Acute inflammation has a short onset and a short duration. It consists of hemodynamic changes, production of an exudate, and the presence of granular leukocytes. Chronic inflammation has a long onset and a long duration. It displays a presence of nongranular leukocytes and a more extensive formation of scar tissue.
Acute inflammation: vascular and cellular events
- 5 cardinal signs of inflammation (4) originally by Roman physician Celsius in 1st Century AD; Galen, a Greek physician added functio laesa in the second century.
- serve as reminder to athlete of injury and to prevent the athlete from exceeding safe limits and reinjuring area
- redness (rubor)
- swelling (tumor)
- heat (calor)
- pain (dolor)
- loss of function (functio laesa)
Three phases: acute, reactive, or substrate inflammatory phase; the repair and regeneration phase; and the remodeling phase.
Phase I: Acute phase
The acute phase of inflammation is the initial reaction of body tissue to an irritant or injury and is characteristic of the first 3 or 4 days after injury. Acute inflammation is the fundamental reaction designed to protect, localize, and rid the body of some injurious agent in preparation for healing and repair. The main causes of inflammation are trauma, chemical agents, thermal extremes, and pathogenic organisms.
First hour. At the time of trauma, before the usual signs of inflammation appear, a transitory vasoconstriction occurs, causing decreased blood flow. At the moment of vasoconstriction, coagulation begins to seal broken blood vessels, followed by the activation of chemical influences. Vasoconstriction is replaced by dilation of venules, arterioles, and capillaries in the immediate area of the injury.
Second hour. Vasodilation brings with it a slowing of blood flow, increased blood viscosity, and stasis, which leads to swelling (edema). With dilation also comes exudation of plasma and concentration of red blood cells (hemoconcentration). Much of the plasma exudate results from fluid seepage through the intact vessel lining, which becomes more permeable, and from higher pressure within the vessel. Permeability is relatively transient in mild injuries, lasting only a few minutes, with restoration to a pre-injury state in 15 to 30 minutes. In slightly more severe situations there may be a delayed response with a late onset of permeability. In such cases, permeability may not appear for hours and then appears with some additional irritation and a display of rapid swelling lasting for an extended period.
A redistribution of leukocytes occurs within the intact vessels, caused in part by a slowing of circulation. These leukocytes move from the center of the blood flow to become concentrated and then line up and adhere to the endothelial walls. This process is known as margination, or pavementing, and occurs mainly in venules. The leukocytes pass through the wall of the blood vessel by ameboid action, known as diapedesis, and are directed to the injury site by chemotaxis (a chemical attraction to the injury). It should be noted that ameboid motion is a slow process, taking about 6 hours. With an injury there is also an increase in lymph flow because of a high interstitial tissue pressure.
In phase I of acute inflammation, mast cells and leukocytes are in abundance. Mast cells are connective tissue cells that contain heparin (a blood anticoagulant) and histamine. Basophils, monocytes, and neutrophils are the major leukocytes. Basophils leukocytes are believed to bring anticoagulant substances to tissues that are inflamed and are present during both acute and chronic inflammatory healing phases. The neutrophils representing about 60% to 70% of the leukocytes arrive at the injury site before the larger monocytes. They immigrate from the bloodstream. Neutrophils emigrate from the bloodstream through diapedesis and phagocytosis to ingest smaller debris than do monocytes. Phagocytosis is the process of ingesting material such as bacteria, dead cells, and other debris associated with disease, infection, or injury. Opsonin is a protein substance in the blood serum that coats microorganisms and other cells, making them more amenable to phagocytosis. The phagocyte commonly accomplishes this process by projecting cytoplasmic pseudopods, which engulf the object and ingest the particle through enzymes. When the neutrophils disintegrates, it gives off enzymes called lysozomes, which digest engulfed material. These enzymes act as irritants and continue the inflammatory process. Neutrophils also have chemotactic properties, attracting other leukocytes to the injured area. The monocyte, which is a nongranular leukocyte, arrives on the scene into large macrophages that have the ability to ingest large particles of bacteria or cellular debris.
Chemical mediators for the inflammatory process are stored and given off by various cells. Histamine, the first chemical to appear in inflammation, is given off by blood platelets, basophils leukocytes, and mast cells. It is a major producer of arterial dilation, venule, and capillary permeability. Serotonin is a powerful vasoconstrictor found in platelets and mast cells. With an increase in blood there is an increase in local metabolism. Permeability is produced by the contraction of the endothelial cells of the capillary wall, producing a gap between cells. Gaps allow plasma to leak proteins, platelets, and leukocytes. Plasma proteases, with their ability to produce polypeptides, act as chemical mediators. A major plasma protease in inflammation is bradykinin, which increases permeability and causes pain.
Heparin is also given off by mast cells and basophils and temporarily prevents blood coagulation. In addition, in the early stages of acute injury, prostaglandins and leukotrienes are produced. Both of these substances stem from arachidoic acid; however, prostaglandins are produced in almost all body tissues. They are stored in the cell membranes phospholipids. Leukotrienes alter capillary permeability and, it is believed, play a significant role, along with prostaglandin, in all aspects of the inflammatory process. Prostaglandins apparently encourage, as well as inhibit, inflammation depending on the conditions that are prevalent at the time.
Inflammation response Mediators
vasoconstriction serotonin from platelets and mast cells
vasodilation histamine from platelets, basophils, and mast cells
prostaglandin from arachidonic acid
leukotrienes from arachidonic acid
bradykinin from body fluids
margination and pavementing loss of micro-circulation, increase in blood viscosity
emigration of leukocytes leukocytes pass through capillary walls (diapedesis)
chemotaxis leukocytes attract other leukocytes
phagocytosis leukocytes, debris, complement, opsonization
Bleeding and exudate
The extent of fluid in the injured area is highly dependent on the extent of damaged vessels and the permeability of the intact vessel. Blood coagulates in three stages. In the initial stage thromboplastin is formed. In the second stage prothrombin is converted into thrombin under the influence of thromboplastin with calcium. In the third stage, thrombin changes from soluble fibrinogen into soluble fibrin. The plasma exudate then coagulates into a network of fibrin and localizes the injured area.
Phase II: Repair phase
The term repair is synonymous with healing, whereas regeneration refers to restoration of destroyed or lost tissue. Healing, which extends from the inflammatory phase (48 to 72 hours to approximately 6 weeks), occurs when the area has become clean through the removal of cellular debris, erythrocytes, and the fibrin clot. Tissue repair is accomplished through three processes: by resolution, in which there is little tissue damage and normal restoration; by the formation of granulation tissue, occurring if resolution is delayed, and by regeneration the replacement of tissue by the same tissue. The formation of scar tissue after trauma is a common occurrence; however, because scar tissue is less viable than normal tissue, the less scarring the better. When mature, scar tissue represents tissue that is firm, fibrous, inelastic, and devoid of capillary circulation. The type of scar tissue known as adhesion can complicate the recovery of joint or organ disabilities. Healing by scar tissue begins with an exudate, a fluid with a large content of protein and cellular debris that collects in the area of the injury site. From the exudate, a highly vascular mass develops known as granulation tissue. Infiltrating this mass is a proliferation of immature connective tissue (fibroblasts) and endothelial cells. Gradually the collagen protein substance, stemming from fibroblasts, forms a dense, fibrous scar. Collagenous fibers have the capacity to contract approximately 3 to 14 weeks after an injury and even as long as 6 months afterward in more severe cases.
During this stage, two types of healing occur. Primary healing, healing by first intention, takes place in an injury that has even and closely opposed edges, such as a cut or incision. With this type of injury, if the edges are held in very close approximation, a minimum of granulation tissue is produced. Secondary healing, healing by secondary intention, results when there is a gaping lesion and large tissue loss leading to replacement by scar tissue. External wounds such as lacerations and internal musculoskeletal injuries commonly heal by secondary intention.
Phase III: Remodeling Phase
Remodeling of the traumatized area overlaps that of repair and regeneration. Normally in acute injuries the first 3 to 6 weeks are characterized by increased production of scar tissue and increased strength fibers. Strength of scar tissue continues to increase from 3 months to 2 years after injury. Ligamentous tissue takes as long a 1 year to become completely remodeled. To avoid a rigid, non-yielding scar, there must be a physiological balance between synthesis and lysis. There is simultaneous synthesis of collagen by fibroblasts and lysis by collagenase enzymes. The tensile strength of collagen apparently is specific to the mechanical forces imposed during the remodeling phase. Forces applied to the ligament during rehabilitative exercise will develop strength specifically in the direction that force is applied. If too early or excessive strain is placed on the injury, the healing process is extended. For proper healing of muscles and tendons, there must be careful consideration to mobilize the site. Early mobilization can assist in producing a more viable injury site; on the other hand, too long a period of immobilization can delay healing. The ideal of collagen remodeling is to have the healed area contain a preponderance of mature collagenous fibers that have a number of cross-linkages. As stated, collagen content and quality may be deficient for months after injury.
If acute inflammation reaction fails to be resolves in 1 month, it is termed a sub-acute inflammation. If it lasts for months or even years, the condition is termed chronic. Major chemicals found during chronic inflammation are the kinins (especially bradykinin), which also cause vasodilation, increased permeability, and pain. Prostaglandin, also seen in chronic conditions, causes vasodilation. Prostaglandin can be inhibited by aspirin.
Soft tissue healing
All tissues of the body can be defined as soft tissue except for bone. The human body has four types of soft tissue: epithelial tissue, which consists of the skin and the lining of vessels and many organs; connective tissue, which consists of tendons, ligaments, cartilage, fat, blood vessels, and bone; muscle, which can be skeletal, cardia, or visceral and nervous tissue, which consists of the brain, spinal cord, and nerves.
Articular cartilage has limited capacity to heal. Cartilage has little or no direct blood supply. When chondrocytes are destroyed and the matrix is disrupted, healing is variable. Articular cartilage that fails to clot and as no perichondrium heals and repairs slowly. On the other hand, if the affected area includes the subchondral bone, which has a greater blood supply, granulation tissue is formed and the healing process proceeds normally.
Ligament healing follows the same course of healing as other vascular tissue. If proper immediate and follow-up management is done, a sprained ligament will undergo the acute, repair, and remodeling phases in approximately the same time period as other vascular tissues.
During the repair phase, collagen fibers realign in reaction to joint stress and strains. Full ligament healing with scar maturation may take as long as twelve months.
Skeletal muscle healing
Skeletal muscles cannot undergo the mitotic activity required to replace cells that have been injured. In other words, regeneration of new myofibers is minimal. Skeletal muscle healing and repair follow the same process as other soft tissue developing tensile strength according the Wolffs law.
Wolffs law states that after injury both bone and soft tissue will respond to the physical demands placed on them, causing them to remodel or realign along lines of tensile force. Therefore it is critical that injured structures be exposed to progressively increasing loads throughout the rehabilitation process.
Because of the nature of nerve cells, they cannot regenerate after they have died. Regeneration can take place within a nerve fiber. The closer the injury is to the nerve cell, the more difficult regeneration becomes.
For nerve regeneration to occur, an optimal environment must be present. If peripheral nerve regeneration occurs, it is at a rate of only 3 to 4 mm per day. Injured nerves within the central nervous system do not regenerate as well as peripheral nerves do.
Modifying Soft-Tissue healing
The healing process is unique in each athlete. Age and general nutrition can play a role in healing. The older athlete may be more delayed in healing than younger athletes are. The injuries of an athlete with poor nutritional status may heal more slowly than normal. Athletes with certain organic disorders may heal slowly. For example, blood conditions such as anemia and diabetes often inhibit the healing process.
1. Drugs to treat the inflammation. There is a current trend toward the use of antiprostaglandin medications, or nonsteroidal anti-inflammatory drugs (NSAIDs). The intent of this practice is to decrease vasodilation and capillary permeability.
2. Therapeutic modalities. Both cold and heat are used for different conditions. In general, heat stimulates acute inflammation and cold acts as an inhibitor. Conversely, in chronic conditions, heat may severe as a depressant. A number of electrical modalities are used for the treatment of inflammation stemming from sports injuries.
3. Therapeutic exercise. A major aim of soft-tissue rehabilitation through exercise is pain-free movement, full-strength power, and full extensibility of associated muscles. The ligamentous tissue, if related to the injury, should become pain free and have full tensile strength and full range of motion. The dynamic joint stabilizers should regain full strength and power. Immobilization of a part after injury or surgery is not always good for all injuries. When a part is immobilized over an extended period of time, adverse biochemical changes occur in collagenous tissue. Early mobilization used in exercise rehabilitation that is highly controlled may enhance the healing process.
The osteoblast is the cellular component of bone and forms its matrix; the osteocyte both forms and destroys bone, and osteoclasts destroy and resorb bone. The constant ongoing remodeling of bone is caused by osteocytes; osteoclasts are related mainly to pathological responses. Osteoclasts come from the cambium layer of the periosteum, which is the fibrous covering of the bone, and are involved in bone healing. The inner cambium layer, in contrast to the highly vascular and dense external layer, is more cellular and less vascular. It serves as a foundation for blood vessels and provides a place for attaching muscles, tendons, and ligaments.
Acute fracture healing
Acute fracture healing follows the same three phases that soft tissue does but is more complex. In general acute fracture healing has five stages: hematoma formation, cellular proliferation, callus formation, ossification, and remodeling.
Acute inflammation usually lasts approximately four days. When a bone fractures, there is trauma to the periosteum and surrounding soft tissue. With hemorrhaging, a hematoma accumulates in the medullary canal and surrounding soft tissue in the first 48 to 72 hours. The exposed ends of vascular channels become occluded with clotted blood accompanied by dying of the osteocytes, disrupting the intact blood supply. The dead bone and related soft tissue begin to elicit a typical inflammatory reaction, including vasodilation, plasma exudates, and inflammatory cells.
The hematoma in a bony fracture, like in a soft-tissue injury, begins its organization in granulation tissue and gradually builds a fibrous junction between the fractured ends. At this time the environment is acid, but it will slowly change to neutral or slightly alkaline. A major influx of capillary buds that carry endosteal cells from the bones cambium layer occurs. These cells first produce a fibrous callus, then cartilage, and finally a woven bone. When there is an environment of high oxygen tension, fibrous tissue predominates, whereas when oxygen tension is low, cartilage develops. Bone will develop at the fracture site when oxygen tension and compression are in the proper amounts.
The soft callus, in general, is an unorganized network of woven bone formed at the ends of the broken bone that is later absorbed and replaced by bone. At the soft-callus stage, both internal and external calluses are produced that bring an influx of osteoblasts that begin to immobilize the fracture site. The internal and external calluses are formed by bone fragments that grow to bridge the fracture gap. The internal callus grows rapidly to create a rigid immobilization. Beginning in the three to four weeks, and lasting three to four months, the hard callus forms. Hard callus is depicted by a gradual connecting of bone filament to the woven bone at the fractured ends. Less than satisfactory immobilization produces a cartilaginous rather than bony union.
With adequate immobilization and compression, the bone ends become crossed with a new haversian system that will eventually lead to the laying down of primary bone. The ossification stage is the completion of the laying down bone. The fracture has been bridged and firmly united. Excess has been resorbed by osteoclasts.
Remodeling occurs after the callus has been resorbed and trabecular bone is laid down along the lines of stress. Complete remodeling may take many years. The influence of biochemical stimulation (piezoelectric effect) is the basis for development of new trabecular bone to be laid down at a point of greatest stress. This influence is predicted on the fact that bone is electropositive on its convex side and electronegative on its concave side. The convex considered the tension side, whereas the concave is the compression side. Significantly, osteoclasts are drawn to a positive electrical charge and osteoblasts to a negative electrical charge. Remodeling is considered complete when a fractured bone has been restored to its former shape or has developed a shape that can withstand imposed stresses.
Management of Acute Fractures
1. If there is poor blood supply to the fractured area and one of the parts of the broken bone is not properly supplied by the blood, that part will die and union or healing of the fracture will not take place. This condition is known as avascular necrosis and often occurs in the head of the femur, the navicular of the wrist, the talus of the ankle, and isolated bone fragments.
2. Poor immobilization of the fracture site, resulting from poor casting by the physician and permitting motion between the bone parts, may not only prevent proper union but may also, in the event that union does transpire, cause deformity to develop.
3. Infection can materially interfere with the normal healing process, particularly in the case of a compound fracture, which offers an ideal situation for development of a severe streptococcal or staphylococcal infection.
Pain receptors, known as nociceptors, or free nerve endings, are sensitive to extreme mechanical, thermal, and chemical energy. They are commonly found in meninges, periosteum, skin, teeth, and some organs.
A nociceptive neuron transmits pain information to the spinal cord via the unmyelinated C fibers and the myelinated A-delta fibers. The smaller C fibers carry the impulses at a rate of 0.5 to 2.0 m per second and larger A-delta fibers at a rate of 5 to 30 m per second. When a nociceptor is stimulated there is release of a neuropeptide (substance P) that initiates an electrical impulse along the afferent fiber toward the spinal cord. The faster A-delta afferent fiber impulse moves up the spinal cord at a moderately rapid speed to the thalamus, which gives a precise location of the acute pain, which is perceived as being bright, sharp, or stabbing. In contrast the slower-conducting smaller unmyelinated C fibers are concerned with pain that is diffused, dull, aching, and unpleasant. It also terminates in the thalamus, with projections to the limbic cortex that provide an emotional aspect to this pain. Nociceptive stimuli are at close to an intensity that produces tissue damage.
The nervous system is powered electromechanically. Chemicals released by a presynaptic cell cross a synapse, stimulating or inhibiting a postsynaptic cell. This is called a neurotransmitter. Two types of chemical neurotransmitters that mediate pain are the endorphins and serotonin. They are generated by noxious stimuli, which activate inhibition of pain transmission.
Stimulation of the periaqueductal gray area (PGA) of the midbrain and the raphe nucleus in the pons and medulla causes analgesia. Analgesia is produced by the stimulation of opiods, morphine-like substances manufactured in the PGA and many other areas of the central nervous system. These endogenous opoid peptides are known as endorphins and enkephalins.
Noradrenergic neurons stimulating norepinephrine can also inhibit pain transmission. Serotonin has also been identified as a neuromodulator.
1. Fast or slow fast pain is localized and carried through A-delta axons located in the skin. Slow pain is perceived as aching, throbbing, or burning. It is conducted through the C-fibers.
2. Acute or chronic acute pain is less than 6 months. Chronic pain has a duration longer than 6 months.
3. Projected (referred) pain. Such pain occurring away from actual sire of irritation. Example Kehrs sign indicates an involved spleen.
Common to musculoskeletal injuries is the cyclic condition of pain-spasm-hypoxia-pain. Disrupting this cycle can occur trough a variety of means such as heat or cold, electrical stimulation-induced analgesia, or selected pharmacological approaches.
The gate theory and TENS
The gate theory, as developed by Melzack and Wall, sets forth the idea that the spinal cord is organized in such a way that pain or other sensations may be experienced. An area located in the dorsal horn causes inhibition of the pain impulses ascending to the cortex for perception. The area, or gate, within the dorsal horn is composed of T cells and substantia gelatinosa. T cells apparently are neurons that organize stimulus input and transmit the stimulus to the brain. The substantia gelatinosa functions as a gate-control system. It determines the stimulus input sent to the T cells from peripheral nerves. If the stimulus from a noxious material exceeds a certain threshold, pain is experienced. Apparently the smaller and slower nerve fibers carry pain impulses, and larger and faster nerve fibers carry other sensations. Impulses from the faster fibers arriving at the gate first inhibit pain impulses. In other words, stimulation of large, rapidly conducting fibers can selectively close the gate against the smaller pain fiber input. This concept explains why acupuncture, acupressure, cold, heat, and chemical skin irritation can provide some relief against pain. It also provides a rationale for the current success of TENS.