Microcytic Anaemia & Iron Deficiency

Question 1

Where is haemoglobin synthesised

Answer 1

In the cytoplasm of red cell precursors

Question 2

What are the building blocks for Hb

Answer 2

Iron, porphyrin ring, globins

Question 3

Pathophysiology of microcytic anaemia

Answer 3

• lack of iron or porphyrin ring or globins
• unable to synthesis Hb
• as nucleus is intact, cells keep dividing
• signal to stop dividing (Hb accumulation) is delayed
• cell division occurs in excess
• smaller cells & little Hb
  (Microcytic) (Hypochromic)
• hypochromic, microcytic anaemia

Question 4

What does a hypochromic, microcytic anaemia indicate

Answer 4

Deficient haemoglobin synthesis:
a cytoplasmic defect

Question 5

Hypochromic microcytic anaemia aetiology

Answer 5

T - Thalassaemia
A - Anaemia of chronic disease
I - Iron deficiency (most common)
L - Lead poising
S - (congenital) sideroblastic anaemia

Globin deficiency - T
Haem iron deficiency - A & I
Haem porphyrin synthesis deficiency - L & S

Question 6

Iron functions & dangers

Answer 6

• required for oxygen transport (Hb & myglobin)
• required for electron transport
• potentially toxic - can generate free radicals (& so needs a chaperone molecule)

Question 7

What molecule does circulating iron bind to? Where does it travel to?

Answer 7

• Circulating iron is bound to TRANSFERRIN.
• It is transferred to the bone marrow MACROPHAGES that regulate iron uptake by transferrin receptor expression
• They ‘feed’ iron to RED CELL PRECURSORS

Question 8

Where is iron stored and in what form is it stored as?

Answer 8

Iron is stored as FERRITIN mainly in the LIVER

Question 9

What tests can be carried out to assess iron status

Answer 9

● Functional iron
−Haemoglobin

● Transported iron
−Serum iron
−Transferrin
−Transferrin saturation

● Storage iron
−Serum ferritin

Question 10

What is transferrin and what is its function?

Answer 10

A protein with two binding sites for iron that transports its from donor tissues to tissues expressing transferrin receptors

Donor tissues - intestinal cells, macrophages, hepatocytes
Tissue expressing transferrin receptors - above & ERYTHROID MARROW CELLS i.e. RBC PRECURSORS

Question 11

% saturation of transferrin with iron is a measure of iron supply. Name two causes of reduced saturation and one cause of increased saturation.

Answer 11

– reduced in iron deficiency
– reduced in anaemia of chronic disease
– increased in genetic haemachromatosis

NOTE - low transferrin does not mean iron deficiency

Question 12

What is ferritin and what is its function?

Answer 12

Intracellular protein that stores up to 4000 Fe3+ ions.
Mainly found in liver,
Tiny amounts in other tissues, macrophages & serum

Question 13

What does serum ferritin indicate

Answer 13

Serum ferritin indirectly reflects iron storage

Question 14

What two tests can confirm iron deficiency

Answer 14

• Microcytic anaemia (decreased functional iron) &
• Reduced storage iron (low serum ferritin)

NOT - Reduced transport iron (low serum transferrin)

Question 15

Iron deficiency aetiology

Answer 15

C - Coeliac disease (Fe absorbed in proximal small bowel)
A - Achlorhydria/ Anti-acids (Non-haem Fe absorption requires acidic env)
V - Vegetarians (lack of Fe in diet)
E - Excess blood/iron loss (GI bleed/ heavy menstrual bleed/ haematuria)

Question 16

Iron deficiency (microcytic anaemia) treatment

Answer 16

1) Treat cause (definitive)
- review diet
- review meds e.g. anti-coagulants, PPIs
- coeliac/ menorrhagia/ malignancy etc treatment

2) Iron supplements (symptomatic)

Question 17

Iron deficiency (microcytic anaemia) treatment monitoring & findings

Answer 17

What should you expect
- Rise in Hb concentration, reticulocytes & MCV (4-6 weeks)
- Rise in ferritin (once Hb returns to normal) (2-3 months)

If improvement does not occur
- check compliance
- check the ability of bone marrow to up regulate RBCs
- check if the cause of iron deficiency is still present

Question 18

Name some signs of chronic lack of iron/ longstanding iron deficiency anaemia

Answer 18

• Pruiritis
• Koilonychia & brittle nails
• Brittle hair
• Angular stomatitis

Question 19

What is sideroblastic anaemia

Answer 19

Excess iron build up in mitochondria (blue granules around nucleus) due to failure to incorporate iron in to haem.

Can be hereditary or acquired eg MDS, lead poisoning, alcohol excess

Question 20

Iron deficiency screening tests to work out aetiology

Answer 20

GI investigations (even without symptoms) => bleeding
Coeliac screen (all) => coeliac
Review drugs => PPIs, H2RA etc
Review diet => haem (meat) & non heam (veg.)

Question 21

Why can serum ferritin be raised despite iron deficiency

Answer 21

Ferritin is an acute phase protein and so can be raised in acute inflammation

Question 22

What molecule competes with iron absorption in the proximal small bowel

Answer 22

Calcium

Question 23

What is the difference between absolute and functional iron deficiency

Answer 23

Absolute - True lack of iron
Functional - Sufficient iron but can’t use it properly e.g. AOCD