The Injury Response Process

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The Injury Response Process
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Stress

• Influence the bodies physiological functions to
  provide best healing environment
• Positive and negative
• At the cellular level
• Adapts
• Alters and recovers
• Dies

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Trauma

• Macro
• Micro

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Neurotransmitters

• Acetylcholine
• Increases permeability to Na K
• Inhibitory to the Heart (Vagus nerve)
• Dopamine
• Epinephrine
• Norepinephrine
• Serotonin
• Strong inhibitor
• Thought to inhibit pain chronic
• Mood behavior
• Substance P
• Produces pain
• Peptide found in spinal cord pathways

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Injury Process

• Primary response
• Tissue destruction
• Secondary response
• Hypoxia
• Result of ischemia
• Creates ATP shortage as a result of lack of oxygen

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Inflammatory Response

• Acute Inflammation
• Short onset and duration
• Change in hemodynamics, production of exudate,
  granular leukocytes
• Chronic Inflammation
• Long onset and duration
• Presence of non-granular leukocytes and extensive
  scar tissue

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The Healing Process

• Inflammatory Response Phase
• 0-14 days
• Fibroblastic Repair Phase
• 2 days-6 weeks
• Maturation Remodeling Phase
• 3 weeks-2 years
• The Healing process is a continuum

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Acute Inflammatory Response

• Begins immediately following injury
• Vascular (Hemodynamics) and cellular responses
• Local Vasodilation (Rubor)
• Fluid Leakage into extravascular spaces (Tumor)
• Blocking of Lymphatic drainage (Calor)

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Cardinal Signs of Inflammation

• Rubor (redness)
• Tumor (swelling)
• Calor (heat)
• Dolor (pain)
• Functio laesa (loss of function)

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Inflammation Cont.

• Other cardinal signs of inflammation
• Distension of tissue and chemical irritation of
  nerve endings this causes pain (Dolor)
• Loss of Function
• Acute response usually lasts between 24 and 48
  hours
• Subacute phase is complete within 2 weeks

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Inflammation Cont.

• Phagocytosis
• Destroys bacteria and clears debris
• Essential for repair process to proceed further
• Works through amoeboid action and diapedesis
• Diapedesis outward movement of elements of the
  blood through intact vessel walls

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Vascular Response

• Trauma causes hemorrhage, vascular disruption,
  and cell death
• Immediate vasoconstriction at and around injury
  site
• Mediated by norepinephrine
• Lasts from few seconds to few minutes
• Continued constriction must be mediated by
  serotonin

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Vascular Response Cont.

• If Serotonin is released
• Found in mast cells
• Triggered by platelet adhesion to naked collagen,
  which is present in connective tissue
• Collagen becomes exposed when injury occurs to
  blood vessel endothelial wall

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Vascular Response cont.

• Platelet adherence to collagen also causes
  release of ADP
• Which in turn causes additional platelet
  adherence
• This formation, at the site of injury along the
  endothelial wall, creates an unstable plug
• This is a temporary slowing or stopping of blood

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Vascular Response cont.

• During initial vasoconstriction, opposing
  endothelial walls are pressed together
• This contact causes a stickiness that will last
  long after active vasoconstriction (5 - 10) has
  started to relax

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Cellular Mediators

• Histamine
• platelets, mast cells and basophils to enhance
  permeability and arterial dilation
• Serotonin
• provides for vasoconstriction
• Bradykinin
• plasma protease that enhances permeability and
  causes pain. Also chemotactic
• Heparin
• provided by mast cells and basophils to prevent
  coagulation
• Leukotrienes and prostaglandins
• located in cell membranes and develop through the
  arachadonic acid cascade
• Leukotrienes alter permeability
• Prostaglandin add and inhibit inflammation

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Vascular Response cont.

• Microtrauma causes the release of Hagemann factor
  XII
• Which is an enzyme present in blood
• Initiates clotting by converting prothrombin to
  thrombin which in turn converts fibrinogen to
  fibrin
• Fibrin plugs seal damaged lymphatics and confine
  reaction to a localized area

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Vascular Response cont.

• Immediately after injury, leukocytes begin to
  adhere to endothelium of venules
• Within 1 hour, entire endothelium margin covered
  with neutrophilic leukocytes. (neutrophilic
  margination)

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Vascular Response cont.

• Histamine is released from mast cells, basophils,
  and platelets
• This causes vasodilatation and an increase in
  cell wall permeability to small molecular weight
  plasma proteins.
• These are albumin, globulins, and fibrinogen
• Transport protein
• Plasma protein
• Plasma cell to assist with clotting

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Edema

• Collection of fluid
• Histamine action lasts less than 30
• Transudate with fibrinogen then forms fibrin
  which in turn forms plugs for lymphatics and
  confines the inflammatory reaction
• Other factors involved for continued permeability

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The Cellular Reaction

• Neutrophils
• Phagocytosis and debridement
• Release proteolytic enzymes and collagenase
• Chemotactic attraction
• 24 hours, max of several days

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Mononuclear cells

• Monocytes and Lymphocytes
• Monocytes
• When they get into the tissue spaces they are
  transformed into macrophage cells
• This cell is considered the most important
  regulatory cell in the inflammatory response
• The presence of the macrophage is essential to
  wound healing, it must be present in order for
  healing to occur

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Macrophages cont.

• Macrophages produce collagenase and proteoglycan
  degrading enzymes
• Macrophage phagocytic activity most efficient
  with oxygen present
• They tolerate hypoxic situations very well
• Macrophages release fibronectin which attracts
  fibroblasts

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Macrophages cont.

• Play a role in localizing the inflammatory
  response
• Help adhere fibroblasts to fibrin during the
  transition to the proliferative phase
• This may enhance the deposition of collagen fibers

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Platelets

• Considered along with macrophages to be one of
  the most important regulatory cells
• Releases platelet - derived growth factor (it
  attracts fibroblasts) also is shown that it
  attracts macrophages, monocytes, and neutrophils

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Prostaglandins

• Cell membranes phospholipid content is broken
  down into phospholipase A2
• results in the formation of Arachidonic acid
• Oxidation of arachidonic acid produces a series
  of substances called leukotrienes
• alter capillary permeability during the
  inflammatory reaction
• Arachadonic acid is converted by COX through a
  series of steps to Prostaglandins

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Prostaglandins cont.

• Pgs have very important and multiple roles in the
  inflammatory phase
• De - activation of COX by steroids and NSAIDs
  (such as aspirin) is counterproductive to the
  resolution of the acute inflammatory response
• but may contribute in a chronic inflammatory
  response

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Chronic Inflammation

• May last for several years or months
• May be from unresolved acute inflammation
• Not characterized by the cardinal signs of
  inflammation
• Repeated microtrauma or presence of a foreign
  substance
• Characterized by the replacement of leukocytes
  with macrophages, lymphocytes, and plasma cells
• Associated with wounds that are habitually sealed
  by necrotic tissue

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Repair (Proliferation) Phase

• Begins within 72 hours following injury
• Granulation
• Requires the presence of fibroblasts,
  myofibroblasts, endothelial cells, and is
  regulated by growth factors
• Re-epithelialization
• Neovascularization
• Begins on periphery
• Contraction (Fibroplasia)
• Weak type III collagen
• High water content

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Repair Phase cont.

• Granulation tissue formation proceeds when debris
  removed
• macrophages and fibroblasts must be present
• gel matrix of collagen, hyaluronic acid, and
  fibronectin nourish the macrophages and
  fibroblasts through the newly formed vascular
  network

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Repair

• Re-epithelialization occurs through leap frogging
• best if hydrated
• low friction
• initiated by loss of contact

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Repair

• Fibroplasia
• fibroblasts change into myofibroblasts
• contract to close wound
• FGF responsible for change
• collagen production begins about 5 days after
  myofibroblast migration

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Maturation Phase

• May last a year or longer
• Type III to Type I