7.cirrhosis (pathology)

1. CIRRHOSIS OF LIVERCIRRHOSIS OF LIVER
 Cirrhosis is defined as diffuse process characterized by fibrosis andCirrhosis is defined as diffuse process characterized by fibrosis and
the conversion of normal liver architecture into structurally abnormalthe conversion of normal liver architecture into structurally abnormal
nodules.nodules.
 There is persistent & progressive necrosis of HepatocytesThere is persistent & progressive necrosis of Hepatocytes
 It is the end stage condition of liverIt is the end stage condition of liver
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2. Characteristics are:Characteristics are:
 BridgingBridging FibrousFibrous septa in the form of delicate bands from Portal tosepta in the form of delicate bands from Portal to
central, portal to portal & central to central or broad scarscentral, portal to portal & central to central or broad scars
 ParenchymalParenchymal NodulesNodules, are formed by regeneration of hepatocytes., are formed by regeneration of hepatocytes.
 Disruption of theDisruption of the architecturearchitecture of the entire liver.of the entire liver.
The parenchymal cell injury and fibrosis are diffuse, extendingThe parenchymal cell injury and fibrosis are diffuse, extending
throughout the liver.throughout the liver.
Necrosis of hepatocytesNecrosis of hepatocytes
IrreversibleIrreversible
Progressive disorderProgressive disorder
Entire Liver is involvedEntire Liver is involved
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3. Cirrhosis can be classifiedCirrhosis can be classified histologicallyhistologically into three types.into three types.
Micro nodular cirrhosisMicro nodular cirrhosis
 Is characterized by small nodules about 1 mm in diameter and isIs characterized by small nodules about 1 mm in diameter and is
seen in alcoholic cirrhosis.seen in alcoholic cirrhosis.
Macro nodular cirrhosisMacro nodular cirrhosis
 Is characterized by larger nodules of > 3mm in diameter .Is characterized by larger nodules of > 3mm in diameter .
( Viral Hepatitis)( Viral Hepatitis)
Mixed typesMixed types
 (Alcoholic cirrhosis with time)(Alcoholic cirrhosis with time)
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4. Aetiologicl ClassificationAetiologicl Classification
 Alcoholic Cirrhosis (60-70%)Alcoholic Cirrhosis (60-70%)
 Chronic viral hepatitis (10%)Chronic viral hepatitis (10%)
 Biliary Cirrhosis (5-10%)Biliary Cirrhosis (5-10%)
 Cryptogenic (unknown) (10-15%)Cryptogenic (unknown) (10-15%)
 Haemochromatosis (5%)Haemochromatosis (5%)
 αα1-antitrypsin deficiency1-antitrypsin deficiency
 Wilson's diseaseWilson's disease
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5. Alcoholic Liver DiseaseAlcoholic Liver Disease
ALD comprises of 3 distinct forms of Liver diseasesALD comprises of 3 distinct forms of Liver diseases
 Hepatic steatosis/ fatty LiverHepatic steatosis/ fatty Liver
 Alcoholic hepatitisAlcoholic hepatitis
 CirrhosisCirrhosis
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6. HaemochromatosisHaemochromatosis
 Is defined as the excessive accumulation of body iron, most ofIs defined as the excessive accumulation of body iron, most of
which deposited in the parenchymal cell of various organ particularlywhich deposited in the parenchymal cell of various organ particularly
liver & pancreasliver & pancreas
TypesTypes
 Hereditary/primary/idiopathicHereditary/primary/idiopathic
 Secondary – occuring as a secondary complications to a variety ofSecondary – occuring as a secondary complications to a variety of
diseasesdiseases
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7. Wilson’s DiseaseWilson’s Disease
 Is an autosomal recessive disorder of copper metabolism & isIs an autosomal recessive disorder of copper metabolism & is
marked by accumulation of toxic levels of copper in many tissues inmarked by accumulation of toxic levels of copper in many tissues in
many tissues & organs principally the liver, brain & eyemany tissues & organs principally the liver, brain & eye
 Primary biPrimary bi
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8. Biliary cirrhosisBiliary cirrhosis
Primary intrahepatic biliary cirrhosisPrimary intrahepatic biliary cirrhosis
 An autoimmune disease marked by the slow progressive destructionAn autoimmune disease marked by the slow progressive destruction
of the small intrahepatic bile ducts.of the small intrahepatic bile ducts.
 Bile builds up in the liver and over time damages the tissue.Bile builds up in the liver and over time damages the tissue.
 This can lead to scarring, fibrosis and cirrhosisThis can lead to scarring, fibrosis and cirrhosis
Secondary biliary cirrhosisSecondary biliary cirrhosis
 Results from obstruction to the major extra hepatic ductResults from obstruction to the major extra hepatic duct
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9. Alpha1 antitrypsin deficiencyAlpha1 antitrypsin deficiency
Is an autosomal recessicve disorder marked by abnormally low levels ofIs an autosomal recessicve disorder marked by abnormally low levels of
ofof αα1-antitrypsin in serum1-antitrypsin in serum
Predominantly synthesized in Hepatocytes & to less extent inPredominantly synthesized in Hepatocytes & to less extent in
macrophagemacrophage
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10. The major mechanisms that combine to create cirrhosis areThe major mechanisms that combine to create cirrhosis are
 Hepatocellular death,Hepatocellular death,
 Regeneration ,Regeneration ,
 Progressive fibrosis and vascular changes.Progressive fibrosis and vascular changes.
 The development of cirrhosis requires that cell death occur over longThe development of cirrhosis requires that cell death occur over long
periods of time and be accompanied by fibrosis.periods of time and be accompanied by fibrosis.
 Regeneration is a normal compensatory response to cell death.Regeneration is a normal compensatory response to cell death.
 Fibrosis is a wound-healing reaction that progresses to scarFibrosis is a wound-healing reaction that progresses to scar
formation when the injury involves not only the parenchyma but alsoformation when the injury involves not only the parenchyma but also
the supporting connective tissue.the supporting connective tissue.
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11.  In the normal liver, interstitial collagens (types I and III) areIn the normal liver, interstitial collagens (types I and III) are
concentrated in portal tracts and around central veins, withconcentrated in portal tracts and around central veins, with
occasional bundles in the space of Disse.occasional bundles in the space of Disse.
 The collagen (reticulin) coursing alongside hepatocytes isThe collagen (reticulin) coursing alongside hepatocytes is
composed of delicate strands of type IV collagen in the space ofcomposed of delicate strands of type IV collagen in the space of
Disse.Disse.
 Ito cells (Lipocytes) & hepatocytes synthesize collagenIto cells (Lipocytes) & hepatocytes synthesize collagen
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12. PathogenesisPathogenesis
The central pathogenetic process in cirrhosis is progressive fibrosis dueThe central pathogenetic process in cirrhosis is progressive fibrosis due
to excess of collagen production & its depositionto excess of collagen production & its deposition
 In cirrhosis, types I and III collagen are deposited all over the lobule,In cirrhosis, types I and III collagen are deposited all over the lobule,
creating delicate or broad septal tracts.creating delicate or broad septal tracts.
 Continued deposition of collagen in the space of Disse isContinued deposition of collagen in the space of Disse is
accompanied by the loss of fenestrations in the sinusoidal endothelialaccompanied by the loss of fenestrations in the sinusoidal endothelial
cells.cells.
 In the process -exchange of solutes between hepatocytes and plasmaIn the process -exchange of solutes between hepatocytes and plasma
is disturbedis disturbed
 In particular, hepatocellular secretion of proteins (e.g., albumin,In particular, hepatocellular secretion of proteins (e.g., albumin,
clotting factors) is greatly impaired.clotting factors) is greatly impaired.
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13. -Ito cells (perisinusoidal stellate cells) become activated during the-Ito cells (perisinusoidal stellate cells) become activated during the
development of cirrhosis, and transform into myofibroblast-like cells.development of cirrhosis, and transform into myofibroblast-like cells.
-And are stimulated to produce collagen & may be due to :-And are stimulated to produce collagen & may be due to :
 Chronic inflammation, with production of inflammatory cytokines suchChronic inflammation, with production of inflammatory cytokines such
as tumor necrosis factor (TNF)-alpha, transforming growth factoras tumor necrosis factor (TNF)-alpha, transforming growth factor
(TGF)- beta, and interleukin-1 by endogenous cells (Kupffer cells,(TGF)- beta, and interleukin-1 by endogenous cells (Kupffer cells,
endothelial cells, hepatocytes, and bile duct epithelial cells)endothelial cells, hepatocytes, and bile duct epithelial cells)
 Direct stimulation by Toxins or their metabolitesDirect stimulation by Toxins or their metabolites
 Distortion of extracellular matrixDistortion of extracellular matrix
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14. 1414

15.  Contraction of these "myofibroblasts“ (Ito Cells) constricts theContraction of these "myofibroblasts“ (Ito Cells) constricts the
sinusoidal vascular channels.sinusoidal vascular channels.
 Remaining hepatocytes are stimulated to regenerate, and theyRemaining hepatocytes are stimulated to regenerate, and they
proliferate as spherical nodules within the confines of the fibrousproliferate as spherical nodules within the confines of the fibrous
septa.septa.
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16. The net outcome isThe net outcome is
 A fibrotic, nodular liver in which delivery of blood to hepatocytes isA fibrotic, nodular liver in which delivery of blood to hepatocytes is
severely compromised, as is the ability of hepatocytes to secreteseverely compromised, as is the ability of hepatocytes to secrete
substances into plasma.substances into plasma.
 Disruption of the interface between the parenchyma and portalDisruption of the interface between the parenchyma and portal
tracts obliterates biliary channels as well.tracts obliterates biliary channels as well.
Thus, the cirrhotic patient may develop jaundice and even hepaticThus, the cirrhotic patient may develop jaundice and even hepatic
failure, despite having a liver of normal mass.failure, despite having a liver of normal mass.
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17. Pathogenesis(ALT)Pathogenesis(ALT) Injurious AgentInjurious Agent
Liver cell necrosisLiver cell necrosis
Chronic inflammationChronic inflammation
Fibrosis Reactive hyperplasia of hepatocytes /Nodular re-growthFibrosis Reactive hyperplasia of hepatocytes /Nodular re-growth
Vascular damage and derangementVascular damage and derangement
Increased supply to other partsIncreased supply to other parts Diminished supply to some partsDiminished supply to some parts
 Disruption of lobular circulationDisruption of lobular circulation Obstruction of portal circulationObstruction of portal circulation
 Interference with hepatic functionInterference with hepatic function portal HTNportal HTN
..
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18. 1818
•Very low power microscopic view of the liver.
•The parenchyma shows darker tan nodules of varying sizes.
•These nodules are composed of hepatocytes.
•The paler areas in between are collagen.

19.  Nodular , firm liver. The nodules seen here are larger than 3 mm and,Nodular , firm liver. The nodules seen here are larger than 3 mm and,
hence, this is an example of "macronodular" cirrhosis.hence, this is an example of "macronodular" cirrhosis.
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20.  micronodular cirrhosis. The regenerative nodules are quite small, averagingmicronodular cirrhosis. The regenerative nodules are quite small, averaging
less than 3 mm in size. The most common cause for this is chronic alcoholism.less than 3 mm in size. The most common cause for this is chronic alcoholism.
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21.  Here is another example of micronodular cirrhosis. Note that theHere is another example of micronodular cirrhosis. Note that the
liver also has a yellowish hue, indicating that fatty change (alsoliver also has a yellowish hue, indicating that fatty change (also
caused by alcoholism) is present.
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22.  A close-up view of a micronodular cirrhosis in a liver with fatty changeA close-up view of a micronodular cirrhosis in a liver with fatty change
demonstrates the small, yellow nodules.demonstrates the small, yellow nodules. 2222

23.  macronodular cirrhosis. Viral hepatitis (B or C) is the most common cause formacronodular cirrhosis. Viral hepatitis (B or C) is the most common cause for
macronodular cirrhosis. Wilson's disease and alpha-1-antitrypsin deficiency alsomacronodular cirrhosis. Wilson's disease and alpha-1-antitrypsin deficiency also
can produce a macronodular cirrhosis.can produce a macronodular cirrhosis.
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24.  Microscopically with cirrhosis, the regenerative nodules of hepatocytesMicroscopically with cirrhosis, the regenerative nodules of hepatocytes
are surrounded by fibrous connective tissue that bridges between portalare surrounded by fibrous connective tissue that bridges between portal
tracts. Within this collagenous tissue are scattered lymphocytestracts. Within this collagenous tissue are scattered lymphocytes
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25. CLINICAL FEATURES OF HEPATIC CIRRHOSISCLINICAL FEATURES OF HEPATIC CIRRHOSIS
 Hepatomegaly (although liver may also be small)Hepatomegaly (although liver may also be small)
 JaundiceJaundice
 AscitesAscites
 Circulatory changes - Spider telangiectasia, palmar erythema, cyanosisCirculatory changes - Spider telangiectasia, palmar erythema, cyanosis
 Endocrine changes - Loss of libido, hair loss,Endocrine changes - Loss of libido, hair loss,
Men: gynaecomastia, testicular atrophy, impotenceMen: gynaecomastia, testicular atrophy, impotence
Women: breast atrophy, irregular menses, amenorrhoeaWomen: breast atrophy, irregular menses, amenorrhoea
 Haemorrhagic tendency- Bruises, purpura, epistaxis, menorrhagiaHaemorrhagic tendency- Bruises, purpura, epistaxis, menorrhagia
 Portal hypertension - Splenomegaly, collateral vessels, varicealPortal hypertension - Splenomegaly, collateral vessels, variceal
bleeding, fetor hepaticusbleeding, fetor hepaticus
 Hepatic (portosystemic) encephalopathyHepatic (portosystemic) encephalopathy
 Other features - Pigmentation, digital clubbingOther features - Pigmentation, digital clubbing
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26. Complications of Hepatic CirrhosisComplications of Hepatic Cirrhosis
 Portal hypertensionPortal hypertension
 AscitisAscitis
 Renal failureRenal failure
 Hepatic encephalopathyHepatic encephalopathy
 InfectionsInfections
 Hepatocellular carcinomaHepatocellular carcinoma
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27. PORTAL HYPERTENSION / PHTPORTAL HYPERTENSION / PHT
 PHT is characterized by prolonged elevation of the portal venousPHT is characterized by prolonged elevation of the portal venous
pressure (normally 2-5 mmHg).pressure (normally 2-5 mmHg).
 Pts developing C/F or Complications of PTH usually have portalPts developing C/F or Complications of PTH usually have portal
venous pressures (PVP) above 12 mmHg.venous pressures (PVP) above 12 mmHg.
PathogenesisPathogenesis
 PVP is determined by the portal flow and portal vascular resistance.PVP is determined by the portal flow and portal vascular resistance.
 Increased vascular resistance is usually the main factor producingIncreased vascular resistance is usually the main factor producing
portal hypertension, irrespective of its causeportal hypertension, irrespective of its cause
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28. CAUSES OF PORTAL HYPERTENSIONCAUSES OF PORTAL HYPERTENSION
IntrahepaticIntrahepatic
 Cirrhosis – most commonCirrhosis – most common
 Massive fatty changes, miliary TB, SchistosomiasisMassive fatty changes, miliary TB, Schistosomiasis
PosthepaticPosthepatic
 Right sided heart failure (Common)Right sided heart failure (Common)
 Obstructon of hepatic vein - Budd-Chiari syndrome (Hepatic veinObstructon of hepatic vein - Budd-Chiari syndrome (Hepatic vein
thrombosis)thrombosis)
PrehepaticPrehepatic
 Portal vein thrombosisPortal vein thrombosis
 Massive splenomegalyMassive splenomegaly
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29. 2929

30. PathophysiologyPathophysiology
 PHT leads to reduction in the flow of blood to the liver andPHT leads to reduction in the flow of blood to the liver and
simultaneously to the collateral vessels,simultaneously to the collateral vessels,
 Allowing portal blood to bypass the liver and enter the systemicAllowing portal blood to bypass the liver and enter the systemic
circulation directly.circulation directly.
 Collateral vessel formation is widespread but occurs especially theCollateral vessel formation is widespread but occurs especially the
oesophagus, stomach, rectum and in the anterior abdominal walloesophagus, stomach, rectum and in the anterior abdominal wall
 Half or more (and occasionally almost all) of the portal blood flowHalf or more (and occasionally almost all) of the portal blood flow
can be shunted directly to the systemic circulation.can be shunted directly to the systemic circulation.
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31. Clinical featuresClinical features
Result principally from portal venous congestion and collateral vesselResult principally from portal venous congestion and collateral vessel
formation.formation.
 Splenomegaly is a cardinalSplenomegaly is a cardinal
 Collateral vessels may be visible on the anterior abdominal wall andCollateral vessels may be visible on the anterior abdominal wall and
occasionally several radiate from the umbilicus to form a caputoccasionally several radiate from the umbilicus to form a caput
medusae.medusae.
 The most important collateral vessels occur in the oesophagus andThe most important collateral vessels occur in the oesophagus and
stomach, where they can cause severe bleeding.stomach, where they can cause severe bleeding.
 Rectal varices also cause bleedingRectal varices also cause bleeding
 Fetor hepaticus results from portosystemic shunting of blood, whichFetor hepaticus results from portosystemic shunting of blood, which
allows mercaptans to pass directly to the lungsallows mercaptans to pass directly to the lungs
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32. Clinical effects OF PORTAL HYPERTENSIONClinical effects OF PORTAL HYPERTENSION
4 major clinical effects are4 major clinical effects are
 AscitesAscites
 Portosystemic venous shuntPortosystemic venous shunt
Caput medussa, Oesophagastric Varices bleeding, rectalCaput medussa, Oesophagastric Varices bleeding, rectal
hemorroids etchemorroids etc
 Congestive splenomegalyCongestive splenomegaly
 Hepatic encephalopathyHepatic encephalopathy
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33. 3333

34. 3434
AscitisAscitis
 Abnormal accumulation of fluid in the peritoneal cavityAbnormal accumulation of fluid in the peritoneal cavity
CausesCauses
Common causesCommon causes
 Cirrhosis of liverCirrhosis of liver
 Cardiac failureCardiac failure
 Malignant disease – hepatic, peritonealMalignant disease – hepatic, peritoneal
OthersOthers
 Hypoproteinaemia - Nephrotic syndrome, Protein losing enteropathy,Hypoproteinaemia - Nephrotic syndrome, Protein losing enteropathy,
MalnutritionMalnutrition
 Hepatic venous occlusionHepatic venous occlusion
 Infection – T.B., BacterialInfection – T.B., Bacterial
 Lymphatic obstructionLymphatic obstruction

35.  In Cirrhosis of liver, Ascites is due to In Cirrhosis of liver, Ascites is due to
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36. Hepatic Failure / Hepatocellular FailureHepatic Failure / Hepatocellular Failure
 Is a state that occurs due to loss of 80 to 90% hepatic functionsIs a state that occurs due to loss of 80 to 90% hepatic functions
Failure can beFailure can be
 Acute – with rapid onset e.g. in cases of massive necrosis due toAcute – with rapid onset e.g. in cases of massive necrosis due to
poisoning, less commonly acute hepatitispoisoning, less commonly acute hepatitis
 Chronic & sometimes recurring of slow onset e.g. in cirrhosis orChronic & sometimes recurring of slow onset e.g. in cirrhosis or
chronic hepatitischronic hepatitis
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37. HEPATIC (PORTOSYSTEMIC) ENCEPHALOPATHYHEPATIC (PORTOSYSTEMIC) ENCEPHALOPATHY
 Hepatic encephalopathy is a neuropsychiatric syndrome caused byHepatic encephalopathy is a neuropsychiatric syndrome caused by
liver disease.liver disease.
 As encephalopathy progresses, confusion is followed by coma.As encephalopathy progresses, confusion is followed by coma.
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38. Aetiopathosenesis (acute & chronic )Aetiopathosenesis (acute & chronic )
 The basic cause is same in both forms but the mechanism isThe basic cause is same in both forms but the mechanism is
somewhat differentsomewhat different

Diminished detoxification of toxic intestinal nitrogenous compoundsDiminished detoxification of toxic intestinal nitrogenous compounds
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Increased in blood
NH3 etc
Toxic effect on
brain
Appearance of
abnormal amines in
systemic circulation
Interference with
neurotransmission

39. CLINICAL GRADING OF HEPATIC ENCEPHALOPATHYCLINICAL GRADING OF HEPATIC ENCEPHALOPATHY
Clinical grade Clinical signsClinical grade Clinical signs
Grade 1 Poor concentration, slurred speech, slowGrade 1 Poor concentration, slurred speech, slow
mentation,mentation,
disordered sleep rhythmdisordered sleep rhythm
Grade 2 Drowsy but easily rousable, occasional aggressiveGrade 2 Drowsy but easily rousable, occasional aggressive
behaviour, lethargicbehaviour, lethargic
Grade 3 Marked confusion, drowsy, sleepy but responds toGrade 3 Marked confusion, drowsy, sleepy but responds to
pain andpain and
voice, gross disorientationvoice, gross disorientation
Grade 4 Unresponsive to voice, may or may not respond toGrade 4 Unresponsive to voice, may or may not respond to
painfulpainful
stimuli, unconsciousstimuli, unconscious
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40. Hepatorenal syndromeHepatorenal syndrome
 Refers to the appearance of renal failure in a person with severeRefers to the appearance of renal failure in a person with severe
liver disease without primary abnormalities of the kidneysliver disease without primary abnormalities of the kidneys
themselves.themselves.
 Kidney function promptly improves if hepatic failure is reversed.Kidney function promptly improves if hepatic failure is reversed.
 Although the exact cause is unknown, evidence points to splanchnicAlthough the exact cause is unknown, evidence points to splanchnic
and systemic vasodilation, leading to severe reduction of renaland systemic vasodilation, leading to severe reduction of renal
blood flow.blood flow.
 Onset of this syndrome is typically heralded by a drop in urineOnset of this syndrome is typically heralded by a drop in urine
output, associated with rising blood urea nitrogen and creatinineoutput, associated with rising blood urea nitrogen and creatinine
values.values.
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