Erythropoiesis

Question 1

Briefly describe the sites of erythropoiesis in the foetus

Answer 1

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

Question 2

Briefly describe the sites of erythropoiesis after birth

Answer 2

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)

Question 3

Outline the different stages of erythropoiesis

Answer 3

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.

Question 4

Describe proerythroblasts

Answer 4

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

Question 5

Describe early erythroblasts (polychromatophils)

Answer 5

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’

Question 6

Describe the late erythroblast (normoblast)

Answer 6

The nucleus is very condensed in preparation for ejection

Question 7

Describe reticulocytes

Answer 7

These cells have no nucleus and they have some ribosomes/ribosomal RNA which shows as dark markings which separates them from erythrocytes.

Question 8

What is diapedis?

Answer 8

The action of squeezing through the pores of the capillary membrane.

Question 9

How are new red blood cells transferred into the circulation?

Answer 9

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.

Question 10

Outline the characteristics of a mature red blood cell

Answer 10

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

Question 11

Why do red blood cells require energy?

Answer 11

Erythrocytes require ATP to power Na+ pumps and GLUT1 transporters in the membrane

Question 12

How do red blood cells obtain their energy for metabolism?

Answer 12

Anaerobic glycolysis and pentose phosphate pathway for NADPH production

Question 13

What protein regulates erythropoiesis?

Answer 13

EPO

Question 14

Where is EPO produced?

Answer 14

By the fibroblasts in the connective tissue around the proximal tubule in the kidney AND in type 1 (glomus) cells of the carotid body.

Question 15

How is EPO produced?

Answer 15

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.

Question 16

Why is EPO produced in the kidney and carotid body cells?

Answer 16

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.

Question 17

How does EPO cause an increase in red blood cell production?

Answer 17

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.

Question 18

Why do red blood cells repel each other?

Answer 18

They have a negative surface charge due to sialic acid-containing glycoproteins in their membrane

Question 19

What is erythrocyte sedimentation rate?

Answer 19

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

Question 20

What can cause an increase in erythrocyte sedimentation rate?

Answer 20

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.

Question 21

What may elevated ESR (erythrocyte sedimentation rate) indicate?

Answer 21

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.

Question 22

What types of cell can common myeloid progenitors differentiate into?

Answer 22

Myeloblasts, megakaryocytic, mast cells and erythrocytes

Question 23

What types of cell do myeloblasts give rise to?

Answer 23

Granulocytes: basophils, neutrophils, eosinophils, monocytes

Question 24

What type of cell gives rise to granulocytes?

Answer 24

Myeloblast (from the common myeloid progenitor cell)

Question 25

What are the two main progenitor cells involved in the production of blood cells?

Answer 25

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)

Question 26

What type of cell gives rise to lymphocytes and T killer cells?

Answer 26

Common lymphoid progenitor

Question 27

What types of cell can common lymphoid progenitors differentiate into?

Answer 27

Natural killer cells and small lymphocytes. The small lymphocyte differentiate as into T and B lymphocytes

Question 28

What is the life-span of red blood cells?

Answer 28

120 days

Question 29

How are old (senescent) red blood cells detected?

Answer 29

• 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.

Question 30

How are senescent/old red blood cells destroyed?

Answer 30

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

Question 31

What is the role of the haemoxygenase enzyme in the splenic macrophages?

Answer 31

Involved in breaking apart the haem group and removing the iron

Question 32

What is biliverdin?

Answer 32

It is the opened up haem group with the iron removed

Question 33

How are destroyed red blood cells removed from the body?

Answer 33

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.

Question 34

What gives urine it’s yellow colour?

Answer 34

Urobilinogen

Question 35

What is unconjugated bilirubin?

Answer 35

Bilirubin that is bound to albumin and has just left the splenic macrophages on it’s way to the liver.

Question 36

What is conjugated bilirubin?

Answer 36

Bilirubin hat has been attached to glucuronic acid or other compound in order to increase it’s solubility by action of hepatocytes