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GI > Iron in health and disease > Flashcards

Iron in health and disease Flashcards

1
Q

Where is the majority of body iron found?

A

Haem

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2
Q

Haem groups are found where?

A

In global chains

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3
Q

Which iron ion is present in haem?

A

Fe2+ (ferrous ion)

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4
Q

What is haem made up of?

A

Protoporphyrin ring + Fe

Porphyyrin ring + Fe3+ -> haem

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5
Q

Where in the global chain do iron ions sit?

A

Fe2+, ferrous ion, sits in the porphyrin ring

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6
Q

Where is iron absorbed?

A

duodenum

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7
Q

Name the membrane proteins involved in iron absorption and their actions

A

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

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8
Q

Which types of factors regulate iron absorption?

A

Intraluminal
Mucosal
Systemic

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9
Q

What are the intraluminal factors?

A

Solubility of inorganic iron,
Haem iron easier to absorb,
Reduction of ferric (2+) to ferrous (3+).

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10
Q

What are the mucosal factors?

A

(expression of iron transporters)
DMT-1 at mucosal surface
Ferroportin at serial surface

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11
Q

What are the systemic factors?

A

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.

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12
Q

What are the 3 compartments of iron status assessment?

A

Functional iron, Transport iron/supply to tissues, and storage iron.

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13
Q

What determines the functional iron compartment?

A

Haemoglobin concentration

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14
Q

How many iron binding sites does transferrin have?

A

2

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15
Q

Describe the role of transferrin.

A

Transports iron from donor tissues (macrophages, intestinal cells, hepatocytes) to tissues expressing transferrin receptors.

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16
Q

Name a tissue rich in transferrin receptors.

A

Erythroid marrow - bone marrow producing RBCs.

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17
Q

What is measured to determine iron supply? And how is this done?

A

transferrin saturation;
- serum iron/total iron binding capacity (to transferrin) x100%
- reflects the proportion of diferric transferrin
= % saturation of transferrin with iron.

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18
Q

Normal transferrin saturation?

A

20-50%

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19
Q

Name for iron bound to transferrin?

A

Holotransferrin

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20
Q

Unbound transferrin name?

A

Apotransferrin

21
Q

What is the storage compartment of iron status?

A

Storage iron:

Serum ferritin & tissue biopsy (rarely needed)

22
Q

What is ferritin?

A

A serum intracellular protein which stored up to 4000 ferric ions (Fe3+)

23
Q

What is an indirect measure of storage iron?

A

A tiny amount of serum ferritin reflects intracellular ferritin synthesis.

24
Q

Examples of when serum ferritin would be raised.

A

Infection, malignancy, liver injury - it acts as an acute phase protein

25
Q

Name 3 disorders of iron metabolism

A

iron deficiency
iron malutilisation aka ‘anaemia of chronic disease’
iron overload

26
Q

What are the consequences of negative iron balance?

A

In order of progression over time:

  1. exhaustion of iron stores
  2. iron deficient erythropoiesis
  3. microcytic anaemia
  4. epithelial changes
27
Q

What is iron deficient erythropoiesis?

A

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.

28
Q

What is microcytic anaemia?

A

Smaller and paler RBCs

29
Q

What epithelial changes are signs of low iron?

A

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.

30
Q

What does ‘hypo-chromic microcytic anaemia’ mean?

A

deficient haemoglobin synthesis

31
Q

What are the 2 types of hypo-chromic microcytic anaemias?

A

Haem deficiency

Globin deficiency

32
Q

What causes haem deficiency?

A

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.

33
Q

What causes global deficiency?

A

Thalassaemias - inherited blood disorders characterised by abnormal Hb production.

34
Q

What confirms iron deficiency?

A

The combination of anaemia and reduced storage iron.

decreased haemoglobin iron + low serum ferritin

35
Q

What can cause chronic blood loss?

A

Menorrhagia - excessive blood flow during periods.
Gastrointestinal; tumours, ulcers, NSAIDs, parasitic infection.
Haematuria - RBCs in urine

36
Q

Describe how occult blood loss could occur.

A

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.

37
Q

Is iron deficiency anaemia a sign, a symptom, or a diagnosis?

A

A symptom.
Iron replacement therapy may relieve this symptom without treating the underlying problem.
Investigations are essential to identify diagnosis.

38
Q

Describe normal haemoglobin recycling.

A

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

39
Q

What is inflammatory macrophage iron block?

A

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.

40
Q

What is the a primary cause of iron overload?

A

hereditary haemochromatosis

41
Q

What is a secondary cause of iron overload?

A

Transfusional

Iron loading anaemias

42
Q

What is the definition of a primary iron overload?

A

Long-term excess iron absorption with parenchymal, rather than macrophage, iron loading.

43
Q

What is hereditary haemochromatosis?

A

Decreased synthesis of hepcidin
Increased iron absorption
Results in gradual iron accumulation with risk of end-organ damage.

44
Q

Clinical features of hereditary haemochromatosis?

A 
Weakness/fatigue
Joint pains
Impotence
Arthritis 
Cirrhosis 
Diabetes
Cardiomyopathy

Presents usually middle age / later
Iron overload >5g

45
Q

What is the treatment option of hereditary haemochromatosis?

A

Weekly venesection - 450-500ml (200-250mg iron).

Initial aim is to exhaust iron stores (<20 micrograms/l).
Then keep ferritin <50 micrograms/litre

46
Q

Sources of iron-loading anaemias?

A

Repeated red cell transfusions, and excessive iron absorption related to over-active erythropoiesis.

47
Q

Disorders of iron-loading anaemias?

A

Massive infective erythropoiesis;
thalassaemia syndromes, sideroblastic anaemias.

Refractory hypoplastic anaemias;
red cell aplasia, myelodysplasia (MDS)

48
Q

Treatment of secondary iron overload?

A

Venesection not an option.

Iron chelating agents:
Desferrioxamine (SC or IV)
Deferiprone (oral)
Deferasirox (oral)

GI (6 decks)

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