L3 (physiology)-FACTORS AFFECTING ERYTHROPOIESIS FUNCTION OF HB (1).pdf

Factors affecting erythropoiesis & haemoglobin function ILOs By the end of this lecture, students will be able to 1. Describe the role of erythropoietin in relevance to RBCs formation. 2. Discuss the role of factors required for erythropoiesis in relevance to development of anemia 3. Determine the f...

Factors affecting erythropoiesis & haemoglobin function ILOs By the end of this lecture, students will be able to 1. Describe the role of erythropoietin in relevance to RBCs formation. 2. Discuss the role of factors required for erythropoiesis in relevance to development of anemia 3. Determine the function of haemoglobin in relation to its structure. Red blood cells (RBCs): Red blood cells transport hemoglobin, which is the main carrier of O2 in the circulation. In normal adults, the red blood cells occupy about 45% of the volume of the blood; this percentage of RBCs in relation to whole blood is the “haematocrite value”. A normal RBC count ranges from 4.5 to 5.5 million cells per microliter (µL) of blood. RBC counts for men are often toward the high end of this range; those for women are often toward the low end. Function: Red blood cells are highly specialized for their oxygen transport function. Because mature RBCs have no nucleus, all of their internal space is available for oxygen transport. Red blood cells contain the protein hemoglobin (Hb), which gives them the ability to carry oxygen. In the pulmonary capillaries, RBCs pick up oxygen and oxyhemoglobin is formed. In the systemic capillaries, hemoglobin gives up much of its oxygen and becomes reduced hemoglobin. Hemoglobin is also able to bond to carbon dioxide (CO 2), and does transport some CO2 from the tissues to the lungs. But hemoglobin accounts for only about 10% of total CO2 transport Life Span: Red blood cells live for approximately 120 days. Red blood cells formation (Erythropoiesis): Erythropoiesis is the process of formation of red blood cells. During embryonic life, the erythropoiesis occurs in the liver. In postnatal and adult life, it occurs in the red bone marrow. Page 1 of 6 Factors affecting erythropoiesis: Various substances are necessary for development and maturation of erythrocytes. I)- General factors II)- Maturation factors III)- Factors necessary for hemoglobin formation I)- General factors: A)- Hormones: 1)-Erythropoietin hormone: Most of erythropoietin (90%) is formed in the kidney, the rest is formed in the liver. Hypoxia is responsible for production of erythropoietin. Lack of O2 stimulates formation of erythropoietin. On the other hand, when O2 transport to tissues rises above normal, the rate of erythropoietin formation decreases (negative feedback mechanism) (figure 1). Oxygen is a major regulating factor for erythropoiesis. If the body is in a state of hypoxia, or lack of oxygen, the kidneys produce erythropoietin, which stimulates the red bone marrow to increase the rate of RBC production. This will occur following hemorrhage or if a person stays for a time at a higher altitude. As a result of the action of erythropoietin, more RBCs will be available to carry oxygen and correct the hypoxic state. 2)-Other hormones: Some hormones are required for erythropoiesis as they promote tissue metabolism in general. These are: Thyroxine Male hormones (androgens) Growth hormone B) - Vitamins: Vitamin C influences general metabolism and growth of body tissues including bone marrow. It is not specific for red blood cell formation. Page 2 of 6 Figure (1): Function and regulation of erythropoietin hormone C) - Liver: A healthy liver is essential for normal red blood cell formation. The liver manufactures globin and stores iron, copper, vitamin B12 and folic acid. It also secretes small amount of erythropoietin. D) - Bone marrow: It is the factory in which red cells and most other blood cells are formed. Destruction of bone marrow by irradiation, chemicals, drugs or bacterial toxins will lead to deficiency of all blood cells which is called “aplastic anemia” II) - Maturation factors: Vitamin B12 and folic acid are essential for maturation of red blood cells. They are important for nuclear maturation and cell division of red cell precursors, and are called maturation factors. Page 3 of 6 Animal food is the main source of vitamin B12. Vitamin B12 is also called the extrinsic factor because its source is external, our food. Parietal cells of the stomach lining produce the intrinsic factor, a chemical that combines with the vitamin B12 in food to prevent its digestion and promote its absorption in the small intestine. Once absorbed, vitamin B12 is stored in large quantities in the liver and is released slowly as needed by the bone marrow and other tissues. The normal liver can store enough vitamin B12 to meet the requirements for many months. III) - Factors necessary for hemoglobin formation: Protein: Animal protein that are present in the liver, kidney and muscles are superior in production of haemoglobin (globin fraction) compared to plant-derived proteins. Animal proteins contain the essential amino acids, which are neither stored nor formed in the body. Iron: Iron is necessary for the formation of the heme part of hemoglobin. 70% of the iron in the body is present in hemoglobin. Copper and cobalt: Copper and cobalt act as catalyst in hemoglobin synthesis. Copper is necessary for iron reabsorption from gastrointestinal tract. Cobalt is essential for utilization of iron during hemoglobin formation. N.B: Proteins, vitamins, iron and copper are nutritional factors that are required for erythropoiesis. Haemoglobin (Hb): The average Hb concentration in blood is 16+ 2 g/dl in men and 14 g +2 /dl in women. The function of Hb is to carry O2 and CO2. Each Hb molecule contains 4 heme fractions. Each heme fraction can carry one molecule of O2, so the hemoglobin molecule can carry up to 4 molecules of O2. In a normal person about 20 mL of O2 can be carried in combination with Hb in each 100 mL arterial blood when fully saturated. Page 4 of 6 Combination of haemoglobin with oxygen: (figure 2) The most important feature of the haemoglobin is its ability to combine loosely and reversibly with O2. Haemoglobin binds O2 to form oxyhaemoglobin. O2 is attached to the Fe++ (ferrous iron) in the haem. Figure (2): Combination of haemoglobin with oxygen Derivatives of Hb: 1)- Oxyhaemoglobin: This is formed by the combination of Hb with O2 by the process of oxygenation. The iron remains in the ferrous state in this compound. 2)- Deoxy or reduced Hb: When O2 is released from oxyhaemoglobin, it is called reduced Hb. 3)-Carbaminohaemoglobin: This is formed by combination of Hb with CO2. CO2 can be easily released from this. The affinity of Hb to CO2 is 20 times more than for O2 Page 5 of 6 4)-Caboxyhaemoglobin: The combination of Hb with carbon monoxide (CO) produces this compound. The affinity of Hb for CO is 200 times more than its affinity for O2 5)- Methaemoglobin: If the blood is exposed to various drugs and oxidizing agents, the Fe++ in the Hb molecule will be converted to ferric iron (Fe+++) forming methaemoglobin which is unable to carry O 2. Page 6 of 6