Pathology of Hepatitis - Lecture

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Pathology of Hepatitis - Lecture

  1. 1. Never offer the devil (desire) a ride,He always want to be in the driving seat…!-- BK
  2. 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.
  3. 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
  4. 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.
  5. 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
  6. 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 - ?
  7. 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.
  8. 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.
  9. 9. 9Pathology ofCommon Liver DisordersDr. Venkatesh M. Shashidhar.Assoc.Prof & Head of Pathology
  10. 10. 10• 1.5 kg, wedge shape• 4lobes, Right, left, (Caudate,Quadrate)• Double blood supply• Hepatic arteries• Portal – Venous bloodNormal
  11. 11. Normal Liver - InfantMuch larger, both lobes big, palpable below costal margin
  12. 12. 12CT Upper abdomen - NormalLiverStomachSpleen
  13. 13. 13Normal Liver – MicroscopyAcinus – showing zones 1, 2 & 3.Portal TriadCentral Vein
  14. 14. 14Structure of Liver LobulePortal Triad: Art, Vein, BDGIT Venous bl.HeartIVCLiver failure inCirrhosis…?
  15. 15. 15Acinus LobuleFunctional AnatomicZone 1 – Toxin damage. Zone 3 – Ischemic damageToxins IschemiaToxinsIschemia
  16. 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. 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. 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. 19. A wise man watches his faults moreclosely than his virtues; othersreverse the order.--Napoleon Hill
  20. 20. 20Pathology of Viral HepatitisDr. Venkatesh M. Shashidhar.Assoc.Prof & Head of Pathology
  21. 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. 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. 23. 23Viral Hepatitis A: Serology
  24. 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. 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. 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. 27. 27Pathogenesis of Hepatitis A & B:
  28. 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. 29. 29Pattern of Liver Damage• Zonal – Toxin/Hypoxia• Bridging – Viral & severe• Interface – CAH, Immune• Apoptotic – Acute Viral
  30. 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. 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. 32. 32Acute viral Hepatitis: Swelling & Apoptotic cells.• Diffuse Inflammation.• Necrosis & Apoptosis.• Liver enzymes raised.
  33. 33. 33Liver Biopsy – CPH:Inflammation• Portal Inflammation.• No Necrosis• Liver enzymes normal
  34. 34. 34Chronic Active Hepatitis(CAH):• Portal & Diffuse Inflammation.• Necrosis & Apoptosis.• Liver enzymes abnormal.
  35. 35. 35Viral – Steatosis - AlcoholicMicrovesicular (viral) Macrovesicular (alcoholic)
  36. 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. 37. 37Fulminant Hepatitis:
  38. 38. 38Clinical Spectrum of HBV inf:
  39. 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. 40. Laboratory DiagnosisViral Hepatitis
  41. 41. 41Viral Hepatitis C: Serology
  42. 42. Hepatitis B – Lab result interpret
  43. 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. 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. 45. 45Other Hepatitis
  46. 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. 47. Autoimmune Hepatitis:47• Clinical & pathology similarto Chronic hepatitis.• Female predominance(70%)• Elevated serum IgG• High titers ofautoantibodies.• Autoimmune diseases.
  48. 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. 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. 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
  51. 51. 51Pathology of Cirrhosis
  52. 52. 52NormalCirrhosis CirrhosisEnd stage of manydiffuse liver damages.Resulting in scaring &regenerating nodules(liver failure due toloss of archetecture)NodularShrunken
  53. 53. 53Clinical Features - Pathogenesis• Hypoalbuminemia/edema• Hyperammonemia/CNS coma.• Hypoglycemia• Palmar erythema• Spider angiomas• Hypogonadism• Gynecomastia• Weight loss• Muscle wasting• Ascites• Splenomegaly• Esophageal varices• Hemorrhoids• Caput medusae-abdominal skin• Coagulopathy• Hepatic encephalopathy• Hepatorenal syndrome• Decreased Albumin synthesis• Hepatorenal syndrome• Glycogen metabolism.• Excess Oestrogens• Excess Oestrogens• Excess Oestrogens• Excess Oestrogens• Decreased metabolism.• Decreased metabolism• Portal Hypertension• Portal Hypertension• Portal Hypertension• Portal Hypertension• Portal Hypertension• Coag factory synthesis.• Detoxification.• ? Renal ischemia
  54. 54. 54MRI CirrhosisNodularShrunken
  55. 55. 55Liver Biopsy – CirrhosisReg. noduleFibrous septa
  56. 56. 56Liver Biopsy – CirrhosisReg. noduleFibrous septa
  57. 57. 57Liver Needle Biopsy – Cirrhosis:(Blue collagen stain)Reg. noduleFibrous septa
  58. 58. 58Etiology of Cirrhosis• Alcoholic liver disease 60-70%• Viral hepatitis 10%• Biliary disease 5-10%• Primary hemochromatosis 5%• Cryptogenic cirrhosis 10-15%• Wilson‘s, 1AT def rare
  59. 59. 59Pathogenesis:• Hepatocyte injury leading to necrosis.– Alcohol, virus, drugs, toxins, genetic etc..• Chronic inflammation - (hepatitis).• Bridging fibrosis.• Regeneration of remaining hepatocytesProliferate as round nodules.• Loss of vascular arrangement results inregenerating hepatocytes ineffective.
  60. 60. 60Cirrhosis – Portal hypertension• Cirrhosis-obstruction• Portalhypertension• Splenomegaly• transudation -Ascites
  61. 61. 61ClinicalFeaturesHepatic encephalopathy
  62. 62. 62Gynaecomastia in Cirrhosis????
  63. 63. 63Palmar erythema & Spider nevi? Pathogenesis
  64. 64. Primary Biliary Cirrhosis• Autoimmune.• Females 6:1.• Pruritis, jaundice,hepatosplenomegaly (initial).• Intrahepatic Bile duct inflammation• Cholestasis (bile stained liver)64
  65. 65. Neonatal cholestasis / Cirrhosis• Infections;– CMV, Syphilis, Septicemia.• Extrahepatic biliary atresia.• Drugs & Toxins– Nutrition, drugs.• α1-Antitrypsin deficiency– Protease inhibitor (inflam).– Mild hepatitis  cirrhosis.• Cystic fibrosis.• Idiopathic– Indian child hood cirrhosis.65
  66. 66. 66Normal / Cirrhosis Liver
  67. 67. 67Hepatocellular CarcinomaNormal - Carcinoma
  68. 68. 68Hepatic Adenoma: rareadenomaadenoma
  69. 69. 69Nutmeg Liver:• Chronic PassiveCongestion – Heart failure.• Central zone (Zone-3) –congestion and necrosis.• Hemorrhage – RBCs inzone-3 - Mottledappearance (nutmeg).• Symptoms similar tochronichepatitis, Ascites, distended abdomen, ankleedema, Hepaticencephalopathy, confusion.
  70. 70. 70Liver Metastasis:• Multiple• Cleardemarcation• Hemorrhage /Central necrosis(+/-)• Microscopydepends on type.
  71. 71. 71Learn 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
  72. 72. AlcoholicLiver Disease
  73. 73. 73Incidence is increasing…!
  74. 74. 74Chronic Alcoholism:• Clinical Features:
  75. 75. 75Alcoholic Liver Injury:• Ethyl alcohol : Common cause ofacute/Chronic liver disease• Alcoholic Liver disease - Patterns– Fatty change,– Acute hepatitis (Mallory Hyalin)– Chronic hepatitis with Portal fibrosis– Chronic Liver failure– Cirrhosis• All reversible except cirrhosis stage.
  76. 76. 76Alcoholic Liver Injury: Pathogenesis• Acetaldehyde – metabolite – hepatotoxic• Diversion of metabolism to alcohol• Fat storage – fatty change. Cell swelling..• Rupture Fat necrosis  severeinflammation  fibrosis.• Alcohol stimulates collagen synthesis• Inflammation, Portal bridging fibrosis• Micronodular cirrhosis.
  77. 77. 77Alcoholic Liver Injury: Pathogenesis• Diversion of fat metabolismto alcohol – fat storage.• Acetaldehyde – hepatotoxic– denatures Proteins• Increased peripheral releaseof fatty acids.• Alcohol stimulates collagensynthesis• Mutant ALDH2 gene withlow activity enzyme isobserved in Caucasians butis found in some 40% ofOrientals (autosomaldominant).Acetaldehyde
  78. 78. 78Alcoholic Liver DamageIto Cells
  79. 79. 79High RiskIntermediateLow RiskSafe drinking…
  80. 80. 80Risk of Alcohol injury1 Unit = 10ml = 8gm
  81. 81. 81Alcohol Toxicity:Liver Fatty change ToxicityAcute hepatitisAlcoholic cirrhosisNervous system Wernicke syndrome Thiamine deficiencyKorsakoff syndrome Toxicity and thiamine deficiencyCerebellar degeneration Nutritional deficiencyPeripheral neuropathy Thiamine deficiencyCardiovascular system Cardiomyopathy ToxicityHypertension VasopressorGastrointestinal tract Gastritis ToxicityPancreatitis ToxicitySkeletal muscle Rhabdomyolysis ToxicityReproductive system Testicular atrophy ?Spontaneous abortion ?Fetal alcohol syndrome Growth retardation ToxicityMental retardation, Birthdefects.
  82. 82. 82Alcoholic Liver Damage
  83. 83. Alcoholic Hepatitis:83• Centrilobular necrosis. Ballooned degenerating hepatocytes (BC) Mallory bodies(MB) Many Neutrophils, few lymphocytes & Macrophages.• The central vein(or terminal hepatic venule (THV), is encased in connectivetissue (C) (central sclerosis). Fat-laden hepatocytes (F) are evident in the lobule.The portal tract displays moderate chronic inflammation.
  84. 84. 84Alcoholic Hepatits - Mallorys hyalin
  85. 85. 85Alcoholic hepatitis & Mallory Hyalin:
  86. 86. 86Alcoholic Fatty Liver
  87. 87. 87Alcoholic Fatty Liver
  88. 88. 88Alcoholic Fatty Liver
  89. 89. Diffuse fatty liver - un-enhanced CT.Hamer O W et al. Radiographics 2006;26:1637-1653©2006 by Radiological Society of North AmericaNormal
  90. 90. 90Alcoholic Fatty Liver - CT
  91. 91. 91Alcoholic Fatty Liver - CT
  92. 92. 92Alcoholic Fatty liver:
  93. 93. 93Alcoholic Fatty Liver - collagen stain
  94. 94. 94Alcoholic Cirrhosis:
  95. 95. 95Alcoholic Fatty Liver - collagen stain
  96. 96. 96Alcoholic Liver Injury: Complications• Pancreatitis – Acute or Chronic. Due toischemic damage to pancreas.• Alcoholic hepatitis – similar to viral hepatitis.• Fulminant hepatitis• Alcoholic Cirrhosis – Micronodular.Alcohol & Medical studentshttp://www.m-c-a.org.uk/about_us/about_mca
  97. 97. Miscellaneous Conditions97
  98. 98. Primary Biliary Cirrhosis• Autoimmune, Chronic, progressive• Destruction of intrahepatic bile ducts, portalinflammation & scarring – cholestasis.• Leading to cirrhosis and liver failure.• Females common (6:1)• Insidious onset of Pruritis & cholestatic jaundice.• Markedly high ALP, +ve antimitochondrial Ab.• Histopathology: Portal inflammation, bilestasis, bile plugs & lakes, Later stages cirrhosis– Firm fibrotic, nodular, greenish, Shrunken.
  99. 99. Macronodular Cirrhosis - PBC
  100. 100. PBC – Microscopy:
  101. 101. Cholestasis: Bile ―plugs‖, Bile ―lakes‖Bile PlugsBile Lakes
  102. 102. Biliary Atresia in a 3m child.Dark bile stained liver tissue, cirrhosis & death before 2 years of age.
  103. 103. 103Hepatosplenic schistosomiasis:• Schistosoma Mansoni /haematobium• Granulomas in the liver.• Fibrotic reaction around egg• Pipe stem Portal Fibrosis• Cirrhosis, spleenomegaly,ascitis.
  104. 104. 104Hepatosplenic schistosomiasis:• Schistosoma Mansoni /haematobium• Granulomas in the liver.• Fibrotic reaction around egg• Pipe stem Portal Fibrosis• Cirrhosis, spleenomegaly,ascitis.
  105. 105. "Its not the will to win, but the willto prepare to win that makes thedifference."- - Bear Bryant 1913-1983, Football Coach
  106. 106. 106CPC-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 & Pathologicaltypes.• Pathology of cirrhosis – Classification, morphology &Complications.• Pathology of Alcoholic Liver disease – Pathophysiology,types & complications.
  107. 107. 107CPC-2.2– Minor Pathology CLI:• Hemosiderosis & Hemochromatosis.• Pathogenesis of Hepatic coma, Liver failure.• Primary Biliary cirrhosis.• Hepatocellular carcinoma.• Liver cysts & tumours – adenoma, hyperplasia & cancer.• Amoebic liver abscess & Hydatid disease of liver.• Congenital liver disorders – enzyme disorders.
  108. 108. 108Clinical Case Study
  109. 109. 109Case # 2 - ? Diagnosis• 60yr Male, 8 month slowly developing weakness,mild icterus.• PE: Mild Abdominal tenderness, Noorganomegaly. Mild Scleral icterus.• Labs: ALT: 52 (N= 8-33 U/L)• AST: 58 (N= 4-36 U/L)• Alk Phos: 150 (N= 20-130 u/L)• Bilirubin 3.9 (N= 0.1-1.2 mg/dL) (direct 1.8)• T Protein 4.8 (N= 6.0-7.8 g/dL)• Albumin 2.5 (N= 3.2-4.5 g/dl)• PT = 16 sec (N= 11-14.7 sec )• Differential diagnosis?• What further investigations?
  110. 110. 110Diagnosis pathway:• 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 Activehepatitis. (In CPH LFT will be normal)ALT: 52AST: 58Alk Phos: 150Bilirubin 3.9 (direct 1.8)
  111. 111. 111• 28y Male, 3 weeks after visiting eastTimor, presents with malaise, fatigue, lossof appetite. Mild icterus. AST & ALT mildelevation. Total bil 3.9mg/dl (Direct 2.8).Which of the following would be positive?
  112. 112. 112Alcohol Metabolism:
  113. 113. 113Chronic Hepatitis:• Passive CPH• Limited Periportalinflammation.• Mild Periportal fibrosis• No hepatocyteNecrosis.• LFT normal or mildchange.• Late cirrhosis• Active CAH• ExtensiveInflammation• More fibrosis.• Necrosis ofhepatocytes.• LFT abnormal.• Early cirrhosis & othercomplication.
  114. 114. “Nearly all men can stand adversity,but if you want to test a manscharacter, give him power!”— Abraham Lincoln

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