Review of Inflammation and Fever 1. Inflammation 2 A non-specific response to injury or necrosis...

Review of Inflammationand Fever

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Inflammation

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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

Stages of Inflammation

• Vascular stage• Cellular stage• Tissue repair

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Response at site of injury:blood vessels briefly constrict,

then dilateEdema:

due to increased pressure in vessels

blood vessels become permeable

plasma forced into tissues = transudate

Exudates - small proteins and cells

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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)

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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.

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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.

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• 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 pus12

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Platelets – stop bleeding in injured vesselshistamines

Plasma protein systems – Complement – MAC, vasodilation,

opsonization

ClottingKinins – signal endothelial cells to shrink

bradykinins contributes to painImmunoglobulins

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• Other mediators:–Prostaglandins–Platelet-activating factor–Cytokines–Nitric oxide

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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

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Excessive inflammation• Prolonged pain• Swelling impairs function • Therapies:

– Temperature • Cold - 10 on 10 off (or alternate heat and cold)

– Elevation and pressure– Drug therapy

• Antihistamines, nonsteroidal anti-inflammatory agents, corticosteroids

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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

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Excessive inflammation• Pain is intense or prolonged and swelling

impairs function of organ• Cold – 10 minutes only• Drugs – steroids• Elevation – decreases blood flow

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Resolution or Tissue Repair

• Inflammatory phase• Proliferative phase• Remodeling phase

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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 – lymphatics21

Repair – scar formation

Processes

fill the wound

cover the wound

shrink the wound

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Impairment of inflammation

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Excess bleeding

Circulation at site of injury

Bone marrow health

Immune response function

Nutritional status:

protein, methionine, zinc, vitamin C, copper

Fever (pyrexia)

• Called “hallmark of infection”• Many infections are called fevers:

– Typhoid fever, rheumatic fever, etc.

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Normal thermoregulation

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Body temperature is maintained within ± 1oFVaries over the course of the day

Cells constantly produce heat by metabolism

Mechanisms to lose heat:dilation of surface blood vesselssweating

Body temperature is set and controlled by the hypothalamus

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.

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• 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

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• 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

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Prostaglandins inhibited by non-steroidal anti-inflammatory drugs (aspirin, tylenol, motrin etc.)

(although overdose of aspirin raises body temp.)

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Benefits of fever

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Increased temperature kills microorganisms and adversely affects their growth and reproduction

Decrease serum levels of iron, copper and zinc – needed for bacterial reproduction

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

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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

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• 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

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