Heme

• Hemoglobin


  Comprise approx 95% of the cytoplasmic content of RBCs
• Free (non-RBC) hemoglobin


  Generated from hemolysis, is rapidly salvaged to preserve its iron and amino acid components. If the capacity exceeded, it is excreted by the kidneys
• Concentration of Hemoglobin within RBCs

  34g/dL
• Molecular weight of Hemoglobin

  64,000 Daltons
• Main functions of Hemoglobin


  • Transport oxygen from the lungs to tissues and transport carbon dioxide from the tissues to the lungs for exhalation
  • Contributes to acid-base balance by binding and releasing hydrogen ions and transports nitric oxide, a regulator of vascular tone
• Hemoglobin Structure


  Composed of two pairs of polypeptide chains and four heme groups (Every heme is imbedded in each of the four polypeptide chains)<|>Can carry up to four molecules of oxygen
• Most predominant Hemoglobin in adults

  HbA1c - 4-6% of HbA circulate in this form
• Heme


  Consists of a ring of carbon, hydrogen, and nitrogen atoms called protoporphyrin IX, with a central atom of divalent ferrous iron (Fe2+)<|>When the ferrous irons are oxidized to the ferric state (Fe3+), they no longer can bind oxygen
• Oxidized hemoglobin


  Methemoglobin
• Globin Structure


  2 identical pairs of unlike polypeptide, which differs in amino acid sequences. Each chain is designated by a Greek letter
• Hemoglobin Biosynthesis

  1. Globin Biosynthesis: Six structural genes code for six globin chains (α and ζ - short arm of chromosome 16, ε,γ,δ, and β - short arm of chromosome 11)

  2. Newborn: 80% HgbF, 20% HgbA1

  3. 1 Year old: 95% Hgb A1, 3.5% Hgb A2, 1-2% HgbF
• Normal Hemoglobin Variants


  • HbA
  • HbA2
  • HbF
• Hemoglobin Ontogeny

  Fetal hemoglobin (HbF) has higher affinity for oxygen compared to adult hemoglobin (HbA)
• Systemic Regulation of Erythropoiesis

  1. Hypoxia is detected by cells found in the kidneys

  2. These cells will produce erythropoietin to increase production of RBCs
• Individuals living at high altitudes have slightly higher hemoglobin as a compensatory mechanism to provide more oxygen to the tissues in oxygen-thin air
• Hemoglobin Functions


  • Transport oxygen from the lungs to tissues
  • Transport carbon dioxide from the tissues to the lungs for exhalation (maintains acid-base balance)
  • Transport nitric oxide
• Oxygen Transport


  Main function of hemoglobin is to readily bind oxygen molecules in the lung<|>Approx 1.34mL of oxygen is bound by each gram of hemoglobin
• Partial pressure of oxygen (PO2)


  Amount of oxygen needed to saturate 50% of Hgb, aka the P50 value
• Hemoglobin-Oxygen Dissociation Curve


  Plots the percent oxygen saturation of Hgb versus PO2<|>Sigmoidal curve indicates low hemoglobin affinity for oxygen at low oxygen tension and high affinity for oxygen at high oxygen tension
• Reference interval for arterial oxygen saturation


  96% to 100%
• Bohr effect


  A shift in the hemoglobin-oxygen dissociation curve due to a change in pH (or hydrogen ion concentration)
• Hemoglobin F (HbF)


  Has P50 of 19-21 mmHg resulting in a left shift<|>Increased affinity for oxygen compared to Hb A due to its weakened ability to bind 2,3-BPG
• Advantages of HbF

  • High affinity to oxygen=more effective O2 withdrawal from maternal circulation
• Disadvantages of HbF

  • Delivers O2 less readily to tissues
  • Is compensated by increased RBC production to ensure adequate oxygenation, mediated by erythropoietin
  • RBC count, hemoglobin conc, and hematocrit of a newborn is HIGHER than adult levels, but they gradually decrease to normal physiologic levels by 6 months of age
• Hemoglobin-Oxygen Dissociation Curve Shifts

  Shift to the left: Higher affinity for oxygen, lower oxygen delivery to the tissues<|>Shift to the right: Lower affinity for oxygen, higher oxygen delivery to the tissues
• Triggers for hemoglobin-oxygen dissociation curve shifts

  • Shift left: Multiple transfusions of 2,3-BPG depleted blood, lower body temp
  • Shift right: Hypoxia, increased body temp
• 2,3-BPG (DPG)


  Decreased 2,3-BPG: Hemoglobin assumes an (R) form, higher affinity for oxygen<|>Increased 2,3-BPG: Hemoglobin assumes a (T) form, lower affinity for oxygen
• pH effect on hemoglobin-oxygen dissociation curve

  Alkalosis (↑pH): Shift left, lower oxygen delivery to tissues<|>Acidosis (↓pH): Shift right, higher oxygen delivery to tissues
• Carbon Dioxide Transport


  Hemoglobin binds and transports carbon dioxide, contributing to acid-base balance
• Nitric Oxide Transport


  Hemoglobin binds, inactivates, and transports nitric oxide<|>Nitric oxide causes relaxation of vascular wall smooth muscle and vasodilation
• Dyshemoglobins


  Hemoglobins that are unable to transport oxygen, including methemoglobin, sulfhemoglobin, and carboxyhemoglobin
• Methemoglobin


  Contains an oxidized or ferric (Fe3+) state of iron<|>Brownish/bluish in color, has a higher affinity to Oxygen than Hemoglobin<|>If accumulates 30% of the total hemoglobin, the patient presents with symptoms of cyanosis and hypoxia<|>Caused by oxidants such as nitrites, decreased in HiB reductase, or in patients who inherit the Hb M disease<|>Treatment: Ascorbic acid or Methylene blue
• Sulfhemoglobin


  Formed by irreversible oxidation of hemoglobin by sulfonamides, phenacetin, acetanilide, phenazopyridine<|>Cannot transport oxygen; patients suffer from cyanosis<|>Cannot be converted back to hemoglobin<|>Greenish hemoglobin
• Carboxyhemoglobin


  Carbon monoxide + Heme; 240x the affinity of Hgb to O2 (silent killer)<|>Can be normal at 0.2-0.8%<|>Produced by exhaust of automobiles and from industrial pollutants<|>At 10-15%, headaches and dizziness are experienced; 50% causes coma and convulsions<|>Cherry-red blood<|>Treatment: Hyperbaric oxygen therapy