The document provides an overview of liver pathology, including conditions such as fatty liver, cirrhosis, alcoholic liver diseases, and liver tumors. It details the causes, histological features, and clinical implications of various liver disorders, as well as classifications of hepatic tumors. Additionally, it discusses liver function tests and indications for liver biopsy, emphasizing the importance of recognizing liver disease and its complications.

1. HEPATOBILLIARY
SYSTEM

2. TOPIC TO COVER
SPECIMENS
• CVC Liver
• Fatty Liver
• Cirrhosis
• Amoebic abscess
• Tumours of Liver,
Hepatocellular carcinoma
• Liver metastasis
SLIDES
• Fatty Liver
• Cirrhosis
• CHARTS -Jaundice

3. Normal liver histology

4. Chronic Venous Congestion (CVC)- Liver
Cut section of liver- alternate dark and light
areas are seen- known as “Nutmeg
appearance”

5. CVC liver histology
Hepatocytes around central
vein- necrosis (centrilobular
necrosis)- due to
deoxygeneated blood
Intermediate hepatocytes
undergo fatty change
Periportal hepatocytes are
normal due to adequate
perfusion.
Causes: Right sided heart failure-most common
Others –Constrictive pericarditis, tricuspid stenosis, obstruction of
inferior vena cava and hepatic vein

6. Alcoholic liver diseases and cirrhosis
• Spectrum of liver injury associated with acute and
chronic alcoholism
• Three stages
1) Alcoholic steatosis (fatty liver)
2) Alcoholic hepatitis
3) Alcoholic cirrhosis

7. Fatty change: abnormal accumulation of triglycerides within cytosol of cell
Gross: enlarged ,soft, yellow ,greasy to touch, inferior border become round,

8. Microscopy
-Microvesicular
steatosis(centrilobular)
-Macrovesicular
-No inflammaton, No
fibrosis
-special stain for fat –
Sudan IV,III, Oil red
O, Osmic acid
Causes:
- Alcoholism-most
common
-PEM, Malnutrition,
-drugs, toxins
(CCl4,Chloroform)

9. Alcoholic hepatitis :Develops acutely after the bout of heavy drinking ,
Gross: enlarged; yellow (steatosis) firm (increased fibrosis)
Histologically
• Hepatocellular necrosis :
in centrilobular zone
• Ballooning degeneration
• Mallory bodies
eosinophilic
intracytoplasmic hyaline
inclusions represents
(aggreagates of
intermediate filaments)
• Inflammatory infiltrate
• Fibrosis: pericellular
and perivenular

11. Cirrhosis
• Term was 1st coined by Laennec in 1826
• Diffuse scarring of liver characterized by loss of normal
lobular architecture and formation of regenerative nodules.
• End-stage disease
• Defined by 4 characteristics:-
• involves entire liver
• loss of normal architecture
• parenchymal nodules separated by fibrotic bands
• alternate necrotic and regenerative areas

12. Morphological classification Etiological classification
Micronodular( nodules <3mm)
Eg. Alcoholic
cirrhosis (Laennac cirrhosis)
 Macronodular (nodules>3mm)
Eg. Cirrhosis asso with chronic
hepatitis
 Mixed
Alcoholic liver diasease
Viral hepatitis (postnecrotic
cirrhosis
Biliary cirrhosis
Pigment cirrhosis in
hemochromatosis
Cirrhosis in Wilson’s disease
Cirrhosis in 1 antitrypsin
deficiency
Indian childhood cirrhosis
Storage diseases
Cardiac cirrhosis

13. Causes of micronodular and macronodular cirrhosis
Micronodular Cirrhosis Macronodular Cirrhosis
Alcoholism (early stage) Alcoholism(late stage)
Primary biliary cirrhosis Viral hepatitis
Extrahepatic biliary cirrhosis Autoimmune hepatitis
Hemochromatosis Alpha 1 antitrypsin deficiency
Indian chilhood cirhosis Wilsons disease
Hepatotoxins, drugs

14. • Alcoholic cirrhosis- Most common cause of cirrhosis(60-70%)
• Laennec’s cirrhosis, nutritional cirrhosis, micronodular cirrhosis
• begins as micro-nodular cirrhosis ,
• the liver large, fatty and weighing usually above 2 kg
• Later the liver shrinks to less than 1 kg in weight,
• non-fatty, having macronodular cirrhosis (nodules larger than 3 mm in
diameter), resembling post-necrotic cirrhosis.-producing hobnail liver
• On cut section, spheroidal or angular nodules of fibrous septa are seen.

15. Microscopy : distorted liver architecture , uniform-sized
micronodules, devoid of central veins, thick fibrous septa
dividing the nodule, showing lymphoplasmacytic
inflammation and reactive bile duct proliferation in the septa

16. Masson Trichome
produce muscle fibers -Red
Collagen–blue or green
cell nuclei- black
Reticulin stain –highlighted
reticulin fiber -black

17. • Portal hypertension and its major
effects such as ascites,splenomegaly and
development of collaterals (e.g.
oesophagealvarices, spider naevi etc) as
discussed below.
• Progressive hepatic failure
• hepatocellular carcinoma,
• Chronic pancreatitis,
• Steatorrhoea
• Gallstones usually of pigment type,.
• Infections due to impaired phagocytic
activity of reticulo endothelial system.
• bleeding disorders and
anaemia ,hypoalbuminaemia
• Endocrine disorders In males
gynaecomastia, testicular atrophy and
impotence, whereas women
amenorrhoea
• Hepatorenal syndrome leading to
renal failure , in late stages of cirrhosis.
Clinical features and complications of cirrhosis

18. Liver Cirrhosis

19. Amoebic Liver Abscess
- Less common than pyogenic
liver abscess
- caused by the spread of
Entamoeba
histolytica from intestine
- Solitary
- located in the right lobe in
the posterosuperior portion.
- Can exceed 10 cm in
diameter
- The centre of the abscess
contains large necrotic
area having reddish-
brown, thick pus
resembling anchovy
or chocolate sauce.
- The abscess wall consists of
irregular shreds of necrotic
liver tissue

20. Pyogenic liver abscess
• Most liver abscesses are of
bacterial (pyogenic) origin
• The commonest organisms are
gram-negative bacteria e.g E.
coli; Pseudomonas, Klebsiella,
Enterobacter
• liver is enlarged , single or
multiple yellow abscesses, 1
cm or more in diameter
surrounded by thick fibrous
capsule.
• common in right lobe of the
liver
• Microscopically: multiple
small neutrophilic abscesses
with areas of extensive necrosis
liver parenchyma

21. Benign Malignant
Epithelial tumors
arising from
hepatocytes
Hepatocellular
adenoma
 Hepatocellular
carcinoma
 Hepatoblastoma
Epithelial tumors
arising biliary
epithelium
Bile duct
adenoma
 Cholangiocarcinoma
Combined
Hepatocellular and
cholangiocarcinoma
Mesodermal tumors Hemangioma Angiosarcoma
Classification of primary hepatic tumors

22. Hepatocellular adenoma:
• Women in reproductive age
group,
• taking oral contraceptives,
hormone therapy and with
pregnancy -estrogen's effects.
• asymptomatic, but large ones
may cause right upper
quadrant discomfort.
• Rarely, peritonitis and shock
due to rupture and
intraperitoneal hemorrhage..

23. Cavernous
hemangioma
Most common
benign lesion

24. Hepatocellular carcinoma
• Most common primary malignant tumor
• Peak incidence in 5th
and 6th
decade
• Common in men than women, 3:1
• Occur most commonly in cirrhotic liver -HBV, HBC
• Food contaminants aflatoxins B1–mycotoxins
(carcinogenic)

25. Gross morphology
1. Unifocal
2. Multifocal
3. Diffusely infiltrating

26. Unifocal HCC:
single, yellow
brown, large mass
with areas of
necrosis ,
hemorrhage
Multifocal HCC:
Multiple masses 3-
5cm in diameter
scattered throughout
the liver

27. Microscopy
• The tumor cells resembles that of hepatocytes but vary with degree
of differentiation
• Well differentiated, moderately differentiated and poorly
differentiated
• The tumor cells shows 4 growth patterns
1) Trabecular-most common pattern, made up of 2-8 cells wide
layers seperated by vascular spaces
2) Pseudoglandular/acinar
3)Compact/solid
4) Scirrhous

28. Trabecular
pattern
The cell are polygonal and shows vesicular nuclei with prominent
nucleoli , abundant eosinophilic granular cytoplasm
Nuclear pleomorphism, mitosis,Tumor giant cells , Intranuclear
pseudoinclusion, cholestasis

29. Pseudoglandular
pattern
Solid pattern

30. Fibrolamellar hepatocellular carcinoma
• Clinicopathological variant
• Young Male and Female adults
• 20-40 years
• M:F = 1:1
• No association with HBV, cirrhosis.
• Better prognosis
• Single large hard scirrhous with fibrous bands.

32. Metastatic Tumours
• More common than primary tumors
• Stomach, Breast, lung, colon,oesaphagus, pancreas, leu/lym
• Sarcomas rarely metastases
• Noncirrhotic liver
• Gross: liver is enlarged and shows multiple, spherical,
nodular masses which shows characteristic central
umbilication due to central necrosis

33. Metastasis in liver
Large nodules with central
umbilication, in between
normal parenchyma is seen

35. NORMAL BILIRUBIN METABOLISM

36. JAUNDICE
• Yellowish discouloration of skin, sclera, and mucous membranes due to increased level
of serum bilirubin.
• Clinically evident when serum bilirubin level exceeds 2.0 mg/dl.
• Normal Serum bilirubin level-0-1 mg/dl
• Direct bilirubin level- 0.3 mg/dl
• Indirect bilirubin level- 0.7 mg/dl
• Jaundice classify :
1)According to type of bilirubin increased in plasma :
-unconjugated (Indirect) hyperbilirubinemia
-conjugated (direct) hyperbilirubinemia
2) According to etiology:
- Hemolytic
- Hepatocellular
- Obstructive
3)According to site of disease:
-Prehepatic
-Hepatic
-Posthepatic

37. • Pre hepatic jaundice:
- Haemolytic anaemia
- Ineffective erythropoiesis ( megaloblastic
anaemia, thalassemias)
- Resorption of large hematoma unconjugated
• Hepatic Jaundice
- Gilbert's syndrome
- Crigler–Najjar syndrome
- Physiological jaundice of newborn
- Hepatocellular disease: hepatitis, cirrhosis
- Intrahepatic cholestasis: Dubin–Johnson syndrome
- Primary biliary cirrhosis, primary sclerosing cholangitis,
biliary atresia
• Post hepatic jaundice: Conjugated
- Carcinoma head of pancreas,
- Ca ampulla of vater,
- Gallstone , sticture of common bile duct

38. Parameter Pre hepatic Hepatocellular Post hepatic
Basic mechanism haemolysis Deficient uptake,
conjugation or
excretion by
hepatocytes
Defective excretion
due to obstruction of
biliary tract
Type of serum
bilirubin raised
Mainly unconjugated unconjugated +
conjugated
Mainly conjugated
Urine bilirubin absent Present Present
Urine urobilinogen increased variable decreased
causes Haemolytic anaemia Viral hepatitis Common duct stone
Prothrombin time normal Abnormal that is not
corrected with
vitamin K
Abnormal that is
corrected with
vitamin K
Additional features Features of
haemolysis on blood
smear
Marked rise of serum
ALT and AST
Marked rise of ALP

39. Liver Function Test
Liver chemistry test Clinical implication of abnormality
ALT Hepatocellular damage
AST Hepatocellular damage
Bilirubin Cholestasis, impair conjugation, or biliary obstruction
ALP Cholestasis, infiltrative disease, or biliary obstruction
PT Synthetic function
Albumin Synthetic function
GGT Cholestasis or biliary obstruction
Bile acids Cholestasis or biliary obstruction
5`-nucleotidase Cholestasis or biliary obstruction
LDH Hepatocellular damage, not specific

41. LIVER BIOPSY
• Easy and safe, useful supplement to LFT.
• Indications:
1)hepatomegaly of unknown cause
2) distinguish -surgical and medical jaundice
3) diagnosis of primary /secondary neoplasms.
4) presence of systemic disease.
5) observe effectiveness of treatment
• contraindications: hydatid cyst,suspected haemangiomas, subphrenic abscess, bleeding diathesis
• disadvantages: small biopsy, bile duct peritonitis
• tests done: frozen section, routine HP, glycogen demonstration

42. Vim Silverman Liver biopsy needle