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The liver and its diseases PowerPoint Presentation
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The liver and its diseases

The liver and its diseases

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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