What is myasthenia?
-Weakness of the muscles
What is myalgia?
-Muscle pain
What is myocardium?
-The muscle component of the heart
What is myopathy?
-Any disease of the muscles
What is myoclonus?
-Any sudden spasm of the muscles
What is sarcolemma?
-The outer membrane of a muscle cell
What is sarcoplasm?
-Cytoplasm of muscle cells
What is sarcoplasmic reticulum?
-The smooth endoplasmic reticulum of muscle
What are two characteristics of all types of muscle?
- Contractility
- Conductivity
What are the three types of muscle?
- Skeletal muscle
- Smooth muscle
- Cardiac muscle
Which types of muscle are striated?
- Skeletal muscle
- Cardiac muscle
Which type of muscle is non-striated?
-Smooth muscle
Where are skeletal muscle cells derived from?
-Mesodermally-derived multipotent myogenic stem cells
How do multinucleated skeletal muscle cells develop?
-Myogenic stem cells-> myoblasts which fuse together to form primary myotube with a chain of multiple central nuclei
Why are skeletal muscle nuclei displaced to the periphery?
-The synthesis of actin and myosin filaments displace the nuclei
What are the three types of muscle fibre?
- Narrow red
- Intermediate
- Wide white
Which muscle fibre is small in diameter?
-Red
Which muscle fibre has poor vasculature?
-White
Which muscle cell has a poor store of myoglobin?
-White
Which muscle fibre has the most mitochondria?
-Red
What are the contractions like in red skeletal muscle fibres?
-Slow, repetitive, weak
What are the contractions like in white skeletal muscle fibres?
-Fast and strong
How do the red and white skeletal muscle fibres fatigue?
- Red-> slowly
- White-> radiply
Which skeletal muscle fiber has the most neuromuscular junctions?
-White
Give an example of where red and white skeletal muscle fibres are found
- Red-> postural muscles of the back
- White-> extraocular muscles and the fingers
Describe the structural organisation of muscle units from bone to myofilaments
- Bone
- Tendon
- Muscle
- Fasicle
- Muscle fibre
- Myofibrils
- Myofilaments (actin and myosin)
How can you tell a fascicle from a muscle fibre?
-The fibre will have multiple nuclei on its sarcolemma
What is epimysium?
-Connective tissue sheath which surrounds the entire muscle
What is perimysium?
-Connective tissue sheath which surrounds fascicles
What is endomysium?
-Connective tissue sheath which surrounds muscle fibres
What is another name for a muscle fibre?
-Muscle cell
What are the different anatomical arrangements of muscles?
- Circular
- Convergent
- Multipennate
- bipennate
- Unipennate
- Parallel
- Fusiform
What is a myotendinous junction?
-Where the muscle and tendon meet
How is skeletal muscle arranged at a myotendinous junction?
-The fibres interdigitate with tendon collagen bundles
What two types of skeletal muscle are found in the tongue?
-Extrinsic and intrinsic muscles
What are the extrinsic muscles of the tongue attached to?
-The have insertions into bone and cartilage
What are the functions of the extrinsic tongue muscles?
-To protrude, retract and move the tongue from side to side
What is the function of the intrinsic muscles of the tongue?
-Allow the tongue to change shape but not position
How are nuclei arranged in muscle fibres?
-In rows at the periphery of the cell
What structures does the perimysium contain?
- Nerves
- Blood vessels
What structures do endomysium contain?
- Capillaries
- Nerves
What are myofibrils made up of?
-Myofilaments (thin actin and thick myosin)
How are myofilaments arranged?
-In a strict banding pattern of A and I bands
What shade is the A band of a myofibril?
-Dark
What shade is an I band of a myofibril?
-Light
Where is the Z line located?
-In the centre of an I band
What is a sarcomere?
-A contractional unit from Z line to Z line
What myofilament(s) do the A binds contain?
-Both actin and myosin as they overlap
What myofilament(s) do the I bands contain?
-Actin only
What is the H zone?
-The segment within an A band which only contains myosin
Where is the M line?
-In the centre of an H zone
What is a pneumonic for remembering these bands?
-MHAZI (M is in H in A, Z is in I)
Which bands decrease in size during contraction and which stay the same length?
- I and H zones get smaller
- A remains the same
What happens to the size of the sarcomere during contraction?
-It decreases
What is the structure of an actin myofilament?
-Contains actin, troponin and tropomyosin which form a helix by troponin attaching to tropomyosin which then wraps around actin
What can troponin be used as a marker for?
-Cardiac ischaemia
Describe the structure of myosin
- An individual myosin molecule has a rod-like structure from which two heads protrude
- Each thick filament is made up many myosin molecules in such a way that the ‘heads’ protrude in a multidirectional way
- The filaments are devoid of myosin heads in the centre of the filament (where there is no overlap)
- The heads extend towards the actin filaments
What is the role of calcium in muscle contraction?
- Influx of calcium into the the muscle fibril
- Binds to troponin causing a conformational change leading to dissociation from the tropomyosin, and causing tropomyosin to change position, exposing the active site of actin
- This allows the myosin head to bind to actin and contraction to begin
Describe the sequence of events in the sliding filament model
- Myosin head attaches to actin filament as ATP is hydrolysed
- Working stroke-> myosin head pivots and bends as it pulls on the actin filment, sliding it towards the M line
- Release of ADP and Pi
- A new ATP molecule binds to myosin causing the myosin cross-bridge to detach
- ATP hydrolysis causes the cycle to repeat
What is the cause of rigor mortis?
-Lack of ATP results in myosin heads staying bound to actin
What is a neuromuscular junction?
-The point at which an axon meets muscle containinf a small terminal swelling of the axon and a synaptic cleft
Describe the mechanism of innervation of muscle and excitation contraction coupling
- Nerve impulse along motor neurone arrives at neuromuscular junction
- Influx of calcium at the synaptic bulb causes the release of acetylcholine
- Acetylcholine diffuses across the synaptic cleft and fuses with nicotinic receptors located on the sarcolemma of the muscle causing depolarisation
- This cause voltage-gated Na+ to open, causing the action potential to enter
- Action potential (depolarisation) spreads along sarcolemma down T tubules and to two sarcoplasmic reticulum
- This causes the opening of voltage gated calcium channels at the terminal cisternae of the two adjacent sarcolasmic reticulum; calcium is released into the sarcoplasm
- Resulting in the sliding filament model
What happens to the calcium after the action poteltial is complete?
-Returned to the sarcoplasmic reticulum by active transport
What is the triad in skeletal muscle contraction?
-One T tubule causes calcium release from two sarcoplasmic reticulum
Describe the histology of cardiac muscle in longitudial section
- Striations
- Centrally positioned nuclei(one or two per cell)
- Intercalated discs
- Branching
Why does cardiac muscle contain intercalated discs?
-For electrical and mechanical coupling with adjacent cells
Describe cardiac muscle in transverse section
- Centrally positioned nuclei
- Endomysium bearing rich supply of capillaries
- Some lobular profiles which represent branching
Are myofibrils arranged in bands in cardiac muscle?
-Yes however myofilaments of actin and myosin form continuous masses in cytoplasm
What other structures are present in the cytoplasm of cardiac muscle?
- Mitochondria
- Sarcoplasmic reticulum
How are intercalated discs associated with Z lines?
-Intercalated discs lay over the Z lines (Z lines become obscured in LM)
Why does cardiac muscle contain many gap junctions?
-For electrical coupling
What is the function of adherens-type junctions in cardiac muscle?
-To anchor the cells and provide anchorage for actin filaments
Where in skeletal muscle are the T tubules located?
-At the A I band junction
Where do T tubules lie within cardiac muscle?
-At the points of intercalated discs and Z lines
What is meant by cardiac muscle having a diad not a triad?
-One T tubule serves on sarcoplasmic reticulum
How does muscle contraction occur in cardiac muscle?
-Same as skeletal muscle except electrical impulse is generated from the heart itself
Where are purkinje fibre located?
-Ventricle walls
-What generates the action potential in the heart and how does this travel to the ventricles?
- SAN generates
- Passes to AVN into ventricles
What is the function of the purkinje fibres?
-Transmit the action potential from the AVN to the ventricles to allow rapid conduction enabling ventricles to contract in a synchronous manner
Describe the characteristics of the purkinje fibres
- Large cells
- Abundant glycogen
- Sparse myofilaments
- Extensive gap junctions
Describe the histology of smooth muscles
- Spindle-shaped (fusiform)
- Have a central nucleus
- Non striated, no sarcomeres, no T tubules
What is the mechanism of contraction of smooth muscle? (simply)
-Actin-myosin interactions
How do contractions of smooth muscle differ from cardiac and skeletal contractions?
- Slower
- More sustained
- Require less ATP
Which of the muscle types is capable of being stretched?
-Smooth
What generic stimuli cause smooth muscle to contract?
- Nerves (ach)
- Hormones
- Drugs
What conformation do lots of smooth muscle cells make?
- Sheets
- Bundles
- Layers
-Where is smooth muscle most frequently located?
-The contractile walls of passageways or cavities
eg vascular structures, the GI, respiratory and genitourinary tract
When can smooth muscle become clinically significant?
- High bp
- Dysmenorrhoea
- Asthma
- Atherosclerosis
- Abnormal gut mobility
What are myofibroblast cells?
-Specialised smooth muscle cells involved in wound healing which produce a collagenous matrix but also contract the wound
What are myoepithelia?
-Specialised smooth muscle cells known as satellite cells which form a basketwork around the secretory units of some exocrine glands to help secretion via contraction eg sweat, salivary, mammory and iris
Outline the contraction of smooth muscle
- Thick and thin myofilaments are arrananged diagonally within a cell, spiralling down the long axis
- Smooth muscle contracts in a twisting way
- Requires Ca2+ (binds to CaM, binds to MLCK, phosphorylates myosin-> sliding filament model)
- Intermediate filaments attach to dense bodies in the sarcoplasm
Describe the nature of repair of skeletal muscle
- Cannot divide
- Can regenerate-> mitotic activity of satellite cells result in hyperplasia after muscle injury
- Satellite cells fuse with existing muscle to increase muscle mass
Describe the nature of repair of cardiac muscle
- Not capable of regeneration
- Following damage fibroblasts invade, divide and lay down scar tissue
Describe the nature of smooth muscle repair
- Retain mitotic activity and form new smooth muscle cells
- Evident in pregnant uterus which undergoes hypertrophy and hyperplasia
Describe the process of skeletal muscle remodelling
- The contractile proteins actin and myosin can increase/decrease in number
- This is known as remodelling and is a continual process
- All the myofilaments can be replaced within two weeks
How does atrophy of skeletal muscle occur?
-Destruction of the myofilaments during remodelling is greater than replacement
How does hypertrophy of skeletal muscle occur?
-Replacement of the myofilaments during remodelling is greater than destruction
What is the cause of hypertrophy in skeletal muscle?
-Increased demand, ie exercise
What happens to skeletal muscle cells when they undergo hypertrophy?
- Increase metabolic demand
- Sarcoplasmic reticulum swelling
- Increased mitochondria
- Increased Z line width
- Increased ATPase
- Increased density of T tubules
- Increased contractile proteins
What are the main causes of atrophy?
-Immobility, age, denervation
How long after denervation does re-innervation need to occur for full use?
-3 months
What increases uptake of acetylcholine at the neuromuscular junction?
-Motor neurone is embedded into the muscle with the muscle having a highly-folded endplate to increase surface area
What terminates acetylcholine in the synaptic cleft?
-Acetylcholine esterase
What causes myasthenia gravis?
-Autoimmune destruction of the endplate ach receptors, specifically by IgG
What does autoimmune destruction of the achR in myasthenia gravis do to the endplate?
-Causes the loss of junctional fold resulting in widening of the synaptic cleft
What are the signs and symptoms of myasthenia gravis?
- Fatiguability and sudden falling
- Drooping upper eyelids (ptosis)
- Blurred vision
Why does sudden falling occur in myasthenia gravis?
-Muscles fail die to lack of excitation caused by the lack of AchR
Why are the eyes one of the first structures to be effected in myasthenia gravis?
-Have a low amount of muscle and therefore are effected easier
Why do the symptoms in myasthenia gravis fluctuate?
-Based on general state of health
What are the treatment options for myasthenia gravis?
- Acetylcholinesterase inhibitors (pyridostigmine)
- Immune suppressants
- Plasmapheresis
- Thymectomy
How can acetylcholinesterase inhibitors treat myasthenia gravis?
-Ach not as quickly broken down so it can stimulate muscles for longer
How can plasmapheresis treat myasthenia gravis?
-Removal of specific IgG from serum
How can a thymectomy treat myasthenia gravis?
-Thymus is producing abnormal lymphocytes, removal will stop production
How does botulism disrupt the neuromuscular junctions?
-Reduces acetylcholine release and thus decreases excitation of muscles
How does organophosphate poisoning disrupt neuromuscular junctions?
-Decreased production of acetylcholinesterases; ach stays active for longer; overexcitation of muscles
What type of disorder is muscular dystrophy?
-Genetic
How is muscular dystrophy characterised?
-By progressive muscle weakness and wasting
What is the cause of muscular dystrophy?
-Complete absence of the protein dystrophin (protein for stength) causing the muscles to tear apart upon contraction
What is the consequences of muscle fibres tearing?
- Muscle wastage
- The enzyme creatine phosphokinase is liberated into the serum causing calcium to enter the cell resulting in necrosis
- Pseudohypertrophy (swelling) occurs before fat and connective tissue replace muscle fibres
Outline the pathophysiology of malignant hyperthermia
- Large quantities of calcium released from sarcoplasmic reticulum of skeletal muscle due to altered calcium channel gated kinetics so ca2+ is not taken back up into SR
- Causes hypermetabolic state
- Sustained Ca2+ elevation allows excessive stimulation of glycolytic metabolism
- Causes respiratory and metabolic acidosis
- Causes rigidity due to all muscles contracting at once
- High heat generation due to hypermetabolic state
What type of disease and what are triggering agents of malignant hyperthermia?
- Inherited disease
- Anaesthetic gases
How can some people have malignant hyperthermia and never know?
-Never exposed to a trigger
