Anemia is generally defined as a reduction in the number or volume of circulating red blood cells (erythrocytes) or an alteration in hemoglobin.
Technically, anemia is not a disease but a symptom of any number of disorders. There are over 400 types of anemia, but many of them are rare. Even more startling is the fact that, presently, more than half of the world’s population will experience some form of anemia in their lifetime.
Generally, the origin of anemia is classified as either nutritional or non-nutritional.
Anemias of a nutritional origin are those that stem from a deficiency of some nutrient, mainly iron, vitamin B12, or folic acid (B9); but they can also result from a deficiency of other nutrients, including vitamins B2 (riboflavin), B6 (pyridoxine), C, A, D, E, and K; as well as zinc, copper, calcium, and protein. The lack of certain enzymes can also cause anemia.
Non-nutritional causes are those that produce a decreased development of the red blood cell (RBC) precursors, decreased erythropoiesis (erythrocyte formation), or an increase in the destruction of RBCs.
Anemia is frequently associated with scurvy and may be indicative of a folic acid deficiency (macrocytic) or an iron deficiency (hypochromic). Nevertheless, patients have responded well with just the addition of vitamin C alone, suggesting that there may be a role that ascorbates plays in the maintenance of normal pools of reduced folates.
However, there is no real evidence to suggest that folate is ascorbate dependent. In the case of iron deficiency, though, it is known that adding vitamin C will increase iron absorption.
Anemias can be classified using two basic approaches:
- etiology (pathophysiology): the causes of erythrocyte and hemoglobin depletion
- morphology: the characteristic changes in the erythrocytes red blood cells (RBCs), size, shape, and color
An etiologic classification is based on the various conditions that can result from any of the physiologic changes and helps determine direction for planning care. A morphologic classification provides an orderly method for ruling out certain diagnoses when establishing a cause for a particular anemia.
Such morphologic changes in the red blood cell are described in this manner:
- Cell size: (Terms that refer to cellular size end with “cytic”.)normocytes (normal)microcytes (smaller than normal)macrocytes (larger than normal)anisocytes (various sizes)
- Cell shape:poikilocytes (irregularly-shaped cells)spherocytes (globular cells)drepanocytes (sickle cells)
- Cell color: (generally refers to the staining characteristics which reflects the hemoglobin concentration. Terms that describe hemoglobin content end with “chromic”.)normochromic (sufficient or normal amounts of hemoglobin)hyperchromic (containing an unusually high concentration of hemoglobin in its cytoplasm)hypochromic (containing an abnormally low concentration of hemoglobin)
These changes produce the following categories of anemias:
- Macrocytic-normochromic anemias (pernicious and folate-deficiency)
- Microcytic-hypochromic anemias (iron-deficiency, sideroblastic, thalassemia)
- Normocytic-normochromic anemias (aplastic, posthemorrhagic, hemolytic, chronic disease, sickle cell)
Macrocytic-normochromic anemia, also known as megaloblastic anemia, produces large, abnormally shaped erythrocytes but normal hemoglobin concentrations. The unusually large stem cells (megaloblasts) in the bone marrow mature into abnormally large erythrocytes (macrocytes) in the circulation.
Megaloblastic stem cells are larger at all maturational stages than normal stem cells (normoblasts). In addition, the nucleus of the megaloblast is unusually small in relation to the size of the cell. As the cell matures and begins to synthesize hemoglobin, chromatin in the nucleus fails to clump normally, although the hemoglobin content remains normal.
Defective DNA synthesis, caused by deficiencies of vitamin B12 or folic acid (B9), produces a pattern of ineffective erythropoiesis (cell formation), causing premature cell death with reduced numbers of mature erythrocytes.
It is unknown why such a deficiency would cause this outcome, but suggested mechanisms include a delay in nuclear maturation and an imbalance in the normal distribution of RNA and DNA. Nuclear functions or DNA replication and cell division are blocked or delayed. However, RNA and protein synthesis, both cytoplasmic functions proceed normally. The imbalance in the RNA/DNA ratio causes derangement of cell growth.
Microcytic-hypochromic anemia produces small, abnormally small erythrocytes and reduced hemoglobin concentrations. However, hypochromia can occur even in cells of normal size. This type of anemia results from a variety of conditions that are caused by disorders of iron metabolism, porphyrin and heme synthesis, or globin synthesis.
Normocytic-normochromic anemia produces a destruction or depletion of normal or mature erythrocytes. Although the erythrocytes are relatively normal in size and in hemoglobin content, they are insufficient in number. This type does not share any common cause, pathologic mechanism, or morphologic characteristics and is less common than the others. The five distinct anemic conditions exemplify the diversity of this classification.
- Aplastic anemia (caused from depressed stem cell proliferation resulting in bone marrow aplasia)
- Posthemorrhagic anemia (caused from an abnormal amount of blood loss)
- Hemolytic anemia (premature destruction [lysis] of mature erythrocytes in the circulation)
- Anemia of chronic disease (chronic infection or inflammation or malignancy causes an abnormally increased demand for new erythrocytes)
- Sickle cell anemia (congenital dysfunction of hemoglobin synthesis causing abnormal cell shapes)
Data used to identify anemia types include the erythrocyte indicators:
- mean corpuscular volume (MCV), measures the average erythrocyte volume
- mean corpuscular hemoglobin (MCH), measures the average amount of hemoglobin per erythrocyte
- mean corpuscular hemoglobin concentration (MCHC), measures the average concentration of hemoglobin in erythrocytes. (See more under Lab Tests.)
Anemias associated with decreased RBCs can occur for any number of reasons. Some anemias arise from failure or inability of the bone marrow to synthesize RBCs properly. Others occur because the body cannot synthesize or absorb a specific component necessary for RBC production.
Such anemias resulting from a decreased production of RBCs include iron deficiency anemia, Vitamin B12 (pernicious) anemia, folic acid (B9) deficiency anemia, and aplastic anemia. Of those suffering from anemia, 20% are women and 50% are children.
Anemia is sometimes the first detectable sign of arthritis, infection, or certain major illnesses, including cancer. Drug use, hormonal disorders, chronic inflammation in the body, surgery, infections, peptic ulcers, hemorrhoids, diverticular disease, heavy menstrual bleeding, repeated pregnancies, liver damage, thyroid disorders, rheumatoid arthritis, bone marrow disease, and dietary deficiencies can all lead to anemia. There are also a number of hereditary disorders that cause anemia, especially sickle cell disease and thalassemia. Even heavy milk drinkers are more prone to developing iron deficiency anemia.
According to the Iron Institute, who gathered definitions from medical dictionaries and encyclopedias as well as reliable internet sites, anemia has a wide variety of definitions. Even though all of them are correct to some extent, none of them is a complete definition.
The following are just a few which will explain why it is so difficult to umbrella over 400 anemias into one convenient description. Anemia is:
- a condition in which the number of RBCs is below normal
- a reduction in total circulating RBC mass, diagnosed by a decrease in hemoglobin concentration
- a hemoglobin level below 12 g/dl
- any condition resulting from a significant decrease in the total body erythrocyte mass
- a decrease in the circulating RBC mass and a corresponding decrease in the oxygen-carrying capacity of the blood
- a decreased ability of RBCs to provide adequate oxygen supplies to body tissues
- a reduction in the hemoglobin concentration to below 13.5 g/dl in an adult male and to below 11.5 g/dl in an adult female
- any condition characterized by an abnormal decrease in the body’s total RBC mass
- a condition in which either RBCs or the amount of hemoglobin (oxygen-carrying protein) in the RBC is low
- a condition in which a person has inadequate amounts of iron to meet body demands
- a decrease in the amount of RBCs in the blood caused by having too little iron
- having fewer than the normal number of RBCs or less hemoglobin than normal in the blood
- decreases in numbers of RBCs or hemoglobin content caused by blood loss, deficient erythropoiesis, excessive hemolysis, or a combination of these changes
- a blood disorder that results from a shortage of hemoglobin in the RBCs, the disk-shaped cells that carry oxygen to all parts of the body
- an abnormal reduction in RBCs
- a condition when the amount of RBCs or hemoglobin becomes low, causing the tissues of the body to be deprived of oxygen-rich blood
- a reduction in the number of RBCs in the body
- a condition in which the blood is low on healthy RBCs, the reduction of circulating RBCs per cubic millimeter, the amount of hemoglobin per 100 ml, or the volume of packed red cells per 100 ml of blood
- a condition in which hemoglobin levels are too low to provide for the oxygen demands of the body
- decreased or absent iron stores; decreased serum ferritin; low serum iron; low transferrin saturation; increased iron-binding capacity hypochromic, microcytic, erythrocytes
- a decreased amount of hemoglobin in the blood
- a reduction in hemoglobin
- below normal hemoglobin
Literally, however, “anemia” means without blood! This is also an absurd definition because people cannot live without blood, but they can live with anemia.
Symptoms of anemia often go unrecognized. The first signs of its development may be a loss of appetite, constipation, headaches, noises in the ears, irritability, and/or difficulty concentrating or with memory.
Established anemia produces such symptoms as weakness, fatigue, coldness of the extremeties, depression, dizziness, overall pallor (pale complexion), pale and brittle nails (lack of iron), pale lips and eyelids, pallor in the palms of the hands, soreness in the mouth, restless leg syndrome, and a cessation of menstruation and/or a loss of libido. Pallor results when blood flow is diverted away from the skin, or other areas, in order to meet the more critical needs of the body, as the brain and heart.
These symptoms are caused by the inability of anemic blood to supply body tissues with enough oxygen. Activity intolerance is a common problem since physical activity increases the demand for oxygen. If there are not enough oxygen-circulating erythrocytes to provide sufficient oxygen, individuals become physically weak and unable to engage in normal physical activity without experiencing profound fatigue.
In very advanced cases, swelling of the ankles and other evidence of heart failure may appear.
Although pallor of the skin is a sign of anemia, it is not the most reliable sign because many other factors can affect complexion and skin color. When changes in the pallor of the skin, nail beds, and conjunctiva are all noticed, the cause is likely anemia.
Jaundice of the skin and sclera can occur as a result of hemolysis and the release of bilirubin into the blood stream where it eventually finds its way into the skin and mucous membranes. Bleeding under the skin and bruises in response to the slightest trauma often are present in anemic and leukemic patients. A bluish tint to the skin (cyanosis) can indicate hypoxia caused by inadequate numbers of oxygen-carrying erythrocytes.
Swollen and bleeding gums can occur as a result of nutritional deficiencies and inadequate blood supply to mucous membranes. Breakdown of the oral mucosa can further aggravate anemia by making chewing, tongue movements, and swallowing difficult.
Bleeding into the joints is not unusual in certain kinds of anemia, especially sickle cell disease. Patients may report joint pain or they may be observed moving more slowly than usual and with apparent discomfort. In addition, the joints appear red and swollen.
Until recently, RLS (restless leg syndrome) was basically ignored as being a symptom of anything despite it being a prevalent disorder affecting up to 15% of adult populations. The syndrome is characterized by a strong urge to move the extremeties that usually becomes worse at night, peaking somewhere in the middle of the night.
While much of the clinical intervention has focused on the dopaminergic system (dopamine is a chemical synthesized by the adrenals), there is a growing body of evidence that suggests an iron deficiency cause. High dose, intravenous iron therapy brought on complete relief of symptoms in 21 out of 22 RLS patients for periods of three to nine months, even though the majority had normal iron levels prior to treatment.
When anemia is severe or sudden in onset, peripheral blood vessels constrict so as to direct available blood flow chiefly to the vital organs. A number of systemic symptoms result from this lifesaving maneuver.
- Kidneys: Decreased blood flow is sensed by the kidneys, causing the renal renin-angiotensin response to activate, resulting in salt and water retention.
- Skin: Decreased oxygen delivery to the skin results in impaired healing and loss of elasticity.
- Hair: Decreased oxygen delivery to the hair results in thinning and early graying.
- Nervous system: If anemia, that is, poor oxygen delivery, is because of vitamin B12 deficiency, the nervous system will be affected as myelin degeneration may occur with loss of nerve fibers in the spinal cord. Numbness (paresthesias), gait disturbances, extreme weakness, spasticity, and reflex abnormalities can result.
- Gastrointestinal tract: Decreased oxygen supply to the gastrointestinal tract often produces abdominal pain, nausea, vomiting, and anorexia.
- Other areas: The skin, mucous membranes, lips, nailbeds, and conjunctiva become either pale as a result of reduced hemoglobin concentration, or yellowish as a result of the presence of products of red blood cell breakdown (hemolysis). Low grade fever (less than 101°F) occurs in some anemic individuals and may be the result of leukocyte pyrogens being released from ischemic tissues.
Some types of anemia include the following:
- Achrestic anemia is a megaloblastic type, morphologically resembling pernicious anemia but with multiple other causes.
- Aplastic anemia is a form generally unresponsive to specific anti-anemia therapy and is often accompanied by granulocytopenia (a sudden drop in the production of leukocytes) and thrombocytopenia (a decrease in the number of platelets in circulating blood), in which the bone marrow may not necessarily be lacking cells or a normal cellular structure (acellular) but still fails to produce adequate numbers of blood elements. The term actually is all-inclusive, generally encompassing several clinical syndromes.
- Autoimmune hemolytic anemia (AIHA) is a general term used to cover a large group of anemias involving auto-antibodies against red cell antigens.
- Cooley’s anemia is the homozygous form of beta-thalassemia.
- Deficiency anemia refers to a nutritional deficiency that causes anemia.
- Drug-induced immune hemolytic anemia is, as the name suggests, an immune hemolytic anemia caused by drugs, classified by such mechanisms as: the penicillin type, in which the drug, acting as a hapten is bound to the red cell membrane which induces the formation of specific antibodies; the methyldopa type, in which the drug, possibly by inhibition of suppressor T cells, indicates the formation of anti-Rh antibodies; and the stibophen or “innocent bystander” type, in which the circulating drug-antibody immune complexes binds non-specifically to red cells.
- Erythroblastic anemia (see Cooley’s anemia).
- Hemolytic anemia is caused by a shortened survival of mature erythrocytes and the ability of bone marrow to compensate for their decreased life span. It may be hereditary or acquired and usually results from an infection or chemotherapy, or occurs as part of an autoimmune process. Hypochromic anemia occurs when there is a decrease in hemoglobin that is proportionately much greater than the decrease in the number of erythrocytes.
- Hypoplastic anemia is the result of the incapacity of blood-forming organs. Such anemias as Diamond-Blackfan, Pearson’s, transient, erythroblastopenia of childhood (TEC), and Fanconi’s are classified under hypoplastic anemia.
- Hypoplastic congenital anemia, also called erythrogenesis imperfecta and Fanconi’s syndrome, is an idiopathic progressive form occurring in the first year of life and without leukopenia and thrombocytopenia. It is unresponsive to hematinics (an agent that improves the quality of the blood) and requires multiple blood transfusions to sustain life.
- Iron-deficiency anemia is characterized by low or absent iron stores, low serum iron concentration, low transferrin saturation, elevated transferrin (total iron-binding capacity), low hemoglobin concentration or hematocrit, and hypochromic and microcytic red blood cells. Its frequent occurrence in children is usually the result of prolonged milk feeding without the provision of a variety of foods.
- Lederer’s anemia is an acute hemolytic form of short duration and unknown etiology.
- Macrocytic anemia results when the erythrocytes become much larger than normal.
- Mediterranean anemia (see Cooley’s anemia)
- Megaloblastic anemia is characterized by the presence of megaloblasts in the bone marrow. Megaloblasts are large, nucleated, immature progenitors of an abnormal erythrocytes and form in certain types of anemia. These cells are irregular in shape and size but contain normal concentrations of hemoglobin and the numbers are below normal. This reaction involves the abnormal production of red cells, white cells, and platelets. There are two types of megoblastic anemias and both are the result of a deficiency (B9 or B12).
- Microcytic anemia is characterized by a decrease in size of erythrocytes.
- Myelopathic, or myelophthisic, anemia is caused by the destruction or crowding out of hematopoietic tissues by space-occupying lesions. (Hematopoietic pertains to or affecting the formation of blood cells.)
- Normochromic anemia occurs despite the hemoglobin content of the red blood cells, as measured by the MCHC (mean corpuscular hemoglobin concentration), is still within the normal range.
- Normocytic anemia is characterized by proportionate decreases in hemoglobin, packed red cell volume, and the number of erythrocytes per cubic millimeter of blood.
- Nutritional anemia, also known as “deficiency anemia”, is caused by a deficiency of an essential substance in the diet, and may be caused by poor dietary intake or by malabsorption.
- Pernicious anemia is a serious form that results from a lack of vitamin B12, generally because of a decreased secretion by the gastric mucosa of IF (intrinsic factor) essential to the formation of erythrocytes and the absorption of vitamin B12. This condition may be secondary to an illness or idiopathic (formed from unknown causes). Treatment consists of regular, lifetime administrations of the vitamin either as injections or sublingual tablets.
- Sickle cell anemia, sometimes called sickle cell disease, is a genetically determined defect of hemoglobin synthesis associated with poor physical development and skeletal anomalies.
- Spur-cell anemia occurs when the red cells have a bizarre spiculated shape and are destroyed prematurely, primarily in the spleen. It is an acquired form occurring in severe liver disease and represents an abnormality in the cholesterol content of the red cell membrane.
- Von Jaksch’s anemia, also known as pseudoleukemica infantum, is an anemic leukemia of infants and probably not a distinct disease. It is a syndrome caused by many factors: malnutrition, chronic infection, malabsorption, or other conditions. There seems to be some developmental basis for the inability of these babies to react to infectious processes in a normal manner. This disease follows, or is associated with, some severe nutritional or infectious disease and is characterized by anemia of increasing severity, splenomegaly and myeloid leucocytosis, together with the symptoms of the underlying disease. It is possible that symptoms of severe malnutrition ordinarily supposed to be the cause of the anemia, may really be the earlier symptoms of the disease itself, as an entity caused by developmental defect in the spleen and red bone marrow. It was once considered to be a specific entity in children under the age of three.