Role of red blood cells PDF

Role of red blood cells Blood is composed of: Red blood cells 45% of blood White blood cells 1% of blood Platelets...

Role of red blood cells Blood is composed of: Red blood cells 45% of blood White blood cells 1% of blood Platelets 1% of blood Plasma 45% of blood Clotting factors Antibodies Electrolytes Proteins plasma may also have some oxygen dissolved Function of red blood cells: Transport of oxygen to tissues and carbon dioxide away from tissues Structure of red blood cells Flexible, bi-concave disk (can lead to haemolysis if damaged Allows for passage through small capillary blood vessels Haemoglobin within red cells Increase the oxygen carrying capacity of blood ~70% Cell surface proteins Clinically significant proteins include those that define blood group Role of red blood cells 1  No nucleus or mitochondria Increases flexibility of cell Rely on glycolysis for energy No nucleus means cells/tissues cannot be regenerated Lack of mitochondria results in reliance on anaerobic respiration These result in a limited life span, whereby the spleen will then remove it. The importance of gas transport Anaerobic respiration only produces 2 ATP while aerobic respiration produces 36 ATP Role of red blood cells 2  Red cells require energy too Red cells produce energy by anaerobic pathways Embden Meyerhof pathway Pentose Phosphate pathway Why do red cells need energy? Role of red blood cells 3  Maintain glycolysis and provide ongoing energy for cell functions Maintain iron in Hb in reduced Fe2+ state, in which oxygen can bind Protect metabolic enzymes, Hb and membrane proteins from damage Preserve membrane structure In summary, it is to keep the red cells healthy How oxygen is transported by red cells: haemoglobin Haemoglobin increase oxygen carrying capacity of blood 70- fold Haemoglobin = haem + globin Haem = iron bound to porphyrin ring Globin = protein chains that bind haem Iron binds oxygen temporarily and reversibly Each hemoglobin A (HbA) (~95% in adults) molecule is made of: 2 alpha globin chains 2 beta globin chains Other combination of globin chains include HbA2 (~3%): 2 alpha + 2 delta Role of red blood cells 4  HbF (foetal Hb): 2 alpha + 2 gamma from sickle cell disease, results in more HbF Haemoglobin variants / haemoglobinopathies How oxygen is transported by red cells: oxygen binding Lung alveoli pCO2 in lung is lower than tissue, higher local pH, increases haemoglobin’s higher affinity for oxygen, favouring the generation of oxyhaemogobin and delivery of oxygen away from the lungs Body tissues pCO2 in lung is higher than tissue, lower local pH, favoring dissociation of oxygen from oxyhaemoglobin, releasing oxygen to tissues Other factors that shift the haemoglobin-oxygen dissociation curve: Temperature High metabolic rate increases thermal energy production as by-product Role of red blood cells 5  Increases temperature of local blood vessels and capillaries, shifts the curve to the right / decreased oxygen affinity Higher metabolism = more oxygen delivery 2,3-DPG - has a more significant effect during pregnancy Shifts curve right / decreased oxygen affinity Regulated in lots of different states / conditions include pregnancy (increased foetal O2 delivery) and lower O2 situations (eg high altitude) Where are red cells made? How are red blood cells made and how is this regulated? Role of red blood cells 6  MEP is a pluripotent stem cell Haemoglobin builds up as the stage develops This explains the more reddish color Process of erythropoiesis (ie red cell production) begins from haemoapoetic stem cells in the bone marrow This process produces 2 million red blood cells per minute Sequential maturation steps; increase haemoglobin in the cytoplasm and then ejection of the nucleus What influences red cell production Erythropoietin >90% made in the kidney Increases production in response to anaemia or hypoxaemia increasing EPO level resulting in more RBC Availability of Iron B12 and Folate Globin Chain production Inherited disorders Role of red blood cells 7  What can go wrong in red cell production? Bone marrow failure Broad range of disorders Often with reduce production of other blood cell types Inherited and acquired causes Includes cancer and immune mediated conditions Problems with globin production Inherited loss of one of more globin genes (most commonly beta) leads to reduced or absent globin production. Collectively known as thallassemias (genetic conditions) Role of red blood cells 8  Lack of components required for red cells and haem production B12 and folate required for DNA synthesis and red cell proliferation lack mainly occurs during vegetarian or vegan diets Iron required for haem synthesis Lack of these limits red cells and/or haem production All gained from dietary source Iron deficiency Role of red blood cells 9  Iron required for haem synthesis, key to oxygen transport Iron absorbed for the diet and then recycled Decreased iron → decreased haemoglobin → small, pale red cells with decreased O2 carrying capacity Decreased iron availability: decreased absorption and/or increased loss (EG from bleeding) Lack of stimulus Impaired kidney function leads to a loss of appropriate EPO production in response to hypoxia Role of red blood cells 10  What can go wrong in red cell function? Cell intrinsic issues Red cell membrane defects Different red cell shapes Increased red cell breakdown EG hereditary spherocytosis (rare, inherited disorder) spleen will remove the red cell if damage is detected Red cell enzyme production problems Can increase red cell breakdown Eg glucose 6 phosphate dehydrogenase (G6PD) deficiency Role of red blood cells 11  Most ocmmon enzyme deficiency gloablly triggers (such as stress, some foods / medications) increase oxidative stress G6PD cannot be increased to compensate, red cells break down Haemoglobin variants Sickle cell Inheritance abnormal beta globin chain (both copies) Red cells that change shape or “sickle” when they deoxygenate Lots of important consequences to this but includes increased breakdown of red cells Lots of fluid is given to hydrate, similar to ischaemia, sticky Role of red blood cells 12  Cell extrinsic Haemolysis Red cell breakdown / destruction Lots of ways this can happen due to red cell extrinsic factors One example is immune mediated haemolysis Role of red blood cells 13  Inappropriate targeting of red cells by the immune system Antibodies target proteins on the red cell surface Labels red cells for destruction by other specialised immune cells Requires frequent transfusion until the autoimmune disease stops Role of red blood cells 14  Treatments Not just one solution, blood transfusion may not be appropriate, also religious obligations etc Replace what is lacking for RBC production/function, if possible eg iron supplementation in iron deficiency Improve O2 transport to tissues eg red cell concentrate blood transfusion, if patient severely unwell Other treatments Replacement Replacement of B12, folate, iron Erythropoeietin Transfusion Transplant Targeting specific diseases Different treatments for specific bone marrow failure disorders Immune modulation Evolving therapies Gene therapy Role of red blood cells 15 Role of red blood cells 16