Unit III: Homeostasis Defense Against Blood Loss

1. Unit III: HomeostasisDefense Against Blood Loss Chapter 17 pp. 586-593

2. Leukocytes (WBCs) • 5,000 to 10,000 WBCs/L • Conspicuous nucleus • Travel in blood before migrating to connective tissue • Protect against pathogens

3. Leukocyte Descriptions • Granulocytes • neutrophils(60-70%) - fine granules; 3 to 5 lobed nucleus •  in bacterial infections • eosinophils (2-4%) - large rosy granules; bilobed nucleus •  in parasitic infections or allergies • basophils (<1%) - large, violet granules •  in chicken pox, sinusitis, diabetes • Histamine and heparin

4. Leukocyte Descriptions • Agranulocytes • lymphocytes (25-33%) - round, uniform dark violet nucleus •  in diverse infections and immune responses • monocytes (3-8%) • largest WBC; ovoid, kidney-, or horseshoe- shaped nucleus •  in viral infections and inflammation

5. Leukopoiesis • Leukocyte life cycle • multipotent stem cells CFU’s • myeloblasts – form neutrophils, eosinophils, basophils • monoblasts - form monocytes • lymphoblasts - form 3 types of lymphocytes • Colony-stimulating factors (CSF) • WBCs provide long-term immunity (weeks-decades)

6. Abnormal Leukocyte Counts • Leukopenia - low WBC count (<5000/L) • causes: radiation, poisons, infectious disease • effects: elevated risk of infection • Leukocytosis = high WBC count (>10,000/L) • causes: infection, allergy and disease • differential count - distinguishes % of each cell type • Leukemia = cancer of hemopoietic tissue • myeloid and lymphoid - uncontrolled WBC production • acute and chronic - death in months or  3 years • effects – deficiency of competent formed elements; impaired clotting

7. Platelets CSFs Progenitor Cell Multipotent Stem cell Megakaryocytes Platelets • Normal Count - 130,000 to 400,000 platelets/L • Functions: • vasoconstrictors • platelet plugs • secrete clotting factors • initiate formation of clot-dissolving enzyme • phagocytize bacteria; chemically attract neutrophils and monocytes to sites of inflammation • secrete growth factors

8. Hemostasis • All 3 pathways involve platelets

9. HemostasisVascular Spasm Knife blade Blood vessel injury • Prompt constriction of the broken vessel • Stimuli • pain receptors • smooth muscle injury • platelets release serotonin (vasoconstrictor) Vascular spasm

10. HemostasisPlatelet Plug Formation • broken vessel exposes collagen • platelet pseudopods • contract and draw walls of vessel together platelet plug • degranulation • serotonin (vasoconstrictor) • ADP attracts and degranulates more platelets • thromboxane A2 (an eicosanoid) Release of chemicals (ADP, PDGF, Ca2+, platelet factors) Plasma in vessel lumen Platelet aggregation Endothelium Platelet adhesion to damaged vessel Basal lamina Vessel wall Contracted smooth muscle cells Platelet plug may form Interstitial fluid Cut edge of vessel wall

11. HemostasisCoagulation • “Clotting” • conversion of plasma protein fibrinogen into insoluble fibrin threads to form framework of clot • Extrinsic mechanism • factors released by damaged tissues • Intrinsic mechanism • factors found in blood (platelet degranulation) • Procoagulants (clotting factors) • activate one factor and it will activate the next to form a reaction cascade

12. Coagulation Pathways • Extrinsic mechanism • initiated by Factor III • fewer steps • 15 seconds formation • Intrinsic mechanism • initiated by factor XII • cascade to factor XI to IX to VIII to X • 3-6 minutes formation • Calcium required for either pathway Common Pathway Extrinsic Pathway Intrinsic Pathway Factor X Tissue factor complex Factor X activator Prothrombinase Thrombin Prothrombin Factor VII Factors IX, VIII Fibrin Fibrinogen Factor XI Factor III Factor XII Tissue damage Contracted smooth muscle cells

13. Factor XII Factor XI Fate of Blood Clots Factor IX • Reaction Cascade • Clot retraction occurs within 30 minutes • growth factor secreted by platelets • Fibrinolysis (dissolution of a clot) • Plasminogen  plasmin, a fibrin-dissolving enzyme (clot buster) Factor VIII Reaction cascade (time) Factor X Prothrombin activator Thrombin Fibrin

14. Prevention of Inappropriate Clotting • Platelet repulsion • Thrombin dilution • by rapidly flowing blood • Natural anticoagulants • heparin (from basophils and mast cells) interferes with formation of prothrombin activator • antithrombin (from liver) deactivates thrombin before it can act on fibrinogen

15. Hemophilia • Genetic lack of any clotting factor • Sex-linked recessive (on X chromosome) • hemophilia A missing factor VIII (83% of cases) • hemophilia B missing factor IX (15% of cases) • note: hemophilia C missing factor XI (autosomal) • Physical exertion causes bleeding • hematomas • transfusion of plasma or purified clotting factors

16. Coagulation Disorders • Thrombosis - abnormal clotting in unbroken vessel • most likely to occur in leg veins of inactive people • Embolism - clot traveling in a vessel • pulmonary embolism - clot may break free, travel from veins to lungs • Infarction may occur if clot blocks blood supply to an organ (MI or stroke) • 650,000 Americans die annually of thromboembolism

17. Anticoagulants • Salts, heparin • Coumarin • Vitamin K deficiency • Needed for synthesis of clotting factors • Aspirin • Suppresses formation of thromboxane A2 • Medicinal leeches