PATHOLOGY OF THE

LIVERNafea Sami, MRCPath

Department of Pathology

College of Medicine

University of Anbar

HISTOLOGY OF

THE LIVER

• HEPATIC LOBULES vs. ACINI

1 2 3

Portal tract

Centralvein

Portal tract

Traditional conception of liver

histology, arbitrarily divided into

centrilobular, periportal

(peripheral) & midlobular zones

Acini are defined by micro-

circulatory layout of liver, with a

central axis (portal tract & its

afferent vessels), surrounded by 3

zones

HISTOLOGY OF

THE LIVER• Portal triads: contain a

bile duct, a small hepatic

artery and a portal vein

branch, surrounded by

type I & III collagen

• Central vein (tributary

of hepatic vein) with

blood to hepatic

parenchyma flowing

from the portal triads to

the central veins

DISEASES OF

THE LIVER

• Hepatic injury

• Jaundice & cholestasis

• Hepatic failure

• Cirrhosis

• Inflammatory disorders: hepatitis, abscesses

• Drug & toxin-related diseases: alcohol liver disease

• Inborn error of metabolism & pediatric liver disease: Hemochromatosis, Wilson’s disease, neonatal hepatitis & Reye’s syndrome

• Intrahepatic biliary tract disease: PBC, PSC

• Circulatory disorders

• Tumors

HISTOLOGIC PATTERNS OF

HEPATIC INJURY

• Inflammation: acute or chronic hepatitis; portal or

lobular

• Degeneration: ballooning, foamy, steatosis

• Necrosis: coagulative or lytic (hydropic); Councilman

bodies; centrilobular, focal, piece-meal, bridging,

submassive, massive

• Fibrosis: portal, central, bridging

• Cirrhosis: regenerative nodules sorrounded by fibrosis

HISTOLOGIC PATTERNS OF HEPATIC INJURY

STEATOSIS• Fat (neutral fat,

triglycerides) in

liver cells

indicates defect in

lipid metabolism

or lipoprotein

synthesis or

unusual amounts

of adipose or

dietary lipids

brought to liver

HISTOLOGIC PATTERNS OF HEPATIC INJURY

HEPATOCYTE SWELLING• Swelling or

hydropic

change is a

result of

defects in

membrane

and/or

mitochondrial

function .

Histologic patterns of hepatic injury

NECROSIS• Coagulative

necrosis: poorly

staining mummified

hepatocytes

• Councilman bodies:

dead hepatocytes

• Lytic necrosis:

hepatocytes swell &

rupture

PHYSIOLOGY OF THE LIVER

BILIRUBIN METABOLISM• Aging RBCs HEME MACROPHAGE

Heme

oxygenase

Biliverdin

reductase

BILIVERDIN

BILIRUBIN-Albumin complex

BILIRUBIN

GLUCORONIDES

UDP

U

R

O

B

I

L

I

N

O

G

E

N

beta-glucuronidase

PHYSIOLOGY OF

THE LIVER• In addition to bilirubin, the liver secretes 12-36 g

bile acids/day: carboxylated steroid molecules derived from cholesterol & hydroxyl groups– Cholic acid & chenodeoxycholic acid

– Secreted as taurine & glycine conjugates

– 10-20% are deconjugated in ileum

– 0.2-0.6 g/d fecal loss matched by de novo liver synthesis

• Functions of hepatic bile:– 1) Primary pathway for elimination of water-insoluble

bilirubin, excess cholesterol & xenobiotics

– 2) Emulsification of dietary fat in gut lumen

PATHOLOGY OF THE LIVER

JAUNDICE• Jaundice: yellowish discoloration of skin & sclera

(icterus) due to systemic retention of bilirubin (> 2 mg/dl)

• Equilibrium between bilirubin production & clearance is disturbed:

– 1) Excessive production

– 2) Reduced hepatocellular uptake

– 3) Impaired conjugation

– 4) Decreased hepatocellular excretion

– 5) Impaired bile flow

• Kernicterus: accumulation of bilirubin in brain

TYPES OF

JAUNDICE

• UNCONJUGATED BILIRUBIN– Water-insoluble

– Tightly complexed to serum albumin

– Cannot be excreted in urine

– Free form is toxic

– Lab test: Total bilirubinminus direct bilirubin

• CONJUGATED BILIRUBIN

– Water-soluble

– Loosely bound to serum albumin

– Excess amounts are excreted in urine

– Nontoxic

– Lab test: measured by direct bilirubin

LAB EVALUATION OF LIVER DISEASE

LIVER FUNCTION TESTS• Tests of hepatocyte integrity

– ASL (SGOT)*

– ALT (SGPT)*

– LDH

• Tests of biliary excretory function– Serum Bilirubin*

– Alkaline phosphatase*

– Gamma-glutamyl transpeptidas

• Tests of hepatocyte function– Albumin*

– Prothrombine time*

– Ammonia

– Aminopyrine breath test; galactose elimination