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The liver and its diseases

The liver and its diseases. Emyr Wyn Benbow University of Manchester. LIVER DISEASE. By the end of this talk, you should know about Normal anatomy and physiology of the liver Common diseases affecting the liver Viral hepatitis Causes of chronic hepatitis Alcoholic liver disease

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The liver and its diseases

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  1. The liver and its diseases Emyr Wyn Benbow University of Manchester

  2. LIVER DISEASE By the end of this talk, you should know about • Normal anatomy and physiology of the liver • Common diseases affecting the liver • Viral hepatitis • Causes of chronic hepatitis • Alcoholic liver disease • Causes of cirrhosis • Clinical consequences of liver disease

  3. LIVER DISEASE NORMAL STRUCTURE AND FUNCTION • right upper quadrant of abdomen • 1200-1500g in adult • peritoneal covering • 4 anatomical lobes (right-left-caudate-quadrate)

  4. LIVER DISEASE NORMAL STRUCTURE AND FUNCTION • 2 functional lobes (right-left) in 8 segments • related to afferent blood supply

  5. LIVER DISEASE NORMAL STRUCTURE AND FUNCTION • hepatic artery from coeliac axis • portal vein from gut • venous outflow via hepatic veins to inferior vena cava

  6. LIVER DISEASE Functional unit is the ACINUS

  7. LIVER DISEASE

  8. LIVER DISEASE NORMAL METABOLIC ACTIVITIES CARBOHYDRATES • forms and stores glycogen • released under hormonal control

  9. LIVER DISEASE NORMAL METABOLIC ACTIVITIES PROTEINS • deamination of amino acids • formation of urea • synthesis of albumin, α-1-antitrypsin, clotting factors

  10. LIVER DISEASE NORMAL METABOLIC ACTIVITIES LIPIDS • fatty acid oxidation • triglyceride and cholesterol synthesis • bile salt metabolism • cholesterol + amino acid • allow micelle formation in gut

  11. LIVER DISEASE NORMAL METABOLIC ACTIVITIES VITAMINS • fat soluble vitamins require bile salts for absorption • A, D, K, B12 stored in the liver • vitamin K needed for hepatic production of prothrombin (factor II) • 25-hydroxylation of vitamin D takes place in liver

  12. LIVER DISEASE NORMAL METABOLIC ACTIVITIES INACTIVATION OF HORMONES • oestrogens/steroids conjugated to glucuronic acid • may inactivate insulin and thyroxine

  13. LIVER DISEASE NORMAL METABOLIC ACTIVITIES DRUG DETOXIFICATION • microsomal enzymes on endoplasmic reticulum (cytochrome p450 systems) • enzyme induction may occur

  14. LIVER DISEASE NORMAL METABOLIC ACTIVITIES BILIARY EXCRETION • bilirubin is unconjugated (fat soluble) before liver cell membrane, transported across, conjugated to glucuronic acid (water soluble), secreted in bile • bile acids and cholesterol metabolism are important in gall stone formation

  15. LIVER DISEASE HEPATITIS Inflammation of the liver Causes • viruses • alcohol • drugs • autoimmune disease

  16. LIVER DISEASE VIRAL HEPATITIS Hepatitis A • infectious • epidemic • oral-faecal transmission • 2-6 weeks incubation period

  17. LIVER DISEASE VIRAL HEPATITIS Hepatitis B • serum • sporadic • blood-borne orsexual transmission • 6 weeks to 6 months incubation period

  18. LIVER DISEASE VIRAL HEPATITIS Hepatitis C • transfusion related • blood-borne transmission • 2 weeks to 6 months incubation period

  19. LIVER DISEASE VIRAL HEPATITIS Hepatitis D • delta agent • needs hepatitis B for disease Hepatitis E • very similar to HAV Epstein-Barr Virus • infectious mononucleosis Cytomegalovirus • immunosuppressed patients

  20. LIVER DISEASE VIRAL HEPATITIS • asymptomatic subclinical disease • acute clinical jaundice • acute massive necrosis (< 2%) • chronic hepatitis

  21. LIVER DISEASE VIRAL HEPATITIS • chronic hepatitis > 6 months (especially hepatitis B and C) • grade of disease = portal and lobular inflammation, interface hepatitis • stage of disease = fibrosis (portal, bridging, nodules) and cirrhosis • may lead to cirrhosis and ultimately hepatocellular carcinoma

  22. LIVER DISEASE ALCOHOL • 1 unit of alcohol = 10ml or 8g pure ethanol • equivalent to half pint of beer, glass of wine, half measure of spirits

  23. LIVER DISEASE ALCOHOL • calculate by Beck’s: 275ml x 5.0%ABV = 1.375 units • recommended ‘safe’ limits: 14 units/week for women 21 units/week for men

  24. LIVER DISEASE ALCOHOL • 1unit of alcohol = 10ml or 8g • calculate by white wine • 125ml x 12%ABV = 1.5 units • 175ml x 12%ABV = 2.1units • 250ml x 12%ABV = 3 units

  25. LIVER DISEASE ALCOHOL • alcohol absorbed from upper small intestine, then via portal vein to liver • some metabolism in stomach by alcohol dehydrogenase • alcohol converted to acetaldehyde and excreted by conversion to carbon dioxide in citric acid cycle • cytochrome p4502E1 involved

  26. LIVER DISEASE ALCOHOL • variations related to weight, gender and body fat • rate of metabolism variable • can be induced, tolerance increases • roughly equivalent to 1 unit per hour

  27. LIVER DISEASE

  28. LIVER DISEASE ALCOHOL • fatty change reversible • alcoholic hepatitis reversible Mallory’s hyaline • fibrosis reversible pericellular • cirrhosis irreversible

  29. LIVER DISEASE ALCOHOLIC LIVER DISEASE • fatty change - reversible • alcoholic hepatitis - reversible - Mallory’s hyaline • pericellular fibrosis - reversible • cirrhosis - irreversible H&E Oil Red O

  30. LIVER DISEASE ALCOHOLIC LIVER DISEASE • fatty change - reversible • alcoholic hepatitis - reversible Mallory’s hyaline • pericellular fibrosis - reversible • cirrhosis – irreversible Mallory’s hyaline

  31. LIVER DISEASE ALCOHOLIC LIVER DISEASE • fatty change - reversible • alcoholic hepatitis - reversible Mallory’s hyaline • pericellular fibrosis - reversible • cirrhosis – irreversible

  32. LIVER DISEASE ALCOHOLIC LIVER DISEASE • fatty change - reversible • alcoholic hepatitis - reversible Mallory’s hyaline • pericellular fibrosis - reversible • cirrhosis - irreversible

  33. Alcohols: ethanol • llegal intoxication is 0.08 g/dL • 0.2 g/dL is drunk, 0.3 is smashed, 0.4 is out cold • lethal toxicity • > 0.4g/dL in alcohol naïve • > 0.5g/dL in anyone • but very variable

  34. Alcohols: ethanol • but some have survived far higher levels than these potentially fatal values, up to 1.3g/dL • death due to respiratory depression • synergy with other respiratory depressants

  35. Alcohols: ethanol Elimination • average elimination rate 0.015 g/dL/hr • from legal intoxication to undetectable takes about 5 hours • alcoholics may eliminate up to 0.05 g/dL/hr • post mortem production of alcohol up to 0.05g/dL

  36. LIVER DISEASE NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) • fatty change • non-alcoholic steatohepatitis (NASH) • fibrosis • cirrhosis • changes identical to alcohol • associated with obesity, diabetes, hyperlipidaemia, some drugs

  37. LIVER DISEASE CIRRHOSIS - disease of all of the liver with parenchymal nodules and surrounding fibrosis CAUSES • alcohol • viruses • metabolic diseases • autoimmune

  38. LIVER DISEASE CIRRHOSIS - CAUSES • alcohol • viruses • especially HBV and HCV • metabolic diseases • autoimmune Orcein- HBsAg IHC-HBsAg

  39. LIVER DISEASE CIRRHOSIS - CAUSES • alcohol • viruses • metabolic diseases • iron, copper, glycogen storage disease, lipid disorders, -1 antitrypsin deficiency • autoimmune Perls’ -1ATD, DPAS -1ATD,IHC

  40. LIVER DISEASE CIRRHOSIS - CAUSES • alcohol • viruses • metabolic diseases • autoimmune • “lupoid”, young women: anti-nuclear and anti-smooth muscle antibodies • primary biliary cirrhosis: middle aged women, anti-mitochondrial antibodies AiCH

  41. LIVER DISEASE CIRRHOSIS – EFFECTS Liver failure • protein synthesis: low albumin • coagulation factors: bleeding • jaundice • encephalopathy: confusion Portal hypertension Hepatocellular carcinoma

  42. LIVER DISEASE Cirrhosis – effects Liver failure Portal hypertension • ascites • varices • splenomegaly Hepatocellular carcinoma

  43. LIVER DISEASE CIRRHOSIS – EFFECTS LIVER FAILURE PORTAL HYPERTENSION HEPATOCELLULAR CARCINOMA • very common carcinoma where HBV endemic (SE Asia, Africa) • very poor prognosis, about 6-9 months • Raised serum alpha-fetoprotein levels AFP HCC

  44. LIVER DISEASE Summary Be aware of • drug metabolism • risks of viral hepatitis • bleeding tendency in chronic liver disease • increased risk of alcoholism in medical profession

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