7. Physiology of Skeletal Muscle Adaptation/Repair, Muscle Disorders Flashcards
Muscle Fatigue
• Due to prolonged heavy work: above \_\_\_\_ of maximal aerobic capacity. • Decreased capacity of muscular work and reduced efficiency of performance. – Lower \_\_\_\_. – Longer \_\_\_\_ time. – Requires a period of \_\_\_\_. • Types: – Psychological: • Depends on \_\_\_\_ of the individual. – Muscular: • Results from \_\_\_\_ depletion. – Synaptic: • Depletion of \_\_\_\_ in the neuromuscular junction.
70%
velocity and force of contraction
relaxation
rest
emotional state
ATP
acetylcholine
Muscle Fatigue Mechanisms
• High-frequency stimulation fatigue:
– Induced by stimulation at a rate ____ than necessary for a ____.
– Failure in the conduction of action potentials in ____.
– ____ recovery: tens of seconds.
– Rarely (if ever) happens in vivo: ____ mechanisms.
• Low-frequency stimulation fatigue:
– Induced by prolonged or repeated ____.
– Due to metabolism:
• Depletion of energy stores (ATP) and buildup of ____.
• Reduction in Ca2+ trafficking from the SR: lower ____, increased ____
time.
– Longer ____.
higher fused tetanus T tubules rapid neural safety
tetanic stimulation crossbridge metabolites peak force relaxation recovery
Adaptation and Myoplasticity
• ____: Ability of skeletal muscle to remodel.
• Quantity: e.g. ____ (enlargement) of the muscle organ.
• Quality: e.g. switch in Myosin Heavy Chain ____ (from Fast IIb to Fast IIa),
____ (from glycolysis to oxidative phosphorylation).
• Adaptation: • More effective \_\_\_\_ exercise. • Depends on type of \_\_\_\_ (training): resistance, plyometric (max. force, short intervals), endurance. • Easily reversible when stimulus is diminished or removed (inactivity): \_\_\_\_. • Muscle adapts in different ways: • \_\_\_\_ adaptation. • \_\_\_\_ adaptation. • \_\_\_\_ adaptation.
myoplasticity
hypertrophy
gene expression
metabolism
aerobic or resistance
exercise
atrophy
metabolic
cellular
neural
Metabolic Adaptations
• Heavy work, untrained muscle: • Low O2 availability: \_\_\_\_. • Accumulation of pyruvate: negative feedback on glycolysis. • Adaptation: • Reduction of pyruvate to \_\_\_\_: allows glycolysis to continue. • Regeneration of \_\_\_\_. • Production of lactate → \_\_\_\_
If forcing an untrained muscle to take heavy work > training provides additional vascularization; in an untrained muscle there is low ____, therefore the availability of oxygen is low > obligated to use ____ as a source of energy
Accumulation of pyruvate, acts on a feedback mechanism and stops the pathway (glycolysis can only be maintained for a ____ time)
Lactate is an acid, and must be eliminated, but it doesn’t happen rapidly; it will be regenerated back to pyruvate but it will occur in the liver later
Generation of lactate is evidence of ____ or muscle “shortness?”, and the oxygen-deficit phenomena
glycolysis
lactate
NAD+
oxygen deficit phenomenon
vascularization
glycolysis
limited
heavy work
Metabolic Adaptations: Oxygen Deficit
- Difference between oxygen uptake of the body during ____ of exercise and during a similar duration in a ____ of exercise.
- Allows short-term ____ metabolism.
- Must be re-payed:
- During ____ in the TCA cycle.
- During regeneration of ____ stores from oxidative phosphorylation ATP.
• Recovery phase after heavy exercise: O2 consumption and lung ventilation rates remain
elevated.
Why muscles working anaerobically create an overall oxygen-deficit for the body and muscles themselves:
Lactate must be oxidized in the liver (uses energy and oxygen)
After contraction, stores of ATP and creatine phosphate are low > mitochondria regenerated the stores by using ATP that was created during ox phos after the exercise
After heavy exercise, the rates of oxygen consumption are still ____, compared to the body at rest
The oxygen deficit is not as acute, the consumption is not just related to the single exercise
early stages steady state anaerobic lactic acid oxidation creatine-P
very high
Metabolic Adaptations: Myoglobin Content
Similar ____, different ____.
The quaternary structure of hemoglobin confers ____.
tertiary structure
quaternary structure
allosteric properties
Myoglobin avidly binds oxygen
- Mb facilitates diffusion of O2 in exercising muscles.
- Mb most abundant in muscles adapted for aerobic exercise: ____.
Muscles that are rich in ox phos > ____ (slower, but efficient) > contain myoglobin
Myoglobin has oxygen bound to molecule when the pressure of oxygen is ____ > a very good mechanism to store oxygen inside the cells themselves
Only when intracell concentration of oxygen is ____ > myoglobin release oxygen atoms that can be used in ox phos; also provides a very ____ of oxygen to those muscles
red/dark fibers
red fibers
very low
low
Cellular Adaptations
• Changes in skeletal muscle configuration and structure:
– ____ activation.
– ____ to existing fibers.
• Occurs with ____ and ____.
• Hypertrophy vs hyperplasia:
– ____: muscle fibers growing in size → increase in cross-sectional area.
– ____: muscle fibers growing in number (more common in ____).
Activation of ____ produces a bigger, thicker fiber > increase in cross-sectional area (hypertrophy) (skeletal muscle cell is a ____ cell, fused, contain many nuclei) > exert more force; result of resistance training and overloading our muscles
Can also see presence of hyperplasia, increase in actual number of muscle fibers
satellite cell fusion resistance training overloading hypertrophy hyperplasia development
satellite cells
sintitial
Mechanical Properties in Muscle Hypertrophy
• Hypertrophy:
– Increase in cross-sectional area (CSA). – Increase in ____.
• Force-velocity relationships:
– Increase in maximum load (____ > ____).
– No change in ____, but…
– a stronger (“trained”) muscle moves an isotonic load (X) at a greater ____
• Enhanced ____ output.
cross-sectional area (CSA) P0t, P0ut maximum no-load velocity (V0) velocity (Vt > Vut) power
Neural Adaptations
• Recall the muscle physiology lecture:
• Motor unit: Neuron + innervated muscle fibers.
• ____: Increasing force via recruitment of additional
motor units.
• ____: Increasing force via greater neural discharge
frequency.
• Maximum muscle force then requires:
• Activation of all ____.
• Maximal ____.
number coding
rate coding
motor units
rate coding
Neural Adaptations
• Neural adaptation: • Increased \_\_\_\_ recruitment. • Decreased \_\_\_\_ of motor unit recruitment. • Decreased \_\_\_\_ recruitment. • Increased neural coordination • Increased activation of \_\_\_\_ motor units.
• Timeline of muscle adaptation: • Early changes: \_\_\_\_ adaptation. • Later changes: \_\_\_\_ (increasing CSA). • Years: \_\_\_\_, no gains from training (anabolic steroids!).
MU
neural inhibition
antagonist
agonist
neural
hypertrophy
plateau
Neural Adaptations
Training the muscles, you change both the ____
Compare increase in force during long term training with the types of adaptation that take place; most training studies: most adaptation that takes place is ____ (by reorganizing and remodeling the coordination and neural control); if training increase, neural stimulation hits a plateau but ____ is still increasing, but now a recruitment of satellite cells is now taking place, but eventually the muscle strength is maximized
Only way to increase force afterwards is to take substances that increase the hypertrophy beyond what is normal
spatial and temporal summation
neural
force
Muscle De-training and Atrophy
- ____:
- Mild decrease in skeletal muscle functionality due to lack of exercise.
- Atrophy: ____ in muscle function.
- Occurs with immobilization, ____ rest, aging, ____ flight.
- ____ decrease in muscle mass and fiber diameter.
- Large reduction in ____ and/or load.
- Significant reduction in metabolic and exercise capacity in ____ weeks.
- Complete loss of training adaptations in a few ____.
de-training
severe bed space 30-50% recruitment frequency 1-2 months
Mechanisms Associated with Muscle Growth and Atrophy
Going from untrained muscle to trained muscle > activation of ____ and high levels of ____
Atrophy state > high rates of ____ and ____ (decrease in diameter of muscle)
satellite cells
protein synthesis
protein degradation
apoptosis
- Muscle Damage and Repair: Stages of Muscle Damage
Begin with normal muscle and induce with ____ contractions (good at creating damage) > numerous effects > used to study the damage the muscles show following use
1.– During exercise: Mechanical (strain) damage: • Myofibril damage: – Disrupted sarcomeres → Effect on \_\_\_\_ → Lower force. • Sarcolemma damage. – \_\_\_\_ dysfunction (reversible) → Lower force. • SR damage. – Ca2+ influx. » Protease activation – damage to \_\_\_\_. » Phospholipase activation – damage to \_\_\_\_.
- After exercise: ____ response.
If fiber dies, there is an ____ decrease in force
Swelling and soreness is due to a ____ due to a fact that cells are dying and leaking their contents outside
eccentric optimal length excitation/coupling cytoskeleton sarcolemma inflammatory irreversible inflammatory process
- Muscle Damage and Repair: Eccentric vs Concentric Contractions
Concentric contraction = contraction while ____
Eccentric contraction = contraction while ____
shortening
lengthening
- Muscle Damage and Repair: Sarcomere Damage
• Damage occurs during ____ (eccentric) movements.
• Extent of injury more related to ____ than force or velocity.
• ____ fibers become overstretched, which become damaged.
• Damage to the Z disk (known as Z-disk streaming):
– Massive loss of Z disk integrity following muscle
injury.
– Z disk structure is disrupted and Z disks are not in ____
with each other (arrowheads).
– Muscle cell separation from the ____ and
____ (asterisks).
• Affects ____ fibers more than ____ fibers.
If Z-disks are compromised > myofilaments have no structure to which they can attach, and they have no structure onto which they can exert a ____
lengthening length weaker line basal lamina endomysium
fast
slow
force
- Muscle Damage and Repair: Myofibril Damage
• Hypertrophy and myofibril proliferation:
– Myofibrils increase in mass and CSA from addition of actin/myosin to ____.
– Myofibrils reach critical mass where forceful actions tear Z disks ____.
– Myofibrils may ____.
When you have too many filaments because the cell has become larger, the angle at which the filaments attach themselves to the Z-disk is not ____; when filaments contract, the forces that act on Z-disks come at an ____ > Z-disk breaches (streaming)
periphery
longitudinally
split
flat
angle
- Muscle Damage and Repair: Sarcolemma Damage
• Damage to the sarcolemma:
– EM photo:
• Muscle of a runner after a ____ race, showing damage to the sarcolemma.
Even ____ muscles can undergo damage like this
marathon
well-trained
- Muscle Damage and Repair: Stages
• Degenerative (____ response) phase (panel B):
– ____ (blue-stained cells: neutrophils and monocytes) and ____ of muscle fibers (arrows).
– Loss of muscle architecture.
• ____ phase (panel C):
– Activation of ____, differentiation, and fusion into ____.
– Regenerating fibers: ____ caliber (still showing ____ nuclei).
acute
inflammatory response
rapid necrosis
regenerative satellite cells myotubes smaller centrally-located
- Muscle Damage and Repair: Molecular Events
A. Damage to the myofiber.
B. Activation of ____: expansion of the
myogenic cell population.
C. Differentiation: myogenic cells differentiate into
____.
D. Myoblasts ____ to the damaged myofiber (myocyte,
muscle cell) for repair; or to ____ for new
myofiber formation.
E. Growth of repaired or new myofiber.
F. A subset of myoblasts reenters the ____ to replenish the satellite cell pool for subsequent muscle repair.
Similar to training, except no ____ and increase in ____ of the muscle fiber
satellite cells myoblasts fuse each other quiescent state
damage
cross-sectional area
- Muscle Damage and Repair: Myostatin
• Myostatin:
– Belongs to the ____ superfamily.
– ____ regulator of muscle growth and
differentiation.
• “Double-muscled cattle”: – 20% more muscle. – Natural mutations in the Myostatin gene. – Muscle \_\_\_\_. – Low \_\_\_\_ (very lean meat).
TGF-beta
negative
hypertrophy and hyperplasia
fat
- Muscle Damage and Repair: Human Myostatin Null Case
- ____ for a loss-of-function mutation in the Myostatin gene:
- Increased muscle bulk and strength.
- ____: Protruding muscles of the patient’s thigh and calf (arrowheads in panel A).
- At 4.5 years of age, able to hold two 3-kg dumbbells in horizontal suspension with his arms extended.
- No major ____, and intellectually ____.
- Panel C, muscle cross-sectional planes of patient and normal infants.
- Pedigree (panel D): Solid symbols indicate family members exceptionally ____.
Pedigree > shows members of his family that were known to be very strong (although never ____ to see if they were mutants for myostatin)
homozygote hyperplasia medical problems normal strong
genetically studied
- Muscle Disorders
• Skeletal muscle disorders:
– Primary muscle disease (usually ____): ____
– Disorders of neuromuscular transmission: e.g. ____.
– ____ and ____ disorders.
genetic muscular dystrophies myasthenia gravis aging metabolic
- Muscle Disorders: Dystrophies
• Dystrophies:
– ____ diseases.
– Severe muscle weakness, atrophy and destruction of myofibers.
– Many linked to mutations in genes for components of the
____ and ____ complexes.
congenital
dystroglycan
sarcoglycan
- Muscle Disorders: Dystrophies
Mutations in any of these genes (dystroglycan/sarcoglycan) interrupts the structures that connect ECM with interior of cell
Another mutation is common in dystrophin, connects DGC with the contractile mechanism of the cell > results in ____
Fragility of myofibrils > mutations in proteins that connect myofilaments with DGC and SGC, thereby stabilizing the myofilaments
Congenital muscle dystrophy: ____
Limb-girdle muscular dystrophies (sarcoglycanopathies): ____
Duchenne’s muscular dystrophy: ____
Fragility of the myofibrils: ____, ____, ____
DMD laminin 2 carcoglycan complex dystrophin desmin plectin ab-crystalin
- Muscle Disorders: Duchenne’s Muscular Dystrophy (DMD)
• Deficiency in Dystrophin.
• Dystrophin stabilizes the sarcolemma by linking the cytoskeleton and the ECM: ____ during contraction.
• ____ inheritance:
– 1/3600 male births.
– Affected persons (males): normal at birth and manifest the disease
in early childhood.
– Carrier females: asymptomatic or mild ____ and
____.
• Symptoms:
– Fast progression.
– First: muscles of the ____ – difficulty in getting up from
seated position.
– Progressive muscle weakness and wasting; vomiting (delayed
____); ____ pain; difficulty walking.
– Death commonly results from failure of ____ muscles.
Most of myofibers in slide are normal (stained deep-red) except for one that is degenerating (internal structure of cell is lost) due to the fact that dystrophin is mutated
All cells don’t die at ____, but it is a fast progression during infancy
myofiber integrity X-linked muscle weakness cramps pelvic girdle gastric emptying abdominal respiratory
same time
- Muscle Disorders: Duchenne’s Muscular Dystrophy (DMD)
• Positive Gowers’ sign:
• Indicates weakness of the ____ muscles,
namely those of the ____.
• The sign describes a patient that has to use their hands and arms to “walk” up their own body from a squatting position due to lack of hip and thigh muscle strength.
Pseudohypertrophy (enlarging) of ____ and ____ muscles:
• Muscle tissue eventually
replaced by ____ and ____ tissue (pseudohypertrophy).
proximal
lower limbe
tongue
calf
fat
connective
- Muscle Disorders: Duchenne’s Muscular Dystrophy (DMD)
• No ____.
• Treatments:
– ____: control symptoms to improve quality of life.
– ____ drugs can slow the loss of muscle strength.
– ____ may help to maintain muscle strength and function. ____ is often needed.
– Other treatments may include:
• Assisted ____ (used during the day or night).
• Drugs to help heart function, such as ____ inhibitors, beta-blockers, and ____.
• ____ appliances (such as braces and wheelchairs) to improve mobility.
• Proton pump inhibitors (for people with ____).
cure palliative steroid physical therapy speech therapy
ventilation angiotensin-converting enzyme diuretics orthopedic gastroesophageal reflux
- Muscle Disorders: Merosin*-deficient congenital muscular dystrophy type 1A (MDC1A)
• Autosomal recessive mutation of the LAMA2 gene, encoding ____.
• Prevalence 1/30,000.
• Congenital ____ and ____, and progressive
muscle weakness, ____.
• Neural defects, including aberrant ____ of peripheral nerves.
• Difficulty ____, gastro-esophageal reflux and ____.
Merosin = laminin; no laminin 2 present, ____ cannot bind, and the linkage between the inside of cell and ECM is broken
Anywhere with a ____ containing a laminin 2 gene is affected > neural defects
B > section of muscle > organization is completely broken and some are degenerating and an invasion of ECM or adipose
C/D > in normal individuals (D) there is a neat basal lamina surrounding every muscle cell, in diseased (C) muscle cells are not surrounded by laminin because they don’t have any (genetically gone)
laminin 2 hypotonia joint contractures non-ambulatory myelination chewing chest infections
dystroglycan
basal lamina
- Muscle Disorders of Neuromuscular Transmission: Myasthenia Gravis
• Failure of neuromuscular transmission due to blockage and destruction of ____ by autoantibodies.
• ____ autoimmune disease.
• MG is characterized by:
– Muscle weakness, aggravated by repeated ____.
– Muscles with the ____ are affected first.
ACh receptors
organ-specific
contraction
smallest MU
- Muscle Disorders of Neuromuscular Transmission: Myasthenia Gravis
• Symptoms:
– Typical clinical presentation:
• ____: weakness of ocular muscles causing drooping of the eyelid.
• ____: double vision.
• Progression:
– May include ____, limb girdle muscles, and ____.
• Treatment:
– ____ to directly improve muscle function.
– ____ to reduce the autoimmune process.
Can result in ____ due to respiratory muscles being affected
In close association with receptor > there is an ____ that stops the signal of Ach interacting with its receptor (hydrolyzes Ach)
Acetylcholinesterase inhibitors: inhibit the enzyme from breaking down ____, thereby increasing the likelihood that any nearby acetylcholine can bind one of the free receptors not bound by autoantibody
ptosis
diplopia
facial muscles
respiratory muscles
acetylcholinesterase inhibitors
immunosuppressant drugs
asphyxiation
acetylcholinesterase
acetylcholine
- Muscle Disorders of Neuromuscular Transmission: Myasthenia Gravis
At the dental practice:
• General muscle weakness:
– Difficulties for self-care (hair washing and shaving) and oral self-care (tooth brushing).
• Intolerant of ____:
– Operatory light directed away from the patient’s eyes.
– Dark protective eyewear.
- Facial muscle weakness.
- Access to ____.
• ____ muscle weakness.
• Dysphagia:
– Weakness of the ____ and ____ muscles.
– Muscle fatigue associated with chewing and swallowing.
– Difficulty breathing due to defective airway clearing.
– Patient may be in ____, but not appear to be ____.
bright lights
oral cavity
masticatory
tongue
posterior pharyngeal
crisis
distressed
- Muscle Disorders: Aging and Metabolic
- ____ muscle mass.
- Increased ____ for muscle to contract in response to nervous stimuli.
- Reduced ____.
- Increased ____ time.
- ____ of muscle fibers.
- Decreased ____ of capillaries in muscle.
reduced time stamina recovery loss density
- Muscle Disorders: Aging and Metabolic
- Abnormal deposition of fat:
- ____.
- ____ resistance
- Lower ____
• In adipocytes located in the ____
tissue between myofibers (panel A).
• Within the ____ of myofibers as lipid
droplets (panel B).
A > adipocytes located in connective tissue that is separating the skeletal muscle fibers, in normal person > shouldn’t be any adipose cells in layer of ____
B > sometimes adipose is deposited inside the cell as ____ lipid droplets > uses ____ that stains fat ____ > affects the function of the skeletal muscle cells
aging
insulin
oxidative capacity
interstitial connective
sarcoplasm
endomysium
very small
oil red O
red
