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The The pathologypathology of the of the liver, liver, bile ducts bile ducts and and pancreaspancreas

Richard PalmqvistDocent, ST-läkare,Klin Pat Lab, Labcentrum

Vt-2006

The lecture in summaryThe lecture in summary• Introduction, histology & physiology in brief• General phenomenon• Specific diseases of the

liverbile ductspancreas

with focus on infectionsautoimmune diseasescongenital diseasestumours

HistologyHistology

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FunctionsFunctions of the liverof the liver

• Synthesis and secretion of bile• Storage of glycogen and fat• Involved in control of blood glucose levels,

aminoacids and fatty acids• Synthesis of cholesterol• Inactivation and metabolism of toxic molecules• Storage place for Fe, Cu, fat soluble vitamins etc• Synthesis of proteins• Phagocytosis of erythrocytes

IcterusIcterus

• Clinically: Yellow skin, yellow sclera etc

BilirubinBilirubinmetabolismmetabolism

• Unconjugatedhyperbilirubinemia

• Conjugatedhyperbilirubinemia

NOTE Important picture

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Liver Liver steatosissteatosis• Fatty upload in hepatocytes• Unspecific reaction• No symptoms• Reversible

Causes:• Toxic reaction, inadequate

nutriment, circulationdisturbance, etc

• Classical example: Alcohol

Liver Liver cirrhosiscirrhosis• Develops through prolonged destruction of liver cells followed by a chronic inflammation and increased formation of fibrosis

• Not reversible (not easily anyway!)

• Viable hepatocytes will proliferate (regeneration)

”Degeneration - Fibrosis - Regeneration”

Etiologi example:alcohol, virushepatitis, autoimmune diseases (ex PBC)

Liver Liver cirrhosiscirrhosis contcont´́dd

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Liver Liver cirrhosiscirrhosis contcont´́dd

Liver Liver cirrhosiscirrhosis gives system symptomsgives system symptoms

NOTE! Read portal hypertension by yourself!

Virus Virus hepatitishepatitis

• Hepatitis A (HAV)• Hepatitis B (HBV)• Hepatitis C (HCV)• Hepatitis D• Hepatitis E

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HepatitisHepatitis virus virus pathogenesispathogenesis

• Infection• Viruses to the liver • Virusreplication• Acute liver cell

damageRestitutio ad integrum

Chronic hepatitis

Fatale fulminant liver necrosis

Subclinical disease

HepatitisHepatitis C C infectioninfection -- whatwhat happenshappens??

CausesCauses to to ChronicChronic HepatitisHepatitis”Chronic hepatitis should be regarded as a

disease with varying etiology”

• HBV• HCV• HDV• Autoimmune hepatitis• Drog-induced hepatitis

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ConditionsConditions sharingsharingpathologicalpathological features with features with classicalclassical forms of forms of chronicchronic

hepatitishepatitis

• Wilsons disease• α-1-Antitrypsin deficiency• Primär Biliär Cirrhos• Primär Scleroserande Cholangitis

Reasons to Reasons to performperform liver liver biopsybiopsyin in chronicchronic hepatitishepatitis

• Diagnosis• Underlying causes• Grading of inflammatory activity• Staging of fibrosis• Follow up of treatment

PrimaryPrimary BiliaryBiliary CirrhosisCirrhosis (PBC)(PBC)

• Kvinnor/Män 10:1• Intrahepatic bile duct

destruction• Granulomatous

disease• Mitochondrial

autoantibodies• Cirrhosis end stage

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PrimaryPrimary SclerosingSclerosingCholangitisCholangitis

• Men/Women 2:1• Ulcerative colitis in 60 %• Intra + extrahepatic bile

ducts• Endoscopic Retrograde

Cholangiography (ERCP) for diagnosis or (MRCP)

ERCP in PSC

AlcholicAlcholic hepatitishepatitis• Steatohepatitis, acute• Common in western

countries• Toxic effect• Cirrhosis end stage• Histology: Acute

inflammation and fibrosis around central vein. Mallory bodies. Steatosis.

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NonNon--alcoholicalcoholicsteatohepatitissteatohepatitis (NASH)(NASH)

• The same histological pattern as alcoholicsteatohepatitis.

• Metabolic diseases. Overweight.• Pathological laboratory tests• Future common health care problem• Can develop cirrhosis

DrugsDrugs

• Many pharmaceuticaldrugs harms the liver

• Directly toxic effect or through metabolitis

• Examples: Paracetamol, Methotrexate, Tetracylins

CongenitalCongenital diseasesdiseases

• Gilberts syndrom• Crigler Najjar´s disease• Hemochromatosis• Mb Wilson• α-1-Antitrypsin deficiency

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Benign liver Benign liver tumourstumours

• Cysts• Hemangioma• Adenoma (hepatoma

and bile duct adenoma)• Focal Nodular

Hyperplasia (not neoplasia)

PrimaryPrimary malignantmalignant tumourstumours

• Hepatocellular cancer (80%)

• Cholangiocellularcancer

• Hepatoblastom• Hemaangiosarkom

NOTE! Liver metastasesis the most common malignancy in the liver!

HepatocellularHepatocellular cancercancer

• Geography• Livercirrhosis,

hepatitis viruses, paracites, toxin exposition is predisposing

•Higly differentiated•Satellite tumours common•Vascular growth tendency

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CholelithiasisCholelithiasis

• 1/10 Swedes• Often no symptoms• Increasing age• Women - estrogens?

• Adipositas• Ethnical groups• Diet• Metabolic conditions

CholelithiasisCholelithiasis formationformation

CholecystitisCholecystitis• Acute• Chronic

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Acute Cholecystitis• Before patient has often episodes with biliary colic

(=gallstensanfall)

• Symptoms acute cholecystitis: Abdominal pain in upper right quadrant, Mild jaundice(20%)

• Acute illness often subsides

• But in some cases persistent pain, fever, leukocytosis → surgery

Complications to cholelithiasisand cholecystitis

• Empyema• Perforation

peritonitis• Ascending cholangitis

BileBile ductduct obstructionobstruction

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Gall Bladder CancerGall Bladder Cancer

• Adenocarcinoma• Elderly• Poor prognosis

PancreasPancreas -- MalformationsMalformations

• Pancreas annulare

• Heterotropic pancreas tissue, sometimesincluding insulae

AcuteAcute PancreatitisPancreatitis

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AcuteAcute pancreatitispancreatitis

ChronicChronic pancreatitispancreatitis

PancreasPancreas tumourstumours

• Pseudocysts• Retentionscysts• Congenital cysts• Cystadenom

• Adenocarcinom• Elderly• Poor prognosis• Men > Women• 60-70 % caput

pancreaticus• Common type from

duct epithelium. Fibrotic.

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PancreascancerPancreascancer