Structure and Function of Red Blood Cells PDF

Dr. Ng Chin Theng  Learning outcomes Describe the morphologic characteristics of a mature RBC. Describe the cytoskeleton of RBC. Describe the structure and function of haemoglobin A. Describe the differences in the structure and functions of haemoglobins A and F. Describe th...

Dr. Ng Chin Theng  Learning outcomes Describe the morphologic characteristics of a mature RBC. Describe the cytoskeleton of RBC. Describe the structure and function of haemoglobin A. Describe the differences in the structure and functions of haemoglobins A and F. Describe the blood indices and their clinical significance.  Characteristic of RBCs Circular biconcave disk shape 7.5 μm in diameter 2.0 μm thickness ≤ 1.0 μm in the center Advantages of biconcave shape Due to greater surface area as compared to volume, it can take in some quantity of fluid before getting haemolyzed. That means it can resist haemolysis to certain extent when placed in hypotonic solution. O2 and CO2 exchange occurs easily because of greater surface area. It exhibits remarkable deformability because of its typical shape. This is especially important while the cells are passing through the small capillaries.  Size of the cell goes on decreasing with subsequent stages Synthesis of hemoglobin (Hb) Anucleated  More room for Hb Bi-concavity o Squeeze through capillary pores o Remain the wall tension with increasing cell volume No mitochondria  Anaerobic fermentation No ER  Have cytoplasmic enzymes  Capable of metabolizing glucose and forming small amounts of ATP  Maintain membrane transport of ions  Maintain pliability of the cell membrane  Keep the iron of the cells’ hemoglobin in the ferrous form rather than ferric form  Prevent oxidation of the proteins in the RBCs G6PD ; G6P 6 phosphogluconate + NADPH NADPH maintains levels of glutatione, an antioxidant Deficiency leads to hemolysis when they are exposed to oxidative stress  Cytoskeleton of RBC Maintain the shape and flexibility of the red cell membrane In hereditary spherocytosis,  Mutation in cytoskeletal proteins (spectrin, band3, ankyrin)  Spherical shaped – trapping, destruction  Congenital hemolytic anemia  RBCs Carry hemoglobin in the circulation In an adult, RBCs are produced in the bone marrow Average life span is around 120 days Old RBCs are fragile  rupture during passage through some narrow spaces of the circulation Self-destruct in the spleen when squeeze through the red pulp of the spleen Normal RBC count Adult male: 4.5 - 6.5 ×1012/L Adult female: 3.9 - 5.6 ×1012/L Hematocrit / Packed cell volume Percentage of whole blood volume composed of red blood cells Adult male: 40- 52% Adult female: 36- 48% Hemoglobin Men: average 15 g of Hb/100 mL of cells Women: average 14 g of Hb/100 mL 1 gram of Hb is capable of combining with 1.34 mL of O2 Normal men: 20 mL of O2 /100 mL of cells Normal women: 19 mL of O2 /100 mL of cells  What is hemoglobin? Haemoglobin is a protein containing haem which is iron containing porphyrin known as iron porphyrin IX. Protein globin combines with haem to form a haemoglobin.  Succinyl-CoA, formed in the Krebs metabolic cycle binds with glycine to form a pyrrole molecule 4 pyrroles combine to form protoporphyrin IX, which then combines with iron to form the heme molecule Each heme molecule combines with a long polypeptide chain, a globin synthesized by ribosomes, forming a subunit of Hb called a hemoglobin chain Four of these bind together loosely to form the whole hemoglobin molecule  Hemoglobin Is a globular molecule made up of four subunits Red, oxygen-carrying pigment in the RBCs Heme groups  binds O2 to ferrous ion (Fe2+) Globins - four protein chains  Eg: two alpha and two beta chains CO2 in blood is bound to globin moiety Mw= 64450  Reactions of hemoglobin Methemoglobin (dark-colored) : contain Fe3+ Fe2+  Fe3+ NADH-methemoglobin reductase Methemoglobin hemoglobin Oxygen binds to the Fe2+ in the heme moiety of hemoglobin to form oxyhemoglobin  CO2 in combination with Hb to form carbaminohemoglobin Deoxyhemoglobin (reduced Hb) Form of hemoglobin without oxygen CO reacts with Hb to form carbon monoxyhemoglobin (carboxyhemoglobin) Hb has higher affinity towards CO; 250X Displace oxygen, ↓oxygen-carrying capacity of blood  The affinity of Hb for oxygen is affected by  pH  Temperature  Concentration of 2,3-bisphosphoglycerate (2,3-BPG) in the red cells ↑ temperature, low pH, ↓ affinity of Hb for oxygen ↑ 2,3-BPG, ↓ affinity of Hb for oxygen 2,3-BPG and H+ compete with oxygen for binding to deoxygenated Hb, ↓ the affinity of Hb for oxygen  Varieties of hemoglobin Different varieties of hemoglobin are due to variations in the different subunit chains, heme moiety is same in all types Different types of chains, depending on the amino acid composition of the polypeptide chain  Alpha (α) chains  Beta (β) chains  Gamma (γ) chains  Delta (δ) chains  Adult hemoglobin Adult hemoglobin is of two types: Hemoglobin Hb A Globin contains two alpha and two beta chains (α2β2) About 2.5% of the Hb is Hb A2, in which β chains are replaced by δ chains (α2δ2) Hemoglobin A1c  has a glucose attached to the terminal valine in each β chain  ↑ in the blood of patients with poorly controlled diabetes mellitus  0.3 - 1.0 % of West African and American black : Hb S (contain faulty beta chains) The amino acid valine is substituted for glutamic acid in each of the two β chains When this hemoglobin is exposed oxygen, it precipitates into long crystals inside the RBC Sickle-shaped cells, fragile : sickle cell anemia  Fetal hemoglobin Hemoglobin F (Hb F) Globin contains two alpha and two gamma chains (α2γ2) Hb concentration of fetal blood is about 50 % greater than that of the mother – Allow the fetal blood to transport as much O2 to the fetal tissues Soon after birth, Hb F is replaced by Hb A Hb F binds 2,3-BPG less avidly  has a higher oxygen affinity than maternal hemoglobin, allowing for maternal-to-fetal oxygen transport. Showing that fetal blood can carry a greater quantity of oxygen than maternal blood for a given blood PO2  Functions of RBCs Transport of hemoglobin – O2 The Hb is an excellent acid-base buffer Contain carbonic anhydrase, an enzyme that catalyzes the reversible reaction between CO2 + H2O ↔ H2CO3 Maintenance of viscosity Hb combines reversibly with O2 Hb combines with O2 as the blood passes through the lungs 97% of O2 is transported in this way If the PO2 tissue ↑, O2 binds with the Hb If the PO2 tissue ↓, O2 is released from Hb Transport of CO2 in combination with Hb to form carbaminohemoglobin Account for 23% of total CO2 transport  Reversible reactions  CO2 is easily released into the alveoli, where the PCO2 is lower than in the pulmonary capillaries  RBCs contain carbonic anhydrase CA is an enzyme that catalyzes the reversible reaction between CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3- This rxn makes it possible for transportation of CO2 in the form of HCO3– from the tissues to the lungs, where it is reconverted to CO2 and expelled into the atmosphere Tissue  RBC indices & significance Mean Corpuscular Volume (MCV) The MCV is the average or mean volume of a single red blood cell expressed in cubic micrometers (μm3 or femtoliters, fL) Mean Corpuscular Hemoglobin (MCH) The MCH is the average hemoglobin content (weight of Hb) in a single red blood cell expressed in pictograms (pg)  RBC indices & significance Mean Corpuscular Hemoglobin Concentration (MCHC) The MCHC represents the relationship between the red cell volume and its degree or percentage saturation with hemoglobin, that is, how many parts or volumes of a red cell are occupied by Hb The MCHC represents the actual Hb concentration in red cells only Expressed in grams/deciliter (g/dL)  Red cell indices MCV, MCH and MCHC are calculated from hemoglobin, hematocrit, and red blood cell count as follows:  Type of anaemia is determined by determining blood indices mainly:  MCV (mean corpuscular volume)  MCH (mean corpuscular haemoglobin)  MCHC (mean corpuscular haemoglobin concentration) Normal MCV varies from 80 to 95 fL – Microcytic (size of the cell smaller than normal) – Normocytic (size of the cell normal) – Macrocytic (size of the cell is larger than normal) Normal MCH varies from 27 to 34 pg – Hypochromic (MCH is lesser than normal) – Normochromic (MCH is normal) – Hyperchromic (MCH is more than normal) Normal MCHC varies from 30 to 35 g/dL  Disclaimer The texts, tables, figures and images contained in this course presentation are not my own, they can be found on: References supplied or The web