Muscular System and DMD PDF

Tom’s Story Tom seemed like most other young boys, though his mother noted that he was slow to crawl and didn’t start walking until he was 18 months. At the age of three, his mother was concerned by how often he would fall. She took him to a specialist who performed a neurological assessment. What...

Tom’s Story Tom seemed like most other young boys, though his mother noted that he was slow to crawl and didn’t start walking until he was 18 months. At the age of three, his mother was concerned by how often he would fall. She took him to a specialist who performed a neurological assessment. What do you think is involved in this assessment? Student Guided Notes One of the tests the doctor asked Tom to perform is to sit on the floor and then move to a standing position. The doctor looked concerned when Tom went through several steps to stand up. On the chart he wrote the term “Gowers Maneuver.” The doctor said they would need to do blood tests to see if there was something wrong with Tom’s muscles. Gowers Maneuver Muscular System Functions: - movement of the body - maintaining posture - generates body heat - role in other body systems (respiration, digestion, urination) Types of Muscle Skeletal – striated, voluntary Smooth – involuntary (digestive) Cardiac - heart If there is a problem with Tom’s muscles, how could this affect his entire body? Muscle Fiber Structure Muscles are composed of many FIBERS that are arranged in bundles called FASCICLES These fibers are found within muscle cells, called myocytes. Individual muscles are separated by FASCIA, which also forms tendons. Three Different Types of Connective Tissue EPIMYSIUM = outermost layer, surrounds entire muscle. PERIMYSIUM = separates and surrounds fascicles (bundles of muscle fibers) ENDOMYSIUM = surrounds each This model of the muscles uses individual muscle fiber straws to represent fibers. Green = endomysium Yellow = perimysium Blue = epimysium Muscle Layers Muscle Fiber Endomysium Perimysium Epimysium  Perimysium Epimysium Endomysium What tissue surrounds the fascicles? Muscles Cells (Myocytes) Sarcolemma = muscle fiber membrane Sarcoplasm = inner material surrounding fibers (like cytoplasm) Sarcoplasmic Reticulum - transport Myofibrils = individual parallel muscle fibers within sarcoplasm Nucleus Sarcolemma Mitochondrion Sarcoplasm Myofibril Myofibrils are made of ACTIN = thin filaments MYOSIN = thick filaments Myofilaments ACTIN (thin) and MYOSIN (thick) -- form dark and light bands A band = dArk thick (myosin) I band = lIght thIn (actin)  A B C D E F Assignment: S arcomere Color ing It is important to remember the hierarchy fascicles myofibrils myofilaments actin myosin Tom’s Tests Elevated Creatine Kinase (CK) levels - if these levels are high, it means that the muscles have deteriorated by some abnormal process. Based on his high levels of CK, a muscle biopsy is ordered. Blood is also sent for genetic testing. Healthy muscle tissue Tom’s muscle tissue. What do you notice about Tom’s muscles?  The sample of muscle is also stained to look at the levels of DYSTROPHIN protein. Dystrophin is a protein located between the sarcolemma and the myofilaments. It is a cohesive protein, that maintains the structure of the muscle fibers. Tom’s Prognosis - DMD is a fatal disease, as eventually muscle weakness affects the heart and diaphragm. Treatment Options for DMD - 1. Corticosteroids to slow progression 2. Physical therapy to strengthen muscles 3. Surgery (tracheostomy, pacemakers) 4. Gene Therapy - EXONDYS51 -newly approved for those with a specific mutation (exon51) -repairs the gene that makes dystrophin Muscles and the Nervous System Some disorders of the muscles relate to the signals between the muscle and nerves - NEUROMUSCULAR JUNCTION NEUROMUSCULAR JUNCTION - where a nerve and muscle fiber come together MOTOR END PLATE - folded area where muscle and neuron communicate SYNAPSE - gap between the neuron and motor end plate (synaptic cleft) SYNAPTIC VESICLES - where neurotransmitters are stored *these are released into the cleft and tell the muscle to contract  Neuromuscular Junction 1. Neuron 2. Sarcolemma (or motor end plate) 3. Vesicle 4. Synapse 5. Mitochondria 6. Receptors 7. Acetylcholine  vesicles The neurotransmitter that cross the gap is ACETYLCHOLINE , which is stored in vesicles ACH is broken down by CHOLINESTERASE SLIDING FILAMENT THEORY (MODEL) The theory of how muscle contracts is the sliding filament theory. The contraction of a muscle occurs as the thin filament slide past the thick filaments. What is needed: ATP Calcium Myosin and Actin Acetylcholine Cholinesterase Energy Source -ATP is produced by CELLULAR RESPIRATION Why do you breathe more which occurs in the mitochondria when exercising? -Creatine phosphate increases regeneration of ATP * Only 25% of energy produced during cellular respiration is used in metabolic processes - the rest is in the form of HEAT. Do you think these supplements work - maintains body temperature. to increase muscle growth? Why or why not? Creatine kinase is elevated in people who have suffered heart attacks and people with DMD. It leaks out of muscles that have been damaged. Biomarkers are substances that can indicate damage to muscles. They can be used to diagnose diseases like DMD or to determine if a patient is having a heart attack (infarction)  Muscles and Exercise Muscle Fatigue - muscle loses ability to contract after prolonged use Muscle Cramp - a sustained involuntary contraction Oxygen Debt - not have enough oxygen causes lactic acid to accumulate in the muscles → Soreness Changes in Muscles Hypertrophy - muscles enlarge Atrophy - muscles become small and weak due to disuse In patients with muscular dystrophy, the muscles can become larger even as they become weaker. This is due to scar tissue and fat replacing working muscle cells. Muscles and Death - What is rigor mortis? A few hours after a person or animal dies, the joints of the body stiffen and become locked in place. This stiffening is called rigor mortis. Depending on temperature and other conditions, rigor mortis lasts approximately 72 hours. Crime Scene Investigation Disorders of the Muscular System Tetanus causes cholinesterase to not break down the acetylcholine in the synapse. This results in a person's muscles contracting and not relaxing. A tetanus shot must be administered shortly after exposure to the bacteria. Once you develop tetanus, there is no cure. What is Myotonia? delayed relaxation of the skeletal muscles after voluntary contraction, electrical stimulation, or even being startled. These “fainting” goats have myotonia congenita  Symptoms Myasthenia Gravis? A drooping eyelid Blurred vision - Means "grave muscular weakness." Slurred speech - Autoimmune disease Difficulty swallowing Weakness / Fatigue - Acetylcholine receptors are damaged ALS ALS, or amyotrophic lateral sclerosis, is a progressive neurodegenerative disease. The motor nerves degenerate and stop sending messages to the muscles, causing atrophy. Symptoms get worse over time. A-myo-trophic comes from the Greek language. "A" means no. "Myo" refers to muscle, and "Trophic" means nourishment – "No muscle nourishment." When a muscle has no nourishment, it "atrophies" or wastes away. Muscular Dystrophy What type does Tom have? Many forms which all cause a weakening of the muscles Myotonic Duchenne Becker Oculopharyngeal Distal Limb-Girdle Emery-Dreifuss