Alcohol induced metabolic alterations - A Case based discussion
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Transcript of Alcohol induced metabolic alterations - A Case based discussion
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Alcohol induced Metabolic Alcohol induced Metabolic AlterationsAlterations
Namrata Chhabra, M.D.
1Namrata Chhabra, M.D.Biochemistry
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AlcoholAlcohol
Everything comes at a price
2Namrata Chhabra, M.D.Biochemistry
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3Namrata Chhabra, M.D.Biochemistry
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Major pathway of Alcohol metabolism
4Namrata Chhabra, M.D.Biochemistry
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Products of Alcohol Metabolism
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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.
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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.
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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).
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Laboratory Findings
Test Result Reference1) Blood glucose-50mg/dl 65-110 mg/dL2) Lactate 20.3 mmol/L 0.44- 1.8mmol/L3) Urea Nitrogen- 38.6mg/dl 8-25 mg/dL4) Creatinine- 1.24mg/dl 0.7-1.5mg/dL5) Uric acid- 9.8 mg/dL 3-7 mg/dL6) Blood alcohol -550 mg/dl No alcohol
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Laboratory findings (contd.)
Test Result Reference7) 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/L10) HCO3- 14.1 mmol/l 22-28 mmol/l.
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Laboratory findings (contd.)
Test Result Reference11) pH 7.21 7.35-7.4512) pCO2 13.8 mmHg 35-45 mm
Hg13) 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
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What is your
diagnosis ?
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• The patient has multiple problems• Circulatory failure• GI bleeding on a background of known
Cirrhosis with Portal hypertension• Many other ??
Some Hints???
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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
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• 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
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17
Hypoglycemia results from an imbalance between demand and supply of glucose
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Which of the following conditions best explains the underlying cause of hypoglycemia in this
patient?
A. Impaired activity of Glycogen phosphorylaseB. Impaired activity of Glucose-6-PhosphataseC. Impaired activity of Pyruvate KinaseD. Reduced availability of substrates of
Gluconeogenesis
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A) Impaired activity of Glycogen phosphorylase?
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B) Impaired activity of Glucose-6-Phosphatase ?
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C)Impaired activity of Pyruvate kinase?
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D)Reduced availability of substrates of gluconeogenesis
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Alcohol metabolism affects availability of substrates of
gluconeogenesis
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Correct answer is -D
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2) What is the cause of Lactic Acidosis in this patient ?
A. Reversal of reaction catalyzed by lactate dehydrogenase
B. Impaired activity of PDH complexC. Suppressed TCA cycleD. All of the above.
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A) Reversal of reaction caused by Lactate dehydrogenase?
Pyruvate is converted to lactate to regenerate NAD +.
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B) Impaired activity of PDH complex ?
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C) Suppressed activities of TCA cycle enzymes?
TCA cycle
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34
The correct answer is D
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• The very low pH indicates a severe acidosis. • The combination of a low pCO2 and low
bicarbonate indicates that it is metabolic acidosis.
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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
ROME
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A.G
Cl- mEq/L
A.G
Cl- mEq/L
Na+
mEq/L Na+
mEq/LNa+
mEq/L
A.G
HCO3-
mEq/L HCO3-
mEq/L
HCO3-
mEq/L
Cl- mEq/L
A B C
A- Normal Ion DistributionB- High anion gap metabolic acidosisC- Normal anion gap acidosis
Anion Gap38Namrata Chhabra, M.D.Biochemistry
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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.
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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.
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• 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.
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• 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?
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A. Inhibition of salvage pathway of purine nucleotide biosynthesis
B. Overactive denovo pathway of purine nucleotide biosynthesis
C. Overactive xanthine oxidaseD. Impaired excretion of uric acid
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A) Inhibition of salvage pathway?
PRPP Synthetase
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B. Overactive denovo pathway of purine nucleotide biosynthesis
PRPP Synthetase
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C. Over active Xanthine oxidase ?
PRPP Synthetase
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D. Impaired uric acid excretion ?
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The correct answer is D-Impaired uric acid excretion
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• Additionally hyperuricemia in chronic alcoholism is also due to some other factors
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Excess purine nucleotide degradation
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High purine content in alcoholic beverages ?
• The higher purine content in some alcoholic beverages such as beer is also an additional factor.
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• 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
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• Cirrhosis and portal hypertension with bleeding varices and
• Sepsis, resulting in shock, • Lactic acidosis, anemia and• Renal failure.
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Implications of excess Acetate
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