Inflammation and

Tissue Repair
Lecture 8

Objectives
• Acute inflammation
• Cardinal signs
• Vascular and cellular stages
• Local and systemic manifestations
• Chronic inflammation
• Manifestations

Inflammation
• Inflammation is an automatic
response to cell injury
• Neutralizes harmful agents
• Removes dead tissue
 Damaged cells release
inflammatory mediators

Local Systemic
Response Response

Vascular White blood

stage cell response
Cellular Acute-phase
stage response

Acute Inflammation
• Vascular stage
• Chemicals released from tissues,
cells
• Brief vasoconstriction
• Vasodilation

Vascular Stage
 Kinds of Exudate
• Serous
• Hemorrhagic
• Fibrinous
• Purulent

White Blood Cells

• Granulocytes
• Neutrophils first at site of injury
• Monocytes
• Monocytes  macrophages
• Mast cells
• Degranulation

Inflammatory Mediators
• Leukocytes release inflammatory
mediators
• Histamine and serotonin
• Leukotrienes
• Platelet-activating factor
• Cytokines
Inflammatory Mediators
• Histamine
• Temporary, rapid vasoconstriction
• Dilation of postcapillary venules
• Retraction of endothelial cells
• Activity controlled by H1 and H2
receptors on host target cells

Inflammatory Mediators
• H1 receptors promote inflammation
• H2 receptors inhibit inflammation
• Suppress leukocyte function and mast
cell degranulation
• Serotonin: found in platelets;
actions similar to histamine

Inflammatory Mediators
• Leukotrienes
• Released from mast cell
• Cause smooth muscle contraction
• Increased vascular permeability
• Neutrophil / eosinophil chemotaxis
Inflammatory Mediators
• Prostaglandins
• Increased vascular permeability
• Neutrophil chemotaxis
• Induce pain
• Smooth muscle contraction

Inflammatory Mediators
• Platelet Activating Factor (PAF)
• Generated from lipids in cell membranes
• Platelet aggregation
• Chemotaxis
• Vasodilation

Inflammatory Mediators
• Other inflammatory mediators travel
in the plasma
• Kinins
• Coagulation
g and fibrinolysis
y p
proteins
• Complement system
• C-reactive protein
Cellular Stage

Cellular Stage
Degranulation
Histamine

Vascular effects

Dilation increased,
permeability

Exudation

Cellular Stage
Degranulation
Neutrophil
chemotactic factor

Neutrophils attracted
to site

Phagocytosis
 Cellular Stage
Degranulation

Eosinophil
chemotactic factor

Eosinophils
attracted to site
Inhibition of
Phagocytosis vascular effects

Cellular Stage
Synthesis
Leukotrienes (SRS-A)

Vascular effects

Dilation increased,
permeability

Exudation

Cellular Stage
Synthesis
Prostaglandins (E-series)

Vascular effects Pain

Dilation increased,
permeability

Exudation
 Cellular Stage

Local Manifestations
• Redness
• Swelling
• Heat
• Pain
• Loss of function

Systemic Manifestations
of Inflammation
• Three primary systemic changes:
1. Fever
2. Leukocytosis
3. Increased circulating plasma proteins
 Acute-Phase Response
• Leukocytes release interleukins,
TNF
• Fever, lethargy
• Skeletal muscle breakdown
• Liver makes fibrinogen and
C-reactive protein

Fever
Pyrogenic compounds enter brain

Raise set point for thermostat

in hypothalamus

Body thinks it’s too cold

Heat production “Chill”

Shivering Vasoconstriction

Fever
Temperature rises to new set point

Body thinks it’s warm enough

Lowers temperature Fever

Sweating Vasodilation
 Chronic Inflammation
• Longer duration than acute
• Occurs for various reasons
• Microorganism survive in macrophage
• Toxins damage tissues
• Irritation by chemicals, particulate
matter, physical irritants

Chronic Inflammation
• Macrophages accumulate in
damaged area
• Nonspecific chronic inflammation
• Granulomatous
G l t inflammation
i fl ti

Tissue Repair
• Growth factors stimulate local cells
to divide
• Tissue organization controlled by
extracellular matrix
• New cells laid down
• Tissue regeneration
• Fibrous tissue repair
• Granulation tissue  scar tissue
 Summary
• Inflammation describes local
response to tissue injury
• Classic signs: redness, swelling,
local heat,
heat pain,
pain loss of function
• Vascular and cellular stages
• Chemical mediators
• Acute and chronic inflammation

Inflammation and
Tissue Repair
p
Lecture 8