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Alcoholics – Episode 289 - Step 1, Step 2CK, Step 3Alcohol withdrawal must be treated with benzodiazepine. Long acting benzo for prophylaxis – chlordiapoxide – to prevent sequelae of alcohol withdrawal.Vignette where delirium tremens is tested – person needs surgery after being in an accident. Treat alcohol use disorder with naltrexone or acamprosate. Get into AA. Where is alcohol absorbed? Stomach and small intestine (duodenum). Then goes to liver to be metabolized. Alcohol → acetaldehyde → acetic acid. CYP2E1 metabolizes alcohol. Alcohol has zero order elimination (phenytoin, ethanol, aspirin (PEA = 0 order) – all eliminated in fixed amount per unit of time). ↑Acetic acid → ↑Acetyl CoA. (A.CoA is used to make triglycerides. So, fatty liver develops.)Acetaldehyde dehydrogenase (AADH) is found in stomach and liver. But women have less AADH in gastric lining and therefore, women have higher bioavailability of alcohol compared to men. HY: Know the enzymes that metabolize alcohol!! Men v. women differences!Both enzymes that metabolize alcohol are dehydrogenases. Therefore, they produce NADH. Therefore, any reaction where NADH is a reactant is going to have more reactants to work with. What are these reactions?Pyruvate → lactate (this happens in glycolysis to make NAD+)Acetoacetate → beta hydroxybutarateDihydroxyacetone phosphate → glycerol 3 phosphate (from here, can make triglycerides 3TG. So, alcoholics develop fatty liver from buildup of 3TG.Because of the buildup of lactate, alcoholics will have lactic acidosis! So, on exam, pick the answer choice that has low bicarb. Because of buildup of beta hydroxybutarate, alcoholics will also have ketoacidosis.Alcoholics have high anion gap metabolic acidosis.Pyruvate is necessary for gluconeogenesis. Alcoholics have depleted pyruvate in the process of making lactic acid, so they are hypoglycemic. NBME: 2 AST: 1 ALT (or think appreciably higher). Why? Alcohol kills mitochondria. AST is a mitochondrial enzyme. Death of mitochondria releases lots of AST.For lipid metabolism – need lots of smooth endoplasmic reticulum. Important enzyme for smooth ER is GGT. Therefore, alcoholics have elevated GGT. (HY)Excretion in kidney: lactic acid and beta hydroxybutarate are excreted from the body by the same transporters that also excrete uric acid. Because of competition, there can be an underexcretion of uric acid resulting in gout. There can also be nephrolithiasis. Alcohol prevents reabsorption of folate in gut. This results in low folate and megaloblastic anemia. DNA synthesis will slow down and MCV > 100. Folate deficiency: Homocysteine levels will be increased but methylmalonic acid will be normal.Alcohol is toxic to muscle. If an alcoholic passes out for hours, muscle is not being used. This results in rhabdomyolysis. Released myoglobin affects kidneys and causes acute tubular necrosis. If urine analysis shows 3+ blood but microscopy shows NO RBC, then you are dealing with myoglobin and muscle breakdown. Vignette stem: red urine and increased creatinine. Alcohol is metabolized by CYP 450 system, specifically CYP2E1. In chronic alcoholism, CYP450 is revved up! Other drugs will be metabolized quickly. In acute alcoholism, CYP 450 is inhibited, so other drug metabolism is inhibited. Heme pathway will be worse, such as porphyria cutania tarda or acute intermittent porphyria. Disulfram used for alcoholic prevention. First use, naltrexone and acamprosate. Aside: metronidazole or flagyl can cause disulfram like reaction. Alcoholism can cause infertility including erectile dysfunction. Any cells that have high mitochondrial content will be killed off. In men, this results in smaller testes, lower testosterone levels (therefore, low libido). Abnormal philtram (indistinct or barely distinct, smooth groove between mouth and nose), VSD (cardiac defect) in fetal alcoholic syndrome. Esophagus tear: Mallory Weiss tear present in alcoholics or blood in expectorate. Hemodynamically stable otherwise in MW syndrome. Boerhaave syndrome: hemodynamically unstable and requires immediate surgery. If you see presentation of subcutaneous emphysema, person in shock, pneumopericardium, pneumomediastinum. Use water soluble contrast enema or gastrography and NOT barium.Liver failure → portal hypertension → esophageal varices (BIG problem). Damage to acinar cells of pancreatic enzymes → acute pancreatitis. In chronic pancreatitis, pancreas is calcified and low insulin leading to diabetes and fat malabsorption with oily stool. Must stve pancrealipese as treatment. Answer is almost always not pancreatic resection.Cerebellum: atrophy of purkinje fibers and cerebral cortex atrophy due to mitochondrial death and apoptosis. Shearing of bridging veins leads to subdural hematoma because the brain is atrophied, and the smaller brain is dancing around in a fixed box. Wernicke-Korsakoff: thiamine (B1) deficiency. Wernicke: Triad of confusion, ophthalmoplegia (nystagmus), ataxia (movement problem). This is reversible. Korsakoff: Amnesia (retrograde or anterograde), confabulation (problem with memory source, person agreeing with false statements). This is irreversible.Caused by:Low reabsorption of thiamineEnzymes that convert thiamine to its active co-factor form such as thiamine diphosphate or thiamine pyrophosphate are destroyed by alcohol. So the processes that need thiamine as a co-factor to work are no longer working. Thiamine is stored in the liver and now liver is doing all the work of storing fat which is not their primary job. That is job of adipose tissue. TC uses TLC for NANCY?!?Branching AA use TLC for NANCY?!?Treat in ED: give IV thiamine before IV glucose to people with hypoglycemia.WK present in person missing stomach (gastrectomy), chronic malnourished (immigrant who eats polished rice which is not fortified with thiamineLoss of thiamine means lower ATP produced as energy generating pathways require thiamine to work. Mamillary bodies of brain: atrophy or infarctionCardiac muscle: needs tons of ATP. Dilated ischemic cardiomyopathy. Called Beri-Beri in NBME exams. Thiamine requires magnesium to work Hypomagnesemia – can cause hypocalcemia (do not respond to calcium repletion), hypokalemia (do not respond to potassium repletion), prolonged QT interval.Treatment for methanol poisoning: fomepizole as it inhibits alcohol dehydrogenase. ................
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