Erythrocytes: Creation, Function and Destruction Flashcards
Describe the breakdown of the blood volume.
- 70kg adult = ~5L blood volume.
- 40% cells
- 60% plasma
- This is expressed as ‘packed cell volume’ or ‘haematocrit’ - typically 0.4 or 40%.
What is the ratio of red blood cells to white blood cells.
- Red blood cells are 500x more numerous that white blood cells - approximately 2.4x1013.
What is the replacement rate of red blood cells? Why?
Red blood cells need to replace 1% per day to make up for the expected lifespan of 100-120 days.
Describe the structure of red blood cells and relate this to function.
- Red blood cells are subjected to high pressures and squeezed thorugh narrow capillaries every minute.
- Biconcave disc
- No nucleus
- Pliable, high surface area / volume
- Bag of Hb and enzymes for glycolysis
- Unable to divide or make new proteins
- Able to maintain membrane integrity and prevent oxidation
- Main functions:
- O2 and CO2 transport, acid/base balance
Describe the formation of blood.
- Embryological stem cells form blood islands in the yolk sac.
- Cells migrate to the liver, then the spleen, then the bone marrow in the fetus.
- At birth, marrow is widely distributed retreating to axial skeleton by adulthood.
What are the constituents of bone marrow stroma?
- Fibroblasts
- Macrophages
- Endothelium
- Fat cells
What are the growth factors of bone marrow?
- Interleukin 3
- Erythropoietin (EPO- RBCs)
- Androgens
- Thyroxine
- Growth hormone
What is reticulin?
Remnants of mRNA left once the nucleus of a maturing RBC has been extruded. It is removed by the spleen in 1-2 days.
When and why would it be useful to measure reticulocytes?
- It is a useful measure of marrow response to anaemia or treatment (eg. 5-10 fold rise).
- Stained by new methylene blue on slide or on automated count.
How much iron should an adult have?
Where is this iron in the body?
- Adults have 3000-5000mg of iron
- 2/3 is in Hb
How is iron content in the body maintained?
- Daily diet contains 10-20mg of which 1-2mg are absorbed in ferrous form - higher need in pregnancy / blood loss.
- Fe2+ transported into duodenal enterocytes (small intestine absorptive cells).
- Hepcidin regulates iron absorption and release from macrophages:
- Increase in inflammatory disease = less available iron.
- Body has no mechanism to excrete iron.
How is iron lost?
- Menstrual loss
- Minor trauma
- Gi - ~1ml blood per day
- Blood sampling
- Very small amounts in urine / skin shedding
How is iron transported?
- Transferrin is responsible for the transport and recycling of iron.
- Transferrin receptors are increased in iron defficiency.
What is ferritin?
Insoluble form of iron storage. This is a good measure of the body’s iron stores.
Describe the body’s folic acid / folate need.
- Daily requirement 0.1mg
- ~0.25mg in diet - green veg and fruit
- Absorbed in upper small intestine
- Liver stores 10-20mg ie. only 100-200 days
- Deficiency can be due to:
- Poor intake
- Absorption
- Increased need
Describe the body’s B12 / cobalamin need.
- Daily requirement = 1µg.
- Diet may contain 5µg but all in animal derived products.
- Gastric parietal cells produce ‘intrinsic factor’ - binds B12.
- Atrophic gastritis - cannot produce intrinsic factor so B12 cannot be absorbed even if dietary intake is sufficient.
- B12 absorbed in terminal ileum.
- Transported on transcobalamin II via portal circulation to the liver.
- Dietary defecit in vegans or pernicious anaemia - antibodies to intrinsic factor associated with gastric atrophy.
What are B12 and folate (folic acid) required for?
- Both are required in RBC production.
- B12 is required in change from 5-methyl tetrahydrofolate (THF) to THF.
Describe the properties of erythropoietin.
- Glycosylated 165 amino acid protein.
- Production:
- 90% renal
- 10% liver
- No body stores, so switched on by:
- Tissue hypoxia or anaemia
- High altitude
- EPO producing tumours eg, renal
- Drives erythropoiesis in the bone marrow.
- Useful recombinant drug for renal anaemia (underproduction) and myelodysplasia (increased drive to erythropoiesis).
What is the role of hypoxia inducible factor?
Senses O2 levels in peritubular cells.
Describe the effect of low O2 on EPO production and vice versa.
- At low O2 levels, mRNA for EPO is increased and EPO is produced.
- So, the lower the tissue pO2, the higher the EPO production.
- The higher the pO2, the lower the EPO production.
What causes changes in the RBC membrane?
Inherited mutations can cause shape changes.
Eg. spherocytosis.
What factor is responsible for the flexibility and resilience of RBCs?
- Spectrin gives RBCs flexibility and resilience.
- Abnormal production of spectrin causes odd shapes and forms rouge RBCs.
How is O2 carried in the blood?
It binds to haem which is anchored to the globin chains of haemoglobin or myoglobin.
Describe the structure of adult haemoglobin.
- Haemoglobin needs:
- 2 α chains (chromosome 16) zeta (early fetal) then alpha.
- 2 β chains (chromosome 22) epsilon, then gamma, then delta, then beta.
- It is a tetramer with 4 globin chains, each of which has a haem group attached.
What causes thalassaemia?
An inherited defect in globin chain production
What causes sickle cell disease?
One amino acid change in a Hb beta chain
Show diagramatic representation of a sickle cell compared with a normal RBC.
What can this cause?
- Sickle cells (abnormal haemoglobin) can cause blockage of vessels.
Why can’t erythrocytes produce proteins for energy?
Becauase they have no nucleus
What is the role of RBC enzymes?
- RBCs cannot make proteins because they have no nucleus, but they do need enough enzymes to make energy.
- RBC enzymes control the whole glycolytic pathway from glucose to lactate and pyruvate.
- These provide energy for:
- Maintaining membrane integrity
- Preventing oxidation of enxymes and Fe2+
- Maintaining gradients of K+ and Ca2+
What is caused by RBC enzyme deficiencies (eg. pyruvate or G6DP deficiency)?
These deficiencies can cause anaemia by haemolysis - increased rate of RBC breakdown.
What is the key function of RBCs?
- Key function is to bind Hb to O2 at high O2 tension and release it at low O2 tension.
- Basically delivery of oxygen and removal or carbon dioxide.
What happens to the oxygen dissociation curve during acidosis or an increase in temperature?
- Acidosis and increased temperature will cause right shift.
- Hence, DELIVER MORE O2 TO THE TISSUES.
What is the effect of 2,3DPG on the oxygen dissociation curve?
- It produces a right shift of the O2 curve, hence more oxygen is released to the tissues.
- 2,3 DPG enters the globin chains, releasing oxygen.
- 2,3 DPG increased in exercise / anaemia / high altitude.
What is myoglobin?
- Store of oxygen in skeletal muscle for immediate use.
- 1 haem group and 1 globin chain.
What is the secondary function of erythrocytes?
-
Acid-base balance
- Regulation of free H+ ions in body fluids
- pH normally 7.35-7.45
- pH is measured on log scale, so pH 7 is 10x greater H+ concentration as pH of 8.
Why is acid-base balance important?
- Enzymes work optimally at physiological pH.
- Cell membranes become leaky in acidosis.
- Neurones become less able to transmit in acidosis - they become hyperactive in alkalosis.
Describe the buffer system: red cell bicarbonate.
- Within the red cells, CO2 is produced from tissue all the time.
- This passes out of the tissue and enters the red cells.
- The reaction that happens within the red cells (diagram) is in constant equilibrium; increase in hydrogen ions will push the reaction to the left, this is catalysed by carbonic anhydrase.
- The majority of CO2 carried in the blood is not carried as CO2, but rather as bicarbonate.
- Bicarbonate ions leave the RBC and enter the plasma.
- The hydrogen ions are either bound within RBCs, or leave the RBCs and are replaced by chloride ions.
What happens to RBCs in the lungs?
- Deoxygenated RBCs enter the lungs by passive diffusion and become oxygenated.
- This process must happen very quickly to get the bicarbonate to turn back into CO2 which we then breathe out.
- Red cells then passively absorb the O2.
Describe the buffer system: haemoglobin.
- H+ combines with Hb after loss of O2.
- Low pH decreases hB affinity for O2.
- CO2 + Hb ↔︎ HbCOO- + H+
Describe the loss / destruction of RBCs.
- As RBCs age:
- Membrane becomes more rigid
- Loss of glycolytic enzymes
- Neoantigens exposed on the cell surface
- Some RBCs are lost from:
- GI tract
- Into soft tissues
- Menstrual loss
- Some RBC destroyed within the body
Describe RBC destruction in circulation and spleen/liver recycling.
- Free Hb ‘mopped up’ by haptoglobin - cleared by the liver. Any excess can appear in the urine.
- Globin chains broken up into amino acids.
- Iron bound to transferrin and returned to macrophages.
- Porphyrin ring becomes bilirubin-bound to albumin and ‘conjugated’ to glucuronide - excreted in bile.
