Pathology of Hepatitis

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Pathology of Hepatitis

  1. 1. Never offer the devil a ride.<br />He will always want to be in the driving seat…!<br />BK<br />
  2. 2. 2<br />CPC 4.2.2<br />George, 62 year old farmer from Tully, presents to his GP with fatigue. His wife has asked him to consult you as his eyes look a bit yellow'. <br />Fatigue: Progressing 2wk. Unable to get out. <br />nausea : no <br />vomiting/haematemesis : no <br />Anorexia, wt loss: yes thinks lost a bit of weight. <br />bowel habit : constipated, stool pale, no blood.<br />
  3. 3. 3<br />CPC 4.2.2<br />Fever: no <br />Bleeding/bruising : no <br />cough/dyspnoea : no<br />previous episodes : 2 x episodes fatigue last 2 years; first attack preceeded by 2 weeks of fever. saw GP - blood tests : 'showed liver not working so well'. then felt better and has not been to see GP since. This time he feels much worse. <br />other PMH of note? 'never sees doc'; has never been in hospital; no regular medication <br />no OTC/herbal remedies <br />SH : married; 3 adult children. Moved to Australia from Greece 26 years ago. Banana farmer <br />
  4. 4. 4<br />Laboratory Investigations:<br />FBC: Hb 13.8 g/dl, PCV 45%; WBC 7000/mm3, 70% N, 25% L; Platelets 200,000/mm3 <br />Blood film: Normocytic, normochromic cells <br />Bilirubin: Total serum Bilirubin = 98 μmol/l, (Direct 67)<br />Liver enzymes: <br />Aspartate amino transferase (AST) = 62 U/l <br />Alanine amino transferase (ALT) = 110 U/l <br />Alkaline Phosphatase = 116 U/I <br />Serum Protein: Total protein = 61 g/l, Albumin = 20 g/l, <br />Hepatitis B Surface Antigen (HbsAg): Positive <br />
  5. 5. 5<br />Differential Diagnosis:<br />Viral fever -? <br />Yellow fever, Relapsing fever, Dengue, Ebola, <br />Leptospirosis (common in Tully) - ?<br />Hepatitis – Acute / Chronic - ?<br />Chronic Hepatitis B – why chronic?<br />History & presentation in Hep. A & C ?<br />Other causes of Jaundice?<br />Alcoholic liver disease ?<br />Toxins, chemical, Reyes syndrome?<br />Anemia - ?<br />Malignancy - ?<br />
  6. 6. 6<br />Jaundice Clinical Diagnosis<br />
  7. 7. 7<br />Pathology of HepatitisViral & Alcoholic<br />Dr. Venkatesh M. Shashidhar.<br />Assoc.Prof & Head of Pathology<br />
  8. 8. 8<br />1.5 kg, wedge shape<br />4 lobes, Right, left, (Caudate, Quadrate)<br />Double blood supply<br />Hepatic arteries<br />Portal – Venous blood<br />Normal<br />
  9. 9. 9<br />CT Upper abdomen - Normal<br />Liver<br />Stomach<br />Aorta<br />Spleen<br />Lung<br />Lung<br />
  10. 10. Normal Liver - Infant<br />Much larger, both lobes, below costal margin – palpable*<br />
  11. 11. 11<br />Normal Liver<br />
  12. 12. 12<br />Normal Liver – MicroscopyAcinus – showing zones 1, 2 & 3.<br />Central Vein<br />Blood Flow<br />Portal Triad<br />
  13. 13. 13<br />Structure of Liver Lobule<br />Portal Triad: Art, Vein, BD<br />
  14. 14. 14<br />Acinus LobuleFunctional Anatomic<br />3<br />Zone 1 – Toxin damage. Zone 3 – Ischemic damage<br />
  15. 15. Jaundice<br />15<br /><ul><li>Overproduction of bilirubin
  16. 16. Impaired bilirubin uptake.
  17. 17. Block in metabolism
  18. 18. Impaired transport.
  19. 19. Obstruction to bile excretion.</li></li></ul><li>16<br />Liver Function Tests: Interpretation<br />Synthesis / function defect.<br />Total protein & albumin low, PT prolonged why?<br />Bile Obstruction.<br />Alk Phos – markedly increased – why?<br />Hepatocyte Injury.<br />ALT, AST - high. – why?<br />Alk Phos – moderately increased. – why?<br />Other:<br />GGT – increased with alcohol use. – why?<br />Viral serology - <br />Auto-Antibody panel. <br />Clinical Features<br /><ul><li>Fever
  20. 20. Fatigue
  21. 21. Indigestion
  22. 22. Fat intolerance
  23. 23. urine/stool*
  24. 24. Jaundice
  25. 25. Bleeding
  26. 26. Edema
  27. 27. Abd. Distension
  28. 28. Confusion
  29. 29. Coma</li></li></ul><li>17<br />Clinical Features - Pathogenesis<br /><ul><li>Hypoalbuminemia
  30. 30. Hyperammonemia
  31. 31. Hypoglycemia
  32. 32. Palmarerythema
  33. 33. Spider angiomas
  34. 34. Hypogonadism
  35. 35. Gynecomastia
  36. 36. Weight loss
  37. 37. Muscle wasting
  38. 38. Ascites
  39. 39. Splenomegaly
  40. 40. Esophagealvarices
  41. 41. Hemorrhoids
  42. 42. Caput medusae-abdominal skin
  43. 43. Complications of Hepatic Failure
  44. 44. Coagulopathy
  45. 45. Hepatic encephalopathy
  46. 46. Hepatorenal syndrome</li></ul>Decreased Albumin synthesis<br />Hepatorenal syndrome<br />
  47. 47. Jaundice in liver failure<br />18<br />
  48. 48. 19<br />Diseases of Liver:<br />Hepatitis: Inflammation of Liver<br />Viral, Alcohol, immune, Drugs, Toxins, parasites<br />Acute, Chronic & Fulminant – types.<br />Billiary obstruction – gall stones.<br />Cirrhosis – diffuse scarring & regeneration.<br />Carcinoma - Hepatocellular & Bile duct.<br />Congenital: metabolic, cysts, tumors.<br />
  49. 49. Viral Hepatitis:<br />
  50. 50. 21<br />Viral Hepatitis: Introduction<br />Viral Hepatitis:<br />Specific – Heptitis B, C, D (serum),A, E<br />Non-Specific - Many viruses CMV, EBV, etc.<br />Acute, Chronic (CPH, CAH), Fulminant.<br />Specific viral hepatitis important cause of morbidity & mortality.<br />Horizontal transmission – Blood.. Sex.<br />Vertical transmission – Mother to fetus.<br />Hepatitis  Cirrhosis  Hepatic Ca. (not in A/E)<br />
  51. 51. 22<br />Viral Hepatitis: Microbiology<br />
  52. 52. 23<br />Hepatitis A<br />'faecal-oral' spread, Travel / exposure. <br />Relatively short incubation period (2-6wk)<br />Epidemics common, may be sporadic. <br />Direct cytopathic virus (immune in B & C)<br />No carrier state – prolonged immunity.<br />Usually mild illness, full recovery usual.<br />Rarely – severe or fulminant.<br />IgM Ab is diagnostic. (no IgG tests).<br />
  53. 53. 24<br />Viral Hepatitis A: Serology<br />
  54. 54. 25<br />Hepatitis B<br />Spread by blood, Sex & vertical.<br />Relatively long incubation period (4-26wk)<br />liver damage by antiviral immune reaction <br />carrier state exists.<br />Relatively serious infection – chronic, <br />Complications: cirrhosis, carcinoma.<br />Diagnosis: Viral serology (HBsAg) <br />
  55. 55. 26<br />Viral Hepatitis B: Serology<br />Sequence of serologic markers for hepatitis B viral hepatitis demonstrating (A) acute infection with resolution and (B) progression to chronic infection. <br />
  56. 56. 27<br />Pathogenesis of Hepatitis A & B:<br />
  57. 57. 28<br />History Hep B Virus:<br />In 1965 - Dr. Blumberg who was studying haemophilia, found an antibody in two patients which reacted against an antigen from an Australian Aborigine. Later the antigen was found in patients with serum type hepatitis and was initially designated "Australia Antigen". Later proved to be hepatitis B virus surface antigen (HBsAg). Dr. Blumberg was awarded the Nobel Prize in 1976. <br />
  58. 58. 29<br />Pathogenesis:<br />Ingestion / inoculation<br />Replication - Viremia<br />Liver – major site replication.<br />Cellular immune response.<br />Apoptosis, necrosis of hepatocytes.<br />Inflammation - Hepatitis <br />Bridging Hepatocyte necrosis (Central vein, portal triad)<br />Fibrosis – patchy/bridging<br />Cirrhosis – extensive fibrosis with loss of archetecture & regenerating nodules.<br />Liver Failure, Coma, Carcinoma..<br />
  59. 59. 30<br />Pattern of Liver Damage<br />Zonal – Toxin/Hypoxia<br />Bridging – Viral & severe<br />Interface – CAH, Immune<br />Apoptotic – Acute Viral<br />
  60. 60. 31<br />Spectrum of Viral Hepatitis:<br />Carrier state / Asymptomatic phase<br />Acute hepatitis – fever, icterus.<br />Chronic Hepatitis – non specific.<br />Chronic Persistent Hepatitis (CPH)<br />Chronic Active Hepatitis (CAH)<br />Fulminant hepatitis – massive necrosis<br />Cirrhosis – total fibrosis.<br />Hepatocellular Carcinoma<br />
  61. 61. 32<br />Acute Hepatitis:<br />Swelling and Apoptosis<br />Piecemeal or Bridging, panacinar necrosis<br />Diffuse Inflammation – lymphocytes, Macrophages.<br />Ground glass hepatocytes – HBV<br />Mild fatty change – HCV.<br />Portal inflammation and Cholestasis<br />
  62. 62. 33<br />Acute viral Hepatitis:<br />
  63. 63. 34<br />Acute viral Hepatitis:Apoptotic cells.<br />
  64. 64. 35<br />Acute viral Hepatitis:Apoptotic cell.<br />
  65. 65. 36<br />Acute viral Hepatitis:<br />
  66. 66. 37<br />Acute viral Hepatitis:<br />
  67. 67. 38<br />Acute viral Hepatitis C:<br />
  68. 68. 39<br />Ground glass Hepatocytes:<br />
  69. 69. 40<br />Chronic Hepatitis:<br />Persistent CPH<br />Limited Periportal inflammation. <br />Mild Periportal fibrosis<br />No hepatocyte Necrosis.<br />LFT normal or mild change.<br />Late cirrhosis <br />Active CAH<br />Extensive Inflammation <br />More fibrosis.<br />Necrosis of hepatocytes.<br />LFT abnormal.<br />Early cirrhosis & other complication.<br />
  70. 70. 41<br />Liver Biopsy – viral Hepatitis-C<br />
  71. 71. 42<br />Liver Biopsy - CAH:<br />
  72. 72. 43<br />Chronic Active viral Hepatitis:<br />
  73. 73. 44<br />Chronic Persistent Hepatitis:<br />
  74. 74. 45<br />Liver Biopsy – CPH:<br />Inflammation<br />No Necrosis<br />
  75. 75. 46<br />Acute - Hepatitis - Chronic<br />
  76. 76. 47<br />Viral – Steatosis - Alcoholic<br />Microvesicular (viral) Macrovesicular(alcoholic)<br />
  77. 77. 48<br />Fulminant Hepatitis:<br />Hepatic failure with in 2-3 weeks.<br />Reactivation of chronic or acute hepatitis<br />Massive necrosis, shrinkage, wrinkled<br />Collapsed reticulin network<br />Only portal tracts visible<br />Little or massive inflammation – time<br />More than a week – regenerative activity<br />Complete recovery – or - cirrhosis.<br />
  78. 78. 49<br />Fulminant Hepatitis:<br />
  79. 79. 50<br />Fulminant Hepatitis:<br />
  80. 80. 51<br />Fulminant Hepatitis:<br />
  81. 81. 52<br />Fulminant Hepatitis:confluent necrosis().<br />
  82. 82. 53<br />Clinical Spectrum of HBV inf:<br />
  83. 83. 54<br />Outcomes of HBV Infection:<br />
  84. 84. “Nearly all men <br />can stand adversity, <br />but if you want to <br />test a man's character, <br />give him power”<br />—  Abraham Lincoln<br />
  85. 85. Laboratory DiagnosisViral Hepatitis<br />
  86. 86. 57<br />Viral Hepatitis C: Serology<br />
  87. 87. Hepatitis B – Lab result interpret<br />
  88. 88. 59<br />Cirrhosis <br />End stage of diffuse liver disease. scaring with regenerating nodules. (liver failure)<br />Normal Cirrhosis <br />
  89. 89. The past has gone and future you cannot see.<br />The present, when you can do something, that is the Gift (Present) with which you can make your future & past memorable.<br />- Sai Baba<br />"The past, the present and the future are really one: they are today."<br />-Harriet Beecher Stowe<br />
  90. 90. Alcoholic Liver Disease<br />
  91. 91. 62<br />Incidence is increasing…!<br />
  92. 92. 63<br />Chronic Alcoholism:<br />Clinical Features:<br />
  93. 93. 64<br />Alcoholic Liver Injury:<br />Ethyl alcohol : Common cause of acute/Chronic liver disease<br />Alcoholic Liver disease - Patterns<br />Fatty change, <br />Acute hepatitis (Mallory Hyalin)<br />Chronic hepatitis with Portal fibrosis <br />Chronic Liver failure<br />Cirrhosis<br />All reversible except cirrhosis stage.<br />
  94. 94. 65<br />Alcoholic Liver Injury: Pathogenesis<br />Acetaldehyde – metabolite – hepatotoxic<br />Diversion of metabolism to alcohol <br />Fat storage – fatty change. Cell swelling..<br />Rupture Fat necrosis  severe inflammation  fibrosis.<br />Alcohol stimulates collagen synthesis<br />Inflammation, Portal bridging fibrosis<br />Micronodular cirrhosis.<br />
  95. 95. 66<br />Alcoholic Liver Damage<br />Ito Cells<br />
  96. 96. 67<br />Alcoholic Liver Injury: Pathogenesis<br />Diversion of fat metabolism to alcohol – fat storage.<br />Acetaldehyde – hepatotoxic – denatures Proteins<br />Increased peripheral release of fatty acids.<br />Alcohol stimulates collagen synthesis<br />Mutant ALDH2 gene with low activity enzyme is observed in Caucasians but is found in some 40% of Orientals (autosomal dominant).<br />Acetaldehyde<br />
  97. 97. 68<br />Safe drinking…<br />High Risk<br />Intermediate<br />Low Risk<br />
  98. 98. 69<br />Risk of Alcohol injury<br />1 Unit = 10ml = 8gm<br />
  99. 99. 70<br />Alcoholic Liver Damage<br />
  100. 100. 71<br />Alcohol Toxicity:<br />
  101. 101. 72<br />Alcoholic Fatty Liver<br />
  102. 102. 73<br />Alcoholic Fatty Liver<br />
  103. 103. 74<br />Alcoholic Fatty Liver<br />
  104. 104. 75<br />Alcoholic Fatty Liver<br />
  105. 105. Diffuse fatty liver - un-enhanced CT.<br />Normal<br />Hamer O W et al. Radiographics 2006;26:1637-1653<br />©2006 by Radiological Society of North America<br />
  106. 106. 77<br />Alcoholic Fatty Liver - CT<br />
  107. 107. 78<br />Alcoholic Fatty Liver - CT<br />
  108. 108. 79<br />Alcoholic Liver- Mallory's hyalin <br />
  109. 109. 80<br />Alcoholic Fatty change:<br />
  110. 110. 81<br />Alcoholic Fatty change & Mallory Hyalin:<br />
  111. 111. 82<br />Alcoholic Fatty Liver<br />
  112. 112. 83<br />Alcoholic Fatty Liver - collagen stain<br />
  113. 113. 84<br />Alcoholic Cirrhosis:<br />
  114. 114. 85<br />Alcoholic Fatty Liver - collagen stain<br />
  115. 115. Alcoholic Hepatitis:<br />86<br /><ul><li>Centrilobular necrosis. Ballooned degenerating hepatocytes (BC) Mallory bodies (MB) Many Neutrophils, few lymphocytes & Macrophages.
  116. 116. The central vein(or terminal hepatic venule (THV), is encased in connective tissue (C) (central sclerosis). Fat-laden hepatocytes (F) are evident in the lobule. The portal tract displays moderate chronic inflammation.</li></li></ul><li>87<br />Alcoholic Liver Injury: Complications<br />Pancreatitis – Acute or Chronic. Due to ischemic damage to pancreas.<br />Alcoholic hepatitis – similar to viral hepatitis.<br />Fulminant hepatitis<br />Alcoholic Cirrhosis – Micronodular.<br />Alcohol & Medical students<br />http://www.m-c-a.org.uk/about_us/about_mca<br />
  117. 117. Drug Induced Zonal Hepatitis:<br />88<br /><ul><li>Autopsy specimen in a case of acetaminophen overdose.
  118. 118. Prominent hemorrhagic necrosis of the centrilobular zones of all liver lobules.
  119. 119. greater activity of drug-metabolizing enzymes in the central zones.
  120. 120. Other agents that produce such injury are carbon tetrachloride, acetaminophen, toxins of the mushroom Amanita phalloides.
  121. 121. Patients either die in acute hepatic failure or recover without sequelae.</li></li></ul><li>Reye Syndrome:<br />89<br /><ul><li>Acute disease of children
  122. 122. Microvesicular steatosis, hepatic failure, and encephalopathy.
  123. 123. Cerebral edema and fat accumulation are reported in the brain.
  124. 124. The symptoms usually begin after a febrile illness, commonly influenza or varicella infection, and are said to correlate with the administration of aspirin,
  125. 125. Pathogenesis remains unknown.
  126. 126. Uncommon, possibly as a result of decreasing use of aspirin in children.</li></li></ul><li>Toxemia of Pregnancy:<br />90<br /><ul><li>Hypertension, proteinuria, edema and coagulation abnormalities (pre-eclampsia) and convulsions and coma (eclampsia).
  127. 127. HELLP syndrome (hemolysis, elevated liver enzymes and low platelet count) can also occur in pre-eclamptic women.
  128. 128. Patchy hemorrhages over capsule
  129. 129. Intravascular coagulation
  130. 130. Fibrin thrombi in portal vessels.
  131. 131. Hepatocellular necrosis.</li></li></ul><li>91<br />Pathology of Cirrhosis<br />
  132. 132. 92<br />Cirrhosis <br />End stage of diffuse liver disease. scaring with regenerating nodules. (liver failure)<br />Normal Cirrhosis <br />
  133. 133. 93<br />Post hepatitis Liver Cirrhosis<br />Shrunken, irregular nodularity, (macro nodular) fibrous septa.<br />
  134. 134. 94<br />MRI Cirrhosis<br />
  135. 135. 95<br />Liver Biopsy – Cirrhosis:<br />
  136. 136. 96<br />Liver Biopsy – Cirrhosis<br />
  137. 137. 97<br />Liver Biopsy – Cirrhosis<br />
  138. 138. 98<br />Introduction<br />Cirrhosis is common end result of many chronic liver disorders.<br />Diffuse scarring of liver – follows hepatocellular necrosis of hepatitis.<br />Inflammtion – healing with fibrosis - Regeneration of remaining hepatocytes form regenerating nodules.<br />Loss of normal architecture & function.<br />
  139. 139. 99<br />Etiology of Cirrhosis<br />Alcoholic liver disease 60-70%<br />Viral hepatitis 10%<br />Biliary disease 5-10%<br />Primary hemochromatosis 5%<br />Cryptogenic cirrhosis 10-15%<br />Wilson’s, 1AT def rare<br />
  140. 140. 100<br />Alcoholic Cirrhosis<br />
  141. 141. 101<br />Micronodular cirrhosis:<br />
  142. 142. 102<br />Pathogenesis:<br />Hepatocyte injury leading to necrosis.<br />Alcohol, virus, drugs, toxins, genetic etc..<br />Chronic inflammation - (hepatitis).<br />Bridging fibrosis.<br />Regeneration of remaining hepatocytes Proliferate as round nodules.<br />Loss of vascular arrangement results in regenerating hepatocytes ineffective.<br />
  143. 143. 103<br />Clinical Features<br />Hepatic encephalopathy<br />
  144. 144. 104<br />Pathogenesis of Ascitis:<br />Hepatorenal Syndrome<br />
  145. 145. 105<br />Cirrhosis – Portal hypertension<br />Cirrhosis-obstruction<br />Portal hypertension<br />Splenomegaly<br />transudation - Ascites<br />
  146. 146. 106<br />Causes of Portal Hypertension:<br />
  147. 147. 107<br />Ascitis in Cirrhosis<br />
  148. 148. 108<br />Cirrhosis:<br />
  149. 149. 109<br />Ascitis in Cirrhosis<br />
  150. 150. 110<br />Gynaecomastia in Cirrhosis<br />?<br />?<br />?<br />?<br />
  151. 151. 111<br />Ascitis in congenital Cirrhosis<br />
  152. 152. 112<br />Normal / Cirrhosis Liver<br />
  153. 153. 113<br />Micronodular cirrhosis:<br />
  154. 154. 114<br />Biliary Cirrhosis<br />
  155. 155. 115<br />Cirrhosis with bile stasis<br />
  156. 156. 116<br />Cirrhosis with bile stasis<br />
  157. 157. 117<br />Primary Biliary Cirrhosis - Micronodular<br />
  158. 158. 118<br />Liver Biopsy – Cirrhosis<br />
  159. 159. 119<br />Palmar erythema & Spider nevi<br />? Pathogenesis<br />
  160. 160. 120<br />Hepatocellular Carcinoma<br />
  161. 161. 121<br />Cirrhosis with carcinoma:<br />
  162. 162. 122<br />Nutmeg Liver:<br />Chronic Passive Congestion – Heart failure.<br />Venous stasis - right atrium - hypoperfusion retrograde congestion – IVC & SVC.<br />Central zone (Zone-3) – congestion and necrosis.<br />Hemorrhage – RBCs in zone-3 - Mottled appearance (nutmeg).<br />Symptoms are similar to those of chronic hepatitis - Ascites, distended abdomen, ankle edema, Hepatic encephalopathy, confusion.<br />
  163. 163. 123<br />Nutmeg Liver-Cardiac Sclerosis<br />
  164. 164. 124<br />Liver Metastasis:<br />Multiple<br />Clear demarcation<br />Hemorrhage / Central necrosis (+/-)<br />Microscopy depends on type.<br />
  165. 165. Miscellaneous Conditions<br />125<br />
  166. 166. 126<br />Hepatosplenic schistosomiasis:<br />Schistosoma Mansoni / haematobium<br />Granulomas in the liver.<br />Fibrotic reaction around egg <br />Pipe stem Portal Fibrosis<br />Cirrhosis, spleenomegaly, ascitis.<br />
  167. 167. 127<br />Hepatosplenic schistosomiasis:<br />Schistosoma Mansoni / haematobium<br />Granulomas in the liver.<br />Fibrotic reaction around egg <br />Pipe stem Portal Fibrosis<br />Cirrhosis, spleenomegaly, ascitis.<br />
  168. 168. "It's not the will to win, but the will to prepare to win that makes the difference."<br />Bear Bryant1913-1983, Football Coach<br />
  169. 169. 129<br />CPC-2.2– HBS–Hepatitis<br />Basic science - Core Learning Issues: <br />anatomy and histology of the liver & Spleen <br />Portal circulation.<br />Liver Functions & Bilirubin metabolism (RBC, Hb)<br />Viral Hepatitis – epidemiology,virology.<br />Pathology Core Learning Issues: <br />Pathology of liver, Hepatitis. Causes, types, gross & microscopic morphology. <br />Jaundice – clinical and pathological types<br />Acholuric, obstructive, hemolytic, hepatic.<br />Laboratory investigations. <br />Pathology of cirrhosis & its complications.<br />
  170. 170. 130<br />51y M, Alcoholic: Look at Arrow ? Pathogenesis.<br />Porta-systemic shunt<br />Hyper-oestrogenemia<br />Portal hypertension<br />Hypo-albuminemia<br />Decreased vit-K<br />
  171. 171. Pathogenesis - typical of which virus?<br />HAV<br />HBV<br />HCV<br />HDV<br />Non Specific<br />
  172. 172. 42y M, alcoholic, recurrent fatigue. Liver biopsy. ? Diagnosis<br />Acute Hepatitis<br />Chronic Active hepatitis.<br />Chronic Persistant hepatitis.<br />Fulminant Hepatitis.<br />Cirrhosis.<br />
  173. 173. A 42year travelling salesperson has routine medical test for insurance. Following initial testing he was advised liver biopsy. This is a image of his Liver Biopsy. What is the most likely diagnosis?<br />Acute Viral Hepatitis<br />Alcoholic hepatitis.<br />Chronic viral Hepatitis. <br />Post viral cirrhosis.<br />Alcoholic Cirrhosis.<br />
  174. 174. 69y Female, Chronic bronchitis. Died following chronic Cardiac failure. Liver specimen. Likely diagnosis?<br />Alcoholic Hepatitis <br />Dubin-Johnson Syndrome<br />Alcoholic cirrhosis<br />Nutmeg liver<br />Metastatic deposits<br />
  175. 175. 135<br />HBsAg Positive, <br />Anti HBcAg Positive<br />Anti HBcAg IGM Negative<br />Anti HBsAg Negative<br />Viral serology interpretation:<br />Acute Viral Hepatitis<br />Immunised against Hep. B<br />Chronic Hepatitis B<br />Hepatitis B carrier stage<br />Fulminant hepatitis B<br />
  176. 176. 136<br />HBsAg Negative, <br />Anti HBcAg Negative<br />Anti HBcAg IGM Negative<br />Anti HBsAg Positive<br />Viral serology interpretation:<br />Acute Viral Hepatitis<br />Immunised against Hep. B<br />Past Hepatitis B<br />Hepatitis B carrier stage<br />Fulminant hepatitis B<br />
  177. 177. 137<br />HBsAg Negative, <br />Anti HBsAg Positive<br />Anti HBcAg Positive<br />Anti HBcAg IGM Negative<br />Viral serology interpretation:<br />Acute Viral Hepatitis B<br />Immunised against Hep. B<br />Past Hepatitis B<br />Hepatitis B carrier stage<br />Carrier state of Hepatitis B<br />
  178. 178. 138<br />Protein (Total) 59 g/L<br />Albumin 30 g/L<br />Globulin 29 g/L<br />Bilirubin (Total) 27 μmol/L<br />ALP 71 U/L<br />GGT 523 U/L<br />ALT 79 U/L<br />AST 151 U/L<br />Lab Investigations interpretation:<br />Alcoholic Liver disease<br />Acute Viral Hepatitis.<br />Past Hepatitis B<br />Hepatitis B carrier stage<br />Carrier state of Hepatitis B<br />
  179. 179. 139<br />Lab Investigations interpretation: <br />Urea 5.8 mmol/L<br />Creatinine 80 μmol/L<br />Protein (Total) 66 g/L <br />Albumin 35 g/L<br />Globulin 31 g/L<br />Bilirubin (Total) 192 μmol/L<br />Bilirubin (Conj.) 130 μmol/L<br />ALP 203 U/L<br />GGT 470 U/L<br />ALT 6055 U/L<br />AST 4860 U/L<br />Alcoholic Liver disease<br />Past Hepatitis B<br />Acute Viral Hepatitis.<br />Hepatitis B carrier stage<br />Carrier state of Hepatitis B<br />
  180. 180. 28y M, alcoholic, homosexual icterus and fever. Liver biopsy. ? diagnosis<br />Acute viral hepatitis<br />Hemolytic anemia<br />Chronic persistent hepatitis<br />Alcoholic fatty liver.<br />Alcoholic Hepatits.<br />
  181. 181. 62 year Male, malaise, lethargy since 2 years. Liver mildly enlarged. No jaundice. Liver function tests normal. Image from liver biopsy. Most likely diagnosis? <br />Alcoholic fatty liver. <br />Acute viral hepatitis.<br />Fulminant hepatitis.<br />Chronic viral hepatitis.<br />Alcoholic Cirrhosis.<br />
  182. 182. 34y M, icterus and fever. Liver biopsy. ? diagnosis<br />Acute Hepatitis<br />Chronic Persistent Hepatitis.<br />Chronic active Hepatitis<br />Fulminant Hepatitis<br />Cirrhosis<br />
  183. 183. 22y M, alcoholic, 3wk fatigue, icterus & fever. Liver biopsy. ? Identify the structure<br />Mallory hyaline<br />Apoptotic cell<br />Viral inclusion<br />Hepatocyte necrosis<br />Inflammatory cell<br />
  184. 184. 56y chronic alcoholic, 2 days fever, abdomen distended, tender, tap yielded cloudy yellow fluid with 98% neutrophils, Blood culture E.coli. Patient dies 3 days later. Image shows his liver.<br />A1 antitrypsin deficiency<br />HEV infection<br />Hereditary hemochromatosis<br />Primary sclerosing cholangitis<br />Alcoholic cirrhosis<br />
  185. 185. 58y M, alcoholic, distended abdomen & icterus. Liver biopsy. ? diagnosis<br />Chronic active hepatitis.<br />Chronic Persistant hepatitis.<br />Hepatocellular carcinoma.<br />Cirrhosis<br />Chronic alcoholic hepatitis.<br />
  186. 186. 146<br />51y M, Alcoholic: Look at Arrow ? Pathogenesis.<br />Porta-systemic shunt<br />Hyper-oestrogenemia<br />Portal hypertension<br />Hypo-albuminemia<br />Decreased vit-K<br />
  187. 187. 51y M, Alcoholic, surgery for pigmented skin lesion: Liver specimen. Likely diagnosis?<br />Amoebic Liver abscesses<br />Multiple Liver Infarcts<br />Alcoholic Hepatitis<br />Macronodular cirrhosis<br />Metastatic deposits<br />
  188. 188. 59y Male, Alcoholic, presents with fatigue, anorexia. Normal liver function tests. Liver specimen. Likely diagnosis?<br />Dubin-Johnson Syndrome<br />Alcoholic cirrhosis<br />Alcoholic Hepatitis<br />Fatty Liver<br />Metastatic deposits<br />
  189. 189. 22y M, alcoholic, 3wk fatigue, icterus & fever. Liver biopsy. ? Identify the structure<br />Mallory hyaline<br />Apoptotic cell<br />Viral inclusion<br />Hepatocyte necrosis<br />Inflammatory cell<br />
  190. 190. 28y Male, 3 weeks after visiting east Timor, presents with malaise, fatigue, loss of appetite. Mild icterus. AST & ALT mild elevation. Total bil 3.9mg/dl (Direct 2.8). Which of the following would be positive?<br />Anti HBs<br />IgM anti-HDV<br />Anti HCV<br />IgM anti HAV<br />Anti HBc<br />
  191. 191. 28y Male, 3 weeks after visiting east Timor, presents with malaise, fatigue, loss of appetite. Mild icterus. AST & ALT mild elevation. Total bil 3.9mg/dl (Direct 2.8). Which of the following would be positive?<br />Anti HBs<br />IgM anti-HDV<br />Anti HCV<br />IgM anti HAV<br />Anti HBc<br />
  192. 192. 41y Female, increasing malaise, 10kg weight loss since last year. Developed coma and died. Specimen of her Liver. Most likely etiologic agent?<br />Aspirin abuse<br />Ferrous sulphate<br />Acetaminophen<br />Aflatoxins<br />Raw Oysters.<br />
  193. 193. A 48y man referred following high ALT in health screening. HCV immunoassay +ve. Past h/o appendectomy 10 years ago. Examination is normal. Which of the following tests would determine if he has Chronic HCV infection?<br />Repeat EIA for anti HCV Ab.<br />Recombinant immunoblot assay (RIBA)<br />Alpha-fetoprotein levels.<br />HCV RNA test.<br />Direct, indirect & total bilirubin assay.<br />
  194. 194. 154<br />Learn from the mistakes of others. You can't live long enough to make them all yourself…!<br />61% of 5th year students exceeded ‘sensible’ limits<br />Drugs and alcohol were taken mainly for pleasure and were perceived as a normal part of life for many students… Capability of advising patients…?<br />http://www.lycaeum.org/research/researchpdfs/1996_webb_1.pdf<br />
  195. 195. 155<br />CPC-2.2– Major Pathology CLI:<br />Pathology of Acute & Chronic Liver injury. <br />Hepatitis – Causes, Types, Pathophysiology, Gross & Microscopic Pathology. Complications. <br />Common types: Viral (Specific & Non specific), Alcoholic & Drug induced. <br />Pathophysiology of Jaundice, Clinical & Pathological types. <br />Pathology of cirrhosis – Classification, morphology & Complications. <br />Pathology of Alcoholic Liver disease – Pathophysiology, types & complications. <br />
  196. 196. 156<br />CPC-2.2– Minor Pathology CLI:<br />Hemosiderosis & Hemochromatosis. <br />Pathogenesis of Hepatic coma, Liver failure. <br />Primary Biliary cirrhosis. <br />Hepatocellular carcinoma. <br />Liver cysts & tumours – adenoma, hyperplasia & cancer.<br />Amoebic liver abscess & Hydatid disease of liver.<br />Congenital liver disorders – enzyme disorders. <br />
  197. 197. 157<br />Clinical Case Study<br />
  198. 198. 158<br />Case # 2 - ? Diagnosis<br />60yr Male, 8 month slowly developing weakness, mild icterus. <br />PE: Mild Abdominal tenderness, No organomegaly. Mild Scleral icterus.<br />Labs: ALT: 52 (N= 8-33 U/L)<br /> AST: 58 (N= 4-36 U/L)<br /> Alk Phos: 150 (N= 20-130 u/L)<br /> Bilirubin 3.9 (N= 0.1-1.2 mg/dL) (direct 1.8)<br /> T Protein 4.8 (N= 6.0-7.8 g/dL)<br /> Albumin 2.5 (N= 3.2-4.5 g/dl)<br /> PT = 16 sec (N= 11-14.7 sec ) <br />Differential diagnosis?<br />What further investigations?<br />
  199. 199. 159<br />Diagnosis pathway:<br />ALT: 52<br />AST: 58 <br />Alk Phos: 150<br />Bilirubin 3.9 (direct 1.8)<br />Jaundice?<br />Mild increase, Mixed (combined)<br />Synthesis?<br />Total protein, albumin – Low & PT abnormal. <br />Obstruction & Bilirubin Clearance ?<br />Alk Phos is up a bit – but not high – some obstruction.<br />Hepatocyte Direct Injury:<br />ALT & AST are up a bit, but not dramatically.<br />Discussion:<br />Chronic Mild compromise - chronic Active hepatitis. (In CPH LFT will be normal)<br />
  200. 200. 160<br />28y Male, 3 weeks after visiting east Timor, presents with malaise, fatigue, loss of appetite. Mild icterus. AST & ALT mild elevation. Total bil 3.9mg/dl (Direct 2.8). Which of the following would be positive?<br />
  201. 201. 161<br />Alcohol Metabolism:<br />

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