Abnormal Hemoglobin PDF

Abnormal Hemoglobin Normal Breakdown of Hemoglobin • Macrophages breaks down heme from globin and degrades them • 85% of heme comes from mature RBCs • 15% of heme from immature RBCs Blood Circulation: Ferrin/Iron goes to liver for storage Formation of Bilirubin: Heme turns via Heme oxygenase à biliv...

Abnormal Hemoglobin Normal Breakdown of Hemoglobin • Macrophages breaks down heme from globin and degrades them • 85% of heme comes from mature RBCs • 15% of heme from immature RBCs Blood Circulation: Ferrin/Iron goes to liver for storage Formation of Bilirubin: Heme turns via Heme oxygenase à biliverdin turns via Biliverdin reductase à Bilirubin Bile formation: Bilirubin-Albumin complex goes to liver à turns into Bilirubin in liver Jaundice, Icterus • 2 causes o á Bilirubin due to Hemolysis o â Excretion of Bilirubin due to Liver damage and Bile duct obstruction • Leads to Yellow skin and sclerae due to increased bilirubin in blood • Classifications of Jaundice o Hemolytic Jaundice (pre-hepatic): Normal feces and urine - Sickle cell anemia What are the ways Jaundice occurs (increased bilirubin)? - Malaria Due to Hemolysis, Liver damage, bile duct obstruction - Injection of hypotonic saline o Obstructive (post hepatic): Dark urine w pale stools - Bile stones - Hepatic and pancreatic tumors o Hepatocellular: variable color of urine/feces (normal or dark) - Cirrhosis - Hepatitis - Prolonged bile duct obstructions - Manifestations: • Reduced uptake of unconjugated bilirubin from circulation • Reduced uptake of conjugated bilirubin, urobilinogen from enterohepatic circulation • Impaired conjugation of bilirubin • Impaired hepatocellular excretion of conjugated bilirubin into bile • Excess Fe3+ o Hemochromatosis: Iron overload from increased iron intake or repeated transfusions o Hereditary Hemochromatosis: Excess absorption of iron due to genetic disorder Blood Levels Hemolytic/Pre-Hepatic Hepatocellular/Hepatic Obstructive/Post-Hepatic Urine Bilirubin Absent Absent/Increased Increased Urine Urobilinogen Increased Increased/Decreased Decreased Urine Color Normal Normal/Dark: varies Dark Stool Color Normal Normal/Pale: varies Pale Jaundice in Newborns • More susceptible to jaundice due to âbilirubin glucuronyl transferase activity • Excess unconjugated bilirubin in blood can diffuse to basal ganglia causing toxic encephalopathy Normal Hb Form Chain Composition Fraction in Normal Adults Found in: Hb A α2β2 90% Adult Hb F α2 γ2 --Fetus and Adult Sickle Cell disease occurs due to abnormal hemoglobin • Causes breakdown of RBC • Clumping of cells and clogging of small blood vessels • Accumulation of sickled cells in spleen Categories of Hemoglobinopathies (2 categories) • Conformational change of Hb due to AA sequence alterations (HbS, HbC, HbSC) o Hb S disease (sickle cell anemia) • High prevalence of Hb S due to heterozygous state against malaria caused by Plasmodium falciparum • Glutamic acid is replaced with valine • Factors that increase sickle cell severity: o â O2 tension o á CO2 o á acidity o á2,3-BPG o á Temperature o Hb C disease: Glutamic acid is replaced with lysine o Hb SC disease: Glutamic acid on one beta chain replaced with valine, and replaced on the other with lysine • Decreased production of Hb causes Thalasemia: â production of alpha and beta globin chains o α-Thalasemia: â α o β-Thalasemia: â β o Thalasemia results in Anemia o Premature death of RBCs o â size of RBCs (microcytic anemia) o â Hb (hypochromic anemia) Alpha Thalasemia: normally 4 alpha present that bind to chromosome 16 # of deficient alphas Manifestations One None (silent carrier) Two None to mild hemolytic anemia Three Four Hereditary Persistence of Fetal Hemoglobin (HPFH) • HbF production switches to HbA production (switching) • HPFH occurs when Hb F production remains high Review Heme is converted to bilirubin in _______. a. erythrocytes b. hepatocytes c. kidney cells d. macrophages e. the large intestine d Which of the following designations represents HbF? a. α2β2 b. α2 γ2 c. α 2δ2 d. δ2 β2 e. γ2δ2 b Beta Thalasemia normally 2 beta globin chains bind to chromosome 11 # of deficient betas Genetic or Dz State One β-thalasemia minor Two β-thalasemia major