ERYTHROCYTES NUMBER AND HEMOGLOBIN CONCENTRATION INVESTIGATION



 

1. The topic studied actuality.

Erythrocytic stability to hemolysis is decreased at some diseases. Erythrocytes indexes determining is widely used all over the world for anemias differential diagnostics. Dentists can deal with anemias connected with salivary glands (for instance, parotid) pathology.

Erythrocytes morpho-functional indexes can be changed at oral cavity diseases in part of salivary glands, at phlegmons and abscesses.

2. Study aims:

To know: erythrocytes and hemoglobin structure, functions and normal value, representation about color index, erythrocytes hemolysis and influenced factors as well as erythropoiesis and its regulation.

To be able to: count Er and Hb level in blood as well as color index.

 

Pre-auditory self-work materials.

 

3.1.Basic knowledge, skills, experiences, necessary for study the topic:

Subject To know To be able to
Medical biological chemistry Data about hemoglobin structure  
Biophysics Data about erythrocytes hemolysis Assess osmotic hemolysis of erythrocytes
Medical Biology Data about microscope main structural parts Work with microscope, investigate hyperosmotic and hypoosmotic state in sodium chloride different-concentrated solutions
Histology, Cytology and Embryology Data about microscope main structural parts, representations about erythropoiesis and its regulation Work with microscope, recognize preparations of erythropoiesis at its different stages, tell about erythropoiesis on Chertkov-Vorobiyev scheme
Pathophysiology About anemias reasons, types, main developmental mechanisms Assess anemias types on the base of given indexes of erythrocytes number, hemoglobin concentration, colour index

 

3.2. Topic content

It is interesting to know

· If to put one erythrocyte on another one than one can receive the “column” more than 60 km in height.

· All erythrocytes surface is equal to 4000 m2 in one human being.

· To count all erythrocytes in one human being one needs 475000 years if to count them with the velocity equal to 100 red blood cells in 1 min.

· There exists plant hemoglobin – legoglobin or leghemoglobin. It is present in the legumes (beans). Hem is produced by plant, while proteinic part – by bacterias that live on these plants and convert atmospheric nitrogen to nitrogen-containing fertilizations. It is an example of double symbiosis in alive nature.

· Current research is being conducted in an attempt to develop artificial hemoglobin. One chemical that has been used in clinical trials is a perfluorochemical emulsion called Fluosol DA, a white liquid with a high oxygen affinity. Although the usefulness of hemoglobin substitutes is currently limited because artificial hemoglobin is destroyed fairly quickly in the body, future work may uncover more successful substitutes that can provide long-term relief for patients with blood disorders. The use of artificial hemoglobin could eliminate some of the disadvantages of using blood for transfusions. With artificial hemoglobin, transfusion reactions would not occur because of mismatched blood, and transferring diseases such as hepatitis or AIDS would be eliminated. In addition, artificial hemoglobin could be used when blood is not available. 

INTRODUCTION AND NORMAL VALUE

Erythrocytes or red blood cells (RBC) are the non-nuc­leated formed elements in the blood. The red colour of these cells is due to the presence of the colouring matter-hemoglobin in these cells. The word “erythros” means red.

Normal Values:

· in adult men – 4,5-5,5 x 1012/l;

· in adult women – 3,7-4,5 x 1012/l;

· in newborns – up to 7,0 x 10 12/l;

· adult ciphras – up to adolescence.

MORPHOLOGY OF RED BLOOD CELLS

NORMAL SIZE

· diameter – 7,0-7,7 mcm – in normocytes; less than 6,0 mcm – microcytes, more than 7,7 mcm macrocytes;

· width – 2 mcm;

· volume – 76-100 mcm;

· surface square – 140-150 mcm2

 

2.2 p

FIGURE 2: Dimensions of red blood cell. A: Surface view. B. Sectioned view

Normally, the red blood cells are disc shaped and bicon­cave (dumb-bell shaped). The biconcave contour of red blood cells has the following mechanical advantages.

1. It helps in equal and rapid diffusion of oxygen and other substances into the interior of the cell.

2. Large surface area is provided for absorption or removal of different substances.

3. Minimal tension is offered on the membrane when the volume of cell alters.

4. While passing through minute capillaries, these cells can squeeze through the capillaries very easily.

PROPERTIES OF RED BLOOD CELLS

1. ROULEAUX FORMATION

When blood is taken out of the blood vessel, the red blood cells pile up one above another like the pile of coins. This property of the red blood cells is called rouleaux (pleural = rouleau) formation (Fig.3).

2. SPECIFIC GRAVITY

The specific gravity of red blood cell is 1.092 to 1.101.

3. PACKED CELL VOLUME

When the blood is collected in a centrifuge tube along with proper anticoagulant and centrifuged for a period of 30 minutes at a speed of 3000 rpm (revolutions per minute), the red blood cells settle at the bottom of the tube leaving the clear plasma at the top. The red blood cells form 45% of the total blood. This is called the packed cell volume or hematocrit. The volume of plasma is 55%.

4. SUSPENSION STABILITY

During circulation, the red blood cells remain suspended uniformly in the blood. This property of the red blood cells is called the suspension stability or sedimentation absence.

FIGURE 3: Rouleau formation Courtesy: Dr Nivaldo Medieiros

 

This figure demonstrates “coin columns” formation or erythrocytes sedimentation that has been described in lesson number 31.

VARIATIONS IN NUMBER OF RED BLOOD CELLS

PHYSIOLOGICAL VARIATIONS

A. Increase in the red blood cell count is known as poly­cythemia. If it occurs in physiological conditions, it is called physiological polycythemia. Although some authors determine polycytemy as erythrocytes, leucocytes and platelets amount increase and the term “erythrocytosis” is used for erythrocytes increase designation. It occurs in the following conditions:

1. Age    

At birth, the red blood cell count is 8 -10 millions/cu mm of blood. The count decreases within 10 days after birth due to destruction of cells causing physiological jaundice in some infants. However, in infants and growing children, the cell count is at a level higher than the value in adults.

2. Sex

Before puberty and after menopause in females the red blood cell count is similar to that in males. During repro­ductive period of females, the count is less than in males (4.5 millions/cu mm).

3. High Altitude

The inhabitants of mountains (above 10,000 feet from mean sea level) have an increased red blood cell count of more than 7 millions/cu mm. This is due to hypoxia in high altitude. During hypoxia, the erythropoietin is released from the kidneys. The erythropoietin in turn stimulates the bone marrow to produce more red blood cells.

4. Muscular Exercise

There is a temporary increase in red blood cell count after exercise. This is because of mild hypoxia and contraction of spleen, which is the reservoir of blood.

5. Emotional Conditions

The red blood cell count is increased during the emotional conditions like anxiety, because of sympathetic stimula­tion.

6. Increased Environmental Temperature

The increase in the atmospheric temperature increases red blood cell count.

7. After Meals

There is a slight increase in the red blood cell count after taking meals.

B. Decreasein red blood cell count (erythropeny) occurs in the follow­ing physiological conditions:

1. High Barometric Pressures

At high barometric pressures as in deep sea, when the oxygen tension of blood is higher, the red blood cell count decreases.

2. After Sleep

The red blood cell count decreases slightly after sleep.

3. Pregnancy

In extracellular fluid volume, increases the plasma volume also resulting in hemodilution. So, there is a relative reduction in the red blood cell count.

VARIATIONS IN SIZE OF RED BLOOD CELLS

The size of the red blood cells alters in various conditions.

Microcytes

Microcytes are the red blood cells of small size and are present in the following conditions:

1. Iron deficiency anemia

2. Prolonged forced breathing and

3. Increased osmotic pressure in blood

Macrocytes

Macrocytes are the red blood cells with larger size. The macrocytes are present in the following conditions:

1. Megaloblastic anemia

2. Muscular exercise and

3. Decreased osmotic pressure in blood

4. Disease of Minkovsky-Shoffar – when erythrocytes are big and spheric

Anisocytes

The red blood cells with unequal size are called the aniso­cytes. This happens in pernicious (zyancobalamin-deficient) anemia.

So, one can tell about about 3 states:

· microcytosis;

· macrocytosis;

· anisocytosis.

Erythrocytes size assessment is rather essential at anemias differential diagnostics.

VARIATIONS IN SHAPE OF RED BLOOD CELLS

The following are the abnormal shape of red blood cells. Some of these abnormal shapes of the red blood cells occur in different types of anemia. Examples:

· crenation – shrinkage as in hypertonic solution;

· spherocytosis – globular form as in hypotonic solution;

· elliptocytosis – elliptical shape as in certain types of anemia;

· sickle cells or drepanocytes – crescentic shape as in sickle cell anemia;

· planocytes – flattened;

· pear-shaped;

· racket-shaped;

· flask-shaped;

· hammer-shaped;

· stomatocytes – concave from one side;

·  echinocytes – “hedgehogs”;

· acantocytes – like the previous ones, but “needles” are wider and less in amount; as a rule, these change is irreversible one comparatively to the previous one;

· codocytes – target cells – erythrocytes with a fovea in the center of red cell et all.

Poikylocytosis – different-shaped erythrocytes presence in one blood smear if discocytes level is less than 90% while other-shaped erythrocytes percentage is more than 90%. 

 

LIFESPAN AND FATE OF RED BLOOD CELLS

RBC life duration is 60-120 days (in males – on 10-20 days longer). They are formed in bone marrow from reticulocytes. At this stage reaching capillary wall is stretched, vessel is opened and Er are washed into blood stream, where they are transformed into young Er (normocytes) after 35-45 hours. Er die in liver, spleen. Destructed Er amount corresponds to formed Er amount. This closed system with all mass of Er circulating into organism received the name erythron.

Average lifespan of red blood cell is about 120 days in men and 110 days in women. The senile red blood cells are destroyed in reticuloendothelial system.

When the cells become older (120 days), the cell membrane becomes more and more fragile. The diameter of the capillaries is less or equal to that of red blood cell. The younger red blood cells can pass through the capillaries easily. However, because of the fragile nature, the older cells are destroyed while trying to squeeze through the capillaries. The destruction occurs mostly in the capillaries of spleen because the splenic capillaries have a thin lumen. So, the spleen is usually called graveyard of red blood cells. The destroyed red blood cells are fragmented. From the fragmented parts, the hemoglobin is released. The iron and globin parts of the hemoglobin are separated with the production of bilirubin. Iron combines with the protein-apoferritin to form ferritin, which is stored in body. Globin also enters the protein depot. The bilirubin is excreted by liver through bile.

Daily 10% red blood cells, which are senile, get destroyed in normal young healthy adults. This causes release of about 0.6 g% of hemoglobin into the plasma. From this 0.9 to 1.5 mg% bilirubin is formed.

DETERMINATION OF LIFESPAN OF RED BLOOD CELL

The lifespan of the red blood cell is determined by radioisotope method. The red blood cells are tagged with radioactive substances like radioactive iron or radioactive chromium. The life of red blood cell is determined by studying the rate of loss of radioactive cells from circulation.

FUNCTIONS OF RED BLOOD CELLS

1. Respiratory – O2 and CO2 transport. Erythrocytes transport oxygen from the lungs to the tissues. The hemoglobin in red blood cell combines with oxygen and 97% of oxygen is transported as oxyhemoglobin.Red blood cells transport carbon dioxide from the tissues to the lungs. The hemoglobin in red blood cell combines with carbon dioxide and form carbhemoglobin. About 30% of carbon dioxide is transported in this form.

2. Metabolic – participation in proteins, fats and carbohydrates, water and salts exchange. When Er passes into capillary arterial end, than it gives water and oxygen soluble in it id est wrinkles. On the contrary, it swells in venous end because it takes water, carbonic dioxide and metabolism products. Er help in plasma homeostasis support. It deals not only to salts but also to proteins. Hyperproteinemy is accompanied by proteins active absorbtion by Er, hypoproteinemy – proteins giving by Er into plasma. For example, fibrinogen is adsorbed on Er membrane if its level is more than 1,5 g/l in plasma. If fibrinogen content is diminished (for example, at intensive blood intravascular coagulation) than Er give fibrinogen into plasma. Er are glucose carriers.

3. Transport - oxygen, carbonic dioxide, aminoacids, proteins, enzymes, hormones, fats, carbohydrates, cholesterol, medicines, different biologically-active substances (proglandines, leucotrienes, cytokines et al.), microelements. For instance, aminoacids are transported by erythrocytes in bigger extent than by plasma.

4. Buffer (hemoglobin buffer).

5. Participation in iron metabolism.

6. Bile-formation regulation and participation in biliary pigments metabolism.

7. Antitoxic function.

8. Participation in vascular-platelet hemostasis, blood coagulation and fibrinolysis.

9. Red blood cells carry the blood group antigens like A agglutinogen, B agglutinogen and Rh factor. This helps in determination of blood group and blood transfusion.

10. Er play significant role in organism specific and nonspecific resistance (in part, antioxidant function, binding lg G and complement).

11. Er are erythropoiesis regulators because they contain erythropoietic factors that come into bone marrow at Er destruction and encourage Er formation.

ERYTHROPOIESIS is the process by which the origin, develop­ment and maturation of erythrocytes occur. Hemopoiesis is the process which includes origin, development and maturation of all the blood cells.

SITE OF ERYTHROPOIESIS

          IN FETAL LIFE

During embryonic life, the erythropoiesis occurs in three stages.

1) Mesoblastic stage: During the first two months of intrauterine life, the primitive red blood cells are produced from mesenchyme of yolk sac.

2) Hepatic stage: From third month of intrauterine life, liver is the main organ that produces red blood cells. Some erythrocytes are also produced from spleen and lymphoid organs.

3) Myeloid stage: During the last three months of intra­uterine life, the red blood cells are produced from red bone marrow and liver.

IN POSTNATAL LIFE AND IN ADULTS

In newborn babies, growing children and adults, the red blood cells are produced only from the red bone marrow.

1. Up to the age of 5 to 6 years: The red blood cells are produced in red bone marrow of all bones.

2. From the 6th year up to the 20th year: The red blood cells are produced by red bone marrow of long bones and all the membranous (flat) bones.

3. After the age of 20 years: The red blood cells are produced from all membranous bones like vertebra, sternum, ribs, scapula, iliac bones and skull bones and from the ends of long bones. After 20 years of age, the shaft of the long bones becomes yellow bone marrow because of fat deposition and looses the erythropoietic function.

During disorders of bone, the red blood cells are produced in spleen.

FIGURE 4: Stem cells. L-Lymphocyte. R-Red blood cell. N-Neutrophil. B-Basophil. E-Eosinophil. M-Monocyte. P-Platelet

STAGES OF ERYTHROPOIESIS

The various stages between stem cell and matured red blood cell are as follows (Fig. 5):

1. Proerythroblast

2. Early normoblast                      

3. Intermediate normoblast

4. Late normoblast

5. Reticulocyte and

6. Matured erythrocyte.

 

 

Erythrocyte Platelets Neutrophils Eosinophil Basophil Monocyte Lymphocyte

FIGURE 5: Stages of erythropoiesis. CFU-E = Colony forming unit— Erythrocyte, CFU-M = Colony forming unit— Megakaryocyte, CFU-GM = Colony forming unit— Granulocyte/Monocyte.

RETICULOCYTE

This is otherwise known as immature red blood cell. It is slightly larger than matured red blood cell. The cytoplasm contains the reticular network or reticulum formed by remnants of disintegrated organelles. Due to the reticular network, the cell is called reticulocyte. The reticulum of reticulocyte is stained by supravital stain.

In newborn babies, the reticulocyte count is 2 to 6%, i.e. 2 to 6 reticulocytes are present for every 100 red blood cells. The number of reticulocytes is reduced during the first week after birth. Later, the reticulocyte count remains constant at or below 1 % of red blood cells. The number may increase whenever there is increased production and release of red blood cells into the circulation.

The reticulocyte is also basophilic due to the presence of remnants of Golgi apparatus, mitochondria and other organelles of cytoplasm. During this stage, the cells can enter the capillaries through the capillary membrane from source of production. The cells enter the blood through the capillary membrane by means of a process called diapedesis.

MATURED ERYTHROCYTE

Now, the reticular network disappears and the cell becomes the matured red blood cell. The matured red blood cell is biconcave and it is smaller in size with a diameter of 7.2 microns. It attains the biconcave shape. It is with hemoglobin and without nucleus.

It requires seven days for the development of matured red blood cell from proerythroblast. It takes five days for the development of reticulocyte. The reticuloctye takes two more days to become the matured red blood cell.

FACTORS NECESSARY FOR ERYTHROPOIESIS

Various substances are necessary for the development and maturation of erythrocytes. These factors are classi­fied into 3 categories, namely:

a) General factors

b) Maturation factors and

c) Factors necessary for hemoglobin formation.

 

According to other classification, there are 2 main erythropoiesis ways:

1) specific – only due to erythropoietin action;

2) non-specific – due to:

· vitamins;

· microelements;

· hormones.

Specific and noon-specific regulatory ways belong to erythropoiesis humoral regulation.

GENERAL FACTORS

Erythropoiesis is influenced by a variety of general factors namely:

1. Erythropoietin

2. Hormones

3. Hemopoietic growth factors

4. Colony stimulating factors and

5. Vitamins

1. Erythropoietin

This is complex polypeptide. Its amount is increased at:

· bleedings;

· low oxygen partial pressure;

· ascent to height (in the mountains);

· muscular activity.

It is also called hemopoietin or erythrocyte stimulating factor. Erythropoietin belongs to the substances with relatively slow metabolism. Its half-duration life period in blood is more than 1,5 hours. About 10% of circulating erythropoietin is released from organism wih urine. Erythropoietin daily excretion with urine comprises 0,9-4,0 Activity Units.

Chemistry

Erythropoietin is a glycoprotein containing syalic acids. Its molecular weight is 46000 Da. It is synthesized in the form of pro-erythropoietin (193 amino acids) without specific activity. It comes in plasma in unactive state wher under specific enzyme – erythrogenin – action – is transformed into active erythropoietin (it consists of 168 amino acids).

Source of Secretion

Erythropoietin is secreted by peritubular capillaries of kidneys (juxta-glomerular apparatus mainly but epitheliocytes as well), uterus, salivary glands (especially submandibular ones), monocytes-macrophages, liver (during embryogenesis). Macrophagal erythropoietin is of huge importance in erythropoiesis regulation because of central position of macrophages-monocytes in bone marrow erythroid insulas. Macrophage feeds erythroid insula with erythropoietin, ferritin, iron, vitamins and other substances. Such erythroid insulas begin their presence from the term of erythropoiesis in yolk sac.

Stimulant for Secretion

Hypoxia is the stimulant for the secretion of erythropoietin. Hypoxy is accompanied by enzymes activation in kidney structures (they are sensitive to hypoxy). Phospholipase A2 releasing leads to prostaglandins E1 and E2 increasing, than adenylatecyclase level rising up and finally cAMP concentration and activity increasing in kidney peritubular cells producing erythropoieitn. Epinephrin and norepinephrin also increase cAMP and cGMP level in kidneys.  

Actions of Erythropoietin

Erythropoietin causes formation and release of new red blood cells into circulation. After secretion, it takes 4 to 5 days to show the action. The hormone promotes the following processes:

1. Production of proerythroblasts from the stem cells in CFU-E of the bone marrow.

2. Development of proerythroblasts into matured red blood cells through the normoblastic stages—early, intermediate and late normoblasts and reticulocyte.

3. Release of matured erythrocytes into blood through the capillary membrane from bone marrow. Even some reticulocytes (immature erythrocytes) are released along with matured red blood cells.

4. It stimulates synthesis of DNA-dependent RNA.

5. Rhibosomal RNA synthesis starts in 15 min after the cell contact with erythropoietin, DNA – in 2 hors, ferritin-containing proteins – in 4 hours.

6. The result of cellular metabolism change is erythroid cells proliferative and hemoglobin-synthesizing ability enforcement.

7. Increasing blood stream in vessels surrounding erythropoietic tissue in bone marrow.

8. Reticulocytes exit increasing from bone marrow sinusoids into blood.

9. Mitosis number increasing in erythroid cells row.

10. One or several mitotic cycle excluding.

 

It is very important that the specific erythropoietin-binding receptor structure was deshiphrated by the scientists.

 

Synthesis regulation

It is realized at the genetic level. The 7th chromosome is responsible for this. Kidney structure sensitive to hypoxy represents hem-containing protein (hemoprotein) of peritubular cells binding oxygen molecule. Hemoprotein oxyform inhibits transcription of genes responsible for erythropoietin at sufficient oxygenation. On the contrary, hemoprotein deoxyform lacks its oxygen molecule, its affinity to the gene-operator is decreased and erythropoietin synthesis is activated.

Main regulator of erythropoietin production is oxygen level in blood or, if to be more exact, blood oxygen availability for tissues depending, in turn, on:

- oxygen level in blood;

- hemoglobin ability to give oxygen;

- tissues increased needs.

Erythropoietin production is stimulated in mountains where pO2 is decreased in atmospheric air as well as bleeding decreasing blood oxygenous capacity.

Erythropoietin content is 0,01-0,08 IU/ml in a human being plasma. But it can rise in 1000 and more times at hypoxy. Erythropoetin has 2 forms alpha- and beta- than are differed only by carbohydrates number and possessing practically equal biological activity.

2. Hormones:

· Thyroxine - in addition to erythropoietin, thyroxine also forms an important general factor for erythropoiesis. Thyroxine accelerates the process of erythropoiesis at many levels. In hyperthyroidism, polycythemia is common.

· Hypophyseal erythropoietical hormone, ACTH, STH - enforce erythropoiesis.

· Suprarenal glands – glucocorticoids, adrenaline - enforce erythropoiesis.

· Parathyroid - parathormone - enforces erythropoiesis.

· Female sexual organs – erythropoiesis weakening.

· Male sexual organs - enforce erythropoiesis.

3. Hemopoietic Growth Factors

Hemopoietic growth factors or growth inducers are the interleukins and stem cell factor (steel factor). Generally these factors induce the proliferation of pluripotent stem cells.

Interleukins (IL) are glycoproteins which belong to the cytokines family. The interleukins involved in erythropoie­sis are.interleukin-3 (IL-3), interleukin-6 (IL-6) and inter-leukin-11 (IL-11). IL-3 is secreted by T lymphocyte. IL-6 is secreted by T lymphocytes, endothelial cells and macrophages. IL-11 is secreted by osteoblasts.

4. Colony Stimulating Factors

The colony stimulating factors (CSF) cause the forma­tion of colony forming blastocytes. There are three types of colony stimulating factors.

1) Granulocyte CSF (G-CSF) secreted by monocytes and endothelial cells.

2) Granulocyte-Monocyte CSF (GM-CSF) secreted by monocytes, endothelial cells and T lymphocytes

3)  Monocyte CSF ( M-CSF) secreted by monocytes and endothelial cells.

5. Vitamins

Some vitamins are also necessary for the process of erythropoiesis. The deficiency of these vitamins cause anemia associated with other disorders. The vitamins, which are necessary for erythropoiesis are:

Vitamin B: Its deficiency causes anemia and pellagra.

Vitamin C: Its deficiency causes anemia and scurvy.

Vitamin D: Its deficiency causes anemia and rickets.

MATURATION FACTORS

Vitamin B12, intrinsic factor and folic acid are necessary for the maturation of red blood cells.

1.Vitamin B12 (Cyanocobalamin)

This is essential for maturation of erythrocytes. The deficiency of vitamin B12 causes pernicious anemia. So, Vitamin B12 is called antipernicious factor.

Source of Vitamin B12

Vitamin B12 is called extrinsic factor because it is obtained mostly from diet. Its absorption from the intestine requires the presence of intrinsic factor of Castle. Vitamin B12 is stored in the liver and muscle (mostly liver). Where necessary, it is transported to the bone marrow to promote maturation of red blood cells. It is also produced inthe large intestine by the intestinal flora.

Action of Vitamin B12

Vitamin B12 is essential for synthesis of DNA. Its deficit leads to failure in maturation of the cell and reduction of the cell division. Also, the cells are larger with fragile and, weak cell membrane.

Intrinsic Factor of Castle

This is produced in gastric mucosa. This is essential for the absorption of vitamin B12 from intestine into the blood. In the absence of intrinsic factor, vitamin B12 is not absorbed. This happens in severe gastritis, ulcers and gastrectomy. The deficiency of intrinsic factor also causes pernicious anemia since the vitamin B12 is not absorbed. The extrinsic and intrinsic factors are together call Hematinic principle.

3.Folic Acid

This is also essential for maturation. This is required for the synthesis of DNA. In the absence of folic acid, the synthesis of DNA is reduced causing failure of maturation. This leads to anemia in which the cells are large and appear in megaloblastic (proerythroblastic) stage. And the anemia due to the folic acid deficiency is called megaloblastic anemia.

FACTORS NECESSARY FOR HEMOGLOBIN FORMATION

Various materials are essential for the formation of globin in the red blood cells. The deficiency of the substances decreases the production of hemoglobin leading to anemia.

These factors are as follows:

First class proteins and amino acids: Proteins of highly biological value are essential for the formation of hemoglobin. Amino acids derived from these proteins are required for the synthesis of protein part of hemoglobin, the globin.

Iron: Iron is necessary for the formation of heme part of the hemoglobin.

· Copper: This is necessary for the absorption of iron from the gastrointestinal tract. when copper absence RBC maturate only till reticulocytic stage.

Cobalt and nickel: Cobalt and nickel are essential for the utilization of iron during hemoglobin formation.

Vitamins: Vitamin C, riboflavin, nicotinic acid and pyridoxine are also essential for the formation of hemoglobin.

 

Vitamins action can be described as follows:

Vitamins: of B-group are the most essential:

· B12 (cyancobalamine) - haemopoiesis factor. It is synthesized by microorganisms, ray fungi and some weads. Cobalt is essential for cyancobalamine formation. This vitamin comes into human organism with liver, meat, eggs. This vitamin takes part in haemoglobin synthesis. It is accumulated into liver; its depot is very large (for 5-10 years).

· B9 (folic acid) – is contained in plant food, liver, eggs. It participates in globin synthesis influencing on erythroblasts.

· B6 (pyridoxine) catalyzes folic acid formation and cyancobalamine action.

· B2 (rhibophlavine) participates in iron consumption, it also is necessary for hemoglobin synthesis.

· C (ascorbic acid) – encourages iron releasing from intestine and regulates hemoglobin synthesis.

· A (retinol) and E (tocopherol) – influence on hemopoietic tissue functions, protect Er membrane from free radicals action.

 


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