USMLE Review

6/1/11
Normal Structure and function
•Zone 1 – periportal
•Zone 3
• near the central vein
(low oxygen)
• high cyp450
(susceptible drug injury)
• “centrilobular
necrosis”
• outflow obstruction
“centrilobular
congestion” – “nutmeg
liver” (i.e. cardiac,
budd-chiari)
• Foregut:
– Portal venous
drainage
– Stomach, liver,
gallbladder,
spleen, proximal
duodenum
• ~80% bilirubin from
hemoglobin breakdown
• Heme oxygenase in
reticuloendothelial cells in
spleen and Kupffer cells
• B = bilirubin
• UGT = UDP-Glucuronyl Transferase
• BG = glucuronidated bilirubin (i.e.
conjugated)
 Common; fasting can
make apparent

Adult

< 10%
normal

Adult Adult
• ~90%+ bile acids actively resorbed in terminal
ileum
• Remaining bile acids converted to
urobilinogen in colon
– Some of this resorbed (shows in urine)
– Some in stool (color of stool)
• Ursodeoxycholic
acid ‘favorable’
bile acid
• Oral therapy can
increase pool to
~40% of bile acids
• More soluble bile
Table 62-2 -- Relative Frequencies of Various Forms of Neonatal Cholestasis
Modified from Balistreri WF. Neonatal cholestasis: Lessons from the past, issues for the future. Semin Liver Dis 1987; 7:61.

DISORDER FREQUENCY
Idiopathic neonatal
30-35
hepatitis
Extrahepatic biliary atresia 30 • Unconjugated
α1-Antitrypsin deficiency 7-10
Intrahepatic cholestatic hyperbilirubinemia
syndromes (Alagille
syndrome, Byler's disease,
5-6 common (lasts < 2
others)
Hepatitis
weeks)
(cytomegalovirus, rubella,
herpes simplex virus,
3-5 • Neonatal cholestasis
others)
Choledochal cyst 2-4
(conjugated
Bacterial sepsis 2 hyperbilirubinemia
Endocrinopathy
Biliary atresia – no (hypothyroidism, ≈1
after 2 weeks)
extrahepatic ducts panhypopituitarism)
Galactosemia ≈1
(need Kasai surgery) Inborn errors of bile acid
≈1
metabolism
Other metabolic disorders ≈1

Alagille syndrome – paucity of

intrahepatic ducts
• Hepatocyte functions
– Synthesize protein (albumin, INR = synthetic function;
low in cirrhosis)
– Metabolize drugs
- Phase I reactions are those that modify the structure of the
drug
- Phase II reactions involve adding a hydrophilic moiety to the
drug or reactive metabolite formed from phase I reaction.
Addition of this moiety then allows for excretion in the urine or
the bile of the drug
- CYP450 system is responsible for performing ~70-80% of all
phase I reactions. There are >30 different isoforms. Activity
can be influenced by genetic background, age, nutritional
status.
• Alkaline phosphatase can come from other sources (GGT
confirms liver)
• AST can come from muscle or RBC (unconjugated
hyperbilirubinemia + AST = hemolysis)
• Liver Failure
– Jaundice and Encephalopathy (confusion with high
ammonia)
– Prolonged INR (poor synthetic function)
– 50% cases from tylenol
• 90% of APAP metabolized via glucuronidation or
sulfation (phase II reactions)
• 10% via CYP450 system
• Treat N-acetylcysteine
• AST>ALT (2:1)
• AST rarely ever > 300
• Mallory bodies (can see
with other things though
– NASH, Wilson’s)
• Fatty liver = energy/mitochondrial problems
– NAFLD
– Alcohol
– Fatty liver pregnancy (LCHAD deficiency)
– Reyes
– Depakote
• Sclerosing cholangitis
– Primary (i.e. PSC)
– Secondary (bile duct
injury)
• Complications:
– Cholangitis
– Cholangiocarcinoma
– Jaundice
• Cirrhosis = pre-malignant; all cirrhosis patients
should get U/S every 6 months
• HCC only in cirrhosis (exception HBV)
• Spreads to bone and chest
• Budd-Chiari syndome (hepatic vein thrombosis)
– Hypercoaguable cause most of time
– Outflow obstruction; liver swelling (hepatomegaly),
ascites
• Portal vein thrombosis
– Can result from hypercoaguable state or slow flow
(i.e. cirrhosis)
– Can result from intra-abdominal infection (i.e.
phlebitits)
– Manifest with increased varices
 Hemochromatosis
• Common genetic disorder
• 95% related to HFE gene
mutation
– C282Y homozygous
– ?compound heterozygotes
• Non-HFE hemochromatosis
• Ferritin > 1000 predicts
cirrhosis
• Timely phlebotomy prevents
disease
• Liver transplant curative
 Hemochromatosis

Ferritin – hundreds, >1000?

Fe/TIBC = Saturation; > 80%
Wilson’s disease

Young, eye
findings,
mental illness
or dementia

& psychiatric problems

Only acute Wilson’s; also alkaline

phosphatase extremely low
 Alpha-1-antitrypsin

Inability to export A1AT (protease

inhibitor) from endoplasmic
reticulum in liver
PAS(+)globules on biopsy
Check mutations and A1AT levels
‘Pi’ MM (normal), MZ, ZZ, SS,
SZ
‘Pi’ null have no liver disease
Heterozygotes may be more
likely to have liver disease
No treatment
 Autoimmune hepatitis Central vein

Bile duct
• Range of presentations
– Acute liver failure
– Chronic elevation of liver
tests
– Chronic asymptomatic
disease (present as
cirrhosis)
• Diagnostic tests
– ANA, smooth muscle
antibody, ?anti-LKM
– SPEP or quantitative
immunoglobulins
– Frequently liver biopsy
Portal vein
 Primary biliary cirrhosis
• ~95% Women
• Predominant Alkaline phosphatase elevation
• ~95% AMA (+)
• Ursodiol
• Pruritus, jaundice, hypercholesterolemia,
woman, middle age
 Gallbladder

• Almost always stones

• “acalculous cholecystitis” – very ill
• Hepatobiliary scan (HIDA); looks for tracer entering gallbladder
• Fever
• Murphy’s sign (RUQ pain with inspiration while palpating)
• Stones can recur in common duct
 Pancreas

• Epigastric pain (severe) radiating to back, nausea, vomiting

• Alcohol & gallstone
• Some medications – prednisone, imuran, sulfa
• Can become critically ill quick
• Aggressive hydration, supportive care
• Can develop pseudocysts (amylase rich fluid)
 Pancreas divisum

• ~7-10% of
population
• Can be
cause of
idiopathic
pancreatitis

The pancreas develops from two parts whose ducts are in continuity with the common
bile duct. One part is ventral and the other dorsal to the intestinal tract before
rotation. The rotation brings the two parts together with separate ducts. The duct of
the dorsal (larger) part later becomes continuous, enters that of the ventral part which
enters the duodenum with the common bile duct. However, in a congenital
malformation (pancreas divisum) the other two parts of the pancreas remain distinct,
each with its own duct.
Pancreas Cancer

• Painless jaundice (head)

• Painful weight loss (body/tail)