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Pathology of Hepatitis
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2. 2 CPC 4.2.2 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'. Fatigue: Progressing 2wk. Unable to get out. nausea : no vomiting/haematemesis : no Anorexia, wt loss: yes thinks lost a bit of weight. bowel habit : constipated, stool pale, no blood.
3. 3 CPC 4.2.2 Fever: no Bleeding/bruising : no cough/dyspnoea : no 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. other PMH of note? 'never sees doc'; has never been in hospital; no regular medication no OTC/herbal remedies SH : married; 3 adult children. Moved to Australia from Greece 26 years ago. Banana farmer
50. 21 Viral Hepatitis: Introduction Viral Hepatitis: Specific – Heptitis B, C, D (serum),A, E Non-Specific - Many viruses CMV, EBV, etc. Acute, Chronic (CPH, CAH), Fulminant. Specific viral hepatitis important cause of morbidity & mortality. Horizontal transmission – Blood.. Sex. Vertical transmission – Mother to fetus. Hepatitis Cirrhosis Hepatic Ca. (not in A/E)
52. 23 Hepatitis A 'faecal-oral' spread, Travel / exposure. Relatively short incubation period (2-6wk) Epidemics common, may be sporadic. Direct cytopathic virus (immune in B & C) No carrier state – prolonged immunity. Usually mild illness, full recovery usual. Rarely – severe or fulminant. IgM Ab is diagnostic. (no IgG tests).
54. 25 Hepatitis B Spread by blood, Sex & vertical. Relatively long incubation period (4-26wk) liver damage by antiviral immune reaction carrier state exists. Relatively serious infection – chronic, Complications: cirrhosis, carcinoma. Diagnosis: Viral serology (HBsAg)
55. 26 Viral Hepatitis B: Serology Sequence of serologic markers for hepatitis B viral hepatitis demonstrating (A) acute infection with resolution and (B) progression to chronic infection.
57. 28 History Hep B Virus: 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.
58. 29 Pathogenesis: Ingestion / inoculation Replication - Viremia Liver – major site replication. Cellular immune response. Apoptosis, necrosis of hepatocytes. Inflammation - Hepatitis Bridging Hepatocyte necrosis (Central vein, portal triad) Fibrosis – patchy/bridging Cirrhosis – extensive fibrosis with loss of archetecture & regenerating nodules. Liver Failure, Coma, Carcinoma..
69. 40 Chronic Hepatitis: Persistent CPH Limited Periportal inflammation. Mild Periportal fibrosis No hepatocyte Necrosis. LFT normal or mild change. Late cirrhosis Active CAH Extensive Inflammation More fibrosis. Necrosis of hepatocytes. LFT abnormal. Early cirrhosis & other complication.
77. 48 Fulminant Hepatitis: Hepatic failure with in 2-3 weeks. Reactivation of chronic or acute hepatitis Massive necrosis, shrinkage, wrinkled Collapsed reticulin network Only portal tracts visible Little or massive inflammation – time More than a week – regenerative activity Complete recovery – or - cirrhosis.
88. 59 Cirrhosis End stage of diffuse liver disease. scaring with regenerating nodules. (liver failure) Normal Cirrhosis
89. The past has gone and future you cannot see. The present, when you can do something, that is the Gift (Present) with which you can make your future & past memorable. - Sai Baba "The past, the present and the future are really one: they are today." -Harriet Beecher Stowe
96. 67 Alcoholic Liver Injury: Pathogenesis Diversion of fat metabolism to alcohol – fat storage. Acetaldehyde – hepatotoxic – denatures Proteins Increased peripheral release of fatty acids. Alcohol stimulates collagen synthesis Mutant ALDH2 gene with low activity enzyme is observed in Caucasians but is found in some 40% of Orientals (autosomal dominant). Acetaldehyde
124. The symptoms usually begin after a febrile illness, commonly influenza or varicella infection, and are said to correlate with the administration of aspirin,
138. 98 Introduction Cirrhosis is common end result of many chronic liver disorders. Diffuse scarring of liver – follows hepatocellular necrosis of hepatitis. Inflammtion – healing with fibrosis - Regeneration of remaining hepatocytes form regenerating nodules. Loss of normal architecture & function.
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? Acute Viral Hepatitis Alcoholic hepatitis. Chronic viral Hepatitis. Post viral cirrhosis. Alcoholic Cirrhosis.
175. 135 HBsAg Positive, Anti HBcAg Positive Anti HBcAg IGM Negative Anti HBsAg Negative Viral serology interpretation: Acute Viral Hepatitis Immunised against Hep. B Chronic Hepatitis B Hepatitis B carrier stage Fulminant hepatitis B
176. 136 HBsAg Negative, Anti HBcAg Negative Anti HBcAg IGM Negative Anti HBsAg Positive Viral serology interpretation: Acute Viral Hepatitis Immunised against Hep. B Past Hepatitis B Hepatitis B carrier stage Fulminant hepatitis B
177. 137 HBsAg Negative, Anti HBsAg Positive Anti HBcAg Positive Anti HBcAg IGM Negative Viral serology interpretation: Acute Viral Hepatitis B Immunised against Hep. B Past Hepatitis B Hepatitis B carrier stage Carrier state of Hepatitis B
178. 138 Protein (Total) 59 g/L Albumin 30 g/L Globulin 29 g/L Bilirubin (Total) 27 μmol/L ALP 71 U/L GGT 523 U/L ALT 79 U/L AST 151 U/L Lab Investigations interpretation: Alcoholic Liver disease Acute Viral Hepatitis. Past Hepatitis B Hepatitis B carrier stage Carrier state of Hepatitis B
179. 139 Lab Investigations interpretation: Urea 5.8 mmol/L Creatinine 80 μmol/L Protein (Total) 66 g/L Albumin 35 g/L Globulin 31 g/L Bilirubin (Total) 192 μmol/L Bilirubin (Conj.) 130 μmol/L ALP 203 U/L GGT 470 U/L ALT 6055 U/L AST 4860 U/L Alcoholic Liver disease Past Hepatitis B Acute Viral Hepatitis. Hepatitis B carrier stage Carrier state of Hepatitis B
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? Anti HBs IgM anti-HDV Anti HCV IgM anti HAV Anti HBc
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? Anti HBs IgM anti-HDV Anti HCV IgM anti HAV Anti HBc
192. 41y Female, increasing malaise, 10kg weight loss since last year. Developed coma and died. Specimen of her Liver. Most likely etiologic agent? Aspirin abuse Ferrous sulphate Acetaminophen Aflatoxins Raw Oysters.
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? Repeat EIA for anti HCV Ab. Recombinant immunoblot assay (RIBA) Alpha-fetoprotein levels. HCV RNA test. Direct, indirect & total bilirubin assay.
194. 154 Learn from the mistakes of others. You can't live long enough to make them all yourself…! 61% of 5th year students exceeded ‘sensible’ limits Drugs and alcohol were taken mainly for pleasure and were perceived as a normal part of life for many students… Capability of advising patients…? http://www.lycaeum.org/research/researchpdfs/1996_webb_1.pdf
195. 155 CPC-2.2– Major Pathology CLI: Pathology of Acute & Chronic Liver injury. Hepatitis – Causes, Types, Pathophysiology, Gross & Microscopic Pathology. Complications. Common types: Viral (Specific & Non specific), Alcoholic & Drug induced. Pathophysiology of Jaundice, Clinical & Pathological types. Pathology of cirrhosis – Classification, morphology & Complications. Pathology of Alcoholic Liver disease – Pathophysiology, types & complications.
199. 159 Diagnosis pathway: ALT: 52 AST: 58 Alk Phos: 150 Bilirubin 3.9 (direct 1.8) Jaundice? Mild increase, Mixed (combined) Synthesis? Total protein, albumin – Low & PT abnormal. Obstruction & Bilirubin Clearance ? Alk Phos is up a bit – but not high – some obstruction. Hepatocyte Direct Injury: ALT & AST are up a bit, but not dramatically. Discussion: Chronic Mild compromise - chronic Active hepatitis. (In CPH LFT will be normal)
200. 160 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?