Definition of Anaemia, Causes and Classification of Anaemia
Definition of Anaemia
- Anaemia is defined as a decrease in the number of circulating red blood cells or a decrease in haemoglobin level in relation to age and gender.
Normal haemoglobin levels differ from person to person
- 14-16 mg/dl (140-160g/l) in males
- 12-14mg/dl (120-140/l) in females
Anaemia Causes and Classification
- Increased red cell destruction (haemolysis)
- Excessive bleeding (haemorrhage)
- Reduced red cell production (aplasia)
Note: The aforementioned causes are used to classify anaemia.
- Normal red cells have a lifespan of about 120 days before being taken by the reticuloendothelial system and degraded.
- Damaged red cells are removed from the circulation by the mononuclear phagocyte system.
- Red cell destruction occurs primarily within the phagocytic cells of the spleen and liver.
- Anaemias associated with accelerated red cell destruction are known as haemolytic anaemias.
All forms of haemolytic anaemia share certain characteristics, include:
- An increased rate of red cell destruction.
- Compensatory increase in erythropoiesis, resulting in reticulocytosis.
- Retention of red cell destruction products by the body (including iron)
The Cause of Haemolytic Anaemia
- The most common causes of these are antibodies, which have the ability to agglutinate red cells in vitro either directly or after the addition of anti-human globulin (the Coombs test).
The cells are coated with insufficient IgG to render them highly sensitive to destruction in the spleen and liver, resulting in haemolytic anaemia as seen in:
- Rhesus incompatibility
- Drug sensitisation
- Drugs can cause haemolysis by induction of antibodies as explained above or
- damage to cell membrane by toxins and drug interference with enzyme processes in the cell
- Cold agglutinin antibodies, which are seen in certain infections, usually haemolyze red cells in the circulation due to the action of bound activated complement. These antibodies appear during the recovery phase of certain infections.
- Malaria is a common cause of anaemia in our environment due to direct destruction of red cells by parasites or immune responses (humoral antibodies and cellular antibodies).
- Direct damage to the red cell membrane caused by a toxin produced by microorganisms, their byproducts, or when they die.
- Intrinsic red cell abnormality (haemoglobinopathies) – regardless of the defect, there is reduced membrane stability, which leads to membrane fragment loss during shear stress exposure in the circulation. Here are some examples of these conditions:
- Sickle cell anaemia (common in our environment)
- In hereditary spherocytosis, a defect in the red cell membrane causes the cell to become spheroid, less deformable, and vulnerable to splenic sequestration.
- Glucose-6 Phosphate Dehydrogenase Deficiency (G-6-PD deficiency)
- Because iron is easily conserved and recycled, red cell regeneration can keep up with hemolysis.
- As a result, these anemias are almost always associated with a significant erythroid hyperplasia within the marrow and an increased reticulocyte count in peripheral blood.
Haemolysis, regardless of cause, results in:
- When the haeme pigment is converted rapidly to bilirubin, there is an increase in unconjugated bilirubin in the blood (hyperbilirubinaemia) and jaundice.
- Hemolytic jaundice is the type of jaundice that caused by hemolytic anaemia
- In most cases of haemolytic anaemia, the mononuclear phagocyte system undergoes reactive hyperplasia, resulting in splenomegaly.
- In chronic haemolytic anaemia, changes in iron metabolism lead to increased iron absorption from the gut.
- Because the pathways for excreting excess iron are limited, this frequently causes iron to accumulate, resulting in systemic haemosiderosis or, in severe cases, secondary haemochromatosis.
Anaemia due to hemorrhage
- In the case of acute blood loss, the immediate threat to the patient is hypovolaemia (shock) rather than anaemia.
- If the patient survives, haemodilution begins immediately and reaches its full effect within 2 to 3 days, revealing the extent of red cell loss.
- The anaemia is normocytic and normochromic.
- A rise in erythropoietin levels, which stimulates increased red cell production within several days, aids recovery from blood loss anaemia.
- The onset of the marrow response is marked by reticulocytosis.
- Chronic blood loss, such as hookworm infestation, depletes iron stores gradually.
- Iron is required for haemoglobin synthesis and effective erythropoiesis, and its deficiency results in chronic anaemia of underproduction.
Anaemia due to Decreased Red Cell Production
- This category includes anaemia caused by a lack of dietary iron, folic acid, and vitamin B12.
Other disorders that suppress erythropoiesis include:
- Those associated with bone marrow failure (aplastic anaemia)
- The replacement of bone marrow by tumor or inflammatory cells (myelodysplastic anaemia)
Anaemia Caused by Nutritional Deficiencies and Marrow Suppression
- Iron deficiency anaemia
- Folate deficiency anaemia
- Vitamin B12 (cobalamin) deficiency anaemia: pernicious anaemia
- Aplastic anemia
Iron Deficiency Anaemia
- Iron is required for haemoglobin synthesis; approximately 80% of functional body iron is found in haemoglobin, with the remainder found in myoglobin and iron-containing enzymes.
- The amount of iron stored in the liver, spleen, bone marrow, and skeletal muscle is 20%.
- Because free iron is extremely toxic, the storage iron pool is tightly bound to ferritin (protein-iron complex) or haemosiderin.
- Iron is transported in plasma by transferring, an iron-binding glycoprotein that is synthesized in the liver.
- Total body iron is approximately 3-6gm, with an average daily input of 1mg/day and a daily output (loss) of approximately 1mg via skin desquamation and other secretions. 0.5 to 1mg of extra loss occurs in females during menstrual flow.
Iron deficiency anaemia develops when this balance is disrupted in any of the following ways:
- Increased output as a result of acute or chronic blood loss.
- Reduced input as a result of a poor diet or malabsorption.
- Increased body demand, such as during pregnancy or rapid growth in childhood.
- Iron deficiency develops slowly, regardless of the cause.
- Iron deficiency, for whatever reason, causes hypochromic (less haemoglobin) microcytic (small cells) anaemia.
- The bone marrow is hypercellular, with many small, poorly hemoglobinized normoblasts and no stainable iron.
A lack of essential iron-containing enzymes in cells throughout the body can result in other changes such as:
- Tongue and gastric mucosal atrophies, which can lead to malabsorption
- These changes are seen in people who have severe and long-term iron deficiency.
Folate deficiency anaemia
- A folic acid (tetrahydrofolate) derivative serves as an intermediary in the transfer of one carbon unit in a variety of body reactions. Purine synthesis, homocysteine to methionine conversion (also requires vitamin B12), and deoxythymidylate monophosphate synthesis are the most important metabolic processes that rely on one-carbon transfers.
- DNA synthesis necessitates these reactions. Megaloblastic anaemia is caused by the inhibition of DNA synthesis.
- Those with a poor diet (the economically deprived and the elderly) or increased metabolic needs are at a higher risk of clinically significant folate deficiency (pregnant women and patients with chronic haemolytic anaemia).
- Folate is found in nearly all foods, but it is easily destroyed by cooking for 10 to 15 minutes.
As a result, fresh uncooked vegetables and fruits are the best sources of folate.
- Phenytoin and a few other drugs inhibit folate absorption, whereas methotrexate inhibits folate metabolism.
- Following absorption, folate is transported in the blood and undergoes a series of metabolisms before being involved in the synthesis of purines, the building blocks of DNA, and its deficiency accounts for the insufficient DNA synthesis seen in megaloblastic anaemia.
Vitamin B12 (cobalamin) deficiency anaemia: pernicious anaemia
- Vitamin B12 deficiency, also known as cobalamin deficiency, causes a megaloblastic macrocytic anaemia similar to that caused by folate deficiency; however, vitamin B12 deficiency can also cause a demyelinating disorder involving the peripheral nerves and the spinal cord.
- Pernicious anaemia refers to vitamin B12 deficiency caused by insufficient gastric production or defective intrinsic factor function.
- The intrinsic factor is essential for vitamin B12 absorption.
- Long-term malabsorption is the primary cause of vitamin B12 deficiency anaemia (Pernicious anaemia).
- It’s a condition in which multipotent myeloid stem cells are suppressed, resulting in bone marrow failure.
Aplastic anaemia etiology and pathogenesis:
- Aplastic anaemia is idiopathic in more than half of cases.
- In some cases, this is due to activated T-cells suppressing stem cell function.
- Drugs, infectious agents, or other unidentified environmental insults first antigenically alter stem cells.
- This causes a cellular immune response in which activated T cells produce cytokines like interferon- and TFN, which inhibit normal stem cell growth and development.