Haemopoiesis, Eythropoiesis And Iron Flashcards

1
Q

What are the two types of biopsies that can be taken from bon marrow?

A

Trephine biopsy

Bone marrow aspirate

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2
Q

What is the reticuloendothelial system?

A
A network in blood and tissues which is part of the immune system containing phagocytic cells:
Monocytes
Macrophages 
Kupffer cells
Tissue histiocytes 
Microglial cells in CNS
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3
Q

What are the main organs involved in the reticuloendothelial system?

A

Spleen and liver

**all blood goes through spleen, the RE cells dispose of blood cells, in particular damaged or old red cells

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4
Q

What is MCV-mean cell volume?

A

Looks at size of red blood cells

Can help to distinguish between types of anaemia

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5
Q

What are red cells’ functions?

A
  • deliver oxygen to the tissues
  • carry hameoglobin
  • maintain Haemoglobin in its reduced (ferrous) state
  • generate ATP-maintain osmotic equilibrium
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6
Q

What is the benefit of having a large surface area to volume ratio in red blood cells?

A

Flexibility

And increase area for gas exchange

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7
Q

What gene is responsible for the synthesis of haemoglobin?

A

Globin gene clusters on chromosomes 11 and 16 (expressed at different stages of life)

*foetal Haemoglobin is alpha and gamma subunits
Adult Haemoglobin is alpha and beta

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8
Q

What are the functions of the globin chains on haemoglobin?

A
  • Protect haem molecule from oxidation
  • Confer solubility
  • Permits variation in Oxygen affinity (shape change)
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9
Q

Explain haemoglobin catabolism. What cell performs this?

A

Reticuloendothelial cells

Broken down into heme and globin (protein- broken down into amino acids and recycled)

Iron is removed from the heme and this leaves something that is converted to biliverdin.

Biliverdin is converted to bilirubin in the liver which is converted further to conjugated bilirubin. This is excreted in urine or used to produce bile salts where it becomes urobilinogen which is excreted in faeces

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10
Q

What controls erythropoiesis?

A

Hormone- erythropoietin (produced from kidney)

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11
Q

When and how does the kidney produce erythropoiesis?

A

Reduced pO2 detected in interstitial peritubular cells in the kidneys stimulates the release of erythropoietin. This causes increased maturation and release of red blood cells from bone marrows which increase pO2

*negative feedback

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12
Q

What is the effect on someone’s RBCs if they have kidney problems?

A

They are likely to be anaemic because there is no stimulation of RBC release and maturation because there is no erythropoietin produced

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13
Q

In what forms will you find Iron within the body (available and stored forms)?

A

Available forms (available for use/ functional):

  • Haemoglobin
  • myoglobin (Oxygen reserves in muscles)
  • tissue iron (enzyme systems eg cytochromes)
  • transported iron (“serum iron”)

Stored forms:

  • ferritin (soluble)
  • haemosiderin (macrophage iron- insoluble iron-stain for)
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14
Q

Where does most of the active iron in the body from?

A

Break down of RBC

Not from gut absorption

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15
Q

What are the two outside sources of iron and where is it found?

A

Haem iron- meat

Non-haem iron- pulses and beans

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16
Q

Why is haem iron better than non-haem iron?

A

Because haem iron is present in the ferrous (Fe2+) form which is more desirable

Non haem iron is in the ferric (Fe3+) form and needs to be converted to ferrous form before it can be used which is less desirable

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17
Q

How is iron transported?

A

Bound to transferrin protien

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18
Q

How is iron taken into cells eg RBC?

A

By binding of iron-transferrin complex to transferrin receptors (TfR)

Erythrocytes have the most TfRs

19
Q

What does iron absorption depend upon?

A

Dietary factors (iron levels are sense by vili of enterocytes)

Body iron stores and erythropoiesis

20
Q

What are the control mechanism for the absorption of iron?

A
  • Regulation of transporters (transferrin)
  • Expression of receptors eg HFE and TfR
  • Hepcidin and cytokines (chemicals)
  • Cross talk between the epithelial cells and other cells like macrophages
21
Q

How does hepcidin work to negatively regulate iron absorption?

A

Produced in liver, released from kidneys

Binds to ferroportin and degrades it which stops the iron being transported from the gut to the blood and thus stops iron from being absorption (there is a build up of iron in the enterocytes)

It also has an effect on macrophages. It degrade the ferroportin and prevents it from giving the iron it has (that is gains from breaking old RBCs down) to other RBCs.

**the iron cannot be used, it is not functional

22
Q

When is hepcidin synthesis increased?

A

During iron overload

23
Q

When is hepcidin production decreased?

A

When there is high erythrocyte activity

24
Q

What are the reasons for iron deficiency?

A

Insufficient intake/poor absorption

Increased use:
Physiological eg pregnant
Pathological eg bleeding (heavy periods)

25
Q

What are the signs and symptoms of iron deficiency?

A

Physiological effects of anaemia:

  • tiredness
  • reduced oxygen carrying capacity (pallor, reduced exercise tolerance)
  • cardiac symptoms- angina, palpitations, development of heart failure
Signs:
Pallor
Tachycardia
Increased respiratory rate
Epithelial changes (large painful,slightly swollen tongue/ spooning of nails)
26
Q

What are the blood parameters and blood film features that can indicate someone has an iron deficiency?

A
  • hypochromic: low haemoglobin content (pale cells)
  • microcytic: small RBC-low mean cell volume
  • anisopoikilocytosis- change in size and shape ie pencil cells, target cells
  • low serum ferritin, serum iron and %transferrin in saturdation, raised TIBC
  • low reticulocyte haemoglobin content (CHR)
27
Q

What is the common way to measure iron status?

A

Measure ferritin

Reduced levels indicate iron deficiency

But normal or increase levels do not exclude iron deficiency

28
Q

What can be used to measure functional iron deficiencies (amount getting to erythroid cells)? What is the issue with this test?

A

CHR (reticulocyte haemoglobin content)

CHR is also low in people with thalasaemia so it could not be used in those patients

29
Q

How do you treat iron deficiency?

A

Dietary advice
Oral iron supplements
Intramuscular iron injections
Intravenous iron (can cause anaphylactic shock)
Transfusion (only if there is severe anaemia with imminent cardiac compromise)

30
Q

Why is iron excess harmful?

A

Fe2+ can produce free radicals (hydroxyl and lipid ones). This leads to damage of the membranes,nucleic acids and proteins

Excess iron also deposited in tissues which can be harmful

31
Q

How do you treat hereditary haemochromatosis?

A

Venesection

32
Q

How can blood transfusions lead to iron overloads?

A

400ml blood= 200 mg of iron

Therefore many transfusions can result in too much iron

33
Q

How do you treat transfusion associated haemosiderosis?

A

Iron chelating agents eg desferrioxamine

These delay but don’t stop the inevitable effects of iron overload

34
Q

Why is free iron bad?

A

It is toxic to cells as it acts as a catalyst in the formation of free radicals from reactive oxygen species.

34
Q

Name a substance and the food/drink that contains it that increase iron absorption

A

Citrate in citrus fruits

34
Q

Name a substance and the food/drink that it is found in that decrease iron absorption

A

Tannins in tea and coffee

35
Q

What is hereditary haemochromatosis?

A

Autosomal recessive disease characterised by excessive absorption of dietary iron.

36
Q

Why is excessive iron absorption an issue? (Ie in hereditary haemochromatosis)

A

There is no system for excretion of excess iron, iron accumulates in tissues and organs disrupting normal function.

37
Q

Which organs are most susceptible to disrupted function due to XS iron absorption?

A
Liver
Adrenal glands,
Heart, 
Joints,
Pancreas
38
Q

What are the symptoms of hereditary haemochromatosis?

A
Cirrhosis
Adrenal insufficiency 
Heart failure 
Arthritis 
Diabetes

(Think about the organs most affected by iron excess)

39
Q

What is the defective gene on chromosome 6 that causes hereditary haemochromatosis?

A

HFE

40
Q

How does a defected HFE gene result increase uptake of iron?

A

It normally binds to the transferrin receptor to reduce the affinity for iron bound transferrin. But a defective HFE protein cannot reduce the affinity therefore there is greater cellular uptake

41
Q

What are the treatments for hereditary haemochromatosis?

A

Therapeutic phlebotomy to remove the XS iron