Structural and Functional Properties of Respiratory Muscles & Pathological Factors Affecting Their Function

I. INTRODUCTION

II. STRUCTURAL PROPERTIES

A. Muscle Fibers — Types and Distribution

Note: MHC 2b is not expressed in human muscle; type IIx is the human equivalent.

• ~55% Type I fibers
• ~21% Type IIa fibers
• ~23% Type IIx fibers
• Other respiratory muscles (intercostals, abdominals, sternomastoids, scalenes) contain ≥60% highly oxidative fibers

• Type I + IIa fibers → sustained rhythmic contraction at rest
• Type IIa fibers → additional recruitment during exercise
• Type IIx fibers → high power for coughing and sneezing

B. Morphologic Characteristics

• Muscle fibers are arranged in parallel bundles, each bundle containing hundreds of fibers
• Each fiber = hundreds of myofibrils → each myofibril = hundreds of sarcomeres in series
• Force production ∝ number of myofibrils in parallel; velocity/displacement ∝ number of sarcomeres in series
• Mitochondrial density in the diaphragm is twofold greater than in limb muscles → oxygen uptake capacity of diaphragm far exceeds that of limb muscles
• Capillary density in the diaphragm is approximately twice that of limb muscles → maximal blood flow is correspondingly greater

C. Motor Unit Organization

• All fibers within one motor unit are the same fiber type
• Four motor unit types in respiratory muscles:
  • Type S (slow, fatigue-resistant) — express slow MHC
  • Type FR (fast fatigue-resistant) — express MHC 2a
  • Type FI_int (fast, intermediate fatigue) — express MHC 2x
  • Type FF (fast fatigable) — express MHC 2b
• Fast motor units develop forces ~110 mN; slow motor units ~30–60 mN
• Recruitment follows the size principle — smallest (slow) motor units recruited first

III. ANATOMY OF RESPIRATORY MUSCLES

A. Primary Inspiratory Muscles

• Innervated by phrenic nerve (C3–C5)
• Has two anatomical parts:
  • Costal portion — attached to lower rib cage
  • Crural portion — attached to vertebral ligaments; passes on either side of the esophagus (acts as lower esophageal sphincter)
• Central tendon — insertion point of both portions; also forms inferior pericardium
• Accounts for 75% of intrathoracic volume change during quiet inspiration
• Excursion: 1.5 cm (quiet breathing) to 7 cm (deep inspiration)

1. Craniocaudal descent → directly increases thoracic volume (piston action)
2. Appositional component → ↑ abdominal pressure acts through the zone of apposition (25–30% of rib cage internal surface at FRC) to expand lower rib cage
3. Insertional component → axially-oriented diaphragmatic fibers pull lower rib caudally → cephalad motion and outward rotation of lower ribs

• Run obliquely downward and forward from rib to rib
• Contraction elevates lower ribs → sternum moves outward → increases anteroposterior diameter
• Either diaphragm or external intercostals alone can maintain adequate ventilation at rest

• Most important inspiratory portion of intercostal musculature
• Active during quiet breathing; produce ~60% of rib cage inspiratory action
• Greatest mechanical advantage among intercostal muscles

• Sternocleidomastoid and Scalene muscles — elevate the thoracic cage
• Scalenes elevate ribs 1 and 2; active even in quiet breathing in some conditions

B. Expiratory Muscles

• Expiration is passive at rest (due to elastic recoil)
• Internal intercostals — run obliquely downward and posteriorly; pull rib cage downward → forced expiration
• Abdominal muscles (rectus abdominis, transversus abdominis, internal/external obliques):
  • Pull rib cage downward and inward
  • Increase intra-abdominal pressure → push diaphragm upward
  • Critical for cough generation

C. Upper Airway Muscles

• Laryngeal abductors open the glottis early in inspiration
• Laryngeal adductors close the glottis during swallowing to prevent aspiration

IV. FUNCTIONAL PROPERTIES

A. Force-Length Relationship

• Maximal tension generated at optimal sarcomere length
• With hyperinflation: diaphragm shortens → capacity to generate force is reduced
• Chronic hyperinflation (e.g., COPD): sarcomere dropout occurs as adaptation — muscle accommodates shortening with fewer sarcomeres rather than altered filament overlap → force-generating capacity is partially restored

B. Respiratory Muscle Strength Assessment

• Maximal inspiratory pressure (MIP/PImax) — measured at the mouth
• Maximal expiratory pressure (MEP/PEmax)
• Transdiaphragmatic pressure (Pdi) — via esophageal and gastric balloon catheters
• Sniff nasal inspiratory pressure (SNIP) — useful when MIP maneuver cannot be performed
• Non-volitional tests: Electrical/magnetic phrenic nerve stimulation (twitch Pdi)

C. Endurance

• Respiratory muscle fatigue occurs when energy supply < energy demand
• Fatigue threshold (Tlim): when Pdi/Pdi_max × Ti/Ttot exceeds ~0.15–0.18
• Endurance is inversely related to:
  • Increased inspiratory load (resistance + elastance)
  • Reduced blood flow/oxygen delivery

V. PATHOLOGICAL FACTORS AFFECTING RESPIRATORY MUSCLE FUNCTION

A. Mechanical/Geometric Factors

• Diaphragm is flattened and operates at a shortened length → reduced force-generating capacity
• Dynamic hyperinflation adds intrinsic PEEP (auto-PEEP) → increased inspiratory threshold load
• Critically reduces inspiratory reserve volume (IRV)
• Result: inspiratory muscle weakness + increased work of breathing

• Kyphoscoliosis, pectus excavatum → alter the length-tension relationship
• Scoliosis worsens restrictive lung disease and further impairs muscle mechanics

B. Neuromuscular Diseases

• Duchenne MD (DMD): X-linked, dystrophin absent; progressive weakness from age 2–3 years; respiratory muscles affected later; expiratory muscles fail first → impaired cough; FVC declines 6–11%/year; MIP < 50% predicted → restrictive disease; death from respiratory failure in 20s
• Becker MD: dystrophin reduced; later onset; milder respiratory involvement

• Symmetrical proximal weakness; inflammatory infiltration of diaphragm and intercostals
• Dermatomyositis: complement-mediated microangiopathy, perifascicular inflammation
• Polymyositis: cell-mediated, endomysial inflammation
• Respiratory muscle involvement usually less severe than limb muscle involvement

• ALS: degeneration of upper + lower motor neurons → progressive respiratory failure
• Spinal Muscular Atrophy (SMA): loss of anterior horn cells; severe diaphragmatic weakness in type 1

• Bilateral phrenic palsy → severe respiratory compromise; paradoxical diaphragm movement on sniff fluoroscopy
• Causes: cardiac surgery, trauma, neuralgic amyotrophy, tumors

• Autoimmune destruction of nicotinic acetylcholine receptors at neuromuscular junction
• Fatigable weakness; respiratory crisis (myasthenic crisis) may require ventilation

C. Metabolic and Electrolyte Disorders

D. Pharmacological and Toxic Causes

• Corticosteroids (chronic): steroid myopathy → type IIb fiber atrophy; respiratory muscle weakness; seen in severe asthma, COPD, organ transplant patients
• Aminoglycosides, calcium channel blockers, neuromuscular blocking agents: impair neuromuscular transmission
• Organophosphate poisoning: irreversible acetylcholinesterase inhibition → sustained depolarization → paralysis

E. Respiratory Muscle Fatigue

• Occurs when load placed on muscles exceeds their capacity (high resistive + elastic load + reduced blood flow)
• Central fatigue: reduced drive from CNS motor cortex
• Peripheral fatigue: failure at neuromuscular junction or within the contractile apparatus
• Biochemical: ATP depletion, lactate accumulation, inorganic phosphate ↑, intracellular pH ↓
• Clinical features: tachypnea, paradoxical breathing (thoracoabdominal asynchrony), CO₂ retention, respiratory failure

F. Systemic and Chronic Diseases

• COPD: combined hyperinflation-induced geometric disadvantage + systemic muscle wasting (elevated TNF-α, oxidative stress, disuse atrophy); type I → type IIb fiber shift
• Congestive Heart Failure: reduced cardiac output → decreased blood flow to respiratory muscles → early fatigue + dyspnea
• Sepsis / Critical Illness: ventilator-induced diaphragm dysfunction (VIDD); cytokine-mediated proteolysis; oxidative stress; diaphragm atrophy can begin within 18–69 hours of mechanical ventilation
• Hypothyroidism: type I fiber atrophy, reduced contractility, myopathy → respiratory failure
• Diabetes: peripheral neuropathy + microangiopathy affecting phrenic nerve and diaphragm

VI. ASSESSMENT OF RESPIRATORY MUSCLE DYSFUNCTION — SUMMARY

VII. KEY POINTS FOR EXAM ✦

1. Diaphragm = 75% of quiet inspiration; innervated by phrenic nerve (C3–C5); transection above C3 → fatal without ventilation
2. Human diaphragm: ~55% Type I, 21% IIa, 23% IIx fibers; MHC 2b absent in humans
3. Diaphragm mitochondrial density = 2× limb muscle; capillary density = 2× limb muscle → fatigue-resistant design
4. 3 mechanisms of diaphragmatic action: craniocaudal descent, appositional, insertional
5. Expiration is passive at rest — internal intercostals + abdominals activate in forced expiration/cough
6. Hyperinflation → sarcomere dropout (chronic adaptation) → shortened diaphragm; reduced force
7. Fatigue threshold: Pdi/Pdimax × Ti/Ttot > 0.15–0.18
8. DMD: FVC declines 6–11%/year; respiratory death in 20s; expiratory muscles fail first
9. Steroid myopathy → type IIb fiber atrophy → respiratory muscle weakness
10. VIDD (ventilator-induced diaphragm dysfunction): atrophy begins within 18–69 hours of mechanical ventilation
11. Electrolyte disorders causing respiratory failure: hypophosphatemia is the most clinically important
12. Cough requires intact expiratory muscles (MEP > 60 cmH₂O threshold for effective secretion clearance)