Microcytic Red Blood Cell Disorders

Question 1

Define microcytosis.

Answer 1

Microcytosis is a condition where red blood cells are smaller than normal.
An MCV of less than 80 femtoliters (fL) in adults is indicative of microcytosis.

Question 2

What is the normal range for Mean Corpuscular Volume in adults?

Answer 2

80 - 100 femtoliters

Question 3

What is the most common cause of microcytic disorders?

Answer 3

iron deficiency

Question 4

What are the hallmark features of microcytic anaemias?

Answer 4

microcytosis, hypochromia

Question 5

Outline causes of iron deficiency.

Answer 5

🩸 poor dietary intake
🩸 chronic blood loss (e.g. gastrointestinal bleeding, heavy menstrual periods)
🩸 increased demand e.g. during pregnancy
🩸 malabsorption e.g. celiac disease

Question 6

Microcytic anaemias can be classified into three categories. What are these three categories?

Answer 6

(1) Disorders of iron metabolism
(2) Disorders of globin synthesis
(3) Disorders of porphyrin and heme synthesis

Question 7

List disorders of iron metabolism as causes of microcytic anaemias.

Answer 7

(1) Iron deficiency
(2) Anaemia of chronic disease
(3) Atransferrinemia
(4) Rare familial microcytic anaemias

Question 8

Explain how iron deficiency can lead to microcytic anaemia.

Answer 8

With iron deficiency, there will be reduced haemoglobin production. To compensate for the lack of haemoglobin, the bone marrow produces smaller red blood cells, known as microcytes. These cells have a reduced capacity to carry oxygen.

Question 9

Explain how chronic disease can result in microcytic anaemia.

Answer 9

Chronic diseases such as infections, autoimmune disorders and cancers trigger an inflammatory response in the body. This response involves the release of cytokines. One of the cytokines, interleukin-6 (IL-6), stimulates the liver to produce hepcidin. Hepcidin will inhibit the release of iron from macrophages and the absorption of iron from the intestine. This leads to a decrease in the amount of iron available for erythropoiesis.

Question 10

Discuss atransferrinemia as a cause of microcytosis.

Answer 10

🩸 Atransferrinemia is an extremely rare genetic disorder. It is caused by mutations in the transferrin (TF) gene. It is inherited in an autosomal recessive pattern.
🩸 Due to the lack of transferrin, iron cannot be properly transported to the bone marrow for red blood cell production, leading to microcytic anaemia.

Question 11

List four disorders of globin synthesis and give a brief description of each.

Answer 11

🩸 Thalassaemias: These are genetic disorders resulting in reduced or absent production of one of the globin chains (alpha or beta) that make up haemoglobin, leading to microcytic anaemia.

🩸 Unstable haemoglobin diseases: Conditions where mutations cause hemoglobin to be unstable, leading to hemolysis (breakdown of red blood cells) and anaemia.

🩸 HbE disease, HbE trait: HbE is a variant of hemoglobin common in Southeast Asia. HbE disease occurs when an individual inherits two HbE genes, leading to mild hemolytic anaemia. HbE trait (one HbE gene) usually causes no symptoms.

🩸 HbC disease: Caused by a mutation in the beta globin gene, leading to the production of hemoglobin C. Individuals with HbC disease (two HbC genes) may have mild hemolytic anemia and splenomegaly. HbC train (one HbC gene) typically causes no symptoms.

Question 12

What are two main types of thalassemia?

Answer 12

(a) Alpha thalassemia: Caused by mutations in the genes responsible for producing the alpha globin chains of haemoglobin.

(b) Beta thalassemia: Caused by mutations in the genes responsible for producing the beta globin chains of haemoglobin.

Further notes:
Carriers of a single defective gene (thalassemia trait) may have mild microcytic anemia but usually do not experience significant health problems.

Question 13

Sideroblastic anaemias are a group of disorders resulting from defective heme sythesis. List causes of sideroblastic anaemias.

Answer 13

(a) Defective ALA synthesis as a result of Vitamin B6 deficiency/abnormal metabolism. Certain medications [e.g. isoniazid and chloramphenicol] and toxins can inhibit ALA synthase or interfere with its function.

(b) Lead poisoning: Lead interfers with multiple enzymes in the heme synthesis pathway, including ALA dehydratase and ferrochelatase, leading to the accumulation of ALA and other precursors.

(c) Deficiency of heme synthetase/ferrochelatase

(d) Deficiency of Coproporphyrinogen Oxidase

(e) Unknown causes

Question 14

Sideroblastic anaemias are characterized by ringed sideroblasts in bone marrow. What are “ringed sideroblasts”?

Answer 14

Ringed sideroblasts are erythroblasts (immature red blood cells) with iron-loaded mitochondria arranged in a ring around the nucleus.

[The iron deposition is abnormal and indicates a defect in heme synthesis, leading to ineffective erythropoiesis.]

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Question 15

List tests used to detect and define microcytic anemia.

Answer 15

🩸 Complete Blood Count (CBC)
🩸 Peripheral Blood Smear

Question 16

List tests to distinguish between the major disorders of microcytic anemia.

Answer 16

🩸 Serum ferritin: Measures iron stored in the body. Low levels suggest iron deficiency anemia.
🩸 Serum iron: Measures the amount of circulating iron in the blood.
🩸 Total Iron-Binding Capacity: Low levels suggest iron deficiency anemia.
🩸 Transferrin saturation: Calculated from serum iron and TIBC, it reflects the percentage of transferrin that is saturated with iron. Low transferrin saturation suggests iron deficiency.
🩸 Serum transferrin receptors: Helps distinguish between iron deficiency anemia and anemia of chronic disease. Elevated sTfR levels are typically seen in iron deficiency anemia.
🩸 Hemoglobin electrophoresis: Identifies abnormal hemoglobin variants, which is crucial for diagnosing thalassemia and other hemoglobinopathies.
🩸 Lead Levels: Particularly in cases where lead poisoning is suspected as a cause of microcytic anemia.