Hepat

Hepatitis D virus (HDV) Pathogenesis:

♦ It is also called Delta virus. Ingestion of virus
♦ HDV replicates only in HBV infected cells and ↓
acquire HBsAg on the surface. From GIT
General Properties ↓
- Genome: Small, SS circular RNA Reaches to liver
- Viral diameter: 35-37 nm ↓
- Genome is surrounded by delta antigen core, Replicates in cytoplasm of hepatocytes
which in turn is surrounded by HBsAg antigen
↓
core.
Viral progeny related to G.B. and then
- Since HDV is dependent on HBV for its
excreted clinical manifestation in faeces.
replication and transmission, it is called as:
Defective virus. Clinical Features
Mode of infection Incubation period: 2 - 6 week
- Simultaneous infection (coinfection) with HBV - - Symptoms and course resemble with HAV
most common mode. disease.
- HDV superinfection: of an HBV carrier is most - Causes only acute and milder liver disease.
commonly observed in intra venous drug user.
- Recovery is complete however, it can be
Clinical Features serious in pregnant lady.
- Clinical outcome are similar to those of acute - HEV do not become chronic and has not carrier
and chronic hepatitis B. state.
- The presence of 'δ' agent (HDV) increases the V
Diagnosis:
severity of HBV infection.
Made on the basis of
- Causes fulminant hepatitis which may result in
i. Clinical data
hepatic encephalopathy and massive hepatic
necrosis. ii. Liver enzymes are elevated
Hepatitis E virus iii. Detection of Anti HEV antibody by ELISA
♦ Belong to family calciviridae. iv. Demonstration of virus by Immunofluorescent.

♦ HEV, Enteric or epidemic ,is excreted in stools and Hepatitis G virus

spread by faeco-oral route. ♦ Enveloped
General properties ♦ Genome: ssRNA
- Naked, icosahedral virus 27-30 nm in diameter. ♦ Family →Flaviviridae with HCV
- ssRNA→ Genome.
Clinical Features
- Only one type of serotype exists.
- HGV infected person are asymptomatic
- It is refered as "Hepatitis E like virus".
Diagnosis:
Mode of transmission
- ELISA with HGV - 2 envelope antigen produced
I. Few oral route in CHO cells are useful to test for Ab in sera.
II. Usual mechanism: By water contamination.

FAST TRACK BASIC SCIENCE MBBS -237-

 Microbiology

Distinguishing features of Hepatitis viruses [03, 05, 06]

Hepatitis A
Features Hepatitis B virus Hepatitis C virus Hepatitis D virus Hepatitis E virus
virus
1. Common name Infectious Serum hepatitis Non A, Non B Delta agent Enteric Non A,
hepatitis hepatitis Non B
2. Family Picorna Hepadna Flavi Unclassified Calci
3. Virion diameter 27nm 42nm 30-60 nm 35nm 30-32nm
4. Symmetry Icosahedral Spherical Spherical Spherical Icosahedral
5. Envelope No Yes (HBsAg) Yes Yes (HBsAg) No
6. Genome +ssRNA dsDNA +ssRNA -ssRNA +RNA
7. Transmission Faecal oral Parenteral, sexual Parenteral, sexual Parenteral, sexual Feco- oral abrupt
Insidious abrupt
8. Severity Mild Occasionally Usually subclinical Co-infection with Severe in
severe HBV, occasionally pregnancy
severe, super
infection with
HBV often severe
9. Chronicity/ No Yes Yes Yes No
carrier state
10. Associated No Primary hepato Hepato cellular Cirrhosis, No
V disease cellular Carcinoma Fulminant
carcinoma, hepatitis
cirrhoisis
11. Incubation 15-45 30-180 13-160 30-180 15-60
period
12. Laboratory Symptoms and Symptoms and Symptoms, anti Anti - HDV ELISA HEV and Anti HEV
diagnosis anti HAV IgM serum level HCV ELISA IgM
HBsAg, HBeAg
and anti HBcAgM

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 Hepat

SPECIAL POINTS FOR MCQs

HAV
1. Infectious hepatitis, Non enveloped 27 nm
2. Ether resistant RNA virus, No chronic case
3. Hepatitis virus genus of the picorna family.
4. In activated by boiling, formalin UV radiation.
5. Transmitted by Feco-oral route
6. Carrier state doesn't exist of HAV
7. HAV is only the hepatitis virus that can be cultured.
8. Prophylatic vaccines are available for HAV and HBV.
HBV
9. Is a DNA virus.
10. Hepadna virus contains DNA polymerase and RNA dependent reverse transcriptase.
11. Dane particle is HBV
12. HBV strain in india (i) AYw, Adn
13. HBV has maximum perinatal transmission risk.
14. Oncogenicty is present in Hepatitis B especially after neonatal infection.
15. Carrier state is present in Hepatitis B.
16. HBV may present in blood and other body fluids and excretions such as saliva, breast milk semen
vaginal secretion, urine bile etc.
17. Feces is not known to be infectious.
18. HBsAg is the first viral marker to appear in blood after infection it remains in circulation throughout
icteric course of disease. In a typical case it disappear within roughly 2 months but last for 6 months.
V
19. HBcAg is not demonstrable in circulation but antibody, anti HBe appear in serum, a week or two
week after appearance of HBsAg.
20. Anti HbeAg is the Ab marker to be seen in blood.
21. Epidemiological marker of Hep B is: Core Ab.
22. HBeAg (HB envelope Ag) appears in blood concurrently with HBsAg.
23. HBeAg is an indicator of intrahepatic viral replication and its presence in blood indicates high
infectivity.
24. For diagnosis of HBV infection simultaneous presence of IgM HBV indicates recent infection.
25. Presence of IgG, anti HBe indicates remote infection.
26. H-B vaccine is cell fraction derived.
27. Incubation period of HBV is 45 to 180 days.
28. Anti HBsAg indicates resistance of Hep. B.
29. Best route of giving hepatitis B vaccine is intramuscular deltoid.
30. Core antigen of Hep B virus is present in dane particle. (KU 013)
31. Co- infection of viral Hepatitis is caused by →Hep B and Hep D virus.
32. Carcinoma following viral hepatitis is seen Hep B and Hep C.
33. Affected hepatocytes in hepatitis appear, Ground glass appearance.
34. Antibody to HBsAg may not be detected soon after disappearance of HBsAg. This is called
window period.

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 Microbiology

Hepatitis C virus
35. Before its identification was labelled non A, non B hepatitis.
36. Genome: Linear, SS positive sense, RNA virus (Enveloped)
37. HCB belongs to family Flaviviridae
38. Cause of post transfusion hepatitis, Causes chronic hepatitis.
HDV
39. It is Delta hepatitis agent or HDV is a defective RNA virus, Resembles plant virus
40. Confect with and requires the helper function of HBV (or other hepadnaviruses) for its replication
and expression.
HEV
41. Previously labeled "Epidemic or enterically transmitted non A, non B hepatitis."
42. HEV is an enterically transmitted virus.
43. Mortality in pregnancy is a feature of HEV.
44. Hepatic encephalopathy in pregnancy is seen.
45. Fulminant hepatic failure can occur with Hep. C in pregnancy.
HePG
46. Also called GB virus, is RNA blood borne virus which resembles HCV.
47. Lamuvudine responsive.
Note: Transmission by faeco-oral route: Hepatitis A and E. Spreads by percutaneous route: Hepatitis B, C and D.
Clonorchis sinensis
48. Also called Chinese of liver fluke.
49. Intermediate host: 1st intermediate host: Snail (Genus Bulinus), 2nd intermediate host: Fish
(Cyprindae fresh water)
50. Infective stage of clonorchis is: Metacercariae
V 51. Attain maturity in bile duct
52. Egg: Bile stained.
Granulosus
53. Is hydatid worm, Definitive host: Dog, No. of proglottied in E. granulosus is 3.
54. Hydatid cyst has
a. Outer laminated layer b.Inner Germinal layer c. Outer most Adventitial layer
55. Causes hydatid disease, it is zoonosis.
56. Liver is most common organ affected followed by lungs, muscles, bones and kidney.
57. Echinococciosis is caused larval stages of parasites.
58. Man is an accidental intermediate host. Other intermediate host are sheep and cattle.
59. Serological assay (weinberg reaction) is specific example of complement fixation test used in detection.
60. Hydatid fluid is slightly acidic and causes anaphylactic symptoms.
Fasciola Hepatica
61. Commonly called sheep liver fluke.
62. Disease caused by it is called "liver rot".
63. Definitive host: Sheep, goat
64. Intermediate host: Snail of genus Lymnea.
65. Egg is bile stained.
66. Halozoun is caused by eating raw liver of infected sheep.
67. Infective stage to man: Metacercaria.
68. Infective stage to snail: Miracidium.
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 Hepat

pathology
SYLLABUS
Jaundice: (p. 243)
Types and pathogenesis
Cirrhosis of the Liver:(p. 248)
Definition, aetiologic and morphologic types.
Morphology with special reference to alcoholic cirrhosis.
Viral Hepatitis: (p. 251)
Aetiology, gross and microscopic features, sequelae of acute viral hepatitis.
Portal Hypertension: (p. 253)
Definition, types, major clinical consequences.
Hepatocellular Failure: (p. 256)
Definition, types, major clinical consequences.
Liver abscess-Amoebic and Pyogenic: (p. 256)
Gross and microscopic features, complications.
Tumors of Liver: (p. 257)
Classification, hepatocellular carcinoma.
V
Hepatoblastoma: Gross and microscopic features.
Chronic Cholecystitis: (p. 258)
Aetiology, gross and microscopic features, complications.
Cholelithiasis: (p. 260)
Pathogenesis.Morphology, complications.
Carcinoma of Gall Bladder: (p. 262)
Gross and morphology, complications.

FAST TRACK BASIC SCIENCE MBBS -241-

 Pathology

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 Hepat

PATHOLOGY

JAUNDICE Pathophysiology of Jaundice

Past Questions: ♦ Both unconjugated bilirubin and conjugated
1. Write a note on differential diagnosis of bilirubin (bilirubin glucuronides) may accumulate
Jaundice. [3][013] systemically.
Bilirubin
♦ Jaundice is defined as clinical sign characterized by
↓
a yellowish discoloration of skin, mucous ↓ ↓
membrane due to deposition of bilirubin. Unconugated Conjugated
♦ Icterus: Symptoms with yellowish of sclera. ↓ ↓
Insoluble in water Water soluble
♦ Clinically jaundice is detectable at 2 to 2.5mg/ml
↓ ↓
or above. Toxic Non toxic
♦ Bilirubin level Condition ↓ ↓
Exist in tight complexes Only loosely bound to
- >1 mg/dl → Hyperbilirubinemia
with serum albumin albumin
- 1–2 mg/dl → Latent Jaundice ↓ ↓
- >2mg/dl → Overt Jaundice Cannot be excreted in the Excreted in the urine
urine
Type of Jaundice
Pathogenesis
I. Based on Pathology
- In the normal adult, serum bilirubin level varies
1. Prehepatic Jaundice (Hemolytic Jaundice) between 0.3 and 1.2 mg/dl, and rate of
V
2. Hepatic Jaundice (Hepatocellular Jaundice) systemic bilirubin production is equal to the
3. Post hepatic Jaundice (obstructive Jaundice) rate of hepatic uptake, Conjugation and biliary
II. Based on presence of bilirubin and bile excretion.
salts in urine. - Jaundice becomes evident when the serum
bilirubin level rise above 2 to 2.5 mg/dl and as
1. Chlouric Jaundice: Presence of bilirubin and
high of 30–40 mg/dl can occur with severe
bile salt in urine → conjugated bilirubinemia.
disease.
2. Achloluric Jaundice: Absence of bilirubin and
- Jaundice occurs when equilibrium between
bile salt in urine → unconjuagated
production and clearance is disturbed by one
bilirubinemia.
or more of following mechanism.
III. Congenital Hyperbilirubinemia
causes
Unconjugated I. Excessive‚ Extrahepatic ⎪⎫ unconjugated
production of bilirubin ⎬ hyperbilir
a. Gilberts syndrome II. Reduced hepatocyte uptake⎭⎪
ubinemia
b. Ciggler Najjar syndrome Type 1 and 2
Conjugated
III.
IV.
Impaired conjugation
Decreased hepatocellular ⎫produce
⎬conjugated
predominantly
a. Dubin Johson syndrome excretion
b. Rotor syndrome V. Impaired bile outflow ⎭hyperbilirubinemia
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 Pathology

Etiology ♦ Etiology
A. Predominatly unconjugated
Etiology
hyperbilirubinemia
I. Excess production of bilirubin
Hemolysis Ineffective
- Hemolytic anemias erythropoiesis
- Resorption of blood from internal
hemorrhage (Alimentary tract bleeding, Intrinsic Extrinsic
hematomas) i. Hemo- i. Incompatible blood
globinopathies transfusion
- Ineffective erythropoiesis syndromes (e.g. ii. Hereditary ii. Malaria
pernicious anemia, thalassemia) spherocytosis
iii. G6PD deficiency
II. Reduced hepatic uptake
- Drug interference with membrane carrier Features
system.
- ↑sed serum unconjgated bilirubin (<6mg/dl)
- Some cases of Gillbert syndrome.
- ↓sed excretion of urobilinogen in urine.
III. Impaired bilirubin conjugation
- Dark brown color of feces due to
- Physiologic jaundice of the newborn (↓sed stercobilinogen.
UGT1A1 activity decreased excretion)
- Achloruric Jaundice: abscence of bilirubin and
- Breast milk Jaundice (due to β– bile salts in urine.
glucoronidase in milk)
- Show Indirect Vanden Berg reaction.
- Genetic deficiency of UGT1A1 activity (CNS
V type – I & type II)
Clinical presentation
• Splenomegaly
- Diffuse hepatocellular disease (e.g. viral or
• Anemia
drug–induced hepatitis, cirrhosis)
• Mild to moderate Jaundice
B. Predominantly conjugated
Hyperbilirubinemia Hepatic Jaundice
- Deficiency of canalicular membrane ♦ It is also hepatocellular jaundice which is due
transporter (Dubin Johnson syndrome, Rotor abnormality in liver parenchyma.
syndrome) ♦ This is due to impaired uptake, conjugation or
- Impaired bile flow. secretion of bilirubin.
Pre Hepatic Jaundice ♦ Defect in a generalized liver dysfunction.
♦ Result from excess production of bilirubin beyond ♦ In this case, hyperbilirubinemia is usually
the ability of lliver to onjugate it following accompanied by other abnormalities in markers of
hemolysis. Thus, there occurs retention of liver function.
unconjugated bilirubin. Causes
♦ So there becomes high plasma concentration of I. Inflammation: Hepatitis A, B, C virus
unconjugated bilirubin (normal concentration ∼
II. Chemical/Drugs: Acetaminophen, Alcohol.
0.5 mg/dl)

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 Hepat

III. Genetic error of bilirubin metabolism: Causes

• Gilbert's syndrome a. Intrahepatic
• CriglerNajar syndrome i. Liver cell damage/ blockage
• Dubin Johnson syndrome • Drugs/ chemical toxin
• Rotor's syndrome
• Dubin-Johnson syndrome
• Specific protein metabolism
• Hepatitis-viral, chemical
→ Wilson's disease
• Infiltrative tumors
→ α1 antitrypsin
ii. Intrahepatic biliary hypoplasia atresia
IV. Autoimmune:
iii. Primary biliary cirrhosis
• Chronic Active Hepatitis
b. Extrahepatic
V. Neonatal Jaundice: Physiological
- Obstruction of bile ducts
Clinical presentation & feature
• Intraluminal gallstones
- Anorexia, nausea, vomiting fever with chills &
rigor. • Compression/obstruction from tumors
(Pancreatic tumors, cholangiocarcinoma)
- Hepatomegly, mild to moderate Jaundice.
- Stool : • Congenital choledochal cyst

• Dark & urine mustard oil colored urine . • Extrahepatic biliary atresia

- Blood bilirubin: Both direct and indirect • Stenosis–postoperative or inflammatory.

positive (Biphasic) vanden Berg reaction. Clinical presentation V
Post hepatic Jaundice - Itching , pruritus and xanthoma of skin.
♦ It is also called obstructive Jaundice, and caused - Stool: Clay colored with steatorrhoea.
by obstruction of the biliary tree.
Neonatal Jaundice
♦ Plasma bilirubin is conjugated, and other biliary
♦ Common in premature infants.
metabolites, such as bile acids accumulate in the
plasma. ♦ Transient: resolves in first 10 days.

Features: ♦ Yellowish discoloration of skin and mucus

- Characterized by pale colored stool (absence of membrane due to excessive amount of bilirubin in
fecal bilirubin or urobilin) and dark urine (↑sed blood of neonates (28 days since birth) due to
conjugated bilirubin) either congenital or acquired defect in bilirubin
metabolsim.
- In a complete obstruction, urobilin is absent
from the urine. Type of Neonatal Jaundice
- Characterized by conjugated hyperbilirubinemia A. Physiological
- Vanden Berg reaction: Direct positive. B. Pathological
A. Physiological Jaundice
- Mild transient unconjugated hyperbilirubinemia.

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 Pathology

- Appears after 24 hrs of birth c. Neonatal hepatitis, congenital hepatic

- Peak in 4–5 days, disappear after 2 wk. fibrosis.
- Serum bilirubin level not more than 5–12 mg/dl • Criggler Najjar syndrome type 1 and type II
- Nappies not stained. • Metabolic: α1 antitrypsin deficiency,
Etiologies glactosaemia.
i. Short life span of RBC Laboratory investigation (03,13)
ii. Transition from placental circulation to self Pre hepatic Hepatic Post hepatic
circulation. No. bilirubin Bilirubin ↑ Bilirubin
iii. Conjugating enzyme UGT1A1 is immature (normal,
(less conjugation) ↑,↓)
Urine
iv. Meconium contains β-Glucuronidase ↑urobilinogen ↑Urobilinogen ↓Urobilinogen
(deconjugating) enzyme activity. Bile salt–Nil bile salt–Nil present
v. Exacerbated by breastfeeding, as a result of
Dark Pale Clay colored
the presence of bilirubin deconjugating
Faeces Urobilinogen Urobilinogen Absent
enzymes in breast milk.
↑sed ↓sed
Management
RBC: ↑ Bilirubin– ↑ conjugated
• Resolves gradually within 2 wks.
- ↑ Reticulocyte mixed Bilirubin
• Phototherapy (450 nm)
Count, comb's ↑↑ AST, ↑↑ ALP, γGT
• Restrict the sulfa drugs in mother ↑↑ ALT
test ↑ AST, ↑ ALT
/neonates. Blood
V −↑ Bilirubin (100 ↑ ALP, ↑ γGT ↑ PT
B. Pathological Jaundice µmol/Lit) ↑ PT (not (correctable
- Elevated bilirubin when T/t is required. unconjugated correctable with vit. K)
with vit. K)
- Appearance of jaundice since birth or within 24
hrs. Complication
- Unconjugated serum bilirubin level. - Kernicterus
• 5mg/dl – 1 day
st
- Deafness
• 10 mg/dl – 2 day nd
- Cerebral palsy
• 15 mg/dl – 3 day rd
- Acute Brain
Persist for > 2 weeks. - Encephalopathy
Etiologies Kernicterus
• Hemolysis - It is neurological syndrome resulting from
a. ABO or Rh incompatibility deposition of free unconjugated bilirubin in
b. Thalassemia, the brain causing bilirubin toxicity.
c. Other hematological disorders. - It is more common in children due to immature
• Non hemolytic causes blood brain barrier.

a. Prematurity - Occurs when bilirubin level is more than 20-

25mg/dl.
b. Cephalohematoma sepsis
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 Hepat

Pathogenesis Treatment
Unconjugated Hyperbilirubinemia (> 20-25mg/dl in • Can be treated with small doses
serum) Phenobarbital or stimulated UDP glucoronyl
transferase activity.
Decreased bilirubin
Immature BBB of Crigler Najjar syndrome
binding capacity
infant - Autosomal recessive and dominate
of serum
- Extremely rare < 200 cases worldwide – gene
Bilirubin cross BBB and deposited in cerebrum and
frequency is < 1:1000.
cerebellum
- High incidence in the plain people of
↓
Pennsylvania (Amish and Mennonites)
Leads to damage and gliosis
- Characterized by complete absence or marked
↓
↓ in bilirubin conjugation.
Toxic Encephalopathy
- Present with a severe unconjugated hyper
Clinical Features
bilirubinemia that usually present at birth.
- Mental retardation
- Two type : Distinguish between:
- Encephalitis
- Psychosis CNS Type – I CNS Type – II
Treatment i. Autosomal recessive i. Autosomal dominant
- Phototherapy ii. Complete absence of ii. Decreased UGT1A1
- Medication UGT1A1 activity activity
- Treat underlying cause iii. Mutation: in exon of iii. Exon 1 & 2 of UGT1A1
Gilbert's disease 1, 2, 3, 4 & 5 of
- It is benign liver disorder UGT1A1 gene
- 1/2 of the affected individual inherite it iv. Serum unconjugated iv. <20 mg/dl V
- Characterized by mild, fluctuating ↑ in bilirubin > 25–50
mg/dl
unconjugated bilirubin caused by ↓ sed ability
of the liver to conjugate bilirubin – often v. Bile contain v. Contain some
correlated with fasting or illness. unconjugated monoconjugated
bilirubin bilirubin
- Males > Females, Autosomal recessive.
- Onset of symptoms in teen, early 20 year or 30 vi. Jaundice appear vi. After 24 hrs of birth
within 14 hrs of birth
year.
- Serum unconjugated bilirubin < 3mg/dl vii. Associated with vii. Not associated.
kernicterus
Causes
viii. Is fatal: no viii. Being course: treatment
• ↓ sed activity of UGT1A1enzyme activity due treatment is with phenobarbitone,
to mutation in promoter region of effective phototherapy
UGT1A1gene→ ↓sed conjugation ↓
unconjugated bilirubin.
Dubin – Johnson syndrome
• ↓ RBC survival rate: more RBC lysis. - Autosomal recessive disorder
Diagnosis: - Characterized by impaired biliary secretion of
i. By serum unconjugated bilirubin estimation conjugated bilirubin and present with
by keeping patient on test. conjugated hyperbilirubinemia that is usually
ii. Nicotinic acid test. mild.

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 Pathology

- Serum bilirubin level: Describe the morphological changes of alcoholic

• 3–15 mg/dl (Di > monoconjugated) cirrhosis. (2+3+5=10) [05, 03]
4. Morphology of alcoholic liver disease [4] [10]
- The liver is darkly pigmented because of coarse
pigmented granules within the cytoplasm of
hepatocytes. Definition (05,06,08)
Cirrhosis is defined as the end stage of chronic
- Bromosulfathelein test:
liver disease, is characterized by three features:
• Biphasic. I. Bridging fibrous septae:
Pathogenesis • Delicate bands or broad scars lining portal
Mutation in gene for MRP–2 proteins (multidrug tract with one another and portal tracts
resistance protein) with terminal hepatic veins.
II. Parenchymal nodules:
↓
• Containing proliferating hepatocytes
Regurgitation of bilirubin (Conjugated) in blood encircled by fibrosis, with diameters varying
↓ from vary small (< 3mm,micronodules) to
large (several cm macronodules)
Urine yellow – yellow stained nappies in children.
III. Disruption of the architecture of the entire
Rotor's Syndrome liver
- Autosomal recessive Classification of cirrhosis (05,06,08)
- Characterized by familial conjugated a. Aetiologic type
hyperbilirubinaemia with mild chronic jaundice i. Alcoholic liver disease (60% – 70%)
- Differs from Dubin Johnson syndrome in having ii. Viral hepatitis (10%)
V iii. Biliary cirrhosis (5% – 10%)
no brown pigment in liver cells
- Has excellent prognosis iv. Primary hemochromatosis (5%)
v. Cryptogenic cirrhosis (10% – 15%)
- Probable causes
vi. Cirrhosis in Wilson's disease (rare)
i. Decreased hepatic uptake and storage
vii. Cirrhosis in α1-antitrypsin deficiency (rare)
ii. Decreased biliary excretion
viii. Cardiac cirrhosis
CIRRHOSIS OF THE LIVER ix. Indian childhood cirrhosis
Past Questions: x. Post necrotic cirrhosis (10%)
1. Define cirrhosis of liver. Describe the xi. Cirrhosis in non-alcoholic steatohepatitis
morphological and etiological types of cirrhosis. xii. Miscellaneous forms of cirrhosis Metabolic,
Explain the morphology of alcoholic cirrhosis. infectious, GI, infiltrative)
(2+5 =10) [08] b. Morphologic type
2. Define cirrhosis of liver and describe the different I. Micronodular
types of cirrhosis. Give gross and microscopic - Nodules less than 3mm in diameter
appearance of alcoholic cirrhosis. (2+3+5=10) [06]
- Believed to be caused by alcohol
3. Define cirrhosis of liver. Give the morphological hemochromatosis
and etiological classifications of cirrhosis.
• Cholestatic causes of cirrhosis
• Hepatic venous outflow obstruction
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 Hepat

II. Macronodular cirrhosis - Continued deposition of collagen in the space

- Nodules larger than 3mm of disse within preserved parenchyma
- Believed to be secondary to chronic viral accompanied by loss fenestration in the
hepatitis sinusoidal endothelial cells.
III. Mixed - In the process, the sinusoidal space comes to
- Some parts of liver show micronodular resemble a capillary membrane rather than a
and some show macronodular. channel for exchange of solutes between
- Mixed pattern is kind of incomplete hepatocytes and plasma.
expression of micronodular cirrhosis - Hepatocellular secretion of proteins greatly
- All portal tracts and central veins are not impaired.
involved by fibrosis but instead some of - Major source of excess collagen in cirrhosis is
them are spared.
perisinusoidal stellate cells, which lie in the
Pathophysiology space of disse.
In normal liver:
Stellate cell
- Interstitial collagen (type I and III) are
concentrated in portal tracts and around ↓
the central veins with occasional bundles in
Normal function Activated
the space of disse.
- The collagen coursing alongside ↓ ↓
hepatocytes is composed of delicate strands Storage and ↑ mitotic activity
of type IV collagen in the space of Disse. metabolism of vitamin ↓
Pathogenesis A Resting lipocyte
- The central pathological process in cirrhosis ↓ V
are:
Transitional myofibroblast
• Hepatocytes injury (by Alcohol, virus,
↓
drug, toxin etc)
↑sed capacity for synthesis
• Chronic inflammation
& secretion of extracellular
• Bridging fibrosis
matrix
• Regeneration of remaining hepatocytes
↓
proliferate as round nodules.
Cirrhosis
• Loss of vascular arrangement results in
ineffective regeneration of hepatocytes . - Stimuli for stellate cells

Progressive fibrosis and reorganization of the • Chronic inflammation: Production of

vascular microarchitecture of the liver inflammatory cytokines-TNF, lymphotoxin
↓ and TL–1
In cirrhosis type I and Type III collagen are • Cytokine production by endogenous cells
deposited in the lobule, creating delicate or kupffer cells, epithelial cells, hepatocytes,
broad septal tracts
and bile duct epithelial (cell): TGF–β, PDGF
↓
and lipid peroxidation products.
New vascular channels in the septae connect the
vascular structure in the portal region and • Disruption of the extracellular matrix, as
terminal hepatic veins, shunting blood around satellite cells are extraordinarily responsive
the parenchyma to the status of their substrate.

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 Pathology

- Direct stimulation of stellate cells by toxins. - Net outcome: Fibrotic nodular tires→ delivery
- Throughout the process of liver damage and of blood to hepatocyte severely compromised.
fibrosis, remaining hepatocytes are stimulated - The ability of hepatocyte to secret substance
to regenerate and proliferate as spherical into plasma is compromised.
nodules within the confines of the fibrous
septae.

Morphology (with reference to alcoholic Microscopic

cirrhosis) [05,06,08,10] - Loss of normal lobular architecture
Gross - Hepatic parenchyma with nodules
- At first, cirrhotic liver is yellow tan, fatty separated by fibrous Septa connecting
and enlarged (22 kg) • Central to portal vein
- Later becomes brown, shrunken, non fatty • Portal to portal vein
(<1 kg) • Regenerative nodules with disorganized
- Begins as micronodular cirrhosis but later masses of hepatocytes.
turn to macronodular pattern. - Necrosis, inflammation and bile duct
- With time nodularity becomes more proliferator.
prominent, scattered larger nodules create a
hobnail appearance on the surface of liver.

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 Hepat

♦ The mature HBV vision is a 42 – nm, spherical

double layered "Dane particle" that has an outer
surface envelope of protein, lipid, and
carbohydrate enclosing an electron dense, 28 nm
slightly hexagonal.
♦ The genome of HBV is a partially double stranded
circular DNA molecule having 320 nucleotides.
♦ HBV consist of 4 open reading frames (ORF)
I. S–region
- Include pre S1, pre S2 and 's' gene, encoded
pre S1 protein, Pre–S2 protein and HBsAg.
- Pre S1Protein + pre S2 protein + HBsAg→
large protein
- Pre S2 Protein + HBsAg – Middle protein.
- HBsAg – major protein.
II. C–region
VIRAL HEPATITIS - Included pre C and C region, encode HBeAg
and HBcAg
Past Questions:
III. X–region :
1. Morphology of liver in viral hepatitis. [2000, 12] - Encoded HBsAg
♦ Viral hepatitis is a group of systemic infection IV. P–region
affecting the liver predominantly caused by 5
- Encoded DNA polymerase
kinds of viruses.
♦ Viral hepatitis may be divided into 5 types according
♦ HB infection has 3 antigen– antibody system V
to etiology, that is hepatitis A, B, C, D and E. I. HBsAg –Anti HBs system
♦ Viral hepatitis – Historical perspective II. HBcAg – Anti HBc system
"Infectious" III. HBeAg – Anti HBe system
"Serum"
Viral hepatitis
→ HBV & HDV → HAV ♦ For serologic diagnosis: ) refer microbiology
♦ The marker of molecular biology of HBV
Non A, Non B I. HBV-DNA polymerase: Possess the ability of
reverse transcriptase
HEV HCV II. HBxAg: Related to chronicity, activity of
(Enterically (Parenterally hepatitis B or liver cancer.
transmitted) transmitted) Clinicopathologic syndromes of viral
hepatitis
♦ Hepatitis A and E shows acute hepatitis, hepatitis
I. Acute asymptomatic hepatitis: with recovery
B, C and D predispose to a chronic hepatitis and is
(serological evidence only)
related to liver cirrhosis and hepatic cancer.
II. Acute symptomatic hepatitis: with recovery,
♦ The course of acute hepatitis is about 2–4 months
generally. anicteric or icteric
III. Chronic hepatitis: Without or with progression
Hepatitis B virus (HBV)
to cirrhosis
♦ HBV is a kind of hepadna virus IV. Fulminant hepatitis: With massive to
submassive hepatic necrosis.

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 Pathology

Pathogenesis of HBV infection V. Kupffer cells: Undergo hypertrophy and

- Mode of transmission: hyperplasia.
i. Blood or blood product VI. The portal tracts: Infiltrated with a mixture
ii. Sexual transmission of inflammatory cells (mononuclear).
Inflammatory spill over into adjacent
- After entry, it reaches to hepatocyte with
parenchyma, with hepatocyte necrosis.
minimal CPE.
VII.Regenerative changes: Hepatocyte
- Infection consist of
proliferation
I. Proliferative phase
VIII.Sinusoidal reactive changes: Accumulation of
II. Integrative phase Phagocytosed cellular debris in kupffer cells,
I. Proliferative phase influx of mononuclear cells into sinusoids.
• During this phase HBV – DNA is present in IX. Interface hepatitis
episome with formation of complete virion
X. Mild fatty change: HCV
and all associated antigens.
XI. Cholestasis: Canalicular bile plug.
• Cell expression of viral HBsAg and HBcAg in
association with MHC class I molecules leads to Chronic hepatitis
activation of CD8+ cytotoxic T lymphocytes. I. Changes share with acute hepatitis
• Hepatocyte destruction occurs if a cytotoxic a. Hepatocyte injury, necrosis and
T lymphocyte interacts with infected regeneration
hepatocyte. b. Sinusoidal cell reactive changes.
II. Integrative phase
II. Portal tracts
• For the infected hepatocytes that are not
• Inflammation confined to portal tract
destroyed by immune system, an
integrative phase may occur in which viral • Spill over into adjacent parenchyma with
DNA is incorporated into the host genome. necrosis of hepatocytes (Interface
V • With cessation of viral replication within hepatitis)
hepatocytes, there is appearance of • Bridging inflammation and necrosis.
antiviral antibodies, infectivity ends and
III. Fibrosis
liver damage subsides.
• Portal deposition
• Because of the HBV–DNA integrated into
host genome, the risk of hepatocellular • Or portal and periportal fibrosis
carcinoma persists. • Formation of bridging fibrous septae.
Morphology [KU 02,12] IV. Lymphoid aggregates:
Acute hepatitis Within portal tracts and focal sublobular
I. Enlarged, reddened: liver greenish if • Bile duct epithelial proliferation (regions
cholestatic.
of hepatocyte)
II. Ballooning Degeneration: Diffuse swelling
of hepatocyte-Cytoplasm contains scattered • Both in HCV and HBV.
eosinophilic remanants of cytoplasmic V. Cirrhosis:
organelles. • Regenerating nodules, end stage
III. Apoptosis: Hepatocyte shrink, become outcome.
intensely eosinophilic and have fragmented VI. Ground glass Hepatocytes:
nuclei.
• HBV hepatocytes may exhibit of
IV. Bridging Necrosis (Piecemeal): Connecting
portal to portal central to central or portal cytoplasm packed with spheres and
to central region of adjacent lobules. tubules of HBsAg producing a finely
granular eosinophilic cytoplasm.
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Pattern of viral hepatitis ♦ Portal veins have no valves and thus obstruction
- Carrier state / Asymptomatic phase anywhere in the portal system raises pressure in
all the veins proximal to obstruction.
- Acute hepatitis
- Chronic hepatitis Types:
a. Chronic persistent Hepatitis (CPH) - Based on the site of obstruction to portal
venous blood flow, portal hypertension is
b. Chronic active hepatitis (CAH)
categorized into 3 mains types
- Fulminant hepatitis
I. Prehepatic portal HTN
- Cirrhosis
II. Intrahepatic portal HTN
- Hepatocellular carcinoma
III. Posthepatic portal HTN
PORTAL HYPERTENSION Etiology
♦ Increase in pressure in portal system of circulation 1. Prehepatic portal HTN
due to obstruction to portal blood flow is called a. Obstructive thrombosis: portal vein
portal hypertension. thrombosis most common.
♦ Portal hypertension occur when portal pressure is b. Narrowing of the portal vein: Before it
higher than 5 mmHg.
ramifies within the liver

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 Pathology

c. Massive splenomegaly: Shunt excess blood i. ↑sed resistance to portal flow at the level of
into the splenic vein. sinusoids.
d. Infection in the abdominal cavity. ii. ↑ in portal blood flow resulting from a
e. Omphalophlebitis hyperdynamic circulation.
f. A–V fistula between hepatic artery and I.
portal vein.
Sinusoidal endothelial
2. Intraphepatic portal HTN cell
Type: Contraction of
vascular
i. The presinusoidal level
smooth muscle ↓ in NO Endothelin (ET–1),
ii. The sinusoidal level
cells and production angiotensinogen
iii. The postsinusoidal level myofibroblast and eicosanoids
Causes
a. Cirrhosis
b. Schistosomiasis Disruption of blood
flow by scarring ↑ sed resistance to
c. Massive fatty change
and the formation portal outflow at the
d. Diffuse fibrosing Granulomatous disease level of the sinusoids
of parenchymal
like
nodules Portal HTN
→ Sarcoidosis, Miliary TB
→ Disease affecting the portal micro
II. Anastomoses between the arterial & portal
circulation
System in fibrous septa
Portal HTN in cirrhosis
V ↓
• ↑sed resistance to portal flow at the Imposing arterial pressure on the low pressure portal
level of the sinusoids. venous system
• Compression of terminal hepatic veins ↓
by perivenular scarring. Portal HTN

• Expansile parenchymal nodules. III. Decreased function of the mononuclear

3. Posthepatic portal HTN – Cause phagocyte system and shunting of blood from
the portal to systemic circulation
a. Budd-chiari syndrome (Hepatic vein
↓
thrombosis)
Reduced clearance of bacterial DNA absorbed from
b. Constrictive pericarditis gut
c. Severe right sided heart failure. ↓
d. Hepatic vein outflow obstruction. 'No' production
↓
Pathophysiology:
Splanchnic arterial vasodilation
- The portal vein contributes 2/3rdof total
↓
hepatic blood flow. ↑sed venous efflux into the portal venous system
- Indirectly regulated by vasoconstriction and ↓
vasodilation of the splanchic arterial bed. ↑sed portal venous blood flow
- In portal HTN, following events happen. ↓
Portal HTN

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Major clinical consequences of portal HTN • Same concentration of solutes such as

1. Ascites glucose, sodium, potassium as in blood.
2. Formation of portosystemic venous shunt • Mesothelial cells and mononuclear
3. Congestive splenomegaly leucocytes scant.
4. Hepatic encephalopathy • Influx of neutrophils–secondary
infection.
• Red cells in ascitic fluid: Disseminated
intra-abdominal cancer.
• Long standing ascites: Seepage of
peritoneal fluid through
transdiaphragmatic lympathics→
hydrothorax.
Pathogenesis of Ascites
Involves following mechanism
1. Sinusoidal HTN:
→ Alternation of starling's force and
dividing fluid into space of disse→
which is then removed by hepatic
lymphatics.
→ Hypoalbuminemia
2. Percolation of hepatic Lymph into
V
peritoneal cavity
→ Normal thoracic duct lymph flow -
800 to 1000 ml/day.
→ In cirrhosis →Hepatic lymph flow
approach 20 L/day, exceeding
thoracic duct capacity.
→ Hepatic lymph: rich proteins and low
in TG.
3. Intestinal fluid intake:
→ Portal HTN: ↑sed perfusion pressure
Ascites
in intestinal capillaries
- Collection of excess fluid in the peritoneal
cavity. → Osmotic action of protein rich ascitic
fluid promotes movement of
- Clinically detectable when at least 500ml of
additional fluid out of intestinal
fluid is accumulated.
capillaries.
Ascitic fluid
4. Renal retension of sodium and water
• Serous fluid
• <3gm/dl of protein (largely albumin) → Due to secondary hyperaldosteronism.

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 Pathology

HEPATOCELLULAR FAILURE 2. Combination of toxicity and immune

♦ It is end point of progressive damage to the liver mediated hepatocyte destruction→
as part of chronic liver disease, either by insidious Hepatitis virus infection.
destruction of hepatocytes or by repetitive II. Chronic liver disease:
discrete wave of parenchymal damage. • Most common route for hepatic failure
Pathophysiology III. Hepatic dysfunction without overt necrosis.
- The alternations that cause liver failure fall into • Hepatocytes may be viable but unable to
3 categories. perform normal metabolic function
I Acute liver failure • tetracycline toxicity, acute fatty liver of
II. Chronic liver disease pregnancy, Reye syndrome.
III. Hepatic dysfunction without overt necrosis Clinical presentation
I. Acute liver failure
- Jaundice
• Defined as an acute liver illness that is - Hypoalbuminemia
associated with encephalopathy within 6
- Hyperammonemia
month after the initial diagnosis.
- Fetor hepaticus
Acute liver failure - Palmar erythema
- Spider angiomas of the skin
Fulminant liver failure Sub-fulminant liver
Complication
↓ failure
Encephalopathy ↓ - Hepatic encephalopathy
develops rapidly, Encephalopathy develops - Hepatorenal syndrome
within 2 weeks of the within 3 months of the - Hepatopulmonary syndrome
onset of jaundice onset of jaundice
V
LIVER ABSCESS
• Etiology of Acute liver failure Past Questions:
1.Drugs or toxin
1. Amoebic liver abscess (5)[06]
2.Acetaminophen
3.Halothane Amoebic liver abscess
4.Antimycobacterial drug (rifampicin, ♦ It is less common than pyogenic liver abscesses
isoniazid) and share many features with latter.
5. Anti-depressant: Monoamine oxidase ♦ Caused by the spread of E. histolytica from
inhibitors intestinal lesion.
6. Carbontetrachloride and mushroom ♦ The trophozoite form of amoebae invade colonic
poisoning (Amanita phalloides)
mucosa forming flask–shaped ulcer with narrow
7. Hepatitis A virus (HAV) → 4% neck and broad base.
8. Hepatitis B virus (HBV) → 8%
♦ Occurs more in male than female M:F = 7:1
9. Autoimmune hepatitis unknown causes
→ (15% of cases)
Morphology [06]
10.Hepatitis C (HCV) infection→rarely Gross:
causes massive hepatic necrosis. - Solitary or less often multiple discrete
• Mechanism of hepatocellular necrosis: abscess, sometimes exceeding 10cm in
diameter.
1. Direct toxic damage→Acetaminophen,
- More often located in right lobe in
mushroom toxins.
posterosuperior portion.
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- Abscesses have a scant inflammatory - Multiple small neutrophilic abscess with

reaction at their margin and shaggy fibrin area of necrosis of affected parenchyma.
lining. - The adjacent viable area shows pus and
- Because of hemorrhage into cavities, the blood clots in the portal vein, inflammation,
abscesses are sometimes filled with a congestion and proliferating fibroblast.
chocolate coloured, ordorless and pasty Complication:
material. i. Pleuro-pulmonary complication: Pleural-
- Abscesses become purulent secondary to effusion empyema pneumonia and
bacterial infection. hepatopleural or hepato-bronchial fistula.
Microscopic ii. Intraperitoneal rupture of abscess, peritonitis
- Abscesses are necrosed and necrotic area and ascites.
consists of degenerated liver cells, iii. Intrapericardial rupture and pericardial
leukocytes, RBC and strand of connective effusion.
tissue debris. iv. Septic shock
- On PAS staining show trophozoites of E. v. Hemobilia and Jaundice.
histolytica.
vi. Perforation into a hollow viscous like colon,
Pyogenic liver abscess stomach and duodenum.
♦ Most liver abscesses are of pyogenic (bacteria) in
origin. TUMOR OF LIVER
♦ The commonest infecting organisms are gram- Classification Hepatic tumor
negative bacteria chiefly E. coli, pseudomonas, Benign Malignant
klebsiella and entrobacter, and a number of a. Hepatocellular tumor a. Hepatocellular (liver
anaerobic organism, actimycetes. - Hepatocellular cell) carcinoma
♦ Bacteria that can infect the liver directly: tumor (liver cell) - Hepatoblastoma
adenoma (embryoma) V
- S. aureus in setting of toxic shock syndrome.
- S. typhi in setting of typoid fever. b. Biliary tumors b. Cholangiocarcinoma
- T. pallidum in secondary or tertiary syphilis. - Bile duct adenoma - Combined
(cholangioma) hepatocellular and
♦ M > F; M:F = 3: 1
cholangiocarcinoma
Morphology
c. Mesodermal tumors c. Angiosarcoma
Gross: - Haemangioma - Embryonal sarcoma
- Occur in right lobe of liver than left lobe.
Hepato-cellular carcinoma
- Solitary or multiple lesions ranging from
millimeter to massive lesions. ♦ Also called hepatoma/liver cell carcinoma
- Multiple small abscesses: in case of ♦ Most common primary hepatic malignant tumor
bacteremic spread through arterial and Etiology
portal system. i. Viral infections (HBV – 85%)
- Solitary large abscess: In case of direct ii. Chronic alcoholism
extension and trauma.
iii. Cirrhosis
- Biliary abscess: purulent and multiple.
iv. Food contaminates (primary contaminants)
- Single abscess has thick fibrous capsule.
Microscopic v. Chemical carcinoma (butter yellow,
- Show typical microscopic features of nitrosamines)
abscess. vi. Hereditary hemochromatosis.

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 Pathology

Morphology 3. Lymph node metastasis-perihilar, peripancreatic

Gross: and paraaortic.
- HCC may appear grossly as 4. Extensive spread of carcinoma within the liver.

a. Unifocal → Usually large mass Hepatoblastoma

b. Multifocal →Widely distributed nodules of ♦ It most common malignant tumor of liver in
variable size. young childhood.
c. A diffusely infiltrative cancer, permeating ♦ Usually fatal within a few years if not resected and
widely and sometimes involving the entire causes death by hemorrhage, hepatic failure or
liver. wide spread metastasis.
- HCC are usually paler than the surrounding Morphology
liver substance and sometimes take on a green
Gross
hue when composed of well differentiated bile
secreting bile. - Tumor → circumscribed lobulated mass,
- All pattern of hepatocellular carcinomas have have areas of cystic degeneration,
strong propensity for invasion of vascular hemorrhage and necrosis.
channels. Microscopic
- Extensive intrahepatic metastases ensue, and - Hepatoblastoma consists of two anatomic
occasionally long snakelike masses of tumor variants.
invade the portal vein. a. Epithelial type
Microscopic
• Composed of small polygonal fetal cells
- HCC range from well differentiated to highly
or even small embryonal cell.
anaplastic lesions.
• Form acini, tubules or papillary
V - Cells of well differentiated and moderately
structures vaguely recapitulating liver
well differentiated tumors, hepatocytic in
origin, are deposed in trabecular pattern or development.
in an acinar, pseudoglandular pattern. b. Mixed epithelial and mesenchymal type
- Tumor cells in poorly differentiated forms • Contain foci of mesenchymal
→ become pleomorphic appearance with differentiation that may consist of
numerous anaplastic giant cells, small and primitive mesenchyme, osteoid,
completely undifferentiated cells or even cartilage and striate muscle.
resemble spindle cell sarcoma.
CHRONIC CHOLECYSTITS
Fibrolamellar carcinomas
♦ Chronic cholecystitis may be a sequel to repeated
- Distinctive variant of HCC
bouts of mild to severe acute cholecystitis.
- No association with HBV or cirrhosis risk factor
- Usually presents a single large, hard 'Scirrhous' ♦ Associated with cholelithiasis in more than 90% of
tumor with fibrous bands coursing through it. cases.
- Microscopically: Composed of well ♦ Presents biliary colic to indolent right upper
differentiated polygonal cells growing in nests quadrant pain and epigastric distress.
or cord and separated by parallel lamellae of Etiology:
dense collagen bundles.
- Obstruction
Metastasis
- Gallstones (in 90% case)
1. Venous invasion into hepatic venous system.
- Tumor
2. Hematogenous spread to lungs
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 Hepat

Pathogenesis Advanced case

Obstruction, gallstones,tumors • There is marked subepithelial and
↓ subserosal fibrosis, accompanied by
Prevents the bile from leaving the gall bladder mononuclear cell infiltration.
Bile gets trapped • G.B wall has buried crypts epithelium →
↓ due to reactive proliferation of mucosa
Acts an irritant which causes cellular infiltration and fusion of mucosal fold.
within 3–4 days
• Out pouching of the mucosa through the
↓
G.B. wall form RokitanskyAschoff Sinus
Elicits inflammatory process
(contain bile).
↓
G.B. becomes enlarged and edematous • Porcelain G.B. :
↓ → Extensive dystrophic calcification
Occlusion along with bile stasis causes the within the gall bladder wall.
mucosal lining of the G.B. to become
• Xanthogranulomatus cholecytitis:
necrotic
↓ It is a rare condition characterized by:
Bacterial growth occur due to ischemia → Thickened wall
↓ → Shrunken, nodular and chronically
Chronic inflammation inflamed
↓
→ Foci of necrosis and hemorrhage.
Chronic cholecystitis
• Hydrops of the gall bladder:
Morphology
Gross: → It a condition in which atrophic, V
chronically obstructed G.B.
- Serosa→Usually smooth and glistening may
be dulled by subserosal fibrosis. → May contain only clear secretions.
• Dense fibrous adhesion→May remain as Complication
sequel of preexisting acute inflammation. i. Bacterial super infection: Cholangitis or sepsis.
• On sectioning, wall is invariably ii. G.B. perforation and local abscess formation.
thickened, and has an opaque gray white iii. G.B. rupture with diffuse peritonitis
appearance.
iv. Biliary enteric (cholecystenteric) fistula:
- In uncomplicated case:
- Drainage of bile into adjacent organ
• The lumen contains fairly clear, green
- Entry of air and bacteria into biliary tree
yellow, mucoid bile and usually stones.
- Potentially, gallstone induced intestinal
• Mucosa–preserved (generally)
obstruction (ileus)
Microscopic
v. Aggravation of pre-existing medical illness,
- Degree of inflammation is variable.
with cardiac pulmonary, renal or liver
Mild case: decomposition.
• Only scattered lymphocytes, plasma cells
vi. Porcelain Gallbladder: with increased risk of
and macrophages are found in the mucosa
cancer.
and in the sub-serosal fibrous tissue.

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 Pathology

CHOLELITHIASIS
♦ The presence of gall stones in the G.B. is called
cholelithiasis
♦ Types of gall stone: 2 types
i. Cholesterol stones
ii. Pigment stones
♦ Person at risk of developing cholelithiasis
- Can be abbreviated by '4F' acronym for 'fat'
female, fertile (multipara) and forty.
Cholesterol stones
♦ Contain more than 50% of crystalline cholesterol
monohydrate.
Risk factors
i. Demography: Northern Europeans, North and
South America, native Americans, Mexican–
Americans.
ii. Advancing age
iii. Female gender
iv. Oral contraceptives
V iv. Pregnancy
vi. Obesity and metabolic syndrome
vii. Rapid weight reduction
viii. Gallbladder stasis
ix. Inborn disorder of bile acid metabolism
x. Hyperlipidemia syndrome
Pathogenesis of cholesterol stones [03,07,08]
- There are four contributing factors for Morphology [08]
cholesterol cholelithiasis given as follows:
- 100% pure (rarely) down to around 50%
i. Supersaturation of bile with cholesterol
- Single to multiple
ii. Gallbladder hypomotility→ promotes - Surface of multiple stones may be rounded or
nucleation faceted
iii. Acceleration of cholesterol nucleation - With increased proportion of calcium
carbonate, phosphate and bilirubin, the stones
iv. Mucus hypersecretion in G.B traps the crystals
show discolouration and may be lamellated
permitting their aggregation into stones.
and gray white to black (mixed gallstones)
- Stones composed largely of cholesterol are
radiolucent.
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 Hepat

- Calcium carbonate is found in 10% to 20% Types of pigment stones

cholesterol stones to render them radiopaque. I. "Black" pigment stone
- Pure cholesterol stones: Pale yellow, round to
- Found in sterile Gallbladder bile
ovoid & have finely granular hard external surface.
- On transection - Consists of oxidized polymers of calcium salts
• Reveals a glistening radiating crystalline of unconjugated bilirubin, small amount of
palisade. calcium carbonate calcium phosphate, and
Pigment Stones mucin glycoprotein and some cholesterol
♦ Are complex mixtures of abnormal insoluble monohydrate crystals.
calcium salts of unconjugated bilirubin along with
II. "Brown" pigment stone
insoluble calcium salts.
♦ Risk factors of pigment stones: - Found in infected intrahepatic or extrahepatic
i. Demography: ducts.
- Asians more than western - Consist of pure calcium salts of unconjugated
- Rural more than urban bilirubin, mucin, glycoprotein, a substantial
ii. Chronic hemolytic syndrome cholesterol fraction, and calcium salts of
iii. Biliary infection palmitate and stearate.
iv. GIT disorder
Morphology of pigment stones:
- Ileal disease
- Ileal resection or bypass "Black" pigment stone
Pathogenesis of pigment stones: • Rarely > 1.5 cm in diameter
- Cystic fibrosis with pancreatic insufficiency. • Present in great number
• Crumble to the touch
Hemolytic Biliary Severe ileal V
syndromes infection dysfunction • Usually speculated and molded
• 50% to 75% of black stones are radiopaque.
↑ed secretion of Release of microbial
conjugated bilirubin β–glucuroniadase "Brown" pigment stones
in bile, however causes hydrolysis of • Laminated and soft
about 1% of bilirubin bilirubin glucuronides
glucuronides are (Deconjguation)
• May have a soaplike or greasy consistency.
deconjugated in
biliary tree. The large
Complication of Gall stones:
amount of 1. Cholecystitis
unconjugated
bilirubin produced 2. Empyema
may exceed solubility 3. Perforation
Elevated levels of unconjugated 4. Fistulas
bilirubin in bile
5. Inflammation of biliary tree → Cholangitis
6. Obstructive cholestasis or pancreatic with
Insoluble calcium salts of conjugated ensuing problem.
bilirubin along with inorganic calcium salts
7. "Gall stone ileus" or Bouveret's syndrome

Note: Small stone or gravel → are most dangerous

Pigment stones

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 Pathology

CARCINOMA OF GALL-BLADDER - Tumor are scirrhous and have a very firm

♦ Most common malignancy of the extra hepatic consistency.
biliary apparatus ii. Exophytic pattern
- Growth into the lumen as an irregular,
♦ F>M
cauliflower mass but at the same time
♦ Age: 70 invades the underlying wall.
♦ The most common risk factor: - Luminal portion may be necrotic,
- Cholelithiasis (in 95% of case) hemorrhagic and ulcerated.
♦ Only 0.5% of patients with gallstones develop G.B. Microscopic
cancer after > 20 yrs - Most carcinomas of G.B. are adenocarcinomas.
Common sites of involvement - Some are papillary in architecture.
i. Fundus and the neck - About 5% are squamous cell carcinomas or
ii. About 20% involve the lateral walls. have adenosqumous differentiation.
- A minority → exhibit carcinoid
- Differentiation
Morphology
• Well to moderately differentiated
Gross
• Infiltrative and poorly differentiated to
- Carcinoma of G.B. exhibit two pattern of
undifferentiated.
growth
- Malignant glandular structure is present within
i. Infiltrating
a densely fibrotic gallbladder wall.
ii. Exophytic
Metastasis
i. Infiltrating type pattern
- Invasion of liver centrifugally by the time of
V - More common
discovery of the GB tumor
- Appears as a poorly defined area of diffuse
- Extended to the cystic duct and adjacent bile
thickening and indurations of GB wall that
ducts and portal–hepatic lymph-nodes.
may cover several sequale or may involve
the entire G.B. - Seeding: peritoneum, GIT and lungs.

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 Hepat

SPECIAL POINTS FOR MCQs

Jaundice
1. Clinically jaundice is detectable at 2–2.5mg/dl or more
2. Overt jaundice is seen when bilirubin level > 2mg/dl.
3. Conjugated hyperbilirubinemia is encountered in structure jaundice, Dubin-johnson syndrome.
4. Unconjugated hyperbilirubinemia is encountered in prehepatic jaundice, Gilbert's syndrome and
CNS Type 1 and 2.
5. Most sensitive liver function test to differentiate type of jaundice is urine urobilinogen.
6. Urine bilirubin excretion is increased in extra hepatic biliary atresia.
7. Delta bilirubin form which remains detectable in serum for sufficient time after recovery from
diseases.
8. Kernicterus often develop in crigler-Najjar syndrome type I.
9. Clay colored stool, itching, pruritus and xathoma of skin are characteristic clinical presentation of
obstructive jaundice.
10. Bile salt is present in urine in posthepatic jaundice.
11. Gilbert syndrome is due to ↓ ed activity of UGT1A1 enzyme activity due to mutation in promoter
region of UGT1A1 gene.
12. Child having CNS type I dies within 2yr of life.
13. Urobilinogen is absent in urine in posthepatic jaundice is due to mutation in gene for MRP–2
protein.
14. In Dubin Johnson syndrome, liver has dark brown pigment.
15. γGT,ALP is exclusively ↑ed in post-hepatic jaundice. V
Viral – Hepatitis
16. Hepatitis – B
- Acute infection → has HBsAg (+), IgM anti HBc (+) (+→Present,- absent)
- Resolved infection →HBsAg (–), IgG antiHBs (+)
- Vaccination →HBsAg (–), anti HBs (+)
17. Acute hepatitis – features
- Zonal necrosis
- Bridging hepatic necrosis
- Hepatic cell necrosis
- ↑ liver size and redness
- Kupffer cell hypertrophy and hyperplasia
- Lobular disarray
- Focal necrotic spot
- Council man apoptotic bodies are seen in acute hepatitis
18. Chronic active hepatitis
Characterized by
- Piece meal necrosis
- Bridging necrosis
- Rossette and pseudolobule formation
- Ground glass appearance of hepatocytes
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 Pathology

- Councilman bodies (2013)

- Kuffer cell hyperplasia.
19. Chronic persistent hepatitis
- No piece meal necrosis
- Mononuclear infiltrate confined to portal tract
- Septae into parenchyma
20. Inactive carrier of hepatitis – B: Features
- HBsAg(+) → Greater than 6 months
- HBeAg(–), anti HBe(+)
- HBV DNA < 105copies/ml
- Normal liver enzymes
Note: In case of chronic hepatitis – B HBV DNA is greater than 105 copies/ml and has ↑ed liver enzymes.
21. Hepatitis – C
- Paucity of inflammation
- ↑ed in activation of sinusoidal lining.
- Lymphoid aggregates (fatty change)
- Bile duct damage in portal tract
- Cause of post transfusion hepatitis
- Causes chronic hepatitis
22. Hepatitis – D
V - HDV is "defective" because it does not have gene for its protein.
- Can replicate in cells only infected with HBV.
- HDV uses surface antigen of HBV (HBsAg) as its enveloped protein.
- HBV is helper virus for HDV.
- HDV is an enveloped virus.
- HDV is an RNA virus
- Genome of HDV is small and encodes only one protein the delta antigen.
- HDV genome is a ribozyme i.e. has ability to self cleave and self ligate.
- Infection with hepatitis D can be prevented by vaccinating susceptible persons with hepatitis
B vaccine.
23. Hepatitis E
- Main cause of sporadic cases of hepatitis in adult.
- Worst prognosis in pregnancy with hepatitis E.
- Common route of spread of HEV is feco-oral.
24. Alcoholic hepatitis – Features:
- Liver cell necrosis
- Perivenular distribution
- Pericellular fibrosis, infiltration by neutrophils, and mallory's hyaline.

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 Hepat

- Neutrophilic accumulation is relatively unique to alcoholic injury and may contribute

hepatocellular injury.
- Mallory's hyaline is an eosinophilic intracellular inclusion composed of condensed
cytoskeletal filaments
- Mallory's hyaline may occasionally be seen in other form of liver injury including Indian
childhood cirrhosis, morbid obesity, primary biliary cirrhosis, wilson's disease, Alcoholic
cirrhosis and following Jejunoileal by pass.
- Mallory's hyaline is not present in secondary biliary cirrhosis.
- Other common pathologic finding in alcoholic hepatitis include steatosis, bridging necrosis,
bile duct proliferation, cholestasis and mitochondrial enlargement within hepatocytes.
- Large giant cells are found in Neonatal hepatitis.
25. Cirrhosis, portal HTN, Hepatocellular failure, Hepatic tumor.
- Cirrhosis has 3 characteristic feature (i) Bridging fibrous septae (ii) Parenchymal nodules (iii)
disruption of the architecture of the entire liver.
- Most common cause of cirrhosis is chronic alcoholism.
- Micronodular cirrhosis (<3mm in diameter)
- Macronodular cirrhosis (>3mm in diameter)
- Fibrogenesis in cirrhosis is caused by Myofibroblast & hepatocytes.
- Focal nodular cirrhosis occur in cystic fibrosis.
- Fatty change in liver is seen with use of tetracycline.
- In cirrhosis, there is nodular and diffuse fibrosis.
- Gandy Gamma bodies in spleen is associated with CML, sickle cell anemia and cirrhosis
with portal HTN.
- Pipestem cirrhosis is seen in schistosomiasis.
- Micronodular cirrhosis does not include post necrotic cirrhosis etiology type. V
- Patient of haemochromatosis induced cirrhosis more often may develop hepatocellular
carcinoma as a late complication.
- In primary biliary cirrhosis: feature
• Elevated cholesterol in blood.
• Familial occurrence and autoimmune in origin.
• Common in women (not in men)
- Portal vein thrombosis is intrahepatic causes of portal HTN.
- Major risk factor in pathogenesis of HCC in developed countries is alcoholic cirrhosis.
- Periportal fatty degeneration is seen in protein energy malnutrition.
- Most common malignancy of hepatic nodule is hemangioma.
- Jaundice is not associated with HCC.
- HCC is characterized by →Hepatomegly, ↑ ALP, ↓ α-fetoproteins.
- Budd chiari syndrome is occlusion of hepatic vein (i.e. hepatic vein thrombosis)
- The commonest benign solid epithelial tumor of liver is Hamartoma.
- Mid zonal necrosis in liver may occur in yellow fever.
- Hydatid cyst of liver is not indication for doing liver biopsy.
- In cirrhosis, stellate cell proliferation is stimulated in particular by PDGF, TNF (tumor
necrosis factor) is potent stimulus for change in Myofibroblastic phenotype.
- Ascites becomes clinically detectable when ascetic fluid accumulation is 500ml.
- Ascitic fluid is serous fluid and has < 3gm/dl of protein (Albumin predominantly)

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 Pathology

26. Disease Causative drugs / chemical toxin

Angiosarcoma liver → Vinylchloride, Aflatoxin, Thorotrast
Peliosis hepatitis → Steroids, Danazol
Hepatic vein → OCP, cytotoxic drugs
thrombosis
Veno occlusive disease → Pyrozziline alkaloids, cytotoxic drugs
- Most sensitive liver function is prothrombin time.
- Laennec cirrhosis: Broad expanses of tough, pale scar tissue created by ischemic necrosis
and fibrous obliteration of nodules.
27. Liver Abssces
- In amoebic liver abscess, trophozoites of E. histolytica are best demonstrated at, margin of
abscess with viable liver tissue.
- The most common site of hydatid cysts is liver.
- Vascular lesion in liver is due to chlorpromazine.
- Characteristic features of amoebic ulcer (colon) is flask shaped.
- Amoebic liver abscess is more common in right lobe in posterior superior portion.
- Massive abscess is characteristic feature of pyogenic abscess.
28. Gall stones, Cholecystitis, carcinoma of G.B
- Small stones of gravel is the most dangerous.
- Biliary infarct is related to extra hepatic cholestasis.
- Cholesterol stones consist of >50% of crystalline cholesterol monohydrate.
- Rapid wt. reduction is risk factor for pigment stone.
V - Stones composed largely of cholesterol are radiolucent.
- Black and brown pigment stones are found in sterile G.B. and infected intrahepatic duct
respectively.
- Rokitansky Aschoff sinus are seen in chronic cholecystitis.
- Carcinoma of G.B. is most common malignancy of the extrahepatic biliary tract.
- Cholelithiasis is most common risk factor in pathogenesis of carcinoma of G.B. (in 95% of
case)
- Hepatic adenomas are associated with OCP.
- Adenomyomas of G.B. are always located in fundus.
- Pigment gall stones are usually multiple and multifaceted.
- A premalignant condition for carcinoma of liver is Hepatitis B virus.
- Heparlobatum is due to syphilis.
- In fitz Hugh Lurtis syndrome, pain is due to perihepatis.
- Perivascular fibrosis is characteristics feature of alcoholic liver.
- Major source of collagen in cirrhosis is Ito cell (Hepatic stellate cell)
- The most common genetic disorder causing liver disease in children is α1- antitrypsin
deficiency.
- Proteins in hepatocytes are seen in alcoholic liver disease.
- Chronic hepatitis has not micronodular cirrhosis.

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