Leukocytes (WBCs) Leukocytes: The only blood components that are complete cells Less numerous than RBCs 4800-10800/ul of blood (on average) Can leave capillaries via diapedesis Diapedesis is prompted by endothelial cell adhesion molecules (CAMs) In tissue (loose connective or lymph), they mount inflammatory or immune response They move through tissue spaces (ameboid) Classified as: Granulocytes Agranulocytes

Percentages of Leukocytes Figure 17.9

Granulocytes Granulocytes: Contain cytoplasmic granules Granules stain specifically (acidic, basic, or both) with Wright’s stain Include: Eosinophils (acidic) Basophils (basic) Neutrophils (both) Larger and usually shorter-lived than RBCs Have lobed nuclei All are variably phagocytic cells

Neutrophils Most numerous of WBCs (50-70%) Have two types of granules that take up both acidic and basic dyes Have multilobed nucleus (3-7 lobes) Increase exponentially during acute infection Active phagocytes Contain potent antimicrobial proteins (defensins) They are the “bacteria slayers” of the body

Eosinophils Eosinophils: Account for 2–4% of WBCs Red stained bilobed or 8-shaped nuclei Have large acidophilic, lysosome-like granules Lead the body’s attack against parasitic worms Lessen severity of allergies by phagocytizing immune complexes

Basophils Account for 0.5-1% of WBCs U- or S-shaped nuclei Functionally similar to mast cells Have large, purplish-black (basophilic) granules Produce histamine (contained in granules) Histamine is: An inflammatory chemical Acts as a vasodilator Attracts other WBCs

Agranulocytes Agranulocytes: Lack visible cytoplasmic granules Found in bloodstream but much more abundant in lymphoid tissues Include: Lymphocytes Monocytes Lymphocytes & Monocytes are: Structurally similar Functionally distinct and unrelated cell types

Lymphocytes Lymphocytes: Types of lymphocytes: Account for 25% or more of WBCs The smallest of the leukocuyes (RBC size) Have large, dark-purple, circular nuclei Have a thin rim of blue cytoplasm Found mostly enmeshed in lymphoid tissue A small proportion circulatse in the blood Types of lymphocytes: T cells: Function in immune response Act directly against grafts, tumors and virus-infected cells B cells Give rise to plasma cells, which produce antibodies

Monocytes Monocytes: account for 3–8% of leukocytes are the largest leukocytes abundant pale-blue cytoplasms purple-staining, U- or kidney-shaped nuclei leave the circulation and enter tissues, Once in tissues, they differentiate into macrophages Increase dramatically in number during chronic infections

Macrophages Macrophages: Are in-tissue-differentiated monocytes They are: Highly mobile Actively phagocytic Activate lymphocytes to mount an immune response

Leukocytes Figure 17.10

Leukopoiesis Is the production of WBCs Stimulated by chemical messengers (glycoproteins) from: Bone marrow Mature WBCs Chemical messengers include Interleukins (number naming, e.g., IL-1, IL-2) Colony-stimulating factors (CSFs); (named fater the cell type they stimulate, e.g., granulocyte-CSF ) All leukocytes originate from hemocytoblasts

Accumulated lysosomes Stem cells Hemocytoblast Myeloid stem cell Lymphoid stem cell Committed cells Myeloblast Myeloblast Myeloblast Monoblast Lymphoblast Developmental pathway Promyelocyte Promyelocyte Promyelocyte Promonocyte Prolymphocyte Accumulated lysosomes Eosinophilic myelocyte Basophilic myelocyte Neutrophilic myelocyte Granules appearance; division stops Eosinophilic band cells Basophilic band cells Neutrophilic band cells Nuclei arc Eosinophils Basophils Neutrophils Monocytes Lymphocytes (a) (b) (c) (d) (e) Nuclear segmentation Leaving bone marrow Enetring circulation Agranular leukocytes Some become Granular leukocytes Some become Figure 17.11

Leukocytes Disorders Leukocytosis: Leukopenia: Leukemia: WBC count over 11,000/mm3 Normal response to bacterial or viral invasion Leukopenia: A decrease in WBCs number below 4000/mm3 Leukemia: Cancerous conditions of the lymphoid tissues Characterized by: Uncontrolled proliferation of abnormal WBCs Reduction in: RBC number Platelets number

Platelets Platelets function: Platelets: Their granules contain: Fragments of megakaryocytes Blue-stained outer region purple granular center Their granules contain: Ca2+, enzymes, platelet-derived growth factor (PDGF), and other substances Platelets function: Form a plug temporarily sealing broken blood vessels

Genesis of Platelets The stem cell for platelets is the hemocytoblast The hormone regulating genesis is called thrombopoietin The sequential developmental pathway is as shown: Stem cell Developmental pathway Hemocytoblast Megakaryoblast Promegakaryocyte Megakaryocyte Platelets Figure 17.12

Hemostasis A series of reactions to stop bleeding Three phases occur in rapid sequence: Vascular spasms: Immediate vasoconstriction Platelet aggregation: Plug formation Coagulation: Blood clotting

Platelet Plug Formation Upon damage of endothelium of blood vessels: Collagen fibers exposed Platelets adhere tenaciously to exposed fibers Endothelial cells synthesize a large plasma protein (von Willebrand factor) Protein factor bridges & stabilizes platelets-collagen binding Platelets: Swell Form spiky processes Become sticky Granules of swollen platelts break They release several chemicals

Platelet Plug Formation (cont’d): Release chemicals include: ADP: A potent aggregating agent Causes more platelets to stick and release their contents Thromboxane A2: Enhances vascular spasms Enhances platelets aggregation Serotonin: Functions similar to Thromboxane A platelet plug is formed within one minute

Coagulation: A set of reactions in which blood is : Transformed from a liquid to a gel It follows two pathways: Intrinsic (endothelium) Extrinsic (tissue) The final three steps of these reactions involve: Formation of prothrombin (plasma protein) activator Prothrombin is converted into thrombin (an enzyme) Thrombin polymerizes fibrinogen (soluble plasma protein) into fibrin (insoluble form) Insoluble fibrin forms a mesh The mesh traps RBCs (starting clotting)

Figure 17.13a

Clot Retraction and Repair Involves the stabilization of the clot: By squeezing serum out of fibrin strands Thru the contraction of platelets proteins (actin & myosin) Repair: Rebuilding of blood vessel wall: Involves Platelet-derived growth factor (PDGF) PDGF stimulates the division of : Smooth muscle cells Fibroplast cells (connective tissue patch) Restoration of endothelial lining: Involves Vascular endothelial growth factor (VEGF) VEGF stimulates endothelial cells multiplication

Hemostasis Disorders (Thromboembolytic Conditions): Thrombus: A clot that develops and persists in an unbroken blood vessel Thrombi can block circulation, resulting in tissue death Coronary thrombosis: Thrombus in blood vessel of the heart Can lead to fatal heart attack

Hemostasis Disorders (Thromboembolytic Conditions): Embolus: A thrombus that breaks away from a vessel wall & freely floats in the blood stream When trapped by narrow vessels it results in embolism Pulmonary emboli: Emboli that become trapped in the lungs Can impair the ability of the body to obtain oxygen Cerebral emboli: Emboli that become trapped in the brain May cause a stroke

Prevention of Undesirable Clots Substances used to prevent undesirable clots: Aspirin: Inhibits thromboxane A2, therfore, Interfers with platelet aggregation & plug formation Heparin An anticoagulant Used clinically for pre- & postoperative cardiac care Warfarin An anticoagulant found in rat poison Interfers with Vit K production of some procoagulants Used for those prone to atrial fibrillation

Assigment Chapter 17 List the chapter-indicated diagnostic blood tests Explain the diagnostic use of each test