Acid base balance simplified

Acid base basics for medical and dental students

1. Acid base balance Dr.S.Sethupathy , M.D., Ph.D ., Professor & HOD of Biochemistry RMMC, AU

2. Metabolism is the basis of life. Metabolism is possible only because of enzymes. Enzyme activity is influenced by pH of the surrounding medium. So maintenance of acid base balance is crucial for life. Importance

3. Acid is a protein (H + ) donor Example HCl H + + Cl Base is a proton (H + ) acceptor. NaOH + HCl NaCl + H 2 O Strong acids completely dissociate into their constituent ions in solution - HCl Weak acids partially dissociate – lactic acid, carbonic acid

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6. 6 The Body and pH Homeostasis of pH is tightly controlled Extracellular fluid = 7.4 Blood = 7.35 – 7.45 < 6.8 or > 8.0 death occurs Acidosis ( acidemia ) below 7.35 Alkalosis ( alkalemia ) above 7.45

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8. It is a mixture of weak acid and its salt or weak base and its salt, which resist pH change on addition of a small amount of strong acid or alkali . Example : Bicarbonate buffer Na + HCO 3 - / H 2 CO 3 The buffering capacity depends on actual concentrations of salt and acid, and its ratio. Buffering capacity is maximum in the range of 1 unit ± of its pK value. Buffers

9. 9 Bicarbonate buffer Sodium Bicarbonate (NaHCO 3 ) and carbonic acid (H 2 CO 3 ) Maintain a 20:1 ratio : HCO 3 - : H 2 CO 3 HCl + NaHCO 3 ↔ H 2 CO 3 + NaCl NaOH + H 2 CO 3 ↔ NaHCO 3 + H 2 O

10. 10 Phosphate buffer Major intracellular buffer H + + HPO 4 2- ↔ H 2 PO4 - OH - + H 2 PO 4 - ↔ H 2 O + H 2 PO 4 2-

11. 11 Protein Buffers Includes hemoglobin, proteins in ICF Carboxyl group gives up H + Amino Group accepts H + Some Side chains of amino acid residues can buffer H + - lysine, arginine, histidine

12. Weak acids dissociate only partially in the solution. Conjugate base is the unprotonated form of corresponding acid. For example: Cl - , HCO 3 - Weak acid H 2 CO 3 H + + HCO 3 - Proton ( conjugate base) Conjugate base of weak acid is strong. Strong acid HCl H + + Cl - (conjugate base) Conjugate base of strong acid is weak.

13. The dissociation of an acid is a freely reversible reaction . So at equilibrium, the ratio of dissociated and undissociated particles is constant. ( Ka is the dissociation constant) Ka = H + + A - dissociated / HA un dissociated H + - proton A - - conjugate base or anion Dissociation constant

14. It is the pH at which the acid is half dissociated. It is negative logarithm of acid dissociation constant Ka to the base 10. At pK value, Salt : acid ratio is 1:1. pKa = - log 10 Ka P pKa value

15. pH = pKa + log 10 ( salt / acid ) Due to metabolism mainly acids are produced. The acids are of two types. 1.Fixed acids or non volatile acids Example phosphoric , sulfuric acids, organic acids such as pyruvic , lactic, ketoacids . 2.Volatile acid- carbonic acid Carbonic acid is being volatile, it is eliminated by lungs as CO 2. Fixed acids are excreted by kidneys. Henderson- Hasselbalch equation

16. pKa of carbonic acid is 6.1. pH = 6.1 + log 10 (bicarbonate/ carbonic acid – 0.03 x pa CO2 ) { paCO2- 40mm of Hg} =6.1 + log 10 (24/1.2) = 6.1 + 1.3 = 7.4 Arterial blood pH = 7.4 Bicarbonate represents alkali reserve and it is twenty times more than carbonic acid to ensure high buffering efficiency. Alkali reserve

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18. Histidine residue of hemoglobin can act as acid or base. Histidine amino acid has pKa value of 6.5 and it is efficient buffer . Deoxygnatered hemoglobin in tissues accepts H + ions to form HHb . ( KHb / HHb buffer ) Oxygenated hemoglobin releases H + ions in lungs. Amino groups of hemoglobin interact with CO 2 to form carbamino hemoglobin . Hemoglobin buffer system

19. Action of hemoglobin buffer In the tissues, CO 2 diffuses into erythrocytes and gets converted to carbonic acid by carbonic anhydrase. H 2 O + CO 2 H 2 CO 3 H 2 CO 3 H + + HCO 3 - KHb accepts H + and releases K + . Bicarbonate diffuses into the plasma where its concentration low. To maintain electrical neutrality, Chloride ( Cl - ) enters the erythrocytes. This is called chloride shift.

20. Hb Buffer – tissue event

21. In the lungs, oxygenation of hemoglobin releases H + which combines with bicarbonate to form carbonic acid by carbonic anhydrase . Carbonic acid dissociates into water and CO 2 . CO 2 is expired out by lungs. Chloride comes out in exchange for HCO 3 - to maintain electrical neutrality.

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23. pH = pKa + log {bicarbonate (metabolic component)/ carbonic acid-paCO 2 (Respiratory component)} Respiratory component is maintained by lungs and Metabolic component is maintained by kidneys. Carbonic acid is a volatile acid so it is eliminated by lungs. The rate of respiration is controlled by the chemoreceptors in the respiratory centre which are sensitive to pH change of blood.

24. Functions Reabsorption of bicarbonate involves the reabsorption of bicarbonate filtered without excretion of H + ions. Excretion of H+ ions Here there is net gain of bicarbonate for each H + excretion. As the H + ion excretion increases, the excretion of H + against concentration gradient becomes difficult. So in the distal convoluted tubules, urinary buffers buffer the free H + ions. Renal regulation of pH

25. Reabsorption of bicarbonate

26. Excretion of H + ions

27. Two important urinary buffers are 1. Phosphate buffer 2. Ammonia The maximum limit of acidification of urine is 4.5. Normally 70 meq acid is excreted daily. In metabolic acidosis, this can raise to 400 meq /day. Urinary buffers

28. Phosphate buffer

29. Ammonia buffer

30. Normal values -Arterial pH = 7.35 – 7.45 paO 2 = 80-100 mm of Hg paCO 2 = 35-45 mm of Hg HCO 3 - = 23-27 mmol /L Na + = 135-145 mmol /L K + = 3.5-5 mmol /L Cl - = 96-106 m/L

31. pH: 7.35 – 7.45 PCO2: Males: 35 – 48 mm Hg Females: 32 – 45 mm Hg HCO3: 22 – 27 mEq /L Base Excess: Newborn (0 – 7 days): -10 to -2 mmol /L Infant (1 week – 1 year): -7 to –1 mmol /L Child (1 – 16 years): -4 to +2 mmol /L Adult (>16 years): -3 to +3 m Capillary blood gas - pediatric

32. Warm the area for 3-10 mins not > than 42 C – arterialization - 0.2 ml Lithium heparin – fill 2 capillary tubes without air bubble –cap both ends Within 15 mins – analyze > 30 mins , clotted sample – discard Critical values pCO2: < 15 and > 70 mm Hg pH : < 7.2 and > 7.6 CBG sampling

33. Respiratory acidosis - failure of ventilation depression of respiratory centre due to disease or drug-induced respiratory depression, head injury. Paralysis of muscles ( eg , myasthenia gravis, muscular dystrophy) Airway obstruction- foreign body –trachea , asthma or chronic obstructive pulmonary disease (COPD). Obesity hypoventilation syndrome The biochemical findings are: pH < 7.35 paCO 2 > 45 mm of Hg ( Hypercapnia ). Renal compensation occurs in 3-5 days. This increase of bicarbonate is called compensatory metabolic alkalosis .

34. It is caused by hyperventilation. The causes for hyperventilation are: Anxiety, salicylate poisoning , artificial ventilation and pulmonary embolism. The biochemical findings are pH is increased > 7.45 paCO 2 ­ is decreased < 35 mm of Hg Bicarbonate is normal in uncompensated condition. In compensatory metabolic acidosis, bicarbonate will be decreased. Kidney responds to decrease in paCO 2 and excretes more bicarbonate. Respiratory alkalosis

35. It can be due to 1.Increased acid production 2. Decreased removal of acids by kidneys (renal failure ) 3.loss of bicarbonate Increased acid production: The causes are lactic acidosis in shock, septicemia , ketoacidosis in Von Gierkes’s disease, diabetes mellitus and starvation. Loss of bicarbonate due to diarrhoea (gastroenteritis). Metabolic acidosis

36. The sum of cations and anions in ECF are always equal. Cations Na + + K + - 95% - anions Cl + HCO 3 A ccount for only 86% among the measured electrolytes. AG represents the plasma anions - not routinely measured (albumin, phosphates, sulphates, organic anions). So there is a difference among measured cations and anions. The unmeasured anions constitute the anion gap. Anion Gap = [Na + + K + ] – [ Cl - + HCO 3 - ] = [135 + 4] – [100 + 25] = 139 – 125 = 14 meq /l. The anion gap ranges between 8-16 meq /l. Anion gap

37. Based on anion gap, Metabolic acidosis can be grouped into : High anion gap metabolic acidosis and normal anion gap metabolic acidosis. High anion gap acidosis It is caused by increased production of unmeasured anions such as lactate, ketone bodies. Normal anion gap acidosis ( Hyperchloremic acidosis): when there is loss of both anion and cations , normal anion gap acidosis will be there. The causes are : Diarrhea , intestinal fistula due to loss of bicarbonate , Na + , K + . Renal tubular acidosis Carbonic anhydrase inhibitors: loss of HCO 3 -, Na + , K + occurs.

38. Metabolic Acidosis - causes ketoacidosis diabetic, alcoholic, starvation lactic acidosis acute renal failure toxins renal tubular acidosis GIT loss of HCO 3 diarrhoea drainage of pancreatic or bile juice

39. There will be deep and rapid respiration called Kussmaul respiration . Chest pain, headache, palpitation, altered mental status. When pH<7.2 and bicarbonate <10 mmol /L , there will be depressed myocardial contractility. pH is decreased- < 7.35 HCO 3 is decreased- < 24 mmol /l paCO2 is normal or decreased during compensation.   Compensation by lungs paCO 2 will be reduced by 1 mm of Hg for every 1 mmol of drop in bicarbonate. Treatment Treatment of the cause and administration of Bicarbonate.

40. pH is increased due to rise in HCO 3 - . It is seen in vomiting (loss of H+ ions), intake of antacids, in patients consuming more milk (Milk-alkali syndrome). Increased loss of acid by kidney: hyperaldosteronism , Cushing’s syndrome. Thiazide and loop diuretics In vomiting, HCl is lost and so bicarbonate accumulates. Plasma Cl - _ is decreased. This is called hypochloremic alkalosis. Metabolic alkalosis

41. pH is increased > 7.45 HCO 3 - > 27 mmol /L paCO 2 is normal if uncompensated and is increased in case of compensatory respiratory acidosis. So paCO 2 will be increased by hypoventilation. In metabolic alkalosis paCO 2 is increased by 1 mm of Hg for every 1 mol /L rise in bicarbonate. Metabolic alkalosis

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