I. Physical Characteristics of Blood:
    A. Temperature: approx. 38^oC
    B. pH: 7.35-7.45
    C. Ave. Volume: 5-6 liters (11 pints)
    D. Amount/Body Weight: 8% of body weight
    E. Composition:
         1. 55% Liquid portion
         2. 45% Formed elements

II. Soluble Components of Blood:
      A. Serum (liquid portion without clotting factors)
      B. Plasma (liquid portion + clotting factors)
          1. Plasma contains many sorts of proteins including albumins, globulins, clotting factors, complement, regulatory enzymes, as well as electrolytes and hormones.
          2. Albumins: most abundant plasma proteins; carriers for many molecules (sterols, bilirubin, hormones, ions...)
          3. Globulins: many different types of proteins including immunoglobulins and...
                 a. alpha₁-anti-trypsin (AAT): major globulin; inactivates proteases; important in counteracting endogenous proteolytic activity such as during coagulation, inflammation; AAT-deficency associated with emphysema and liver disease;
                 b. Haptoglobulin: binds free hemoglobin from lysed RBCs; increases under stress, acute inflammation, infections; decreases with massive hemolysis, burns, transfusion mismatches
                 c. Transferrin: binds free Fe³⁺, transports in blood,

III. Blood cells (Formed Elements):  All blood cells are produced in red bone marrow
     A. Erythrocytes: 4.8-5.4 x 10⁶/mm³; produce about 2.5 million/sec; 120 day lifespan
          1. Reticulocytes: immature RBCs (>1%)
          2. Hematocrit = % RBC in blood (volume); male = 40-54%; female = 38-46%
          3. Anemia: decreased hematocrit; many forms and causes:
              a. Iron-deficiency anemia: most common, inadequate iron absorption or excessive excretion
              b. Pernicious anemia: lack of intrinsic factor needed for B₁₂ absorption
              c. Hemolytic anemia: destruction of RBCs leaving "ghosts"
              d. Thalassemia: inherited form of hemolytic anemia - altered form of Hb
              e. Aplastic anemia: loss of erythropoesis in red bone marrow
              f. Sickle-cell anemia: misshapen RBCs from altered Hb causes poor vascular circulation and hemolysis
     E. Polycythemia: increased hematocrit (over 65%); may be spurious or secondary to renal disease
    F. Erythropoetin: hormone to stimulate RBC synthesis; given to counteract bone marrow deficits (chemoth.)
    G. Erythrocyte and Hemoglobin (Hb) Production and Recycling:
       1. Spleen, liver, red bone marrow - macrophage phagocytize damaged/dead RBCs;
       globin & heme are separated;
       globin digested & amino acids recycled;
        2. The Fate of Heme...
            a. Fe³⁺ separated from heme ---> biliverdin ---> bilirubin ---> into blood to liver
            b. bilirubin added to bile into small intestine...
            c. bilirubin ---> urobilinogen in lrg int. ---> into kidney
                (excreted as urobilin) or lrg int. (excreted as stercobilin)
        3. The Recycling of Fe³⁺...
            a. Fe³⁺ bound by transferrin ---> into blood ---> transport to liver...
            b. stored in the "F &H Wharehouse" (ferritin & hemosiderin) to be used later...
            c. bound again to transferrin ---> into blood to bone marrow for new Hb synthesis.
    H. Factors required for RBC synthesis:
       1.  Fe³⁺: necessary diet nutrient
       2. Vit B₁₂: used for erythropoeisis in red bone marrow
       3. Intrinsic factor: produced by stomach parietal cells - aids Vit B₁₂ absorption in small intestine
       4. Erythropoetin:  hypoxia induces kidneys to increase erythropoetin secretion
       5. Protein: amino acids used to produce globin

IV. Leukocytes: 5-10,000/mm³
  A. Granulocytes:
    1. Neutrophils (50-70%); 3 day lifespan; major phagocyte & granulocyte; attracted by inflammatory factors and complement; granules with hydrolytic enzymes; cell dies after degranulation/phagocytosis
       a. "Band" is immature neutrophil (band-shape nucleus);
       b. "Seg" is mature neutrophil (segmented nucleus).
       c. Neutrophilia: increase %; common with acute bacterial infections
       d. Neutropenia: decrease %; common with anemias, viral infections, radiation/chemotherapy;
           i)  Neutropenia can result in lowered immune protection especially to bacterial/fungal infections.
    2. Eosinophils (2-4%); major anti-helminth protection (myelin basic protein released); also contributes to some hypersensitivity reactions and phagocytosis of bacteria.
    3. Basophils (<1%); granulocytic, nonphagocytic; major inflammatory cell, releases histamines, proteases and granulocyte-attracting factors.
    4. Monocytes (2-8%); only last 8-12 hrs in circ. then migrate to tissue = major function to become macrophage in tissue; play key role in "antigen presentation", express MHC-II.
    5. Platelets (thrombocytes) (240-400,000/mm³); crucial to help activate blood clot formation, for platelet plug; spleen acts as reserve site;
    6. Lymphocytes (20-30%) mononuclear cells; mediate/regulate specific immune responses (antibody formation, anti- viral and anti-tumor protection)
     a. B-cell: produce immunoglobulins (mature in bone marrow)
     b. T-cell: activate/regulate B-cells, major immune regulatory cells (mature in thymus)
     c. NK cell: natural killer cell; non-specific anti-tumor cytolytic cell

V. Hemostasis:
   A. Vascular Spasm:
          Smooth muscle contraction - decreases blood flow in damaged vessels 

   B. Platelet Plug Formation:
         Platelet adhesion to exposed collagen
         Platelet activation, platelet release reaction,
         Platelet aggregation; increased adhesion (via ADP)

   C. Coagulation: (all steps require Ca²⁺ )
        Stage 1: produce prothrombinase (factors 10/5) via extrinsic and intrisic pathway
        Stage 2: produce thrombin, via common pathway
        Stage 3: produce fibrin threads
   
        1. Extrinsic Pathway: (initiated by factor outside blood vessels)
                Thromboplastin (TF) leaks into blood from tissues
                TF ---> 7 ---> 10/5 = prothrombinase

        2. Intrisic Pathway: (initiated by factors within blood vessels)
                Exposed collagen or basement membrane of endothelial cells initiates pathway
                12 ---> 11 ---> ⁷9/8^pp ---> 10/5 = prothrombinase
                    hemophilia A = lack of  factor VIII, is sex-linked
                    hemophilia B = lack of factor IX; is sex-linked
                    hemophilia C = lack of factor XI; not sex-linked

        3. Common Pathway:
                 Prothrombinase (10/5) * 
                         *prothrombin ---> thrombin **
                                **fibrinogen is converted to fibrin threads ("CLOT")
                                **factor XIII activation (fibrin stabilizing factors)
                                **accelerates prothrombinase (10/5) formation (positive feedback)
                                **increases platelet activation (positive feedback)
                                 - - fibrin traps & inactivtes thrombin (negative feedback)

VI. Major Blood Group Antigens:
   A. ABO Antigens
   Isoagglutinin glycolipid antigens controlled by various alleles of the I gene (i = nonexpression of I gene)
      I^AI^A or I^Ai = results in A blood type
      I^BI^B  or I^Bi = results in B blood type
      I^AI^B  = results in AB blood type
      i i = results in O blood type
Individuals with Type A blood contain antibodies to Type B blood (anti-B antibodies)
Individuals with Type B blood contain antibodies to Type A blood (anti-A antibodies)
Individuals with Type AB blood contain no antibodies to either Type A or Type B blood
Individuals with Type O blood contain antibodies to both Type A or B blood (anti-A and anti-B antibodies)

   B. Inheritance of Blood Types
If person with AB blood and O blood have children, a Punnett square illustrates possible offspring blood types:
 

This shows 50% offspring will be A i (A blood type) and 50% will be B i (B blood type)
More Examples:
 

    C. ABO Compatibility in Blood Transfusions
Individuals with Type A blood contain antibodies to Type B blood (anti-B antibodies)
Individuals with Type B blood contain antibodies to Type A blood (anti-A antibodies)
Individuals with Type AB blood contain no antibodies to either Type A or Type B blood
Individuals with Type O blood contain antibodies to both Type A or B blood (anti-A and anti-B antibodies)

This table summarizes ABO tranfusion compatability:
 

    Important for Rh- mother pregnant with Rh+ child
        Sensitization of mother during delivery induces high levels of anti-Rh IgG antibodies; (block with Rhogam)
        During pregnancy with subsequent Rh+ child, anti-Rh IgG can cross placenta and cause hemolytic disease of newborn (less problem if Rhogam is administered during first delivery)

    Transfusions are typically restricted to matching Rh+ donor to Rh+ recipient.
    Rh - recipients should not be given Rh+ blood transfusion.
    Rh - blood can be transfused into Rh- or Rh+ recipient.  (much like O blood can be given to any blood type)

                                   "Universal Donor" = O -          "Universal Recipient" = AB +

       E. Blood Typing
  A small sample of blood is mixed with known reagents containing anti-A, or anti-B or anti-Rh.
       A positive reaction is where clumping (agglutination) occurs (antibody binds to RBCs in the blood)
       A negative reaction is where no agglutination occurs (antibody does not bind to RBCs)
  Severe (life-threatening) mismatch transfusion reactions can occur if donor and recipient do not match ABO type
  Check out this Cool Blood-Transfusion Game
 

       F. Other Blood Group Antigens
   Lewis, Kel, Duffy, and others also exist and can have clinical importance in some transfusion reactions.