Alcohol Related Liver Disease

• Metabolism: (of lipids, proteins, hormones, CHOs, drugs, toxins, foreign compounds) • Synthesis: (of cholesterol, clotting factors, plasma proteins) • Storage: (of glycogen, vitamins, minerals) • Metabolism and excretion of bilirubin

• Steatosis: fatty build up in liver • Acute and chronic alcoholic hepatitis • Fibrosis: any degree of scarring in liver • Cirrhosis: due to long term damage, extreme scarring, will result in liver failure, irreversible

Because the liver is the main site of alcohol metabolism

Fatty build up in the liver, usually resolves upon cessation of alcohol consumption

Fibrosis describes any degree of scarring in the liver. It can be reversed if aetiological agent is removed.

More extensive scarring accompanied with regenerative nodules

• The hepatitis fatty acid (FA) pool is a balance of FA influx from diet, adipose tissue lipolysis, creation of new lipids and disposal of FAs. • An increased uptake and reduced clearance of FAs leads to accumulation of lipids and development of steatosis. • Alcohol interferes with lipid metabolism: the breakdown of alcohol by ADH releases NADH causing the cell to inhibit the breakdown of FAs while simultaneously to increase the synthesis of FAs, creating more lipids than needed and leading to a false sense of energy.

• ADH pathways overwhelmed so alcohol oxidation by MEOS and catalase increases • The MEOS and catalase pathways are more likely to produce harmful by-products that contribute to inflammation

• Alcohol mediated liver steatosis • Inflammatory immune response and oxidative damage 3.Intestinal permeability and consequent intestinal microbiome changes

Infection (due to bacterial overgrowth) and pro inflammatory changes

• **Increased alcohol consumption • obesity • genetics** • being african/hispanic • being female

• Abdo pain and tenderness: inflammation of liver due to steatosis • Dry mouth • Anaemia: due to liver having an input in iron homeostasis • Skin colour changes (jaundice in extreme cases): bruising due to lack of clotting factors, low platelet count, TPO synthesised in liver • Numbness in extremeties 6.Neurological problems: build up of toxins makes its way to brain • Thrombocytopenia: low platelet count due to TPO (thrombopoetin) being synthesised in liver

• Liver panel done to assess liver function • Liver enzymes AST:ALT ratio greater than 1 an indication of ARLD • Raised GGT (liver enzyme) linked to ARLD • Low albumin count in liver disease • Increase in bilirubin

1. FBC -> PLT levels 2. Clotting screen 3. Serum ferritin (increase with ARLD)

• Biopsy

Fatty deposits marked by areas of clearing

Collagen deposition (staining changes)

Collagen deposition and changes to vasculature

• Portal hypertension • Ascites • Cancer

Increased pressure within the portal venous system

• Cirrhosis and scarring of liver -> architectural changes • Blood forced through smaller blood vessels • Increased resistance • Increased blood pressure

A condition where fluid collects in spaces within the abdo (especially the peritoneal cavity)

• Portal hypertension and vasodilation combined with: • Reduced plasma protein synthesis (esp albumin) and therefore reduced oncotic pressure

• Abdo swelling • Abdo discomfort • Weight gain • Early satiety • Shortness of breath