Haem 9 Flashcards
Hb function
It needs iron for holding onto oxgygen
HOWEVER, it is also the storage mechanism, like the reservoir for iron
Why does iron deficiency lead to anaemia
Low iron=low Hb=anaemia
How long do red cells live
and how much iron is needed per day to make the huge numbers of red cells
120 days
20mg/day (lcukily not all through diet, as it is recycld)
How is iron lost through thte body and thus how much needs to be replaced
How much do we eat per day
Desqaumated cells of skin and gut
Bleeding (mensutration or path.)
Men: 1mg/day
Women- 2mg/day
Eat 12-15mg per day.
Why is most iron in the diet NOT absorbed
Where is iron found in the diet
Can’t absorb ferric iron Fe3+
(Can only absorb ferrous iron Fe2+)
- Meat and fish
- Veg
- Whole grain cereal
- Chocolate
Effect of orange juice and tea on iron in the diet
- Orange juice helps
- cups of tea make it worse
What affects absorption of iron
DIET increase in haem iron or ferrous iron
INTESTINE: acid (duodenum) favours ferrous form (i.e. vit C), ligand (meat)
SYSTEMIC:
- iron deficiency
- anaemia/hypoxia
- pregnancy
Why is iron better absorbed with meat
It is already in haem group
We said that iron deficiency can increase iron absorption… how
Hepcidin (which inhibits ferroportin, which transports iron into the blood) is high when there is high iron
These genes have iron responsive elements
NOTE THAT HIGH IRON causes this (
How is iron carried in the plasma, and what about in the cells
t/f transferrin only carries iron
Transferrin….. in the circulation
In the cells it is ferritin
F. carries other metals too
Usual transferrin saturation
20-40%
Which lab tess can be done with transferrin
- Transferrin
- Total iron binding capacity, TIBC
- Transferrin saturation
What erythropoieten action, and why is it released in response to anaemia
Anaemia leads to tissue hypoxia. This increases erythropoietin
Increase differentiation of red cell precursors, stimulates existing red cells to survive and grow
(1. survive, 2. grow, 3. differentiate)
What is anaemia of chronic disease and cause
NO OBVIOUS CAUSE EXCEPT THAT THE PATIENT IS ILL
i.e. not bleeding, no bone marrow infiltration, no Fe or b12 def.
What are genera signs of unwell
- C-reactive protein
- Erythrocyte Sedimentation Rate
- Acute phase response- increases in
- ferritin
- FVIII
- fibrinogen
- immunoglobulins
Common conditions ass. with ACD
Chronic infections e.g. TB/HIV
Chronic inflammation e.g. RhA/SLE
Malignancy
Miscellaneous e.g. cardiac failure
Pathogenesis of ACD
NOT iron deficient, but the increase CYTOKINES dysregulate flow.
Block flow out of duodenal cells to red cells
Block UTILISATION of iron
Cytokine action in ACD
and what is the overall result
- Stop erythropoietin increasing
2. Stop iron flowing out of cells
3. Increase production of ferritin
4. Increase death of red cells
Thereofre,
- make less red cells
- more red cells die
- less availability of iron
Which cytokines are involved in ACD
TNF-A and IL
4 causes of iron deficiency
- Bleeding (menstruation/GI bleeding)
- Increased use e.g. growth/pregnancy
- Dietary deficiency e.g. vegetarian (don’t get haem group from meat and fish)
- Malabsorption e.g. coeliac
Note that the most common cause is bleeding
Who would Gi investigations be done in for the case of iron deficiency
Male
Women over 40
Post menopausal women
Women with scanty menstrual loss
These people have no reason to have low iron… could be bleeding, colon or gastric cancer
What are full GI investigations
Upper GI endoscopy - oesophagus, stomach, duodenum
Take duodenal biopsy
Colonoscopy
If nothing found (small bowel meal and follow through)
If Gi are negative,what other tests
when would you not need to do anything
Urinary blood loss, and anti-coeliac antibodies
If there was a menstruating women younger than 40 with heavy periods or who has had multiple pregnancies with no GI symptoms, do nothing.
How to work out that anaemia is definitely iron deficient… which lab parameters will be used
Lab parameters
- MCV (mean cell volume)
- Serum iron
- Ferritin
- Transferrin
(= total iron binding capacity, TIBC) - Transferrin saturation
What causes low MCV, and low Hb
- Iron deficiency
- Thalassaemia trait
- Anaemia of chronic disease (can be low but also normal, so)
If there is a low MCV and Hb with a low serum iron, does this prove iron deficient anaemia
No! Serum iron is not a good reflection of the total iron….
It is low in iron deficiency and ACD (where total body iron is normal but serum could be low due to impaired flow)
But in thalassaemia trait serum iron is normal, so it rules this out
How is thalassaemia trait confirmed
Low MCV + Hb…. and
- Haemoglobin electrophoresis
- confirms an additional type of haemoglobin is present
How can ACD and iron deficiency be distinguished
Both low Hb, MCV and serum iron….
But with ferritin:
Low in iron decifiency and
HIGH in chronic disease (acute phase protein and because there is actually increased ferritin production due to cytokines)
Where is ferritin normally found
Intracellularly, but leaks into the blood and is good representative of iron stores
T/F ferritin is always high in response to ACD and always low in IDA
F:
For IDA, we would expect low ferritin because iron stores in cells are low
HOWEVER, if normal… might not be okay, might have iron deficiency and chronic disease
e.g. peptic ulcer + RhA
What would make you think that the ferritin might not be reliable if you suspect Fe deficiency but the ferritin is in fact normal
Raised CRP
Raised ESR
(suggests chronic disease, so the increased ferritin due to this could counteract the reduced ferritin due to iron deficiency)
Transferrin in chronic disease vs iron deficiency, and trasnferrin saturation
TRANSFERRIN:
ID: Transferrin increased to try to bind more iron
ACD: Proteins are usually not made so well when v ill, so transferrin will be low (or normal)
TRANSFERRIN SATURATION:
ID: The saturation will be MUCH reduced. Firstly because the transferrin has gone up and secondly because there is less iron to bind it.
ACD: Normal (the amount of transferrin might be a bit lower, but the iron might be too because of impaired flow)
What further investigations can be done
Endoscopy and colonoscopy Duodenal biopsy Anti-helicobacter antibodies Anti-coeliac antiodies ? Abdo ultrasound to look at kidneys ? Dipstick urine ? Pelvic ultrasound to exclude fibroids
What would you do for man with low ferritin
Rule out coeliac then GI investigations
In iron deficiency
Hb ? MCV ? Serum iron ? Ferritin ? Transferrin ? Transferrin saturation ?
Hb- Low MCV- low Serum iron- low Ferritin- low Transferrin- high Transferrin sat- low
ACD Hb ? MCV ? Serum iron ? Ferritin ? Transferrin ? Transferrin saturation ?
Hb low MCV low or N Serum iron low Ferritin high or N Transferrin normal/low Transferrin sat. normal
What finding on slide indicated iron deficiency
Pencil cells is definitely iron deficient
What is the most common cause of iron defoiciency worldwide
GI bleeding due to hookworm infection
When would you not be bothered about further investigations for Fe deficiency
Menstruating woman <40 ….if heavy periods OR multiple pregnancies and no GI symptoms do nothing
