Tissue Healing & Inflammation – Exam Review

Big Picture & Context

• Athletic trainers function as the "axle" of true sports-medicine care; the term “sports medicine” itself is unregulated and often used as marketing by many professions (orthopedists, PCPs, chiropractors, etc.)

• Healing is governed by natural law; clinicians cannot “speed-up” biology, only keep it inside optimal guardrails

• A body part is attached to a person: psychological state (fear, social loss, depression, motivation) has huge influence on pain perception and adherence to rehab

Analogy Bank (used repeatedly by lecturer)

• Farming: you cannot "cram" a crop; you must till, seed, fertilize → same with tissue healing stages

• House fire: injury site = burning house; mast cells call 911, neutrophils = police/first truck, macrophages = specialized firefighters, contractors = later remodeling cells; more responders arrive only if the blaze is large (greater tissue damage)

• Pickup sticks: initial fibrin scar = haphazard pile; cross-friction and movement line up fibers like rubbing hand over sticks

• Paper-clip bend → stress-reaction → fracture; “hair of the dog” training through pain worsens micro-trauma

Common Clinical Myth Examples

• “Just tape me up / brace / give me ibuprofen” leads to chronic ankle instability

• Over-icing or goal of “stopping inflammation” is counter-productive; inflammation is the door you must open to enter healing room

• Universal use of e-stim or heat without intent; modalities are tools, not cures

Injury Classifications

• Macro-trauma (acute, single overload: sprain, ACL rupture, fracture)

• Micro-trauma (chronic, repetitive: shin splints, tendinosis, bursitis)

• Tissue visco-elasticity & creep: prolonged or repetitive load causes progressive deformation; requires REST days to restore baseline

• Stress vs. strain curve: surpassing yield → failure; applies to marathon example (miles 12–26 exceed tissue capacity)

3 Phases of Tissue Healing (time frames are averages)

1. Inflammation (0–5 days)

   • Immediate vasoconstriction ➜ coagulation ➜ vasodilation

   • Cardinal signs: rubor, calor, tumor, dolor, loss of function

   • Cellular order: mast cells call neutrophils (first 24 h) ➜ macrophages (~48 h) ➜ T-cells (longer term)

   • Key events: platelet plug, fibrin clot scaffold, release of chemical mediators (histamine, serotonin, heparin, prostaglandins, leukotrienes)

2. Proliferation / Repair (≈ 3 days – 6 weeks)

   • Fibroblasts lay type III collagen on fibrin scaffold ("scar matrix")

   • Angiogenesis & granulation tissue increase oxygen/nutrient delivery

   • Cross-links initially random (pickup sticks) → must be stressed & aligned

   • Window for manual therapy, controlled ROM, cross-friction, graded loading

3. Maturation / Remodeling (6 weeks – years)

   • Type III collagen replaced by stronger type I

   • Tensile strength approaches 80–90 % of original but never identical

   • Continued realignment along lines of stress via progressive exercise

Cellular & Chemical Detail

• Mast cells: sentinel “911 operators,” release histamine (vasodilation, itch), prostaglandins (pain), cytokines

• Neutrophils: bulk "shock-troop" phagocytes; die off in 24–48 h

• Macrophages

  • M1 = pro-inflammatory cleanup

  • M2 = anti-inflammatory, orchestrate repair; excessive ice after first ~24 h can delay M2 dominance

• Platelets + Fibrin: form temporary mechanical plug and biochemical scaffold

• Lymphatics: parallel drainage network; manual lymphatic drainage, compression & elevation exploit gravity to evacuate protein-rich third--space fluid

Arachidonic Acid Cascade (AAC)

Phospholipids --(phospholipase A2)--> Arachidonic Acid
        |                             |
        |                             +-- Lipoxygenase path → HPETE → leukotrienes (bronchoconstriction, chemotaxis)
        |
        +-- Cyclo-oxygenase (COX-1/2) → prostaglandins & thromboxane

• Pharmacologic choke-points

  • Corticosteroids (injection/oral): inhibit phospholipase A2 = shut down entire AAC (powerful, but systemic side-effects unless local)

  • NSAIDs (ibuprofen, naproxen): block COX → ↓ pain & platelet aggregation; BUT delay bone healing, contraindicated for fractures & early tissue repair

  • Aspirin (ASA): prototype COX inhibitor, unique irreversible platelet effect → used for cardioprotection

  • Acetaminophen (Tylenol): analgesic, antipyretic; NOT an NSAID, metabolized in liver, overdose → hepatotoxicity

  • Celecoxib (Celebrex): selective COX-2 inhibitor, spares gastric COX-1 (fewer ulcers) but costly, Rx-only

  • Inhaled steroids or β-agonists (albuterol) target lipoxygenase-associated bronchoconstriction in asthma

Modalities & Their Intent

• Cryotherapy

  • Evidence supports use for pain modulation & limiting excessive secondary swelling within first 24 h

  • Over-application (>24–48 h, high frequency) may inhibit leukocyte shift to M2 & prolong healing

• Compression / Elevation: combat hydrostatic pressure & gravity to enhance lymph return

• Manual lymphatic drainage, instrument-assisted soft-tissue mobilization (Graston), cupping (negative pressure): mechanically move third-space fluid & realign scar fibers

• Heat: generally reserved for sub-acute/remodeling phases to enhance extensibility & blood flow; avoid in acute inflammatory window

• E-stim: predominantly temporary pain-gate effect; lacks strong evidence for accelerating healing; often over-used

Visco-Elastic Creep & Training Load

• Tissue held at constant low load lengthens over time (stretching >45–60 s)

• Chronic overload without recovery (daily bench press, extreme CrossFit, marathon without base) drives tissue past plastic zone → rhabdomyolysis or overuse injuries

• Rest & periodization are essential extrinsic modifiers

Factors That Impede or Alter Healing

Intrinsic

• Age, diabetes, tumor burden, vascular supply, nutritional status (adequate protein, vitamins A/C, minerals)

• Genetic / congenital conditions (e.g., hemophilia → defective clotting)

• Arthrogenic muscular inhibition (AMI): joint effusion shuts down quadriceps via neural reflex
  Extrinsic

• Mechanical stress/strain (premature aggressive rehab)

• Infection, repeated trauma, foreign bodies

• Medications (early NSAIDs, systemic steroids, chemotherapeutics)

• Poor patient adherence, psychosocial stress, depression

Tissue-Specific Nuances

• Bone: ORIF permits primary bone healing; callus eventually stronger & thicker than original (\text{Wolff's Law})

• Skeletal muscle, skin, ligament: good regenerative capacity when approximated & stressed appropriately

• Cartilage, meniscus, tendon: poor vascularity → slower; location-dependent (red-red vs white-white zones)

• Nerve: \approx 1\;\text{mm/day} axonal regrowth; functional return months-years, sometimes incomplete

• Cardiac & CNS neurons: considered permanent tissue; scarring rather than true regeneration

Concussion & Re-Injury Statistics (mentioned)

• After one concussion → 1.7\times higher risk of second

• After two → 4.8\times higher risk of third and onward

• Mirrors pattern of ankle sprain → chronic ankle instability when initial management is insufficient

Ethical / Practical Take-Aways

• “Do no harm” ≠ over-treat; interventions must align with phase physiology & intent

• Patient education on natural timelines counters cultural urge for quick fixes (taping, pills, premature return to play)

• Mental health & social belonging (e.g., athletes sidelined from team) must be addressed alongside cellular repair

• Best practice: ask daily “Better, worse, or the same?” to fine-tune rehab dosage

Quick Reference Cheat-Sheet

• 0–24 h: protect, compression/elevate, judicious ice for pain, NO early NSAIDs for fracture
• 24 h–2 wk: controlled ROM, manual lymph drainage, begin light isometrics; avoid over-icing
• 2 wk–6 wk: progressive loading, cross-friction to align collagen, watch for AMI, teach proprioception
• >6 wk: strength, power, sport-specific drills, mental readiness screening; continue monitoring swelling/pain spikes

“Stay inside the guardrails of biology; you can’t bulldoze a cornfield into harvest, and you can’t bully tissue into healing.”