Erythropoiesis Flashcards

1
Q

Outline blood composition

A

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)

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2
Q

Outline the composition of Erythrocytes

A

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

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3
Q

Describe the structure and erythrocytes

A

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.

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4
Q

Outline typical erythrocyte properties in a dog

A

Uniform size
Central pallor (concave)

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5
Q

Outline typical erythrocyte properties in a cat

A

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

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6
Q

Outline typical erythrocyte properties in a horse

A

Rouleaux formation (clustering of RBC in standing blood)

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7
Q

Outline typical erythrocyte properties in a ruminant

A

Crenation (spiky appearance)
Variation in size

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8
Q

Outline typical erythrocyte properties in a camelid

A

Ellipsoid

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9
Q

Outline typical erythrocyte properties in a the avian and reptile species

A

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

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10
Q

Explain how the structure of erythrocytes relates to function

A

-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

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11
Q

Outline the main role of erythrocytes

A

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

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12
Q

Describe the binding of O2 and CO2 to haem groups

A

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)

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13
Q

How is erythrocyte binding and release affected in hypoxic tissues

A

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

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14
Q

Explain the role of haemoglobin of vasodilation

A

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.

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15
Q

Explain the binding of CO to Haem groups

A

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

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16
Q

Discuss the changes occurring during erythropoiesis

A
17
Q

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

A

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)

18
Q

Describe how bone Marrow has adapted for erythropoiesis

A

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.

19
Q

Briefly Explain the process of Erythropoiesis

A

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

20
Q

List the material, molecules Erythropoiesis requires adequate amounts of

A

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

21
Q

Outline the role and importance of iron

A

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.

22
Q

Describe the three common types of iron deficiency

A
  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

  1. Blood loss
    Internal or external parasites
  2. Haemorrhage
    Internal or external
23
Q

How is physiological anaemia in newborn piglets countered?

A

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

24
Q

Outline the source and effect of erythropoietin.

A

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)

25
Q

How is Erythrocyte production regulated

A

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

26
Q

Outline the removal of erythrocytes

A

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.
27
Q

Outline how the erythrocytes are broken down and components recycled

A

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

28
Q

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

A

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.

29
Q

Describe the importance of metabolism of iron in the body

A

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

30
Q

Describe iron transport between cells process utilising transferrin

A

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

31
Q

Describe how iron is stored

A

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.

32
Q

Outline hemosiderin and its role in organ damage

A

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.

33
Q

Outline the clinical relevance of abnormal RBC breakdown

A

Mycoplasma haemofelis

Neonatal erythrolysis
-foals, kittens

-Blood group incompatibility

  • Maternal antibodies taken up through colostrum lyse RBCs