Erythropoiesis

Question 1

Outline blood composition

Answer 1

Extracellular fluid & cells
-Fluid (plasma)
92% water
7% protein
1% other

-Cells
Erythrocytes (90%)
Leucocytes
neutrophils
basophils
eosinophils
T lymphocytes
B lymphocytes
NK cells
monocytes
Thrombocytes (platelets)

Question 2

Outline the composition of Erythrocytes

Answer 2

Haemoglobin represents 95% of erythrocyte protein

(1) Globin
two pairs of polypeptides:
x2 alpha & x2 beta (or gamma, delta or epsilon)

(2) central haem group containing an iron atom that can bind a molecule of O2

Question 3

Describe the structure and erythrocytes

Answer 3

Around 7 micrometers in diameter
Typical lipid bilayer membrane of globular proteins
- Biconcave disc shape which increases surface area (20-30%)
- Elasticity/deformability so they are able to pass through capillary diameters as small as 3-4μ

Failure of Na+ ion movement across erythrocyte cell membranes leads to swelling and loss of the normal biconcave disc morphology.

Question 4

Outline typical erythrocyte properties in a dog

Answer 4

Uniform size
Central pallor (concave)

Question 5

Outline typical erythrocyte properties in a cat

Answer 5

Smaller erythrocytes
Anisocytosis (variation in size)
Scarce central pallow (less concave)

Question 6

Outline typical erythrocyte properties in a horse

Answer 6

Rouleaux formation (clustering of RBC in standing blood)

Question 7

Outline typical erythrocyte properties in a ruminant

Answer 7

Crenation (spiky appearance)
Variation in size

Question 8

Outline typical erythrocyte properties in a camelid

Answer 8

Ellipsoid

Question 9

Outline typical erythrocyte properties in a the avian and reptile species

Answer 9

Nucleated
Larger
Early stages are rounded and may be binucleate
Occasional cells lose their nucleus and are termed erythroplastids.

Question 10

Explain how the structure of erythrocytes relates to function

Answer 10

-Erythrocytes are metabolically active.
This is because energy is required to maintain electrolyte gradients across the plasma membrane and of haemoglobin molecules.

-There are no organelles
As there is no mitochondria, energy is derived by anaerobic metabolism of glucose, which is important as it allows avoidance of consumption of any oxygen they are carrying

-No nucleus in mammalian erythrocytes so division is by stem cells, this is because it creates an increased space for haemoglobin and allows biconcave shape

Question 11

Outline the main role of erythrocytes

Answer 11

Haemoglobin allows for the transport of O2 from lungs to the cells , and also, to an extent, the transport of CO2 from cells to the lungs

CO2 dissolved in plasma (70%) and 30% in the haemoglobin.
Achieved because the reaction of CO2 with water to form carbonic acid by use of enzymes carbonic acid anhydrase. This causes release of hydrogen molecules which affect pH of the blood creating hydrogen carbonate which is dissolved in plasma to be transported to the lungs

Question 12

Describe the binding of O2 and CO2 to haem groups

Answer 12

In regions of high oxygen concentration (e.g. in the lung):
Globin releases CO2 and iron binds to O2 (oxyhaemoglobin)

In areas of low oxygen concentrations:
O2 is released and CO2 bound (carbaminohaemoglobin)

Question 13

How is erythrocyte binding and release affected in hypoxic tissues

Answer 13

In hypoxic tissues (lack of O2) a carbohydrate (2,3-diphosphoglyceride) is released and that facilitates release of O2 from erythrocytes.

Question 14

Explain the role of haemoglobin of vasodilation

Answer 14

Haemoglobin also binds nitric oxide – a neurotransmitter that causes dilation of blood vessels. By doing this it permits maximal tissue perfusion for supply of oxygen/removal of waste products.

Question 15

Explain the binding of CO to Haem groups

Answer 15

Carbon monoxide has greater affinity for haem than oxygen; carbon monoxyhemoglobin can lead to a ‘healthy?’ cherry red colour of mucous membranes.

Question 16

Discuss the changes occurring during erythropoiesis

Question 17

Define Erythropoiesis and briefly outline where it occurs in the embryo and then in puberty

Answer 17

Formation of red blood cells (erythrocytes) during the formation of blood.

Formed from stem cells (as mature RBC dont contain nuclei)

Embryo:
Occurs in the yolk sac, liver ( and to an extent the spleen), - shift to the bone marrow in later foetal stages

After puberty:
Primarily in marrow of membranous bones (ribs, vertebrae, sternum, pelvis)

Question 18

Describe how bone Marrow has adapted for erythropoiesis

Answer 18

Sinusoidal capillaries with larger intercellular gaps to allow passage of cells

Inactive marrow is replaced by fat (yellow marrow), but can regain activity by extension from active tissue and from circulating stem cells.

Question 19

Briefly Explain the process of Erythropoiesis

Answer 19

Pluripotent stem cell will develop into a normoblast, this occurs through various stages where the nucleus becomes progressively small. The normoblast still has a distinct nucleus but when it undergoes division its products reticulocytes and erythrocytes will either have remints of a nucleus or no nucleus respectively. These are the two cell types found in circulating blood. Reticulocyte concentration becomes more prominent after blood loos as the bone marrow releases these cells to compensate

Question 20

List the material, molecules Erythropoiesis requires adequate amounts of

Answer 20

protein
iron
copper
folic acid
vitamins (B2, B6, B12)

Question 21

Outline the role and importance of iron

Answer 21

Some forms of iron can be reactive and toxic. However it is key component of erythrocytes, where 70% of supply is used for hemoglobin, as it acts as a limiting factors for bacterial growth.
The additional 30% is bound to ferritin, a storage molecule, found in macrophages within liver, spleen and bone marrow.
Some (<0.1%) bound to protein (transferrin) in plasma.

Question 22

Describe the three common types of iron deficiency

Answer 22

1. Physiological anaemia in newborns
   Example: piglets

Markedly reduced RBC numbers in 1st 2-3 days of life
Iron store used up within 1-2 days
Sow milk contains very little iron
Rapid growth due to breeding

2. Blood loss
   Internal or external parasites
3. Haemorrhage
   Internal or external

Question 23

How is physiological anaemia in newborn piglets countered?

Answer 23

Early iron injection within a few days following birth.
Rapid increase in erythropoiesis leading to increased piglet growth rate

Question 24

Outline the source and effect of erythropoietin.

Answer 24

Erythropoetin (EPO)
Hormone that controls rate of erythrocyte production
“Blood boosting drug” Doping horse racing

Source

early embryonic/foetal/early neonatal life where it is expressed in yolk sac, liver and kidney (also spleen and bone marrow).

adult life it is produced in the kidney (renal interstitium)

Question 25

How is Erythrocyte production regulated

Answer 25

Increase in renal secretion of EPO which is transported to bone marrow, increasing erythrocyte production as EPO binds to receptors on CFU-E which are the erythroid cells precursors.
EPO also accelerates release of reticulocytes into the blood which allows restoration of oxygen transport.

It is not the number of erythrocytes that regulates the secretion of EPO but the tissue needs for oxygen

Question 26

Outline the removal of erythrocytes

Answer 26

As they age, normal RBCs:
- Lose sialic acid residues from their surface , exposing galactose moieties that induce their phagocytosis by macrophages

• Become more fragile.
• May become swollen due to failure of normal membrane function.

Question 27

Outline how the erythrocytes are broken down and components recycled

Answer 27

Macrophage phagocytosis erythrocytes. Break down of hemoglobin into globin and haem.

Globin split into amino acids and bilirubin, and both go back into bloodstream

Iron transported as iron transferrin complex to go back into the bone marrow an liver.
The bone marrow will use the iron for production of erythrocytes

Liver will store iron as ferritin, and it will also cause the excretion of bilirubin in bile

Question 28

List the average erythrocyte life spans in cat, dogs, horses and cattle

Answer 28

70 days cat
120 days dog, human
145 days horse
160 days cattle

The normal lifespan of compatible transfused erythrocytes is much shorter!! In dogs it is approximately 21 days.

Question 29

Describe the importance of metabolism of iron in the body

Answer 29

Free iron is toxic to cells as it acts as a catalyst in the formation of free radicals from reactive oxygen species - can cause lots of tissue damage.

Iron molecules released from haem
- conveyed to bone marrow by transferrin
- stored as insoluble iron in macrophages and hepatocytes as ferritin

Question 30

Describe iron transport between cells process utilising transferrin

Answer 30

Within the serum of the blood iron interacts with transferrin. If it arrives at cell surface with transferrin receptor the Transferrin-iron complexes will bind.
The cell internalises the complex, where the pH is lowered due to endosome. The lower pH changes the structure of the transferrin iron complex which leads to dissociation of iron from transferrin-receptor-complex. The transferrin-receptor complex dissociate at the cell surface due to the rise in pH and the transferrin can then bind a to a new iron molecule

Question 31

Describe how iron is stored

Answer 31

Stored as ferritin. Which is the primary intracellular iron-storage protein keeping iron in a soluble and non-toxic form. So it can be released in a controlled fashion. It is a buffer against iron deficiency and iron overload.

Question 32

Outline hemosiderin and its role in organ damage

Answer 32

Intracellular complex of ferritin, denatured ferritin and other material.

Iron within deposits of hemosiderin is very poorly available to supply iron when needed.

Large deposits may lead to organ damage.

Question 33

Outline the clinical relevance of abnormal RBC breakdown

Answer 33

Mycoplasma haemofelis

Neonatal erythrolysis
-foals, kittens

-Blood group incompatibility

• Maternal antibodies taken up through colostrum lyse RBCs