lecture 1 - basic princ liver path-jhl livlef1.2009 · 2010. 3. 19. · liver function tests ......

CVCV

Kiernan’s lobulePTPT

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

T t t iTransporter proteinsBSEP (bile salt export pump)

FIC-1(familial intrahepatic cholestasis-1)

OATP(organic aniontransport pump)p p p)

tightjunction

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

CVCV

PTPTPTPT

HepatitisHepatitisI fl tiInflammation

+Hepatocyte Apoptosis/Necrosis

Time Course: Acute / ChronicCauses: Virus / DrugsCauses: Virus / Drugs

Acute Hepatitis

Chronic Hepatitis

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

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

PTPT

Classification of Chronic HepatitisClassification of Chronic Hepatitis

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

RERRER

PTPT plasmacellsplasmacells

LALA PTPT

interfaceinterfaceinterface hepatitisinterface hepatitis

Chronic HCV: portal Lymphoid aggregates Autoimmune chronic hepatitis

PTPTPTPTPTPT

copper andcopper-binding

protein(orcein stain)( )

Alpha-1-antitrypsin deficiency Wilson disease: copper overload

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)( ) ( )

Steatohepatitis

Ballooned hepatocytesBallooned hepatocytes

Mallory-DenkMallory-DenkCVCV

Mallory-DenkbodyMallory-Denkbody

fibrosis(pericentral)fibrosis(pericentral)

CV

Cholestasis

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

CHOLESTASISCHOLESTASIS

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

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

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)

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

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

NormalNormalsplenoportogram

Cirrhotic liverCirrhotic liver

Enlarged shortgastric veinggastric + esoph.varices

Splenoportogram incirrhosis

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