INFLAMMATORY-RESPONSE PHASE

Once a tissue is injured, the process of healing begins immediately (Fig. 2-1).1,7 The destruction of tissue
produces direct injury to the cells of the various soft tissues. Cellular injury results in altered metabolism
and the liberation of materials that initiate the inflammatory response. Cellular injury is characterized
symptomatically by redness, swelling, tenderness, and increased temperature.2,11 Response
Inflammation is a process by means of which leukocytes and other phagocytic cells and exudate are
delivered to the injured tissue. This cellular reaction generally is protective, tending to localize or dispose
of injury by-products (e.g., blood, damaged cells) through phagocytosis, thus setting the stage for repair.
Locally, vascular effects, disturbances of fluid exchange, and migration of leukocytes from the blood to
the tissues occur.18

Signs of Inflammation

· Redness

· Swelling

· Tenderness to touch

· Increased temperature

Vascular Reaction

The vascular reaction involves vascular spasm, formation of a platelet plug, blood coagulation, and
growth of fibrous tissue.17 The immediate response to damage is a vasoconstriction of the vascular walls
that lasts for approximately 5-10 minutes. This spasm presses the opposing endothelial linings together
to produce a local anemia that is rapidly replaced by hyperemia of the area owing to dilation. This
increase in blood flow is transitory and gives way to slowing of the flow in the dilated vessels, which then
progresses to stagnation and stasis. The initial effusion of blood and plasma lasts for 24-36 hours.

Chemical Mediators

Three chemical mediators, histamine, leucotaxin, and necrosin, are important in limiting the amount of
exudate and swelling following injury. Histamine released from the injured mast cells causes vasodilation
and increased cell permeability, owing to swelling of endothelial cells, and then separation between the
cells. Leucotaxin is responsible for margination in which leukocytes line up along the cell walls. It also
increases cell permeability locally, thus affecting passage of the fluid and white blood cells through cell
walls by diapedesis to form exudate. Therefore, vasodilation and active hyperemia are important in
exudate (plasma) formation and supplying leukocytes to the injured area. Necrosin is responsible for
phagocytic activity. The amount of swelling that occurs is directly related to the extent of vessel damage.

Function of Platelets

Platelets do not normally adhere to the vascular wall. However, injury to a vessel disrupts the
endothelium and exposes the collagen fibers. Platelets adhere to the collagen fibers to create a sticky
matrix on the vascular wall, to which additional platelets and leukocytes adhere and eventually form a
plug. These plugs obstruct local lymphatic fluid drainage and thus localize the injury response.

Clot Formation

The initial event that precipitates clot formation is the conversion of fibrinogen to fibrin. This
transformation occurs because of a cascading effect beginning with the release of a protein molecule
called thromboplastin from the damaged cell. Thromboplastin causes prothrombin to be changed into
thrombin, which in turn causes the conversion of fibrinogen into a very sticky fibrin clot that shuts off the
blood supply to the injured area. Clot formation begins around 12 hours following injury and is
completed by 48 hours. As a result of a combination of these factors, the injured area becomes walled
off during the inflammatory stage of healing. The leukocytes phagocytize most of the foreign debris
toward the end of the inflammatory phase, setting the stage for the fibroblastic phase. This initial
inflammatory response lasts for approximately 2-4 days following initial injury.

Chronic Inflammation

A distinction must be made between the acute inflammatory response as described in the preceding
section and chronic inflammation. Chronic inflammation occurs when the acute inflammatory response
does not eliminate the injuring agent and fails to restore tissue to its normal physiologic state. Chronic
inflammation involves the replacement of leukocytes with macrophages, lymphocytes, and plasma cells.
These cells accumulate in a highly vascularized and innervated loose connective tissue matrix in the area
of injury.9 In Chronic Inflammation Leukocytes Are Replaced with

· Macrophages

· Lymphocytes

· Plasma cells

The specific mechanisms that convert an acute to a chronic inflammatory response currently are
unknown; however, they seem to be associated with situations that involve overuse or overload with
cumulative microtrauma to a particular structure.4,9 Likewise, there is no specific time frame in which
the classification of acute is changed to chronic inflammation.

FIBROBLASTIC-REPAIR PHASE

During the fibroblastic phase of healing, proliferative and regenerative activity leading to scar

formation and repair of the injured tissue follows the vascular and exudative phenomena of

inflammation (Fig. 2-2).8 The period of scar formation referred to as fibroplasia begins within the first
few hours following injury and may last for as long as 4-6 weeks. During this period many of the signs
and symptoms associated with the inflammatory response subside. The patient may still indicate some
tenderness to touch and will usually complain of pain when particular movements stress the injured
structure. As scar formation progresses, complaints of tenderness or pain gradually disappear.15
During this phase, growth of endothelial capillary buds into the wound is stimulated by a lack of oxygen.
Thus, the wound is now capable of healing aerobically. Along with increased oxygen delivery comes an
increase in blood flow that delivers nutrients essential for tissue regeneration in the area.3

Granulation Tissue Consists of

· Capillaries

· Collagen

· Fibroblasts

The formation of a delicate connective tissue called granulation tissue occurs with the breakdown of the
fibrin clot. Granulation tissue consists of fibroblasts, collagen, and capillaries. It appears as a reddish
granular mass of connective tissue that fills in the gaps during the healing process. As the capillaries
continue to grow into the area, fibroblasts accumulate at the wound site, arranging themselves parallel
to the capillaries. Fibroblastic cells begin to synthesize an extracellular matrix that contains protein fibers
of collagen and elastin, a ground substance that consists of nonfibrous proteins called proteoglycans,
glycosaminoglycans, and fluid. On about day 6 or 7, fibroblasts also begin producing collagen fibers that
are deposited in a random fashion throughout the forming scar. As the collagen continues to proliferate,
the tensile strength of the wound rapidly increases in proportion to the rate of collagen synthesis.20 As
the tensile strength increases, the number of fibroblasts diminishes to signal the beginning of the
maturation phase.

The Extracellular Matrix Contains

· Collagen

· Elastin

· Ground substance

This normal sequence of events in the repair phase leads to the formation of minimal scar tissue.
Occasionally, a persistent inflammatory response and continued release of inflammatory products can
promote extended fibroplasia and excessive fibrogenesis that can lead to irreversible tissue damage.19
Fibrosis can occur in synovial structures, as is the case with adhesive capsulitis in the shoulder; in
extraarticular articular tissues including tendons and ligaments; in bursa; or in muscle.

MATURATION-REMODELING PHASE

The maturation-remodeling phase of healing is a long-term process (Fig. 2-3). This phase features a
realignment or remodeling of the collagen fibers that make up the scar tissue according to the tensile
forces to which that scar is subjected. Ongoing breakdown and synthesis of collagen occur with a steady
increase in the tensile strength of the scar matrix. With increased stress and strain, the collagen fibers
realign in a position of maximum efficiency parallel to the lines of tension. The tissue gradually assumes
normal appearance and function, although a scar is rarely as strong as the normal injured tissue. Usually
by the end of approximately 3 weeks, a firm, strong, contracted, nonvascular scar exists. The maturation
phase of healing may require several years to be totally complete.

FACTORS THAT IMPEDE HEALING

Extent of Injury

The extent of the inflammatory response is determined by the extent of the tissue injury. Microtears of
soft tissue involve only minor damage and most often are associated with overuse. Macrotears involve
significantly greater destruction of soft tissue and result in clinical symptoms and functional alterations.
Macrotears generally are caused by acute trauma.

Factors That Impede Healing

· Extent of injury

· Edema

· Hemorrhage

· Poor vascular supply

· Separation of tissue

· Muscle spasm

· Atrophy

· Corticosteroids

· Keloids and hypertrophic scars

· Infection

· Humidity, climate, and oxygen tension

· Health, age, and nutrition

Edema

The increased pressure caused by swelling retards the healing process, causes separation of tissues,
inhibits neuromuscular control, produces reflexive neurologic changes, and impedes nutrition in the
injured part. Edema is best controlled and managed during the initial first aid management period.22

Hemorrhage
Bleeding occurs with even the smallest amount of damage to the capillaries. Bleeding produces the
same negative effects on healing as does the accumulation of edema, and its presence produces
additional tissue damage and thus exacerbation of the injury.

Poor Vascular Supply

Injuries to tissues with a poor vascular supply heal poorly and slowly. This is likely related to a failure in
the delivery of phagocytic cells initially and also of fibroblasts necessary for formation of scar.

Separation of Tissue

Mechanical separation of tissue can significantly impact the course of healing. A wound that has smooth
edges that are in good apposition will tend to heal by primary intention with minimal scarring.
Conversely, a wound that has jagged separated edges must heal by second intention with granulation
tissue filling the defect and excessive scarring.16

Muscle Spasm

Muscle spasm causes traction on the torn tissue, separates the two ends, and prevents. Both local and
generalized ischemia may result from spasm.

Atrophy

Wasting away of muscle tissue begins immediately with injury. Strengthening and early mobilization of
the injured structure retards atrophy.

Corticosteroids

Use of corticosteroids in the treatment of inflammation is controversial. Steroid use in the early stages of
healing has been demonstrated to inhibit fibroplasia, capillary proliferation, and collagen synthesis, and
increases in tensile strength of the healing scar. Steroid use is debatable in the later stages of healing and
with chronic inflammation.

Keloids and Hypertrophic Scars

Keloids occur when the rate of collagen production exceeds the rate of collagen breakdown during the
maturation phase of healing. This process leads to hypertrophy of scar tissue, particularly around the
periphery of the wound.

Infection

The presence of bacteria in the wound can delay healing and may cause excessive granulation tissue and
large deformed scars.

Humidity, Climate, and Oxygen Tension

Humidity significantly influences the process of epithelization. Occlusive dressings stimulate the
epithelium to migrate twice as fast without crust or scab formation. The formation of a scab occurs with
dehydration of the wound and traps wound drainage, which promotes infection. Keeping the wound
moist provides an advantage for the necrotic debris to go to the surface and be shed. Oxygen tension
relates to the neovascularization of the wound, which translates into optimal saturation and maximal
tensile strength development. Circulation to the wound can be affected by ischemia, venous stasis,
hematomas, and vessel trauma.

Health, Age, and Nutrition

The elastic qualities of the skin decrease with aging. Degenerative diseases such as diabetes and
arteriosclerosis also become a concern of the older patient and may affect wound healing. Nutrition is
important for wound healing. In particular, vitamins C (scurvy), K (clotting), and A and E (collagen
synthesis); zinc for the enzyme systems; and amino acids play critical roles in the healing process.

Figure 2-1. The inflammatory response phase.

2-2. The fibroblastic-repair phase.

Figure 2-3. The maturation-remodeling phase.

INJURY MANAGEMENT USING MODALITIES

Traditionally in a clinical setting, injuries have been classified as being either acute injuries that result
from trauma or chronic injuries that result primarily from overuse. This operational definition is not
necessarily correct. If active inflammation is present that includes the classic symptoms of tenderness,
swelling, redness, and so on, the injury should be considered acute and must be treated accordingly,
using rest, ice, compression, and elevation.

7 Even if active inflammation persists for months following initial injury it should still be considered
acute. Classification of an injury should be made according to the existing signs and symptoms that
indicate the various stages of the healing process, and not according to time frames or mechanisms of
injury. Once the signs of acute inflammation are no longer present, the injury may be considered to be
chronic. Inflammation may be considered chronic when the normal cellular response in the
inflammatory process is altered, replacing leukocytes with macrophages and plasma cells, along with
degeneration of the injured structure. Based on this definition of acute and chronic injury, the
rehabilitation progression following injury may be determined by the four phases of healing. These
phases overlap, and the estimated time frames for each phase show extreme variability between
patients. Table 2-1 summarizes the various modalities that may be used in each of the four phases.

INITIAL ACUTE INJURY PHASE

Modality use in the initial treatment phase should be directed toward limiting the amount of swelling
and reducing pain that occurs acutely. The acute phase is marked by swelling, pain to touch or with
pressure, and pain on both active and passive motion. In general, the less initial swelling, the less the
time required for rehabilitation. Traditionally, the modality of choice has been and still is ice. Cryotherapy
is known to produce vasoconstriction, at least superficially and perhaps indirectly in the deeper tissues,
and thus limits the bleeding that always occurs with injury. Ice bags, cold packs, and ice massage may all
be used effectively. Cold baths should be avoided because the extremities must be placed in a gravity-
dependent position. Cold whirlpools also place the extremities in the gravitydependent position and
produce a massaging action that is likely to retard clotting. The importance of applying ice immediately
following injury for limiting acute swelling through vasoconstriction has probably been overemphasized.
The initial use of ice is more important for producing analgesia, which occurs through stimulation of
sensory cutaneous nerves that blocks or reduces pain by way of the gating mechanism.

Treatment Tip

Immediately following injury the therapist should use cryotherapy, some type of compression
device,along with elevation to control swelling initially. Additionally, electrical stimulating currents may
be used to help provide analgesia, and ultrasound can be used to facilitate healing. Immediate
compression has been demonstrated to be an effective technique for limiting swelling. An intermittent
compression device may be used to provide even pressure around an injured extremity. The pressurized
sleeve mechanically reduces the amount of space available for swelling to accumulate. Units that
combine both compression and cold have been shown to be more effective in reducing swelling than
using compression alone. Regardless of the specific techniques selected, cold and compression should
always be combined with elevation to avoid any additional pooling of blood in the injured area owing to
the effects of gravity.

Electrical stimulating currents may also be used in the initial phase for pain reduction. Parameters should
be adjusted to maximally stimulate sensory cutaneous nerve fibers, again to take advantage of the gate
control mechanism of pain modulation. Intensities that produce muscle contractions should beavoided
because they may increase clotting time.

Ultrasound has been demonstrated to be effective in facilitating the healing process when used
immediately following injury and certainly within the first 48 hours. Low spatial-averaged intensities
below 0.2 W/cm2 produce nonthermal physiologic effects that alter the permeability of cell membranes
to sodium and calcium ions important in healing.

The low-power laser has also been shown to be effective in pain modulation through the stimulation of
trigger points and may be used acutely. The injured part should be rested and protected for at least the
first 48-72 hours to allow the inflammatory phase of the healing process to proceed naturally.

INFLAMMATORY-RESPONSE PHASE
The inflammatory response phase begins as early as day 1 and may last as long as day 6 following injury.
Clinically, swelling begins to subside and eventually stops altogether. The injured area may feel warm to
the touch, and some discoloration usually is apparent. The injury is still painful to the touch, and pain is
elicited on movement of the injured part. As in the initial injury stage, modalities should be used to
control pain and reduce swelling. Cryotherapy should still be used during the inflammatory stage. Ice
bags, cold packs, or ice massages provide analgesic effects. The use of cold also reduces the likelihood of
swelling, which may continue during this stage. Swelling subsides completely by the end of this phase. It
must be emphasized that heating an injury too soon is a bigger mistake than prolonged use of ice. Many
therapists elect to stay with cryotherapy for weeks following injury; in fact, some never switch to the
superficial heating techniques. This procedure is simply a matter of personal preference that should be
dictated by experience. Once swelling has stopped, the therapist may elect to begin contrast baths with
a longer cold-to-hot ratio. An intermittent compression device may be used to decrease swelling by
facilitating resorption of the by-products of the inflammatory process by the lymphatic system. Electrical
stimulating currents and low-power laser can be used to help reduce pain. After the initial stage, the
patient should begin to work on active and passive range of motion. Decisions regarding how rapidly to
progress with exercise should be determined by the response of the injury to that exercise. If exercise
produces additional swelling and markedly exacerbates pain, then the level or intensity of the exercise is
too great and should be reduced. Therapists should be aggressive in their approach to rehabilitation, but
the approach will always be limited by the healing process.