Erythrocytes: Creation, Function and Destruction Flashcards
1
Q
Describe the breakdown of the blood volume.
A
- 70kg adult = ~5L blood volume.
- 40% cells
- 60% plasma
- This is expressed as ‘packed cell volume’ or ‘haematocrit’ - typically 0.4 or 40%.
2
Q
What is the ratio of red blood cells to white blood cells.
A
- Red blood cells are 500x more numerous that white blood cells - approximately 2.4x1013.
3
Q
What is the replacement rate of red blood cells? Why?
A
Red blood cells need to replace 1% per day to make up for the expected lifespan of 100-120 days.
4
Q
Describe the structure of red blood cells and relate this to function.
A
- 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
5
Q
Describe the formation of blood.
A
- 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.
6
Q
What are the constituents of bone marrow stroma?
A
- Fibroblasts
- Macrophages
- Endothelium
- Fat cells
7
Q
What are the growth factors of bone marrow?
A
- Interleukin 3
- Erythropoietin (EPO- RBCs)
- Androgens
- Thyroxine
- Growth hormone
8
Q
What is reticulin?
A
Remnants of mRNA left once the nucleus of a maturing RBC has been extruded. It is removed by the spleen in 1-2 days.
9
Q
When and why would it be useful to measure reticulocytes?
A
- 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.
10
Q
How much iron should an adult have?
Where is this iron in the body?
A
- Adults have 3000-5000mg of iron
- 2/3 is in Hb
11
Q
How is iron content in the body maintained?
A
- 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.
12
Q
How is iron lost?
A
- Menstrual loss
- Minor trauma
- Gi - ~1ml blood per day
- Blood sampling
- Very small amounts in urine / skin shedding
13
Q
How is iron transported?
A
- Transferrin is responsible for the transport and recycling of iron.
- Transferrin receptors are increased in iron defficiency.
14
Q
What is ferritin?
A
Insoluble form of iron storage. This is a good measure of the body’s iron stores.
15
Q
Describe the body’s folic acid / folate need.
A
- 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
16
Q
Describe the body’s B12 / cobalamin need.
A
- 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.
17
Q
What are B12 and folate (folic acid) required for?
A
- Both are required in RBC production.
- B12 is required in change from 5-methyl tetrahydrofolate (THF) to THF.
18
Q
Describe the properties of erythropoietin.
A
- 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).
19
Q
What is the role of hypoxia inducible factor?
A
Senses O2 levels in peritubular cells.
20
Q
Describe the effect of low O2 on EPO production and vice versa.
A
- 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.
21
Q
What causes changes in the RBC membrane?
A
Inherited mutations can cause shape changes.
Eg. spherocytosis.
22
Q
What factor is responsible for the flexibility and resilience of RBCs?
A
- Spectrin gives RBCs flexibility and resilience.
- Abnormal production of spectrin causes odd shapes and forms rouge RBCs.
23
Q
How is O2 carried in the blood?
A
It binds to haem which is anchored to the globin chains of haemoglobin or myoglobin.
24
Q
Describe the structure of adult haemoglobin.
A
- 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.
25
What causes thalassaemia?
An inherited defect in globin chain production
26
What causes sickle cell disease?
One amino acid change in a Hb beta chain
27
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.
28
Why can't erythrocytes produce proteins for energy?
Becauase they have no nucleus
29
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+
30
What is caused by RBC enzyme deficiencies (eg. pyruvate or G6DP deficiency)?
These deficiencies can cause anaemia by haemolysis - increased rate of RBC breakdown.
31
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.**
32
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.
33
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.
34
What is myoglobin?
* Store of oxygen in skeletal muscle for immediate use.
* 1 haem group and 1 globin chain.
35
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.
36
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.
37
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.
38
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.
39
Describe the buffer system: haemoglobin.
* H+ combines with Hb after loss of O2.
* Low pH decreases hB affinity for O2.
* CO2 + Hb ↔︎ HbCOO- + H+
40
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
41
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.
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