Normal erythropoiesis 2 Flashcards
What are the 2 states iron can exist in ?
Fe2+ and Fe3+ (transition metal)
What is iron required for in the body and why can it potentially be problematic ?
Iron is essential in the following:
- Oxygen transport - Hb, myoglobin
- Electron transport - Mitochondrial production of ATP
Iron is potentially toxic and needs to be handled safely by the body as it generates free radicals
How much iron is absorbed and excereted each day ?
1mg per day is absorbed and excreted
What are the sites in the body for which iron is stored/is present ? and which has the highest amount of iron?
- Liver stores - 500mg
- Plasma - 4mg
- Erythroid marrow - 150mg
- Red cell Hb - 2500mg
- Macrophages store - 500mg
==> most of the iron in the body is in Hb
What protein stores iron and what protein is used to transport iron ?
Ferrtin stores iron and releases it in a controlled fashion
Circulating iron is bound to transferrin i.e. iron in plasma
What is the function of ferritin and describe the key features of its structure ?
- Large intracellular protein
- Spherical protein stores up to 4000 ferric ions (iron)
- Essentially it stores iron
- There is small levels of ferritin in the serum so it can be measured
Describe the key features of transferrin and state its function
- Protein with two binding sites for iron atoms
- Transports iron from donor tissues (macrophages, intestinal cells and hepatocytes) to tissues expressing transferrin receptors (especially erythroid marrow)
- Basically transports iron from storage sites i.e. macrophages, liver to the bone marrow
How much iron can be moved to the bone marrow in a day ?
roughly 20mg so its a quick transport of iron in the plasma
What are the avaliable tests to assess iron status ?
Functional iron:
- Haemoglobin
Transported iron:
- Serum iron
- Transferrin
- Transferrin saturation
Storage iron:
- Serum ferritin
What does increased and decreased transferrin indicate ?
- Reduced in iron deficiency
- Reduced in anaemia of chronic disease
- Increased in genetic haemachromatosi
What does a low serum ferritin indicate ?
Iron deficiency anaemia
What are the causes of iron deficiency anaemia ?
Not eating sufficient to meet physiological requirements:
- RELATIVE deficiency – normal amount of iron in diet but a high demand - esp women of child bearing age and children
- ABSOLUTE deficiency – lack of iron in diet - vegetarian diets
- In general unlikely in men
Chronic blood loss - usuaully GI cause
Not absorbing enough – malabsorption:
- Coeliac disease or any inflamm conditions of GI tract
- achlorhydria
What are the causes of chronic blood loss resulting in iron deficiency anaemia ?
Menorrhagia - heavy blood loss
Gastrointestinal
- Tumours
- Ulcers
- Non-steroidal anti-inflammatory agents
Haematuria
What is meant by occult blood loss ?
- Occult gastrointestinal (GI) bleeding refers to the initial presentation of a positive fecal occult blood test result and/or iron deficiency anemia when there is no evidence of visible blood loss to the patient or physician
- Even very small amounts of blood loss which may not be symptomatic i.e. seen as malena can over time result in iron deficiency
What are the things tested for in a FBC?
- Hb
- MCV
- MCH
- Hct
- WBC’s
- RBC’s
- Platelets
Appreciate this regarding menstrual loss and how it can result in iron deficiency anaemia
- Average 30-40ml/month
- Equivalent to 15-20mg/month of iron lost - 1mg lost to every 2ml of blood
- Average daily intake 1mg/day
- Iron status precarious
- Heavy menstrual blood loss >60ml
- I.e. >30mg iron/month lost (we can only upregaulate intake of iron up to a couple mg per day)
What do you need to rememeber about iron deficiency anaemia ?
It is not a diagnosis it is a symptom and requires further investigations in most patients
What are the risk factors for developing iron deficiency anaemia ?
- Female (menstruation)
- Exstremes of age
- Lactation
- Pregnancy
- Poverty
What are the general symptoms of anaemia (talking about anaemia as a whole) ?
- Fatigue
- Faintness
- SOB/dyspnoea (laboured breathing)
- Palpitations
- Headache
- Tinnitus
- Anorexia
- Angina, intermittent claudication if pre-existing coronary artery disease
What are the general signs of anaemia ?
- Pallor
- Pale conjunctiva
- Pale palmar creases
- Tachycardia
- Postural hypotension
- Signs of congestive heart failure e.g. ankle swelling Murmur
What are the signs of aneamia which are specific to iron deficiency anaemia ?
- Brittle nails and koilonychia (spoon shaped nails)
- Atrophic glossitis (bald/ smooth tongue thats often painful)
- Brittle hair
- Angular cheilosis/stomatitis - ulceration of corners of mouth
- Plummer vinson syndrome - dysphagia, iron-deificency anaemia, oesophageal webs and glossitis
How is iron-deficiency anaemia confirmed ?
1st do a FBC - this will show a hypochromic (low MCH) microcytic (low MCV) anaemia (low Hb)
the follow this up with serum ferritin levels - if low <15 then this is confirmatory of iron deficiency anaemia
- If ferritin levels not low it does not rule out iron deificiency anaemia do a serum iron test, total iron binding capacity (level of transferrin in blood) allows % transferrin saturation to be worked out - serum iron will be low, TIBC will be increased and % saturation of transferrin is low
- or diagnostic trials of iron treatment can be considered in premenopausal women with a history of menorrhagia, or pregnant women
After confirming iron-deficiency anaemia what is done next?
Screen all for coeilacs disease - using coeliac serology (presence of anti-endomysial antibody or tissue transglutaminase antibody)
Then the decision needs to be made whether or not to do further investigations
Who is it usually unnecessary to do further investigations for after screening for coeliacs disease in iron deficiency anaemia ?
- Otherwise healthy young people in whom the history clearly suggests a cause (for example regular blood donors).
- Menstruating young women with no history of gastrointestinal symptoms or family history of colorectal cancer.
- Pregnant women — investigations (to determine an underlying cause or the presence of complications) are not usually needed if anaemia develops during pregnancy unless the anaemia is severe, the history and examination suggest an alternative cause of iron deficiency (for example inflammatory bowel disease), or there is no response to iron supplementation.
For everyone else iron-deficiency anaemia warrants fruther investigations what are they?
- Test the urine for blood.
- Refer for upper and lower gastrointestinal (GI) investigations. - gastroscopy, sigmoidoscopy, barium enema, or colonoscopy are all options
- Somtimes stool microscopy recommended in people where they have been to the tropics etc and a GI parastic infection could be causing the GI bleeding
What is the treatment of iron-deificiency anaemia ?
- Treat the underling cause
- Treat the anaemia with oral ferrous sulphate as primary choice
How quickly should you expect iron levels to rise when on treatment ?
10g/L/week - checked around 3-4wks
If not expected increase then can check if there has been an increase in recticulocytes production which would indicate that treatment is starting to work
What are other treatment options if ferrous sulphate not tolerated ?
- Ferrous gluconate
- Ferrous fumerate
How long is iron-deficiency treatment continued for ?
- After doing initial 3-4wk check, check Hb around 2-4 months and then Once Hb returns to normal continue treatment for 3 months afterwards to replenish iron stores
- Then monitor someones FBC every 3 months for 1 year
What are some of the side effects to oral iron treatment ?
- Nausea
- Abdo discomfort
- diarrhoea
- constipation
- black stools
How often is PO iron replacement given typically ? and now how often is it thought to be better given as and why?
Typically PO iron replacement is given TDS. However it is now thought that giving it once/day or even once every second day would be better. This is because following initial dose of PO iron hepicidin activity then increases over the next 24hrs resulting in impaired absorption of subsequent doses of iron.
This is meant to result in similar increases in iron levels but also less of the GI side effects as the hepicidin isnt then causing the subsequent 2 doses of iron to be stuck in the duodenal cells and macrophages resulting in ‘GI side effects and non-compliance’
