T2 L6 Intro to pathophysiology of skeletal muscle Flashcards
What does skeletal muscle respond to in endurance exercise?
Total contractile activity
What does skeletal muscle respond to in resistance training?
Loading and stretch
How many muscle fibres in biceps brachii?
200,000
What happens during hypertrophy in the muscle?
Synthesis of myofilaments
Addition of sarcomeres
Satellite cell activation
Angiogenesis and vascularisation
What is angiogenesis?
Physiological process through which new blood vessels form from pre-existing vessels
What adaptions to the muscle does endurance exercise cause?
Slight increase in fibre diameter
Increased blood supply to increase oxidative capacity
Increase mitochondrial content
Fibres become slower
Gradual transformation of type IIX to type IIA fibres
What adaptions to the muscle does non-endurance exercise cause?
Conversion to type IIX from IIA
Increase in numbers of sarcomeres and myofilaments causing an increase in type IIX fibre size leading to increased power
Larger muscles
When should ice be used on a muscle?
To reduce swelling by reducing perfusion
After acute injury such as a sprain
After exercise in overuse injury
What is a sprain?
Injury to a ligament
When should heat be used on a muscle?
To relax & loosen tissues
Use before activities that irritate chronic injuries such as a strain
Increases blood flow
What is a strain?
Injury to a muscle or tendon
What can cause a strain?
Chronic activities which:
- develop over-stretching of muscle fibres
- pulling too far on a muscle
- pulling a muscle in one direction while it is contracting in the other direction
What is aspirin used for?
Musculoskeletal pain
Chronic disease e.g. osteoarthritis
Sports injuries - combined with ice after exercise
What does aspirin do?
NSAID
Reduces pain and inflammation
What is the mechanism of aspirin?
Inhibits COX which reduces synthesis of prostaglandins
Part of arachidonic acid pathway
What are the risks of aspirin?
Gastro-intestinal adverse effects
Stomach bleeding
Ulcers
What are the anabolic effects of testosterone?
Increases protein synthesis
Decreases catabolism by opposing cortisol and glucocorticoids
Reduces fat
- increases BMR
- increases differentiation to muscle rather than fat cells
What are the effects of anabolic steroid abuse in males?
Testes atrophy
Sterility
Baldness
What are the effects of anabolic steroid abuse in females?
Breast / uterus atrophy
Menstrual changes
Facial hair
Deepening of voice
What is the effect of space flight on muscles?
Decrease in relative muscle mass (predominantly weight-bearing muscles)
Transition of type I fibres to type IIa/X fibres
What is the effect of bed rest on muscles?
Transition of type I fibres to type IIA Weight-bearing muscle atrophy - decrease muscle protein synthesis - myofibrillar breakdown - decrease in strength - loss of type I fibres
Why does bed rest have an effect on muscles?
Reduces hydrostatic pressure gradient in CVS
Reduces muscle force production
Eliminates compression on bones
Lowers total energy expenditure
Describe the features of type I fibres
Slow contraction Small High fatigue resistance Aerobic activity Low power High mitochondrial density High capillary density High oxidative capacity Low glycolytic capacity
Describe the features of type IIA fibres
Moderately fast contraction Medium Long-term anaerobic activity Medium power High mitochondrial density Intermediate capillary density High oxidative capacity High glycolytic capacity
Describe the features of type IIX fibres
Fast Large Short-term anaerobic High power Medium mitochondrial density Low capillary density Intermediate oxidative capacity High glycolytic capacity
Describe the features of type IIB fibres
Very fast contraction Very large Low resistance to fatigue Short-term anaerobic activity Very high power Low mitochondrial density Low capillary density Low oxidative capacity High glycolytic capacity
How do muscles regenerate during inflammation & degeneration of damaged muscle tissue?
Previous quiescent myogenic cells (satellite cells) are activated
Proliferate, differentiate and fuse on extant fibres
Contribue to forming multinucleate myofibres
What is HGF?
Hepatocyte growth factor
Paracrine cellular factor important in myogenesis and muscle regeneration
What is caveolin 1?
Integral membrane protein which is involved in receptor-independent endocytosis
What are myosatellite cells?
Progenitor cells in muscles (satellite cells)
Essential for regeneration and growth
Most are quiescent and activated by mechanical strain to proliferate and differentiate
What is myalgia?
Muscle pain
What causes myalgia?
Injury
Overuse
Infections
Auto-immune
What is myopathy?
Muscular weakness due to muscular muscle fibre dysfunction
What is paresis?
Weakness of voluntary movement or partial loss of voluntary movement or impaired movement
What are fasciculations?
Involuntary visible twitches in single motor units
Commonly occur in motor neuron disease
Appear as brief ripples under skin
What are fibrillations?
Involuntary spontaneous contractions of individual muscle fibres
What is rhabdomyolysis?
Rapid breakdown of skeletal muscle
What are the causes of rhabdomyolysis?
Trauma Drugs - statins or fibrates Hyperthermia Ischaemia to skeletal muscle - compartment syndrome - thrombosis
What is compartment syndrome?
Increased pressure within one of body’s compartments which contains muscles & nerves
What are the symptoms of rhabdomyolysis?
Myalgia
Vomiting & confusion
Darkened urine
Why is there a risk of kidney failure in rhabdomyolysis?
Cellular proteins (especially myoglobin) is released into the blood and clots renal glomeruli
Urine becomes tea coloured, no urine production 12h after injury
Leads to hyperkalaemia
What is the treatment for rhabdomyolysis?
Intravenous fluids to treat shock
Haemodialysis
What is the CPK isoform in skeletal muscle?
CK-MM
What is the CPK isoform in cardiac muscle?
CK-MB
What does myoglobin do?
Buffers O2
Why does rigor mortis occur?
ATP is depleted after death
Muscle cell doesn’t re-sequester Ca2+ in SR leading to increase in cytosolic Ca2+
Ca2+ allows cross-bridge cycle contraction until ATP and creatine-phosphate run out.
Without ATP the myosin stops after the power stroke and is still bound to actin
When does rigor mortis end?
When muscle tissue degrades after 3 days
What is myasthenia gravis?
Progressive muscle weakness and fatiguability
Depletion of nicotinic acetylcholine receptor
What are the symptoms of myasthenia gravis?
Ptosis
Diplopia
Weakness in eyelid and extraoccular muscles
Dysphagia
What are the treatment options for myasthenia gravis?
AChE inhibitors e.g. neostigmine Edrophonium Thymectomy Immunosuppressive drugs Plasmapheresis
How does neostigmine help myasthenia gravis?
Increases ACh activity at NMJ –> ACh released from nerve terminals into synapse aren’t catabolised –> bind to remaining AChR for a long time
What is plasmapheresis?
Removal of anti-AChR antibodies from bloodstream
What is spinal muscular atrophy?
Floppy baby syndrome
Death of lower motor neurons in anterior horn of spine
What causes spinal muscular atrophy?
Genetic defect
SMN1 gene
Autosomall recessive
What is malignant hyperthermia?
Rare genetic susceptibility to gas anaesthetics
Mutation in RyR + gas anaesthetic leads to Ca2+ release
Describe the process occurring in malignant hyperthermia
Ca2+ release
SERCA works too hard to pump Ca2+ back into SR
Increase O2 consumption –> increased CO2 –> acidosis, tachypnoea, muscles & body overheat –> muscles are damaged –> hyperkalaemia –> muscles become rigid
What treatment can be used in malignant hyperthermia?
Dantrolene sodium can stop abnormal calcium release by inhibiting ryanodine receptor
What are muscular dystrophies?
Group of inherited disorders
Severe and progressive muscle wasting
What is Duchenne muscular dystrophy?
Progressive loss of muscle tissue which is replaced by fibrofatty connective tissue
Mutation of gene for dystrophin protein
X-linked
Gower’s sign
What is Gower’s sign?
Patient has to use hands and arms to walk up own body to stand up
Indicates weakness of hip and thigh muscles associated with muscular dystrophy
