# Clinical Cases: Muscle Tissue - Skeletal ## Case 1: Duchenne Muscular Dystrophy ### Clinical Image ![Duchenne Muscular Dystrophy - Calf Pseudohypertrophy](case_01_image.jpg) *Source: [Wikipedia - Duchenne Muscular Dystrophy](https://en.wikipedia.org/wiki/Duchenne_muscular_dystrophy) - CC BY-SA 3.0* ### Case Presentation A 5-year-old boy is brought to the pediatrician because his parents notice he has difficulty climbing stairs and rising from the floor. He uses a characteristic "Gower maneuver" - placing his hands on his thighs and "walking up" his legs to stand from a sitting position. Physical examination reveals enlarged, firm calves (pseudohypertrophy) despite overall muscle weakness, particularly in the proximal muscles. He has a waddling gait and lumbar lordosis. Laboratory studies show markedly elevated serum creatine kinase (CK) at 15,000 U/L (normal <200), indicating ongoing muscle damage. Genetic testing reveals a frameshift deletion in the dystrophin gene on the X chromosome. Muscle biopsy shows variation in fiber size, degenerating and regenerating fibers, increased endomysial connective tissue, and immunohistochemistry confirms absent dystrophin staining. The diagnosis is Duchenne muscular dystrophy (DMD). The family is counseled that this is a progressive condition with wheelchair dependence typically by age 12 and cardiorespiratory complications. ### Key Learning Points - Dystrophin is a critical protein linking the intracellular cytoskeleton (actin) to the extracellular matrix via the dystrophin-associated glycoprotein complex - Without dystrophin, the sarcolemma is damaged during contraction, leading to muscle fiber necrosis - Pseudohypertrophy occurs because destroyed muscle is replaced by fat and fibrous tissue, enlarging the calf but weakening it - The elevated CK reflects ongoing muscle cell membrane damage and release of intracellular contents - Understanding the normal organization of skeletal muscle (sarcolemma, endomysium, dystrophin) explains the pathophysiology --- ## Case 2: Myasthenia Gravis ### Clinical Image ![Myasthenia Gravis - Ptosis](case_02_image.jpg) *Source: [Wikipedia - Myasthenia Gravis](https://en.wikipedia.org/wiki/Myasthenia_gravis) - CC BY-SA 3.0* ### Case Presentation A 35-year-old woman presents with drooping eyelids (ptosis) and double vision (diplopia) that worsens throughout the day and improves after rest. Over the past month, she has also developed difficulty chewing during meals and her voice becomes nasal after prolonged speaking. Physical examination reveals bilateral ptosis that worsens with sustained upgaze (fatigable weakness). An ice pack test is performed: application of ice to the eyelids for 2 minutes produces noticeable improvement in ptosis. Laboratory studies reveal positive acetylcholine receptor (AChR) antibodies. Electromyography shows a decremental response to repetitive nerve stimulation. CT chest reveals a thymoma. She is diagnosed with myasthenia gravis. Treatment is initiated with pyridostigmine (an acetylcholinesterase inhibitor that prolongs acetylcholine action at the neuromuscular junction) and she is scheduled for thymectomy. ### Key Learning Points - Myasthenia gravis is an autoimmune disease where antibodies attack nicotinic acetylcholine receptors at the neuromuscular junction - Receptor destruction reduces the number of available receptors, causing the end plate potential (EPP) to fall below threshold for action potential generation - Fatigable weakness occurs because with repeated stimulation, acetylcholine stores deplete and fewer receptors are available - The ice test works because cooling slows acetylcholinesterase activity, prolonging ACh action - Treatment with acetylcholinesterase inhibitors increases ACh concentration at the remaining receptors --- ## Case 3: Malignant Hyperthermia ### Clinical Image ![Malignant Hyperthermia - Ryanodine Receptor](case_03_image.jpg) *Source: [Wikipedia - Malignant Hyperthermia](https://en.wikipedia.org/wiki/Malignant_hyperthermia) - CC BY-SA 4.0* ### Case Presentation A 28-year-old man undergoes general anesthesia for appendectomy. Twenty minutes after induction with sevoflurane (a volatile anesthetic), the anesthesiologist notes rising end-tidal CO2, tachycardia (HR 130), and masseter muscle rigidity. His temperature rapidly rises from 37C to 40C. Arterial blood gas shows pH 7.15 with elevated pCO2 and lactate. A diagnosis of malignant hyperthermia is immediately suspected. The volatile anesthetic is discontinued, 100% oxygen is administered, and dantrolene (a ryanodine receptor antagonist that blocks calcium release from the sarcoplasmic reticulum) is given intravenously. Active cooling measures are initiated. His temperature stabilizes and muscle rigidity resolves. He recovers fully. Subsequent genetic testing confirms a mutation in the RYR1 gene encoding the ryanodine receptor. His family members are counseled to undergo genetic testing before any surgery. ### Key Learning Points - Malignant hyperthermia results from mutations in the ryanodine receptor (RyR1), the calcium release channel in the sarcoplasmic reticulum - Triggering agents (volatile anesthetics, succinylcholine) cause the mutant channel to open abnormally, releasing massive amounts of calcium - Uncontrolled calcium release causes sustained muscle contraction (rigidity), generating enormous heat and depleting ATP - Understanding the normal triad structure (T-tubule, terminal cisternae, RyR1) and excitation-contraction coupling explains this hypermetabolic crisis - Dantrolene directly blocks RyR1, stopping calcium release and allowing the muscle to relax --- ## Summary: Skeletal Muscle Disorders These cases illustrate how understanding normal skeletal muscle structure and function is essential for understanding disease: | Disorder | Structure Affected | Pathophysiology | Clinical Presentation | |----------|-------------------|-----------------|----------------------| | **Duchenne MD** | Dystrophin (sarcolemma-ECM link) | Membrane damage during contraction, muscle necrosis | Progressive weakness, pseudohypertrophy, elevated CK | | **Myasthenia Gravis** | Acetylcholine receptors (NMJ) | Autoantibodies reduce receptor number, EPP fails to reach threshold | Fatigable weakness, ptosis, diplopia, improves with rest | | **Malignant Hyperthermia** | Ryanodine receptor (SR) | Uncontrolled Ca2+ release, sustained contraction | Hyperthermia, rigidity, hypermetabolism during anesthesia | Each condition affects a specific component of the muscle contraction apparatus, and understanding normal histology and physiology is essential for diagnosis and treatment.