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Hepatobiliary system
Hepatic lobule
At center = Central vein
Portal triad = Bile duct + Portal vein + Hepatic Artery
Right next to portal triad is Zone 1
Right next to central vein is Zone 3
Middle is the Zone 2
Zone 1 is most susceptible to toxin damage
Zone 3 is most susceptible to ischemic injury
Cords of Hepatocytes
In between these cords we can see Sinusoids
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In between Hepatocytes and sinusoids there is a space known as : Space of Disse
Space of Disse contains : Ito cells/ stellate cells
Two functions:
1. Vitamin A storage
2. Fibrosis: Cirrhosis of liver
In between hepatocytes – Canal of Herring
Canal of Herring contains Oval cells (Stem cells)
Kupffer cells: Present of endothelial side of sinusoids.
What are Kupffer cells: Macrophages in liver
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Liver Function Test
1. Synthetic ability of liver
S. Albumin
PT (Prothrombin time/ Clotting factor)
Decreased Clotting factors: PT Increases
Normal Prothrombin time: 11 -15 sec
BUN:
2. Liver cell necrosis:
AST (Aspartate transaminase)/ SGOT -also elevated in Myocardial infarction
ALT (Alanine Transaminase) /SGPT – Most specific for liver
LDH (Lactate Dehydrogenase)
AST/ALT ratio: >2 =ALD, <1=NALD
3. Liver excretory functions:
S. Bilirubin
U. Bilirubin
4. Tests for cholestasis
ALP (Alkaline phosphatase)
GGT (Gamma- Glutamyl transpeptidase)
S. nucleotidase
All three are increased in Cholestasis
More specific/ indicative of Alcohol misuse: GGT
ALP also increased with increase in B one turn over
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Bilirubin Metabolism
Hemoglobin breaks down into heme and globin
Heme is acted by heme oxygenase and results in formation of biliverdin which is acted
by biliverdin reductase that will result in formation of Bilirubin (unconjugated/indirect
bilirubin: water insoluble, can cause blood brain barrier and can cause – Kernicterus)
Bilirubin roams around with albumin in the body
Unconjugated bilirubin enters the liver.
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Direct Bilirubin : Conjugated Bilirubin
Total bilirubin = Direct bilirubin + Indirect Bilirubin
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Jaundice
1. Increased Unconjugated Bilirubin
Hemolytic anemia
Criggler Najar Syndrome :1,2
Gilbert Syndrome
2. Increased Conjugated Bilirubin
Obstruction
Biliary diseases
Dubbin Johnson SYNDROME
Rotor syndrome
Increased Unconjugated Bilirubin:
Criggler Najar Syndrome: 1 Criggler Najar Syndrome: 2 Gilbert syndrome
UGT complete deficiency UGT partial deficiency Very mild deficiency of UGT
100% fatal Rx- Phenobarbitone Stress (infection): Manifest
Autosomal recessive (Increase UGT activity in m/c Autosomal dominant >
liver) Autosomal recessive
Autosomal dominant >
Autosomal recessive
Increased Conjugated Bilirubin:
A. Obstruction
Stone
Stricture
Cancer
Clonorchis sinensis
B. Biliary diseases
a) Primary Biliary Cirrhosis:
Intra hepatic bile duct
d/t anti-mitochondrial Ab (AMA)
Female
b) Primary Sclerosing Cholangitis
Extra hepatic bile duct
d/t p-ANCA
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Male
Microscopic appearance: Onion Skinning
d/d Onion -Skinning
1. Cell injury: Myelin figures
2. Lysosomal storage disorder: Tay sachs
3. SLE: Spleen
4. Blood vessel: Hyperplastic arteriosclerosis (Malignant HTN)
5. Liver: Primary sclerosing Cholangitis
C. Dubbin Johnson syndrome
Defect in excretion of conjugatedAfraTafreeh.com
bilirubin
Defect in MRP-2
Pigmented Liver: d/t: Epinephrine
D. Rotor syndrome
Defect in excretion of conjugated bilirubin
Non- Pigmented Liver
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Biliary Disease
Causes of Cirrhosis:
1. Alcoholic Liver Disease
2. Biliary Disease
3. Cryptogenic Cirrhosis
4. Drug induced hepatitis
5. Autoimmune hepatitis
6. Enzyme deficiency
7. Hemochromatosis
8. Wilsons disease
9. Viral hepatitis
a. Alcoholic Liver Disease
b. Biliary Disease
c. Cryptogenic Cirrhosis / Nonalcoholic fatty Liver disease
Nonalcoholic or ethanol <20 micro gram/ week
Causes: Diabetes, Obesity, Triglycerides, Syndrome X
Sequence:
Non- Alcoholic fatty liver (NAFL) Non-Alcoholic steatohepatitis Cirrhosis
Diagnosis: NALD vs ALD
NALD ALD
AST/ALT <1 >2
Biopsy -ALD
History
m/c/c death in NALD : Cardiovascular causes
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Autoimmune hepatitis and Drug induced Hepatitis
a) Autoimmune hepatitis Type – 1
Ab +
ANA
AMA
b) Autoimmune hepatitis Type – 2
Anti LKM Antibodies
Liver-Kidney-Microsomal
Anti LKM -1 Antibodies: a/w Hepatitis C
Anti LKM -2 Antibodies: a/w Drugs
Anti LKM -3 Antibodies: a/w Hepatitis D
c) Autoimmune hepatitis Type – 3
Ab a/g LSA
Liver soluble antigen
Microscopic Examination:
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a) Interference Hepatitis
b) Emperipolesis
c) Hepatic Rosette
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Enzyme deficiency
Alpha-1 antitrypsin deficiency
Anti -elastase
PiMM : Normal Alpha 1 antitrypsin
PiMZ: Heterozygous
PiZZ : Alpha 1 Antitrypsin deficiency: Homozygous
Alpha-1 antitrypsin deficiency effect two organs:
Liver: Cirrhosis
Panacinar emphysema
Diagnosis: PAS +Diastase resistant, Inclusions inside hepatocytes.
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Hepatocellular Carcinoma
Male
20-40 years
Risk factors:
Hepatitis B
Hepatitis C
Cirrhosis
Alcohol
Tyrosinemia
Aflatoxin (Aspergillus flavus -> peanut contaminant)
Preneoplastic Conditions:
Hepatic adenoma
Small cell dysplastic nodule - : Risk of HCC
Large cell dysplastic nodule
HCC Fibrolamellar Variant
20-40 years Age 9-20 years
Male > Female Sex Male =Female
(In India: Female > Male)
Hepatitis B Risk Factor Not a/w Hepatitis B
Hepatitis C Not a/w Hepatitis C
Negative Microscopic Fibrosis/ Collagen
examination
AFP Tumor Neurotensin-1
marker
Hematogenous Spread Lymphatic
Prognosis Better
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Hemochromatosis
Iron overload
Classification:
a) Primary Cause: 6p:
Genetic HLA gene
HFE gene (chr 6p) HFE gene
HAMP gene (Hepcidin)
Hemojuvelin (Juvenile hemochromatosis)
b) Secondary Cause
Non-Genetic
Blood transfusion
Bantus Siderosis
(Increased oral Fe)
(African)
Triad: AfraTafreeh.com
Other organs:
Hypopituitary axis: Hypogonadism
Heart: Restrictive cardiomyopathy
Diagnosis:
Most accurate:
Blood test: Transferrin saturation
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Biopsy:
Diagnosis:
Drug of choice: Iron chelators, e.g. Desferrioxamine
Treatment of choice: Phlebotomy
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Wilson disease
Cu increase
Due to decrease in Ceruloplasmin: defect ATP 7B gene
Diagnosis:
Most sensitive- Cu deposition in organs: Coppe r: Rhodamine, Rubeanic acid
Note: Orcein is stain for ceruloplasmin
Most specific- Urinary excretion of copper
Treatment: Copper chelating drugs
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Viral Hepatitis
Hepatitis Hepatitis B Hepatitis Hepatitis D Hepatitis E
A C
Incubation 2-6 2-26 weeks 4-26 2-26weeks 4-5weeks
period weeks weeks
Chronicity - 5-10 % >80% Superinfection Only if
>90% immunocompromised
Hep D Hep B
10% Co-
infection
Hep B +Hep D
Diagnosis
PCR: Viral load
Antibody: IgM, Ig G
Diagnosis of Hepatitis B
HBsAg : Australia Antigen
HBeAg: Active disease, infectivity, Viral replication
Anti-HbcAg: Never seen in blood (Always remain within viral particle), First Ab: marker of
window period
HBV-DNA: PCR
Qualitative marker of HBV replication: Hbe Ag
Quantitative marker of HBV replication: HBV DNA
Note:
m/c Acute Viral Hepatitis: Hepatitis A
M/c Acute Viral hepatitis:
Child: Hepatitis A
Elderly: Hepatitis E
M/c Chronic viral hepatitis: Hepatitis C
m/c/c Cirrhosis: Hepatitis C
m/c Viral Hepatitis:
H.C.C
Carrier state Hepatitis B
a/w Blood Transfusion
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Microscopic Examination:
Hepatitis B: Ground glass appearance of hepatocytes: due to distension of S.E.R by virions
Hepatitis C: Lymphoid aggregates, Macro -vesicular steatosis
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Muscle: Red
Collagen: Blue
Nuclei: Blue back
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Miscellaneous topics
1. Peliosis Hepatitis: Reversible Sinusoidal dilation
Causes:
TB
OCP
AIDS
Cancers
2. Budd Chiari Syndrome:
Hepatic Vein Obstruction due to Hepatic Vein thrombosis
m/c due to Polycythemia
Radiological IOC: Hepatic V enography
3. Congenital anomalies of biliary tree:
a. Von Meyenberg disease
Bile duct hamartoma
a/w PKD
b. Carolis disease
Dilatation of intrahepatic bile duct
Increased risk of cance r
c. Alagille syndrome
Absence of intrahepatic bile duct
Jagged 1 NOTCH signaling pathway
d. Nutmeg liver
Seen in CVC Liver Chronic venous congestion
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Due to right sided heart failure
e. Reye’s syndrome/ Jamshedpur fever
h/o child with viral illness and you give treatment with Aspirin -> it results in
mitochondrial dysfunction
Resulting in increased ammonia
Ammonia attaches to brain = Coma, Convulsions
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f. Cholangiocarcinoma
Bile duct carcinoma
a. Classification: Extrahepatic and Intrahepatic
Extrahepatic
m/c Perihilar region
@ fusion of Left and Right Hepatic duct
Klatskin’s tumor
Risk factors:
C- Clonorchis sinensis, Opisthorchis sinensis
C-Carolis disease
C-Choledocholithiasis, Choledochal cyst
Microscopically:
Adenocarcinoma,
Increased amount of desmoplastic reaction,
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Hard consistency
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Nodular Hyperplasia of liver
No fibrosis
No cirrhosis
1. Focal Nodular Hyperplasia
m/c in females
a/w OCP
Central Stellate Scar
2. Nodular Regenerative Hyperplasia
a/w change in intrahepatic blood flow
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m/c/c: R.A
Other causes: Hyper viscosity, MPN
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Liver Tumors
m/c Liver tumor: Metastasis: m/c Colo-rectal carcinoma
Primary Liver tumors:
a. Benign
Cavernous Hemangioma (m/c benign)
Hepatic Adenoma: Female, OCP well encapsulated lesion
b. Malignant:
m/c malignancy is: Hepatocellular carcinoma
m/c malignancy in children: Hepatoblastoma
m/c sarcoma occurring in liver: Angiosarcoma
Note- Angiosarcoma is due to Vinyl Chloride, arsenic, Thorotrast
(Thorium based dye)
