LACTIC ACIDOSIS

Pancreatic Hypersecretion REF: Bailey & love 25^th edition page 229, Sabiston Textbook of Surgery, 18th ed chapter 48 “Extensive Ileal resection causes Gastric Hypersecretion, not pancreatic hypersecretion”

Complications of short bowel syndrome include peptic ulceration related to gastric hypersecretion, cholelithiasis because of interruption of the enterohepatic cycle of bile salts, and hyperoxaluria as a result of the increased absorption of oxalate in the colon predisposing to renal stones. Some patients with short bowel syndrome develop a syndrome of slurred speech, ataxia and altered affect. The cause of this syndrome is fermentation of malabsorbed carbohydrates in the colon to D-lactate and absorption of this metabolite. If the distal two thirds of the ileum, including the ileocecal valve, is resected, significant abnormalities of absorption of bile salts and vitamin B₁₂ may occur, resulting in diarrhea and anemia. Treatment necessitates the use of a low carbohydrate diet. Regular parenteral vitamin B12 is required.

Proximal and distal renal tubular acidosis is associated with non anion gap metabolic acidosis. In this, the reciprocal changes in chloride and bicarbonate result in a normal anion gap.

• Lactic acidosis
• Ketoacidosis: Diabetic, alcoholic, starvation
• Toxins: Ethylene glycol, methanol, salicylates, propylene glycol and pyroglutamic acid
• Acute and chronic renal failure

Ref: Harrison’s Principles of Internal Medicine, 18th edn, chapter 47

B i.e. PDH complex

Ans. B i.e. Thiamine

• Vitamin B, (Thiamine) in form of thiamin diphosphate (TDP) or TPP act as a coenzyme for transketolase (in PPP) and 3 dehydrogenase multienzyme complexes i.e. Branched chain, Alpha ketoglutarate and Pyruvate – dehydrogenase enzymes. (Mn “Truly Dehydrated- B AP”)
• Thiamin has a central role in energy yielding metabolism (especially of carbohydrates) as it is required for pyruvate dehydrogenase (converting pyruvate to acetyl CoA in carbohydrate metabolism)Q and a-ketoglutarate dehydrogenase (in citric acid cycle). So its requirement increases on excess intake of carbohydrateQ. And for the same reasons thiamine deficiency causes decreased energy productionQ.
• Because of role of TDP in pyruvate dehydrogenase; thiamin deficiency in subjects on high carbohydrate diet results in increased plasma pyruvate and lactate eventually 1/ t potentially life threatening lactic and pyruvic acidosisQ.
• Thiamin deficiency IR – beriberi, Wernicke- korsakoff syndromeQ, polyneuritis and lactic acidosisQ. Thiamin nutritional status is best assessed by erythrocyte transketolase activationQ.

C i.e. Lactic acidosis

Ans. is ‘a’ i.e., Phenformin; > ‘b’ i.e., Metformin

“Because of higher risk of lactic acidosis, phenformin was withdrawn in many countries and has been banned in India since 2003”.

Ans. is ‘c’ i.e., Phenformin

Answer is D (Tolbutamide) :

Oral hypoglycemics of the biguanide group (Metformin & Phettfelrmin) are known to cause Lactic acidosis. It is not a complication of sulfonylureas such as Tolbutamide, Chlorpropamide etc.

Lactic acidosis

• Lactic acid is produced from pyruvate when oxidative metabolism is reduced and glycolysis is increased.
• Lactic acidosis occurs when the rate of production of lactic acid from pyruvate in muscle, skin brain and erythrocytes exceeds the rate of removal by liver and kidney.

The ingestion of methanol (wood alcohol) causes metabolic acidosis and its metabolites formaldehyde and formic acid cause severe optic nerve and central nervous system damage. Lactic acid^e, Aceto-acids and other unidentified organic acids contribute to the acidosis.

Ans. D: Metformin

Medicinal and toxic causes of lactic acidosis

• Acetaminophen
• Alcohols and glycols (ethanol, ethylene glycol, methanol, propylene glycol)
• Antiretroviral nucleoside analogs (zidovudine, didanosine, lamivudine)
• Beta-adrenergic agents (epinephrine, ritodrine, terbutaline)
• Biguanides (phenformin, metformin)
• Cocaine
• Cyanogenic compounds (cyanide, aliphatic nitriles, nitroprusside)
• Sugars and sugar alcohols (fructose, sorbitol, and xylitol),
• Salicylates
• Strychnine
• Sulfasalazine
• Valproic acid
• Diethyl ether, 5-fluorouracil
• Halothane, propofol
• Isoniazid

Ans. D i.e. Ureterosigmoidostomy

Anion gap

Increased anion gap is seen in:

–        Starvation,

–        Salicylate poisoning,

–        Renal failure etc.