Liver Function Tests Flashcards
liver - major metabolic functions
*nutrient processing (amino acid synthesis, glycogen synthesis and storage, etc)
*lipid metabolism
*vitamin & mineral storage
*plasma protein synthesis (albumin, clotting factors [INR])
*bile secretion
*detoxification
important hepatic enzymes that we measure using liver function tests
*AST
*ALT
*alkaline phosphatase
*GGT
alanine-amino transferase (ALT)
*transaminase that regulates amino acid homeostasis by catalyzing the transfer of an amino group between alanine and pyruvate
*location: mainly hepatocytes
*important role in gluconeogenesis
*requires pyridoxal-PO4 (vitamin B6) as cofactor
aspartate-amino transferase (AST)
*transaminase that regulates amino acid homeostasis by catalyzing the transfer of an amino group between aspartate and glutamate
*location: hepatocytes (also muscle, heart, intestine)
normal ratio of AST:ALT
AST:ALT < 1 (except in alcoholic hepatitis)
impact of hepatocyte injury on AST and ALT levels
*hepatocyte injury (by viruses, toxins, or hypoxia) releases AST and ALT into plasma
*finding elevated levels of AST and ALT indicates that the hepatocytes are “sick”
alkaline phosphatase (ALP)
*location: canalicular membrane, bile duct epithelium
*assists with phosphate reabsorption and detoxification of lipopolysaccharides
*also present in BONE, intestine, and kidney
*plays role in BILE FORMATION AND SECRETION
gamma-glutamyl transpeptidase (GGT)
*location: canalicular membrane, bile duct epithelium
*not present in other tissues (but harder to assay than alkaline phosphatase)
impact of bile duct obstruction on alkaline phosphatase levels
*bile duct obstruction increases ALP synthesis and release into plasma
important plasma proteins measured in liver function tests
*albumin
*clotting factors
albumin
*hepatic synthesis (most abundant plasma protein)
*slow turnover: half-life = 20 days (level affected by nutrition, hydration, acute inflammation, renal disease)
*limited utility in assessing acute liver injury
clotting factors
*hepatic synthesis (except factor VIII and vonW factor)
*note - synthesis of II, VII, X, require vitamin K
*rapid turnover: half-life = 6-60 hours
*INR measures collective function of I, II, V, VII, X
*useful to assess acute liver injury, MELD score
what does INR measure
*collective function of clotting factors: I, II, V, VII, and X
*useful to assess acute liver injury
bilirubin synthesis
- macrophages: RBC destruction, heme degradation, & bilirubin synthesis
- liver: bilirubin uptake, bilirubin conjugation (UDP-glucuronyl transferase), secretion into bile
- intestine: bacterial degradation, urobilinogen absorption, stercobilin excretion
- kidney: urobilinogen uptake; urobilin excretion (pigments the urine)
causes of elevated unconjugated (indirect) bilirubin
*hemolytic anemia (increased red cell destruction)
*decreased UDP glucuronyl transferase activity (Crigler-Najjar & Gilbert’s syndromes; neonatal jaundice)
causes of elevated conjugated (direct) bilirubin
*hepatocyte bilirubin transporter dysfunction (Dubin-Johnson and Rotor syndromes)
causes of elevated conjugated + unconjugated bilirubin (total bili)
*hepatocyte injury or dysfunction
*bile duct obstruction
causes of elevated ALT & AST
*hepatocyte cell injury or necrosis
causes of elevated alkaline phosphatase
*bile duct obstruction
*cholestasis (pathophysiological cessation of bile flow)
hemolytic anemias - pathophysiology
*decreased RBC lifespan; increased RBC destruction -> overwhelms the transport capacity of OATP
*extra-vascular and/or intra-vascular
*causes: autoimmune, mechanical, vasculitis, infections, toxins, drugs, hemoglobinopathies, leukemias
hemolytic anemias - clinical findings
*schistocytes
*nucleated RBCs
*RBC agglutination
hemolytic anemias - lab findings
*total bilirubin: mildly elevated
*direct bilirubin: NORMAL
*urine: bilirubin (-); INCREASED UROBILINOGEN
*plasma: increased LDH; decreased haptoglobin
*CBC: increased reticulocytes; increased RDW
hemolytic anemias - clinical course
*can be indolent or fulminant
*severe cases: hemoglobinuria, CHF, ARDS, shock, renal failure
Gilbert’s syndrome - pathophysiology
*decreased activity of UDP-glucuronyl transferase (activity ~25% of normal)
*dominant or recessive inheritance of UGT1A1 gene SNPs
*very common
Gilbert’s syndrome - clinical findings
faint “lemon yellow” scleral icterus
Gilbert’s syndrome - lab findings
*total bilirubin: mildly elevated
*direct bilirubin: NORMAL
*urine bilirubin: NEGATIVE
*plasma: ALT, AST, AP normal
Gilbert’s syndrome - clinical course
*first noticed in teens/young adults
*increased bilirubin found on routine labs
*transient mild jaundice with fasting, stress, exercise, illnesses
*without established Dx, patients may be rejected for insurance
Crigler-Najjar Syndrome - pathophysiology
*serious impairment of UDP-glucuronyl transferase activity
*type I: absent UDP-GT activity
*type II: ~10% UDP-GT activity
*recessive UGT1A1 gene SNPs
*very rare
Crigler-Najjar Syndrome - lab findings
*type I: total bilirubin = extremely elevated
*type II: total bilirubin = elevated
*direct bilirubin & LFTs NORMAL
note - the elevated total bili is due to elevated unconjugated (indirect) bilirubin (because it is not getting conjugated effectively)
Crigler-Najjar Syndrome - clinical course
*type I: jaundiced at birth; pale stool; severe risk of kernicterus with acute and chronic neurological damage
*type II: jaundice may appear later after birth; lower risk of kernicterus
Crigler-Najjar Syndrome - treatment
*type I: phototherapy, exchange transfusions; liver transplantation
*type II: phototherapy, phenobarbital (induces P450 enzymes, including UDP-GT
physiologic jaundice of newborn - pathophysiology
delayed onset of UDP-glucuronyl transferase activity
physiologic jaundice of newborn - lab findings
*total bilirubin = elevated
*direct bilirubin & LFTs normal
physiologic jaundice of newborn - clinical course
*benign if bili < 20
*if > 20, kernicterus
physiologic jaundice of newborn - treatment
phototherapy
how does phototherapy affect neonatal jaundice
*makes unconjugated bilirubin water-soluble (without the need to be conjugated)
Dubin-Johnson syndrome - pathophysiology
*defective canalicular MRP2
*recessive inheritance
*bilirubin is conjugated but not excreted
Dubin-Johnson syndrome - lab findings
*total bilirubin: mildly elevated
*most bilirubin is conjugated (direct)
*urine bilirubin: positive
*plasma: ALT, AST, AP normal
*normal urine coproporphyrin
*abnormal copro-I/III ratio = 4:1
Dubin-Johnson syndrome - clinical course
*liver has BLACK PIGMENTATION
*hyperechoic appearance on ultrasound
*gallbladder not visualized on HIDA or OCG
Dubin-Johnson syndrome - treatment
*benign condition (no treatment)
Rotor syndrome - pathophysiology
*defective sinusoidal OATP
*bilirubin is conjugated but not excreted
Rotor syndrome - lab findings
*total bilirubin: mildly elevated
*most bilirubin is conjugated (direct)
*urine bilirubin: positive
*plasma: ALT, AST, AP normal
*increased urine coproporphyrin
*copro-I/III ratio = 1:4
Rotor syndrome - clinical course
*normal liver appearance
*normal radiological gallbladder visualization
note - contrast these to the findings in Dubin-Johnson (where the liver is black)
Rotor syndrome - treatment
benign condition (no treatment)
what are the “LFTs”
*liver function tests:
-total bilirubin
-ALT
-AST
-alkaline phosphatase
-INR
physical exam findings indicative of liver disease
*scleral icterus
*hepatomegaly
*spider hemangioma
*palmar erythema
*gynecomastia
*abdominal distension, shifting dullness, fluid wave
*peripheral edema
*signs of CHF
*ecchymoses
*asterixis
*caput medusa
*corneal rings
imaging for evaluation of liver disease
*start with RUQ ultrasound!
