29-09-21 – Red Blood Cells – Creation, Function and Destruction Flashcards
How much more numerous are red blood cells than white blood cells?
How often are they replaced?
What is their lifespan?
- RBC are 500% more numerous than WBC
- They need to replace 1% everyday to make up for an expected lifespan of 100 days to 3 months.
What are red blood cells?
What are they unable to do compared to regular cells?
What is their structure like?
Why is it this way?
How can RBCs protect themselves?
What are the main functions of RBC?
- Red blood cells can be described as bags of haemoglobin (Hb) and enzymes for glycolysis
- Red blood cells can not divide or make new proteins. They circulate, dies, and are then replaced.
- Their structure is a biconcave disc and they contain no nucleus – this disc allows them to be pliable (flexible) and have a high surface area/volume for transporting oxygen
- This pliability is important as RBCs are subjected to high pressures and squeezed through narrow capillaries
- They are able to maintain membrane integrity and prevent oxidation
- Their main function is O2 and CO2 transport and acid/base balance in order to maintain the pH of the blood.
How are erythrocytes (RBCs) produced?
What is this process called?
How is it regulated?
What are 5 growth factors that drive maturation?
- Embryological stem cells form “blood islands” in yolk sac
- These cells then migrate to the liver, then to the spleen, then to the bone marrow of a foetus.
- The red blood cells then develop around macrophages, by obtaining iron from the store of iron in the macrophage. Iron absorption and release from macrophages is regulated by Hepcidin
- This process is known as erythropoiesis , which is the production of RBCs in the bone marrow.
- Growth factors that drive maturation:
- Erythropoietin (main one)
- Androgens
- Thyroxine
- Growth hormone
- Interleukin -3
How does distribution of active bone marrow change with age?
- At birth, marrow is widely distributed, but retreats to the axial skeleton by adulthood.
What are reticulocytes and reticulin?
How long does reticulin stay in the body?
What can they be used for?
What is it measured in?
What stains reticulin?
- Reticulocytes are newly produced, relatively immature RBCs
- Reticulocytes extrude reticulin, which are the remnants of ribosomal Mrna left after the nucleus has been extruded by the Reticulocytes.
- Reticulin is removed by the spleen in 1-2 days
- It is a useful measure of marrow response to anaemia or treatment as it gives indication of number of RBCs being released from the marrow.
- Reticulin levels are expressed as a % of absolute number e.g 1-2% or 50-100x10^9/l
- Reticulin can be stained by methylene blue.
How much iron is present in adults?
What is most of it used for?
What are the 2 types of iron and how are they obtained through diet?
How is it absorbed?
- Adults have 3-5g of iron, 2/3 of which is used for Haemoglobin
- Haem iron is found in meat-based products
- Non-haem iron is found in leafy green veg, nuts legumes etc
- Fe2+ (ferrous iron) is absorbed into duodenal cells, which are cells of the intestinal lining
What 5 ways is iron lost from the body?
- Menstrual loss
- Minor trauma
- Blood sampling
- Small amounts of urine/skin shed
- GI absorbs 1ml blood per day
How is iron transported into cells?
What is the protein responsible for this?
- Transferrin is a glycoprotein that is responsible for transport of iron.
- Transferrin containing iron binds to transferrin receptors, which enter the cell via receptor mediated endocytosis.
- The iron is dropped off in the cell, the transferrin receptors return to the cell membrane, and the transferrin is released back outside the cell.
What is the name given to Fe2+ and Fe3+ ions?
What happens to Fe2+ ions when they meet oxygen?
- Fe2+ - ferrous ion
- Fe3+ - Ferric ion
- Ferrous ions are soluble at neutral pH, but in the presence of oxygen, aqueous Fe2+ is converted into insoluble ferric oxide hydroxide (Fe3+)
Where can folic acid/folate and B12/cobalamin be found?
What are they needed for (AID IN PROD)?
- Folate is obtained from diet – green veg/fruit
- Cobalamins obtained from diet – animal products
- Both of these are required for red blood cell production
- They are involved in the production or uridine (involved in RNA synthesis) into thymidine (involved in DNA synthesis)
What is erythropoietin?
Where is it formed?
What is its purpose?
What 4 things can stimulate its production?
What cells sense low O2 levels and stimulate its production?
What can it be used to treat?
CMRA
- Erythropoietin is a glycosylated 165 amino acid protein
- 90% is produced in kidneys and 10% in the liver
- Erythropoietin is the main driver of erythropoiesis (RBC production) in the bone marrow.
- There are no body stores of Erythropoietin, but its production can be stimulated by:
- Tissue hypoxia
- Anaemia
- High altitude
- Epo producing tumours, such as in the kidney (renal)
- Perinephric cells can sense low O2 levels, so Mrna production for epo is increase and epo is produced
- Erythropoietin can be used as a recombinant drug for renal anaemia caused by chronic renal failure (underproduction) and myelodysplasia (blood cancer causing a lack of healthy blood cells)
What are the structures and content of red blood cells?
- Membrane
- Haemoglobin
- Enzymes
What does the membrane of the RBC contain?
What is this made from?
Where does this connect?
What quality does it contribute to RBCs?
- The RBC has a lipid bi-layer with a protein skeleton bound into it
- This skeleton is made from alpha and beta spectrin strands interweaving.
- This skeleton is attached to transmembrane proteins of the cell
- It provides the shape and springiness that are required of red blood cells.
What is haemoglobin?
What is its structure like?
What is its purpose?
What is the difference in haemoglobin in adults and foetuses?
What are 2 conditions associated with defective haemoglobin?
- Haemoglobin is a quaternary protein consisting of 4 subunits, with 4 haem molecules
- It contains 2 alpha chains and 2 beta chains, with a haem unit for each globin chain.
- The purpose of the haem unit is to bind oxygen, which allows RBCs to transport O2 around the body.
- Hb A (adult) = 2 alpha, 2 beta
- Hb F (foetal) = 2 alpha, 2 gamma
- Thalassaemia – an inherited defected in globin chain production
- Sickle cell disease – one amino acid change ain beta chain
What pathway is found in red blood cells?
What enzyme catalyses this reaction?
What 3 things is energy from this pathway used for?
What can deficiencies in this enzyme cause?
- RBCs contain a glycolytic pathway that breaks down glucose and ends with pyruvate and lactate, and energy in the form of ATP.
- Pyruvate kinase is the enzyme that catalyses this reaction
- This energy is used for:
- Maintaining membrane integrity
- Preventing oxidation of enzymes and Fe2+
- Maintain gradients of K+ and Ca2+
- Pyruvate kinase deficiencies can cause anaemia by haemolysis – increased rate of RBC breakdown.
When is O2 bound to haemoglobin on the oxygen dissociation curve?
What causes a left and right shift of the curve?
Where do these right and left shifts represent Hb and O2 affinity?
- Hb and O2 are bound at high tension (PO2)
- O2 is released from Hb at low tension
- Acidosis causes a right shift in the curve, allowing more oxygen to be released from Hb to the tissues
- Alkalosis causes a left shift in the curve, allowing more oxygen to be bound to Hb in the lungs.
What molecule causes a right shift in the O2 dissociation curve?
How does it do this?
What 3 times are levels of this molecule increased?
- During an intermediate step of glycolysis, a molecule called 2,3 DPG produces a right shift of the oxygen dissociation curve, allowing more O2 to be released to the tissues.
- 2,3 DPG does this by entering the globin chains and releasing O2, making deoxyhaemoglobin
- Levels of 2,3 DPG can be increased through exercise, anaemia, and at high altitude
What is myoglobin?
Where is it found?
What is it used for?
Where does its oxygen dissociation curve sit in relation to haemoglobin?
What happens after myoglobin stores are used?
- Myoglobin is a dark red pigment found only in muscles
- It acts as a last-ditch small oxygen reserve for severe exertion.
- Its dissociation curve lies a long way to the left of haemoglobin
- After Myoglobin stores are used, anaerobic respiration takes place.
What makes up 60% of the buffer capacity in the body?
What is the equation?
What is this reaction catalysed by?
Where does this occur?
- Bicarbonate makes up 60% of buffer capacity in the body.
Increased pH (alkalosis): Shift left, decreasing H⁺ and HCO₃⁻ concentrations.
Decreased pH (acidosis): Shift right, increasing H⁺ and HCO₃⁻ concentrations.
- This equation is catalysed by Carbonic Anhydrase as a catalyst
- The CO2 is the waste product of cells that is picked up by the RBC during gas exchange in the lungs.
What makes up 30% of the buffer capacity in the body?
What is the equation?
- Haemoglobin is responsible for 30% of the buffer capacity in the body.
- During gas exchange in the lungs, H+ ions present decrease the pH, resulting in Hbs affinity for O2 decreasing
- This causes the Hb to release the O2 to the tissues
- The Hb then combines with the H+ ion to increase the pH back up to the physiological level.
