1. MLAB 1415- Hematology Keri Brophy-Martinez Chapter 6: Hemoglobin

2. Hemoglobin What is it? Iron- bearing protein which is the main component of the RBC Gives the red cell its color Synthesis Majority synthesized at the polychromatophilic normoblast stage Regulation Stimulated by tissue hypoxia Hypoxia causes the kidneys to increase production of EPO, which increases RBC and hemoglobin production Function Carry oxygen from the lungs to the tissues Remove CO 2 Buffering action, maintains blood pH as it changes from oxyhemoglobin (carrying O 2 ) to deoxyhemoglobin ( without O 2 )

3. Hemoglobin Reference Ranges Adults Male 14-17.4 g/dL Female12-16.0 g/dL Children Birth 13.5-20.0 g/mL 6-12 years 11.5-15.5 g/mL **Refer to inside cover of text for other age ranges

4. Structure 4 polypeptide Subunits Heme group Porphyrin ring Ferrous iron Globin chain 2 Alpha Chains 2 Beta chains

5. Hemoglobin Synthesis Synthesis Occurs in the mitochondria of developing red cells as they mature in the bone marrow Processes necessary for normal synthesis Adequate iron supply & delivery Adequate synthesis of protoporphyrins Adequate globin synthesis

6. Heme Synthesis Chain of Events Iron delivery & supply Iron is delivered to the reticulocyte by transferrin Synthesis of protoporphyrins Occurs in the mitochondria of RBC precursors Mediated by EPO and vitamin B 6 Protoporphyrin + iron = heme

7. Globin Synthesis Chain of Events The rate of globin synthesis is proportional to the rate of porphyrin synthesis. Proper globin synthesis depends on genes. The precise order of amino acids in the globin chains is critical to the structure and function of hemoglobin. Chain designations are as follows Alpha α, beta β, delta δ, epsilon ε, gamma γ, zetaζ

8. Normal hemoglobins Embryonic Hemoglobins Gower 1- zeta (2), epsilon (2) Gower 2- alpha (2), epsilon (2) Portland-Zeta (2), gamma (2) Fetal hemoglobin Hemoglobin F- alpha(2), gamma (2) Adult hemoglobins Hemoglobin A- alpha (2), beta (2) ~95% Hemoglobin A2- alpha(2), delta(2) ~1.5-3.7% Hemoglobin F- alpha(2), gamma (2) <2 %

9. Hemoglobin Synthesis

10. Oxygen transport The amount of O 2 bound to hemoglobin and released to tissues depends on PO 2 and PCO 2, but also the affinity of hemoglobin for O 2. Oxyhemoglobin: hemoglobin with oxygen Deoxyhemoglobin: hemoglobin without oxygen Oxygen affinity is the ease with which hemoglobin binds and releases oxygen.

11. Oxygen Affinity Determines the proportion of O 2 released to the tissues or loaded onto the cell at a given oxygen pressure. Increases in oxygen affinity means hemoglobin has an increased affinity for O 2, so it binds more. However, it does not want to give it up. Decreases in oxygen affinity, cause O 2 to be released.

13. Bohr Effect Alterations in blood pH, shifts oxygen dissociation curve In acidic pH, the curve shifts to the right Results in an enhanced capacity to release O 2 where it is needed

14. Oxygen Dissociation Curve Right-Shift Hgb has less attraction for O 2 Hgb willing to release O 2 to tissue Examples: anemia, acidosis Even though there may be less RBC’s, they act more efficiently to deliver O 2 to target

15. Oxygen Dissociation Curve Left shift Hgb has more attraction for O 2 Hgb less willing to release O 2 to tissue Examples: presence of abnormal Hgb’s, alkalosis

16. Carbon Dioxide Transport Three mechanisms of transport Dissolution in the plasma Formation of bicarbonic acid Binding to carbaminohemoglobin

17. Nonfunctional hemoglobins What do they do? Hypoxia Inadequate amount of O 2 in the blood Cyanosis Presence of > 5 g/dl deoxyhemoglobin in blood Patient appears blue

18. Nonfunctional hemoglobins Carboxyhemoglobin Oxygen molecules bound to heme are replaced by carbon monoxide. Slightly increased levels of carboxyhemoglobin are present in heavy smokers and as a result of environmental pollution. Can revert to oxyhemoglobin. Methemoglobin Iron in the hemoglobin molecule is in the ferric (Fe 3 ) state instead of the ferrous (Fe 2 ) state. Incapable of combining with oxygen. Can occur as a result of strong oxidative drugs or to an enzyme deficiency (more discussion to follow). Can revert to oxyhemoglobin Sulfhemoglobin Hemoglobin molecule contains sulfur. Caused by certain sulfur-containing drugs or chronic constipation. Cannot revert to oxyhemoglobin and may cause death.

19. References McKenzie, S. B. (2010). Clinical Laboratory Hematology (2nd ed.). Upper Saddle River, NJ: Pearson Education, Inc..