Muscle Injury and Healing

Skeletal muscle constitutes approximately 40% of body mass and is a highly organized tissue capable of both force generation and regeneration.

Hierarchical organization:

• Muscle fiber (myofiber): Multinucleated syncytium, 10-100 μm diameter
• Myofibril: Contractile unit containing sarcomeres
• Sarcomere: Z-line to Z-line, contains actin and myosin
• Fascicle: Bundle of fibers surrounded by perimysium
• Muscle belly: Multiple fascicles within epimysium

Fiber types and susceptibility:

Satellite cell biology:

• Location: Between sarcolemma and basal lamina
• Quiescent state: Express Pax7, remain dormant
• Activation: Injury releases HGF, FGF, triggers proliferation
• Differentiation: Express MyoD, Myf5, myogenin, MRF4
• Self-renewal: Asymmetric division maintains pool

Satellite cells are essential for postnatal muscle growth and regeneration. Without satellite cells, damaged muscle cannot regenerate and heals only by fibrosis.

Injury classification by mechanism:

Myotendinous junction vulnerability:

The myotendinous junction (MTJ) is the most common site of muscle strain injury. Features contributing to vulnerability include:

• Stress concentration: Transition from compliant muscle to stiff tendon
• Structural complexity: Interdigitating membrane folds
• Force transmission zone: All contractile force passes through MTJ
• Limited blood supply: Watershed region

The MTJ membrane folds increase surface area 10-20 fold for force transmission but remain the weak link in the muscle-tendon unit.

Molecular regulation of healing:

The critical balance:

Muscle healing represents a competition between regeneration (restoration of functional muscle) and fibrosis (scar formation). Understanding factors that influence this balance is essential.

Factors favoring regeneration:

• Satellite cell availability and activation
• Adequate blood supply
• Early controlled mobilization
• Preserved basal lamina scaffold
• Limited injury extent
• Young age

Factors favoring fibrosis:

• Satellite cell depletion
• Poor vascularity
• Prolonged immobilization
• Extensive basal lamina disruption
• Large injury gap
• Repeated injury to same area
• Advanced age

TGF-β: The fibrosis switch:

Transforming growth factor beta (TGF-β) plays a central role in determining regeneration vs fibrosis:

• Physiological levels: Promotes matrix production for scaffold
• Excessive levels: Induces fibroblast proliferation and collagen deposition
• Therapeutic target: TGF-β inhibition reduces fibrosis in animal models

Clinical implications:

• Early mobilization promotes satellite cell activity and reduces fibrosis
• Severe injuries with large gaps tend toward fibrosis
• Repeated injuries to same location create progressively more scar
• Complete ruptures may require surgical approximation to allow regeneration

History:

• Mechanism of injury (eccentric loading, direct trauma)
• Precise location of pain
• Immediate vs delayed onset
• Audible pop or tearing sensation
• Functional limitations
• Previous injury to same muscle

Examination:

Imaging:

Ultrasound:

• First-line imaging for acute injuries
• Dynamic assessment possible
• Identifies hematoma, fiber disruption
• Operator dependent

MRI:

• Gold standard for injury characterization
• Grades edema and fiber disruption
• Identifies extent and location
• Useful for surgical planning in Grade III

MRI Grading:

• Grade I: Edema, no fiber disruption (less than 5% cross-section)
• Grade II: Partial fiber disruption (5-50% cross-section)
• Grade III: Complete disruption or more than 50% involvement

📊 Management Algorithm

Click to expand

Surgical considerations (Grade III injuries):

NSAIDs - Controversial role:

Current recommendations:

• Limit NSAID use to first 48-72 hours if needed for pain
• Avoid prolonged use during repair phase
• Paracetamol preferred for ongoing analgesia

Corticosteroids:

• Generally contraindicated
• Risk of delayed healing
• Risk of tendon rupture (at MTJ)
• May be considered for specific indications (e.g., severe contusion with compartment concerns)

PRP (Platelet-Rich Plasma):

• Theoretical benefit from growth factors
• Mixed clinical evidence
• Not currently standard of care
• May have role in chronic non-healing injuries

Emerging therapies:

• Growth factor therapy (IGF-1, HGF)
• Anti-TGF-β agents (reduce fibrosis)
• Stem cell therapies
• Gene therapy approaches

Most emerging therapies remain experimental.

Myositis ossificans (Heterotopic Ossification):

• Bone formation within muscle tissue
• Most common after contusion injury
• Risk factors: Aggressive early treatment, repeat trauma, hematoma aspiration
• Prevention: Avoid aggressive stretching, heat in early phase
• Treatment: Observation, excision after maturation (6-12 months)

Compartment syndrome:

• Rare but serious complication
• Usually after severe contusion or crush injury
• Pain out of proportion, pain with passive stretch
• Urgent fasciotomy required

Chronic muscle dysfunction:

• Persistent weakness
• Reduced flexibility
• Re-injury susceptibility
• May result from excessive fibrosis

Re-injury:

• Most common complication
• Previous injury is strongest risk factor
• Usually occurs in same location
• Prevention: Complete rehabilitation before return to sport

Common MCQ themes:

1. Healing phases: Know the timeline and key events
2. Satellite cells: Location, markers, function
3. Fiber types: Which is most susceptible to injury
4. Myotendinous junction: Why it is vulnerable
5. Eccentric injury: Mechanism and examples
6. Treatment: POLICE vs RICE, early mobilization
7. Regeneration vs fibrosis: Factors affecting balance
8. Complications: Myositis ossificans, re-injury

High-yield facts:

• Satellite cells express Pax7 (quiescent) and MyoD (activated)
• Type IIb fibers are most susceptible to strain
• MTJ is most common injury site
• Destruction phase: days 0-3
• Repair phase: days 3-21
• Remodeling phase: day 21 onwards
• M1 macrophages are pro-inflammatory
• M2 macrophages promote repair
• TGF-β promotes fibrosis
• Early mobilization reduces fibrosis