1. Chapter 10: Tissue Response to Injury

2. Inflammatory Response
Acute Inflammation
Short onset and duration
Change in hemodynamics, production of exudate, granular leukocytes
Chronic Inflammation
Long onset and duration
Presence of non-granular leukocytes and extensive scar tissue

3. Cardinal Signs of Inflammation
Rubor (redness)
Tumor (swelling)
Color (heat)
Dolor (pain)
Functio laesa (loss of function)

4. Phases of the Inflammatory Response
(3 separate phases)
1. Acute phase
2. Repair phase
3. Remodeling phase

5. Phase I: Acute Phase
Initial reaction to an injury occurring 3 hours to 4 days following injury
Goal
Protect
Localize
Decrease injurious agents
Prepare for healing and repair
Caused by trauma, chemical agents, thermal extremes, pathogenic organisms

6. External and internal injury result in tissue death and cell death
Decreased oxygen to area increases cell death
Phagocytosis will add to cell death due to excess digestive enzymes
Rest, ice, compression & elevation are critical to limiting cell death

7. First hour
Vasoconstriction and coagulation occur to seal blood vessels and chemical mediators are released
Immediately followed by vasodilation or blood vessel
Second hour
Vasodilation decreases blood flow, increased blood viscosity resulting in edema (swelling)

8. Second hour (continued)
Exudate increases (high concentration of RBC’s) due to increased vessel permeability
Permeability changes generally occur in capillary and venules
Margination occurs causing leukocytes to fill the area and line endothelial walls
Through diapedesis and chemotaxis leukocytes move to injured area

9. Cellular response
Mast cells (connective tissue cells) and leukocytes (basophils, monocytes, neutrophils) enter area
Mast cells with heparin and histamine serve as first line of defense
Basophils provide anticoagulant
Neutrophils and monocytes are responsible for small and large particles undergoing phagocytosis - ingestion of debris and bacteria

10. Cellular mediation
Histamine provided by platelets, mast cells and basophils to enhance permeability and arterial dilation
Serotonin provides for vasoconstriction
Bradykinin is a plasma protease that enhance permeability and causes pain.
Heparin is provided by mast cells and basophils to prevent coagulation
Leukotrienes and prostaglandins are located in cell membranes and develop through the arachadonic acid cascade
Leukotrienes alter permeability
Prostaglandin add and inhibit inflammation

11. Complimentary systems
Enzymatic proteins that destroy bacteria and other cells through their impact on cell lysis
Bleeding and exudate
Amount dependent on damage
Initial stage: thromboplastin is formed
Second stage: Prothrombin is converted to thrombin due to interaction with thromboplastin
Third stage: thrombin changes from soluble fibrinogen to insoluble fibrin coagulating into a network localizing the injury

13. Phase II: Repair Phase
Phase will extent from 48 hours to 6 weeks following cleaning of fibrin clot, erythrocytes, and debris
Repaired through 3 phases
Resolution (little tissue damage and normal restoration)
Restoration (if resolution is delayed)
Regeneration (replacement of tissue by same tissue)

15. Scar formation Less viable than normal tissue, may compromise healing
Firm, inelastic mass devoid of capillary circulation
Develops from exudate with high protein and debris levels resulting in granulation tissue
Invaded by fibroblasts and and collagen forming a dense scar and while normally requiring 3-14 weeks may require 6 months to contract

16. Primary healing (healing by first intention)
Closely approximated edges with little granulation tissue production
Secondary healing (heal by secondary intention)
Gapping, tissue loss, and development of extensive granulation tissue
Common in external lacerations and internal musculoskeletal injuries

17. Regeneration Related to health, nutrition and tissue type
Dependent on levels of:
debris (phagocytosis)
endothelial production (hypoxia and macrophages stimulate capillary buds)
production of fibroblasts (revascularization allows for enhanced fibroblast activity and collagen production which is tied to Vitamin C, lactic acid, and oxygen

18. Phase III: Remodeling Overlaps repair and regeneration
First 3-6 weeks involves laying down of collagen and strengthening of fibers
3 months to 2 years allowed for enhanced scar tissue strength
Balance must be maintained between synthesis and lysis
Take into consideration forces applied and immobilization/mobilization time frames relative to tissue and healing time

20. Chronic Inflammation
Result of failed acute inflammation resolution within one month termed subacute inflammation
Inflammation lasting months/years termed chronic
Results from repeated microtrauma and overuse
Proliferation of connective tissue and tissue degeneration

21. Characteristics of Chronic Inflammation
Proliferation of connective tissue and tissue degeneration
Presence of lymphocytes, plasma cell, macrophages(monocytes) in contrast to neutrophils (during acute conditions)
Major chemicals include
Kinins (bradykinin) - responsible for vasodilation, permeability and pain
Prostaglandin - responsible for vasodilation but can be inhibited with aspirin and NSAID’s

22. Factors That Impede Healing
Extent of injury
Edema
Hemorrhage
Poor Vascular Supply
Separation of Tissue
Muscle Spasm
Atrophy
Corticosteroids
Keloids and Hypertrophic Scars
Infection
Humidity, Climate, Oxygen Tension
Health, Age, and Nutrition

23. Soft Tissue Healing Cell structure/function
All organisms composed of cells
Properties of soft tissue derived from structure and function of cells
Cells consist of nucleus surrounded by cytoplasm and encapsulated by phospholipid cell membrane
Nucleus contains chromosomes (DNA)
Functional elements of cells (organelles) include mitochondria, ribosomes, endoplasmic reticulum, Golgi apparatus & centrioles

24. Tissues of the Body Bone - not classified as soft tissue
4 types of soft tissue
Epithelial tissue
Skin, vessel & organ linings
Connective tissue
Tendons, ligaments, cartilage, fat, blood, and bone
Muscle tissue
Skeletal, smooth, cardiac muscle
Nerve tissue
Brain, spinal cord & nerves

25. Soft Tissue Adaptations
Metaplasia - transformation of tissue from one type to another that is not normal for that tissue
Dysplasia - abnormal development of tissue
Hyperplasia- excessive proliferation of normal cells in normal tissue arrangement
Atrophy- a decrease in the size of tissue due to cell death and re-absorption or decreased cell proliferation
Hypertrophy - an increase in the size of tissue without necessarily changing the number of cells

26. Cartilage Healing Limited capacity to heal
Little or no direct blood supply
Chrondrocyte and matrix disruption result in variable healing
Articular cartilage that fails to clot and has no perichondrium heals very slowly
If area involves subchondral bone (enhanced blood supply) granulation tissue is present and healing proceeds normally

27. Ligament Healing Follows similar healing course as vascular tissue
Proper care will result in acute, repair, and remodeling phases in same time required by other vascular tissue
Repair phase will involve random laying down of collagen which, as scar forms, will mature and realign in reaction to joint stresses and strain
Full healing may require 12 months

28. Skeletal Muscle Healing
Skeletal muscle cannot undergo mitotic activity to replace injured cells
New myofibril regeneration is minimal
Healing and repair follow the same course as other soft tissues developing tensile strength (Wolff’s Law)

29. Nerve Healing Cannot regenerate after injury
Regeneration can take place within a nerve fiber
Proximity of injury to nerve cell makes regeneration more difficult
For regeneration, optimal environment is required
Rate of healing occurs at 3-4 mm per day
Injured central nervous system nerves do not heal as well as peripheral nerves

30. Modifying Soft-Tissue Healing
Varying issues exist for all soft tissues relative to healing (cartilage, muscle, nerves)
Blood supply and nutrients is necessary for all healing
Healing in older athletes or those with poor diets may take longer
Certain organic disorders (blood conditions) may slow or inhibit the healing process

31. Management Concepts Drug utilization
Anitprostaglandin agents used to combat inflammation
Non-steroidal anti-inflammatory agents (NSAID’s)
Medications will work to decrease vasodilatation and capillary permeability

32. Therapeutic Modalities
Thermal agents are utilized
Heat stimulates acute inflammation (but works as a depressant in chronic conditions)
Cold is utilized as an inhibitor
Electrical modalities
Treatment of inflammation
Ultrasound, microwave, electrical stimulation (includes transcutaneous electrical muscle stimulation and electrical muscle stimulation

33. Therapeutic Exercise
Major aim involves pain free movement, full strength power, and full extensibility of associated muscles
Immobilization, while sometimes necessary, can have a negative impact on an injury
Adverse biochemical changes can occur in collagen
Early mobilization (that is controlled) may enhance healing

34. Fracture Healing
Potential serious bone fractures are part of athletics
Time is necessary for proper bone union to occur and is often out of the control of a physician
Conservative treatment will be necessary for adequate healing to occur

35. Bone undergoes constant remodeling through osteocyte activity
Osteocytes cellular component of bone
Osteoblasts are responsible for bone formation while osteoclasts resorb bone
Cambium (periosteum)
A fibrous covering involved in bone healing
Vascular and very dense
Inner cambium
less vascular and more cellular.
Provides attachments for muscle, ligaments and tendons

36. Acute Fracture of Bone
Follows same three phases of soft tissue healing
Less complex process
Acute fractures have 5 stages
Hematoma formation
Cellular proliferation
Callus formation
Ossification
Remodeling

38. Hematoma Formation
Trauma to the periosteum and surrounding soft tissue occurs due to the initial bone trauma
During the first 48 hours a hematoma within the medullary cavity and the surrounding tissue develops
Blood supply is disrupted by clotting vessels and cellular debris
Dead bone results in an inflammatory response (vasodilation, exudate cell migration)

39. Cellular Formation
Granulation forms constructing fibrous union between fractured ends
Capillary buds allow endosteal cells influx from cambium layer
Cells evolve from fibrous callus to cartilage, to woven bone
High oxygen tension = fibrous tissue
Low oxygen tension = cartilage tissue
Bone growth will occur with optimal oxygen tension and compression

40. Callus Formation Soft callus is a random network of woven bone
Osteoblasts fill the internal and external calluses to immobilize the site
Calluses are formed by bone fragments that bridge the fracture gap
The internal callus creates a rigid immobilization early

41. Hard callus formation occurs after 3-4 weeks and lasts 3-4 months
Hard callus is a gradual connection of bone filaments to the woven bone
Less than ideal immobilization produces a cartilagenous union instead of a bony union

42. Ossification
Adequate immobilization and compression will result in new Haversian systems developing
Haversian canals allow for the laying down of primary bone
Ossification is complete when bone has been laid down and the excess callus has been resorbed by osteoclasts.

43. Remodeling
Occurs following callus resorption and trabecular bone is laid along lines of stress
Bioelectric stimulation plays a major role in completing the remodeling process
Osteoblasts are attracted to the electronegative (concave/compression) side
Osteoclasts are attracted to the electropositive (convex/tension) side
The process is complete when the original shape is achieved or the structure can withstand imposed stresses

44. Acute Fracture Management
Must be appropriately immobilized, until X-rays reveal the presence of a hard callus
Fractures can limit participation for weeks or months
A clinician must be certain that the following areas do not interfere with healing
Poor blood supply
Poor immobilization
Infection

45. Poor blood supply Poor immobilization
Bone may die and union/healing will not occur (avascular necrosis)
Common sites include:
Head of femur, navicular of the wrist, talus, and isolated bone fragments
Relatively rare in healthy, young athletes except in navicular of the wrist
Poor immobilization
Result of poor casting allowing for motion between bone parts
May prevent proper union or result in bony deformity

46. Infection
May interfere with normal healing, particularly with compound fractures
Severe streptococcal and staphylococcal infections
Modern antibiotics has reduced the risk of infections
Closed fractures are not immune to infections within the body or blood
If soft tissue alters bone positioning, surgery may be required to ensure proper union

47. Healing of Stress Fractures
Result of cyclic forces, axial compression or tension from muscle pulling
Electrical potential of bone changes relative to stress (compression, tension, or torsional)
Constant stress axially or through muscle activity can impact bone resorption, leading to microfracture

48. If osteoclastic activity is not in balance with oesteoblastic activity bone becomes more susceptible to fractures
To treat stress fractures a balance between osteoblast and osteoclast activity must be restored
Early recognition is necessary to prevent complete cortical fractures
Decreased activity and elimination of factors causing excess stress will be necessary to allow for appropriate bone remodeling

49. Pain Major indicator of injury Pain is individual and subjective
Factors involved in pain
Anatomical structures
Physiological reactions
Psychological, social, cultural and cognitive factors

50. Nociception
Pain receptors -free nerve endings sensitive to extreme mechanical, thermal and chemical energy
Located in meninges, periosteum, skin, teeth, and some organs
Pain information transmitted to spinal cord via myelinated C fibers and A delta fibers
Nociceptor stimulation results in release of substance P

51. Signal travels along afferent nerves to the spinal cord
A delta fiber (fast) transmit information to the thalamus concerning location of pain and perception of pain being sharp, bright or stabbing
C fibers (slower conduction velocity) deal with diffused, dull, aching and unpleasant pain
C fibers signal also passed to limbic cortex providing emotional component to pain
Nociceptive stimuli is at or close to an intensity which would result in tissue injury

52. Endogenous Analgesics
Nervous system is electrochemical in nature
Chemicals called neurotransmitters are released by presynaptic cell
Two types mediate pain
Endorphins
Seretonin
Neurotransmitters release stimulated by noxious stimuli- resulting in activation of pain inhibition transmission

53. Analgesia is the result of opioids release
Stimulation of periaqueductal gray matter (PGA) and raphe nucleus of pons and medulla cause analgesia
Analgesia is the result of opioids release
Morphine like substance manufactured in the PGA and CNS
Endorphins and enkephalins
Other pain modulators
Norepinephrine (noradrenergic
Seretonin also will serve as neuromodulator

54. Pain Categories Pain sources Fast versus slow pain
Acute versus chronic
Projected or referred pain

55. Pain sources Cutaneous, deep somatic, visceral and psychogenic
Cutaneous pain is sharp, bright and burning with fast and slow onset
Deep somatic pain originates in tendons, muscles, joints, periosteum and blood vessels
Visceral pain begins in organs and is diffused at first and may become localized
Psychogenic pain is felt by the individual but is emotional rather than physical

56. Acute versus Chronic Pain
Fast versus Slow Pain
Fast pain localized and carried through A-delta axons
Slow pain is perceived as aching, throbbing, or burning (transmitted through C fibers)
Acute versus Chronic Pain
Acute pain is less than six months in duration
Chronic pain last longer than six months
Chronic pain classified by IASP as pain continuing beyond normal healing time

57. Projected (Referred) Pain
Pain which occurs away from actual site of injury/irritation
Unique to each individual and case
May elicit motor and/or sensory response
A-alpha fibers are sensitive to pressure and can produce paresthesia
Three types of referred pain include: myofascial, sclerotomic, and dermatomic

58. Myofascial Pain
Trigger points or small hyperirritable areas within muscle resulting in bombardment of CNS
Acute and chronic pain can be associated with myofascial points
Often described as fibrositis, myositis, myalgia, myofasciitis and muscular strain
Two types of trigger points (active and latent)
Active points cause obvious complaint
Latent points are dormant potentially causing loss of ROM

59. Sclerotomic and dermatomic pain
Trigger points do not follow patterns
Trigger point area referred to as reference zone which may or may not be proximal to the point of irritation
Sclerotomic and dermatomic pain
Deep pain with slow or fast characteristics
May originate from sclerotomic, myotomic or dermatomic nerve irritation/injury
Sclerotomic pain transmitted by C fibers causing deep aching and poorly localized pain
Can be projected to multiple areas of brain causing depression, anxiety, fear or anger

60. Autonomic changes result (vasomotor control, BP and sweating
Dermatomic pain (irritation of A-delta fibers) is sharp and localized
Projects to the thalamus and cortex directly

61. Gate Theory
Area in dorsal horn of spinal cord causes inhibition of pain impulses ascending to cortex
T-cells will transmit signals to brain
Substantia gelatinosa functions as gate determining if stimulus sent to T-cells
Pain stimuli exceeding threshold results in pain perception
Stimulation of large fast nerves can block signal of small pain fiber input
Rationale for TENS, accupressure/puncture, thermal agents and chemical skin irritants

62. Central Biasing Theory

63. Release of B-Endorphins

64. Variation of Pain Sensitivity
Hyperesthesia, paresthia or analgesia
Pain modulation
Mixture of physical and psychological factors
Pain management is a challenge to treat
Generally acute pain management in athletic training setting

65. Pain assessment Pain Treatment
Self report is the best reflection of pain and discomfort
Assessment techniques include:
visual analog scales (0-10, marked no pain to severe pain)
verbal descriptor scales (marked none, slight, moderate, and severe)
Pain Treatment
Must break pain-spasm-hypoxia-pain cycle through treatment
Agents used; heat/cold, electrical stimulation-induced analgesia, pharmacological agents

66. Heat/Cold Induced analgesia
Heat increases circulation, blood vessel dilation, reduces nociception and ischemia caused by muscle spasm
Cold applied for vasoconstriction and prevention of extravasation of blood into tissue
Pain reduced through decrease in swelling and spasm
Induced analgesia
Utilize electrical modalities to reduce pain
TENS and acupuncture commonly used to target Gate Theory

67. Pharmacological Agents
Oral, injectable medications
Commonly analgesics and anti-inflammatory agents

68. Psychological Aspects of Pain
Pain can be subjective and psychological
Pain thresholds vary per individual
Pain is often worse at night due to solitude and absence of external distractions
Personality differences can also have an impact
A number of theories relative to pain exist and it physiological and psychological components
Athlete, through conditioning are often able to endure pain and block sensations of minor injuries