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Year 2 Gastrointestinal > Pathology of the liver I > Flashcards

Pathology of the liver I Flashcards

1
Q

hepatocyte integrity refers to what structure specifically?

A

membrane

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2
Q

why is LDH not as specific for liver damage?

A

RBCs also use LDH

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3
Q

what is the role of albumin?

A

transporter of heme and FAs

maintains blood osmolarity

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4
Q

what enzymes are elevated in response to bile flow blockage?

A

alkaline phosphatase
5-NT
GGT

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5
Q

where are 5-NT and GGT located?

A

bile duct epithelium

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6
Q

which type of bilirubin has conjugated sugars? is it more or less soluble?

A

direct (measured directly in the lab)

more soluble

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7
Q

why is unconjugated bilirubin referred to as indirect?

A

because the value is obtained by subtracting direct from total bilirubin

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8
Q

at what bilirubin levels do you start getting symptoms of jaundice?

A

above 2 mg / dL

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9
Q

what is the normal range for bilirubin?

A

0.1 - 1.0 mg / dL

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10
Q

what are the general mechanisms of jaundice and cholestasis?

A
  1. isolated disorders
  2. liver disease
  3. bile duct obstruction
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11
Q

prehepatic hyperbilirubinemia will involve what type of bilirubin? what is the main cause? what is the mechanism?

A

unconjugated

RBCs

heme gets into macrophages - heme - biliverdin - bilirubin-albumin

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12
Q

where does conjugation of bilirubin occur, specifically?

A

hepatocyte ER

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13
Q

hepatic hyperbilirubinemia will involve what type of bilirubin?

A

unconjugated

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14
Q

posthepatic hyperbilirubinemia will involve what type of bilirubin?

A

conjugated

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15
Q

what enzyme is responsible for conjugation of bilirubin?

A

UGT1A1

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16
Q

which form of bilirubin can be excreted?

A

bilirubin monoglucuronide

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17
Q

what type of bilirubin metabolism errors will result in elevation of unconjugated bilirubin?

A

overproduction
reduced uptake
defective conjugation

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18
Q

what type of bilirubin metabolism errors will result in elevation of conjugated bilirubin?

A

defective excretion

defective secretion

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19
Q

gilbert syndrome and crigler-najjar syndrome involve which general dysfunction in bilirubin metabolism?

A

reduced glucuronyl transferase activity

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20
Q

what is the only autosomal dominant disorder of bilirubin metabolism?

A

crigler-najjar syndrome type II

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21
Q

how is bilirubin metabolism affected by crigler-najjar syndrome type I?

A

absent

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22
Q

how is bilirubin metabolism affected by crigler-najjar syndrome type II?

A

decreased UGT1A1 activity

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23
Q

how is bilirubin metabolism affected by gilbert syndrome?

A

decreased

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24
Q

how is bilirubin metabolism affected by dubin johnson syndrome?

A

impaired biliary excretion of bilirubin glucuronides due to mutation in canalicular multidrug resistance protein 2

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25
what is the liver pathology associated with dubin johnson syndrome?
pigmented cytoplasmic globules BLACK LIVER
26
which syndrome of bilirubin metabolism is associated with kernicterus?
crigler-najjar syndrome type I
27
what is the liver histology appearance for crigler-najjar syndrome type I?
normal
28
when do the crigler-najjar syndromes present?
birth
29
what is the liver histology appearance for crigler-najjar syndrome type II?
normal
30
what is the most serious consequence of crigler-najjar syndrome type I?
kernicterus - unconjugated bilirubin in brain
31
what is the protein defect in dubin johnson syndrome?
multidrug resistant protein 2
32
patients with dubin johnson syndrome have an increase in which isomer of urinary coproporphyrins?
isomer 1
33
which bilirubin metabolism syndrome is associated with asymptomatic jaundice?
rotor syndrome
34
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
35
what are the components of normal bile?
``` cholic chenodeoxycholic acid taurine / glycine salts cholesterol lecithin bilirubin bicarbonate ```
36
what is the role of lecithin in bile?
protects epithelium
37
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
38
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
39
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
40
what are the sequalae of progressive familial intrahepatic cholestasis?
``` cholestasis fat malabsorption fat soluble vitamin deficiency osteopenia liver failure ```
41
what are the diffuse infiltrative diseases leading to hepatic disorders with cholestasis? will the bile be conjugated or unconjugated?
granulomatous disorders malignancy conjugated
42
what are the two most common causes of posthepatic jaundice?
gall stones | cancer of head of pancreas
43
what are the physical symptoms of cholestasis?
``` pruritis jaundice clay colored stool dark urine bleeding diathesis xanthomas osteoporosis ```
44
what are the clinical values for cholestasis?
increased alkaline phosphatase increased GGT increased 5-NT hyperbilirubinemia above 1.2 hyperlipidemia
45
what is the cause of feathery degeneration in cholestasis?
swollen hepatocytes (check)
46
what is the cause of ascending cholangitis?
infection due to cholestasis over time
47
what is bridging fibrosis as seen in cirrhosis?
bridging between microscopic structures of the liver
48
what are the steps in the pathogenesis of cirrhosis?
hepatocyte necrosis progressive fibrosis regenerative hepatocyte nodules altered vascular flow disruption of hepatocyte function
49
what cell drives much of the fibrosis in cirrhosis? why?
kupffer cell - induces stellate cell to become myofibroblast
50
what cytokine is responsible for much of the collagen elaboration in cirrhosis?
TGF-B
51
what is found in between the micronodules in micronodular cirrhosis?
fibrosis | lymphocytes (check)
52
what are the lab values associated with decompensated cirrhosis / portal hypertension?
``` decreased albumin increased serum albumin increased transaminases increased GGT increased prothrombin time ```
53
why are estrogen levels higher decompensated cirrhosis / portal hypertension?
cannot be broken down in liver
54
what is the equation for serum ascites albumin gradient (SAAG)?
(albumin concentration of serum) - (albumin concentration of ascitic fluid)
55
what is the SAAG value for portal hypertension? non portal hypertension?
portal HTN - over 1.1 non portal HTN - less than 1.1
56
hepatic failure indicates what % loss of function?
80%
57
what are the clinical signs of hepatic failure?
encephalopathy coagulopathy jaundice multiple organ failure
58
chronic liver failure occurs in the context of what disorder?
decompensated cirrhosis
59
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
60
what are the clinical signs of hepatorenal syndrome?
normal kidney oliguria / anuria increased BUN, creatinine low urinary sodium concentration
61
what is the hallmark of hepatorenal syndrome?
intense renal vasoconstriction with predominant arterial vasodilation
62
is tubular function preserved in hepatorenal syndrome?
yes
63
what is hepatopulmonary syndrome?
triad of chronic liver disease hypoxemia intrapulmonary vascular dilations
64
what is the cause of hepatopulmonary syndrome?
ventilation perfusion mismatch - limited oxygen diffusion due to rapid blood flow through vessels
65
what is the cause of hepatic encephalopathy?
increased ammonia brain diffusion with edema
66
asterixis, abnormal EEG, lethargy, and decerebrate posture indicate what condition?
hepatic encephalopathy

Year 2 Gastrointestinal (38 decks)

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