Iron Deficiency Flashcards
Where is Iron normally found?
Found in many PROTEINS
inc. myoglobin, catalase, cytochrome P450 etc.
BUT most iron found in Hb
Link between Iron and Hb?
Low Iron = Low Hb = anaemia
What is the role of Iron in Hb?
Iron (specifically FERROUS) found in the
HAEM part
of Hb and its role is to hold onto O2
Iron homeostasis?
RBCs live for ~120 days!
Need around 20mg iron/day to replace lost RBCs
BUT
we can recycle iron!
How can iron be lost in the body?
o Desquamated cells of skin & gut
o Menstruation (bleeding)
How much iron do men and women need?
Men = 1mg/day
Women = 2mg/day
Where can we get iron from but what is an issue of this?
- Human diet
o provides ~12-15mg/day
o e.g. meat & fish (haem iron), veg, chocolate, whole grain cereal
BUT
most iron eaten is NOT absorbed
o can NOT absorb ferric iron (Fe3+)
o can only absorb ferrous iron (Fe2+)
How can you tackle the problem with iron absorption from diet? What makes it worse?
Orange Juice AIDS absorption of iron
Cups of tea makes it WORSE
o turns iron into the FERRIC form
o can lead to chronically low levels of FERROUS!
Factors affecting absorption of Iron?
Diet
o increase in haem iron (ferrous iron)
Intestine o acid in the duodenum o ligand (meat)
Systemic
o Iron deficiency (anaemia/hypoxia, preganacy)
Factors that INCREASE iron absorption?
Iron deficiency
Anaemia/hypoxia
Pregnancy
How is iron absorbed in the gut?
- Iron freely transports into the cell from the gut lumen
- FERROPORTIN facilitates transport of iron into the blood
o HEPCIDIN inhibits ferroportin
Hepcidin is regulated
o has iron-responsive elements within their gene
o so iron part of complex that switches on its transcription
Ferroportin is found in
o enterocytes (dudodenum)
o macrophages (spleen)
o hepatocytes
How is Iron held onto in the circulation?
TRANSFERRIN!
- Iron taken into cells
- Protein shell forms around it
o forms FERRITIN micelles - Once iron enters plasma via. ferroportin, is linked to transferrin which transports it around the body
Characteristics of Transferrin and how it can be measured?
Usually 20-40% saturated with iron
o NEED it because iron is TOXIC & INSOLUBLE
o Transferrin levels
o Total Iron Binding Capacity (TIBC)
o Transferrin saturation
CAN all therefore be measured
Can TF enter cells directly?
NO
o bind with the TF-R and is internalised as a whole
As pH DROPS:
o iron is released
o TF-R are recycled
EPO?
Erythropoietin
Produced in kidneys
o production increased in response to hypoxia
o triggers more RBC precursors to be released
o the precursors survive longer and will survive, grow and differentiaite
ACD?
Anaemia of Chronic Disease
What is ACD?
Anaemia seen in patients who have a chronic disease
Cause of ACD?
Patient will NOT show classic causes of anaemia
i.e. bleeding
bone marrow infilitration
have a iron/B12 or folate deficiency
There is NO obvious cause
Laboratory signs of ACD?
- Higher levels of C-reactive protein (CRP)
o an acute phase protein (inflammation/infection) - Higher Erythrocyte Sedimentation Rate (ESR)
o rises in inflammation/infection - Acute phase response - increases in:
o Ferritin (usually reflects iron stores BUT is acutely ill levels shoot up as an acute phase protein so no longer good measure of iron during acute illness)
o F8
o Fibrinogen
o Igs (esp. IgG)
Conditions associated with ACD?
o Chronic infections e.g. TB/HIV
o Chronic inflammation
o Malignancy
o Miscellaneous e.g. cardiac failure
What normally causes the pathogenesis of ACD?
Due to CYTOKINE release
e.g. TNFalpha & ILs
How does this pathogenesis demonstate itself in ACD?
The cytokines:
o prevent usual flow of iron from dudodenum to RBCs
o stop EPO increasing
o stop iron flow out of cells
o increase ferritin production
o increase RBC death
SO makes less RBCs = more RBCs die = less iron available
Major cause of iron deficiency?
BLEEDING
e.g. menstrual OR GI
Minor causes of iron deficiency?
Increased use of iron
e.g. growth/pregnancy
Dietary deficiency
e.g. vegetarian
Malabsorption
e.g. coeliac
What type of investigation do you do if suspect iron deficiency?
Full GI investigation
When should an investigation be carried out if suspect iron deficiency?
Good diet & NO coeliac Abs
o MALE
o Woman
- over 40
- post-menopausal woman
- woman w scanty menstrual loss
What is involved in the investigation for possible iron deficiency suspection?
A FULL GI investigation
o Upper GI endoscopy (oesophagua, stomach, dudodeum)
o dudodenal biopsy
o colonoscopy
If found NOTHING, do a small bowel meal and follow through
What are other possible investigations if suspect iron deficiency?
- Menstruating women <40 years
o if heavy periods OR multiple pregnancies
o NO GI symptoms
o DO NOTHING!! - Check for urinary blood loss
- Abs for coeliac disease
What are the laboratory parameters important when checking for iron deficiency?
- MCV
- Serum iron
- Ferritin
- Transferrin (TIBC)
- Transferrin saturation
CASE STUDY!
Mrs Jones:
Hb = 100g/L
MCV = 72
What does this show?
BOTH are LOW
Hb NR = 120-150
MCV NR = 80-100
CASE STUDY!
Is Mrs Jones iron deficient? Why?
Cannot tell as there are 3 causes of a low MCV
- Iron deficiency
- Thalassaemia trait
- ACD (could also have had normal MCV for this!)
CASE STUDY!
Next parameter shows her Serum Iron is LOW
Is she iron deficient? Why?
NO - but can rule our thalassaemia trait!
In thalassaemia trait, serum iron is NORMAL
o to confirm would normally carry out Hb electrophoresis
o confirms an additional type of Hb present
Iron deficiency & ACD would both show LOW serum iron
CASE STUDY!
Next parameter shows Ferritin LOW
Is she iron deficient? Why?
Ferritin NR (10-200)
Ferritin is:
o LOW in iron deficiency
o HIGH in chronic diease
CASE STUDY!
Is ferrtin a good indicator for iron deficiency?
NO - as she could have underlying CD & iron deficiency
e.g. RhA with a bleeding ulcer
In this case, ferritin can be normal DESPITE iron deficiency
CASE STUDY!
What lab tests can then be done to shows that ferritin is not ideal?
CRP = RAISED ESR = RAISED
Shows that there is some acute condition that is causing a rise in all the acute phase proteins
SO
ferritin can NOT be relied upon
CASE STUDY!
Next parameter shows transferrin saturation which is at 4%
What does this show?
Transferrin sat. NR = 20-40%
Transferrin:
o INCREASES in iron deficiency
o NORMAL or LOW in ACD
Transferrin sat.:
o LOW in iron deficiency
- as more transferring & less iron
o NORMAL in ACD
- as iron & transferrin have BOTH gone down so saturation is normal
CASE STUDY!
So what does Mrs Jones have?
Iron Deficient Anaemia
CASE STUDY!
What further investigations could you do for Mrs Jones after assessing the diagnosis
Remember, the parameters on blood tests may show both iron deficiency & ACD so need to do further tests to discover source of bleeding!
o Endoscopy/colonoscopy o Duodenal biopsy o Anti-helicobacter Abs o Anti-coeliac Abs o Other - inc. abdo ultrasound (kidneys), dipstick urine, pelvic US to excluse fibrosis
Man of ANY AGE with a LOW ferritin?
Does suggest iron deficiency!
Needs to have a upper and lower GI endoscopy to look for a source of bleeding
Classic iron deficiency:
Hb MCV Serum iron Ferritin Transferrin Transferrin sat.
Hb = LOW
MCV = LOW
Serum iron = LOW
Ferritin = LOW
Transferrin = HIGH
Transferrin sat. = LOW
Classic ACD:
Hb MCV Serum iron Ferritin Transferrin Transferrin sat.
Hb = LOW
MCV = LOW or N
Serum iron = LOW
Ferritin = HIGH or N
Transferrin = N or LOW
Transferrin sat. = N
What does this suggest and extra test?
Hb = 10 MCV = 66 Serum iron = N Ferritin = N Transferrin = N Transferrin sat. = N
Thalassemia trait!
Hb = LOW MCV = LOW Serum iron = N Ferritin = N Transferrin = N Transferrin sat. = N
If iron deficiency OR ACD, serum iron would also be LOW!
Would do Hb electrophoresis to confirm!
What does this suggest?
Hb = 10 MCV = 78 Serum iron = LOW Ferritin = N Transferrin = LOW Transferrin sat. = N
RhA with bleeding ulcer!
Hb = LOW MCV = LOW Serum iron = LOW Ferritin = N Transferrin = LOW Transferrin sat. = N
