Acid-Base Balance

1. Acid-Base Balance

2. Back to Basics: An acid is a substance that increases H+ concentration, thus reducing pH. A base is a proton acceptor ., bases decrease H+ concentrations and raise the pH.

3. Acids are produced continuously during normal metabolism, although the blood concentration of free hydrogen ion ( H+) vary between narrow limits. The acids handled by the body daily are about 20,000 mmol of volatile and 40- 80 mmol of non-volatile acids.

4. Relatively constant H+ concentrations are important physiologically, as small changes in pH affect enzyme activity and thus metabolism. The immediate defense against changing H+ concentrations is provided buffers, while excretion is regulated by adaptive responses in the lungs and kidney.

5. The changes in ECF (H+) conc. or (pH) are regulated by : • Buffers: v. rapid temporarily traps acids or bases • Respiratory response: rapid gets rid of or retains CO2 • Renal response: slow excretes of fixed acids & retains or excretes HCO3-

6. Acid Production in the Body

8. Volatile Acids: CO2: The product of oxidation of substrate for utilization, mainly CHO and fat, is carbon dioxide. Although CO2 is not an acid, it dissolves in H2O to form H2CO3 ,so accumulation of CO2 may lower body pH . As CO2 is excreted through lungs it can be viewed as being volatile acid

9. CO2 H+ + HCO3- ↔ H2CO3 ↔ CO2 + H2O Removed by lungs

10. Non Volatile Acids: These are of 2 types: organic and inorganic

11. Organic acids : mainly lactic acid and ketone bodies. Lactate is produced continuously from the anaerobic metabolism of glucose, particularly in erythrocytes( no mitochondria) and skeletal muscle (strenuous exercising) These are converted to glucose in the liver

12. Ketone bodies are formed of fatty acids metabolism in the liver As organic acids are almost fully metabolized , under normal circumstances they contribute little to net acid excretion

13. Inorganic Acids: They are two main sources, sulphur-containing amino acids and phosphorus –containing organic compounds. Inorganic acidic anion must be excreted from the body by kidney

14. Buffers • Buffers are solutions of weak acids or bases which contain both dissociated and undissociated forms.

15. Buffers • Buffers limit the change of pH that would be caused by addition of strong acid or base • Buffers act effectively at pH = pK ( also its concentration determine its efficiency

16. Back to Basics: • K: The relative strength of weak acids are expressed quantitatively as dissociationconstants, that express the tendency to ionize. • pK= is the pH at which equal quantities of acid and its conjugate base exit.

17. Back to Basics: • HA↔ H+ + A- • K =[ H+][A- ] [HA]

18. [ H+]= K [HA] [A-]

19. Take the log of both sides: • Log [ H+]= logK [HA] [A-] Multiply through by -1 • -Log [ H+]= - log K -log [HA] [A-]

20. pH = pK + log [A-] [HA]

21. pH = pK + 0 so pK is the pH at which 50% of the acid is dissociated or it is a pH at which equal amounts of the acid and its conjugate base exist.

22. For Carbonic Acid-Bicarbonate system: • 7.4 = 6.1 + log [HCO3-] • [H2CO3]

23. For Carbonic Acid-Bicarbonate system: • 7.4 -6.1 = log [HCO3-] [H2CO3] 1.3 = log [HCO3-] [H2CO3]

24. Disturbance of the Acid-Base Status • Acidosis : pH < 7.4 HCO3- < 20/1 H2CO3 • ↓ HCO3- = metabolic • ↑ H2CO3- = respiratory • Alkalosis: • pH > 7.4 HCO3- > 20/1 H2CO3 • ↑ HCO3- = metabolic • ↓ H2CO3- = respiratory

25. Carbonic Acid -Bicarbonate Buffer System • ( H2CO3 – HCO3- ) The equilibrium reactions of the buffer system H+ + HCO3-H2CO3(Reaction 1) H2CO3CO2+ H2O(Reaction 2) Excreted by the Lungs Accordingly,the addition of H+ causes the equilibrium to be shifted to the right (towards CO2production & excretion by the lungs)

26. Carbonic Acid -Bicarbonate Buffer System • ( H2CO3 – HCO3- ) cont. In case of increased H+ production, H2CO3- HCO3-bufferwill reduce H+ as follows: • H+ + HCO3-H2CO3(Reaction 1) • H2CO3CO2+ H2O (Reaction 2) First Stage: In this case, pH of blood may be within normal range i.e. not much affected However, amount of buffer (HCO3-) is reduced (COMPENSATED ACIDOSIS) End Stage: Continuous reduction of buffer (HCO3-) until it is depleted (no more buffer) The end in lowering pH of blood to below normal limits i.e. acidemia (UNCOMPENDSATED ACIDOSIS)

27. Disorders of Acid-Base Balance • Increase in H+ concentrations results in a decrease in pH of blood (acidosis) • Decrease in H+concentrations results in an increase in pH of blood (alkalosis) Alkalosis or Acidosisdescribes any abnormality in H+ balance whether: 1- Compensated Alkalosis or Acidosis • Noblood pH changes (pH of blood is within normal range). • Buffer concentrations are abnormal • Compensatory mechanisms try to restore pH to normal if pH is changed. 2-Uncompensated alkalosis or acidosis (alkalaemiaoracidaemia) • AbnormalpHof blood (above or below normal range)

28. Relation between pH & buffer Assessment of Acid-Base Balance Henderson-Hasselbach Equation Normal pH of blood is not an indication of acid-base balance. Accordingly, in order to assess acid-base balance status of blood , we should assess pH& buffer concentration of blood [HCO3-] pH= 6.1 + log --------------------------------- pCO2+ 0.225

29. Assessment of Acid-Base Balance cont. In order to asess acid-base status: Blood pH & blood bicarbonate buffer are to be measured Bicarbonate buffer measurement: 1- INDIRECTLY From arterial blood sample Using blood gas analyzer to measure pH& PCO2in arterial blood Blood Bicarbonatein blood can be measured indirectlyby Henderson- Hasselbach Equation 2- DIRECTLY From venous blood Samples: Used to measure HCO3-directly [HCO3-] pH= 6.1 + log --------------------------------- PCO2+ 0.225

30. Role of Lungs in Acid Base Balance

31. CO2 + H2O +HbO2 ECF Tissues CO2 O2 Erythrocyte CO2 Carbonic anhydrase HCO3- HCO3- +H+ Cl - Cl - O2 + HHb

32. Role of Kidney in Acid Base Balance

36. Acid-base Acid-Base Balance Disturbances 1- Acidosis: - Metabolic - Respiratory 2- Alkalosis: - Metabolic - Respiratory DIAGNOSIS IS CONFIRMED BY LABORATORY INVESTIGATIONS OF pH, pCO2 (to calculate blood bicarbonate) & pO2 Sample: Arterial Blood using Procedure: Blood Gas Analysis

37. Metabolic Acidosis Causes: First Cause Increased production of H+ 1- Increased endogenous acid production. - Diabetic ketoacidosis (increased ketone bodies in blood) - Lactic acidosis (increased lactic acid in blood). 3-Ingestion of acids (or substance that produces an acid) - Poisons: as salicylate (aspirin) overdose - Methanol ingestion - Ethylene glycol poisoning. 4-Decreased acid (H+) excretion by the kidney: - Chronic renal failure.

38. Metabolic Acidosis Compensatory Mechanisms in Cases of Increased H+ Production 1- RESPIRATORY COMENSATORY MECHANISMS H + is increased in cells. It reacts with HCO3-. As a result, CO2 is produced & then exhaled by lungs (increase respiration)H++ HCO3-H2CO3  CO2 + H2O End Results: 1- Exhaustion of bicarbonate buffer with shift of reactions to CO2 production 2- Stimulation of the respiratory center to eliminate excess CO2 formed

39. Metabolic Acidosis • Compensatory Mechanisms in Cases of Increased H+ production cont. • 2- RENAL COMENSATORY MECHANISMS • Increase excretion of H+ & production of HCO3- by the kidney • 1- In tubular cells, ammonia is produced from glutamine & is excreted to the tubular lumen. • In the lumen, it combines with H+ to give ammonium (NH4+) which can not be reabsorbed • into the tubular cells and thus lost in urine (H+ trap). • 2- Increased production of HCO3- by renal tubular cells (to compensate for HCO3- loss)

40. Metabolic Acidosis Causes: Second cause Loss of Bicarbonate (HCO3-): Causes of decreased HCO3- in blood: 1- Renal Causes: 1-Failure to form HCO3- in tubular cells of the kidney Inhibition of carbonic anhydrase of the tubular cells by drugs 2-Failure to reabsorb HCO3- by renal tubules (in renal tubular acidosis, RTA) 2- Loss of HCO3- (by diarrhea) The compensatory mechanisms The respiratory one by increasing in CO2 exhalation

41. LABORATORY DIAGNOSIS OF METABLOIC ACIDOSIS H+ is increased. It reacts with HCO3. HCO3 is reduced.CO2 is produced {then exhaled by lungs (increase respiration)}H++ HCO3-H2CO3(Reaction 1)H2CO3CO2 + H2O (Reaction 2) CO2 is produced (increased) & then exhaled by lungs (increase respiration) Sample: Arterial Blood Equipment: Blood Gas Analyzer Results pH: Low HCO3-: Low pCO2: Low: asCO2 is produced then exhaled by lungs by increasing respiration PO2: Normal

42. Metabolic Alkalosis The primary abnormality in metabolic alkalosis is the increased plasma bicarbonate level. (HCO3-). Causes: Less common Intake of a large amounts of sodium bicarbonate: (if intake is more than 1000 mmol/day) More common Loss of H+ (acids) from the body: 1- From the kidneys(increased excretion of acids, H+ ions): 1- Mineralcorticoid (aldeserone) excess 2- Severe potassium deficiency 2- From the GIT(increased loss acids, H+ ions): vomiting

43. Metabolic Alkalosis Compensatory Mechanisms In Metabolic Alkalosis 1-Respiratory compensation H+ is reduced. So, the reaction is directed as follows Respiratory depression leads to CO2 retention CO2 production is increased by respiratory depression CO2+ H2O H2CO3 H++ HCO3-HCO3- is excreted by the kidney (by decreasing reabsorption) & H+ is produced (to lower pH) 2-Renal compensation By decreasing HCO3- reabsorption & regeneration by renal tubules

44. In metabolic alkalosis:H+ is reduced. So, the reaction is directed as followsCO2 production is increased by respiratory depression (compensatory)CO2+ H2O H2CO3(Reaction 1)H2CO3H+ + HCO3-(Reaction 2) LABORATORY DIAGNOSIS OF METABLOIC ALKALOSIS Sample: Arterial Blood Equipment: Blood Gas Analyzer Results: pH: High HCO3-: High pCO2 : High (due to compensatory respiratory depression)