PATHOLOGY REVISION CLASSES

with
A/PROF KHOO JOON JOON
TOPIC: LIVER, GALLBLADDER & BILIARY TRACT
DISORDERS
DATE:
VENUE:
Liver
Biliary Tract
Gallbladder
 LIVER
• INFLAMMATION: HEPATITIS
• ALCOHOLIC LIVER DISEASE
• CIRRHOSIS
• OTHER DISORDERS:
• HEPATOCELLULAR CARCINOMA
HEPATITIS
• Duration
• Pattern of hepatocyte injury and inflammation
• Any scarring present
 Acute hepatitis & Chronic hepatitis

ACUTE HEPATITIS CHRONIC HEPATITIS

• Short duration
• More hepatocyte death & less
inflammation
• Inflammatory cells = neutrophils
• Less or no scarring
• Over longer duration
• Less hepatocyte death & more
inflammation
• Inflammatory cells =
mononuclear cells (incl T
lymphocytes)
• More scarring
Viral hepatitis
• Hepatitis A & E = causes acute
hepatitis
• Hepatitis B,C, D = potential to
cause chronic hepatitis
• Hepatitis B transmitted by blood,
birth
• Hepatitis D (defective virus) so
require co-infection with Hep B
• Hepatitis E = endemic in equatorial
regions and frequently epidemic
Autoimmune Hepatitis
• Female
• No serologic evidence of virus infection
• Ig G high
• Autoantibodies ( antinuclear Ab,
anti-smooth muscle AB, anti-microsomal,
etc)
• Associated with other autoimmune
disorders
• Similar histology with acute and chronic
hepatitis (of viral origin)but
• Fibrosis more rapid
• Hepatocyte injury, inflammation & marked
rapid scarring
ACUTE VIRAL HEPATITIS
Chronic hepatitis

Collapse of the hepatocyte and replaced by fibrosis (scarring) and

chronic inflammatory cells
ALCOHOLIC LIVER DISEASE
• Pathogenesis

• Alcoholic steatosis (Fatty liver)

• Alcoholic steatohepatitis
• Alcoholic cirrhosis
 Alcoholic Liver Disease
• Alcohol ingestion causes ethanol to be metabolised instead and fat
accumulates
• Hepatocellular steatosis – lipid droplets in the hepatocytes
• The breakdown of alcohol – acetaldehyde component is toxic and
illicit inflammatory reaction
• This lead to steatohepatitis (Alcoholic hepatitis) – neutrophilic
infiltration with Mallory-Denk bodies & lipid droplets
• Ethanol itself & the its metabolism by-products are toxic and this
causes fibrosis (both brought about by the ethanol toxicity and the
inflammation)
• This leads to Steatohepatitis with fibrosis (Alcoholic cirrhosis)
 Non-alcoholic Fatty Liver Disease (NAFLD)
• Similar histology as Alcoholic liver disease
• Steatosis, steatohepatitis & cirrhosis
• Seen in metabolic syndrome, obesity, type 2 diabetes, dyslipidemia
CIRRHOSIS
• End stage process –multiple causes
• Chronic hepatitis (B &C)
• Alcoholic & non alcoholic steatohepatitis
• Others- biliary disease, autoimmune hepatitis, etc
• Features
• Diffuse (most areas of liver)
• Fibrosis (septa formation)
• Regenerative nodules
• Complications of cirrhosis
• Liver function affected
• Portal hypertension
• Risk of HCC
Clinical rating system of cirrhosis
• The Child Pugh System scoring (to determine prognosis)
• Serum albumin
• Bilirubin
• INR
• Ascites
• encephalopathy
Child Pugh score for cirrhosis mortality
• Bilirubin --- (score 1-3) <34.2umol/L, 34.2-51.3umol/L,>51.3 umol/L
• Albumin ---- (score 1-3) ->35g/L, 28-35 g/L, <28g/L
• INR -----------(score 3) - <1.7, 1.7-2.2, .2.2
• Ascites--------(score 3) – absent, slight, noderate
• Encephalopathy (score 3) – no, grade 1-2, grade 3-4
Portal hypertension
• Causes: Pre-hepatic, hepatic or post-hepatic
• How does cirrhosis cause portal HPT
• The fibrosis (scarring) in cirrhosis cause
• increased vascular (sinusoids) resistance (by fibrotic bands)
• arterial venous shunting as well as
• Compression of nodules on the vessels
• Portal HPT results in
• Ascites, porta-systemic venous shunting, congestive splenomegaly, hepatic
encephalopathy
Portal systemic circulation
 ASCITES
• Revise causes of ascites
• Transudate, exudate
• SAAG (serum ascites albumin gradient)
• High gradient ( transudate) >1.1 (movement of fluid is due to
pressure)
• Low gradient (exudate) <1.1 (infections, malignancy : peritoneum
becomes permeable/leaky)
• Pathogenesis of ascites (how does ascites form?)
• Investigation
• Biochemistry (albumin, glucose, amylase)
• Culture (for infection)
• Cytology (microscopy) – cells
• Inflammtory cells (neutrophils, lymphocytes)
• RBC
• Mesothelial cells
• Malignant cells
Other disoders
• Gilbert Syndrome
• Fairly common
• Benign (decreased levels of transferase)
• Mild fluctuating unconjugated hyperbilirubinemia
• With fever/ stress
Other disoders
• Alpha 1 trypsin deficiency
• AR
• Low levels of protease inhibitor
• Mutant protein accumulates in hepatocyte and cause damage – cirrhosis
• Cytoplasmic globules (PAS +)
• Patient present with cholestasis, chronic hepatitis, cirrhosis and pulmonary
disease
Alpha 1 antitrypsin deficiency
• Accumulation of mutant protein as
cytoplasmic globules in hepatocyte
• Present as cholestasis, chronic hepatitis,
cirrhosis
• Lung present as panlobular emphysema
Other disoders
• Hematochromatosis
• Hereditary, defect in HFE gene cause no regulation in intestinal absorption of
iron
• Haemosiderin (iron) deposition in organs – liver, pancreas (DM), heart (RC),
joints (pseudogout – ca pyrophospate), skin
• Cirrhosis, diabetes, skin pigmentation
Hematochromatosis
 Differences Between Monosodium Urate and Calcium Pyrophosphate Dehydrate
Crystals with Synovial Analysis
Characteristic MSU CPPD

Birefringence Strong Weak

Shape Needle-like, sharp edges Rhomboid, rod-like
Color parallel to polarizer Yellow Blue
Color perpendicular to polarizer Blue Yellow
Other disoders
Nutmeg liver
• Occurs in congestive cardiac failure
• Right sided cardiac failure --- congestion of centrilobular sinusoids
• Left sided failure leads to ishaemic necrosis at centrrilobular
heaptocytes and bile ducts
• Resultant centrilobular haemorrhagic necrosis
• Mottled appearance -- > to nut meg appearance
Liver masses
• Benign lesions
• Hepatic adenoma , associated with females taking OCP
(mass, may rupture cause haemorrhage)
• Non neoplastic
• Amoebic liver abscess
• Hydatid cyst
Amoebic liver abscess
• The pus in the abscess appear as red anchovy sauce like
• The material obtained may show trophozoites under direct
microscopy
Hydatid cysts
Liver neoplasms
• Benign lesions
• Hepatic adenoma , associated with females taking OCP
(mass, may rupture cause haemorrhage)
• Non neoplastic
• Amoebic liver abscess
• Hydatid cyst
• Malignant
• Metastatic (from colon, lung or breast)
• Primary
• Hepatocellular carcinoma
HEPATOCELLULAR CARCINOMA
• Associations with infection HBV and HCV, cirrhosis, aflatoxin exposure
• Due to the chronic inflammation & cellular regeneration – perdispose
to chance of carcinoma
• Gross appearance
• Unifocal, multifocal or diffusely infiltrative
• Histology
• Hepatocytes poorly to well differentiated
Risk factors for Hepatocellular carcinoma
Metastatic carcinoma to liver

Multiple
Rounded lesions
Size varies (almost same “cohort”)
Usually in the parenchyma
 BILIARY TRACT DISORDERS
Primary biliary cirrhosis
• Middle aged females
• Associated conditions: Sjogren synd,
scleroderma.
• Auto antibodies + (anti mitochondrial),
raised ALP
• Destruction of intrahepatic bile ducts
(small & medium sized intrahepatic
ducts)
• Portal inflammation (non-suppurative:
lymphocytes & plasma cells)
• & scarring
• Radiology: Normal
• ** ↑alkaline phosphatase
• ** ↑ conjugated bilirubin
• Chronic destructive
• Cholangitis of intrahepatic bile ducts
Primary sclerosing cholangitis
• Median age 30 yrs, males
• Associated conditions: IBD
• Anti mitochondrial ab less frequent +,
ANCA + more frequent
• Fibrosis & destruction of Extrahepatic and
intrahepatic ducts in all sizes
• Large size ducts – chronic inflammation &
edema
• Small ducts – fibrosis (onion skin
appearance)
• Risk of malignancy (cholangiocarcinoma)
• Radiology: strictures, beading of large
ducts, pruning of smaller ducts
• ** ↑alkaline phosphatase
• ** ↑ conjugated bilirubin
• Fibrosing cholangitis, with
periductal fibrosis
PRIMARY SCLEROSING CHOLANGITIS
Radiology: strictures, beading of large ducts, pruning of smaller ducts
 Primary sclerosing cholangitis

Primary Biliary cirrhosis

GALLBLADDER: cholelithiasis
• Cholesterol stones
• Pure cholesterol stones yellow gold colour
• Mostly radiolucent
• May contain calcium carbonate, phosphates & bilirubin
• Oviod and firm
• Pigment stones
• Contain calcium salts of unconjugated bilirubin
• Small , numerous (faceted)
• More radio opaque
• Cholecystitis almost always occurs (10% occurs without any
gallstones)
Gallstones: cholesterol stones & pigment stones
Neoplasms
• Gallbladder adenocarcinoma
• More in females
• Elderly
• Associated with gallstones or parasitic infection
• Reason: recurrent trauma & chronic inflammation
• Cholangiocarcinoma
• Adenocarcinoma arising from intrahepatic and extrahepatic biliary ducts
• Age: elderly
• Risk : PSC, infestation by clonorchis sinensis (liver fluke)
Clonorchis senensis (liver fluke)
Embryonated eggs are discharged in the biliary ducts
and in the stool . Eggs are ingested by a suitable snail
intermediate host . Each egg releases a miracidia ,
which go through several developmental stages
(sporocysts , rediae , and cercariae ). The cercariae are
released from the snail and after a short period of free-
swimming time in water, they come in contact and
penetrate the flesh of freshwater fish, where they
encyst as metacercariae . Infection of humans occurs by
ingestion of undercooked, salted, pickled, or smoked
freshwater fish . After ingestion, the metacercariae
excyst in the duodenum and ascend the biliary tract
through the ampulla of Vater . Maturation takes
approximately 1 month. The adult flukes (measuring 10
to 25 mm by 3 to 5 mm) reside in small and medium
sized biliary ducts. In addition to humans, carnivorous
animals can serve as reservoir hosts.
Investigations for Liver, biliary tract disorders & Gallbladder
disease
• Blood investigations:
a. Liver function tests
b. Other parameters : Antibodies, Ig G, tumour markers
c. Viral serology
• Imaging :
• Ultra sound of liver, gallbladder
• CT scan /MRI/ Radiology (ERCP)
• Biopsy
• Liver biopsy for histological diagnosis, for iron content assay
• Gallbladder removal
• Others :
• Ascites fluid for Ix
• Aspirate of liver cyst for parasites ( direct microscopy)
 LIVER FUNCTION TESTS
conjugated or non conjugated obstruction or breakdown
Bilirubin Excretory function RBC
Alanine transaminase
(ALT) hepatocyte integrity hepatocytes death
Alkaline phosphatas
(ALP) canalicular & sinusoidal membranes cholestasis
cholestasis (if with raised
GGT microsomal enzyme ALP)
Albumin Synthesis half life 20 days
Prothrombin time vit K dependent coagulating factors
Thank you
Thank you