MEH - Haemopoiesis Flashcards

1
Q

Where are most red blood cells, platelets and white blood cells produced?

A

Bone marrow

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2
Q

Where is bone marrow mainly distributed in adulthood?

A

Pelvis, sternum, skull, ribs, vertebrae

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3
Q

How are blood cells produced?

A

A multipotential haematopoietic stem cell becomes either a common myeloid progenitor or a common lymphoid progenitor.

The lymphoid progenitors form B and T lymphocytes, and the myeloid progenitors form thrombocytes, monocytes, basophils, neutrophils and eosinophils

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4
Q

What cells are included in the reticuloendothelial system (RES)?

A

Monocytes, macrophages, kupffer cells, tissue histiocytes, microglial cells in CNS

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5
Q

What do RES cells in the spleen dispose of?

A

Damaged or old red blood cells

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6
Q

What are the functions of red blood cells?

A

Primary - to deliver oxygen to the tissues

  • carry haemoglobin
  • maintain haemoglobin in its reduced (ferrous) state
  • generate energy (ATP)
  • maintain osmotic equilibrium
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7
Q

Do red blood cells have a cell membrane?

A

Yes, a lipid bilayer. They also have membrane proteins inserted into it

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8
Q

At what age does the switch from foetal to adult haemoglobin occur?

A

Around 3-6 months of age

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9
Q

What is the function of the globin chains?

A
  • protect haem molecule from oxidation
  • confer solubility
  • permits variation in oxygen affinity
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10
Q

What shape is an oxygen dissociation curve?

A

Sigmoidal

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11
Q

Why do people with too many red blood cells get jaundiced?

A

Excess of red blood cell destruction causes an excess of bilirubin formation which leads to jaundice

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12
Q

What is the function of the RES?

A

Cells identify and mount an appropriate immune response to foreign antigens

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13
Q

What are the main organs of the RES?

A

Spleen and liver

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14
Q

What is a peripheral blood count of haemoglobin used to measure with regards to red blood cells?

A

Their effectiveness. Normal range is 130-180 g/L (or 115-165 g/L for females)

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15
Q

What is a red blood count used to measure with regards to red blood cells?

A

How many red blood cells are present. Normal range is 4.5-6.5 x 10^12/L (3.9-5.6 in women)

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16
Q

What is a peripheral blood count of mean cell volume used to measure with regards to red blood cells?

A

How large the cells are. Normal range is 80-100 fL

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17
Q

How large are red blood cells?

A

8 micrometres diameter, and they can fit through the capillaries with a diameter of 3.5 micrometres

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18
Q

True or false - haemoglobin exists in three configurations?

A

False - it exists in two (oxyhaemoglobin/relaxed, and deoxyhaemoglobin/tight)

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19
Q

Which chromosome is the gene for the globin chain formation found on?

A

The globin gene clusters on chromosome 11 and 16.

20
Q

How is erythropoiesis controlled by oxygen levels in the body?

A
  • reduced pO2 detected in interstitial peritubular cells in kidney
  • increased production of erythropoietin (hormone)
  • this stimulates maturation and release of red cells from bone marrow
  • haemoglobin rises
  • pO2 rises
  • erythropoietin production falls
21
Q

What are the two main metabolic pathways in red cells?

A

1) glycolysis - generates ATP

2) pentose phosphate - generates NADPH

22
Q

True or false - there is no mechanism of excreting iron?

A

True

23
Q

Give some examples of ‘available’ iron

A
  • haemoglobin
  • myoglobin
  • tissue iron (enzyme systems)
  • transported iron (‘serum iron’)
24
Q

Give some examples of ‘stored’ iron

A
  • ferritin

- haemosiderin (macrophage iron)

25
Q

How do macrophages obtain iron?

A

They ‘eat’ old senescent red blood cells. Mainly occurs in splenic macrophages and Kupffer cells of the liver

26
Q

Roughly how much iron enters and leaves the body each day?

A

1-2 mg

27
Q

Roughly how much iron is required each day in the diet?

A

10-15 mg

28
Q

What is the diffference between haem and non-haem iron?

A

Haem iron is from meat sources, while non-haem is from beans, cereals etc

29
Q

What form is haem iron in?

A

Enters enterocyte and released as Fe2+, so it is FERROUS

30
Q

What form is non-haem iron in?

A

Mainly Fe3+ (FERRIC) - reduced to ferrous iron before being transported across the intestinal epithelium

31
Q

How does iron enter the bloodstream from the stomach acid?

A
  • found in Fe3+ form in stomach acid
  • binds to transferrin and enters cells through apical surface of the duodenum and upper jejunum
  • becomes Fe3+ again in cell
  • reduced to Fe2+ then moves through cell membrane into blood via ferroportin
32
Q

How is iron taken into cells (eg RBCs)?

A

Iron-transferrin complex binds to transferrin receptor (TfR). Erythroid cells contain the highest number of these receptors.

33
Q

Which vitamin enhances absorption of iron?

A

Vitamin C

34
Q

Give some examples of regulators of iron absorption

A
  • regulation of transporters
  • expression of receptors
  • hepcidin and cytokines
  • crosstalk between the epithelial cells and other cells eg macrophages
35
Q

How does hepcidin control iron uptake?

A
  • high levels of iron are detected causing the liver to secrete hepcidin
  • hepcidin degrades ferroportin, a protein involved in moving iron out of cells
  • this prevents iron release from macrophages and iron absorption from the gut
36
Q

What are the symptoms of anaemia?

A
  • tiredness
  • reduced O2 carrying capacity leading to pallor, reduced exercise tolerance
  • angina, palpitations, heart failure
  • epithelial changes
37
Q

What would a test showing a lowered ferritin level show about an individual?

A

They are likely to be iron deficient

38
Q

Give some features likely to be observed in a blood film of an anaemic patient

A
  • hypochromic (low Hb content)
  • microcytic (low mean cell volume)
  • anisopoikilocytosis (change in size and shape of RBCs)
  • low reticulocyte haemoglobin content
39
Q

How is iron deficiency treated?

A
  • dietary advice
  • oral iron supplements
  • intramuscular iron injections
  • intravenous iron
  • transfusion (only in severe cases)
40
Q

Why is free iron considered dangerous?

A

When binding capacity of transferrin is exceeded, Fe2+ can produce highly reactive hydroxyl and lipid radicals, which damage the lipid membrane nucleic acids and proteins. Excess iron is deposited in tissues

41
Q

What is haemochromatosis?

A

A disorder of iron excess resulting in end organ damage due to iron deposition

42
Q

What does haemochromatosis cause?

A

Liver cirrhosis, diabetes mellitus, hypergonadism, cardiomyopathy, arthropathy and skin pigmentation

43
Q

How is hereditary haemochromatosis inherited?

A

Autosomal recessive mutation in a gene designated HFE on the chromosomes

44
Q

How does a gene mutation cause haemochromatosis?

A
  • Normally, HFE protein competes with transferrin for binding to the transferrin receptor
  • mutated HFE can’t bind, so transferrin has no competition
  • too much iron enters cells
45
Q

What is transfusion associated haemosiderosis?

A

Accumulation of iron in the bodies of patients who have received frequent blood transfusions, eg patients with thalassaemia