University:
Western Sydney University
Course:
MEDI 2003 | Clinical Sciences 2
Academic year:

2024
Views:

482

Pages:

4
Author:

Mariam A. A.

• • • Pharmacokinetics of ethanol Absorption o Oral o Both water and fat soluble o Rapidly absorbed from stomach, small intestine (>80%) and colon o Maximal blood concentration within 30-90 minutes o Total absorption is unaffected by food (just the speed) o Can also be absorbed and exhaled through the lungs Distribution o Uniformly distributed throughout tissues and body fluids including the brain o Readily crosses the placenta to expose foetus ▪ Foetal alcohol syndrome: mental and physical defects Metabolism o >95% is metabolised by alcohol dehydrogenase ▪ 85% in the liver ▪ 15% in the stomach 1 Oxidation of ethanol to acetaldehyde (alcohol dehydrogenase containing coenzyme NAD+) • Rate is constant (zero order kinetics) because ADH is saturated 2 Acetaldehyde is oxidised to acetic acid and then to CO2 + H2O via citric acid cycle • Acetaldehyde is approx. 30 x more toxic than alcohol → severe toxicity results if not converted • Disulfiram (medication) inhibits ALDH • Acetate is a precursor for FA synthesis • Elimination o Minor routes are: ▪ Urinary excretion ▪ Exhalation Alcoholic liver disease (3 overlapping forms) • Hepatic steatosis o Aka fatty change, fatty/adipose degeneration o Abnormal retention of lipids within a liver cell • Alcoholic hepatitis o Inflammation of the liver caused by EtOH • Cirrhosis o Replacement of liver tissue by fibrous scar tissue and regenerative nodules (lumps that occur when damaged tissue is regenerated) → progressive loss of liver function Hepatic steatosis • Occasional moderate amounts of EtOH → small lipid droplets (microvesicular) o E.g. 3 bottles of wine per week • Chronic EtOH intake → large lipid globules (macrovesicular) → compress and displace nucleus to periphery of hepatocyte • Excess supply of alcohol/acetate leads to FA synthesis o Alcohol dehydrogenase + acetaldehyde dehydrogenase generates excessive acetate and NADH → used in the production of FAs o Impaired biosynthesis and secretion of lipoproteins → decreased peripheral catabolism of fat Alcoholic hepatitis • Regarded as earliest stage of liver disease • Pathology o Ballooning degeneration o • ▪ Hepatocytes swell up with excess fat, water and protein ▪ Swelling blocking nearby biliary ducts → diffuse cholestasis ▪ Necrotic damage Inflammation ▪ Necrotic changes → cellular debris → trigger neutrophilic invasion ▪ Ordinarily the amount of debris is removed by Kupffer cells however inflammation they become overloaded → neutrophils spill into parenchyma Treatment o Most patients the illness is mild → no specific treatment required, alcohol use must be stopped, good nutrition + supplemental vitamins and minerals including folate and thiamine o Severe alcoholic hepatitis (major sign = acute development of encephalopathy): high risk of early death (rate 50% of greater within 30 days) ▪ Patients should be in ICU until liver function is stable ▪ May benefit over the short term from specific therapies directed towards reducing liver injury, enhancing hepatic regeneration and suppressing inflammation • Glucocorticosteroids are used for this although benefits not completely proven Alcoholic cirrhosis: irreversible and final form of alcoholic liver disease • Hepatic cell death leads to inflammation