Evaluation of Liver Function Flashcards
Hepatocyte system functions
1 Metabolic reactions
2 Macromolecular synthesis
3 Macromolecular degradation
4 Metabolism of xenobiotics
Three systems in the liver
1 Hepatocyte
2 Biliary system
3 Reticuloendothelial system (RES)
Biliary system functions
1 Metabolism of bilirubin and bile salts
2 Involves transport of bilirubin into the hepatocyte, its conjugation to glucoronic acid, its secretion into bile canaliculi and the enterohepatic system
Reticuloendothelial system (RES) functions
1 Immune system function
2 Production of heme and globin metabolites
Synthesis of hormones (angiotensinogen, insulin like growth factor 1)
Biochemical hepatocytic system
Site of clearance of insulin, parathyroid hormone, estrogen, cortisol
Biochemical hepatocytic system
Site of metabolism of ammonia to urea
Biochemical hepatocytic system
Site of synthesis of albumin and coagulation factors (except von Willebrand factor)
Biochemical hepatocytic system
Hepatic metabolism
Bilirubin is transported into the hepatocyte, where it is converted into the diglucoronide form and secreted into canaliculi
Reticuloendothelial system
Kuppfer cells
Kuppfer cells
1 Major site of defense against intestinal bacteria
2 Primary location for removal of antigen-antibody complexes from the circulation
3 Breakdown of hemoglobin from dead erythrocytes, giving rise to bilirubin, which, together with bilirubin from the spleen, enters the hepatocyte
Normal hemoglobin variants
HbF (infant)
HbA (adult)
Pathway of bilirubin
(Review)
Urobilinogen and urobilin may be
1 Reabsorbed from the gut
2 Reexcreted in the liver
3 Excreted in the urine
Bilirubin metabolism
After canalicular excretion, it is further metabolized by intestinal bacteria in the intestine forming urobilinogen and urobilin
Neonatal bilirubin reference ranges
Full term 0-24 hr: 2.0-6.0 mg/dL Full term 24-48 hr: 6:0-10.0 mg/dL Full term 3-5 days: 4.0-8.0 mg/dL Premature 0-24 hr: 1.0-8.0 mg/dL Premature 24-48 hr: 6.0-12.0 mg/dL Premature 3-5 days: 10.0-14.0 mg/dL
Causes of elevated serum levels of unconjugated bilirubin
1 Hemolysis (e.g. Sickle cell anemia) 2 Gilbert's syndrome 3 Crigler Najjar Syndrome 4 Cirrhosis 5 Toxic substances
Affected infants develop severe unconjugated hyperbilirubinemia leading to kernicterus causing severe motor dysfunction and retardation
Crigler Najjar Syndrome Type 1
Treatment of Crigler Najjar Syndrome Type 1
Phototherapy
Interferences in neonatal bilirubin test
1 Dietary pigments
2 Light
Specimen in neonatal bilirubin test
Serum
Plasma
Neonatal bilirubin reaction principle
1 Serum is diluted with phosphate buffer at pH 7.4
2 Absorbance is determined at 454 and 540 nm (oxyhemoglobin)
3 Concentration is determined from a standardized curve using adjusted (subtracted) absorbance from the sample (dual-wavelength narrow bandpass spectrophotometer)
Fibrosis leading to decrease in cellular mass and alteration in blood flow
Cirrhosis
Causes of elevated serum levels of conjugated bilirubin
1 Dubin-Johnson Syndrome 2 Rotor syndrome 3 Biliary obstruction 4 Ascending cholangitis 5 Gram negative sepsis
Dubin-Johnson Syndrome clinical manifestations
1 Mild jaundice
2 Total bilirubin, 2-5 mg/dL
3 Intense dark pigmentation of the liver due to accumulation of lipofuscin pigment
Blockade of the excretion of bilirubin into the canaliculi
Dubin-Johnson Syndrome
Causes Dubin-Johnson Syndrome
Defects in the adenosine triphosphate (ATP)-binding cassette (ABC) canalicular multispecific organic anion transporter, MRP2/cMOAT/ABCC2
Suppress neonatal conjugation of bilirubin
1 Progesterone
2 Other hormones in breast milk
3 Betaglucoronidase
T or F. Hyperbilirubinemia may be more pronounced due to blood group differences of mother and child (group O mothers)
T
Causes an increase in supply of heme for degradation to bilirubin
Higher turnover of neonatal erythrocytes shortly after birth in order to replace fetal hemoglobin (HbF) with hemoglobin A
Causes of physiological jaundice of the newborn
1 Short-term or transient immaturity of the liver
2 Short-term delay in ability to produce UDPG-transferase for conjugation
Physiological jaundice of the newborn tests
1 Slight increase in bilirubin in the first few days of life when compared to the normal adult bilirubin level. Peaks at around 2-4 days but may remain elevated for up to 2 weeks.
2 Associated with increased total and unconjugated bilirubin but near-normal conjugated bilirubin
3 Serum hepatic enzyme levels are typically normal since there is no associated cell inflammation
Hemolytic disease of newborns
1 Fetal cells entering mother’s blood stream at birth
2 Maternal memory cells generate IgG antibodies directed against Rh factor expressed on fetal RBCs
3 Results in mild to severe anemia in second fetus
Rotor syndrome
1 Viral in etiology
2 Does not cause liver hyperpigmentation
Most common cause of hyperbilirubinemia in adults
Cholelithiasis
