Hepatic Pathology

Lecture

Palangka Raya University

Faculty of Medicine

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DISEASES OF LIVER
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 Pathology of liver
• General features
• Infections of liver
• Metabolic diseases
• Circulatory diseases
• Drug & toxin induced diseases
• Neoplasms of liver

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General features

Pattern of hepatic injuries

Five general responses of liver to injury

1-Degeneration & accumulation

2-Necrosis & apoptosis
3-Inflammation
4-Regeneration
5-Fibrosis

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1- Degeneration &
accumulation
Ballooning degeneration: 
Caused by moderate to severe toxic or
immune injury.
Moderate injury is reversible.
Severe injury  swelling of hepatocyte
with clear spaces and clumped intracellular
organs.
Feathery degeneration:  cholestatic
liver injury cause swelling of hepatocyte
with diffuse foamy appearance
Deposition of iron, copper ,
triglyceride fat etc:
Deposition of triglyceride fat is called
steatosis .
if nucleus is not displaced by tiny fat
droplets  Microvesicular steatosis
Single large drop of fat displaces nucleus
Macrovesicular steatosis
2- Necrosis & Apoptosis:
Ischaemic coagulative necrosis
:Nucleus is lysed and cell is
mummified .
Apoptotic cell death.:
Occurs in individual cell.
Cell is shrunken, pyknotic and
eosinophilic
Lytic necrosis:
Cell osmotically swell and rupture
leaving broken pieces of cells.
Zonal distribution of necrosis (in Liver)
Centrilobular ( Ischaemic, drug ,toxin)
Midzonal
Periportal (eclampsia )
Bridging necrosis :
Massive necrosis 5
 Five general responses of liver to injury

3- Inflammation 4- Regeneration 5- Fibrosis

Injury to liver cell Damaged hepatocytes Occurs due to
causes infiltration of has ability to regenerate inflammation or direct
inflammatory cells  is except in severe damage. toxic effect
called Hepatitis

If connective tissue frame When there is

Toxic or ischaemic
necrotic liver cell invites
inflammatory changes
irreversible injury
work is intact after injury fibrosis occurs in
then regenration is perfect. damaged cell
Otherwise some With fibrosis liver is
disorganization divided in irregular
of histology after nodule of proliferating
regeneration liver cell  is called
cirrhosis

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 Hepatic failure
Liver failure is the inability of the liver to perform its normal synthetic and
metabolic function as part of normal physiology.

Two forms are recognized

Acute liver failure is the appearance of severe complications rapidly after the
first signs of liver disease (such as Jaundice), and indicates that the liver
has sustained severe damage (loss of function of 80-90% of liver cells).

Chronic liver failure usually occurs in the context of cirrhosis, Cirrhosis is the
result of many possible causes, such as excessive alcohol intake, hepatitis
B or C, autoimmune, hereditary and metabolic causes (such as iron or
copper overload or non alcoholic fatty liver ).

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 Hepatic failure
Causes of acute liver failure Major manifestation of Acute or chronic liver
1- Acute viral hepatitis failure
2-Drug reaction:- 1-Jaundice
Acetaminophen
Anaesthetic agents, 2-Hepatic encephalopathy
halothane
AntiTB drugs- rifampin 3-Hepatorenal syndrome
isoniazide
Antidepressants 4-Hepatopulmonary syndrome
( monoamine oxidase),
5-Hyperkinetic circulation
Nonsteroidal anti-inflammatory.
3- Carbon tetrachloride poisoning 6-Coagulation defects
4- Acute alcoholic hepatitis,
5-Mushroom poisoning, 7-Ascities & oedema
6-Eclampsia of pregnancy
8-Endocrine changes
Causes of Chronic liver failure
1-Cirrhosis of liver 9-Skin changes
2-Chronic active hepatitis
3-chronic cholestasis 10- Foetor Hepaticus

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1- Jaundice: due to damage the liver cells can not metabolize bilirubin so jaundice
occurs. In acute hepatitis the damage is usually more severe so jaundice is deep but
in cirrhosis ( chronic ) the jaundice is mild.

2- Hepatic encephalopathy:-there is CNS manifestation in severe liver damage due

to disturbances of liver function. The toxic product ammonia & nitrogenous
product can not be metabolised by damaged liver which reach to CNS to produce
disturbances in personality, consciousness, intelligences , speech ultimately leads to
coma and death.

3- Hyperkinetic circulation: There is peripheral vasodilatation, increased cardiac

output. Splanchnic blood flow is increased but renal blood flow is decreased
leading to Renal hypofunction.

4- Hepatorenal Syndrome:-develops in 10% of cases of acute or chronic liver failure.

There is renal failure due to acute or chronic liver failure without any cause of renal
diseases. There is oliguria , uraemia with normal tubular function. This is functional
disorder because kidney histology is normal. There is defect in renal perfusion due
to pulling of blood in portal circulation.
Diagnosis of this condition is made by exclusion of other causes that produces renal
damage.

5- Hepatopulmonary syndrome: there is pulmonary vasodilatation with intra

pulmonary arterivenous shunting. Perfusion to ventilation proportion is disturbed
that leads to impaired pulmonary function. Clubbing of finger & cyanosis.
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6- Coagulation defect :-includes DIC, thrombocytopenia, & increased fibrin
degradation product due to reduced synthesis of coagulation factor by
liver.

7-Ascities & oedema:- in cirrhosis protein synthesis is reduced by liver 

hypoalbuminaemia  plasma osmotic pressure is reduced & hydrostatic
pressure is increased due to portal hypertension  oedema & ascities

8- In alcoholic cirrhosis: Gynaecomastia & hypogonadism in male due to

reduced sensitivity to androgen. In female atrophy of breast & gonads.

9-In alcoholic cirrhosis:-arterial spiders in neck, face, dorsum of hand &

forearm due to development of collaterals.

Foetor hepaticus : in acute & chronic liver failure there is sweetish smell
in breath due to inability of liver to detoxify sulfur containing substances
absorbed from intestine .

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 Liver cell necrosis
Necrosis of liver cell occurs due various injuries by
1- Trauma, 2- Toxin, 3- Microorganism, 4- Circulatory changes.

Three types of necrotic injuries

 Diffuse Necrosis: all the cells in a group of lobule of liver are affected.
Ex: Viral hepatitis & Drug toxicity
 Zonal Necrosis : Three zones are described.
* Centrilobular ( Zone 3 )
** Located around central vein.
** Commonest
** Ischaemic injury in shock & CHF
** Drug , Chloroform , carbon tetrachloride Poisoning
* Midzonal: ( Zone 2 )
** Uncommon
** Yellow fever
** Viral Hepatitis ( some necrotic cells become acidophilic rounded-
* Periportal ( Zone 1 ) - Councilman Body
** Close to portal tract
** Phosphorus poisoning
** Eclampsia
 Focal Necrosis: Small groups of liver cells irregularly distributed in
lobule are damaged.---Microbiological injury
** Miliary TB , Viral Hepatitis, Typhoid fever, & other organism
** Some drugs induced injury.
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 Circulatory disturbances of liver
1- Chronic Venous Congestion (in Right Heart failure)
( passive congestion & centrilobular necrosis )

2- Hepatic venous obstruction:-

a) - Budd- Chiari Syndrome
b) - Hepatic veno -occlusive Disease;

3- Portal venous Obstruction :- a) -Intrahepatic

* Cirrhosis
* Tumour invasion
* Congenital hepatic fibrosis
* Schistosomiasis
b) -Extra hepatic :-
Portal vein obstruction
* Intra abdominal Cancers
* Intra-abdominal sepsis
* Myeloproliferative Disorder
* Thrombosis after surgery
Peliosis Hepatis
4- Hepatic arterial obstruction :- rarely accidental ligation of hepatic artery.

5- Liver infarction :- also rare as liver has dual blood supply from portal vein &
hepatic artery.
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 Chronic Venous Congestion of liver - CVC

( passive congestion & centrilobular necrosis )

Right sided Cardiac decompensation passive congestion in liver
Gross: liver is slightly enlarged , tense, cyanotic and have rounded edge.
M/S: Congestion of centrilobular sinusoids
Centrilobular hepatocytic atrophy after some time

Left sided hear failure or Shock hepatic hypo perfusion & hypoxia
centrilobular hepatocytes undergo ischaemic coagulative necrosis
( centrilobular necrosis due to hypoperfusion + retrograde congestion )

Gross: Centrilobular hemorrhagic necrosis

Variegate mottled appearance ( called Nutmeg Liver )

M/S: There is well marked difference between necrotic pericentral and periportal
hepatocytes

Lab/F: mild to moderate transient elevation of serum transaminases.

Cardiac sclerosis : Uncommon complication of long term CCF c/z by distinct

pattern of liver fibrosis
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 • Microscopically, the nutmeg pattern results from congestion around the
central veins, as seen here. This is usually due to a "right sided" heart failure.

If the passive congestion is pronounced, then there can

be centrilobular necrosis, because the oxygenation in
zone 3 of the hepatic lobule is not great. The light brown
pigment seen here in the necrotic hepatocytes around
the central vein is lipochrome.

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CIRRHOSIS OF LIVER
Cirrhosis is a condition in which the liver
slowly deteriorates and malfunctions due to
chronic injury. scar tissue replaces healthy
liver tissue, partially blocking the flow of
blood through the liver.
Cirrhosis disturb the functions of liver like
Control infections ,remove bacteria and toxins
from the blood, process nutrients, hormones,
and drugs ,regulation of blood clotting , bile
production to help absorb fats, including
cholesterol—and fat-soluble vitamins

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Main causes of Cirrhosis
Main causes
Alcoholic liver disease 60-70 %
Viral hepatitis 10 %
Biliary diseases 5-10 %
Primary Hemochromatosis 5%
ά-1 antitrypsin deficiency - rare
Cryptogenic cirrhosis 10-15 %
• Morphological classification
of cirrhosis
Micronodular
Macronodular
Mixed
Etiological classification
Alcoholic Cirrhosis
Post necrotic cirrhosis
Biliary cirrhosis
Cardiac Cirrhosis
Indian childhood cirrhosis
Nonalcoholic
Steatohepatitis cirrhosis
Cryptogenic Cirrhosis

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 Alcoholic liver disease
Excessive alcohol consumption
leads to alcoholic liver disease. Mallory hyaline
Three components of it are
1. Fatty liver.
2. Alcoholic hepatitis and
3. Cirrhosis.

Alcoholic hepatitis is c/z by

Balooning necrosis,
Mallory hyaline(intracellular CK)
Neutrophils and fibrosis.
Grossly mottled yellowish red
nodules show progression to
cirrhosis
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Fatty liver
• Accumulation of fat in
hepatocytes leads to fatty
liver
• Liver is grossly enlarged ,
palpable with blunt edge
and non tender , slices
float in water
• Microscopy shows
presence of fat in
cytoplasm
• It is reversible until
fibrosis sets in.

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 Cirrhosis of liver

Grossly mottled
yellowish red
nodules show
progression to
cirrhosis
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 Acute Viral hepatitis.
• HBV Identified in 1965-
identified an antigen called Acute hepatitis (Microscopic )
Australia antigen-np1977
• It is a global problem.
• 300 million carrier
• Biopsy shows ground glass
cytoplasm , ballooning
degeneration , cholestasis ,
bile plugs , dropout with
macrophages , loss of radial
array , kupffer cell
hyperplasia, lymphocytosis
and bridging necrosis.
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 Chronic hepatitis
• Necrosis lobular in
distribution , portal tract
inflammation
• Piecemeal or interphase
necrosis ,
• bridging necrosis,
• bridging fibrosis
• regenerative
nodules\leading to
postnecrotic cirrhosis

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 Outcome of HVB infection
• Acute infection …..subclinical infection (60-65%)
• …………….acute inf (20-25%)
• …………… carrier (5-10%)
• …………….chronicity (4%)
• 10% of the above chronic infection suffer …chronic hepatitis
…
• 20-50% of these patients end up in cirrhosis
• (10% of them end up in hepatocellular carcinoma)

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 Primary carcinoma liver

• Can be hepatocellular 90 % / cholangiocarcinoma 10%

• Most common visceral cancer
• In developing countries vertical transmission of infection
from mother to baby leading to carrier state and cancer
occurs around 40 yr
• In developed countries after 60yrs because of cirrhosis
due to HCV or alcohol or hemochromatosis

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 Pathogenesis.

• HBV virion integrates and as

regeneration occurs mutations
take place.
• protein X is produced
• It has insulin GF-property and
binds to p-53 resulting in its
growth suppressor activity.
• Aflotoxins in some food
integrate with liver cell DNA
and mutating p-53, (in
subsaharan Africa and china
genetically people may lack
enzymes for detoxifying
aflotoxins )
• Cirrhosis due to HCV or
alcohol
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• Gross. :- it can start as
unifocal nodule , multifocl Primary Carcinoma Liver Gross
nodule or diffusely
infilrative type.
• All cause liver enlargement
• Nodule may look pale or
greenish
• Invasion of tumour to portal
vein / IVF seen
• Microscopy.:-
Pattern varies from well
differentiated to highly
anaplastic

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 Morphology continue
• Trabecular , acinar , pseudo • Primary Carcinoma of liver
glandular patterns can occur.
Microscopic
• Poorly differentiated ones can
have small cell , spindle cell or
giant cell varieties
• Fibrolamellar carcinoma is a
special variant characterized
by single hard/ scirrhous
nodule.
• Cells are oncocytic and dense
lamellae of fibrosis is seen.
• Cells can be small or large,
inreased N/C ratio , nucleoli
and intranuclear inclusions

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 SECONDARY TUMOURS
• Metastasis to liver from other organs is more common
than primary
• Most from breast ,lung ,colon and stomach ca
• Metastasis from cancer anywhere in the body can be
found in liver.
• Liver is enlarged , nodular with umbilication
• They can be asymptomatic.

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SECONDARY TUMOURS

Metastasis to liver from

other organs is more
common than primary
Most from breast , lung ,
colon and stomach ca
Metastasis from cancer
anywhere in the body
can be found in liver.
Liver is enlarged ,
nodular with
umbilication
They can be
asymptomatic.
Cells metastatic to liver from
Breast Carcinoma 35
 Acute Cholecystitis
• Inflammation of the gall
bladder can be bacterial or
nonbacterial ,most are due to
calculi.
• Acute.(90%) by stone, causing
obstruction
• Can occur without stone-
trauma , burns , post op and
multiorgan failure , sepsis etc
• Intra luminal pressure and
action of enzymes digesting
the mucosa are two important
mechanisms.
GB is Swollen and tense with bile
Red or greenish black
Serosa covered with fibrin
Stone in the neck
Gangrenous if necrosis and
haemorrhagic
Empyema if pus ,
emphysematous if filled with
gas
Non specific inflammatory
changes like edema ,
congestion and inflammatory
cells present
Salmonella can cause
ac.cholecystitis
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 Chronic cholecystitis

• Thickening of the wall –subserosal

• Adhesions
• Lumen contains bile and stones
• Fibrosis , lymphocytes and Rokitansky Aschoff sinuses
• Dystrophic calcification-porcelain gall bladder ,
xanthogranulomatous cholecystitis .
• if contains clear fluid it is hydrops

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 Liver abscesses
Most liver abscess Hydatid cyst

** Bacteria ( most
often)
Other less common are
** Amoeba
** Hydatid cyst
** Actinomycotic (rare )

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 Hepatic Tuberculosis:

Occurs as a result of miliary

tuberculosis.
Liver biopsy shows typical
epithelioid granuloma with
Langhen's type of giant
cells and caseation
necrosis and AFB.

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