CHAPTER 14: Inflammation, Tissue Repair, and Wound Healing

Cardinal Signs of Inflammation

Rubor (redness)
Tumor (swelling)
Calor (heat)
Dolor (pain)
Functio laesa (loss of function)
Factors Involved in Protective Responses and Bodily Repair
Inflammatory reaction: damage cells release inflammatory mediators which stimulate
inflammation
Immune response
Tissue repair and wound healing
Causes of Inflammation
Immune response to infectious microorganisms
Trauma
Surgery
Caustic chemicals
Extremes of heat and cold
Ischemic damage to body tissues
Granulomatous Inflammation
Associated with foreign bodies such as: splinters; sutures; silica, asbestos
Associated with microorganisms that cause: Tuberculosis; Syphilis, sarcoidosis; deep
fungal infections; brucellosis
Vascular Changes that May Occur with Inflammation
An immediate transient response: Occurs with minor injury
An immediate sustained response: Occurs with more serious injury and continues
for several days and damages the vessels in the area
A delayed hemodynamic response: Involves an increase in capillary permeability
that occurs 4 to 24 hours after injury
Cellular Stage of Acute Inflammation
Phagocytic white blood cells enter the injured tissue: destroying infective
organisms; removing damaged cells; releasing more inflammatory mediators to
control further inflammation and healing
Two types of leukocytes participate in the acute inflammatory response:
Granulocytes (neutrophils, eosinophils, and basophils)
Monocytes (the largest of the white blood cells)
*The immediate effect of platelets to plug a wound; the function of both histamine from
mast cells and serotonin from platelets in vasoconstriction and activation of further
clotting mechanisms
Direction of Cellular Response

Margination, adhesion, transmigration

Cytokines: Adhesion molecules
Selectins, integrins, and immunoglobulin
Initiation of adhesion
Aggregation of inflammatory cells
Movement into underlying tissue
*The interaction of adhesion molecules, chemokines, and cytokines in leukocyte adhesion,
migration, and phagocytosis, which are part of the cellular phase of inflammation.
*The cellular phase of inflammation is very tightly controlled by the cytokines. Cytokines
are chemical road signs that organize the response.

Inflammatory Mediators
Histamine
Cytokines
Arachidonic acid metabolites
Eicosanoids (Prostaglandins; Leukotrienes; Omega-3 polyunsaturated fatty
acids
Platelet-activating factor
Plasma proteins
Classification of Inflammatory Mediators by Function
Those with vasoactive and smooth muscleconstricting properties
Chemotactic factors such as complement fragments and cytokines
Plasma proteases that can activate complement and components of the clotting
system
Reactive molecules and cytokines liberated from leukocytes, which when released
into the extracellular environment can damage the surrounding tissue
QUESTION
Which of the following molecules will induce endothelial cell retraction?
A. Omega-3 fatty acids
B. Leukotrienes
C. Histamine
D. VCAM
ANSWER
C. Histamine - Rationale: Histamine is the primary activator of endothelial
retraction and increased permeability of the vessels.
Types of Inflammatory Exudates
Serous Exudates: Watery fluids low in protein content; Result from plasma
entering the inflammatory site
Hemorrhagic Exudates: Occur when there is severe tissue injury that causes
damage to blood vessels or when there is significant leakage of red cells from the
capillaries
Membranous or Pseudomembranous Exudates: Develop on mucous membrane
surfaces; Are composed of necrotic cells enmeshed in a fibropurulent exudate

Purulent or Suppurative Exudates: Contain pus; composed of degraded white

blood cells, proteins, and tissue debris
Fibrinous Exudates: Contain large amounts of fibrinogen and form a thick and
sticky meshwork

Basic Patterns of Inflammation

Acute inflammation: Of relatively short duration; nonspecific early response to
injury; Aimed primarily at removing the injurious agent and limiting tissue damage
Chronic inflammation: Longer duration lasting for days to years; A recurrent or
progressive acute inflammatory process or a low-grade smoldering response that
fails to evoke an acute response
Chronic Versus Acute Inflammation
Acute inflammationself-limited and of short duration
Infiltration of neutrophils
Exudate
Chronic inflammationself-perpetuating and may last for weeks, months, or
even years
Infiltration by mononuclear cells (macrophages) and lymphocytes
Proliferation of fibroblasts
Most Prominent Systemic Manifestations of Inflammation
Acute-phase response
Alterations in white blood cell count (leukocytosis or leukopenia)
Fever
Sepsis and septic shock (severe)
QUESTION
Permanent cells, once damaged, can easily be regenerated and their functions recovered?
True or False
ANSWER
False - Rationale: Many cells in the body cannot be replaced once they die. Neurons
and cardiac cells are such examples.
Types of Structures of Body Organs and Tissues
Parenchymal: Tissues contain the functioning cells of an organ or body part (e.g.,
hepatocytes, renal tubular cells)
The Stromal Tissues: Consist of the supporting connective tissues, blood vessels,
extracellular matrix, and nerve fibers
Types of Body Cells
Labile: Continue to divide and replicate throughout life, replacing cells that are
continually being destroyed
Stable: Normally stop dividing when growth ceases
Permanent Cells: Cannot undergo mitotic division

Healing by Primary or Secondary Intention

The objective of the healing process is to fill the gap created by tissue destruction
and to restore the structural continuity.
Primary healingsmall, clean wound
Secondary healinggreat loss of tissue with contamination
Basic Components of the Extracellular Matrix (ECM)
Fibrous structural proteins: Collagen and elastin fibers
Water-hydrated gels that permit resilience and lubrication: Proteoglycans and
hyaluronic acid
Adhesive glycoproteins that connect the matrix elements to each other and to
cells: Fibronectin and laminin
Basic Forms of the ECM
Basement Membrane: Surrounds epithelial, endothelial, and smooth muscle cells
Interstitial Matrix: Present in the spaces between cells the connective tissue and
between the epithelium and supporting cells of blood vessels
Stages of Wound Healing
Inflammatory phase (healing process as cleaning out the wound)
Proliferative phase (regenerating the missing or damaged tissue)
Maturational or remodeling phase (maturation to regain function)
Steps in Development of a New Capillary Vessel
Proteolytic degradation of the parent vessel basement membrane, allowing for
formation of a capillary sprout
Migration of endothelial cells from the original capillary toward an angiogenic
stimuli
Proliferation of the endothelial cells behind the leading edge of the migrating cells
Maturation of the endothelial cells and proliferation of pericytes (for capillaries) and
smooth muscle cells (for larger vessels)
QUESTION
Which of the following will promote wound healing?
A. Malnutrition
B. Increased blood flow and oxygen delivery
C. Infection
D. Foreign bodies
ANSWER
B. Increased blood flow and oxygen delivery - Rationale: Increasing blood flow and
oxygen delivery is one of the main objectives of the inflammatory response. This
will allow for greater energy production and faster removal of dead material.
Factors Regulating the Healing Process
Action of chemical mediators and growth factors that mediate the healing process
Interactions between the extracellular and cell matrix

Two Phases of Scar Formation

Emigration and proliferation of fibroblasts into the site of injury
Deposition of the ECM by these cells
* Explain the effects of malnutrition; ischemia and oxygen deprivation; impaired immune
and inflammatory responses; and infection, wound separation, and foreign bodies on
wound healing.
No tissue functions well under these conditions, and wound healing is no different.
Causes of Impaired Wound Healing
Malnutrition
Impaired blood flow and oxygen delivery
Impaired inflammatory and immune responses
Infection
Wound separation
Foreign bodies
Age effects