SEARCH RESULTS FOR: Unconjugated-Hyperbilirubinemia

Unconjugated Hyperbilirubinemia

Pre-hepatic causes of ↑ bilirubin production Pathologic Unconjugated Neonatal Hyperbilirubinemia: Pathogenesis and clinical findings Hemolytic disease of the newborn** Isoimmune- mediated hemolysis Rhesus (Rh) factor incompatibility Maternal sensitization against Rh-positive fetal cells Maternal antibodies against Rh factor attack fetal RBCs ABO incompatibility Native maternal antibodies against non- native blood types attack fetal RBCs Sepsis** Widespread systemic inflammation Cytokines & complement factors damage RBC membranes Disseminated intravascular coagulation** (clotting proteins become overactive) Clots form in systemic circulation Small clots shear & damage RBCs in circulation Red blood cell (RBC) enzyme defects Glucose-6 phosphatase dehydrogenase (G6PD) deficiency** G6PD protects RBCs against oxidative damage ↑ RBC sensitivity to oxidative stress (during acute stressors) Pyruvate kinase deficiency (PKD) Abnormal glycolysis & cellular energy production ↓ RBCs life spans RBC membrane defects Hereditary spherocytosis RBCs are abnormally round (spherocytes) RBC membranes easily damaged in circulation Bilverdin reductase Hereditary elliptocytosis RBCs are abnormally elongated or oval converts bilverdin to Sickle cell Abnormal hemoglobin (HbS) RBCs become abnormally unconjugated bilirubin disease** polymerizes under ↓ O2 sickle shaped Hemoglobinopathies Thalassemia's** Defective hemoglobin chains in RBCs Irregularly shaped RBCs trapped in spleen RBC sequestration ↑ Production of RBCs (Polycythemia**) Accumulation of blood (i.e. Cephalohematoma, hemorrhage) ↑ RBC load & turnover Causes of ↓ hepatocellular bilirubin clearance Genetic defects in uridine diphosphate glucuronosyltransfe rase (UGT) enzyme (conjugates bilirubin in liver) Gilbert syndrome Unconjugated bilirubin ↓ UGT production remains insoluble & cannot Crigler–Najjar be excreted in bile syndrome Type II Crigler–Najjar syndrome Type I No UGT production Breast milk jaundice Breast milk contains β-glucuronidase Causes of ↑ entero-hepatic bilirubin circulation Intestinal obstruction Obstruction blocks bile flow from liver to intestines Breastfeeding jaundice Inadequate milk intake (volume depletion/dehydration) ↑ Reabsorption of bilirubin in the intestines **See corresponding Calgary Guide slide Legend: Macrophages engulf old or damaged RBCs in spleen & liver ↑ Hemolysis (RBC breakdown) RBCs release cellular contents including heme (from hemoglobin) Heme oxygenase converts heme to bilverdin ↑ Unconjugated (indirect) bilirubin accumulation in blood ↑ Total serum bilirubin levels Excess bilirubin deposition into elastin- rich tissues (eg. skin, sclera) due to ↑ affinity for elastin Pathologic neonatal jaundice (yellow discoloration of skin within first 24 hours of life) Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 13, 2025 on www.thecalgaryguide.com Authors: Merry Faye Graff Khushi Arora Reviewers: Annie Pham Emily J. Doucette Danielle Nelson* * MD at time of publication Hemolytic anemia** ↓ Bilirubin conjugation β-glucuronidase deconjugates bilirubin Bilirubin builds up in hepatic system Unconjugated bilirubin crosses blood-brain barrier Bilirubin-induced neurologic dysfunction (BIND) Kernicterus (bilirubin- induced neurological damage) Scleral icterus (yellowing of sclera in eyes)