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Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility

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Page 1: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility
Page 2: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility
Page 3: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility
Page 4: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility
Page 5: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility

CVCV

Kiernan’s lobulePTPT

Page 6: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility
Page 7: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility

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

Page 8: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility
Page 9: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility

T t t iTransporter proteinsBSEP (bile salt export pump)

FIC-1(familial intrahepatic cholestasis-1)

OATP(organic aniontransport pump)p p p)

tightjunction

Page 10: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility

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

Page 17: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility

Acute Hepatitis

Page 18: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility
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Chronic Hepatitis

Def.: Inflammation of the liver continuing without improvementcontinuing without improvement for 6 mos. or longerf g

Page 21: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility

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

Page 22: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility

PTPT

Page 23: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility
Page 24: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility
Page 25: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility

Classification of Chronic HepatitisClassification of Chronic Hepatitis

Page 26: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility

Ground-glass inclusions (HBsAg) in hepatocytes: chronic HBV

RERRER

Page 27: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility

PTPT plasmacellsplasmacells

LALA PTPT

interfaceinterfaceinterface hepatitisinterface hepatitis

Chronic HCV: portal Lymphoid aggregates Autoimmune chronic hepatitis

Page 28: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility

PTPTPTPTPTPT

copper andcopper-binding

protein(orcein stain)( )

Alpha-1-antitrypsin deficiency Wilson disease: copper overload

Page 29: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility

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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Page 33: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility

CV

Page 34: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility

Cholestasis

*Impaired bile secretionp(stagnation of bile flow in the liver)

Page 35: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility

CHOLESTASISCHOLESTASIS

Page 36: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility

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

Page 37: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility

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

Page 38: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility
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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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Page 43: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility

Activated stellate (Ito) cells in cirrhosis: smooth muscle actinimmunostain

Activated stellate (Ito) cells in cirrhosis: smooth muscle actinimmunostain

Page 44: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility
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Page 47: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility

NormalNormalsplenoportogram

Page 48: Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 · 2010. 3. 19. · Liver Function Tests ... Microsoft PowerPoint - Lecture 1 - Basic Princ Liver Path-JHL LivLef1.2009 [Compatibility

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