Chapter 2. Tissue Behavior, Injury, Healing, and Treatment

At the completion of this chapter, the reader will be able to:

1. Describe the various types of stress that can be applied to the body.

2. Describe the various physiological processes by which the body adapts to stress.

3. Define the various common mechanisms of injury.

4. Describe the etiology and pathophysiology of musculoskeletal injuries associated with various types of body tissue.

5. Outline the pathophysiology of the healing process and the various stages of healing.

6. Describe the methods used to enhance healing and the factors that can impede the healing process.

7. Outline the more common surgical procedures available for musculoskeletal injuries.

8. Outline the principles behind postsurgical rehabilitation.

9. Describe the detrimental effects of immobilization.

Tissues in the body are designed to function while undergoing stresses of everyday living. This ability to respond to stress is due to the differing viscoelastic properties of musculoskeletal tissue, with each tissue responding to stress in an individual manner based on design. One of the contributing factors to maintaining musculoskeletal health is the ability of the biological tissues to withstand various stresses and strains that occur during activity—body weight, friction, and air or water resistance are all types of stresses that commonly act on the body. Maintaining this health is a delicate balance, because insufficient, excessive, or repetitive stresses can prove deleterious. The healing process is an intricate phenomenon that occurs following an injury or disease.

Kinetics is the term applied to the forces acting on the body. Posture and movement are both governed by the control of forces. The same forces that move and stabilize the body also have the potential to deform and injure the body.1 A wide range of external and internal forces are either generated or resisted by the human body during the course of daily activities. Examples of these external forces include ground reaction force, gravity, and applied force through contact. Examples of internal forces include muscle contraction, joint contact, and joint shear forces (Fig. 2-1). Under the right circumstances, the body is able to respond to these stresses. The terms stress and strain have specific mechanical meanings. Stress or load is given in units of force per area, and is used to describe the type of force applied. Stress is independent of the amount of a material, but is directly related to the magnitude of force and inversely related to the unit area.2 Strain is defined as the change in length of a material due to an imposed load divided by the original length.2 The two basic types of strain are linear strain, which causes a change in the length of a structure, and shear strain, which causes a change in the angular relationships within a structure. It is the concentration of proteoglycans in solution (see Chap. 1) that is responsible for influencing the mechanical properties of the tissue, including compressive stiffness, sheer stiffness, osmotic pressure, and regulation of hydration.3

The inherent ability of a tissue to tolerate load can be observed experimentally in graphic form. When any stress is plotted on a graph against the resulting strain for a given material, the shape of the resulting load-deformation curve depends on the kind of material involved. The load-deformation curve, or stress–strain curve, of a structure (Fig. 2-2) depicts the relationship between the amount of force applied to a structure and the structure's response in terms of deformation or acceleration. The horizontal axis (deformation or strain) represents the ratio of the tissue's deformed length to its original length. The vertical axis of the graph (load or stress) denotes the internal resistance generated as a tissue resists its deformation, divided by its cross-sectional area. The load-deformation curve can be divided into four regions, each region representing a biomechanical property of the tissue (Fig. 2-2):

• Toe region. Collagen fibers have a wavy, or folded, appearance at rest. When a force that lengthens the collagen fibers is initially applied to connective tissue, these folds are affected first. As the fibers unfold, the slack is taken up (see Crimp later). The toe region is an artifact caused by this take-up of slack, alignment and/or seating of the test specimen. The length of the toe region depends upon the type of material and the waviness of the collagen pattern.
• Elastic deformation region. Within the elastic deformation region, the structure imitates a spring—the geometric deformation in the structure increases linearly with increasing load, and after the load is released the structure returns to its original shape. The slope of the elastic region of the load-deformation curve from one point in the curve to another is called the modulus of elasticity or Young's modulus, and represents the extrinsic stiffness or rigidity of the structure—the stiffer the tissue, the steeper the slope. Young's modulus is a numerical description of the relationship between the amount of stress a tissue undergoes and the deformation that results. The ratio of stress to strain in an elastic material is a measure of its stiffness. Mathematically, the value for stiffness is found by dividing the load by the deformation at any point in the selected range. All normal tissues within the musculoskeletal system exhibit some degree of stiffness. Young's modulus is independent of specimen size and is, therefore, a measure of the intrinsic stiffness of the material. The greater the Young's modulus for a material, the better it can withstand greater forces. Larger structures will have greater rigidity than smaller structures of similar composition.
• Plastic deformation region. The end of the elastic deformation range and the beginning of the plastic deformation range represents the point where an increasing level of stress on the tissue results in progressive failure and microscopic tearing of the collagen fibers. Further increases in strain result in microscopic damage and in permanent deformation. The permanent change results from the breaking of bonds and their subsequent inability to contribute to the recovery of the tissue. Unlike the elastic region, removal of the load in this region will not result in a return of the tissue to its original length.
• Failure region. Deformations exceeding the ultimate failure point (Fig. 2-2) produce mechanical failure of the structure, which in the human body may be represented by the fracturing of bone or the rupturing of soft tissues.

Biological tissues are anisotropic, which means they can demonstrate differing mechanical behavior as a function of test direction. The properties of extensibility and elasticity are common to many biologic tissues. Extensibility is the ability to be stretched and elasticity is the ability to return to normal length after lengthening or shortening.4

A number of protective mechanisms exist in connective tissue to help respond to stress and strain including crimp, viscoelasticity, creep and stress relaxation, plastic deformation, and stress response.

Crimp

The crimp of collagen is one of the major factors behind the viscoelastic properties of connective tissue. Crimp, a collagen tissue's first line of response to stress, is different for each type of connective tissue, providing each with different viscoelastic properties. Collagen fibers are oriented obliquely when relaxed. However, when a load is applied, the fibers line up in the direction of the applied force as they uncrimp. Crimping is seen primarily in ligaments, tendons, and joint capsules. and occurs in the toe phase of the stress-strain curve (Fig. 2-2).

Viscoelasticity

Viscoelasticity is the time-dependent mechanical property of a material to stretch or shorten over time, and to return to its original shape when a force is removed. The mechanical qualities of a tissue can be separated into categories based on whether the tissue acts primarily like a solid, a fluid, or a mixture of the two. Solids are described according to their elasticity, strength, hardness, and stiffness. Bone, ligaments, tendons, and skeletal muscle are all examples of elastic solids. Biological tissues that demonstrate attributes of both solids and fluids are viscoelastic. The viscoelastic properties of a structure determine its response to loading. For example, a ligament demonstrates more viscous behavior at lower loads whereas, at higher loads, elastic behaviors dominate.5

Creep and Stress Relaxation

Creep and stress relaxation are two characteristics of viscoelastic materials that are used to document their behavior quantitatively.4

Creep is the gradual rearrangement of collagen fibers, proteoglycans, and water that occurs because of a constantly applied force after the initial lengthening caused by crimp has ceased. Creep is a time-dependent and transient biomechanical phenomenon. Short duration stresses (<15 minutes) do not have sufficient time to produce this displacement; however, longer times can produce it. Once creep occurs, the tissue has difficulty returning to its initial length (see below).

Stress relaxation is a phenomenon in which stress or force in a deformed structure decreases with time, while the deformation is held constant.4 Unlike creep, stress relaxation responds with a high initial stress that decreases over time until equilibrium is reached and the stress equals zero, hence the label “relaxation”. As a result, no change in length is produced.

Thus, stress to connective tissues can result in no change, a semipermanent change, or a permanent change to the microstructure of the collagenous tissue. The semipermanent or permanent changes may result in either microfailure or macrofailure.

Plastic Deformation

Plastic deformation of connective tissue occurs when a tissue remains deformed and does not recover its prestress length. Once all of the possible realignment has occurred, any further loading breaks the restraining bonds, resulting in microfailure. On average, collagen fibers are able to sustain a 3% increase in elongation (strain) before microscopic damage occurs.6 Following a brief stretch, providing the chemical bonds remain intact, the collagen and proteoglycans gradually recover their original alignment. The recovery process occurs at a slower rate and often to a lesser extent. The loss of energy that occurs between the lengthening force and the recovery activity is referred to as hysteresis. The more chemical bonds that are broken with applied stress, the greater the hysteresis. If the stretch is of sufficient force and duration and a sufficient number of chemical bonds are broken, the tissue is unable to return to its original length until the bonds are re-formed. Instead, it returns to a new length and to a new level of strain resistance. Increased tissue excursion is now needed before tension develops in the structure. In essence, this has the effect of decreasing the stabilizing capabilities of the connective tissue.

Stress Response

Exercises may be used to change the physical properties of both muscles/tendons and ligaments, as both have demonstrated adaptability to external loads with an increase in strength: weight ratios.7–9 The improved strength results from an increase in the proteoglycan content and collagen cross-links.7–9

Soft-tissue injuries of all types are extremely common in the general population. Studies have shown that there is a linear relationship between soft-tissue injuries and aging, with fewer than 10% of individuals younger than 34 years being affected, in contrast to 32–49% of those older than 75 being affected.10 Whether a stress proves to be beneficial or detrimental to a tissue is very much dependent on the physiologic capacity of the tissue to accept load. This capacity is dependent on a number of factors, among them:

• Health of the tissue. Healthy tissues are able to resist changes in their shape. Any tissue weakened by disease or trauma may not be able to adequately resist the application of force.
• Age. Increasing age reduces the capacity of the tissues to cope with stress loading.
• Proteoglycan and collagen content of the tissue. Both increasing age and exposure to trauma can result in unfavorable alterations in the proteoglycan and collagen content of the tissue.
• Ability of the tissue to undergo adaptive change. All musculoskeletal tissue has the capacity to adapt to change. This capacity to change is determined primarily by the viscoelastic property of the tissue.
• The speed at which the adaptive change occurs. This is dependent on the type and severity of the insult to the tissue. Insults of low force and longer duration may provide the tissue an opportunity to adapt. In contrast, insults of a higher force and shorter duration are less likely to provide the tissue time to adapt. The distinction between sudden and repetitive stress is important. An acute stress (loading) occurs when a single force is large enough to cause injury on biological tissues; the causative force is termed macrotrauma. A repetitive stress (loading) occurs when a single force itself is insufficient to cause injury on biological tissues. However, when repeated or chronic stress over a period of time causes an injury, the injury is called a chronic injury, and the causative mechanism is termed microtrauma. Etiologic factors for microtraumatic injuries are of two basic types: intrinsic or extrinsic. Intrinsic factors are physical characteristics that predispose an individual to microtrauma injuries and include muscle imbalances, leg length discrepancies, and anatomical anomalies.11 Extrinsic factors, which are the most common cause of microtrauma injuries, are related to the external conditions under which the activity is performed. These include training errors, type of terrain, environmental temperature, and incorrect use of equipment.11

Injuries to the soft tissues can be classified as primary or secondary.

• Primary or macrotraumatic injuries can be self-inflicted, caused by another individual or entity, or caused by the environment.12–15 These injuries include fractures and dislocations, which are outside the scope of practice for a physical therapist, and subluxations, sprains, and strains, which make up the majority of conditions seen in the physical therapy clinic. For the purposes on the intervention, primary injuries are generally classified into acute, subacute, or chronic.
  • Acute. This type of injury is usually caused by macrotrauma and indicates the early phase of injury and healing, which typically lasts approximately 7–10 days.
  • Subacute. This phase occurs after the acute phase and typically lasts from 5–10 days after the acute phase has ended.
  • Chronic. This type of injury can have several definitions. On the one hand it may indicate the final stage of healing that occurs 26–34 days after injury. On the other hand the term may be applied to an injury that lasts longer than normal and does not appear to be improving due to a persistent inflammatory state. The persistent inflammatory state results in an accumulation of repetitive scar adhesions, degenerative changes, and other harmful effects referred to as subclinical adaptations.

Fortunately, the majority of tissue injuries heal without complication in a predictable series of events (Fig. 2-3). The most important factor regulating the regional time line of healing is sufficient blood flow.17 Complications such as infection, compromised circulation, and neuropathy have an adverse effect on the healing process and can cause great physical and psychological stress to the involved patients and their families.

Stages of Tissue Healing

The general stages of soft tissue healing are described here, whereas the healing of specific structures is described later under the relevant headings. After microtrauma, macrotrauma, or disease, the body attempts to heal itself through a predictable series of overlapping events that include coagulation and inflammation (acute), which begins shortly after the initial injury; a migratory and proliferative process (subacute), which begins within days and includes the major processes of healing; and a remodeling process (chronic), which may last for up to a year depending on the tissue type and is responsible for scar tissue formation and the development of new tissue.12,17–21

Whereas simplification of the complex events of healing into separate categories may facilitate understanding of the phenomenon, in reality these events occur as an amalgamation of different reactions, both spatially and temporally.22

Coagulation and Inflammation Stage

An injury to the soft tissue triggers a process that represents the body's immediate reaction to trauma.17,23 The reaction that occurs immediately after a soft tissue injury includes a series of repair and defensive events. Following an injury to the tissues, the cellular and plasma components of blood and lymph enter the wound. Capillary blood flow is disrupted, causing hypoxia to the area. The blood congeals and, through several steps, a clot is formed. This initial period of vasoconstriction, which lasts 5–10 minutes, prompts a period of vasodilation, and the extravasation of blood constituents.17 Extravasated blood contains platelets, which secrete substances that form a clot to prevent bleeding and infection, clean dead tissue and nourish white cells. These substances include macrophages and fibroblasts.24 Coagulation and platelet release results in the excretion of platelet-derived growth factor (PDGF),25 platelet factor 4,26 transforming growth factor-alpha (TGF-α),27 and transforming growth factor-beta (TGF-β).28 The main functions of a cell-rich tissue exudate are to provide cells capable of producing the components and biological mediators necessary for the directed reconstruction of damaged tissue while diluting microbial toxins and removing contaminants present in the wound.22

Inflammation is mediated by chemotactic substances, including anaphylatoxins that attract neutrophils and monocytes.

• Neutrophils. Neutrophils are white blood cells of the polymorphonuclear (PMN) leukocyte subgroup (the others being eosinophils, and basophils) that are filled with granules of toxic chemicals (phagocytes) that enable them to bind to microorganisms, internalize them, and kill them.
• Monocytes. Monocytes are white blood cells of the mononuclear leukocyte subgroup (the other being lymphocytes). The monocytes migrate into tissues and develop into macrophages, providing immunological defenses against many infectious organisms. Macrophages serve to orchestrate a “long term” response to injured cells subsequent to the acute response.29

The white blood cells of the inflammatory stage serve to clean the wound debris of foreign substances, increase vascular permeability, and promote fibroblast activity.29 Other cell participants include local immune accessory cells, such as endothelial cells, mast cells, and tissue fibroblasts. The PMN leukocytes, through their characteristic “respiratory burst” activity, produce superoxide anion radical, which is well known to be critical for defense against bacteria and other pathogens.30 Superoxide is rapidly converted to a membrane permeable form, hydrogen peroxide (H2O2), by superoxide dismutase activity or even spontaneously.29 Release of H2O2 may promote formation of other oxidants that are more stable (longer half-life) including hypochlorous acid, chloramines, and aldehydes.29 The phagocytic cells that initiate the innate immune response produce a set of proinflammatory cytokines (e.g., TNF-α, IL-1, and IL-6) in the form of a cascade that amplifies the local inflammatory response, influences the adaptive immune response, and serves to signal the CNS of an inflammatory response. The extent and severity of this inflammatory response depend on the size and the type of the injury, the tissue involved, and the vascularity of that tissue.15,20,31–33

Local vasodilation is promoted by biologically active products of the complement and kinin cascades22:

• The complement cascade involves 20 or more proteins that circulate throughout the blood in an inactive form.22 After tissue injury, activation of the complement cascade produces a variety of proteins with activities essential to healing.
• The kinin cascade is responsible for the transformation of the inactive enzyme kallikrein, which is present in both blood and tissue, to its active form, bradykinin. Bradykinin also contributes to the production of tissue exudate through the promotion of vasodilation and increased vessel-wall permeability.34

Because of the variety of vascular and other physiological responses occurring, this stage of healing is characterized by swelling, redness, heat, and impairment or loss of function. The edema is due to an increase in the permeability of the venules, plasma proteins, and leukocytes, which leak into the site of injury, resulting in edema.35,36 New stroma, often called granulation tissue, begins to invade the wound space approximately 4 days after injury.35,36 The complete removal of the wound debris marks the end of the inflammatory process.

Clinically, this stage is characterized by pain at rest or with active motion, or when specific stress is applied to the injured structure. The pain, if severe enough, can result in muscle guarding and a loss of function.

Two key types of inflammation are recognized: the normal acute inflammatory response and an abnormal, chronic, or persistent inflammatory response. Common causes for a persistent chronic inflammatory response include infectious agents, persistent viruses, hypertrophic scarring, poor blood supply, edema, repetitive mechanical trauma, excessive tension at the wound site, and hypersensitivity reactions.37,38 The monocyte-predominant infiltration, angiogenesis, and fibrous change are the most characteristic morphologic features of chronic inflammation. This perpetuation of inflammation involves the binding of neutrophilic myeloperoxidase to the macrophage mannose receptor.39

Migratory and Proliferative Stage

The second stage of soft tissue healing, characterized by migration and proliferation, usually occurs from the time of the initial injury and overlaps the inflammation phase. Characteristic changes include capillary growth and granulation tissue formation, fibroblast proliferation with collagen synthesis, and increased macrophage and mast cell activity. This stage is responsible for the development of wound tensile strength.

After the wound base is free of necrotic tissue, the body begins to work to close the wound. The connective tissue in healing wounds is composed primarily of collagen, types I and III,40 cells, vessels, and a matrix that contains glycoproteins and proteoglycans. Proliferation of collagen results from the actions of the fibroblasts that have been attracted to the area and stimulated to multiply by growth factors, such as PDGF, TGF-β, fibroblast growth factor (FGF), epidermal growth factor, and insulin-like growth factor-1, and tissue factors such as fibronectin.22 This proliferation produces first fibrinogen and then fibrin, which eventually becomes organized into a honeycomb matrix and walls off the injured site.41

The wound matrix functions as a glue to hold the wound edges together, giving it some mechanical protection while also preventing the spread of infection. However, the wound matrix has a low tensile strength and is vulnerable to breakdown until the provisional extracellular matrix (ECM) is replaced with a collagenous matrix. The collagenous matrix facilitates angiogenesis by providing time and protection to new and friable vessels. Angiogenesis occurs in response to the hypoxic state created by tissue damage as well as to factors released from cells during injury.22

The process of neovascularization during this phase provides a granular appearance to the wound as a result of the formation of loops of capillaries and migration of macrophages, fibroblasts, and endothelial cells into the wound matrix. Once an abundant collagen matrix has been deposited in the wound, the fibroblasts stop producing collagen, and the fibroblast-rich granulation tissue is replaced by a relatively acellular scar, marking the end of this stage.

This fibrous tissue repair process occurs gradually and can last anywhere from 5 to 15 days to approximately 10 weeks, depending on the type of tissue and the extent of damage.42 Upon progressing to this stage, the active effusion and local erythema of the inflammation stage are no longer present clinically. However, residual effusion may still be present at this time and resist resorption.43,44

Remodeling Stage

An optimal wound environment lessens the duration of the inflammatory and proliferative phases and protects fragile tissue from breakdown during early remodeling. The remodeling phase involves a conversion of the initial healing tissue to scar tissue. This lengthy phase of contraction, tissue remodeling, and increasing tensile strength in the wound can last for up to 1 year. Fibroblasts are responsible for the synthesis, deposition, and remodeling of the ECM. Following the deposition of granulation tissue, some fibroblasts are transformed into myofibroblasts, which congregate at the wound margins and start pulling the edges inward, reducing the size of the wound. Increases in collagen types I and III and other aspects of the remodeling process are responsible for wound contraction and visible scar formation. Epithelial cells migrate from the wound edges and continue to migrate until similar cells from the opposite side are met. This contracted tissue, or scar tissue, is functionally inferior to original tissue and is a barrier to diffused oxygen and nutrients.45 Eventually, the new epidermis becomes toughened by the production of the protein keratin. The visible scar changes color from red or purple that blanches with slight pressure to nonblanchable white as the scar matures.

Imbalances in collagen synthesis and degradation during this phase of healing may result in hypertrophic scarring or keloid formation with superficial wounds. If the healing tissues are kept immobile, the fibrous repair is weak and there are no forces influencing the collagen—if left untreated, the scar formed is less than 20% of its original size.46 Contraction of the scar results from cross-linking of the collagen fibers and bundles, and adhesions between the immature collagen and surrounding tissues, producing hypomobility. In areas where the skin is loose and mobile, this creates minimal effect. However, in areas such as the dorsum of the hand where there is no extra skin, wound contracture can have a significant effect on function. Consequently, controlled stresses must always be applied to new scar tissue to help prevent it from shortening.17,33 Scarring that occurs parallel to the line of force of a structure is less vulnerable to reinjury than a scar that is perpendicular to those lines of force.47

Normally, the remodeling phase is characterized by a progression to pain-free function and activity. Clinically, the chronic inflammatory response is characterized by the signs and symptoms of acute inflammation (redness, heat, edema, and pain), but at a much less pronounced level. In the ideal world, the injured patient makes a smooth transition through the various stages of healing, and the sharp and burning acute pain is replaced by a duller ache, which then subsides to a point where no pain is felt. However, a persistent chronic inflammatory response results in the continued release of inflammatory products and a local proliferation of mononuclear cells. The macrophages remain in the inflamed tissue if the acute inflammation does not resolve, and begin to attract large numbers of fibroblasts, which invade and produce increased quantities of collagen.11 This failure during the healing phase continuum can result in chronic pathologic changes in the tissue. Often, the increased collagen production results in decreased extensibility of a joint or soft tissue structure. Characteristics of this chronic inflammation include a physiologic response that is resistant to both physical and pharmacologic intervention, resulting in a failure to remodel adequately, an imperfect repair, and a persistence of symptoms.37,49 In addition, fibrosis can occur in synovial structures, and in extra-articular tissues, including tendons and ligaments; in bursa; or in muscle.

Many factors can determine the outcome of the tissue injury, including those listed in Table 2-1. The focus of the rehabilitation should be to improve an individual's range of motion, flexibility, strength, and coordination to a level that approximate the demands of the desired activity (speed, agility, strength, power, endurance, etc.).

As outlined in Chapter 1, muscles primarily function to mechanically transmit the forces generated by the skeletal muscle cells to provide movement.

Behavior

There are approximately 430 skeletal muscles in the body, each of which can be considered anatomically as a separate organ. Of these 430 muscles, about 75 pairs provide the majority of body movements and postures.50 Like any collagenous tissue, the musculotendinous unit exhibits viscoelastic properties (stress relaxation, creep, hysteresis, etc.) allowing it to respond to load and deformation appropriately, with the rate of deformation being directly proportional to the applied force when considering the viscous property. Three important factors can influence muscle performance:51

• Age. With aging, the cross-sectional area of muscle decline and the number of muscle fibers decreases by about 39% by age 80.52 Type I muscle fibers are not affected much by aging, but type II fibers demonstrate a reduction in cross-sectional area of 26% from age 20 to 80, most likely a result of denervation.53 These changes seem to be secondary to the declining demand of the muscle and lack of physical activity, and thus can be minimized or even reversed with adequate training.52
  • Temperature. Collagenous tissues have an inverse temperature-elastic modulus relationship, especially at higher temperatures, which means that temperature elevation results in increased elasticity and decreased stiffness.54 This would suggest that warming a muscle may confer a protective effect against muscle strain injury as warmer muscles must undergo greater deformation before failure. However, somewhat contradictory, a warm muscle may be prone to injury because it undergoes greater deformation to attain a given load.
  • Immobilization or disuse. The effect of rigid immobilization on muscle has been well detailed (see Detrimental Effects of Immobilization later). However the results of restricted motion, in which joint and associated muscles are not allowed to move through the complete range, have not been well studied. Biomechanically, muscle immobilized in a shortened position develops less force and stretches to a shorter length before injury than does a nonimmobilized muscle. Muscle immobilized in a lengthened position responds differently; greater force and a greater change in length are required to cause a tear than in nonimmobilized muscle.

Injury

Muscle injury can result from excessive strain, excessive tension, contusions, lacerations, thermal stress, and myotoxic agents, such as some local anesthetics, excessive use of corticosteroids, and snake and bee venoms.55 The majority of muscle injuries (>90%) are caused either by excessive strain of the muscle or by contusion.56 Muscle strains may be graded by severity (Table 2-2). Muscle injuries are the most common injury in sports, with an incidence varying from 10 to 55% of all injuries sustained in sport events.57,58 A number of factors contribute to muscle strain injury including51

• inadequate flexibility
• inadequate strength or endurance
• dyssynergistic muscle contraction
• insufficient warm-up
• inadequate rehabilitation from previous injury.

A distraction strain occurs in a muscle to which an excessive pulling force is applied, resulting in overstretching.58 A contusion may occur if a muscle is injured by a heavy compressive force, such as a direct blow. At the site of the direct blow, a hematoma may develop. Two types of hematoma can be identified:59

1. Intramuscular. This type of hematoma is associated with a muscle strain or bruise. The size of the hematoma is limited by the muscle fascia. Clinical findings may include pain and loss of function.

2. Intermuscular. This type of hematoma develops if the muscle fascia is ruptured and the extravasated blood spreads into the interfascial and interstitial spaces. The pain is usually less severe with this type.

Healing

Skeletal muscle has considerable regenerative capabilities, and the process of skeletal muscle regeneration after injury is a well-studied cascade of events.60–62 The essential process of muscle regeneration is similar, irrespective of the cause of injury, but the outcome and time course of regeneration vary according to the type, severity, and extent of the injury.60,63,64 Broadly speaking, there are three phases in the healing process of an injured muscle: the destruction phase, the repair phase, and the remodeling phase.59

Destruction Phase

The muscle fibers and their connective tissue sheaths are totally disrupted, and a gap appears between the ends of the ruptured muscle fibers when the muscle fibers retract.62 This phase is characterized by the necrosis of muscle tissue, degeneration, and an infiltration by PMN leukocytes as hematoma and edema form at the site of injury.

Repair Phase

The repair phase usually involves the following steps:

• Hematoma formation. The gap between the ruptured ends of the fibers is at first filled by a hematoma. During the first day, the hematoma is invaded by inflammatory cells, including phagocytes, which begin disposal of the blood clot.62
• Matrix formation. Blood-derived fibronectin and fibrin cross-link to form a primary matrix, which acts as a scaffold and anchorage site for the invading fibroblasts.61,62 The matrix gives the initial strength for wound tissue to withstand the forces applied to it.65 Fibroblasts begin to synthesize proteins of the ECM.
• Collagen formation. The production of type I collagen by fibroblasts increases the tensile strength of the injured muscle. An excessive proliferation of fibroblasts can rapidly lead to an excessive formation of dense scar tissue, which creates a mechanical barrier that restricts or considerably delays complete regeneration of the muscle fibers across the gap.59,62

During the first week of healing the injury site is the weakest point of the muscle–tendon unit. This phase also includes regeneration of the striated muscle, production of a connective-tissue scar, and capillary ingrowth. The regeneration of the myofibers begins with the activation of satellite cells, located between the basal lamina and the plasma membrane of each individual myofiber.66

Satellite cells, myoblastic precursor cells, proliferate to reconstitute the injured area.64 During muscle regeneration, it is presumed that trophic substances released by the injured muscle activate the satellite cells.67 Unlike the multinucleated myofibers, these mononuclear cells maintain mitotic potential and respond to cellular signals by entering the cell cycle to provide the substrate for muscle regeneration and growth.66

The satellite cells proliferate and differentiate into multinucleated myotubes and eventually into myofibers, which mature and increase in length and diameter to span the muscle injury. Many of these myoblasts are able to fuse with existing necrosed myofibers and may prevent the muscle fibers from completely degenerating.66

The final stage in the regenerative process involves the integration of the neural elements and the formation of a functional neuromuscular junction.68,69 Provided that the continuity of the muscle fiber is not disrupted and the innervation, vascular supply, and ECM are left intact, muscle will regenerate without loss of normal tissue architecture and function.70

Remodeling Phase

In this phase, the regenerated muscle matures and contracts with reorganization of the scar tissue. There is often complete restoration of the functional capacity of the injured muscle.

The pathology of skeletal muscle damage varies, depending on the initiating cause. Muscle damage can occur during the prolonged immobility of hospitalization and from external sources such as mechanical injury.71 One of the potential consequences of muscle injury is atrophy. The amount of muscle atrophy that occurs depends on the usage prior to bed rest and the function of the muscle.71 Antigravity muscles (such as the quadriceps) tend to have greater potential for atrophy than antagonist muscles (such as the hamstrings). Research has shown that a single bout of exercise protects against muscle damage, with the effects lasting between 6 weeks72 and 9 months.73

Muscle resistance to damage may result from an eccentric exercise-induced morphologic change in the number of sarcomeres connected in series.74 This finding appears to support initiating a reconditioning program with gradual progression from lower intensity activities with minimal eccentric actions to protect against muscle damage.71,75

Treatment

The tensile strength of the healing muscle tissue increases over time. However, whereas normal intramuscular collagenous tissue has a greater proportion of type I collagen than type III collagen, initially after injury, type III collagen demonstrates a significant increase over type I collagen in the area of repair. Over time, the proportion of type I to type III collagen returns to normal. Controlled mobility and stress are key considerations in the post injury period to allow scar formation, muscle regeneration, correct orientation of new muscle fibers, and the normalization of the tensile properties of muscle. The following principles should guide the clinician when rehabilitating a muscle injury:51

• Prevention is easier than treatment.
• Intervention depends on the stage of healing.
• Controlled mobility and activity are best.
• Medications and modalities are important adjuncts to care.
• It is important to develop strong, flexible tissue using pain as the guiding factor.

Muscle and Aging

With age, there is a reduction in the ability to produce and sustain muscular power. This age-related phenomenon, termed senescence sarcopenia, can result in a 20–25% loss of skeletal muscle mass.76

Sarcopenia has important consequences. The loss of lean body mass reduces function, and loss of approximately 40% of lean body mass is fatal.77,78 Sarcopenia is distinct from wasting—involuntary weight loss resulting from inadequate intake, which is seen in starvation, advanced cancer, or acquired immunodeficiency syndrome.

While a variety of studies have investigated the underlying mechanisms and treatments of age-related muscle loss, very few epidemiologic studies have looked at the prevalence, incidence, pathogenesis, and consequences of sarcopenia in elderly populations. It is likely that the determinants of sarcopenia are multifactorial and include genetic factors, environmental factors, and age-related changes in muscle tissue.79

The effects of aging on muscle morphology have been studied. Aging causes a decrease in muscle volume,80 with type II fiber apparently being more affected by gradual atrophy.81 Specifically, there is a disproportionate atrophy of type IIa muscle fibers with aging. These losses of muscular strength and muscle mass can have important health consequences, because they can predispose the elderly to disability, an increased risk of falls and hip fractures, and a decrease in bone mineral density.

As outlined in Chapter 1, tendons primarily function to transmit force between muscle and bone.82

Behavior

The organization of the tendon determines its mechanical behavior. Because tendons have more parallel collagen fibers than ligaments, and less realignment occurs during initial loading, the toe region of the load-deformation curve is smaller in tendons than in ligaments.83 As force is applied to the tendon, a straightening of the crimp results in the toe region in the load-deformation curve, where little force is required to change tendon length.82 As the load increases beyond the toe region, the collagen fibrils stretch, creating the linear region of the load-deformation curve.82 Most tendons likely function in the toe and early linear regions under physiological loading conditions.84 The total amount of load the tendon can resist and the amount it stretches during loading depend on its cross-sectional area, composition, and length. However, tendons can adapt structurally or materially to changes in the mechanical environment as a result of load conditions.84 The compliance of tendons varies. Tendons of the digital flexors and extensors are very stiff, and their length changes very little when muscle forces are applied through them. In contrast, the tendons of some muscles, particularly those involved in locomotion and ballistic performance, are more elastic. For example, the Achilles tendon is stretched during the late stance phase in gait as the triceps surae is stretched as the ankle dorsiflexes. Near the beginning of the plantar flexion contraction, the muscle activation ceases and energy stored in the stretched tendon helps to initiate plantar flexion.

Injury

Tendons that transmit large loads under eccentric and elastic conditions are more subject to injury.85 Most tendon injuries tend to occur from loading (sudden overload or repetitive), or rapid unloading. However, mechanical overload does not seem to be the only factor to explain a tendon injury and may even be merely a permissive factor, allowing the tendon problem to become symptomatic.86

While it is easy to understand why a sudden overload could damage a tendon, it is not fully understood why the application of normal loads, repeated frequently, cause tendon damage. Repetitive loading can occur as a result of external factors, such as anatomic predisposition resulting from inflexibility, weakness, or malposition, excessive compression and friction.87–89

Muscle physiology experiments have shown the force increases as the velocity of active muscle lengthening (eccentric) increases, while the opposite is true during concentric (shortening) muscle activations (see Chap. 1). Indeed, the tendon is exposed to larger loads during eccentric loading, especially if the movement occurs rapidly.91,92 Almost all concentric contractions are preceded by a lengthening (eccentric) while the muscle is active. This activation pattern stretches the elastic elements in the muscle–tendon unit and contributes to movement if the muscle is allowed to immediately shorten after being lengthened.84

Terminology regarding tendon pathology has been somewhat confusing. Tendon injuries are typically classified as either acute or chronic.

• Acute injuries. Acute injuries include those in which the time and method of injury are known.84 Acute injuries include tendon rupture and partial tendon tears. The term tendinitis implies an acute inflammatory reaction of the tendon, which is described as a microscopic tearing and inflammation of the tendon tissue, commonly resulting from tissue fatigue rather than direct trauma. Tendinitis can be graded according to severity:
  • Grade I: Pain only after activity; does not interfere with performance; often generalized tenderness; disappears before the next exercise session.
  • Grade II: Minimal pain with activity; does not interfere with intensity or distance; usually localized tenderness.
  • Grade III: Pain interferes with activity; usually disappears between sessions; definite local tenderness.
  • Grade IV: Pain does not disappear between activity sessions; seriously interferes with intensity of training; significant local signs of pain, tenderness, crepitus, and swelling.
  • Grade V: Pain interferes with sport and activities of daily living; symptoms often chronic or recurrent; signs of tissue changes and altered associated muscle function.
• Chronic injuries. Chronic tendon injuries are not typically associated with a known onset or with inflammation, but involve repetitive loading that damages the tendon. Chronic injuries of the tendon can be separated into superficial and intratendon pathology. Paratenonitis is an inflammation of the outermost layer of the tendon, and may be accompanied by synovitis of the tendon sheath, referred to as tenosynovitis. Tendinosis is an intratendinous degenerative lesion without an inflammatory component (the suffix “-osis” is indicative of a degenerative process rather than an inflammatory disorder). Although these two pathologic processes can occur together, they are generally regarded as distinct independent conditions.95

A tendinosis is characterized by the presence of dense populations of fibroblasts, vascular hyperplasia, and disorganized collagen.96 The disorganized collagen is termed angiofibroblastic hyperplasia.97 Degenerative tendinopathy occurs in approximately one-third of the population older than 35 years of age.98 Although it is commonly presumed that pain results from an inflamed structure, it is not clear why tendinosis is painful, given the absence of acute inflammatory cells, nor is it known why the collagen fails to mature. Necropsy studies have shown that these degenerative changes also may be present in asymptomatic tendons.99 The degree of degeneration increases with age and may represent part of the normal aging process.100 The degeneration appears to be activity related, as well.100

The typical clinical finding for tendinopathy is a strong but painful response to resistance of the involved musculotendinous structure.

Healing

Acute tendon injuries that disrupt vascular tissues within the tendon result in a well studied healing process involving three overlapping phases:101

• Inflammation: this occurs as a hematoma forms within erythrocytes and activated platelets. This is followed by the infiltration of inflammatory cells, including neutrophils, monocytes, and macrophages that migrate to the injury site to remove debris. Shortly after, chemotactic signals induce fibroblasts to start synthesizing collagen.95
• Repair: this phase involves the deposition of collagen and tendon matrix components.
• Remodeling: during this phase the collagen becomes more structured and organized, although the injured site never achieves the original histologic or mechanical features of a healthy uninjured tendon.

Unlike most soft tissue healing, healing tendons pose a particular problem as they require both extensibility and flexibility at the site of attachment.16,102–104 Following injury, the initial inflammatory stage triggers an increase in glycosaminoglycans (GAG) synthesis within days, rapidly followed by synthesis of types I and III collagen, such that the healing wound can be subjected to low levels of force within a matter of days.84,102–105

Treatment

While the treatment for tendinopathy is relatively straightforward, tendinopathies are difficult to grade in terms of providing guidance for treatment or prognosis. In either case, a judicious application of force must be used to encourage the new collagen fibrils to align in the direction of force application.84 The major difference between the treatment of a tendinitis and a tendinosis is that controlling inflammation is the focus of the former, whereas loading based rehabilitation is the focus of the latter. Table 2-3 outlines some guidelines for treatment. Treatment of tendinosis involves a multifaceted approach, which includes84

• the identification and removal of all negative internal and/or external forces/factors
• the establishment of a stable baseline for treatment
• the determination of the tensile load starting point
• a progression of the loading program according to the patient's symptoms. Studies have shown that exercise, particularly eccentric-based exercise (Table 2-3), has positive effects on the mechanical and structural properties of tendons:
  • Nakamura and colleagues106 demonstrated that eccentric exercises contributed to stable angiogenesis in early tendon injury whereas concentric exercises did not. Daily eccentric exercises were clinically beneficial and not harmful to tendon microcirculation.
  • Knobloch and colleagues107 showed in a controlled study that in tendinosis lesions, an eccentric loading program resulted in a significant decrease in the paratenon vascularity and pain while not changing the oxygen saturation of the paratenon tissues.
  • Shalabi and colleagues108 demonstrated decreased tendon volume, decreased MRI signal in the tendinosis lesions, and improved clinical pain scores in patients with Achilles tendinosis who were treated with eccentric training regimens.

Conversely, immobilization adversely affects the biomechanical properties of a tendon, resulting in decreased tensile strength, increased stiffness, and a reduction in total weight.83

• The control of pain.
• Addressing the entire kinetic chain.

In addition, other modes of conservative treatment can be incorporated including:95

• Extracorporeal shockwave therapy (ESWT). Chen and colleagues109 demonstrated that ESWT promoted tendon healing in a collagenase induced tendinopathy of a rat tendon. Rompe and colleagues110 showed in a randomized controlled trial that eccentric exercise, combined with ESWT, was more effective than eccentric exercise alone. In contrast, Zwerver and colleagues111 found that when ESWT was used as a solitary treatment during the competitive season it demonstrated no benefit over placebo treatment in the management of actively competing jumping athletes with patellar tendinopathy who had symptoms for less than 12 months.112
• Nonsteroidal anti-inflammatory agents (NSAIDs) and corticosteroids. Although steroids have been commonly used in the treatment of tendinosis, their benefit appears to be limited to short-term improvement in pain (i.e., <6 weeks), as there is no evidence to suggest long-term improvement.113 This lack of efficacy is likely explained by the absence of inflammation as a significant factor in tendinosis pathology.
• Sclerosing treatments. Several studies have demonstrated that sclerosing treatment aids in the neovascularization of tendinosis lesions.114,115
• Platelet-rich plasma (PRP). PRP appears to be a promising intervention for tendinosis lesions.116,117
• Nitric oxide. Nitric oxide is an important cell signal molecule, and appears to be involved in numerous tissue types' responses to mechanical loading, modulating tendon healing, and collagen synthesis.118
• Matrix metalloproteinase inhibitors. This is a recent intervention for tendinosis. Matrix metalloproteinase inhibitors aim to decrease the catabolic enzymatic activity in tendinosis lesions.119

If the patient fails to improve completely within 6–14 weeks, the clinician must consider the following possibilities:84

• Incorrect loading magnitude or progression
• Incorrect diagnosis
• Noncompliance
• An unrecognized external factor.

As outlined in Chapter 1, ligaments function to bind bones together at or near the margins of bony articulation.

Behavior

Because of their function as joint stabilizers, when a ligament is damaged, there is a loss of normal kinematic relationships between the connected bones, with the degree of loss based on severity. Structural changes occur in ligaments as a function of age. In middle-age, both ligaments and bone insertion sites begin to weaken, resulting in progressive losses in structural strength, and in the elderly ligaments lose mass, stiffness, strength, and viscosity.5 Hormone levels can also affect ligaments producing gender-specific alterations. For example, it has been reported that joint and ligament laxity can change during pregnancy due to the presence of the hormone relaxin, and during different phases of the menstrual cycle.120,121 Finally, ligament complexes are extremely sensitive to load and load history, such that load deprivation causes a rapid deterioration in ligament biochemical and mechanical properties, which results in a net loss in ligament strength and stiffness.122–124 Conversely, movement has been shown to maintain normal ligament behavior, although it is not clear how much movement is required to maintain baseline ligament behaviors.125 Exercise appears to increase ligament strength and stiffness.

Injury

In any particular position of a joint, several ligaments around the joints are likely to be in a taut state. If an external load is then applied to that joint, those ligaments that are taut will absorb the greatest amount of energy. If the load is sufficient to deform a taut ligament past its elastic (recovery) limit, the ligament will fail, and other ligaments, or structures will simultaneously become recruited into tension.5 Depending on the size of the load, subsequent injury may also occur to these other ligaments, or structures. It is, therefore, unlikely for a truly isolated ligament injury ever to occur.5 Point tenderness, joint effusion, and a history of trauma, are all characteristic of a ligamentous injury. Ligament injuries, referred to as sprains, may be graded by severity (Table 2-4). Stress tests applied perpendicular to the normal plane of joint motion can help distinguish between grade II and grade III ligament injuries. In grade III injuries, significant joint gapping occurs with the application of the stress test.126 However, because of patient discomfort and guarding against possible pain, it is difficult to assess joint laxity by clinical examination alone. Currently, clinicians often use ancillary tests such as arthrometry or magnetic resonance imaging when diagnosing and grading soft tissue injuries.

Healing

The process of ligament healing follows the same course of repair as with other vascular tissues. However, intra-articular ligaments such as the anterior cruciate ligament (ACL) do not heal as well as extra-articular ligaments, because intra-articular ligaments have a limited blood supply and the synovial fluid may significantly hinder an inflammatory response.83 The healing of extra-articular ligaments, however, occurs in four overlapping phases.

Phase I: Hemorrhagic

After disruption of the tissue, the gap is filled quickly with a blood clot (hematoma). PMN leukocytes and lymphocytes appear within several hours, triggered by cytokines released within the clot. The PMN leukocytes and lymphocytes respond to autocrine and paracrine signals to expand the inflammatory response and recruit other types of cells to the wound.69

Phase II: Inflammatory

Macrophages arrive within 24–48 hours and are the predominant cell type within several days. Macrophages perform phagocytosis of necrotic tissues and also secrete multiple types of growth factors that induce neovascularization and the formation of granulation tissue. By the third day after injury, the wound contains macrophages, PMN leukocytes, lymphocytes, and multipotential mesenchymal cells, growth factors, and platelets. The growth factors are not only chemotactic for fibroblasts and other cells, but also stimulate fibroblast proliferation and the synthesis of collagen types I, III, and V, as well as noncollagenous proteins.127,128

Phase III: Proliferation

The last cell type to arrive within the wound is the fibroblast. Although debate continues, it currently is thought that fibroblasts are recruited from neighboring tissue and the systemic circulation.129 These fibroblasts have abundant rough endoplastic reticulum and begin producing collagen and other matrix proteins within 1 week of injury. By the second week after disruption, the original blood clot becomes more organized because of cellular and matrix proliferation. Capillary buds begin to form. Total collagen content is greater than in the normal ligament or tendon, but collagen concentration is lower and the matrix remains disorganized.

Phase IV: Remodeling and Maturation

Phase IV is marked by a gradual decrease in the cellularity of the healed tissue. The matrix becomes denser and longitudinally oriented. Collagen turnover, water content, and the ratio of collagen types I to III begin to approach normal levels over several months.130 An integrated sequence of biochemical and biomechanical signals are critical to ligament remodeling. These signals regulate the expression of structural and enzymatic proteins, including degradation enzymes such as collagenase, stromelysin, and plasminogen activator.127 The healed tissue continues to mature but will never attain normal morphologic characteristics or mechanical properties. Ligament injuries can take as long as 3 years to heal to the point of regaining near-normal tensile strength,131 although some tensile strength is regained by about the fifth week following injury, depending on the severity.19,132–134 A ligament may have 50% of its normal tensile strength by 6 months after injury, 80% after 1 year, and 100% only after 1–3 years.135–137

Treatment

Immobilization and disuse dramatically compromise the structural material properties of ligaments, resulting in a significant decrease in the ability to resist strains and absorb energy.83 Forces applied to the ligament during its recovery help it to develop strength in the direction that the force is applied.135–139 Several studies have shown that actively exercised ligaments are stronger than those that are immobilized thus, it is important to minimize periods of immobilization and progressively stress the injured ligaments while exercising caution relative to biomechanical considerations for specific ligaments.140 The current concept is that very low cyclical loads on ligaments promote scar proliferation and material remodeling, thus making the scar stronger and stiffer structurally141,142 and, possibly, materially.5 In conjunction with exercise it appears that the use of ice immediately after ligament injury decreases bleeding, swelling, and inflammation,143 whereas heat, used after the first 48 hours appears to increase blood flow. However it is not known whether ice or heat have any effect on scar formation, or on the quality or quantity of ligament healing.

The surgical repair of torn ligament ends has been noted in the past to induce faster and stronger healing through a process that is likened to regeneration rather than scar formation.5,144 However, although surgically repaired extra-articular ligaments heal with decreased scar formation and are generally stronger than unrepaired ligaments initially, this strength advantage might not be maintained as time progresses.16

Currently, a number of biological approaches are being used to improve ligament repair including the use of growth factors and gene therapy:5

• Growth factors. Growth factors are molecules that modify cell proliferation or the secretion of proteins. Thus far, the uses of growth factors in ligament healing have demonstrated variable results.
• Gene therapy. Gene therapy refers to the modification of the genetic expression of cells. Introduction of marker and therapeutic genes into ligaments using vectors has demonstrated initial success with evidence of functional alterations.145 In addition, gene transfer has been used to manipulate the healing environment, opening the possibility of gene transfer to investigate ligament development.145

The amount of motion available at a joint is based on a number of factors, including the shape of the articulating surfaces, the health of the joint and the surrounding tissues, and the load-deformation history of the joint. In order to discuss these concepts, it is important to have an understanding of the normal barriers that can be felt during movement. Three distinct areas or zones are recognized:146

• Neutral zone: the zone in which there is little or no internal resistance offered by the tissues to movement and the range in which the crimp of the tissue is being taken up. Increases in the size of the neutral zone result in the feeling or perception that the crimp is taken up later in the range of motion. Such increases can occur because of injury, and joint instability, joint degeneration, muscle dysfunction (leading to loss of muscular control of the movement).147 In contrast, the size of the neutral zone may be decreased by osteophyte formation, surgical fusion, muscle spasm, muscle strengthening, or adaptive tissue shortening.
• Elastic zone: the zone in which the first barrier or restriction of movement occurs. This zone occurs at the end of the neutral zone after the crimp has been taken up and tension starts to build within the tissues. The elastic zone extends from the crimp area through the physiological barrier (end of active movement) and toward the anatomic barrier (end of passive movement). The elastic zone can be increased by injury to the joint structures, mobilization techniques, and muscle lengthening, and be decreased by osteophyte formation, surgical fusion or repair, muscle hypertrophy, or immobilization.
• Plastic zone: the zone in which deformation of the tissues is extended beyond the tissues elastic recoil and the tissue begins to deform. If the deformation is sufficient, injury may occur.

Behavior

A door hinge and doorstop are a good analogy when describing joint motion behavior, in which the hinge represents the joint, and the doorstop represents the restriction imposed by the integrity of the joint and the surrounding tissues. Just as the doorstop prevents the door from swinging too far and damaging the wall, the integrity of the joint and its surrounding structures serve to prevent the joint moving past the normal range of motion and incurring injury.

Three descriptors are used to describe normal and abnormal joint motion:

• Hypomobile. If the movement of a joint is less than that considered normal, or when compared with the same joint on the opposite extremity, it may be deemed hypomobile. Hypomobility can be secondary to any of the following:148
  • Joint fixation. This can occur when the joint is stuck at the extreme of range of motion secondary to a sudden macrotrauma, a prolonged or repeated microtrauma, or a microtrauma imposed on instability. Clinical findings associated with a joint fixation include limitation of gross motion or conjunct rotation toward the limitation. Also the clinician notes that the end feel in the direction opposite the fixation is abnormal and has a rather firm capsular end feel (see Chap. 4).
  • Myofascial hypomobility. This is caused by muscle shortening (scars, contracture, or adaptive tissue changes). Clinical findings for myofascial hypomobility include an elastic end feel and a constant-length phenomenon. The constant length phenomenon occurs when the amount of movement available at one joint is dependent upon the position in which another joint is held. For example, during a supine straight leg raise, due to the anatomy (length) of the hamstrings, the amount of available hip flexion is decreased if the knee is maintained in a fully extended position as opposed to when the knee is allowed to flex.
  • Articular hypomobility. This can be caused by intra-articular swelling or an intra-articular bleed. Clinical findings for an articular hypomobility include a spasm, or empty end feel, often accompanied with a capsular pattern (see Chap. 4).
  • Pericapsular hypomobility. This is caused by capsular or ligamentous shortening, which creates a capsular pattern of restriction that does not demonstrate the constant length phenomenon. In addition a premature firm/hard capsular end feel exists if the joint is not inflamed, or possibly a spasm end feel if the joint is inflamed.
• Hypermobile. A joint that moves more than is considered normal, or when compared with the same joint on the opposite extremity may be deemed hypermobile. Laxity, a function of the ligament and joint capsule resistance, is a term used to imply that an individual has excessive joint range of motion, but has the ability to control the movement of the joint in that extra range. Hypermobility may occur as a generalized phenomenon or be localized to just one direction of movement, as follows:
  • Generalized hypermobility. The more generalized form of hypermobility, as its name suggests, refers to the manifestations of multiple joint hyperlaxity, joint hypermobility, or articular hypermobility. This type of hypermobility can be seen in acrobats, gymnasts, and those individuals who are “double jointed.” In addition, generalized hypermobility occurs with genetic diseases that include joint hypermobility as an associated finding, such as Ehlers–Danlos syndrome, osteogenesis imperfecta, and Marfan's syndrome.
  • Localized hypermobility. Localized hypermobility is likely to occur as a reaction to neighboring stiffness. For example, a compensatory hypermobility may occur at a joint when a neighboring joint or segment is injured. The injury to the neighboring joint results in a decrease in motion at the injured joint. This decrease in movement of the neighboring joint is often the result of the body's initial response to trauma, which is a reflexive increase in tone of muscles in an attempt to stabilize the affected area. Over time, the prolonged increased tonus may result in a decreased blood supply and an increase in the buildup of lactic acid. In addition, the nociceptor's response in the muscle or the joint capsule may result in an inhibition of the segmental muscles, which, in turn, may lead to uncoordinated movements and produce myofascial trigger points.

• Unstable. The term instability, specifically related to the joint, has been the subject of much research.150–165 In contrast to a hypermobile joint, an unstable joint is associated with a potential or real pathologic state as it involves a disruption of the osseous and ligamentous structures of that joint as the result of some applied external load. Instability implies that an individual has increased joint range of motion but does not have the ability to stabilize the joint (loss of neuromuscular control). This loss of control results in pain, weakness, and transitory deformity. Joint stability may be viewed as a factor of joint integrity, elastic energy, passive stiffness, and muscle activation.
  • Joint integrity. Joint integrity is enhanced in those ball-and-socket joints with deeper sockets or steeper sides, as opposed to those that are planar and shallower. Joint integrity is also dependent on the attributes of the supporting structures around the joint and the extent of any joint disease.
  • Muscle activation. Muscles and tendons (see Chap. 1) can provide static stabilization (isometric contraction) and dynamic stabilization (agonist concentric and antagonist eccentric contractions—see Chap. 12). Passive stability can also be provided when the contractile unit is on stretch. Intrinsic muscle factors affecting stabilization include temporal summation, length tension relationships, force velocity relationships, and muscle architecture (see Chap. 1). Muscle activation can provide two forms of stabilization through the use of stabilizer and mobilizer muscles. The stabilizer muscles contract first to provide a stable base from which the mobilizer muscles can function to position a joint for functional use. In the spine, the stabilizer muscles are divided into two groups: local stabilizers and global stabilizers (see Chap. 28).146 From a rehabilitation standpoint, before retraining the mobilizer muscles, the clinician must ensure that the stabilizer muscles are performing correctly. This is the concept behind core stabilization or stabilization retraining progressions (see Chaps. 12 and 14).
  • Passive stiffness. Passive stiffness is provided by the ligaments, capsules, skin, joints, bones, and other collagenous tissue. An injury to these passive structures causing inherent loss in the passive stiffness results in joint laxity.166 Individual joints have passive stiffness that increases toward the joint end range. Dysfunction of the passive system is due most commonly to mechanical injury, overuse or repetitive stress, joint degeneration, or a disease process (e.g., rheumatoid arthritis).146
  • Muscle activation. The central and peripheral nervous systems provide control through neural feedforward and feedback mechanisms from both active (muscle spindles, Golgi tendon organs) and passive systems (joint afferents) all of which help determine position, load, and joint demands while simultaneously controlling the contractile system to initiate conscious and unconscious movement (see Chap. 3).146 Muscle activation increases stiffness, both within the muscle and within the joint(s) it crosses.167 However, the synergist and antagonist muscles that cross the joint must be activated with the correct and appropriate activation in terms of magnitude or timing. A faulty motor control system may lead to inappropriate magnitudes of muscle force and stiffness, allowing a joint to buckle or undergo shear translation.167

Pathologic breakdown of the above factors may result in clinical instability. Instability is most obvious in movements that are executed too quickly or in cases where the loads placed on the joint are too great for the patient to control. For assessment purposes, instability can be divided into three types:

• Translational: refers to a loss of control of the small, arthrokinematic joint movements that occur when the patient attempts to stabilize the joint during movement.
• Anatomical: refers to excessive or gross physiological movement in the joint, which can lead to abnormal patterns of coupled and translational movements.168
• Functional: occurs when the severity of the instability adversely affects a patient's function and can include both translational and anatomical instability. Functional instability may result in169–171 the following:
  • Long-term nonacute pain or short-term episodic pain;
  • Early morning stiffness;
  • Inconsistent function and dysfunction (e.g., full range of motion but abnormal movement, which may include angulation, hinging, or deviation);
  • A feeling of apprehension or giving way.

Methods to enhance joint stability are provided in Chapter 12.

Injury

Using the door hinge and stop analogy again, it can be seen that both too much motion (resulting in damage to the wall) and too little motion (resulting in an inability to get through the door opening) can be disadvantageous. Similar consequences can be seen at a joint: a hypermobile joint may have insufficient stability to prevent damage occurring, whereas a hypomobile joint may provide insufficient motion at the joint for it to be functional. Hypermobile joints usually preserve their stability under normal conditions, remaining functional in weight bearing, and within certain limits of motion.

Pathologic barriers, which can occur anywhere in the range of motion, are restrictions to movement that occur as a result of a pathologic process. The causes of pathologic barriers include microtrauma or macrotrauma, muscle spasm, edema, pain, and adaptive shortening or lengthening of the tissue. Three types of pathologic barriers are recognized:146

• Motion barrier. This type of barrier is related to muscle hypertonus, muscle spasm, adaptive muscle shortening, or muscle pain.
• Collagen barrier. This type of barrier results from a pathologic process affecting collagenous tissues, and usually results in adaptive shortening or pain, shifting the motion barrier to the left (earlier into the range of motion), resulting in a decrease in range of motion.
• Neurodynamic barrier. This type of barrier is the result of a pathologic process of neural tissues that must undergo lengthening and shortening in the course of range of motion and is manifested by the presence of neurological signs that commonly restrict movement (see Chap. 11).

Healing

The healing of the joint surfaces, or joint cartilage, is described in the next section (Cartilage Behavior, Injury, Healing, and Treatment).

Treatment

It is essential to distinguish patients who have greater mobility in all their joints (generalized hypermobility) from those who for some other reason have one or a few joints that are more mobile than the rest (localized hypermobility). While intervention is unlikely to be either warranted or of benefit with generalized hypermobility, the intervention for a localized hypermobility should address any neighboring hypomobility.

Behavior

In adults, the articular cartilage matrix is separated from the subchondral vascular spaces by the subchondral plate. Nutrition of the articular cartilage occurs by diffusion from the synovial fluid. Without a direct supply of nutrients from blood vessels or lymphatics, chondrocytes depend primarily on anaerobic metabolism. Chondrocytes are responsible for the development, maintenance, and repair of the ECM by a group with degradative enzymes (see Chap. 1). Chondrocytes in loaded joints experience hydrostatic compressive, tensile, and shear forces.

Provided these forces are applied at an appropriate level, normal articular cartilage structure, and function will be maintained. Specifically, intermittent hydrostatic pressure is believed to maintain healthy cartilage in contrast to shear stresses, prolonged static loading, or the absence of loading.174 In contrast, immobilization results in degenerative changes that are similar to those seen in osteoarthritis. The development of disease such as osteoarthritis is associated with dramatic changes in cartilage metabolism. This occurs when there is a physiological imbalance of degradation and synthesis by chondrocytes.175

The biomechanical behaviors of articular cartilage are best understood when the tissue is used as a biphasic medium.173 Articular cartilage consists of two phases: a fluid phase and a solid phase. Water is the principal component of the fluid phase, contributing up to 80% of the wet weight of the tissue. The solid phase is characterized by the ECM, which is porous and permeable.176 The relationship between proteoglycan aggregates and interstitial fluid provides compressive resistance to cartilage through negative electrostatic repulsion forces.173 The initial and rapid application of articular contact forces during joint loading causes an immediate increase in interstitial fluid pressure, which causes the fluid to flow out of the ECM, generating a large frictional drag on the matrix.177 This fluid pressure provides a significant component of total load support, thereby reducing the stress acting upon the solid collagen–proteoglycan matrix.178 When the compressive load is removed, interstitial fluid flows back into the tissue. The low permeability of articular cartilage prevents fluid from being quickly squeezed out of the matrix, and the two opposing bones and surrounding cartilage confine the cartilage under the contact surface, which serves to restrict mechanical deformation.173

Articular cartilage is viscoelastic and exhibits time-dependent behavior when subjected to a constant local deformation.54

Injury

As articular cartilage is avascular, it is not capable of producing an inflammatory response, which is an important component of repair. Multiple factors are involved in cartilage breakdown including174

• an imbalance between ECM synthesis and degradation
• stress deprivation (immobilization, bed rest)
• developmental etiologies leading to abnormal force transmission (developmental hip dysplasia, coxa valgus, genu valgum)
• joint surface incongruously and joint instability
• disease (rheumatoid arthritis)

Injuries to articular cartilage can be divided into three distinct types:

• Type 1 injuries (superficial) involve microscopic damage to the chondrocytes and ECM (cell injury).
• Type 2 injuries (partial thickness) involve microscopic disruption of the articular cartilage surface (chondral fractures or fissuring).83 This type of injury has traditionally had an extremely poor prognosis because the injury does not penetrate the subchondral bone and, therefore, does not provoke an inflammatory response.83
• Type 3 injuries (full-thickness) involve disruption of the articular cartilage with penetration into the subchondral bone, which produces a significant inflammatory process.83

Healing

The body's response to articular cartilage defects resulting from trauma upon impact loading depends on the lesion depth.174 However, it is well known that the capacity of cartilage for repair is limited. The healing of articular cartilage is described here. Injuries of the articular cartilage that do not penetrate the subchondral bone become necrotic and do not heal. These lesions usually progress to the degeneration of the articular surface.179 Although a short-lived tissue response may occur, it fails to provide sufficient cells and matrix to repair even small defects.180,181

Injuries that penetrate the subchondral bone undergo repair as a result of access to the blood supply of the bone. These repairs usually are characterized as fibrous, fibrocartilaginous, or hyaline-like cartilaginous, depending on the species, the age, and the location and size of the injury.182 However, these reparative tissues, even those that resemble hyaline cartilage histologically, differ from normal hyaline cartilage both biochemically and biomechanically. Thus, by 6 months, fibrillation, fissuring, and extensive degenerative changes occur in the reparative tissues of approximately half of the full-thickness defects.183,184 Similarly, the degenerated cartilage seen in osteoarthrosis does not usually undergo repair but instead progressively deteriorates.179

Current surgical options for full thickness cartilage defects are simple arthroscopic debridement, abrasion arthroplasty, microfracture, autologous chondrocyte cell implantation, mosaicplasty with either autologous tissue or fresh allograft.83,185,186 Current research is focused on inducing the newly attracted or transplanted chondrocytes to become mature chondrocytes using growth factors. Bone morphogenic proteins (BMPs) are members of the TGF-superfamily and have a regulatory role in the differentiation of cartilage-forming and bone-forming cells.83

Treatment

Frequent exercise in animals has demonstrated hypertrophy of chondrocytes, an increase in the pericellular matrix, and an increase in the number of cells per chondron.

Behavior

Bone matrix comprises three elements: organic, mineral, and fluid. It is the mineral content that distinguishes bone from other connective tissues, and provides the bone with its characteristic stiffness, while providing a mineral storage system. Collagen orientation in growing and mature bone has been linked to the mechanical behavior of individual layers of bone (lamellae), and the different types of bone. During normal activity, cortical bone sustains loads well within the linear region of the load-deformation curve, so that the bone bends but does not sustain permanent deformation (elastic deformation). However, even when maintained within the linear region, if loads are sustained repetitively over short period of time, changes to the bone may result (plastic deformation). For example, compressive forces shorten bone, and tensile forces elongate bone. Bone is strongest in compression and weakest in tension. Forces acting on bone include muscle contractions, gravity, and forces from outside the body, such as trauma.

When loads are sustained that exceed the linear region, microarchitectural damage can occur. Trabecular, or cancellous bone, is anisotropic in nature, which means its mechanical behavior differs in different directions or among various parts of the structure.

Injury

An injury to a bone is referred to as a fracture. A number of different types of fractures and fracture patterns are recognized (Fig. 2-4) (Table 2-5).

Healing

Bone healing is a complex physiologic process that follows an orderly cascade of events. The striking feature of bone healing, compared with healing in other tissues, is that repair is by the original tissue, not scar tissue. Regeneration is perhaps a better descriptor than repair. This is linked to the capacity for remodeling that intact bone possesses. Like other forms of healing, the repair of bone fracture includes the processes of inflammation, repair, and remodeling; however, the type of healing varies, depending on the method of treatment. In classic histologic terms, fracture healing has been divided into two broad phases: primary fracture healing and secondary fracture healing (Fig. 2-5).

• Primary osteonal (cortical) healing, involves a direct attempt by the cortex to reestablish itself once it has become interrupted. In primary cortical healing, bone on one side of the cortex must unite with bone on the other side of the cortex to reestablish mechanical continuity.
• Secondary callus healing involves responses in the periosteum and external soft tissues with the subsequent formation of a callus. The majority of fractures heal by secondary fracture healing.

Within these broader phases, the process of bone healing involves a combination of intramembranous and endochondral ossification (see Chap. 1). These two processes participate in the fracture repair sequence by at least four discrete stages of healing: the hematoma formation (inflammation or granulation) phase, the soft callus formation (reparative or revascularization) phase, the hard callus formation (maturing or modeling) phase, and the remodeling phase.188

• Hematoma formation (inflammatory) phase. Initially, the tissue volume in which new bone is to be formed is filled with the matrix, generally including a blood clot or hematoma (Fig. 2-5).83 At this phase, the matrix within the injury site is bordered by local tissues, which also are often traumatized resulting in focal necrosis and reduced blood flow.83 An effective bone healing response will include an initial inflammatory phase characterized by the release of a variety of products, including fibronectin, PDGF, and TGF, an increase in regional blood flow, invasion of neutrophils and monocytes, removal of cell debris, and degradation of the local fibrin clot.
• Soft callus formation (reparative or revascularization) phase. This phase is characterized by the formation of connective tissues, including cartilage, and formation of new capillaries from preexisting vessels (angiogenesis). During the first 7–10 days of fracture healing, the periosteum undergoes an intramembranous bone formation response, and histologic evidence shows formation of woven bone opposed to the cortex within a few millimeters of the site of the fracture. Differentiation is strongly influenced by the local oxygen tension and mechanical environment, as well as by signals from local growth factors.83 By the middle of the second week, abundant cartilage overlies the fracture site, and this chondroid tissue initiates biochemical preparations to undergo calcification. Thus, the callus becomes a triple-layered structure consisting of an outer proliferating part, a middle cartilaginous layer, and an inner portion of new bony trabeculae (Fig. 2-5). The cartilage portion is usually replaced with bone as the healing progresses. During the period of casting, submaximal isometrics are initiated.
• Hard callus formation (modeling) phase. This phase is characterized by the systematic removal of the initial matrix and tissues that formed in the site, primarily through osteoclastic and chondroclastic resorption, and their replacement with more organized lamellar bone (woven bone) aligned in response to the local loading environment.83 The calcification of fracture callus cartilage occurs by a mechanism almost identical to that which takes place in the growth plate. This calcification can occur either directly from mesenchymal tissue (intramembranous) or via an intermediate stage of cartilage (endochondral or chondroid routes). Osteoblasts can form woven bone rapidly, but the result is randomly arranged and mechanically weak. Nonetheless, bridging of a fracture by woven bone constitutes so-called clinical union. Once cartilage is calcified, it becomes a target for the ingrowth of blood vessels. Radiographically, a fracture is considered healed when there is progressive callus formation to the point where the fracture line is no longer visible. At this point, range of motion exercises are usually initiated.
• Remodeling phase. By replacing the cartilage with bone, and converting the cancellous bone into compact bone, the callus is gradually remodeled. During this phase, the woven bone is remodeled into stronger lamellar bone by the orchestrated action of osteoclast bone resorption and osteoblast bone formation (Fig. 2-5).

Radiologically or histologically, fracture gap bridging occurs by three mechanisms188:

1. Intercortical bridging (primary cortical union). This mechanism occurs when the fracture gap is reduced by normal cortical remodeling under conditions of rigid fixation. This mode of healing is the principle behind rigid internal fixation.189

2. External callus bridging by new bone arising from the periosteum and the soft tissues surrounding the fracture. Small degrees of movement at the fracture stimulate external callus formation.190 This mode of healing is the aim in functional bracing191 and intramedullary nailing.

3. Intramedullary bridging by endosteal callus. Normal periods of immobilization following a fracture range from as short as 3 weeks for small bones to about 8 weeks for the long bones of the extremities. Once the cast is removed, it is important that controlled stresses continue to be applied to the bone, because the period of bone healing continues for up to 1 year.192,193

The three key determinants of fracture healing are the blood supply and the degree of motion experienced by the fracture ends.

• Angiogenesis is the outgrowth of new capillaries from existing vessels. The degree of angiogenesis that occurs depends on well-vascularized tissue on either side of the gap and sufficient mechanical stability to allow new capillaries to survive. Angiogenesis leads to osteogenesis.
• The amount of movement that occurs between fracture ends can be stimulatory or inhibitory to the cascade of bone formation, depending on their magnitude. Excessive interfragmentary movement prevents the establishment of intramedullary blood vessel bridging. However, small degrees of micromotion have been shown to stimulate blood flow at the fracture site and stimulate periosteal callus.194 Successful restoration of osseous morphology and internal architecture is conditional on the remodeling process. According to Wolff's law, bone remodels along lines of stress.195 Bone is constantly being remodeled as the circumferential lamellar bone is resorbed by osteoclasts and replaced with dense osteonal bone by osteoblasts.196
• The environment is another factor, which modulates the repair process; hormones have impact on osteoblastic and osteoclastic activity (Table 2-6).

Augmented Healing

To date, a number of techniques have been developed to accomplish a quicker and more complete healing of fractures. These include the following:

• Pulsed electromagnetic fields (PEMF). A technique most commonly used for the treatment of nonunion fractures, failed fusions, and congenital pseudarthrosis. PEMF uses electrical energy to direct a series of magnetic pulses through injured tissue such that each magnetic pulse induces a tiny electrical signal that stimulates cellular repair.
• Ultrasound. There is some evidence that pulsed ultrasound may reduce fracture healing time for fractures by stimulating a local hyperemia, an increase in aggregate gene expression, increased mineralization, and more rapid endochondral ossification.197
• Direct current. Direct current stimulation surrounding the fracture site has been observed to decrease the oxygen tension with a concomitant rise in local pH in the region of the anode.198,199
• Demineralized bone matrix (DBM). DBM derived from human tissues has demonstrated the ability to aid in the stimulation of an osteoinductive and an osteoconductive response allowing for improved bone growth and fusion.200–202 There are currently two types:
  • Osteoinductive: there are several commercially available DBM substances available, each with different amounts of DBM containing osteoinductive proteins.
  • Osteoconductive: osteoconductivity refers to the ability of some materials to serve as a scaffold on to which bone cells can attach, migrate, and grow and divide. In this way, the bone healing response is “conducted” through the graft site.

Treatment

Deciding the mode of fracture management requires a multifaceted approach. The initial medical approach involves stabilization of the fracture site, which prevents further blood loss and resets muscle tension. A decision is then made by the medical team as to whether surgery is required or whether a conservative approach would be more beneficial.

Surgical Options for Fractures

The advantage of operative treatment is the anatomical reduction of fracture fragments and early mobilization.

Percutaneous Pinning

Percutaneous pinning is a minimally invasive form of internal fixation in which fractures are pinned using Kirschner wires. The pins are driven through the skin and cortex of the bone, across the reduced fracture, and into the opposite cortex.203 This mode is commonly used in fractures of the phalanges, metacarpals, distal radius, proximal humerus, and metatarsals. The disadvantage of this type of treatment is that the pins can bend or break within the bone, and no absolute stability is provided.

External Fixation

This mode of treatment maintains traction and alignment of the bone without the need to confine the patient to a bed. The threaded traction pins are inserted into the bone proximal and distal to the fracture site, and the fracture is manually reduced and fixed in position with carbon fiber bars spanning the fracture site outside the skin.203 Using fine wires in a circular fixator, across the subchondral metaphysis, is least damaging to the medullary blood supply.188 This type of fixation may provide enough stability to allow rapid endosteal healing without external callus.204

Open Reduction and Internal Fixation

The aim of this mode of treatment is to anatomically reduce and provide absolute stability to as many of the fracture fragments as possible.203 A fracture that is rigidly internally fixed produces no periosteal callus and heals by a combination of endosteal callus and primary cortical union.188

Locking Plates

Locking plates are fracture fixation devices with threaded screw holes, which allow screws to thread to the plate and function as a fixed-angle scaffold.

Intramedullary Nailing

Fracture fixation with intramedullary nails provide relative stability—unless the nail is locked proximally and distally and has tight fixation at the fracture site, the fixation may have rotational and angular instability.203 An intermedullary nail blocks endosteal healing but allows enough movement to trigger periosteal callus.188 Early mobilization of patients after femoral and tibial rodding is a major advance compared to the prolonged immobilization in traction.203

Most fractures, especially upper extremity, can be managed without surgery if acceptable reduction can be achieved by closed means. Nonoperative treatment is usually reserved for nondisplaced fractures with a low risk of displacement, for displaced fractures that are stable after acceptable reduction is achieved, or for patients for whom anesthesia and surgery are contraindicated.203 A variety of nonoperative devices can be used to treat fractures:203

• Splints and fracture braces: noncircumstantial coapted devices that lie along one or more surfaces of an extremity that are made of a prefabricated material (molded plastic) or plaster, and secured with elastic bandage. The aim of this type of splinting is to immobilize or passively correct stable fractures and their use is usually temporary, used for days to a few weeks.
• Casting: provides rigid circumferential support into which appropriate holes and three-point fixation can be incorporated. Casting more effectively immobilizes fracture fragments than either splinting or bracing. Particularly useful for maintaining reduction of ankle, tibia, pediatric forearm, and distal radius fractures.
• Skeletal traction: traction is applied either manually or via weights and pulleys to overcome the shortening force of muscles across the fracture site. The configuration of the skeletal traction varies according to the specific bone involved, but its use is dwindling due to the successful development of surgical reduction and internal fixation.

Although many musculoskeletal conditions can be treated conservatively, surgical intervention is often indicated for cases in which a sufficient traumatic or degenerative injury has occurred. Over the years, the number of surgical procedures for orthopaedic conditions has increased considerably. However, although surgery can often correct the presenting problem, for the postsurgical patient to return to an appropriate level of function, some form of postsurgical rehabilitation is usually required. Indeed, a number of studies have reported that skilled intervention following most surgical procedures of the musculoskeletal system allows patients to achieve greater independence and control over their lives in a shorter timeframe than patients who do not receive these interventions.205,206

Postsurgical Complications

Although surgical procedures can offer many benefits, they are not without their complications. Some of the more serious of these complications include the following:

• Postsurgical infection. Postsurgical infections are perhaps the greatest challenge facing the modern-day surgeon. At any one time, 9% of hospitalized patients are being treated for an nosocomial infection.207Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus spp., and Escherichia coli remain the most frequently isolated pathogens. An increasing proportion of infections are caused by antimicrobial-resistant pathogens, such as methicillin-resistant S. aureus (MRSA), or by Candida albicans.208 Microorganisms may contain or produce toxins and other substances that increase their ability to invade a host, produce damage within the host, or survive on or in host tissue. For example, many gram-negative bacteria produce an endotoxin that stimulates cytokine production. In turn, cytokines can trigger the systemic inflammatory response syndrome that sometimes leads to multiple system organ failure.208 In certain kinds of surgical procedures, some patient characteristics have been found to be possibly associated with an increased risk of an infection. These include coincident remote site infections or colonization, diabetes, cigarette smoking, systemic steroid use, obesity (>20% of ideal body weight), extremes of age, poor nutritional status, and perioperative transfusion of certain blood products.208–210 Although physical therapists are not directly involved in surgical procedures, they are a potential mode of transmission for infections. Hand washing has been found to be an important infection control measure, although improving compliance with hand washing has been a challenge for most hospital infection control programs.211
• Venous thromboembolism. A thrombus, or blood clot, is an obstruction of the venous or arterial system. If a thrombus is located in one of the superficial veins, it is usually self-limiting. Venous thromboembolism is a vascular disease that manifests as deep vein thrombosis (DVT) or pulmonary embolism (PE). A DVT most commonly appears in the lower extremity and is typically classified as being either proximal (affecting the popliteal and thigh veins) or distal (affecting the calf veins). Proximal DVT is the more dangerous form of lower extremity DVT because it is more likely to cause life-threatening PE (see later).

Certain patients are at increased risk for DVT212–216:

• Strong risk factors include fracture (pelvis, femur, and tibia), hip or knee replacement, major general surgery, major trauma, or spinal cord injury. A recent study indicated that up to 60% of patients undergoing total hip replacement surgery may develop a DVT without preventative treatment.217,218
• Moderate risk factors include arthroscopic knee surgery, central venous lines, chemotherapy, congestive heart or respiratory failure, hormone replacement therapy, malignancy, oral contraceptive therapy, cerebrovascular accident, pregnancy/postpartum, previous venous thromboembolism, and thrombophilia.
• Weak risk factors include bed rest greater than 3 days, immobility due to sitting (e.g., prolonged air travel), increasing age, laparoscopic surgery, obesity, pregnancy/antepartum, and varicose veins.

The association of DVT with venous stasis, vessel wall damage, and hypercoagulability was first proposed by Virchow in 1859.219

Two-thirds of the fatalities resulting from DVT occur within 30 minutes of the initial symptoms.221–223 Both DVT and PE can be symptomatic or asymptomatic. Clinical signs of a DVT have traditionally been described as including swelling of the extremity, tenderness or a feeling of cramping of the calf muscles that increases when the ankle is dorsiflexed (positive Homan's sign) or with weight bearing, vascular prominence, elevated temperature, tachycardia, and inflammation and discoloration or redness of the extremity. However, a purely clinical diagnosis is fraught with a high incidence of false positives and negatives. Musculoskeletal conditions that may mimic symptoms associated with DVT include hematoma, myositis, tendinitis, Baker's cyst, synovitis, osteomyelitis, and tumors.224 The clinical decision rule described by Wells and colleagues225–229 (Table 2-7) is being most commonly recommended for outpatients suspected of having DVT.230,231 More accurate diagnostic procedures, outside the scope of physical therapy, include contrast venography, Doppler and B-mode ultrasound, venous duplex imaging, impedance plethysmography, and I-125 fibrinogen uptake.

• Prevention is the key with DVT. Methods of prevention may be classified as pharmacological and nonpharmacological. Pharmacological prevention includes anticoagulant drugs such as low-dose Coumadin (warfarin), low-molecular-weight heparin, adjusted-dose heparin, and heparin-antithrombin III combination. These drugs work by altering the body's normal blood-clotting process. Second tier drugs include dextran, aspirin, and low-dose subcutaneous heparin. Nonpharmacological prevention attempts to counteract the effects of immobility, including calf and foot/ankle exercises, and compression stockings. A recent study has shown that substantial hyperemia (a mean 22% increase in venous outflow) occurs after the performance of active ankle pumps for 1 minute, and venous outflow remains greater than the baseline level for 30 minutes reaching a maximum 12 minutes after these exercises.218 Although this does not provide sufficient evidence that exercise alone prevents DVT, it suggests that the active ankle pump does influence venous hemodynamics. Finally, inferior vena caval (IVC) filters and Greenfield filters may be employed with a patient who has a contraindication to anticoagulation, previous complications with anticoagulants, or if anticoagulants have proved ineffective in the past.
• Pulmonary embolus.232 This is a part of the spectrum of diseases associated with venous thromboembolism. Under normal conditions, microthrombi (tiny aggregates of red cells, platelets, and fibrin) are formed and lysed continually within the venous circulatory system. This dynamic equilibrium ensures local hemostasis in response to injury without permitting uncontrolled propagation of a clot. Under pathological conditions, microthrombi may escape the normal fibrinolytic system to grow and propagate. PE occurs when these propagating clots break loose and embolize to block pulmonary blood vessels. PE most commonly results from DVT occurring in the deep veins of the lower extremities, proximal to and including the popliteal veins and in the axillary or subclavian veins (deep veins of the arm or shoulder). PE is an extremely common and highly lethal postsurgical condition that is a leading cause of death in all age groups. A good clinician actively seeks the diagnosis as soon as any suspicion of PE whatsoever is warranted, because prompt diagnosis and treatment can dramatically reduce the mortality rate and morbidity of the disease. Unfortunately, the diagnosis is missed more often than it is made because PE often causes only vague and nonspecific symptoms. Symptoms that should provoke a suspicion of PE must include chest pain, chest wall tenderness, back pain, shoulder pain, upper abdominal pain, syncope, hemoptysis, shortness of breath, painful respiration, new onset of wheezing, any new cardiac arrhythmia, or any other unexplained symptom referable to the thorax. It is important to remember that many patients with PE are initially completely asymptomatic and most of those who do have symptoms have an atypical presentation. Pulmonary angiography remains the criterion standard for the diagnosis of PE but is rapidly being replaced by multidetector computed tomographic angiography (MDCTA), since the latter modality is significantly less invasive, is easier to perform, and offers equal sensitivity and specificity.
• Poor wound healing. Wound-healing abnormalities cause great physical and psychological stress to the affected patients and are extremely expensive to treat. The rate of healing in acute surgical wounds is affected by both extrinsic factors (surgical technique, tension of wound suturing, maintenance of adequate oxygenation, cigarette smoking, prevention or eradication of infection, and types of wound dressing) and intrinsic factors (presence of shock or sepsis, control of diabetes mellitus, and the age, nutritional, and immune status of the patient).233 Although many studies have documented relationships between malnutrition and poor wound healing, the optimal nutrient intake to promote wound healing is unknown. It is known, however, that vitamins A, C, and E, protein, arginine, zinc, and water play a role in the healing process.234
• Scars and adhesions. Surgery is a form of controlled macrotrauma to the musculoskeletal system. The tissues respond to this trauma in much the same way that they do to any other form of trauma or injury. As part of the postsurgical rehabilitation process, the involved structure is usually immobilized to protect the surgical site from injury. However, prolonged immobilization of a connective tissue can produce significant changes in its histochemical and biomechanical structure. These changes include a fibrofatty infiltration that can progress into fibrosis, creating adhesions around the healing site, and an increase in the microscopic cross-linking of collagen fibers resulting in an overall loss of extensibility of the connective tissues.123,235–238 Unlike normal connective tissue, which is mature and stable with limited pliability, scar tissue is more vulnerable to breakdown.19,41,239–241 Fortunately, controlled and skilled therapeutic interventions can reverse the detrimental effects of short-term immobilization. These include mobilization of the connective tissue with passive mobility techniques or active range of motion that help to restore the extensibility of the tissue. To assist with the overall healing of the incision, scar mobilization techniques may be performed to the patient's tolerance with lotion.

Continuous immobilization of connective and skeletal muscle tissues can cause some undesirable consequences. These include the following:

• Cartilage degeneration.241–245 Immobilization of a joint causes atrophic changes in articular cartilage through a reduction in the amount of matrix proteoglycans and cartilage softening.242 Softened articular cartilage is vulnerable to damage during weight bearing. The reduction of the matrix proteoglycans concentration has been demonstrated to be highest in the superficial zone but also occurs throughout the uncalcified cartilage, diminishing with distance from the surface of articular cartilage.246
• Decreased mechanical and structural properties of ligaments. One study9 showed that after 8 weeks of immobilization, the stiffness of a ligament decreased to 69% of control values, and even after 1 year of rehabilitation, the ligament did not return to its prior level of strength.

• Decreased bone density.122,123,192,235,248 The interactions among systemic and local factors to maintain normal bone mass are complex. Bone mass is maintained because of a continuous coupling between bone resorption by osteoclasts and bone formation by osteoblasts, and this process is influenced by both systemic and local factors.249 Mechanical forces acting on bone stimulate osteogenesis, and the absence of such forces inhibits osteogenesis. Marked osteopenia occurs in otherwise healthy patients in states of complete immobilization or weightlessness.250,251 In children, bone has a high modeling rate and appears to be more sensitive to the absence of mechanical loading than bone in adults.252
• Weakness or atrophy of muscles (Table 2-8). Muscle atrophy is an imbalance between protein synthesis and degradation. After modest trauma, there is a decrease in whole body protein synthesis253 rather than increased breakdown. With more severe trauma, major surgery, or multiple organ failure, both synthesis and degradation increase, the latter being more enhanced.254,255

The cause of muscle damage during exercised recovery from atrophy involves an altered ability of the muscle fibers to bear the mechanical stress of external loads (weight bearing) and movement associated with exercise. Strenuous exercise can result in primary or secondary sarcolemmal disruption, swelling or disruption of the sarcotubular system, distortion of the contractile components of myofibrils, cytoskeletal damage, and extracellular myofiber matrix abnormalities.71 These pathologic changes are similar to those seen in healthy young adults after sprint running or resistance training.71 It appears that the act of contracting while the muscle is in a stretched or lengthened position, known as an eccentric contraction, is responsible for these injuries.256

The clinician must remember that the restoration of full strength and range of motion may prove difficult if muscles are allowed to heal without early active motion, or in a shortened position, and that the patient may be prone to repeated strains.131 Thus, range-of-motion exercises should be started once swelling and tenderness have subsided to the point that the exercises are not unduly painful.131

• 1. Explain the difference between primary and secondary injuries.

• 2. Outline the differences between a microtrauma and a macrotrauma.

• 3. What are the three main stages of wound healing?

• 4. What are neutrophils?

• 5. What is the function of monocytes in the inflammation stage of wound healing?

Answers