TYPES OF ANEMIA AND ITS CAUSES

• Iron deficiency anemia. This is the most common type of anemia worldwide. Iron deficiency anemia is caused by a shortage of iron in your body. Your bone marrow needs iron to make hemoglobin. Without adequate iron, your body can't produce enough hemoglobin for red blood cells.
• Without iron supplementation, this type of anemia occurs in many pregnant women. It is also caused by blood loss, such as from heavy menstrual bleeding, an ulcer, cancer and regular use of some over-the-counter pain relievers, especially aspirin.
• Vitamin deficiency anemia. In addition to iron, your body needs folate and vitamin B-12 to produce enough healthy red blood cells. A diet lacking in these and other key nutrients can cause decreased red blood cell production.
  Additionally, some people may consume enough B-12, but their bodies aren't able to process the vitamin. This can lead to vitamin deficiency anemia, also known as pernicious anemia.
• Anemia of chronic disease. Certain diseases — such as cancer, HIV/AIDS, rheumatoid arthritis, kidney disease, Crohn's disease and other chronic inflammatory diseases — can interfere with the production of red blood cells.
• Aplastic anemia. This rare, life-threatening anemia occurs when your body doesn't produce enough red blood cells. Causes of aplastic anemia include infections, certain medicines, autoimmune diseases and exposure to toxic chemicals.
• Anemias associated with bone marrow disease. A variety of diseases, such as leukemia and myelofibrosis, can cause anemia by affecting blood production in your bone marrow. The effects of these types of cancer and cancer-like disorders vary from mild to life-threatening.
• Hemolytic anemias. This group of anemias develops when red blood cells are destroyed faster than bone marrow can replace them. Certain blood diseases increase red blood cell destruction. You can inherit a hemolytic anemia, or you can develop it later in life.
• Sickle cell anemia. This inherited and sometimes serious condition is an inherited hemolytic anemia. It's caused by a defective form of hemoglobin that forces red blood cells to assume an abnormal crescent (sickle) shape. These irregular blood cells die prematurely, resulting in a chronic shortage of red blood cells.
• Other anemias. There are several other forms of anemia, such as thalassemia and malarial anemia.

Erythropoiesis and its regulation

Because of the inability of erythrocytes (red blood cells) to divide to replenish their numbers, the old ruptured cells must be replaced by totally new cells. They meet their demise because they don’t have the usual specialized intracellular machinery, which controls cell growth and repair, leading to a short life span of 120 days.

This short life span necessitates the process erythropoiesis, which is the formation of red blood cells. All blood cells are formed in the bone marrow. This is the erythrocyte factory, which is soft, highly cellar tissue that fills the internal cavities of bones.

During intrauterine development, the early stages of life, erythrocytes are produced first by the yolk sac and then by the developing spleen during the third month of gestation, until the bone marrow is formed in the seventh month and takes over erythrocyte production exclusively.

ERYTHROCYTE DIFFERENTIATION

Erythrocyte differentiation takes place in 8 stages. It is the pathway through which an erythrocyte matures from a hemocytoblast into a full-blown erythrocyte. The first seven all take place within the bone marrow. After stage 7 the cell is then released into the bloodstream as a reticulocyte, where it then matures 1-2 days later into an erythrocyte. The stages are as follows:

1. Hemocytoblast, which is a pluripotent hematopoietic stem cell
2. Common myeloid progenitor, a multipotent stem cell
3. Unipotent stem cell
4. Pronormoblast
5. Basophilic normoblast also called an erythroblast.
6. Polychromatophilic normoblast
7. Orthochromatic normoblast
8. Reticulocyte

REGULATION OF ERYTHROPOIESIS

Thinking logically you might suspect that because the primary function of erythrocytes is to transport O2 in the blood, the primary stimulus for erythrocyte production is low O2 levels. You would be correct, but low O2 levels do not stimulate erythropoiesis by acting directly on the bone marrow.

Instead, it stimulates the kidneys to secrete the hormone erythropoietin into the blood, and this hormone in a domino effect stimulates the bone marrow to produce erythrocytes.

Erythropoietin acts on derivatives of undifferentiated cells that have already been committed to becoming red blood cells (RBC’s), stimulating the proliferation and maturation of these cells into mature RBCs.

This increase in erythropoietic activity elevates the number of circulating RBCs, thereby raising the O2 carrying capacity of the blood and restoring the delivery of O2 to the body tissues to normal. Once the O2 level in the tissues of the kidneys is brought back to normal, erythropoietin secretion is turned down until it is needed again. This is an example of a negative feedback mechanism.

                                   

NORMAL MORPHOLOGY OF RED BLOOD CELL

The erythrocyte, commonly known as a red blood cell (or RBC), is by far the most common formed element: A single drop of blood contains millions of erythrocytes and just thousands of leukocytes. Specifically, males have about 5.4 million erythrocytes per microliter (µL) of blood, and females have approximately 4.8 million per µL. In fact, erythrocytes are estimated to make up about 25 percent of the total cells in the body. As you can imagine, they are quite small cells, with a mean diameter of only about 7–8 micrometers (µm). The primary functions of erythrocytes are to pick up inhaled oxygen from the lungs and transport it to the body’s tissues, and to pick up some (about 24 percent) carbon dioxide waste at the tissues and transport it to the lungs for exhalation. Erythrocytes remain within the vascular network. Although leukocytes typically leave the blood vessels to perform their defensive functions, movement of erythrocytes from the blood vessels is abnormal.

Shape and Structure of Erythrocytes

Erythrocytes are biconcave disks; that is, they are plump at their periphery and very thin in the center . Since they lack most organelles, there is more interior space for the presence of the hemoglobin molecules that, as you will see shortly, transport gases. The biconcave shape also provides a greater surface area across which gas exchange can occur, relative to its volume; a sphere of a similar diameter would have a lower surface area-to-volume ratio. In the capillaries, the oxygen carried by the erythrocytes can diffuse into the plasma and then through the capillary walls to reach the cells, whereas some of the carbon dioxide produced by the cells as a waste product diffuses into the capillaries to be picked up by the erythrocytes. Capillary beds are extremely narrow, slowing the passage of the erythrocytes and providing an extended opportunity for gas exchange to occur. However, the space within capillaries can be so minute that, despite their own small size, erythrocytes may have to fold in on themselves if they are to make their way through. Fortunately, their structural proteins like spectrin are flexible, allowing them to bend over themselves to a surprising degree, then spring back again when they enter a wider vessel. In wider vessels, erythrocytes may stack up much like a roll of coins, forming a rouleaux, from the French word for “roll.”

INTRODUCTION OF ANEMIA

Anemia is a condition that develops when your blood lacks enough healthy red blood cells or hemoglobin. Hemoglobin is a main part of red blood cells and binds oxygen. If you have too few or abnormal red blood cells, or your hemoglobin is abnormal or low, the cells in your body will not get enough oxygen. Symptoms of anemia -- like fatigue -- occur because organs aren't getting what they need to function properly.Anemia is the most common blood condition in the U.S. It affects about 3.5 million Americans. Women, young children, and people with chronic diseases are at increased risk of anemia. Important factors to remember are:

Certain forms of anemia are hereditary and infants may be affected from the time of birth. Women in the childbearing years are particularly susceptible to iron-deficiency anemia because of the blood loss from menstruation and the increased blood supply demands during pregnancy. Older adults also may have a greater risk of developing anemia because of poor diet and other medical conditions.

There are many types of anemia. All are very different in their causes and treatments. Iron-deficiency anemia, the most common type, is very treatable with diet changes and iron supplements. Some forms of anemia -like the mild anemia that develops during pregnancy - are even considered normal. However, some types of anemia may present lifelong health problems.