Department of Pathology College of Medicine Nafea Sami ...
Transcript of Department of Pathology College of Medicine Nafea Sami ...
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