Miller-Tendon/muscle Flashcards
Review skeletal muscle architecture
Review the sarcomere
A band: Contains actin and myosin
I band: Contains actin only
H band: Contains myosin only
M line: Interconnecting site of the thick filaments
Z line: Anchors the thin filaments
Review muscle anatomy
Sarcolemma: plasma membrane surrounding cell
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Extends into cell surrounding myofibrils
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Forms the transverse tubules (Fig. 1.41).
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Multiple nuclei: typically located adjacent to sarcolemma
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Sarcoplasmic reticulum (SR)
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Smooth endoplasmic reticulum that surrounds the individual myofibrils
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Stores calcium in intracellular membrane–bound channels.
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Ryanodine receptors (e.g., RYR-1) regulate the release of calcium from the SR and serve as a connection between the SR and sarcolemma-derived transverse tubule.
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Abnormality of ryanodine receptors is implicated in persons susceptible to malignant hyperthermia.
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Dantrolene decreases loss of calcium from the SR.
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Contractile elements
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Sarcomere: basic functional unit of muscle contraction
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Myofibrils
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Set of sarcomeres parallel to axis of cell
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(1–3 μm in diameter and 1μ2 cm long)
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Sarcomere organization causes the banding pattern (striations) seen in skeletal muscle (Table 1.23; see Fig. 1.40).
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Costamere connects the sarcomere to the sarcolemma at the Z disc.
What is the sarcoplasmic reticulum?
Sarcoplasmic reticulum. Action potentials travel down the transverse tubules, causing release of calcium from the outer vesicles.
review muscle contracture
Contractile elements
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Sarcomere: basic functional unit of muscle contraction
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Myofibrils
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Set of sarcomeres parallel to axis of cell
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(1–3 μm in diameter and 1μ2 cm long)
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Sarcomere organization causes the banding pattern (striations) seen in skeletal muscle (Table 1.23; see Fig. 1.40).
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Costamere connects the sarcomere to the sarcolemma at the Z disc.
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Z disc (or line) represents terminus of sarcomere
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Contains desmin, α-actinin, and filamin
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A-band (or dark band) represents thick filaments.
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Thick filaments composed of myosin
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Also contains myosin [H-band], M protein, C protein, titin, and creatine kinase
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I-band represents thin filaments.
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Primarily composed of actin
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Also contains
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Troponin: has binding site for Ca
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Tropomyosin: prevents myosin-actin interaction
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Attach to Z disc
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Involved in delayed-onset muscle soreness (DOMS)
review the gross anatomy of muscle:
Contractile elements
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Sarcomere: basic functional unit of muscle contraction
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Myofibrils
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Set of sarcomeres parallel to axis of cell
•
(1–3 μm in diameter and 1μ2 cm long)
•
Sarcomere organization causes the banding pattern (striations) seen in skeletal muscle (Table 1.23; see Fig. 1.40).
•
Costamere connects the sarcomere to the sarcolemma at the Z disc.
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Z disc (or line) represents terminus of sarcomere
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Contains desmin, α-actinin, and filamin
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A-band (or dark band) represents thick filaments.
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Thick filaments composed of myosin
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Also contains myosin [H-band], M protein, C protein, titin, and creatine kinase
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I-band represents thin filaments.
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Primarily composed of actin
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Also contains
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Troponin: has binding site for Ca
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Tropomyosin: prevents myosin-actin interaction
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Attach to Z disc
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Involved in delayed-onset muscle soreness (DOMS)
review the motor endplate
The α-motoneuron and the myofibers it innervates
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Each myofiber is innervated by a single axon but an axon can innervate multiple myofibers
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Smaller and more delicate muscles have fewer myofibers per motor unit (<5 fibers per unit in extraocular muscles but as many as 1800 fibers per unit in gastrocnemius muscle)
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Contraction
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Response to mechanical or electrochemical stimuli generated at the motor end plate (neuromuscular junction) where the axon contacts an individual myofiber (Fig. 1.42).
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Depolarization reaches motor neuron axon terminal, and acetylcholine (ACh) is released from presynaptic vesicles.
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ACh diffuses across the synaptic cleft (50 nm) and binds to postsynaptic receptors on sarcolemma, which begin depolarization.
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Myasthenia gravis is due to IgG antibodies to the Ach receptor. Manifests initially as ptosis and diplopia. Weakness worse with muscle use.
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Botulinum A injections reduce spasticity by blocking presynaptic acetylcholine release. Commonly used for spastic muscles in cerebral palsy.
Sarcoplasmic reticulum releases calcium.
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Ca binds to troponin and causes conformational change, which stops tropomyosin inhibition of myosin-actin cross-bridges.
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Myosin binds to actin, hydrolyzes ATP, and “pushes” actin on thin filament, leading to muscle contraction
isometric
muscle length remains unchanged
planks
isokinetic
Muscle tension is generated as muscle maximally contracts at a constant velocity over a full ROM.
best for maximizing strength
isotonic
Muscle tension is constant
i.e biceps curls
what is the cause of myathenia gravis?
Myasthenia gravis is due to IgG antibodies to the Ach receptor. Manifests initially as ptosis and diplopia. Weakness worse with muscle use.
Type 1 muscle fibers
Type I
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Slow-twitch, oxidative, “red” fibers (mnemonic: “slow red ox”)
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Aerobic
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Have more mitochondria, enzymes, and triglycerides (energy source) than type II fibers
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Low concentrations of glycogen and glycolytic enzymes (ATPase)
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Enable performing endurance activities, posture, balance
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Are the first lost without rehabilitation
type II muscle fibers
Fast-twitch, glycolytic, “white” fibers
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Anaerobic
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Contract more quickly and have larger, stronger motor units (increased ATPase) than type I fibers
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Less efficient than type I but with large amount of force per cross-sectional area, high contraction speeds, and quick relaxation times
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Well suited for high-intensity, short-duration activities (e.g., sprinting)
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Rapid fatigue
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Low intramuscular triglyceride stores
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Two subtypes:
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Type IIA is intermediate.
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Type IIB is most fatigable and has highest anaerobic capacity.
review the energy source for muscle
review strength training
Strength training—increased tension and decreased repetitions
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Induces hypertrophy (increased cross-sectional area) of fast-twitch (type II) fibers
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Induces myofibrillar muscle protein synthesis (MPS)
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Improves neural activation
review endurance training
decreased tension and increased repetitions
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Induces hypertrophy of slow-twitch fibers
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Increases capillary density, mitochondria, and oxidative capacity
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Increases resistance to fatigue and cardiac output
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Improves blood lipid profiles
which athletes have which kind of muscles?
Specific training can selectively alter fiber composition.
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Endurance athletes—higher percentage of slow-twitch fibers
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Sprinters and athletes in “strength” sports—higher percentage of fast-twitch fibers
review creatine
Creatine supplementation can increase work produced in the first few maximum-effort anaerobic trials but does not increase peak force production.
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Creatine shifts fluid intracellularly; the shift may present a risk for dehydration, although cramps are the more common side effect.
what is decorin?
Decorin—most predominant proteoglycan in tendons. Regulates tendon diameter and provides cross-links between collagen fibers. Also shown to have antifibrotic properties via inhibition of TGF-β1.
tgf-b and muscle injury
TGF-β stimulates proliferation of myofibroblasts and increases fibrosis
review the stages of tendon healing
Three stages of tendon healing
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Inflammation
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Hematoma formation following by resorption
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Type III collagen is produced at the injury site by tenocytes.
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Weakest stage of repair
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Proliferation: maximal type III collagen production
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Remodeling:
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Begins at 6 weeks
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Decreases cellularity
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Type I collagen predominates
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Two mechanisms:
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Intrinsic: recruitment of local stem/progenitor cells from endotenon and epitenon
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Extrinsic: cells from surrounding tissue invade damaged area.
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Faster but primary source of adhesions
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Achilles, patellar, and supraspinatus tendons are prone to rupture at hypovascular areas.
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Achilles tendon is hypovascular 4–6 cm proximal to calcaneal insertion.
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Responsive to different cytokines and growth factors
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PDGF genes transfected into tenocytes show collagen formation.
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VEGF genes transfected into tenocytes show TGF-βupregulation and adhesion formation.
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When exposed to PMNs (as with inflammation), tenocytes upregulate genes for inflammatory cytokines, TGF-β, and MMPs while suppressing type I collagen expression.
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Surgical tendon repairs: weakest at 7–10 days
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Maximum strength achieved at 6 months, reaching two-thirds of original strength.
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No evidence in favor of a trough (exposing tendon to cancellous bone) over direct repair to cortical bone.
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Motion and mechanical loading have beneficial effects on tenocyte function.
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Immobilization decreases strength at tendon-bone interface.
review the mechanical properties of tendons
Anisotropic: properties vary depending on direction of applied force
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Viscoelastic: properties vary depending on rate of force application
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Creep: increasing deformation under constant load
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Stress relaxation: decreasing stress with constant deformation (elongation)
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Hysteresis: during loading and unloading, the unloading curve is different from the loading curve. The difference between the two represents the amount of energy that is lost during loading.
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Stress-strain curve
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Rest: collagen fibers are “crimped.”
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Toe region: flattening of crimp; nonlinear; tendon stretched easily
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Linear region: intermediate loads
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Failure
surgical tendon repair pearls
Surgical tendon repairs: weakest at 7–10 days
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Maximum strength achieved at 6 months, reaching two-thirds of original strength.
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No evidence in favor of a trough (exposing tendon to cancellous bone) over direct repair to cortical bone.
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Motion and mechanical loading have beneficial effects on tenocyte function.
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Immobilization decreases strength at tendon-bone interface.
ligament overview
Characteristics
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Originates and inserts on bone
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Stabilizes joints and prevents displacement of bones
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Contains mechanoreceptors and nerve endings that facilitate joint proprioception
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Like tendon, displays viscoelastic behavior
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Structure and composition
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Composition
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Similar to that of tendon
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Water: 60%–70% of total weight
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Collagen: 80% of dry weight
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90% type I collagen; also types III, V, VI, XI, and XIV collagen
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More collagen type I is seen at the origin and insertion, with collagen III seen midsubstance.
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Elastin (1% dry weight)
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Proteoglycans (1% dry weight)—function in water retention and contribute to viscoelastic behavior
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Fibroblast
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Primary cell, oriented longitudinally
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Functions to synthesize ECM, collagen, and proteoglycans
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Epiligament
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Similar to that in epitenon; carries the neurovascular and lymphatic supply of tendons
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Compared with tendon
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Less total collagen but more type III collagen
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More proteoglycans and therefore more water
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Less organized collagen fibers that are more highly cross-linked and intertwined
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“Uniform microvascularity”—receives supply at insertion site by the epiligamentous plexus
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Insertion
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Similar to that of tendon
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Direct (fibrocartilaginous) insertion
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Four layers: tendon, fibrocartilage, mineralized fibrocartilage, and bone
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More common
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Deep fibers attach at 90-degree angles
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Indirect
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Superficial fibers insert into the periosteum and deep fibers insert into bone via Sharpey fibers (perforating calcified collagen fibers).
ligament injury
Knee and ankle ligaments are most commonly injured
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Ligaments do not plastically deform.
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They “break, not bend.”
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Midsubstance ligament tears are common in adults.
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Avulsion injuries are more common in children.
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Typically occurs between unmineralized and mineralized fibrocartilage layers
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Healing
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Increased number of collagen fibers but
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Fewer mature cross-links (45% of normal at 1 year)
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Decrease in mass and diameter
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Three phases, as in bone
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Inflammatory—early acute mediators (PMNs and then macrophages), with production of type III collagen and growth factors
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Proliferative—around 1–3 weeks, with replacement of type III collagen by type I collagen (Think of macrophages as weakening the structure—weakest point.)
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Remodeling and maturation
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Factors that impair ligament healing
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Intraarticular ligamentous injury
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Old age, smoking, NSAID use
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Diabetes mellitus
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Alcohol use
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Local injection of corticosteroids
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Factors that improve ligament healing experimentally
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Extraarticular ligamentous injury
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Compromised immunity
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IL-10 (antiinflammatory)
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IL-1 receptor antagonists
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Mesenchymal stem cells
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Scaffolds (such as collagen–platelet-rich plasma hydrogels)
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Neuropeptides
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Calcitonin gene–related peptide
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Immobilization
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Adversely affects ligament strength: elastic modulus decreases
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In rabbits, breaking strength reduced dramatically (66%) after 9 weeks of immobilization.
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Effects reverse slowly upon remobilization.
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Prolonged immobilization disrupts collagen structure, which may not return to normal within insertion sites.
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Exercise
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Improves mechanical and structural properties
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Increases strength, stiffness, and failure load
Review intervertebral disks
Allow spinal motion and stability
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Also function as cushioning for axial loads on the spine
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Two components
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Central nucleus pulposus
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Derived from notochord
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Hydrated gel with compressibility
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Low collagen (type II)/high proteoglycan (and glycosaminoglycan) content
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Proteoglycans make up higher percentage of dry weight.
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With time, the nucleus pulposus undergoes loss of proteoglycans and water (desiccation).
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Surrounding annulus fibrosis
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Derived from mesoderm
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Extensibility and increased tensile strength
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High collagen (type I)/low proteoglycan content
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Proteoglycans make up lower percentage of dry weight.
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Superficial layer contains nerve fibers.
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Composition:
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Water (85%)
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Proteoglycans
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Type II collagen (20% of dry weight) in the nucleus pulposus
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Type I collagen (60% of dry weight) in the annulus fibrosis
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Neurovascularity
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Dorsal root ganglion gives rise to the sinuvertebral nerve, which then innervates the superficial fibers of the annulus.
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Avascular—nutrients and fluid diffuse from the vertebral end plates. This diffusion is impaired by calcification with aging.
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Aging disc
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Early degenerative disc disease is an irreversible process, with IL-1β stimulating the release of MMPs, nitric oxide, IL-6, and prostaglandin E2 (PGE2).
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Decreased water content and conversion to fibrocartilage
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A result of decreased hydrostatic pressure due to fewer large proteoglycans (aggrecan)
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Fibronectin cleavage or fragmentation is also associated with degeneration.
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Increase in keratan sulfate concentration and decrease in chondroitin sulfate
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Increase in relative collagen concentration, with no change in absolute quantity
review the aging intervertebral disk
Early degenerative disc disease is an irreversible process, with IL-1β stimulating the release of MMPs, nitric oxide, IL-6, and prostaglandin E2 (PGE2).
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Decreased water content and conversion to fibrocartilage
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A result of decreased hydrostatic pressure due to fewer large proteoglycans (aggrecan)
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Fibronectin cleavage or fragmentation is also associated with degeneration.
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Increase in keratan sulfate concentration and decrease in chondroitin sulfate
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Increase in relative collagen concentration, with no change in absolute quantity
Avascular—nutrients and fluid diffuse from the vertebral end plates. This diffusion is impaired by calcification with aging.
where is the annulus fibrosis derived from?
mesoderm
where is the central nucleus derived from?
Central nucleus pulposus
review nerve architecture
review the action potential:
Neurotransmitters cross synapse and trigger opening of Na+ channel.
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This triggers voltage-gated Na+ channels (responsible for generation of AP) in axon hillock when membrane potential increases to −50 mV.
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Membrane potential spikes to 30 mV as membrane depolarizes.
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Potential propagates down axon and triggers voltage-gated Ca2+ channel at axon terminus.
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Ca2+ enters axon and triggers neurotransmitter release
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Voltage-gated K+ channels stay open longer than Na+channels.
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Leads to hyperpolarization (−75 mV)
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Propagation faster in myelinated and larger nerves
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Absolute refractory period
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Period when voltage-gated Na+ channels cannot be activated
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Responsible for antegrade propagation of signal
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Relative refractory period
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Period when larger than normal stimuli propagate a second AP
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Result of the hyperpolarization phase of the previous
review the clinical situations that act on the presynaptic junction:
Myasthenia gravis is due to IgG antibodies to the Ach receptor. Manifests initially as ptosis and diplopia. Weakness worse with muscle use.
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Botulinum A injections reduce spasticity by blocking presynaptic acetylcholine release. Commonly used for spastic muscles in cerebral palsy.
how to tendons and ligaments attach to bones?
Similar to that of tendon
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Direct (fibrocartilaginous) insertion
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Four layers: tendon, fibrocartilage, mineralized fibrocartilage, and bone
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More common
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Deep fibers attach at 90-degree angles
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Indirect
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Superficial fibers insert into the periosteum and deep fibers insert into bone via Sharpey fibers (perforating calcified collagen fibers).
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