Session 9: Anaemia (and iron) Flashcards

Question

Describe the absorption of iron supplements and response to iron supplements

Answer 1

Absorption of iron supplements: * Duodenum and jejunum * Ferrous state * Maximal absorption in first few weeks of treatment (works best initially) * Absorption inhibited by antacids, H2 blockers, PPIs, tetracyclines, calcium, phytates * Absorption enhanced by ascorbic acid * Take between meals Response to oral iron * Increase in Hb by 20g/l in 3 weeks (if not as high as expected, suggests ongoing blood loss somewhere) * Clinical improvement in symptoms * Changes in reticulocyte count * Increase in Mean Cell Volume * Increase in serum ferritin

Answer 2

Macrocytosis (megaloblastic anaemia) with hypersegmented (multilobular) neutrophils – (usually caused by first two) B12 deficiency * Many years to become Vit B12 deficient (compared to iron deficiency); patients adapt =\> present late * Vegetarians / vegans * Gastric (pernicious anaemia) and intestinal causes – Schilling test (used to determine pernicious anaemia) * NB: pernicious anaemia’s proper meaning is megaloblastic anaemia caused by atrophic gastritis, parietal cell loss and lack of intrinsic factor only; pernicious anaemia involves the presence of an autoantibody to intrinsic factor required to absorb Vit B12. * Oral (if no malabsorption) or IM hydroxycobalamine repacement Folate deficiency * Months to become deficiency * Diet * Malabsorption * Excess use e.g. sickle cell/hereditary spherocytosis * Drugs e.g. anticonvulsants, co-trimoxazole Myelodysplasia-other dysplastic features on film

Answer 3

Check B12/folate Check thyroid function tests/ liver function tests (can occur in hypothyroidism, liver failure, heavy alcohol – can be detected by a Gamma-glutamyl transpeptidase blood test) Check immunoglobulins (monoclonal gammopathy of undetermined significance – M protein, myeloma) Consider referral for Bone Marrow exam…MDS/other (myelodysplastic syndrome)

Answer 4

Anaemia of chronic disease * Associated with chronic inflammation/infection * Cytokine driven reduction in serum iron (causes increased hepcidin carrier molecule =\> reduced gut iron absorption + recycled iron pushed into stores i.e. none for red cells). * Reduction in erythropoietin production * Reduction in lifespan of red cells * Can be normocytic normochromic anaemia or microcytic anaemia * Ferritin normal or raised * Serum iron reduced * Normal transferrin saturation (if reduced indicates associated iron deficiency) Mixed deficiency of iron and Vit B12/folate (normal MCV, high red cell distribution width) BM failure - normally causes macrocytic but some cause normocytic

Answer 5

Iron transports and stores oxygen Iron is an integral part of many enzymes including: * Energy metabolism * Neurotransmitter production * Collagen formation * Immune system Function BUT the human body does not have a mechanism for excreting iron so the quantity of body iron has to be carefully controlled (excess iron can be harmful) In the body, iron is found in two forms: 1. Active Iron: Predominantly haemoglobin (carries oxygen to tissues) but also * Myoglobin (oxygen reserve in muscles) * Tissue Iron: (enzyme systems cytochromes) * Transported iron: ‘serum iron’ 2. Iron stores: there are 2 types * Ferritin within the blood, soluble * Haemosiderin is macrophage iron and insoluble; iron deposits e.g. in bone marrow

Answer 6

As there is no pathway for excretion of iron, the concentration of iron can only be regulated by absorption to match losses. Absorption needs to match losses to avoid iron overload or deficiency. 1-2mg of iron enters and leaves the body each day. Daily iron requirements vary between ages: * Iron is present in breast milk * Breast milk does not contain a high concentration of iron but it is very well absorbed - ~50% breast milk iron is absorbed, compared to only a 7% absorption from formula * By about 6 months of age, however, infants should be introduced to foods containing iron. * Iron requirement is very high during pregnancy – very common for pregnant women to become iron deficient as the foetus requires a lot of iron.

Answer 7

In our diet, two types of iron are found: Haem (e.g. meat, seafood) vs non-Haem iron (e.g. spinach, beans, cereal, lentils) Need 10-15mg of iron per day in diet Iron supplementation of diet e.g. cereals Haem iron is the better iron because it is already in ferrous form (Fe2+) – absorbed more readily across the gut border. Non-Haem Iron: * Mainly exists in the Fe3+ (= ferric) * Reduced to ferrous iron before being transported across the intestinal epithelium Different proteins involved in absorbing haem vs non-haem iron.

Answer 8

Iron is absorbed across the apical surface of the duodenum and upper jejunum. When it is transported in the blood, it is attached to Transferrin Transported in the blood to liver, macrophages and bone marrow. Ferrorportin transports Fe2+ across the border Once Fe2+ inside the enterocyte, it can either be: * Stored as ferritin or * Transported into the blood stream Iron is exported out of the cell by ferroportin. Fetal enterocytes (cells of the intestinal lining) have receptors for Lactoferrin - primary source of iron in infants. When taking iron supplements or eating iron, it is very important how you take it or what you take it with: Vitamin C present in e.g. orange juice, enhances absorption of iron as ascorbic acid reduces Fe3+ to Fe2+ so it more readily absorbed and transported across the membrane Tea, chapattis and antacids amongst others inhibit absorption of iron as they precipitate/chelate iron.

Answer 9

Iron is taken into cells e.g. Red Blood Cells by binding of iron-transferrin complex to transferring receptor (TfR) Erythroid cells contain the highest number of TfRs. A soluble form, soluble TfR (sTfR) is a good indicatior of functional iron levels. 20% of iron might be lost e.g. in bleeding, skin and hair and nails. 80% of iron is recycled in the body Macrophages are a good place to store iron and deliver iron to RBCs when needed

Answer 10

Depends on dietary factors, body iron stores and erythropoiesis. Dietary iron levels are sensed by the villi of enterocytes Control mechanisms: * Regulation of transporters * Expression of receptors e.g. HFE and Tf receptor * Other humoral and tissue derived factors like hepcidin and cytokines * Crosstalk between the epithelial cells and other cells like macrophages

Answer 11

Secreted by the liver and excreted by the kidneys Synthesis increased in iron overload * Transgenic mice constructed to over-express hepcidin died shortly after birth with iron deficiency (they were not able to absorb iron from the gut) * Hepcidin production is decreased by high erythropoietic activity. * It degrades ferroportin, preventing iron from be released into the blood stream. REMEMBER most (80%) of active iron comes recycling within the body e.g. breakdown of RBC and NOT gut absorption

Answer 12

vMacrophages ‘eat’ old senescent RBCs, releasing iron during Hb breakdown. Iron is then recycled. - Mainly splenic macrophages and Kupfer cells of the liver - 95% of stored iron in liver tissue is found in hepatocytes as ferritin. - Hemosiderin constitutes the remaining 5% and is found predominately in Kupffer cells. v*Ferritin and transferrin receptor expression are regulated mainly at the post transcriptional level by iron regulatory proteins (IRP1 and IRP2)*

Answer 13

Iron deficiency is a symptom not a diagnosis so you always need to consider the CAUSE. * Insufficient intake (e.g. vegetarians and vegans are at risk of insufficient intake of iron in particular)/poor absorption (e.g. due to a GI disorder) * Increased use physiological e.g. pregnancy. * Increased use pathological e.g. bleeding * Rough estimates of the cause: * 25% Menstruation * 13% AIDS/NSAID use * Colonic carcinoma * Gastric carcinoma * Benign gastric ulceration * 5% blood donation * 5% of celiac disease * 15% other

Answer 14

Tests would reveal: * Low Hb * Small Red blood cells (low mean cell volume) * RBCs change shape and size e..g become pencil cells, hypochrmia – very pale), microcytosis, target cells. * Low serum ferritin, serum iron and %transferrin saturation, raised TIBC (Total Iron Binding Capacity) * Serum ferritin is produced y the liver and is the single most important measure of iron status, particularly iron store * Reduced levels indicate iron deficiency BUT Limitation: acute or chronic inflammation, malignancy, liver disease and alcoholism can cause increased serum ferritin levels SO normal or increased levels of serum ferritin do not exclude iron deficiency (as liver could be damaged)

Answer 15

If you suspect iron deficiency, investigate the cause: * Dietary history * GI investigations Iron replacement: Dietary advice (e.g. eat iron with orange juice not tea etc) Supplements: give advice on how to take such as take on an empty stomach but consider what factors affect absorption and often side effects might be strong – cause constipation, diarrhoea, nausea. Intravenous: there is the rsk of anaphylaxis and death Intramuscular: risks of anaphylaxis, unpredictable absorption and local complications (e.g. pain, staining of the skin, sarcoma formation).

Answer 16

Iron excess: When the amount of iron exceeds binding capacity of transferring Free iron is dangerous as it acts as a free radical and can damage cells Reduced Fe (Fe2+) can produce highly reactive hydroxyl and lipid radicals, which can damage lipid membranes, nucleic acids and protein Excess iron is deposited in tissues – Haemosiderin is deposited in liver, pancreas, heart, joints and skin. Very hard to eliminate.

Answer 17

Transfusion associated haemosiderosis occurs in haematology patients, especially ones with chronic anaemia and are dependent on regular transfusions Desferrioxamine is a liquid drug given over a 16 hour period through a pump (not very convenient) or pleasant). Oral iron chelating agents (bind, prevent iron absorption) are available but not as good as desferrioxamine therefore can only be used in combination rather than as a sole treatment Close monitoring is required.