Iron Deficiency Anaemia

Iron Metabolism

The main source of Iron is through dietary intake. Iron can be found in many food sources, such as red meats, and cereal. Iron is an important component in synthesizing RBCs. In a normal adult, 15-20mg of iron is needed daily. Before knowing what causes Iron Deficiency Anaemia (IDA), we should know the metabolism of iron in our body.

The above shown is a Haem molecule, and in the middle of what we call a Haem pocket, is an Iron atom. So with decreased iron intake, there will be slower and lesser haemoglobin synthesis in our blood.

Iron, in the ferrous form (Fe²⁺), is being absorbed into the plasma in the duodenum and upper jejunum location. Fe²⁺ is carried across the enterocyte microvilli by active transport, facilitated by Divalent metal transporter (DMT-1). This process, which involves releasing Fe²⁺ from the enterocyte into the plasma, is regulated by ferroportin.

Fe²⁺ has to be reduced to Fe³⁺ (Ferric form) before binding to apoferritin. After apoferritin binds to Fe³⁺, it forms a water soluble protein-iron complex, called Ferritin. Ferritin is then transported by Transferrin to the bone marrow for erythropoiesis.

In the bone marrow…
Erythroid progenitors expresses transferrin receptors (TfR), which recognizes and binds to ferritin. These cells then utilizes the iron in the Ferritin to synthesize haemoglobin, during erythrocyte maturation. In the Bone marrow, Macrophages serves as an iron source for the Erythroid progenitors for Haem synthesis.

In IDA

There are 3 stages of IDA progression.

In stage 1:

There is a progressive loss of Iron Storage, but there is still enough storage iron to maintain Transport & Functional iron. Therefore, erythrocytes development are still normal at this stage. However, stage 1 IDA is evident with low levels of ferritin.

In stage 2:

At this stage, the storage iron is already low, so RBC production relies on transport iron. Anaemia may not be present at this stage, but there will be progressive loss of Hb. So Hb may be within the reference range, but stage 2 IDA will be evident with low levels of ferritin and serum iron.

In stage 3:

All iron sources (storage & transport iron) will be depleted, and patients would be suffering from anaemia. As shown above, iron is needed for RBC production and Hb synthesis, therefore, in IDA, there will be decreased Hb and affected RBC production. When we view the Peripheral Blood Film (PBF) of these patients, their RBCs will appear hypochromic and microcytic.

Laboratory and clinical diagnosis

In the clinical situation when doctors observe for any clinical presentations, they might find patients to be having Glossitis, angular stomatitis, koilonychia.

Glossitis: Inflammation of the tongue, which causes the tongue to swell, so it will have a shiny appearance.

Angular stomatitis: Inflammation at the corners of the mouth.

Koilonychia: Spoon shaped fingernail

So upon such observations, the doctor might do a blood test and order for a Full Blood Count (FBC), and PBF. FBC will show:
- Low Hb (for patients at the late stage)
- Low MCV (microcytic cells)
- Low MCHC
- Low MCH (hypochromic cells)
- Low Haematocrit (decreased RBC production)

As only RBCs are affected, the White Blood Cells and Platelets in this case will be normal, unless other complications occurs.

In their PBF, we can see anisocytosis (RBCs of various sizes), poikilocytosis (red blood cells of various shapes), or we can observe elliptocytosis (pencil cells).
To remember these 3 observations, I remember them as APE.

Discrepancies

There are certain cases which can falsely elevate the ferritin levels in IDA:

-        -  Liver dysfunction: Hepatocytes are damaged in level disease, which releases the ferritin into plasma.

-        -  Increased haem turnover: Haemolysis and trauma will also release ferritin.

-        -  Inflammatory lesions: Includes malignancy, infections and inflammation. The mechanism to why inflammation causes ferritin elevations are unclear, however, serum ferritin can be used as an inflammatory marker.

Treatment

There are 2 kinds of treatment for IDA:

I)                   Oral Iron Therapy

II)                Intra-muscular parental iron