Flashcards in Erythropoiesis Deck (36)
Briefly describe the sites of erythropoiesis in the foetus
Mesoblastic stage - from week 3 this occurs in the yolk sac and mesothelium of the placenta
Hepatic stage - at 6 week stage it occurs mainly in the foetal liver and spleen
Myeloid stage - at around 3 months onwards the bone marrow becomes the principle source
Briefly describe the sites of erythropoiesis after birth
0-5 years - occurs in the bone marrow of all bones
5-25 years - occurs only in the marrow of the long bones
25 years + - occurs in the membranous bones (vertebrae, sternum, ribs, cranial bones and ilium)
Outline the different stages of erythropoiesis
Haematopoietic stem cells (haemocytoblasts) in the yellow bone marrow --> differentiate into a committed stem cell known as common myeloid progenitor (proerythroblast). This pro erythroblast undergoes successive transformations to form an early erythroblast (polychromatophil normoblast) and then late erythroblast (orthochromatic normoblast). The nucleus progressively shrinks and cytoplasm becomes filled with haemoglobin and this is a normoblast (erythroblast). The nucleus is then expelled and the cell becomes a reticulocyte and is released into the blood.
Large cells with a round nucleus with a finely stippled chromatin pattern and they stain quite well with H&E and appear light-dark blue
Describe early erythroblasts (polychromatophils)
The nuclear material is beginning to condense and get smaller as well as produce haemoglobin. The cytoplasm here is grey and not blue.
Polychromatic simply means 'many coloured'
Describe the late erythroblast (normoblast)
The nucleus is very condensed in preparation for ejection
These cells have no nucleus and they have some ribosomes/ribosomal RNA which shows as dark markings which separates them from erythrocytes.
What is diapedis?
The action of squeezing through the pores of the capillary membrane.
How are new red blood cells transferred into the circulation?
Red blood cells pass from the bone marrow (where they are produced) into the blood capillaries by diapedesis which is the action of squeezing through the pores of the capillary membrane.
Outline the characteristics of a mature red blood cell
Red blood cells are round, biconcave disc-shaped. They have smooth contours and the diameter is approximately 7m. There is ordinarily no variation in the size and shape of the erythrocytes in normal physiology. They stain well with eosin (pink) and they stain more so at the periphery than in the centre. These cells can also deform relatively easily
Why do red blood cells require energy?
Erythrocytes require ATP to power Na+ pumps and GLUT1 transporters in the membrane
How do red blood cells obtain their energy for metabolism?
Anaerobic glycolysis and pentose phosphate pathway for NADPH production
What protein regulates erythropoiesis?
Where is EPO produced?
By the fibroblasts in the connective tissue around the proximal tubule in the kidney AND in type 1 (glomus) cells of the carotid body.
How is EPO produced?
Erythropoietin secreting cells (type 1/glomus cells and renal fibroblasts) are sensitive to hypoxia. Therefore, if hypoxia occurs, the reason is assumed to be a reduced carriage of oxygen and therefore this stimulates the cells to release EPO.
Why is EPO produced in the kidney and carotid body cells?
EPO is produced by these regions of the body as they are dependent on consistent blood supply, however there supply isn’t affected by exercise or changes in blood pressure and therefore the oxygen supply they receive is largely determined by the level of haemoglobin in the arterial blood. In the kidney there is a tightly regulated glomerular filtration rate, and therefore it requires a steady usage of oxygen so haemoglobin levels must be maintained, and similarly, the carotid body is associated with the cerebral circulation which also requires steady oxygen supply and is therefore dependent on haemoglobin levels being sufficient.
How does EPO cause an increase in red blood cell production?
EPO diffuses out of the region and travels to the bone marrow where it acts on erythropoietic stem cells and leads to an increase in red blood cell production.
Why do red blood cells repel each other?
They have a negative surface charge due to sialic acid-containing glycoproteins in their membrane
What is erythrocyte sedimentation rate?
The rate at which red blood cells clump and form stacks (known as rouleaux) which settle faster in a blood test as a result of their increased density
What can cause an increase in erythrocyte sedimentation rate?
Inflammatory reactions or bacterial infections release molecules into the blood which reduce the negative charge on the RBC surface and therefore makes them more capable of sticking to each other.
What may elevated ESR (erythrocyte sedimentation rate) indicate?
A raised ESR level is used as a non-specific marker of infection (in the blood) as the reduction of the negative charge on the surface of RBCs caused by inflammation/bacterial infection leads to the increased density of RBCs.
What types of cell can common myeloid progenitors differentiate into?
Myeloblasts, megakaryocytic, mast cells and erythrocytes
What types of cell do myeloblasts give rise to?
Granulocytes: basophils, neutrophils, eosinophils, monocytes
What type of cell gives rise to granulocytes?
Myeloblast (from the common myeloid progenitor cell)
What are the two main progenitor cells involved in the production of blood cells?
Common MYELOID progenitor - gives rise to erythrocytes, myeloblasts (granulocytes), megakaryocytic and mast cells
Common LYMPHOID progenitor - gives rise to natural killer cells and lymphocytes (T, B and plasma eventually)
What type of cell gives rise to lymphocytes and T killer cells?
Common lymphoid progenitor
What types of cell can common lymphoid progenitors differentiate into?
Natural killer cells and small lymphocytes. The small lymphocyte differentiate as into T and B lymphocytes
What is the life-span of red blood cells?
How are old (senescent) red blood cells detected?
- cell surface antigens are different to those in young RBCs which aids splenic macrophages identifying them
- rise in methaemoglobin level in the cell
- lack of deformability or their rigidity as this allows them to become trapped int the splenic capillaries.
How are senescent/old red blood cells destroyed?
Erythrocyte becomes trapped in splenic capillaries and is engulfed by splenic macrophages. Here it is rupture by osmotic lysis and the haem group is removed from the globin proteins and these proteins are broken down into amino acids. The haem group is broken down by haemoxygenase enzyme and the iron atom removed for re-use. The opened up haem structure with the iron removed is known as biliverdin
What is the role of the haemoxygenase enzyme in the splenic macrophages?
Involved in breaking apart the haem group and removing the iron
What is biliverdin?
It is the opened up haem group with the iron removed
How are destroyed red blood cells removed from the body?
After splenic macrophages have broken down the haem and protein to form biliverdin and amino acids respectively, the biliverdin is converted into bilirubin by biliverdin reductase enzyme in the splenic macrophage. This bilirubin can then bind to albumin in the macrophage and be released into the blood, where it travels to the liver and is attached to glucuronic acid by the hepatocytes in order to increase solubility (this is conjugated bilirubin), this then travels to the small intestine where bacteria convert it into urobilinogen; most of this is egested in the faeces, but some is reabsorbed by the portal vein and it circulates to the kidney where it is then excreted in the urine (gives urine it's yellow colour). Some urobilinogen may also be further oxidised by intestinal bacteria to form stercobilin which is egested in the faeces also.
What gives urine it's yellow colour?
What is unconjugated bilirubin?
Bilirubin that is bound to albumin and has just left the splenic macrophages on it's way to the liver.