Collagen filament
[
a,a,
A
Cross-link Amino acid chainsIntramolecular Cross-links
Collagen filament
[
Collagen filament
[
B
Figure 4-2 Collagen bonding increases tensile strength: (A) Weak intramolecular cross-links form between amino acid chains within one collagen filament. (8) Stronger intermolecular cross-links form from one coJiagen filament to another. Source: Reprinted from Hardy, A., Biology of Scar Tissue, Physical Therapy, Dec. 1989, Vol. 69, No 12, with permission of the American Physical Therapy Association.
techniques may be appropriate at this time. Soft tissue mobilization designed to break up scar tissue will inflame the wound, leading to further deposition of collagen5,6
The final stage of scar formation is the matu ration or remodeling phase. This stage may last from 3 weeks to 12 months.13 During this phase, collagen must change in order to reach maxi mum function. A reduction in wound size, a realignment of collagen fibers, and an increase in the strength of the scar are all characteristic of this phase. Arem and Madden 12 confirmed
that a physical change in scar length could be
achieved through the application of low load,
long duration stress during this phase. During this time, the scar tissue is responsive to manual therapy but the progress will be somewhat slowed. Without controlled stress or mobiliza tion during this phase, however, tensile strength of the scar will not improve and optimal function wiJl be diminished.
Cycle or Fibrosis and Decreasing Mobility in Connective Tissue
The fibrotic process is histologically distinct from the scar formation process. The fibrotic process in connective tissue is a "homogenous"
process involving an entire tissue area or the entire tissue "fabric," and does not have clear cut stages as does the scar tissue formation pro cess. The fibrotic process is cyclical in nature, whereas the scar formation process is a linear process that has a distinct end. The fibrotic pro cess in connective tissue can continue as long as the irritant is present.
The fibrotic process is generally initiated by the production of an irritant, possibly trau matic exudates from nearby acutely inflamed traumatized tissue or a low-grade irritation/ inflammation of the tissue. The low-grade irrita tion may be caused by arthrokinematic dysfunc tion, poor posture, overuse, habit patterns, or structural or movement imbalances. A rotator cuff irritation, for example, may be caused by a poor tennis service, poor sleeping postures, oc cupational overuse syndromes, and other causes. The mechanical irritant produces a low-grade inflammation, which then starts the process. With an inflammatory response, macrophages are activated to clean and debride the area. In
flammatory exudates, along with damaged col lagen and other waste products, are carried away. The increased metabolic activity in the area stimulates the body to increase the area's vascu larity. With increased vascularity and debride ment of damaged collagen (from microtrauma), fibroblasts are activated to replace lost colla gen. Since the inflammatory process is gener ally painful, the joint is not being moved in proper fashion. The collagen begins to be laid down in more haphazard arrangement since ad equate stress is not being placed on the tissue, and cross-linking with other preexisting col lagen fibers begins. At one point, myofibroblasts appear in similar fashion as in the scar process. The myofibroblasts, which contain significant amounts of actin and myosin in the cytoplasm, anchor to adjacent collagen fibers and contract, shrinking the tissue. The tissue shrinkage results in further dysfunctional movement, which, in turn, creates more mechanical stresses and more chronic irritant (Figure
4-3).
As long as an ir ritant is present, the cycle continues.Chronic irritant Abnormal movement (biomechanics)
,
Shrinkage of connective tissue\
Increased myofibroblastic activity,
Increased production of connective tissueMacrophages activated
\
Increased vascularityJ
Increased fibroblastic activity/
(fibrosis)and S3
Response of Myofascial Tissue to Immobilization
Connective tissue has a characteristic his tological and biomechanical response to im mobilization. Most of the currently available
research, focuses on animal studies in
which an area of the body is immobilized for a of timc, after which the connective tissue is histologically and biomechanically
Several factors must be considered before ap the results of these studies to the rehabil itative population. The f irst is that these are animal the results of which should be
app! jed to the human
tion. and of greater clinical importance, many of the studies that are discussed in this chapter deal with the response of " or non traumatized, connective tissue to immobi lization, and do not address the re sponses of traumatized and/or scar tissue. In
the orthopedic connective tissue
that has been immobilized has also been trauma tized. Trauma does affect the and bio mechanics of the
Also into the is the process of
scar formation, and the effects of immobiliza tion on the scar tissue. All of these clinical scenarios are addressed in detail because the response of normal connective tissues to im mobilization provides a basis for
traumatized conditions.
Nontrallmatized Connective Tissue
is subjected to
immobilization, connective cells
exhibit changes within 4 to [0 14.15 In
to connective tis
sues to limit mobility. Much of the animal studies on immobilized connective tissue
were by Amiel, Woo and
their associates. In studies primar
ily knee animals were immo
bilized internal fixation for periods from 2
to 9 weeks. A was from the proximal
one-third of the femur to the distal one-third of
the tibia to avoid the
knee joint. The animals were then sacrificed at various times of immobilization and the ticular tissues were
histochemical and biomechanically. From a the authors found fibro
fatty especially in the folds
and recesses. The the the
amount of infiltrate found, with a change in the infiltrate's appearance, which became more fibrotic. This created
adhesions in the recesses and capsular folds. and histochemical
showed several significant the primary
one being a Joss in ground
with no loss. The
components of lost ground substance were the and water. The authors re a 30 percent to 40 percent loss in both sul fated and nonsulfated groups. Since the purpose of the nonsulfated group
is to bind water, the water loss is explained.
As noted in the chapter, one of the purposes of the ground substance is to lubricate the area between
fibers. fiber lubrication is associated with the maintenance of the so-called critical interfiber distance. This the distance that must be maintained between
allow them to
microadhesions between fibers. W hen the criti
cal interfiber distance is not the col-
fibers approximate and cross-linked by newly
Also, because coHagen fibers are laid down ac
to the stresses lack of ap
in immobile connective tissue is The
collagen then binds adjacent
the extensibility of the tissue
Several factors why
amounts of ground substance are lost,
gen is not. the half-life of nontraumatized collagen is 300 to 500 days whereas the half-life of substance is L 7 to 7 days23 25 with immobilization times of less than 12
Figure 4-4 Drawing showing the laying down of newly synthesized collagen, forming cross-links onto existing collagen f ibers. These cross-links are be lieved to be responsible for decreased extensibility in immobilized connective tissue. Source: Reprinted from Donatelli, R. and Owens-Burkhart, B., Effects of Immobilization on the Extensibility of Periarticu lar COJlnective Tissue, Journal of Orthopaedic and Sports PhySical Therapy, Vol. 3, pp. 67-72, with per mission of the Orthopaedic and Sports Sections of the American Physical Therapy Association.
collagen synthesis occurs at the same rate as collagen degradation. After 12 weeks, however, the rate of collagen degradation exceeds the rate
of synthesis, and net amounts of collagen are lost.26
Biomechanical analyses indicated that ten times the torque required to move a normal joint was required to move the immobilized joints. After several repetitions, the amount of torque required to move the immobilized joint was re duced to three times that of a normal joint. The biomechanicat implication is that fibrofatty macroadhesions and microscopic adhesions in the form of increased collagen cross-linking contributed to the decreased extensibility of the connective tissue. 16-21
Scholl meier et at immobilized the forelimbs of 10 beagles for 12 weeks. At the end of that time, the passive range of motion of the gle nohumeral joints was markedly decreased and intraarticular pressure was raised during move ments. The capsule showed hyperplasia of the synovial lining and vascular proliferation of the capsular wall. Functional and structural changes began to reverse after remobilization and re turned to normal limits after 12 weeksY
A more recent study, which looked at rat ankles immobilized for 2 to 6 weeks, found slightly different results. This study found that dense connective tissues remodel in such a way that mobility is unaffected after 2 weeks of im-
Figure 4-5 Electron micrograph of normal ligament (left) and healing scar at 2 weeks (right). Source. Reprinted from Injury and Repair of the Musculoskeletal SoJi Tissues (p 112) by SL.-Y. Woo and J.A. Buckwalter with permission of the American Academy of Orthopaedic Surgeons, © 1987.
Histopathology of Myofascia and Physiology of Myojascia Manipulation 55
mobilization but markedly limited after 6 weeks of immobilization28 The authors attribute these changes to dense connective tissue undergoing remodeling between the 2 and 6 week periods. Earlier studies implied that cyclic mobilization of the immobilized joints caused rupture of the remodeled tissues, which limited early mobility. In Figure 4-6, following each yield point, the angle of the slope of the curve is unchanged. This supports the idea that rupture of the remodeled tissue that initially limited motion had not oc cllrred; rather discrete adhesions between folds of tissues were responsible for this.
Langenskiold et al performed a study on im mobilized, healthy rabbits. The authors found that casting for 5 to 6 weeks significantly de creased knee flexion. The resumption of normal activity, however, was able to restore 90% of joint mobility after 3 weeks. When immobiliza
tion was increased to 7 to 8 weeks, only 28% of knee flexion returned after 10 weeks of re conditioning. It took as long as 12 months for some of the animals to regain full mobility.29 The study suggests that the longer the period of immobilization, the more difficult it becomes to regain normal tissue structure and mobility.
75 (j) Q) OJ 50 Q) c 0 25 0 0 0 0 20 40
Loading Time (seconds)
:j:
In a study performed by Evans et al,22 ex perimentally immobilized rat knees were remo bilized either by high-velocity manipulation, by range of motion, or both. The investigators found that, with manipulation, the macroadhe sions were ruptured, and partial joint mobility was restored. If joint motion was allowed subse quent to the manipulation, functional range was regained.
Range of joint motion, along with freedom of movement, produced the same effect, although more gradually; after 35 days the joints were histologically indistinguishable. Rat knee joints immobilized for more than 30 days, however, did not regain full functional range. Again, the re sults suggest that movement restores the normal histological makeup of connective tissue, but the longer the period of immobilization, the lower the potential for achieving optimal results.
In summary, immobilization of connective tissue genera lly results in loss of ground sub stance with no net collagen loss (with immo bilization periods of less than 12 weeks). The loss of ground substance also allows for signifi cant water loss. Histologically, this results in decreased tissue extensibility due to the inability
'iI
Figure 4-6 Diagrammatic representation of the qualitative difference in pattern of dorsiflexion between limbs casted for six weeks (n and all other limbs (t). In all ankles casted for 6 weeks, the curve exhibited intermediate plateaus ( ), followed by small but sudden slipping further into dorsiflexion (*), suggesting rupture of an adhesion with each slip. Source. Reprinted from Reynolds, C.A., Cummings, G.S., and Andrew, PD. et aI., The Effect of Nontraumatic Immobilization on Ankle Dorsiflexion, Journal a/Orthopaedic and Sports Therapy, Vol.
23, No. I, p. 31, with permission of the Orthopaedic and Sports Sections of the American Physical Therapy Association.
of the fibers to maintain the critical in-
and the formation
of microscopic cross-links, At the mac
roscopic level, immobilization causes the forma tion of f ibrofatty macroadhesions that become progressively more f ibrotic with increased im mobilization times, The studies also indicate that all periarticular connective tissues responded in the same basic fashion, and cap su Ie surrounding fascia all had the same basic response to immobilization, Remobilization of the tissues causes a reversal of
the immobilization time has not been unreason More research is needed on duration
and within the
connective tissues. Clinicians need to consider
the changes in the immobilized
connective tissues and accordingly. Before
weakened cells
gentle mid-range movement and from
excessive forces; but after 6 treatment protocols should incorporate sufficient stress to induce connective remodeling to accommodate
until full is
achieved28
Traumatized Connective Tissue
questions have arisen about how traumatized connective tissue response to im mobility differs from that of nontraumatized tissue. The previous studies have dealt with the response of nontraumatized connective tissue to immobilization. Some consider internal fixation
of a limb to be a form of im
mobilization, even though the f ixation is located some distance from the tissue studied, In a
human were casted for a of several weeks and then examined. The range of motion lost
the immobilization within one treatment session of 20 minutes. The implication of this
of the previous immobilization studies is that when connective tissues of Jomts are immobilized in the presence of inflammatory joint contractures occur, and result
from and of connective
limb is immobilized without present, no con tracture occurs, even after weeks5,6 Apparently, a catalyst is needed to begin the process of con tracture the is traumatic exudate. Also, methods of fixation may affect tissue changes,
The other factor in the different results re ported in the two studies may be the method of fixation, The fixation oflhe previous stud
no movement, whereas the cast f ixation in the Flowers may have
allowed movement to prevent tissue
can be seen clinically for in the fixation methods of distal radial fractures, When the fracture is casted, a less than optimal union occurs, usually with the formation of extra callus, From a rehabilitation standpoint, the functional range of motion of the wrist, hand, and radio-ulnar joints is usually restored. If the fracture is fixated with an external f ixator, the union is Iy much cleaner, with less callus formation. Functional range of motion is typically not fully however, especially in the wrist and radio-ulnar
The clinical
patients for rehabili
tation or surgery and subse
quent immobilization will have connective tissue changes as described. Second, a combina tion of two processes is occurring-scar forma tion and f ibrosis. Scar formation occurs in areas that sustained direct insult and are in need of Fibrotic changes occur
in tissues the scar area that were not
directly traumatized but affected chemically by the traumatic exudates. Traumatic exudates in fi ltrate these
and,
in the connective tissues,
Scar tissue versus Scar formation
and fibrosis are two different histo
logical processes, some similarities
exist. Scar formation is a localized response, with activity limited to a traumatized area, but
57 Histopathology
of the connective tissue. Limitation in mobility caused by scar tissue results from the lack of ex tenstbil ity of the scar tissue and from the adhe
sions formed with healthy connective
tissue. Limitation in mobility caused fibrotic
results from the lack of of
the entire tissue. And as
fixation methods may a part. im
mobilization (immobilizer or cast) may allow sufficient movement to dampen the effects of immobilization,
For example, a shoulder may be frozen due to a macroscopic scar adhesion in the folds of
the inferior A manipulation under anes
thesia would tear the scar adhesion and restore A frozen shoulder may also be caused a where the entire capsule shrinks (the analogy here is the size 5 and a
size 8 sock is
The distinction is that homogenous
in the rather than a scar
adhesion, limit motion, A manipulation under anesthesia may not be as successful in such a case, since an entire tissue is for the immobi The benefit of the increased mobil
the potentia I to
fabric and the restimulation of the fibrotic
Muscle Tissue
The response of muscle tissue to immobiliza tion is less simplistic and more multifactorial than the response of connective tissue to immo
bilization, a contractile a muscle
can be or actively immobilized and/or the muscle may be immobiJized in a shortened or lengthened position. The muscle may be in
nervated or or slow
twitch or predominantly fast twitch. Being a highly metabolic the immobilized muscle
can metabolic
depending on its activity level. The purpose of this section is to outline the histological response of muscle tissue to immobilization and to review the various factors in Im mobilized muscle that are the most applicable to myofascial manipulation,
and Manipulation
One of the classic works on muscle response
to immobilization was Tabery et
aPI In this study, cat soleus muscles were im mobil ized at various lengths and for various
of time. The animals were immobilized cast. Some of the animals were sacri
ficed and the muscles were and
histologically Biomechanically, the
was increased in the mus cles immobilized in the shortened position, ably because of the connective tissue
within and surrounding the muscle, Muscles immobilized in the lengthened position had no
in the length-tension
characteristics. From a
the muscles immobilized in the shortened posi
tion had a 40% loss with an over
aU decrease in fiber length. The muscles im
mobilized in the position exhibited
a 19% increase in sarcomeres and an overall increase in fiber After 4 weeks of re mobilization, the number of sarcomeres in the muscles returned to normal. This study illus trates the principle that muscle tissue will
to change in by or
sarcomeres in order to keep sarcomeres at mal lengths.
In a follow-up study muscle
were studied. Sciatic nerves were stimulated for I
either the shortened or lengthened
muscles stimulated in the shortened range had a 25% loss of sarcomeres after 12 hours of
contraction. Sarcomeres were recov
ered in the muscles between 48 and 72 hours, The implication of these studies is that muscles shortened lose sarcomeres at a much slower pace than muscles actively shortened.
Kauhallen al immobilized the vastis inter medius of t3 rabbits in a shortened position for 2 to 28 days, After 3 days of immobilization, the muscle a J 5% decline in muscle
fiber diameter. changes were
and muscle fiber diameter had de creased to 56%. By 4 severe fibrotic
diameter had decreased to 47% of control values.33
Leivo et aP4 also immobilized the vastis in termedius of rabbits into the extended position. Progressive disorganization of myofibrils with breaking up of Z bands and an increase in the number and size of plasmic lipid vacuoles was seen with increased duration of immobilization. This study, as does the prior study, suggests that adverse mechanisms are in effect at the onset of disuse atrophy.
Kannus et aps found that, after 3 weeks of immobilization, there was a significant decrease