Liver and Gall bladder Pathology | Hasnat Hussain (Reus-11)

Liver & GB Pathology

Q.1) Tabulate the differences b/w hepatitis A, B and C viruses. Briefly describe
LFTs.
ANS:
Difference b/w hepatitis A, B and C viruses:

Features Hepatitis A virus Hepatitis B virus Hepatitis C virus

Type of virus RNA DNA RNA
Route of Fecal-oral Parenteral, sexual, Parenteral
transmission (contaminated perinatal
water or food)
Incubation period 2-6 weeks 2-26 weeks 4-26 weeks
Frequency of Never 5-10% More than 80%
chronic liver disease
Detection of serum Detection of HBsAg ELISA, PCR
Diagnosis IgM or antibody to
HBcAg, PCR

Liver function tests:

1. Tests to check hepatocytes integrity
i. Measurement of cytosolic hepatocellular enzymes (increased in liver diseases)
 Serum aspartate aminotransferase (AST)
 Serum alanine aminotransferase (ALT)
 Serum lactate dehydrogenase (LDH)
2. Tests to check biliary excretory function
i. Measurement of substances normally secreted in bile (increased in liver
diseases)
 Serum bilirubin
 Urine bilirubin
 Serum bile acids
ii. Plasma membrane enzymes (due to canaliculus damage) (increased in liver
diseases)
 Serum alkaline phosphatase

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 Liver and Gall bladder Pathology | Hasnat Hussain (Reus-11)

 Serum gamma-glutamyl transpeptidase (GGT)

3. Tests to check hepatocytes synthetic function
i. Proteins secreted into blood
 Serum albumin (decreased in liver diseases)
 Coagulation factors (decreased in liver diseases)
ii. Hepatocytes metabolism
 Serum ammonia (increased in liver diseases)
 Hepatic demethylation (decreased in liver diseases) checked by
aminopyrine breath test

Q.2) Classify hepatitis on the basis of etiology and pathogenesis. How will you
diagnose acute HBV in lab? What is the sequelae of chronic HCV infection?
ANS:
Classification of hepatitis:
1. Infectious hepatitis
 Viral  A, B, C, D and E
 Bacterial  staphylococcus aureus, klebsiella
 Parasitic  echinococcus granulosus, amoeba
2. Chemical hepatitis
 Alcohol
3. Drugs induced hepatitis
 Rifampicin
 Pyrazinamide
4. Secondary hepatitis
 Wilson’s diseases
 Ascending cholangitis
 Hemochromatosis
5. Autoimmune hepatitis

Lab diagnosis of acute hepatitis B:

1. Detection of HBsAg in blood
 Appears before the onset of symptoms
 Peaks during full-blown disease
2. Detection of HBeAg, HBV-DNA, and DNA polymerase

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 Liver and Gall bladder Pathology | Hasnat Hussain (Reus-11)

 Persistence of HBeAg is an important indicator of viral replication, infectivity

and progression to chronic disease.
3. Detection of serum IgM anti-HBc antibodies
 Appear shortly before the onset of symptoms
4. Serum aminotransferases
 Raised (hepatocellular injury)
5. Serum bilirubin
 Raised (jaundice)

Sequelae (complications) of chronic hepatitis C:

 Cirrhosis
 Hepatocellular carcinoma (HCC)
 Coagulation disorders
 Immune complex mediated disease e.g. vasculitis, GMN
 Cryoglobulinemia
 Insulin resistance
 Porphyria
 Carrier state (transmits to others, but khud kuch nai hota)

Q.3) Define cholelithiasis. What are the risk factors for gall stones? What are
the four defects involved in the formation of cholesterol gall stones?
ANS:
Cholelithiasis:
“Stone formation in the gallbladder or bile ducts.”

Risk factors for gall stones:

 Old age (forty)
 Females
 Obesity (fat)
 Hyperlipidemia
 Gallbladder stasis
 Metabolic syndrome
 Oral contraceptives

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 Liver and Gall bladder Pathology | Hasnat Hussain (Reus-11)

 Pregnancy
 Rapid weight loss
 Genetic disorders of bile acid metabolism

Four defects involved in the formation of cholesterol gall stones:

 Supersaturation
 Hypomotility of GB
 Accelerated cholesterol crystal nucleation
 Hypersecretion of mucus in the GB

Q.4) Define acute pancreatitis. What are the causes? How will you diagnose it
in the lab? Enumerate complications of acute pancreatitis.
ANS:
Acute pancreatitis:
“Acute inflammation of pancreas.”
Causes:
1. Metabolic
 Alcoholism
 Hyperlipoproteinemia
 Hypercalcemia
 Drugs
2. Genetic
 Trypsin mutations
3. Mechanical
 Gallstones
 Trauma
 Surgery
 Endoscopy
4. Vascular
 Shock
 Vasculitis
5. Infections
 Mumps

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 Liver and Gall bladder Pathology | Hasnat Hussain (Reus-11)

Lab diagnosis:
 Elevation of serum amylase during the first 24 hours
 Elevation of serum lipase after 72-96 hours
 Leucocytosis
 Hyperglycemia
 Glycosuria
 Hypocalcemia
 Serum bilirubin may be increased
 Ultrasound of the abdomen
 X-rays of the abdomen
 CT scan  enlarged, inflamed pancreas

Complications:
 Pancreatic abscesses
 Pancreatic pseudocysts formation
 Pancreatic ascites
 Shock
 DIC
 Renal failure
 Acute respiratory distress syndrome (ARDS)

Q.5) Define jaundice. Classify jaundice in infancy and childhood. Enumerate

the complications of hepatitis C.
ANS:
Jaundice:
“Yellow discoloration of the skin, sclera and other mucous membranes due
hyperbilirubinemia that exceeds 2 mg/dL.”
Also called icterus.

Classification of jaundice of infancy and childhood:

Indirect hyperbilirubinemia
1. Physiological jaundice

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 Liver and Gall bladder Pathology | Hasnat Hussain (Reus-11)

2. Jaundice due to hemolytic anemias

 ABO incompatibility
 G6PD deficiency
3. Jaundice due to polycythemia
4. Breast milk jaundice
5. Jaundice due to glucoronyl transferase deficiency
 Ciggler naggar syndrome
 Gilbert syndrome
6. Jaundice due to metabolic disorders
 Galactosemia
 Niemann-pick disease

Direct hyperbilirubinemia
1. Jaundice due to bile flow obstruction
 Biliary atresia
 Bile duct stenosis
 Cystic fibrosis
2. Jaundice due to hepatocytes injury
 Infections
 Drugs
 Genetic abnormalities

Complications of hepatitis C:
 Enumerated previously.

Q.6) Tabulate the differences b/w hepatitis A, B and C viral diseases. Describe
LFTs.
ANS:

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 Liver and Gall bladder Pathology | Hasnat Hussain (Reus-11)

Differences b/w hepatitis A, B and C:

Features Hepatitis A Hepatitis B Hepatitis C
Causative agent HAV HBV HCV
Route of Fecal-oral Parenteral, sexual, Parenteral
transmission (contaminated perinatal
water or food)
Incubation period 2-6 weeks 2-26 weeks 4-26 weeks
Frequency of Never 5-10% More than 80%
chronic liver disease
Detection of serum Detection of HBsAg ELISA, PCR
Diagnosis IgM or antibody to
HBcAg, PCR
Risk for HCC No Yes Yes
Prognosis Excellent Worse with age Moderate
Management Vaccination (no Vaccination (no IFN-alpha and
cure) cure) ribavirin (curable)

Liver function tests:

 Described previously.

Q.7) An old man of 50 years age has the following LFT report; (i) serum
bilirubin 10 mg/dL (ii) serum SGPT 55 U/L (iii) serum AST 50 U/L (iv) serum
alkaline phosphatase 1200 U/L and (iv) serum albumin 2 gm/dL.
(a) Diagnosis?
(b) Causes?
(c) What other investigations will you advise for this patient?
ANS:
Dx: Obstructive, post hepatic or surgical jaundice
Causes:
 Stones in common bile duct
 Carcinoma of the head of pancreas

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 Liver and Gall bladder Pathology | Hasnat Hussain (Reus-11)

 Stricture of the common bile duct

 Worms in the common bile duct
 Primary sclerosing cholangitis

Other investigations:
 Ultrasound abdomen
 CT scan abdomen
 MRCP/ERCP
 Liver biopsy
 P-ANCA antibodies detection

Q.8) A biopsy report of a 55 years old lady admitted to the hospital for the
complaints of abdominal distension and pallor, reveals loss of normal lobular
architecture with replacement of liver parenchyma by haphazardly
regenerating nodules surrounded by coarse fibrous septa.
(a) Diagnosis?
(b) Enlist five important and common causes.
(c) Enumerate five complications of this disease.
(d) What is the most important complication of ascites in this disease?
(e) Name any four poor prognostic signs of this disease.
ANS:
Dx: Hepatic Cirrhosis
Causes:
 Alcoholism (most common cause)
 Viral hepatitis (B and C)
 Non-alcoholic fatty liver disease
 Wilson’s disease
 Hemochromatosis

Complications:
 Portal hypertension
 Ascites

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 Liver and Gall bladder Pathology | Hasnat Hussain (Reus-11)

 HCC
 Hepatic encephalopathy
 Hepato-renal syndrome
 Infections
 Gallstones

Most important complication of ascites in this disease:

 Hydrothorax

Poor prognostic signs:

 Very high serum bilirubin (more than 50 mg/dL)
 Very low serum albumin (less than 3 g/dL)
 Prolonged prothrombin time
 Ascites
 Hepatic encephalopathy

Q.9) A 10 years old child is brought to casualty for pain in abdomen, fever,
vomiting for 3 days. Relevant lab investigations reveals serum ALT 750 IU/ml
and positive IgM anti HAV.
(a) Diagnosis? Causative agent and its incubation period.
(b) What is the usual course of the disease and what is its mortality rate?
(c) Write one sentence comment on the chronicity and carrier state.
(d) How is it transmitted and what is the clinical significance of IgG anti-HAV?
ANS:
Dx: Acute Hepatitis A (IgM anti-HAV means acute infection)
Causative agent:
 HAV
Incubation period:
 2-6 weeks

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 Liver and Gall bladder Pathology | Hasnat Hussain (Reus-11)

Course of the disease:

The course of acute hepatitis A is usually benign and self-limited. It can be divided into four
clinical phases.
1. An incubation period  2-6 weeks, during which the patient remains asymptomatic
despite active replication of the virus. In this phase transmission occurs.

2. A pre-icteric phase  loss of appetite, fatigue, abdominal pain, nausea and vomiting,
fever, diarrhoea, dark urine and pale stools

3. An icteric phase  during which jaundice develops and total bilirubin levels
exceeding 20 - 40 mg/l. Patients often seek medical help at this stage of their illness.
The icteric phase generally begins within 10 days of the initial symptoms. Physical
examination of the patient by percussion can help to determine the size of the liver
and possibly reveal massive necrosis.

4. A convalescent period  resolution occurs slowly but patient usually recovers

completely.

Mortality rate:
 0.1-0.3 %

Chronicity and carrier state:

 HAV does not cause chronic hepatitis or a carrier state.

Transmission:
 Ingestion of contaminated water and food
 Close contact with infected persons
 Ingestion of uncooked oysters or clams (rare cases)

Clinical significance of IgG anti-HAV:

 IgM anti-HAV declines a few months after the acute hepatitis A infection and is
followed by the appearance of IgG anti-HAV.

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 Liver and Gall bladder Pathology | Hasnat Hussain (Reus-11)

 IgG anti-HAV persists for years and indicates lifelong immunity against reinfection by
all strains of HAV.

Q.10) Define cirrhosis. Classify cirrhosis on the basis of size of nodules. Briefly
discuss the lab diagnosis of hepatitis B infection and sequence of raise and fall
of serological markers of HBV.
ANS:
Cirrhosis:
“A pathological condition of liver seen in various chronic liver diseases, characterized by
diffuse transformation of the entire liver into regenerative parenchymal nodules
surrounded by fibrous bands and variable degrees of vascular (porto-systemic) shunting”

Classification on the basis of size of nodules:

 Micronodular
 Macronodular
 Mixed

Lab diagnosis of hepatitis B:

Acute Hepatitis B
1. Detection of HBsAg in blood
 Appears before the onset of symptoms
 Peaks during full-blown disease
2. Detection of HBeAg, HBV-DNA, and DNA polymerase
 Persistence of HBeAg is an important indicator of viral replication, infectivity
and progression to chronic disease.
3. Detection of serum IgM anti-HBc antibodies
 Appear shortly before the onset of symptoms
4. Serum aminotransferases
 Raised (hepatocellular injury)
5. Serum bilirubin
 Raised (jaundice)

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 Liver and Gall bladder Pathology | Hasnat Hussain (Reus-11)

Chronic Hepatitis B
1. Detection of anti-HBs antibodies in the blood
 Appear after the acute disease is over
2. Detection of IgG anti-HBc in the blood
 Appear after IgM anti-HBc antibodies have fallen

Sequence of raise and fall of serological markers of hepatitis B:

 First of all HBsAg, HBeAg and HBV-DNA are raised
 Then, IgM anti-HBc is raised
 Then, anti-HBe antibodies are raised
 At last, IgG anti-HBc and anti-HBs antibodies are raised indicating the disease
going towards chronicity.

Q.11) A 50 years old multiparous and obese female developed repeated

attacks of colicky right upper quadrant pain, nausea, vomiting and intolerance
to fatty meals. Ultrasound revealed thickened gall bladder wall and gall
stones.
(a) Diagnosis?
(b) Morphology?
(c) Complications?
ANS:
Dx: Chronic cholecystitis

(*intolerance to fatty meals chronic cholecystitis mein ho ga acute cholecystitis mein nahi,
baqi symptoms dono mein ek jaise hain)
(*the 4 F’s  fat, female, fertile, forty or fifty)

Morphology:
Gross
 Gallbladder is usually contracted, but may be normal or enlarged.
 The wall of the gallbladder is thickened. On cut section it’s grey-white due to dense
fibrosis or may be even calcified.

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 Liver and Gall bladder Pathology | Hasnat Hussain (Reus-11)

 The mucosal folds may be intact, thickened, or flattened and atrophied.

 The lumen commonly contains multiple gall stones.
Microscopic
 Mild to moderate inflammation and fibrosis
 Buried epithelial crypts
 Out pouching of the epithelium through the wall
 Extensive dystrophic calcification is seen in some cases, then the GB is called
porcelain GB

Complications:
 Bacterial superinfection
 GB perforation
 Abscess formation
 GB rupture leading to peritonitis
 Biliary-enteric fistula (connection b/w bile ducts and GIT)
 GB cancer

Q.12) What are the different types of acute cholecystitis? What could be the
possible sources of acute cholecystitis? Enumerate the complications of acute
cholecystitis.
ANS:
Types of acute cholecystitis:
 Calculous (with gallstones)
 Acalculous (without gallstones)

Sources of acute cholecystitis (causes):

Acute calculous cholecystitis (90% cases)
 Obstruction in the neck of the gallbladder or in the cystic duct by a gallstone.
Acute acalculous cholecystitis (10% cases)
 Non-biliary surgery
 Burns

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 Liver and Gall bladder Pathology | Hasnat Hussain (Reus-11)

 Sepsis
 DM
 Infections
 Immunosuppression

Complications of acute cholecystitis:

 Bacterial superinfection
 GB perforation
 Abscess formation
 GB rupture leading to peritonitis
 Biliary-enteric fistula (connection b/w bile ducts and GIT)
 GB cancer

Q.13) Some of the army jawans in their camp in flood affected area have
developed loss of appetite and vomiting. On examination there is tenderness
in the right upper quadrant of the abdomen. The urine shows the presence of
bile pigments.
(a) Diagnosis?
(b) Tests you should perform on this patient?
(c) How will you correlate the lab tests with the pathogenesis?
ANS:
Dx: Acute hepatitis
Lab tests:
 Serum ALT
 Serum bilirubin
 Serum alkaline phosphatase
 PT (prothrombin) and PTT (partial thromboplastin)
 Hepatitis A, B, C, D and E screening tests (serology)

Correlation of lab tests with the pathogenesis:

 Serum bilirubin, ALT and alkaline phosphatase will guide me that whether the cause
is hepatic or post-hepatic

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 Liver and Gall bladder Pathology | Hasnat Hussain (Reus-11)

 Viral serology will let me know if it is caused by HAV, HBV, HCV, HDV or HEV
 PT and PTT will let me know the coagulation status of the patient

Q.14) Classify gall bladder stone. Give its etiology and pathogenesis.
Enumerate complications of gallstones.
ANS:
Classification of GB stones:
 Cholesterol gallstones
 Pigment gallstones
 Mixed gallstones

Etiology (risk factors):

 Described previously.

Pathogenesis:
Cholesterol stones
 Female, old age, oral contraceptives, pregnancy, GB stasis, obesity, hyperlipidemia 
Supersaturation of bile with cholesterol + Hypomotility of GB + accelerated
cholesterol crystals nucleation + hypersecretion of mucus in the GB  cholesterol
gall stones
Pigment stones
 Chronic haemolysis , alcoholic cirrhosis, chronic biliary tract infection, demographic
and genetic factors (rural setting, Asian countries)  unconjugated
hyperbilirubinemia  bilirubin and calcium conjugation  pigment gallstones

Complications of gallstones:
 Cholecystitis
 Empyema
 GB perforation
 Fistula formation
 Cholangitis

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 Liver and Gall bladder Pathology | Hasnat Hussain (Reus-11)

 Obstructive jaundice
 Pancreatitis
 Intestinal obstruction
 GB cancer

Q.15) Classify cirrhosis.

ANS:
Classification of cirrhosis:
1. Morphological classification
 Micronodular
 Macronodular
 Mixed
2. Etiologic classification
 Alcoholic cirrhosis (most common)
 Post-necrotic cirrhosis
 Biliary cirrhosis
 Pigment cirrhosis
 Cirrhosis in Wilson’s disease
 Cardiac cirrhosis
 Cirrhosis in non-alcoholic fatty liver disease
 Cryptogenic cirrhosis (idiopathic)

Prepared By: Hasnat Hussain (Reus-11) 

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