Pathophysiology of Skeletal Muscle Flashcards
Plasticity of skeletal muscle: exercise
- muscle is extremely …
- adapts to changes in functional demand: fill in blanks

- muscle is extremely plastic
- adapts to changes in functional demand:

Endurance exercise responds to total … activity
Endurance exercise responds to total contractile activity
Resistance training responds to … and …
Resistance training responds to loading and stretch
Muscle plasticity: adaptations
- adaptations:
- s…
- e.g. size, capillarisation
- … properties
- e.g. fibre type transitions
- s…
- adaptability occurs from … into maturity
- adaptations:
-
structural
- e.g. size, capillarisation
-
contractile properties
- e.g. fibre type transitions
-
structural
- adaptability occurs from embryogenesis into maturity
… = The formation and development of a network of capillaries to a part of the body
Capillarisation = The formation and development of a network of capillaries to a part of the body
Structural adaptation
- Total … of muscle fibres … at birth:
- e.g. 200,000 – biceps brachii
- But - muscles can grow: H…
- synthesis of myofilaments
- addition of sarcomeres
- satellite cell activation
- angiogenesis & vascularisation
- some muscles enlarge by between 15-50%
- Total number of muscle fibres fixed at birth:
- e.g. 200,000 – biceps brachii
- But - muscles can grow: hypertrophy
- synthesis of myofilaments
- addition of sarcomeres
- satellite cell activation
- angiogenesis & vascularisation
- some muscles enlarge by between 15-50%
Structural adaptation
- Total number of muscle fibres fixed at birth:
- e.g. 200,000 – biceps brachii
- But - muscles can grow: hypertrophy
- synthesis of myofilaments
- addition of sarcomeres
- satellite cell activation
- angio… & vascularisation
- some muscles enlarge by between ..-..%
- Total number of muscle fibres fixed at birth:
- e.g. 200,000 – biceps brachii
- But - muscles can grow: hypertrophy
- synthesis of myofilaments
- addition of sarcomeres
- satellite cell activation
- angiogenesis & vascularisation
- some muscles enlarge by between 15-50%
Structural adaptation
- Total number of muscle fibres fixed at birth:
- e.g. 200,000 – biceps brachii
- But - muscles can …: hypertrophy
- … of myofilaments
- addition of ….
- satellite cell activation
- angiogenesis & vascularisation
- some muscles enlarge by between 15-50%
- Total number of muscle fibres fixed at birth:
- e.g. 200,000 – biceps brachii
- But - muscles can grow: hypertrophy
- synthesis of myofilaments
- addition of sarcomeres
- satellite cell activation
- angiogenesis & vascularisation
- some muscles enlarge by between 15-50%
Effect of endurance exercise
- e.g. distance running, cycling or swimming (… force, … contractile frequencies)
- … fibre diameter (slight), blood supply ( oxidative capacity), mitochondrial content
- will express increased in oxidative enzymes
- fibres become slower
- gradual transformation of type IIX to type IIA (or to type I?)
- e.g. distance running, cycling or swimming (low force, high contractile frequencies)
- Increased fibre diameter (slight), blood supply ( oxidative capacity), mitochondrial content
- will express increased in oxidative enzymes
- fibres become slower
- gradual transformation of type IIX to type IIA (or to type I?)
Effect of endurance exercise
- e.g. distance running, cycling or swimming (low force, high contractile frequencies)
- Increased fibre … (slight), blood supply ( oxidative capacity), … content
- will express increased in oxidative enzymes
- fibres become …
- gradual transformation of type IIX to type IIA (or to type I?)
- e.g. distance running, cycling or swimming (low force, high contractile frequencies)
- Increased fibre diameter (slight), blood supply ( oxidative capacity), mitochondrial content
- will express increased in oxidative enzymes
- fibres become slower
- gradual transformation of type IIX to type IIA (or to type I?)
Effect of endurance exercise
- e.g. distance running, cycling or swimming (low force, high contractile frequencies)
- Increased fibre diameter (slight), … supply ( oxidative capacity), mitochondrial content
- will express increased in … enzymes
- fibres become slower
- gradual transformation of type … to type … (or to type I?)
- e.g. distance running, cycling or swimming (low force, high contractile frequencies)
- Increased fibre diameter (slight), blood supply ( oxidative capacity), mitochondrial content
- will express increased in oxidative enzymes
- fibres become slower
- gradual transformation of type IIX to type IIA (or to type I?)
Effect of endurance exercise
- e.g. distance running, cycling or swimming (low force, high contractile frequencies)
- … fibre diameter (slight), blood supply ( oxidative capacity), mitochondrial content
- will express increased in oxidative enzymes
- fibres become …
- gradual transformation of type IIX to type IIA (or to type I?)
- e.g. distance running, cycling or swimming (low force, high contractile frequencies)
- Increased fibre diameter (slight), blood supply ( oxidative capacity), mitochondrial content
- will express increased in oxidative enzymes
- fibres become slower
- gradual transformation of type IIX to type IIA (or to type I?)
Non-endurance exercise
- conversion to type II…
- from type II…
- greater muscle force & strength
- Increase in type II… fibre size due to increase in numbers of sarcomeres & myofilaments
- results in much larger muscles (bulk)
- conversion to type IIX
- from type IIA
- greater muscle force & strength
- Increase in type IIX fibre size due to in numbers of sarcomeres & myofilaments
- results in much larger muscles (bulk)
Non-endurance exercise
- conversion to type IIX
- from type IIA
- … muscle force & strength
- Increase in type IIX fibre size due to increase in numbers of sarcomeres & myofilaments
- results in much larger muscles (…)
- conversion to type IIX
- from type IIA
- greater muscle force & strength
- Increase in type IIX fibre size due to in numbers of sarcomeres & myofilaments
- results in much larger muscles (bulk)
Ice and Heat - Exercise
- Ice - To reduce swelling by reducing …
- After an acute injury (s..)
- After exercise in overuse injury
- Heat - To relax and loosen tissues
- Use before activities that irritate chronic injuries (s…)
- Increases blood flow
- Ice - To reduce swelling by reducing perfusion
- After an acute injury (Sprain)
- After exercise in overuse injury
- Heat - To relax and loosen tissues
- Use before activities that irritate chronic injuries (Strain)
- Increases blood flow
Ice and Heat - Exercise
- Ice - To reduce swelling by reducing perfusion
- After an … injury (Sprain)
- After exercise in overuse injury
- Heat - To relax and loosen tissues
- Use before activities that irritate … injuries (Strain)
- Increases blood flow
- Ice - To reduce swelling by reducing perfusion
- After an acute injury (Sprain)
- After exercise in overuse injury
- Heat - To relax and loosen tissues
- Use before activities that irritate chronic injuries (Strain)
- Increases blood flow
Ice and Heat - Exercise
- Ice - To reduce swelling by reducing perfusion
- After an acute injury (Sprain)
- After exercise in overuse injury
- Heat - To … and … tissues
- Use before activities that irritate chronic injuries (Strain)
- … blood flow
- Ice - To reduce swelling by reducing perfusion
- After an acute injury (Sprain)
- After exercise in overuse injury
- Heat - To relax and loosen tissues
- Use before activities that irritate chronic injuries (Strain)
- Increases blood flow
A … is an injury to a ligament, whereas a … is an injury to a muscle or tendon
A sprain is an injury to a ligament, whereas a strain is an injury to a muscle or tendon
A sprain is an injury to a …, whereas a strain is an injury to a … or …
A sprain is an injury to a ligament, whereas a strain is an injury to a muscle or tendon
Aspirin and Musculoskeletal Pain
- Aspirin is an … - So is ibuprofen
- Reduces … and …
- Used for musc-skel pain
- Chronic diseases
- Osteoarthritis
- Sports injuries
- Combined with ice
- Often after exercise
- Chronic diseases
- Aspirin is an NSAID - So is ibuprofen
- Reduces pain and inflammation
- Used for musc-skel pain
- Chronic diseases
- Osteoarthritis
- Sports injuries
- Combined with ice
- Often after exercise
- Chronic diseases
Aspirin and Musculoskeletal Pain
- Aspirin is an NSAID - So is ibuprofen
- Reduces pain and inflammation
- Used for musc-skel pain
- … diseases
- Osteoarthritis
- … injuries
- Combined with ice
- Often after exercise
- … diseases
- Aspirin is an NSAID - So is ibuprofen
- Reduces pain and inflammation
- Used for musc-skel pain
-
Chronic diseases
- Osteoarthritis
-
Sports injuries
- Combined with ice
- Often after exercise
-
Chronic diseases
Aspirin and Musculoskeletal Pain
- Aspirin is an NSAID - So is ibuprofen
- Reduces pain and inflammation
- Used for musc-skel pain
- Chronic diseases
- Os…
- Sports injuries
- Combined with …
- Often … exercise
- Chronic diseases
- Aspirin is an NSAID - So is ibuprofen
- Reduces pain and inflammation
- Used for musc-skel pain
- Chronic diseases
- Osteoarthritis
- Sports injuries
- Combined with ice
- Often after exercise
- Chronic diseases
Aspirin and Musculoskeletal Pain - Mechanism
- Inhibits …
- Reduces synthesis of prostaglandins
- Part of … acid pathway
- Arachidonic acid and prostaglandins have many effects
- Gastro-intestinal adverse effects of chronic aspirin
- Stomach bleeding
- Ulcers
- Gastro-intestinal adverse effects of chronic aspirin
- Inhibits COX
- Reduces synthesis of prostaglandins
- Part of arachidonic acid pathway
- Arachidonic acid and prostaglandins have many effects
- Gastro-intestinal adverse effects of chronic aspirin
- Stomach bleeding
- Ulcers
- Gastro-intestinal adverse effects of chronic aspirin
Aspirin and Musculoskeletal Pain - Mechanism
- Inhibits COX
- Reduces synthesis of …
- Part of arachidonic acid pathway
- Arachidonic acid and prostaglandins have many effects
- …-… adverse effects of chronic aspirin
- Inhibits COX
- Reduces synthesis of prostaglandins
- Part of arachidonic acid pathway
- Arachidonic acid and prostaglandins have many effects
-
Gastro-intestinal adverse effects of chronic aspirin
- Stomach bleeding
- Ulcers
-
Gastro-intestinal adverse effects of chronic aspirin
Aspirin and Musculoskeletal Pain - Mechanism
- Inhibits COX
- Reduces synthesis of prostaglandins
- Part of arachidonic acid pathway
- Arachidonic acid and prostaglandins have many effects
- Gastro-intestinal adverse effects of chronic aspirin
- … bleeding
- U..
- Gastro-intestinal adverse effects of chronic aspirin
- Inhibits COX
- Reduces synthesis of prostaglandins
- Part of arachidonic acid pathway
- Arachidonic acid and prostaglandins have many effects
- Gastro-intestinal adverse effects of chronic aspirin
- Stomach bleeding
- Ulcers
- Gastro-intestinal adverse effects of chronic aspirin
Testosterone has anabolic & androgenic effects
- Anabolic effects of testosterone:
- … protein synthesis
- … catabolism (by opposing cortisol & glucocorticoids)
- … fat: increase BMR, increase differentiation to muscle (rather than fat cells)
- Anabolic steroid abuse
- Used to increase muscle size and strength
- Large doses required – leads to damaging side effects (kidney, liver, heart, mood changes)
- male – testes atrophy, sterility, baldness
- female – breast/uterus atrophy, menstrual changes, facial hair, deepening of voice
- Anabolic effects of testosterone:
- Increases protein synthesis
- Decreases catabolism (by opposing cortisol & glucocorticoids)
- Reduces fat: increase BMR, increase differentiation to muscle (rather than fat cells)
- Anabolic steroid abuse
- Used to increase muscle size and strength
- Large doses required – leads to damaging side effects (kidney, liver, heart, mood changes)
- male – testes atrophy, sterility, baldness
- female – breast/uterus atrophy, menstrual changes, facial hair, deepening of voice
Testosterone has anabolic & androgenic effects
- Anabolic effects of testosterone:
- Increases protein synthesis
- Decreases … (by opposing cortisol & glucocorticoids)
- Reduces …: increase …, increase differentiation to muscle (rather than … cells)
- Anabolic steroid …
- Used to increase muscle size and strength
- Large doses required – leads to damaging side effects (kidney, liver, heart, mood changes)
- male – testes atrophy, sterility, baldness
- female – breast/uterus atrophy, menstrual changes, facial hair, deepening of voice
- Anabolic effects of testosterone:
- Increases protein synthesis
- Decreases catabolism (by opposing cortisol & glucocorticoids)
- Reduces fat: increase BMR, increase differentiation to muscle (rather than fat cells)
- Anabolic steroid abuse
- Used to increase muscle size and strength
- Large doses required – leads to damaging side effects (kidney, liver, heart, mood changes)
- male – testes atrophy, sterility, baldness
- female – breast/uterus atrophy, menstrual changes, facial hair, deepening of voice
Anabolic steroid abuse
- Used to increase muscle size and strength
- Large doses required – leads to damaging side effects (…, liver, heart, … changes)
- Male – testes …, sterility, baldness
- Female – breast/uterus atrophy, menstrual changes, facial hair, deepening of voice
- Used to increase muscle size and strength
- Large doses required – leads to damaging side effects (kidney, liver, heart, mood changes)
- Male – testes atrophy, sterility, baldness
- Female – breast/uterus atrophy, menstrual changes, facial hair, deepening of voice
Anabolic steroid abuse
- Used to increase … size and strength
- Large doses required – leads to damaging side effects (kidney, liver, heart, mood changes)
- Male – testes atrophy, sterility, baldness
- Female – breast/uterus atrophy, … changes, … hair, … of voice
- Used to increase muscle size and strength
- Large doses required – leads to damaging side effects (kidney, liver, heart, mood changes)
- Male – testes atrophy, sterility, baldness
- Female – breast/uterus atrophy, menstrual changes, facial hair, deepening of voice
Anabolic steroid abuse
- Used to increase muscle size and strength
- Large doses required – leads to damaging side effects (kidney, liver, heart, mood changes)
- Male – … atrophy, sterility, baldness
- Female – …/… atrophy, menstrual changes, facial hair, deepening of voice
- Used to increase muscle size and strength
- Large doses required – leads to damaging side effects (kidney, liver, heart, mood changes)
- Male – testes atrophy, sterility, baldness
- Female – breast/uterus atrophy, menstrual changes, facial hair, deepening of voice
Anabolic steroid abuse
- Used to increase muscle size and strength
- … … required – leads to damaging side effects (kidney, liver, heart, mood changes)
- Male – testes atrophy, s…, b…
- Female – breast/uterus atrophy, menstrual changes, facial hair, deepening of voice
- Used to increase muscle size and strength
- Large doses required – leads to damaging side effects (kidney, liver, heart, mood changes)
- Male – testes atrophy, sterility, baldness
- Female – breast/uterus atrophy, menstrual changes, facial hair, deepening of voice
Effect of spaceflight
- Exposed to … … (long-term exposure)
- … in weight bearing in bones and muscles, over time, transition of Type 1 (slow) fibres to Type IIA/IIX fibres (Faster fibres)
- Lose slow fibres, gain fast fibres
- Decrease in relative muscle mass - all muscles undergo some atrophy, but predominantly weight bearing muscles
- Exposed to zero gravity (long-term exposure)
- Decrease in weight bearing in bones and muscles, over time, transition of Type 1 (slow) fibres to Type IIA/IIX fibres (Faster fibres)
- Lose slow fibres, gain fast fibres
- Decrease in relative muscle mass - all muscles undergo some atrophy, but predominantly weight bearing muscles
Effect of spaceflight
- Exposed to zero gravity (long-term exposure)
- Decrease in weight bearing in bones and muscles, over time, transition of Type … (slow) fibres to Type …fibres (Faster fibres)
- Lose slow fibres, gain fast fibres
- Decrease in relative muscle mass - all muscles undergo some atrophy, but predominantly weight bearing muscles
- Exposed to zero gravity (long-term exposure)
- Decrease in weight bearing in bones and muscles, over time, transition of Type 1 (slow) fibres to Type IIA/IIX fibres (Faster fibres)
- Lose slow fibres, gain fast fibres
- Decrease in relative muscle mass - all muscles undergo some atrophy, but predominantly weight bearing muscles
Effect of spaceflight
- Exposed to zero gravity (long-term exposure)
- Decrease in weight bearing in bones and muscles, over time, transition of Type 1 (…) fibres to Type IIA/IIX fibres (… fibres)
- Lose … fibres, gain … fibres
- Decrease in relative muscle mass - all muscles undergo some atrophy, but predominantly weight bearing muscles
- Exposed to zero gravity (long-term exposure)
- Decrease in weight bearing in bones and muscles, over time, transition of Type 1 (slow) fibres to Type IIA/IIX fibres (Faster fibres)
- Lose slow fibres, gain fast fibres
- Decrease in relative muscle mass - all muscles undergo some atrophy, but predominantly weight bearing muscles
Effect of spaceflight
- Exposed to zero gravity (long-term exposure)
- Decrease in weight bearing in bones and muscles, over time, transition of Type 1 (slow) fibres to Type IIA/IIX fibres (Faster fibres)
- Lose slow fibres, gain fast fibres
- Decrease in … … mass - all muscles undergo some …, but predominantly … bearing muscles
- Exposed to zero gravity (long-term exposure)
- Decrease in weight bearing in bones and muscles, over time, transition of Type 1 (slow) fibres to Type IIA/IIX fibres (Faster fibres)
- Lose slow fibres, gain fast fibres
- Decrease in relative muscle mass - all muscles undergo some atrophy, but predominantly weight bearing muscles
Effect of bed-rest
- Muscles of posture are not being consistently used
- Transition of type … fibres to type …
- Weight-bearing muscle …
- Decrease muscle protein synthesis
- Myofibrillar breakdown
- Decreased strength (due to ¯ size)
- Loss of type … fibres
- Treat by resuming minor activity early, Add physiotherapy to prevent contractures.
- Muscles of posture are not being consistently used
- Transition of type I fibres to type IIA
- Weight-bearing muscle atrophy
- Decrease muscle protein synthesis
- Myofibrillar breakdown
- Decreased strength (due to ¯ size)
- Loss of type I fibres
- Treat by resuming minor activity early, Add physiotherapy to prevent contractures.
Effect of bed-rest
- Muscles of posture are not being consistently used
- Transition of type I fibres to type IIA
- Weight-bearing muscle atrophy
- Decrease muscle protein …
- … breakdown
- Decreased … (due to ¯ size)
- Loss of type … fibres
- Treat by resuming minor activity early, Add physiotherapy to prevent contractures.
- Muscles of posture are not being consistently used
- Transition of type I fibres to type IIA
- Weight-bearing muscle atrophy
- Decrease muscle protein synthesis
- Myofibrillar breakdown
- Decreased strength (due to ¯ size)
- Loss of type I fibres
- Treat by resuming minor activity early, Add physiotherapy to prevent contractures.
Effect of bed-rest
- Muscles of posture are not being consistently used
- Transition of type I fibres to type IIA
- Weight-bearing muscle atrophy
- Decrease muscle protein synthesis
- Myofibrillar breakdown
- Decreased strength (due to ¯ size)
- Loss of type I fibres
- Treat by resuming minor activity early, Add … to prevent ….
- Muscles of posture are not being consistently used
- Transition of type I fibres to type IIA
- Weight-bearing muscle atrophy
- Decrease muscle protein synthesis
- Myofibrillar breakdown
- Decreased strength (due to ¯ size)
- Loss of type I fibres
- Treat by resuming minor activity early, Add physiotherapy to prevent contractures.
Summary Fibre Types
Dont need to memorise

Contracture
- If limb immobilised for long periods:
- Process of growth is …
- … are removed in series from myofibrils
- Resulting in … of muscle called a contracture
- Patients with paralysed limbs must have physical therapy to prevent contractures occurring
- If limb immobilised for long periods:
- Process of growth is reversed
-
Sarcomeres are removed in series from myofibrils
- Resulting in shortening of muscle called a contracture
- Patients with paralysed limbs must have physical therapy to prevent contractures occurring
Contracture
- If limb immobilised for long periods:
- Process of growth is reversed
- Sarcomeres are removed in series from myofibrils
- Resulting in shortening of muscle called a contracture
- Patients with … limbs must have … … to prevent contractures occurring
- If limb immobilised for long periods:
- Process of growth is reversed
- Sarcomeres are removed in series from myofibrils
- Resulting in shortening of muscle called a contracture
- Patients with paralysed limbs must have physical therapy to prevent contractures occurring
Skeletal muscle cells are multinucleate
- They develop as …
- Which are mononucleate
- Then the … fuse
- The … are peripheral
- The multinucleate cells do not divide
- Mitosis with multiple nuclei usually impossible
- Skeletal muscles are enlarged by:
- Fibre enlargement
- Increased vascularisation
- They develop as myoblasts
- Which are mononucleate
- Then the myoblasts fuse
- The nuclei are peripheral
- The multinucleate cells do not divide
- Mitosis with multiple nuclei usually impossible
- Skeletal muscles are enlarged by:
- Fibre enlargement
- Increased vascularisation

Skeletal muscle cells are multinucleate
- They develop as myoblasts
- Which are mononucleate
- Then the myoblasts fuse
- The nuclei are peripheral
- The … cells do not divide
- … with multiple nuclei usually impossible
- Skeletal muscles are enlarged by:
- Fibre enlargement
- Increased vascularisation
- They develop as myoblasts
- Which are mononucleate
- Then the myoblasts fuse
- The nuclei are peripheral
- The multinucleate cells do not divide
- Mitosis with multiple nuclei usually impossible
- Skeletal muscles are enlarged by:
- Fibre enlargement
- Increased vascularisation

Skeletal muscle cells are multinucleate
- They develop as myoblasts
- Which are mononucleate
- Then the myoblasts fuse
- The nuclei are peripheral
- The multinucleate cells do not divide
- Mitosis with multiple nuclei usually impossible
- Skeletal muscles are enlarged by:
- … enlargement
- Increased …
- They develop as myoblasts
- Which are mononucleate
- Then the myoblasts fuse
- The nuclei are peripheral
- The multinucleate cells do not divide
- Mitosis with multiple nuclei usually impossible
- Skeletal muscles are enlarged by:
- Fibre enlargement
- Increased vascularisation

Skeletal muscle cells are multinucleate
- They develop as myoblasts
- Which are mononucleate
- Then the myoblasts fuse
- The nuclei are …
- The multinucleate cells do not divide
- Mitosis with … nuclei usually impossible
- Skeletal muscles are enlarged by:
- Fibre enlargement
- … vascularisation
- They develop as myoblasts
- Which are mononucleate
- Then the myoblasts fuse
- The nuclei are peripheral
- The multinucleate cells do not divide
- Mitosis with multiple nuclei usually impossible
- Skeletal muscles are enlarged by:
- Fibre enlargement
- Increased vascularisation

Muscle Regeneration
- During … and … of damaged muscle tissue
- previous quiescent myogenic cells, called satellite cells, are activated
- These proliferate, differentiate and fuse onto extant fibres
- They contribute to forming multinucleate myofibers
- During inflammation and degeneration of damaged muscle tissue
- previous quiescent myogenic cells, called satellite cells, are activated
- These proliferate, differentiate and fuse onto extant fibres
- They contribute to forming multinucleate myofibers

Muscle Regeneration
- During inflammation and degeneration of damaged muscle tissue
- previous … myogenic cells, called … cells, are activated
- These proliferate, differentiate and fuse onto extant fibres
- They contribute to forming multinucleate myofibers
- During inflammation and degeneration of damaged muscle tissue
- previous quiescent myogenic cells, called satellite cells, are activated
- These proliferate, differentiate and fuse onto extant fibres
- They contribute to forming multinucleate myofibers

Muscle Regeneration
- During inflammation and degeneration of damaged muscle tissue
- previous quiescent myogenic cells, called … cells, are activated
- These proliferate, differentiate and fuse onto … fibres
- They contribute to forming … myofibers
- During inflammation and degeneration of damaged muscle tissue
- previous quiescent myogenic cells, called satellite cells, are activated
- These proliferate, differentiate and fuse onto extant fibres
- They contribute to forming multinucleate myofibers

Myosatellite cells
- … cells in muscle
- Also called “satellite cells”
- NOT related glial satellite cells
- Essential for … & …
- Most are quiescent
- Activated by mechanical strain
- Activation —> proliferation & differentiation
-
Progenitor cells in muscle
- Also called “satellite cells”
- NOT related glial satellite cells
- Essential for regeneration & growth
- Most are quiescent
- Activated by mechanical strain
- Activation —> proliferation & differentiation
Myosatellite cells
- Progenitor cells in muscle
- Also called “satellite cells”
- NOT related glial satellite cells
- Essential for regeneration & growth
- Most are q…
- Activated by mechanical …
- Activation —> p… & d…
- Progenitor cells in muscle
- Also called “satellite cells”
- NOT related glial satellite cells
- Essential for regeneration & growth
- Most are quiescent
- Activated by mechanical strain
- Activation —> proliferation & differentiation
… = opposite of active. Not dividing, low metabolism, little or no observable activity.
Quiescent = opposite of active. Not dividing, low metabolism, little or no observable activity.
Myalgia
- … pain
- Causes of myalgia:
- Injury, overuse, infections, auto-immune
- Can by associated with …
- Muscle pain
- Causes of myalgia:
- Injury, overuse, infections, auto-immune
- Can by associated with Rhabdomyolysis
Myalgia
- Muscle pain
- Causes of myalgia: (4)
- Can by associated with Rhabdomyolysis
- Muscle pain
- Causes of myalgia:
- Injury, overuse, infections, auto-immune
- Can by associated with Rhabdomyolysis
myalgia = …
pain in a muscle or group of muscles.
Myopathy =
Muscular weakness due to muscular muscle fibre dysfunction
Myopathy
- Muscular … due to muscular muscle fibre …
- Cf. neuropathy & neurogenic disorders
- Failure to contract cause possibly muscle or nerve
- Cf. neuropathy & neurogenic disorders
- Systemic vs. familial
- Dystrophies: familial, progressive
- Stuck in degeneration-regeneration cycle
- Eventually regenerative ability is lost
- Muscular weakness due to muscular muscle fibre dysfunction
- Cf. neuropathy & neurogenic disorders
- Failure to contract cause possibly muscle or nerve
- Cf. neuropathy & neurogenic disorders
- Systemic vs. familial
- Dystrophies: familial, progressive
- Stuck in degeneration-regeneration cycle
- Eventually regenerative ability is lost
Myopathy
- Muscular weakness due to muscular muscle fibre dysfunction
- Cf. neuropathy & neurogenic disorders
- Failure to contract cause possibly muscle or nerve
- Cf. neuropathy & neurogenic disorders
- s.. vs. f…
- Dystrophies: familial, progressive
- Stuck in degeneration-regeneration cycle
- Eventually regenerative ability is lost
- Muscular weakness due to muscular muscle fibre dysfunction
- Cf. neuropathy & neurogenic disorders
- Failure to contract cause possibly muscle or nerve
- Cf. neuropathy & neurogenic disorders
- Systemic vs. familial
- Dystrophies: familial, progressive
- Stuck in degeneration-regeneration cycle
- Eventually regenerative ability is lost
Myopathy
- Muscular weakness due to muscular muscle fibre dysfunction
- Cf. neuropathy & neurogenic disorders
- Failure to contract cause possibly muscle or nerve
- Cf. neuropathy & neurogenic disorders
- Systemic vs. familial
- D…: familial, progressive
- Stuck in degeneration-regeneration cycle
- Eventually … ability is lost
- Muscular weakness due to muscular muscle fibre dysfunction
- Cf. neuropathy & neurogenic disorders
- Failure to contract cause possibly muscle or nerve
- Cf. neuropathy & neurogenic disorders
- Systemic vs. familial
-
Dystrophies: familial, progressive
- Stuck in degeneration-regeneration cycle
- Eventually regenerative ability is lost
Myopathy
- Muscular … due to muscular muscle fibre dysfunction
- Cf. neuropathy & neurogenic disorders
- Failure to … cause possibly muscle or nerve
- Cf. neuropathy & neurogenic disorders
- Systemic vs. familial
- Dystrophies: familial, progressive
- Stuck in degeneration-regeneration cycle
- Eventually regenerative ability is lost
- Muscular weakness due to muscular muscle fibre dysfunction
- Cf. neuropathy & neurogenic disorders
- Failure to contract cause possibly muscle or nerve
- Cf. neuropathy & neurogenic disorders
- Systemic vs. familial
- Dystrophies: familial, progressive
- Stuck in degeneration-regeneration cycle
- Eventually regenerative ability is lost
Paresis =
- weakness of voluntary movement, or
- partial loss of voluntary movement or
- impaired movement
Paresis
- weakness of … movement, or partial loss of … movement or … movement
- Usually referring to a limb - From Greek “to let fall”
- weakness of voluntary movement, or partial loss of voluntary movement or impaired movement
- Usually referring to a limb - From Greek “to let fall”
Involuntary Twitches
- … : involuntary visible twitches in single motor units (neurogenic), which commonly occur in lower motor neuron diseases such as damage to anterior horn cell bodies characteristic of ALS or polio
- clinically appear as brief ripples under the skin
- … : involuntary spontaneous contractions of individual muscle fibres (myogenic) invisible to the eye but identified by electromyography
-
fasciculations : involuntary visible twitches in single motor units (neurogenic), which commonly occur in lower motor neuron diseases such as damage to anterior horn cell bodies characteristic of ALS or polio
- clinically appear as brief ripples under the skin
- fibrillations : involuntary spontaneous contractions of individual muscle fibres (myogenic) invisible to the eye but identified by electromyography
Involuntary Twitches
- fasciculations : involuntary … twitches in single motor units (neurogenic), which commonly occur in … motor neuron diseases such as damage to anterior horn cell bodies characteristic of ALS or polio
- clinically appear as brief ripples under the skin
- fibrillations : involuntary spontaneous contractions of individual muscle fibres (myogenic) … , identified by …
- fasciculations : involuntary visible twitches in single motor units (neurogenic), which commonly occur in lower motor neuron diseases such as damage to anterior horn cell bodies characteristic of ALS or polio
- clinically appear as brief ripples under the skin
- fibrillations : involuntary spontaneous contractions of individual muscle fibres (myogenic) invisible to the eye but identified by electromyography
Involuntary Twitches
- fasciculations : involuntary visible twitches in single motor units (neurogenic), which commonly occur in lower motor neuron diseases such as damage to anterior horn cell bodies characteristic of ALS or polio
- clinically appear as brief ripples under the skin
- fibrillations : involuntary spontaneous contractions of individual muscle fibres (myogenic) invisible to the eye but identified by electromyography
- fasciculations : involuntary visible twitches in single motor units (neurogenic), which commonly occur in lower motor neuron diseases such as damage to anterior horn cell bodies characteristic of ALS or polio
- clinically appear as brief ripples under the skin
- fibrillations : involuntary spontaneous contractions of individual muscle fibres (myogenic) invisible to the eye but identified by electromyography
are fibrillations visible to the eye? (involuntary skeletal muscle twitches)
no - require electromyography
Rhabdomyolysis
- Rapid … of skeletal muscle
- Not … muscle, not …
- Risk of kidney failure
- Cellular proteins (esp myoglobin) released into blood can “clog” renal glomeruli
- Urine is “tea coloured”, no urine produced 12 hours after injury
- Leads to electrolyte changes: hyperkalaemia
- Treatment:
- Intravenous fluids (to treat shock)
- possibly haemodialysis, etc
- Rapid breakdown of skeletal muscle
- Not cardiac muscle, not myocardial infarct
- Risk of kidney failure
- Cellular proteins (esp myoglobin) released into blood can “clog” renal glomeruli
- Urine is “tea coloured”, no urine produced 12 hours after injury
- Leads to electrolyte changes: hyperkalaemia
- Treatment:
- Intravenous fluids (to treat shock)
- possibly haemodialysis, etc
Rhabdomyolysis
- Rapid breakdown of skeletal muscle
- Not cardiac muscle, not myocardial infarct
- Risk of … …
- Cellular proteins (esp myoglobin) released into blood can “clog” renal glomeruli
- Urine is “… coloured”, no urine produced 12 hours after injury
- Leads to … changes: hyperkalaemia
- Treatment:
- Intravenous fluids (to treat shock)
- possibly haemodialysis, etc
- Rapid breakdown of skeletal muscle
- Not cardiac muscle, not myocardial infarct
- Risk of kidney failure
- Cellular proteins (esp myoglobin) released into blood can “clog” renal glomeruli
- Urine is “tea coloured”, no urine produced 12 hours after injury
- Leads to electrolyte changes: hyperkalaemia
- Treatment:
- Intravenous fluids (to treat shock)
- possibly haemodialysis, etc
Rhabdomyolysis
- Rapid breakdown of skeletal muscle
- Not cardiac muscle, not myocardial infarct
- Risk of kidney failure
- Cellular proteins (esp myoglobin) released into blood can “clog” renal glomeruli
- Urine is “tea coloured”, no urine produced 12 hours after injury
- Leads to electrolyte changes: h…
- Treatment:
- … fluids (to treat …)
- possibly …, etc
- Rapid breakdown of skeletal muscle
- Not cardiac muscle, not myocardial infarct
- Risk of kidney failure
- Cellular proteins (esp myoglobin) released into blood can “clog” renal glomeruli
- Urine is “tea coloured”, no urine produced 12 hours after injury
- Leads to electrolyte changes: hyperkalaemia
- Treatment:
- Intravenous fluids (to treat shock)
- possibly haemodialysis, etc
… is a condition in which damaged skeletal muscle (Ancient Greek-…) tissue breaks down rapidly (Greek -…).
Rhabdomyolysis = Rhabdomyolysis is a condition in which damaged skeletal muscle (Ancient Greek: rhabdomyo-) tissue breaks down rapidly (Greek -lysis).
Serum levels CPK: Diagnostic
- Creatine Phosphokinase
- CK or CPK abbreviations used interchangeably
- The …, not creatine phosphate
- distinct forms of CPK found in different tissues
- skeletal muscle CPK isoform is CK-…
- cardiac muscle CPK isoform is CK-…
- when tissue damaged and cells lyse there is a release of tissue specific CK from cells into blood
- Elevations in CK-MM occur after skeletal muscle trauma or necrosis
- muscular dystrophies, polymyositis and rhabdomyolysis
- Test = “Total CK” (CK-MM is not a clinical test)
- Creatine Phosphokinase
- CK or CPK abbreviations used interchangeably
- The enzyme, not creatine phosphate
- distinct forms of CPK found in different tissues
- skeletal muscle CPK isoform is CK-MM
- cardiac muscle CPK isoform is CK-MB
- when tissue damaged and cells lyse there is a release of tissue specific CK from cells into blood
- Elevations in CK-MM occur after skeletal muscle trauma or necrosis
- muscular dystrophies, polymyositis and rhabdomyolysis
- Test = “Total CK” (CK-MM is not a clinical test)
Serum levels CPK: Diagnostic
- Creatine Phosphokinase
- CK or CPK abbreviations used interchangeably
- The enzyme, not creatine phosphate
- distinct forms of CPK found in different tissues
- … muscle CPK isoform is CK-MM
- … muscle CPK isoform is CK-MB
- when tissue … and cells … there is a release of tissue specific CK from cells into blood
- Elevations in CK-MM occur after skeletal muscle trauma or necrosis
- muscular dystrophies, polymyositis and rhabdomyolysis
- Test = “Total CK” (CK-MM is not a clinical test)
- Creatine Phosphokinase
- CK or CPK abbreviations used interchangeably
- The enzyme, not creatine phosphate
- distinct forms of CPK found in different tissues
- skeletal muscle CPK isoform is CK-MM
- cardiac muscle CPK isoform is CK-MB
- when tissue damaged and cells lyse there is a release of tissue specific CK from cells into blood
- Elevations in CK-MM occur after skeletal muscle trauma or necrosis
- muscular dystrophies, polymyositis and rhabdomyolysis
- Test = “Total CK” (CK-MM is not a clinical test)
Serum levels CPK: Diagnostic
- Creatine Phosphokinase
- CK or CPK abbreviations used interchangeably
- The enzyme, not creatine phosphate
- distinct forms of CPK found in different tissues
- skeletal muscle CPK isoform is CK-MM
- cardiac muscle CPK isoform is CK-MB
- when tissue damaged and cells lyse there is a release of tissue specific CK from cells into blood
- Elevations in CK-… occur after skeletal muscle … or …
- muscular dystrophies, polymyositis and rhabdomyolysis
- Test = “Total CK” (CK-MM is not a clinical test)
- Creatine Phosphokinase
- CK or CPK abbreviations used interchangeably
- The enzyme, not creatine phosphate
- distinct forms of CPK found in different tissues
- skeletal muscle CPK isoform is CK-MM
- cardiac muscle CPK isoform is CK-MB
- when tissue damaged and cells lyse there is a release of tissue specific CK from cells into blood
- Elevations in CK-MM occur after skeletal muscle trauma or necrosis
- muscular dystrophies, polymyositis and rhabdomyolysis
- Test = “Total CK” (CK-MM is not a clinical test)
Serum levels CPK: Diagnostic
- Creatine Phosphokinase
- CK or CPK abbreviations used interchangeably
- The enzyme, not creatine phosphate
- distinct forms of CPK found in different tissues
- skeletal muscle CPK isoform is CK-MM
- cardiac muscle CPK isoform is CK-MB
- when tissue damaged and cells lyse there is a release of tissue specific CK from cells into blood
- Elevations in CK-MM occur after skeletal muscle trauma or necrosis
- muscular dystrophies, polymyositis and rhabdomyolysis
- Test = “… …” (CK-MM is not a clinical test)
- Creatine Phosphokinase
- CK or CPK abbreviations used interchangeably
- The enzyme, not creatine phosphate
- distinct forms of CPK found in different tissues
- skeletal muscle CPK isoform is CK-MM
- cardiac muscle CPK isoform is CK-MB
- when tissue damaged and cells lyse there is a release of tissue specific CK from cells into blood
- Elevations in CK-MM occur after skeletal muscle trauma or necrosis
- muscular dystrophies, polymyositis and rhabdomyolysis
- Test = “Total CK” (CK-MM is not a clinical test)
Creatine phosphokinase (CPK) - Measurement is important clinically:
- distinct forms of CPK found in different tissues
- … muscle CPK isoform is CK-MM
- … muscle CPK isoform is CK-MB
- distinct forms of CPK found in different tissues
- skeletal muscle CPK isoform is CK-MM
- cardiac muscle CPK isoform is CK-MB
Myoglobin: Diagnostic
- Myoglobin “ … O2”
- Protein + Haem group
- “… coloured”
- In plasma indicates … or MI
- Can lead to renal failure
- Urine tested for myoglobin
- Diagnostic: Hyperkalaemia
- When muscle cells lyse
- They release K+
- This increases serum K+
- Nb: ò serum K = cause of rhabdo,
- Increased K = result of rhabdo
- Myoglobin “ Buffers O2”
- Protein + Haem group
- “tea coloured”
- In plasma indicates rhabdomyolysis or MI
- Can lead to renal failure
- Urine tested for myoglobin
- Diagnostic: Hyperkalaemia
- When muscle cells lyse
- They release K+
- This increases serum K+
- Nb: ò serum K = cause of rhabdo,
- Increased K = result of rhabdo

Myoglobin: Diagnostic
- Myoglobin “ Buffers O2”
- Protein + Haem group
- “tea coloured”
- In plasma indicates rhabdomyolysis or MI
- Can lead to … failure
- … tested for myoglobin
- Diagnostic: Hyperkalaemia
- When muscle cells lyse
- They release K+
- This increases serum K+
- Nb: ò serum K = cause of rhabdo,
- Increased K = result of rhabdo
- Myoglobin “ Buffers O2”
- Protein + Haem group
- “tea coloured”
- In plasma indicates rhabdomyolysis or MI
- Can lead to renal failure
- Urine tested for myoglobin
- Diagnostic: Hyperkalaemia
- When muscle cells lyse
- They release K+
- This increases serum K+
- Nb: ò serum K = cause of rhabdo,
- Increased K = result of rhabdo

Myoglobin: Diagnostic
- Myoglobin “ Buffers O2”
- Protein + Haem group
- “tea coloured”
- In plasma indicates rhabdomyolysis or MI
- Can lead to renal failure
- Urine tested for myoglobin
- Diagnostic: …
- When muscle cells lyse
- They release K+
- This increases serum K+
- Nb: ò serum K = cause of rhabdo,
- Increased K = result of rhabdo
- Myoglobin “ Buffers O2”
- Protein + Haem group
- “tea coloured”
- In plasma indicates rhabdomyolysis or MI
- Can lead to renal failure
- Urine tested for myoglobin
- Diagnostic: Hyperkalaemia
- When muscle cells lyse
- They release K+
- This increases serum K+
- Nb: ò serum K = cause of rhabdo,
- Increased K = result of rhabdo

Myoglobin: Diagnostic
- Myoglobin “ Buffers O2”
- Protein + Haem group
- “tea coloured”
- In plasma indicates rhabdomyolysis or MI
- Can lead to renal failure
- Urine tested for myoglobin
- Diagnostic: Hyperkalaemia
- When muscle cells lyse
- They release K+
- This increases serum K+
- Nb: decreased serum K = … of rhabdo,
- Increased K = … of rhabdo
- Myoglobin “ Buffers O2”
- Protein + Haem group
- “tea coloured”
- In plasma indicates rhabdomyolysis or MI
- Can lead to renal failure
- Urine tested for myoglobin
- Diagnostic: Hyperkalaemia
- When muscle cells lyse
- They release K+
- This increases serum K+
- Nb: decreasd serum K = cause of rhabdo,
- Increased K = result of rhabdo

Myoglobin: Diagnostic
- Urine tested for myoglobin - what does the patient have?

- Rhabdomyolysis

Rigor Mortis
- ATP … after death
- Muscle cell does not … Ca2+ into SR
- Increases … Ca2+
- Ca2+ allows crossbridge cycle contraction
- Until ATP & creatine-P run out
- W/o ATP -> myosin stops just after … stroke
- With myosin still bound to actin
- Rigor mortis ends when muscle tissue degrades after … days
- ATP depleted after death
- Muscle cell does not resequester Ca2+ into SR
- Increases Cytosolic Ca2+
- Ca2+ allows crossbridge cycle contraction
- Until ATP & creatine-P run out
- W/o ATP à myosin stops just after power stroke
- With myosin still bound to actin
- Rigor mortis ends when muscle tissue degrades after 3 days
Myasthenia gravis
- … muscle weakness and fatigability
- Often starts with … muscles
- Caused by depletion of nAChR
- Arises as the immune system inappropriately produces auto-antibodies against nAChR
-
Progressive muscle weakness and fatigability
- Often starts with eye muscles
- Caused by depletion of nAChR
- Arises as the immune system inappropriately produces auto-antibodies against nAChR
Myasthenia gravis
- Progressive muscle … and …
- Often starts with eye muscles
- Caused by depletion of …
- Arises as the immune system inappropriately produces auto-antibodies against nAChR
- Progressive muscle weakness and fatigability
- Often starts with eye muscles
- Caused by depletion of nAChR
- Arises as the immune system inappropriately produces auto-antibodies against nAChR
Myasthenia gravis
- Progressive muscle weakness and fatigability
- Often starts with eye muscles
- Caused by depletion of …
- Arises as the immune system inappropriately produces …-… against …
- Progressive muscle weakness and fatigability
- Often starts with eye muscles
- Caused by depletion of nAChR
- Arises as the immune system inappropriately produces auto-antibodies against nAChR
myasthenia gravis arises as the immune system inappropriately produces …
auto-antibodies against nAChR
Myasthenia gravis - Features
- … depolarisation of muscle fibres
- many fibres do not reach …
- repeated stimulation -> neuromuscular …
- symptoms include ptosis, diplopia,
- with weakness in eyelid and extraocular muscles
- proximal muscle weakness
-
less depolarisation of muscle fibres
- many fibres do not reach threshold
- repeated stimulation -> neuromuscular fatigue
- symptoms include ptosis, diplopia,
- with weakness in eyelid and extraocular muscles
- proximal muscle weakness

Myasthenia gravis - Features
- less depolarisation of muscle fibres
- many fibres do not reach threshold
- repeated stimulation -> neuromuscular fatigue
- symptoms include p.., d…
- with … in eyelid and extraocular muscles
- proximal muscle …
- less depolarisation of muscle fibres
- many fibres do not reach threshold
- repeated stimulation -> neuromuscular fatigue
- symptoms include ptosis, diplopia,
- with weakness in eyelid and extraocular muscles
- proximal muscle weakness

Myasthenia Gravis: Treatment & Diagnostics
- … inhibitors
- Pyridostigmine
- Increase … activity at NMJ. ACh released from nerve terminals into synapse not rapidly catabolised but can bind to the remaining … for longer time
- Edrophonium (a/k/a tensilon): short-lived … inhibitor for diagnosis, temporarily improves symptoms eg ptosis
- Pyridostigmine
- Other category of treatment is directed at immune system
- Thymectomy – reduces symptoms in 70% of patients. Exact mechanism unknown. Rebalance immune system?
- Use of immunosuppressive drugs e.g. corticosteroids
- Plasmapheresis = removal of anti AChR antibodies from blood stream
-
AChE inhibitors
- Pyridostigmine
- Increase ACh activity at NMJ. ACh released from nerve terminals into synapse not rapidly catabolised but can bind to the remaining AChRs for longer time
- Edrophonium (a/k/a tensilon): short-lived AChE inhibitor for diagnosis, temporarily improves symptoms eg ptosis
- Pyridostigmine
- Other category of treatment is directed at immune system
- Thymectomy – reduces symptoms in 70% of patients. Exact mechanism unknown. Rebalance immune system?
- Use of immunosuppressive drugs e.g. corticosteroids
- Plasmapheresis = removal of anti AChR antibodies from blood stream
Myasthenia Gravis: Treatment & Diagnostics
- AChE inhibitors
- Pyridostigmine
- Increase ACh activity at NMJ. ACh released from nerve terminals into synapse not rapidly catabolised but can bind to the remaining AChRs for longer time
- E… (a/k/a tensilon): short-lived AChE inhibitor for diagnosis, temporarily improves symptoms eg ptosis
- Pyridostigmine
- Other category of treatment is directed at immune system
- Thymectomy – reduces symptoms in …% of patients. Exact mechanism unknown. Rebalance immune system?
- Use of immunosuppressive drugs e.g. corticosteroids
- Plasmapheresis = removal of anti AChR antibodies from blood stream
- AChE inhibitors
- Pyridostigmine
- Increase ACh activity at NMJ. ACh released from nerve terminals into synapse not rapidly catabolised but can bind to the remaining AChRs for longer time
- Edrophonium (a/k/a tensilon): short-lived AChE inhibitor for diagnosis, temporarily improves symptoms eg ptosis
- Pyridostigmine
- Other category of treatment is directed at immune system
- Thymectomy – reduces symptoms in 70% of patients. Exact mechanism unknown. Rebalance immune system?
- Use of immunosuppressive drugs e.g. corticosteroids
- Plasmapheresis = removal of anti AChR antibodies from blood stream
Myasthenia Gravis: Treatment & Diagnostics
- AChE inhibitors
- Pyr…
- Increase ACh activity at NMJ. ACh released from nerve terminals into synapse not rapidly catabolised but can bind to the remaining AChRs for longer time
- Edrophonium (a/k/a tensilon): …-lived AChE inhibitor for diagnosis, temporarily improves symptoms eg p..
- Pyr…
- Other category of treatment is directed at immune system
- Thymectomy – reduces symptoms in 70% of patients. Exact mechanism unknown. Rebalance immune system?
- Use of … drugs e.g. corticosteroids
- Plasmapheresis = removal of anti AChR antibodies from blood stream
- AChE inhibitors
-
Pyridostigmine
- Increase ACh activity at NMJ. ACh released from nerve terminals into synapse not rapidly catabolised but can bind to the remaining AChRs for longer time
- Edrophonium (a/k/a tensilon): short-lived AChE inhibitor for diagnosis, temporarily improves symptoms eg ptosis
-
Pyridostigmine
- Other category of treatment is directed at immune system
- Thymectomy – reduces symptoms in 70% of patients. Exact mechanism unknown. Rebalance immune system?
- Use of immunosuppressive drugs e.g. corticosteroids
- Plasmapheresis = removal of anti AChR antibodies from blood stream
Myasthenia Gravis: Treatment & Diagnostics
- AChE inhibitors
- Pyridostigmine
- Increase ACh activity at NMJ. ACh released from nerve terminals into synapse not rapidly catabolised but can bind to the remaining AChRs for longer time
- Edrophonium (a/k/a tensilon): short-lived AChE inhibitor for diagnosis, temporarily improves symptoms eg ptosis
- Pyridostigmine
- Other category of treatment is directed at immune system
- T… – reduces symptoms in 70% of patients. Exact mechanism unknown. Rebalance immune system?
- Use of immunosuppressive drugs e.g. …
- … = removal of anti AChR antibodies from blood stream
- AChE inhibitors
- Pyridostigmine
- Increase ACh activity at NMJ. ACh released from nerve terminals into synapse not rapidly catabolised but can bind to the remaining AChRs for longer time
- Edrophonium (a/k/a tensilon): short-lived AChE inhibitor for diagnosis, temporarily improves symptoms eg ptosis
- Pyridostigmine
- Other category of treatment is directed at immune system
- Thymectomy – reduces symptoms in 70% of patients. Exact mechanism unknown. Rebalance immune system?
- Use of immunosuppressive drugs e.g. corticosteroids
- Plasmapheresis = removal of anti AChR antibodies from blood stream
Spinal Muscular Atrophy (SMA)
- a/k/a … … Syndrome
- One of most common genetic causes of … death
- Severity and time of onset can … greatly
- Death of lower motor neurons in anterior horn of spine
- Muscle atrophy —> hypotonia & muscle weakness
- Via apoptosis
- Fibre type grouping
- Sensory system is spared (b/c not in anterior horn)
- Muscle atrophy —> hypotonia & muscle weakness
- Caused by genetic defect
- SMN1 gene
- Required for survival of anterior horn neurons
- Autosomal recessive
- Other genes cause similar syndromes
- SMN1 gene
- a/k/a Floppy Baby Syndrome
- One of most common genetic causes of infant death
- Severity and time of onset can vary greatly
- Death of lower motor neurons in anterior horn of spine
- Muscle atrophy —> hypotonia & muscle weakness
- Via apoptosis
- Fibre type grouping
- Sensory system is spared (b/c not in anterior horn)
- Muscle atrophy —> hypotonia & muscle weakness
- Caused by genetic defect
- SMN1 gene
- Required for survival of anterior horn neurons
- Autosomal recessive
- Other genes cause similar syndromes
- SMN1 gene
Spinal Muscular Atrophy (SMA)
- a/k/a Floppy Baby Syndrome
- One of most common genetic causes of infant death
- Severity and time of onset can vary greatly
- Death of … motor neurons in anterior horn of spine
- Muscle … —> hypotonia & muscle weakness
- Via A…
- Fibre type grouping
- Sensory system is spared (b/c not in anterior horn)
- Muscle … —> hypotonia & muscle weakness
- Caused by genetic defect
- SMN1 gene
- Required for survival of anterior horn neurons
- Autosomal recessive
- Other genes cause similar syndromes
- SMN1 gene
- a/k/a Floppy Baby Syndrome
- One of most common genetic causes of infant death
- Severity and time of onset can vary greatly
- Death of lower motor neurons in anterior horn of spine
- Muscle atrophy —> hypotonia & muscle weakness
- Via apoptosis
- Fibre type grouping
- Sensory system is spared (b/c not in anterior horn)
- Muscle atrophy —> hypotonia & muscle weakness
- Caused by genetic defect
- SMN1 gene
- Required for survival of anterior horn neurons
- Autosomal recessive
- Other genes cause similar syndromes
- SMN1 gene
Spinal Muscular Atrophy (SMA)
- a/k/a Floppy Baby Syndrome
- One of most common genetic causes of infant death
- Severity and time of onset can vary greatly
- Death of lower motor neurons in anterior horn of spine
- Muscle atrophy —> h… & muscle …
- Via apoptosis
- … … grouping
- Sensory system is spared (b/c not in anterior horn)
- Muscle atrophy —> h… & muscle …
- Caused by genetic defect
- SMN1 gene
- Required for survival of anterior horn neurons
- Autosomal recessive
- Other genes cause similar syndromes
- SMN1 gene
- a/k/a Floppy Baby Syndrome
- One of most common genetic causes of infant death
- Severity and time of onset can vary greatly
- Death of lower motor neurons in anterior horn of spine
- Muscle atrophy —> hypotonia & muscle weakness
- Via apoptosis
- Fibre type grouping
- Sensory system is spared (b/c not in anterior horn)
- Muscle atrophy —> hypotonia & muscle weakness
- Caused by genetic defect
- SMN1 gene
- Required for survival of anterior horn neurons
- Autosomal recessive
- Other genes cause similar syndromes
- SMN1 gene
Spinal Muscular Atrophy (SMA)
- a/k/a Floppy Baby Syndrome
- One of most common genetic causes of infant death
- Severity and time of onset can vary greatly
- Death of lower motor neurons in anterior horn of spine
- Muscle atrophy —> hypotonia & muscle weakness
- Via apoptosis
- Fibre type grouping
- … system is spared (b/c not in anterior horn)
- Muscle atrophy —> hypotonia & muscle weakness
- Caused by … defect
- SMN1 gene
- Required for survival of anterior horn neurons
- Autosomal …
- Other genes cause similar syndromes
- SMN1 gene
- a/k/a Floppy Baby Syndrome
- One of most common genetic causes of infant death
- Severity and time of onset can vary greatly
- Death of lower motor neurons in anterior horn of spine
- Muscle atrophy —> hypotonia & muscle weakness
- Via apoptosis
- Fibre type grouping
- Sensory system is spared (b/c not in anterior horn)
- Muscle atrophy —> hypotonia & muscle weakness
- Caused by genetic defect
- SMN1 gene
- Required for survival of anterior horn neurons
- Autosomal recessive
- Other genes cause similar syndromes
- SMN1 gene
Spinal Muscular Atrophy (SMA)
- Death of … motor neurons in anterior horn of spine
- Muscle atrophy —> hypotonia & muscle weakness
- Via …
- … type grouping
- … system is spared (b/c not in anterior horn)
- Muscle atrophy —> hypotonia & muscle weakness
- Caused by genetic defect
- Autosomal …
- Death of lower motor neurons in anterior horn of spine
- Muscle atrophy —> hypotonia & muscle weakness
- Via apoptosis
- Fibre type grouping
- Sensory system is spared (b/c not in anterior horn)
- Muscle atrophy —> hypotonia & muscle weakness
- Caused by genetic defect
- Autosomal recessive
Fibre Type Grouping
- During … … atrophy
- Cycles of … are followed by collateral …
- Surviving axons innervate surrounding fibres
- Resulting in fibre type grouping
- In healthy muscles (Figure A), motor units are intermingled. During reinnervation, nearby surviving neurons re-innervate the denervated fibres, resulting in clusters (Figure B)
- During spinal muscular atrophy
- Cycles of denervation are followed by collateral reinnervation
- Surviving axons innervate surrounding fibres
- Resulting in fibre type grouping
- In healthy muscles (Figure A), motor units are intermingled. During reinnervation, nearby surviving neurons re-innervate the denervated fibres, resulting in clusters (Figure B)

Fibre Type Grouping
- During spinal muscular …
- … of denervation are followed by collateral reinnervation
- Surviving axons … surrounding fibres
- Resulting in fibre type grouping
- In healthy muscles (Figure A), motor units are intermingled. During reinnervation, nearby surviving neurons re-innervate the denervated fibres, resulting in clusters (Figure B)
- During spinal muscular atrophy
- Cycles of denervation are followed by collateral reinnervation
- Surviving axons innervate surrounding fibres
- Resulting in fibre type grouping
- In healthy muscles (Figure A), motor units are intermingled. During reinnervation, nearby surviving neurons re-innervate the denervated fibres, resulting in clusters (Figure B)

Fibre Type Grouping
- During spinal muscular atrophy
- Cycles of denervation are followed by collateral reinnervation
- Surviving axons innervate surrounding fibres
- Resulting in fibre type grouping
- In healthy muscles (Figure A), motor units are …. During reinnervation, nearby surviving neurons re-innervate the denervated fibres, resulting in … (Figure B)
- During spinal muscular atrophy
- Cycles of denervation are followed by collateral reinnervation
- Surviving axons innervate surrounding fibres
- Resulting in fibre type grouping
- In healthy muscles (Figure A), motor units are intermingled. During reinnervation, nearby surviving neurons re-innervate the denervated fibres, resulting in clusters (Figure B)

Fibre Type Grouping
- During … muscular atrophy
- Cycles of denervation are followed by collateral reinnervation
- Surviving axons innervate surrounding fibres
- Resulting in fibre type grouping
- In healthy muscles (Figure A), motor units are intermingled. During reinnervation, nearby surviving neurons …-… the … fibres, resulting in clusters (Figure B)
- During spinal muscular atrophy
- Cycles of denervation are followed by collateral reinnervation
- Surviving axons innervate surrounding fibres
- Resulting in fibre type grouping
- In healthy muscles (Figure A), motor units are intermingled. During reinnervation, nearby surviving neurons re-innervate the denervated fibres, resulting in clusters (Figure B)

Malignant Hyperthermia
- Genetic (…) susceptibility to gas …
- Eg sevoflurane
- Mutation in RyR means gas … -> Ca2+ release
- Autosomal Dominant
- Channel is susceptible if any of subunits are
- Result: SERCA works too hard (to pump Ca back into SR)
- Increased O2 consumption, Increased CO2, acidosis, tachypnea, muscles overheat, the body overheats, muscles are damaged (rhabdomyolysis), hyperkalaemia, muscles become rigid
- Genetic (rare) susceptibility to gas anaesthetics
- Eg sevoflurane
- Mutation in RyR means gas anaesthetic -> Ca2+ release
- Autosomal Dominant
- Channel is susceptible if any of subunits are
- Result: SERCA works too hard (to pump Ca back into SR)
- Increased O2 consumption, Increased CO2, acidosis, tachypnea, muscles overheat, the body overheats, muscles are damaged (rhabdomyolysis), hyperkalaemia, muscles become rigid
Malignant Hyperthermia
- Genetic (rare) susceptibility to gas anaesthetics
- Eg sevoflurane
- … in … means gas anaesthetic -> Ca2+ release
- Autosomal …
- Channel is susceptible if … of subunits are
- Result: SERCA works too hard (to pump Ca back into SR)
- Increased O2 consumption, Increased CO2, acidosis, tachypnea, muscles overheat, the body overheats, muscles are damaged (rhabdomyolysis), hyperkalaemia, muscles become rigid
- Genetic (rare) susceptibility to gas anaesthetics
- Eg sevoflurane
-
Mutation in RyR means gas anaesthetic à Ca2+ release
- Autosomal Dominant
- Channel is susceptible if any of subunits are
- Result: SERCA works too hard (to pump Ca back into SR)
- Increased O2 consumption, Increased CO2, acidosis, tachypnea, muscles overheat, the body overheats, muscles are damaged (rhabdomyolysis), hyperkalaemia, muscles become rigid
Malignant Hyperthermia
- Genetic (rare) susceptibility to gas anaesthetics
- Eg sevoflurane
- Mutation in RyR means gas anaesthetic - > Ca2+ release
- Autosomal Dominant
- Channel is susceptible if any of subunits are
- Result: … works too hard (to pump Ca back into SR)
- Increased O2 consumption, Increased CO2, acidosis, tachypnea, muscles overheat, the body overheats, muscles are damaged (rhabdomyolysis), hyperkalaemia, muscles become rigid
- Genetic (rare) susceptibility to gas anaesthetics
- Eg sevoflurane
- Mutation in RyR means gas anaesthetic à Ca2+ release
- Autosomal Dominant
- Channel is susceptible if any of subunits are
- Result: SERCA works too hard (to pump Ca back into SR)
- Increased O2 consumption, Increased CO2, acidosis, tachypnea, muscles overheat, the body overheats, muscles are damaged (rhabdomyolysis), hyperkalaemia, muscles become rigid
Malignant Hyperthermia
- Genetic (rare) susceptibility to gas anaesthetics
- Eg sevoflurane
- Mutation in RyR means gas anaesthetic -> Ca2+ release
- Autosomal Dominant
- Channel is susceptible if any of subunits are
- Result: SERCA works too hard (to … … … into SR)
- Increased O2 consumption, Increased CO2, acidosis, tachypnea, muscles …, the body …, muscles are damaged (R…), hyperkalaemia, muscles become …
- Genetic (rare) susceptibility to gas anaesthetics
- Eg sevoflurane
- Mutation in RyR means gas anaesthetic à Ca2+ release
- Autosomal Dominant
- Channel is susceptible if any of subunits are
- Result: SERCA works too hard (to pump Ca back into SR)
- Increased O2 consumption, Increased CO2, acidosis, tachypnea, muscles overheat, the body overheats, muscles are damaged (rhabdomyolysis), hyperkalaemia, muscles become rigid
Malignant Hyperthermia
- Genetic (rare) susceptibility to gas …
- Eg sevoflurane
- Mutation in RyR means gas … -> Ca2+ release
- Autosomal Dominant
- Channel is susceptible if any of subunits are
- Result: SERCA works too hard (to pump Ca back into SR)
- Increased O2 …, Increased …, a… , tachy…, muscles overheat, the body overheats, muscles are damaged (rhabdomyolysis), hyper…, muscles become rigid
- Genetic (rare) susceptibility to gas anaesthetics
- Eg sevoflurane
- Mutation in RyR means gas anaesthetic -> Ca2+ release
- Autosomal Dominant
- Channel is susceptible if any of subunits are
- Result: SERCA works too hard (to pump Ca back into SR)
- Increased O2 consumption, Increased CO2, acidosis, tachypnea, muscles overheat, the body overheats, muscles are damaged (rhabdomyolysis), hyperkalaemia, muscles become rigid
Malignant Hyperthermia is autosomal …
dominant
Malignant hyperthermia
- If anaesthetic received - and nothing is done…
- Muscle cells … and … their contents
- Plasma CK-… increases
- Kidney failure possible: urine red from myoglobin
- Dantrolene sodium can stop the abnormal calcium release
- Inhibits ryanodine receptor
- If anaesthetic received - and nothing is done…
- Muscle cells open and leak their contents
- Plasma CK-MM increases
- Kidney failure possible: urine red from myoglobin
- Dantrolene sodium can stop the abnormal calcium release
- Inhibits ryanodine receptor
Malignant hyperthermia
- If anaesthetic received - and nothing is done…
- Muscle cells open and leak their contents
- Plasma CK-MM increases
- … failure possible: … red from myoglobin
- Dantrolene sodium can stop the … calcium release
- Inhibits ryanodine receptor
- If anaesthetic received - and nothing is done…
- Muscle cells open and leak their contents
- Plasma CK-MM increases
- Kidney failure possible: urine red from myoglobin
- Dantrolene sodium can stop the abnormal calcium release
- Inhibits ryanodine receptor
In malignant hyperthermia - … … can stop the abnormal calcium release (Inhibits ryanodine receptor)
In malignant hyperthermia - dantrolene sodium can stop the abnormal calcium release (Inhibits ryanodine receptor)
In malignant hyperthermia - dantrolene sodium can stop the abnormal calcium release (Inhibits … receptor)
In malignant hyperthermia - dantrolene sodium can stop the abnormal calcium release (Inhibits ryanodine receptor)
In … … - dantrolene sodium can stop the abnormal calcium release (Inhibits ryanodine receptor)
In malignant hyperthermia - dantrolene sodium can stop the abnormal calcium release (Inhibits ryanodine receptor)
In malignant hyperthermia - dantrolene sodium can stop the abnormal … release (Inhibits ryanodine receptor)
In malignant hyperthermia - dantrolene sodium can stop the abnormal calcium release (Inhibits ryanodine receptor)
Muscular dystrophies
- Group of … disorders
- Severe and progressive … of muscle
- Muscle weakness
- Due to myopathy, not neuropathy
- Waddling gate
- Contractures
- Cardiorespiratory muscle involvement
- Group of inherited disorders
- Severe and progressive wasting of muscle
- Muscle weakness
- Due to myopathy, not neuropathy
- Waddling gate
- Contractures
- Cardiorespiratory muscle involvement

Muscular dystrophies
- Group of inherited disorders
- Severe and progressive wasting of muscle
- Muscle …
- Due to …, not …
- Waddling gate
- Contractures
- Cardiorespiratory muscle involvement
- Group of inherited disorders
- Severe and progressive wasting of muscle
- Muscle weakness
- Due to myopathy, not neuropathy
- Waddling gate
- Contractures
- Cardiorespiratory muscle involvement

Muscular dystrophies
- Group of inherited disorders
- Severe and progressive wasting of muscle
- Muscle weakness
- Due to myopathy, not neuropathy
- … gate
- C…
- … muscle involvement
- Group of inherited disorders
- Severe and progressive wasting of muscle
- Muscle weakness
- Due to myopathy, not neuropathy
- Waddling gate
- Contractures
- Cardiorespiratory muscle involvement

Muscular dystrophies
- Group of inherited disorders
- … and … wasting of muscle
- Muscle weakness
- Due to …, not neuropathy
- Waddling gate
- Contractures
- Cardiorespiratory muscle involvement
- Group of inherited disorders
-
Severe and progressive wasting of muscle
- Muscle weakness
- Due to myopathy, not neuropathy
- Waddling gate
- Contractures
- Cardiorespiratory muscle involvement

Duchenne muscular dystrophy
- …-linked disease
- affects 1:3500 live … births
- one third of cases arise spontaneously
- progressive loss of muscle tissue
- replaced by fibrofatty connective tissue
- Mutation: gene for dystrophin protein
- x-linked disease
- affects 1:3500 live male births
- one third of cases arise spontaneously
- progressive loss of muscle tissue
- replaced by fibrofatty connective tissue
- Mutation: gene for dystrophin protein

Duchenne muscular dystrophy
- x-linked disease
- affects 1:… live male births
- one third of cases arise spontaneously
- … loss of muscle tissue
- replaced by fibrofatty connective tissue
- Mutation: gene for dystrophin protein
- x-linked disease
- affects 1:3500 live male births
- one third of cases arise spontaneously
- progressive loss of muscle tissue
- replaced by fibrofatty connective tissue
- Mutation: gene for dystrophin protein

Duchenne muscular dystrophy
- x-linked disease
- affects 1:3500 live male births
- one third of cases arise spontaneously
- progressive loss of muscle tissue
- replaced by … connective tissue
- Mutation: gene for … protein
- x-linked disease
- affects 1:3500 live male births
- one third of cases arise spontaneously
- progressive loss of muscle tissue
- replaced by fibrofatty connective tissue
- Mutation: gene for dystrophin protein

Duchenne muscular dystrophy
- x-linked disease
- affects 1:3500 live male births
- one … of cases arise spontaneously
- progressive loss of muscle tissue
- replaced by fibrofatty … tissue
- Mutation: gene for dystrophin protein
- x-linked disease
- affects 1:3500 live male births
- •one third of cases arise spontaneously
- progressive loss of muscle tissue
- replaced by fibrofatty connective tissue
- Mutation: gene for dystrophin protein

…’ sign is a medical sign that indicates weakness of hip and thigh muscles associated with muscular dystrophy. The patient that has to use his hands and arms to “walk” up his own body from a squatting position.
Gowers’ sign is a medical sign that indicates weakness of hip and thigh muscles associated with muscular dystrophy. The patient that has to use his hands and arms to “walk” up his own body from a squatting position.

Gower’s sign is a medical sign that indicates weakness of hip and thigh muscles associated with … … The patient that has to use his hands and arms to “walk” up his own body from a squatting position.
Gowers’ sign is a medical sign that indicates weakness of hip and thigh muscles associated with muscular dystrophy. The patient that has to use his hands and arms to “walk” up his own body from a squatting position.

Summary of Pathophysiology of of Skeletal Muscle
- Lack of muscle use can lead to c… or atrophy
- Duchenne muscular dystrophy – dystrophin (…-linked)
- Exercise training —> hyper…
- Rhabdomyolysis
- Crush injury
- Diagnostic Tests
- Oxygen carrier in urine: myoglobin
- Energy for contraction: creatine phosphokinase
- Biopsy to show regeneration: fibre type grouping
- EC coupling: rigor mortis & malignant hyperthermia
- Pharmacology: AChE Inhibitors (MG - myasthenia gravis), Dantrolene (MH - malignant hyperthermia)
- Insufficient neural signalling: myasthenia gravis & SMA (spinal muscular atrophy)
- Lack of muscle use can lead to contractures or atrophy
- Duchenne muscular dystrophy – dystrophin (X-linked)
- Exercise training —> hypertrophy
- Rhabdomyolysis
- Crush injury
- Diagnostic Tests
- Oxygen carrier in urine: myoglobin
- Energy for contraction: creatine phosphokinase
- Biopsy to show regeneration: fibre type grouping
- EC coupling: rigor mortis & malignant hyperthermia
- Pharmacology: AChE Inhibitors (MG - myasthenia gravis), Dantrolene (MH - malignant hyperthermia)
- Insufficient neural signalling: myasthenia gravis & SMA (spinal muscular atrophy)
Summary of Pathophysiology of of Skeletal Muscle
- Lack of muscle use can lead to contractures or atrophy
- Duchenne muscular dystrophy – dystrophin (X-linked)
- Exercise training —> hypertrophy
- Rhab…
- Crush injury
- Diagnostic Tests
- Oxygen carrier in urine: …
- Energy for …: creatine phosphokinase
- Biopsy to show …: fibre type grouping
- EC coupling: … mortis & malignant …
- Pharmacology: AChE Inhibitors (MG - myasthenia gravis), Dantrolene (MH - malignant hyperthermia)
- Insufficient neural signalling: myasthenia gravis & SMA (spinal muscular atrophy)
- Lack of muscle use can lead to contractures or atrophy
- Duchenne muscular dystrophy – dystrophin (X-linked)
- Exercise training —> hypertrophy
-
Rhabdomyolysis
- Crush injury
- Diagnostic Tests
- Oxygen carrier in urine: myoglobin
- Energy for contraction: creatine phosphokinase
- Biopsy to show regeneration: fibre type grouping
- EC coupling: rigor mortis & malignant hyperthermia
- Pharmacology: AChE Inhibitors (MG - myasthenia gravis), Dantrolene (MH - malignant hyperthermia)
- Insufficient neural signalling: myasthenia gravis & SMA (spinal muscular atrophy)
Summary of Pathophysiology of of Skeletal Muscle
- Lack of muscle use can lead to contractures or atrophy
- Duchenne muscular dystrophy – dystrophin (X-linked)
- Exercise training —> hypertrophy
- Rhabdomyolysis
- Crush injury
- Diagnostic Tests
- Oxygen carrier in urine: myoglobin
- Energy for contraction: creatine …
- Biopsy to show regeneration: … … grouping
- … coupling: rigor mortis & malignant hyperthermia
- Pharmacology: … Inhibitors (MG - myasthenia gravis), Dantrolene (MH - malignant hyperthermia)
- Insufficient neural signalling: myasthenia gravis & SMA (spinal muscular atrophy)
- Lack of muscle use can lead to contractures or atrophy
- Duchenne muscular dystrophy – dystrophin (X-linked)
- Exercise training —> hypertrophy
- Rhabdomyolysis
- Crush injury
- Diagnostic Tests
- Oxygen carrier in urine: myoglobin
- Energy for contraction: creatine phosphokinase
- Biopsy to show regeneration: fibre type grouping
- EC coupling: rigor mortis & malignant hyperthermia
- Pharmacology: AChE Inhibitors (MG - myasthenia gravis), Dantrolene (MH - malignant hyperthermia)
- Insufficient neural signalling: myasthenia gravis & SMA (spinal muscular atrophy)
Summary of Pathophysiology of of Skeletal Muscle
- Lack of muscle use can lead to contractures or atrophy
- Duchenne muscular dystrophy – dystrophin (X-linked)
- Exercise training —> hypertrophy
- Rhabdomyolysis
- Crush injury
- Diagnostic Tests
- Oxygen carrier in urine: myoglobin
- Energy for contraction: creatine phosphokinase
- Biopsy to show regeneration: fibre type grouping
- EC coupling: rigor mortis & malignant hyperthermia
- Pharmacology: AChE Inhibitors (MG - myasthenia gravis), … (MH - malignant hyperthermia)
- Insufficient … signalling: myasthenia gravis & SMA (spinal muscular atrophy)
- Lack of muscle use can lead to contractures or atrophy
- Duchenne muscular dystrophy – dystrophin (X-linked)
- Exercise training —> hypertrophy
- Rhabdomyolysis
- Crush injury
- Diagnostic Tests
- Oxygen carrier in urine: myoglobin
- Energy for contraction: creatine phosphokinase
- Biopsy to show regeneration: fibre type grouping
- EC coupling: rigor mortis & malignant hyperthermia
- Pharmacology: AChE Inhibitors (MG - myasthenia gravis), Dantrolene (MH - malignant hyperthermia)
- Insufficient neural signalling: myasthenia gravis & SMA (spinal muscular atrophy)
Summary of Pathophysiology of of Skeletal Muscle
- Lack of muscle use can lead to contractures or …
- … muscular dystrophy – dystrophin (X-linked)
- Exercise training —> hypertrophy
- Rhabdomyolysis
- … injury
- Diagnostic Tests
- Oxygen carrier in urine: myoglobin
- Energy for contraction: creatine phosphokinase
- Biopsy to show regeneration: fibre type grouping
- EC coupling: rigor mortis & malignant hyperthermia
- Pharmacology: AChE Inhibitors (M……), Dantrolene (MH - malignant hyperthermia)
- Insufficient neural signalling: myasthenia gravis & SMA (…..)
- Lack of muscle use can lead to contractures or atrophy
- Duchenne muscular dystrophy – dystrophin (X-linked)
- Exercise training —> hypertrophy
- Rhabdomyolysis
- Crush injury
- Diagnostic Tests
- Oxygen carrier in urine: myoglobin
- Energy for contraction: creatine phosphokinase
- Biopsy to show regeneration: fibre type grouping
- EC coupling: rigor mortis & malignant hyperthermia
- Pharmacology: AChE Inhibitors (MG - myasthenia gravis), Dantrolene (MH - malignant hyperthermia)
- Insufficient neural signalling: myasthenia gravis & SMA (spinal muscular atrophy)