Pathology of the liver I Flashcards
hepatocyte integrity refers to what structure specifically?
membrane
why is LDH not as specific for liver damage?
RBCs also use LDH
what is the role of albumin?
transporter of heme and FAs
maintains blood osmolarity
what enzymes are elevated in response to bile flow blockage?
alkaline phosphatase
5-NT
GGT
where are 5-NT and GGT located?
bile duct epithelium
which type of bilirubin has conjugated sugars? is it more or less soluble?
direct (measured directly in the lab)
more soluble
why is unconjugated bilirubin referred to as indirect?
because the value is obtained by subtracting direct from total bilirubin
at what bilirubin levels do you start getting symptoms of jaundice?
above 2 mg / dL
what is the normal range for bilirubin?
0.1 - 1.0 mg / dL
what are the general mechanisms of jaundice and cholestasis?
- isolated disorders
- liver disease
- bile duct obstruction
prehepatic hyperbilirubinemia will involve what type of bilirubin? what is the main cause? what is the mechanism?
unconjugated
RBCs
heme gets into macrophages - heme - biliverdin - bilirubin-albumin
where does conjugation of bilirubin occur, specifically?
hepatocyte ER
hepatic hyperbilirubinemia will involve what type of bilirubin?
unconjugated
posthepatic hyperbilirubinemia will involve what type of bilirubin?
conjugated
what enzyme is responsible for conjugation of bilirubin?
UGT1A1
which form of bilirubin can be excreted?
bilirubin monoglucuronide
what type of bilirubin metabolism errors will result in elevation of unconjugated bilirubin?
overproduction
reduced uptake
defective conjugation
what type of bilirubin metabolism errors will result in elevation of conjugated bilirubin?
defective excretion
defective secretion
gilbert syndrome and crigler-najjar syndrome involve which general dysfunction in bilirubin metabolism?
reduced glucuronyl transferase activity
what is the only autosomal dominant disorder of bilirubin metabolism?
crigler-najjar syndrome type II
how is bilirubin metabolism affected by crigler-najjar syndrome type I?
absent
how is bilirubin metabolism affected by crigler-najjar syndrome type II?
decreased UGT1A1 activity
how is bilirubin metabolism affected by gilbert syndrome?
decreased
how is bilirubin metabolism affected by dubin johnson syndrome?
impaired biliary excretion of bilirubin glucuronides due to mutation in canalicular multidrug resistance protein 2
what is the liver pathology associated with dubin johnson syndrome?
pigmented cytoplasmic globules
BLACK LIVER
which syndrome of bilirubin metabolism is associated with kernicterus?
crigler-najjar syndrome type I
what is the liver histology appearance for crigler-najjar syndrome type I?
normal
when do the crigler-najjar syndromes present?
birth
what is the liver histology appearance for crigler-najjar syndrome type II?
normal
what is the most serious consequence of crigler-najjar syndrome type I?
kernicterus - unconjugated bilirubin in brain
what is the protein defect in dubin johnson syndrome?
multidrug resistant protein 2
patients with dubin johnson syndrome have an increase in which isomer of urinary coproporphyrins?
isomer 1
which bilirubin metabolism syndrome is associated with asymptomatic jaundice?
rotor syndrome
what is the main dysfunction in progressive familial intrahepatic cholestasis (PFIC)? what are the symptoms?
biliary epithelial transporters
failure to thrive, hepatic failure, need for liver transplant
what are the components of normal bile?
cholic chenodeoxycholic acid taurine / glycine salts cholesterol lecithin bilirubin bicarbonate
what is the role of lecithin in bile?
protects epithelium
which gene is mutated in PFIC-1? which protein does it encode for? what is the result?
ATP8B1
canalicular ATPase
problem shunting substance into canalicular system
which gene is mutated in PFIC-2? which protein does it encode for? what is the result?
ABC11
bile salt export pump
cannot expore bile
which gene is mutated in PFIC-3? which protein does it encode for? what is the result?
ABC4
MDR3
phosphatidyl choline transfer - phospholipids cannot get into cell
what are the sequalae of progressive familial intrahepatic cholestasis?
cholestasis fat malabsorption fat soluble vitamin deficiency osteopenia liver failure
what are the diffuse infiltrative diseases leading to hepatic disorders with cholestasis? will the bile be conjugated or unconjugated?
granulomatous disorders
malignancy
conjugated
what are the two most common causes of posthepatic jaundice?
gall stones
cancer of head of pancreas
what are the physical symptoms of cholestasis?
pruritis jaundice clay colored stool dark urine bleeding diathesis xanthomas osteoporosis
what are the clinical values for cholestasis?
increased alkaline phosphatase
increased GGT
increased 5-NT
hyperbilirubinemia above 1.2
hyperlipidemia
what is the cause of feathery degeneration in cholestasis?
swollen hepatocytes (check)
what is the cause of ascending cholangitis?
infection due to cholestasis over time
what is bridging fibrosis as seen in cirrhosis?
bridging between microscopic structures of the liver
what are the steps in the pathogenesis of cirrhosis?
hepatocyte necrosis
progressive fibrosis
regenerative hepatocyte nodules
altered vascular flow
disruption of hepatocyte function
what cell drives much of the fibrosis in cirrhosis? why?
kupffer cell - induces stellate cell to become myofibroblast
what cytokine is responsible for much of the collagen elaboration in cirrhosis?
TGF-B
what is found in between the micronodules in micronodular cirrhosis?
fibrosis
lymphocytes (check)
what are the lab values associated with decompensated cirrhosis / portal hypertension?
decreased albumin increased serum albumin increased transaminases increased GGT increased prothrombin time
why are estrogen levels higher decompensated cirrhosis / portal hypertension?
cannot be broken down in liver
what is the equation for serum ascites albumin gradient (SAAG)?
(albumin concentration of serum) - (albumin concentration of ascitic fluid)
what is the SAAG value for portal hypertension? non portal hypertension?
portal HTN - over 1.1
non portal HTN - less than 1.1
hepatic failure indicates what % loss of function?
80%
what are the clinical signs of hepatic failure?
encephalopathy
coagulopathy
jaundice
multiple organ failure
chronic liver failure occurs in the context of what disorder?
decompensated cirrhosis
what is hepatorenal syndrome? what is the cause?
renal failure that occurs in the setting of cirrhosis or fulminant liver failure - sometimes in context of HTN, usually without other kidney diseases
alteration in blood flow
what are the clinical signs of hepatorenal syndrome?
normal kidney
oliguria / anuria
increased BUN, creatinine
low urinary sodium concentration
what is the hallmark of hepatorenal syndrome?
intense renal vasoconstriction with predominant arterial vasodilation
is tubular function preserved in hepatorenal syndrome?
yes
what is hepatopulmonary syndrome?
triad of
chronic liver disease
hypoxemia
intrapulmonary vascular dilations
what is the cause of hepatopulmonary syndrome?
ventilation perfusion mismatch - limited oxygen diffusion due to rapid blood flow through vessels
what is the cause of hepatic encephalopathy?
increased ammonia brain diffusion with edema
asterixis, abnormal EEG, lethargy, and decerebrate posture indicate what condition?
hepatic encephalopathy