1

2

3

4

5

Portal tract

Bile ductArtery

PortalVein

Limiting plate

Progenitor /Stem cell

Canal ofHering

Portal fibroblast / myofibroblast

Central Vein

Sinusoid

Kupffer cell

Pit cell (NK cell)Stellate cell(Ito cell)

Space of Disse

sieveplate

6

Transporter proteinsBSEP (bile salt export pump)

FIC-1(familial intrahepaticcholestasis-1)

OATP(organic aniontransport pump)

tightjunction

Cholestatic enzymes• Total bilirubin/direct bilirubin• AP (alkaline phosphatase)• GGT (gamma glutamyl transferase)• 5’NT (5’ nucleotidase)

Hepatitic enzymes• AST (aspartate aminotransferase)• ALT (alanine aminotransferase)

Synthetic proteins• Total protein• Albumin

Liver Function Tests(LFT’s)

7

8

9

HepatitisInflammation

+Hepatocyte Apoptosis/Necrosis

Time Course: Acute / ChronicCauses: Virus / Drugs

10

Acute Hepatitis

11

Chronic Hepatitis

Def.: Inflammation of the livercontinuing without improvementfor 6 mos. or longer

12

Causes of Chronic Hepatitis

1. Hepatitis viruses: HBV, HCV2. Autoimmune hepatitis3. Drugs4. Metabolic diseases:

-AAT deficiency-Wilson’s disease

5. Cryptogenic

13

14

Classification of Chronic Hepatitis

Fatty Liver•Triglyceride vacuoles in hepatocytes•Fatty liver is the most common cause of increased serum AST & ALT in the U.S.•MAJOR CAUSES:

-alcohol—obesity—diabetes—steroidsTypesTypes

Large droplet (common) Small droplet (uncommon) (macrovesicular) (microvesicular)

15

CVMallorybody

fibrosis(pericentral)

Ballooned hepatocytes

Steatohepatitis

16

CV

17

Cholestasis

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

18

CHOLESTASIS:impaired bile secretion

Surgical Jaundice:Large bile duct obstruction

Medical Jaundice:Intrahepatic disease(sepsis/drugs/hepatitis/Bile salt transporter dis.)

Cirrhosis-Def.: 2 components:

diffuse fibrosis +regenerative nodules

-Multifactorial etiology-Gross types: Micronodular (< 3mm)

Macronodular (>3 mm)-Complications:

-portal HTN-liver cell failure-HCC

19

20

21

22

23

24

25

26

RECAPRECAP1. Liver gross + lobule /acinus2. Micro: space of Disse / Stellate cells /

periportal limiting plate /progenitor cells in canalof Hering

3. Acute hepatitis: Hepatitis virus A-E, drugs4. Chronic hepatitis: def. /causes / grading + staging5. Fatty liver (large/small droplet), steatohepatitis6. Cholestasis: bile duct obstruct. /

intrahepatic—including transporter proteins7. Cirrhosis: gross types, causes, complications8. Portal hypertension: pre-hepatic /

INTRAHEPATIC / post-hepatic