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The Cardiovascular System: Blood

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Title: The Cardiovascular System: Blood


1
The Cardiovascular System Blood Blood
Components
  • Biology 1612
  • Anatomy Physiology II

2
INTRODUCTION
  • Blood inside blood vessels, interstitial fluid
    around body cells, and lymph inside lymph vessels
    constitute ones 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.
  • The branch of science concerned with the study of
    blood, blood-forming tissues, and the disorders
    associated with them is called hematology.

3
Blood Components
4
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

5
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

6
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

7
Techniques of Blood Sampling
  • Venipuncture
  • sample taken from vein with hypodermic needle
    syringe
  • median cubital vein
  • 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

8
COMPONENTS OF BLOOD
  • Blood consists of 55 plasma and 45 formed
    elements.
  • 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.

9
Components of Blood
  • Hematocrit
  • 55 plasma
  • 45 cells
  • 99 RBCs
  • lt 1 WBCs and platelets

10
Blood Plasma
  • 0ver 90 water
  • 7 plasma proteins
  • created in liver
  • confined to bloodstream
  • albumin
  • maintain blood osmotic pressure
  • globulins (immunoglobulins)
  • antibodies bind to foreignsubstances called
    antigens
  • form antigen-antibody complexes
  • fibrinogen
  • for clotting
  • 2 other substances
  • electrolytes, nutrients, hormones, gases, waste
    products

11
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)

12
FORMATION OF BLOOD CELLS
  • Blood cells are formed from pluripotent
    hematopoietic stem cells.
  • 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.

13
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

14
Blood Doping
  • Injecting previously stored RBCs before an
    athletic event
  • more cells available to deliver oxygen to tissues
  • Dangerous
  • increases blood viscosity
  • forces heart to work harder
  • Banned by the International Olympic Committee

15
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

16
Hematopoiesis
17
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

18
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

19
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

20
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 hematopoiesis is stimulated by
    several hematopoietic growth factors. These
    hematopoietic growth factors stimulate
    differentiation and proliferation of the various
    blood cells.

21
Red Blood Cells or Erythrocytes
  • Contain oxygen-carrying protein hemoglobin that
    gives blood its red color
  • 1/3 of cells 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

22
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.

23
Hemoglobin
  • Globin protein consisting of 4 polypeptide chains
  • One heme pigment attached to each polypeptide
    chain
  • each heme contains an iron ion (Fe2) that can
    combine reversibly with one oxygen molecule

24
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

25
RBCs
  • Production of abnormal hemoglobin can result in
    serious blood disorders such as thalassemia and
    sickle cell anemia.
  • The blood test, hemoglobin A1c, can be used to
    monitor blood glucose levels in diabetics

26
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

27
Recycling of Hemoglobin Components
  • In macrophages of liver or spleen
  • globin portion broken down into amino acids
    recycled
  • heme portion split into iron (Fe3) and
    biliverdin (green pigment)

28
Fate of Components of Heme
  • Iron(Fe3)
  • 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

29
Erythropoiesis Production of RBCs
  • Erythrocyte formation, called erythropoiesis,
    occurs in adult red bone marrow of certain bones.
  • The main stimulus for erythropoiesis is hypoxia.
  • 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

30
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

31
Normal Reticulocyte Count
  • Should be .5 to 1.5 of the circulating RBCs
  • 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

32
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).
  • 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.

33
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

34
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.

35
Function of WBCs
  • WBCs leave the blood stream by emigration.
  • Some WBCs, particularly neutrophils and
    macrophages, are active in phagocytosis.
  • The chemical attraction of WBCs to a disease or
    injury site is termed chemotaxis.

36
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.
  • Bone marrow transplants may be used to treat
    several types of anemia, leukemia, and numerous
    other blood disorders.

37
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

38
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

39
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

40
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

41
Eosinophil Function
  • Leave capillaries to enter tissue fluid
  • Release histaminase
  • slows down inflammation caused by basophils
  • Attack parasitic worms
  • Phagocytize antibody-antigen complexes

42
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

43
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

44
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 lt1 (up if allergy reaction or
    hypothyroid)

45
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

46
PLATELETS
  • Thrombopoietin stimulates myeloid stem cells to
    produce platelets.
  • Myeloid stem cells develop into
    megakaryocyte-colony-forming cells that develop
    into megakaryoblasts.
  • 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.

47
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.

48
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

49
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

50
STEM CELL TRANSPLANT FROM BONE MARROW AND
CORD-BLOOD
  • Bone marrow transplant replaces diseased marrow
    with healthy marrow.
  • Patients diseased marrow is destroyed.
  • Healthy marrow is supplied by a donor or the
    patient.
  • There are several problems with this method.

51
Cord-blood transplant
  • Stem cells are taken from the umbilical cord and
    frozen
  • This method offers several advantages over marrow
    transplant.

52
HEMOSTASIS
  • A clot is a gel consisting of a network of
    insoluble protein fibers (fibrin) in which formed
    elements of blood are trapped.
  • 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.
  • 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.

53
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.

54
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)

55
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

56
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, Ca2, serotonin, fibrin-stabilizing
    factor, enzymes that produce thromboxane A2
  • Steps in the process
  • (1) platelet adhesion (2) platelet release
    reaction (3) platelet aggregation

57
Platelet Adhesion
  • Platelets stick to exposed collagen underlying
    damaged endothelial cells in vessel wall

58
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

59
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

60
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 Ca2,
    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 Ca2 convert prothrombin into
    thrombin
  • thrombin converts fibrinogen into fibrin threads

61
Overview of the Clotting Cascade
  • Prothrombinase is formed by either the intrinsic
    or extrinsic pathway
  • Final common pathway produces fibrin threads

62
Extrinsic Pathway
  • Damaged tissues leak tissue factor
    (thromboplastin) into bloodstream
  • Prothrombinase forms in seconds
  • In the presence of Ca2, clotting factor X
    combines with V to form prothrombinase

63
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 Ca2 and clotting factors
    XII, X and V

64
Final Common Pathway
  • Prothrombinase and Ca2
  • catalyze the conversion of prothrombin to
    thrombin
  • Thrombin
  • in the presence of Ca2 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

65
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

66
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

67
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

68
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

69
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 Ca2
  • Thrombolytic agents are injected to dissolve
    clots
  • directly or indirectly activate plasminogen
  • streptokinase or tissue plasminogen activator
    (t-PA)

70
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 Ca2 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.

71
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.

72
ABO Group
  • In the ABO system, agglutinogens (antigens) A and
    B determine blood types.
  • Plasma contains agglutinins (antibodies),
    designated as a and b, that react with
    agglutinogens that are foreign to the individual.

73
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

74
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

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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

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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

77
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.

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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
    donors cells and recipients plasma
  • Donor plasma is too diluted to cause problems

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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

80
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).
  • Typing is the determination of blood types,
    whereas cross-matching is the mixing of donor and
    recipient blood for compatibility.

81
DISORDERS HOMEOSTATIC IMBALANCES
  • Anemia
  • Sickle-cell
  • Hemophilia
  • Disseminated intravascular clotting
  • Acute leukemia
  • chronic leukemia

82
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)

83
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

84
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

85
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

86
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.
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