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 hemaglobin 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

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