Chapter 18
LIVER
&
BILIARY TRACT
EMBRYOLOGY
The liver & the gallbladder are derived as outpocketing of the foregut.
NORMAL LIVER
DUCT
SYSTEM
N
O
FIBROUS
TISSUE
PORTAL
“TRIAD”
CENTRAL
VEIN
PATTERNS OF HEPATIC INJURY
• Degeneration:
– Degeneration--- Ballooning and “feathery”.
– Fat (steatosis)– Micro, marcro or mixed.
– Pigment (hemosiderin, bile, both intrinsic)
• Inflammation: Viral or Toxic
– Regeneration
– Fibrosis
• Neoplasia: 99% metastatic, 1% primary
BALLOONING DEGENERATION
“FEATHERY” DEGENERATION
FATTY LIVER
[Link] fatty change or steatosis
“MICRO”-VESICULAR STEATOSIS
• Toxic
• Obesity
• Alcohol
• Diabetes
“MACRO”-VESICULAR STEATOSIS
“Golden” pigment stained with Prussian Blue stain to make it
blue. Hemosiderin
APOPTOSIS
APOPTOSIS
INFLAMMATION
• PORTAL TRIADS
(early)
• SINUSOIDS
(more severe)
MILD “TRIADITIS”
More severe portal infiltrates with sinusoidal infiltrates also
Hepatic Regeneration
• The LIVER is
classically cited as the
most
“REGENERATIVE”
of all the organs!
FIBROSIS
• FIBROSIS is the end stage of
MOST chronic liver diseases,
and is ONE (of TWO) absolute
criteria needed for the
diagnosis of cirrhosis.
• What’s d other? Ans - Irregular nodules
CIRRHOSIS
• PORTAL-to-PORTAL (bridging)
FIBROSIS
• The “normal” hexagonal
“ARCHITECTURE” is
replaced by NODULES
•
CIRRHOSIS
Alcoholic
• Biliary (Primary or Secondary)
• Laennec’s
• Advanced (kind of a “redundant” adjective)
• Post-necrotic
• Micronodular
• Macronodular
ALL CIRRHOSIS IS:
• IRREVERSIBLE
• End stage of CLD, over years/months
• Associated with severe nodular
regeneration.
• Represents a significant risk for primary
liver neoplasm, e.g. PLCC
Cirrhosis
Normal
metastatic
metastatic cancer
N
O
FIBROUS
TISSUE
BETWEEN
PORTAL
AREAS
IRREGULAR NODULES SEPARATED BY PORTAL-to-PORTAL FIBROUS BANDS
TRICHROME
CIRRHOSIS, TRICHROME STAIN
CIRRHOSIS, TRICHROME STAIN
DEFINITIONS:
• CIRRHOSIS is the name of
the disease as demonstrated by
the anatomic changes
• LIVER FAILURE is the
series and sequence of
abnormal pathophysiologic
events
“SPIDER” ANGIOMA, CIRRHOSIS
Common
Clinical/Pathophysiological
Events
• Portal Hypertension WHY? WHERE?
• Ascites WHY? (Heart/Renal?)
• Splenomegaly WHY? Hepatomegaly?
• Jaundice WHY?
• “Estrogenic” effects WHY?
• Coagulopathies (II, VII, IX, X) WHY?
• Encephalopathy WHY?
Hepatic Enzymology
• Transaminases (AST/ALT), aka (SGOT/SGPT),
and LDH are “hepatic INTRACELLULAR”
enzymes, and are primarilly indicative of
hepatocyte damage.
• Alkaline Phosphatase (AlkPhos), Gamma-GTP
(Gamma-glutamyl transpeptidase), and 5’-
Nucleotidase (5’N) are MEMBRANE
enzymes and are primarilly indicative of bile
stasis/obstruction
Intracellular = DAMAGE
AST/ALT/LDH
Membrane = OBSTRUCTION
AlkPhos/GGTP/5’N
JAUNDICE
Where else?
Bilirubin: (0.3-1.2 mg/dl)
UN-conjugated (IN-direct)
Conjugated (direct)
JAUNDICE
• Hemolytic (UN-conjugated)
• Obstructive (Conjugated)
JAUNDICE
• Excessive production
• Reduced hepatic uptake
• Impaired conjugation
• Defective Transportation
Neonatal Jaundice
• Neonatal, genetic
– Gilbert Syndrome (5-10% ↓ glucuronyl-transferase)
– Dubin-Johnson Syndrome (transport problem)
• Neonatal, NON-genetic
– MASSIVE differential diagnosis, i.e.,
everything
CHOLESTASIS
• Def: Suppression of bile flow
• Associated with membrane
enzyme elevations, “primarily”,
ie, AP/GGTP/5’N
• Familial, drugs (steroids and many common
antibiotics), but bottom line is
OBSTRUCTION
Bile “plugs”, Bile “lakes”
VIRAL HEPATITIS
• A, B, C, D, E
• They all look the same, ranging from a
few extra portal triad lymphocytes, to
“FULMINANT” hepatitis
• Associated with full recovery
(usual), chronic progression over
years leading to cirrhosis (not rare),
risk of hepatoma (uncommon), or
death (uncommon)
VIRAL HEPATITIS
• Jaundice, urine dark, stool chalky
• Usual viral “prodrome”
• Upper respiratory infection
• All have multiple antigen (virus) and
antibody (serology) serum tests
• “Councilman” bodies on biopsy are
very very nice to find. Why?
Chiefly Portal Inflammation
FULMINANT HEPATITIS
“FULMINANT” Acute Viral Hepatitis
“Councilman” Bodies……Diagnostic? Probably!
B
LESS common than B (one fourth)
C
LESS dangerous than B in the acute phase
MORE likely to go chronic than B
MORE closely linked with hepatoma than B
NON-Viral hepatitides
• Staph aureus (toxic shock)
• Gram-Negatives (cholangitis)
• Parasitic:
– Malaria
– Schistosomes
– Liver flukes (Fasciola hepatica)
• Ameba (abscesses)
• AUTOIMMUNE
• ALCOHOLIC HEPATITIS
DRUGS/TOXINS
• Steatosis (ETOH)
• Centrolobular necrosis (TYLENOL)
• Diffuse (massive) necrosis
• Hepatitis
• Fibrosis/Cirrhosis (ETOH)
• Granulomas
• Cholestasis (BCPs, steroids)
“Metabolic” Liver Disease
• Steatosis (i.e., “fat”, fatty change,
fatty “metamorphosis”)
• Hemochromatosis (vs. hemosiderosis)
– Hereditary (Primary)
– Iron Overload (Secondary), e.g., hemolysis,
increased Fe intake, chronic liver disease
• Wilson Disease (Toxic copper levels)
• Alpha-1-antitrypsin (NATURAL protease inhibitor)
• Neonatal Cholestasis
PAS positive inclusions with alpha-1-antitrypsin deficiency
INTRAHEPATIC
BILE DUCTS
Points of Interest
• INTRA-hepatic vs. EXTRA-hepatic
• PRIMARY biliary cirrhosis is a bona-fide
AUTOIMMUNE disease of the INTRA-hepatic
bile ducts
• SECONDARY biliary cirrhosis is caused by
chronic obstruction/inflammation/both of
the intrahepatic bile ducts
• CHOLANGITIS, or inflammation of the
INTRA-hepatic bile ducts, is associated with
chronic bacterial (often gram negative rods)
infections, or Crohns/Ulcerative colitis (IBD)
CIRCULATORY
Disorders
Points of Interest
• Infarcts are rare. WHY?
• Passive congestion with “centrolobular”
necrosis, is EXTREMELY COMMON in CHF,
and a VERY COMMON cause of cirrhosis,
i.e., “cardiac” cirrhosis
• Various semi reliable clinical and anatomic
findings are seen with disorders of:
– Portal Veins
– Hepatic veins/IVC
– Hepatic arteries
Miscellaneous
• Hepatic Diseases are seen often with
–Pregnancy
• PRE-Eclampsia/Eclampsia (HTN, proteinuria,
edema, coagulopathies, DIC)
• Fatty Liver
• Cholestasis
–Transplant—Bone Marrow or other
Organs
• Drug Toxicities
• GVH
BENIGN LIVER TUMORS
• …..are, in most cases, really regenerative
nodules
• Have been historically linked to BCPs
• Can really be neoplasms of blood vessels
also
MALIGNANT LIVER TUMORS
• 99% are metastatic, i.e., SECONDARY, esp. from
portal drained organs
• Just about every malignancy will wind up
eventually in the liver, like the lungs
• PRIMARY liver malignancies, i.e., hepatomas, aka
hepatocellular carcinomas, arise in the
background of already very serious liver disease
chronic hepatitis/cirrhosis, are slow growing, and
do NOT metastasize readily
• CHOLANGIOCARCINOMAS are malignancies if
the INTRA-hepatic bile ducts and look MUCH more
like adenocarcinomas than do hepatomas
HEPATIC ANGIOMA
HEPATOMA, or
HEPATOCELLULAR
CARCINOMA
CHOLANGIOCARCINOMA
EXTRAHEPATIC
BILE DUCTS
&
GALLBLADDER
MAIN
CONSIDERATIONS
• Anomalies
• Stones (Clolesterol/Bilirubin)
• (Chole[docho]lithiasis)
• Inflammation
(Cholecystitis/Cholangitis)
• Cysts
• Neoplasms
Anomalies
• Congenitally absent
Gallbladder
• Duct Duplications
• Bilobed Gallbladder
• Phrygian Cap
• Hypoplasia/Agenesis
Phrygian Cap
Cholelithiasis
Factors
• Bile supersaturated with
cholesterol
• Hypomotility
• Cholesterol “seeds” in bile, i.e.,
crystals
• Excess mucous in gallbladder
Cholesterolosis of gallbladder mucosa
Cholesterolosis of gallbladder mucosa
Cholecystitis
• Acute: fever, leukocytosis, RUQ pain
• Chronic: Subclinical or pain
• Ultrasound can detect stones well
• HIDA (biliary) nuclear study can help
• Go hand in hand with stones in
gallbladder or ducts
• If surgery is required, most is
laparoscopic
Choledochal Cysts
• Dilatations of the common
bile duct usually in children.
Adenocarcinoma of the
gallbladder
