Gi Exam 1: Lft Basics

Front 1

what LFT are markers of hepatocellular injury

Back 1

aminotransferases: ALT and AST (with liver injury or cell death these enzymes are released and hence increase serum levels)

Front 2

what LFTs are markers of cholestasis

Back 2

alkaline phosphatase (AP), gamma glutamyl transferase (GGT), bilirubin

Front 3

what are the LFT markers of hepatic synthetic function

Back 3

PT, albumin, bilirubin

Front 4

why is bilirubin conjugated for excretion

Back 4

to prevent free bilirubin from being by the kidneys

Front 5

what is bilirubin

Back 5

the breakdown product of the heme from hemoglobin

Front 6

what is the advantage of conjugating bilirubin

Back 6

it becomes water soluble and then can be excreted in the bile (and then GI tract)

Front 7

what enzymes is responsible for conjugating bilirubin in the liver

Back 7

UGT

Front 8

name two inherited unconjugated hyperbilirubinemias

Back 8

gilbert's and crigler-najjar syndrome. both are from defects in UGT

Front 9

name two inherited conjugated hyperbilirubinemias

Back 9

dubin-johnson syndrome and rotor syndrome

Front 10

is bilirubin normally convalently bound to albumin

Back 10

no

Front 11

what is bilirubin delta

Back 11

the fraction of Bc covalently bound to albumin (this happens when serum levels of bilirubin are high). it has the same half life as albumine due to the covalent binding- 20 days. Normally the levels are so low that they can be ignored.

Front 12

what does total bili measure

Back 12

Bc + Bu + Bd

Front 13

what does direct bili measure

Back 13

Bc + Bd

Front 14

what does indirect bili measure

Back 14

tbili - direct bili = Bu

Front 15

with unconjugated hyperbilirubinemia is the urine of normal color or darkly pigmented

Back 15

normal color since the Bu does not get excreted by the kidneys

Front 16

does Bu appear in the urine

Back 16

NO, Bu is not water soluble. Only Bc is filtered by the kidneys (Note: Bu may appear in the urine if there is spillage from nephrotic syndrome)

Front 17

where are urobilinogens excreted

Back 17

mostly in the feces but some is reabsorbed into the circulation and some is picked up by the liver for excretion and some is excreted in the urine

Front 18

is ALT specific to the liver

Back 18

yes

Front 19

is AST specific to the liver

Back 19

no, it is also found skeletal and cardiac muscle, kidney, brain, pancreas, intestines, lungs, leukocytes and erythrocytes

Front 20

is AP specific to the liver

Back 20

no, its also found in bone and placenta

Front 21

is GGT specific for liver injury

Back 21

no

Front 22

is GGT sensitive for liver injury

Back 22

yes very, it is elevated even with minor damage sucj as alcohol ingestion

Front 23

is GGT sensitive for liver injury

Back 23

yes very, it is elevated even with minor damage such as alcohol ingestion

Front 24

what would the LFTs look like in hemolysis

Back 24

only the tbili would be increased

Front 25

what AST:ALT ratio would you expect in alcoholic hepatitis

Back 25

over 2:1

Front 26

what are the 2 blood supplies to the liver?

Back 26

hepatic artery (high pressure, low volume) and hepatic portal vein (low pressure, high volume)

Front 27

if left, right, and middle hepatic veins are occluded by thrombus, what happens?

Back 27

the caudate veins are responsible for drainage of liver --> caudate lobe will expand

Front 28

what are the 3 structures contained in the portal tract?

Back 28

portal venule, hepatic arteriole, interlobular bile duct

Front 29

define the limiting plate

Back 29

interface b/w portal connective tissue and adjacent hepatocytes

Front 30

what is interface hepatitis?

Back 30

hepatitis leads to jagged irregular limiting plate on histology

Front 31

what are the constituents of bile?

Back 31

bilirubin, bile salts, drug metabolites

Front 32

sinusoid endothelium is different from other endothelial membranes in what 2 ways?

Back 32

1. has no basement membrane 2. has fenestrations

Front 33

name the 5 basic functions of the liver

Back 33

PRODUCTION OF BILE (fat absorption, elimination of waste products), METABOLISM (carb, protein, fat), STORAGE (glycogen, TGs, iron, copper, ADEK), DETOXIFICATION (ammonia->urea, EtOH + drugs and metabolites), SYNTHESIS (albumin, coag factors, complement proteins)

Front 34

name the 7 tests given in basic LFTs

Back 34

ALT, AST, alkaline phosphatase, gamma-glutamyl transferase, bilirubin, PT, albumin

Front 35

which LFTs are markers of hepatocellular injury?

Back 35

aminotransferases (ALT, AST)

Front 36

which LFTs are markers of cholestasis

Back 36

alkaline phosphatase (AP), gamma-glutamyl transferase (GGT), bilirubin

Front 37

which LFTs are markers of hepatic synthetic function?

Back 37

prothrombin time (PT), albumin, bilirubin

Front 38

is bilirubin made in the liver? why is it tested in LFTs?

Back 38

bilirubin is not made in the liver, but it is conjugated in the liver

Front 39

what happens when a RBC gets tired and dies

Back 39

hemoglobin is broken down into amino acids + iron + heme --> amino acids + iron are recycled, heme is catabolized to bilirubin

Front 40

describe the bilirubin pathway

Back 40

naked bilirubin (Bu) is noncovalently and tightly bound to albumin for transport in the serum --> in the liver, bilirubin is conjugated to glucuronic acid and becomes water soluble --> conjugated bilirubin (Bc) is excreted in the bile --> enters GI tract and ampulla border --> bacteria in the GI tract metabolize bilirubin to urobilinogens (largely eliminated in the feces)

Front 41

unconjugated bilirubin ____ in the urine

Back 41

unconjugated bilirubin NEVER APPEARS in the urine, unless there is spillage of albumin (e.g., nephrotic syndrome

Front 42

where do urobilinogens end up

Back 42

urobilinogens are largely eliminated in the feces, a small fraction is absorbed into the circulation, a portion is picked up by liver for re-excretion, another portion is excreted in the urine

Front 43

what happens to bilirubin in the liver (4 processes)

Back 43

1. bilirubin uptake 2. intracellular binding 3. bilirubin glucoronidation (conjugation) facilitated by uridine glucoronosyltransferase (UGT) 4. excretion of conjugated bilirubin into bile canaliculi

Front 44

inherited unconjugated hyperbilirubinemias are genetic abnormalities in UGT that cause which 3 diseases?

Back 44

gilbert's syndrome, crigler najjar syndrome type I and II

Front 45

inherited conjugated hyperbilirubinemias result in genetic abnormalities in Bc excretion are caused by what 2 diseases?

Back 45

dubin-johnson syndrome, rotor syndrome

Front 46

what is bilirubin delta?

Back 46

Bc bound COVALENTLY to albumin (occurs when Bc is significantly elevated in the plasma), has ~20 day half-life (same as albumin), is not excreted

Front 47

after a stone is removed in CBD, why is there an initial drop in bilirubin levels followed by a slow decrease to normal levels?

Back 47

because there is a fast drop-off as the Bu and Bc is cleared from the serum, but Bdelta takes a long time to clear b/c it is covalently bound to albumin (t1/2 = 20 days)

Front 48

what is direct bilirubin?

Back 48

Bc + Bdelta

Front 49

how is indirect bilirubin measured?

Back 49

total bili - direct bilirubin

Front 50

hyperbilirubinemia typically produces the clinical sign of ___

Back 50

jaundice

Front 51

what are the 3 etiologic categories of jaundice?

Back 51

pre-hepatic, hepatocellular, obstructive

Front 52

pre-hepatic jaundice is usually due to ____, w/_____ of bilirubin, resulting in ______

Back 52

pre-hepatic jaundice is usually due to HEMOLYSIS, w/OVERPRODUCTION of bilirubin, resulting in UNCONJUGATED HYPERBILIRUBINEMIA

Front 53

with hemolytic anemia, will urine be of normal color or darkly pigmented?

Back 53

normal (unconjugated bilirubin is not filtered by the kidneys --> will not appear in the urine)

Front 54

hepatocellular jaundice is commonly caused by ____, and results in decreased bilirubin ___, ___, and ___

Back 54

hepatocellular jaundice is commonly caused by DRUGS or VIRAL HEPATITIS, and results in decreased UPTAKE, CONJUGATION, and EXCRETION of bilirubin

Front 55

what lab values are expected w/drug-induced jaundice or viral hepatitis jaundice? is the urine dark?

Back 55

mixed Bu and Bc hyperbilirubinemia, urine often dark

Front 56

obstructive jaundice is often caused by ___, and lab values show ___.

Back 56

obstructive jaundice is often caused by CHOLEDOCOHLITHIASIS, which leads to a strikingly high hyperbilirubinemia of almost entirely CONJUGATED BILIRUBIN.

Front 57

define choledocholithiasis

Back 57

gallstone migrating out of gallbladder and lodging in common bile duct

Front 58

in choledocholithiasis (obstructive jaundice), what will urine look like? stool? will the urine contain urobilinogens?

Back 58

urine will be very dark (high levels of conjugated bilirubin excreted by kidneys), stool will be light, urine will not contain urobilinogens (b/c bilirubin is blocked from entering the colon)

Front 59

AST and ALT are the most frequently used indicators of _____

Back 59

AST and ALT indicate NECROINFLAMMATORY LIVER DISEASES. note: elevated serum levels do not reflect increased enzyme synthesis, but rather enzyme release due to liver cell injury and death

Front 60

ALT is found ___, AST is found ___

Back 60

ALT is found almost exclusively in the liver, AST is found in low levels in other organs

Front 61

true or false: ALT can be used to screen for liver damage.

Back 61

true. ALT is elevated in even minor hepatocellular injury, but note that current standards for normal may be high in patients w/subclinical liver disease (chronic HCV, nonalcoholic fatty liver dz)

Front 62

aminotransferase levels rely on what two things? is there a correlation b/w the height of ALT and severity of parenchymal damage?

Back 62

aminotransferase levels depend on the amount released and the rate of clearance. there is no strict correlation, but is a good rough estimate of severity of liver damage.

Front 63

what danger should you watch out for in aminotransferase level evaluation?

Back 63

normal levels do not exclude chronic disease. advanced cirrhosis is associated w/decrease in ALT synthesis, can also see fluctuating aminotransferase levels in chronic hep c despite ongoing necroinflammation (AST:ALT ratio can be helpful)

Front 64

liver alkaline phosphatase is an indicator of ___, but does not differentitae between ___ and ___

Back 64

liver AP is an indicator of CHOLESTASIS, but does not differentiate b/w intra- and extrahepatic

Front 65

if AP levels are disproportionately high (>1000 U/L) compared to bilirubin concentration, what should be on your differential?

Back 65

granulomatous disorders (sarcoidosis, Tb) and infiltrative lesions (tumors, absces), primary biliary cirrhosis, primary sclerosing cholangitis

Front 66

Gamma-glutamyltransferase can help confirm ____ of an elevated ___.

Back 66

elevated GGT levels can help confirm the HEPATIC ORIGIN of an elevated AP level

Front 67

GGT is a ___ but ___ indicator of liver injury

Back 67

sensitive, non-specific (alcohol and many meds can cause increase in GGT levels)

Front 68

a decrease in GGT levels can be useful in what setting?

Back 68

shows abstinence from alcohol in alcohol abuse patients

Front 69

is liver synthetic function disrupted early or late in liver disease?

Back 69

late. the liver's synthetic capacity has a large reserve.

Front 70

true or false: albumin is produced exclusively in the liver.

Back 70

true. represents up to 20% of liver's total protein synthesizing capacity

Front 71

albumin is ___ and ___ as an indicator of liver function

Back 71

non-sensitive, non-specific

Front 72

albumin concentrations are a marker of ___in cirrhosis

Back 72

albumin is a marker of DECOMPENSATION (and prognosis) in cirrhosis

Front 73

true or false: hypoalbuminemia in decompensated cirrhosis is exclusively due to reduced hepatic synthesis

Back 73

false. also due to third spacing (edema, ascitis) and dilutional peripheral hypoalbuminemia

Front 74

in addition to chronic liver disease, hypoalbuminemia can result from ___

Back 74

protein loss. includes nephrotic syndrome, burns, enteropathy

Front 75

which factors of the extrinsic pathway of the coagulation cascade are made by the liver?

Back 75

all of them! --> PT is a sensitive parameter that estimates global hepatic protein synthetic capacity (these have short 1/2-lives)

Front 76

what are the vitamin-k dependent factors? (you should know these in your sleep!)

Back 76

2, 7, 9, 10, protein c, protein s

Front 77

describe the lab values seen in hemolysis

Back 77

isolated modest elevation in TBili

Front 78

describe the lab values seen in choledocholithiasis

Back 78

modest elevation in AST and ALT (ALT>AST), elevated AP and GGT, elevated Tbili (mostly direct or conjugated)

Front 79

describe the lab values seen in alcoholic hepatitis

Back 79

high AST and ALT w/AST level 2x ALT level, AP and GGT are high, TBili is high

Front 80

modest elevation in GGT is a ___

Back 80

non-specific lab finding --> may be due to alcohol use, usually requires no further investigation

Front 81

describe the lab values seen in early primary biliary cirrhosis

Back 81

AP and GGT are high, AST and ALT and Tbili may be at upper borders of normal

Front 82

describe the lab values seen in cirrhosis

Back 82

high AST, ALT on upper limit of normal, slightly high AP and GGT, slightly high TBili, low Albumin, high PT

Front 83

describe the lab values seen in multiple liver metastases

Back 83

can present w/surprisingly few lab abnormalities, may see high AP and GGT, total bilirubin may be normal (b/c of remaining ducts that may still function)

Front 84

what does an LFT test w/all normal values but very elevated AP suggest?

Back 84

bone disease --> recall that LFTs are non-specific markers of liver disease

Front 85

describe the lab values seen in tylenol overdose

Back 85

very high AST and ALT, slightly high AP and GGT, very high TBili, very high PT, normal albumin (acute liver injury)