Innate Defenses:
Inflammation
Objectives
1. Describe acute inflammation including cardinal signs, vascular and cellular responses
2. Differentiate local signs of inflammation from systemic manifestations
3. Discuss plasma derived mediators of inflammation
4. Name the cellular derived inflammatory mediators
5. Identify a role of each different WBC in the inflammatory process
6. Discuss mechanisms of fever
Additional Outcomes for Inflammation
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Discuss steps leading to phagocytosis and the process of phagocytosis itself
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Discuss the role of the mast cell in acute inflammation.
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Describe inflammation’s role in immune defense
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Compare and contrast acute, subacute & chronic inflammation.
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Discuss inflammation’s role in wound healing
Immunity
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First line of defense
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Innate resistance
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Second line of defense
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Skin, gag reflex
Inflammation
Third line of defense
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Adaptive (acquired) immunity
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Associated with antibodies (longest to develop)
First Line of Defense
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Physical and mechanical barriers
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
Skin

Linings of the gastrointestinal, genitourinary, and respiratory tracts
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Sloughing off of cells
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Coughing and sneezing
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Flushing
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Vomiting
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Mucus and cilia
Biochemical barriers

Synthesized and secreted saliva, tears, ear wax, sweat, and mucus

Antimicrobial peptides

Normal bacterial flora
2nd Line of Defense - Inflammation
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Inflammation is an automatic response (almost instantaneous) to cell injury that:

Neutralizes harmful agents

Removes dead tissue

Establishes an environment suitable for healing
Inflammatory response

Caused by a variety of materials
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Infection, mechanical damage, ischemia, nutrient deprivation, temperature
extremes, radiation, etc.

Local manifestations

Systemic manifestations
Inflammation overview from Med-Surg Text,
CD or online site
Inflammatory Response
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Sequential response to cell injury

Neutralizes and dilutes inflammatory agent

Removes necrotic materials

Establishes an environment suitable for healing and repair
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Mechanism of inflammation basically same regardless of injuring agent
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Inflammation is always present with infection
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Infection is not always present with inflammation
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Etiology may be from
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•

Heat
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Radiation
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Trauma

Allergens

Infection
Intensity of the response depends on

Extent and severity of injury

Reactive capacity of injured person
Inflammatory response can be divided into

Vascular response

Cellular response
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Formation of exudates (carries away the clotted tissue)

Healing
Inflammatory Response
Vascular Response
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After cell injury, arterioles in area briefly undergo transient vasoconstriction
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After release of histamine and other chemicals by the injured cells, vessels dilate, resulting in
hyperemia
Vascular Response
***MAST CELL:Causes the release of histamines and the production of prostaglandins (MAJOR CELL)
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Vasodilation

Results in hyperemia (exesive blood in part of body)

Increased blood flow in the area

Raises filtration pressure
Inflammatory Response
Vascular & Chemical Response
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Vasodilation chemical mediators

Endothelial cell retraction

Increased capillary permeability

Movement of fluid from capillaries into tissue spaces
Inflammatory Response
Vascular Response
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Fluid in tissue spaces
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Initially composed of serous fluid

Later contains plasma proteins, primarily albumin
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Proteins exert oncotic pressure that further draws fluid from blood vessels
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Tissue becomes edematous
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As plasma protein fibrinogen leaves blood, it is activated to fibrin by products of the injured cells
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Fibrin strengthens a blood clot formed by platelets
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In tissue, clots trap bacteria to prevent spread
Plasma Protein Systems
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Coagulation (clotting) system
–
–
Forms a fibrinous meshwork at an injured or inflamed site
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Prevents the spread of infection
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Keeps microorganisms and foreign bodies at the site of greatest inflammatory
cell activity
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Forms a clot that stops bleeding
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Provides a framework for repair and healing
Main substance is an insoluble protein called fibrin
Inflammatory Response
Cellular Response
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Blood flow through capillaries in the area of inflammation slows as fluid is lost and viscosity
increases
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Neutrophils and monocytes move to the inner surface of the capillaries and then migrate
through the capillary wall to the site of the injury
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Chemotaxis
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Directional migration of WBCs along concentration gradient of chemotactic factors
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Mechanism for accumulating neutrophils and monocytes at site of injury
Margination, Diapedesis,
and Chemotaxis
Diapedesis: the passage of red or with blood corpuscles through the walls of the vessels that contain
them without damage to the vessels.
Inflammatory Response
Cellular Response
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Chemotactic factors

Bacterial-derived
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Complement-derived (C5a, C3a)
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Lipid-derived
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Platelet-derived
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Coagulation-related
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Chemokines- any of a group of low-molecular=weight cytokines, such as interleukin-8,
identified on the basis of their ability to induce chemotaxis or chemokinesis in
leukocytes in inflammation.
Neutrophils (If indicated by lab as high, there is inflammation somewhere)

First leukocytes to arrive at site of injury (6 to 12 hours) (PMN: Polymorphonucleated
leukocytesl)
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Phagocytize bacteria, other foreign material, and damaged cells
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Short life span (24 to 48 hours)

Pus is composed of
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Dead neutrophils accumulated at the site of injury
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Digested bacteria
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Other cell debris
Bone marrow releases more neutrophils in response to infection, resulting in elevated
WBC (SEG: segmented neutrophils, teenager neutrophil)
Phagocytosis
Leukocytes
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Leukocytes migrate to the injured area
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Leukocytes express adhesive proteins
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Attach to the blood vessel lining
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Squeeze between the cells
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Follow the inflammatory mediators to the injured area
Phagocytosis
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Steps

Adherence
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Engulfment
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Phagosome formation
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Fusion with lysosomal granules/toxic oxygen production (free radical formation)
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Destruction of the target
Opsonin: an antibody or complement split product that, on attaching to foreign material,
microorganisms, or other antigens, enhances phagocytosis of that substance by leukocytes
and other macrophages.
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Monocytes (biggest type of Leukocytes)

Second type of phagocytic cells to migrate to site of injury from circulating blood

Attracted to the site by chemotactic factors
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Arrive within 3 to 7 days after the onset of inflammation
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On entering tissue spaces, monocytes transform into macrophages

Assist in phagocytosis of inflammatory debris

Macrophages have a long life span and can multiply
Macrophage (finalize the cleanup)

Important in cleaning the area before healing can occur
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May stay in damaged tissues for weeks
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Cells may fuse to form a multinucleated giant cell
Lymphocytes (REALY IMPORTANT!!)
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Arrive later at the site of injury (activates immune response)
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Primary role of lymphocytes involve
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Cell-mediated immunity
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Humoral immunity
Cellular Response in Inflammation
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Eosinophils (small role allergic reaction)

Released in large quantities during an allergic reaction
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Release chemicals that act to control the effects of histamine and serotonin
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Involved in phagocytosis of allergen–antibody complex
Basophils

Carry histamine and heparin in their granules that are released during inflammation

Have limited phagocytic capabilities
Mast Cell Degranulation
Cyclooxygenase: COX inhibitors
Prostaglandins= (vascular permeability)-pain
Steroids stop arachidonic acid formation
***NSAID’s, Aspirin, Steroids brakes this cycle!!!***
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Chemical mediators
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Histamine (increases vascular permeability)
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Serotonin:
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Kinins (e.g., bradykinin-pain)
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Complement components (C3a, C4a, C5a=inflammation)
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Prostaglandins and leukotrienes
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Cytokines-promote & inhibit inflammation
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IL1-promote fever
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IL1,6-systemic effects on Inflammation
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Cytokines
Example of Cytokines in COPD
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Complement system (Plasma protein system)

Major mediator of the inflammatory response

When activated, the components occur in sequential order involving two pathways

Each activated complex can act on the next component
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Complement can kill bacteria on its own in its final two stages (Direct kill)
Inflammatory Response
Complement System
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Major functions of the complement system
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Enhanced phagocytosis
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Increased vascular permeability

Causes Chemotaxis
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Promotes Cellular lysis
Complement system
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Activation increases phagocytosis through opsonization and chemotaxis
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The entire complement sequence of C1 to C9 must be activated for cell lysis to occur

C8 and C9, the final components of the complement system, pierce the cell surface,
causing rupture of the cell membrane and lysis
Plasma Protein Systems
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Kinin system

Functions to activate and assist inflammatory cells
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Primary kinin is bradykinin

•
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Causes dilation of blood vessels, pain, smooth muscle contraction, vascular
permeability, and leukocyte chemotaxis
Prostaglandins (pain)

Synthesized from the phospholipids of cell membranes of most body tissues, including
blood cells

Phospholipids are converted to arachidonic acid, which is then oxidized by two different
pathways

Series E and I prostaglandins are potent vasodilators and inhibit platelet and neutrophil
aggregation
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Prostaglandins are generally considered proinflammatory, contributing to increased
blood flow, edema, and pain
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Drugs that inhibit prostaglandin synthesis
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Nonsteroidal antiinflammatory drugs
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Aspirin
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Corticosteroids
Exudate
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Consists of fluid and leukocytes that move from the circulation to the site of injury

Nature and quantity depend on the type and severity of the injury and the tissues
involved
Exudative Fluids
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Serous exudate
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Fibrinous exudate
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Thick, clotted exudate: indicates more advanced inflammation
Purulent exudate
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Watery exudate: indicates early inflammation
Pus: indicates a bacterial infection
Hemorrhagic exudate
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Exudate contains blood: indicates bleeding
Inflammatory Response
Clinical Manifestations
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Local response to inflammation

Redness
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~Heat~~
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**Pain**
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Swelling()
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Loss of function>
Systemic response to inflammation

Increased WBC count with a shift to the left (Leukocytosis) (more immature cells
produced)
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Malaise
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Nausea and anorexia
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Increased pulse and respiratory rate (tykipnea)
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Fever
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The causes of the systemic response are poorly understood, but it is probably due to
complement activation and the release of cytokines

Some of the cytokines are IL-1, IL-6, and tumor necrosis factor

Fever
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Onset is triggered by release of cytokines
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Cytokines cause fever by initiating metabolic changes in the temperatureregulating center
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Epinephrine released from the adrenal medulla increases metabolic rate –to
achieve proper temp
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Patient then experiences chills and shivering
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Body is hot, yet person seeks warmth until the circulating temperature reaches
core body temperature
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Beneficial aspects of fever include increased killing of microorganisms, increased
phagocytosis, and increased proliferation of T lymphocytes
Production of Fever
Inflammatory Response
Types of Inflammation
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Acute
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Healing occurs in 2 to 3 weeks, usually leaving no residual damage

Neutrophils are the predominant cell type at the site of inflammation
Subacute

Has same features as acute inflammation but persists longer

May be cause of vascular damage that leads to atherosclerosis

Oral inflammation & Pancreatic Ca

Alzheimer’s disease
Chronic
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May last for years

Injurious agent persists or repeats injury to site

Predominant cell types involved are lymphocytes and macrophages

May result from changes in immune system (e.g., autoimmune disease)
Inflammatory Response
Healing Process
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Regeneration

Replacement of lost cells and tissues with cells of the same type
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Ability to regenerate depends on cell type
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Constantly dividing cells that rapidly regenerate
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Skin, bone marrow, lymphoid organs, as well as mucous membrane cells
of the urinary, reproductive, and GI tracts
Replacement of lost cells and tissues with cells of the same type
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Stable cells such as liver, bone, kidney, and pancreas regenerate in response to
injury
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Permanent cells such as neurons and skeletal and cardiac muscle do not divide
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Neurons are replaced by glial cells, and new neurons may be produced by stem
cells
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Skeletal and cardiac muscle will be repaired with scar tissue
Repair

Healing as a result of lost cells being replaced with connective tissue

Repair is more complex than regeneration

Repair is the most common type of healing and usually results in scar formation
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Initial phase–lasts 3 to 5 days
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Granulation phase–lasts from 5 days to 3 weeks
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Maturation phase and scar contraction–lasts from 7 days to several months or
years
Wound Healing Process
Watch the wound healing video in class and again in lesson on S360