Review of Inflammation
and Fever
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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
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Stages of Inflammation
• Vascular stage
• Cellular stage
• Tissue repair
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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
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Functions of transudates and exudates:
•
dilute toxins from dead cells
•
pain – limits use; prevents additional
injury
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carry blood cells and proteins to site
(antibodies and complement)
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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 pus
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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
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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 Creactive 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 – lymphatics
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Repair – scar formation
Processes
fill the wound
cover the wound
shrink the wound
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Impairment of inflammation
Excess bleeding
Circulation at site of injury
Bone marrow health
Immune response function
Nutritional status:
protein, methionine, zinc, vitamin C,
copper
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Fever (pyrexia)
• Called “hallmark of infection”
• Many infections are called fevers:
– Typhoid fever, rheumatic fever, etc.
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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
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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 antiinflammatory drugs (aspirin, tylenol, motrin
etc.)
(although overdose of aspirin raises body
temp.)
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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
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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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