Haematology 3- iron & haem metobalism

• What are the two oxidation states of iron mentioned?

  Ferrous (Fe$^{2+}$) and ferric (Fe$^{3+}$)
• How does iron participate in redox reactions?


  By switching reversibly between Fe$^{2+}$ and Fe$^{3+}$ states
• Why is excess iron considered toxic?


  It forms free radicals
• What are the key components involved in iron transport?

  • Ferric reductase (e.g., duodenal cytochrome B)
  • Haem transporter
  • Divalent metal transporter 1 (DMT1)
  • Ferroportin
  • Transferrin
• What dietary factor enhances iron absorption?

  Ascorbic acid (vitamin C)
• What role does hepcidin play in iron absorption regulation?


  It regulates iron absorption based on iron availability
• What happens to dietary iron after absorption in enterocytes?


  Most is incorporated into ferritin, not transferred into blood
• How does low iron affect DMT1 synthesis?


  • Ribosomes synthesize more DMT1 when iron stores are low
  • DMT1 mRNA has iron response elements that protect it from degradation
• What activates hypoxia-inducible factor 2 α (HIF-2 α)?


  Decreased O$_{2}$ supply
• What are common causes of iron deficiency?


  Chronic blood loss, growth spurts, pregnancy, lactation, acute hemorrhage
• What are the symptoms of iron deficiency?


  Pallor, weakness, fatigue
• What is the primary component of haem in the body?


  95% of metabolically-active iron
• What is the process of haem synthesis primarily associated with?


  • Occurs mostly in the bone marrow (85%)
  • Liver is a significant non-erythrocyte source
  • First step occurs in mitochondria
• What is the role of PBG synthase in haem synthesis?


  It condenses δ-ALA to form PBG
• What inhibits PBG synthase?


  Lead (Pb) molecules
• What happens during the cyclization of PBG in haem synthesis?


  • 4 PBG molecules combine to form a linear tetrapyrrole
  • Loses 4 x CO$_{2}$ and re-enters mitochondria as protoporphyrinogen IX
• What is the function of ferrochelatase in haem synthesis?


  It adds Fe$^{2+}$ to protoporphyrin IX to form haem
• How is haem production regulated in the liver and erythroid cells?


  • Haem is a negative regulator of δ-ALA synthase
  • Heavy metals inhibit PBG synthase and ferrochelatase
• What occurs during haem degradation?


  • Macrophages oxidize haem to ferric state to produce hemin
  • Biliverdin is produced from hemin by haem oxygenase
• What is the color of bilirubin produced from biliverdin?


  Yellow
• How is bilirubin transported from the spleen to the liver?


  By binding to serum albumin
• What happens to bilirubin in the liver?


  • It is conjugated with glucuronic acid to form bilirubin diglucuronide
  • This process is catalyzed by UDP glucuronosyl transferase 1A1
• What is the fate of urobilinogen in the body?


  Most is cleared by the liver and re-secreted in bile
• What causes the yellow color of urine?

  Oxidation of urobilin to urobilin
• What is jaundice and its cause?


  • Yellow discoloration of skin and sclera
  • Caused by hyperbilirubinemia
• What is the difference between unconjugated and conjugated bilirubin?


  Unconjugated bilirubin is lipid-soluble and can enter the brain, while conjugated bilirubin is water-soluble
• What is the primary cause of pre-hepatic jaundice?


  Increased production or impaired hepatic uptake of bilirubin
• How does haemolysis affect bilirubin levels?


  It increases total plasma bilirubin due to excess unconjugated fraction
• What enzyme is responsible for the conjugation of bilirubin?

  Uridine diphosphate (UDP) glucuronosyl transferase 1A1
• What do intestinal bacteria do to bilirubin?


  They de-conjugate it to form uncoloured urobilinogen
• What happens to some urobilinogen in the ileum?


  Some is absorbed into the ileum
• How is most urobilinogen processed in the body?


  Most is cleared by the liver and re-secreted in bile
• How much urobilinogen is secreted in urine daily?


  A small amount greater than 4 mg/day
• What does oxidized urobilin contribute to?


  It contributes to the yellow color of urine
• What is stercobilin and how is it formed?


  Stercobilin is formed by the reduction of urobilin by intestinal bacteria
• What is jaundice also known as?

  Icterus
• What causes the yellow discoloration in jaundice?


  It is caused by hyperbilirubinemia
• What type of bilirubin is tightly bound to albumin?


  Unconjugated bilirubin
• Why is unconjugated bilirubin lipid-soluble?


  Because it is tightly bound to albumin
• What can unconjugated bilirubin cause in infants?


  It can cause bilirubin encephalopathy/kernicterus