1. H + homeostasis The mechanisms by which the body keeps the plasma [H + ] constant 

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6. Three Major Mechanisms Buffering Expulsion or retention of CO 2 Generation / reclamation of HCO 3 – /excretion of H + 

7. Body buffers (I) Extracellular HCO 3 - /H 2 CO 3 HPO 4 2 - /H 2 PO 4 - Plasma proteins

8. Body buffers (II) Intracellular HCO 3 - /H 2 CO 3 HPO 4 2 - /H 2 PO 4 - Proteins & Amino-acids

9. Buffering H + + HCO 3 - ⇄H 2 CO 3 ⇄CO 2 +H 2 O H + is buffered Bicarbonate is consumed To stop the backward reaction which will lead to production of H + ions, CO 2 must be excreted To generate base from the backward reaction H + must be excreted 

10. Respiratory mechanisms Hyperventilation H 2 CO 3 ⇌ H 2 O + CO 2  Carbon dioxide diffuses through the CNS to the respiratory centre and stimulates hyperventilation Hypoventilation less than normal PCO 2 results in hypoventilation 

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13. Metabolic/Renal mechanisms Excretion of H + Bicarbonate generation Bicarbonate reabsorption / reclamation 

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17. The proton pump. The proton pump excretes H + and generates bicarbonate

18. Parameters used in assessing acid-base balance Plasma pH Arterial PCO 2 Plasma [bicarbonate] Anion gap (AG) 

19. Parameters used in assessing acid- base balance: Reference ranges Plasma pH: 7.35-7.45 corresponding to [H + ] of 43-36 nmol/L (7.4) av Arterial PCO 2 : 4.8-5.8 kPa (5.3) av Plasma [bicarbonate]: 21-28 mmol/L (25) av Anion gap: 13-18 mmol/L (15.5) av

20. Parameters used in assessing acid-base balance Others: Actual bicarbonate Standard bicarbonate Base excess PO 2

21. Definitions Standard bicarbonate: The concentration of bicarbonate in plasma of a blood specimen that has following collection been equilibrated with O 2 and CO 2 mixtures at 37  C. Conditions: fully oxygenated and PCO 2 5.3 kPa or 40 mm Hg

22. Definitions Base excess: The amount of strong acid that would be required to titrate one litre of fully oxygenated blood to a pH of 7.4 ([H + ]= 40 nm/L) at 37  C under conditions where PCO 2 is 5.3 kPa or 40 mm Hg

23. pH / Henderson-Hasselbalch Equation using the dynamics of the bicarbonate buffer pH = pK + 1og l0 [HCO 3 - ] [H 2 CO 3 ] pH = 6.10 + 1og l0 [HCO 3 - ] S.PCO 2 pH = ~ [base] [acid ] S=solubility coefficient of CO 2 = 0.23 mmol/J if PCO 2 is expressed in kPa and 0.03 mmol/J if PCO 2 is expressed in mmHg 

24. Anion gap Based on the electroneutrality of plasma [total cations] = [total anions] ([Na + ] + [K + ] +[Ca + ]) = ([Cl - ]+[HCO 3 - ]+ [pyruvate]+[acetoacetate]+[lactate]+[urate] +[citrate] ) ([Na + ] + [K + ]) -([Cl - ]+[HCO 3 - ]) = Anion Gap (AG). 

25. Key to solving acid-base problems: Look at the plasma pH Is there acidaemia or alkalaemia? Find the primary cause (parameters with a change consistent with or supporting the change in pH) Find the secondary or compensatory changes (parameters with a change not consistent with or opposing the change in pH) 

26. Simple acid-base disturbances pH< 7.35PCO 2 AGHCO 3     pH >7.45PCO 2 AGHCO 3     

27. Simple acid-base disturbances pH< 7.35PCO 2 AGHCO 3 Acute respiratory acidosis  Chronic respiratory acidosis  Metabolic acidosis  Mixed acidosis  pH >7.45PCO 2 AGHCO 3 Acute respiratory alkalosis  Chronic respiratory alkalosis  Metabolic alkalosis  Mixed alkalosis  

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29. Mechanisms of acid-base disturbances: Metabolic acidosis Addition of hydrogen ions to body fluids in excess of the excretory capacity (Processes that add hydrogen ions to body fluids faster than the body can excrete) Starvation ketosis Diabetic ketoacidosis Lactic acidosis Ingestion of substances that are acidic or yield acidic metabolites e.g. NH 4 Cl, methanol, paraldehyde, salicylates  (here, there is nothing wrong with the kidneys)

30. Mechanisms of acid-base disturbances: Metabolic acidosis Failure to excrete hydrogen ions at the normal rate (here, there is something wrong with the kidneys) Inadequate production of ammonia by the kidney e.g. chronic renal failure Inability to maintain the blood-urine H + concentration gradient (pH 7.4 : 6) DRTA, Oliguria /Anuria: e.g. acute renal failure 

31. Mechanisms of acid-base disturbances: Metabolic acidosis Loss of bicarbonate from the body From the GIT e.g. severe diarrhoea, fistulous drainage, uretero-sigmoidostomy Proximal renal tubular acidosis (PRTA; failure to generate or reclaim bicarbonate) e.g. Fanconi syndrome, carbonate dehydratase inhibitors; e.g. acetazolamide) 

32. Mechanisms of acid-base disturbances: Respiratory acidosis Increased alveolar PCO 2 leading to increased arterial PCO 2 Lung disease e.g. chronic airways obstruction, respiratory distress syndrome Weakness of respiratory muscles e.g. poliomyelitis CNS disease e.g. encephalitis, meningitis Drug overdose e.g. hypnotics, anaesthetics 

33. Mechanisms of acid-base disturbances: Metabolic alkalosis Metabolic Alkalosis Loss of hydrogen ions from the body Loss of H + in vomit Diuretics (potassium non-sparing diuretics) Na + , K +  increased excretion of H + ([H + ]  ) Mineralocorticoid excess Na + , K +  increased excretion of H +  [H + ]  Glucocorticoid excess Na + , K +  increased excretion of H +  [H + ]  K + depletion if severe  increased excretion of H +  [H + ]  

34. Mechanisms of acid-base disturbances: Metabolic alkalosis Addition of base to body fluids in excess of the excretory capacity NaHCO 3 infusions Ingestion of alkali e.g. NaHCO 3, MgO, CaCO 3 Milk-alkali syndrome (treatment of peptic ulcer). 

35. Mechanisms of acid-base disturbances: Respiratory alkalosis Respiratory alkalosis Lowered alveolar PCO 2 Voluntary overbreathing, hysteria Artificial ventilation Drug overdose e.g. salicylate poisoning sometimes 

36. Salicylate toxicity: blood [salicylate]> 30mg dL Accidental in children Deliberate in young adults In the treatment of: Rheumatoid arthritis Dermatosis 

37. Salicylate toxicity Initially there is stimulation of the respiratory centre ⇒ low PCO 2, low HCO - 3, and respiratory alkalosis Salicylates alter peripheral metabolism ⇒ production of various organic acids e.g. lactic acid ⇒ metabolic acidosis with  anion gap 

38. Salicylate toxicity Adults: Mixed respiratory alkalosis and metabolic acidosis Children: Metabolic acidosis 

39. Salicylate toxicity: other features Sweating Vomiting Dehydration A metabolic alkalosis can occur as a result of vomiting 

40. Salicylate toxicity: useful laboratory measurements Total body K + : (  ) Plasma total CO 2 : (  ) Plasma [urea]: (  ) 

41. Salicylate toxicity: Management Initially and in case of spasm of pyloric sphincter: Gastric lavage After significant absorption of salicylate: Forced alkaline diuresis 