Alcoholic Liver Dx Flashcards
Most common cause of chronic liver dx worldwide
Alcohol
Upper treshold of alcohol in women
14 units/week
Upper treshold of alcohol in men
21 units/week before , now 14 too
Risk factors for ALD
Drinking pattern - common In continuous drinking
Gender -increasing in women
Genetics - patatin-like phospholipase domain-containing 3 (PNPLA3) gene or aka adiponutrin in the pathogenesis of ALD and NAFLD
Nutrition- Obesity increases the incidence of liver dx
Pathophysiology
Alcohol reaches peak blood concentrations @20 minutes -> metabolised almost exclusively by the liver via one of two pathways ->
80% metabolized to acetaldehyde by the mitochondrial enzyme alcohol dehydrogenase -> Acetaldehyde metabolized to acetyl-CoA and acetate by aldehyde dehydrogenase -> generates NADH from NAD -> Acetaldehyde forms adducts with cellular proteins in hepatocytes -> activate immune system -> cell injury
20% of alcohol metabolised by microsomal ethanol-oxidising system (MEOS) pathway Cytochrome CYP2E1 -> oxidises ethanol to acetate. -> releases oxygen free radicals -> lipid peroxidation and mitochondrial damage -> CYP2E1 enzyme also metabolises acetaminophen hence chronic alcoholics more susceptible to hepatotoxicity from low doses of paracetamol.
pro-inflammatory cytokines may also be involved in hepatic damage in alcoholic hepatitis due to endotoxin released into blood because of increased gut permeability leading to release of tumour necrosis factor alpha (TNF-o) and interleukin 1 (IL-1), IL-2 and IL-8 from immune cells ->implicated in the pathogenesis of liver fibrosis
Histology of ALD
Lipogranuloma
Neutrophil infiltration
Macrovesicular steatosis
Fibrosis and cirrhosis
Central hyaline sclerosis
Mallory’s hyaline
Pericellular fibrosis
General ALD clinical features
Enlarged liver
Stigmata or CLD- palmar erythema
3 types of ALD
Fatty liver
Alcoholic hepatitis
Cirrhosis
Clinical features of alcoholic fatty liver dx
Elevated transaminases
No hepatomegaly
Good prognosis
Steatosis disappears after 3 months
Alcohol hepatitis clinical features
Jaundice may take 6 months to resolve
Hepatomegaly
Portal hypertension possible
Bad prognosis (1/3 dead )
Alcoholic cirrhosis clinical features
Variceal hemorrhage
Ascites
ALD investigations
Alcohol misuse and duration in history
Biological markers - macrocytosis with no anemia in alcohol misuse, raised GGT, jaundice
Liver biopsy for liver damage
Pt and bilirubin for Maddrey score
Glasgow score which uses the age, white cell count and renal function, in addition to PT and bilirubin, to assess prognosis l
Management of ALD
Cessation of alcohol consumption single most important and prognostic factor
Nutrition
Drugs - glucocorticoids for short term improvement in mortality to consider
Liver transplant
