LECTURE 9 Blood & CVS THE LECTURE- Body Fluids.ppt

CARDIOVASCULAR PHYSIOLOGY Blood as part of Body Fluids Tsiri Agbenyega  HOUSE RULES Be Punctual Read Constantly Attend all practical classes Listen and analyze This is not a dictation class All cell phones to vibration  Study Objectives Syllabus Introduced at the beginning of e...

CARDIOVASCULAR PHYSIOLOGY Blood as part of Body Fluids Tsiri Agbenyega  HOUSE RULES Be Punctual Read Constantly Attend all practical classes Listen and analyze This is not a dictation class All cell phones to vibration  Study Objectives Syllabus Introduced at the beginning of every topic Interactive Sections (ask questions)  Outline Function Components Normal Features Abnormal Features  Learning Objectives After completing the Section on blood, you will be expected to know, to describe and interpret data about blood: Need to know COMPOSITION of Blood COMPONENTS of Blood FUNCTIONS of Blood (all components) Function, parameters, development, abnormalities associated with RBC: WBC PLATELETS PROTEINS  BLOOD Functions: a) Transport Gases Nutrients Waste products Hormones b) Defense Antibodies Leucocytes  Composition of Blood 8% of Normal Body Weight 55% Plasma [Fluid Part] 45% cells mainly Erythrocytes because 99% of the cells called Hematocrit Plasma - fluid portion of blood Solvent for K+ Na+ Ca2+ C - HC03 , Inorganic & organic ions: clots on standing If whole blood allowed to stand Clot forming Remove clot Liquid part is Serum SERUM Same composition as plasma {Fibrinogen, Prothrombin V & VIII absent)  Protein Content of Blood Protein: albumin: from liver Globulin , , , Fibrinogen and clotting factors Oncotic pressure (Impermeability to capillary walls) Buffering capacity of blood [15%] Transport of hormones Drugs Metabolites  Erythrocytes Function Transport (Hemoglobin) Carbonic anhydrase for converting CO2 » HCO 3- for transport Buffer 50% Shape and size of RBC Biconcave: 83 Cubicµ {75 um -Thick 2um} Shape is variable without rupturing the cell Indices: Determine the oxygen carrying capacity RBC 5.4 million/µL (4.7 million in females) Varies with age: high in newborn Lowest in 4 –11 months High at altitude PCV – Hematocrit : only tells the volume/plasma affected by fluid content :{47 males- 42 females} High- dehydration Hemoglobin g / dL Men: 13.8 to 18.2 g/dL Women: 12.1 to 15.1 g/dL Derived Indices: not measured directly (MCV) Mean Corpuscular Volume fL (87) Hct x 10 RBC (106/ µL) (MCH): Mean Corpuscular Hb (pg) (29) Hb x 10 RBC(10-6/µL) (MCHC) Mean Corpuscular Hb Conc : (34) Hb x 100 Hct concentration of Hb / RBC Determines size and concentration MCV > 95 =macrocytes < 80 =microcytes Indication of Fe def MCH < 25 hypochromic Mean Cell Diameter -500 cells» 7.5µm Females RBC, Hb, PCV less than males from age 13 onwards.– puberty  RBC Production: Embryonic Life : Liver Spleen Lymph Nodes After birth: Bone marrow All bones - till 5 years then, long bones becomes fatty till 20 years Then only membraneous bone and Humerus & femur RBC : Progenitor: Common Stem Cells Start as Proerythroblast Normoblast 16hrs Basilophil erythroblasts 16hrs Polychromatophil erythroblasts Orthochromatic erythroblasts [Late normoblast] Reticulocytes 1 – 2 only Erythrocytes  RBC Production RBC no nucleus Nucleated RBC immature Reticulocytes 1% in blood; if more-then an increased production RBC Production Regulate within normal range Factors:Tissue Oxygenation Reduced Hormone erythopoietin 90-95% from kidney 5-10% from liver Erythropoietin stimulates RBC production Stimulates the formation of pro- erythroblast and subsequent maturation  RBC Production Feedback RBC Erythropoietin RBC Erythropoietin Conditions that cause low tissue oxygenation Reduced blood volume Anemia Low Hb  Blood flow (cardiac failure) Pulmonary disease (ventilation/perfusion mismatch)  Factors needed for RBC formation Vitamin B12 (Cyanocobalamin) Need for DNA synthesis RBC Rapidly forming, thus need a lot of B12 Lack of it Abnormal cell: Big size (megaloblasts) DNA not produced but RNA Excess production of all cells Constituents thus bigger, fragile cells Abnormal Cells A form of anemia pernicious anemia A form of anemia (pernicious anemia) Diet normal in B12 absorption of B12 abnormal due to atrophic gastric mucosa Abnormal gastric juice Intrinsic factor is usually secreted from parietal cells [not in PA] Intrinsic factor + Vit B12 makes it absorbable Not affected by enzymes Stored in liver: Store can last 1 year or longer in defective absorption Folic Acid : also required for the formation of DNA: Deficiency: Pernicious anemia  IRON metab For Hemoglobin Myoglobin Cytochrones oxidase Catalase 4g Total Body iron 65% in Hb 4% myoglobin 5-30% stored in liver ferritin hemosiderin  Fe ctd absorbed in Fe2+ dietary form Fe3+ gastric secretion forms soluble complexes with Fe3+ converting it to Fe 2+ Inhibitors of Fe (partial gastrectomy) low Fe absorption absorption oxalates phosphates phytic acid complex with Fe and make it insoluble  Fe ctd Fe + apot-ransferin transport form transferrin in blood Storage form apo-ferritin Ferritin Large pools [and insoluble hemosiderin low levels of transferrin (ß globulin] Low transport of Fe to form Hb Fe loss in faeces 0.1 mg daily in men but with women Menstrual loss 1.2mg Absorbed by all parts of GIT active process absorption rate is slow But if low Fe store then Rate abt. 5x inc High Fe store, Rate reduced Feedback : Absorption controlled by apoferritin {ferritin saturated so non released from transferrin} Usually 1/3 saturated Transferrin becomes saturated Prevent mucosal absorption because mucosal cells have somuch iron Fe is excreted in the stool When stores are full then liver reduces the production of apotransferrin So reduces the danger of Fe overload but overload occurs when extreme amounts of Fe is taken orally: Overload can occur You dodge the gut and give either IM or IV Fe deficiency: transferrin is increased  Life Span 120 days : metabolic processes become weaker metabolic processes produce ATP to maintain cell wall cells become fragile lyse when they pass through small passages especially the spleen Lysed cells phagocylosed by Macrophages and Kupfer cells Spleen and bone marrow Hb Structure: BIOCHEMISTRY Heme + 4 subunits 4 chains of aa or polypeptide Fe containing Compound Hemoglobin A 2 ß2 A2 2 2 HbF 2 2  Anemia Deficiency of normal RBCs Reduced production Aplastic: Bone marrow Low Fe Fe deficiency (microcytic) Low Folic acid Low Vitamin B12 Excessive loss Hemorrhage Excessive breakdown Hemolytic: Fragile Red Cells: Hemolyze easily Heriditary Spheromytosis SCD Hemoglobin S. Thalassemias  Effects of Anemia Fall in blood viscosity  Resistance to flow (also due to vasodilatation after tissue hypoxia) Venous return  Cardiac Output ie increased workload on the heart  Pulse  Respiratory Rate Change in Indices : Direct and derived MCH MCV MCHC  POLYCYTHEMIA 20 to Cardiac F Cardiac disease with right to left shunt Physiologic: High altitude Tumor Polycythemia Rubra vera: abnormal production of RBC and White cells  POLYCYTHEMIA RBC 20: Cardiac F Physiologic: High altitude Tumor Polycythemia Rubra vera: abnormal production of RBC and White cells  LEUCOCYTES (WBC) Total 4000-11000/µL of blood Main function- defense Granulocytes - Because when they are stained granular substances are seen in the cytoplasm neutral Neutrophils Acid Eosinophils Basic Basophils Lymphocytes Some in marrow, more in lymph nodes, Thymus and spleen Monocytes Bone marrow Platelets Leukocytes (WBCs) Cells  Mechanisms of Action Fight against invasion by virus and bacteria foreign bodies etc Macrophages Main mechanism: Destroy invading organism: phagocytosis Abs and sensitize lymphocytes To destroy invaders  Functions Granulocyes mainly concerned with Inflammatory and allergic Rn Basophils Histamin and Heparin release Responsible for hypersensitivity Rns urticaria Rhinitis anaphylactic Shock Eosinophils attack parasites also involved in the allergic process (Inactivate mediators of the allergic Rn) Level increased in allergic Reactions Neutrophils ingest and kill bacteria responsible for the formation of pus Average half-life in circulation. 6hrs  Neutrophils To maintain blood levels, high daily production They pass through the endothelial wall by squeezing in between the cells: to enter tissues Process called Diapedesis Most enter the gut and are lost Invasion by bacteria Inflammatory response Stimulation of bone marrow: Neutrophils attracted by [chemotaxis] to areas of infection other factors coat bacteria: opsonize IgG So that they are engulfed (phagocytosis) Monocytes Circulate for 72 hours into the blood Enter tissues Tissue Macrophages Include Kupffer Cells liver Pulmonary Alveolar Macrophages Tissue Macrophage System New Name Reticulo endothelial System Old name They are attracted to bacteria by Chemotaxis stimuli Engulf and kill bacteria  Lymphocytes Main role is producing antibodies ability to remember a previous exposure humo cellul ral ar Antibody production  T-Lymphocytes  Mediated by B  Reaction to foreign Lymphocytes protein  Delayed allergic  Plasma cells Rns  Rejection of foreign tissue  Immune Response Non specific Protecting against foreign substance without the need to recognise their specific identities Specific depends on the recognition of the substances or the cells to be attached Plasma cells: Differentiate from B cells The leucocytes use the blood mainly for transport Macrophages derived from monocytes Mast cells differential from Basophils  Blood Group Incompatibility Membrane antigen Agglutinogens ( a lot of agglutinogens Most important A and B agglutinogens Classification in A, B, AB or O depending on the type of agglutinogen present in the red cell Antibodies exist against these antigens (Agglutinogen) Also known as agglutinins (1gM)  A-B-O GROUP BLOOD TYPES Agglutinogen Agglutinin A B B A AB - O AB  Transfusion of Blood Practical aspects Group and cross match Transfusion into an individual A A, AB Normal A B, Abnormal B B, AB Normal B B Normal O O, A, B, AB Normal AB AB, O,A, B Abnormal Universal Recipients AB Universal Donor O  Transfusion Lab Testing Clinic and dilution factor Donor Dilution of Agglutinins from donor “important” Recipient  Abnormal Reactions Incompatibility Agglutination Hemolysis Anemia Jaundice Renal tubular Damage Renal Failure  Rhesus incompatibility Rhesus or Rh factor Many antigens but the most important is D D or Rh+ve has agglutinogen D- no antibody Rh – ve no agglutinogen D But has the capacity to form agglutinnin D or Anti D when it comes into contact with cells with Agglutinogen D  Transfusion Agglutination Previous exposure to +ve blood Hemolysis RH+ve Anti D RH-ve  Rhesus incompatibility Hemolytic disease of newborn Mother is Rh-ve Father +ve Baby +ve Mother’s anti D (IgG) crosses over into fetal circulation Fetal circulation Agglutination in utero Hemolysis (Erythroblastosis fetalis) Anemia, jaundice, kernicterus-Basal ganglia, Heart failure hydrops fetalis  Anti D antibody During post partum period Prevent antibody formation by the mother Give antibody against anti D Hemostais To Stop Bleeding  Hemostsis Whole blood allowed to clot and clot removed SERUM plasma minus clotting factor II, V & VIII and fibrinogen Plasma clots on standing Hemostasis Elimination of bleeding Stopping bleeding  Hemostasis Source of bleeding: Arterioles Capillaries Venules Events to be Hemostatic mechanisms more effective for these Bigger arteries: bleeding can’t be stopped easily Venous bleeding usually stops because of low blood pressure Balance of clotting with anti clotting features to prevent intra vascular coagulation  Hemostasis Local Response Vasoconstriction Contraction of smooth muscles reduces blood flow to the region Endothelial surfaces stick together after coming into contact due to serotonin and the vasoconstrictors Platelet Plug (to seal the defect on the blood vessel) Formed form megakaryocytes: giant cells from bone marrow Patelets aggregate (when stimulated) at the sight of injury Stimulus for platelet aggregation Collagen fibres from vessels ADP from the platelets (secretory granules ) are secreted when platelets start aggregating Thromboxane A2 Formed Arachodonic acid in platelets Formation inhibited By the drug Aspirin Von Williebrand factor Produced endothelical cells and platelets Forms a bridge between the vessel walls and the first layers of the platelets. It binds to collagen and platelets bind to it. Thrombin Platelet Activating factor from endothelial cells Inhibitor of platelet inhibition Prostacycline Adventitia (Thromboxane A2 action opposed) Keeps it localised Prevents formation in normal vessels  CLOTTING: Hemostatic Plug Initial event in the clot: Platelet plug Thrombocytopenic purpura clot formation deficient Abnormal Cells: Thrombaestenic Purpura  Blood clot A protective mechanism that prevents excessive blood from being lost after injury Transformation of blood into a solid gel: Blood clot By the conversion of a protein fibrinogen to fibrin monomers Polymerization: insoluble  What is a clot? Fibrinogen to fibrin, Tough, insoluble polymerized protein which forms a network of fibers around the platelets that have stuck to the edge of the wound and to each other. The network entangles the blood cells, and contracts, squeezing out the serum and leaving a clot, which dries to form a scab. This prevents further loss of blood, and also prevents bacteria getting into the wound. Normal clotting takes place within five minutes.  CLOTTING FACTORS I. Fibrinogen II. Prothrombin III. Thromboplastin IV. Calcium V. Labile Factor VII. Stable Factor VIII Antihemophilic Factor A IX. Christmas Factor X. Staurt Prower Factor XI. Plasma Thromboplastin Antecedent XII. Hageman Factor XIII. Fibrin Stabilizing Factor Clotting cascade  Intrinsic Pathway Intrinsic Pathway. is activated by trauma inside the vascular system, activated by platelets, exposed endothelium, chemicals, or collagen. T his pathway is slower than the extrinsic pathway, but more important. It involves factors XII, XI, IX, VIII.  Extrinsic Pathway The extrinsic pathway of blood coagulation. Upon the introduction of cells, particularly crushed or injured tissue, blood coagulation is activated and a fibrin clot is rapidly formed. T the pathway of blood coagulation activated by tissue factor, a protein extrinsic to blood, is known as the extrinsic pathway  INTRINSIC SYSTEM CLOTTING CASCADE HMW Kininogen, Kallikrein XII XIIa HMW Kininogen EXTRINSIC SYSTEM XI XIa TPL, TFI VIIa VII IX IXa VIII PL, Ca++, VIIIa X Xa PL, Ca2+ Va V Prothrombin Thrombin Fibrinogen Fibrin Stabilization XIII XIIIa Clotting Anticoagulation Mechanisms Prevent excessive clotting Break down excess clots Produce only a limited amount of clotting factors Antithrombin III circulating protease inhibitor Blocks activity of some clotting factors by binding to them, IX, X, XI active forms of XII Activity facilitated by Heparin Aid in the binding of antithrombin III to the factors  The fibrinolytic system Endothelial Cells except Central Micro circulation - produce Thrombomodulin Protein C a naturally occurring anticoagulant Protein C also inactivates inhibitors of tissue [plasminogen activator] Produces Plasmin or Fibrinolysin Fibrin Degradation Product  Anticouagulants Principle : Prevents formation of clotting factors Prevent activation or action of clotting factor Prevent aggregation of platelets Break down clot  Anticoagulants Aspirin reduced thromboxane A2 formation Thus reduces platelet aggregation Used to prevent or may reduce clot formation and thus prevent heart disease Antithrombin III Circulating protease inhibitor binds to these proteins IX, X, XI, XII Heparin blocks action of IX, X, XI, XII By aiding anti thrombin III [inactivated by protamine] When bound to heparin, protamine prevents heparin from enhancing the anticoagulant effect of AT-III  Anticoagulants Prostacycline Streptokinase Dicoumarol (warfarin) Inhibit the action of vitamin K used in the clotting factors II, VII X IX and [protein C] [protein S]  Clotting Disorders Liver Disease No absorption of Vit K [Bile] Fall in Synthesis of plasma proteins Platelet dysfunction Low levels of platelets [thrombocytopenic purpura] abnormal platelets [thromboaesthenic purpura] easy bruising multiple subcutaneous hemorrhage Deficiency of Von Willibrand factor Lack of platelet aggregation  Clotting problems Lack of clotting factors Mostly congenital and inherited Lack of factor VIII [anti-hemophilic factor] Hemophilia A Gene is found in X chromosome X- Linked Replace with Plasma fraction: Contains factor VIII. Problem AIDS Now Genetic Engineering Abnormal Intra-vascular clotting Inside ------thrombus Due to change of inner wall eg arteriosclerotic plagues Prone to sluggish flow: usually veins Prolonged prostration Post operative Break away--Emboli  Estimating Clotting Bleeding from a minor wound ceases before a clot is fully formed i.e. bleeding time is usually shorter than clotting time Test of Hemostasis Bleeding time Denotes deficiency in platelets Extrinsic Pathway deficiency Vascular Disorders Clotting Time Reduction in factors II, V, VII, IX, X, XI, XII Abnormal Intrinsic and common pathways Taking Blood containers, Oxalate, citrate bottle remove or reduce Ca++ Heparin Bleeding Test Bleeding time earlobe 3 –6 minutes May be affected by Degree of hyperemia Nature of cut Check time it takes to clot 12 seconds Clotting Disorders Clotting time Collect blood in clean TT and agitate for 30 seconds until clotting 5-8 minutes Depends on tube size thus-standardized Cleanliness Prolonged in Hemophiliacs Prothrombin Time Estimates the total quantity of prothrombin Take sample add oxalate to remove Ca++ Then add Ca++ Extrinsic pathway initiated + tissue Thromboplastin Check time it takes to clot 12 seconds  WEBSITES Google. Cardiovascular System Animation