Acid base disorders

Concepts of acid base balance and its disorders are very important for practice of medicine.It is for the benefit of medical and students of allied fields.

1. ACID BASE DISORDERS Dr.S.Sethupathy , M.D.,Ph.D ., Professor of Biochemistry, Rajah Muthiah Medical College, Annamalai university

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

3. 3 The body produces more acids than bases Acids take in with foods Acids produced by metabolism of lipids and proteins Cellular metabolism produces CO 2 . CO 2 + H 2 ↔ H 2 CO 3 ↔ H + + HCO 3 -

4. Acid is a protein (H + ) donor Eg : 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 eg . HCl Weak acids partially dissociate – lactic acid, carbonic acid

5. 5 Human Body and pH Homeostasis of pH is tightly regulated ECF= 7.4 Blood = 7.35 – 7.45 < 6.8 or > 8.0 death occurs Acidosis ( acidemia ) below 7.35 Alkalosis ( alkalemia ) above 7.45

6. It is a mixture of weak acid and its salt or weak base and its salt Buffers resist pH change Example : Bicarbonate buffer NaHCO 3 / H 2 CO 3 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

7. Buffers distribution

8. Defense against acid load

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 - 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 Eg . phosphoric, sulfuric acids , organic acids such as pyruvic, lactic , ketoacids . 2.Volatile acid- carbonic acid Carbonic acid ,being volatile 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

17. Histidine residue of hemoglobin can act as acid or base. Histidine has pKa value of 6.5 and it is efficient buffer . Deoxyhemoglobin 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

18. Action of hemoglobin buffer In tissues , CO 2 diffuses into erythrocytes to form 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 .

19. In lungs , oxygenation of haemoglobin 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.

20. 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.

21. 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

22. Reabsorption of bicarbonate CA-Carbonic anhydrase

23. Reabsorption of bicarbonate

24. 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

25. Excretion of H +

26. Excretion of H + ions

27. Urinary Phosphate buffer

28. Phosphate buffer

29. Urinary Ammonia buffer

30. Ammonia buffer

31. Acid Base Imbalance

32. Arterial blood gas reference values

33. Term Symbol Normal value Range Unit H+ H+ 40 36-44 nmol/L pH pH 7.4 7.36-7.44 - CO2 tension PaCO2 40 36-44 mm Hg Base exces BE –2 to +2 mmol/L Total CO2 TCO2 25 23-27 mmol/L Actual HCO3 HCO3 24 22-26 mmol/L Standard HCO3 SBC 24 22-26 mmol/L O2 saturation SaO2 98 95-100 % O2 tension PaO2 95 80-100 mmHg

34. 36 Compensation If underlying problem is metabolic, hyperventilation or hypoventilation can help : respiratory compensation . If problem is respiratory, renal mechanisms can bring about metabolic compensation .

35. 37 Acidosis Principal effect of acidosis is depression of the CNS through ↓ in synaptic transmission. Generalized weakness Deranged CNS function the greatest threat Severe acidosis causes Disorientation coma death

36. 38 Alkalosis Alkalosis causes over excitability of the central and peripheral nervous systems. Numbness Lightheadedness It can cause : Nervousness muscle spasms or tetany Convulsions Loss of consciousness Death

37. Types of Acid Base Disorders

38. HCO3 – level is 24 mEq /L The normal range is 22-26. When HCO3– level falls below 22 mEq /L (in conditions like acute watery diarrhea, renal tubular acidosis, addition of lactic acid and ketoacids ) metabolic acidosis results . When the HCO3– levels exceeds 26 mEq /L (in conditions like persistent vomiting, increased renin-angiotensin activity, loop diuretics) it is termed as metabolic alkalosis. Kidney regulates HCO3– homeostasis.

39. 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

40. Clinical features In severe acidosis when pH falls below 7.20 (H+ ion concentration >63 nEq /L), grave features like poor myocardial performance, arrhythmias, hypotension, pulmonary edema and hyperkalemia occur. Similarly in severe alkalosis when the pH exceeds 7.5 (H+ ion concentration <28 nEq /L) features like mental confusion, muscular irritability, seizures, arrhythmias, generalized tissue hypoxia and hypokalemia occur. Identification of these clinical features is difficult in a sick child presenting pre-dominantly with the features of primary disease.  Normal hydrogen ion concentration in our body is 40 nmol /l and the acceptable range is 36-44 nmol /L .

41. Anion Gap It is a measure of unmeasured anions A small amount of anion that cannot be measured by biochemical investigations is named as anion gap: (Na+ + K+) = ( Cl – + HCO3–) + AG (Unmeasured anions) (Anion gap) (135 + 04) = (100 + 24) + other anions Anion gap = 8-16 mmol /L High anion gap acidosis (HAGMA) Normal anion gap acidosis (NAGMA)

42. Increased anion gap ( Normochloremic acidosis) Normal anion gap ( Hyperchloremic acidosis) Lactic acidosis Diarrhea Shock Rental tubular acidosis Asphyxia Uretero sigmoidostomy Cyanide Poisoning Parenteral alimentation Salicylate poisoning Rapid ECF expansion Paraldehyde poisoning Exogenous chlorides Biguanides poisoning CaCl2, MgCl2, NH4Cl Organic acidemias Cholestyramine Inborn errors of carbohydrate and Carbolic anhydrase inhibitors pyruvate metabolism Small bowel/ biliary fistula Ketoacids   Diabetes mellitus   Starvation   Sulphuric/phosphoric   acids   Renal failure  

43. Metabolic acidosis (HCO3) For every 1 mEq /L fall in HCO3 PaCO2 should fall by 1 mm of Hg (1-1.5) Metabolic alkalosis (HCO3) For every 1 mEq /L increase HCO3– paCO2 should increase by 1 mm of Hg (0.5-1)

44. Normal PaCO2 value - 40 mm Hg (5.3K Pa) - 36-44 mm Hg. PaCO2 above > 44 mm Hg respiratory acidemia due to ventilatory failure Decrease of PCO2 (<36 mm Hg) due to respiratory alkalosis . 95% ofCO2 produced is transported by the RBC 5% by plasma in dissolved (dCO2) and 0.1% as chemically dissolved (carbonic acid ). The total CO2 (TCO2 ) includes dCO2 and H2CO3. For every 20 mm of Hg increase of PaCO2, pH falls by 0.1 unit For every 10 mm of Hg fall of PaCO2, pH increases by 0.1.

45. 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

46. Respiratory acidosis The biochemical findings are: pH < 7.35 paCO 2 > 45 mm of Hg ( Hypercapnia ). Renal compensation occurs in 3-5 days. compensatory metabolic alkalosis. Acute respiratory acidosis 1mmol increase- for every 10 mm of Hg PaCO2 Chronic respiratory acidosis, 3.5 mmol of bicarbonate for every 10mmof Hg PaCO2

47. 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

48. 56 Respiratory Alkalosis Conditions that stimulate respiratory center: Oxygen deficiency at high altitudes Pulmonary disease and Congestive heart failure – caused by hypoxia Acute anxiety ,Fever , anemia Early salicylate intoxication Cirrhosis, Gram-negative sepsis

49. 57 Compensation of Respiratory Alkalosis Mechanism:  Renal loss of bicarbonate causes a further fall in plasma bicarbonate (in addition to the acute drop due to the physicochemical effect and protein buffering). Magnitude:  An average 5 mmol /l decrease in [HCO3 - ] per 10mmHg decrease in pCO2 from the reference value of 40mmHg. This maximal response takes 2 to 3 days to reach. Limit:  The limit of compensation is a [HCO3 - ] of 12 to 15 mmol /l.

50. 58 Diagnosis of Acid-Base Imbalances Note whether the pH is low (acidosis) or high (alkalosis) Decide which value, pCO 2 or HCO 3 - , is outside the normal range and could be the cause of the problem. If the cause is a change in pCO 2, the problem is respiratory. If the cause is HCO 3 - the problem is metabolic.

51. 59 3. Look at the value that doesn’t correspond to the observed pH change. If it is inside the normal range, there is no compensation occurring. If it is outside the normal range, the body is partially compensating for the problem . A patient is in intensive care because he suffered a severe myocardial infarction 3 days ago. The lab reports the following values from an arterial blood sample: pH 7.3 HCO3- = 20 mEq / L ( 22 - 26) pCO2 = 32 mm Hg (35 - 45)

52. 60 Diagnosis Metabolic acidosis With compensation

53. Winter’s formula Predicted pCO2 = 1.5 x HCO3 + 8 ± 2 ( measured bicarbnate ) Measured pCO2 = Predicred pCO2 (Pure Metabolic acidosis ) Measured pCO2 > Predicred pCO2 (Metabolic acidosis & Respiratory acidosis) Measured pCO2 < Predicred pCO2 (Metabolic acidosis & Respiratory alkalosis)

54. pH: 7.35 – 7.45 PCO2: Males: 35 – 48 mm Hg Females: 32 – 45 mm Hg HCO3: 22 – 27 mEq /L Base Excess: New born (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

55. 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

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