Flashcards in Iron in health and disease Deck (48):
Where is the majority of body iron found?
Haem groups are found where?
In global chains
Which iron ion is present in haem?
Fe2+ (ferrous ion)
What is haem made up of?
Protoporphyrin ring + Fe
Porphyyrin ring + Fe3+ -> haem
Where in the global chain do iron ions sit?
Fe2+, ferrous ion, sits in the porphyrin ring
Where is iron absorbed?
Name the membrane proteins involved in iron absorption and their actions
DMT-1 (divalent metal transporter) - transports iron into the duodenal enterocyte.
Ferroportin - facilitates iron export from the enterocyte.
Trensferrin - receives iron from ferroportin to transport elsewhere.
Hepcidin - down-regulates ferroportin
Which types of factors regulate iron absorption?
What are the intraluminal factors?
Solubility of inorganic iron,
Haem iron easier to absorb,
Reduction of ferric (2+) to ferrous (3+).
What are the mucosal factors?
(expression of iron transporters)
DMT-1 at mucosal surface
Ferroportin at serial surface
What are the systemic factors?
Hepcidin - the major negative regulator of iron uptake.
Produced in the liver in response to iron load and inflammation.
Down-regulates ferroportin - iron is 'trapped' in duodenal cells and macrophages.
What are the 3 compartments of iron status assessment?
Functional iron, Transport iron/supply to tissues, and storage iron.
What determines the functional iron compartment?
How many iron binding sites does transferrin have?
Describe the role of transferrin.
Transports iron from donor tissues (macrophages, intestinal cells, hepatocytes) to tissues expressing transferrin receptors.
Name a tissue rich in transferrin receptors.
Erythroid marrow - bone marrow producing RBCs.
What is measured to determine iron supply? And how is this done?
- serum iron/total iron binding capacity (to transferrin) x100%
- reflects the proportion of diferric transferrin
= % saturation of transferrin with iron.
Normal transferrin saturation?
Name for iron bound to transferrin?
Unbound transferrin name?
What is the storage compartment of iron status?
Serum ferritin & tissue biopsy (rarely needed)
What is ferritin?
A serum intracellular protein which stored up to 4000 ferric ions (Fe3+)
What is an indirect measure of storage iron?
A tiny amount of serum ferritin reflects intracellular ferritin synthesis.
Examples of when serum ferritin would be raised.
Infection, malignancy, liver injury - it acts as an acute phase protein
Name 3 disorders of iron metabolism
iron malutilisation aka 'anaemia of chronic disease'
What are the consequences of negative iron balance?
In order of progression over time:
1. exhaustion of iron stores
2. iron deficient erythropoiesis
3. microcytic anaemia
4. epithelial changes
What is iron deficient erythropoiesis?
Evidence of iron deficiency without anaemia (i.e. normal haemoglobin level)
Loss of bone marrow iron stores while haemoglobin and serum iron levels remain normal.
What is microcytic anaemia?
Smaller and paler RBCs
What epithelial changes are signs of low iron?
Skin - pale
Koilonychia - aka spoon nails, thin and brittle nails which are either flat or concave in shape.
Angular stomatitis - inflammation of one or both corners of the mouth. Itchy or painful, red and crusty with skin breakdown.
What does 'hypo-chromic microcytic anaemia' mean?
deficient haemoglobin synthesis
What are the 2 types of hypo-chromic microcytic anaemias?
What causes haem deficiency?
Lack of iron for erythropoiesis:
- iron deficiency (low body iron)
- anaemia of chronic disease (normal body iron)
Congenital sideroblastic anaemia - very rare - bone marrow produces ringed sideroblasts instead of healthy RBCs. The body has iron available but can't incorporate it into Hb - oxygen can't be transported efficiently.
What causes global deficiency?
Thalassaemias - inherited blood disorders characterised by abnormal Hb production.
What confirms iron deficiency?
The combination of anaemia and reduced storage iron.
(decreased haemoglobin iron + low serum ferritin)
What can cause chronic blood loss?
Menorrhagia - excessive blood flow during periods.
Gastrointestinal; tumours, ulcers, NSAIDs, parasitic infection.
Haematuria - RBCs in urine
Describe how occult blood loss could occur.
GI blood loss of 8-10ml /day (4-5mg iron) can occur without any symptoms or signs of bleeding.
The maximum dietary iron absorption of iron is around 4-5mg/day.
Therefore negative iron balance can occur.
Is iron deficiency anaemia a sign, a symptom, or a diagnosis?
Iron replacement therapy may relieve this symptom without treating the underlying problem.
Investigations are essential to identify diagnosis.
Describe normal haemoglobin recycling.
Old RBC digested by activated macrophage; splits haem + globin.
Haem -> porphyrin -> bilirubin AND Haem -> iron -> ferritin (transferritin transports it to marrow erythroblasts).
Globin -> amino aicds
What is inflammatory macrophage iron block?
Increased transcription of ferritin mRNA stimulated by inflammatory cytokines (released from activated macrophages) so ferritin synthesis increased.
Increased plasma hepcidin blocks ferroporin-mediated release of iron.
Results in impaired iron supply to marrow erythroblasts and eventually hypo-chromic red cells.
What is the a primary cause of iron overload?
What is a secondary cause of iron overload?
Iron loading anaemias
What is the definition of a primary iron overload?
Long-term excess iron absorption with parenchymal, rather than macrophage, iron loading.
What is hereditary haemochromatosis?
Decreased synthesis of hepcidin
Increased iron absorption
Results in gradual iron accumulation with risk of end-organ damage.
Clinical features of hereditary haemochromatosis?
Presents usually middle age / later
Iron overload >5g
What is the treatment option of hereditary haemochromatosis?
Weekly venesection - 450-500ml (200-250mg iron).
Initial aim is to exhaust iron stores (<20 micrograms/l).
Then keep ferritin <50 micrograms/litre
Sources of iron-loading anaemias?
Repeated red cell transfusions, and excessive iron absorption related to over-active erythropoiesis.
Disorders of iron-loading anaemias?
Massive infective erythropoiesis;
thalassaemia syndromes, sideroblastic anaemias.
Refractory hypoplastic anaemias;
red cell aplasia, myelodysplasia (MDS)