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Blood Cells

 

Blood Cells
Blood cells are formed in the bone marrow. All blood cells arise from the same bone marrow stem cells. Stem cells are immortal, meaning they never die (at least not until you do). Stem cells are also undifferentiated. meaning they have not yet developed into a particular cell type. Furthermore, stem cells are pluripotent, meaning they have the potential to become any type of blood cell. These immortal, undifferentiated, pluripotent stem cells give rise to erythrocytes, leukocytes and platelets. The diagram below illustrates the different types of blood cells. Leukocytes, also known as white blood cells, are a group of related cell types that involved in immune function. Leukocytes include neutrophils, eosinophils, basophils, lymphocytes and monocytes.

 

Erythrocytes

Erythrocytes, also known as red blood cells (RBCs), function to transport oxygen in the blood. The shape of erythrocytes is ideal for this function. Seen from the top, erythrocytes appear to be circular, but a side view shows that they are actually biconcaved discs. This shape increases the surface area-to-volume ratio of the cell, thus increasing the efficiency of diffusion of oxygen and carbon dioxide into and out of the cell. Erythrocytes also have a flexible plasma membrane. This feature allows erythrocytes, which have a 7mm diameter, to squeeze through capillaries as small as 3 mm wide. Erythrocytes contain tremendous amounts of hemoglobin, the protein that binds oxygen. In order to make room for more hemoglobin to carry more oxygen, erythrocytes loose their nucleus and other organelles as they develop in the bone marrow. Because they lack a nucleus and other cellular machinery, erythrocytes cannot repair themselves when damaged, consequently they have a limited life span of about 120 days. The removal of old and dying erythrocytes is carryied out by the spleen. Erythrocytes, which represent the most numerous cell type in the body die at a rapid rate, 2-3 million erythrocytes die every second. Erythrocyte production must equal erythrocyte death or the cell population would decline. Erythrocytes are produced through a process called erythropoesis.

 

Erythropoesis

The body must have a way to assess the concentration of erythrocytes in the blood such that erythrocytes are produced at a rate that matches the body's needs. The regulation and production of RBCs is called erythropoesis. The mechanism of erythropoesis occurs in the following way. The kidney monitors the level of oxygen in the blood. If oxygen levels are low then the kidney secretes a hormone called erythropoetin. Erythropoetin enters the blood stream and travels throughout the body. All cells are exposed to erythropoetin, but only red bone marrow cells, which have erythropoetin receptors, respond to the hormone. Erythropoetin stimulates the production of erythrocytes in the bone marrow. These erythrocytes leave the bone marrow and move into the blood stream. As the erythrocyte population increases, the oxygen carrying capacity of the blood increases. When the kidney senses that oxygen levels are adequate, it responds by slowing the secretion of erythropoetin. This negative feedback loop ensures that the size of the erythrocyte population remains relatively constant and that the oxygen carrying capacity of the blood is always sufficient to meet the needs of the body.

 

The gene encoding erythropoetin was recently cloned by a local biotech company (Amgen).Through recombinant DNA technology erythropoetin is now produced in large quantities and is available for clinical use.

Clinical uses of recombinant erythropoetin include:

  1. It is used to boost erythrocyte production prior to surgery as a way to decrease the volume of transfused donor blood required.
  2. Its is used to boost erythrocyte production following chemotherapy for cancer. Chemotherapy targets fast growing cells. Cancer cells are fast-growing and therefore die, but erythrocytes, which are also fast growing cells, suffer decline following chemotherapy.

 

 

Hematocrit

Whole blood is composed of plasma (liquid), cells and platelets. If whole blood is placed into a tube and centrifuged, the cells and the plasma will separate. The erythrocytes, which are heavy, will pack into the bottom of the tube, the plasma will be at the top of the tube, and the leukocytes and platelets will form a thin layer (buffy coat) between the erythrocytes and the plasma. The hematocrit is defined as the percentage of whole blood made up of erythrocytes. This value is determined by dividing the height of the erythrocytes by the total height of the blood in the tube and multiplying by 100.

Hematocrits vary depending on sex and environmental conditions, but there is a range of values that is considered normal. Average hematocrit values are:

  • males.......... 40-50%
  • females....... 38-45%
  • athletes........ > 50%

Any activity or condition that consistently lowers oxygen levels in the blood will cause an increase in erythropoesis and a subsequent rise in the hematocrit.

Factors that will raise the hematocrit include:

  • Exercise. During aerobic exercise blood oxygen levels are lowered due to rapid consumption of oxygen by active skeletal muscle. This stimulates an increase in erythropoesis, which increases hematocrit, which increases the oxygen carrying capacity of the blood. Thus regular aerobic exercise raises the hematocrit.
  • Living at high altitude. The air is thinner at higher altitude, therefore fewer molecules of oxygen enter the lungs with each breath. Oxygen levels in the blood are lower when breathing such thin air. A person that moves from Santa Barbara, which is at sea level, to Denver, Colorado, which has an altitude of 5000', will experience a rise in hematocrit as compensatory response to the thin air.
  • Injection of recombinant erythropoetin. Some endurance athletes use erythropoetin (illegally) to increase their hematocrit as a way to increase stamina.

     

Primary Polycythemia

Primary polycythemia is a condition that is characterized by an excess of circulating erythrocytes and an elevated hematocrit. This condition is caused by a tumor-like condition of the bone marrow resulting in over-stimulation of erythropoesis. The hematocrit raised as high as high as 70-80%. The increase in blood viscosity assiciated with very high hematocrits causes sluggish circulation (lowering delivery of oxygen to tissues) and high blood pressure.

 

Anemia

Anemia is a condition that is characterized by a reduction in the oxygen carrying capacity of the blood. This reduction is caused by inadequate levels of hemoglobin, inadequate numbers of erythrocytes (low hematocrit) or both.

Symptoms of anemia are variable, but may include:

  1. Fatigue. One of the most common and debilitating symptoms of anemia is fatigue (lack of energy), particularly with exercise. Oxygen is required to metabolize fuel molecules (sugars, fats and proteins) to obtain energy. A person with a low hematocrit cannot carry enough oxygen in the blood to meet their energy demands.
  2. Increased heart rate. The body increases heart rate to compensate for the low oxygen carrying capacity of the blood. If more blood is moved faster through the tissue then tissues get more oxygen per unit time.
  3. Shortness of breath. An anemic person may feel short of breath and then breath faster to alleviate the feeling. This is a compensation for the poor delivery of oxygen to the tissues.
  4. Low blood pressure. The viscosity of the blood drops as the hematocrit decreases. A decrease in blood viscosity directly lowers total peripheral resistance (TPA) to the flow of blood, thus lowering mean arterial blood pressure (MAP).
  5. Pale Skin. Hemoglobin is bright red when oxygenated and less red when deoxygenated. Because the redness of skin is due to the redness of blood, the skin of an anemic person (who has less oxygen in the blood) will less red (paler) than the average person.

Causes of Anemia

As mentioned earlier, anemia is characterized by either low hemoglobin, low hematocrit, or both. There are several situations that can lead to this state. The causes of anemia include:

  1. Dietary deficiencies of iron, vitamin B12 or folic acid.
  2. Hemorrhage
  3. Hemolysis
  4. Bone marrow failure
  5. Kidney disease

Dietary deficiencies

  • Iron is required for the production and function of hemoglobin. In the absence of adequate iron, hemoglobin production slows down. Low hemoglobin can lower the hematocrit.
  • Vitamin B12 and Folic Acid are required for DNA synthesis prior to cell division. In the absence of these nutrients production of erythrocytes is reduced. The hematocrit is low and many erythrocytes are huge, fragile cells called macrocysts. B12 deficiency can be caused by a lack of intrinsic factor, this is called pernicious anemia. Intrinsic factor, which is produced in the stomach, is required for efficient absorption of B12 out of the small intestine and into the blood.

 

Hemorrhage refers to a significant loss of blood through bleeding. Hemorrhagic anemia is due to blood loss that is greater than the rate at which erythrocytes can be replaced. Blood loss may be due to injury, donating blood, ulcers, heavy menstruation, etc.

Hemolysis refers to the lysis (breaking) of erythrocytes. Hemolytic anemia is due to a high rate of erythrocyte lysis in the blood stream. Sickle cell anemia, which is caused by defective hemoglobin, is a genetic form of hemolytic anemia. Under conditions of low oxygen (as during exercise) the hemoglobin within erythrocytes crystallizes. This causes the RBCs to adopt a sickled shape, which makes them fragile and easily lysed.

Bone marrow failure leads to a reduction in the production of erythrocytes. This may be due to cancer or toxic drugs.

Kidney disease can lead to a reduction in the synthesis of erythropoetin, resulting in a low hematocrit.

 


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(Revised October 11 1999)
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