Structure & Function of RBC PDF

Structure and functions of red blood cells December 2023 Learning Outcomes 1. Explain regulation of erythropoiesis and importance of vitamin B12, folic acid and iron for RBC production. 2. Explain the features of red blood cells (RBC) by describing their life span, count, shape, hemoglobin concent...

Structure and functions of red blood cells December 2023 Learning Outcomes 1. Explain regulation of erythropoiesis and importance of vitamin B12, folic acid and iron for RBC production. 2. Explain the features of red blood cells (RBC) by describing their life span, count, shape, hemoglobin concentrations. 3. Explain the meaning of mean corpuscular volume (MCV), microcytosis, macrocytosis; mean corpuscular hemoglobin; and the mean corpuscular hemoglobin concentration (MCHC). 4. Describe how we can measure hematocrit value and what it reflects 5. Explain how red blood cells transport oxygen and CO2. 6. Describe the metabolic pathways that RBC are using for energy production. 7. Explain the erythrocyte sedimentation rate (ESR) and the factors affecting ESR 8. Explain the blood groups and how we can identify blood types RED BLOOD CELLS (RBC, ERYTHROCYTES) Special shape - biconcave discs. Diameter: 7.8 µm Thickness: 2.5 µm at the thickest point and 1 µm or less in the center. Volume: 90 to 95 µm2 RBC are elastic and flexible, and they readily bend as they pass through small blood vessels Cytoskeleton creates the unique shape of RBCs The number of red blood cells in adult males is 4.6-6.2 millions/µl, in adult females is 4.2-5.4 millions/µl (red blood cell count , RBCC or RCC). Genesis of RBC Erythrocytes lose their organelles as they mature à more space for hemoglobin Reticulocyte contains remnants of the golgi apparatus, mitochondria, and a few other cytoplasmic organelles, normally disappears within 1 to 2 days Number of reticulocytes in circulation is less than 1% of all RBCs Guyton & Hall: Textbook of Medical Physiology 12th Edition, by J.E.Hall • Mature RBCs have no organelles • No mitochondria • Glycolysis àATP • No new enzyme, cannot renew membrane components • Older cells are more fragile and rupture easily Regulation of red blood cell formation The hormone erythropoietin (EPO) released by the kidneys (and to a lesser extent the liver) in response to prolonged oxygen deficiency. Regulation of red blood cell formation • low oxygen à EPO begins to be formed within minutes to hours. • about 5 days later new red blood cells appear in the circulating blood • EPO stimulate the production of proerythroblasts from hematopoietic stem cells in the bone marrow. Guyton & Hall: Textbook of Medical Physiology 12e Lifecycle of an RBC • RBCs are subjected to mechanical stress. • After ≈120day, the RBC cell membrane ruptures, or the damage is detected by phagocytic cells. • Old RBCs are destructed in the spleen, liver and bone marrow A macrophage phagocytizing multiple RBCs Hemolysis: destruction of red blood cell membrane à the release of their contents (Hb) Characteristics of RBC • Hb – 14-17 g/dL in males, 12-16 g/dL in females • Mean corpuscular volume (MCV, mean red cell volume femtoliters/cell): 80-100 fL • Mean corpuscular hemoglobin (MCH): 20-29 pg • Mean corpuscular hemoglobin concentration (MCHC): 34g/dL Mean corpuscular Hb concentration (%) = (Hbx100)/Hct 31%–36% Hb/cell • Red cell distribution width, RDW (%) - measure variation in red blood cell volume and size pico = 10-12 femto = 10-15 Red cell distribution width, RDW (%) Simple measure of red blood cell (RBC) size heterogeneity (i.e., anisocytosis), RDW is easily calculated by dividing the standard deviation (SD) of erythrocyte volumes for the mean corpuscular volume (MCV). • Abnormality in the morphology (form/shape) of the erythrocytes may indicate presence of a disorder • Abnormally small cells (microcytosis) • Abnormally large cells (macrocytosis) • Pale (hypochromic) • Because of the continuing need to replenish RBCs, the erythropoietic cells of the bone marrow are among the most rapidly growing and reproducing cells in the entire body. • Their maturation and rate of production are affected greatly by a person’s nutritional status. • Especially important: vitamin B12 and folic acid. They are essential for DNA synthesis, because they are required for formation of thymidine triphosphate, one of the essential building blocks of DNA Vitamin B12 (Cyanocobalamin) and folic acid • Lack of vitamin B12 or folic acid causes abnormal and diminished DNA and, consequently, failure of nuclear maturation and cell divisionà failing to proliferate rapidly • The erythroblastic cells of the bone marrow produce mainly larger than normal RBCs called macrocytes, which have a flimsy membrane and are often irregular, large, and oval instead of the usual biconcave disc. • These poorly formed cells, after entering the circulating blood, are capable of carrying oxygen normally, but their fragility causes them to have a short life, half to one-third normal. Functions of the Red Blood Cells • Primary function is to facilitate O2 transport from the lungs to the cells & CO2 transport from cells to lung • Transport hemoglobin • carries oxygen from the lungs to the tissues • they contain a large quantity of carbonic anhydrase, which catalyzes the hydration of CO2 to form H2CO3. Carbonic anhydrase increase the rate of this reaction several thousandfold CO2+ H2O H2CO3 (Carbonic acid) • Hb is an excellent acid-base buffer H+ + HCO3- (Bicarbonate) Oxygen transport • Over 98% of O2 binds the iron-containing protein hemoglobin in red blood cells. • Remaning dissolves in plasma. More oxygen is released as the blood concentration of carbon dioxide increases, as blood becomes more acidic, or as blood temperature increases. 15 Carbon Dioxide Transport Carbon dioxide is transported in one of three forms: -dissolved in plasma (7%) - bond to hemoglobin (carbaminohemoglobin, 23%) - in the form of bicarbonate ion (70%) 16 Hemoglobin (Hb) = Heme + globin chains. Hb have four globular protein chains , each wrapped around heme group. Hem group = a porphyrin ring with and iron atom in the center Iron atom can combine reversibly with one molecule of oxygenà a Hb molecule can transport 4 molecules of oxygen. A single red blood cell contains about 250 million hemoglobin molecules, each of these tiny cells can accumulate about 1 billion molecules of oxygen! Measurement of oxy/deoxyhemoglobin ratio (oxygen saturation) Pulse oximetry Oxyhemoglobin is bright red, and deoxyhemoglobin is darker. A pair of small light-emitting diodes (LEDs) facing a photodiode through a translucent part of the patient's body, usually a fingertip or an earlobe. One LED is red, with wavelength of 660 nm, and the other is infrared, 905, 910, or 940 nm. Absorption at these wavelengths differs significantly between oxyhemoglobin and its deoxygenated form; therefore, the oxy/deoxyhemoglobin ratio can be calculated from the ratio of the absorption of the red and infrared light There are several isoforms of globin proteins in Hb (alpha, beta, gamma, and delta) Adult hemoglobin (hemoglobin A) HbA • Most of the HbA1 have 2 α chains and 2 β chains α2β2 • About 2.5% HbA2 2 alpha chains and 2 delta chains HbA1C - Glucose binds covalently to Hb Amount of HbA1C is directly related to exposure to glucose over the preceding 812 weeks. Used to monitor long term fluctuations of blood glucose levels Recommended HbA1C ratio <5.7% Other types of hemoglobin • Fetal hemoglobin (HbF): • Gamma globin instead of β chains - α2γ2 • Higher O2 affinity – facilitates O2 movement from the mother • Hemoglobin S. • abnormal variant, α subunits are normal and the β subunits are abnormal (αA2βS2). • Lower O2 affinity • causes sickle cell disease. In its deoxygenated form, HbS forms sickle-shaped rods in the red blood cells, distorting the shape of the red blood cells. This deformation of the red blood cells can result in occlusion of small blood vessels. The RBC can engage in two metabolic pathways: • • • • glycolysis (consumes 90% of glucose) the pentose shunt (consumes the remaining 10% of glucose) The cell generates its ATP exclusively by glycolysis. An important constituent of the RBC is 2,3-diphosphoglycerate (2,3-DPG) . RBCs use DPG mutase to convert 1,3diphosphoglycerate (1,3-DPG), part of the normal glycolytic pathway, into 2,3-DPG. In RBCs, the cytosolic concentration of 2,3-DPG is normally 4 to 5 mM, about the same as the concentration of hemoglobin. 2,3-DPG acts on hemoglobin by reducing the O 2 affinity of hemoglobin. Erythrocyte sedimentation rate (ESR) • The blood is drawn into a special tube with marks. • The tube is placed in a rack in a strictly vertical position for 1 hour at room temperature • The distance of fall of erythrocytes, expressed as millimeters in 1 hour, is the ESR. Erythrocyte sedimentation rate (ESR) After an hour http://www.medicine.mcgill.ca/physio/vlab/bloodlab/esr.htm Erythrocyte sedimentation rate (ESR) RBC density is greater than that of plasma. But normally RBC do not settle very much in an hour. Increased levels of plasma fibrinogen and globulins cause the RBC to clump together, stack up and form a red column called rouleaux. RBC form large aggregates called rouleaux Average values in healthy men are: <15mm/hr; in healthy females <20mm/hr. often >40 mm in certain inflammatory disorders Erythrocyte sedimentation rate (ESR) RBCs in rouleaux formation are heavier and settle faster. So the ESR reflects mainly changes in the plasma proteins that accompany acute and chronic infections, inflammatory diseases and some cancers. RBC form large aggregates called rouleaux • Some factors that decrease ESR: abnormally shaped RBC (sickle cells, spherocytosis) • Technical factors: short ESR tubes, low room temperature, delay in test performance (>2 hours), clotted blood sample, excess anticoagulant, bubbles in tube. Erythrocyte sedimentation rate (ESR) • Almost any acute stress to the body (trauma, infection, disease) induces a reaction called the acute-phase response. • In response to inflammatory cytokines, the liver rapidly synthesizes and secretes into the circulatory system several proteins that aid in the host response to the threat. • e.g. fibrinogen causes RBCs to cluster and increases their effective density. • When blood from a patient with hyperfibrinogenemia is placed in a glass tube, the RBCs fall more quickly under the influence of gravity than when the blood is from a healthy subject. • It is not specific (i.e. many different conditions can cause it to increase), • the ESR is still widely used by clinicians to assess the presence and severity of inflammation. • It is a simple technique, that can be easily performed . Blood group system • The ABO blood group is based on the presence (or absence) of two major protein antigens on red blood cell membranes—antigen A and antigen B. • People with red blood cells that are covered with A or B molecules are said to have type A blood or type B blood, respectively. If both molecules, A and B, are present, the blood is type AB; if neither is present, it is called type O. Blood Groups and Transfusions Knowing about a person’s blood type is important for blood transfusions. Inappropriate combinations between the blood groups of the recipient and the donor can lead to potentially fatal agglutination, because the recipient’s immune system will have antibodies against the donor’s red blood cells. A person’s erythrocytes have on their surfaces one of four antigen combinations: only A, only B, both A and B, or neither A nor B. Blood Groups and Transfusions • A person with type A blood can receive type A or O, not type B or AB blood, because his or her blood contains anti- B immunoglobulin (Ig) M antibodies. • A person with type B can receive type B or O blood. Those with AB blood can receive blood from anyone and are, therefore, universal recipients. Type O persons can receive blood from a type O person only but can donate to all groups and are, thus, called universal donors. Rhesus factors (Rh) • They are unique cell surface proteins. The Rh system is complex, involving three genes producing Rh antigens C, D, and E. • Rh D, the most important, is found in the blood of 85% of people, who are classified as Rh+ (Rhesus positive). The remaining 15% are said to be Rh− (Rhesus negative). • More than 600 additional red blood cell antigens have been described since the discovery of the ABO and Rh blood systems in the early 20th century, but they are considered minor antigens. • They might be included in the screening of patients with frequent blood transfusions. Minor antigens, for example, are part of the Duffy, Kell, Kidd, MNS, and P antigen systems. Why is it important to know Rh factor • It is important in pregnant women because a baby’s life can be endangered if it inherits Rh+ blood from its father but the mother is Rh−. • Late in pregnancy, or at parturition, the baby’s blood may cross to the mother’s system, where the erythrocytes are recognized as foreign and antibodies are formed against them. These antibodies pose a serious threat to any future Rh+ babies of hers in following pregnancies. • Similar problems of incompatibility between mother and child generally do not exist for the ABO blood groups because the antibodies formed belong to the IgM class and cannot cross the placenta