204_Pathophysiology_Skeletal_Muscle_Practise_Questions 2023-04-03 (1).ppt

Module 204 Pathophysiology of Skeletal Muscle Practise Questions Dr. Harry Witchel What is malignant hyperthermia? • MH is a genetic disorder in which patients are susceptible to a dangerous hyperthermic state triggered by volatile anaesthetics. The cause is a mutation in the Ryanodine receptor,...

Module 204 Pathophysiology of Skeletal Muscle Practise Questions Dr. Harry Witchel What is malignant hyperthermia? • MH is a genetic disorder in which patients are susceptible to a dangerous hyperthermic state triggered by volatile anaesthetics. The cause is a mutation in the Ryanodine receptor, which as a result releases calcium indiscriminately, Click reveal answer leading to over-activity oftoSERCA. This high ATP-ase activity leads to enormous heat generation, which can cause destruction of the muscle tissue (rhabdomyolysis), and consequent multi-organ failure What is myasthenia gravis? • MG is an autoimmune disorder in which autoantibodies are made against the nicotinic ACh receptor, reducing AChR numbers, so Click to reveal answer transmission of neuromuscular junction signalling is attenuated. This results in proximal muscle weakness and muscle fatigue. List some common symptoms for myasthenia gravis. • Proximal muscle weakness, which includes their being easily fatigued. The most common Click to reveal answer symptoms are eye lid and eye muscle symptoms (e.g. ptosis, partial closure of upper lid, and diplopia, double vision due to lack of eye convergence). Atropine is an anti-cholinergic agent. Why doesn’t the drug atropine lead to symptoms of myasthenia gravis? • The symptoms of myasthenia gravis arise from failure of cholinergic activity in the neuromuscular junction • Atropine block metabotropic cholinergic receptors  Atropine does not affect the nicotinic receptors at the Click to reveal answer Neuromuscular junction • Thus, atropine is acting at completely different sites/receptors than the nicotinic problems arising from MG List some treatments for myasthenia gravis. • Acetylcholine-esterase inhibitors (eg pyridostigmine).  It increases signalling of ACh by increasing the amount of ACh in the synapse during endogenous neural activity Click to reveal answer • Reduction of immune activity (thymectomy, or corticosteroids, but these have many adverse effects) How does rigor mortis occur (in terms of excitation-contraction coupling)? • • • ATP is depleted after death SERCA (Ca2+ pump) ceases to resequester Ca2+ Cytosolic Ca2+ Ca2+ allows crossbridge cycle contraction  • • answer W/o ATP  myosin stops just after power stroke  • Until ATP & creatine-P Click runs out to reveal With myosin still bound to actin Thin and thick filaments are bound together, and sarcomere cannot expand Rigor mortis ends when muscle proteins degrade ~ 3 days after death Name two plasma markers from skeletal muscle that could be used to indicate rhabdomyolysis – and what does each one do normally? • • • Total (CK-MM) – allows buffering of high energy phosphate bonds between ATP and creatine Plasma K+. Normally K+ is 50X higher intracellularly than extracellularly (because of the Na/K pump), so if large number of to revealcontents, answer plasma K+ may increase. myocytes release theirClick intracellular Myoglobin – stores O2 in myocytes. Myoglobinuria is a sign suggesting rhabdomyolysis. Plasma myoglobin increases after skeletal or cardiac muscle damage Why does the number of muscle fibres not increase (or increases by very little) during the course of life? • Skeletal muscle does not (in general) proliferate; it grows by hypertrophy. Click to reveal answer • Proliferation via mitosis tends to be quite difficult in multinucleate cells  Because there cannot be a mitotic spindle List the changes in fibre type ratio that accompany muscle atrophy during extensive bed rest. • An increase in type IIa (non-oxidative, fast twitch) fibres with respect to type I (oxidative, slow twitch) Click to reveal answer • Diminution of all fibre types, (but weight-bearing muscles (with mostly type I fibres) are most affected) List 4 differences between type I and type IIb skeletal muscle fibres • • • • • • • • • Type IIb Type I • Fast twitch Slow twitch • More glycolytic /anaerobic More aerobic • Less myoglobin More myoglobin Click to reveal•answer Slower calcium resequest Faster calcium resequest • Fatigue sensitive More fatigue resistance • Larger diameter Thinner diameter • Lighter in colour Darker in colour List the adaptations that skeletal muscle makes to exercise. • Size (increase, hypertrophy) • Capillarisation /Click Vascularisation to reveal answer (increase) • Fibre type transitions List the general processes that a tissue would undergo when it is either becoming larger or smaller. • • • • Hypertrophy Atrophy Necrosis Proliferation Click to reveal answer When muscles hypertrophy, list the processes by which hypertrophy occurs. • • • • Synthesis of myofilaments Addition of sarcomeres Click to reveal answer Satellite cell activation Vascularisation What are the main effects in muscle of endurance exercise? • • • • Mainly, increase in blood supply (vascularisation). Increase in mitochondria. Click to reveal answer Increase in oxidative enzymes. To a smaller extent, fibre diameter changes, fibre types may change. What are the main muscular effects of non-endurance exercise? • Increase in Type IIx fibre size  Increased number of sarcomeres and myofilaments Click to reveal answer • To a lesser extent, conversion of Type IIa fibres to Type IIx fibres Describe the difference between a sprain and a strain. A sprain is an injury to connective tissues, such as ligaments. A strain is an injury to muscles, to reveal answer such as throughClick overuse. An acute sprain may be treated most likely with ice, a strain may be treated BEFORE exercise with heat. What is the effect of space flight on skeletal muscle? A decrease in muscle mass though atrophy, predominantly in weight bearing muscles. Click to reveal answer To a lesser extent, transition of some Type I fibres to Type IIa or Type IIx fibres. What would you do to minimise with muscle atrophy due to bed rest? Treat by resuming minor activity early. Add physiotherapy totoprevent contractures. Click reveal answer What is a contracture? It is shortening of a myofibre (muscle) by removal of sarcomeres. This results in joints Click to reveal answer that cannot extend fully. Describe histologically skeletal muscle cells. Long, cylindrical, multinucleate, peripheral nuclei. Extensive striation. Click to reveal answer What are myosatellite cells? They are small cells that abut myofibres that are important in regeneration and skeletal muscle growth. to reveal answer They are generallyClick quiescent, but they are activated upon inflammation and degeneration (damage of muscle). Once activated, these cells proliferate and differentiate on extant fibres, helping to repair them. Describe the differences between fasciculations and fibrillations. Both are quite small, involuntary muscle twitches. Fasciculations are neurogenic and therefore affect an entire motor unit (ie multiple myofibres); they can be seen as brief ripples beneath the skin . Clickthey to reveal answer Fibrillations are myogenic; affect only single myofibres. Fibrillations cannot be seen visibly, but are detected by electromyography. They are often associated with denervated muscle fibres. Name 3 causes of rhabdomyolysis. • Crush injury (e.g. after earthquakes, car crashes) • Adverse effects of statins or fibrates (or other toxins) • Malignant hyperthermia (& other genetic diseases of Click to reveal answer muscle) • Hyperthermia • Diabetic ketoacidosis When diagnosing a patient with rhabdomyolysis, what signs and symptoms would you expect to find? • • • • • • • Muscle pains (Potentially) vomiting and confusion decrease in urine production Urine may be tea coloured – myoglobin Click to reveal answer in plasma & urine Potential for kidney failure Possibly electrolyte changes, including hyperkalemia Increases in serum creatine phosphokinase Explain the mechanism of spinal muscular atrophy. Death of lower motor neurons due to lack of survival factors in the anterior horn of the spine. Click to reveal answer Leads to muscle atrophy, hypotonia and muscle weakness. Name the pathology shown in B (right) and explain what is being stained. “Fibre type grouping”. These are photomicrographs of cross sections of skeletal muscle. The type 2 tissues are stained black, while type 1 are counter stained. Fibre type grouping results from “spinal muscle atrophy” and Click to reveal answer from chronic denervating diseases (that have denervation-renervation cycles). What is the mechanism of fibre type grouping in spinal muscular atrophy? Cycles of denervation and collateral reinnervation mean that surviving axons innervate denervated fibres. Thus, Click to reveal answer all fibres in a region may be innervated by the same lower motor neuron. This motor neuron determines fibre type, so all fibres next to one another become the same fibre type. How is malignant hyperthermia treated? Patients who begin the process can be treated with dantroleneClick sodium, which inhibits the to reveal answer ryanodine in receptor. Explain the mechanism of Duchenne muscular dystrophy. A mutation in a dystrophin protein (x-linked) means that there is progressive loss of muscle tissue due to rounds Click to reveal answer of degeneration and regeneration of muscle fibres. These are replaced by fibrofatty tissue, resulting in muscle wasting and muscle weakness.