Lecture 10-Muscle Tissue (Function And Disease) Flashcards
Compare and Contrast Cardiac and Smooth muscle
Differences
- smooth muscle does not contain sarcomeres
- electrical conduction requires specialised cells in cardiac muscle (SAN and AVN)
- no troponin in smooth muscle
In common
-Nuuclei are central not peripheral
-Only one contractile cell type
-acts as a syncytium (wave-like function). One muscle cell linked to another
-Myocytes communicative through gap junctions
(Cardiomyocytes-intercalated disks)
Cardiac innervation can occur two ways . What are they and what do they do?
Parasympathetic - slows down intrinsic heart rate by acting on the SAN in the atria
Sympathetic- increases the heart rate by action on the ventricles
How does the sympathetic pathway increase heart rate /contraction?
- neurotransmitter (adrenaline) released from sympathetic nerve and acts on the sarcolemma (plasma membrane )
- induces electrical signal which depolarises the sarcolemma . Depolarisation spreads down t tubules into sarcoplasmic reticulum .
- channels in SR undergo conformational changes in which its shape changes to allow calcium to pass through
- calcium released into sarcoplasm and binds to troponin calcium (c) on actin
- actin-myosin binding site is exposed for myosin head to bind
Innervation of skeletal muscle
- nerve impulse releases acetylcholine (only nt involved in skeletal)
- binds to receptor on the sarcolemma
- initiates an action potential along the muscle
Each fibre has its own nerve point
The events leading up to contraction of skeletal muscle
- initiation: nerve impulse along motor neurone axon arrives at neuromuscular junction
- impulse causes release of acetylcholine into synaptic cleft causing depolarisation of sarcolemma
- sodium channels open and enter the skeletal muscle cell
- depolarisation spreads over sarcolemma and into t tubules
- voltages sensor proteins of t tumble membrane change their conformation
- gated calcium ion release channels of adjacent terminal cistern are are activated by the step above
- calcium ions are rapidly released into the sarcoplasm
- calcium binds to TnC subunit of troponin and contraction cycle is initiated
- calcium ions are returned to the terminal cisternae of sarcoplasmic reticulum
What is the pathophysiology of myasthenia gravis?
An autoimmune disease in which antibodies block the acetylcholine receptor on the end plates of a muscle cell
Clinical features of myasthenia gravis
Reduced synaptic transmission
Intermittent muscle weakness
End plate invaginations in synaptic clefts reduced
Symptoms of myasthenia gravis
Drooping eyelids -Ptosis
Structure of a myosin molecule
Rod like structure from which 2 heads protruding
- thick filaments consists of many myosin molecules whose heads protrude at opposite ends of filaments
- 2 twists of myosin complex
Structure of actin molecule
Two protein components that includes F acting fibres and G actin globules
A tropomyosin-troponin complex sits over binding sites
Features of the functional contraction unit
- tropomyosin molecules coil around the actin helix reinforcing it
- a troponin compels is attached to each topomyosin molecule
- in the centre of the sacromere, there are no myosin heads ion the thick filaments
- myosin heads extend towards rage actin filaments in regions of potential overlap
Role of ionic calcium in the contraction mechanism
- binding of Calcium to TnC of troponin causing a conformational change which moves tropomyosin from actin’s binding site
- this allows myosin heads to bind to actin and contraction begins
The mechanism of the sliding filament theory
- ATP bings to myosin head and causes it change shape
- atpase hydrolysis atp and stays attached to the myosin head which causes a conformational change
- as adp and inorganic phosphate leaves myosin head, another conformational change in which the working stroke occurs
- once atp and inorganic phosphate has left atp binding site is revealed
Always continues in the presence of calcium ions and atp
What happens to the actin and myosin lengths during contraction?
The lengths stay the same
Only the sarcomeres shorten
Z Lines come together
Skeletal muscles work as levers in synergy and this are in compartments
Features of this compartments
-they are muscles with similar action grouped together
-surrounded by thick dense fascia
-based on location
Anterior
Posterior
Lateral medial
Why does compartment syndrome occur ?
How is treated ?
- limbs are divided into compartments delineated by fascia (band of sheet of connective tissue )
- trauma in one compartment could cause internal bleeding which exerts pressure on blood vessels and nerves
Treated by fasciotomy-covered by skin graft
What does compartment syndrome result in?
- deep constant poorly localised pain aggravated by passive stretch of muscle group
- paresthesia(pins and needles)
- compartments may feel tense and firm cause of swelling
- swollen shiny skin with sometimes obvious bruising
- prolonged capillary refill time
Definition of muscle tone
Muscle tone is defined as the tension in a muscle at rest
Definition of muscle strength
The muscle ability to contract and create force in response to resistance
What is muscle tone regulated by?
- motor neurone activity
- muscle elasticity
- use
- gravity
When destruction of muscle is greater than replacement , what occurs?
Atrophy -wasting of muscle tissues
When replacements of muscles is greater than destruction , what occurs ?
Hypertrophy - bigger muscles
How long does it take to replace contractile proteins ?
2 weeks
Whats the mechanism for muscle Hypertrophy?
- over-stretching of muscles such that A and I bands can no longer re-engage
- new muscle fibrils are produced
- new sarcomeres are added in the middle of existing sarcomeres
- new muscle fibres arise from mesenchymal cells
What’s the mechanism is muscle atrophy ?
Disuse-bed rest, limb immobilisation, age
Surgery - denervation of muscle (nerve regeneration takes 3 months)
Disease -Muscular dystrophies
Loss of proteins , reduced fibre diameter , loss of muscle power
Key features of Duchene muscular dystrophy
- most common type of dystrophy
- diagnosis is based on results of muscle biopsy, increased levels of creating kinase in the blood, electromyography and genetic testing
- generally affects only boys as its inherited through x-linked recessive pattern
- mutation of dystrophin gene
- muscle cells replaced by adipose tissue
Duchene Muscular Dystrophy
What does the absence of Dystrophin allow ?
- Excess calcium to enter muscle cell
- calcium taken up by mitochondria
- water taken with it
- mitochondria burst
- muscle cell burst (rhabdomyolysis)
- creative kinase and myoglobin levels extremely high in blood
What is creative kinase and what can it be used to measure ?
An enzyme in metabolically active tissues e.g muscle
Used to measure to diagnose heart attacks
Released into the blood by damaged skeletal muscle and brain tissue
What can a rise is creatine kinase result from ?
- intramuscular injections (vaccinations)
- vigorous physical exercise
- a fall (elderly)
- rhabdomyolysis(severe muscle break down )
- muscular dystrophy (weakening and breakdown of skeletal muscles overtime)
- acute kidney injury (myoglobin not being cleared )
Key features of botulism toxin and Botox
- toxin produced by bacterium
- prevents the release of acetylcholine
- causes non contractile state of skeletal muscle : flaccid paralysis
- clinically used to treat muscle spasms (cervical dystonia)
- use cosmetically to treat wrinkles ( Botox)
Key features of Organophosphate poisoning (pesticides)
- inhibits the function of acetylycholinesterase by binding to it
- ach activity at junction is potentiated
Cholinergic Toxidrome (organophosphate poisoning ) -Too much acetylcholine in neuromuscular junction
What are the Muscarinic symptoms? (muscles )
S-salivation L-Lacrimation U-Urination D-Defecation G-GI cramping E-Emesis (vomiting )
Cholinergic Toxidrome (organophosphate poisoning ) -Too much acetylcholine in synaptic junction
What are the Nicotinic symptoms? (Nerves )
M-Muscle cramps T-Tachycardia W-Weakness T-Twitching F-Fasciculations (spontaneous contractions of muscle fibres)
