Review of InflammationReview of Inflammationand Feverand Fever

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InflammationInflammation

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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

Stages of InflammationStages of Inflammation

n Vascular stageVascular stagen Cellular stageCellular stagen Tissue repairTissue 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, watery

Exudates - small proteins and cells move out of blood vessles because of increased permeability

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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 StageCellular Stage

n Marked by movement of white blood cells Marked by movement of white blood cells (leukocytes) to the area of injury.(leukocytes) to the area of injury.

n When fluid is lost from blood, blood When fluid is lost from blood, blood becomes more viscous. becomes more viscous.

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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 capillariesand enter tissues by transmigration or

emigration.

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n Biochemicals released by leukocytes and tissue Biochemicals released by leukocytes and tissue cells serve as signals to coordinate all body cells serve as signals to coordinate all body defenses.defenses.

n ““calling molecules”calling molecules”n Movement of leukocytes – chemotaxisMovement of leukocytes – chemotaxisn Neutrophils then macrophagesNeutrophils then macrophagesn Steps of phagocytosis:Steps of phagocytosis:

– Adherence plus Adherence plus opsonization (marked for digestion)opsonization (marked for digestion)

– EngulfmentEngulfment

– Intracellular killingIntracellular killing

n die - form pusdie - form pus13

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n Other mediators:Other mediators:–ProstaglandinsProstaglandins

–Platelet-activating factorPlatelet-activating factor–Cytokines, Cytokines, signaling moleculessignaling molecules

–Nitric oxideNitric oxide

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Systemic manifestations of Systemic manifestations of inflammationinflammationn Release of cytokines in Acute-phase response:Release of cytokines in Acute-phase response:

– Affects hypothalamus and may cause feverAffects hypothalamus and may cause fever– Affects bone marrow, ↑ neutrophil productionAffects bone marrow, ↑ neutrophil production– Affects the CNS causing lethargyAffects the CNS causing lethargy– Affects liver to produce more fibinogen and C-Affects liver to produce more fibinogen and C-

reactive protein, which increases the ESR reactive protein, which increases the ESR ((erythrocyte sedimentation rateerythrocyte sedimentation rate, to measure , to measure inflammation)inflammation)

n LymphadenitisLymphadenitis– inflammation of a lymph node inflammation of a lymph node

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Excessive inflammationExcessive inflammationn Prolonged painProlonged painn Swelling impairs function Swelling impairs function n Therapies:Therapies:

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

– Elevation and pressureElevation and pressure

– Drug therapyDrug therapyn Antihistamines, nonsteroidal anti-inflammatory Antihistamines, nonsteroidal anti-inflammatory

agents, corticosteroidsagents, corticosteroids

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Chronic InflammationChronic Inflammation

n May last for weeks, months or yearsMay last for weeks, months or years– Recurrent acute inflammation or low-grade Recurrent acute inflammation or low-grade

responsesresponsesn Characteristics:Characteristics:

– Infiltration by macrophages and lymphocytesInfiltration by macrophages and lymphocytes– Proliferation of fibroblasts instead of exudatesProliferation of fibroblasts instead of exudates– Cause may be foreign matter, viruses, bacteria, Cause may be foreign matter, viruses, bacteria,

fungi or larger parasitesfungi or larger parasites

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Excessive inflammationExcessive inflammationn Pain is intense or prolonged and swelling Pain is intense or prolonged and swelling

impairs function of organimpairs function of organn Cold – 10 minutes onlyCold – 10 minutes onlyn Drugs – steroidsDrugs – steroidsn Elevation – decreases blood flowElevation – decreases blood flow

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Resolution or Tissue RepairResolution or Tissue Repair

n Inflammatory phaseInflammatory phasen Proliferative phaseProliferative phasen Remodeling phaseRemodeling 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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Fever (pyrexia)Fever (pyrexia)

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

– Typhoid fever, rheumatic fever, etc.Typhoid fever, rheumatic fever, etc.

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Normal thermoregulationNormal 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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n Many non-infectious disorders can also Many non-infectious disorders can also produce feverproduce fever

n NON-SPECIFICNON-SPECIFICn Patterns of fever:Patterns of fever:

– Intermittent feverIntermittent fever– Remittent feverRemittent fever– Sustained or continuous feverSustained or continuous fever– Recurrent or relapsing feverRecurrent or relapsing fever

n Heart rate increases with feverHeart rate increases with fever

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n Hypothalamus :Hypothalamus :

– releases TSH to increase production of T3 & releases TSH to increase production of T3 & T4T4

– releases ACTH which increases release of releases ACTH which increases release of glucocorticoidsglucocorticoids

– Causes increase of release of epinephrineCauses increase of release of epinephrine

– Decreases production of ADH 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 feverBenefits of fever

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Increased temperature kills microorganisms and adversely affects their growth and 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 31

n Infants under 3 months of age have difficulty Infants under 3 months of age have difficulty regulating temperatureregulating temperature

n Young children can develop very high fevers, Young children can develop very high fevers, sometimes seizure can be inducedsometimes seizure can be induced

n Body temperature is lowered in the elderly, so Body temperature is lowered in the elderly, so fevers are not as highfevers are not as high

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