liver Flashcards
role of fetal liver
major site of hematopoiesis in fetus: mesodermal hematopoietic stem cells migrate from mesonephros → to liver at 3 wk GA (source of fetal blood cell until BM at 28 wks GA)
portal triad
portal vein
hepatic artery
bile ductule
blood supply to liver
portal vein (from mesenteric veins, gastric vein): toxins + nutrition from GI hepatic artery: O2 blood
hepatocytes role
make proteins energy, vitamin, mineral storage metabolize drugs/toxins make bile → dump bile into bile canaliculi (opposite flow to sinusoid flow → bile ductule → hepatic duct → common hepatic duct...) excrete bilirubin
zone affected first by ischemia + hypotension
zone 3: pericentral vein zone (farthest from O2 blood source - hepatic artery)
zone affected first by viral hepatitis
zone 1: periportal zone (next to portal vein)
zone most sensitive to metabolic toxins (acetaminophen overdose, site of alcoholic hepatitis)
zone 3: pericentral vein zone
zone with highest concentration of P450 enzymes
zone 3: pericentral vein zone
examples of proteins made by liver
coag factors complement albumin apolipoproteins: lipid transport transferrin: iron transport ceruloplasmin: copper transport others: cholesterol phosopholipids
examples of drug + toxin metabolism of liver
P450 enzymes
UDP glucoronyl transferase
ALT and AST: transaminases
steroid hormones → inactive metabolites (need for breakdown of estrogen, progesterone, testosterone, vitamin D, cortisol, thyroid hormone)
storage role of liver
glucose as glycogen
store cholesterol with TG in liver (esp VLDL)
iron bound to ferritin
B12, ADEK
role of bile
breakdown fats
carrier for excretion of bilirubin
complication of excess unconjugated bilirubin for several months in newborn
kernicterus: unconjugated bilirubin in brain → chorea cerebral palsy hearing loss gaze abnormalities brain damage → death
neuro effects of excess unconjugated bilirubin in newborn (occur in hrs-days)
bilirubin is neurotoxic:
lethargy
hypotonia
prevent kernicterus
phototherapy: convert bilirubin to isomer that can excrete
AR mutation in promotor for UDP-glucoronyltransferase gene →↓ amounts of UDP-glucoronyltransferase enzyme
conjugate bilirubin more slowly → slight elevation of INDIRECT bilirubin
benign and asymptomatic unless infection or alcohol (incidental finding)
Gilbert syndrome
complete absence of UDP-glucoronyltransferase enzyme
can’t conjugate bilirubin and excrete it into the bile
jaundice + ↑ INDIRECT bilirubin in first few days of life
may have NEURO sx
if no treatment: kernicterous (die in a couple years)
type I crigler-najjar syndrome
treatment of type 1 crigler-najjar syndrome
phototherapy
plasmaphoresis - remove unconjugated bilribubin bound to albumin
definitive: liver transplant (makes UDP-GT)
mutated UDP-glucoronyltransferase enzyme
jaundice + ↑ INDIRECT bilirubin in first few days of life (but less than type I)
type II crigler-najjar syndrome
distinguish type I vs type II crigler-najjar syndrome
give phenobarbital (barbiturate): induces liver enzyme production (even UDP-GT) type II pr Gilbert: ↓ bilirubin type I: no change (no UDP-GT in liver!)
problem putting conjugated bilirubin back into bile → conjugated bilirubin trapped in hepatocytes → turns liver BLACK
↑ DIRECT serum bilirubin
benign - no treatment necessary
dubin-johnson syndrome
milder form of dubin-johnson syndrome
mild elevation in DIRECT bilirubin
liver DOESN’T turn black
rotor syndrome
stages of alcoholic liver disease
steatosis (fatty liver)
alcoholic hepatitis
alcoholic cirrhosis
fat droplets in cytosol of hepatocytes seen in HEAVY drinks
REVERSIBLE if stop drinking
steatosis: fatty liver
inflammation + steatosis
swollen necrotic hepatocytes
neutrophils in liver parenchyma
MALLORY bodies: intracytoplasmic eosinophilic inclusions of keratin
alcoholic hepatitis
RUQ pain anorexia jaundice low-grade fever ↑AST>ALT (AST >2x the ALT, A Scotch and Tonic = AST) enlarged, swollen liver
alcoholic hepatitis
IRREVERSIBLE
scarring + fibrosis
palpate hard, nodular liver edge
enlarged OR shrunken liver
AST/ALT: may be high, normal, low (trashed liver)
residual nodules of hepatocytse with collagen + sclerosis (blue on trichrome stain) surrounding them (replaced necrotic hepatocytes)
sclerosis located around central vein (zone 3)
alcoholic cirrhosis
complications of cirrhosis
liver failure: no hepatocytes
portal HTN: blood can’t flow through sinusoids (causes hepatosplenomegaly) → portal vein