44. Blood (HT) Flashcards
What is the proper name for RBCs?
Erythrocytes
Is haemoglobin acidic or basic? What type of dye does it bind?
- It is basic
- Binds acidic dyes, like eosin (stains pink)
What important organelles are erythrocytes lacking?
- Nucleus
- Mitochondria
What is a blood film?
A thin layer of blood on a microscope slide, stained in a way that allows the study of cells.
How do erythrocytes arrange themselves in a blood stain? What is this called?
- They tend to pile up in stacks due to their surface area
- This is called “rouleaux”
What maintains the shape of erythrocytes?
Cytoskeleton, including spectrin, ankyrin and other membrane proteins.
What does the shape of erythrocytes depend on?
Water content -> Affected by solutes, especially ions
Draw the different possible shapes of erythrocytes.
The discocyte is the standard shape (when isotonic). Stomatocyte is when in hypotonic solution, while echinocyte is when in hypertonic solution.
Why must erythrocytes be able to deform?
In order to pass through capillaries.
What is the size of an erythrocyte?
7μm
What property of blood does the deformity of erythrocytes contribute to?
- Viscoelasticity
- This is when a fluid exhbits both fluid and elastic properties at the same time
- The elastic properties are due to the deformity of the erythrocytes
Which part of a vessel do erythrocytes tend to keep to?
The central axis.
How do erythrocytes appear in blood film?
What is the normal number of erythrocytes per litre of blood?
5 x 1012 cells/L
How can the viscosity of blood be described?
‘Anomalous’ viscosity
Describe the anomalous viscosity of blood.
- Viscosity of blood increases as blood velocity decreases (up to 10x increase) because:
- Formation of rouleaux (stacks of RBCs) and adherence of erythrocytes to vessel wall
- Shear forces insufficient to deform erythrocytes, so they appear more rigid
Give some factors that can increase the anomalous viscosity of blood.
- Rigidity of membrane (e.g. spectrin defect)
- Age of erythrocytes
- Inclusions inside cells (e.g. sickled cells)
Give some advantages of erythrocytes being anucleate.
- Better SA:V ratio
- Improved deformability
- Less work for heart to pump (since less mass)
Give some disadvantages of erythrocytes being anucleate.
- No protein synthesis or repair, so cells wear out
- Cells can’t change proteins under different conditions
What is the normal turnover time for erythrocytes?
120 days
What is the name for RBC production?
Erythropoiesis
What is the consequence of erythrocytes not containing mitochondria?
They rely on glycolysis.
What are the main energy requirements of erythrocytes?
Energy for ion pumps.
How much haemoglobin is there in the adult body?
About 750g.
What two things does haemoglobin transport?
Oxygen and carbon dioxide
Describe the structure of haemoglobin.
- 2 alpha chains
- 2 beta chains
- Haem prosthetic group -> One Fe2+ per haem
What conditions must be kept in erythrocytes for proper haemoglobin function?
- Reducing conditions
- Otherwise the iron will oxidise to Fe3+ (methaemoglobin)
Aside from haemoglobin, what are the other contents of erythrocytes?
- Enzymes
- Ions
What types of enzymes are found in erythrocytes?
Glucose metabolising enzymes:
- In anaerobic glycolysis
- In pentose phsophate shunt
What is the enzyme involved in the pentose phosphate shunt in erythrocytes and why is it important?
- G6PDH
- It generates NADPH (using glucose), which slows the accumulation of oxidised proteins that are associated with erythrocyte ageing
- This maintains glutathionine in its reduced state
Give an example of an ion that is important to maintain in erythrocytes, how it is maintained and the clinical relevance of this.
- K+
- High intracellular K+ maintained by sodium-potassium pump
- Red cell lysis can be life-threatening because severe hyperkalaemia occurs
What is a crenated erythrocyte?
One placed in a hypertonic solution, so that it shrivels into a echinocyte shape.
What makes the erythrocyte cell membrane semi-permeable?
Aquaporins
Describe the structure of erythrocyte membranes.
- Anchoring proteins -> Spectrin, ankyrin, band 3
- Glycoproteins with carbohydrate external -> e.g. Blood group substances
How do erythrocytes become aged?
Oxidation products build up.
What is glucose required for in erythrocytes?
Maintianing reducing conditions and for ion pumps.
Where and by what are aged erythrocytes destroyed?
In the spleen (and liver) by macrophages.
What factors may shorten the lifespan of erythrocytes?
- Abnormal shape
- Haemoglobin mutation (e.g. sickle cell anaemia)
- Cytoskeleton proteins altered
- Accelerated clearance
- Overactive phagocytosis in spleen and liver (e.g. autoimmune disease or overactive macrophages)
What is the normal rate of erythrocyte production in a healthy human per hour?
About 1 x 1010 per hour
What are some sources of erythropoietic stem cells?
- Bone marrow (in adult)
- Liver (in foetus)
- Embryonic yolk sac
- Early embryonic aorto-gonado-mesonephros region
- Umbilical cord blood at partuition
How can you test for ‘stem’-ness? (Experimental evidence)
In a host where bone marrow erythropoeitic cells are destroyed by radiation or chemo-treatment:
- Transplant cells to be tested
- Determine whether all blood cell types are reconstituted fully
- The host’s bone marrow can be transplanted into further recipients for treatment purposes
Describe briefly the development of erythrocytes.
- Begins with a stem cell (hemocytoblast)
- Turns into committed cell (proerythroblast)
- Then developmental pathway:
- Phase 1 - Ribosome synthesis
- Phase 2 - Haemoglobin accumulation
- Phase 3 - Ejection of nucleus
- During developmental pathway, goes from early erythrocyte to late erythrocyte to normoblast to reticulocyte to erythrocyte
What chemical controls erythropoiesis?
Erythropoietin (EPO)
Describe the EPO system.
What stimuli can trigger the EPO response?
Hypoxia due to:
- Decreased RBC count
- Decreased availability of O2 to blood
- Increased tissue demands for O2
What organ releases erythropoietin (EPO)?
Kidney (and the liver to a smaller extent)
Draw the graph showing erythropoietin levels in response to haemoglobin levels.
Draw a diagram to show a summary of erythrocyte turnover.
What is haematocrit?
The percentage volume of RBCs in blood.
What is the approximate composition of blood?
- About 50% plasma
- About 50% cells and platelets
- 5,000,000 RBC per microlitre
- 7,000 WBC per microlitre
- 250,000 platelets per microlitre
What is anaemia?
A decrease in the total amount of red blood cells (RBCs) or haemoglobin in the blood.
What are the main general causes of anaemia?
- Decreased production
- Disturbed proliferation and differentaition of stem cells
- Disturbed proliferation and maturation of erythrocytes
- Increased destruction (generally haemolytic anaemias)
- Intrinsic (internal) abnormalities -> e.g. Sickle-cell anemia due to abnormal haemoglobin
- Extrinsic (external) abnormalities
- Antibody mediated
- Mechanical trauma
- Blood loss
What is mean corpuscular volume (MCV)?
The average volume of an erythrocyte.
Draw a chart to show the different types of anaemia.
- Microcytic = Small RBCs
- Normocytic = Normal RBCs
- Macrocytic = Large RBCs
What three deficiencies that cause anaemia do you need to know about?
- Iron
- Vitamins
- Folate
- VItamin B12
How does iron deficiency cause anaemia and what type of anaemia is it?
- Iron is required to produce haemoglobin, which cannot occur if iron levels are too low
- It results in microcytic anaemia
How does folate or vitamin B12 deficiency cause anaemia and what type of anaemia is it?
- It causes there to be large, spherical erythrocytes that do not function properly and there are fewer of them
- This is a type of macrocytic anaemia
Describe some types of haemoglobinopathies and how they may affect an erythrocyte.
- Mutations in the subunits of haemoglobin (alpha or beta)
- Cause improper function of the haemoglobin
- Sickle-cell anaemia is an example of this
- Diminished production of one of the two types of subunit
- Mutations that produce this are called thalassemias
- Hemoglobin chain imbalance damages and destroys RBC, thereby producing anemia
- Abnormal associations of otherwise normal subunits
Describe the pathophysiology of sickle-cell anaemia.
- In haemoglobin, the alpha chain is normal, but there is a mutation in the beta chain, giving the molecule the structure, a2bS2.
- People who have one sickle mutant gene and one normal beta gene have sickle cell trait which is benign.
- The loss of red blood cell elasticity is central to the pathophysiology of sickle cell disease.
- In low oxygen conditions, RBC sickling occurs due to the mutation.
- Although reoxygenation may return the cell to its normal shape, repeated episodes of sickling damage the cell membrane and decrease the cell’s elasticity.
- As a consequence, these rigid permanently-sickled blood cells are unable to deform as they pass through narrow capillaries, leading to vessel occlusion and ischaemia.
- The actual anaemia of the illness is caused by haemolysis, the destruction of the red cells, because of their shape. Although the bone marrow attempts to compensate by creating new red cells, it does not match the rate of destruction.
What are the two most important blood group systems?
- ABO system
- Rh system
Describe the principle of the rhesus blood group system.
- The rhesus system includes five antigens D, C, c, E, and e
- A person may be classified as rhesus positivie or negative based on the presence of the D antigen
- This is symoblised by a + or - after the ABO group name
Describe the dangers of the rhesus blood group system in pregnancy.
What is the number of erythrocytes per litre of blood? [IMPORTANT]
5 x 1012
What is the proper name for white blood cells?
Leucocytes
What is the number of leucocytes per litre of blood? [IMPORTANT]
7 x 109