Chapter 10:
Tissue Response to Injury
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
Cardinal Signs of
Inflammation
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Rubor (redness)
Tumor (swelling)
Color (heat)
Dolor (pain)
Functio laesa (loss of function)
Phases of the Inflammatory
Response
(3 separate phases)
• 1. Acute phase
• 2. Repair phase
• 3. Remodeling phase
Phase I: Acute Phase
• Initial reaction to an injury occurring 3
hours to 4 days following injury
• Goal
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Protect
Localize
Decrease injurious agents
Prepare for healing and repair
• Caused by trauma, chemical agents,
thermal extremes, pathogenic organisms
• External and internal injury result in
tissue death and cell death
• Decreased oxygen to area increases cell
death
• Phagocytosis will add to cell death due to
excess digestive enzymes
• Rest, ice, compression & elevation are
critical to limiting cell death
• First hour
– Vasoconstriction and coagulation occur to
seal blood vessels and chemical mediators
are released
– Immediately followed by vasodilation or
blood vessel
• Second hour
– Vasodilation decreases blood flow, increased
blood viscosity resulting in edema (swelling)
• Second hour (continued)
– Exudate increases (high concentration of
RBC’s) due to increased vessel permeability
– Permeability changes generally occur in
capillary and venules
– Margination occurs causing leukocytes to fill
the area and line endothelial walls
– Through diapedesis and chemotaxis
leukocytes move to injured area
• Cellular response
– Mast cells (connective tissue cells) and
leukocytes (basophils, monocytes,
neutrophils) enter area
– Mast cells with heparin and histamine serve
as first line of defense
– Basophils provide anticoagulant
– Neutrophils and monocytes are responsible
for small and large particles undergoing
phagocytosis - ingestion of debris and
bacteria
• Cellular mediation
– Histamine provided by platelets, mast cells
and basophils to enhance permeability and
arterial dilation
– Serotonin provides for vasoconstriction
– Bradykinin is a plasma protease that
enhance permeability and causes pain.
– Heparin is provided by mast cells and
basophils to prevent coagulation
– Leukotrienes and prostaglandins are located
in cell membranes and develop through the
arachadonic acid cascade
– Leukotrienes alter permeability
– Prostaglandin add and inhibit inflammation
• Complimentary systems
– Enzymatic proteins that destroy bacteria
and other cells through their impact on cell
lysis
• Bleeding and exudate
– Amount dependent on damage
– Initial stage: thromboplastin is formed
– Second stage: Prothrombin is converted to
thrombin due to interaction with
thromboplastin
– Third stage: thrombin changes from soluble
fibrinogen to insoluble fibrin coagulating
into a network localizing the injury
Phase II: Repair Phase
• Phase will extent from 48 hours to 6
weeks following cleaning of fibrin clot,
erythrocytes, and debris
• Repaired through 3 phases
– Resolution (little tissue damage and normal
restoration)
– Restoration (if resolution is delayed)
– Regeneration (replacement of tissue by same
tissue)
• Scar formation
– Less viable than normal tissue, may
compromise healing
– Firm, inelastic mass devoid of capillary
circulation
– Develops from exudate with high protein
and debris levels resulting in granulation
tissue
– Invaded by fibroblasts and and collagen
forming a dense scar and while normally
requiring 3-14 weeks may require 6 months
to contract
• Primary healing (healing by first intention)
– Closely approximated edges with little
granulation tissue production
• Secondary healing (heal by secondary
intention)
– Gapping, tissue loss, and development of
extensive granulation tissue
– Common in external lacerations and internal
musculoskeletal injuries
• Regeneration
– Related to health, nutrition and tissue type
– Dependent on levels of:
• debris (phagocytosis)
• endothelial production (hypoxia and
macrophages stimulate capillary buds)
• production of fibroblasts (revascularization
allows for enhanced fibroblast activity and
collagen production which is tied to Vitamin C,
lactic acid, and oxygen
–
Phase III: Remodeling
• Overlaps repair and regeneration
• First 3-6 weeks involves laying down of
collagen and strengthening of fibers
• 3 months to 2 years allowed for enhanced
scar tissue strength
• Balance must be maintained between
synthesis and lysis
• Take into consideration forces applied
and immobilization/mobilization time
frames relative to tissue and healing time
Chronic Inflammation
• Result of failed acute inflammation
resolution within one month termed
subacute inflammation
• Inflammation lasting months/years
termed chronic
– Results from repeated microtrauma and
overuse
– Proliferation of connective tissue and tissue
degeneration
Characteristics of Chronic
Inflammation
• Proliferation of connective tissue and tissue
degeneration
• Presence of lymphocytes, plasma cell,
macrophages(monocytes) in contrast to
neutrophils (during acute conditions)
• Major chemicals include
– Kinins (bradykinin) - responsible for
vasodilation, permeability and pain
– Prostaglandin - responsible for vasodilation
but can be inhibited with aspirin and NSAID’s
Factors That Impede Healing
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Extent of injury
Edema
Hemorrhage
Poor Vascular
Supply
• Separation of Tissue
• Muscle Spasm
• Atrophy
• Corticosteroids
• Keloids and
Hypertrophic Scars
• Infection
• Humidity, Climate,
Oxygen Tension
• Health, Age, and
Nutrition
Soft Tissue Healing
• Cell structure/function
– All organisms composed of cells
– Properties of soft tissue derived from
structure and function of cells
– Cells consist of nucleus surrounded by
cytoplasm and encapsulated by phospholipid
cell membrane
– Nucleus contains chromosomes (DNA)
– Functional elements of cells (organelles)
include mitochondria, ribosomes, endoplasmic
reticulum, Golgi apparatus & centrioles
Tissues of the Body
• Bone - not classified as soft tissue
• 4 types of soft tissue
– Epithelial tissue
• Skin, vessel & organ linings
– Connective tissue
• Tendons, ligaments, cartilage, fat, blood, and
bone
– Muscle tissue
• Skeletal, smooth, cardiac muscle
– Nerve tissue
• Brain, spinal cord & nerves
Soft Tissue Adaptations
• Metaplasia - transformation of tissue from one type to
another that is not normal for that tissue
• Dysplasia - abnormal development of tissue
• Hyperplasia- excessive proliferation of normal cells in
normal tissue arrangement
• Atrophy- a decrease in the size of tissue due to cell
death and re-absorption or decreased cell
proliferation
• Hypertrophy - an increase in the size of tissue without
necessarily changing the number of cells
Cartilage Healing
• Limited capacity to heal
• Little or no direct blood supply
• Chrondrocyte and matrix disruption
result in variable healing
• Articular cartilage that fails to clot and
has no perichondrium heals very slowly
• If area involves subchondral bone
(enhanced blood supply) granulation
tissue is present and healing proceeds
normally
Ligament Healing
• Follows similar healing course as
vascular tissue
• Proper care will result in acute, repair,
and remodeling phases in same time
required by other vascular tissue
• Repair phase will involve random laying
down of collagen which, as scar forms,
will mature and realign in reaction to
joint stresses and strain
• Full healing may require 12 months
Skeletal Muscle Healing
• Skeletal muscle cannot undergo mitotic
activity to replace injured cells
• New myofibril regeneration is minimal
• Healing and repair follow the same
course as other soft tissues developing
tensile strength (Wolff’s Law)
Nerve Healing
• Cannot regenerate after injury
• Regeneration can take place within a nerve
fiber
• Proximity of injury to nerve cell makes
regeneration more difficult
• For regeneration, optimal environment is
required
• Rate of healing occurs at 3-4 mm per day
• Injured central nervous system nerves do
not heal as well as peripheral nerves
Modifying Soft-Tissue Healing
• Varying issues exist for all soft tissues
relative to healing (cartilage, muscle,
nerves)
• Blood supply and nutrients is necessary
for all healing
• Healing in older athletes or those with
poor diets may take longer
• Certain organic disorders (blood
conditions) may slow or inhibit the
healing process
Management Concepts
• Drug utilization
– Anitprostaglandin agents used to combat
inflammation
– Non-steroidal anti-inflammatory agents
(NSAID’s)
– Medications will work to decrease
vasodilatation and capillary permeability
• Therapeutic Modalities
– Thermal agents are utilized
• Heat stimulates acute inflammation (but works
as a depressant in chronic conditions)
• Cold is utilized as an inhibitor
– Electrical modalities
• Treatment of inflammation
• Ultrasound, microwave, electrical stimulation
(includes transcutaneous electrical muscle
stimulation and electrical muscle stimulation
• Therapeutic Exercise
– Major aim involves pain free movement, full
strength power, and full extensibility of
associated muscles
– Immobilization, while sometimes necessary,
can have a negative impact on an injury
• Adverse biochemical changes can occur in
collagen
– Early mobilization (that is controlled) may
enhance healing
Fracture Healing
• Potential serious bone fractures are part
of athletics
• Time is necessary for proper bone union
to occur and is often out of the control of
a physician
• Conservative treatment will be necessary
for adequate healing to occur
• Bone undergoes constant remodeling
through osteocyte activity
• Osteocytes cellular component of bone
– Osteoblasts are responsible for bone
formation while osteoclasts resorb bone
• Cambium (periosteum)
– A fibrous covering involved in bone healing
– Vascular and very dense
• Inner cambium
– less vascular and more cellular.
– Provides attachments for muscle, ligaments
and tendons
Acute Fracture of Bone
• Follows same three phases of soft tissue
healing
• Less complex process
• Acute fractures have 5 stages
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Hematoma formation
Cellular proliferation
Callus formation
Ossification
Remodeling
Hematoma Formation
• Trauma to the periosteum and surrounding
soft tissue occurs due to the initial bone
trauma
• During the first 48 hours a hematoma
within the medullary cavity and the
surrounding tissue develops
• Blood supply is disrupted by clotting vessels
and cellular debris
• Dead bone results in an inflammatory
response (vasodilation, exudate cell
migration)
Cellular Formation
• Granulation forms constructing fibrous
union between fractured ends
• Capillary buds allow endosteal cells
influx from cambium layer
• Cells evolve from fibrous callus to
cartilage, to woven bone
• High oxygen tension = fibrous tissue
• Low oxygen tension = cartilage tissue
• Bone growth will occur with optimal
oxygen tension and compression
Callus Formation
• Soft callus is a random network of woven
bone
• Osteoblasts fill the internal and external
calluses to immobilize the site
• Calluses are formed by bone fragments
that bridge the fracture gap
• The internal callus creates a rigid
immobilization early
• Hard callus formation occurs after 3-4
weeks and lasts 3-4 months
• Hard callus is a gradual connection of
bone filaments to the woven bone
• Less than ideal immobilization produces
a cartilagenous union instead of a bony
union
Ossification
• Adequate immobilization and
compression will result in new Haversian
systems developing
• Haversian canals allow for the laying
down of primary bone
• Ossification is complete when bone has
been laid down and the excess callus has
been resorbed by osteoclasts.
Remodeling
• Occurs following callus resorption and
trabecular bone is laid along lines of stress
• Bioelectric stimulation plays a major role
in completing the remodeling process
– Osteoblasts are attracted to the
electronegative (concave/compression) side
– Osteoclasts are attracted to the electropositive
(convex/tension) side
• The process is complete when the original
shape is achieved or the structure can
withstand imposed stresses
Acute Fracture Management
• Must be appropriately immobilized, until Xrays reveal the presence of a hard callus
• Fractures can limit participation for weeks or
months
• A clinician must be certain that the following
areas do not interfere with healing
– Poor blood supply
– Poor immobilization
– Infection
• Poor blood supply
– Bone may die and union/healing will not occur
(avascular necrosis)
– Common sites include:
• Head of femur, navicular of the wrist, talus, and
isolated bone fragments
– Relatively rare in healthy, young athletes
except in navicular of the wrist
• Poor immobilization
– Result of poor casting allowing for motion
between bone parts
– May prevent proper union or result in bony
deformity
• Infection
– May interfere with normal healing,
particularly with compound fractures
– Severe streptococcal and staphylococcal
infections
– Modern antibiotics has reduced the risk of
infections
– Closed fractures are not immune to
infections within the body or blood
• If soft tissue alters bone positioning,
surgery may be required to ensure
proper union
Healing of Stress Fractures
• Result of cyclic forces, axial compression
or tension from muscle pulling
• Electrical potential of bone changes
relative to stress (compression, tension, or
torsional)
• Constant stress axially or through muscle
activity can impact bone resorption,
leading to microfracture
• If osteoclastic activity is not in balance
with oesteoblastic activity bone becomes
more susceptible to fractures
• To treat stress fractures a balance
between osteoblast and osteoclast activity
must be restored
• Early recognition is necessary to prevent
complete cortical fractures
• Decreased activity and elimination of
factors causing excess stress will be
necessary to allow for appropriate bone
remodeling
Pain
• Major indicator of injury
• Pain is individual and subjective
• Factors involved in pain
– Anatomical structures
– Physiological reactions
– Psychological, social, cultural and cognitive
factors
Nociception
• Pain receptors -free nerve endings
sensitive to extreme mechanical, thermal
and chemical energy
• Located in meninges, periosteum, skin,
teeth, and some organs
• Pain information transmitted to spinal
cord via myelinated C fibers and A delta
fibers
• Nociceptor stimulation results in release
of substance P
• Signal travels along afferent nerves to the
spinal cord
– A delta fiber (fast) transmit information to the
thalamus concerning location of pain and
perception of pain being sharp, bright or
stabbing
– C fibers (slower conduction velocity) deal with
diffused, dull, aching and unpleasant pain
– C fibers signal also passed to limbic cortex
providing emotional component to pain
• Nociceptive stimuli is at or close to an
intensity which would result in tissue injury
Endogenous Analgesics
• Nervous system is electrochemical in
nature
• Chemicals called neurotransmitters are
released by presynaptic cell
• Two types mediate pain
– Endorphins
– Seretonin
• Neurotransmitters release stimulated by
noxious stimuli- resulting in activation of
pain inhibition transmission
• Stimulation of periaqueductal gray
matter (PGA) and raphe nucleus of pons
and medulla cause analgesia
• Analgesia is the result of opioids release
– Morphine like substance manufactured in
the PGA and CNS
– Endorphins and enkephalins
• Other pain modulators
– Norepinephrine (noradrenergic
– Seretonin also will serve as neuromodulator
Pain Categories
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Pain sources
Fast versus slow pain
Acute versus chronic
Projected or referred pain
• Pain sources
– Cutaneous, deep somatic, visceral and
psychogenic
– Cutaneous pain is sharp, bright and burning
with fast and slow onset
– Deep somatic pain originates in tendons,
muscles, joints, periosteum and blood vessels
– Visceral pain begins in organs and is
diffused at first and may become localized
– Psychogenic pain is felt by the individual but
is emotional rather than physical
• Fast versus Slow Pain
– Fast pain localized and carried through Adelta axons
– Slow pain is perceived as aching, throbbing,
or burning (transmitted through C fibers)
• Acute versus Chronic Pain
– Acute pain is less than six months in
duration
– Chronic pain last longer than six months
– Chronic pain classified by IASP as pain
continuing beyond normal healing time
• Projected (Referred) Pain
– Pain which occurs away from actual site of
injury/irritation
– Unique to each individual and case
– May elicit motor and/or sensory response
– A-alpha fibers are sensitive to pressure and
can produce paresthesia
– Three types of referred pain include:
myofascial, sclerotomic, and dermatomic
• Myofascial Pain
– Trigger points or small hyperirritable areas
within muscle resulting in bombardment of
CNS
– Acute and chronic pain can be associated
with myofascial points
– Often described as fibrositis, myositis,
myalgia, myofasciitis and muscular strain
– Two types of trigger points (active and
latent)
– Active points cause obvious complaint
– Latent points are dormant potentially
causing loss of ROM
– Trigger points do not follow patterns
– Trigger point area referred to as reference
zone which may or may not be proximal to
the point of irritation
• Sclerotomic and dermatomic pain
– Deep pain with slow or fast characteristics
– May originate from sclerotomic, myotomic
or dermatomic nerve irritation/injury
– Sclerotomic pain transmitted by C fibers
causing deep aching and poorly localized
pain
– Can be projected to multiple areas of brain
causing depression, anxiety, fear or anger
– Autonomic changes result (vasomotor
control, BP and sweating
– Dermatomic pain (irritation of A-delta
fibers) is sharp and localized
– Projects to the thalamus and cortex directly
• Gate Theory
– Area in dorsal horn of spinal cord causes
inhibition of pain impulses ascending to
cortex
– T-cells will transmit signals to brain
– Substantia gelatinosa functions as gate
determining if stimulus sent to T-cells
– Pain stimuli exceeding threshold results in
pain perception
– Stimulation of large fast nerves can block
signal of small pain fiber input
– Rationale for TENS, accupressure/puncture,
thermal agents and chemical skin irritants
Central
Biasing
Theory
Release of
BEndorphins
Variation of Pain Sensitivity
• Hyperesthesia, paresthia or analgesia
• Pain modulation
– Mixture of physical and psychological
factors
– Pain management is a challenge to treat
– Generally acute pain management in athletic
training setting
• Pain assessment
– Self report is the best reflection of pain and
discomfort
– Assessment techniques include:
• visual analog scales (0-10, marked no pain to
severe pain)
• verbal descriptor scales (marked none, slight,
moderate, and severe)
• Pain Treatment
– Must break pain-spasm-hypoxia-pain cycle
through treatment
– Agents used; heat/cold, electrical
stimulation-induced analgesia,
pharmacological agents
• Heat/Cold
– Heat increases circulation, blood vessel
dilation, reduces nociception and ischemia
caused by muscle spasm
– Cold applied for vasoconstriction and
prevention of extravasation of blood into
tissue
– Pain reduced through decrease in swelling
and spasm
• Induced analgesia
– Utilize electrical modalities to reduce pain
– TENS and acupuncture commonly used to
target Gate Theory
• Pharmacological Agents
– Oral, injectable medications
– Commonly analgesics and antiinflammatory agents
Psychological Aspects of Pain
• Pain can be subjective and psychological
• Pain thresholds vary per individual
• Pain is often worse at night due to solitude and
absence of external distractions
• Personality differences can also have an impact
• A number of theories relative to pain exist and
it physiological and psychological components
• Athlete, through conditioning are often able to
endure pain and block sensations of minor
injuries