6. Erythropoiesis Flashcards
What are the different sites of erythropoiesis prior to birth?
3rd week of development - yolk sac and mesothelial layers of the placenta
6th week - liver and spleen - this is where they are being
3rd month onwards - bone marrow now becomes the principle source of erythrocytes
What are the different sites of erythropoiesis after birth?
Up to 5 years old - bone marrow in all bones
5-25 years - bone marrow of long bones
Over 25 years - Produced in the bone marrow of membranous bones i.e. vertebrae, sternum, ribs, cranial bones, ilium
Briefly describe red and yellow bone marrow and what is meant by ‘myeloid tissue’
Red bone marrow is the site of erythropoiesis
Yellow bone marrow contains large amounts of fat droplets and cells
Myeloid tissue is another term for bone marrow
Give the stages of erythropoiesis
Haemocytoplast (haematopoietic stem cell) in the bone marrow
This differentiates into a common myeloid progenitor cell (proerythroblast) and is committed at this stage
Many transformations then occur to become an erythroblast with a condensed nucleus
The cytoplasm then becomes filled with Hb. and a reticulocyte is formed (immature erythrocyte) once the nucleus is expelled and released into the blood
What is a normoblast?
This is a late late erythroblast?
SO haemocytoplast to proerythroblast to normoblast to reticulocyte to erythrocyte
How does a proerythroblast appear histologically?
Large, round cell
Large staining nucleus
Bright blue rim of cytoplasm surrounds the large staining nucleus
IMAGE ON THE MILLAR PP
How does a normoblast appear histologically?
From the image of the proerythroblast:
The nucleus becomes very condensed (is then finally ejected and the cell becomes a reticulocyte)
How can you differentiate reticuloytes from erythrocytes histologically?
There are obvious dark markings visible in reticulocytes
These are ribosomes/ribosomal RNA
“Diapedesis”
The passing of erythrocytes through the pores in the capillary membranes into the blood capillaries from the bone marrow
What is the RBC in a healthy adult?
Men - 5.2 million per microlitre
Women - 4.7 million per microlitre
Just need to remember that it is around 5 million per microlitre
What is the lifespan of an erythrocyte and why?
120+/-30 days - this remains remarkably constant in healthy adults
These wear out quickly due to a developed reduced oxygen carrying capacity - they become rigid and cannot pass through capillaries
What is the MCV in normal RBCs and in macro and microcytic anaemia?
Normal RBC - 90 fl
Microcytic anaemia - <80 fl
Macrocytic - >100 fl
Describe how the process of erythropoeisis is controlled
Controlled via EPO - erythroprotien
EPO is produced in the kidney via fibroblasts in the proximal tubule of the cortex of the kidney
EPO has an effect once the cell has committed i.e. on myeloid progenitor cells/proerythroblasts - it acts to speed up the maturation of the erythroblasts and increases their release into the circulation
Why is erythropoiesis be controlled by EPO?
Because oxygen levels around the proximal tubule of the cortex of the kidney are constant and changes due to e.g. exercise do not have an impact
The EPO releasing cells themselves are sensitive to hypoxia - these can then cause an increased/decreased release of EPO
What is the link between kidney damage and anaemia?
Kidney damage can lead to microcytic anaemia
This is because kidney damage will result in reduced EPO production
How do erythrocytes produce ATP and why do they require ATP?
Erythrocytes do not have mitochondria so cannot use oxidative metabolism to make ATP
SO produce it via anaerobic glycolysis and also use the pentose phosphate pathway for NADPH
Require ATP for sodium pumps in the membrane and also for GLUT1 transporters which take up glucose
What else can a common myeloid progenitor cell differentiate into?
Can differentiate into any of the myeloid red cell family
Megakaryotes
Erythrocytes
Mast cells
Myeloblasts
Name the different myeloblasts
Basophil
Neutrophil
Eosinophil
Monocyte which can then differentiate into a macrophage
What other cell lineage is there other than myeloid?
Lymphoid - haemoblasts can differentiate into lymphocytes
State the different lymphoid cells
Common lymphoid progenitor cell can differentiate into a natural killer cell or a small lymphocyte
A small lymphocyte can then differentiate into T lymphocyte or B lymphocyte
B lymphocyte can then differentiate into a plasma cell
How are erythrocytes removed from the body?
Erythrocytes are disposed of as they pass through the spleen
Believed that antigens of old erythrocytes differ to the antigens of young erythrocytes and hence allows their detection by splenic macrophages
OR may be due to increased levels of methaemoglobin in the cell
OR detected by their increased rigidity - become trapped in the splenic capillaries - when trapped, can be engulfed by splenic macrophages
Describe the mechanism of action of splenic macrophages
Haem and globin are separated
Globin is broken down into amino acids
Haem prosthetic groups are broken open by haemoxygenase enzyme
The iron atom is removed for reuse
Biliverdin is left as a result - this is green in colour
How is biliverdin converted to bilirubin?
Via biliverdin reductase
This process occurs in the macrophage
What happens to the bilirubin formed from the biliverdin?
Binds to albubin in splenic macrophages and is released in the blood - is unconjugated
Then reaches the liver and is attached to glucaronic acid which is more soluble
The bilirubin is now conjugated
The conjugated bilirubin passes to the small intestine in bile and is converted to urobilinogen via bacteria
Most urobilinogen passes out of the body in the faeces and about 10% is passed back in the portal vein to the spleen and is passed to the to the kidney and excreted in the urine (provides yellow colour)
What is the ESR?
Erythrocyte sedimentation rate
What is the charge on an erythrocyte and what does this mean?
Negative surface charge - means that they normally repel one another
What alters the ESR?
Inflammation - causes the negative charge to be reduced - erythrocytes can clump together - the ESR is increased
What is a raised ESR indicative of?
Raised ESR is a specific marker for infection/inflammation in the blood
What is a rouleux?
This is a clump of erythrocytes due to a loss of negative charge - occurs during inflammation
