Pathophysiology of skeletal muscle Flashcards
Muscle is extremely plastic and adapts to changes in functional demand.
During (1) endurance exercise (2) resistance training muscles respond to:
(1) Total contractile activity
(2) Loading and stretch
When does adaptation of muscle occur?
From embryogenesis into maturity
What kind of structural adaptations can muscle undergo?
What limits this?
How does the muscle grow? By how much can muscle grow in this way?
Size, capillarisation
Total number of muscle fibres fixed at births
Muscle growth occurs by hypertrophy
- synthesis of myofilaments
- addition of sarcomeres
- satellite cell activation
- angiogenesis and vascularisation
- Enlargement by 15-50%
Give an example of an endurance exercise?
What adaptation occur in muscle in response to this type of exercise?
e.g. distance running, swimming, cycling
- increased fibre diameter, blood supply (increase oxidative capacity) and mitochondrial content
- fibres became slower (graded transformation of IIX –> IIA –> I)
Give an example of a non-endurance exercise?
What adaptation occur in muscle in response to this type of exercise?
What is the outcome?
e.g. walking, short distance running, cycling
- conversion of type IIX–> IIA. This means that muscle contracts with greater force and strength
- increase in IIX fibre size due to increase in numbers of sarcomeres and myofilaments –> increase in POWER
Muscles get bigger
What is the impact of using ICE on skeletal muscle?
When would you do this?
- reduce swelling by decreasing perfusion to site (vasoconstriction)
- AFTER an acute injury i.e. sprain and in overuse injury
What is the impact of using HEAT on skeletal muscle?
When would you do this?
- relax and loosen tissues
- increased blood flow
- BEFORE activities that irritate chronic injuries i.e. sprain
ASPIRIN IS USED IN TREATMENT OF MSK INJURIES
Describe it using the following parameters
- MOA
- Effect
- Indication
- Side effects
- NSAID: inhibits COX, decreases synthesis of prostaglandins (part of arachidonic acid pathway)
- Reduces pain and inflammation
- Used for MSK pain in OS and sports injuries + ice
- Side effects: GI- stomach ulcers –> bleeding
State the anabolic effects of testosterone
- Increases protein synthesis
- Decreases catabolism (opposes cortisol and glucocorticoids)
- Decreases fat: increases BMR (basal metabolic rate), increases differentiation into muscle
What are the effects of testosterone in abuse?
- Increase muscle size and strength
- Kidney, liver, heart, mood changes
- MALES: testes atrophy, sterility, baldness
- FEMALES: breast/uterus atrophy, menstrual changes
What is the effect of spaceflight on muscle?
- transition of type I–> IIA/X
- decrease in relative muscle mass- mall muscles atrophy but predominantly weight bearing muscles
What is the effect of bed rest on muscle?
How are these effects avoided/treated?
- transition of type I –> IIA
- weight bearing muscle atrophy due to decreased protein synthesis, myofibrillar breakdown, decrease strength
Resume minor activity early + physiotherapy to prevent contractures
Define a contracture
- process of growth is reversed, sarcomeres removed in series from myofibrils resulting in shortening of muscle
- caused by immobilisation of limb for long periods of time
Briefly describe the nucleic arrangement of skeletal muscle
What does this mean for mitosis?
- Multinucleate (they develop as myoblasts which are mononucleate and later fuse together)
- Nuclei are peripheral
Skeletal muscle enlarged by fibre enlargement and increased vascularisation as mitosis is impossible as they cant divide
Consider muscle regeneration
When does it happen?
How?
- during inflammation and degeneration of damaged muscle tissue
- previous quiescent (resting) myogenic cells (satellite cells) are activated. They proliferate, differentiate and fuse onto existing fibres–> contribute to forming multinucleate myofibers
What are myosatellite cells?
- progenitor cells in muscle. Essential for regeneration and growth
- activated by mechanical strain
AKA satellite cells
Define the following terms
- myalgia
- myopathy
- paresis
- muscle pain cause by injury, overuse, infection, AID. It is associated with rhabdomyolysis
- muscle weakness due to muscular muscle fibre dysfunction. It can be systemic (enocrine, inflammatory) or dystrophies (familial) which are progressive. In dystrophies, muscle is stuck in degen-regen cycle and eventually regeneration loses
- weakness of voluntary movement or partial loss/impaired movement
Define the following terms
- fasciculations
- fibrillations
- involuntary visible twitches in single motor units commonly occurring in LMN diseases. Clinically appear as brief ripples under skin. Neurogenic
- Involuntary spontaneous contractions of individual muscle fibres (myogenic) invisible to eye, identifiable by electromyography
What is rhabdomyolysis
Which organ is most at risk?
Presentation
Signs and symptoms
- rapid breakdown of skeletal muscle
Risk of kidney failure
- myoglobin released from breakdown into blood can ‘clog’ renal glomeruli
- urine becomes tea coloured until eventually no urine produced after 12 hours
- hyperkalaemia (when muscle cells lyse they release K+)
- muscle pain, vomiting, confusion, dark urine
What are the causes of rhabdomyolysis?
Trauma: crush injury
Drugs: adverse effects of fibrates and statins
Hyperthermia: causes loss of membrane integrity
Ischaemia to skeletal muscle- thrombosis, compartment syndrome
How do you diagnose rhabdomyolysis?
SERUM LEVELS CPK
- CK-MM is the isoform found in skeletal muscle. This is elevated after skeletal muscle trauma or necrosis (muscular dystropies, polymyositis, rhabdomyolysis)
- Test: total CK
MYOGLOBIN
- “buffers O2”. In plasma indicates rhabdomyolysis or MI (leading to renal failure)
- Test: urine
Describe physiological process that causes rigor mortis
- ATP depletes after death so muscle cell doesnt sequestes Ca in SR –> increase cytosolic calcium –> crossbridge cycle contraction until ATP and creatine phosphate run out
- Myosin stops just after power stroke with myosin still bound to actin
- Ends when muscle tissue degrades after 3 days
Describe physiological process that causes myasthenia gravis
- progressive muscle weakness and fatigability, often starts with eye muscles
- CAUSE: depletion of nAChR and arises as immune system inappropriately produces auto-ABs agaist nAChR
- -> less depolarisation of muscle fibres (many dont reach threshold). Repeated stimulation causes neuromuscular fatigue
What are the symptoms of myasthenia gravis?
Population affected?
- ptosis
- diplopia (weakness in extraocular and eyelid muscles)
- Adults
How do you treat myasthenia gravis?
- AChE inhibitors
- Thymectomy
- Plasmapheresis
What is spinal muscle atrophy (floppy baby syndrome)?
Presentation? (Physiological and clinical)
- death of LMN in anterior horn of spine causing atrophy which leads to hypotonia and weakness (via apoptosis)
- caused by defect in SMN1 gene: autosomal recessive
- Common genetic cause of infant death
- Fibre type grouping: cycles of denervation followed by collateral innervation. Surviving axons innervate surrounding fibres
- Sensory system spared
Describe malignant hyperthermia
- prevalence
- cause
- pathophysiology and resulting clinical signs
- treatment
- RARE genetic susceptibility to gas anesthetics (e.g. sevoflurane)
- RyR mutation, autosomal dominant
- SERCA works too hard (using lots of ATP) causing increase o2 consumption, increased o2 acidosis, tachypnoea, muscles overheat
- -> body overheats, muscle damage (rhabdomyolysis), hyperkalaemia, muscle rigidity
–> Kidney failure (red urine = myoglobin)
- Treat: Dantrolene sodium (inhibits RyR)
Describe muscular dystrophy
- what is it
- prevalence
- cause
- hallmark
- progressive loss of muscle tissue, replaced by fibrofatty CT
- 1:3500 male births (1/3 spontaneous)
- X linked disease, mutation in dystrophin protein
- Gowers sign- indicates weakness of hip and thigh muscles
How do muscular dystrophies present?
- waddling gait
- contractures
- cardiorespiratory muscle involvement
