Hemoglobin Metabolism & Heme Synthesis PDF

Synthesis Rodak's 6th Ed., Chapter 7, pg. 91. Hemoglobin Metabolism & Heme Prepared by: Hazel B. Velasco, RMT, DTA, MPH(inp.),...

Synthesis Rodak's 6th Ed., Chapter 7, pg. 91. Hemoglobin Metabolism & Heme Prepared by: Hazel B. Velasco, RMT, DTA, MPH(inp.), 07/10/2023 1 MLS(ASCPi)cm  07/10/2023 Hemoglobin Structure: Hemoglobin Composed of: - Two (2) pairs of polypeptide chain Comprise of approx 95% of the - Four (4) heme groups cytoplasmic content of RBCs. (Every heme is imbedded in each of the four Free (non-RBC) hemoglobin – generated polypeptide chains.) from hemolysis, is rapidly salvaged to - Can carry up to four (4) molecules of oxygen. preserve its iron and amino acid - Most predominant Hb in adults is? components. If the capacity exceeded, it - HbA1c – 4-6% of HbA circulate in this form. Prepared by: Hazel B. Velasco, RMT, DTA, MPH(inp.), is excreted by the kidneys. Conc of Hemoglobin within RBCs – 34g/dL Molecular weight – 64,000 Daltons Main function: 1. Transport oxygen from the lungs to tissues and transport carbon dioxide MLS(ASCPi)cm from the tissues to the lungs for exhalation. 2. Contributes to acid-base balance by binding and releasing hydrogen ions and transports nitric oxide, a regulator of vascular tone. 2  07/10/2023 Heme Structure Heme consists of a ring of carbon, hydrogen, and nitrogen atoms called protoporphyrin IX, with a central atom of divalent ferrous iron (Fe2+). Prepared by: Hazel B. Velasco, RMT, DTA, MPH(inp.), When the ferrous irons are oxidized to the ferric state (Fe3+), they no longer can bind oxygen. Oxidized hgb is aka methemoglobin. Globin Structure MLS(ASCPi)cm 2 identical pairs of unlike polypeptide, which differs in amino acid sequences. Each chain is designated by a Greek letter. 3  Hemoglobin Biosynthesis Prepared by: Hazel B. Velasco, RMT, DTA, MPH(inp.), 07/10/2023 4 MLS(ASCPi)cm  Normal Hemoglobin 07/10/2023 Variants: Globin Biosynthesis Six structural genes code for six Prepared by: Hazel B. Velasco, RMT, DTA, MPH(inp.), globin chains. α and ζ – short arm of chromosome 16 ε,γ,δ, and β – short arm of chromosome 11 Newborn: 80% HgbF, 20% HgbA1 1 Year old: 95% Hgb A1, 3.5% Hgb A2, 1- 2% HgbF MLS(ASCPi)cm 5 Hemoglobin 07/10/2023 Systemic Regulation Ontogeny of Erythropoiesis Hypoxia occurs when: 1. Insufficient hgb quantity 2. Defective Hgb molecule Hypoxia is detected by __________ found in Prepared by: Hazel B. Velasco, RMT, DTA, MPH(inp.), the kidneys. These cells will produce __________ to increase production of RBCs. In general, reference intervals for Hgb concentration are as follows: MLS(ASCPi)cm Note: - Individuals living at high altitudes have slightly higher hemoglobin as a compensatory mechanism to provide more oxygen to the tissues in oxygen-thin air. 6  07/10/2023 Prepared by: Hazel B. Velasco, RMT, DTA, MPH(inp.), Hemoglobin Function 1. TO TRANSPORT OXYGEN 2. TO TRANSPORT CARBON DIOXIDE (MAINTAINS ACID-BASE BALANCE) 3. TO TRANSPORT NITRIC OXIDE MLS(ASCPi)cm 7  07/10/2023 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. Prepared by: Hazel B. Velasco, RMT, DTA, MPH(inp.), 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. - The curve is sigmoidal, which indicates low hemoglobin affinity for MLS(ASCPi)cm oxygen at low oxygen tension and high affinity for oxygen at high oxygen tension. - Reference interval for arterial oxygen saturation: 96% to 100%. 8  07/10/2023 HEMOGLOBIN-OXYGEN DISSOCIATION CURVE Shift to the Shift to the left right Trigger Multiple Hypoxia, situations: transfusions increased of 2,3-BPG body temp. depleted blood, lower body temp. Prepared by: Hazel B. Velasco, RMT, DTA, MPH(inp.), 2,3-BPG Decreased 2,3- Increased 2,3- (DPG) BPG (formerly BPG (formerly DPG) DPG) Affinity for Higher Lower affinity oxygen affinity for for oxygen oxygen pH ↑pH ↓pH (Acidosis) (Alkalosis) Hgb form: Assumes an Assumes a (T) MLS(ASCPi)cm (R) form form Result: Lower oxygen Higher oxygen delivery to the delivery to the tissues tissues A shift in the curve due to a change in pH (or hydrogen ion concentration) is termed the Bohr effect.  9  07/10/2023 Hb F - Has P50 of 19-21 mmHg resulting Carbon Dioxide Transport in a left shift - Increased affinity for oxygen compared to Hb A due to its weakened ability to bind 2,3-BPG. (May be attributed to the difference in γ and β chain binding. Advantages: Prepared by: Hazel B. Velasco, RMT, DTA, MPH(inp.), High affinity to oxygen=more effective O2 withdrawal from maternal circulation. Disadvantages: - Delivers O2 less readily to tissues. - Is compensated by increased RBC production to ensure adequate oxygenation, mediated by (what cytokine? ) - Thus, the RBC count, hemoglobin MLS(ASCPi)cm conc, and hematocrit of a newborn is HIGHER than adult levels. - But they gradually decrease to normal physiologic levels by 6 months of age as the γ-β switching 10 is completed and most of the Hb F is replaced by Hb A.  Methemoglobin Sulfhemoglobin Carboxyhemoglobin 07/10/2023 Nitric Oxide Transport Contains an oxidized or Ferric (Fe3+) state of Formed by irreversible oxidation of hemoglobin by Carbon monoxide + Heme; 240x the iron. sulfonamides, phenacetin, affinity of Hgb to - Binds, inactivates, and transport acetanilide, or O2 (silent killer) Nitric oxide Brownish/bluish in color, phenazopyridine Can be normal at - Nitric oxide causes relaxation of has a higher affinity to 0.2-0.8% Oxygen than Cannot transport Produced by vascular wall smooth muscle and Hemoglobin. oxygen; patients exhaust of vasodilation. suffer from automobiles and - When released, free nitric oxide has If accumulates 30% of cyanosis from industrial Prepared by: Hazel B. Velasco, RMT, DTA, MPH(inp.), a very short half-life, but some the total hemoglobin, Cannot be pollutants the patient presents converted back to At 10-15%, enters RBCs and can bind to with symptoms of hemoglobin headaches and cysteine in the b chain of cyanosis and hypoxia Greenish dizziness are hemoglobin, forming S- hemoglobin experienced; 50% Caused by oxidants such causes coma and nitrosohemoglobin. as nitrites, decreased in No treatment, convulsions HiB reductase, or in prevention only patients who inherit the * Cherry-red blood Dyshemoglobins Hb M disease MLS(ASCPi)cm *Chocolate-brown Treatment: - Hemoglobins that are UNABLE to blood Hyperbaric oxygen transport oxygen. therapy - Includes methemoglobin, Treatment: Ascorbic acid or sulfhemoglobin, and Methylene blue carboxyhemoglobin. 11  07/10/2023 Reading Assignment: Prepared by: Hazel B. Velasco, RMT, DTA, MPH(inp.), Iron Kinetics and Laboratory Assessment. Rodak's 6 Ed., Ch. 8, pg. 104 th MLS(ASCPi)cm 12