1. Acid-Base Balance Prof. Omer Abdel Aziz

2. Objectives Definition Regulation Disturbances

3. Acid-Base Balance pH = - Log [H + ] Plasma pH (ECF) 7.4 + 0.05, conc 0.00004meq/L. acidosis metabolic alkalosis respiratory IC pH 7.2 pH 7 to 7.7 is compatible with life.

4. Regulation 1.Buffers. 2. Respiratory. 3. Renal.

5. 1- Buffers: A buffer is a substance which can easily combine or dissociate with H+ in solution. Main buffers are: I. Blood 1- Carbonic acid CO 2 + H 2 O CA H 2 CO 3 H + +HCO 3 2- Plasma proteins 3- Hb II.Interstitial fluid : H 2 CO 3

6. Buffers cont. III. ICF : 1- Protein 2- Phosphates IV. CSF 1- H 2 CO 3 2- Phosphate V. Urine 1- H 2 CO 3 2- Phosphate 3- NH 3 ammonia

7. Henderson - Hasselbach equation Common equation for a buffer HA H + + A - HA = Weak acid undissociated A - : anion ; HCO 3 Addition of a strong acid H+ combine with A- to form more HA (weak acid)

8. H & H cont. Addition of an alkali H + combine with OH - to form water and more HA dissociate to give more H + According to the law of mass action K : [H + ] [A - ] [HA] K is the equilibrium constant

9. H & H cont. H&H put this in pH form pH = - Log [H + ] pK = - Log [H + ] [A - ] [HA] = Log [H + ] + - Log [A - ] [HA]

10. H & H cont. -Log [H+] = PK + Log [A-] [HA] pH = PK + Log [A-] [HA] And this is called Henderson – Hassebalch equation.

11. H & H cont. When applied on H 2 CO 3 /HCO 3 system pH = PK + Log [HCO 3 ] [H 2 CO 3 ] In body fluids H 2 CO 3 is in equilibrium with CO 2 H 2 CO 3 CO 2 + H 2 O: pH = PK (6.1) + Log [HCO 3 ] [CO2]

12. H & H cont. [CO 2 ] is determined by its partial pressure PaCO 2 and its solubility coefficient (0.0301 mmol/L/mm Hg) Then pH = 6.1 + Log [HCO 3 ] 0.0301 PaCO 2

13. H & H cont. By measuring pH + PaCO2 [HCO3] can be calculated. [CO2] can be regulated by the respiratory system & HCO3 can be regulated by the kidney.

14. 2. Respiratory regulation 2. Respiratory regulation Respiratory center is sensitive to [H + ] : I. [H + ] stimulate respiration CO 2 expired PCO 2 pH II. [H+] respiration CO 2 retention CO 2 PCO 2 pH

15. 3- Renal regulation

16. Functions of the kidneys 1. Excretion of waste products. 2. Formation and excretion of urine. 3. Water balance. 4. Acid base balance. 5. Reservation of nutrients. 6. Endocrine function.

18. Sources of acids Aminoacids: ammonium, phosphoric acid and sulforic acid :50 meq/d. CO2 from metabolism: 12500 meq/d. Lactic acid : exercise. Acetacetic acid & hydroxybutyric acid: diabetic ketoacidosis. Ingestion of acidifying salts: ammonium chloride.

19. Renal regulation Renal regulation I. H + excretion Kidneys secrete H + by the proximal tubules (Na+-H+ exchange: secondary active transport), distal tubules & collecting ducts (mechanism involves aldosterone from intercalated -I cells).

20. H + comes from H 2 CO 3 dissociation which is formed by carbonic anhydrase catalysis and the bicarbonate ion diffuses into the interstitial fluid. For each H + secreted one sodium ion and bicarbonate ion enter the interstitial fluid

21. Urine pH is 4.5-8, urine buffer enhances H + excretion. Urine pH of 4.5 corresponds to the maximum H + gradient against which secretion can occur: Limiting pH. Buffers in urine assist this secretion: bicarbonate, phosphate and ammonia.

23. Renal cont. Renal excretion of H + is affected by: 1. Acid secretion increases with high PCO 2 2. Depletion of K enhances H + secretion. 3. Carbonic anhydrase inhibition inhibits acid secretion. 4. Aldosterone enhances H + secretion.

24. II. HCO3 excretion If low in plasma it will be reabsorbed totally. If it is more than 28 meq/L it is secreted

26. Disturbance of acid-base balance An increase in [H+] acidosis (metabolic or respiratory). A decrease in [H+] Alkalosis (metabolic or respiratory).

27. Metabolic acidosis pH low, [H+] high in plasma, HCO3 low PaCO2 low or normal. Causes: 1. Sever exercise. 2. Shock. 3. Diabetic ketoacidosis. 4. Lactic acidosis (side effect of some antidiabetics).

28. Metabolic acidosis cont. 5. Acute alcohol intoxication. 6. Sever liver failure. 7. Ingestion of NH 4 CL. 8. Salicylates poisoning. 9. Acute α chronic renal failure. 10. Renal tubular acidosis. 11. Diarrhoea α fistulae HCO 3

29. Symptoms: 1. Clinical picture of the cause. 2. Increased respiratory rate due to H +, in severe case will become deep and quick (Kussmaul Resp.). 3. Dehydration : fluid & electrolyte imbalance.

30. Diagnosis: By measuring arterial pH. If PaCO 2 is measured, HCO 3 can be calculated from Henderson Hasselbach equation if HCO 3 is 15 mmol/IL moderate < 10 : severe.

31. Compensatory mechanisms: 1. Respiratory : resp. CO 2 pH. 2. Renal : H+ excretion, HCO 3 production from glutamate. Treatment: 1-In sever cases NaHCO 3 2-Rehydration. 3-Treatment of cause.

32. Metabolic alkalosis Increased pH, increased HCO3, decreased [H], PaCO2 normal or increased. Causes: 1-Vomiting. 2-Hypokalaemia. 3-Excessive diuretics. 4Intake of NaHCO3 in patients with renal failure.

33. Compensatory mechanisms 1- Respiratory: decreased ventilation leads to increased PCO2 which will decrease pH. 2- Renal: little role, bicarbonate excretion if its concentration exceeds 28. Symptoms: 1- None. 2- Tetany.

34. Metabolic alk. Cont. 3-Apathy, personality changes,delirium, stupor 4-Sever chronic alkalosis renal failure. Treatment: 1.Treat the cause. 2.IV fluids. 3.In case of diuretics : stop + carbonic anhydrate inhibitor, acetazolamide.

35. Respiratory acidosis pH [H + ] PaCO 2 HCO 3 Causes: 1. Inspiration of 7% CO 2. 2. Emphysema. 3. Chronic bronchitis. 4. Respiratory center depression. 5. Respiratory muscles paralysis. 6. Obesity. 7-Respiratory failure

36. Compensatory mechanisms By the kidney: increased H secretion and bicarbonate retention. Symptoms and treatment: -According to the underlying cause.

37. Respiratory alkalosis High pH, low H, low PaCO2, low HCO3. Causes: all causes leading to increased ventilation. 1- Voluntary hyperventilation. 2- Hysteria. 3- Mechanical ventilation. 4- Lobar pneumonia. 5- Pulmonary embolism. 6- Meningitis.

38. Resp. alk. Cont. 7- Enchephalitis. 8-Salicylates poisoning. 9- Liver failure. 10- Asthma. Compensatory mechanism: By the kidney excreting bicarbonate. Treatment: for the cause.

39. Metabolic acidosis: Anion gap ( delta):( Na + - (Cl + HCO 3 ) normal 8-14 mmol/L. Increased in diabetic ketoacidosis and lactic acidosis.

40. Summary Normal pH is 7.4. Regulation by buffers, lung and kidneys. Renal regulation is either by H secretion or bicarbonate absorption or secretion. Renal compensation occurs in acid base disturbances

41. Thank you