1. Review of Inflammation and Fever 1

2. Inflammation 2 A non-specific response to injury or necrosis that occurs in a vascularized tissue. Signs: Redness, heat,swelling, pain, and loss of function

3. Stages of Inflammation n Vascular stage n Cellular stage n Tissue repair 3

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6. Response at site of injury: blood vessels briefly constrict, then dilate Edema: due to increased pressure in vessels blood vessels become permeable plasma forced into tissues = transudate, watery Exudates - small proteins and cells move out of blood vessles because of increased permeability 6

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8. Functions of transudates and exudates: dilute toxins from dead cells pain – limits use; prevents additional injury carry blood cells and proteins to site (antibodies and complement) carry toxins and wastes from site (mostly through lymphatic system) 8

10. Cellular Stage n Marked by movement of white blood cells (leukocytes) to the area of injury. n When fluid is lost from blood, blood becomes more viscous. 10

11. Release of chemical mediators and cytokines cause the leukocytes to increase production of adhesion molecules. Leukocytes –neutrophils, macrophages – phagocytic cells, leave the capillaries and enter tissues by transmigration or emigration. 11

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13. n Biochemicals released by leukocytes and tissue cells serve as signals to coordinate all body defenses. n “calling molecules” n Movement of leukocytes – chemotaxis n Neutrophils then macrophages n Steps of phagocytosis: –Adherence plus opsonization (marked for digestion) –Engulfment –Intracellular killing n die - form pus 13

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15. n Other mediators: –Prostaglandins –Platelet-activating factor –Cytokines, signaling molecules –Nitric oxide 15

16. Systemic manifestations of inflammation n Release of cytokines in Acute-phase response: –Affects hypothalamus and may cause fever –Affects bone marrow, ↑ neutrophil production –Affects the CNS causing lethargy –Affects liver to produce more fibinogen and C- reactive protein, which increases the ESR (erythrocyte sedimentation rate, to measure inflammation) n Lymphadenitis –inflammation of a lymph node 16

17. Excessive inflammation n Prolonged pain n Swelling impairs function n Therapies: –Temperature n Cold - 10 on 10 off (or alternate heat and cold) –Elevation and pressure –Drug therapy n Antihistamines, nonsteroidal anti-inflammatory agents, corticosteroids 17

18. Chronic Inflammation n May last for weeks, months or years –Recurrent acute inflammation or low-grade responses n Characteristics: –Infiltration by macrophages and lymphocytes –Proliferation of fibroblasts instead of exudates –Cause may be foreign matter, viruses, bacteria, fungi or larger parasites 18

19. Excessive inflammation n Pain is intense or prolonged and swelling impairs function of organ n Cold – 10 minutes only n Drugs – steroids n Elevation – decreases blood flow 19

20. Resolution or Tissue Repair n Inflammatory phase n Proliferative phase n Remodeling phase 20

21. Resolution and repair: resolution – restoration of normal tissue structure and function. repair – replacement of destroyed tissue with scar tissue. Débridement, suturing Vessel dilation and permeability are reversed Leukocyte migration ends Exudate is drained away – lymphatics 21

22. Repair – scar formation Processes fill the wound cover the wound shrink the wound 22

23. Fever (pyrexia) n Called “hallmark of infection” n Many infections are called fevers: –Typhoid fever, rheumatic fever, etc. 23

24. Normal thermoregulation 24 Body temperature is maintained within ± 1 o F Varies over the course of the day Cells constantly produce heat by metabolism Mechanisms to lose heat: dilation of surface blood vessels sweating Body temperature is set and controlled by the hypothalamus

25. With infection (or some toxins) : some bacteria release biochemicals into blood stream – exogenous pyrogens (esp. lipopolysaccharides of Gram-negative bacteria) – these signal white blood cells (monocytes/macrophages) to produce their own biochemicals – endogenous pyrogens (interleukins or interferons) – induce synthesis of prostaglandins – cause hypothalmus to raise its set point. 25

26. n Many non-infectious disorders can also produce fever n NON-SPECIFIC n Patterns of fever: –Intermittent fever –Remittent fever –Sustained or continuous fever –Recurrent or relapsing fever n Heart rate increases with fever 26

27. n Hypothalamus : –releases TSH to increase production of T3 & T4 –releases ACTH which increases release of glucocorticoids –Causes increase of release of epinephrine –Decreases production of ADH 27

28. Prostaglandins inhibited by non-steroidal anti- inflammatory drugs (aspirin, tylenol, motrin etc.) (although overdose of aspirin raises body temp.) 28

29. Benefits of fever 29 Increased temperature kills microorganisms and adversely affects their growth and reproduction

30. Causes lysosomal breakdown and autodestruction of cells, preventing viral replication in infected cells Increased leukocyte motility Facilitates the immune response – activation of T cells Enhances phagocytosis Production of interferon increased 30

31. But fever is bad when: too high – impairs neurological and/ respiratory functions increased work load of heart in patients with heart disease or stroke damage to hypothalamus can cause temp. to become dangerously high Can cause complications in pregnancy Fever over 106 o F requires emergency care 31

32. n Infants under 3 months of age have difficulty regulating temperature n Young children can develop very high fevers, sometimes seizure can be induced n Body temperature is lowered in the elderly, so fevers are not as high 32