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Ellie's MEH > Sesh 5- Haemopoiesis, Iron and Anaemia > Flashcards

Sesh 5- Haemopoiesis, Iron and Anaemia Flashcards

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1
Q

What is the normal range for blood platelet count?

A

150-400 X 10^9/L

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2
Q

What is the lifespan of a red blood cell?

A

120 days

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3
Q

What happens to the globin chains following Hb breakdown?

A

Broken down into their constituent amino acids which are then recycled

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4
Q

What is bilirubin excreted as in the faeces?

A

Stercobilin

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5
Q

What are the 2 main metabolic pathways in red blood cells?

A
  1. glycolysis

2. pentose phosphate pathway

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6
Q

Where is EPO produced, and in response to what?

A

Peritubular cells of the kidney in response to hypoxia

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7
Q

What is the action of EPO?

A

Stimulates maturation and release of red blood cells from the bone marrow

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8
Q

Why are the levels of iron in the body tightly controlled?

A

There is no specific mechanism for its excretion

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9
Q

Name 2 ways iron is stored in the body.

A
  1. 95% Ferritin in hepatocytes

2. 5% as Haemosiderin in Kupffer cells

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10
Q

Where does most active Fe come from?

A

Rbc (Hb) breakdown

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11
Q

Why are haem iron sources better than non-haem sources?

A

They don’t have to be converted from the ferric (Fe 3+) to the ferrous form (Fe 2+) to be transported across the intestinal epithelium

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12
Q

Roughly how much iron do we need in our diet per day?

A

10-15 mg

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13
Q

What does Fe2+ bind before being absorbed into the small intestine?

A

Transferrin

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14
Q

In what parts of the small intestine is iron absorbed?

A

Duodenum and upper jejunum

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15
Q

How is iron exported out of the enterocyte into the bloodstream?

A

Bound to ferroportin

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16
Q

How is iron transported in the bloodstream?

A

Bound to transferrin

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17
Q

How is iron taken into red blood cells?

A

Iron-transferrin complex binds to transferrin receptor

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18
Q

Which cells have the highest number of transferrin receptors?

A

Erythroid cells

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19
Q

What is the effect of vitamin C on iron absorption?

A

Enhances absorption of non-haem iron

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20
Q

Name 3 things that inhibit Fe absorption

A
  1. Tea
  2. Chapatis
  3. Antacids
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21
Q

What is hepcidin?

A

A negative regulator of iron absorption produced by the liver

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22
Q

What is the action of hepcidin?

A
  • Binds ferroportin for internalisation and degradation
  • Fe can’t pass from enterocytes into the blood
  • Recycled Fe from macrophages cannot enter blood
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23
Q

What 3 things is hepcidin regulated by?

A
  • HFE gene
  • Inflammatory cytokines
  • Transferrin Receptor
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24
Q

In what circumstance would hepcidin synthesis and release be up-regulated?

A

Iron overload

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25
List some signs of iron deficiency
- Pallor and pale conjunctiva - Tachycardia - Increased respiratory rate - Glossitis - Angular stomatitis - Koilonychia- spooning of nails
26
What epithelial changes are associated with iron deficiency?
- Glossitis - Angular stomatitis - Koilonychia
27
Red blood cells on a blood film from a patient with iron deficiency would be ____chromic and ______cytic.
1. Hypo | 2. Micro
28
What is the problem with using serum ferritin to assess iron deficiency?
- It is an acute phase protein that would be raised in inflammation, malignancy, liver disease, alcoholism etc - Normal or increased ferritin levels don't exclude iron deficiency
29
What is a better test to identify functional Fe deficiency?
CHr test- tests reticulocyte Hb content
30
What needs to be done once a patient is identified to have Fe deficiency?
Need to find underlying cause
31
List some causes of Fe deficiency
1. Inadequate dietary Fe intake 2. Increased loss of Fe e.g. via bleeding stomach ulcer 3. Excessive Fe use e.g. pregnancy 4. Heavy periods etc etc
32
How would you advise a patient to take their iron supplement tablets?
- Take on an empty stomach - Take with orange juice - Don't take with tea
33
How can Fe2+ cause damage to lipid membranes, DNA and proteins?
Can cause production of hydroxyl and lipid radicals
34
What is haemochromatosis?
A disorder of iron excess resulting in end organ damage due to iron deposition
35
What is hereditary haemochromatosis due to?
An autosomal recessive inherited mutation in the HFE gene
36
Why do patients with hereditary haemochromatosis have excess iron in cells?
HFE protein is mutated, so it can no longer compete with transferrin for the transferrin receptor on cells
37
What is the treatment for hereditary haemochromatosis?
Venesection
38
How much iron is contained in a 400ml bag of blood?
200mg
39
Fe3+ is the ______ form of iron, and Fe2+ is the ______ form.
1. Ferric | 2. Ferrous
40
Which form of iron can be absorbed into the intestinal enterocytes?
The ferrous form
41
The ___________ count provides a good estimate of the amount of erythropoiesis going on in the patient's marrow.
Reticulocyte
42
Name 4 proteins involved in vertical interaction between the red blood cell plasma membrane and its cytoskeleton. What disorder is caused by mutations in these proteins?
1. Ankyrin 2. Spectrin 3. Band 3 protein 4. Protein 4.2 - Hereditary spherocytosis
43
In which organs/tissues are the highest concentrations of stored iron found?
- Liver - Spleen - Bone marrow
44
What is pancytopenia?
-Below normal levels of red blood cells, white blood cells and platelets
45
What 2 main factors underlie the aetiology of anaemia of chronic disease?
1. Increased macrophage activity reduces rbc lifespan | 2. Increased cytokine production e.g. IL-6 increase hepcidin production- reduces intestinal Fe absorption
46
Vit B12 and folate deficiency can give rise to what form of anaemia?
Megaloblastic anaemia- a macrocytic anaemia
47
Why would anaemia due to vit B12 deficiency present later than folate deficiency?
-Can store via B12 for long time, so won't become deficient for years
48
Which mutation underlies sickle cell anaemia?
Substitution from glutamate to valine in beta- globin chain of Hb.
49
In brief, what does thalassaemia result from?
Genetic reduction or absence of production of Hb's alpha or beta chains, resulting in excess of the other type, which then precipitates.
50
What are target cells, and in what patients might they be seen?
- Nucleated, immature red blood cells that have escaped the marrow and are present in the periphery. - Seen in blood film of patients with thalassaemia
51
What 2 errors in rbc metabolism can lead to haemolytic anaemia?
1. Glucose-6-phosphate dehydrogenase deficiency | 2. Pyruvate kinase deficiency
52
What is myelofibrosis?
Haemopoetic tissue in marrow replaced by fibrotic tissue, leading to pancytopenia.
53
What is polycythaemia vera?
Myeloproliferative neoplasm in bone marrow causes excessive production of rbc's, resulting in an increased haematocrit >55%
54
Why can anaemia arise from chronic kidney disease?
Kidneys don't produce enough EPO to stimulate adequate erythropoiesis
55
What is a major complication of polycythaemia vera?
Arterial thrombosis
56
Despite increased haemolysis, which is the mean cell volume often normal in patients with hereditary spherocytosis?
-Increased reticulocyte count- larger than spherocytes and red blood cells, so compensate
57
What type of anaemia does lack of intrinsic factor result in and why?
- Pernicious anaemia | - Cannot absorb vitamin B12- needed for DNA synthesis
58
Why does pyruvate kinase deficiency lead to haemolytic anaemia?
- Red blood cells cannot make ATP - Na/K ATPase can't function so K moves out of rbcs - Rbcs shrink, so are broken down
59
Which gene is commonly mutated in many myeloproliferative neoplasms?
JAK2
60
What are the main sites of haematopoiesis in an adult?
- Skull - Ribs - Vertebrae - Pelvis - Sternum
61
How might you treat a patient with polycythaemia vera?
- Venesection to reduce haematocrit - Aspirin to reduce risk of thrombosis - Only use cytoreduction agents if venesection poorly tolerated, or patient is progressing
62
Roughly when does the switch from foetal to adult Hb occur?
3-6 months old
63
What facilitates Fe2+ uptake from the GIT lumen into enterocytes?
Divalent metal transporter 1 (DMT1)
64
Define anaemia.
A Hb concentration lower than the normal range.
65
Why might 2,3-BPG concentration increase in anaemia?
To shift the oxygen dissociation curve to right, so O2 is more readily released to the tissues

Ellie's MEH (12 decks)

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