bicarbonate ( HCO 3 - ) Normal value of HCO 3 - in plasma under actual condition is 24 ± 2 mmol/L HA + NaHCO 3  NaA + H 2 CO 3 determined by the amount of nonvolatile acid produced in metabolism --- Metabolic parameter

17. 4. Anion gap (AG) = UA - UC Na + (140) HCO 3 - (24) Cl - (104) UC (11) UA (23) mEq/L = Na + - ( HCO 3 - +Cl - ) = 140 - ( 24+104 ) = 12±2mEq/L  dAG =  dUA =  dHCO 3 -

18. Summary The maintenance of H + concentration of body fluid in a normal range is very important for life. Normal value of arterial pH is 7.35 – 7.45, which is determined by the HCO 3 - /H 2 CO 3 ratio, and regulated by buffering, lung and renal regulation. Buffers act to minimize changes in pH induced by acid or base load; PaCO 2 is controlled by alteration of pulmonary ventilation; HCO 3 - in plasma is regulated by renal reabsorption and regeneration of HCO 3 - coupled with equivalent H + excretion.

19. Simple acid-base disorders Metabolic acidosis Primary decrease in plasma HCO 3 - Causes of metabolic acidosis: High AG type ----  Fixed acid   HCO 3 - 1.  Production of fixed acids 2. Retention of fixed acids ---  GFR 3. Acid intake – salicylate etc.

20. Normal AG type ---- hyperchloremic 1.  HCO 3 - reabsorption or regeneration in renal tubules: Renal tubular acidosis ( RTA ) Renal failure Carbonic anhydrase inhibitor 2. HCO 3 - losses in alimentary tract: Diarrhea 3. HCl, NH 4 Cl intake 4. Hyperkalemia

21. § Hyperchloremia in normal AG type due to  reabsorption of Cl - RTA   HCO 3 - reabsorption  Cl - reabsorption Diarrhea   Ald  NaCl reabsorption § Paradoxical alkaluria in acidosis Renal tubular acidosis ---  HCO 3 - reabsorption or  H + excretion Hyperkalemia   renal H + excretion

22. Compensation of metabolic acidosis: 1) Extracellular buffering --- immediately HA + NaHCO 3  NaA + H 2 CO 3 2) Respiratory compensation  Ventilation in few min, maximal in 12-24 h d PaCO 2 = 1.2 d HCO3 - ± 2 3) Intracellular buffering --- in 2-4h 4) Renal compensation begin in several h, maximal in 3-5d

23. Respiratory acidosis Primary increase of PaCO 2 Causes: 1) External respiratory dysfunction 2)  PCO 2 in inspired air

24. Compensation of respiratory acidosis 1. Buffering ---- immediately CO 2 H2OH2O H 2 CO 3 HCO 3 - HHb KHb K+K+ K+K+ H+H+ H 2 CO 3 HCO 3 - Cl -

25. 2. Renal compensation Acute --- d [ HCO 3 - ] = 0.1 d PaCO 2 ± 1.5 Chronic ---d [HCO 3 - ] = 0.4 d PaCO 2 ± 3

26. Pathophysiological changes caused by acidosis Cardiovascular system 1) Decrease of myocardial contractility – pH<7.2  Responsiveness of  -adrenoceptor Contraction Ca 2+ influx SR [Ca 2+ ]i↑ Binding to Troponin H+H+

27. 2) Cardiac arrhythmia Acidosis  hyperkalemia  arrhythmia 3) Vasodilation  Responsiveness of  -adrenoreceptor

28. Central nervous system depression, coma ( pH < 6.9 ) 1)  GABA ----  glutamate decarboxylase activity 2)  Oxidase activity   ATP 3) Cerebral vasodilation   intracranial pressure What kind of acidosis has more effect on CNS, metabolic or respiratory?

29. H + (-) Na + Na + Ald Ald ATPase [K + ] e K + channel K + K + [K + ] e H + (-) Mg 2+(-) Urine flow K + Hyperkalemia --- 1) [H + ] e exchange for [K + ] i 2) Decreased excretion of K + by distal renal tubules Tubular l Principal cell Interstitial fluid

30. Metabolic alkalosis Primary increase of HCO 3 - Causes: 1) Excess bicarbonate load ---- intake 2) Gastric H + loss ---- vomiting Why HCO 3 - in plasma is increased? 3) Renal H + loss Diuretics ---  distal urine flow Hyperaldosteronism --- activation of H + pump and Na + -K + pump 4) Hypokalemia

31. Compensation of metabolic alkalosis 1) Buffering --- in cells 2) Respiratory compensation ---incomplete 3) Renal compensation --- tremendous

32. The causes of paradoxical aciduria? What kind of metabolic alkalosis is saline responsive? or saline resistant? vomiting? diuretics? primary hyperaldosteronism?

33. Respiratory alkalosis Primary decrease of PaCO 2 Cause ---- alveolar hyperventilation Hypoxia, psychoneurosis, fever etc. Compensation Buffering Renal compensation Acute -----dHCO 3 = 0.2 d PaCO 2  2.5 Chronic ---dHCO 3 = 0.5 d PaCO 2  2.5

34. Functional and Metabolic Changes caused by alkalosis Central nervous system Dysphoria, confusion, seizure, coma etc. 1)  GABA 2) Hypoxia from: hypoventilation, cerebral vasoconstriction left-shift of oxyhemoglobin dissociation curve  Neuromuscular excitability ---- cramping  ionic calcium in plasma Hypokalemia --- paresis, arryhthmia

35. Analysis of simple acid-base disorder

38. Mixed acid-base disorders Double acid base disorders Metabolic Metabolic acidosis alkalosis Respiratory Respiratory acidosis alkalosis

39. COPD  O 2  HCO 3 -   PaCO 2  pH  CO 2  PaCO 2  HCO 3 -  pH  HCO3 - /  PaCO2    pH COPD + O2  PaCO 2  HCO 3 -  pH + Diuretics   HCO 3 -  PaCO 2  pH   HCO 3 - /   PaCO 2  pH normal

40. Renal failure   HCO 3 -   PaCO 2  pH Vomiting   HCO 3 -   PaCO 2  pH N HCO 3 - / N PaCO 2  pH normal All these parameters are normal, how to find out the acid-base disorder?

41. Triple acid-base disorders Metabolic Metabolic acidosis alkalosis Respiratory Respiratory acidosis alkalosis

42. Exp: COPD   O 2   HCO 3 -   PaCO 2  pH  CO 2   PaCO 2   HCO 3  pH Diuretics   HCO 3 -  PaCO 2  pH  HCO 3 -  PaCO 2   pH

43. Summery Metabolic acidosis is induced by primary decrease of HCO - 3 owing to increased production or retention of fixed acides or HCO - 3 loss. Metabolic alkalosis is induced by primary increase of HCO - 3 due to H + loss. Respiratory acidosis or alkalosis is induced by primary increase or decrease of CO 2 caused by hypoventilation or hyperventilation.

44. Acidosis depresses activity of CNS and myocardial contractility, and induces cardiac arrhythmia and vasodilation. Alkalosis results in dysfunction of CNS and cramping. Different kinds of acid-base disorders may coexist in patients.