Blood Physiology PDF

Blood It is viscous fluid that is considered as a special type of connective tissue which circulates within the cardiovascular system.  It is composed of cells suspended in clear yellowish fluid called plasma Composition of blood - 55% is composed of plasma. - 45% is made of three...

Blood It is viscous fluid that is considered as a special type of connective tissue which circulates within the cardiovascular system.  It is composed of cells suspended in clear yellowish fluid called plasma Composition of blood - 55% is composed of plasma. - 45% is made of three major types of cells. Cellular elements of the blood: 1-The red blood cells (erythrocytes). 2-The white blood cells (leucocytes). 3-The platelets (thrombocytes). Physical properties of blood 1-Color: ֎Arterial blood is bright red ֎Venous blood is dark red 2- Specific gravity ֎1090 for erythrocytes ֎1030 for plasma ֎ 1060 for whole blood 3- Viscosity -It means that the fluids resist the change in their shape. -The viscosity of blood is five times as the viscosity of water. -It is formed from blood cells and plasma proteins. 4-Osmotic pressure (a) Crystalloid osmotic pressure: It is about 4000mm/Hg. It is not effective in water absorption. It created by crystalloids (electrolytes) (b) Colloid osmotic pressure: It is due to plasma proteins it is 30mmHg. It is effective in water absorption. It is created mainly by albumin. 5-PH: ֎ PH of arterial blood is 7.4. ֎ PH of venous blood is 7.3. General functions of blood 1-Respiration Blood carries O2 from the lungs to the tissues and CO2 from the tissues to the lungs. 2-Nutrition Blood carries foodstuffs absorbed from intestine to the cells which need them. 1 3-Excretion: Carries the waste products of cellular metabolism to the excretory organs. 4-Carriage: The blood only carries hormonal secretion from the endocrinal glands to the target tissues. 5-Immunity: Transports leucocytes, antibodies. 6- Regulation of blood temperature (a) Blood distributing heat all over the body (b) Blood stores a great quantity of heat 7- Blood clotting 8- Water balance 9- Regulation of acid base balance 10-Regulation of ionic equilibrium 11-Regulation of arterial blood pressure Composition of plasma: Plasma contains: Important Types and site of formation of plasma proteins: globulins Types Albumin Alpha (1 and 2), beta1 and 2 Fibrinogen Prothrombin and gamma globulins. % 4-4.5 gm % 2.5 – 2.7 gm%. 200 - 400 mg%. 10 mg%. M.W 70000 90000- 200000 400000. 69000. Liver except Site of γ globulins synthesized in liver liver Liver formation lymphoid tissues by plasma cells Maintaining Main Blood clotting Blood plasma colloid Defense function function Blood viscosity clotting pressure. 2 The main functions of plasma proteins 1- Nutrition: Plasma proteins are used in protein metabolism. 2- Blood clotting: Fibrinogen and prothrombin are essential for coagulation of the blood 3- Viscosity: By fibrinogen and globulins. 4- Important for ESR: ESR is dependent on fibrinogen and globulins. 5- Immunity: Gamma globulins used to exert passive immunity. 6- Carrier: Plasma proteins carry e.g. hormones, thyroxin, vitamin A & minerals, so preventing their rapid elimination in the urine. 7- Capillary permeability: Plasma proteins close pores in cement substance. So, they maintain normal capillary permeability. 8- Buffering action: They behave as weak acids bind with (Na) in alkaline pH of the blood. 9- Osmotic pressure: Mainly by albumin due to: A- Its high concentration. B- Its small molecular weight. Osmotic pressure of Plasma proteins is important for the reabsorption of fluids from the tissue spaces at the capillary venous end by antagonizing the filtering force of capillary blood pressure. N.B Albumin/ Globulin ratio = A/G ratio. Normally A/G ratio is about 1.2 0r 1.6. A/G ratio is decreased in A/G ratio is increased in 1- Decreased albumin formation as in liver diseases.  Dehydration (↑albumin concentration) 2-Increased albumin loss as in kidney diseases.  Certain genetic conditions affecting globulin 3-Infections due to increased formation of production ( ↓gamma globulins immunoglobulins (γ globulin). Red blood cells (RBCS) ֎They are non-nucleated cells. ֎Also known as erythrocytes (erythro= red). ֎Red color is due to presence of coloring pigment known as hemoglobin. ֎Normal shape: Biconcave discs. 3 ֎Normal size: 7.2 μ (6.9 to 7.4 μ) Life span: Average lifespan of RBC is about 120 days. After the life time the senile (old) RBCs are destroyed in reticuloendothelial system. Normal Value: ֎In adult males, it is 5-5.5 million/cubic mm. ֎In adult females, it is 4-4.5 million/cubic mm. ֎In newly born infant, it is 7 million/cubic mm. Functions of erythrocytes: (1) Functions of hemoglobin (HB): 1. Respiratory function: It carries O2 from lungs to the tissues and CO2 form tissues to lungs. 2. Buffering action: Hemoglobin takes part in maintenance of the acid base balance via buffering of tidal CO2. (2) Functions of the capsule: a) Biconcave shape of RBCs: increases surface area for the gas exchange. b) The capsule is plastic as a bag so, RBCs can be deformed into almost any shape and it can be easily pass through the narrow capillaries. c) The capsule keeps the carbonic anhydrase enzyme inside RBCs, This enzyme is important for carriage of CO2. d) The capsule is permeable to anions e.g. Cl- and HCO3-, e) The capsule is impermeable to Na+ “outside”. f) The capsule is impermeable to K+ and histamine “inside the capsule”: If K+ and histamine released outside cause vasodilatation that decrease arterial blood pressure. g) The capsule is impermeable to hemoglobin: So, it prevents: ֎ Destruction of hemoglobin by the reticulo-endothelial cells that leads to formation of bile pigment: hemolytic jaundice. ֎It prevents the marked increase in the osmotic pressure of plasma from 30mmHg to 150mmHg due to release of hemoglobin into plasma. ֎ Release of hemoglobin into the kidney & formation of acid hematin that block 4  tubules leading to acute renal failure. Erythropoiesis Definition: It is the process of formation of RBCs. Sites of erythropoiesis: 1- In embryonic life: RBCs are formed in yolk sac. 2- During the middle trimester of pregnancy: RBCs are formed in liver & spleen. 3- During the last three months & after birth: RBCs are formed in bone marrow. 4- In children: all bones contain red marrow. This gradually decreases with age. 5- At age of 20 years: the red marrow becomes restricted to the flat bones (as vertebrae & ribs) and upper ends of long bones. Stages of erythropoiesis: ֎ Proerythroblasts ֎ Erythroblasts ֎Normoblasts ֎Reticulocytes then mature ֎Erythrocytes. Factors affecting erythropoiesis: 1- O2 supply to tissues: All conditions that decrease O2 supply to tissues (hypoxia: increased production of RBCs. Causes of Hypoxia: 1. High altitude. 2. Anemia. 3. Increased O2 demand in athletes. 4. Chronic respiratory diseases. Effect of hypoxia Stimulate release of erythropoietin hormone that increase RBCS production. Site of release of erythropoietin Hormone: ֎85-90% from the kidney. ֎ 10-15 % from the liver. 2-Healthy bone marrow: Destruction of bone marrow decreased formation of RBCs ( Aplastic anemia). 3- Healthy Liver ֎Store iron, Vitamin B12 ֎Synthesis of globin, erythropoietin hormone 5 4- Dietary factors 1- Proteins of high biological value (rich in the essential amino acids). 2- Minerals: Iron Copper and cobalt as Co-factors for formation of Hb. Cobalt as a part of vit. B 12. 3- Vitamins: ֎ Vitamin C. ֎ Vitamin B &Folic acid (Maturation factors). 12 5- Hormones ֎ Erythropoietin. ֎ Thyroxine: General metabolic stimulant. ֎Androgen: Stimulate release of erythropoietin Iron absorption: The dietary iron is readily absorbed in the ferrous state, mostly in the upper part of the small intestine Anemia Definition: Anemia is defined as the decrease in oxygen carrying capacity of the blood either due to decrease number of RBC’s or decrease Hb content. Classification of anemia: 1-According to size of RBC’s and Hb concentration 1-Normocytic normochromic anemia 2-Microcytic hypochromic anemia 3-Macrocytic hypochromic anemia 2-According causes 1-Aplastic anemia: It is normocytic normochromic anemia. It is due to bone marrow destruction by ֎Irradiation as X-ray. ֎ Bacterial toxins. ֎Chemical toxins. 2-Maturation failure anemia: It is a macrocytic anemia. It may be: (a) Pernicious anemia: It is commonly due to failure of absorption of vitamin B12 due to lack of intrinsic factor. (b) Folic acid deficiency anemia: 3-Nutritional deficiency anemia: The commonest is iron deficiency anemia. It is microcytic hypochromic anemia. 6 4-Blood loss anemia: It may be due to: (a) Chronic blood loss: This is microcytic hypochromic anemia. (b) Acute blood loss :This leads to normocytic normochromic anemia 5-Hemolytic anemia: It may be hereditary or acquired A. Hereditary causes: a) Spherocytosis : RBCs are spherical & small in size. b) Sickle cell anemia due to abnormal hemoglobin that when exposed to O2 lack leads to its damage. c) Thalassemia there is also abnormal hemoglobin. B. Acquired causes: Malaria, snake venom, bacterial toxins , in compatible blood transfusion Most of these cause lead to normocytic normochromic except thalassemia leads to microcytic hypochromic anemia. Type of anemia Normocytic Normochromic Microcytic hypochromic Macrocytic Size of RBCs Normal Decreased Increased Hemoglobin content Normal Decreased Decreased Common causes 1- Blood loss 1. Iron deficiency 1. Vit.B12 deficiency 2- Hemolysis 2. Thalassemia 2. Folic acid deficiency 3- Aplastic 3. Chronic blood loss 7  White blood cells (WBCS): ֎Life span: Lifespan of WBCs is not constant. ֎WBCS count: 4000-11000/ cubic mm. Common properties of WBCs 1-Margination: The leucocytes attracted to the capillary endothelial surface. 2-Diapedesis: The leucocytes can squeeze through narrow pores by sliding of small portion of the cell at the pore being momentarily constricted until it passes. 3-Motility: The granulocytes have amoeboid movement by sending out pseudopodia. The other leucocytes are less motile. 4-Chemotaxis: Certain substances attract the leucocytes "+ve Chemotaxis" and other substances repel leucocytes “-ve Chemotaxis”. e.g. inflamed tissues, some bacterial toxins. 5-Phagocytosis: It is a property of neutrophils and monocytes. It means that the cell can ingest the bacteria. 8 Common functions of leucocytes Neutrophils Important in inflammation. Have properties of margination, diapedesis, motility, chemotaxis and phagocytosis Eosinophil Phagocytic but less motile. Increased in allergic reactions and parasitic infestation. Basophils Non phagocytic. Synthetize histamine and heparin. Monocytes Tissue macrophages. Highly phagocytic for bacteria and large particles. Lymphocytes B lymphocytes: antibody formation. T lymphocytes: increased in chronic inflammation. Hemostasis and blood coagulation: Hemostasis: Means stoppage of blood loss from injured blood vessel. Mechanisms of haemostasis: 1-Vasoconstriction 2-Plateletplugs formation 3-Clotting of the blood 4- Clot retraction 5-Repair of the damaged blood vessel 1-Vascular spasm (Vasoconstriction) a) Local myogenic contraction of the blood vessel: This is initiated by direct damage to the vascular wall causes spreading of action potential along the vessel wall and results inn constriction of the blood vessel b) Local axon reflex: Which is initiated by pain impulses originated from the direct damage to the vascular wall. c) Vasoconstrictor substances: Especially those released by the platelets e.g. serotonin and thromboxane A 2 9  2-Platelet plugs formation 1) Platelet Adhesion: The platelets become sticky and adhere to collagen in the injured wall & to protein called Vonwillebrand factor that spread throughout the plasma 2) Platelet activation: The platelets begin to swell, and develop pseudopods. Their contractile proteins contract cause release of granules that contain multiple active factors 3) Platelet Aggregation: Platelets secrete ADP and thromboxane A , which activate more and 2 more platelets and adhere to the originally activated platelets. - Vicious cycle of activation and aggregation results in formation of platelet plug to close the injured blood vessel. 3- Clot formation: Clots are formed by the conversion of the soluble fibrinogen into insoluble fibrin network with blood cells in its meshes. 4-Clot retraction: It means shrinkage of the blood clot to decrease the lumen of the damaged vessel and the clot become firmer by: a) Retractozyme that secreted by platelets and b) Contraction of platelets themselves by activation of their contractile proteins (actin, myosin) 5. Repair of damaged blood vessel: Platelet-derived growth factor (PDGF) causes growth of fibroblasts, endothelial cells, smooth muscle cells, converted to fibrous tissue within 1-2 week Blood coagulation mechanism Clotting factors 1. All the clotting factors are plasma proteins especially beta globulin, except factor III (Tissue factor or thromboplastin) and factor IV (calcium). 2. All the clotting factors circulate in the blood except factor III (tissue factor) which is derived from tissue and composed of lipoproteins 3. All the clotting factors circulate in the blood in inactive form. Important 4. Some clotting factors need Vitamin K for their synthesis in the liver (II,VII,IX,X), so they are called vit K dependent factors 5. All the clotting factors completely consumed during blood coagulation except V&VIII 10 Clotting factors are: 12 factors (from I to XIII) but no VI factor Factor I Fibrinogen Factor II Prothrombin Factor III Thromboplastin (tissue factor) Factor IV Calcium Factor V Labile factor or proaccelerin or accelerator globulin Factor VII Stable factor or pro-convertin Factor VIII Anti-hemophilic factor A or anti-hemophilic globulin Factor IX Christmas factor or anti-hemophilic factor B Factor X Stuart Prower factor Factor XI Plasma thromboplastin antecedent (PTA) Factor XII Hageman factor or glass factor. Factor XIII Fibrin stabilizing factor. Mechanism of Blood coagulation: -The coagulation mechanism is responsible for conversion of soluble fibrinogen to insoluble fibrin by complex reaction: (cascade reactions or theory)  Blood coagulation can be concluded in the following four stages: (1) Formation of prothrombin activator. (2) Conversion of prothrombin into thrombin. (3) Conversion of fibrinogen into soluble fibrin. (4) Conversion of soluble fibrin into insoluble fibrin 1) Formation of prothrombin activator -Extrinsic mechanism -Intrinsic mechanism (1) Formation of prothrombin activator By extrinsic By intrinsic mechanism mechanism 11 Extrinsic pathway: Intrinsic pathway 12  Extrinsic mechanism Intrinsic mechanism 1-It is initiated by a factor not normally found in 1-All needed clotting factors are found in the blood but added externally from the injured blood. tissue. i.e. it depends on the intrinsic components of blood. 2-Initiated by injury of blood vessel 2-It is initiated by contact with rough surface. 3-It occurs in vivo only 3-It occurs in vivo and vitro 4-It is rapid (occurs within 12-16 seconds) 4-It is slow (occurs within 3-6 minutes) Fibrinolytic system (Lysis of blood clots) Lysis of blood clot inside the blood vessel can be done as following: 2. Plasminogen is a plasma protein produced by liver. 3. When a clot is formed  the injured tissue and vascular endothelium release tissue plasminogen activator (t-PA) which converts plasminogen to plasmin. Plasminogen tissue plsaminoge n activator   Plasmin. 4. Plasmin lyses fibrin, fibrinogen, factor V, VIII, prothrombin and factor XII. 5. Plasmin removes the clot formed inside the small blood vessels and open them. 6. Excess plasmin is inhibited by 2 plasmin inhibitor. Prevention of intravascular blood clotting (Intravascular anticoagulant) Normally, blood clotting inside the blood vessels is prevented by: 1. Smooth endothelial surface. 2. Presence of layer of glycocalyx (polysaccharide) on the endothelium: It repels the clotting factor & blood platelets. 3. Thrombomodulin (protein) bound to the endothelial membrane. ֎Thrombomodulin bind with thrombin. ֎ Thrombomodulin–thrombin complex activates a plasma protein C (which synthesized in liver)  then, protein C inactivates factor Va & VIIIa. 4. Fibrin fibers (that are formed during clotting) adsorb about 85%-90% of thrombin. 5. Antithrombin III (antithrombin–heparin factor) destructs the remaining portion of thrombin. 6. Heparin is a powerful anticoagulant found in the circulation 13  Functions of Platelets 1) Local vasoconstriction of the injured vessels: due to release of serotonin and thromboxane A. 2 2) Platelet plug formation. 3) Blood coagulation due to release of platelets phospholipids. 4) Clot retraction due to release of retractozyme. 5) Repair of injured blood vessel by PDGF Bleeding disorders: Definition: Conditions that cause excessive bleeding in the human. ֎ Hemophilia ֎Purpura ֎Vitamin K deficiency Causes of vitamin K deficiency 1- Failure of synthesis of vitamin K: ֎ Sterile intestine (newborns) ֎ Prolonged intake of antibiotics. 2- Failure of absorption: Obstructive jaundice 3- Liver diseases 4- Dicumarol toxicity (competitive inhibition of vitamin K). Clinically : There are spontaneous punctuate hemorrhages usually beneath the skin and mucous membrane (which is called petechiae , these petechiae appear as purplish spots ) Hemophilia Purpura Hereditary Sex linked inherited disease Not inherited Affect males only. Affect males& females Affected sex Transmitted from female to males. Females will be carrier. 1-Hemophilia A: deficiency of factor 1. Thrombocytopenic purpura: decreased VIII platelet count less than 50000/mm3 2-Hemophilia B: deficiency of factor 2. Thromboasthenic purpura: decreased Types IX. platelet function. 3-Hemophilia C: deficiency of factor 3. Idiopathic purpura: unknown cause. XI. Coagulation Time Prolonged Normal Bleeding Time Normal Prolonged 14  Anticoagulants Definition: They are substances that prevent or delay blood coagulation I-In vitro 1- Cold: delay clotting. 2- Collect blood in paraffin or silicone lined vessels. 3- Decalcifying agents: K oxalate, Na citrate, EDTA 4-Heparin. II-In Vivo Heparin Dicoumarol Origin Animal in origin Plant in origin Latent period of action After minutes After two days Duration of action 4-6 hours Days Route of administration I.V. or I.M. injection Oral Mechanisms of action Anti-thrombin anti- Competitive inhibition of vit K anti prothrombin activator prothrombin anti- F VII, IX and X. Site of action In vivo, in vitro In vivo only Dose test Total coagulation time Prothrombin time Anti-dote Protamin sulphate Vit K. 15