1. Review of Inflammation and Fever

2. Inflammation
A non-specific response to injury or necrosis that occurs in a vascularized tissue.
Signs: Redness, heat ,swelling, pain, and loss of function
(Rubor, calor, tumor, dolor)
-- itis refers to an inflammatory condition

3. Stages of Inflammation
Vascular stage
Cellular stage
Tissue repair

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
Exudates - small proteins and cells

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)

9. Cellular Stage
Marked by movement of white blood cells (leukocytes) to the area of injury.
When fluid is lost from blood, blood becomes more viscous. See change in blood flow patterns which allows white cells to move to the edges of the blood stream – margination.

10. 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.

12. Movement of leukocytes – chemotaxis Neutrophils then macrophages
Biochemicals released by leukocytes and tissue cells serve as signals to coordinate all body defenses.
“calling molecules”
Movement of leukocytes – chemotaxis
Neutrophils then macrophages
Steps of phagocytosis:
Adeherence plus opsoniztion
Engulfment
Intracellular killing
die - form pus

14. Platelets – stop bleeding in injured vessels histamines
Plasma protein systems – Complement – MAC, vasodilation, opsonization
Clotting Kinins – signal endothelial cells to shrink bradykinins contributes to pain Immunoglobulins

15. Other mediators: Prostaglandins Platelet-activating factor Cytokines
Nitric oxide

16. Systemic manifestations of inflammation
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
Lymphadenitis

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

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

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

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

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

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

23. Impairment of inflammation
Excess bleeding
Circulation at site of injury
Bone marrow health
Immune response function
Nutritional status:
protein, methionine, zinc, vitamin C, copper

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

25. Normal thermoregulation
Body temperature is maintained within ± 1oF 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

26. 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.

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

28. 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

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

30. Benefits of fever
Increased temperature kills microorganisms and adversely affects their growth and reproduction
Decrease serum levels of iron, copper and zinc – needed for bacterial reproduction

31. 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

32. 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 106oF requires emergency care

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