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Pathology of Hepatitis - Lecture

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Pathology of Hepatitis - Lecture

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  1. Pathology of Hepatitis - Lecture Never offer the devil (desire) a ride,He always want to be in the driving seat…!-- BK

  2. CPC 4.2.3 – 2013 – ―yellow eyes‖• Fatigue / Anorexia..?• Nausea, Vomiting..?• Haematemesis… ?• Itching..?• Fever..?• Abdominal distension slow..?• Bleeding / Bruising..?• 10 stubbies/day /more..?• Many Tattoos..?• BMI – if low / High..?2Mr. T.D. 50 year old, presents to his GP. ‗My stomach appears bigand my wife has noticed a yellow tinge in my eyes‘.CASE STUDY 1Abd distension, fatigue, yellow discoloration of eyes for 1 weekPresenting Symptoms:• Liver failure…• Liver failure…• Portal Hypertension• Obstructive jaundice.• Hepatitis.• Cirrhosis.• Vit-K deficiency.• Alcoholic hepatitis.• Viral Hepatitis (B/C)• Anorexia / Obesity –steatosis.• Differential Diagnosis:• Hepatitis: Alcoholic/Infective/Malignant/Drug/Toxins• Acute / Chronic? Primary/Secondary?• ―HBV / HCV, CMV, Lepto, Dengue, Melioidosis. CPC 4.2.3 – 2013 – ―yellow eyes‖• Fatigue / Anorexia..?• Nausea, Vomiting..?• Haematemesis… ?• Itching..?• Fever..?• Abdominal distension slow..?• Bleeding / Bruising..?• 10 stubbies/day /more..?• Many Tattoos..?• BMI – if low / High..?2Mr. T.D. 50 year old, presents to his GP. ‗My stomach appears bigand my wife has noticed a yellow tinge in my eyes‘.CASE STUDY 1Abd distension, fatigue, yellow discoloration of eyes for 1 weekPresenting Symptoms:• Liver failure…• Liver failure…• Portal Hypertension• Obstructive jaundice.• Hepatitis.• Cirrhosis.• Vit-K deficiency.• Alcoholic hepatitis.• Viral Hepatitis (B/C)• Anorexia / Obesity –steatosis.• Differential Diagnosis:• Hepatitis: Alcoholic/Infective/Malignant/Drug/Toxins• Acute / Chronic? Primary/Secondary?• ―HBV / HCV, CMV, Lepto, Dengue, Melioidosis.

  3. Case2: Mr.GG, 48y, fatigue & yellow…• Abdominal distension, fatigue, yellowsclera – 6 weeks.• Hardware business, Alcohol 40units / wk.• Travel: Thailand, had tattoo / surgery /transfusion.. *• PE: abdomen nil sig. mild RUQtenderness. No organomegaly.• Differential: Acute hepatitis.– CMV, Lepto, Hep A,B,C..– Hepatitis - Alcohol– Chronic hepatitis.– Drugs, toxins,3AST = 1320 U/lALT = 1780 U/lAlk. Phos. = 133 U/lGGT = 192 U/lHep B SerologyHep B sAg +iveHep B sAb <10Hep B cAb IgM +iveHep B e Ag +iveHep B eAb –ive Case2: Mr.GG, 48y, fatigue & yellow…• Abdominal distension, fatigue, yellowsclera – 6 weeks.• Hardware business, Alcohol 40units / wk.• Travel: Thailand, had tattoo / surgery /transfusion.. *• PE: abdomen nil sig. mild RUQtenderness. No organomegaly.• Differential: Acute hepatitis.– CMV, Lepto, Hep A,B,C..– Hepatitis - Alcohol– Chronic hepatitis.– Drugs, toxins,3AST = 1320 U/lALT = 1780 U/lAlk. Phos. = 133 U/lGGT = 192 U/lHep B SerologyHep B sAg +iveHep B sAb <10Hep B cAb IgM +iveHep B e Ag +iveHep B eAb –ive

  4. 4CPC 4.2.2 - 2010• George, 62 year old farmer from Tully, presentsto his GP with fatigue. His wife has asked him toconsult 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.• 2 x episodes fatigue last 2 years preceded by 2weeks of fever. Lab: ―liver not working so well.then felt better and has not been to see GP since.• Banana farmer from Greece - 26 years ago. 4CPC 4.2.2 - 2010• George, 62 year old farmer from Tully, presentsto his GP with fatigue. His wife has asked him toconsult 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.• 2 x episodes fatigue last 2 years preceded by 2weeks of fever. Lab: ―liver not working so well.then felt better and has not been to see GP since.• Banana farmer from Greece - 26 years ago.

  5. 5Laboratory Investigations:• FBC: Hb 13.8 g/dl, PCV 45%; WBC 7000/mm3, 70%N, 25% L; Platelets 200,000/mm3• Blood film: Normocytic, normochromic cells• Bilirubin: Total serum Bilirubin = 98 μmol/l, (Direct 67)• Liver enzymes:• Aspartate amino transferase (AST) = 182 U/l• Alanine amino transferase (ALT) = 55 U/l• Alkaline Phosphatase = 190 U/I• Serum Protein: Total protein = 59 g/l, Albumin = 20 g/l,• Hepatitis B Surface Antigen (HbsAg): PositiveHep B sAg +iveHep B sAb <10Hep B cAb IgM +iveHep B e Ag +iveHep B eAb –ive 5Laboratory Investigations:• FBC: Hb 13.8 g/dl, PCV 45%; WBC 7000/mm3, 70%N, 25% L; Platelets 200,000/mm3• Blood film: Normocytic, normochromic cells• Bilirubin: Total serum Bilirubin = 98 μmol/l, (Direct 67)• Liver enzymes:• Aspartate amino transferase (AST) = 182 U/l• Alanine amino transferase (ALT) = 55 U/l• Alkaline Phosphatase = 190 U/I• Serum Protein: Total protein = 59 g/l, Albumin = 20 g/l,• Hepatitis B Surface Antigen (HbsAg): PositiveHep B sAg +iveHep B sAb <10Hep B cAb IgM +iveHep B e Ag +iveHep B eAb –ive

  6. 6Differential Diagnosis:• Viral fever -?– Yellow fever, Relapsing fever, Dengue, Ebola,– Leptospirosis (common in Tully) - ?• Hepatitis – Acute / Chronic - ?• Chronic Hepatitis B – why chronic?• History & presentation in Hep. A & C ?• Other causes of Jaundice?• Alcoholic liver disease ?• Toxins, chemical, Reyes syndrome?• Hemolytic / Anemia - ?• Malignancy - ? 6Differential Diagnosis:• Viral fever -?– Yellow fever, Relapsing fever, Dengue, Ebola,– Leptospirosis (common in Tully) - ?• Hepatitis – Acute / Chronic - ?• Chronic Hepatitis B – why chronic?• History & presentation in Hep. A & C ?• Other causes of Jaundice?• Alcoholic liver disease ?• Toxins, chemical, Reyes syndrome?• Hemolytic / Anemia - ?• Malignancy - ?

  7. 7CPC23: HBS – Hepatitis & Cirrhosis• Pathology Major CLI:– Acute & Chronic Liver injury.– Pathophysiology of Jaundice, Clinical & Pathological types.– Alcoholic Liver disease – Pathophysiology, types & complications.– Hepatitis – Causes, types, Pathology (Alcohol, viral, Drug)– Pathology of cirrhosis – Types, morphology & Clinical.• Pathology Minor CLI:– Primary Biliary cirrhosis & Primary Sclerosing Cholangitis.– Wilsons disease, α1-Antitrypsin (AAT) deficiency.– Hemosiderosis, Hemochromatosis, Wilson‘s disease.– Liver tumours – adenoma, hyperplasia & cancer.– Cysts: Amoebic liver abscess & Hydatid disease of liver.– Congenital: Gilberts sy, Childhood cirrhosis– Dengue, Ebola virus, Reye‘s sy,– Liver blood supply disorders: Budd-Chiari Sy. 7CPC23: HBS – Hepatitis & Cirrhosis• Pathology Major CLI:– Acute & Chronic Liver injury.– Pathophysiology of Jaundice, Clinical & Pathological types.– Alcoholic Liver disease – Pathophysiology, types & complications.– Hepatitis – Causes, types, Pathology (Alcohol, viral, Drug)– Pathology of cirrhosis – Types, morphology & Clinical.• Pathology Minor CLI:– Primary Biliary cirrhosis & Primary Sclerosing Cholangitis.– Wilsons disease, α1-Antitrypsin (AAT) deficiency.– Hemosiderosis, Hemochromatosis, Wilson‘s disease.– Liver tumours – adenoma, hyperplasia & cancer.– Cysts: Amoebic liver abscess & Hydatid disease of liver.– Congenital: Gilberts sy, Childhood cirrhosis– Dengue, Ebola virus, Reye‘s sy,– Liver blood supply disorders: Budd-Chiari Sy.

  8. "When you speak, speak the truth;perform when you promise;discharge your trust... Withhold yourhands from striking, and from takingthat which is unlawful and bad..."-- From Wings of Fire, book by Dr. APJ Abdul Kalam, Foremer President of India. "When you speak, speak the truth;perform when you promise;discharge your trust... Withhold yourhands from striking, and from takingthat which is unlawful and bad..."-- From Wings of Fire, book by Dr. APJ Abdul Kalam, Foremer President of India.

  9. 9Pathology ofCommon Liver DisordersDr. Venkatesh M. Shashidhar.Assoc.Prof & Head of Pathology 9Pathology ofCommon Liver DisordersDr. Venkatesh M. Shashidhar.Assoc.Prof & Head of Pathology

  10. . 10• 1.5 kg, wedge shape• 4lobes, Right, left, (Caudate,Quadrate)• Double blood supply• Hepatic arteries• Portal – Venous bloodNormal

  11. . Normal Liver - InfantMuch larger, both lobes big, palpable below costal margin

  12. . 12CT Upper abdomen - NormalLiverStomachSpleen

  13. . 13Normal Liver – MicroscopyAcinus – showing zones 1, 2 & 3.Portal TriadCentral Vein

  14. . 14Structure of Liver LobulePortal Triad: Art, Vein, BDGIT Venous bl.HeartIVCLiver failure inCirrhosis…?

  15. . 15Acinus LobuleFunctional AnatomicZone 1 – Toxin damage. Zone 3 – Ischemic damageToxins IschemiaToxinsIschemia

  16. . 16Liver Function Tests: Interpretation• Synthesis / Function.– Total protein & albumin low, PT prolonged why? (vit K..)• Hepatocyte Injury.– ALT, AST, LDH - high. – why?– Alk Phos – moderately increased. – why?• Bile Duct Damage:– Alk Phos – increased – why?• Other:– GGT – increased with alcohol use. – why?– Viral serology -– Auto-Antibody panel.GGT ↑ Alcohol (centrilobular)IgG ↑ Autoimmune hepatitisIgM ↑ Primary biliary cirrhosisIgA ↑ Alcoholic cirrhosisAFP +ve Hep. Cell. CarcinomaAnti-mitochondrialantibody+ve Primary biliary cirrhosisAnti-smoothmuscle, & ANA+ve Autoimmune hepatitis

  17. . 17• Overproduction(Hemolytic - Unconjugated)• Impaired uptake(Hepatitis - mixed)• Block in metabolism(Congenital)• Impaired transport.(Hepatitis, toxins)• Intrahepatic Obst.(Hepatitis)• Extrahepatic Obst.(Obstructive - Congugated)Jaundice Types:

  18. . 18Jaundice Clinical Types:Stool Urine Ser. chem. DiagnosisDark Normal Un.Conj / ID Hemolysis.Pale Dark Conj./D + ALP CholestasisPale Dark ID+D ALT/AST Hepatitis.Variable Variable Variable Cong. Syndr.

  19. . A wise man watches his faults moreclosely than his virtues; othersreverse the order.--Napoleon Hill

  20. . 20Pathology of Viral HepatitisDr. Venkatesh M. Shashidhar.Assoc.Prof & Head of Pathology

  21. . 21Viral 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 ofmorbidity & mortality.• Horizontal transmission – Blood.. Sex.• Vertical transmission – Mother to fetus.• Hepatitis  Cirrhosis  Hepatic Ca. (not in A/E)

  22. . 22Hepatitis 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).

  23. . 23Viral Hepatitis A: Serology

  24. . 24History Hep B Virus:• In 1965 - Dr. Blumberg who wasstudying haemophilia, found anantibody in two patients which reactedagainst an antigen from an AustralianAborigine. Later the antigen was foundin patients with serum type hepatitis andwas initially designated "AustraliaAntigen". Later proved to be hepatitis Bvirus surface antigen (HBsAg). Dr.Blumberg was awarded the Nobel Prizein 1976.

  25. . 25Hepatitis B• Spread by blood, Sex & birth (serum hepatitis..)• Relatively long incubation period (4-26wk)• liver damage by antiviral immune reaction• Carrier & Chronic state exist.• Relatively serious infection – chronic• Complications: cirrhosis, carcinoma.• Diagnosis: Viral serology (HBs, HBc & HBe)IgM anti-HAVantibodyAcute Hepatitis AHBsAg Hepatitis B orcarrier – exp./inf.HBeAg Active hepatitis BinfectionAnti-HCV antibody Hepatitis C virusexposureHCV RNA Active hepatitis Cinfection

  26. . 26Viral Hepatitis B: SerologySequence of serologic markers for hepatitis B viral hepatitis demonstrating (A)acute infection with resolution and (B) progression to chronic infection.

  27. . 27Pathogenesis of Hepatitis A & B:

  28. . 28Pathogenesis:• 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 ofarchetecture & regenerating nodules.• Liver Failure, Coma, Carcinoma..

  29. . 29Pattern of Liver Damage• Zonal – Toxin/Hypoxia• Bridging – Viral & severe• Interface – CAH, Immune• Apoptotic – Acute Viral

  30. . 30Clinical Viral Hepatitis: (A,B,C, D & E)• Carrier state / Asymptomatic phase• Hepatic dysfunction:• Acute hepatitis – fever, icterus.• Chronic Hepatitis – non specific.– Chronic Persistent Hepatitis (CPH)– Chronic Active Hepatitis (CAH)• Fulminant hepatitis – massive necrosis• Cirrhosis – total fibrosis.• Hepatocellular Carcinoma

  31. . 31Viral Hepatitis: MicrobiologyVirus Hep-A Hep-B Hep-C Hep-Eagent ssRNA dsDNA ssRNA ssRNAIncubation 2-6 wk 4-26 wk 2-6 wk 4-6 wkTransm. Faeco-oral Parenteral Parenteral Faeco-oralCarrier None 5-10% Rare/None NoneChronicCirrhosisNoneNone4-10%1-3%80%50%NoneNoneOther Young Mild /fulminant,travel.Long incubat.~ 120dSteatosisSevere.Severe inPregnant

  32. . 32Acute viral Hepatitis: Swelling & Apoptotic cells.• Diffuse Inflammation.• Necrosis & Apoptosis.• Liver enzymes raised.

  33. . 33Liver Biopsy – CPH:Inflammation• Portal Inflammation.• No Necrosis• Liver enzymes normal

  34. . 34Chronic Active Hepatitis(CAH):• Portal & Diffuse Inflammation.• Necrosis & Apoptosis.• Liver enzymes abnormal.

  35. . 35Viral – Steatosis - AlcoholicMicrovesicular (viral) Macrovesicular (alcoholic)

  36. . 36Fulminant 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.

  37. . 37Fulminant Hepatitis:

  38. . 38Clinical Spectrum of HBV inf:

  39. . Failure is a blessing when it pushesone out of a cushioned seat of self-satisfaction and forces him to dosomething useful.--Napoleon Hill

  40. . Laboratory DiagnosisViral Hepatitis

  41. . 41Viral Hepatitis C: Serology

  42. . Hepatitis B – Lab result interpret

  43. . 43Learn from the mistakesof others. You cant livelong enough to makethem all yourself…!61% of 5th year students exceeded ‘sensible’ limitsDrugs and alcohol were taken mainly for pleasure and wereperceived as a normal part of life for many students…Capability of advising patients…?http://www.lycaeum.org/research/researchpdfs/1996_webb_1.pdf

  44. . "The past, the present and thefuture are really one: they aretoday!"-Harriet Beecher StoweThe 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

  45. . 45Other Hepatitis

  46. . Drug Induced Zonal Hepatitis:46• Autopsy specimen in a case ofacetaminophen (paracetamol /NSAID) overdose.• Prominent hemorrhagic necrosisof the centrilobular zones of allliver lobules.• greater activity of drug-metabolizing enzymes in thecentral zones.• Other agents that produce suchinjury are carbon tetrachloride,toxins of the mushroom Amanitaphalloides.• Patients either die in acutehepatic failure or recover withoutsequelae.

  47. . Autoimmune Hepatitis:47• Clinical & pathology similarto Chronic hepatitis.• Female predominance(70%)• Elevated serum IgG• High titers ofautoantibodies.• Autoimmune diseases.

  48. . Reye Syndrome:48• Acute disease of children• Following a febrileillness, commonlyinfluenza or varicellainfection with use ofaspirin.• Microvesicularsteatosis, hepaticfailure, andencephalopathy.• Cerebral edema and fataccumulation in the brain.• Pathogenesis remainsunknown (Aspirin..)Fat stain (oil-red o)

  49. . Toxemia of Pregnancy:49• Abnormal LFT in 3-5% of preg.• Acute Fatty Liver of Pregnancy• Intrahepatic Cholestasis of Preg.• Hypertension, proteinuria, edemaand coagulation abnormalities(pre-eclampsia) with convulsions& coma (eclampsia).• HELLP syndrome(hemolysis, elevated liver enz. &low plt).• Patchy hemorrhages overcapsule, DIC• Fibrin thrombi in portal vessels.• Hepatocellular necrosis.

  50. . Self Study: brief• Primary Biliary cirrhosis & Primary Sclerosing Cholangitis(differences, Male, female, associated conditions etc).• Wilsons disease & α1-Antitrypsin (AAT) deficiency.• Hemosiderosis, Hemochromatosis – differences.• Liver tumours – adenoma, hyperplasia & cancer.• Cysts: Congenital, Amoebic & Hydatid.• Congenital: Gilberts sy, Childhood cirrhosis• Hepatitis in Dengue & Leptospirosis• Reye‘s syndrome.• Budd-Chiari Syndrome.50

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