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Anatomy and Physiology

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					Anatomy and Physiology




  Chapter 12 Blood
         Introduction to Blood
• Blood signifies life
• The blood, heart, and blood vessels form the
  cardiovascular system and link the body’s
  internal and external environments.
• Type of connective tissue whose cells are
  suspended in a liquid material
• Complex mixture of cells, cell fragments, and
  dissolved biochemicals
• Vital in transporting substances between body
  cells and the external environment thereby
  promoting homeostasis.
            Vital Functions
• Transports nutrients, O2, wastes and
  hormones.
• Helps maintain the stability of the
  interstitial fluid.
• Distributes heat.
• Provides protection against infection
  (white blood cells)
• Promotes clotting (platelets)
          Blood Substitutes
• Early efforts have focused on filling
  missing fluid volume and reproduce O2
  carrying role.
• The search for a blood substitute
  intensified:
  – After each word war - injured soldiers needed
    transfusions
  – AIDS pandemic made transfusions dangerous
    unless blood was screened.
• Substitutes must meet several
  requirements:
  – Carry O2 and give it up to tissues
  – Be non-toxic
  – Storeable
  – Function until the body can take over
  – Not provoke an immune response
• RBC substitutes currently in clinical trials
  are of two types:
  – Perfluorocarbons: synthetic chemicals that
    carry dissolved O2. Developed in 1960’s
    Famous photo of mouse breathing in liquid.
  – Substitutes that dismantle RBC’s and isolate
    the O2-carrying hemoglobin and links them in
    various ways. Starting material usually cow’s
    blood or old stored human blood.
• RBC substitutes used
  in the past have
  included wine, ale,
  plant resins, urine,
  and opium
       Blood and Blood Cells
• Whole blood is slightly heavier and 3-4x
  more viscous than water.
• Red blood cells and white blood cells form
  in red bone marrow.
• Platelets are cellular fragments.
• Formed Elements: cellular portion; RBC’s,
  WBC’s and platelets
• Liquid portion: plasma
             Blood Volume
• Volume varies with body size, changes in
  fluid and electrolyte concentrations, and
  the amount of adipose tissue.
• Average-sized adult has blood volume of
  5.3 quarts or 5 liters.
  – Men (1.500 gal) generally have more blood
    than women (0.875 gal)
Composition of a Blood Sample
• Hemocrit (HCT): 45% by volume. Includes
  cells – mostly RBC’s and much smaller
  numbers of WBC’s and platelets
• Plasma: clear, straw-colored liquid which
  is a complex mixture of water, amino
  acids, proteins, carbohydrates, lipids,
  vitamins, hormones, electrolytes, and
  cellular wastes.
Blood consists of a liquid portion (plasma) and a solid portion (RBC’s, WBC’s, platelets). When
blood separates, the WBC’s and platelets form a thin layer called the ―buffy coat‖ between the
plasma and the RBC’s.
 Red Blood Cells / Erythrocytes
• Biconcave discs
  – Shape is an adaptation for transporting gases
  – Increases surface area through which gases can
    diffuse. The combined surface area of all RBC’s in
    human body is roughly 2000x greater than the body’s
    external surface
  – Places the cell membrane closer to the O2-carrying
    hemoglobin within the cell.
• Hemoglobin
  – 1/3 of the cell by volume
  – Protein responsible for the color of blood
  – When hemoglobin combines with O2 (oxyhemoglobin)
    = bright red; When O2 released
    (deoxyhemoglobin)=darker color
Red Blood Cells. A.) The biconcave shape of a red blood cell makes possible its
function. B.) Scanning electron micrograph of human RBC’s. (colored)
• Hypoxia: prolonged O2 deficiency
• Cyanotic:
  – Skin and mucous membranes appear bluish
    due to high concentration of
    deoxyhemoglobin.
  – Can be due to hypoxia or exposure to low
    temperatures which cause superficial vessels
    to constrict slowing blood flow which removes
    more O2 than usual from blood.
• RBC’s have nuclei during early stages of
  development but extrude them as they
  mature.
  – More space for hemoglobin
  – Cannot synthesize proteins or divide
               RBC Counts
• The number of RBC’s in 1 mm3 of blood.
• RBCC, RCC
• Typical range
  – Adult males: 4,600,000 – 6,200,000/mm3
  – Adult females: 4,200,000 – 5,400,000/mm3
• Increasing the number of circulating RBC’s
  increases the bloods O2-carrying capacity.
• Change in RBCC may affect health – routinely
  consulted to help diagnose and evaluate the
  courses of various diseases.
              Hemopoiesis
• RBC formation
• Initially occurs in the yolk sac, liver and
  spleen
• After birth – RBC’s produced almost
  exclusively in tissue lining the spaces in
  bones and red bone marrow
• Average life span of RBC is 120 days
• Many are removed from circulation each
  day but the number of cells circulating
  remains relatively stable.
  – Suggests homeostatic control of the rate of
    hemopoiesis.
• Negative feedback mechanism
  – A hormone, erythropoietin controls the rate of
    hemopoiesis
  – Kidneys and to a lesser extent the liver
    release erythropoietin in response to
    prolonged O2 deficiency.
    • Ex. High altitudes where % of O2 in air is reduced
      stimulate the release of hormone and RBC
      production. When O2 level in air returns to normal,
      hormone decreased and rate of hemopoiesis
      returns to normal.
Low blood oxygen causes the kidneys and liver to release erythropoietin, which
stimulates the production of red blood cells that carry oxygen to tissues.
Origin and
development of
blood cells from
hemocytoblasts
(stem cells) in
bone marrow.
   Dietary Factors Affecting RBC
            Production
• B-complex vitamins (B12 and folic acid)
  – Necessary for DNA synthesis, so all cells with nuclei
    require them to grow and divide.
  – Cell division occurs frequently in hemopoietic tissue
• Iron
  – Required for hemoglobin synthesis and normal RBC
    production.
  – Small intestines absorb iron slowly from food
  – Body reuses much of iron released during
    decomposition of hemoglobin from damaged RBC’s
    so diet needs only include small quantities of iron
                     Anemia
• Too few RBC’s or too little hemoglobin leads to
  reduced O2-carrying capacity
• Person appears pale, lacks energy.
• Pregnant women may become anemic if she
  doesn’t eat iron-rich foods.
  – Her blood volume increases due to fluid retention to
    accommodate the requirements of the fetus.
  – Increased blood volume  decrease in hemocrit
          Sickle Cell Disease
• Single DNA base change causing an incorrect
  amino acid to be incorporated into globin
  causing hemoglobin to crystallize in a low-O2
  environment bending RBC containing
  hemoglobin into a sickle-shape
• Blocks circulation in small vessels causing
  excruciating joint pain and damaging organs.
• Infections are more likely. RBC’s are abnormally
  short-lived, spleen works harder to recycle.
• Children diagnosed at birth. Receive antibiotics
  daily for years to prevent infections.
• Hospitalization for transfusions: sickling crises of
  blocked circulation.
• Bone marrow transplant: complete cure but 15%
  risk of death.
• New treatment: old drug used to treat cancer,
  hydroxyurea. Activates slightly different form of
  hemoglobin in fetus. Sickle hemoglobin cannot
  crystallize as quickly. Sickling is delayed and
  enables RBC’s carrying sickled hemoglobin to
  more quickly reach lungs where fresh O2
  restores normal shape.
        Destruction of RBC’s
• RBC’s elastic and flexible. Bend easily as
  they pass through small blood vessels
• Become more fragile with age and are
  frequently damaged passing through
  capillaries in active muscles.
• Macrophages phagocytize and destroy
  damaged RBC in the spleen and liver.
• Hemoglobin molecules liberated from RBC’s
  broken down into heme (iron-containing portion)
  and globin (a protein)
  – Heme further decomposes into iron and biliverdin
    (greenish pigment)
  – Biliverin is converted to an orange pigment called
    bilirubin. Both pigments are excreted in bile.
• Blood transports iron and protein to hemopoietic
  tissue in red bone marrow to be reused in
  synthesizing new hemoglobin or the liver stores
  the iron-protein complex
Life cycle of a red blood cell. 1.) Small intestine absorbs essential nutrients. 2.) Blood transports
nutrients to red bone marrow. 3.) In the marrow, RBC’s arise from the division of less specialized
cells. 4.) Mature RBC’s are released into the bloodstream, where they circulate for about 120 days.
5.)Macrophages destroy damaged RBC’s in the spleen and liver. 6.) Hemoglobin liberated from
RBC’s is broken down into heme and globin. 7.) Iron from heme returns to red bone marrow and is
reused. 8.) Biliverdin and bilirubin are excreted in bile.
        Physiologic Jaundice
• Seen in newborns a few days after birth
• Along with other forms of jaundice (icterus)
  are characterized by an accumulation of
  bilirubin which turns skin and eyes
  yellowish.
• May be result of immature liver cells that
  ineffectively excrete bilirubin into bile.
• Treatment:
  – Bili lights discovered in 1950’s: (Nurse notes
    improvement after exposure to sunlight,
    except in diaper area) Exposure to fluorescent
    light breaks down bilirubin in tissues.
  – Feedings to promote bowel movements to
    remove wastes.
White Blood Cells / Leukocytes
• Function to protect against infection in
  various ways:
  – Phagocytize bacterial cells in the body
  – Produce proteins (antibodies) that destroy or
    disable foreign particles
• Develop from hemocytoblasts in response
  to hormones – interleukins and colony-
  stimulating factors (CSF’s)
              Diapedesis
• Blood transports WBC’s to sites of
  infection where they can squeeze between
  cells that form blood vessel walls.
• Allows WBC’s to leave blood circulation
  and move through interstitial spaces using
  amoeboid motion (self-propulsion)
            Types of WBC’s
• Differ in size, nature of their cytoplasm,
  shape of the nucleus, and staining
  characteristics.
             Granulocytes
• Leukocytes with granular cytoplasm
• 2x the size of RBC’s
• Develop in the red bone marrow (as do
  RBC’s)
• Life span – ave. 12 hours
• Members of group include
  – Neutrophils
  – Eosinophils
  – Basophils
  The neutrophil has a lobed nucleus with 2-5 components


                      Neutrophils
• Fine granules, stain light purple in neutral
  stain. nucleus with 2-5 lobes
• 54-62% of leukocytes in adults
• One of most mobile and active phagocyte
  of small particles
  – Contain many lysosomes which are organelles
    filled with digestive enzymes that break down
    organic molecules in captured bacteria
  – Often become so engorged with digestive
    products and bacterial toxins that they die.
              Eosinophils
• Coarse, uniformly-sized granules that stain
  deep red in acid stain. Bi-lobed nucleus
• 1-3% of leukocytes
• Only weakly phagocytic, but do attack and
  kill certain parasites
• Helps control inflammation and allergic
  reactions by removing biochemicals
  associated with these reactions.
               The eosinophil has red-staining
               cytoplasmic granules.
The basophil has cytoplasmic granules that stain deep blue.


                          Basophils
• Bi-lobed nucleus, Grannules stain deep
  blue in basic stain
• 1% of leukocytes
• Releases heparin, a blood-clot inhibiting
  substance that helps prevent intravascular
  blood clot formation.
• Releases histamine which increases blood
  flow to injured tissues.
• Play a major role in certain allergic
  reactions. (more in Ch 14)
          Agranulocytes
• Monocytes
• Lymphocytes
                Monocytes
• Arise from red bone marrow
                                        A monocyte
• Largest blood cells. 2-3X diameter of may leave the
                                        bloodstream
  RBC’s                                 and become a
                                        macrophage.
• Nuclei vary in shape (round, kidney-
  shaped, oval, lobed)
• 3-9% of leukocytes
• Live several weeks or months
• One of most mobile and active phagocytic
  leukocyte of larger particles.
        The lymphocyte contains a large, round nucleus.


                 Lymphocytes
• Formed in organs of lymphatic system and in red
  bone marrow
• Only slightly large than RBC’s
• Large, round nucleus with thin rim of cytoplasm
• 25-33% of leukocytes
• Live for years.
• Important in immunity. Some produce antibodies
  that attack specific foreign substances that enter
  the body (more in Ch 14)
 White Blood Cell Counts (WBCC)
• # of WBC’s in mm3 of human blood
• 5,000-10,000 cells/mm3
• May change in response to abnormal conditions
  – Rise in number may indicate infection
  – Exceeding 10,000 / mm3 = leukocytosis and indicates
    an acute infection such as appendicitis
  – Below 5,000/mm3 = leukopenia. May accompany
    typhoid fever, influenza, measles, mumps, chicken
    pox, AIDS, poliomyelitis
• Differential White Blood Cell Count
  (DIFF)
  – Lists percent of types of leukocytes in
    blood sample
  – Relative proportions may change in
    particular diseases
    • Neutrophils increase during bacterial
      infections
    • Eosinophils increase during certain
      parasitic infections and allergic reactions
    • A certain type of lymphocyte drops sharply
      in AIDS
Blood Platelets / Thrombocytes
• Not complete cells
• Arise from very large cells in red bone
  marrow (megakaryocytes) that fragment
  like a shattered plate and release small
  sections of cytoplasm (platelets) into
  circulation
• Megakaryocytes develop from
  hemocytoblasts in response to the
  hormone thrombopoietin
• Lacks nucleus
• Less than ½ size of RBC
• Amoeboid movement
• Circulate for about 10 days
• Varies from 130,000 – 360,000 / mm3 in
  normal blood
• Help close breaks in damaged blood
  vessels and initiate formation of blood
  clots (more later)
               Leukemia
• ―Cancer of the WBC‖
• Symptoms:
  Fatigue          Headaches
  Frequent colds   Fever
  Chills           Sweats
  Bruises          Bone pain
  Slow clotting
• Blood Test: Too few RBC’s and platelets.
  Too many WBC’s.
Leukemia and blood cells. A.) Normal blood cells. B.) Blood cells from a person with
granulocytic leukemia, a type of myeloid leukemia. Note the increased number of
leukocytes.
         Myeloid Leukemia
• Red bone marrow produces too many
  granulocytes but they are immature and
  unable to fight infection.
• Leukemic cells crowd out RBC’s and their
  precursors in the red marrow causing
  anemia and fatigue.
• Thrombocytopenia (platelet deficiency)
• Spread of cancer cells outside of marrow
  weakens surrounding bone.
        Lymphoid Leukemia
• Distinguished by source of cancer cells –
  lymphocytes produced in lymph nodes
• Similar symptoms to myeloid leukemia
• Sometimes no symptoms and is detected
  by a routine blood test.
               Classification
• Acute:
  – Appears suddenly.
  – Progresses rapidly.
  – Without treatment – death within a few months.
• Chronic:
  – Begins slow and remains undetected for months or
    years.
  – Without treatment – life expectancy 3 years.
  – With treatment 50-80% of patients enter remission.
  – Chemotherapy increases chances of long remission
                Treatment
• Correction of symptoms
• Blood transfusions, treating infections,
  drugs that kill cancer cells
• New drug – Gleevec has had success
• Bone marrow transplants can cure
  leukemia but procedure is risky.
• Stem cell transplants using donated
  umbilical cord blood can also cure
  leukemia.
Origin and development of blood cells from hemocytoblasts (stem cells) in bone
marrow.
            Blood Plasma
• Clear, straw-colored, liquid portion in
  which the cells and platelets are
  suspended.
• Approximately 92% water
• Contains complex mixture of organic and
  inorganic biochemicals.
               Functions
• Transports nutrients, gases, and vitamins
• Helps regulate fluid and electrolyte
  balance
• Maintains favorable pH
           Plasma Proteins
• Most abundant of dissolved substances
  (solutes) in plasma
  – Remain in blood and interstitial fluid
  – Ordinarily not used as energy sources
• 3 main groups that differ in chemical
  composition and physiological function
  – Albumins
  – Globulin
  – Fibrinogen
                     Albumins
•   Smallest
•   60% by weight
•   Synthesized by the liver
•   Important determinant of colloid osmotic
    pressure of the plasma
    – Helps to regulate water movement and control blood
      volume.
    – Too large to cross capillary walls so water diffuses
      towards it.
    – Acts opposite blood pressure that tends to force water
      out of capillaries by filtration
                   Edema
• Tissues swell if concentration of plasma
  proteins falls.
  – May result from starvation or a protein-
    deficient diet (requires the body to use protein
    for energy)
  – May result from an impaired liver that cannot
    synthesize plasma proteins.
• As concentration of proteins drops, so
  does osmotic pressure sending fluids into
  intercellular spaces.
                Globulins
• 36% by weight
• 3 types
  – Alpha: synthesized by liver. Function to
    transport lipids and fat-soluble vitamins
  – Beta: same as alpha
  – Gamma: Produced by lymphatic tissues. Type
    of antibodies
                  Fibrinogen
•   4% by weight
•   Largest in size
•   Functions in blood coagulation. (more later)
•   Synthesized in liver.
            Blood Gases
• Most important are oxygen and CO2
• Blood contains a considerable amount of
  nitrogen gas
                (More in Ch16)
            Blood Nutrients
• Amino acids, simple sugars, nucleotides,
  and lipids are absorbed from the digestive
  tract
• Plasma transports glucose from small
  intestine to liver where it is stored as
  glycogen or converted to fat
• Amino acids are transported to the liver to
  manufacture proteins or are used as an
  energy source.
• Lipoprotein complexes: lipids combine with
  proteins and become water-soluble
  – Plasma lipids include: triglycerides (fats),
    phospholipids, and cholesterol
  – Apoproteins on the outer layer of these large
    molecules can combine with receptors on the
    membranes of specific target cells.
  – Vary in density by the proportions of their lipids and
    proteins.
  – Help to transport dietary fats between the liver and
    muscle and adipose tissue
       Non-protein Nitrogenous
            Substances
• Molecules that contain nitrogen atoms but
  are not proteins.
• Amino acids enter plasma from protein
  digestion and from absorption
• Urea and uric acid are products of protein
  and nucleic acid catabolism. Excreted as
  urine.
          Plasma Electrolytes
• A variety of electrolytes are absorbed from the
  intestine or are released as by-products of
  cellular metabolism.
• Sodium and chloride ions are most abundant.
  Other ions include calcium, magnesium,
  bicarbonate, phosphate, and sulfate.
• Bicarbonate ions are important in maintaining
  osmotic pressure and pH of plasma
• Regulated so that concentrations remain
  relatively stable.
               Hemostasis
• The stoppage of bleeding
• Following injury, several actions may help
  limit or prevent blood loss
  – Blood vessel spasm
  – Platelet plug formation
  – Blood coagulation
        Blood Vessel Spasm
• Vasospasm:
  – Cutting or breaking smaller vessels stimulates
    the smooth muscles in its walls to contract.
    May close completely.
  – Effects last only a few minutes to 30 minutes.
• Platelets release serotonin which
  stimulates vasoconstriction and helps
  maintain vessel spasm.
         Platelet Plug Formation
• Platelets adhere to each other and
  collagen underlying the endothelial lining
  at injury sites forming plugs in broken
  vessels.
• May control blood loss from a small break,
  but larger break may require a blood clot
  to halt bleeding.


 Link to animation
Steps in platelet plug formation
         Blood Coagulation
• Most effective hemostatic mechanism
• Causes formation of a blood clot
• Clotting factors:
  – Biochemicals that promote or inhibit
    coagulation
  – Whether or not blood coagulates depends on
    the balance between 2 groups of factors.
    • Normally, anticoagulants prevail = no clots
    • Following injury, biochemicals that favor
      coagulation may increase and blood coagulates.
• The major event in blood clot formation is the
  conversion of soluble fibrinogen (a plasma
  protein) into insoluble threads of fibrin
• Biochemicals that promote clotting:
  – Prothrombin activator: damaged tissue signals this to
    be produced.
  – Prothrombin: alpha globulin continuously produced by
    the liver. It is converted to thrombin by prothrombin
    activator and calcium ions.
  – Thrombin catalyzes a reaction that fragments
    fibrinogen.
  – Long fibrin threads stick to exposed surfaces of
    damaged blood vessels creating a meshwork that
    entraps blood cells and platelets
  – Resulting mass is a blood clot which may block a
    vascular break and prevent further blood loss
A scanning electron micrograph of fibrin threads.
• Serum: clear, yellow fluid that remains
  after clot. Same as plasma, minus the
  clotting factors.
• Works as a positive feedback system
  – The original action stimulates more of the
    same type of action. Promotes unstable
    conditions only operates for a short time (life
    depends on maintenance of stable internal
    conditions)
  – The amount of prothrombin activator in blood
    is directly proportional to the degree of tissue
    damage.
  – Once clot begins to form, it promotes more
    clotting because thrombin also acts directly on
    blood clotting factors.
• Normally:
  – Blood flow prevents massive clot formation
    within the cardiovascular system by rapidly
    carrying excess thrombin away, keeping its
    concentration too low to enhance further
    clotting.
  – Blood coagulation is usually limited to blood
    standing still or moving slowly. Clotting
    ceases where clot contacts circulating blood.
• Lab tests used to evaluate blood
  coagulation mechanisms include:
  prothrombin time (PT) and partial
  thromboplastin time (PPT). Both measure
  the time for fibrin threads to form in a
  sample of plasma.
              Fibroblasts
• Invade blood clots formed in ruptured
  vessels.
• Produce connective tissue with fibers
  throughout clots.
• Help strengthen and seal vascular breaks.
     Clots Dissolve with Time
• Depends on action of a plasma protein
  that can digest fibrin threads and other
  proteins associated with clots.
• Clots that fill large blood vessels are
  seldom removed naturally.
    Abnormal Clot Formations
• Thrombus: a clot abnormally forming in a
  vessel
• Embolus:
  – If a clot dislodges or if a fragment of it breaks
    loose and is carried away by blood flow.
  – Continues to move until it reaches narrow
    place in vessel where it may lodge and block
    flow.
    • Often associated with conditions that
      change endothelial lining of vessels. Ex.
      Atherosclerosis = accumulations of fatty
      deposits.




Artery cross sections. A.) Light micrograph of a normal artery. B.) The inner wall of this
artery changed as a result of atherosclerosis.
• Coronary thrombosis: blood clot forming in
  vessel that supplies the heart
• Cerebral thrombosis: blood clot forming in
  vessel that supplies the brain.
• Infarction: Clot that blocks and kills tissues the
  vessel serves.
• Pulmonary embolism: clot that travels and
  blocks vessel that supplies the lungs. Affects
  portion of organ the blocked vessel supplies.
   Tissue Plasminogen Activators
               (tPA)
• Break up abnormal blood clots and are
  used to treat heart attacks and strokes.
      Coagulation Disorders
• Hemophilia
• Von Willebrand Disease
               Hemophilia
• Inherited clotting disorder
• Abnormalities of different clotting factors
  cause different forms of hemophilia
• Hemophilia A: missing factor VIII. Most
  common.
• Symptoms include severe hemorrhage
  following minor injuries. Frequent
  nosebleeds, large muscular hematomas
  (blood leakage in tissues), and blood in
  urine
      Von Willebrand Disease
• Tendency to bleed and bruise easily
• Inherited clotting disorder
• Less severe than hemophilia
• Lack a plasma protein, von Willebrand factor,
  secreted by endothelial cells lining blood vessel
  walls which enables platelets to adhere to
  damaged blood vessel walls, a key step
  preceding actual clotting.
• Sometimes causes spontaneous bleeding from
  mucous membranes or gastrointestinal and
  urinary tracts.
Blood vessel spasm, platelet plug formation, and blood coagulation provide homeostasis
following tissue damage.
Blood Groups and Transfusions
• Early attempts at transfusions produced a
  variety of results.
  – Some people recovered, others suffered a
    blood reaction in which RBC’s clumped
    obstructing vessels, causing pain and organ
    damage.
  – Scientists determined that blood is of different
    types. Only certain combinations are
    compatible. Blood typing procedures were
    developed.
     Antigens and Antibodies
• Agglutination:
  – The clumping of RBC’s following a transfusion
    reaction
  – Due to a reaction between RBC surface
    molecules called antigens and protein
    antibodies (formerly called agglutinogens and
    agglutinins)
  – Only a few of the many antigens on RBC
    membrane produce serious transfusion
    reactions. Ex. ABC group and Rh group
• Mismatched Transfusion
  – Symptoms include: anxiety, breathing
    difficulty, facial flushing, headache, severe
    pain in neck, chest, and lumbar area
  – RBC’s burst releasing free hemoglobin
  – Macrophages phagocytize the hemoglobin
    converting it to bilirubin (which accumulates to
    cause jaundice)
  – Free hemoglobin in the kidneys may cause
    them to fail
         ABO Blood Group
• Based on the presence or absence of 2
  major antigens on RBC membranes
• A person’s erythrocytes have 1-4 antigen
  combinations on their surface as a result
  of inheritence: A, B, AB, or neither (O)
• The most common ABO blood types are
  O=47%, A=41%, B=9%, AB=3%
Different combinations of antigens and antibodies distinguish blood types. (Cells and
antibodies not drawn to scale)
• After birth (2-8 months) antibodies are
  synthesized in the plasma.
  – When antigen A is absent in RBC’s an
    antibidy called anti-A is produced, etc.
• Anti-A and Anti-B are large and do not
  cross the placenta
  – Pregnant woman and fetus may be of
    different ABO blood types. Agglutination in
    fetus does not occur.
• An antibody of one type will react with an
  antigen of the same type and clump
  RBC’s. This must be avoided during
  transfusions.
• Universal Recipients: type AB persons
  lack both antibodies. Can receive any type
  blood but AB is still best match because
  donated A blood still has some anti-B in it.
• Universal Donor: lacks antigens A and B.
  Could be transfused into persons of any
  blood type. Does contain anti-A and anti-B
  so it must be transfused slowly so persons
  larger blood volume dilutes it minimizing
  chance of reaction.
Agglutination. A.) If RBC’s with antigen A are added to blood containing antibody anti-A,
B.) the antibodies react with the antigens, causing clumping (agglutination). C.)
Nonagglutinated blood. D.) Agglutinated blood.
           Rh Blood Group
• Named after the rhesus monkey in which it
  was first studied.
• Inherited trait
  – If antigen D and other Rh antigens are
    present on RBC membrane = Rh+
  – If RBC lacks Rh antigens = Rh-
  – 15% of U.S. population is Rh-, therefore AB-
    is rarest and O+ is most common.
• Antibodies for Rh (anti-Rh) do not appear
  spontaneously. Only form in Rh- person in
  response to special stimulation
Rh- person recieves transfusion of
           Rh+ blood
• The Rh antigens stimulate the recipient’s
  antibody-producing cells to begin
  producing anti-Rh antibodies.
• Generally initial transfusion has no serious
  consequences, but Rh- person is now
  ―sensitized‖ to Rh+ blood.
• Agglutination will occur if second
  transfusion with Rh+ occurs.
   Rh- woman pregnant with Rh+
              fetus
• First time is uneventful but during birth or
  miscarriage, some infant blood may enter
  maternal circulation and ―sensitize‖ the woman
  causing her to begin producing anti-Rh
  antibodies.
• During second pregnancy with Rh+ fetus, anti-
  Rh antibodies (called hemolysins) cross
  placental membrane and destroy fetal RBC’s.
• Fetus then develops erythroblastosis fetalis
If a man who is Rh positive and a woman who is Rh negative conceive a child who is Rh
positive, the woman’s body may manufacture antibodies that attack future Rh-positive
offspring.
• Extremely rare today because physicians
  carefully track Rh status.
  – Woman who might carry Rh+ fetus is given an
    injection of RhoGAM composed of anti-Rh antibodies
    which bind to and shield and Rh+ fetal cells that might
    contact the woman’s cells and sensitize her immune
    system.
  – RhoGAM must be given within 72 hours of possible
    contact with Rh+ cells including giving birth,
    terminating pregnancy, miscarrying, amniocentesis.
Clinical Terms Related to the
            Blood
             Anisocytosis
• Abnormal variation in size of erythrocytes
         Antihemophilic plasma
• Normal blood plasma that has been
  processed to preserve an antihemophilic
  factor.


  Used to temporarily relieve
  dysfunction of the hemostatic
  mechanism in hemophilia
       Citrated Whole Blood
• Normal blood to which a solution of acid
  citrate has been added to prevent
  coagulation
                                    Dried plasma
     • Normal blood plasma that has been
       vacuum-dried to prevent growth of
       microorganisms
Dried plasma was developed and first used during WWII. Prior to the
United States involvement in the war, liquid plasma and whole blood were
used. The "Blood for Britain" program during the early 1940s was quite
successful (and popular stateside). Nonetheless the decision was made
to develop a dried plasma package for the armed forces because it
reduced breakage and made transport, packaging, and storage much
simpler. [2]
The resulting Army-Navy dried plasma package came in two tin cans
containing 400 cc bottles. One bottle contained enough distilled water to
completely reconstitute the dried plasma contained in the other bottle. In
about three minutes, the plasma would be ready to use and could stay
fresh for around four hours. [3]
By the end of the war the American Red Cross had provided enough
blood for over six million plasma packages. Most of the surplus plasma
was returned stateside for civilian use. Serum albumin replaced dried
plasma for combat use during the Korean War
   Hemorrhagic telangiectasia
• Inherited tendency to bleed from localized
  lesions of capillaries.
                                Patients lose capillary
                                network connects between
                                veins and arteries. Most
                                affected areas are lips,
                                tongue, nasal mucosa,
                                finger tips, lungs, brain,
                                liver, and gastrointestinal
                                tract. Treatments include,
                                iron supplements, laser
                                cautery, antifibrinolytic
                                agents, transfusions
     Heparinized whole blood
• Normal blood to which a solution of
  heparin has been added to prevent
  coagulation
            Macrocytosis
• Abnormally large erythrocytes


                           Larger than 9 micrometers in
                           diameter. Found in folate and
                           B12 deficiencies and liver
                           disease.
             Microcytosis
• Abnormally small erythrocytes


                        Smaller than 7 micrometers in
                        diameter. Lymphocyte (blue, 8
                        micrometers) used as a guide.
                        Found in anemia, thalassaemia,
                        and lead poisoning.
                                  Neutrophilia
     • Increase in the number of circulating
       neutrophils       Shift or transient neutrophilia is generally a very
                                                 short-lived condition, often lasting less than sixty
                                                 minutes. This increase in actively circulating
                                                 neutrophils is usually associated with vigorous
                                                 exercise, but can also develop following an injection
                                                 of epinephrine, a seizure, or an intense emotive
                                                 response, such as fear or rage. All of the neutrophils
                                                 in circulation are fully mature since they simply have
                                                 been transferred from the marginal pool, which in a
                                                 normal adult is comprised of cells that have already
                                                 fully developed in the bone marrow.
When true neutrophilia occurs, however, some of the neutrophils observed in the blood may be
immature forms that were released by the bone marrow before their development was complete
due to an insufficient number of mature cells to meet the demands of the body. Typically this
excessive demand is related to a bacterial infection, which results in the release of
chemoattractants that bind to certain neutrophil receptors and initiate their activity so that they can
aid in the body’s immune response.
                      Packed red cells
 • Concentrated suspension of red blood
   cells from which the plasma has been
                  Packed red blood cells, the most commonly transfused
   removed.       blood component, can restore the blood's oxygen-carrying
                               capacity. This component may be given to a person who is
                               bleeding or who has severe anemia. The red blood cells
                               are separated from the fluid component of the blood
                               (plasma) and from the other cellular and cell-like
                               components. After this step, the red blood cells are
                               concentrated so that they occupy less space, thus the
                               term "packed." Red blood cells can be refrigerated for up
                               to 42 days. In special circumstances—for instance, to
                               preserve a rare type of blood—red blood cells can be
                               frozen for up to 10 years. Transfusing only selected
                               blood components allows the treatment to be
                               specific, reduces the risks of side effects, and can
                               efficiently use the different components from a
Leukocyte depleting filters.   single unit of blood to treat several people.
             Pancytopenia
• Abnormal depression of all the cellular
  components of blood

                 This peripheral blood picture is from an anemic
                 patient with a low white cell count, and a low
                 platelet count. A reduction in all the formed
                 elements of the blood is called a 'pancytopenia'. It
                 often indicates bone marrow failure (leukemia), but
                 can also occur from peripheral destruction of cells,
                 as in hypersplenism (overactive spleen). Also
                 occurs in people with AIDS.
             Poikilocytosis
• Irregularly shaped erythrocytes


                      Lowers blood’s oxygen carrying capacity
                      causing anemia. In all cases, the treatment
                      of poikilocytosis depends on its cause. For
                      example, poikilocytosis can be caused by a
                      vitamin deficiency, in which case the
                      treatment is to take Vitamin B12 or folic
                      acid. It can be caused by a digestive
                      disease, such as celiac disease, in which
                      case the solution may lay in treating the
                      underlying celiac disease so that nutrients
                      can be properly absorbed.
                              Purpura
  • Spontaneous bleeding into the tissues
    through the mucous membranes




Common in typhus and meningitis and in old age when blood vessels damage more
easily. Also a symptom of a variety of other disorders.
                                  Septicemia
     • Presence of disease-causing                                                  The Pope died
       microorganisms or their toxins in the                                        from septic
                                                                                    shock April 2005
       blood.
Septicemia is a serious, life-threatening infection that gets worse very quickly. It can arise from
infections throughout the body, including infections in the lungs, abdomen, and urinary tract. It may
come before or at the same time as infections of the bone (osteomyelitis ), central nervous system
(meningitis ), or other tissues.
Septicemia can rapidly lead to septic shock and death. Septicemia associated with some organisms
(germs) such as meningococci can lead to shock, adrenal collapse, and disseminated intravascular
coagulopathy, a condition called Waterhouse-Friderichsen syndrome.
Septicemia can begin with spiking fevers and chills, rapid breathing and heart rate, the outward
appearance of being seriously ill (toxic) and a feeling of impending doom. These symptoms rapidly
progress to shock with decreased body temperature (hypothermia), falling blood pressure,
confusion or other changes in mental status, and blood-clotting abnormalities evidenced by a
specific type of red spots on the skin (petechiae and ecchymosis).
            Spherocytosis
• Hemolytic anemia caused by defective
  proteins supporting cell membranes of red
  blood cells.
• The cells are abnormally spherical.
                      Though the spherocytes have a smaller
                      surface area through which oxygen and
                      carbon dioxide can be exchanged, they in
                      themselves perform adequately to maintain
                      healthy oxygen supplies. The misshapen but
                      otherwise healthy red blood cells are
                      mistaken by the spleen for old or damaged
                      red blood cells and it thus constantly breaks
                      them down, causing a cycle whereby the
                      body destroys its own blood supply (auto-
                      hemolysis).
                         Thalassemia
 • Group of hereditary hemolytic anemias
   resulting from very thin, fragile
   erythrocytes.




The genetic defect results in synthesis of an abnormal
hemoglobin molecule. The blood cells are vulnerable to
mechanical injury and die easily. To survive, many
people with thalassemia need blood transfusions at
regular intervals.
• See Clinical connection on Thrombotic
  thrombocytopenic purpura (TTP) p324.

				
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