Blood Anatomy and Physiology

Blood Components and Functions

  • Composition of Whole Blood:
    • Whole blood consists of plasma (55%) and formed elements (45%).
    • Plasma is 91% water, 7% proteins, and 2% other solutes.
    • Formed elements include platelets (
    • Leukocytes consist of neutrophils (65-75%), lymphocytes (20-25%), monocytes (3-8%), eosinophils (2-5%), and basophils (0.5-1%).
  • Blood Tissue:
    • Blood is a connective tissue with a watery fluid portion called plasma.
    • Formed elements are blood cells and cell fragments.
    • Functions as a transport medium and mechanism for heat regulation.
  • Blood Plasma:
    • Plasma is whole blood minus the formed elements.
    • It's a clear, straw-colored fluid made up of 90% water and 10% solutes.
      • Solutes include crystalloids and colloids.
      • 6-8% of solutes are proteins:
        • Albumins: Maintain osmotic balance.
        • Globulins: Essential for immunity.
        • Fibrinogen: Key role in blood clotting.
  • Plasma vs. Serum:
    • Plasma is the liquid component of blood minus blood cells.
    • Serum is the liquid component minus blood cells and clotting elements.

Formed Elements

  • Three Main Types:
    • Red blood cells (RBCs) or erythrocytes.
    • White blood cells (WBCs) or leukocytes:
      • Granulocytes.
      • Agranulocytes.
    • Platelets or thrombocytes.

Hematopoiesis

  • Two kinds of connective tissue make blood cells:
    • Myeloid tissue.
    • Lymphoid tissue.
  • Red bone marrow:
    • Found in the adult sternum, ribs, and hip bones.
    • Forms all types of blood cells except lymphocytes.
    • Lymphocytes form in lymphoid tissue.
  • Life Span:
    • Erythrocytes: up to 4 months.
    • Granular leukocytes: few days.
    • Agranular leukocytes: over 6 months.

Blood Volume

  • About 8% of total body weight in average-sized adults.
  • Measured indirectly.
  • Relationship of body fat to blood volume: Less fat, more blood per kilogram of body weight.

Hematocrit

  • Also known as packed cell volume (PCV).
  • Volume percent of RBCs in whole blood.
    • Normal whole blood is about 55% plasma and 45% RBCs (hematocrit of 45%).
  • Anemias: Conditions resulting in decreased RBCs.
  • Polycythemia: Elevated RBCs.
  • Hematocrit test: Normal, Low, and High

Structure of Red Blood Cells

  • Biconcave disks.
  • No nucleus, ribosomes, mitochondria, or other typical organelles.
  • Hemoglobin (Hb):
    • Accounts for more than one third of cell volume.
  • Flexibility is important for function.
  • Spectrin

Function of Red Blood Cells

  • Oxygen and carbon dioxide transport.
    • Hemoglobin.
    • Carbonic anhydrase catalyzes the reaction to make carbonic acid.
    • Carbonic acid dissociates and generates:
      • Bicarbonate ions and hydrogen ions.
        CO2 + H2O
        equiv H2CO3
        equiv H^+ + HCO_3^-

Hemoglobin

  • About 200 to 300 million molecules of hemoglobin in each RBC.
  • Four globin chains:
    • Each attached to a heme group.
  • One hemoglobin plus four oxygen: Oxyhemoglobin.
  • One hemoglobin plus carbon dioxide: Carbaminohemoglobin.
  • Varied hues of red: Relative proportions of oxyhemoglobin and carbaminohemoglobin.

Formation and Population Dynamics of Red Blood Cells

  • Erythropoiesis: Entire process of RBC formation.
    • Begins in red bone marrow.
      • Hematopoietic stem cells (HSCs).
      • Several stages of development.
      • Process takes approximately 4 days.
    • Adults produce over 200 billion RBCs daily, replacing an equal number destroyed.
    • Oxygen deficiency speeds RBC formation.
      • Erythropoietin (EPO) released into the blood from the liver.
      • Kidneys also release EPO.
      • Poiesis means formation.

Life Cycle of Red Blood Cells

  • Life span of circulating RBC: 105 to 120 days.
  • Blood vessel macrophages Phagocytose aged, abnormal, or fragmented RBCs.
  • Hemoglobin breaks down into:
    • Amino acids (globin), iron, and bilirubin.
  • Bone marrow requires:
    • Vitamin B12, iron, amino acids, copper, cobalt, extrinsic factor.

Blood Types

  • Based on cell markers or antigens.
    • A, B, Rh are most important for transfusions and newborn survival.
  • Agglutinins: Antibodies dissolved in plasma that react with specific blood group antigens (agglutinogens).
  • Transfusion reaction: Prevented by blood typing and cross-matching.

ABO System

  • Groups named according to antigens present on RBC membranes:
    • Type A: Antigen A is present on RBCs.
    • Type B: Antigen B is present on RBCs.
    • Type AB: Both antigens A and B are present on RBCs.
    • Type O: Neither antigen A nor antigen B is present on RBCs.

Agglutination

  • Agglutination (clumping together of particles)

Rh System

  • Rh-positive blood: Rh antigen present on RBCs.
  • Rh-negative blood: RBCs have no Rh antigen.
  • Two ways Rh-negative blood develops Rh antigens:
    • Rh-negative person receives Rh-positive blood via transfusion.
    • Rh-negative mother receives Rh-positive blood via fetus: Erythroblastosis fetalis.

Erythroblastosis Fetalis

  • Rh-positive blood cells enter the mother's bloodstream during delivery of an Rh-positive baby. If not treated, the mother's body will produce anti-Rh antibodies.
  • A later pregnancy involving an Rh-negative baby is normal because there are no Rh antigens in the baby's blood.
  • A later pregnancy involving an Rh-positive baby may result in erythroblastosis fetalis. Anti-Rh antibodies enter the baby's blood supply and cause agglutination of RBCs with the Rh antigen.

Components of Circulating Blood

  • Discuss the generalized function, classification, normal appearance, size, shape, and number of leukocytes in circulating blood, and compare and contrast granulocytes and agranulocytes.
  • Discuss the appearance, size, shape, number, function, formation, and life span of platelets in circulating blood.
  • Explain the steps involved in blood coagulation and the factors that oppose and hasten clotting.
  • Discuss disorders of red and white blood cells and clotting disorders.

White Blood Cells

  • Colorless, but appear white when grouped.
  • Two Types:
    • Granulocytes:
      • Neutrophils.
      • Eosinophils (allergic reactions).
      • Basophils.
    • Agranulocytes:
      • Lymphocytes.
      • Monocytes.

Granulocytes

  • Neutrophils:
    • Small, numerous cytoplasmic granules stain very light purple with neutral dyes.
    • Also called polymorphonuclear leukocytes (polys).
    • Capable of diapedesis (migrate out of blood vessels into tissue spaces).
    • Chemotaxis: Process by which chemicals from damaged cells attract neutrophils, which contain lysosomes, to clean up the infection site.
  • Eosinophils:
    • Large, numerous cytoplasmic granules stain orange with acid dyes.
    • 2-5% of circulating WBCs, also numerous in the lining of digestive and respiratory tracts.
    • Protect against parasitic worms, regulate allergic reactions.
  • Basophils:
    • Large, sparse cytoplasmic granules stain dark purple with basic dyes, containing histamine and heparin.
    • Capable of diapedesis.

Agranulocytes

  • Lymphocytes:
    • Smallest of the WBCs, second most numerous (about 25% of circulating WBCs).
    • Very limited pale blue staining in the cytoplasm.
    • Three Main Types:
      • T lymphocytes.
      • B lymphocytes.
      • Natural killer (NK) cells.
  • Monocytes:
    • Largest leukocytes.
    • Dark, kidney bean-shaped nuclei with blue-gray cytoplasm.
    • Mobile and highly phagocytic.

White Blood Cell Numbers

  • 1 mm3 of normal blood usually contains 5000 to 9000 leukocytes.
  • Different percentages for each type.
  • Leukopenia: Decrease in WBC count.
  • Leukocytosis: Increase in WBC count.
  • Clinical significance of numbers: Changes with certain abnormal conditions; differential WBC count.

Formation of White Blood Cells

  • Undifferentiated HSCs are precursors to all blood cells.
  • Two early lines of blood stem cells in leukopoiesis:
    • Myeloid:
      • Granular leukocytes line.
      • Erythrocyte and thrombocyte lines.
    • Lymphoid:
      • Lymphocytes.
  • Dozens of intrinsic and extrinsic regulators in leukopoiesis, including:
    • Colony-stimulating factors.
    • Interleukins (ILs).

Structure and Function of Platelets

  • Small, pale bodies.
  • Irregular spindles or oval disks visible only when circulating.
  • Agglutination, adhesiveness, and aggregation prevent identification in dry smears.
  • Important role in hemostasis (clotting).

Formation and Life Span of Platelets

  • Thrombopoiesis: Controlled by thrombopoietin.
  • Megakaryoblasts form megakaryocytes, which release platelets and can skip intermediate steps when platelets are needed quickly.
  • Huge cells, bizarre shape, stain blue to pink, and variable number of fine granules in cytoplasm, located in red bone marrow, lungs, and spleen.
  • Short life span (about 7 days).

Hemostasis

  • Process that slows and stops bleeding when a vessel is injured and helps in defending against infection.
  • Three Major Phases:
    • Vasoconstriction.
    • Platelet plug formation.
    • Blood clotting (coagulation).

Vasoconstriction

  • Smooth muscle fibers spasm after injury to blood vessel, causing vasoconstriction.
  • Enhanced by thromboxane A2 from platelets, also potent local regulators (e.g., endothelin-1).

Platelet Plug Formation

  • Platelets adhere to the damaged lining of blood vessels within 1-5 seconds after injury, becoming sticky.
  • Secrete chemical signals (ADP, thromboxane A2, arachidonic acid).
  • Control microhemorrhages and may cause intermittent arterial microvascular occlusion in some peripheral vascular diseases.

Blood Clotting (Coagulation)

  • Definite, rapid sequence of chemical reactions.
  • Three Stages of Coagulation:
    • Stage 1: Activation pathways (intrinsic and extrinsic).
    • Stage 2: Thrombin formation.
    • Stage 3: Fibrin clot formation.
    • Stages 2 and 3 form a common pathway to clot formation after Stage 1.

Clot Formation

  • Extrinsic Pathway
  • Intrinsic Pathway

Conditions That Oppose Clotting

  • Normal, smooth endothelial lining of blood vessels.
  • Antithrombins: e.g., heparin.
  • Pharmaceuticals such as coumarin compounds and citrates.

Conditions That Hasten Clotting

  • Rough spot in endothelium (Thrombosis)
  • Immobility (Abnormally slow blood flow)
  • Clots tend to grow once started due to a positive feedback mechanism.

Clot Dissolution

  • Fibrinolysis: Physiological mechanism that dissolves clots.
  • Damaged cells release several substances that activate plasminogen.
  • Plasmin hydrolyzes fibrin strands.
  • Clinical practice uses several kinds of proteins to dissolve clots (e.g., streptokinase (SK) from Streptococcus bacteria).

Fibrinolysis

  • Tissue Damage
  • Lysosomal enzymes
  • Thrombin
  • Tissue plasminogen activator (t-PA)
  • Factor XII
  • Plasminogen
  • Plasmin
  • Fibrin
  • Clot dissolution

The Big Picture: Blood and the Whole Body

  • Blood plasma: Transportation of substances and heat.
  • RBCs: Transportation.
  • WBCs: Defense mechanisms.
  • Platelets: Prevent loss of fluids.
  • Interdependence of organs and systems and blood.

Mechanisms of Disease: Blood Disorders

  • Basic Mechanism: Improper blood cell formation.
  • Red Blood Cell Disorders:
    • Anemia resulting from changes in RBC number.
      • Polycythemia.
      • Aplastic anemia.
      • Pernicious anemia.
      • Folate deficiency anemia.
      • Blood loss anemia.
      • Anemia of chronic disease.
  • Red Blood Cell Disorders:
    • Changes in hemoglobin.
      • Hyperchromic or hypochromic.
      • Iron deficiency anemia.
      • Hemolytic anemia.
  • White Blood Cell Disorders:
    • Changes in WBC number.
      • Leukopenia or leukocytosis.
    • Malignancy.
      • Lymphoid neoplasms.
      • Myeloid neoplasms.
      • Multiple myeloma.
      • Leukemia.
  • White Blood Cell Disorders:
    • Infectious mononucleosis.
  • Clotting Disorders:
    • Thrombus, thrombosis.
    • Embolus, embolism.
    • Hemophilia.
    • Thrombocytopenia.