Microscopic Hypochromic Anaemia - Based on Robbins

(Robbins, Cotran & Kumar - Pathologic Basis of Disease; Robbins & Kumar - Basic Pathology)

Definition

Hypochromic (microcytic) anaemia is a group of anaemias characterised by red cells that are smaller than normal (microcytic) and pale due to reduced haemoglobin content (hypochromic). The underlying defect in all cases is a failure of adequate haemoglobin synthesis, which can result from deficiency of iron, impaired haem synthesis, or defective globin chain production.

The most important and common cause is iron deficiency anaemia - the most common nutritional disorder in the world.

Causes of Hypochromic Microcytic Anaemia

Cause	Mechanism
Iron deficiency anaemia	Insufficient iron for haem synthesis
Anaemia of chronic inflammation	Hepcidin-mediated iron sequestration
Thalassaemias (alpha & beta)	Defective globin chain synthesis
Sideroblastic anaemia	Impaired haem synthesis despite adequate iron

Iron Deficiency Anaemia - The Prototype

Etiology

Iron deficiency arises from four broad causes:

Chronic blood loss - the most important cause in higher-resource countries. Sources include the gastrointestinal tract (peptic ulcers, colon cancer, hemorrhoids) and the female genital tract (menorrhagia, metrorrhagia).
Dietary lack / low bioavailability - most common in lower-resource countries where diets are predominantly vegetarian. Heme iron (from meat) is ~20% absorbable vs. only 1-2% for non-heme iron. Even in high-resource settings, infants fed exclusively on milk, the impoverished, and the elderly are at risk.
Increased demand - pregnancy and infancy are the key examples worldwide.
Malabsorption - celiac disease, gastritis, or post-gastrectomy states.

Stages of Iron Depletion

Iron deficiency develops insidiously through sequential stages:

Depletion of iron stores - serum ferritin falls; stainable iron disappears from bone marrow macrophages on Prussian blue stain. No anaemia yet.
Iron-deficient erythropoiesis - serum iron falls; serum transferrin (total iron-binding capacity, TIBC) rises; transferrin saturation drops below 15%.
Iron deficiency anaemia - haemoglobin synthesis is inadequate; microcytic, hypochromic anaemia appears on peripheral smear.

Morphology (Microscopic Features)

Peripheral blood smear - the hallmark findings are:

Microcytosis - red cells are smaller than normal (MCV < 80 fL)
Hypochromia - the zone of central pallor is enlarged; in established deficiency, haemoglobin is confined to a narrow peripheral rim (normal central pallor = ~1/3 of cell diameter; in IDA the pallor is > 1/3)
Poikilocytosis - "pencil cells" (small, elongated red cells) are characteristically seen
Anisocytosis - variation in red cell size

Iron deficiency anaemia - peripheral blood smear showing hypochromic microcytic red cells with a narrow rim of peripheral haemoglobin. A neutrophil and a few normally haemoglobinised cells (from transfusion) are visible for contrast.

Fig. 14.22 - Iron deficiency anaemia. Peripheral blood smear showing hypochromic microcytic red cells with a narrow rim of peripheral haemoglobin. (Robbins, Cotran & Kumar - Pathologic Basis of Disease)

Bone marrow:

Mild to moderate increase in erythroid progenitors (hyperplasia)
Absent stainable iron in macrophages on Prussian blue stain - a diagnostically significant finding

Laboratory Findings

Parameter	Finding in IDA
Haemoglobin / Haematocrit	Decreased
MCV, MCH, MCHC	Decreased (microcytic, hypochromic)
Serum iron	Low
Serum ferritin	Low (< 12 µg/L)
Total iron-binding capacity (TIBC)	Elevated
Transferrin saturation	Reduced (< 15%)
Serum hepcidin	Low (iron deficiency inhibits hepcidin synthesis)
Reticulocyte count	Low or normal (blunted marrow response)
Platelet count	Often elevated (for unclear reasons)
Erythropoietin	Elevated, but marrow response is blunted

Clinical Features

In most cases, iron deficiency anaemia is mild and asymptomatic. When symptomatic:

General: weakness, listlessness, pallor, fatigue
Nails: koilonychia (spoon-shaped nails), thinning, flattening
Neurological/behavioural: pica (craving for non-foodstuffs such as clay, dirt, ice - the latter called pagophagia)
Tongue/mucosa: atrophic glossitis, alopecia, atrophic changes in gastric mucosa
Rare triad - Plummer-Vinson syndrome: microcytic hypochromic anaemia + atrophic glossitis + oesophageal webs

Depletion of iron-containing enzymes (catalase, cytochromes) throughout the body accounts for many of these non-haematologic manifestations.

Key Concept

"In well-nourished persons, microcytic hypochromic anaemia is not a disease but rather a symptom of another underlying disorder - e.g., colon cancer leading to chronic blood loss." - Robbins & Kumar, Basic Pathology

This principle is clinically critical: every adult with iron deficiency anaemia must be investigated for an occult source of bleeding.

Anaemia of Chronic Inflammation (Differential)

This condition resembles IDA on the smear (it can be normocytic or mildly hypochromic/microcytic) but has a distinct mechanism. IL-6 and other inflammatory mediators drive hepatic hepcidin overproduction, which:

Inhibits ferroportin in macrophages - trapping iron in storage
Starves erythroid precursors of iron despite high total body iron stores
Also directly suppresses erythropoietin production

The key laboratory distinction: ferritin is elevated (an acute-phase reactant) and TIBC is low - the opposite of IDA.

Sources: Robbins, Cotran & Kumar - Pathologic Basis of Disease (pp. 612-615) | Robbins & Kumar - Basic Pathology (p. 393-394)

Prepare a flashcard for iron Deficiency anaemia according to the text above

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Here is your flashcard for Iron Deficiency Anaemia based on the Robbins content:

The card covers all the key points from the earlier note:

Causes (4 categories)
Stages of iron depletion (stores → erythropoiesis → anaemia)
Morphology - peripheral smear and bone marrow findings
Lab findings with the arrows for quick recall
Clinical features including Plummer-Vinson syndrome
IDA vs Anaemia of Chronic Inflammation comparison
The Robbins key pearl at the bottom

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