4b - Iron metabolism and microcytic anaemias Flashcards Preview

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Flashcards in 4b - Iron metabolism and microcytic anaemias Deck (47)
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1
Q

What is Microcytic anaemia?

A
  • Reduced rate of haemoglobin synthesis
  • Erythrocytes smaller than normal (microcytic)
  • Cells often paler than normal (hypochromic) - not as red bc of less
2
Q
  1. What causes Microcytic anaemia?
A
  1. Reduced haem synthesis
  2. Reduced globin chain synthesis: alpha or beta thalassaemia
3
Q

Identify the full list of causes for Microcytic anaemic (hint: acronym - cats have t****)?

A
4
Q

Describe some of the functions of iron

A
  1. Oxygen carriers: Haemoglobin in red cells; Myoglobin in myocytes
  2. Co-factor in many enzymes: Cytochromes (oxidative phosphorylation) Krebs cycle enzymes Cytochrome P450 enzymes (detoxification) Catalase
5
Q

Why is the regulation of iron important?

A
  1. Free iron potentially very toxic to cells
  2. Complex regulatory systems to ensure the safe absorption, transportation & utilisation
  3. MOST IMPORTANT - Body has no mechanism for excreting iron
6
Q

What two common oxidation states does iron exist in?

A
  1. Ferrous iron (Fe2+) - Reduced form. ABSORBED FORM
  2. Ferric iron (Fe3+) most common - Oxidised form.
7
Q

What is dietary iron a mix of?

A

Haem iron (Fe2+) and non-haem (mixture of Fe2+ and Fe3+).

8
Q

Identify some sources of haem and non haem iron

A
9
Q

Where does the absorption of iron occur?

A

•duodeneum and upper jujenum

10
Q

Describe the absorption of dietary iron

A
  • Ingestion if iron in the haem form (meat) or non haem form
  • Duodenum and upper jujenum - intestinal enterocytes – cells where our nutrients are absorbed from the gut BARRIER
  • Chyme is the mixture of food leaving the stomach into the small intestine. Contain haem iron.
  • Movement: Chyme –> Enterocyte –> Blood
  • Food must be absorbed across our enterocyte to get them into the blood
  • Haem can be absorbed by the intestinal enterocyte –> HAEM INSIDE OUR CELL
  • Non haem composed of ferric and ferrous. Can only absorb ferrous (fe2+)
  • So Fe3+ must be converted to Fe2+ - ferrous reductase works in combination with Vitamin c
  • DMT 1 – Divalent metal transporter 1 - two charges – Fe2+ transport. Co transporter – when one iron comes in a H+ ion leaves
  • Fe2+ once in the cell can be stored in the Fe 3+- linked to protein ferritin - function to store iron
  • Ferroportin - allows Fe2+ to pass across the enterocyte into the blood
  • Transferrin – transport molecule. Ferric ion. Two binds sites - can then be tansported around the body
11
Q

Which factors positively affect the absorption of non-Haem iron from food?

A
  • Vitamin C and citrate - prevent formation of inbsoluble iron compounds
  • Vit C help reduces ferric to ferrous iron (works with ferric reductase)
12
Q

Which factors negatively affect the absorption of non-Haem iron from food?

A
  • Tannins (in tea) - found in tea. Combine non haem iron in the intestine. Reduces absorption of iron. Discourage anaemic patients from drinking tea.
  • Phytates (e.g. Chapattis, pulses)
  • Fibre
  • Antacids (e.g. Gaviscon)
13
Q

What is ferous reductase?

A
  • Works in combination with Vitamin C
  • Catalyses: Fe3+ –> Fe2+
  • Found on the apical surfaces of enterocytes
14
Q

What is DMT 1 – Divalent metal transporter 1?

A
  • Located on the apical surface of intestinal enterocyte
  • Co transporter - two charges – Fe2+ transport
  • When one iron comes in a H+ ion leaves
15
Q

What is Ferroportin?

A
  • Found on the basolateral surface of the enterocyte
  • Allows Fe2+ to pass across the enterocyte into the blood
16
Q

What is Transferrin

A
  • Transport molecule of ferric ion (Fe3+)
  • Two binding sites for Fe3+ - can then be transported around the body
17
Q

What are the two types of iron stores

A
  1. Functional
  2. Stored
18
Q

What functional (available) iron is there?

A
  • Haemoglobin (~2000 mg)
  • Myoglobin (~300 mg)
  • Enzymes e.g. cytochromes (~50 mg)
  • Transported iron (in serum mainly in transferrin) (~3 mg)
19
Q

Identify the two main sources of stored iron?

A
  1. Ferritin - Soluble
  2. Haemosiderin - Insoluble
20
Q

What is Ferritin?

A
  • Globular protein complex with hollow core
  • Pores allow iron to enter and be released.
21
Q

What is haemosiderin?

A
  • Aggregates of clumped ferritin particles, denatured protein & lipid.
  • Accumulates in macrophages, particularly in liver, spleen and marrow.
22
Q

Describe the uptake of cellular iron?

A
  1. Fe3+ bound transferrin binds transferrin receptor and enters the cytosol receptor-mediated endocytosis.
  2. Fe3+ within endosome released by acidic microenvironment and reduced to Fe2+ .
  3. The Fe2+ transported to the cytosol via DMT1. 4
  4. Once in the cytosol, Fe2+ can be stored in ferritin, exported by ferroportin (FPN1), or taken up by mitochondria for use in cytochrome enzymes
23
Q

Describe iron recycling

A
  • Most (>80%) of iron requirement met from recycling damaged or senescent red blood cells
  • Old RBCs engulfed by macrophages (phagocytosis)
  • Splenic macrophages and Kupffer cells of liver
  • Macrophages catabolise haem released from red blood cells
  • Amino acids reused and Iron exported to blood (transferrin) or returned to storage pool as ferritin in macrophage.
24
Q

Describe the regulation of iron absorption

A
  • Transporters
  • Receptors
  • Cytokines
  • Hepcidin
  • Enterocytes - sense dietary iron levels
25
Q

What is Hepcidin

A
  • Peptide hormone made by the liver
  • Key negative regulator of iron absorption
  • REDUCES IRON CONCENTRATION (NEGATIVE)
  • Released into bloodstream
  • Effect ferraportin receptor
  • Causes internalisation and degradisation of ferroportin protein –> blocks transport of iron
26
Q

Describe the two effects of Hepcidin on iron

A
  1. Inhibits absorption of iron in the gut
  2. Release of stored iron in reticuloendothelial system
27
Q

What is anaemia of chronic disease?

A

A common cause of anaemia (2nd worldwide after iron deficiency) associated with chronic inflammatory conditions such as rheumatoid arthritis, chronic infections (e.g. tuberculosis) and malignancy

28
Q

How does chronic disease cause anaemia?

A
  • Release of IL6 – can inhibit erythropoesis causing a reduction in RBCs​
  • Reduction in RBC production​
  • Hepcidin – is inhibiting ferroportin ​
  • Reduced amount of iron in the blood plasma
29
Q

Describe the mechanism of anaemia of chronic disease

A
30
Q

Describe the effect of cytokine release in anaemia of chronic disease

A
  1. Increased hepcidin production - reduced iron absorption and iron release from RES)
  2. Reduced EPO production from the kidney - reduced erythropoeisis
31
Q

What are some causes of iron deficiency

A
  1. Insufficient iron in diet e.g. Vegan & vegetarian diets
  2. Malabsorption of iron e.g. Vegan & vegetarian diets
  3. Bleeding e.g. Menstruation, peptic ulcer
  4. Increased requirement e.g. Pregnancy, rapid growth
  5. Anaemia of chronic disease e.g. inflammatory bowel disease
32
Q

What groups are most at risk from iron deficiency

A
  • Infants
  • Children
  • Women of child bearing age
  • Geriatric age group
33
Q

Identify some peripheral blood smear results arising from iron deficiency anaemia

A
  • RBCs are microcytic and hypochromic in chronic cases
  • Anisopoikilocytosis: change in size and shape
  • Sometimes pencil cells and target cells
34
Q

Identify some blood film features of iron deficiency anaemia

A

Full Blood Count

  • Low MCV
  • Low Hb
  • Low MCHC
  • High Platelet count
  • Low serum ferritin/ iron/ tranferrin
  • Low reticulocyte count
35
Q

Identify some epithelial changes that occur in anaemia

A
  • Angular cheilitis
  • Koilonychia (spoon nails)
  • Glossy tongue with atrophy of ling
36
Q

Identify some physiological effects of anaemia

A
  • Tiredness
  • Pallor
  • Reduced exercise tolerance (due to reduced oxygen carrying capacity)
  • Cardiac – angina, palpitations, development of heart failure
  • Increased respiratory rate
  • Headache, dizziness, light-headedness
37
Q
A
38
Q

How do we test for iron deficiency

A
  1. Plasma ferritin - decrease definitively indicates iron deficiency BUT.. Normal or increased ferritin does not exclude iron deficiency
  2. CHr - reticulocyte haemoglobin content
39
Q

How do we treat iron deficiency

A
  • Dietary advice
  • Oral iron supplements
  • Intramuscular iron injections
  • Intravenous iron
  • Blood transfusion
40
Q

Describe the dangers of excess iron

A
  • Exceeds the binding capacity of transferrin
  • Excess iron deposited in organs as haemosiderin
  • Free radical formation & organ damage
41
Q

How does excess iron promote free radical damage

A
  • Fenton reaction
  • Hydroxyl and hydroperoxyl radicals can cause damage to cells: Lipid peroxidation • Damage to proteins • Damage to DNA
42
Q
A
43
Q

Describe two examples of excess iron

A
  1. Transfusion associated haemosiderosis
  2. Hereditary haemochromostosis (HH)
44
Q

Describe Hereditary Haemochromatosis

A

Autosomal recessive disease

Mutation in HFE gene which codes for HFE protein

45
Q

In hereditary haemochromatosis, what is the role of the HFE protein (normally) and how is this this altered?

What impact does this have on iron absorption?

A

Normal

  • HFE interacts with transferrin receptor
  • It reduces its affinity for iron bound transferrin

Mutate HFE

  • Cannot bind to transferrin - loss of negative influence uptake
  • Net effect: Too much iron taken up into cells
46
Q

How do we treat hereditary haemochromatosis

A

Venesection

47
Q
A