Goljan lab eval of liver cell injury, bilirubin metab, LFTs, labs

Question 1

What are the 5 major steps in bilirubin metabolism?

Answer 1

unconjugated bilirubin (UCB);
UCB combines w/ albumin in blood;
Conjugated bilirubin (CB) secreted into intrahepatic bile ducts;
intestinal bacteria convert CB to urobilinogen (UBG)
20% UBG recycled to liver (90%) & kidneys (10%)

Question 2

How is UCB formed?

Answer 2

senescent RBCs phagocytosed by splenic macs=> UCB is end product of heme degradation => UCB is lipid soluble (indirect bilirubin)

Question 3

What is the purpose of UCB combining w/ albumin in blood?

Answer 3

taken up by hepatocytes then conjugated to glucuronic acid to produce CB => water soluble (direct bilirubin)

Question 4

what occurs to CB after being secreted into intrahepatic bile ducts?

Answer 4

temporarily stored in gallbladder;

enters duodenum via common bile duct

Question 5

what occurs after CB is converted to UBG?

Answer 5

UBG is spontaneously oxidized to urobilin which produces brown color of stool

Question 6

What is jaundice due to?

Answer 6

increase in UCB and/or CB

Question 7

Where and why is jaundice first noticed?

Answer 7

sclera => has high affinity for bilirubin

Question 8

How is jaundice classified?

Answer 8

%CB = CB / total bilirubin

Question 9

What are the types of hyperbilirubinemia assoc w/ CB < 20%?

Answer 9

increased production of UCB;

decreased uptake or conjugation of UCB

Question 10

What is the urine bilirubin w/ CB < 20%?

Answer 10

absent in increased production and decreased uptake/conjugation

Question 11

What is the urine UBG w/ CB <20%?

Answer 11

w/ increased UCB production=> increase urine UBG

decreased uptake / conjugation of UCB => normal urine UBG

Question 12

What are disorders assoc w/ hyperbilirubinemia of CB <20% and increased production of UCB?

Answer 12

extravascular hemolytic anemia => spherocytosis, Rh and ABO HCN, warm AIHA

Question 13

What are disorders in hyperbilirubinemia w/ CB <20% and decreased uptake or conjugation of UCB?

Answer 13

Gilbert’s syndrome;
Crigler-Najjar syndrome;
physiologic jaundice of newborn;
breast milk jaundice

Question 14

Epidemiology of Gilbert’s syndrome

Answer 14

familial nonhemolytic jaundice;
common AR or AD (mutation dependent);
>5% of population
2nd most common cause of jaundice;
most common hereditary cause of jaundice;
males > females

Question 15

Pathogenesis of Gilbert’s syndrome

Answer 15

impaired glucuronyl transferase activity (70-75% decrease in activity)

Question 16

When does jaundice occur in Gilbert’s syndrome?

Answer 16

w/ fasting or increase in alcohol or phenobarbital intake

Question 17

Labs and LFTs w/ Gilbert’s syndrome?

Answer 17

serum UCB rarely > 5mg/dL;

other LFTs normal;

Question 18

Bx and Tx for Gilbert’s syndrome

Answer 18

liver Bx not necessary;

no Tx

Question 19

Define Crigler-Najjar syndrome

Answer 19

genetic disorder w/ decreased to absent glucuronyl transferase enzyme

Question 20

If person is develops Crigler-Najjar syndrome w/ absent glucuronyl transferase enzyme, what must be done?

Answer 20

liver transplant is required bc it is incompatible w/ life

Question 21

When and why does physiologic jaundice of newborn occur?

Answer 21

day 3 and caused by normal mac destruction of fetal RBCs and inability of newborn liver to handle excess load

Question 22

What is the cause of breast milk jaundice? Tx?

Answer 22

due to pregnane-3a,2oa-diol;

no Tx

Question 23

What is the CB in mixed type hyperbilirubinemia?

Answer 23

CB 20-50%

Question 24

what is the urine bilirubin and UBG in mixed hyperbilirubinemia?

Answer 24

increased both bilirubin and UBG

Question 25

disorders of mixed hyperbilirubinemia w/ CB 20-50%

Answer 25

viral hepatitis

Question 26

How does viral hepatitis lead to CB 20-50%?

Answer 26

defect in uptake, conjugation of UCB and secretion of CB

Question 27

What is the CB, urine bilirubin and urine UBG in obstructive hyperbilirubinemia?

Answer 27

CB >50%; increase in urine bilirubin; absent urine UBG

Question 28

Main causes of obstructive hyperbilirubinemia w/ CB>50%?

Answer 28

decreased intrahepatic bile flow; | decreased extrahepatic bile flow

Question 29

What are disorders associated w/ decreased intrahepatic bile flow?

Answer 29

drug induced (OCP); primary biliary cirrhosis; Dubin-Johnson syndrome; Rotor's syndrome

Question 30

define Dubin Johnson syndrome in obstructive hyperbilirubinemia. How does it appear grossly?

Answer 30

AR disorder in secretion into intrahepatic bile ducts; | black pigment in hepatocytes

Question 31

Define Rotor's syndrome and its association w/ obstructive hyperbilirubinemia

Answer 31

AR disorder in secretion into intrahepatic bile ducts but NO BLACK pigment in hepatocytes

Question 32

What are disorders w/ decreased extrahepatic bile flow leading to obstructive hyperbilirubinemia?

Answer 32

gallstone in common bile duct; | carcinoma of head of pancreas

Question 33

LFTs for liver cell necrosis

Answer 33

ALT; | AST

Question 34

characteristics of ALT test

Answer 34

specific enzyme fo rliver clel necrosis; present in cytosol; ALT > AST => viral hepatitis

Question 35

characteristics of AST test

Answer 35

present in mitochondria; alcohol damages mitochondria AST > ALT => alcoholic hepatitis

Question 36

LFTs for cholestasis

Answer 36

GGT; | ALP

Question 37

characteristics of GGT test

Answer 37

intra- or extra hepatic obstruction to bile flow; induction of p450 system (alcohol) => increases GGT

Question 38

characteristics of ALP test

Answer 38

normal GGT and increased ALP => not liver (may be osteoblastic bone activity); increased GGT and increased ALP=> liver cholestasis

Question 39

LFTs of hepatocyte function

Answer 39

serum albumin; prothrombin time (PT); BUN; serum ammonia

Question 40

characteristics of serum albumin test

Answer 40

albumin synthesized in liver; | hypoalbuminemia => severe liver disease (cirrhosis)

Question 41

characteristics of PT test

Answer 41

majority of coag factors synthesized in liver; | increased PT => severe liver disease

Question 42

characteristics of BUN test

Answer 42

urea cycle is present in liver; | decreased BUN=> cirrhosis

Question 43

characteristics of serum ammonia test

Answer 43

ammonia is metabolized in urea cycle in liver => derived from large bowel and AA degradation; increased serum ammonia => cirrhosis, Reye's

Question 44

LFTs for immune function

Answer 44

serum IgM; antimitochondrial Ab; Anti-smooth muscle Ab; ANA

Question 45

increased IgM wrt liver disease

Answer 45

primary biliary cirrhosis

Question 46

presence of antimitochondrial Ab

Answer 46

primary biliary cirrhosis

Question 47

presence of Anti-smooth muscle Ab

Answer 47

autoimmune hepatitis

Question 48

presence of ANA

Answer 48

autoimmune hepatitis

Question 49

LFT tumor markers

Answer 49

AFP

Question 50

presence of AFP

Answer 50

hepatocellular CA

Question 51

give lab findings for normal liver function

Answer 51

absent UB; | increased urine UBG

Question 52

lab findings for viral hepatitis

Answer 52

``` 20-50% CB; very high AST; very very high ALT; slightly high ALP; slightly high GGT; high UB and high urine UBG ```

Question 53

lab findings for alcoholic hepatitis

Answer 53

``` 20-50% CB; high AST; slightly elevated ALT; slightly elevated ALP; very high GGT; high UB and urine UBG ```

Question 54

lab findings for cholestasis

Answer 54

``` >50% CB; slightly elevated AST; high ALT; very high ALP; very high GGT; very high UB; absent UBG ```

Question 55

lab findings for hemolysis

Answer 55

``` <20% CB; high AST RBCs; No change in ALT, ALP, GGT; absent UB; high urine UBG ```