Physiology of blood. Physiology of erythrocytes. Respiratory pigments
Carried along in the fluid portion of the blood are tiny red cells so numerous that the blood itself appears red. These cells are called erythrocytes. As they arise in the red marrow of bone, they are nucleated and are called erythroblasts, but shortly before entering the bloodstream, they lose the nucleus and become highly specialized cells, that is, red corpuscles. Their size is fairly constant at about 7,5 to 8,6 microns or an average 7,55 microns in diameter and about 2 microns thick (1 micron equals 1/1000 of a millimeter, or 1/25000 of an inch). The red cell is a biconcave disk, thinner in the middle than at the edge. When observed singly under a microscope by transmitted light, the cells are only faintly colored. Individually they appear slightly yellowish in color.
A chemical factor called erythropoietin controls the production of erythrocytes. The source of the humoral factor is not known, although some evidence indicates that it is formed in the kidneys or by macrophags.
The number of erythrocytes per liter of blood is usually stated as (4,0-5,1)·1012 for men and (3,7-4,7)·1012 for women. It is well known, however, that active young men frequently have more red cells per cubic millimeter. A more accurate estimate, therefore, would be 5450000 red cells per cubic millimeter for men and 4750000 for women. The blood-cell count is also higher in a newborn infant ((5,9-6,7)·1012/L) than it is in older children or adults.
HEMOGLOBIN. Erythrocytes derive their color from a complex protein called hemoglobin. Thus is substance is composed of a pigment, heme, containing iron, and the protein globin. Hemoglobin has the power to attract oxygen molecules and to hold them in a loose chemical combination known as oxyhemoglobin. It is said, therefore, to have a chemical affinity for oxygen. The structure of the hemoglobin molecule has been successfully analyzed by x-ray diffraction and chemical methods. It consists of four folded polypeptide chains of amino acid units. The four chains form the globin, or protein, part of the molecule. In addition there are four atoms of iron, each associated with a pigment, or heme, group of atoms. The heme group provides the red color of the blood and also its oxygen-combining ability. The iron atoms are bivalent or in the ferrous state. It has been estimated that one erythrocyte contains approximately 280 million molecules of hemoglobin (Perutz).
As the blood passes through a capillary network in the thin air sacs of the lungs, oxygen enters into a loose chemical combination with hemoglobin (oxyhemoglobin) and is carried to the tissues. There, as the blood passes through tissue capillaries, the hemoglobin loses oxygen to the tissues and is then referred to as reduced hemoglobin. Arterial blood, after passing through the lungs, is a somewhat brighter red than that found in the veins, but venous blood is never blue. The blue color of veins close to the surface is due to the absorption of red and yellow rays of light and the reflection of blue and green light. Erythrocytes not only function to carry oxygen to the tissues, but indirectly they also function in carrying carbon dioxide away from the tissues.
Anemia. A condition of the blood in which there is a reduction of the number of red cells or reduced hemoglobin is known as anemia.
Often both the red-cell count and the percentage of hemoglobin are reduced. The typical patient with anemia appears pale and weak and has a loss of energy. The oxygen-carrying capacity of the blood is reduced by the loss of hemoglobin.
There are many kinds of anemia. Basically anemia can be caused by inability of the body to manufacture enough hemoglobin or failure of the red marrow of bone in the production of erythrocytes. In the first type there is a lack of an adequate amount of iron in the diet or its absorption and utilization in the production of hemoglobin. In this type of anemia the number of red cells may be normal, but the percentage of hemoglobin is greatly reduced. Occasionally anemia is caused by an abnormal rate of destruction of red cells from chronic bleeding or from some hemolytic substance in the blood.
The failure of the red marrow of bone in the production of erythrocytes results in a very low red-blood-cell count, but individual cells may be normal or large and contaiormal or even above normal amounts of hemoglobin. Pernicious anemia is essentially of this type. Great progress has been made in understanding and treating anemia. The discovery of an antianemic factor in liver has proved of great benefit to victims of pernicious anemia and similar forms. The understanding of the relation between the erythrocyte maturation factor and vitamin B12 has helped greatly in interpreting the factors involved. The reader is referred to discussions of pteroylglutamic acid and vitamin B
Sickle-cell Anemia. We have seen that normal adult hemoglobin A (Hb A) is composed of four polypeptide chains and also contains four heme groups. The four polypeptide chains consist of two alpha chains and two beta chains. The number and location of the amino acids composing each chain has been determined: each alpha chain contains 140 amino acids, and each beta chain consists of 146.
In 1949 Linus Pauling and his coworkers discovered an bnormal hemoglobin (Hbs ) associated with an inherited defect. When the defect is present as a homozygous recessive, nanv red cells of the, blood exhidit a peculiar elongate appearance called sicklindsi. The abnormal cells are rapidly destroyed, giving rise to a condition called sickle-cell anemia. The blood of heterozygous individuals (HaHs) may show some sickling, but these individuals are essentially normal and are not subject to sickle-cell anemia. They do, however, carry the sickle’cell trait. Their hemoglobin is about 60 percent normal Hba and 40 percent Hbs. Sickled cells are not very efficient oxygen carriers although those individuals with sickle-cell trait do not suffer any great deficiency.
It is of considerable interest to geneticists, physiologists, and biochemists that the only chemical difference between the hemoglobins of
THE HEMOCYTOMETER It is possible to make a fairly accurate estimate of the number of red cells per cubic millimeter by actually counting a limited number of cells as they are spread out on a ruled microscope slide called a hemocytometer. This is a glass slide ruled so that in the center there are squares that measure 1/20 by 1/20 of a millimeter. The counting area has a depth of 1/10 of a millimeter.
1. Common characteristic of blood
The blood affords a pathway for the transportation of oxygen and nutrient fluids to cells that are often at a considerable distance from the heart, lungs, or digestive tract. It enables tissues to rid themselves of waste materials even though the tissues are located in the feet or hands and relatively far away from the kidneys. The blood is commonly considered to be a liquid tissue, one in which the intercellular structure is liquid rather than composed of fibers or a more or less solid substance. The circulatory system is concerned with conducting the blood through a series of tubes (arteries, veins, capillaries) to the tissues. The heart acts as a pump to supply the motive force.
Blood is a fluid connective tissue. Blood consist from the plasma and blood cells – erythrocytes, leucocytes and platelets.
Plasma is blood fluid, which has water, organic and nonorganic substances. Erythrocytes is a red blood cells, which contents hemoglobin.
Blood system first was proposed by Lung in 1936. It consist from:
– blood circulated through the circulatory system
– blood forming organs
– blood destroyed organs
– regulatory apparatus.
2. Functions of blood
Most persons are aware that the blood carries oxygen, carbon dioxide, nutritive elements, products of metabolism, hormones and waste materials, but they are commonly unaware that the blood also has many other functions: thermoregulation, maintaining the acid-base balance of the tissues, supporting of oncotic and osmotic pressure, to form a clot, plays an important part in protecting the body from bacteria and other organism that can cause disease or other abnormal conditions. Following is a brief listing of some of the more evident functions.
1. It is the medium by which oxygen is transported from the lungs to the tissues. This is the breathing function of blood by which take place tissue metabolism.
2. Carbon dioxide, a product of the metabolism of cells, is transported from the tissues to the lungs. This is the breathing function of blood which help to carry out products of metabolism.
3. Nutrient materials are absorbed from the intestine and carried to the tissues. This is trophic function of blood.
4. Many organic substances that represent breakdown products of metabolism (urea, uric acid, creatinine, purine wastes) are carried by the blood to the kidneys for excretion. This is excretory function of blood.
5. Hormones, the secretions of ductless or endocrine glands, are distributed throughout the body by the bloodstream. This is a function of hormonal regulation.
6. Like a hot-water heating system in a house, the blood flows from the deeper and warmer parts of the body to the extremities and tends to distribute heat more evenly to all parts of the body. Surface blood vessels in the skin can be dilated so that more blood can come to the surface, thus losing heat more readily, or surface vessels can be constricted to keep more blood away from a cold exterior and thus reduce heat loss. The blood, therefore, is important in the regulation of body temperature. This is the function of temperature regulation.
7. The blood plays an important part in maintaining the acid-base balance of the tissues. Most of the tissues, including the blood, are slightly alkaline in their reaction. The pH of arterial blood is between 7,35 and 7,45. While the metabolism of the body constantly produces numerous acids and acid substances, the tissues themselves and the body fluids remain remarkably constant at a pH that Is a little on the alkaline side.
Metabolic processes commonly form acid products; hence there is a tendency to emphasize the buffering action of alkaline substances against these acid products. Carbonic acid is a weak acid, which is readily neutralized by the bicarbonate of the blood. Carbonic acid breaks down into carbon dioxide and water.
Since CO2 constantly formed in metabolism is regularly eliminated through the lungs, its influence on the acidity of the blood is greatly reduced. The pH of the blood changes very little as the result of acids taken into the bloodstream. Sodium bicarbonate acts as an alkaline reserve to protect the body from the acids produced by its own metabolic processes. Another factor in maintaining the chemical acid-base balance of the blood is the fact that acid substances buffered in the blood are constantly removed by the kidneys. This is a function of supporting the base-acids balance.
8. There is a constant relationship between blood volume and the fluid content of the tissues. The capillary wall acts as a selectively permeable membrane, permitting a constant filtration into the tissues of water molecules and other substances in solution. Small molecules, such as those of oxygen, glucose, or amino acids, pass through the capillary wall readily, but larger protein molecules pass through very slowly, if at all. Filtration, in this case the movement of water and dissolved substances out of the blood stream, is aided by capillary blood pressure.
The blood also contains a number of proteins in colloidal state that tend to attract fluid from the tissues into the bloodstream and hold it there. Food proteins in the process of digestion are broken down to amino acids and absorbed in this form. Recent investigation Indicates that amino acids can enter into the formation of plasma protein, including albumin and globulin. Plasma protein plays an important part in building up osmotic pressure if osmosis is Interpreted as the movement of water through the capillary wall toward the protein. After severe loss of blood, water moves from the tissues into the bloodstream, and the volume of the blood may be quickly restored in this manner. The blood in this case is able to draw on a water reserve normally held in the tissues. This is a function of supporting the water-electrolitic balance.
9. The ability of the blood to form a clot and so reduce bleeding has been of survival value to animals and man. The mechanism of clot formation will be discussed later in the chapter. This is a hemostasis function.
10. The blood plays an important part in protecting the body from bacteria and other organism that can cause disease or other abnormal conditions. Some kinds of white blood cells afford protection by ingesting bacteria or other foreign matter appearing in the blood stream. Another phase of protection is acquired resistance to infections, or acquired immunity. It is well known that in many types of infections the body develops defensive mechanisms that overcome bacteria or neutralize their toxic effects.
The protein fraction of the blood plasma that has become well known through its use in combating disease is gamma globulin. It is the fraction of the blood that contains most of the known antibodies and can be used to combat certain, diseases, such as measles. Its removal from blood plasma does not materially reduce the effectiveness of plasma in the treatment of injuries resulting from wounds or in the treatment of shock. The source of supply, therefore, comes largely from blood donated for emergency uses rather than for combating disease.
It is known that, in the general population, many persons have had various diseases and have developed antibodies against them. The chemical fractionation of pooled blood removes gamma globulin containing these antibodies. When injected into a susceptible person, a specific antibody can give passive protection for a few weeks in the case of a disease such as measles. This procedure can be used to protect susceptible children during local epidemics.
The blood does not always carry substances beneficial to the body. It also can be a pathway for foreign substances that can have a deleterious effect. Alcohol and other drugs, some venom, the metastases of cancer, certain parasites, some forms of bacteria, and toxic substances in general are distributed by way of the bloodstream. This is a protective function of blood.
3. Components of blood
Plasma
Water – 90 percent
Solids – 10 percent
Inorganic chemicals: sodium, calcium, potassium, magnesium, chloride, bicarbonate, phosphate, sulfate – 0,9 percent
Organic chemicals:
Proteins: serum albumin, serum globulin, fibrinogen – 8 percent
Others: – 1,1 percent
Nonproteiitrogenous substances: urea, uric acid, creatine, creatinine, ammonium salts, amino acids
Nonnitrogenous substances: glucose, fats, cholesterol hormones
Gases: oxygen, carbon dioxide, nitrogen
Cells: erythrocytes, or red cells; leukocytes, or white cells; blood platelets, or thrombocytes
Plasma. The liquid portion of circulating blood is called the plasma. It is a straw-colored fluid, very complex chemically, containing a wide variety of substances. The red cells, white cells, and blood platelets float in this liquid medium. In this respect the blood can be regarded as a liquid tissue; it contains cells, but the intercellular substance is liquid rather than some more substantial material.st of the functions of the blood previously mentioned affect the plasma directly. Even though the blood is continuously engaged in transporting absorbed food products and receiving the waste products of cell metabolism, its chemical content is fairly constant. The plasma is about 90 percent water; the remaining 10 percent of materials in solution make blood thicker than water, as the saying goes. Its specific gravity is greater than 1, more nearly 1,025 as an average.
The blood and tissue fluids have been called the internal environment. The concentration of inorganic salts in the internal environment resembles that found in sea water, which constitutes the external environment for a great many animals. It is considered by many that life arose in the sea and that a great deal of development took place there. The salt ions of the blood are mostly chloride, bicarbonate, phosphate, and sulfate of sodium, calcium, potassium, and magnesium. Physiologists have known since the experiments of Sydney Ringer were published, in the period around 1885, that there is a salt balance in the blood. Physiological salt solutions are used to maintain the internal environment of experimental animals during demonstrations, operations on animals, and various other laboratory procedures.
Ringer’s solution has many modifications, but it is essentially as follows:
This solution, or a modification of it, is used more often as a physiological solution for invertebrates and for some vertebrates such as amphibians.
A more recent modification is the Ringer-Locke solution, used especially in mammalian physiology. Since the total salt concentration is higher in the blood of mammals than in lower classes of verte-tes, the Ringer-Locke solution has a higher salt concentration more nearly equal to that of mammalian blood. Through their buffering action, the salts of the blood aid in maintaining an acid-base balance between the blood and the tissues; they are also concerned in maintaining water balance in order that blood cells and tissue cells can carry on their physiological processes in a normal manner.
Nonproteiitrogenous substanceas found in the blood include urea, uric acid, creatine, creatinine, and ammonium sats. These substances represent breakdown products of protein metabolism and are carried by the blood to the organs of excretion.
Protein foods are reduced to amino acids during the process of digestion and are absorbed as such. Amino acids, the building blocks for all proteins found in the body, are therefore present in the blood plasma.
Glucose (or blood sugar), fats, and cholesterol are nonnitrogenous substances present in the blood. Glucose is a simple sugar derived by digestion from more complex sugars. It is absorbed from the intestine and transported to the liver, where much of it js stored as a complex polysaccharide called glycogen. A considerable amount of glucose is absorbed from the blood and stored as glycogen in muscle tissue also.
While the role of glucose iutrition is well recognized, it also acts as a physiological constant in the blood. The sugar level of the blood is fairly constant at an average concentration of about 4,44-6,66 mmol/L. A reduction in the blood sugar level may cause weakness, fainting, or more serious consequences. The kidneys excrete sugar if the sugar level of the blood becomes too high.
Fats are carried by the blood, as well as several fatlike substances, such as cholesterol, and the phospholipids or phosphatides.Fats are absorbed largely by way of the lymphatic system. They break down during digestion into glycerol and fatty acids. The fatty acids are possibly converted into phospholipids before they are absorbed. Cholesterol is.distributed in tissues throughout the body but is found in considerable concentration ierve tissue, adrenal glands, and skin. It is excreted in the bile.
The blood plasma contains hormones, the secretions of ductless glands. It also contains the chemical substances concerned wjth the clotting of the blood.While dissolved gases are transported by the blood, oxygen and carbon dioxide are more closely related to the hemoglobin of red cells, as we shall see later. Only a small amount of carbon dioxide is carried in solution as carbon dioxide, even though it is continuously produced as a waste product of metabolism and constantly absorbed by the blood. After forming carbonic acid, it is buffered by hemoglobin and salts such as sodium phosphate, which remove carbonic acid as such by entering into chemical combination with it. Hemoglobin is one of the chief substances concerned in the transportation of both oxygen and carbon dioxide. Nitrogen is carried in the plasma as an inert gas.
One liter of plasma has 65-
Plasma which are not contain fibrinogen called serum (it is necessary for understanding the immunology, therapy etc.)
Physiological meaning of protein.
Albumins: on 80 % it provide oncotic pressure, contact with bilirubin, fat acids, antibiotics, sulfanilamids. It connect with them and transport them. It produce in liver in average quantity of
Globulins produce in lymphatic nodes, in liver, in bone marrow in average quantity of
Alpha-1-globulins connected with carbonhydrates (for example 2/3 of all glucose connected with alpha-1-globulins. This is glycoproteids.)
Alpha-2-globulins connect 90 % of cupper. This is cerruloplasmin. Its may produced in hormons, for example, thiroxin, connected by vitamin B12. From this protein produce angiotensin (substensis which are take plase in increase of blood pressure).
Beta-globulin carry out 75 % of fats, iron (for examlpe, transferrin).
Gamma-globulins has protective functions (for example, antibodies).
Fibrinogen is a protein which are produced by liver and take place in hemostasis system. Fibrinogen is dissolved form, which transform in insolved form – fibrin and provide coagulative hemostasis (thromb production) and prevent bleedless.
4. Buffer’s system of blood.
A normal person’s arterial pH (pHa) is about 7,40, and this pHa must be kept constant if normal enzyme function is to be maintained. Even extremely small pH deviations lead to weakness and general physiological disability, and further deviations lead to collapse, coma, and death. In fact, the pHa range consistent with human life is only about 6,8 to 7,8, and the normal, healthy person’s pHa at sea level probably never differs from 7,4 by more than 0,15 pH units.
Much of the explanation for why the pHa range consistent with life seems so small derives from the units with which we express it. Physicians and other scientists frequently use logarithms to make large ranges easier to work with. So pH is defined thus:
pH = -log [H+]
A pHa of 7,40 represents a [H+]a of 40×10-9 Eq/L, or 40 nEq/L. The range of pHa consistent with life would represent [H+]a of 15,8 to 158 nEq/L, or a tenfold variation of [H+]a. There are few important substances whose arterial blood concentration could change by a factor of 10 without being life threatening.
The Henderson-Hasselbalch equation relates the pH of a solution with the pKa of a given buffer system and the concentrations of its ionized [A–] and un-ionized [HA] forms at equilibrium:
pH = pKa + log[A–]/[HA]
Thus, for any given buffer system, the ratio of [A–]/[HA] defines a unique pH. Further, in a solution with many buffers, the various [A–]/[HA] ratios must all be consistent with the solution’s pH. Therefore, it is possible to assess the acid-base status of a fluid sample by determining [A–] and [HA] for any buffer system, and using that knowledge together with the pKa of that buffer system. This was the procedure employed before the modern pH electrode came into common use, and it is still a method of choice in assessing acid-base status in fluids not easily reached by a pH electrode (e.g., intracellular fluid). Now that the pH electrode is commonly available and quite dependable, one can simply measure pH and one of the other two variables ([A–] or [HA]) and then calculate the remaining one.
The buffer system that is almost invariably utilized when assessing the acid-base status of human blood is the CO2/HCO–3 system. This is so for at least three reasons: (a) its components are in reasonably high concentration and are easy to analyze; (b) metabolism pours a steady stream of CO2 into the body, and the acid-base disturbance of considerable magnitude is therefore unavoidable if the mechanisms involved in the removal of that CO2 malfunction; and (c) perhaps most important, the acid-base balance of the body is maintained through the control of the two components of this system – the lungs control Pco2 through the control of alveolar ventilation, and the kidneys control [HCO–3]. Thus, the Henderson-Hasselbalch equation for this system might be functionally written, pH=pK+log[kidneys]/[lungs], to emphasize this very important third reason.
Most of the tissues, including the blood, are slightly alkaline in their reaction. The pH of arterial blood is between 7,35 and 7,45. While the metabolism of the body constantly produces numerous acids and acid substances, the tissues themselves and the body fluids remain remarkably constant at a pH that is a little on the alkaline side. The principal reason for this chemical stability is the fact that the blood contains a number of alkaline substances; the chief of these is sodium bicarbonate. Weak acids produced by metabolic processes are constantly buffered by alkaline substances in the blood and in the tissues, while excess alkalinity is buffered by acids. A buffer solution contains substances that afford a reserve of alkalinity and acidity. If a weak acid or base is added to the solution, either substance is buffered by the appropriate reserve substance and a state of chemical equilibrium are maintained. There are four blood buffer system: bicarbonate, phosphate, protein and hemoglobin.
Principles of buffer work. Each buffer consist from weak (feeble) acid and salt of this acid and strong base. Buffer effect caused by connection and keep out ions, which are arrive, by corresponding combination of buffer. In human organism in different condition excel in blood acids products of metabolism, for example, lactic acid, carbon dioxide, etc. That is why factors which has opposite properties of acids properties of buffer system predominate over factors which has opposite properties of bases.
Bicarbonate blood buffer system are the most mobile and rather strong. It connect with the breathing. These system consist from H2CO3 and NaHCO3, which are present in corresponding proportion. Principles of bicarbonate blood buffer work is when into organism get the acid, which are stronger than carbonate (H2CO3), form feeble dissociation carbonate (H2CO3) acid.
Н2СО3 + ОН– ⇄ НСО3– + Н2О
НСО3– + Н+ ⇄ Н2СО3
The activity of this processes are the most in lungs, where the CO2 immediately take out. That is why the concentration of CO2 in blood support in the constant level. That is why pH of blood support in the constant level too.
When into organism get the base form reaction with acid. Connection of HCO–3 drive to despair of CO2 and decrease the secrete of it through the lungs.
increase Н+ deficite of Н+
НСl + NаНСО3 ⇄ NаСl+Н2СО3 ⇄ Н2О + СО2 + Na+ + Сl–
eliminate excrete
by lungs by kidney
Phosphate buffer system (form near 5 % of all buffer capacity) is the mix of one- and two-substitute acid phosphate sodium (NаН2РО4 і Nа2НРО4), where properties of acid has NаН2РО4 and properties of base has Nа2НРО4. The first has a property of weak acid, second has a property of weak base. Acids and bases, which are get into blood, connect with one of the component of buffer system, that is why рН of blood is constant.
Н2РО4– + ОН– ⇄ НРО42– + Н2О
Н2РО42– + Н+ ⇄ Н2РО4–
The capacity of phosphate buffer system is not very big.
Protein buffer system – protein/proteinat neitralisate acids and bases due to presents of amphoteric properties: with the acids they connect in reaction as bases, with the bases as acids.
РtСООН + ОН– ⇄ РtСОО– + Н2О
РtСОО– + Н+ ⇄ РtСООН
Hemoglobin buffer system is the strongest buffer system (more than 50 % of all buffer capacity of blood). System of hemoglobin-oxyhemoglobin has buffer act that is why the oxyhemoglobin in 80 time more acids that renew. Passing of oxide form in redox form prevent moving of blood рН in acid side during it contact with tissues, where it enrichment by Н2СО3. Forming of oxyhemoglobin in lungs capillaries prevent movement of this blood reaction in base side at the expence of moving СО2 and Сl– from erythrocytes in blood plasma and forming NаНСО3. Lungs are regulated educe of СО2 and absorb of О2.
KHb + H2CO3 ⇄ HHb + KHCO3
Value of buffer systems’ work carry out by following indexes:
pH – 7,35-7,54
AB (actual bicarbonate) – 19-25 mEq/L
SB (standard bicarbonate) – 20-27 mEq/L
BB (base buffer) – 40-60 mEq/L
BE, BD (buffer excess, buffer deficit) – ± 2,3 mEq/L
