Gad El - Mawla A. Gad.
Professor of Physiology
COLLEGE OF APPLIED MEDICAL SCIENCES
KING SAUD UNIVERSITY
Blood is a complex reddish fluid which circulates continuously inside the cardiovascular system. Blood has many important functions which are essential for life. So, sudden loss of 30% of the total volume of blood leads to death.
Functions of the blood:
1- It transports:
- O2 from the lungs to the cells of the body.
- CO2 from the cells of the body to the lungs.
- Nutrients from the digestive system to the cells of the body.
- Waste products from the cells of the body to the excretory organs: Kidneys, lungs, sweat glands, liver and large intestine.
- Hormones from the endocrine glands to the cells of the body.
- Enzymes and vitamins to various cells.
2- It regulates:
- The pH of the blood through the buffer systems..
- The body temperature through helping the heat loss from the skin and distributing the heat gained from the active organs.
- The water content of the cells.
3- It protects the body against:
- Blood loss from injured blood vessels by formation of platelet plug and blood clot.
- Toxins and foreign microbes through its content of immune system.
Physical properties of blood
Colour: Arterial blood is bright red in colour due to presence of oxyhaemoglobin, while venous blood is dark (or bluish) red in colour due to presence of reduced hemoglobin.
Specific gravity: It is about 1060 for the whole blood, 1090 for blood cells and 1030 for plasma. ( Specific gravity of water: 1000)
Viscosity: Blood is a viscous fluid. In males it is about 3 – 4 times as viscous as water. Blood viscosity is slightly less in females and more less in children. Blood viscosity is due to red blood cells and plasma proteins. Blood viscosity is an important part of the peripheral resistance which is necessary for maintaining blood pressure at normal level.
Osmotic pressure: It is due to crystalloid and colloid contents. The crystalloid osmotic pressure is about 5000 mm Hg (6.7 atmospheres) and is mainly due to NaCl in plasma. The colloid osmotic pressure is 25 – 30 mm Hg and is due to plasma proteins (mainly albumin).
Composition of blood
Blood is composed of cells and cell like structures suspended in a clear yellowish fluid called the plasma.
A) Blood cells and cell like structures: (45% of the blood volume)
1. Red blood cells (R.B.Cs) or erythrocytes: Their normal count is 5.0 – 5.5 million / mm3 in adult males and 4.5 – 5.0 million / mm3 in adult females.
2. White blood cells (W.B.Cs) or leucocytes: Their normal count is 4.000–11.000 / mm3.
3. Platelets or thrombocytes: Their normal count is 150.000 – 400.000 / mm3.
B) Blood Plasma: (55% of the blood volume)
Plasma is a clear yellowish fluid forming about 55% of the total blood volume or 4 – 5% of the body weight (average 3000 – 3500 ml in adult males). It is the fluid portion of the blood in which the blood cells are suspended and circulated through the body.
Plasma is a part of the extracellular fluid of the body. It is almost identical to the interstitial fluid present between the tissue cells except for one major difference; plasma contains about 7% proteins, while interstitial fluid contains an average of only 2-3% proteins. The reason for this difference is that plasma proteins diffuse only slightly through the capillary pores into the interstitial spaces.
Composition of plasma:
Plasma is composed of 90% water and 10% solids.
The solid content of plasma (10%) are:
A) Organic substances (9%):
1. Plasma proteins (7%): Plasma proteins are, albumin (4%), globulins (2.7%) and fibrinogen (0.3%).
2. Other organic substances (2%): Metabolic end products e.g. urea, uric acid, creatine and creatinine. Nutritive substances e.g. glucose, amino acids, fatty acids and glycerol. Regulator substances e.g. enzymes, hormones, and vitamins which regulate metabolism and growth of the body.
B) Inorganic substances (1%):
Inorganic salts: Cations include, Na+ , K+ , Ca++ & Mg++, Anions include, Cl- , HCO3- , HPO4-- , SO4--, Respiratory gases: O2 and CO2.
Plasma protein concentration 6.0 – 8.0 grams %. Plasma proteins are divided into:
1. Albumin: (3.5 – 5.0 gm%). It is formed in the liver.
2. Globulins: (2.0 – 3.5 gm%). They are subdivided into alpha (a1 & a2), beta (b1 & b2) and gamma (g) globulins.
3. Fibrinogen: (0.2 – 0.4 gm %) It is has formed in the liver and plays an essential role in blood clotting.
Albumin / Globulin (A/G) ratio:
It is the ratio of albumin to globulins in plasma. Normally it ranges from 1.1 to 1.8. It decreases in cases of decreased plasma albumin or increased globulins.
A- Decreased plasma albumin results from:
1- Excessive loss of albumin: from kidney ( as in chronic renal disease) skin ( in cases of severe burns), intestine ( as in case of protein losing enteropathy).
2- Decreased synthesis: as in cases of chronic hepatitis, malnutrition, prolonged starvation.
3- Increased catabolism: as in cases of fevers, hyperthyroidism and Cushing syndrome.
B- Increased immunoglobulin synthesis as in:
Chronic inflammatory states as in chronic hepatitis.
Dynamic state of plasma proteins:
Plasma proteins are continuously formed by the liver, in the same time the tissue macrophages continuously break down plasma proteins into amino acids. Amino acids are transported back into the blood and utilized by the body to form tissue proteins or by the liver to form again plasma proteins. There is a constant state of equilibrium between the plasma proteins, amino acids of the blood and the tissue proteins. The ratio of the total plasma proteins to the total tissue proteins in the body remains relatively constant. Tissue proteins can change to plasma proteins (e.g. during haemorrhage) and plasma proteins can change to tissue proteins (e.g. during starvation).
General function of plasma proteins:
1. Blood clotting:
Most of the factors involved in the process of blood clotting are plasma proteins e.g. fibrinogen, prothrombin etc. So, plasma proteins are essential for blood clotting which is a life-saving process during haemorrhage.
2. Blood viscosity:
Plasma proteins together with red blood cells are responsible for blood viscosity. Plasma is about 1.8 times as viscous as water, whereas the whole blood is 3-4 times as viscous as water. Fibrinogen is the main plasma protein responsible for plasma viscosity because of its elongated molecules and their large molecular weight. Blood viscosity is necessary for maintaining the arterial blood pressure at normal level.
3. Plasma colloid osmotic pressure:
Plasma proteins diffuse only slightly through the capillary pores into the interstitial fluid. So, the concentration of proteins in the plasma (6-8 gm%) equals about three times the concentration of plasma proteins in the interstitial fluid (2-3 gm %). The high concentration of plasma protein inside the blood capillaries causes an osmotic pressure called plasma colloid osmotic pressure which equals 25 – 30 mm Hg. Albumin is responsible for most of this osmotic pressure.
The capillary blood pressure acts as a filtering force which tends to force fluid and its dissolved substances through the capillary pores into the interstitial spaces (at the arterial end). In contrast, the plasma colloid pressure tends to cause fluid movements by osmosis from the interstitial spaces into the blood again (at the venous end).
4. Buffering action:
Plasma proteins act as a buffer system formed of a weak acid (proteinic acid) and its salt with a strong base (Na-proteinate). This buffer helps in keeping the pH of blood constant, if an acid is added to the blood (e.g. lactic acid during muscular exercise), it combines with Na-proteinate to form Na-lactate and proteinic acid (weaker acid) with minimal change in pH of the blood.
Lactic acid(Relatively strong) + Na proteinate Na lactate + Proteinic acid (Relatively weak)
5. Defensive function:
Antibodies are gamma globulins which protect the body against micro organisms and their toxins.
6. Carrier functions:
Plasma proteins act as carriers for many substances because of the large surface area of the protein molecules.
Albumin carries free fatty acids, bilirubin, thyroxin, cortisol, and vitamin A. Globulins carry cholesterol, triglycerides, phospholipids, iron, copper, thyroxin, cortisol, sex hormones and vitamin B12.
Significance of the carrier function of plasma proteins:
a) Transport of the carried substances from the site of binding to the site of their utilization.
b) The combined form acts as a reservoir, from which the free substance is slowly released to the tissues.
c) To prevent the rapid loss of these substances in urine because plasma proteins do not filter through the glomeruli of the kidney because of their large molecular weight.
d) To make the water insoluble substances ( blood lipids) soluble or miscible with water by carrying them on the plasma proteins which are soluble in water.
7. Carriage of CO2:
Plasma proteins help in carriage of CO2 from the tissues to the lungs. CO2 combines with the NH2 group of the plasma proteins forming carb-amino compounds.
8. Regulation of capillary permeability:
Plasma proteins decrease capillary permeability by closing the pores present in the cement substance of the blood capillaries. Decrease plasma proteins is associated with increased capillary permeability.
9. Protein metabolism:
Plasma proteins act as a reserve protein used during starvation to supply the tissues with the amino acids needed for protein synthesis.
10. Regulation of erythrocyte sedimentation rate:
Increase in fibrinogen and globulins as in cases of tissue injury or infections leads to increase erythrocyte sedimentation rate. These plasma proteins increase the tendency of the red blood cells to stick together forming (rouleaux) which increases their rate of sedimentation.
Haemostasis is the arrest of bleeding from a damaged blood vessel. It depends on interaction between the blood vessel wall, circulating platelets and blood clotting factors. Haemostasis occurs by the following mechanisms which follow each other:
1. Local vascular spasm.
2. Formation of a platelet plug.
3. Formation of a blood clot.
4. Fibrosis of the blood clot to close the hole in the blood vessel permanently and/or fibrinolysis of the blood clot to reopen the blood vessel after its closure.
These haemostatic mechanisms are adequate to stop bleeding from small blood vessels. But bleeding from medium or large sized vessels can’t be stopped by these haemostatic mechanisms alone. Application of a tourniquet proximal to the vessels injured or external pressure over the wound are necessary to stop bleeding until the wound and the vessels can be surgically repaired.
1- Local vascular spasm.
An immediate and strong vascular spasm occurs in the injured vessel in response to the injury. The local vascular spasm has the following significance:
a) It leads to slowing (or stopping) of blood flow to the injured area.
b) It allows time for other haemostatic mechanisms to occur and stop bleeding.
c) The reduced blood flow helps contact activation of platelet and clotting factors.
d) As the inner surfaces of the injured vessel are pressed together by the vascular spasm, they become sticky and adhere to each other to close the injured vessel.
The mechanisms responsible for local vascular spasm include:
Myogenic mechanism: contraction of the smooth muscles of the injured blood vessel in direct response to trauma.
Neurogenic mechanism: nervous reflex initiated by pain from the injured vessel.
Chemical mechanism: by the action of vasoconstrictor substances released from blood platelets e.g. serotonin, thromboxan A2 and catecholamines.
2- Formation of a platelet plug:
Platelets adhere to the damaged vessel wall and become activated. They change in shape and stick to each other. After activation platelets contract and release chemical substances e.g. ADP, serotonin, fibrinogen, platelet factor 4, and thromboxan A2 . These substances act on other platelets to activate them. The newly activated platelets become sticky and adhere to the originally activated platelets and to each other producing platelet plug. Platelet plug has the following significance:
1- Platelet plug can stop blood loss completely from a small injury, but if the injury is large, blood clotting may be necessary to stop bleeding.
2- Platelet plug is extremely important for closing the minute ruptures in blood capillaries which occur hundreds of time daily. A person who has very few platelets suffers from appearance of multiple small haemorrhagic areas under the skin.
3- The chemical substances released from the platelets (which from the plug) help the other mechanisms of haemostasis; serotonin and thromboxan A2 produce vaso-constriction of the affected vessels, fibrinogen helps blood clotting, Factor XIII (fibrin stabilizing factor) helps in stabilization of the blood clot, platelet factor 4 (heparin antagonist) neutralizes heparin and prevents its inhibitory effect on the blood clotting, platelet derived growth factor helps repair of the damaged vessels.
3- Formation of a blood clot:
Blood clotting means transformation of blood from a fluid state to a gelatinous mass or to a semisolid state. Normally the blood and the tissues contain more than 50 important substances that affect blood clotting (coagulation). These substances are pro-coagulants (inactive clotting factors), and anti-coagulants. Normally the anticoagulants predominate, and the blood dose not coagulate and circulate in the cardiovascular system in a fluid state. But when a blood vessel is injured, pro-coagulants become activated and react with each other in a special manner to produce blood clotting and prevent bleeding from the injured vessel.
Mechanism of blood clotting:
Blood clotting is a complex process which involves a series of reactions known as coagulation cascade. Blood clotting begins when a certain clotting factor becomes activates, and this factor in turn activates another that activates still another and so on. This series of reactions involves many of the clotting factors and ultimately results in the formation of a blood clot.
Steps of blood clotting:
1- Formation of prothrombin activator:
I) Extrinsic mechanism:
It results from injury of blood vessels and surrounding tissues. This leads to release of tissue thromboplastin (tissue factor or factor III) from the injured tissues. The later reacts and activates clotting factors V, VII, X, in presence of Ca++ ions ( factor IV) to form prothrombin activator. The extrinsic mechanism of blood clotting has a few steps and occurs rapidly, within seconds. The extrinsic mechanism is so named because it is initiated by substances released from the damaged tissues outside the blood itself.
II) Intrinsic mechanism:
The intrinsic mechanism occurs more slowly, usually requiring several minutes. It is so named because all factors necessary for blood clotting are present in the blood itself. It begins by activation of factor XII ( contact factor) when blood comes in contact with rough or foreign surface. The later reacts and activates clotting factors V, VIII, IX, X, XI in presence of Ca++ ions and platelet phospholipids to form prothrombin activator.
2- Conversion of prothrombin (factor II) to thrombin:
The prothrombin activator (produced by extrinsic or intrinsic mechanisms) caused conversion of prothrombin to thrombin in presence of Ca++ ions.
Prothrombin ( factor II ) Thrombin
3- Conversion of fibrinogen (factor I) to fibrin: Thrombin acts on fibrinogen changing it to fibrin monomer. Fibrin monomers bind with each other to form fibrin polymer (fibrin threads) or blood clot.
Fibrin threads adhere to the damaged vessel walls forming a network which traps the blood cells, platelets and plasma forming the blood clot. This clot appears red because of the presence of red blood cells.
4- Fibrosis or fibrinolysis of the blood clot:
Blood clot is a temporary mechanism to stop bleeding until the vessel can be repaired. So, blood clot is followed by fibrosis of the blood clot to close the hole in the blood vessel permanently or fibrinolysis of the clot to reopen the blood vessel after its closure.
A) Fibrosis of the blood clot:
The clot formed in a small hole of a vessel wall is invaded by fibroblasts from the surrounding connective tissue. This process begins within a few hours after clotting and continuing to complete fibrosis of the clot within 1-2 weeks. This process is promoted by the growth factor secreted by the platelets. Fibrosis of the blood clot closes the hole in the vessel permanently.
B) Fibrinolysis of the blood clot:
Larger blood clots which are formed inside the large blood vessels or formed in the tissues outside the blood vessels are slowly dissolved by a fibrinolysis. Fibrinolysis is very important to reopen the blood vessel after its closure and also to remove the blood clots from the tissues.
Red blood cells (erythrocytes)
Red blood cells or erythrocytes are small, circular, biconcave discs which have no nuclei. The average cell diameter is 7.5 m (micron = 1/1000 mm), the thickness at the center is 1 m or less, and at the edge is 2.5 m (biconcave). The shape of the red blood cells can change markedly as the cells pass through the narrow capillaries.
Normal blood standards:
◘Red blood cell count: In adult males: 5.0-5.5 millions /mm3, adult females: 4.5-5.0 millions /mm3 , newly born infants: 6.0-8.0 millions /mm3 , children: 3.5-4.5 millions /mm3 (average 4.0)
◘Haemoglobin content (gram / 100 ml blood): In adult males: 14.0-18.0 gm %, adult females: 12.0-16.0 gm % , newly born infants 18.0 gm %, children:12.0 gm %
◘Haemotocrit value (packed cell volume): In adult males: 45 % , adult females, 41 % , newly born infants 54 % , children: 36 %.
◘Red cell indices: Red cell indices give an idea about the characters of the individual red blood cell. These indices are important for diagnosis of different types of anaemia.
a) Mean corpuscular volume (MCV):It is the average volume of a single red blood cell, it equals 90 ± 7 m3 .
b) Mean corpuscular haemoglobin (MCH):It is the average amount of haemoglobin present in a single red blood cell, it equals 30 ± 3 pico-gram (10 –12 gm).
c) Mean corpuscular haemoglobin concentration (MCHC):It is the percentage ratio of haemoglobin in a single red blood cell in relation to its volume, it equals 33 ± 3 %.
Functions of the red blood cells:
1. Oxygen carriage: The main function of haemoglobin is to carry and transport O2 from the lungs to the tissues.
2. Carbon dioxide carriage: The high content of carbonic anhydrase enzyme in the red cells help CO2 carriage and transport from the tissues to the lung in the form of bicarbonate. CO2 can also combine with the globin part of haemoglobin (unlike O2 which combines with the haem part).
3. Acid base buffer: Haemoglobin is an excellent acid base buffer which is responsible for most of the buffering power of the whole blood.
4. The red cells together with the plasma proteins are responsible for the blood viscosity which is necessary for maintaining the blood pressure at normal level.
5. Functions of the red cell membrane:
a) The great surface area of the cell membrane in relation to the quantity of materials inside has the following significance:
- It gives the red cells its characteristic shape “biconcave discs”.
- Facilitates the exchange of gases (O2 and CO2) in and out of the red cells.
- Facilitates deformation of the cells during passage through the narrow capillaries.
- In case of hydration, the red cells swell and become more spherical, but do not rupture.
b) The cell membrane contains different channels for passage of ions to maintain the normal ionic composition and osmotic pressure of the red blood cells.
c) The surface of the cell membrane contains protein antigens which are responsible for the specific blood groups of the person.
d) The cell membrane keeps haemoglobin and carbonic anhydrase enzyme inside the red cells because if these important substances are set free in the plasma, they may be lost in urine or engulfed and destroyed by phagocytic cells.
Formation of red blood cells ( erythropoiesis ):
Life span of red blood cells:
The red blood cells circulate in the blood for only 100-120 days. The life span of red blood cells is very short in contrast to the nerve and muscle cells which survive during the person’s whole life. The short life span of red cells is due to absence of nucleus and organelles which are important for renewal of cytoplastic enzymes, protein synthesis, cellular growth, repair and division.
Normally about 0.8-1% of all red blood cells ( about 25 trillion cells in adult person) are destroyed daily. The bone marrow produces red blood cells at the same rate ( about 2.5 million cells/second) to maintain the red cell count nearly constant.
Fate of red blood cells:
The old or damaged red blood cells are destroyed by phagocytic cells present in the spleen, liver, and bone marrow. As the red cell ages, its plasma membrane becomes fragile and rupture as the cells squeeze through the narrow capillaries specially of the spleen.
Inside the phagocytic cells, haemoglobin is broken down into haem and globin. The globin part is broken down into amino acids which are reutilized for erythropoiesis or used for protein synthesis in the body.
Iron is removed from the haem part of haemoglobin and released into blood, where it is used again in erythropoiesis or to the liver where it is stored. The remaining part of the haem molecule is converted to bilirubin which is secreted in the bile.
Factors affecting erythropoiesis:
1. Oxygen supply to tissues:
Oxygen transport is the main function of the R.B.Cs. So, the main stimulus for erythropoiesis is hypoxia i.e. decrease O2 supply to tissue. Hypoxia stimulates secretion of erythropoietin hormone from the kidney which stimulates the bone marrow to produce more R.B.Cs. The bone marrow continues to form R.B.Cs until the newly formed cells can carry adequate amount of O2 to the tissues and correct hypoxia. Adequate O2 supply to the tissues inhibits secretion of erythropoietin hormone.
2. Dietary factor:
A) Dietary proteins:
Proteins of high biological value (i.e. contain the essential amino acids) which are present in animal proteins (as meat, liver and kidneys) are needed in the formation of R.B.Cs. Prolonged protein under nutrition leads to anaemia.
B) Metal ions:
(1) Iron (Fe): Iron is essential for R.B.Cs formation because it enters in the formation of haem part of haemoglobin. Iron is present in the food in the ferric form.
(2) Copper (Cu): Copper is essential for normal erythropoiesis. It catalyzes the oxidation of ferrous iron to ferric iron, a reaction that must occur before the carrier protein can combine and transport iron.
(3) Cobalt (Co): Cobalt stimulates erythropoiesis by stimulating erythropoietin release from the kidneys.
◘ Vitamin B12 and (2) Folic acid: Both vitamins are essential for final maturation of red blood cells because they are needed (each in a different way) in the DNA synthesis. So, both vitamins are called maturation factors. Deficiency of either vitamin B12 or folic acid causes maturation failure anaemia. Vitamin B12 is present in diets of animal origin such as meat, fish, eggs and milk. The normal daily requirement is only 1-2 m g/day and the normal store in the liver is about 1-5 mg (i.e. more than 1000 times the daily requirement). Folic acid is present in green vegetables and some fruits. The normal daily requirement of folic acid is 0.1 mg/day. It is stored is the liver (about 10 mg i.e. about 100 times the daily requirement).
◘ Vitamin C: Vitamin C is a strong reducing agent which is important in reducing the ferric from of iron to the ferrous from to facilitate its absorption.
3. Hormonal factors:
□ Androgens increase erythropoiesis by stimulating the production of erythropoietin from the kidney and by stimulating directly the bone marrow. This may explain the increased blood cell count in males than in females.
□ Thyroxin and Glucocorticoids stimulate the general metabolism and also stimulate the bone marrow to produce more R.B.Cs.
□ Growth hormone has an anabolic effect on the bone marrow increasing erythropoiesis.
4. State of liver and bone marrow:
Liver: Healthy liver is essential for normal erythropoiesis because the liver is the main site for storage of vitamin B12, folic acid, iron and copper. In chronic liver disease anaemia occurs.
Bone marrow: Healthy bone marrow is essential for normal erythropoiesis. When the bone marrow is destroyed e.g. by atomic irradiation, deep X ray therapy or drugs, aplastic anaemia occurs.
White blood cells
The white blood cells (leucocytes) lack haemoglobin (in contrast to red blood cells), so they are white unless stained for microscopic examination. They vary in structure, function and number (in contrast to red blood cells which are of uniform structure, identical function, and constant number).
The white blood cells act together to provide the body with powerful defenses against invasion by foreign organisms (bacteria, viruses, parasites or fungi) and also against toxins and tumors. White blood cells are classified into two major classes:
A) Granular leucocytes:
These cells have cytoplasmic granules which contain active substances involved in the inflammatory and allergic reactions. Granular leucocytes are neutrophils, eosinophils, and basophils.
B) Non-granular leucocytes:
These cells do not have granules in their cytoplasm, they are present in blood in three types: monocytes, lymphocytes and occasionally plasma cells.
· Total leucocytic count:
The total count of white blood cells varies widely in different persons and in the same person under different conditions. The total count varies between 4.000 – 11.000 white blood cells/mm3.
· Differential leucocytic count:
The normal percentage of the different types of white blood cells in the adult persons are approximately the following; Neutrophils: 60 – 70 %, Eosinophils: 1 – 5 %, Basophils: 0.5 – 1 %, Monocytes: 3 – 8 %, Lymphocytes: 20 – 30 %
Functions of leucocytes:
Neutrophils move to the infected area by amoeboid movement then attack and destroy bacteria by phagocytosis. Eosinophils are weak phagocytic cells, they represent the first line of defense against parasites, also eosinophils decrease the allergic reactions by releasing substances which neutralize histamine. Basophils secrete heparin which prevents blood clotting, basophils also play an important role in allergic reactions, they release histamine, bradykinin, and lysozomal enzymes. These substances is the cause of the allergic manifestations. Monocytes are powerful phagocytic cells, they are capable of phagocytosis of as many as 100 bacteria and also have the ability to engulf much large particles (whole red blood cells or malarial parasites).
Lymphocytes are of two types; B lymphocytes which is responsible of humeral immunity, in which the B cells are transformed into plasma cells. The later secrete antibodies which kill the invading organisms. And T lymphocytes which is responsible for cellular immunity. The stimulated T cells attack and destroy the virus infected cells as well as the tumor cells and transplanted cells.