Functions of Blood
• Transportation-
   –   oxygen
   –   carbon dioxide
   –   waste
   –   nutrients
   –   hormones
• Regulation-
   – pH
   – temperature
   – influences water content of cells
• Protection-
   – blood loss via clotting mechanisms
   – foreign microbes via white cells
           Physical Properties of Blood
• viscous fluid
    – viscosity is the resistance of a fluid to flow due to cohesion
      between its particles
•   temperature is 38oC (100.4oF)
•   pH range 7.35-7.45 (slightly alkaline)
•   NaCl concentration of 0.9%
•   volume in male, 5-6L, Female 4-5L
•   8% of the total body weight
          Components of Blood
Formed Elements
• Erythrocytes (red blood cells)
• Leukocytes (white blood cells)
  – Granular leukocytes
     • neutrophils
     • eosinophils
     • basophils
  – Agranular leukocytes
     • lymphocytes
     • monocytes
• Platelets (thrombocytes)
            Components of Blood
Plasma
• consist of 91.5% water and 8.5%
   solutes (proteins, nutrients, gases,
   electrolytes, waste products,enzymes,
   and hormones)
• plasma proteins- proteins found and
   confined only in the blood
   – Albumins- manufacture in the liver and is
     responsible for maintaining water balance
     in the blood.
       • Consist of 55% of the total plasma proteins
   – Globulins
       • proteins divided into 3 classes according to
         electrophoretic separation
       • - antibodies produced by certain white cells
         that functions in immunity.
       • 35% of total plasma proteins
   – Fibrinogen- soluble precursor of fibrin
     that functions in the blood clotting
     mechanisms along with platelets.
                Serum Globulins
Alpha-Globulins                   Beta Globulin
• alpha 1-Antichymotrypsin        • beta-2 Microglobulin
• alpha 1-Antitrypsin             • beta-Thromboglobulin
• alpha-Macroglobulins            • Hemopexin
• Antiplasmin                     • Plasminogen
• Antithrombin III                • Properdin
• Ceruloplasmin                   • Sex Hormone-Binding Globulin
• Haptoglobins                    • Transferrin
• Heparin Cofactor II             • complement factor H
• Orosomucoid
• Progesterone-Binding Globulin
• Retinol Binding Proteins
• Transcortin
Plasma is a pale yellow fluid that consists of
about 92% water and 8% other substances,
such as proteins, ions, nutrients, gases, and
waste products.
Plasma is a colloidal solution, which is a
liquid containing suspended substances that do
not settle out of solution. Most of the
suspended substances are plasma proteins,
which include albumins, globulins, and
fibrinogen.
Plasma volume remains relatively constant.
Normally, water intake through the digestive
tract closely matches water loss through the
kidneys, lungs, digestive tract, and skin.
nitrogen
       Red blood cell indices
• Are measurements that describe the size and
  oxygen-carrying protein (hemoglobin)
  content of red blood cells.
• The indices are used to help in the
  differential diagnosis of anemia (a person's
  blood cannot carry as much oxygen as it
  should).
                       Anemia
• A healthy person has an adequate number of correctly
  sized red blood cells that contain enough hemoglobin
  to carry sufficient oxygen to all the body's tissues.
• An anemic person has red blood cells that are
  either too small or too few in number.
   – As a result, the heart and lungs must work harder to make up
     for the lack of oxygen delivered to the tissues by the blood.
• Anemia is caused by many different diseases or
  disorders. The first step in finding the cause is to
  determine what type of anemia the person has. Red
  blood cell indices help to classify the anemias.
                  Anemia (cont)
• Anemia has several general causes:
  – blood loss
     • Blood loss can result from severe hemorrhage or a chronic
       slow bleed, such as the result of an accident or an ulcer.
  – a drop in production of red blood cells
     • Lack of iron, vitamin B12, or folic acid in the diet, as well
       as certain chronic diseases, lower the number of red blood
       cells produced by the bone marrow.
  – a rise in the number of red blood cells destroyed.
     • Inherited disorders affecting hemoglobin, severe reactions to
       blood transfusions, prescription medications, or poisons can
       cause red blood cells to burst (hemolyze) well before the end
       of their usual 120-day lifespan.
• Anemia of any type affects the results of one or more of
  the common blood tests. These tests are the
   –   hematocrit,
   –   hemoglobin
   –   red blood cell count
   –   The hematocrit is a measure of red blood cell mass, or how much
       space in the blood is occupied by red blood cells. The hemoglobin
       test is a measure of how much hemoglobin protein is in the blood.
       The red blood cell count (RBC) measures the number of red blood
       cells present in the blood. Red blood cell indices are additional
       measurements of red blood cells based on the relationship of these
       three test results.
         Red Blood Cell Indices
 Red blood cell count (RBC)
• measures the number of red blood cells present in the
  blood.
Mean corpuscular volume (MCV)
• It measures the average volume of a red blood cell by
  dividing the hematocrit by the RBC.
• The MCV categorizes red blood cells by size.
   – cells of normal size are called normocytic
   – smaller cells are microcytic
   – larger cells are macrocytic
Red cell distribution width (RDW)
• measures the variation in size of the red blood cells.
• Usually red blood cells are a standard size. Certain
  disorders, however, cause a significant variation in cell
  size.
Red blood cell indices
Hematocrit- a measure of red blood
cell mass, or how much space in the
blood
• is the percentage of whole blood
volume composed of RBCs
Normal hematocrits of male (a) 42-52%
and female (b) 37-48%.
Blood is separated into plasma,
erythrocytes, and a small amount of
leukocytes and platelets, which rest on
the erythrocytes.
The hematocrit measurement includes
only the erythrocytes and does not
measure the leukocytes and platelets.
   Red blood cell indices (cont)
Hemoglobin test is a measure of how much hemoglobin
  protein is in the blood.
• The MCHC (mean corpuscular hemoglobin concentration)
  measures the average concentration of hemoglobin in a red
  blood cell.
   – calculated by dividing the hemoglobin by the hematocrit.
• Categorizes red blood cells according to their concentration
  of hemoglobin.
   – Cells with a normal concentration of hemoglobin are called
     normochromic.
   – When examined under a microscope, normal red blood cells that
     contain a normal amount of hemoglobin stain pinkish red with a
     paler area in the center.
Normal Blood Smear
• Categorizes red blood cells according to
  their concentration of hemoglobin (cont).
  – cells with a lower than normal concentration
    are called hypochromic.
  – Cells with too little hemoglobin are lighter in
    color with a larger pale area in the center.
• Because there is a physical limit to the
  amount of hemoglobin that can fit in a cell,
  there is no hyperchromic category.
                    Formation of Blood
Hematopoiesis- the process by which blood cells are formed.
• In embryo there are multiple sites for blood formation
   – liver, spleen, thymus gland, lymph nodes, and red bone marrow
• after birth blood production takes place in the red bone
  marrow of various long and flat bones.
   – Femur, humerus, sternum, ribs, vertebrae, and cranial bones
• All blood cells originate from hemopoietic stem cells
   – these cells differentiate into the five types of blood cells:
       •   erythrocytes
       •    granulocytes- eosinophils, neutrophils, basophils
       •   monocytes
                             agranulocytes
       •   lymphocytes
       •   platelets
Hemocytoblast-
multipotent stem cell
capable of
differentiating into
multiple cells lines
•Red cells
•White cells
•Platelets
         Erythropoiesis
• Proerythroblast is the first committed
  cell, having receptors for the hormone
  erythropoietin (EPO)
   – secreted by the kidney that stimulates
     proerythroblast to mature into erythroblast
• Erythroblast manufactures hemoglobin
  and then discards its nucleus which it is
  them called a reticulocyte (distinguished
  by its network of endoplasmic reticulum)
   – takes 3-4 days
• Reticulocytes enters the blood stream,
  eventually loses its ER, then is a mature
  erythrocyte
                  Erythropoiesis (cont.)
• About .5-1.5% of the circulating RBCs are reticulocytes
• Percentage increases under certain circumstances
       • diseases where blood is destroyed prematurely
       • spending extended amounts of time a high elevations
       • blood loss
   – these conditions stimulate acceleration of RBC production where the bone is in
     such a hurry to replenish the lost RBCs that it lets many developing RBCs into
     circulation a little early
• Reticulocyte count is a blood test that measures how rapidly
  immature red blood cells are made by the bone marrow and then
  released into the blood.
   – Determines whether anemia is being caused by decreased production of red
     blood cells or by increased destruction (or loss) of red blood cells. The increased
     destruction or loss of red blood cells causes the bone marrow to make more
     reticulocytes.
   – Monitors treatment for anemia. For example, a higher reticulocyte count
     indicates that iron replacement treatment or other treatment to reverse the
     anemia is effective.
        Erythropoiesis (cont.)
• The reticulocyte count is usually given as
  the percentage of red blood cells that are
  reticulocytes (the number of reticulocytes
  divided by the total number of red blood
  cells, multiplied by 100).
  – Normal:0.5%–2.0%
  – Newborns have a normal reticulocyte count of
    2.5% to 6.5%. This value drops within 2 weeks
    to 0.5% to 2.0%.
          Erythropoiesis (cont.)
High values
• A high reticulocyte count may indicate
   – increased production of red blood cells by the bone
     marrow, which can be caused by bleeding,
   – a move to high elevation,
   – or certain types of anemia resulting in increased
     destruction of red blood cells (hemolysis).
• The reticulocyte count usually rises after
  successful treatment for pernicious anemia, iron-
  deficiency anemia, or folic acid deficiency
  anemia.
          Erythropoiesis (cont.)
Low values
• A low reticulocyte count may indicate
   – decreased production of red blood cells by the bone
     marrow, which can be caused by aplastic anemia or
     other types of anemia, such as iron-deficiency anemia.
   – exposure to radiation,
   – a long-term (chronic) infection,
   – certain medications that damage the bone marrow.
         Erythropoiesis (cont.)
• Reticulocyte index (RI)- a measurement that
  corrects the reticulocyte count for anemia, giving a
  more accurate picture of reticulocyte count.
Ex: In anemia, the reticulocyte count will be
  inaccurate because the levels of red blood cells
  and hemoglobin are decreased, which makes the
  reticulocyte count appear falsely high.
                     Red Blood Cells
Structure
• biconcave disc
• no nucleus or other organelles
• no mitosis and minimal metabolic activity
   – only cell in the body that carries out anaerobic fermentation indefinitely
• has the red pigment called hemoglobin that carries oxygen
• cell surface has antigens responsible for the various blood types
  (ABO and Rh)
• inner membrane surface has the proteins, spectrin and actin,
  that gives the membrane resilience and durability that is need as
  they squeeze through capillaries
Function
• hemoglobin combines with oxygen and carbon dioxide (5%)
   – globin- 4 proteins chains (two alpha and two beta chains)
   – heme- 4 nonprotein pigments and iron
   – oxygen attaches to iron
            Normal Hemoglobins
• Hemoglobin A- This is the designation for the normal
  hemoglobin that exists after birth. Hemoglobin A is a
  tetramer with two alpha chains and two beta chains (α2β2).
• Hemoglobin A2- This is a minor component of the
  hemoglobin found in red cells after birth and consists of
  two alpha chains and two delta chains (α2δ2). Hemoglobin
  A2 generally comprises less than 3% of the total red cell
  hemoglobin.
• Hemoglobin F- Hemoglobin F is the predominant
  hemoglobin during fetal development. The molecule is a
  tetramer of two alpha chains and two gamma chains (α2 γ2).
   – it binds oxygen more tightly , thus it enables the fetus to extract
     oxygen from the mother’s bloodstream.
       Globin
Heme
                            Red Blood Cell Recycling
Jaundice- yellowish coloration of the eye and skin due to the increase in the blood
concentration of bilirubin.
Neonatal Jaundice
    RBC Production
Erythropoiesis- the process by
  which RBC’s are fromed.
  Anemia- a decreased number of RBC’s
  or hemoglobin.
  Hypoxia- cellular oxygen deficiency.
  Cyanosis- bluish purple discoloration of
  the skin as a result of hypoxia.
  Erythropoietin- hormone secreted from
  the kidney in response to hypoxia that
  acts on the bone marrow where is speeds
  the production of RBC’s.
  Intrinsic factor-secreted by gastric cells
  and needed for the absorption of B12.
  Iron
  Folic acid
 White Blood Cells (Leukocytes)
• Have nuclei
• Do not contain hemoglobin
• Function as part of the bodies immune
  system
• Grouped in to
  – Granular leukocyte
  – Agranular leukocyte
     White Blood Cells (Leukocytes)
Granular leukocytes- have large granules in their
  cytoplasm and have bilobed nuclei.
• Three kinds
  – neutrophils- pale lilac-first responders to foreign
    invasion, phagocytic, release enzymes.
  – eosinophils- red orange-phagocyte, release enzymes that
    combat the effects inflammation in allergic reactions, and
    effective against parasitic infections.
  – basophils- blue-purple-release substances that are
    involved in inflammation and allergic reactions. Also
    called mast cells once in the tissue
      White Blood Cells (Leukocytes)
Agranular leukocytes- cannot visible see granules (so
 described as agranular)
• Lymphocytes-
   – B cell- secretes antibody that is effective in destroying bacteria and
     deactivating toxins
   – T cells- attack viruses, fungi, transplanted tissue, and cancer cells
• Monocytes- most important phagocytic cell. Called
  macrophage when enter the tissue.
Emigration (Diapedesis)- the movement of cells out
 of the vascular system into the tissue
                    White Blood Cells
Major histocompatibility antigen- identification proteins on
 the cell surface of white cells and tissue cells.
Differential white blood cells count- a count of the number
  of kinds of white cells in a sample of 100 white cells.
WBC Life Span
   – most live only a few days as compared to the 120 days of the red
     cell
   – some B and T cells live for years
Leukocytosis- increase in the number of white cells.
Leukopenia- decrease in the number of white cells.
Neutrophil
Eosinophil
Basophil
Monocyte
Sickle Cell Anemia
                Platelets
• produced in the bone marrow
• are membrane enclosed fragments of the
  megakaryocyte
• involved in blood clotting mechanisms
• life span is 5 to 9 days
                       Plasma
• the liquid portion of blood
• consist of 91.5% water and 8.5% solute (plasma
  proteins, gases, electrolytes, waste products,
  enzymes, hormones)
• plasma proteins-
   – Albumin- manufactured in the liver and is responsible
     for maintaining blood volume. Comprise 55% of the
     plasma proteins.
   – Globulins- Comprise 38% of the plasma proteins.
     Produced by the lymphocytes (antibodies) and
     functions in immunity.
   – Fibrinogen- 7% of plasma proteins. Functions in
     blood clotting and is produced by the liver.
                            Hemostasis
                       The stoppage of bleeding
Three mechanisms
• vascular spasm- When the smooth muscle in the vascular wall
  contracts which serves to reduce blood flow to the damaged vessel.
• platelet plug formation- platelet contact with damaged vessel causes
  a series of reactions that results in massive platelet adhesion at site of
  damage (platelet plug). Is reinforced with fibrin threads during
  coagulation.
• blood coagulation (clotting)- The process of clotting that involves a
  series of reactions that eventually lead to the production of fibrin
  threads that serve to reinforce the platelet plug and trap red blood
  cells.
   – Thrombosis- clotting in an unbroken vessel
When blood it allow to remain
stagnant in the blood vessels or
sit in a test tube, it becomes a
gel (clot, thrombus) that
separates from the liquid
(plasma).
Injury to the lining of the
blood vessels exposes
collagen fibers; platelets
adhere and get sticky
Platelets release substances
that causes the vessel to
contract. Sticky platelets
form a plug and initiate the
formation of a fibrin clot
The fibrin seals the
wound until the vessel
wall heals
    Clot Formation
    Stage I can be activated in two
    ways:
    Extrinsic pathway is initiated
    when clotting factors are released
    by the damaged blood vessel and
    perivascular tissue (i.e., the
    factors come from sources other
    than the blood).
    Intrinsic pathway is initiated
    when factor XII is activated or
    released when platelets
    degranulate (i.e., everything
    needed to initiate the pathway is
    present in the blood or platelets).
Hemophilia-a sex linked hereditary
absence of certain clotting factors that
cause defective clotting.
                       Hemostasis (cont.)
• Clot Retraction- the tightening of the fibrin clot that results in the
  pulling of the damaged blood vessels closer together.
• Fibrinolysis- breaking up of the clot.
   – plasminogen (inactive enzyme) is incorporated into the initial clot
   – blood and body tissues release substances that convert plasminogen to plasmin
     (activated plasminogen)
   – plasmin dissolves clot by digesting fibrin
• Anticoagulants- substances that prevent clotting
   – heparin- anticoagulant produced by the mast cells, basophils, and endothelial
     cells lining the blood vessels.
• Thrombus- clotting in an undamaged vessel that can block circulation.
    It also can dislodge and travel down stream ( embolus).
Vitamin K and calcium are needed for formation. Vit. K is essential for
    the production of prothrombin and certain coagulation factors.
It is normally produced by bacteria in the large intestine.
                       ABO Blood Grouping
Isoantigens (agglutinogens)
Isoantibodies (agglutinins)
Transfusions
Agglutinate
Hemolysis
Rh system
Hemolytic disease of the newborn (Erythroblastosis fetalis)- occurs
with an Rh- mother and a Rh+ fetus
Hemolytic Disease of the Newborn (HDN)
Before or during delivery, Rh-positive erythrocytes from the fetus
   enter the blood of an Rh-negative woman through a tear in the
   placenta.
The mother is sensitized to the Rh antigen and produces Rh
   antibodies. Because this usually happens after delivery, there is
   no effect on the fetus in the first pregnancy.