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Never offer the devil a ride. He will always want to be in the driving seat…! BK
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 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
4 Laboratory 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) = 62 U/l  Alanine amino transferase (ALT) = 110 U/l  Alkaline Phosphatase = 116 U/I  Serum Protein: Total protein = 61 g/l, Albumin = 20 g/l,  Hepatitis B Surface Antigen (HbsAg): Positive
5 Differential 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? Anemia - ? Malignancy - ?
6 Jaundice Clinical Diagnosis
7 Pathology of HepatitisViral & Alcoholic Dr. Venkatesh M. Shashidhar. Assoc.Prof  & Head of Pathology
8 1.5 kg, wedge shape 4 lobes, Right, left, (Caudate, Quadrate) Double blood supply Hepatic arteries Portal – Venous blood Normal
9 CT Upper abdomen - Normal Liver Stomach Aorta Spleen Lung Lung
Normal Liver - Infant Much larger, both lobes, below costal margin – palpable*
11 Normal Liver
12 Normal Liver – MicroscopyAcinus – showing zones 1, 2 & 3. Central Vein Blood Flow Portal Triad
13 Structure of Liver Lobule Portal Triad: Art, Vein, BD
14 Acinus			LobuleFunctional 	 		 Anatomic 3 Zone 1 – Toxin damage.    		Zone 3 – Ischemic damage
Jaundice 15 ,[object Object]
Impaired bilirubin uptake.
Block in metabolism
Impaired transport.
Obstruction to bile excretion.,[object Object]
Fatigue
Indigestion
Fat intolerance
urine/stool*
Jaundice
Bleeding
Edema
Abd. Distension
Confusion
Coma,[object Object]
Hyperammonemia
Hypoglycemia
Palmarerythema
Spider angiomas
Hypogonadism
Gynecomastia
Weight loss
Muscle wasting
Ascites
Splenomegaly
Esophagealvarices
Hemorrhoids
Caput medusae-abdominal skin
Complications of Hepatic Failure
Coagulopathy
Hepatic encephalopathy
Hepatorenal syndromeDecreased Albumin synthesis Hepatorenal syndrome
Jaundice in liver failure 18
19 Diseases of Liver: Hepatitis: Inflammation of Liver Viral, Alcohol, immune, Drugs, Toxins, parasites Acute, Chronic & Fulminant – types. Billiary obstruction – gall stones. Cirrhosis – diffuse scarring & regeneration. Carcinoma - Hepatocellular & Bile duct. Congenital: metabolic, cysts, tumors.
Viral Hepatitis:
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)
22 Viral Hepatitis: Microbiology
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).
24 Viral Hepatitis A: Serology
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)
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.
27 Pathogenesis of Hepatitis A & B:
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.
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..
30 Pattern of Liver Damage Zonal – Toxin/Hypoxia Bridging – Viral & severe Interface – CAH, Immune Apoptotic – Acute Viral
31 Spectrum of Viral Hepatitis: Carrier state / Asymptomatic phase 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
32 Acute Hepatitis: Swelling and Apoptosis Piecemeal or Bridging, panacinar necrosis Diffuse Inflammation – lymphocytes, Macrophages. Ground glass hepatocytes – HBV Mild fatty change – HCV. Portal inflammation and Cholestasis
33 Acute viral Hepatitis:
34 Acute viral Hepatitis:Apoptotic cells.
35 Acute viral Hepatitis:Apoptotic cell.
36 Acute viral Hepatitis:
37 Acute viral Hepatitis:
38 Acute viral Hepatitis C:
39 Ground glass Hepatocytes:
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.
41 Liver Biopsy – viral Hepatitis-C
42 Liver Biopsy - CAH:
43 Chronic Active viral Hepatitis:
44 Chronic Persistent Hepatitis:
45 Liver Biopsy – CPH: Inflammation No Necrosis
46 Acute - Hepatitis - Chronic
47 Viral – Steatosis - Alcoholic Microvesicular (viral)	Macrovesicular(alcoholic)
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.
49 Fulminant Hepatitis:
50 Fulminant Hepatitis:
51 Fulminant Hepatitis:
52 Fulminant Hepatitis:confluent necrosis().
53 Clinical Spectrum of HBV inf:
54 Outcomes of HBV Infection:
“Nearly all men  can stand adversity,  but if you want to  test a man's character,  give him power” —  Abraham Lincoln
Laboratory DiagnosisViral Hepatitis
57 Viral Hepatitis C: Serology
Hepatitis B – Lab result interpret
59 Cirrhosis  End stage of diffuse liver disease. scaring with regenerating nodules. (liver failure) Normal        Cirrhosis 
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
Alcoholic Liver Disease
62 Incidence is increasing…!
63 Chronic Alcoholism: Clinical Features:
64 Alcoholic Liver Injury: Ethyl alcohol : Common cause of acute/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.
65 Alcoholic Liver Injury: Pathogenesis Acetaldehyde – metabolite – hepatotoxic Diversion of metabolism to alcohol  Fat  storage – fatty change. Cell swelling.. Rupture Fat necrosis  severe inflammation  fibrosis. Alcohol stimulates collagen synthesis Inflammation, Portal bridging fibrosis Micronodular cirrhosis.
66 Alcoholic Liver Damage Ito Cells
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
68 Safe drinking… High Risk Intermediate Low Risk
69 Risk of Alcohol injury 1 Unit = 10ml = 8gm
70 Alcoholic Liver Damage
71 Alcohol Toxicity:
72 Alcoholic Fatty Liver
73 Alcoholic Fatty Liver
74 Alcoholic Fatty Liver
75 Alcoholic Fatty Liver
Diffuse fatty liver - un-enhanced CT. Normal Hamer O W et al. Radiographics 2006;26:1637-1653 ©2006 by Radiological Society of North America
77 Alcoholic Fatty Liver - CT
78 Alcoholic Fatty Liver - CT
79 Alcoholic Liver- Mallory's hyalin
80 Alcoholic Fatty change:
81 Alcoholic Fatty change & Mallory Hyalin:
82 Alcoholic Fatty Liver
83 Alcoholic Fatty Liver - collagen stain
84 Alcoholic Cirrhosis:
85 Alcoholic Fatty Liver - collagen stain
Alcoholic Hepatitis: 86 ,[object Object]
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.,[object Object]
Drug Induced Zonal Hepatitis: 88 ,[object Object]
Prominent hemorrhagic necrosis of the centrilobular zones of all liver lobules.
greater activity of drug-metabolizing enzymes in the central zones.
Other agents that produce such injury are carbon tetrachloride, acetaminophen, toxins of the mushroom Amanita phalloides.
Patients either die in acute hepatic failure or recover without sequelae.,[object Object]
Microvesicular steatosis, hepatic failure, and encephalopathy.
Cerebral edema and fat accumulation are reported in the brain.
The symptoms usually begin after a febrile illness, commonly influenza or varicella infection, and are said to correlate with the administration of aspirin,
Pathogenesis remains unknown.
Uncommon, possibly as a result of decreasing use of aspirin in children.,[object Object]
HELLP syndrome (hemolysis, elevated liver enzymes and low platelet count) can also occur in pre-eclamptic women.
Patchy hemorrhages over capsule
Intravascular coagulation
Fibrin thrombi in portal vessels.
Hepatocellular necrosis.,[object Object]
92 Cirrhosis  End stage of diffuse liver disease. scaring with regenerating nodules. (liver failure) Normal        Cirrhosis 
93 Post hepatitis Liver Cirrhosis Shrunken, irregular nodularity, (macro nodular) fibrous septa.
94 MRI Cirrhosis
95 Liver Biopsy – Cirrhosis:
96 Liver Biopsy – Cirrhosis
97 Liver Biopsy – Cirrhosis
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.
99 Etiology 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
100 Alcoholic Cirrhosis
101 Micronodular cirrhosis:
102 Pathogenesis: Hepatocyte injury leading to necrosis. Alcohol, virus, drugs, toxins, genetic etc.. Chronic inflammation - (hepatitis). Bridging fibrosis. Regeneration of remaining hepatocytes Proliferate as round nodules. Loss of vascular arrangement results in regenerating hepatocytes ineffective.
103 Clinical Features Hepatic encephalopathy
104 Pathogenesis of Ascitis: Hepatorenal Syndrome
105 Cirrhosis – Portal hypertension Cirrhosis-obstruction Portal hypertension Splenomegaly transudation - Ascites
106 Causes of Portal Hypertension:
107 Ascitis in Cirrhosis
108 Cirrhosis:
109 Ascitis in Cirrhosis
110 Gynaecomastia in Cirrhosis ? ? ? ?
111 Ascitis in congenital Cirrhosis
112 Normal / Cirrhosis Liver
113 Micronodular cirrhosis:
114 Biliary Cirrhosis
115 Cirrhosis with bile stasis
116 Cirrhosis with bile stasis
117 Primary Biliary Cirrhosis - Micronodular
118 Liver Biopsy – Cirrhosis
119 Palmar erythema & Spider nevi ? Pathogenesis
120 Hepatocellular Carcinoma
121 Cirrhosis with carcinoma:

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Pathology of Hepatitis

  • 1. Never offer the devil a ride. He will always want to be in the driving seat…! BK
  • 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
  • 4. 4 Laboratory 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) = 62 U/l Alanine amino transferase (ALT) = 110 U/l Alkaline Phosphatase = 116 U/I Serum Protein: Total protein = 61 g/l, Albumin = 20 g/l, Hepatitis B Surface Antigen (HbsAg): Positive
  • 5. 5 Differential 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? Anemia - ? Malignancy - ?
  • 7. 7 Pathology of HepatitisViral & Alcoholic Dr. Venkatesh M. Shashidhar. Assoc.Prof & Head of Pathology
  • 8. 8 1.5 kg, wedge shape 4 lobes, Right, left, (Caudate, Quadrate) Double blood supply Hepatic arteries Portal – Venous blood Normal
  • 9. 9 CT Upper abdomen - Normal Liver Stomach Aorta Spleen Lung Lung
  • 10. Normal Liver - Infant Much larger, both lobes, below costal margin – palpable*
  • 12. 12 Normal Liver – MicroscopyAcinus – showing zones 1, 2 & 3. Central Vein Blood Flow Portal Triad
  • 13. 13 Structure of Liver Lobule Portal Triad: Art, Vein, BD
  • 14. 14 Acinus LobuleFunctional Anatomic 3 Zone 1 – Toxin damage. Zone 3 – Ischemic damage
  • 15.
  • 19.
  • 26. Edema
  • 29.
  • 46. Hepatorenal syndromeDecreased Albumin synthesis Hepatorenal syndrome
  • 47. Jaundice in liver failure 18
  • 48. 19 Diseases of Liver: Hepatitis: Inflammation of Liver Viral, Alcohol, immune, Drugs, Toxins, parasites Acute, Chronic & Fulminant – types. Billiary obstruction – gall stones. Cirrhosis – diffuse scarring & regeneration. Carcinoma - Hepatocellular & Bile duct. Congenital: metabolic, cysts, tumors.
  • 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)
  • 51. 22 Viral Hepatitis: Microbiology
  • 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).
  • 53. 24 Viral Hepatitis A: Serology
  • 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.
  • 56. 27 Pathogenesis of Hepatitis A & B:
  • 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..
  • 59. 30 Pattern of Liver Damage Zonal – Toxin/Hypoxia Bridging – Viral & severe Interface – CAH, Immune Apoptotic – Acute Viral
  • 60. 31 Spectrum of Viral Hepatitis: Carrier state / Asymptomatic phase 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
  • 61. 32 Acute Hepatitis: Swelling and Apoptosis Piecemeal or Bridging, panacinar necrosis Diffuse Inflammation – lymphocytes, Macrophages. Ground glass hepatocytes – HBV Mild fatty change – HCV. Portal inflammation and Cholestasis
  • 62. 33 Acute viral Hepatitis:
  • 63. 34 Acute viral Hepatitis:Apoptotic cells.
  • 64. 35 Acute viral Hepatitis:Apoptotic cell.
  • 65. 36 Acute viral Hepatitis:
  • 66. 37 Acute viral Hepatitis:
  • 67. 38 Acute viral Hepatitis C:
  • 68. 39 Ground glass Hepatocytes:
  • 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.
  • 70. 41 Liver Biopsy – viral Hepatitis-C
  • 71. 42 Liver Biopsy - CAH:
  • 72. 43 Chronic Active viral Hepatitis:
  • 73. 44 Chronic Persistent Hepatitis:
  • 74. 45 Liver Biopsy – CPH: Inflammation No Necrosis
  • 75. 46 Acute - Hepatitis - Chronic
  • 76. 47 Viral – Steatosis - Alcoholic Microvesicular (viral) Macrovesicular(alcoholic)
  • 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.
  • 82. 53 Clinical Spectrum of HBV inf:
  • 83. 54 Outcomes of HBV Infection:
  • 84. “Nearly all men can stand adversity, but if you want to test a man's character, give him power” —  Abraham Lincoln
  • 86. 57 Viral Hepatitis C: Serology
  • 87. Hepatitis B – Lab result interpret
  • 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
  • 91. 62 Incidence is increasing…!
  • 92. 63 Chronic Alcoholism: Clinical Features:
  • 93. 64 Alcoholic Liver Injury: Ethyl alcohol : Common cause of acute/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.
  • 94. 65 Alcoholic Liver Injury: Pathogenesis Acetaldehyde – metabolite – hepatotoxic Diversion of metabolism to alcohol Fat storage – fatty change. Cell swelling.. Rupture Fat necrosis  severe inflammation  fibrosis. Alcohol stimulates collagen synthesis Inflammation, Portal bridging fibrosis Micronodular cirrhosis.
  • 95. 66 Alcoholic Liver Damage Ito Cells
  • 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
  • 97. 68 Safe drinking… High Risk Intermediate Low Risk
  • 98. 69 Risk of Alcohol injury 1 Unit = 10ml = 8gm
  • 105. Diffuse fatty liver - un-enhanced CT. Normal Hamer O W et al. Radiographics 2006;26:1637-1653 ©2006 by Radiological Society of North America
  • 106. 77 Alcoholic Fatty Liver - CT
  • 107. 78 Alcoholic Fatty Liver - CT
  • 108. 79 Alcoholic Liver- Mallory's hyalin
  • 109. 80 Alcoholic Fatty change:
  • 110. 81 Alcoholic Fatty change & Mallory Hyalin:
  • 112. 83 Alcoholic Fatty Liver - collagen stain
  • 114. 85 Alcoholic Fatty Liver - collagen stain
  • 115.
  • 116.
  • 117.
  • 118. Prominent hemorrhagic necrosis of the centrilobular zones of all liver lobules.
  • 119. greater activity of drug-metabolizing enzymes in the central zones.
  • 120. Other agents that produce such injury are carbon tetrachloride, acetaminophen, toxins of the mushroom Amanita phalloides.
  • 121.
  • 122. Microvesicular steatosis, hepatic failure, and encephalopathy.
  • 123. Cerebral edema and fat accumulation are reported in the brain.
  • 124. The symptoms usually begin after a febrile illness, commonly influenza or varicella infection, and are said to correlate with the administration of aspirin,
  • 126.
  • 127. HELLP syndrome (hemolysis, elevated liver enzymes and low platelet count) can also occur in pre-eclamptic women.
  • 130. Fibrin thrombi in portal vessels.
  • 131.
  • 132. 92 Cirrhosis End stage of diffuse liver disease. scaring with regenerating nodules. (liver failure) Normal Cirrhosis 
  • 133. 93 Post hepatitis Liver Cirrhosis Shrunken, irregular nodularity, (macro nodular) fibrous septa.
  • 135. 95 Liver Biopsy – Cirrhosis:
  • 136. 96 Liver Biopsy – Cirrhosis
  • 137. 97 Liver Biopsy – Cirrhosis
  • 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.
  • 139. 99 Etiology 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
  • 142. 102 Pathogenesis: Hepatocyte injury leading to necrosis. Alcohol, virus, drugs, toxins, genetic etc.. Chronic inflammation - (hepatitis). Bridging fibrosis. Regeneration of remaining hepatocytes Proliferate as round nodules. Loss of vascular arrangement results in regenerating hepatocytes ineffective.
  • 143. 103 Clinical Features Hepatic encephalopathy
  • 144. 104 Pathogenesis of Ascitis: Hepatorenal Syndrome
  • 145. 105 Cirrhosis – Portal hypertension Cirrhosis-obstruction Portal hypertension Splenomegaly transudation - Ascites
  • 146. 106 Causes of Portal Hypertension:
  • 147. 107 Ascitis in Cirrhosis
  • 149. 109 Ascitis in Cirrhosis
  • 150. 110 Gynaecomastia in Cirrhosis ? ? ? ?
  • 151. 111 Ascitis in congenital Cirrhosis
  • 152. 112 Normal / Cirrhosis Liver
  • 155. 115 Cirrhosis with bile stasis
  • 156. 116 Cirrhosis with bile stasis
  • 157. 117 Primary Biliary Cirrhosis - Micronodular
  • 158. 118 Liver Biopsy – Cirrhosis
  • 159. 119 Palmar erythema & Spider nevi ? Pathogenesis
  • 161. 121 Cirrhosis with carcinoma:
  • 162. 122 Nutmeg Liver: Chronic Passive Congestion – Heart failure. Venous stasis - right atrium - hypoperfusion retrograde congestion – IVC & SVC. Central zone (Zone-3) – congestion and necrosis. Hemorrhage – RBCs in zone-3 - Mottled appearance (nutmeg). Symptoms are similar to those of chronic hepatitis - Ascites, distended abdomen, ankle edema, Hepatic encephalopathy, confusion.
  • 164. 124 Liver Metastasis: Multiple Clear demarcation Hemorrhage / Central necrosis (+/-) Microscopy depends on type.
  • 166. 126 Hepatosplenic schistosomiasis: Schistosoma Mansoni / haematobium Granulomas in the liver. Fibrotic reaction around egg Pipe stem Portal Fibrosis Cirrhosis, spleenomegaly, ascitis.
  • 167. 127 Hepatosplenic schistosomiasis: Schistosoma Mansoni / haematobium Granulomas in the liver. Fibrotic reaction around egg Pipe stem Portal Fibrosis Cirrhosis, spleenomegaly, ascitis.
  • 168. "It's not the will to win, but the will to prepare to win that makes the difference." Bear Bryant1913-1983, Football Coach
  • 169. 129 CPC-2.2– HBS–Hepatitis Basic science - Core Learning Issues: anatomy and histology of the liver & Spleen Portal circulation. Liver Functions & Bilirubin metabolism (RBC, Hb) Viral Hepatitis – epidemiology,virology. Pathology Core Learning Issues: Pathology of liver, Hepatitis. Causes, types, gross & microscopic morphology. Jaundice – clinical and pathological types Acholuric, obstructive, hemolytic, hepatic. Laboratory investigations. Pathology of cirrhosis & its complications.
  • 170. 130 51y M, Alcoholic: Look at Arrow ? Pathogenesis. Porta-systemic shunt Hyper-oestrogenemia Portal hypertension Hypo-albuminemia Decreased vit-K
  • 171. Pathogenesis - typical of which virus? HAV HBV HCV HDV Non Specific
  • 172. 42y M, alcoholic, recurrent fatigue. Liver biopsy. ? Diagnosis Acute Hepatitis Chronic Active hepatitis. Chronic Persistant hepatitis. Fulminant Hepatitis. Cirrhosis.
  • 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.
  • 174. 69y Female, Chronic bronchitis. Died following chronic Cardiac failure. Liver specimen. Likely diagnosis? Alcoholic Hepatitis Dubin-Johnson Syndrome Alcoholic cirrhosis Nutmeg liver Metastatic deposits
  • 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
  • 180. 28y M, alcoholic, homosexual icterus and fever. Liver biopsy. ? diagnosis Acute viral hepatitis Hemolytic anemia Chronic persistent hepatitis Alcoholic fatty liver. Alcoholic Hepatits.
  • 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? Alcoholic fatty liver. Acute viral hepatitis. Fulminant hepatitis. Chronic viral hepatitis. Alcoholic Cirrhosis.
  • 182. 34y M, icterus and fever. Liver biopsy. ? diagnosis Acute Hepatitis Chronic Persistent Hepatitis. Chronic active Hepatitis Fulminant Hepatitis Cirrhosis
  • 183. 22y M, alcoholic, 3wk fatigue, icterus & fever. Liver biopsy. ? Identify the structure Mallory hyaline Apoptotic cell Viral inclusion Hepatocyte necrosis Inflammatory cell
  • 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. A1 antitrypsin deficiency HEV infection Hereditary hemochromatosis Primary sclerosing cholangitis Alcoholic cirrhosis
  • 185. 58y M, alcoholic, distended abdomen & icterus. Liver biopsy. ? diagnosis Chronic active hepatitis. Chronic Persistant hepatitis. Hepatocellular carcinoma. Cirrhosis Chronic alcoholic hepatitis.
  • 186. 146 51y M, Alcoholic: Look at Arrow ? Pathogenesis. Porta-systemic shunt Hyper-oestrogenemia Portal hypertension Hypo-albuminemia Decreased vit-K
  • 187. 51y M, Alcoholic, surgery for pigmented skin lesion: Liver specimen. Likely diagnosis? Amoebic Liver abscesses Multiple Liver Infarcts Alcoholic Hepatitis Macronodular cirrhosis Metastatic deposits
  • 188. 59y Male, Alcoholic, presents with fatigue, anorexia. Normal liver function tests. Liver specimen. Likely diagnosis? Dubin-Johnson Syndrome Alcoholic cirrhosis Alcoholic Hepatitis Fatty Liver Metastatic deposits
  • 189. 22y M, alcoholic, 3wk fatigue, icterus & fever. Liver biopsy. ? Identify the structure Mallory hyaline Apoptotic cell Viral inclusion Hepatocyte necrosis Inflammatory cell
  • 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.
  • 196. 156 CPC-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.
  • 198. 158 Case # 2 - ? Diagnosis 60yr Male, 8 month slowly developing weakness, mild icterus. PE: Mild Abdominal tenderness, No organomegaly. 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?
  • 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?