Matriz Cuantitativa de Planeamiento Estratégico (MCPE)

Red Blood Cells or erythrocytes enucleated cells filled with hemoglobin, a protein with quaternary structure. R.B.C.s are made in the red blood marrow cavities of the long bones. They live for approx. 120 days and die, their materials usually recycled by the spleen or liver. The Fe2+ iron returned to the red bone marrow by transferrin, some Fe2+ and Fe3+ iron are

excreted in bile. The part of the

heme group that does not contain iron makes

bilirubin. It is excreted by the

liver into bile, then to the feces where its breakdown product stercobilin colors the feces. Fe+2 ion is bluish

green (like deoxygenated blood), and Fe+3 ion is red (oxygenated). Fe+2 is oxidized by bacteria in the gut.

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Red blood cells are first formed from stem cells that develop into erythroblasts. The erythroblast loses its nucleus; therefore, the RBC is enucleate. Reticulocytes, usually only present in the red marrow and having a faint intracellular net pattern, move into the blood stream after maturation.

Mature red blood cells develop from hemocytoblasts. This development takes about 7 days and involves three to four mitotic cell divisions, so that each stem cell gives rise to 8 or 16 cells.

Development of RBC can be tabulated as follows

Table 3. 1. Development of RBC

Cell Cell diameter

(In micrometer)

Nucleus Cytoplasm Mitosis

Pronormoblast 15-20 Big and strongly

basophilic

Very scanty and basophilic. No Hb + Early normoblast Smaller than pronormoblast

Smaller than that of pronormoblast

Still scanty & basophilic. No Hb

+

Intermediate normoblast

10-12 Smaller than that early normoblast

Hb has now apppeared, so that cytoplasm becomes polychromatophilic + Late normoblast 8-10 Nucleus very

small and deeply stained

Plentiful cytoplasm, Hb present in fair amount: cytoplasm is eosinophilic

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Reticulocyte Almost same as that of matured

erythrocyte

Absent Some RNA still present in the cytoplasm

_

Matured erythrocyte

7.5 Absent Hb ++ _

The young red cell is called a retlculocyte because of a network of ribonucleic acid (reticulum) present in its cytoplasm. As the red cell matures the reticulum disappears. Between 2 and 6% of a new-born baby's circulating red cells are reticulocytes, but this reduces to less than 2% in the healthy adult. However, the reticulocyte count increases considerably in conditions in which rapid erythropoiesis occurs, for example following hemorrhage or acute hemolysis of red cells. A reticulocyte normally takes about 4 days to mature into an erythrocyte.

In health, erythropoiesis is regulated so that the number of circulating erythrocytes is maintained within a narrow range. Normally, a little less than l% of the body's total red blood cells are produced per day and these replace an equivalent number that have reached the end of their life span.

Factors influencing erythropoiesis

Erythropoiesis is stimulated by hypoxia (lack of oxygen). However, oxygen lack does not act directly on the hemopoietic tissues but instead

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stimulates the production of a hormone, erythropoietin. This hormone then stimulates hemopoietic tissues to produce red cells.

Erythropoietin is a glycoprotein. It is inactivated by the liver and excreted in the urine. It is now established that erythropoietin is formed within the kidney by the action of a renal erythropoietic factor erythrogenin on plasma protein, erythropoietinogen. Erythrogenin is present in the juxtaglomerular cells of the kidneys and is released into the blood in response to hypoxia in the renal arterial blood supply.

Various other factors can affect the rate of erythropoiesis by influencing erythropoietin production.

1. Thyroid hormones: Thyroid hormones, thyroid-stimulating hormone, adrenal cortical steroids, adrenocorticotrophic hormone, and human growth hormone (HGH) all promote erythropoietin formation and so enhance red blood cell formation (erythropoiesis). In thyroid deficiency and anterior pituitary deficiency, anaemia may occur due to reduced erythropoiesis. Polycythemeia is often a feature of Cushing's syndrome. However, very high doses of steroid hormones seem to inhibit erythropoiesis.

2. Sex hormones: Androgens stimulate and oestrogens depress the erythropoietic response. In addition to the effects of menstrual blood loss, this

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effect may explain why women tend to have a lower hemoglobin concentration and red cell count than men.

3. Oxygen availability: Plasma levels of erythropoietin are raised in hypoxic conditions (low oxygen levels). This produces erythrocytosis (increase in the number of circulating erythrocytes) and the condition is known as secondary polycythemeia. A physiological secondary polycythemeia is present in the foetus (and residually in the new-born) and in people living at high altitude because of the relatively low partial pressure of oxygen in their environment. Secondary polycythemeia occurs as a result of tissue hypoxia in diseases such as chronic bronchitis, emphysema and congestive cardiovascular abnormalities associated with right-to-left shunting of blood through the heart, for example Fallot's tetralogy.

2. Granulocytes

Granulocytes is the collective name given to three types of white blood cell. Namely these are neutrophils, basophils and eosinophils.

In terms of their formation (granulopoiesis) they all derive from the same type of committed stem cells called myeloblasts. After birth and into adulthood granulopoiesis occurs in the red marrow.

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The process of producing granulocytes is characterised by the progressive condensation and lobulation of the nucleus, loss of RNA and other cytoplasmic organelles, for example mitochondria, and the development of cytoplasmic granules in the cells involved.

The development of a polymorphonuclear leukocyte makes take a fortnight, but this time can be considerably reduced when there is increased demand, as, for example, in bacterial infection. The red marrow also contains a large reserve pool of mature granulocytes so that for every circulating cell there may be 50-100 cells in the marrow.

Mature cells pass actively through the endothelial lining of the marrow sinusoid into the circulation. In the circulation, about half the granulocytes adhere closely to the internal surface of the blood vessels. These are called marginating cells and are not normally included in the white cell count. The other half circulate in the blood and exchange with the marginating population.

Within 7 hours, half the granulocytes will have left the circulation in response to specific requirements for these cells in the tissues. Once a granulocyte has left the blood it does not return. It may survive in the tissues for 4 or 5 days, or less, depending on the conditions it meets.

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The turnover of granulocytes is, therefore, very high. Dead cells are eliminated from the body in feces and respiratory secretions and are also destroyed by tissue macrophages (monocytes).

No precise mechanisms for the control of granulocyte production have, so far, been found. However, in health, the count remains relatively constant so it is likely that homeostatic control mechanisms operation

3. Monocytes

Monocytes are produced in the bone marrow, developing from nucleated precursors, the monoblast and promonocyte. Mature cells have a life in blood of approximately 3-8 hours and, like granulocytes, there is a circulating and marginating pool.

Monocytes are actively phagocytic (engulf other cells) and, on migration into the tissues, they mature into larger cells called macrophages (Derives from the Ancient Greek: macro = big, phage = eat), which can survive in the tissues for long periods. These cells form the mononuclear phagocytic cells of the mononuclear phagocytic system (reticuloendothelial system) in bone marrow, liver, spleen and lymph nodes.

Tissue macrophages (sometimes called histiocytes) respond more slowly than neutrophils to chemotactic stimuli. They engulf and destroy bacteria,

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protozoa, dead cells and foreign matter. They also function as modulators of the immune response by processing antigen structure and facilitating the concentration of antigen at the lymphocyte's surface. This function is essential in order that full antigenic stimulation of both T and B lymphocytes can take place.

4. Lymphocytes

Lymphocytes are round cells containing large round nuclei. The cytoplasm stains pale blue and appears non-granular under light microscopy. However, some cytoplasmic granules and organelles are present.

Morphologically, lymphocytes can be divided into two groups: the more numerous small lymphocytes, with a diameter of 7-10 mm; and large lymphocytes, which have a diameter of 10-14 mm. Lymphocytes are produced in bone marrow from primitive precursors, the lymphoblasts and prolymorphocytes. Immature cells migrate to the thymus and other lymphoid tissues, including that found in bone marrow, and undergo further division, processing and maturation.

5. Platelets

Platelets are produced in bone marrow by a process known as thrombopoiesis. They are formed in the cytoplasm of a very large cell, the

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megakaryocyte. The cytoplasm of the megakaryocyte fragments at the edge of the cell. This is called platelet budding. Megakaryocytes mature in about 10 days, from a large stem cell, the megakaryoblast.

It is likely that there are thrombopoietic feedback mechanisms as the platelet count remains fairly constant in health, and platelet production is reduced following an infusion of platelets and increased following removal of platelets.

Fate of RBC

When RBCs are terminally differentiated; they lose their power to multiply. The life span of erythrocytes is about 120 days and then they are ingested by phagocytic cells in the liver and spleen. Most of the iron in their hemoglobin is reclaimed for reuse. The remainder of the heme portion of the molecule is degraded into bile pigments and excreted by the liver. Some 3 million RBCs die and are scavenged by the liver each second.