Blood

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• Blood

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Overview of Blood Circulation

• Blood leaves the heart via arteries that branch
  repeatedly until they become capillaries
• Oxygen (O2) and nutrients diffuse across
  capillary walls and enter tissues
• Carbon dioxide (CO2) and wastes move from tissues
  into the blood

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Overview of Blood Circulation

• Oxygen-deficient blood leaves the capillaries and
  flows in veins to the heart
• This blood flows to the lungs where it releases
  CO2 and picks up O2
• The oxygen-rich blood returns to the heart

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Composition of Blood

• Blood is the bodys only fluid tissue
• It is composed of liquid plasma and formed
  elements
• Formed elements include
• Erythrocytes, or red blood cells (RBCs)
• Leukocytes, or white blood cells (WBCs)
• Platelets
• Hematocrit the percentage of RBCs out of the
  total blood volume

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Components of Whole Blood
Plasma(55 of whole blood)
Buffy coatleukocyctes and platelets(lt1 of
whole blood)
Formed elements
Erythrocytes(45 of whole blood)
Withdraw blood and place in tube
Centrifuge
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Figure 17.1
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Physical Characteristics and Volume

• Blood is a sticky, opaque fluid with a metallic
  taste
• Color varies from scarlet (oxygen-rich) to dark
  red (oxygen-poor)
• The pH of blood is 7.357.45
• Temperature is 38?C, slightly higher than
  normal body temperature
• Blood accounts for approximately 8 of body
  weight
• Average volume of blood is 56 L for males, and
  45 L for females

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Functions of Blood

• Blood performs a number of functions dealing
  with
• Substance distribution
• Regulation of blood levels of particular
  substances
• Body protection

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Distribution

• Blood transports
• Oxygen from the lungs and nutrients from the
  digestive tract
• Metabolic wastes from cells to the lungs and
  kidneys for elimination
• Hormones from endocrine glands to target organs

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Regulation

• Blood maintains
• Appropriate body temperature by absorbing and
  distributing heat
• Normal pH in body tissues using buffer systems
• Adequate fluid volume in the circulatory system

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Protection

• Blood prevents blood loss by
• Activating plasma proteins and platelets
• Initiating clot formation when a vessel is broken
• Blood prevents infection by
• Synthesizing and utilizing antibodies
• Activating complement proteins
• Activating WBCs to defend the body against
  foreign invaders

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Blood Plasma

• Blood plasma contains over 100 solutes,
  including
• Proteins albumin, globulins, clotting proteins,
  and others
• Nonprotein nitrogenous substances lactic acid,
  urea, creatinine
• Organic nutrients glucose, carbohydrates, amino
  acids
• Electrolytes sodium, potassium, calcium,
  chloride, bicarbonate
• Respiratory gases oxygen and carbon dioxide

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Formed Elements

• Erythrocytes, leukocytes, and platelets make up
  the formed elements
• Only WBCs are complete cells
• RBCs have no nuclei or organelles, and platelets
  are just cell fragments
• Most formed elements survive in the bloodstream
  for only a few days
• Most blood cells do not divide but are renewed by
  cells in bone marrow

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Erythrocytes (RBCs)

• Biconcave discs, anucleate, essentially no
  organelles
• Filled with hemoglobin (Hb), a protein that
  functions in gas transport
• Contain the plasma membrane protein spectrin and
  other proteins that
• Give erythrocytes their flexibility
• Allow them to change shape as necessary

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Erythrocytes (RBCs)
Figure 17.3
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Erythrocytes (RBCs)

• Erythrocytes are an example of the
  complementarity of structure and function
• Structural characteristics contribute to its gas
  transport function
• Biconcave shape that has a huge surface area
  relative to volume
• Discounting water content, erythrocytes are more
  than 97 hemoglobin
• ATP is generated anaerobically, so the
  erythrocytes do not consume the oxygen they
  transport

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Erythrocyte Function

• Erythrocytes are dedicated to respiratory gas
  transport
• Hemoglobin reversibly binds with oxygen and most
  oxygen in the blood is bound to hemoglobin
• Hemoglobin is composed of the protein globin,
  made up of two alpha and two beta chains, each
  bound to a heme group
• Each heme group bears an atom of iron, which can
  bind to one oxygen molecule
• Each hemoglobin molecule can transport four
  molecules of oxygen

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Structure of Hemoglobin
Figure 17.4
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Hemoglobin

• Oxyhemoglobin hemoglobin bound to oxygen
• Oxygen loading takes place in the lungs
• Deoxyhemoglobin hemoglobin after oxygen
  diffuses into tissues (reduced Hb)
• Carbaminohemoglobin hemoglobin bound to carbon
  dioxide
• Carbon dioxide loading takes place in the tissues

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Production of Erythrocytes

• Hematopoiesis blood cell formation
• Hematopoiesis occurs in the red bone marrow of
  the
• Axial skeleton and girdles
• Epiphyses of the humerus and femur
• Hemocytoblasts give rise to all formed elements

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Regulation and Requirements for Erythropoiesis

• Circulating erythrocytes the number remains
  constant and reflects a balance between RBC
  production and destruction
• Too few red blood cells leads to tissue hypoxia
• Too many red blood cells causes undesirable blood
  viscosity
• Erythropoiesis is hormonally controlled and
  depends on adequate supplies of iron, amino
  acids, and B vitamins

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Hormonal Control of Erythropoiesis

• Erythropoietin (EPO) release by the kidneys is
  triggered by
• Hypoxia due to decreased RBCs
• Decreased oxygen availability
• Increased tissue demand for oxygen
• Enhanced erythropoiesis increases the
• RBC count in circulating blood
• Oxygen carrying ability of the blood

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Erythropoietin Mechanism
Imbalance
Start
Normal blood oxygen levels
Stimulus Hypoxia due to decreased RBC count,
decreased availability of O2 to blood, or
increased tissue demands for O2
Imbalance
Increases O2-carrying ability of blood
Reduces O2 levels in blood
Erythropoietin stimulates red bone marrow
Kidney (and liver to a smaller extent) releases
erythropoietin
Enhanced erythropoiesis increases RBC count
Figure 17.6
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Dietary Requirements of Erythropoiesis

• Erythropoiesis requires
• Proteins, lipids, and carbohydrates
• Iron, vitamin B12, and folic acid
• The body stores iron in Hb (65), the liver,
  spleen, and bone marrow
• Intracellular iron is stored in protein-iron
  complexes such as ferritin and hemosiderin
• Circulating iron is loosely bound to the
  transport protein transferrin

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Fate and Destruction of Erythrocytes

• The life span of an erythrocyte is 100120 days
• Old erythrocytes become rigid and fragile, and
  their hemoglobin begins to degenerate
• Dying erythrocytes are engulfed by macrophages
• Heme and globin are separated and the iron is
  salvaged for reuse

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Fate and Destruction of Erythrocytes

• Heme is degraded to a yellow pigment called
  bilirubin
• The liver secretes bilirubin into the intestines
  as bile
• The intestines metabolize it into urobilinogen
• This degraded pigment leaves the body in feces,
  in a pigment called stercobilin
• Globin is metabolized into amino acids and is
  released into the circulation
• Hb released into the blood is captured by
  haptoglobin and phgocytized

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Life Cycle of Red Blood Cells
Figure 17.7
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Erythrocyte Disorders

• Anemia blood has abnormally low oxygen-carrying
  capacity
• It is a symptom rather than a disease itself
• Blood oxygen levels cannot support normal
  metabolism
• Signs/symptoms include fatigue, paleness,
  shortness of breath, and chills

Hemolytic Anemia
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Anemia Insufficient Erythrocytes

• Hemorrhagic anemia result of acute or chronic
  loss of blood
• Hemolytic anemia prematurely ruptured
  erythrocytes
• Aplastic anemia destruction or inhibition of
  red bone marrow

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Anemia Decreased Hemoglobin Content

• Iron-deficiency anemia results from
• A secondary result of hemorrhagic anemia
• Inadequate intake of iron-containing foods
• Impaired iron absorption
• Pernicious anemia results from
• Deficiency of vitamin B12
• Lack of intrinsic factor needed for absorption of
  B12
• Treatment is intramuscular injection of B12
  application of Nascobal

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Anemia Abnormal Hemoglobin

• Thalassemias absent or faulty globin chain in
  hemoglobin
• Erythrocytes are thin, delicate, and deficient in
  hemoglobin
• Sickle-cell anemia results from a defective
  gene coding for an abnormal hemoglobin called
  hemoglobin S (HbS)
• HbS has a single amino acid substitution in the
  beta chain
• This defect causes RBCs to become sickle-shaped
  in low oxygen situations

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Polycythemia

• Polycythemia excess RBCs that increase blood
  viscosity

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Leukocytes (WBCs)

• Leukocytes, the only blood components that are
  complete cells
• Are less numerous than RBCs
• Make up 1 of the total blood volume
• Can leave capillaries via diapedesis
• Move through tissue spaces
• Leukocytosis WBC count over 11,000 per cubic
  millimeter
• Normal response to bacterial or viral invasion

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Granulocytes

• Granulocytes neutrophils, eosinophils, and
  basophils
• Contain cytoplasmic granules that stain
  specifically (acidic, basic, or both) with
  Wrights stain
• Are larger and usually shorter-lived than RBCs
• Have lobed nuclei
• Are all phagocytic cells

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Neutrophils

• Neutrophils have two types of granules that
• Take up both acidic and basic dyes
• Give the cytoplasm a lilac color
• Lobed Nucleus
• Contain peroxidases, hydrolytic enzymes, and
  defensins (antibiotic-like proteins)
• Neutrophils are our bodys bacteria slayers

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Eosinophils

• Eosinophils account for 14 of WBCs
• Have red-staining, bilobed nuclei connected via a
  broad band of nuclear material
• Have red to crimson (acidophilic) large, coarse,
  lysosome-like granules
• Lead the bodys counterattack against parasitic
  worms
• Lessen the severity of allergies by phagocytizing
  immune complexes

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Basophils

• Account for 0.5 of WBCs and
• Have U- or S-shaped nuclei with two or three
  conspicuous constrictions
• Are functionally similar to mast cells
• Have large, purplish-black (basophilic) granules
  that contain histamine
• Histamine inflammatory chemical that acts as a
  vasodilator and attracts other WBCs
  (antihistamines counter this effect)

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Agranulocytes

• Agranulocytes lymphocytes and monocytes
• Lack visible cytoplasmic granules
• Are similar structurally, but are functionally
  distinct and unrelated cell types
• Have spherical (lymphocytes) or kidney-shaped
  (monocytes) nuclei

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Lymphocytes

• Account for 25 or more of WBCs and
• Have large, dark-purple, circular nuclei with a
  thin rim of blue cytoplasm
• Are found mostly enmeshed in lymphoid tissue
  (some circulate in the blood)
• There are two types of lymphocytes T cells and B
  cells
• T cells function in the immune response
• B cells give rise to plasma cells, which produce
  antibodies

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Monocytes

• Monocytes account for 48 of leukocytes
• They are the largest leukocytes
• They have abundant pale-blue cytoplasms
• They have purple-staining, U- or kidney-shaped
  nuclei
• They leave the circulation, enter tissue, and
  differentiate into macrophages

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Monocytes

• Macrophages
• Are highly mobile and actively phagocytic
• Activate lymphocytes to mount an immune response

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Summary of Formed Elements
Table 17.2
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Summary of Formed Elements
Table 17.2
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Production of Leukocytes

• Leukopoiesis is hormonally stimulated by two
  families of cytokines (hematopoietic factors)
  interleukins and colony-stimulating factors
  (CSFs)
• Interleukins are numbered (e.g., IL-1, IL-2),
  whereas CSFs are named for the WBCs they
  stimulate (e.g., granulocyte-CSF stimulates
  granulocytes)
• Macrophages and T cells are the most important
  sources of cytokines
• Many hematopoietic hormones are used clinically
  to stimulate bone marrow

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Leukocytes Disorders Leukemias

• Leukemia refers to cancerous conditions involving
  white blood cells
• Leukemias are named according to the abnormal
  white blood cells involved
• Myelocytic leukemia involves myeloblasts
• Lymphocytic leukemia involves lymphocytes
• Acute leukemia involves blast-type cells and
  primarily affects children
• Chronic leukemia is more prevalent in older people

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Leukemia

• Immature white blood cells are found in the
  bloodstream in all leukemias
• Bone marrow becomes totally occupied with
  cancerous leukocytes
• The white blood cells produced, though numerous,
  are not functional
• Death is caused by internal hemorrhage and
  overwhelming infections
• Treatments include irradiation, antileukemic
  drugs, and bone marrow transplants

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Platelets

• Platelets are fragments of megakaryocytes with a
  blue-staining outer region and a purple granular
  center
• Their granules contain serotonin, Ca2, enzymes,
  ADP, and platelet-derived growth factor (PDGF)
• Platelets function in the clotting mechanism by
  forming a temporary plug that helps seal breaks
  in blood vessels
• Platelets not involved in clotting are kept
  inactive by NO and prostaglandin

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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)

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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

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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

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Platelet Adhesion

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

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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

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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

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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

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Overview of the Clotting Cascade

• Prothrombinase is formed by either the intrinsic
  or extrinsic pathway
• Final common pathway produces fibrin threads

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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

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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

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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

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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

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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

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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

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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

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Hemostasis DisordersThromboembolytic Conditions

• Thrombus a clot that develops and persists in
  an unbroken blood vessel
• Thrombi can block circulation, resulting in
  tissue death
• Coronary thrombosis thrombus in blood vessel of
  the heart

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Hemostasis DisordersThromboembolytic Conditions

• Embolus a thrombus freely floating in the blood
  stream
• Pulmonary emboli can impair the ability of the
  body to obtain oxygen
• Cerebral emboli can cause strokes

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Prevention of Undesirable Clots

• Substances used to prevent undesirable clots
  include
• Aspirin an antiprostaglandin that inhibits
  thromboxane A2
• Heparin an anticoagulant used clinically for
  pre- and postoperative cardiac care
• Warfarin used for those prone to atrial
  fibrillation

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Hemostasis Disorders Bleeding Disorders

• Thrombocytopenia condition where the number of
  circulating platelets is deficient
• Patients show petechiae (small purple blotches on
  the skin) due to spontaneous, widespread
  hemorrhage
• Caused by suppression or destruction of bone
  marrow (e.g., malignancy, radiation)
• Platelet counts less than 50,000/mm3 is
  diagnostic for this condition
• Treated with whole blood transfusions

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Hemostasis Disorders Bleeding Disorders

• Hemophilias hereditary bleeding disorders
  caused by lack of clotting factors
• Hemophilia A most common type (83 of all
  cases) due to a deficiency of factor VIII
• Hemophilia B results from a deficiency of
  factor IX
• Hemophilia C mild type, caused by a deficiency
  of factor XI

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Blood Transfusions

• Whole blood transfusions are used
• When blood loss is substantial
• In treating thrombocytopenia
• Packed red cells (cells with plasma removed) are
  used to treat anemia

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Human Blood Groups

• RBC membranes have glycoprotein antigens on their
  external surfaces
• These antigens are
• Unique to the individual
• Recognized as foreign if transfused into another
  individual
• Promoters of agglutination and are referred to as
  agglutinogens
• Presence or absence of these antigens is used to
  classify blood groups

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Blood Groups

• Humans have 30 varieties of naturally occurring
  RBC antigens
• The antigens of the ABO and Rh blood groups cause
  vigorous transfusion reactions when they are
  improperly transfused
• Other blood groups (M, N, Dufy, Kell, and Lewis)
  are mainly used for legalities

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ABO Blood Groups

• The ABO blood groups consists of
• Two antigens (A and B) on the surface of the RBCs
  
• Two antibodies in the plasma (anti-A and anti-B)
• An individual with ABO blood may have various
  types of antigens and spontaneously preformed
  antibodies
• Agglutinogens and their corresponding antibodies
  cannot be mixed without serious hemolytic
  reactions

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ABO Blood Groups
Table 17.4
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Rh Blood Groups

• There are eight different Rh agglutinogens, three
  of which (C, D, and E) are common
• Presence of the Rh agglutinogens on RBCs is
  indicated as Rh
• Anti-Rh antibodies are not spontaneously formed
  in Rh individuals
• However, if an Rh individual receives Rh blood,
  anti-Rh antibodies form
• A second exposure to Rh blood will result in a
  typical transfusion reaction

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Hemolytic Disease of the Newborn

• Hemolytic disease of the newborn Rh antibodies
  of a sensitized Rh mother cross the placenta and
  attack and destroy the RBCs of an Rh baby
• Rh mother becomes sensitized when Rh blood
  (from a previous pregnancy of an Rh baby or a
  Rh transfusion) causes her body to synthesis Rh
  antibodies
• The drug RhoGAM can prevent the Rh mother from
  becoming sensitized
• Treatment of hemolytic disease of the newborn
  involves pre-birth transfusions and exchange
  transfusions after birth

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Transfusion Reactions

• Transfusion reactions occur when mismatched blood
  is infused
• Donors cells are attacked by the recipients
  plasma agglutinins causing
• Diminished oxygen-carrying capacity
• Clumped cells that impede blood flow
• Ruptured RBCs that release free hemoglobin into
  the bloodstream
• Circulating hemoglobin precipitates in the
  kidneys and causes renal failure

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Blood Typing

• When serum containing anti-A or anti-B
  agglutinins is added to blood, agglutination will
  occur between the agglutinin and the
  corresponding agglutinogens
• Positive reactions indicate agglutination

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Blood Typing