Monday, August 4, 2008

Can someone explain the pathophysiology of how diabetes mellitus causes lactic acidosis


Can someone explain the pathophysiology of how diabetes mellitus causes lactic acidosis?

Diabetes - 2 Answers
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1 :
Diabetes Pathophysiology An understanding of the pathophysiology of diabetes rests upon knowledge of the basics of carbohydrate metabolism and insulin action. Following the consumption of food, carbohydrates are broken down into glucose molecules in the gut. Glucose is absorbed into the bloodstream elevating blood glucose levels. This rise in glycemia stimulates the secretion of insulin from the beta cells of the pancreas. http://www.health.am/db/diabetes-pathophysiology
2 :
Lactic acidosis is the most common cause of metabolic acidosis in hospitalized patients. It is associated with an elevated anion gap and a plasma lactate concentration above 4 meq/L. Impaired tissue oxygenation, leading to increased anaerobic metabolism, is usually responsible for the rise in lactate production. (See "Approach to the adult with metabolic acidosis"). The pathophysiology and causes of lactic acidosis will be reviewed here. The possible role of bicarbonate therapy in such patients is discussed separately. (See "Bicarbonate therapy in lactic acidosis"). PATHOPHYSIOLOGY — A review of the biochemistry of lactate generation and metabolism is important in understanding the pathogenesis of lactic acidosis. Both overproduction and underuse of lactate appear to be operative in most patients. Lactic acid is derived from the metabolism of pyruvic acid; this reaction is catalyzed by lactate dehydrogenase and involves the conversion of NADH into NAD+ (reduced and oxidized nicotine adenine dinucleotide, respectively). Normal subjects produce 15 to 20 mmol/kg of lactic acid per day, most of which is generated from glucose via the glycolytic pathway or from the deamination of alanine [1,2]. Lactic acid is rapidly buffered, in part by extracellular bicarbonate, resulting in the generation of lactate. In the liver and, to a lesser degree, in the kidney, lactate is metabolized back to pyruvate, which is then converted into either carbon dioxide and water (80 percent, catalyzed in part by pyruvate dehydrogenase) or glucose (20 percent, catalyzed in part by pyruvate carboxylase). Both of these processes result in the regeneration of the bicarbonate lost in the initial buffering of lactic acid. And now you know the rest of the story !




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