DISEASES OF LIVER
Assistant of professor
Nechiporenko G.V.
The Major Causes of Liver Diseases
Injury from metabolic disturbances
 Injury from toxins and poisons
 Lesions of the biliary tract
 Certain virus infections
 Hypoxia
 Starvation
 Late pregnancy
 Diabetes mellitus

Fatty Change in Liver
Hepatic fatty change.
The lipids accumulate in the hepatocytes as vacuoles.
These vacuoles have a clear appearance with H&E staining.
Steatosis of Liver
( with Sudan III).
Toxic Dystrophy of Liver
1-centrolobular
necrosis of
hepatocytes
2-peripheral fatty
change of
hepatocytes
Toxic Dystrophy of Liver
(with Sudan III).
VIRAL HEPATITIS
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Hepatitis A virus (HAV), causing a fecally-spread
self-limiting disease;
Hepatitis B virus (HBV), causing a parenterally
transmitted disease that may become chronic;
Hepatitis C virus (HCV), causing chiefly
transfusion-related disease;
Hepatitis D virus (HDV) is associated as
superinfection with hepatitis B virus;
Hepatitis E virus (HEV), causing water-borne
infection;
Hepatitis G virus (HGV), has recently been
discovered.
The pathological changes in the
liver in acute viral hepatitis.
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The liver is slightly enlarged and bile stained.
Hydropic (ballooning) swelling of the hepatocytes.
Centri- zonal and focal necrosis of the hepatocytes with
formation of Councilman bodies.
Necrotic areas and bile tracts infiltrated by
lymphocytes, macrophages, eosinophils and plasma
cells.
Cholestasis in hepatocytes and bile canaliculi.
Kupffer cells show hyperplasia, hypertrophy and
phagocytosis.
Intact reticulum frame work.
Regenerating liver cells.
Liver, acute viral B hepatitis
A cellular
infiltrate
throughout
the hepatic
lobule
obscures the
normalappearing
hepatic
architecture.
Liver, acute viral B hepatitis
Councilman, or
acidophilic,
bodies are
individually
necrotic or
apoptotic
hepatocytes.
They appear as
small cells with
eosinophilic
cytoplasm and, at
times, a dark,
degenerative,
pyknotic
nucleus.
Fulminant hepatitis
Grossly, there are pale yellow areas of necrosis
and collapse of liver lobules.
Liver, fulminant hepatitis
There is
massive
necrosis of
hepatocytes
throughout
the lobules in
fulminant
hepatitis.
Viral
hepatitis C with prominent
necrosis, inflammation and some
steatosis.
Chronic Viral Hepatitis

It develops predominantly in HVC and HVB
cases with progression to cirrhosis.
1.Chronic persistant hepatitis
 2.Chronic active (agressive) hepatitis
 3.Chronic lobular hepatitis
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Liver, chronic persistant viral B
hepatitis
A chronic
inflammatory
infiltrate is
limited to the
portal area. It
does not
extend into
the adjacent
lobule.
Liver, chronic agressive viral B
hepatitis

There is a chronic
inflammatory infiltrate
in the portal areas of
the liver that extends
beyond the portal
area into the adjacent
lobule, where it
encircles hepatocytes,
many of which are
undergoing
degeneration and
necrosis.
Liver, viral B hepatitis

This is an
immunohistoche
mical stain for
HBsAg in a
section of liver.
The "groundglass"
hepatocytes,
which are laden
with HBsAg,
stain dark red.
Chronic Active C Hepatitis of
Liver
The portal-based
inflammatory
infiltrate
develops. Enough
hepatocytes have
been lost and
replaced by
fibrous
connective tissue
so that the
pattern of
bridging necrosis
with fibrosis is
evident.
Chronic Active C Hepatitis of
Liver
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This is the same area shown in the previous image, stained to
highlight collagen fibrosis (blue)
CAUSES of CIRRHOSIS
Alcoholism
 Viral hepatitis (HBV,HCV,HDV)
 Hereditary metabolic diseases (Alpha-1 - antitrypsin
deficiency, Wilson's disease, Hemochromatosis)
 Drugs and toxins
 Biliary disease (primary biliary cirrhosis,
primary sclerosing cholangitis, cholelithiasis
and bacterial cholangitis)
 Parasites (schistostoma, clonorchis)
 Venous outflow obstruction ( Budd-Chiari syndrome,
veno-occlusive disease)
 Idiopathic (15-20%)
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ETIOLOGICAL TYPES of
LIVER'S CIRRHOSIS
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Postinfectious (viral hepatitis, syphilis)
Toxic and Toxic-Allergic (alcohol, poisons, drugs)
Biliary (cholangitis, cholestasis)
Metabolic and Alimentary (deficiency of
proteins, vitamines, lipotropic factors)
Circulatory (chronic congestion in the liver)
Cryptogenic
PATHOGENIC TYPES of
LIVER'S CIRRHOSIS
Postnecrotic (macronodular)
2. Portal or Septal (micronodular or mixed)
3. Biliary (primary and secondary)
1.
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According to the size of the regenerating nodules
cirrhosis is classified into:
-Micronodular cirrhosis: Nodules l-3mm in diameter.
-Macronodular cirrhosis: Nodules from 3mm to
several cm.
-Mixed micro-macronodular cirrhosis.
MORPHOLOGICAL CHANGES
of the LIVER'S TISSUE in
CIRRHOSIS
Degeneration and necrosis of hepatocytes
 Nodular regeneration of hepatocytes
 Diffuse sclerosis
 Diffuse restoration of lobular and vascular
structure of the liver
 Deformation of the liver
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Macronodular Cirrhosis of Liver
The nodules are larger than 3 mm
Macronodular cirrhosis
Viral hepatitis (B or C) is the most common cause
for macronodular cirrhosis
Liver, postnecrotic cirrhosis
The
regenerating
liver cells are
separated by
depressed
scar tissue,
grey bands of
fibrosis.
Micronodular cirrhosis
The regenerative nodules are quite small,
averaging less than 3 mm in size.
Micronodular Cirrhosis of Liver
The regenerative nodules of hepatocytes are surrounded by
fibrous connective tissue that bridges between portal
tracts. Within this collagenous tissue are scattered
lymphocytes as well as a proliferation of bile ducts.
Posthepatitic Cirrhosis of Liver,
trichrome stain
Note the blue-stained dense collagen fibrosis.
Cardiac cirrhosis
Primary biliary cirrhosis
Primary biliary cirrhosis, a rare autoimmune disease
(mostly of middle-aged women) that is characterized by
destruction of bile ductules within the triads of the liver.
Seen here in a portal tract is an intense chronic
inflammatory infiltrate with loss of bile ductules.
Liver, primary biliary cirrhosis
The chronic
inflammation in
the portal areas
is associated
with bile duct
destruction by
the
inflammatory
infiltrate. These
are the
hallmarks of the
florid duct
lesions in
primary biliary
cirrhosis.
Liver, secondary biliary
cirrhosis
The cut surface
is dark green,
due to marked
cholestasis
within the liver.
Regenerative
nodules of liver
parenchyma are
separated by tan
bands of fibrous
tissue.
Secondary micrinodular biliary cirrhosis
after congenital atresia of the biliary
tract, cholestasis
Biliary atresia
Biliary atresia, a
common cause of
neonatal cholestasis,
results from progressive
destruction of the
hepatic and common
bile ducts. This leads to
the development of
cirrhosis in the first year
of life. It is the most
common cause of
referral for liver
transplantation in
children.
The gross picture of the liver in
different types of cirrhosis
NUTRITIONAL
POSTHEPATITIC
POSTNECROTIC
BILIARY
Size:
Decreased
Decreased
Decreased
Increased
Color:
Yellow
Yellow
Yellow
Green
10-15mm
l-6cm
2-5mm
Absent
Present
Absent
Regener 2-3mm
ative
nodules:
Normal Absent
areas:
The Effects of Cirrhosis:
1. Portal hypertension.
It is caused by obstruction to the blood
flow through the liver, pressure of the
regeneration nodules on the hepatic
veins; development of anastomosis
between the branches of the hepatic
artery and portal vein. The higher
arterial pressure is transmitted to the
portal veins.
Portal hypertension leads to
the following effects:
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Chronic venous congestion in the portal area.
Splenomegaly.
Ascites.
Varices of the anastomotic veins between the
portal and systemic circulations:
- At the lower end of the esophagus i.e.
esophageal varices.
- At the lower end of the rectum i.e. piles.
- Around the umbilicus i.e. “caput medusae”.
2. Ascites:
Occurs lately and is caused by:
 Portal hypertension.
 Hypoproteinemia.
 Sodium and water retention due to
hyperaldosteronism.
3. Hypersplenism:
Causes anemia, leucopenia and
thrombocytopenia.
4. Pathological Effects of
Disturbed Hepatic Function
Hepatocellular failure
 It results from loss of a large number of liver
cells from various causes and/or from impaired
their function, especially in hepatic cirrhosis.
A) changes in nitrogen metabolism causing hepatic
encephalopathy
B) failure to remove bilirubin from the blood, to
conjugate it and excrete it in the bile
C) failure to produce plasma proteins in
normal amounts, particulary, albumin,
fibrinogen, prothrombin and other clotting
factors, hypoproteinemia
D) diminished vitamin A formation
E) circulatory disturbances with cyanosis
and hypervolemic circulation
F) Hormonal disturbances with hepatic
metabolism of steroids
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Decrease estrogen inactivation by the liver results
in:
Gynecomastia: enlargement of the male breast.
Atrophy of the testis.
Palmer erythema.
Decrease pubic and axillary hair.
Arterial spider: dilated vessels on the face, neck
and arms.
5. Malignancy especially in
macronodular cirrhosis.
“Caput medusae"
Splenomegaly
Esophageal varices have appeared here as a result
of portal hypertension from cirrhosis of the liver
Hepatocellular carcinoma
Liver, alcoholic hepatic steatosis
(fatty liver)
Liver, alcoholic hepatic
steatosis (fatty liver)

In alcoholic fatty liver,
lipid accumulates within
the cytoplasm of
hepatocytes, creating
large clear vacuoles
within cells. The nuclei in
such cells are compressed
to the periphery of the
cell.
Liver, alcoholic hepatitis
Hepatic steatosis is
noted, especially in
centrilobular regions, in
this case of alcoholic
hepatitis. There is both
a chronic and an acute
inflammatory infiltrate
within hepatic lobules.
Sinusoidal, perivenular,
and portal fibrosis shows
up as blue-stained areas.
.This is Mallory's hyaline, also known as "alcoholic"
hyaline. The globules are aggregates of
intermediate filaments in the cytoplasm resulting
from hepatocyte injury.
Liver, alcoholic cirrhosis
This liver contains
numerous, fairly
uniform, small
nodules of
regenerative
hepatocytes
separated by
depressed areas
of fibrous scar
tissue.
Liver, alcoholic cirrhosis.
In a cut section, the uniform small nodules
of regenerating hepatocytes are more
obvious.
Liver, alcoholic cirrhosis
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Nodules of
regenerating
hepatocytes consist of
disordered cords of
cells of irregular
thickness, many of
which are two or more
cell layers thick. Note
the lack of central
veins in these
regenerative nodules.
The nodules are
surrounded by fibrous
tissue containing
variable amounts of
chronic inflammatory
cells and areas of bile
ductular proliferation.
Alcoholic cirrhosis and
intraintestinal bleeding