Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ......
Transcript of Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ......
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CVCV
Kiernan’s lobulePTPT
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Limiting platePortal fibroblast / myofibroblast
Portal tract
Bile ductArtery
PortalVeinCanal of
Hering
Progenitor /Stem cell
g
Pit cell (NK cell)Stellate cell(Ito cell) Normal
Sinusoid
Kupffer cell( ) Normal
microanatomyof the liver
Central Vein
Space of Disse
sieve
of the liver
Central Veinsieveplate
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T t t iTransporter proteinsBSEP (bile salt export pump)
FIC-1(familial intrahepatic cholestasis-1)
OATP(organic aniontransport pump)p p p)
tightjunction
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Cholestatic enzymes• Total bilirubin/direct bilirubin• AP (alkaline phosphatase)• GGT (gamma glutamyl transferase)• 5’NT (5’ nucleotidase)Liver Function Tests
(LFT’s)
Hepatitic enzymesHepatitic enzymes• AST (aspartate aminotransferase)• ALT (alanine aminotransferase)
Synthetic proteins• Total protein• Albumin
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CVCV
PTPTPTPT
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HepatitisHepatitisI fl tiInflammation
+Hepatocyte Apoptosis/Necrosis
Time Course: Acute / ChronicCauses: Virus / DrugsCauses: Virus / Drugs
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Acute Hepatitis
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Chronic Hepatitis
Def.: Inflammation of the liver continuing without improvementcontinuing without improvement for 6 mos. or longerf g
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Causes of Chronic Hepatitis
1 Hepatitis viruses: HBV HCV1. Hepatitis viruses: HBV, HCV2. Autoimmune hepatitisp3. Drugs 4 M t b li di4. Metabolic diseases:
-AAT deficiencyy-Wilson’s disease
5 C t i5. Cryptogenic
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PTPT
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Classification of Chronic HepatitisClassification of Chronic Hepatitis
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Ground-glass inclusions (HBsAg) in hepatocytes: chronic HBV
RERRER
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PTPT plasmacellsplasmacells
LALA PTPT
interfaceinterfaceinterface hepatitisinterface hepatitis
Chronic HCV: portal Lymphoid aggregates Autoimmune chronic hepatitis
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PTPTPTPTPTPT
copper andcopper-binding
protein(orcein stain)( )
Alpha-1-antitrypsin deficiency Wilson disease: copper overload
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Fatty Liver•Triglyceride vacuoles in hepatocytes•Fatty liver is the most common cause ofyincreased serum AST & ALT in the U.S.
•MAJOR CAUSES:-alcohol—obesity—diabetes—steroids
TypesTypesTypesTypesLarge droplet (common) Small droplet (uncommon)(macrovesicular) (microvesicular)( ) ( )
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Steatohepatitis
Ballooned hepatocytesBallooned hepatocytes
Mallory-DenkMallory-DenkCVCV
Mallory-DenkbodyMallory-Denkbody
fibrosis(pericentral)fibrosis(pericentral)
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CV
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Cholestasis
*Impaired bile secretionp(stagnation of bile flow in the liver)
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CHOLESTASISCHOLESTASIS
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CHOLESTASIS:impaired bile secretionimpaired bile secretion
Surgical Jaundice: Medical Jaundice:I t h ti diSurgical Jaundice:
Large bile duct obstructionIntrahepatic disease(sepsis/drugs/hepatitis/Bile salt transporter dis.)
PTPTPTPT
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CirrhosisCirrhosis-Def.: 2 components:
diff fib idiffuse fibrosis +regenerative nodules
-Multifactorial etiology-Gross types: Micronodular (< 3mm)yp ( )
Macronodular (>3 mm)-Complications:-Complications:
-portal HTN-liver cell failure-HCC
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Cirrhosis: Diffuse fibrosis + nodules of regenerative liver
diffuse fibrosisdiffuse fibrosis
thickened liver-cell platesthickened liver-cell platesthickened liver-cell plates(regenerative hyperplasia)thickened liver-cell plates(regenerative hyperplasia)
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Activated stellate (Ito) cells in cirrhosis: smooth muscle actinimmunostain
Activated stellate (Ito) cells in cirrhosis: smooth muscle actinimmunostain
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NormalNormalsplenoportogram
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Cirrhotic liverCirrhotic liver
Enlarged shortgastric veinggastric + esoph.varices
Splenoportogram incirrhosis
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RECAPRECAPRECAPRECAP1. Liver gross + lobule /acinus2. Micro: space of Disse / Stellate cells /
periportal limiting plate /progenitor cells in canal of Heringof Hering
3. Acute hepatitis: Hepatitis virus A-E, drugs4. Chronic hepatitis: def. /causes / grading + stagingp g g g g5. Fatty liver (large/small droplet), steatohepatitis6. Cholestasis: bile duct obstruct. / intrahepatic—
i l di t t t iincluding transporter proteins7. Cirrhosis: gross types, causes, complications8. Portal hypertension: pre-hepatic /8. Portal hypertension: pre hepatic /
INTRAHEPATIC / post-hepatic