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Muscle pathology is a field of study that focuses on understanding the causes and mechanisms of muscle disorders, including those affecting the skeletal muscles, smooth muscles, and cardiac muscles. Skeletal muscle disorders typically manifest as muscle weakness, cramps, pain, or atrophy, which can be caused by various factors such as disuse, denervation, systemic illness, or malnutrition. To diagnose and evaluate muscle disorders, physicians often rely on muscle biopsies, which involve extracting and examining muscle tissue to identify morphological or biochemical abnormalities. These biopsies play a critical role in differentiating between myopathic and neurogenic disorders, guiding treatment decisions, and improving our understanding of normal muscle physiology. Genetic testing and imaging techniques, such as MRI and ultrasound, also contribute to the field of muscle pathology, aiding in the diagnosis and management of neuromuscular disorders.
| Characteristics | Values |
|---|---|
| Muscle pathology findings | Helpful for differentiating myopathies of various causes |
| Muscle fibers | Categorized into types 1 and 2 according to their biochemical properties |
| Type 1 fibers | Oxidative metabolism |
| Type 2 fibers | Predominantly glycolytic metabolism |
| Type 2A fibers | Exhibit partial oxidative activity |
| Type 2C fibers | Too immature to have clear metabolic activity |
| Muscular dystrophy (MD) | A collective group of inherited non-inflammatory progressive muscle disorders without nerve abnormality |
| MD defects | Genetic code for dystrophin, a 427-kd skeletal muscle protein (Dp427) |
| MD manifestations | Weakness and pseudohypertrophy |
| Muscle biopsy | An established and widely used test |
| Muscle abnormalities | Myopathic or neurogenic |
| Myopathic disorders | Affect primarily the muscle |
| Neurogenic disorders | Caused by damage or disease of motor neurons or peripheral nerves |
| Muscle biopsy selection | Based on the clinical picture |
| Biopsy sample | Moderately affected muscle |
| Muscle disorders | Can be caused by disuse, denervation, systemic illness, chronic glucocorticoid use, and malnourishment |
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What You'll Learn
Muscle pathology findings
The principal muscle pathology findings include muscle fibre atrophy and hypertrophy, necrosis and regeneration, inflammatory infiltration, and abnormal inclusions within muscle fibres. For instance, in muscular dystrophies, the sequence of necrosis and regeneration leads to rounded muscle fibres and an increase in variation in fibre sizes. Additionally, dystrophin deficiency, a cause of muscular dystrophies, results in progressive leakage of intracellular components, intracellular substance, and invasion of macrophages.
Muscle biopsy, a widely used diagnostic procedure, aids in confirming the presence of morphological or biochemical abnormalities that correlate with clinical symptoms. Biopsies are particularly useful in evaluating skeletal muscle abnormalities, differentiating between myopathic and neurogenic disorders, and diagnosing inflammatory myopathies. The choice of muscle for biopsy is crucial, with moderately affected muscles being preferred over severely or slightly affected muscles. Common biopsy sites include the vastus lateralis, gastrocnemius, anterior tibialis, deltoid, and biceps muscles.
Recent advances in genetic analysis have significantly impacted the diagnosis of myopathies. Genetic testing can sometimes replace muscle biopsies, especially when the clinical features are characteristic of a specific diagnosis, such as myotonic dystrophy. However, muscle pathology findings remain valuable, especially when inflammatory myopathy is suspected.
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Muscle biopsy
A muscle biopsy is done to determine the source of the disease process and involves removing a small piece of muscle tissue for examination. The muscle selected for biopsy depends on the location of symptoms, which may include pain or weakness. The muscles often selected for sampling are the bicep (upper arm muscle), deltoid (shoulder muscle), or quadriceps (thigh muscle). The muscle to be biopsied should be moderately affected and must not have excessive weakness or recent injections or injuries, which could interfere with the results.
The procedure for a muscle biopsy involves the following steps: The patient is asked to remove their clothing and is given a gown to wear. The healthcare provider then cleans the skin over the biopsy site with an antiseptic solution. A local anaesthetic is injected to numb the area, and the patient will feel a needle stick and a brief stinging sensation. The provider then inserts a biopsy needle through the numbed skin and into the muscle to take the sample. If a larger sample is required, a small incision is made in the skin, and a larger section of muscle is removed. The tissue sample is then sent to a lab for examination under a microscope.
A muscle biopsy can help diagnose several muscle-related conditions (myopathies) and differentiate between nerve and muscle disorders. It can also aid in establishing specific diagnoses, which provide guidance for treatment and counselling. Some of the conditions that may be diagnosed through a muscle biopsy include muscular dystrophies, inflammatory muscle diseases, diseases of the connective tissue and blood vessels, and infections that affect the muscles.
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Muscular dystrophy
Muscle pathology is a field of study that focuses on the diagnosis and treatment of muscle diseases. It involves understanding the underlying causes, mechanisms, and effects of muscle disorders, including muscular dystrophy.
Duchenne muscular dystrophy (DMD) is the most common form, primarily affecting boys, although girls can exhibit milder symptoms. It causes progressive weakness in the heart and lungs, with symptoms such as difficulty walking, frequent falls, and muscle pain. Becker muscular dystrophy (BMD) is the second most common type, also affecting boys mostly, with symptoms typically appearing in the teenage years. Emery-Dreifuss muscular dystrophy (EDMD) affects male children and young adults, causing muscle weakness in the shoulders, upper arms, and shins, and can also impact the heart. Facioscapulohumeral muscular dystrophy (FSHD) affects the face, shoulders, and upper arms, with symptoms often appearing before age 20. Limb-girdle muscular dystrophy (LGMD) affects individuals of all ages and impacts the upper arms, upper legs, shoulders, and hips. Oculopharyngeal muscular dystrophy (OPMD) weakens the muscles in the eyelids and throat, causing droopy eyelids and swallowing difficulties, usually appearing in middle-aged individuals.
Myotonic dystrophy, the most common adult-onset form, affects both men and women, causing difficulty in muscle relaxation after use. It can impact the heart and lungs and lead to endocrine issues. Congenital muscular dystrophies (CMD) refer to a group of muscular dystrophies present at or near birth, causing overall muscle weakness, joint stiffness, and, in some cases, spinal curvature and breathing issues. Distal muscular dystrophy affects the hands, feet, lower arms, and lower legs.
The diagnosis of muscular dystrophy involves a detailed neurological examination, electrophysiological studies, blood tests, imaging studies, and, in some cases, a muscle biopsy. The treatment focuses on managing symptoms, slowing disease progression, and improving patients' quality of life.
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Skeletal muscle contraction
Each skeletal muscle is an organ consisting of various integrated tissues, including the skeletal muscle fibres, blood vessels, nerve fibres, and connective tissue. Each muscle is wrapped in a sheath of dense, irregular connective tissue called the epimysium, which allows a muscle to contract and move powerfully while maintaining its structural integrity.
Skeletal muscles work with tendons to pull on bones. The collagen in the three tissue layers (the mysia) intertwines with the collagen of a tendon, which, at the other end, fuses with the periosteum coating the bone. The tension created by contraction of the muscle fibres is then transferred through the mysia, to the tendon, and then to the periosteum to pull on the bone for movement of the skeleton.
Skeletal muscle fibres can be quite large for human cells, with diameters up to 100 μm and lengths up to 30 cm in the Sartorius of the upper leg. During early development, embryonic myoblasts, each with its own nucleus, fuse with up to hundreds of other myoblasts to form the multinucleated skeletal muscle fibres. Multiple nuclei mean multiple copies of genes, permitting the production of the large amounts of proteins and enzymes needed for muscle contraction.
The sliding filament model of muscle contraction describes how a skeletal muscle fibre contracts as thin filaments are pulled and then slide past thick filaments within the fibre's sarcomeres. This sliding can only occur when myosin-binding sites on the actin filaments are exposed by a series of steps that begins with Ca++ entry into the sarcoplasm. The sliding filament process is powered by actin and myosin filaments that are organised into repeating arrays called sarcomeres.
The energy for muscle contraction comes from ATP, which is produced by aerobic respiration.
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Muscle disorders
Muscular dystrophy (MD) is a collective group of inherited non-inflammatory but progressive muscle disorders without a central or peripheral nerve abnormality. The disease is characterised by definite fibre degeneration without evidence of morphologic aberrations. MD affects the muscles with weakness and pseudohypertrophy. Dystrophin, a 427-kd skeletal muscle protein, is found to be defective in MD patients, resulting in progressive muscle weakness. The lack of dystrophin leads to cellular instability and progressive leakage of intracellular components.
Myopathies are another group of muscle disorders that can be inflammatory, toxic (drug-induced), or hereditary. Hereditary forms include metabolic myopathies, mitochondrial myopathies, congenital myopathies, and myofibrillar myopathies. Inflammatory myopathies were previously known as polymyositis, dermatomyositis, and inclusion-body myositis, but recent improvements in understanding pathological features have changed their categorizations.
A muscle biopsy is a widely used test to evaluate muscle disorders. It is used to confirm the presence of morphological or biochemical abnormalities that correlate with clinical symptoms. The selection of which muscle to biopsy is based on the clinical picture and the distribution of muscle weakness. Biopsy results aid in establishing specific diagnoses and providing guidance for treatment and counselling.
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