Lecture 4: Iron

deficiency

Learning
objectives

Discuss the absorption, transport and

storage of iron.
Outline the diagnosis of iron
deficiency.
Describe the pathophysiology of iron
deficiency and how this relates to the
clinical and laboratory data.
Outline the potential causes and
therefore treatment of iron deficiency

Hypochromic
anaemia

Hypochromic red blood cells

Paler than normal large central area of pallor

MCV and MCH decreased

Microcytic red blood cells

Smaller than normal assess this by

comparing to normal neutrophil or lymphocyte

Differential diagnosis
Iron deficiency
Thalassaemia

Hypochromic and
microcytic

Iron deficiency

Commonest cause of anaemia worldwide

500 million cases

Defect in Hb synthesis

Microcytic, hypochromic

reduced MCV, MCH and MCHC

Fe
Sickle cell

Daily intake

Diet contains
10-15mg iron
Only 5-10%
normally
absorbed
Need 0.5 3.0 mg/day
depending on
situation

Total
mg/day
Adult male

0.51.0

Postmenopausal female

0.5-1.0

Menstruating female

1.0-2.0

Pregnant female

1.5-3.0

Children

1.1

Female (12-15)

1.6-2.6

Transferrin - Iron
transport around
the
body
Transferrin
binds iron (2 atoms)

Delivers iron to cells possessing transferrin receptors

Transferrin recycled

Most of the iron comes from recycling iron from

rbcs

eg erythroblasts

Rbcs broken down by macrophages of

reticuloendothelial system

Small amount from dietary absorption

Iron storage

Ferritin and haemosiderin

Ferritin
Water-soluble protein-iron
complex
465kDa
Outer shell - apoferritin
22 subunits

Approx. 20% iron

 Inner core - ironphosphate-hydroxide

One apoferritin binds
4000-5000 iron atoms

Haemosiderin
Insoluble protein-iron
storage complex
Varies in composition
Approx. 37% iron
Stain using Perls reaction
(Prussian blue)

Biochemistry

Serum iron/transferrin
receptor/ferritin/haemosiderin

Gives indication of overall body iron status

Reference ranges given in first lecture and
practical schedule
Thalassaemia and iron deficiency are both
hypochromic and microcytic this
biochemistry allows them to be
differentiated

Regulation of
transferrin
Ferritin and transferrin
receptor
andreceptor
mRNA have iron response elements
ferritin
(IRE)

Bind iron regulatory protein (IRP)

when iron stores are low

Iron deficiency leads to increased

binding of IRP to IRE (Iron overload
decreases binding.)

Ferritin

IRE 5 end of mRNA

Binding of IRP blocks translation ferritin not

synthesized

Transferrin receptor

IRE 3 end of mRNA

Binding of IRP stabilizes mRNA so more

transferrin receptor can be made

Scavenges all available iron!!

 Iron deficiency
Reduced ferritin and increased
transferrin receptor

Iron overload
increased ferritin and decreased
transferrin receptor

Ferric v ferrous
iron

In ferritin and hemosiderin - ferric

(3+)
Vitamin C aids mobilization with
conversion to ferrous (2+) form
Ferrous converted back to ferric
by caeruloplasmin
Cu2+ containing enzyme
now Fe2+ binds to plasma transferrin

Other stores of
iron
Myoglobin in muscles
Iron containing enzymes
Haem enzymes cytochromes,
catalase

Absorption of iron
Iron in food
ferric hydroxides
ferric-protein complexes or
haem-protein complexes

Absorption better for haem iron

in ferrous state
Absorption through the
duodenum

Iron deficiency
Stages
Iron depletion
Iron deficient erythropoiesis
Iron deficiency anaemia
HYPOCHROMIC MICROCYTIC
(MCH MCHC MCV all ) Why?

Pathophysiology**

Low HGB, MCHC and MCH - hypochromasia

Fe is needed for production of haemoglobin
Leads to hypochromic cells

Low MCV - microcytosis

The number of cell divisions during
erythropoiesis is determined by the level of
erythroblast haemoglobinization
Lack of haemoglobin leads to more mitotic
divisions
This leads to smaller cells - microcytosis

Clinical features

Not present until final stages

General signs of anaemia plus

Koilonychia (why?)

Angular cheilosis (why?)

Pica

Children - irritability, reduced

psychomotor development

Lab Diagnosis

Red cell indices

Platelet count
raised if associated with haemorrhage

Morphology
microcytic hypochromic
few target cells
pencil and teardrop cells - poikilocytosis

Serum iron falls, TIBC rises

Investigation of a
microcytic
hypochromic
What is the differential diagnosis?
?Thalassaemia hypochromic, microcytic
anaemia and its
What is the cause of the iron
treatment
deficiency?

Treatment for iron

deficiency
First decide what is the
cause?
Oral iron ferrous sulphate
67mg of iron / 200mg anhydrous
tablet
Side effects nausea, abdominal
pain

Iron deficient patient

before and after iron
sulphate treatment

Fig. 3.7 and 3.8

Hoffbrand

Iron overload
The body tightly regulates iron
uptake - there is no method for
disposing of excess iron
Problem if excessive absorption
of many blood transfusions
Iron builds up in tissues/organs
- damage

Transfusion Iron
overload
Common in thalassaemic
patients

Summary
Iron metabolism in the body transferrin, ferritin and
haemosiderin
Iron deficiency - diagnosis
and causes

 Why are the cells

hypochromic?
Why are the cells microcytic?
Why do the patients FBCs
change?
Why do the patients suffer
from the symptoms they have?
Iron overload