Lecture 11:12 — Iron - Introducing Fe PDF

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Introducing Fe...

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Lecture 11/12 — Frankish — Iron Disturbances in Iron Metabolism - Distribution is tightly controlled - Long term and short term storage - Total Fe is roughly 3.5g - Women roughly 2.5 - Long term storage as ferritin in the erythrocytes - Hemociderin - Insoluble - Liver - Marrow - Macrophages

Iron Absorption - Heme iron bypasses absorption restrictions - Fiber phytates, tannates and phosphoproteins can reduce non-heme iron absorption - Ascorbic acid increases iron absorption - Most occurs in the duodenum and upper jejenum - non-heme iron reduced to Fe2+ - Total body iron affects gastric mucosal signalling for further iron absorption — Transferrin can bind to binding receptors — High activity = high iron

Iron Conservation Ageing erythrocytes undergo phagocytosis

Iron Deficiency Anaemia Causes abnormalities in erythrocytes, examples of which include: Poikolocytosis — Abnormally shaped RBCx

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Anisocytosis — Unequally Sized RBCs Hypochromia — Pale RBCs Microcytosis — Small RBCs

Aetiology Most often due to blood loss, can often occur by heavy menstruation — Adolescent girls — growing and low Fe in diet and menstruation

Pathophysiology 1.

Low iron absorbed

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Storage pools deplete and cannot meet the erythroid marrow requirements. — Decrease in Fe for erythropoiesis

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Anaemia with normal erythrocytes

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Microcytosis and haemochromia

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Affects tissues — Results in signs and symptoms

Can result in… pico — Craving to eat dirt pagophagia — Craving to eat ice glossitis — Burning tongue Koilonchyia — Finger nails flatten and become brittle

Treatment - Source the site of bleeding - Treat symptoms by supplementing with Fe salts. - Parenteral Fe only if absolutely necessary or if patient cannot take oral meds.

Side Effects Most often GI irritation and constipation. - Black faeces - Diarrhoea - Vomiting - Constipation - Overdose in children can be fatal — 200-300mg - Vomiting

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- Hypotension - Lethargy - Cardiovascular collapse/Pulmonary Oedema/Hypoglycaemia Treatment involves chelation by desferrioxamine. Higher affinity to bind to Fe than Transferrin.

Hypoproliferative Anaemia Lack of response to erythropoietin — Patients on long term dialysis have return to better erythropoiesis, never returns to normal Can treat with human epo.

Megaloblastic Macrocytic Anaemia Results from a defective DNA synthesis continued normal RNA synthesis, but this results in high cytoplasmic mass — Large RBCs — Loss of shape - Deficiency of B12 - Deficiency of folic acid

Pernicious Anaemia/Megaloblastic Anaemia Usually only available in reasonable amounts in animal proteins - Absorption is complex - Terminal Ileum - Requires Intrinsic Factor by Parietal Cells - B12 bound to proteins in food - Pancreatic proteolytic enzymes cleave this complex - B12 binds to the intrinsic factor and passes the epithelium B12 is slowly absorbed — Takes months before symptoms appear Pernicious anaemia is when intrinsic factor is dysfunctional — Usually autoimmune — Can be due to absent absorptive sites.

Combined System Disease - Degenerative NS changes - Degeneration of peripheral nerves — Axons/myelin sheaths Can cause splenomegaly/hepatomegaly. GI issues often present.

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Anorexia, constipation and diarrhoea.

Neurological Symptoms Peripheral nerves first — Then spinal cord. - Neurologic symptoms sometimes precede haematologic problems. (Can have no haematologic problems if taking folate) - Spasticity - Loss of perception of the extremities - Babinski’s response

Haemotological Symptoms - Macrocytosis - Loss of erythrocyte shape - MCV > 100 fL — femtolitre - Poikilocytosis - Howell-Jolly bodies — Nuclear fragments - Reticulocytopenia — If pt. has not been treated Most macrocytic anaemias are pernicious — Anaemia caused by folate deficiency is possible

Folate-deficiency Anaemia - Prolonged cooking destroys folate - 2-4 mo. store in the liver - EtOH interferes with absorption - Can be due to low intake or intestinal malabsorption - Can be drug-induced — Methotrexate

- Primary symptoms common with anaemia - Indistinguishable from B12-deficiency anaemia. - No neurologic lesions — Only haematological symptoms If someone with B12 deficiency anaemia takes folate — haematologic symptoms alleviated but not the neurologic affects. Therefore it is important to first rule out B12-deficiency anaemia as neurological symptoms can be permanent if untreated.

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Ascorbic acid-deficiency Anaemia - Can be normolytic or microlytic - Treat with Ascorbic acid/folate supplementation

Haemolytic Anaemias Bone marrow production cannot compensate for erythrolysis (phagocytosis in the spleen) Most likely causes include: 1.

RBC sequestration — changes to the vasculature

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Immunological injury Mechanical injury

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Abnormal Hb

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Metabolic problems

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Changes in RBC structure

Hexose Monophosphate Shunt Defects 1.

G6PD deficiency

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Drug-sensitive

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Primaquine, Salicylates, Sulfonamides, Nitrofurans, naphthalene, fava beans

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DKA more likely to cause anaemia than drugs

Results in: - Anaemia - Jaundice - Reticulocytosis Heinz bodies — Denatured Hb inclusions - Only seen early - Do not persist - Removed by the spleen

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