Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. A chronic alcoholic with severe metabolic acidosis presents a difficult diagnostic problem. The most common cause is alcoholic ketoacidosis, a syndrome with a typical history but often misleading laboratory findings. This paper will focus on this important and probably underdiagnosed syndrome. 2. The disorder occurs in alcoholics who have had a heavy drinking-bout culminating in severe vomiting, with resulting dehydration, starvation, and then a beta-hydroxybutyrate dominated ketoacidosis. 3. Awareness of this syndrome, thorough history-taking, physical examination and routine laboratory analyses will usually lead to a correct diagnosis. 4. The treatment is simply replacement of fluid, glucose, electrolytes and thiamine. Insulin or alkali should be avoided. 5. The most important differential diagnoses are diabetic ketoacidosis, lactic acidosis and salicylate, methanol or ethylene glycol poisoning, conditions which require quite different treatment. 6. The diagnostic management of unclear cases should always include toxicological tests, urine microscopy for calcium oxalate crystals and calculation of the serum anion and osmolal gaps. 7. It is suggested here, however, that the value of the osmolal gap should be considered against a higher reference limit than has previously been recommended. An osmolal gap above 25 mosm/kg, in a patient with an increased anion gap acidosis, is a strong indicator of methanol or ethylene glycol intoxication.
 ...
PMID:Severe metabolic acidosis in the alcoholic: differential diagnosis and management. 879 30

The role of the microsomal ethanol-oxidizing system (MEOS) in hepatic ethanol metabolism is reviewed, with focus on its constitutive, ethanol-inducible cytochrome P-4502E1 (2E1). The MEOS was purified and reconstituted using 2E1, phospholipids, and cytochrome P-450 reductase and shown to oxidize ethanol to acetaldehyde, mainly as a monooxygenase and secondarily via hydroxyl radicals, with transcriptional and posttranscriptional regulation. Polymorphism of 2E1 was recognized, and enzymology (including cofactors, role of lipids, inducers, and inhibitors) as well as cellular and tissue distribution were chartered. Physiological functions involve lipid metabolism and ketone utilization in starvation, obesity, and diabetes. The most significant role of 2E1 is its adaptive response to high blood ethanol levels with a corresponding acceleration of ethanol metabolism. The associated free radical production, however, contributes to liver injury in the alcoholic. Most importantly, 2E1 has a unique capacity to activate many xenobiotics (85 of which are listed) to hepatotoxic or carcinogenic products. Induction of 2E1 also results in enhanced production of acetaldehyde, a highly reactive and toxic metabolite. The proliferation of the endoplasmic reticulum associated with 2E1 induction is also accompanied by enhanced activity of other cytochrome P-450s, resulting in accelerated metabolism of, and tolerance to, other drugs, as well as increased degradation of retinol and its hepatic depletion. Some substrates and metabolites, however, are innocuous and may eventually be used as markers of heavy drinking. Recently discovered effective 2E1 inhibitors also have great therapeutic potential.
 ...
PMID:Cytochrome P-4502E1: its physiological and pathological role. 911 22