20 - Muscle Function and Disease Flashcards
What is the similarities and differences between cardiac and smooth muscle contraction?
Similarities
- Act as syncitium
- Communicate through gap junctions (intercalated disc)
- Nuclei central not peripheral
- Act as syncitium
- Have one contractile cell type (not 3 like skeletal)
Differences
- Smooth muscle has no sarcomeres
- No troponins in smooth
- Cardiac is electrical conduction
What is a kranocyte?
- Resides over Schwann cell and produces collagen to make membrane over whole neuromuscular junction
- Anchors nerve to muscle cell
- Keeps neurotransmitter in one area so doesnt affect neighboroughing muscle cells
How does skeletal muscle contract (5 stages)?
- Activation
- Calcium ion mobilisation
- Energy production and fibril contraction
- Ratcheting
- Rest
Explain in detail how the events leading to skeletal muscle contraction?
- Nerve impulse at pre-synaptic neurone
- Vesicles fuse with membrane and release Ach into synaptic cleft
- Ach binds to nicotinic receptor, depolarises membrane by voltage gated Na channels opening and Na entering cell. AchE breaks down Ach to stop continous action potentials
- Depolarisation spreads in t-tubules and causes Ca ion channels to open which causes ryanodine receptors to be activated and release calcium from SER, calcium spark
- Influx of calcium into cytoplasm, which binds to troponin, allowing tropomyosin to move and actin-myosin cross bridges to be formed
- Contraction, power strokes
- Ca release channels close and SERCA moves calcium back out, or PMCA, or mitochondria
- Troponin-tropomyosin slides back over acting so no more actin myosin cross bridges
- Muscle relaxes
What is the structure of a thin filament?
Globular actin and Troponin complex
- Two troponin for every tropomyosin twist.
- Troponin-Tropomyosin block actin binding sites
(can have fibrous actin)
What is the structure of a thick filament?
- Many myosin
- Multiple heads protuding in all directions
What is special about the M section of the sarcomere?
- Myosins have no heads so contraction cannot occur
What is troponin made up of?
I, T, C
What happens first when there is an influx of calcium in the cytoplasm?
- Binds to TnC and causes a conformational change of tropomyosin
- Moves tropomyosin out of the actin binding site into clefts of G-actin spheres
- Myosin can bind to actin
Explain the sliding filament theory
- Calcium binds to troponin-tropomyosin complex and causes actin binding site to be exposed
- Myosin head, that has already been energised by ATP, binds to actin to form cross bridge
- Head tilts towards M-line in a power stroke by release of ADP and Pi, causing actin to slide over myosin
- Myosin dissociates by ATP binding and returns to original position and is reenergised by ATP hydrolysis to form another cross bridge
- Lots of cross bridges causes sarcomere to shorten
- Continues as long as there is sufficient Ca and ATP
When a muscle contracts what happens to the sarcomere?
Z lines get closer together so sarcomere shortens
How does sarcomere return to normal length after calcium is removed?
- Antagonist muscles
- Titin
- Gravity
What is a calcium spark?
Release of calcium from sarcoplasmic reticulum
What is the origin and insertion of a muscle?
What are the five muscle roles?
1. Antagonist: Prime mover
2. Antagonist: Opposite to prime mover
3. Synergist: Assist prime mover
4. Neutraliser: prevent unwanted actions of agonist
5. Fixator: hold one body part still whilst other moves
What are the three types of levers in the human body?
How are muscles separated?
- Compartmentalised by thick dense fascia
- Muscles with similar actions grouped
- Anterior, posterior, lateral and medial
What are the four compartments of the lower leg?
What is compartment syndrome?
Pressure in a compartment as constrained by fascia, which can contrict nerves, lymph and blood vessels
- Can be caused by trauma such as internal bleeding
What are the signs of compartment syndrome?
- Oedema
- Shiny swallen skin
- Deep constant poorly localised pain
- Paraesthesia (nerve compression)
- Prolonged capillary refill time
- Tense and firm
- Passive stretch
How do you treat compartment syndrome?
Fasciotomy (release pressure on deep compartments)
No fasciotomy can lead to amputation
What is muscle tone regulated by?
- Gravity
- Use
- Muscle elasticity
- Motor neuron activity
Why are muscles never fully relaxed?
Due to muscle tone so they are ready to react. Can improve muscle tone with exercise
What is muscle remodelling?
Replacement of contractile proteins
Replacement > Destruction = Hypertrophy
Destruction > Replacement = Atrophy
What can lead to muscle atrophy?
- Disuse (bed rest, sedentary)
- Loss of nerve supply (surgery)
- Disease
- Age
What is the mechanism of muscle hypertrophy and when does it occur?
How?
Overstretching so I and A can no longe engage
Add sarcomeres
Produce new fibres from mesenchymal stem cells
When?
- Regular exercise
- Pregnancy
- Heart disease (compensate for lack of blood flow)
What is rhabdomyolysis and what causes it?
- Striated muscle breakdown
Minor: Lack of oxygen to cells, infection, hyperthermia
Serious: Crush/blast injury, prolonged immobilisation, exposure to toxins, inherited muscle disorders
What can be seen in the blood during rhabdomyolysis and what can this cause?
- Myoglobin: kidney damage
- Na: swelling
- Ca: sustained muscle contraction
- K: Electrolyte imbalance as lots in muscle cells, prevent electrical conduction of cardiomyocytes
- Uric acid
- CK
COMA OR DEATH
Why might CK be high in the blood?
- Rhabdomyolysis
- MI
- Kidney injury (myoglobin not cleared)
- Intramuscular injection
- Vigorous exercise
- A fall
- Muscular dystrophy
What is used to test for MI but what is the disadvantage to it?
- Test troponin I and t levels as cardiac isoforms only found in cardiac
- Release an hour after MI and remain high for over 20 hours, unlike CK
- Can’t measure extent of MI, like you can with CK. Not proportionate
What is rigor mortis?
- After death muscles go into period of sustained contraction due to chemical changes in muscle.
- 6hours after death - several days, starting with eyelids, jaw and neck.
- Quicker onset if environment is cold or deceased performed hard physical work before death
- Due to lack of ATP to break actin-myosin cross bridges
What is the cause of myasthenia gravis?
- Autoimmune
- Antibodies block or destroy Ach receptors
- Endplate invaginations reduced (less receptors)
- Reduced synaptic transmission by 30% causes symptoms like muscle weakness
What are the symptoms of myasthenia gravis?
- Drooping eyelid (ptosis)
- Blurred vision
- Difficulty swallowing
- Impaired speech (dysarthria)
- Weakness in arms, hands, legs, fingers, neck
- Shortness of breath
- Change in facial expression
What is muscular dystrophy?
- Group of muscle disease that result in weakening and breakdown of skeletal muscles over time.
- Generally they are inherited.
- Mutation in dystrophin gene, where dystrophin normally tethers actin to membrane and controls calcium concentration so loss of muscle stability
How do you diagnose muscular dystrophy?
- Muscle biopsy (more fat)
- Increased levels of CK in blood
- Genetic tests
- Electromyography
What is the most common MD and why is it caused?
Duchenne MD
- X-LINKED RECESSIVE (mainly m but f carriers have some symptoms)
- Mutation in dystrophin gene
- XS calcium enters cell and taken up by mitochondria
- Causes water to enter, causing swelling
- Rhabdomyolysis due to bursting
- Muscle cells replaced by adipose
What are the symptoms of Duchenne MD?
- Mainly boys
- Lifespan 15-45
- Braces age 10
- Can’t walk by age 12
What is malignant hyperthermia?
Severe reaction to medications used during general anaesthesia. Triggers cells to release stored Ca ions, causing muscle contraction and this generates lots of heat and causes metabolic acidosis
What are the signs of malignant hyperthermia?
- Tachycardia
- Muscle rigidity
- High fever
- High blood K levels due to rhabdomyolysis
Why do old people get cold?
Muscle atropy
Less muscle, less heat generation
Why can pesticides lead to death?
ORGANOPHOSPHATE POISONING
- Absorbed by inhaling, ingesting or dermal absorption
- Inhibit AchE
- Continuous muscle contraction
What are the signs of cholinergic toxidrome and what can they be caused by?
- Snake venom
- Pesticides
- Both inhibit AchE
What is botulism?
- Toxin produced by bacteria clostridium botulinum
- Blocks neurotransmitter release at end plate
- Flaccid paralysis
SIGNS: VOMITING, WEANESS, FEELING TIRED, TROUBLE SPEAKING, DIARROHEA, SWELLING OF ABDOMEN (no fever or loss of consciousness)
What is botox used for clinically?
- Overreactive bladder
- Treat wrinkles
- Underarm sweating
- Cervical dystonia
- Blepharospasm
Lasts 3-12 months by paralysing muscles and blocking nerves. Can cause issues if gets to diaphragm so trained professional has to do it
How is the cardiac muscle innervated?
- From medulla oblongata
- One pre-synaptic, many post-synaptic as synapse is a gap
Paramsympathetic: Vagus nerve, synapse in ventricle wall. Slows heart down
Sympathetic: Spinal nerve. Increases heart rate
How is smooth muscle stimualted to contract?
- Varicosities releasing neurotransmitters
- Hormones
If a agonist hormone bound to smooth muscle what would happen?
- Stopped when Ca runs out or active myosin dephosphorylated back to circular
If a neurotransmitter bound to smooth muscle how would it contract?
Same as with hormone but calcium spark would be released from mitochondria instead of sarcoplasmic reticulum
What is the unit of contraction in a smooth muscle?
What is a gap junction and what is the importance of them in smooth muscle cells?
Two hexamers of connexin on two membranes that come together to form a hole between the two cells.
Actin can travel between the two muscle cells
How are skeletal muscles innervated?
- Each motor unit is specific to one type of muscle fibre (I,IIa,IIB)
- Boutons at the end of each axon bound to muscle cells
- Boutons contain acetylcholine that they release when there is a nervous impulse
What is the significance of the number of nerve fibres on a single muscle?
- Less nerve fibres, more control
- More fibres, stronger contraction
- Eyes least, calf most
