bilirubin metabolism- reticuloendothelial cells (spleen)- lipid soluble and virtually insoluble in water- unconjugated bilirubin + albumin- blood- space of Disse- enzyme UDP- conjugation with glucuronide- hydrophilic bilirubin- MRP2 (the only energy-dependent step)- colon+ bacteria- urobilinogen- stool or reabsorbrion- urine (small part)+ liver and re-excretion.
MEASUREMENT OF SERUM BILIRUBIN
Conjugated measured by direct reaction and total efter addition of reagent, unconjugated by calculation.
Delta bilirubin- conjugated+albumin (half life of bilirubin like albumin 20d)- not secreted in urine- prolonged hyperbilirubunemia- explains prolonged hyperbilirubinemia dispite of resolution and absence of bilirubin in urine.
CAUSE MECHANISM Ineffective Erythropoiesis Overproduction of bilirubin
Indirect Hyperbilirubinemia Cobalamin deficiency
Hemolytic Disorders Overproduction of bilirubin Folate deficiency
Inherited Profound iron deficiency
Red cell enzyme defects (e.g., glucose-6-phosphate dehydrogenase deficiency) Thalassemia
Sickle cell disease Drugs: Rifampin, Probenecid Impaired hepatocellular uptake
Spherocytosis and elliptocytosis Inherited ConditionsCrigler-Najjar syndrome types I and II Impaired conjugation of bilirubin
Acquired Gilbert's syndrome
Drugs and toxins Other
Hypersplenism Hematoma Overproduction of bilirubin
Immune mediated Direct Hyperbilirubinemia
Paroxysmal nocturnal hemoglobinuria Inherited Conditions
Traumatic: macro- or microvascular injury Rotor's syndrome Dubin-Johnson syndrome Impaired excretion of conjugated bilirubin
Gilbert- A mutation in UDP glucuronyl transferase - reduction in enzyme activity. Crigler-Najjar syndrome, types I (absence of enzyme activity) and II (significantly reduced UDP)- much greater elevations of unconjugated serum bilirubin. Conjugated- Dubin-Johnson syndrome- MRP2 gene, and Rotor.
Vanishing bile duct syndrome Amoxicillin-clavulanic acid Chlorpromazine Dicloxacillin Erythromycins Flucloxacillin
Vitamin K deficiency is identified by demonstrating that subcutaneous administration of vitamin K (e.g., 10 mg) leads to improvement in the prothrombin time; a 30% or more improvement in the prothrombin time is consistent with hypovitaminosis K. Oral vitamin K is not absorbed by the intestine in patients with jaundice.
TESTS TO DETECT HEPATIC FIBROSIS
A fasting hyaluronan level greater than 100 mg/L had a sensitivity of 83% and specificity of 78% for the detection of cirrhosis
FibroTest
Transient elastography- differentiating cirrhosis from absence of cirrhosis but was less accurate for the estimation of lesser degrees of fibrosis.
In one study,[51] MRE was found to be superior to TE for staging liver fibrosis
Serum bile acids are elevated in patients with cholestatic liver diseases but normal in patients with Gilbert's syndrome and Dubin-Johnson syndrome and can be used to make the distinction.
