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Alcohol induced metabolic alterations - A Case based discussion


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I shall proceed through a case based discussion and highlight a few of the metabolic alterations that have been found in the patient under study and of course these are the commonest metabolic alterations that change the whole scenario.
The objective of my discussion is to provide you with a solid foundation of alcohol induced metabolic alterations. The knowledge thus acquired will help you to make spontaneous diagnosis and plan the relevant treatment in the clinical settings.
The case details are with you. There are 3 questions related to the problems the patient is having in this case, and there are 4 options for each of the questions. Using your prior knowledge, try to select the most appropriate answer, you have only one minute to solve the answer.

Published in: Health & Medicine

Alcohol induced metabolic alterations - A Case based discussion

  1. 1. Alcohol induced MetabolicAlcohol induced Metabolic AlterationsAlterations Namrata Chhabra, M.D. 1Namrata Chhabra, M.D.Biochemistry
  2. 2. AlcoholAlcohol Everything comes at a price 2Namrata Chhabra, M.D.Biochemistry
  3. 3. 3Namrata Chhabra, M.D.Biochemistry
  4. 4. Major pathway of Alcohol metabolism 4Namrata Chhabra, M.D.Biochemistry
  5. 5. Products of Alcohol Metabolism 5Namrata Chhabra, M.D.Biochemistry
  6. 6. Case details • A 60 year old man was brought to hospital in a very serious condition. • The patient complained of o Constant vomiting containing several hundred mL of dark brown fluid from the previous two days plus o Several episodes of melaena. 6Namrata Chhabra, M.D.Biochemistry
  7. 7. Past History • Past history of alcoholism, cirrhosis, portal hypertension and a previous episode of bleeding varices was there. • Sclerotherapy for the varices had been performed several months earlier at another hospital. 7Namrata Chhabra, M.D.Biochemistry
  8. 8. Examination • The patient had jaundice and was in distress, sweaty, clammy and tachypnoeic. • BP 98/50 mmHg, pulse 120/min. • Heart sounds - systolic murmur. • Peripheries were cold. • Abdomen was soft and non tender. • Signs of chronic liver disease were present (spider naevi, gynecomastia, and testicular atrophy). 8Namrata Chhabra, M.D.Biochemistry
  9. 9. Laboratory Findings Test Result Reference 1) Blood glucose-50mg/dl 65-110 mg/dL 2) Lactate 20.3 mmol/L 0.44- 1.8mmol/L 3) Urea Nitrogen- 38.6mg/dl 8-25 mg/dL 4) Creatinine- 1.24mg/dl 0.7-1.5mg/dL 5) Uric acid- 9.8 mg/dL 3-7 mg/dL 6) Blood alcohol -550 mg/dlNo alcohol 9Namrata Chhabra, M.D.Biochemistry
  10. 10. Laboratory findings (contd.) Test Result Reference 7) Na+ 131 mmol/l 136-145 mmol/l. 8) Cl- 85 mmol/l 96-106 mmol/l. 9) K+ 4.2 mmol/l 3.5-5.5 mmol/L 10) HCO3- 14.1 mmol/l 22-28 mmol/l. 10Namrata Chhabra, M.D.Biochemistry
  11. 11. Laboratory findings (contd.) Test Result Reference 11) pH 7.21 7.35-7.45 12) pCO2 13.8 mmHg 35-45 mm Hg 13) pO2 103 mmHg 80-100 mm Hg 14) Hb 6.2 G/dL 14-18 G/dL 15) W.B.C. count 18 x103 /mm3 5-10/ mm3 11Namrata Chhabra, M.D.Biochemistry
  12. 12. What is your diagnosis ? 12Namrata Chhabra, M.D.Biochemistry
  13. 13. • The patient has multiple problems • Circulatory failure • GI bleeding on a background of known Cirrhosis with Portal hypertension • Many other ?? Some Hints??? 13Namrata Chhabra, M.D.Biochemistry
  14. 14. Some more hints ?? The patient has • Low Blood glucose (Hypoglycemia) • High Lactate • High Uric acid, BUN and creatinine • Electrolyte imbalance • Acid Base imbalance • Low Hb and high W.B.C. Count 14Namrata Chhabra, M.D.Biochemistry
  15. 15. 15Namrata Chhabra, M.D.Biochemistry
  16. 16. • The blood glucose level in this patient is 50 mg/dL, well below the normal range of 65-110 mg/dL. Let’s find out the cause 16Namrata Chhabra, M.D.Biochemistry
  17. 17. 17 Hypoglycemia results from an imbalance between demand and supply of glucose Namrata Chhabra, M.D.Biochemistry
  18. 18. Which of the following conditions best explains the underlying cause of hypoglycemia in this patient? A. Impaired activity of Glycogen phosphorylase B. Impaired activity of Glucose-6-Phosphatase C. Impaired activity of Pyruvate Kinase D. Reduced availability of substrates of Gluconeogenesis 18Namrata Chhabra, M.D.Biochemistry
  19. 19. A) Impaired activity of Glycogen phosphorylase? 19Namrata Chhabra, M.D.Biochemistry
  20. 20. B) Impaired activity of Glucose-6- Phosphatase ? 20Namrata Chhabra, M.D.Biochemistry
  21. 21. C)Impaired activity of Pyruvate kinase? 21Namrata Chhabra, M.D.Biochemistry
  22. 22. D)Reduced availability of substrates of gluconeogenesis 22Namrata Chhabra, M.D.Biochemistry
  23. 23. 23Namrata Chhabra, M.D.Biochemistry
  24. 24. Alcohol metabolism affects availability of substrates of gluconeogenesis 24Namrata Chhabra, M.D.Biochemistry
  25. 25. 25Namrata Chhabra, M.D.Biochemistry
  26. 26. Correct answer is -D 26Namrata Chhabra, M.D.Biochemistry
  27. 27. 27Namrata Chhabra, M.D.Biochemistry
  28. 28. 28Namrata Chhabra, M.D.Biochemistry
  29. 29. 2) What is the cause of Lactic Acidosis in this patient ? A. Reversal of reaction catalyzed by lactate dehydrogenase B. Impaired activity of PDH complex C. Suppressed TCA cycle D. All of the above. 29Namrata Chhabra, M.D.Biochemistry
  30. 30. A) Reversal of reaction caused by Lactate dehydrogenase? Pyruvate is converted to lactate to regenerate NAD +. 30Namrata Chhabra, M.D.Biochemistry
  31. 31. B) Impaired activity of PDH complex ? 31Namrata Chhabra, M.D.Biochemistry
  32. 32. C) Suppressed activities of TCA cycle enzymes? TCA cycle 32Namrata Chhabra, M.D.Biochemistry
  33. 33. 33Namrata Chhabra, M.D.Biochemistry
  34. 34. 34 The correct answer is D Namrata Chhabra, M.D.Biochemistry
  35. 35. 35Namrata Chhabra, M.D.Biochemistry
  36. 36. • The very low pH indicates a severe acidosis. • The combination of a low pCO2 and low bicarbonate indicates that it is metabolic acidosis. 36Namrata Chhabra, M.D.Biochemistry
  37. 37. Determination of Acid base status pH H+ P CO2 HCO3 - Normal 7.4 40 mEq/L 40mm Hg 24 mEq/L Respiratory acidosis Respiratory Alkalosis Metabolic acidosis Metabolic Alkalosis R O M E 37Namrata Chhabra, M.D.Biochemistry
  38. 38. A.G Cl- mEq/L A.G Cl- mEq/L Na+ mEq/L Na+ mEq/L Na+ mEq/L A.G HCO3 - mEq/L HCO3 - mEq/L HCO3 - mEq/L Cl- mEq/L A B C A- Normal Ion Distribution B- High anion gap metabolic acidosis C- Normal anion gap acidosis Anion Gap 38Namrata Chhabra, M.D.Biochemistry
  39. 39. Normal or high anion gap metabolic acidosis ? • The anion gap is 42 indicating the presence of a high anion gap disorder. • The lactate level of 20.3mmol/l is extremely high and this is responsible for causing high anion gap. 39Namrata Chhabra, M.D.Biochemistry
  40. 40. High anion gap acidosis • High anion gap is also there due to underlying Ketoacidosis. • Acetyl co A fails to get utilized in TCA cycle, and the excess is channeled towards alternative pathways. 40Namrata Chhabra, M.D.Biochemistry
  41. 41. 41Namrata Chhabra, M.D.Biochemistry
  42. 42. • Gouty arthritis is a common finding in chronic alcoholics • Gout results from an increased body pool of urate with hyperuricemia. • It is typically characterized by episodic acute and chronic arthritis, due to deposition of Mono sodium urate crystals in and around joints. 42Namrata Chhabra, M.D.Biochemistry
  43. 43. 43Namrata Chhabra, M.D.Biochemistry
  44. 44. • In the given patient, serum uric acid concentration is higher than normal (9.8 mg/dL). • What is the cause of Hyperuricemia in this patient? 44Namrata Chhabra, M.D.Biochemistry
  45. 45. A. Inhibition of salvage pathway of purine nucleotide biosynthesis B. Overactive denovo pathway of purine nucleotide biosynthesis C. Overactive xanthine oxidase D. Impaired excretion of uric acid 45Namrata Chhabra, M.D.Biochemistry
  46. 46. A) Inhibition of salvage pathway? PRPP Synthetase 46Namrata Chhabra, M.D.Biochemistry
  47. 47. B. Overactive denovo pathway of purine nucleotide biosynthesis PRPP Synthetase 47Namrata Chhabra, M.D.Biochemistry
  48. 48. C. Over active Xanthine oxidase ? PRPP Synthetase 48Namrata Chhabra, M.D.Biochemistry
  49. 49. D. Impaired uric acid excretion ? 49Namrata Chhabra, M.D.Biochemistry
  50. 50. 50Namrata Chhabra, M.D.Biochemistry
  51. 51. The correct answer is D-Impaired uric acid excretion 51Namrata Chhabra, M.D.Biochemistry
  52. 52. • Additionally hyperuricemia in chronic alcoholism is also due to some other factors 52Namrata Chhabra, M.D.Biochemistry
  53. 53. Excess purine nucleotide degradation 53Namrata Chhabra, M.D.Biochemistry
  54. 54. High purine content in alcoholic beverages ? • The higher purine content in some alcoholic beverages such as beer is also an additional factor. 54Namrata Chhabra, M.D.Biochemistry
  55. 55. 55Namrata Chhabra, M.D.Biochemistry
  56. 56. • Urea and creatinine are elevated (renal failure) • Electrolyte imbalance resulting from acidosis and associated renal failure • Low Hb - Bleeding and associate nutritional deficiencies • High W.B.C. Count- Sepsis • Low blood pressure -Circulatory failure 56Namrata Chhabra, M.D.Biochemistry
  57. 57. 57Namrata Chhabra, M.D.Biochemistry
  58. 58. • Cirrhosis and portal hypertension with bleeding varices and • Sepsis, resulting in shock, • Lactic acidosis, anemia and • Renal failure. 58Namrata Chhabra, M.D.Biochemistry
  59. 59. 59Namrata Chhabra, M.D.Biochemistry
  60. 60. 60Namrata Chhabra, M.D.Biochemistry
  61. 61. Implications of excess Acetate 61Namrata Chhabra, M.D.Biochemistry
  62. 62. 62Namrata Chhabra, M.D.Biochemistry
  63. 63. 63Namrata Chhabra, M.D.Biochemistry
  64. 64. 64Namrata Chhabra, M.D.Biochemistry