Physiology of Blood and Body Fluids PDF

 Physiology of Blood and body Fluids By Dr. Rasha Mohammed Ali Lecturer of Medical Physiology, Faculty of Medicine, Assiut University  Blood and body fluid: Part 1  Functions of blood  The plasma proteins and its functions  Red blood c...

 Physiology of Blood and body Fluids By Dr. Rasha Mohammed Ali Lecturer of Medical Physiology, Faculty of Medicine, Assiut University  Blood and body fluid: Part 1  Functions of blood  The plasma proteins and its functions  Red blood cells  Anemia and polycythemia  Functions of white blood cells  Functions of the spleen  Functions of lymph nodes  The blood is a living connective tissue composed by volume of approximately 45% cellular elements and 55% intercellular fluid. Blood is normally confined to the blood vessels and chambers of the heart, and is circulated throughout the body by the heart’s pumping action.  FUNCTIONS OF BLOOD:  1-Transport Medium: a) - O2 from lungs to the tissues and CO2 from tissues to the lungs. b) - Digested absorbed food e.g. glucose, amino acids, polypeptides and fatty acid. c) - Non-volatile waste products, e.g. lactic acid, urea, creatinene.... etc. d) - Active substances as hormones and vitamins. e) - Blood distributes heat liberated from the metabolic processes all over the body. f) The waste products of metabolism to their organs of excretion: CO2, bilirubin.  2-Defensive Functions: White blood cells attack the invading pathogenic organisms and produce antibodies against them.  3-Hemostatic Function: If a blood vessel is injured, blood clot, platelets plug, and vasoconstriction prevent blood loss.  4-Homeostatic Function: Blood helps to maintain the composition of the tissue fluid constant.   5-Regulation of Body Temperature: Blood and interstitial fluids are the main regulators of body temperature  PLASMA Plasma is the complex fluid in which blood cells and platelets circulate. It is defined as whole blood minus the formed elements (cells and platelets). THE PLASMA PROTEINS: 7 gm/100 ml of blood a) Serum albumin: 4.0 gm b) Serum globulin: 2.7 gm. c) Fibrinogen:0.3 gm It gives more viscosity to blood because it is elongated. Albumin-globulin Ratio: (A/G ratio): It is about 1.2-1.6. This ration is decreased in 2 conditions: 1. Liver failure: due to decrease formation of albumin. 2.Renal diseases: due to loss of albumin in urine, because its molecular size is smaller than globulin  Sites of formation of plasma proteins:  1. Albumin, Fibrinogen and Prothrombin: They are formed only in the liver.  2. Gamma globulin: They are formed by cells of the reticuloendothelial systems, which are present in the liver, spleen, bone marrow and lymph glands.  Functions of Plasma Proteins  1) Blood Clotting: Fibrinogen and prothrombin are essential for blood clotting. Plasminogen removes the old blood clots.  2) Regulation of Blood Volume: Through their colloid osmotic pressure (25 mm Hg), they tend to absorb fluids into blood against the filtering force of capillary BP.(10-40 mm Hg). Therefore, they regulate the exchange of fluids between the plasma and tissue fluids.  3)Defensive Function: Gamma globulin contains the antibodies that protect the body against microorganisms and their toxins.   4)Viscosity of the blood: The plasma proteins (mainly fibrinogen) are responsible for the viscosity of plasma. This viscosity helps in keeping normal arterial blood pressure especially the diastolic.  5)Buffering Action: Any buffer system is composed of a weak acid and its salt with a strong base. Plasma proteins are present in the blood in the form of: proteinic acid and sodium proteinate. They help in keeping the pH of blood constant e.g. during muscular exercise excess amounts of lactic acid are poured in blood from contracting muscles.  6-Maintenance of Normal Capillary Permeability: The protein partially blocks the pores of the cement substance which leads to stabilization of the intercellular cement substance.  7-Carriers:Plasma proteins combine loosely with certain important substances e.g. thyroxine, vitamins as vitamin A, metals (Fe, Cu).  8- CO2 Carriage: Plasma proteins help in carriage of CO2 as carbamino protein.  9- Regulation of Erythrocyte Sedimentation Rate: The sedimentation increases if the concentrations of fibrinogen and globulin increase. This has clinical importance.  Red Blood Cells Red blood cells are circular biconcave discs, non-nucleated. Normal Values: 5 million RBCs /UL of blood. Normal adult ranges are : - 5.4 million /UL (plus or minus 0.8 million /UL) in an adult male. - 4.8 million /UL (plus or minus 0.6 million /UL)in an adult female. It is higher in infants and lower in growing children and old persons. It is increased in athletes and at high altitudes. Shape: Circular, biconcave, non-nucleated discs.  Size: 90 cubic microns in volume, 8.5 microns in diameter and 2.5 microns thick.  Wall: The wall of the RBCs is semipermeable membrane which is plastic i.e. it can be momentarily deformed when squeezed in the narrow capillaries. It is not elastic. Thus, when the RBCs absorb some little water, the membrane ruptures easily.  Contents: The RBCs contain 60% water, 34% HB and 6% stroma. They also contain carbonic anhydrase enzyme and k+, Mg2+, Na+, and Cl- ions.  Functions Of RBCs  I)Functions of RBCs Membrane:  1) It allows the RBCs to pass through the narrowest capillaries due to its plasticity.  2) The biconcavity of the membrane gives the RBCs a large surface area which helps the exchange of gases (O2 and CO2).  3) It keeps the enzyme carbonic anhydrase inside the RBCs, (not lost in urine if it passes into plasma). This enzyme is important for CO2 carriage.  4) It is semipermeable and so it regulates the distribution of anions (HB, Cl, HCO3) and cations (Na+ and K+) inside and outside the RBCs.  5) The most important function of the membrane is that it keeps HB. inside the RBCs.  This is useful because if HB. is free in plasma it:  a) May be precipitated in kidney tubules as acid haematein blocking them and inducing anuria.  b) Would increase the osmotic pressure of plasma proteins 5 times, which would prevent tissue fluid formation.  c) Is liable to be engulfed and destroyed by the reticuloendothelial cells.  d)Would be filtered into Bowman’s capsule in the kidney and lost in urine.  II) Functions of RBCs contents:  1) Hemoglobin (HB.) has the following functions:  a) O2 carriage from the lungs to the tissues.  b) Co2 carriage from the tissues.  c) Buffering system in the blood.  2) Carbonic anhydrase is important in Co2 carriage.  Normal blood contains approximately 15 grams of hemoglobin /100ml of whole blood.  Normal adult ranges are male,16.0 g/100ml ± 2.0g/100ml; female, 14.0g/100ml ± 2.0g/100ml.  The oxygen-carrying capacity of blood is defined as the amount of oxygen the hemoglobin in 100ml of whole blood is capable of transporting. Each gram of hemoglobin can combine with 1.34 ml of oxygen. Since normal blood contains approximately 20ml of O2/100ml (15g/100ml **1.34ml O2/g = 20.1 ml O2/100ml).  Origin:  - In fetus, RBCs are formed from stem cells in the yolk sac, liver, spleen and red bone marrow.  - After birth till the age of adolescence, RBCs are formed only in the red bone marrow of ALL bones.  - After 20 years, RBCs are formed only in the membranous bones, e.g., sternum, skull, ribs and vertebrae.  Life Span:120 days ±7 days.  Destruction and Fate:  - The old RBCs are destroyed in the reticulo-endothelial cells.  - Hemoglobin is liberated and splits into globin and haem.  - The haem. part loses iron and is transformed into bile pigments billirubin which pass to the blood.  - The bile pigments are then execrated by the liver into the intestine through the common bile duct.  - Iron is carried by the blood in the form of transferritin either to the bone marrow for resynthesis of RBCs. or to the liver to be stored as ferritin for future use.   Factors Affecting Erythropoisis  I- Oxygen Tension:  1) Lowering of O2 tension in arterial blood stimulates the activity of bone marrow to produce more RBCs e.g. during living at high altitude.  II-Kidney:  - The juxtaglomerular cells of the kidney respond to hypoxia (O2 lack) as in high altitude by forming a substance called “Erythropoietin”. It directly stimulates the bone marrow for more production of RBCs.  III- Food Factors:  1)Proteins: Animal proteins as those in liver, kidney and meat are more effective than other proteins.  2)Iron (Fe): Forms a part of HB. of the RBCs.  3) Copper (Cu) and Cobalt (Co): These elements act as catalysts for Hb. synthesis but do not form a part of Hb. molecule.  4.Vitamins: Only folic acid and vitamin B12 are specific in RBCs regeneration. They are called “Maturation Factors”. Other vitamins, e.g. Vit. C stimulate tissue growth and metabolism in general including the bone marrow.  5.R.B.Cs Maturation Factors: These are vitamin B12 and folic acid. They are needed for the formation of the nucleus of the early RBCs.  VitaminB12  vitamin B12 of food (Extrinsic factor) exists in a combined form with proteins. In order to be absorbed, B12 should be free from protein. This is done by gastric HCl together with gastrointestinal proteolytic enzymes.  -  In the stomach, an enzyme-like substance is secreted by gastric mucosa in the fondus region. This substance is named the “Intrinsic factor” and its function is to help absorption of vitamin B12 from the intestine (lower part of the ileum).  Deficiency of B12 in the body leads to “Pernicious Anaemia”. So, it is “Antipernicious Anaemia Factors”.  Folic Acid  In the body it is converted into an active form: folinic acid.  - Like vitamin B12, it helps the formation of the nucleus of early RBCs.  - Folic acid is absorbed in the jejunum.  IV- Hormones:  a)Specific: erythropoietin hormone.  b)Non-specific: Thyroxine and testosterone.  V- Liver: Healthy liver is essential for normal erythropoiesis because it helps in the manufacture of globin of HB. and stores Fe, Cu and vitamin B12. In diseases of the liver anemia occurs  VI- Bone Marrow: It is the only site in adults for normal erythropoiesis. When it is destroyed, e.g. by x-rays, radium, atomic irradiation's or toxins, all types of blood cells are not formed (Aplastic Anaemia).  THE ANAEMIAS  These are conditions characterized by a in the number of RBCs or their HB. content or both.  Classification of anaemias:  1)Anaemias due to excessive destruction of RBCs:(=Haemolytic Anaemias) by:  a) Chemicals: as in lead poisoning.  b) Disease : as in malaria. c) Increased fragility of RBCs.  2) Anaemias due to excessive loss of RBCs: (= Post hemorrhage Anaemias):  a) Acute : as in rapid hemorrhage.  b) Chronic : as in piles (chronic hemorrhage).  3) Anaemias due to defective formation of RBCs:  a) Nutritional : e.g. in Fe, Cu or protein deficiency.  b) Pernicious : e.g. in vitamin B12 deficiency. c) Aplastic : e.g. in destruction of bone marrow by X-rays.  Pernicious Anaemia  This anemia is characterized by:  1- RBCs: When they are immature. They leave the bone marrow into the blood in megaloblast stage. So, they are nucleated, bigger in size (= Macrocytic) and contain more Hb. (= Hyperchromic).  2- C.N.S.: Degenerative lesions occur in the dorsal and lateral column of the spinal cord in peripheral nerves.  3- Stomach: Atrophy occurs in gastric mucosa (lack of Hcl and pepsin secretion) and failure of intrinsic factor secretion. Lack of Intrinsic Factor secretion leads to lack of absorption of Vit.B.12 from the intestine.  Treatment of Pernicious Anaemia: Injections of vitamin B12 which should be continued through the whole life of the patient if the cause is gastric mucosa atrophy.  Iron Deficiency Anaemia  It is due to prolonged loss of blood (=chronic haemorrhage) as in piles  Decreased Fe in the body leads to O2 lack stimulation of bone marrow to form RBCs but they are smaller than normal (=Microcoytic) and contain less amount of HB. (=Hypochromic).  Treatment: Give ferrous salts by mouth. In severe cases or decreased absorption, give iron by injection.  Polycythemia  Increased number of RBCs, (6-8 million per mm3). - Types and Causes:  1. Physiological Polycythemia: In case of prolonged exposure to low O2 tension, e.g., at high altitudes for several weeks.  2. Polycythemia Vera: The bone marrow forms excessive numbers of RBCs for an unknown cause.  Effects:  1. Increased haematocrite value.  2. viscosity of blood which the peripheral resistance and the blood pressure. 3. Increased cardiac work so heart failure may occur.  They are highly phagocytic. -They engulf microorganisms. -They have the property of diapedesis and chemotaxis which helps them as Neutrophils phagocytes a) They are related in some way to allergy or hypersensitivity where they increase. They may absorb histamine released in allergic conditions. b) They are weak phagocytes. Eosinophils c) They probably release plasminogen needed for lysis and removal of blood clots by fibrinolysis. They secrete heparin (= anticoagulant). b) They are related to allergy. They may secrete or absorb histamine. Basophils Basophils are not phagocytic  a) Formation of antibodies. The whole lymphocyte can act as an antibody. It can also change into plasma cell which is the main producer of antibodies. b) Lymphocytes can change into highly phagocytic Lymphocytes monocytes, but they are not phagocytic themselves. a) They are highly phagocytic. They leave blood to connective tissues (by diapedesis) where they change to macrophages engulfing bacteria. Monocytes b) Tissue repair after inflammation.  Normal count of WBCs: 4,000- leucopenia Leucocytosis 11,000 / m3 Bone marrow Neutrophilia: pyogenic inflammations depression Basophilia: allergic disease Splenomegaly Eosinophilia:allergic and parasitic diseases Autoimmune disorders Lymphocytosis: Tuberculosis Monocytosis: malaria 1. Pregnancy. 2. Delivery. 3. Newly born infants. 5. Eating. 6. Muscular exercise. 7. Emotions.  The spleen 4) Blood Reservoir: The 1) Defense: against splenic blood sinuses can parasite and microbes accommodate a large through: quantity of the circulating a) Phagocytosis by R.E. 2) Blood Formation blood. The stored blood is cells in the spleen.  3) Removal of Old Blood Cells: squeezed out of the spleen b) Antibody formation by to the general circulation lymphocytes and R.E. cells  a) RBCs, during the time of need. Leucocytes and platelets are removed by R.E. cells of spleen.  b) HB. breakdown and bile pigment formation.  Functions of Lymph Nodes  1) Filtration: The phagocytic cells remove foreign particles entering the node e.g. carbon particles in coal mines.  2) Removal of Bacteria: Macrophages in the node phagocytes the bacteria and they are the defense mechanism against local infection.  3) Formation of Lymphocytes: This function resembles that of other lymphoid tissues as the spleen.  4) Production of Antibodies: Lymph nodes produce antibodies which form another defensive mechanism against bacteria besides phagocytosis. These antibodies are produced by the lymphocytes formed by the nodes  " ‫" ﺗﻜﻤﻠﺔ اﻟﺒﺎور اﻷول‬ Neutrophils  They are highly phagocytic. -They engulf microorganisms. -They have the property of diapedesis and chemotaxis which helps them as phagocytes Eosinophils  a) They are related in some way to allergy or hypersensitivity where they increase. They may absorb histamine released in allergic conditions.  b) They are weak phagocytes.  c) They probably release plasminogen needed for lysis and removal of blood clots by fibrinolysis. Ophils Basophils They secrete heparin (= anticoagulant). b) They are related to allergy. They may secrete or absorb histamine. Basophils are not phagocytic Lymphocytes a) Formation of antibodies. The whole lymphocyte can act as an antibody. It can also change into plasma cell which is the main producer of antibodies. b) Lymphocytes can change into highly phagocytic monocytes, but they are not phagocytic themselves. Monocytes a) They are highly phagocytic. They leave blood to connective tissues (by diapedesis) where they change to macrophages engulfing bacteria. b) Tissue repair after inflammation. I  Leucocytosis Normal count of WBCs: 4,000- 11,000 / m3 Neutrophilia: pyogenic inflammations Bone marrow Basophilia: allergic disease Eosinophilia:allergic and parasitic depression diseases Splenomegaly Lymphocytosis: Tuberculosis Autoimmune Monocytosis: malaria disorders 1. Pregnancy. 2. Delivery. 3. Newly born infants. 5. Eating. 6. Muscular exercise. 7. Emotions. The spleen 1) Defense: against parasite and microbes 2) Blood Formation 4) Blood Reservoir: The splenic blood sinuses can accommodate a large through: 3) Removal of old Blood Cells: quantity of the circulating blood. The a) Phagocytosis by R.E. cells stored blood is squeezed out of the in the spleen.  a) RBCs,Leucocytes and spleen to the general circulation during platelets are removed by R.E. cells the time of need. b) Antibody formation by of spleen. lymphocytes and R.E. cells  b) HB. breakdown and bile pigment formation. Functions of Lymph Nodes  1) Filtration: The phagocytic cells remove foreign particles entering the node e.g. carbon particles in coal mines.  2) Removal of Bacteria: Macrophages in the node phagocytes the bacteria and they are the defense mechanism against local infection. II   3) Formation of Lymphocytes: This function resembles that of other lymphoid tissues as the spleen.  4) Production of Antibodies: Lymph nodes produce antibodies which form another defensive mechanism against bacteria besides phagocytosis. These antibodies are produced by the lymphocytes formed by the nodes 1 ‫" " ا ﻧ ﺘ ﻬ ﻲ اﻟ ﺒﺎ ور ر ﻗ ﻢ‬ Blood and Body Fluids: part 2 Blood platelets and platelet plug. Mechanism of blood coagulation Prevention of blood coagulation inside the blood vessels Abnormalities of haemostasis Blood groups Complications of blood transfusion Dehydration BLOOD PLATELETS (Thrombocytes) These are granular non-nucleated oval bodies, about 2-4 micron in diameter. Formation: They are fragments of megakaryocytes which are giant cells present in the bone marrow. They have a short life span (8-12 days). Platelet count of normal blood is from 1/4-1/2 million per mm3. Functions of Platelets Haemostasi Storage and s: Phagocytosis: Platelets Transport: Platelets can phagocytose store and transport particles as carbon and serotonin viruses. A- Marked constriction of the injured vessels due to release of a vasoconstrictor substance called “Serotonin B- Platelets then adhere together and plug the vessel opening. C- Releasing the following factors which help blood coagulation: - A factor helping the formation of thromboplastins. - - A factor helping prothrombin-thrombin reaction. - A factor helping fibrinogen-fibrin reaction. - A factor with anti-heparin activity D- Clot RetractionFibrin contraction is caused by a substance released from the platelets called “Retractozyme”. Hemostasis means prevention of blood loss from blood vessels. Bleeding is stopped by several mechanisms which are: Local Vasoconstriction: Immediately after injury: a) Liberation of serotonin and other vasoconstrictors from platelets. b) Local myogenic contraction of the blood vessel. 2) Formation of the Platelet Plug: The second event in hemostasis is an attempt by the platelets to plus the rent in the vessel. 3) Blood Coagulation: The third mechanism for hemostasis is the formation of the blood clot: Blood clotting takes place in three essential steps: First: Formation of a prothrombin activator substance in response to rupture of the vessel or damage to the blood itself. Second: The prothrombin activator catalyzes the conversion of prothrombin into thrombin. Third: The thrombin acts as an enzyme to convert fibrinogen into fibrin threads, that enmesh platelets, blood cells, and plasma to form the clot itself. III  There are two basic ways in which prothrombin activator can be formed: The extrinsic pathway: that begins with trauma to the vascular wall or to the tissues outside the blood vessels. The intrinsic pathway: that begins in the blood itself. IV  Lysis of Blood Clots:-The plasma proteins contain an euglobulin called plasminogen or profibrinolysin which, when activated, becomes a proteolytic enzyme called plasmin or fibrinolysin. - Plasminogen is activated by thrombin, activated factor XII, lysosomal enzymes from damaged tissue and factor from vascular endothelium. - Plasmin digests the fibrin threads, fibrinogen, factor V, factor VIII, prothrombin, and factor XII. Therefore, it prevents excessive fibrin formation and causes lysis of the clot within a day or two after blood leakage. 3-Collection of blood in siliconized containers which have a very smooth inner surface. Silicone prevents contact activation of factor XII. Abnormalities Of Hemostasis A) Bleeding Tendencies Abnormalities of Blood Platelets: Defect in the Clotting Mechanism V  B-Intravascular Thrombosis Abnormalities of Blood Platelets Thrombocytopenia (Thrombocytopenic 2- Thrombasthenia Purpura) It is a state in which the platelets are very low level of platelets i.e. below normal in quantity but defective in 50.000/cubic millimeter. function which may result in a bleeding a) Idiopathic thrombocytopenia: which tendency. means: the cause is unknown. It may be primary or secondary e.g. in b) Secondary thrombocytopenia: occurs severe uremia and exposure to certain in association with aplasia of the bone drugs as aspirin. marrow e.g. exposure to X ray, radioactive substances, neoplastic deposits, very severe fevers and drug sensitivity. Defect in the Clotting Mechanism 1-Hemophilia: - It is inherited sex-linked disease 2-Vitamin K Deficiency: Prothrombin transmitted by females (mothers) to (factor II) and factors, VII, IX and X require males (infant) but females vitamin K for synthesis by the liver. themselves show no symptoms. Causes of vitamin K deficiency: - There are three types of hemophilia: 1- Sterility of intestine (no bacteria). a) In Hemophilia A (85%) (classical newly born infants. hemophilia) due to deficiency of b) Prolonged use of antibiotics. factor VIII. 2- Failure of absorption of vitamin K as in: - Hemophilia B (10%) (Christmas a) Obstructive jaundice disease) due to lack of factor IX. b) Fatty diarrhea. - Hemophilia C (5%) due to absence 3- Liver diseases. of factor XI. 4- Competitive inhibition with vitamin K as In hemophilia, only the intrinsic pathway with dicumarol. In vitamin K deficiency, both the intrinsic is defective. and extrinsic pathways are defective. B-Intravascular Thrombosis: It is the formation of blood clot inside blood vessels. Contributing Factors: Slowing of blood, e.g., after delivery and operation. Atherosclerosis Complications: 1- Obstruction of arterial supply which leads to ischaemia. 2- Obstruction of venous supply which leads to edema. 3- Embolic formation, i.e., dislodgment of small pieces of the blood clot. e.g., pulmonary emboli. Prevention: - Avoidance of prolonged recumbence. - Use of anticoagulant in susceptible patients. The sites of danger in blood transfusion is that the RBCs of VI  the donor which may be agglutinated by the agglutinins in the plasma of the recipient. The RBCs of the recipient are not usually affected by the agglutinins in the plasma of the donor. This is because the agglutinins in the injected plasma of the donor are very small and immediately will be diluted by the plasma of the recipient. Group “O” is “Universal Donor” because RBCs of group “O” contain no agglutinogens (A or B), so agglutination cannot take place. Group “AB” is “Universal Recipient” because group “AB” has no agglutinins in its plasma. Rh Factor This is an agglutinogen which was discovered in the RBCs of Rhesus monkeys (hence the name “Rh”). - It is present in the RBCs of 85% of people who are thus called “Rh positive” The remaining 15% have no Rh factor in their RBCs and are called “Rh negative”. - In Egypt,“Rh positive”people are higher, about 92%. Remarks on Rh Factor: There are no anti-Rh antibodies in normal blood whether Rh positive or Rh negative. No agglutination on the first incompatible Rh transfusion. Only anti-Rh antibodies are formed. Rh negative blood can be transfused to both Rh positive and Rh negative persons VII  Prevention: - Rh negative female should never receive an Rh positive blood. - When an Rh negative female delivers Rh positive foetus, an anti-D anti-bodies are given to neutralize the D antigen of the Rh positive fetal cells and prevent sensitization of the mother. Treatment: 1.Replacement of the blood of the baby with Rh negative Group O blood. Complications of Blood Transfusion 1- Effect on Donor: a- Shock. b- Anaemia if repeated withdrawal. 2- Effect on Recipient: a) Mechanical effect: i ) air and fat embolism. ii) displacement of clot. b) Infective complications: e.g., infective hepatitis, syphilis, malaria and AIDs. c) Physical complications: i) Overloading (excessive transfusion) leading to heart failure. ii) Pyrogenic reaction (fever and allergy) 3% of cases. d) Haemolytic complication, caused by: i) Incompatible transfusion. ii) Old haemolysed or infected blood. Results in: 1) Clumping of cells which block the capillaries® severe pain in chest and loin. VIII 2) Haemolysed cells liberate (A,B,C and D): A) Haemoglobulin if free in plasma: 1- It will be converted to bile pigments (jaundice). 2- It will pass through the glomeruli of kidneys, precipitate as acid haematin in their tubules blocking them leading to anuria. 3- It will increase the viscosity and colloidal osmotic pressure of the plasma. The work of the heart must be increased markedly. This leads to heart failure. B) Potassium which leads to arrhythmia. C) Toxic substances which produce powerful vasoconstriction of the blood vessels of the kidney, which lead to rapid renal failure (anuria), and death. D) Histamine which leads to hypotension. Dehydration Body Water: Water forms about 60% of total body weight. So, it is about 42 litres in person of 70 kgm body weight. This volume is distributed as follows: 1)Intracellular H2O:( inside the cells) is about 30 liters (70% of total body H2O). 2) Extracellular H2O: (= outside the cells): a. Intravascular (inside blood vessels), i.e. Plasma which is about 3 liters (6% of total body H2O). b. Interstitial (= between cells) is about 9 liters (24% of total body H2O). Dehydration: It is a condition resulting from excessive loss of body fluid (usually H2O + NaCl). 1)Pure H2O Loss: e.g. due to inability to drink as during loss of consciousness. 2) Pure NaCL Loss: e.g. due to very deficient intake or excessive excretion of NaCl in urine. 3.Mixed H2O and NaCl Loss: This is much more common than pure H2O or pure NaCl loss. It may be due to, e.g. excessive sweating, vomiting diarrhea. IX X  Blood Blood platelets and and Body platelet Fluids: part 2 plug. Mechanism of blood coagulation Prevention of blood coagulation inside the blood vessels Abnormalities of haemostasis Blood groups Complications of blood transfusion Dehydration  BLOOD PLATELETS (Thrombocytes) These are granular non- nucleated oval bodies, about 2-4 micron in diameter. Formation: They are fragments of megakaryocytes which are giant cells present in the bone marrow. They have a short life span (8-12 days). Platelet count of normal blood is from 1/4-1/2 million per mm3.  Functions of Platelets Phagocytosis: Platelets can Storage and Haemostasis: phagocytose particles as carbon Transport: Platelets and viruses. store and transport A- Marked constriction of the injured vessels due to serotonin release of a vasoconstrictor substance called “Serotonin B- Platelets then adhere together and plug the vessel opening. C- Releasing the following factors which help blood coagulation: - A factor helping the formation of thromboplastins. - - A factor helping prothrombin-thrombin reaction. - A factor helping fibrinogen-fibrin reaction. - A factor with anti-heparin activity D- Clot RetractionFibrin contraction is caused by a substance released from the platelets called  Hemostasis means prevention of blood loss from blood vessels. Bleeding is stopped by several mechanisms which are: Local Vasoconstriction: Immediately after injury: a) Liberation of serotonin and other vasoconstrictors from platelets. b) Local myogenic contraction of the blood vessel. 2) Formation of the Platelet Plug: The second event in hemostasis is an attempt by the platelets to plus the rent in the vessel. 3) Blood Coagulation: The third mechanism for hemostasis is the formation of the blood clot:  Blood clotting takes place in three essential steps: First: Formation of a prothrombin activator substance in response to rupture of the vessel or damage to the blood itself. Second: The prothrombin activator catalyzes the conversion of prothrombin into thrombin. Third: The thrombin acts as an enzyme to conver t f ibrinogen into f ibrin threads, that enmesh platelets, blood cells, and plasma to form the clot itself.  There are two basic ways in which prothrombin activator can be formed: The extrinsic pathway: that begins with trauma to the vascular wall or to the tissues outside the blood vessels. The intrinsic pathway: that begins in the blood itself.  Lysis of Blood Clots:-The plasma proteins contain an euglobulin called plasminogen or profibrinolysin which, when activated, becomes a proteolytic enzyme called plasmin or fibrinolysin. - Plasminogen is activated by thrombin, activated factor XII, lysosomal enzymes from damaged tissue and factor from vascular endothelium. - Plasmin digests the fibrin threads, fibrinogen, factor V, factor VIII, prothrombin, and factor XII. Therefore, it prevents excessive fibrin formation and causes lysis of the clot within a day or two after blood leakage. 3-Collection of blood in siliconized containers which have a very smooth inner surface. Silicone prevents contact activation of factor XII.  Abnormalities Of Hemostasis A) Bleeding Tendencies Abnormalities of Blood Platelets: Defect in the Clotting Mechanism B-Intravascular Thrombosis  Abnormalities of Blood Platelets Th ro m bo c yt o pe n i a 2- Thrombasthenia (Thrombocytopenic Purpura) It is a state in which the very low level of platelets i.e. platelets are normal in below 50.000/cubic millimeter. quantity but defective in a) Idiopathic thrombocytopenia: function which may result which means: the cause is in a bleeding tendency. unknown. I t may be primary or b) Secondary thrombocytopenia: secondary e.g. in severe o c c u r s i n a sso c i a t i o n w i t h uremia and exposure to aplasia of the bone marrow e.g. certain drugs as aspirin. exposure to X ray, radioactive substances, neoplastic deposits, v e ry sev e re fev e rs and d rug sensitivity.  Defect in the Clotting Mechanism 1-Hemophilia: 2- Vitam in K Def ic iency: Prothrom bin - It is inherited sex-linked disease (factor II) and factors, VII, IX and X require transmitted by females (mothers) to vitamin K for synthesis by the liver. males (infant) but females themselves show no symptoms. Causes of vitamin K deficiency: 1- Sterility of intestine (no bacteria). a) In - There are three types of hemophilia: newly born infants. He m oph i l i a A ( 85% ) ( c l a s s i c a l b) Prolonged use of antibiotics. hemophilia) due to def ic iency of 2- Failure of absorption of vitamin K as in: a) Obstructive jaundice factor VIII. - He m ophilia B (10% ) (Christmas b) Fatty diarrhea. disease) due to lack of factor IX. 3- Liver diseases. - Hemophilia C (5%) due to absence of 4- Competitive inhibition with vitamin K factor XI. as with dicumarol. In h e m op h i l i a , on l y t h e i n t r i n s i c In vitamin K def iciency, both the intrinsic pathway is defective. and extrinsic pathways are defective. defective  B-Intravascular Thrombosis: It is the formation of blood clot inside blood vessels. Contributing Factors: Slowing of blood, e.g., after delivery and operation. Atherosclerosis Complications: 1- Obstruction of arterial supply which leads to ischaemia. 2- Obstruction of venous supply which leads to edema. 3- Embolic formation, i.e., dislodgment of small pieces of the blood clot. e.g., pulmonary emboli. Prevention: - Avoidance of prolonged recumbence. - Use of anticoagulant in susceptible patients. Blood Groups  The sites of danger in blood transfusion is that the RBCs of the donor which may be agglutinated by the agglutinins in the plasma of the recipient. The RBCs of the recipient are not usually affected by the agglutinins in the plasma of the donor. This is because the agglutinins in the injected plasma of the donor are very small and immediately will be diluted by the plasma of the recipient. Group “O” is “Universal Donor” because RBCs of group “O” contain no agglutinogens (A or B), so agglutination cannot take place. Group “AB” is “Universal Recipient” because group “AB” has no agglutinins in its plasma.  Rh Factor This is an agglutinogen which was discovered in the RBCs of Rhesus monkeys (hence the name “Rh”). - It is present in the RBCs of 85% of people who are thus called “Rh positive” The remaining 15% have no Rh factor in their RBCs and are called “Rh negative”. - In Egypt,“Rh positive”people are higher, about 92%. Remarks on Rh Factor: There are no anti-Rh antibodies in normal blood whether Rh positive or Rh negative. No agglutination on the first incompatible Rh transfusion. Only anti-Rh antibodies are formed. Rh negative blood can be transfused to both Rh positive and Rh negative persons antiRh antibodies  Importance of Rh Factor: R H+ f eta l b l ood i s transmitted to maternal ci rcu l a ti on d u ri n g delivery except during delivery Rh antibodies  Prevention: - Rh negative female should never receive an Rh positive blood. - When an Rh negative female delivers Rh positive foetus, an anti-D anti-bodies are given to neutralize the D antigen of the Rh positive fetal cells and prevent sensitization of the mother. Treatment: 1.Replacement of the blood of the baby with Rh negative Group O blood.  Complications of Blood Transfusion 1- Effect on Donor: a- Shock. b- Anaemia if repeated withdrawal. 2- Effect on Recipient: a) Mechanical effect: i ) air and fat embolism. ii) displacement of clot. b) Infective complications: e.g., infective hepatitis, syphilis, malaria and AIDs. c) Physical complications: i) Overloading (excessive transfusion) leading to heart failure. ii) Pyrogenic reaction (fever and allergy) 3% of cases. d) Haemolytic complication, caused by: i) Incompatible transfusion. ii) Old haemolysed or infected blood. Results in: 1) Clumping of cells which block the capillaries severe pain in chest and loin. 2) Haemolysed cells liberate (A,B,C and D):  A) Haemoglobulin if free in plasma: 1- It will be converted to bile pigments (jaundice). 2- It will pass through the glomeruli of kidneys, precipitate as acid haematin in their tubules blocking them leading to anuria. 3- It will increase the viscosity and colloidal osmotic pressure of the plasma. The work of the heart must be increased markedly. This leads to heart failure. B) Potassium which leads to arrhythmia. C) Toxic substances which produce powerful vasoconstriction of the blood vessels of the kidney, which lead to rapid renal failure (anuria), and death. D) Histamine which leads to hypotension.  Dehydration Body Water: Water forms about 60% of total body weight. So, it is about 42 litres in person of 70 kgm body weight. This volume is distributed as follows: 1)Intracellular H2O:( inside the cells) is about 30 liters (70% of total body H2O). 2) Extracellular H2O: (= outside the cells): a. Intravascular (inside blood vessels), i.e. Plasma which is about 3 liters (6% of total body H2O). b. Interstitial (= between cells) is about 9 liters (24% of total body H2O).  Dehydration: It is a condition resulting from excessive loss of body fluid (usually H2O + NaCl). 1)Pure H2O Loss: e.g. due to inability to drink as during loss of consciousness. 2) Pure NaCL Loss: e.g. due to very deficient intake or excessive excretion of NaCl in urine. 3.Mixed H2O and NaCl Loss: This is much more common than pure H2O or pure NaCl loss. It may be due to, e.g. excessive sweating, vomiting diarrhea.