9. Iron deficiency Flashcards
Which proteins in the body require iron?
- Ribonucleotide reductase
- Haemoglobin
- Myoglobin
- Cyclo-oxygenase
- Succinate dehydrogenase
- Cytochrome a, b and c
- Cytochrome P450
- Catalase
Where is iron located in a red cell?
- Iron is in the haem groups associated with globin chains of haemoglobin
- Haem groups are near the surface of the molecule
- Fe2+ (ferrous) state
How much iron do you need every day to re-make red cells and how is this done?
- 20mg a day
- Impossible to absorb this amount
- Iron is recycled when red cells are broken down
How much iron do men and women need to absorb every day?
- Men - 1mg a day
* Women - 2mg a day
How much iron does the normal human diet provide and why is this so different to the amount absorbed?
- 12-15mg a day
- Iron occurs in most natural foods e.g. fish, vegetables etc.
- It is difficult to absorb iron - most that’s eaten is not absorbed
- We can only absorb ferrous (fe2+) iron
- Also depends what else you have in the meal that will depend the level of absorption e.g. orange juice helps increase Fe2+
Why is meat and fish a better source of iron in a diet?
- Iron has already been incorporated into the haem group
* This is very easy to absorb
What 3 main factors affect the absorption of iron?
- Diet: increase haem and ferrous iron
- Intestine: acid in the duodenum
- Systemic factors: iron deficiency, anaemia (increases absorption to compensate) etc.
How is iron absorbed?
1) Iron is absorbed from the gut lumen into the cells
2) Iron is transported by ferroportin
3) Hepcidin regulates ferroportin
4) Fe enters the blood and binds to transferrin
What is hepcidin and how does it work?
- Peptide hormone - 25aa
- If iron levels are high, hepcidin levels increase
- Binds to and induces degradation of ferroportin
- Iron is stuck in the enterocytes and lost from the body when these are shed
Where is ferroportin found?
- Enterocytes of the duodenum
- Macrophages of the spleen, which extract iron from old or damaged cells
- Hepatocytes
How does transferrin work?
- Holds onto Fe in the circulation
- Only 20-40% saturated with iron
- Forms stable complexes with iron and more than 40 other metal ions
- Transferrin-iron interacts with the transferrin receptor and the whole complex is internalised
- As the pH drops, iron is released and transferring receptors are recycled
How is iron kept soluble and non-toxic?
Iron proteins and transport systems maintain a soluble and non-toxic form
How does anaemia affect erythropoietin?
- Anaemia
- Tissue hypoxia
- Increased erythropoietin production in the kidney (and liver)
- Acts on red cell precursors
What is anaemia of chronic disease (ACD)?
- Anaemia seen in people with a chronic infection
- Condition causes stimulation of hepcidin, which decreases iron absorption
- Erythropoiesis may also be reduced
- No obvious cause
What are the laboratory signs of being ill (with an anaemic condition)?
- C-reactive protein increases
- Erythrocyte sedimentation rate increases - due to increased inflammatory proteins
- Acute phases response increases
What are the associated conditions of ACD?
- Chronic infections (TB/HIV)
- Chronic inflammatory disorders (rheumatoid arthritis)
- Underlying malignancy
- Miscellaneous e.g. cardiac failure
What causes ACD?
• Underpinned by cytokine release in unwell patients • Prevent the usual flow of iron from the duodenum to the red cells • Include TNF alpha and interleukins • Cytokines do several things: - stop erythropoietin increasing - stop iron flowing out of cells - increase production of ferritin - increase death of red cells
Why does ACD make anaemia persistent than normal anaemia?
- Normally, erythropoietin production increases to compensate for loss of haemoglobin
- In ACD, erythropoietin production is blunted
What is the most common cause of anaemia?
Iron deficiency
What are 4 of the causes of iron deficiency?
- Bleeding (most common) e.g. menstruation
- Increased use by the body e.g. rapid growth, pregnancy
- Dietary deficiency
- Malabsorption
When would you do a full GI investigation in someone with anaemia?
- Patient is male
* Patient is a post-menopausal woman or has little menstrual loss
What are the full GI investigations to check for bleeding?
• Gastroscopy
• Duodenal biopsy
• Colonoscopy
• If there are no GI abnormalities in the above, look at the small bowel (unusual for this to occur)
- give a small bowel meal (radio-opaque substance) and follow through
• Can also check for anti-helicobacter antibodies and anti-coeliac antibodies (ultrasound on kidneys, urine dipstick)
Which laboratory parameters should you look at in someone who is iron deficient?
- MCV
- Serum iron
- Ferritin
- Transferrin
- Transferrin saturation
What are the 3 causes of a low MCV?
- Iron deficiency
- Thalassaemia trait (heterozygous)
- Anaemia of chronic disease (low or normal MCV)
Why is a low MCV and low serum iron not enough to tell if a patient is iron deficient?
This can also be seen in ACD
If a patient has iron deficiency but normal ferritin, what could this mean?
There is a chronic underlying disease
• check CRP and ESR to check for iron deficiency in this case
If a patient had low Hb (anaemic), low serum iron and low ferritin, does this patient have iron deficiency, and what else could be checked to confirm this?
- Yes
* A low transferrin saturation would confirm this
What are the levels of the following in classic iron deficiency: • Hb • MCV • Serum iron • Ferritin • Transferrin • Transferrin saturation
- Hb - low
- MCV - low
- Serum iron - low
- Ferritin - low
- Transferrin - high
- Transferrin saturation - low
What are the levels of the following in classic anaemia of chronic disease: • Hb • MCV • Serum iron • Ferritin • Transferrin • Transferrin saturation
- Hb - low
- MCV - normal/low
- Serum iron - low
- Ferritin - normal/high
- Transferrin - normal/low
- Transferrin saturation - normal
What are the levels of the following in the classic thalassaemia trait: • Hb • MCV • Serum iron • Ferritin • Transferrin • Transferrin saturation
- Hb - low
- MCV - low
- Serum iron - normal
- Ferritin - normal
- Transferrin - normal
- Transferrin saturation - normal
What are the levels of the following in rheumatoid arthritis with a bleeding ulcer: • Hb • MCV • Serum iron • Ferritin • Transferrin • Transferrin saturation
- Hb - low
- MCV - low
- Serum iron - low
- Ferritin - normal
- Transferrin - high
- Transferrin saturation - low
Describe a blood film in someone with iron deficiency
- Very pale cells - not much haemoglobin
* Pencil cells can be seen (long and thin)
