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ESA2 - Metabolism, Endocrinology and Haematology > Haemopoiesis, Erythropoiesis and Iron > Flashcards

Haemopoiesis, Erythropoiesis and Iron Flashcards

1
Q

Where are blood cells produced?

A

Bone marrow

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2
Q

What are the three main types of blood cells?

A

RBC, platelets and WBC

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3
Q

Where are the main sites of haemopoiesis in the adult?

A

Pelvis, sternum, skull, ribs, vertebrae

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4
Q

Where is a bone marrow trephine usually taken from?

A

Posterior iliac crest

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5
Q

What are the common myeloid progenitors able to differentiate into?

A

Erythrocytes, monocytes, basophils, neutrophil, eosinophils, platelets

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6
Q

What are the common lymphoid progenitors able to differentiate into?

A

T and B lymphocytes, NK cells

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7
Q

What is haemopoiesis driven by?

A

Cytokines

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8
Q

How is the pool of stem cells not depleted?

A

When they proliferate, at least some of their daughter cells remain as HSCs

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9
Q

What are the 3 blood cell lineages?

A

Erythroids (reticulocytes and erythrocytes)
Lymphocytes
Myelocytes (macrophages, granulocytes and megokaryocytes)

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10
Q

What do megokaryocytes give rise to?

A

Platelets

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11
Q

For example, if we wanted a stem cell to develop into more erythocytes, what growth factor would be given?

A

Erythropoietin

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12
Q

For example, if we wanted a stem cell to develop into more platelets, what growth factor would be given?

A

Thrombopoietin

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13
Q

For example, if we wanted a stem cell to develop into more granulocytes, what growth factor would be given?

A

G-CSF

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14
Q

What are some examples of cells contained within the reticuloendothelial system?

A 
Monocytes
Macrophages
Kupffer cells
Tissue histiocytes
Microglial cells in CNS
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15
Q

What is the normal haemoglobin range for an adult male?

A

130-180 g/L

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16
Q

What is the normal haemoglobin range for an adult female?

A

115-165 g/L

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17
Q

What is the normal red blood count range for an adult male?

A

4.5-6.5 x 10^12 /L

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18
Q

What is the normal red blood count range for an adult female?

A

3.9-5.6 x 10^12 /L

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19
Q

What is the normal mean cell volume range?

A

80-100 fL

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20
Q

What is the normal white blood count range?

A

4-11 x 10^9/L

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21
Q

What is the normal platelet count range?

A

150-400 x 10^9 /L

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22
Q

What are the functions of the RBC?

A

1) Carry haemoglobin
2) Maintain haemoglobin in its reduced (ferrous) state
3) Generate energy (ATP)
4) Maintain osmotic equilibrium

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23
Q

How long does a red cell usually last for?

A

Around 120 days

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24
Q

Why is the RBC so flexible?

A

Membrane proteins

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25
Q

Why does the RBC need to be so flexible?

A

To facilitate passage through the microcirculation which has a minimum diameter of 3.5 micrometres (diameter of RBC = 8 micrometres)

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26
Q

What chemical is seen in increased levels in the blood if red cells are being destroyed more rapidly than usual?

A

Bilirubin

27
Q

Where is bilirubin excreted?

A

Bile and urine

28
Q

What are the two main metabolic pathways in red cells?

A

Glycolysis and pentose phosphate pathway

29
Q

Which organ detects reduced oxygen in circulation?

A

Kidneys

30
Q

What would happen to haemoglobin levels in a patient with kidney failure?

A

Decreases (anaemic) as erythropoitein not being released properly

31
Q

True or False:

There are many mechanisms within the body that function to excrete iron

A

False

No mechanism of excreting iron

32
Q

In what ways can iron be present in the body?

A

In haemoglobin, myoglobin, tissue iron, transported iron

Ferritin, haemosiderin

33
Q

Is ferratin soluble?

A

Yes

34
Q

Is haemosiderin soluble?

A

No

35
Q

How much iron enters and leaves the body each day?

A

1-2mg

36
Q

What are the two forms of iron we can obtain through our diet?

A

Haem (eg in meat)

Non-haem (eg in nuts, grains)

37
Q

Why is haem iron a better source than non-haem iron?

A

Enters enterocyte and iron released as Fe2+ - ferrous

As opposed to non-haem - exists in the ferric (Fe3+) form and is reduced to ferrous iron before being transported across the intestinal epithelial

38
Q

What form must iron be in to be absorbed?

A

Ferrous (Fe+)

39
Q

What can happen to iron after it is absorbed into the intestinal lining cells?

A

Can either be stored as ferritin or absorbed into the blood

40
Q

What is iron exported out of the cell by?

A

Ferroportin

41
Q

How is iron taken into red blood cells?

A

By binding of iron-transferrin complex to transferrin receptor

42
Q

Which cells contain the highest numbers of transferrin receptors?

A

Erthyroid cells

43
Q

What vitamin enhances absorption of iron?

A

Vitamin C

44
Q

What things can inhibit the absorption of iron?

A

Tea, chapatis, antacids

45
Q

What things control iron absorption?

A

Regulation of transporters
Expression of receptors (eg transferrin receptor)
Hepcidin and cytokines
Crosstalk between epithelial cells and other cells like macrophages

46
Q

Where are dietary iron levels sensed?

A

Villi of enterocytes

47
Q

What is hepcidin?

A

Protein that regulates iron absorption

48
Q

How does hepcidin work?

A

Hepcidin inhibits iron transport by binding to ferroportin which is located on the basolateral surface of gut enterocytes and the plasma membrane of reticuloendothelial cells (macrophages).

49
Q

What is hepcidin secreted and excreted by?

A

Secreted by liver, excreted by kidneys

50
Q

When is hepcidin synthesis increased?

A

In iron overload

51
Q

What happens to the production of hepcidin when there is high erythopoietic activity?

A

Production is decreased

52
Q

What are the functions of hepcidin?

A

Prevents iron release from macrophages and prevents iron absorption from gut

53
Q

What are some symptoms of iron-deficiency anaemia?

A

Tiredness, reduced exercise tolerance, angina, palpitations

54
Q

What are some signs of iron-deficiency anaemia?

A

Pallor, tachycardia, increased respiratory rate, epithelial changes

55
Q

What are some features of red blood cells in iron-deficiency anaemia?

A

Hypochromic (low Hb content)
Microcytic (small RBC-low MCV)
Change in size and shape (eg pencil cells)

56
Q

What is the most commonly used measure of iron levels?

A

Serum ferratin

57
Q

What do reduced ferratin levels indicate?

A

Iron deficiency

58
Q

Do normal or increased levels of ferratin definitely exclude iron deficiency?

A

No

59
Q

Why is excess iron so dangerous?

A
  • Exceed binding capacity of transferrin
  • Reduced Fe (Fe2+) can produce highly reactive hydroxyl and lipid radicals
  • Damage lipid membranes, nucleic acids and proteins
  • Excess iron deposited in tissues
60
Q

What is haemochromatosis?

A

Disorder of iron excess resulting in end organ damage due to iron deposition

61
Q

What can haemochromatosis cause?

A

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

62
Q

How is hereditary haemochromatosis inherited?

A

Autosomal recessive

63
Q

What is hereditary haemochromatosis caused by?

A

Mutation in gene designated HFE on chromosome 6p21.3

Normally HFE protein competes with transferrin for binding to the transferrin receptor

Mutated HFE cannot bind so transferrin has no competition, meaning too much iron enters cells

64
Q

How is hereditary haemochromatosis treated?

A

Venesection

ESA2 - Metabolism, Endocrinology and Haematology (19 decks)

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