gilbert and criggler najar, hemolytic and physiologic, hepatitis
what is the Gilbert's mutation?
UGT1A1 it is a benign unconjugated hyperbilirubinemia (bili <6) more common in males and is aggravated by stress
how are gilbert's and crigler najjar different?
Gilbert's has 10-33% of normal UGTransferase enzyme activity and C-N has no functional activity of the enzyme.
does crigler-najjar II have enzyme activity?
yes, markedly reduced, but detectable. More than type I.
how is c-n II treated?
phenobarbital to induce UGT enzyme activity
dubin johnson, rotor, PBC, PSC, bile obstructions
mutation of MRP2/cMOAT gene encoding for canalicular transporter that leads to defect in organic anion transport so that conjugated bili cannot get into the bile ductule leading to intermittent jaundice and a BLACK LIVER, scleral icterus, moderately enlarged liver
grossly pigmented (black) liver?
what hyperbilirubinemias are associated with intermittent jaundice?
can you rely on alk phos for intrahepatic cholestasis of pregnancy?
No. Difficult to interpret bc placenta produces it as well
what has higher AST > ALT
why is gender a risk factor for ALD?
gastric mucosal alcohol dehydrogenase activity is lower in women, making them more vulnerable to greater hepatic exposure to ingested alcohol than men
is alcoholic steatosis irreversible?
no--generally considered benign and reversible by itself with the cessation of alcohol
where is alcoholic hepatitis most pronounced in the liver?
zone 3. Combo of steatosis, hepatocellular necrosis, and acute inflammation
what are mallory denk bodies?
damaged cytokeratin intermediate filaments in hepatocytes that appear like eosinophilic cytoplasmic inclusions. A hallmark of alcoholic hepatitis.
which zone is most affected by virus infections?
which zone most affected by ischemia?
highest p450 zone?
pale stool and dark urine?
jaundice in first 24 hours of life?
jaundice after first 24 hours of life - 1 wk?
physiologic jaundice of newborn
treatment for criggler-najar?
phenobarbital--> induces p450 and --> increases liver production of UDP
LFTs in rotor and dubin-johnson?
alk phos levels in hepatitis?
normal! this is a biliary function enzyme.
apoptotic hepatocytes in zone I seen in all viral hepatitis
C282Y HFE gene mutation causing impairment of iron sensing and absorption leading to excess iron absorbed from GI tract so that iron deposits in liver, heart, pituitary, thyroid, pancreas, joints, gonads
triad of hemochromatosis?
cirrhosis, bronze skin, diabetes
women have later onset of this disease
hemochromatosis due to menstruation
how does secondary hemochromatosis occur?
multiple transfusions, excessive iron supplementation, S. African beer brewing vats
treatment for hemochromatosis
family screening, phlebotomize 1-2 times per week to deplete iron stores
what stain is best for hemochromatosis?
prussian blue stain
how are hepcidin levels affected in hemochromatosis?
low hepcidin production, so more iron is absorbed and stored in macrophages
total copper level in wilsons?
free copper level in wilsons?
labs in biliary cirrhosis?
high alk phos, high LDL, high HDL, high bile salts