Haem 9 and 10 - Iron deficiency / Vit B12 and Folic Acid deficiency Flashcards
Most of the iron ins in Hb. So what does low iron mean?
Low iron = low Hb = anaemia
Iron is incorporated into protoporphyrin ring in Haem.
The crucial role is to hold onto O2
Most (but not all) iron is recycled. How might we lose iron?
- Desquamated cells of skin and gut
- Bleeding - menstruation / pathological
Men need about 1mg, women - 2mg/day
Human diet - provides 12-15mg iron/day
Iron can only be absorbed in what state?
Fe2+ (ferrous).
Ferric (Fe3+) cannot be absorbed.
Cups of tea make it worse, orange juice helps
How can iron absorption at the gut be altered?
- Iron enters gut epithelial cell.
- On the basement membrane of the epithelial cell –> ferroportin is the iron transporter to blood.
- Ferroportin levels regulated by hepcidin (small chain aa - produced in liver)
High iron = High hepcidin = low ferroportin = low absorption
Intracellularly, iron can be converted into …… and it is bound to ….. in the plasma.
Iron can be converted into ferritin.
Bound to transferrin in plasma.
Occurs in duodenal cells among other cells
What does transferrin do and how can it be measured?
Holds onto iron in circulation
Can be measured by:
- Measuring transferrin
- Measuring transferrin saturation
(3. Total iron binding capacity, TIBC)
Erythropoietin is released mainly by kidneys in response to hypoxia. What effects does it have
Stimulates red cell precursors to survive, grow and differentiate
What is anaemia of chronic disease? (ACD)
Anaemia in patients who are unwell. No bleeding, no marrow infiltration, no iron/b12/folate deficiency.
No obvious cause except they’re unwell
What are the laboratory signs of being ill (for ACD)
- C-reactive protein (mark of infection/inflammation)
- Erythrocyte sedimentation rate (increases in inflammation)
- Acute phase response - look for increases in ferritin, F8, fibrinogen, immunoglobulins
What are some associated conditions of ACD
- Chronic infections e.g. TB/HIV
- Chronic inflammation e.g. RA/SLE
- Malignancy
- Misc - cardiac failure
Describe the pathogenesis of ACD
Cytokines prevent usual flow of iron from duodenum to RBC (e.g. via transferrin) - block in iron utilisation
Main cytokines involved = TNF-a, ILs
What do cytokines do to prevent iron utilisation in ACD?
Cytokines:
- Stop erythropoietin synthesis
- Stop iron flowing out of cells
- Increase production of ferritin
- Increase death of red cells
Consequences are - make less red cells, more red cells die, less availability of iron (as its stuck in cells/ferritin)
What are the causes of iron deficiency
- MAIN CAUSE = bleeding (menstrual / GI)
- Increased use (e.g. growth/pregnancy)
- Dietary deficiency
- Malabsorption (e.g. coeliacs)
When would you do a full GI investigation?
If good diet and no coeliac antibodies
If: male, women over 40, post-menopausal, woman with scanty menstrual loss
What are full GI investigations?
- Upper GI endoscopy
- Duodenal biopsy
- Colonoscopy
If find nothing - small bowel meal and follow through
If GI tests come back negative, where else could you examine?
Urinary blood loss (kidneys)
Antibodies for coeliac disease
What are the laboratory parameters that could be measured?
- MCV
- Serum iron
- Ferritin
- Transferrin (=Total Iron Binding Capacity, TIBC)
- Transferrin saturation (should be 20-40%)
What are 3 causes of low MCV
- Iron deficiency
- Thalassaemia trait
- ACD (can have low/normal MCV)
i.e. if low MCV, could be due to any of the above causes
Serum iron is not a good reflection of total iron. How is serum iron affected in iron deficiency, ACD, Thalassaemia?
Iron deficiency = low serum iron
ACD = low serum iron
Thalassaemia = normal serum iron
i.e. low serum iron could be due to iron deficiency or ACD, either one
How can we confirm thalassaemia trait
Hb electrophoresis - confirms an additional type of Hb present
Why is ferritin test such a sick test
It is LOW in iron deficiency
HIGH in chronic disease (ACD)
Ferritin is an acute phase protein that goes up when were unwell
HOWEVER, if patient has BOTH iron deficiency AND chronic underlying disease, ferritin may be normal. Eg if they had RA + bleeding ulcer
So, LOW ferritin confirms iron deficiency, but normal ferritin doesn’t exclude iron deficiency. Good way to see if “normal” ferritin isn’t ideal is if they have high CRP/ESR
How is transferrin and transferrin saturation affected in iron deficiency and in ACD
Iron deficiency - transferrin goes up. Low saturation
Chronic disease - transferrin = normal/low. Normal saturation
Upon finding someone is iron deficient, what investigations are done
- Anti-coeliac antibodies
- Anti-helicobacter antibodies
- Duodenal biopsy
- Upper and lower GI Endoscopy (and colonoscopy) - to look for a source of bleeding
What are the lab test results if classic iron deficiency?
EVERYTHING LOW except transferrin
Hb, MCV, Serum iron, Ferritin, Transferrin saturation = low
Transferrin = high
What are the lab test results if ACD?
Hb, serum iron = LOW
MCV, transferrin = LOW / NORMAL
Transferrin saturation = normal
Ferritin = HIGH or normal