MD137 Haematology Lecture 3: Haemoglobin PDF

MD137 Haematology Lecture 3: Haemoglobin Dr. Louise Horrigan Physiology [email protected] University ofGalway.ie Learning To learn: Structure and function of haemoglob...

MD137 Haematology Lecture 3: Haemoglobin Dr. Louise Horrigan Physiology [email protected] University ofGalway.ie Learning To learn: Structure and function of haemoglobin Objectives of Concept of co-operative binding Today’s Lecture Types of haemoglobin Normal and abnormal haemoglobin Continued learning of anaemia Breakdown of haemoglobin Recommended Textbooks for Immunology in addition to main textbook Basic Immunology : Functions and Disorders of the Immune System. Abbas, Abul K., Andrew H. Lichtman, Shiv Pillai, and David L. Baker. 7th Edition Philadelphia, PA: Elsevier, 2024. Print. Immunology for Medical Students. Helbert, Matthew, and Roderick. Nairn. Third ed. Philadelphia, PA: Elsevier, 2017. Print. University ofGalway.ie Each haemoglobin molecule consists of 4 polypeptide chains, each bound to a ring-like haem group. An atom of iron (Fe ) sits at the 2+ centre of each haem. This image is licensed under the Creative Commons Attribution 3.0 Unported license. Source: Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013. Author: OpenStax College Haem attaches to the central Iron has 6 binding sites in iron atom in four positions. total: oxygen binds to the Image from Wikimedia Commons, licensed sixth site. under the Creative Commons Attribution- Share Alike 4.0 International license. Transport of O2 Each molecule of Hb can bind 4 molecules of O2 Oxyhaemoglobin vs deoxyhaemoglobin 1g of Hb can carry 1.34ml O2 O2 saturation is the amount of O2 bound to Hb relative to the amount that can bind At 100% saturation, the haem groups are fully occupied with O2 Normal arterial O2 saturation is 95 – 100% University ofGalway.ie Uptake & Release of O2 from Hb One molecule Oxyhaemoglobin of 02 binds Deoxyhaemoglobin Increasing affinity of Hb for 02 Uptake & release of O2 from Hb Co-operative binding Binding of one molecule of O2 causes a conformational change in the second polypeptide chain, increasing the affinity for the second O2 molecule Binding of the second 02 increases affinity for the third etc. The fourth O2 has 300 times greater affinity than the first Similarly, for oxyhaemoglobin, the first 02 is the most difficult to shed, the fourth is the easiest The cooperative binding of oxygen by haemoglobin enables it to deliver University far more oxygen than it would if the sites were independent. ofGalway.ie Types of Hgb Haemoglobin A (HbA) constitutes 95 – 98% of Hb in the adult Two alpha and two beta polypeptide chains (a2b2) Haemoglobin A2 (HbA2) constitutes 1.5 – 3% of Hb in the adult Two alpha and two delta chains (a2d2) Foetal haemoglobin (a2g2) present at 0.5% in adult life At birth – 80% HbF, 20% HbA Greater affinity for O2 than HbA, facilitating movement of O2 from maternal to foetal circulation g chains have higher affinity for O2 than b chains Embryonic haemoglobins produced by embryonic yolk sac z2e2 (Gower 1) or a2e2 (Gower 2) University ofGalway.ie  Normal developmental profile of haemoglobins Data from Huehns and Shooter (1965) and from Kleihauer (1970) as rendered by Bunn and Forget (1986). The names of the normal embryonic haemoglobins are Gower-1 (ζ2ɛ2), Gower-2 (α2ɛ2), and Portland-1 (ζ2γ2). Hb Portland-2 (ζ2β2) is not usually found. Image taken from Manning et. al. (Protein Sci. 2007) where it was reprinted from Bunn and Forget 1986 by Manning et al. with permission from Elsevier ©1986.) Normal haemoglobin levels The World Health Organization defines anaemia as blood haemoglobin values of less than 7.7 mmol/l (13 g/dl) in men and 7.4 mmol/l (12 g/dl) in women The number of red blood cells, or the concentration of haemoglobin within them, is lower than normal University ofGalway.ie Abnormalities of haemoglobin production: haemoglobinopathies Approximately 5% of the world’s population has a globin variant Inherited disorders Types: 1. Chains produced in decreased amounts or absent a or b thalassemia 2. Abnormal polypeptide chains produced Haemoglobin C, E, I, J, S etc. University ofGalway.ie Haemoglobin S Normal a chains but abnormal b chains Single amino acid substitution (valine for glutamic acid) At low O2 concentrations, Hb changes into a gelatinous material that distorts the biconcave shape Cells cause obstruction Membranes are fragile ‘Sickling’ can cause Intense pain Serious anaemia Sickle cell trait can confer resistance against malaria Image from Professor Bain’s teaching images, Imperial College London Case: History 75 year old female Symptoms of breathlessness and fatigue No bleeding Physical Exam Pale skin but no other findings Image obtained from University of Minnesota Hematography® http://www1.umn.edu/hema/pag es/casestudiesreal.html CBC and differential RBC 3.71 x 1012/L HGB 5.9 g/dL HCT 20.9 % MCV 56.2 fL [reference range = 80-96 fL/red cell] MCH 15.9 pg [reference range = 27-33 pg/cell] MCHC 28.3 g/dL [reference range = 33-36 g/dL] WBC 5.9 x 109/L Neutrophils 82 % Lymphocytes 13% Monocytes 1% Eosinophils 4% Image obtained from University of Minnesota Hematography® Basophils 0% http://www1.umn.edu/hema/pag PLT 383 x 109/L es/casestudiesreal.html Further laboratory study: Iron Profile Serum ferritin