Goljan lab eval of liver cell injury, bilirubin metab, LFTs, labs Flashcards
What are the 5 major steps in bilirubin metabolism?
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%)
How is UCB formed?
senescent RBCs phagocytosed by splenic macs=> UCB is end product of heme degradation => UCB is lipid soluble (indirect bilirubin)
What is the purpose of UCB combining w/ albumin in blood?
taken up by hepatocytes then conjugated to glucuronic acid to produce CB => water soluble (direct bilirubin)
what occurs to CB after being secreted into intrahepatic bile ducts?
temporarily stored in gallbladder;
enters duodenum via common bile duct
what occurs after CB is converted to UBG?
UBG is spontaneously oxidized to urobilin which produces brown color of stool
What is jaundice due to?
increase in UCB and/or CB
Where and why is jaundice first noticed?
sclera => has high affinity for bilirubin
How is jaundice classified?
%CB = CB / total bilirubin
What are the types of hyperbilirubinemia assoc w/ CB < 20%?
increased production of UCB;
decreased uptake or conjugation of UCB
What is the urine bilirubin w/ CB < 20%?
absent in increased production and decreased uptake/conjugation
What is the urine UBG w/ CB <20%?
w/ increased UCB production=> increase urine UBG
decreased uptake / conjugation of UCB => normal urine UBG
What are disorders assoc w/ hyperbilirubinemia of CB <20% and increased production of UCB?
extravascular hemolytic anemia => spherocytosis, Rh and ABO HCN, warm AIHA
What are disorders in hyperbilirubinemia w/ CB <20% and decreased uptake or conjugation of UCB?
Gilbert’s syndrome;
Crigler-Najjar syndrome;
physiologic jaundice of newborn;
breast milk jaundice
Epidemiology of Gilbert’s syndrome
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
Pathogenesis of Gilbert’s syndrome
impaired glucuronyl transferase activity (70-75% decrease in activity)
When does jaundice occur in Gilbert’s syndrome?
w/ fasting or increase in alcohol or phenobarbital intake
Labs and LFTs w/ Gilbert’s syndrome?
serum UCB rarely > 5mg/dL;
other LFTs normal;
Bx and Tx for Gilbert’s syndrome
liver Bx not necessary;
no Tx
Define Crigler-Najjar syndrome
genetic disorder w/ decreased to absent glucuronyl transferase enzyme
If person is develops Crigler-Najjar syndrome w/ absent glucuronyl transferase enzyme, what must be done?
liver transplant is required bc it is incompatible w/ life
When and why does physiologic jaundice of newborn occur?
day 3 and caused by normal mac destruction of fetal RBCs and inability of newborn liver to handle excess load
What is the cause of breast milk jaundice? Tx?
due to pregnane-3a,2oa-diol;
no Tx
What is the CB in mixed type hyperbilirubinemia?
CB 20-50%
what is the urine bilirubin and UBG in mixed hyperbilirubinemia?
increased both bilirubin and UBG
disorders of mixed hyperbilirubinemia w/ CB 20-50%
viral hepatitis
How does viral hepatitis lead to CB 20-50%?
defect in uptake, conjugation of UCB and secretion of CB
What is the CB, urine bilirubin and urine UBG in obstructive hyperbilirubinemia?
CB >50%;
increase in urine bilirubin;
absent urine UBG
Main causes of obstructive hyperbilirubinemia w/ CB>50%?
decreased intrahepatic bile flow;
decreased extrahepatic bile flow
What are disorders associated w/ decreased intrahepatic bile flow?
drug induced (OCP);
primary biliary cirrhosis;
Dubin-Johnson syndrome;
Rotor’s syndrome
define Dubin Johnson syndrome in obstructive hyperbilirubinemia. How does it appear grossly?
AR disorder in secretion into intrahepatic bile ducts;
black pigment in hepatocytes
Define Rotor’s syndrome and its association w/ obstructive hyperbilirubinemia
AR disorder in secretion into intrahepatic bile ducts but NO BLACK pigment in hepatocytes
What are disorders w/ decreased extrahepatic bile flow leading to obstructive hyperbilirubinemia?
gallstone in common bile duct;
carcinoma of head of pancreas
LFTs for liver cell necrosis
ALT;
AST
characteristics of ALT test
specific enzyme fo rliver clel necrosis;
present in cytosol;
ALT > AST => viral hepatitis
characteristics of AST test
present in mitochondria;
alcohol damages mitochondria
AST > ALT => alcoholic hepatitis
LFTs for cholestasis
GGT;
ALP
characteristics of GGT test
intra- or extra hepatic obstruction to bile flow;
induction of p450 system (alcohol) =>
increases GGT
characteristics of ALP test
normal GGT and increased ALP => not liver (may be osteoblastic bone activity);
increased GGT and increased ALP=> liver cholestasis
LFTs of hepatocyte function
serum albumin;
prothrombin time (PT);
BUN;
serum ammonia
characteristics of serum albumin test
albumin synthesized in liver;
hypoalbuminemia => severe liver disease (cirrhosis)
characteristics of PT test
majority of coag factors synthesized in liver;
increased PT => severe liver disease
characteristics of BUN test
urea cycle is present in liver;
decreased BUN=> cirrhosis
characteristics of serum ammonia test
ammonia is metabolized in urea cycle in liver => derived from large bowel and AA degradation;
increased serum ammonia => cirrhosis, Reye’s
LFTs for immune function
serum IgM;
antimitochondrial Ab;
Anti-smooth muscle Ab;
ANA
increased IgM wrt liver disease
primary biliary cirrhosis
presence of antimitochondrial Ab
primary biliary cirrhosis
presence of Anti-smooth muscle Ab
autoimmune hepatitis
presence of ANA
autoimmune hepatitis
LFT tumor markers
AFP
presence of AFP
hepatocellular CA
give lab findings for normal liver function
absent UB;
increased urine UBG
lab findings for viral hepatitis
20-50% CB; very high AST; very very high ALT; slightly high ALP; slightly high GGT; high UB and high urine UBG
lab findings for alcoholic hepatitis
20-50% CB; high AST; slightly elevated ALT; slightly elevated ALP; very high GGT; high UB and urine UBG
lab findings for cholestasis
>50% CB; slightly elevated AST; high ALT; very high ALP; very high GGT; very high UB; absent UBG
lab findings for hemolysis
<20% CB; high AST RBCs; No change in ALT, ALP, GGT; absent UB; high urine UBG
