Diseases of liver

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Diseases of Diseases of liver liver

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Diseases of liver. Discuss the components of the liver Discuss the diseases of liver Define hepatitis List causes of hepatitis Describe the morphological features of hepatitis Define liver fibrosis, liver cirrhosis. List causes of liver cirrhosis - PowerPoint PPT Presentation

Transcript of Diseases of liver

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Diseases of Diseases of liverliver

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By the end of the session the By the end of the session the student should be able to:student should be able to:

Discuss the Discuss the components of the components of the liverliver

Discuss the diseases of Discuss the diseases of liverliver

Define hepatitisDefine hepatitis List causes of hepatitisList causes of hepatitis Describe the Describe the

morphological features morphological features of hepatitisof hepatitis

Define liver fibrosis, Define liver fibrosis, liver cirrhosisliver cirrhosis

List causes of liver List causes of liver cirrhosiscirrhosis

Discuss clinical Discuss clinical features and features and complications of complications of cirrhosiscirrhosis

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The main patterns of The main patterns of morphologic liver injurymorphologic liver injury

1-Degeneration and intracellular 1-Degeneration and intracellular accumulation.accumulation.

2-Necrosis and apoptosis. 2-Necrosis and apoptosis. 3-Regeneration. 3-Regeneration. 4-Inflammation. 4-Inflammation. 5-Fibrosis. 5-Fibrosis. 6-Cirrhosis.6-Cirrhosis.

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The main patterns of morphologic The main patterns of morphologic liver injury (continue)liver injury (continue)2-Necrosis and apoptosis. 2-Necrosis and apoptosis. Cell death may be limited to scattered cells within Cell death may be limited to scattered cells within

the hepatic parenchyma or to the interface the hepatic parenchyma or to the interface between the periportal parenchyma and inflamed between the periportal parenchyma and inflamed portal tracts portal tracts (interface hepatitis)(interface hepatitis)..

With more severe inflammatory or toxic injury, With more severe inflammatory or toxic injury, apoptosis or necrosis of contiguous hepatocytes apoptosis or necrosis of contiguous hepatocytes may span adjacent lobules in a portal-to-portal, may span adjacent lobules in a portal-to-portal, portal-to-central, or central-to-central fashion portal-to-central, or central-to-central fashion (bridging necrosis).(bridging necrosis). Destruction of entire Destruction of entire lobules lobules (submassive necrosis)(submassive necrosis) or most of the liver or most of the liver parenchyma parenchyma (massive necrosis)(massive necrosis) is usually is usually accompanied by hepatic failure.accompanied by hepatic failure.

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The main patterns of morphologic The main patterns of morphologic liver injury (continue)liver injury (continue)3-Regeneration. 3-Regeneration. Cell death or tissue resection (such as in living-donor Cell death or tissue resection (such as in living-donor

transplantation) triggers hepatocyte replication, to transplantation) triggers hepatocyte replication, to compensate for the cell or tissue loss. Hepatocyte compensate for the cell or tissue loss. Hepatocyte proliferation is recognized by the presence of mitoses proliferation is recognized by the presence of mitoses or by the detection of cell cycle markers by or by the detection of cell cycle markers by immunocytochemical staining. immunocytochemical staining.

The cells of the canals of Hering constitute a reserve The cells of the canals of Hering constitute a reserve compartment of progenitor cells for hepatocytes and compartment of progenitor cells for hepatocytes and bile duct cells. Cells of this reserve compartment, bile duct cells. Cells of this reserve compartment, known as known as oval cells,oval cells, proliferate when hepatocytes are proliferate when hepatocytes are unable to replicate or have exhausted their replicative unable to replicate or have exhausted their replicative capacity.capacity.

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The main patterns of The main patterns of morphologic liver injurymorphologic liver injury

4-Inflammation. 4-Inflammation. Injury to hepatocytes associated with Injury to hepatocytes associated with

an influx of acute or chronic an influx of acute or chronic inflammatory cells into the liver is inflammatory cells into the liver is termed termed hepatitishepatitis..

It is classified into acute and chronicIt is classified into acute and chronic

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Causes of acute hepatitisCauses of acute hepatitis Viral hepatitisViral hepatitis

Hepatitis A, B, C, D, and E, Hepatitis A, B, C, D, and E, infectious mononucleosis (Epstein-Barr virus)infectious mononucleosis (Epstein-Barr virus) cytomegalovirus cytomegalovirus Yellow feverYellow fever

AlcoholAlcohol Toxins:  carbon tetrachlorideToxins:  carbon tetrachloride Drugs: Paracetamol,  amoxycillin, antituberculosis Drugs: Paracetamol,  amoxycillin, antituberculosis

medicines, minocycline medicines, minocycline  Ischemic hepatitis (circulatory insufficiency)Ischemic hepatitis (circulatory insufficiency) PregnancyPregnancy Auto immune conditions, e.g., systemic lupus erythematosus Auto immune conditions, e.g., systemic lupus erythematosus

(SLE)(SLE) Metabolic diseases, e.g., Wilson's diseaseMetabolic diseases, e.g., Wilson's disease

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Chronic Hepatitis Chronic Hepatitis Chronic Hepatitis is defined as Chronic Hepatitis is defined as

symptomatic, biochemical, or symptomatic, biochemical, or serologic evidence of continuing or serologic evidence of continuing or relapsing hepatic disease for more relapsing hepatic disease for more than 6 months, with histologically than 6 months, with histologically documented inflammation and documented inflammation and necrosis. necrosis.

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Causes of chronic Causes of chronic hepatitishepatitis

Viral hepatitis: Hepatitis B, hepatitis D, hepatitis Viral hepatitis: Hepatitis B, hepatitis D, hepatitis C (neither hepatitis A nor hepatitis Ecauses chronic hepatitis)C (neither hepatitis A nor hepatitis Ecauses chronic hepatitis)

AutoimmuneAutoimmune Autoimmune hepatitisAutoimmune hepatitis

AlcoholAlcohol DrugsDrugs

methyldopamethyldopa nitrofurantoinnitrofurantoin isoniazidisoniazid ketoconazoleketoconazole

Non-alcoholic steatohepatitisNon-alcoholic steatohepatitis HeredityHeredity

Wilson's diseaseWilson's disease alpha 1-antitrypsin deficiencyalpha 1-antitrypsin deficiency

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morphological features morphological features of Acute Hepatitis of Acute Hepatitis

Gross:Gross: Enlarged, reddened liver; greenish if cholestatic Enlarged, reddened liver; greenish if cholestatic MicroscopicMicroscopic     Hepatocyte injury: swelling (ballooning degeneration) Hepatocyte injury: swelling (ballooning degeneration)     HCV: mild fatty change of hepatocytes HCV: mild fatty change of hepatocytes     Hepatocyte necrosis: isolated cells or clusters     Hepatocyte necrosis: isolated cells or clusters      If severe: bridging necrosis (portal-portal, central-If severe: bridging necrosis (portal-portal, central-

central, portal-central) central, portal-central)   Regenerative changes: hepatocyte proliferation   Regenerative changes: hepatocyte proliferation    Portal tracts     Inflammation: predominantly Portal tracts     Inflammation: predominantly

mononuclear   Inflammatory spillover into adjacent mononuclear   Inflammatory spillover into adjacent parenchyma, with hepatocyte necrosisparenchyma, with hepatocyte necrosis

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morphological features morphological features of Chronic Hepatitisof Chronic Hepatitis

Changes shared with acute hepatitis: Changes shared with acute hepatitis: Hepatocyte injury, necrosis, apoptosis, and regeneration Hepatocyte injury, necrosis, apoptosis, and regeneration Portal tracts  Portal tracts      Inflammation:  Inflammation:         Confined to portal tracts, or   Confined to portal tracts, or         Spillover into adjacent parenchyma, with necrosis of Spillover into adjacent parenchyma, with necrosis of

hepatocytes ("interface hepatitis"),     hepatocytes ("interface hepatitis"),      Bridging inflammation and necrosis Bridging inflammation and necrosis     Fibrosis: Fibrosis:           Portal deposition, Portal deposition, oror            Portal and periportal deposition, Portal and periportal deposition, oror           Formation of bridging fibrous septa Formation of bridging fibrous septa HBV: ground-glass hepatocytes (accumulation of HBsAg) HBV: ground-glass hepatocytes (accumulation of HBsAg) HCV: bile duct epithelial cell proliferation, lymphoid aggregate HCV: bile duct epithelial cell proliferation, lymphoid aggregate

formationformation

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The main patterns of morphologic The main patterns of morphologic liver injury (continue)liver injury (continue)5-Fibrosis. 5-Fibrosis. Fibrous tissue is formed in response to inflammation or Fibrous tissue is formed in response to inflammation or

direct toxic insult to the liver. Deposition of collagen direct toxic insult to the liver. Deposition of collagen has lasting consequences on hepatic patterns of blood has lasting consequences on hepatic patterns of blood flow and perfusion of hepatocytes. flow and perfusion of hepatocytes.

In the initial stages, fibrosis may develop within or In the initial stages, fibrosis may develop within or around portal tracts around portal tracts (portal or periportal fibrosis)(portal or periportal fibrosis) or around the central vein, or fibrous tissue may be or around the central vein, or fibrous tissue may be deposited directly within the sinusoids around single deposited directly within the sinusoids around single or multiple hepatocytes or multiple hepatocytes (pericellular fibrosis).(pericellular fibrosis).

With time, fibrous strands link regions of the liver With time, fibrous strands link regions of the liver (portal-to-portal, portal-to-central, central-to-central), a (portal-to-portal, portal-to-central, central-to-central), a process called process called bridging fibrosis.bridging fibrosis.

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6-Cirrhosis. 6-Cirrhosis. With progressive With progressive parenchymal injury and fibrosis, the parenchymal injury and fibrosis, the liver develops nodules of liver develops nodules of regenerating hepatocytes regenerating hepatocytes surrounded by bands of scar tissue. surrounded by bands of scar tissue. In this process, the normal liver In this process, the normal liver architecture is destroyed, and the architecture is destroyed, and the condition is termed cirrhosis. condition is termed cirrhosis.

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LIVER CIRRHOSISLIVER CIRRHOSISDefinitionDefinition: : the end stage of chronic liver disease, the end stage of chronic liver disease, It It

is a chronic diffuse progressive and irreversible liver is a chronic diffuse progressive and irreversible liver disease characterized by: disease characterized by:

1) 1) Necrosis and degeneration of liver cells. Necrosis and degeneration of liver cells. 2)2) Bridging fibrous septa in the form of delicate bands or Bridging fibrous septa in the form of delicate bands or

broad scars linking portal tracts with one another and broad scars linking portal tracts with one another and portal tracts with terminal hepatic veins. Fibrosis is the portal tracts with terminal hepatic veins. Fibrosis is the key feature of progressive damage to the liver. key feature of progressive damage to the liver.

3)3) 3) 3) Regeneration of liver cells forming regenerating Regeneration of liver cells forming regenerating nodules lacking the normal lobular pattern. nodules lacking the normal lobular pattern.

Parenchymal nodules containing hepatocytes encircled Parenchymal nodules containing hepatocytes encircled by fibrosis, Nodularity results from cycles of hepatocyte by fibrosis, Nodularity results from cycles of hepatocyte regeneration and scarring.regeneration and scarring.

4) 4) Loss of the lobular architecture of the liver.Loss of the lobular architecture of the liver.5) 5) Interference with intrahepatic microcirculation.Interference with intrahepatic microcirculation.

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Classification of cirrhosisClassification of cirrhosis

I- AnatomicalI- Anatomical classificationclassification::

1) Micronodular cirrhosis:1) Micronodular cirrhosis: The liver surface is The liver surface is fine granular, the nodules are 1 or 3 mm in fine granular, the nodules are 1 or 3 mm in diameter and of uniform size and shape. diameter and of uniform size and shape.

2) Macronodular cirrhosis:2) Macronodular cirrhosis: The surface of the The surface of the liver is coarse granular and the nodules vary in liver is coarse granular and the nodules vary in size but usually more than 1 cm in diameter . size but usually more than 1 cm in diameter .

3) Mixed nodular cirrhosis:3) Mixed nodular cirrhosis: The outer and cut The outer and cut surfaces of the liver show marked variation in surfaces of the liver show marked variation in the diameter of the nodules.the diameter of the nodules.

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II- Aetiological classificationII- Aetiological classification::1- Post-hepatitic cirrhosis (HBV and HCV ) .1- Post-hepatitic cirrhosis (HBV and HCV ) .2- Post-necrotic cirrhosis: Secondary to hepatotoxic liver cell 2- Post-necrotic cirrhosis: Secondary to hepatotoxic liver cell

necrosis due to drugs, chemicals or viruses.necrosis due to drugs, chemicals or viruses.3- 3- Alcoholic cirrhosis.Alcoholic cirrhosis.4-4- Biliary cirrhosis (Due to intra and extra-hepatic biliary Biliary cirrhosis (Due to intra and extra-hepatic biliary

obstruction).obstruction).5- 5- Cardiac cirrhosis.Cardiac cirrhosis.6- 6- Immunological (lupoid hepatitis )Immunological (lupoid hepatitis )7- 7- Metabolic cirrhosis: Metabolic cirrhosis:

a- Haemochromatosis (Disturbances in iron metabolism). a- Haemochromatosis (Disturbances in iron metabolism). b- Wilson disease (Disturbances in copper metabolism). b- Wilson disease (Disturbances in copper metabolism). c- Alpha-1 antitrypsin deficiency. c- Alpha-1 antitrypsin deficiency. 8- Malnutrition.8- Malnutrition.9- Syphilitic cirrhosis. 9- Syphilitic cirrhosis. 10- Cryptogenic cirrhosis (unknown cause). 10- Cryptogenic cirrhosis (unknown cause).

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Clinical FeaturesClinical FeaturesAll forms of cirrhosis may be clinically All forms of cirrhosis may be clinically

silent. When symptomatic they lead to silent. When symptomatic they lead to nonspecific manifestations: anorexia, nonspecific manifestations: anorexia, weight loss, weakness, and, in advanced weight loss, weakness, and, in advanced disease, frank debilitationdisease, frank debilitation

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Effects and complications of Effects and complications of liver cirrhosis: liver cirrhosis:

I. Portal hypertension:I. Portal hypertension: It is elevation of the It is elevation of the portal blood pressureportal blood pressure

II. Hepatocellular failureII. Hepatocellular failure:: Occurs due to continuous and progressive loss of Occurs due to continuous and progressive loss of

liver cells and distortion of the hepatic liver cells and distortion of the hepatic circulation. circulation.

III. Liver cell carcinomaIII. Liver cell carcinoma: : The incidence of liver cell carcinoma in cirrhotic The incidence of liver cell carcinoma in cirrhotic

liver is more than that of non cirrhotic one. liver is more than that of non cirrhotic one. Carcinoma is more liable to complicate post-Carcinoma is more liable to complicate post-hepatitic cirrhosis, haemochromatosis and hepatitic cirrhosis, haemochromatosis and alcoholic cirrhosis.alcoholic cirrhosis.