The Cardiovascular System: The Blood Lecture Outline Chapter 19 The Cardiovascular System: The Blood Lecture Outline

INTRODUCTION Blood inside blood vessels, interstitial fluid around body cells, and lymph inside lymph vessels constitute one’s internal environment. To obtain nutrients and remove wastes, cells must be serviced by blood and interstitial fluid. Blood, a connective tissue, is composed of plasma and formed elements. Interstitial fluid bathes body cells (Figure 19.1). The branch of science concerned with the study of blood, blood-forming tissues, and the disorders associated with them is called hematology. Principles of Human Anatomy and Physiology, 11e

Chapter 19 The Cardiovascular System: The Blood Principles of Human Anatomy and Physiology, 11e

Fluids of the Body Cells of the body are serviced by 2 fluids blood composed of plasma and a variety of cells transports nutrients and wastes interstitial fluid bathes the cells of the body Nutrients and oxygen diffuse from the blood into the interstitial fluid & then into the cells Wastes move in the reverse direction Hematology is study of blood and blood disorders Principles of Human Anatomy and Physiology, 11e

Functions of Blood Transportation O2, CO2, metabolic wastes, nutrients, heat & hormones Regulation helps regulate pH through buffers helps regulate body temperature coolant properties of water vasodilatation of surface vessels dump heat helps regulate water content of cells by interactions with dissolved ions and proteins Protection from disease & loss of blood Principles of Human Anatomy and Physiology, 11e

Physical Characteristics of Blood Thicker (more viscous) than water and flows more slowly than water Temperature of 100.4 degrees F pH 7.4 (7.35-7.45) 8 % of total body weight Blood volume 5 to 6 liters in average male 4 to 5 liters in average female hormonal negative feedback systems maintain constant blood volume and osmotic pressure Principles of Human Anatomy and Physiology, 11e

Techniques of Blood Sampling Venipuncture sample taken from vein with hypodermic needle & syringe median cubital vein (see page 717) why not stick an artery? less pressure closer to the surface Finger or heel stick common technique for diabetics to monitor daily blood sugar method used for infants Principles of Human Anatomy and Physiology, 11e

COMPONENTS OF BLOOD Blood consists of 55% plasma and 45% formed elements (Figure 19.1). Blood plasma consists of 91.5% water and 8.5% solutes. Principal solutes include proteins (albumins, globulins, fibrinogen), nutrients, enzymes, hormones, respiratory gases, electrolytes, and waste products. Table 19.1 summarizes the chemical composition of plasma. Principles of Human Anatomy and Physiology, 11e

Components of Blood Hematocrit 55% plasma 45% cells 99% RBCs < 1% WBCs and platelets Principles of Human Anatomy and Physiology, 11e

Blood Plasma 0ver 90% water 7% plasma proteins created in liver confined to bloodstream albumin maintain blood osmotic pressure globulins (immunoglobulins) antibodies bind to foreign substances called antigens form antigen-antibody complexes fibrinogen for clotting 2% other substances electrolytes, nutrients, hormones, gases, waste products Principles of Human Anatomy and Physiology, 11e

Formed Elements of Blood Red blood cells ( erythrocytes ) White blood cells ( leukocytes ) granular leukocytes neutrophils, eosinophils, basophils agranular leukocytes lymphocytes = T cells, B cells, and natural killer cells monocytes Platelets (special cell fragments) Principles of Human Anatomy and Physiology, 11e

FORMATION OF BLOOD CELLS Blood cells are formed from pluripotent hematopoietic stem cells (Figure 19.3). Bone marrow may be obtained through aspiration or biopsy. The sample is then sent to pathology for examination. Originating from the pluripotent stem cells are the myeloid stem cells and lymphoid stem cells. Principles of Human Anatomy and Physiology, 11e

Hematocrit Percentage of blood occupied by cells female normal range 38 - 46% (average of 42%) male normal range 40 - 54% (average of 46%) testosterone Anemia not enough RBCs or not enough hemoglobin Polycythemia too many RBCs (over 65%) dehydration, tissue hypoxia, blood doping in athletes Principles of Human Anatomy and Physiology, 11e

Blood Doping Injecting previously stored RBC’s before an athletic event more cells available to deliver oxygen to tissues Dangerous increases blood viscosity forces heart to work harder Banned by Olympic committee Principles of Human Anatomy and Physiology, 11e

Formation of Blood Cells Most blood cells types need to be continually replaced die within hours, days or weeks process of blood cells formation is hematopoiesis or hemopoiesis In the embryo occurs in yolk sac, liver, spleen, thymus, lymph nodes & red bone marrow In adult occurs only in red marrow of flat bones like sternum, ribs, skull & pelvis and ends of long bones Principles of Human Anatomy and Physiology, 11e

Hematopoiesis Principles of Human Anatomy and Physiology, 11e

Stages of Blood Cell Formation Pluripotent stem cells .1% of red marrow cells replenish themselves as they differentiate into either myeloid or lymphoid stem cells Myeloid stem cell line of development continues: progenitor cells(colony-forming units) no longer can divide and are specialized to form specific cell types example: CFU-E develops eventually into only red blood cells next generation is blast cells have recognizable histological characteristics develop within several divisions into mature cell types Lymphoid stem cell line of development pre-B cells & prothymocytes finish their develop into B & T lymphocytes in the lymphatic tissue after leaving the red marrow Principles of Human Anatomy and Physiology, 11e

Hemopoietic Growth Factors Regulate differentiation & proliferation Erythropoietin (EPO) produced by the kidneys increase RBC precursors Thrombopoietin (TPO) hormone from liver stimulates platelet formation Cytokines are local hormones of bone marrow produced by some marrow cells to stimulate proliferation in other marrow cells colony-stimulating factor (CSF) & interleukin stimulate WBC production Principles of Human Anatomy and Physiology, 11e

Medical Uses of Growth Factors Available through recombinant DNA technology recombinant erythropoietin (EPO) very effective in treating decreased RBC production of end-stage kidney disease other products given to stimulate WBC formation in cancer patients receiving chemotherapy which kills bone marrow granulocyte-macrophage colony-stimulating factor granulocyte colony stimulating factor thrombopoietin helps prevent platelet depletion during chemotherapy Principles of Human Anatomy and Physiology, 11e

Blood Cells Myeloid stem cells give rise to RBCs, platelets, and all WBCs except for lymphocytes. Lymphoid stem cells give rise to lymphocytes. Myeloid stem cells differentiate into progenitor cells or precursor cells (blast cells) which will develop into the actual formed elements of blood. Lymphoid stem cells differentiate into pre-B and prothymocytes which develop into B-lymphocytes and T-lymphocytes, respectively. This process of hemopoiesis (or hematopoiesis) is stimulated by several hematopoietic growth factors. These hematopoietic growth factors stimulate differentiation and proliferation of the various blood cells. Principles of Human Anatomy and Physiology, 11e

Red Blood Cells or Erythrocytes (Figure 19.4a) Contain oxygen-carrying protein hemoglobin that gives blood its red color 1/3 of cell’s weight is hemoglobin Biconcave disk 8 microns in diameter increased surface area/volume ratio flexible shape for narrow passages no nucleus or other organelles no cell division or mitochondrial ATP formation Normal RBC count male 5.4 million/drop ---- female 4.8 million/drop new RBCs enter circulation at 2 million/second Principles of Human Anatomy and Physiology, 11e

Hormones Erythropoietin increases the number of RBC precursors. Thrombopoietin increases the number of platelet precursors. Cytokins (colony-stimulating factors and interleukins) increase the number of WBC precursors. Growth factors, available through recombinant DNA technology, hold great potential for use in patients who cannot normally form the blood cells. Principles of Human Anatomy and Physiology, 11e

Hemoglobin Globin protein consisting of 4 polypeptide chains One heme pigment attached to each polypeptide chain each heme contains an iron ion (Fe+2) that can combine reversibly with one oxygen molecule Principles of Human Anatomy and Physiology, 11e

Transport of O2, CO2 and Nitric Oxide Each hemoglobin molecule can carry 4 oxygen molecules from lungs to tissue cells Hemoglobin transports 23% of total CO2 waste from tissue cells to lungs for release combines with amino acids in globin portion of Hb Hemoglobin transports nitric oxide & super nitric oxide helping to regulate BP iron ions pick up nitric oxide (NO) & super nitric oxide (SNO)& transport it to & from the lungs NO causing vasoconstriction is released in the lungs SNO causing vasodilation is picked up in the lungs Principles of Human Anatomy and Physiology, 11e

RBCs Production of abnormal hemoglobin can result in serious blood disorders such as thalassemia and sickle cell anemia. (Figure 19.15) The blood test, hemoglobin A1c, can be used to monitor blood glucose levels in diabetics Principles of Human Anatomy and Physiology, 11e

RBC Life Cycle RBCs live only 120 days wear out from bending to fit through capillaries no repair possible due to lack of organelles Worn out cells removed by fixed macrophages in spleen & liver Breakdown products are recycled Principles of Human Anatomy and Physiology, 11e

Recycling of Hemoglobin Components In macrophages of liver or spleen globin portion broken down into amino acids & recycled heme portion split into iron (Fe+3) and biliverdin (green pigment) Principles of Human Anatomy and Physiology, 11e

Fate of Components of Heme Iron(Fe+3) transported in blood attached to transferrin protein stored in liver, muscle or spleen attached to ferritin or hemosiderin protein in bone marrow being used for hemoglobin synthesis Biliverdin (green) converted to bilirubin (yellow) bilirubin secreted by liver into bile converted to urobilinogen then stercobilin (brown pigment in feces) by bacteria of large intestine if reabsorbed from intestines into blood is converted to a yellow pigment, urobilin and excreted in urine Principles of Human Anatomy and Physiology, 11e

Erythropoiesis: Production of RBCs Erythrocyte formation, called erythropoiesis, occurs in adult red bone marrow of certain bones (Figure 19.3). The main stimulus for erythropoiesis is hypoxia (Figure 19.6). Proerythroblast starts to produce hemoglobin Many steps later, nucleus is ejected & a reticulocyte is formed orange in color with traces of visible rough ER Reticulocytes escape from bone marrow into the blood In 1-2 days, they eject the remaining organelles to become a mature RBC Principles of Human Anatomy and Physiology, 11e

Feedback Control of RBC Production Tissue hypoxia (cells not getting enough O2) high altitude since air has less O2 anemia RBC production falls below RBC destruction circulatory problems Kidney response to hypoxia release erythropoietin speeds up development of proerythroblasts into reticulocytes Principles of Human Anatomy and Physiology, 11e

Normal Reticulocyte Count Should be .5 to 1.5% of the circulating RBC’s Low count in an anemic person might indicate bone marrow problem leukemia, nutritional deficiency or failure of red bone marrow to respond to erythropoietin stimulation High count might indicate recent blood loss or successful iron therapy Principles of Human Anatomy and Physiology, 11e

WHITE BLOOD CELLS Leukocytes (white blood cells or WBCs) are nucleated cells and do not contain hemoglobin. Two principal types are granular (neutrophils, eosinophils, basophils) and agranular (lymphocytes and monocytes) (Figure 19.7). Granular leukocytes include eosinophils, basophils, and neutrophils based on the straining of the granules. Agranular leukocytes do not have cytoplasmic granules and include the lymphocytes and monocytes, which differentiate into macrophages (fixed and wandering). Leukocytes have surface proteins, as do erythrocytes. They are called major histocompatibility antigens (MHC), are unique for each person (except for identical siblings), and can be used to identify a tissue. Principles of Human Anatomy and Physiology, 11e

WBC Physiology Less numerous than RBCs 5000 to 10,000 cells per drop of blood 1 WBC for every 700 RBC Leukocytosis is a high white blood cell count microbes, strenuous exercise, anesthesia or surgery Leukopenia is low white blood cell count radiation, shock or chemotherapy Only 2% of total WBC population is in circulating blood at any given time rest is in lymphatic fluid, skin, lungs, lymph nodes & spleen Principles of Human Anatomy and Physiology, 11e

Function of WBCs Different WBCs combat inflammation and infection in different ways. Neutrophils and wandering or fixed macrophages (which develop from monocytes) do so through phagocytosis. Eosinophils combat the effects of histamine in allergic reactions, phagocytize antigen-antibody complexes, and combat parasitic worms. Basophils develop into mast cells that liberate heparin, histamine, and serotonin in allergic reactions that intensify the inflammatory response. B lymphocytes, in response to the presence of foreign substances called antigens, differentiate into tissue plasma cells that produce antibodies. T lymphocytes destroy foreign invaders directly. Principles of Human Anatomy and Physiology, 11e

Function of WBCs WBCs leave the blood stream by emigration (Figure 19.8). Some WBCs, particularly neutrophils and macrophages, are active in phagocytosis. The chemical attraction of WBCs to a disease or injury site is termed chemotaxis. Principles of Human Anatomy and Physiology, 11e

WBC examination A differential white blood cell count is a diagnostic test in which specific white blood cells are enumerated. Because each type of WBC plays a different role, determining the percentage of each type in the blood assists in diagnosing the condition. Table 19.2 shows the significance of elevated or depressed counts of the various WBCs. Bone marrow transplants may be used to treat several types of anemia, leukemia, and numerous other blood disorders. (Clinical Application) Principles of Human Anatomy and Physiology, 11e

WBC Anatomy and Types All WBCs (leukocytes) have a nucleus and no hemoglobin Granular or agranular classification based on presence of cytoplasmic granules made visible by staining granulocytes are neutrophils, eosinophils or basophils agranulocytes are monocyes or lymphocytes Principles of Human Anatomy and Physiology, 11e

Neutrophils (Granulocyte) Polymorphonuclear Leukocytes or Polys Nuclei = 2 to 5 lobes connected by thin strands older cells have more lobes young cells called band cells because of horseshoe shaped nucleus (band) Fine, pale lilac practically invisible granules Diameter is 10-12 microns 60 to 70% of circulating WBCs Principles of Human Anatomy and Physiology, 11e

Eosinophils (Granulocyte) Nucleus with 2 or 3 lobes connected by a thin strand Large, uniform-sized granules stain orange-red with acidic dyes do not obscure the nucleus Diameter is 10 to 12 microns 2 to 4% of circulating WBCs Principles of Human Anatomy and Physiology, 11e

Basophils (Granulocyte) Large, dark purple, variable-sized granules stain with basic dyes obscure the nucleus Irregular, s-shaped, bilobed nuclei Diameter is 8 to 10 microns Less than 1% of circulating WBCs Principles of Human Anatomy and Physiology, 11e

Lymphocyte (Agranulocyte) Dark, oval to round nucleus Cytoplasm sky blue in color amount varies from rim of blue to normal amount Small cells 6 - 9 microns in diameter Large cells 10 - 14 microns in diameter increase in number during viral infections 20 to 25% of circulating WBCs Principles of Human Anatomy and Physiology, 11e

Monocyte (Agranulocyte) Nucleus is kidney or horse-shoe shaped Largest WBC in circulating blood does not remain in blood long before migrating to the tissues differentiate into macrophages fixed group found in specific tissues alveolar macrophages in lungs kupffer cells in liver wandering group gathers at sites of infection Diameter is 12 - 20 microns Cytoplasm is a foamy blue-gray 3 to 8% o circulating WBCs Principles of Human Anatomy and Physiology, 11e

Emigration & Phagocytosis in WBCs WBCs roll along endothelium, stick to it & squeeze between cells. adhesion molecules (selectins) help WBCs stick to endothelium displayed near site of injury molecules (integrins) found on neutrophils assist in movement through wall Neutrophils & macrophages phagocytize bacteria & debris chemotaxis of both kinins from injury site & toxins Principles of Human Anatomy and Physiology, 11e

Neutrophil Function Fastest response of all WBC to bacteria Direct actions against bacteria release lysozymes which destroy/digest bacteria release defensin proteins that act like antibiotics & poke holes in bacterial cell walls destroying them release strong oxidants (bleach-like, strong chemicals ) that destroy bacteria Principles of Human Anatomy and Physiology, 11e

Monocyte Function Take longer to get to site of infection, but arrive in larger numbers Become wandering macrophages, once they leave the capillaries Destroy microbes and clean up dead tissue following an infection Principles of Human Anatomy and Physiology, 11e

Basophil Function Involved in inflammatory and allergy reactions Leave capillaries & enter connective tissue as mast cells Release heparin, histamine & serotonin heighten the inflammatory response and account for hypersensitivity (allergic) reaction Principles of Human Anatomy and Physiology, 11e

Eosinophil Function Leave capillaries to enter tissue fluid Release histaminase slows down inflammation caused by basophils Attack parasitic worms Phagocytize antibody-antigen complexes Principles of Human Anatomy and Physiology, 11e

Lymphocyte Functions B cells destroy bacteria and their toxins turn into plasma cells that produces antibodies T cells attack viruses, fungi, transplanted organs, cancer cells & some bacteria Natural killer cells attack many different microbes & some tumor cells destroy foreign invaders by direct attack Principles of Human Anatomy and Physiology, 11e

Complete Blood Count Screens for anemia and infection Total RBC, WBC & platelet counts; differential WBC; hematocrit and hemoglobin measurements Normal hemoglobin range infants have 14 to 20 g/100mL of blood adult females have 12 to 16 g/100mL of blood adult males have 13.5 to 18g/100mL of blood Principles of Human Anatomy and Physiology, 11e

Differential WBC Count Detection of changes in numbers of circulating WBCs (percentages of each type) indicates infection, poisoning, leukemia, chemotherapy, parasites or allergy reaction Normal WBC counts neutrophils 60-70% (up if bacterial infection) lymphocyte 20-25% (up if viral infection) monocytes 3 -- 8 % (up if fungal/viral infection) eosinophil 2 -- 4 % (up if parasite or allergy reaction) basophil <1% (up if allergy reaction or hypothyroid) Principles of Human Anatomy and Physiology, 11e

Bone Marrow Transplant Intravenous transfer of healthy bone marrow Procedure destroy sick bone marrow with radiation & chemotherapy donor matches surface antigens on WBC put sample of donor marrow into patient's vein for reseeding of bone marrow success depends on histocompatibility of donor & recipient Treatment for leukemia, sickle-cell, breast, ovarian or testicular cancer, lymphoma or aplastic anemia Principles of Human Anatomy and Physiology, 11e

PLATELETS Thrombopoietin stimulates myeloid stem cells to produce platelets. Myeloid stem cells develop into megakaryocyte-colony-forming cells that develop into megakaryoblasts (Figure 19.2). Megakaryoblasts transform into megakaryocytes which fragment. Each fragment, enclosed by a piece of cell membrane, is a platelet (thrombocyte). Normal blood contains 250,000 to 400,000 platelets/mm3. Platelets have a life span of only 5 to 9 days; aged and dead platelets are removed by fixed macrophages in the spleen and liver. Principles of Human Anatomy and Physiology, 11e

PLATELETS Platelets help stop blood loss from damaged vessels by forming a platelet plug. Their granules also contain chemicals that promote blood clotting. A complete blood count (CBC) is a test that screens for anemia and various infections. It usually includes counts of RBCs, WBCs, and platelets per μL of whole blood; hematocrit and differential white blood cell count. The amount of hemoglobin in grams per ml is also determined. Table 19.3 summarizes the formed elements in blood. Principles of Human Anatomy and Physiology, 11e

Platelet (Thrombocyte) Anatomy Disc-shaped, 2 - 4 micron cell fragment with no nucleus Normal platelet count is 150,000-400,000/drop of blood Other blood cell counts 5 million red & 5-10,000 white blood cells Principles of Human Anatomy and Physiology, 11e

Platelets--Life History Platelets form in bone marrow by following steps: myeloid stem cells to megakaryocyte-colony forming cells to megakaryoblast to megakaryocytes whose cell fragments form platelets Short life span (5 to 9 days in bloodstream) formed in bone marrow few days in circulating blood aged ones removed by fixed macrophages in liver and spleen Principles of Human Anatomy and Physiology, 11e

STEM CELL TRANSPLANT FROM BONE MARROW AND CORD-BLOOD Bone marrow transplant replaces diseased marrow with healthy marrow. Patient’s diseased marrow is destroyed. Healthy marrow is supplied by a donor or the patient. There are several problems with this method. Principles of Human Anatomy and Physiology, 11e

Cord-blood transplant Stem cells are taken from the umbilical cord and frozen This method offers several advantages over marrow transplant. Principles of Human Anatomy and Physiology, 11e

HEMOSTASIS A clot is a gel consisting of a network of insoluble protein fibers (fibrin) in which formed elements of blood are trapped (Figure 19.10). The chemicals involved in clotting are known as coagulation (clotting) factors; most are in blood plasma, some are released by platelets, and one is released from damaged tissue cells (Table 19.4). Blood clotting involves a cascade of reactions that may be divided into three stages: formation of prothrombinase (prothrombin activator), conversion of prothrombin into thrombin, and conversion of soluble fibrinogen into insoluble fibrin (Figure 19.11). Principles of Human Anatomy and Physiology, 11e

HEMOSTASIS The clotting cascade can be initiated by either the extrinsic pathway or the intrinsic pathway. Normal coagulation requires vitamin K and also involves clot retraction (tightening of the clot) and fibrinolysis (dissolution of the clot). The fibrinolytic system dissolves small, inappropriate clots and clots at a site of damage once the damage is repaired. Plasmin (fibrinolysin) can dissolve a clot by digesting fibrin threads and inactivating substances such as fibrinogen, prothrombin, and factors V, VIII, and XII. Principles of Human Anatomy and Physiology, 11e

Hemostasis Stoppage of bleeding in a quick & localized fashion when blood vessels are damaged Prevents hemorrhage (loss of a large amount of blood) Methods utilized vascular spasm platelet plug formation blood clotting (coagulation = formation of fibrin threads) Principles of Human Anatomy and Physiology, 11e

Vascular Spasm Damage to blood vessel produces stimulates pain receptors Reflex contraction of smooth muscle of small blood vessels Can reduce blood loss for several hours until other mechanisms can take over Only for small blood vessel or arteriole Principles of Human Anatomy and Physiology, 11e

Platelet Plug Formation Platelets store a lot of chemicals in granules needed for platelet plug formation alpha granules clotting factors platelet-derived growth factor cause proliferation of vascular endothelial cells, smooth muscle & fibroblasts to repair damaged vessels dense granules ADP, ATP, Ca+2, serotonin, fibrin-stabilizing factor, & enzymes that produce thromboxane A2 Steps in the process (1) platelet adhesion (2) platelet release reaction (3) platelet aggregation Principles of Human Anatomy and Physiology, 11e

Platelet Adhesion Platelets stick to exposed collagen underlying damaged endothelial cells in vessel wall Principles of Human Anatomy and Physiology, 11e

Platelet Release Reaction Platelets activated by adhesion Extend projections to make contact with each other Release thromboxane A2 & ADP activating other platelets Serotonin & thromboxane A2 are vasoconstrictors decreasing blood flow through the injured vessel Principles of Human Anatomy and Physiology, 11e

Platelet Aggregation Activated platelets stick together and activate new platelets to form a mass called a platelet plug Plug reinforced by fibrin threads formed during clotting process Principles of Human Anatomy and Physiology, 11e

Blood Clotting Blood drawn from the body thickens into a gel gel separates into liquid (serum) and a clot of insoluble fibers (fibrin) in which the cells are trapped If clotting occurs in an unbroken vessel is called a thrombosis Substances required for clotting are Ca+2, enzymes synthesized by liver cells and substances released by platelets or damaged tissues Clotting is a cascade of reactions in which each clotting factor activates the next in a fixed sequence resulting in the formation of fibrin threads prothrombinase & Ca+2 convert prothrombin into thrombin thrombin converts fibrinogen into fibrin threads Principles of Human Anatomy and Physiology, 11e

Overview of the Clotting Cascade Prothrombinase is formed by either the intrinsic or extrinsic pathway Final common pathway produces fibrin threads Principles of Human Anatomy and Physiology, 11e

Extrinsic Pathway Damaged tissues leak tissue factor (thromboplastin) into bloodstream Prothrombinase forms in seconds In the presence of Ca+2, clotting factor X combines with V to form prothrombinase Principles of Human Anatomy and Physiology, 11e

Intrinsic Pathway Activation occurs endothelium is damaged & platelets come in contact with collagen of blood vessel wall platelets damaged & release phospholipids Requires several minutes for reaction to occur Substances involved: Ca+2 and clotting factors XII, X and V Principles of Human Anatomy and Physiology, 11e

Final Common Pathway Prothrombinase and Ca+2 catalyze the conversion of prothrombin to thrombin Thrombin in the presence of Ca+2 converts soluble fibrinogen to insoluble fibrin threads activates fibrin stabilizing factor XIII positive feedback effects of thrombin accelerates formation of prothrombinase activates platelets to release phospholipids Principles of Human Anatomy and Physiology, 11e

Clot Retraction & Blood Vessel Repair Clot plugs ruptured area of blood vessel Platelets pull on fibrin threads causing clot retraction trapped platelets release factor XIII stabilizing the fibrin threads Edges of damaged vessel are pulled together Fibroblasts & endothelial cells repair the blood vessel Principles of Human Anatomy and Physiology, 11e

Role of Vitamin K in Clotting Normal clotting requires adequate vitamin K fat soluble vitamin absorbed if lipids are present absorption slowed if bile release is insufficient Required for synthesis of 4 clotting factors by hepatocytes factors II (prothrombin), VII, IX and X Produced by bacteria in large intestine Principles of Human Anatomy and Physiology, 11e

Hemostatic Control Mechanisms Fibrinolytic system dissolves small, inappropriate clots & clots at a site of a completed repair fibrinolysis is dissolution of a clot Inactive plasminogen is incorporated into the clot activation occurs because of factor XII and thrombin plasminogen becomes plasmin (fibrinolysin) which digests fibrin threads Clot formation remains localized fibrin absorbs thrombin blood disperses clotting factors endothelial cells & WBC produce prostacyclin that opposes thromboxane A2 (platelet adhesion & release) Anticoagulants present in blood & produced by mast cells Principles of Human Anatomy and Physiology, 11e

Intravascular Clotting Thrombosis clot (thrombus) forming in an unbroken blood vessel forms on rough inner lining of BV if blood flows too slowly (stasis) allowing clotting factors to build up locally & cause coagulation may dissolve spontaneously or dislodge & travel Embolus clot, air bubble or fat from broken bone in the blood pulmonary embolus is found in lungs Low dose aspirin blocks synthesis of thromboxane A2 & reduces inappropriate clot formation strokes, TIAs and myocardial infarctions Principles of Human Anatomy and Physiology, 11e

Anticoagulants and Thrombolytic Agents Anticoagulants suppress or prevent blood clotting heparin administered during hemodialysis and surgery warfarin (Coumadin) antagonist to vitamin K so blocks synthesis of clotting factors slower than heparin stored blood in blood banks treated with citrate phosphate dextrose (CPD) that removes Ca+2 Thrombolytic agents are injected to dissolve clots directly or indirectly activate plasminogen streptokinase or tissue plasminogen activator (t-PA) Principles of Human Anatomy and Physiology, 11e

Hemostatic Control Mechanisms Clots are generally localized due to fibrin absorbing thrombin into the clot, clotting factors diffusing through blood, and the production of prostacyclin, a powerful inhibitor of platelet adhesion and release. Substances that inhibit coagulation, called anticoagulants, are also present in blood. An example is heparin. Patients who are at increased risk of forming blood clots may receive an anticoagulant drug such as heparin or warfarin. To prevent clots in donated blood, a substance that removes Ca+2 such as EDTA or CPD may be added to the blood. Despite the anticoagulating and fibrinolytic mechanisms, blood clots sometimes form within the cardiovascular system. Principles of Human Anatomy and Physiology, 11e

HEMOSTASIS Clotting in an unbroken blood vessel is called thrombosis. A thrombus (clot), bubble of air, fat from broken bones, or piece of debris transported by the bloodstream that moves from its site of origin is called an embolus. At low doses aspirin inhibits vasoconstriction and platelet aggregation thereby reducing the chance of thrombus formation. Thrombolytic agents are injected into the body to dissolve clots that have already formed. Streptokinase or tissue plasminogen activator (TPS) are thrombolytic agents. Principles of Human Anatomy and Physiology, 11e

ABO Group In the ABO system, agglutinogens (antigens) A and B determine blood types (Figure 19.12). Plasma contains agglutinins (antibodies), designated as a and b, that react with agglutinogens that are foreign to the individual. Table 19.5 indicates the incidence of ABO and Rh blood types. Principles of Human Anatomy and Physiology, 11e

Blood Groups and Blood Types RBC surfaces are marked by genetically determined glycoproteins & glycolipids agglutinogens or isoantigens distinguishes at least 24 different blood groups ABO, Rh, Lewis, Kell, Kidd and Duffy systems Principles of Human Anatomy and Physiology, 11e

ABO Blood Groups Based on 2 glycolipid isoantigens called A and B found on the surface of RBCs display only antigen A -- blood type A display only antigen B -- blood type B display both antigens A & B -- blood type AB display neither antigen -- blood type O Plasma contains isoantibodies or agglutinins to the A or B antigens not found in your blood anti-A antibody reacts with antigen A anti-B antibody reacts with antigen B Principles of Human Anatomy and Physiology, 11e

RH blood groups Antigen was discovered in blood of Rhesus monkey People with Rh agglutinogens on RBC surface are Rh+. Normal plasma contains no anti-Rh antibodies Antibodies develop only in Rh- blood type & only with exposure to the antigen transfusion of positive blood during a pregnancy with a positive blood type fetus Transfusion reaction upon 2nd exposure to the antigen results in hemolysis of the RBCs in the donated blood Principles of Human Anatomy and Physiology, 11e

Hemolytic Disease of Newborn Rh negative mom and Rh+ fetus will have mixing of blood at birth Mom's body creates Rh antibodies unless she receives a RhoGam shot soon after first delivery, miscarriage or abortion RhoGam binds to loose fetal blood and removes it from body before she reacts In 2nd child, hemolytic disease of the newborn may develop causing hemolysis of the fetal RBCs Principles of Human Anatomy and Physiology, 11e

Transfusions Knowledge of blood types is essential to safe transfusion of blood and may also be used in proving or disproving paternity, linking suspects to crimes, or as a part of anthropology studies to establish a relationship among races. The interactions of the blood types of the ABO system are summarized in Table 19.6. Principles of Human Anatomy and Physiology, 11e

Transfusion and Transfusion Reactions Transfer of whole blood, cells or plasma into the bloodstream of recipient used to treat anemia or severe blood loss Incompatible blood transfusions antigen-antibody complexes form between plasma antibodies & “foreign proteins” on donated RBC's (agglutination) donated RBCs become leaky (complement proteins) & burst loose hemoglobin causes kidney damage Problems caused by incompatibility between donor’s cells and recipient’s plasma Donor plasma is too diluted to cause problems Principles of Human Anatomy and Physiology, 11e

Universal Donors and Recipients People with type AB blood called “universal recipients” since have no antibodies in plasma only true if cross match the blood for other antigens People with type O blood cell called “universal donors” since have no antigens on their cells theoretically can be given to anyone Principles of Human Anatomy and Physiology, 11e

Typing and Cross-Matching Blood for Transfusion The Rh and ABO blood groups may be detected by a simple medical test, blood typing, in which a sample of blood is mixed with serum containing agglutinins to each of the major agglutinogens (AB, B, and Rh) (Figure 19.14). Typing is the determination of blood types, whereas cross-matching is the mixing of donor and recipient blood for compatibility. Principles of Human Anatomy and Physiology, 11e

DISORDERS: HOMEOSTATIC IMBALANCES Anemia Sickle-cell Hemophilia Disseminated intravascular clotting Acute leukemia chronic leukemia Principles of Human Anatomy and Physiology, 11e

Anemia = Not Enough RBCs Symptoms oxygen-carrying capacity of blood is reduced fatigue, cold intolerance & paleness lack of O2 for ATP & heat production Types of anemia iron-deficiency =lack of absorption or loss of iron pernicious = lack of intrinsic factor for B12 absorption hemorrhagic = loss of RBCs due to bleeding (ulcer) hemolytic = defects in cell membranes cause rupture thalassemia = hereditary deficiency of hemoglobin aplastic = destruction of bone marrow (radiation/toxins) Principles of Human Anatomy and Physiology, 11e

Sickle-cell Anemia (SCA) Genetic defect in hemoglobin molecule (Hb-S) that changes 2 amino acids at low very O2 levels, RBC is deformed by changes in hemoglobin molecule within the RBC sickle-shaped cells rupture easily = causing anemia & clots Found among populations in malaria belt Mediterranean Europe, sub-Saharan Africa & Asia Person with only one sickle cell gene increased resistance to malaria because RBC membranes leak K+ & lowered levels of K+ kill the parasite infecting the red blood cells Principles of Human Anatomy and Physiology, 11e

Hemophilia Inherited deficiency of clotting factors bleeding spontaneously or after minor trauma subcutaneous & intramuscular hemorrhaging nosebleeds, blood in urine, articular bleeding & pain Hemophilia A lacks factor VIII (males only) most common Hemophilia B lacks factor IX (males only) Hemophilia C (males & females) less severe because alternate clotting activator exists Treatment is transfusions of fresh plasma or concentrates of the missing clotting factor Principles of Human Anatomy and Physiology, 11e

Disseminated Intravascular Clotting Life threatening paradoxical presence of blood clotting and bleeding at the same time throughout the whole body so many clotting factors are removed by widespread clotting that too few remain to permit normal clotting Associated with infections, hypoxia, low blood flow rates, trauma, hypotension & hemolysis Clots cause ischemia and necrosis leading to multisystem organ failure Principles of Human Anatomy and Physiology, 11e

Leukemia Acute leukemia uncontrolled production of immature leukocytes crowding out of normal red bone marrow cells by production of immature WBC prevents production of RBC & platelets Chronic leukemia accumulation of mature WBC in bloodstream because they do not die classified by type of WBC that is predominant---monocytic, lymphocytic. Principles of Human Anatomy and Physiology, 11e

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