RE CH32 Flashcards
What is a motor unit?
A single motor neuron and all of the muscle fibers (100-200) it innervates
What is the resting membrane potential of skeletal muscle?
-90 mV
High potassium concentration inside and high sodium concentration outside the cell.
What is the neurotransmitter for skeletal muscle?
Acetylcholine
Which muscles have more than one neuromuscular junction?
Extraocular muscles
An increase in conductance of which ion across the nerve membrane leads to release of Ach into the synaptic cleft?
Ca++
The enzyme choline acetyltransferase (CAT) catalyzes the reaction of which two substrates to form Ach?
Acetyl coenzyme A (acetyl CoA) and choline
Are motor end-plate cation channels ligand or voltage-gated?
Ligand-gated
Are nerve axon cation channels ligand or voltage-gated?
Voltage-gated.
In response to Ach binding to ligand-gated channels on the motor end plate, what ion flow occurs?
Net inward Na+ current and net outward K+ current causing membrane to become depolarized.
What is the end plate potential?
The resulting post-junction all membrane voltage change. Varies in strength according to the quantity of ACh released.
What are the five polypeptide subunits in fetal ACh nicotinic receptors?
Two alpha, a beta, gamma, and delta subunits
How does the adult ACh receptor differ from fetal?
Gamma is replaced by an epsilon. this causes an increased cation conductance and shortened open time.
Opening of the cation channels requires ACh occupation at which two polypeptide subunits on the ACh receptor?
Both alpha subunits.
What occurs when ACh binds to prejunctional cholinergic receptors?
Enhanced neurotransmitter mobilization and release
Nondepolarizing neuromuscular blockade produce its effect by binding to pre or postjunctional cholinergic receptors.
Postjunctional
Tetanic fade may be explained by nondepolarizing muscle relaxants binding to where?
Prejunctional cholinergic receptors.
Which enzyme hydrolyzes ACh in the synaptic cleft?
Acetylcholinesterease (AChE)
What is ACh hydrolyzed to?
Choline and acetate
What happens with the choline byproduct of acetylcholine
It is drawn back into the prejunctional nerve terminal for synthesis of new ACh
What is the MOA of cholinesterase inhibitors?
Inhibit the breakdown of of ACh, increasing the ratio of ACh to antagonist, and allwoing ACh to bind to the receptor more frequently.
What situations cause development of extrajunctional receptors?
Stroke, spinal cord transection, burns, direct muscle damage, prolonged immobility.
How quickly do extrajuctional receptors develop after denervation injuries?
48 hours.
What occurs with administration of nondepolarizing muscle relaxants with extrajunctional receptors?
Resistance develops in affected muscles.
Monitoring in pareitc limbs may underestimate the magnitude of neuromusclar blockade in nonparetic muscles
Why should succs be avoided in deinervation injuries?
May produce dangerously high extracellular potassium levels.
What is an isotonic contraction?
Shortening of the muscle length to preform work.
What is an isometric contraction?
Increased tension but no decrease in length of the muscle.
What is a sarcomere?
The basic contractile unit of skeletal muscle
What are thick filaments made up of?
The protein myosin
What is the A band?
The central portion of the sarcomere containing thick filaments.
What is the M line?
In the middle of the A band and contains proteins that link the thick filaments.
What are thin filaments made of?
Actin, troponin, and tropomyosin
What is the I band?
Less dense area of the sarcomere that only contain thin filaments.
What are Z lines or Z disks?
At the end of the sarcomere and connect thin filaments. They interdigitate with thick filaments in the relaxed muscle.
What is the most important protein for the contractile process?
Troponin
Does skeletal muscle have a refractory period?
No
Why are infants at greater risk for respiratory failure?
The infant diaphragm is made up of only 25% slow (type 1) fatigue-resistant fibers compared to the adult diaphragm which is made up of 55% type 1
What are the three metabolic systems that provide ATP to muscle cells?
- Phsphocreatine-creatine system
- Glycogen-lactic acid system
- Aerobic system
Describe the phsophocreatine-creatine system.
The hydrolysis of creatine phosphate to creatine and phosphate releases large amount of energy for conversion of ADP to ATP.
This energy is used for short bursts of muscle power or for the very beginning of a muscle contraction while other energy systems are being turned on.
Describe the glycogen-lactic acid system.
Glyocogenolysis breaks down glycogen to glucose. Glycolysis beaks down glucose to pyruvate and lactate. The energy released from glycolysis is used to convert ADP to ATP for short to moderate periods of muscle contraction.
Describe the aerobic system
When oxygen is plentiful skeletal muscles take up products of the glycolytic pathway and oxidizes them to CO2 and water (oxidative metabolism). This process is slow but meets modest energy demands of skeletal muscle.
What is myasthenia gravis?
An autoimmune disease characterized by a decrease in the number of postsynaptic ACh receptors
What are clinical hallmarks of myasthenia gravis?
Generalized muscle weakness which improves with rest and an inability to sustain or repeat muscular contractions.
What is the response of succs administration to MG patients NOT treated with cholinesterase inhibitors?
More resistant. Dose should be increased to 1.5 - 2 mg/kg
What is the effect of succs administration to MG patients treated with acetylcholinesterase inhibitors?
Normal or prolonged response to succs. May also have prolonged response to other meds metabolized by plasma cholinesterase (ester local anesthetics)
What is the response to non-depolarizing muscle relaxants in patients with MG
Variable.
Why must reversal of NMB be taken with caution?
Overtreatment with an anticholinesterase agent may precipitate a cholinergic crisis.
Where should you check twitches in a MG patient?
Orbicularis oculi - overestimates the degree of muscle relaxation.
What is lambert-eaton myasthenic syndrome (LEMS)?
Rare autoimmune disease that causes derangment in presynaptic voltage gated Ca+ channels leading to a reduction in Ca+ mediated exocytosis of ACh at the neuromuscular nerve terminals.
What are clinical manifestations of LEMS?
Muscle weakness, fatigue, hyopreflexia, involvement of diaphragm, autonomic nervous system dysfunction (impaired gastric motility, orthostatic hypotension, urinary retention)
True/False? LEMS patients are extremely resistant to neuromuscular blockade?
FALSE. They are extremely sensitive. Doses should be reduced and blockade should be closely monitored.
What is duchenne muscular dystrophy (DMD)?
Infiltration of fibrous and fatty tissue into the muscle, followed by a progressive degeneration and necrosis of skeletal, cardiac, and smooth muscle fibers.
What is Malignant Hyperthermia?
An uncontrollable release of calcium by ryanodine receptors in skeletal muscle in response to volatile anesthetics or succinylcholine.
What is the most sensitive and early indicator of MH?
An unanticipated increase in ETco2 out of proportion to minute ventilation.
What are other signs/symptoms of MH?
Tachycardia, tacypnea, skin motteling, cyanosis, muscle rigidity, hyperthermia (late sign)
What is the MOA of dantrolene?
Muscle relaxant that reduces calcium efflux from the sarcoplasmic reticulum, counteracting the abnormal intracellular calcium levels accompanying MH
What is the dose of dantrolene for MH?
2.5 mg/kg IV every 5-10 minutes until symptoms subside. If greater than 20 mg/kg are needed diagnosis should be reassessed.
What is myotonic dystrophy?
A condition of muscle membrane excitability that results in self-sustaining muscle contraction.
What neuromuscular blockade should be avoided in patients with myotonic dystrophy?
Succinylcholine, may produce an intense myotonic contracture for several minutes making ventilation and intubation difficult/impossible
Skeletal muscle is innervate day by efferent motor nerve fibers called ______
Alpha motor neurons
