Macrocytic and Normochromic Red Blood Cell Disorders Flashcards
What is macrocytosis?
Macrocytosis is a condition characterized by red blood cells (RBCs) that are larger than normal. This is typically identified by a mean corpuscular volume (MCV) greater than 100 femtoliters (fL).
How does impaired DNA synthesis contribute to macrocytosis?
Macrocytosis often arises due to impaired DNA synthesis. While DNA synthesis is impaired, RNA synthesis is typically unaffected, leading to an accumulation of cytoplasmic components in slowly dividing cells. This imbalance results in larger-than-normal red blood cells.
How are macrocytic anaemias classified?
Macrocytic anaemia is classified based on the presence of megaloblasts in the bone marrow, giving us two categories:
(1) Megaloblastic Macrocytic Anaemia
(2) Non-Megaloblastic Macrocytic Anaemia
What are key features and characteristics of megaloblasts?
🩸 Both the cell and nuclear sizes are significantly larger than normal red blood cell precursors.
🩸 The amount of cytoplasm is increased and appears deeply basophilic (royal blue) due to the high RNA content.
🩸 The nuclear chromatin has a characteristic open, sieve-like, or stippled appearance, indicating immature and abnormal chromatin condensation.
🩸 There is a lack of synchronization between nuclear and cytoplasmic maturation. While the cytoplasm matures normally, the nucleus remains immature, leading to nuclear-cytoplasmic asynchrony.
🩸 There is increased presence of promegaloblasts and early megaloblasts in the bone marrow, indicating a maturation arrest.
🩸 There is an increase in abnormal mitotic figures, reflecting defective cell division processes.
[Image 1] [Image 2] [Image 3] [Image 4] [Image 5]
Discuss causes of megaloblastic anaemia.
(a) Vitamin B12 Deficiency
This may be as a result of dietary deficiency, absorption issues, certain medications and bariatric surgery.
(b) Folate Deficiency
This may be as a result of dietary deficiency, alcohol misuse and increased demand.
While Folate and Vitamin B12 are essential for DNA synthesis and repair in all cells, why does their deficiency seem to be exemplified in red blood cell formation as opposed to the formation of other cells?
This is because red blood cells are produced at a high rate in the bone marrow, with millions of new cells being regenerated every second to replace the old ones [high turnover rate].
What are non-megaloblastic anaemias?
Non-megaloblastic macrocytic anaemias are a group of anaemias characterized by the presence of macrocytes without megaloblastic changes seen in the bone marrow.
Briefly discuss causes of non-megaloblastic anaemias.
(1) Liver disease: Conditions like cirrhosis or hepatitis can lead to macrocytosis due to altered lipid metabolism affecting red blood cell membranes.
(2) Alcoholism: Chronic alcohol use can directly affect bone marrow function and red blood cell production, leading to macrocytosis.
(3) Hypothyroidism: An underactive thyroid gland can slow down metabolism, leading to larger red blood cells.
(4) Hypoparathyroidism: This condition can also contribute to macrocytosis due to its effects on calcium and bone metabolism.
(5) Protein-Energy Malnutrition, e.g. Kwashiorkor
(6) Reticulocytosis: An increased number of reticulocytes (immature red blood cells) can cause macrocytosis, often seen in response to anaemia or blood loss.
(7) Red Cell Aplasia and Myelodysplasia: These bone marrow disorders can lead to production of abnormally large red blood cells.
(8) Multiple myeloma: This type of blood cancer can affect the bone marrow and lead to macrocytosis.
Further notes:
Multiple myeloma is a type of blood cancer that affects plasma cells in the bone marrow. These cancerous plasma cells produce abnormal antibodies, leading to various complications such as bone pain, kidney dysfunction, anaemia, and increased susceptibility to infections.
What are normochromic normocytic red cell disorders?
Normochromic normocytic red cell disorders are a type of anaemias where the red blood cells (RBCs) are of normal size (normocytic) and have a normal concentration of hemoglobin (normochromic), but their overall number is reduced.
Briefly discuss three broad causes of normocytic normochromic changes/disorders.
(1) Increase in pro-inflammatory cytokines and hence hepcidin levels
🩸 Chronic diseases and infections often lead to increased levels of pro-inflammatory cytokines (e.g. IL-6, TNF-α). These cytokines can inhibit erythropoiesis and reduce the lifespan of existing RBCs.
🩸 Inflammatory cytokines also increase hepcidin levels, which in turn reduces iron absorption from the gut and traps iron in macrophages. This leads to functional iron deficiency, impairing RBC production.
(2) Inappropriate Erythropoietin (EPO) Levels and Decreased Response to EPO
🩸 Erythropoietin is a hormone produced by the kidneys that stimulates RBC production in the bone marrow. In chronic kidney disease or other conditions, EPO production can be insufficient.
🩸 Even when EPO levels are adequate, chronic diseases can cause a decreased response to EPO. This resistance can be due to the effects of inflammatory cytokines or other factors that interfere with the bone marrow’s ability to respond to EPO.
(3) Decreased RBC survival
🩸 Chronic diseases and systemic conditions can lead to a shortened lifespan of RBCs. This can be due to increased destruction of RBCs by the immune system or other mechanisms.
🩸 Conditions like myelodysplastic syndromes or bone marrow infilatration by cancer can suppress the bone marrow’s ability to produce new RBCs, leading to anaemia.
