Blood

• Blood is a specialized connective tissue consisting of cells and fluid extracellular material called plasma
• Propelled mainly by rhythmic contractions of the heart, about 5 L of blood in an average adult moves unidirectionally within the closed circulatory system
• Formed elements circulating in the plasma

  • Erythrocytes (red blood cells)
  • Leukocytes (white blood cells)
  • Platelets
• Serum

  Pale yellow liquid that contains growth factors and other proteins released from platelets during clot formation
• Hematocrit

  The volume of erythrocytes, normally about 44% of the total blood volume in healthy adults
• Blood is a distributing vehicle, transporting O2, CO2, metabolites, hormones, and other substances to cells throughout the body
• Leukocytes have diverse functions and are one of the body's chief defenses against infection
• Composition of plasma

  • Water (92% by weight)
  • Plasma proteins (7% by weight)
  • Other solutes (1% by weight)
• Major plasma proteins

  • Albumin
  • Globulins
  • Fibrinogen
  • Regulatory proteins
• Albumin

  The most abundant plasma protein, made in the liver and serves primarily to maintain the osmotic pressure of the blood
• Globulins

  Made by the liver and other cells, include transferrin and other transport factors, fibronectin, prothrombin and other coagulation factors, lipoproteins and other proteins entering blood from tissues
• Immunoglobulins (antibodies or γ-globulins)

  Secreted by plasma cells in many locations
• Fibrinogen

  The largest plasma protein (340 kD), also made in the liver, which, during clotting, polymerizes as insoluble, cross-linked fibers of fibrin that block blood loss from small vessels
• Complement proteins

  Comprise a defensive system important in inflammation and destruction of microorganisms
• Blood smears are routinely stained with mixtures of acidic (eosin) and basic (methylene blue) dyes, which may also contain dyes called azures that are more useful in staining cytoplasmic granules containing charged proteins and proteoglycans
• Erythrocytes (red blood cells)

  Terminally differentiated structures lacking nuclei and completely filled with the O2-carrying protein hemoglobin
• Erythrocytes

  • Flexible biconcave discs approximately 7.5 μm in diameter, 2.6-μm thick at the rim, but only 0.75-μm thick in the center
  • Normal concentration in blood is approximately 3.9-5.5 million per microliter (μL, or mm³) in women and 4.1-6.0 million/μL in men
• Erythrocyte plasmalemma

  Consists of about 40% lipid, 10% carbohydrate, and 50% protein, including ion channels, the anion transporter called band 3 protein, and glycophorin A
• Erythrocyte cytoplasm lacks all organelles but is densely filled with hemoglobin, the tetrameric O2-carrying protein that accounts for the cells' uniform acidophilia
• Erythrocytes undergo terminal differentiation which includes loss of the nucleus and organelles shortly before the cells are released by bone marrow into the circulation
• Human erythrocytes normally survive in the circulation for about 120 days
• Erythrocyte cytoplasm

  Lacks all organelles but is densely filled with hemoglobin, the tetrameric O₂-carrying protein that accounts for the cells' uniform acidophilia
• Hemoglobin

  Forms oxyhemoglobin when combined with O₂, or carbaminohemoglobin when combined with CO₂. The reversibility of these combinations is the basis for the protein's gas-transporting capacity
• Lacking mitochondria, erythrocytes rely on anaerobic glycolysis for their minimal energy needs
• Lacking nuclei, erythrocytes cannot replace defective proteins
• Erythrocyte lifespan

  About 120 days, after which defects in the membrane's cytoskeletal lattice or ion transport systems begin to produce swelling or other shape abnormalities, as well as changes in the cells' surface oligosaccharide complexes
• Senescent or worn-out RBCs displaying such changes are recognized and removed from circulation, mainly by macrophages of the spleen, liver, and bone marrow
• Leukocytes

  Leave the blood and migrate to the tissues where they become functional and perform various activities related to immunity
• Leukocyte groups

  • Granulocytes
  • Agranulocytes
• Granulocytes

  • Possess two major types of abundant cytoplasmic granules: lysosomes (azurophilic granules) and specific granules that bind neutral, basic, or acidic stains and have specific functions
  • Have polymorphic nuclei with two or more distinct (almost separated) lobes
  • Are terminally differentiated cells with a life span of only a few days
  • Have poorly developed Golgi complexes and rough ER, and with few mitochondria they depend largely on glycolysis for their energy needs
  • Most undergo apoptosis in the connective tissue and billions of neutrophils alone die each day in adults
• Agranulocytes

  • Lack specific granules, but do contain some azurophilic granules (lysosomes)
  • Have a spherical or indented but not lobulated nucleus
• Agranulocyte types


  • Lymphocytes
  • Monocytes
• All leukocytes are key players in the constant defense against invading microorganisms and in the repair of injured tissues, specifically leaving the microvasculature in injured or infected tissues
• Leukocyte migration to sites of injury or infection

  1. Factors termed cytokines are released from various sources and these trigger loosening of intercellular junctions in the endothelial cells of local postcapillary venules

  2. The cell adhesion protein P-selectin appears on the endothelial cells' luminal surfaces following exocytosis from cytoplasmic Weibel-Palade bodies

  3. The surfaces of neutrophils and other leukocytes display glycosylated ligands for P-selectin, and their interactions cause cells flowing through the affected venules to slow down, like rolling tennis balls arriving at a patch of velcro

  4. Other cytokines stimulate the now slowly rolling leukocytes to express integrins and other adhesion factors that produce firm attachment to the endothelium

  5. In a process called diapedesis, the leukocytes send extensions through the openings between the endothelial cells, migrate out of the venules into the surrounding tissue space, and head directly for the site of injury or invasion
• The attraction of neutrophils to bacteria involves chemical mediators in a process of chemotaxis, which causes leukocytes to rapidly accumulate where their defensive actions are specifically needed
• Normal leukocyte count

  4500-11,000 leukocytes per microliter of blood in healthy adults
• Neutrophils

  • Constitute 50%-70% of circulating leukocytes, a figure that includes slightly immature forms released to the circulation
  • Are 12-15 µm in diameter in blood smears, with nuclei having two to five lobes linked by thin nuclear extensions
  • Are usually the first leukocytes to arrive at sites of infection where they actively pursue bacterial cells using chemotaxis and remove the invaders or their debris by phagocytosis
  • Contain two main types of cytoplasmic granules: azurophilic primary granules (lysosomes) and specific secondary granules
  • Azurophilic granules contain myeloperoxidase, lysozyme, and defensins that are toxic to bacteria
  • Specific granules secrete various ECM-degrading enzymes, deliver additional bactericidal proteins, and insert new cell membrane components
  • Contain glycogen that is broken down into glucose to yield energy via the glycolytic pathway
  • Have a half-life of 6-8 hours in blood and a life span of 1-4 days in connective tissues before dying by apoptosis
• Neutrophils look for bacteria to engulf by pseudopodia and internalize them in vacuoles called phagosomes. Immediately thereafter, specific granules fuse with and discharge their contents into the phagosomes that are then acidified by proton pumps. Azurophilic granules then discharge their enzymes into this acidified vesicle, killing and digesting the engulfed microorganisms
• During phagocytosis, a burst of O₂ consumption leads to the formation of superoxide anions (O₂-) and hydrogen peroxide (H₂O₂), which together with myeloperoxidase and halide ions, form a powerful microbial killing system inside the neutrophils
• Apoptotic neutrophils, bacteria, semidigested material, and tissue-fluid form a viscous, usually yellow collection of fluid called pus