Metabolic Acidosis

Brief introduction of metabolic acidosis, causes, investigations and management.

1. Metabolic Acidosis Dr. Muhammad Usama Azhar Post Graduation Resident Internal Medicine

2. Objectives We will learn the following topics: Metabolic Acidosis Definition Causes Investigations Management Interpretation of Blood Gas Analysis Simple and Mixed Acid-Base Disorders

3. What is Acidosis?

4. Acidemia vs Acidosis Acidemia: when blood pH <7.35 Acidosis: is a process that increases [H+] or process which tends to ↓pH (accumulation of acid in body)

5. Mechanism: gain of H+ loss of HCO3 Results in : ↓ pH (7.35 ) ↓ HCO3- (<22mEq/L ) pCO2 depends on compensation

6. Compensation in Metabolic Acidosis Hyper-ventilation to ↓ PaCO 2 = Kasmaul Breathing The maximal compensation takes 12 to 24 hours The increase in ventilation usually starts within minutes, usually well advances at 2 hours of onset, but maximal compensation may take 12 to 24 hours to develop. Compensation can never normalize pH, it can improve it.

7. Anion Gap Anion gap = ([ Na+] ) − ( [Cl−] + [HCO3− ]) As sodium is the main extracellular cation , and chloride and bicarbonate are the main anions, the result should reflect the remaining anions.

8. Normally, this concentration is about 8-16 mmol/l (12±4 ). An elevated anion gap (i.e. > 16 mmol/l) can indicate particular types of metabolic acidosis, particularly certain poisons, lactate acidosis and ketoacidosis.

9. Classfication Metabolic Acidosis can be divide into 2 groups: Raised anion gap acidosis Normal anion gap acidosis

10. High  Anion   Gap Metabolic   Acidosis M-Methanol U-Uremia (chronic kidney failure ) D-Diabetic ketoacidosis P-Propylene glycol I- Infection, Iron, Isoniazid, Inborn errors of metabolism L-Lactic acidosis E-Ethylene glycol

11. High Anion Gap Metabolic Acidosis Endogenous Ketoacidosis Diabetic Alcoholic Starvation Lactic acidosis Uremia Exogenous Methanol Ingesion Ethanol Ethylene glycol Isoniazid Salicylates poisoning

12. Normal  Anion Gap Metabolic Acidosis Bicarbonate loss through Gut Diarrhea Pancreatic fistula Uretero-sigmoidostomy Bicarbonate loss through Kidney Renal tubular acidosis Carbonic anhydrase inhibtors Post-hypocapnea

13. Diabetic Ketoacidosis Due to the overproduction of ketone bodies (Ketosis) leading to accumulation of ketones in plasma (Ketonemia) and urine (Ketonuria ). In starvation states where plasma glucose levels are low or in states of low plasma insulin where uptake of glucose by cells is diminished, fatty acids will be mobilized and transported to tissues (brain, skeletal muscle, heart) for fatty acid oxidation and energy production .

14. Diabetic Ketoacidosis Acetyl CoA from fatty acid oxidation can not be oxidized and is instead converted to the generation of ketone bodies. ( acetoacetate and β -hydroxybutyrate ) which serve as a source of fuel .

15. Lactic Acidosis Dead-end product of glycolysis Occurs when the body must regenerate ATP without oxygen Normal lactic level is maintained at 0.7-1.3 mEq/L Eliminated in liver (50%), kidneys (25%), heart and skeletal muscles Normal Lactate/Pyruvate ratio suggest that the cause is not related to anaerobic metabolism or anoxia

16. Lactic Acidosis Serum lactate > 5 mEq/L Typte1 hypoxia+peripheral generation of Lactate in patient with circulatory failure+ shock . Type2 impaired metabolism of lactate in liver disease and drug+toxin inhibit lactate metabolism(eg:metformin )

17. Metabolic Acidosis in Renal Failure Normal AG acidosis results from failure of the kidney to generate new HCO3- from a reduced rate of synthesis and excretion of NH4 + (usually GFR 20-50ml/min) Increased AG acidosis results from the reduced GFR, with accumulation of sulfates, urates and phosphates. (usually GFR <15-20ml/min )

18. Methanol Poisoning Methanol is metabolized by alcohol dehydrogenase to formaldehyde and then to formic acid High AG: formic acid, lactic acid, and ketoacid Formaldehyde : optic nerve and CNS toxicity Retinal edema, CNS depression, and unexplained metabolic acidosis with high anion and osmolar gaps

19. Normal Anion Gap Metabolic Acidosis Two main causes 1. Renal 2. Extra-renal Urinary Anion Gap= Na + + K + – Cl - = 0 If positive = Renal If negative = Extra-renal

20. Metabolic Acidosis in Severe Diarrhea It is when the bowel movement occurs more than 5 times a day . The person loses a great amount of bicarbonate ions in the stool and therefore the amount of anions decreases . Bicarbonate ions are important for the blood buffer system . Due loss of these ions the buffer system cannot work properly thus making the blood acidic.

21. Renal Tubular Acidosis •Inability of the kidney to reabsorb the filtered HCO3 Inability of the kidney to excrete NH4+

22. Types of RTA T ype 1 RTA: Distal RTA Type 2 RTA: Proximal RTA Type 4 RTA: Hyperkalemic

23. Type 1 (distal) RTA Defective H +  ion secretion by α- intercalated cells in late DCT & CT  → ↑H +  ions (acidemia) Nephrolithiasis (calcium phosphate stones)  is frequently associated with untreated type 1 RTA. Causes : Sjogren’s syndrome, SLE, liver cirrhosis, and toxins (e.g. amphotericin B, lithium)

24. Type 2 (proximal) RTA Impaired HCO 3 – reabsorption in PCT  → ↑ HCO 3 – loss in urine → ↑ Blood acidity Associated with : Multiple myeloma, Fanconi syndrome, and toxins (e.g. Acetazolamide, outdated tetracycline)

25. Type 4 (hyperkalemic) RTA Aldosterone deficiency/resistance in Collecting Tubules Cause : Addison’s disease, diabetic nephropathy, sickle cell disease, and drugs  (e.g. trimethoprim, NSAIDs, ACE inhibitors, spironolactone).

26. Consequences of Acidemia on various Organ System Cardiovascular System: ↓ contractility Arterial vasodilatation ↓ MAP ↓ CO ↓ response to Catecholamine ↑ risk of arrhythmias

27. Consequences of Acidemia on various Organ System Respiratory System: Hyperventilation(compensatory) ↓ Respiratory Muscle Strength Neurological: Cerebral Vasodilation → ↑ ICP

28. Consequences of Acidemia on various Organ System Metabolic: ↑ Potassium ( Due to H+/K+ pump exchanging excess H+ with Intracellular K +) ↑ Bone resoprtion (In chronic cases) ↑ Phosphate concentration in extracellular fluid

29. Sign & Symptoms Neurological: Headache Drowsiness Comatose Seizures Cardiovascular: Tachycardia Arrythmia Hypotension

30. Sign & Symptoms Respiratory: Shortness of breath Deep and rapid breathing Coughing Gastric : Nausea Vomiting Diarrhea

31. Sign & Symptoms Muscular: Cramps Seizures Generalzied Weakness

32. Investigations Blood Gas Analysis (VBGs or ABGs) Blood Glucose Level Serum Electrolytes Serum Ketones (or Urine Ketones) Serum Lactates Urea and Creatinine ECG

33. Management Emergency Management Treat Underlying Cause Replace Losses Specific Therapy

34. Management Emergency Management: I ntubation and ventilation for airway or ventilatory control ; C ardiopulmonary resuscitation; severe hyperkalaemia Treat Undelying Cause: Treat the underlying disorder as the primary therapeutic goal . Consequently,accurate diagnosis of the cause of the metabolic acidosis is very important .

35. Management Replace Losses: Replace losses (e.g. of fluids and electrolytes) where appropriate.Other supportive care (oxygen administration) is useful. In most cases, IV sodium bicarbonate is NOT necessary, NOT helpful, and may even be harmful so is not generally recommended.

36. Management Specific Treatment: There are often specific problems or complications associated with specific causes or specific cases which require specific management. For example : Ethanol blocking treatment with methanol ingestion; Insulin for diabetic ketoacidosis Haemodialysis can remove some toxins

37. Management Alkali Therapy: Indicated in Normal AG Metabolic Acidosis Raised AG Metabolic Acidosis due to non-metabolizable anions HCO 3 - Deficit= 0.5 x Weight (24-[HCO 3 - ]) Severe Acidemia pH <7.0 in case of Raised AG Metabolic Acidosis (50-100mEq IV NaHCO 3 - over 30-45 minutes) Reference: Harrison’s Principles of Internal Medicine

38. Management of DKA Correction of fluid loss with intravenous fluids Correction of hyperglycemia with insulin Correction of electrolyte disturbances, particularly potassium loss Correction of acid-base balance Treatment of concurrent infection, if present

39. Management of Lactic Acidosis Intravenous fluid to promote circulation Oxygen , delivered with a face mask or another way Positive pressure ventilation to deliver oxygen to the lungs Hemodialysis with bicarbonate Individuals who experience lactic acidosis while exercising can stop what they are doing, rehydrate by drinking water, and rest.

40. Management of RTA Type 1 RTA: NaHCO 3 (1-3mEq/kg/d) Type 2 RTA: NaHCO 3 or KHCO 3 (10-15mEq/kg/d) Thiazide diuretics Type 4 RTA: Fludrocortisone (0.1-0.5mg/d) Dietary restriction Furosemide (40-160mg/d)

41. Scenario 20 year young male diabetic patient presented with fever and vomiting for 1 day. He was drowsy and taking deep and rapid breaths. ABGs showed following findings: pH 7.18 P a CO 2 30mmHg P a O 2 55mmHg HCO 3 - 10mmol/L Na + 140mEq/L Cl - 90meq/L What is the interpretation of ABGs?

42. Blood Gas Analysis History taking and physical examination Identify the primary disturbance Check pH-------- acidemia or alkalemia HCO3- & pCO2 analysis---primary disorder Compensatory responses Calculate Anion Gap Assess delta ratio Formulate acid-base diagnosis

43. Blood Gas Analysis History taking and physical examination Identify the primary disturbance Check pH- ------- acidemia or alkalemia HCO3- & pCO2 analysis---primary disorder Compensatory responses Calculate Anion Gap Assess delta ratio Formulate acid-base diagnosis

44. History taking and physical examination Comprehensive history taking and physical examination can often give clues as to the underlying acid-base disorder

45. Blood Gas Analysis History taking and physical examination Identify the primary disturbance Check pH: acidemia or alkalemia HCO3- & pCO2 analysis: primary disorder Compensatory responses Calculate Anion Gap Assess delta ratio Formulate acid-base diagnosis

46. Identify the Primary Disorder Is there alkalemia or acidemia present? pH < 7.35  acidemia pH > 7.45  alkalemia This is  usually  the primary disorder Remember :  an acidosis or alkalosis may be present even if the pH is in the normal range (7.35 – 7.45) You will need to check the PaCO 2 , HCO 3 - and anion gap

47. Blood Gas Analysis History taking and physical examination Identify the primary disturbance Check pH: acidemia or alkalemia HCO3- & pCO2 analysis: primary disorder Compensatory responses Calculate Anion Gap Assess delta ratio Formulate acid-base diagnosis

48. Identify the Primary Disorder Is the disturbance respiratory or metabolic? What is the relationship between the direction of change in the pH and the direction of change in the PaCO 2 ? In primary respiratory disorders, the pH and PaCO2 change in  opposite  directions; in metabolic disorders the pH and PaCO 2  change in the same direction.

49. Identify the Primary Disorder Acidosis Respiratory pH ↓  PaCO 2   ↑ Acidosis Metabolic pH ↓ PaCO 2   ↓ Alkalosis Respiratory pH ↑ PaCO 2   ↓ Alkalosis Metabolic pH ↑ PaCO 2    ↑

50. Blood Gas Analysis History taking and physical examination Identify the primary disturbance Check pH: acidemia or alkalemia HCO3- & pCO2 analysis: primary disorder Compensatory responses Calculate Anion Gap Assess delta ratio Formulate acid-base diagnosis

51. Compensatory Response Is there appropriate compensation for the primary disturbance ? Usually , compensation does  not  return the pH to normal (7.35 – 7.45).

52. Disorder Expected compensation Metabolic acidosis P a CO 2 = 1.5x[HCO 3 - ] + 8 ± 2 Metabolic alkalosis P a CO 2 = 0.9x[HCO 3 - ] + 16 ± 2 Acute respiratory acidosis [HCO 3 - ] = 24 + x 1 Chronic respiratory acidosis [HCO 3 - ] = 24 + x 4 Acute respiratory alkalosis [HCO 3 - ] = 24 - x 2 Chronic respiratory alkalosis [HCO 3 - ] = 24 - x 5 Disorder Expected compensation Metabolic acidosis P a CO 2 = 1.5x[HCO 3 - ] + 8 ± 2 Metabolic alkalosis P a CO 2 = 0.9x[HCO 3 - ] + 16 ± 2 Acute respiratory acidosis Chronic respiratory acidosis Acute respiratory alkalosis Chronic respiratory alkalosis

53. Blood Gas Analysis History taking and physical examination Identify the primary disturbance Check pH: acidemia or alkalemia HCO3- & pCO2 analysis: primary disorder Compensatory responses Calculate Anion Gap Assess delta ratio Formulate acid-base diagnosis

54. Anion Gap Calculate the anion gap AG = [Na+]-( [Cl-] + [HCO 3 -] )=12 ± 2 A normal anion gap is approximately 12 meq/L .

55. Anion Gap It is important to remember what the expected “normal” anion gap for your patient should be, by adjusting for hypoalbuminemia. Calculate corrected sodium before measurement of anion gap.

56. Corrected Anion Gap for Hypoalbuminemia Normal Anion Gap is 12±2 mmol/L (at Serum Albumin level 4g/dL) Corrected AG = AG + (2.5 x (4-albumin) expressed in g/dL Every 1g/dL decrease in serum albumin will decrease 2.5mmol/L of anion gap.

57. Corrected Sodium for Hyperglycemia Corrected Na + = measured Na + + [ 1.6(glucose–100)/100] Glucose is taken in mg/dL. This forumla is according to Katz,1973; correction factor is 2.4 according to Hillier,1999.

58. Blood Gas Analysis History taking and physical examination Identify the primary disturbance Check pH: acidemia or alkalemia HCO3- & pCO2 analysis: primary disorder Compensatory responses Calculate Anion Gap Assess delta ratio Urine anion gap Formulate acid-base diagnosis

59. Delta Ratio If an increased anion gap is present, assess the relationship between the increase in the anion gap and the decrease in [HCO 3 -]. Assess the ratio of the change in the anion gap (∆AG ) to the change in  [HCO3-] (∆[HCO 3 -]): ∆AG/∆[HCO 3 -]

60. Delta Ratio Delta ratio = ∆ Anion gap/∆ [HCO3- ] = (AG-12 )/( 24 - [HCO3- ]) Let’s suppose AG=30, [HCO3- ]= 6, Then Delta ratio = 30-12/24-6 Delta ratio = 18/18 = 1

61. Delta Ratio This ratio should be between 1.0 and 2.0 if an uncomplicated anion gap metabolic acidosis is present. If this ratio falls outside of this range, then another metabolic disorder is present: If   ∆AG/∆[HCO 3 -] < 1.0, then a concurrent non-anion gap metabolic acidosis is likely to be present. If   ∆AG/∆[HCO 3 -] > 2.0, then a concurrent metabolic alkalosis is likely to be present.

62. Scenario 20 year young male diabetic patient presented with fever and vomiting for 1 day. He was drowsy and taking deep and rapid breaths. ABGs showed following findings: pH 7.18 P a CO 2 30mmHg P a O 2 55mmHg HCO 3 - 10mmol/L Na + 140mEq/L Cl - 90meq/L What is the interpretation of ABGs?

63. Blood Gas Analysis History taking and physical examination Identify the primary disturbance Check pH: acidemia or alkalemia HCO3- & pCO2 analysis: primary disorder Compensatory responses Calculate Anion Gap Assess delta ratio Formulate acid-base diagnosis

64. Blood Gas Analysis History = Suspected DKA Identify the primary disturbance Check pH: 7.2 (acidemia) HCO3- & pCO2 analysis: primary disorder Compensatory responses Predicted P a CO 2 = 1.5x[HCO 3 - ] + 8 ± 2 Predicted P a CO 2 = 1.5x10 + 8 ± 2 = 23 ± 2 Measure P a CO 2 > Predicted P a CO 2 = Concomitant Respiratory Acidosis

65. Blood Gas Analysis Calculate Anion Gap AG= Na + - (Cl - + HCO 3 - ) AG= 140 – (90+10) = 140-100= 40 Assess delta ratio Delta ratio = ∆ Anion gap/∆ [HCO3-] = (AG-12)/(24 - [HCO3- ]) =40-12/24-10 =28/14 =2 ( Concomitant Met.Alkalosis)

66. Blood Gas Analysis PaO2 = 55mmHg which is <60mmHg meaning Respiratory Failure Formulate acid-base diagnosis Raised AG Metabolic Acidosis + Metabolic Alkalosis + Respiratory Acidosis and Type II Respiratory Failure