Diseases of Muscle and Neuromuscular Junction
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1 Diseases of Muscle and Neuromuscular Junction Diseases of Muscle and Neuromuscular Junction Neuromuscular Junction Muscle Myastenia Gravis Eaton-Lambert Syndrome Toxic Infllammatory Denervation Atrophy Muscular Dystrophies Congenital Thyrotoxic Ethanol Myopathy Drug Induced Myopathy Infectious Non-Infectious Miscellaneous Duchenne Muscular Dystrophy Central Core Disease (Type 1) Nemaline Myopathy (Type 2) Throtoxic Periodic Paralysis Exophthalmic Opthalmoplegia Hyperthyroidism Dermatomyositis Polymyositis Inclusion Body Myositis Myositis Ossificans
2 Disease of Neuromuscular Junction Myasthenia Gravis o Autoimmune neuromuscular junction disease o Due to circulating autoantibodies that fight against Ach receptors o Reduced activity of Ach leading to fluctuating o Muscle o Fatigability Eaton-Lambert Syndrome Rare autoimmune disorder of Neuromuscular junction Characterized by muscle of the limbs Due to circulating autoantibodies attacking Ca 2+ gated channel of presynaptic terminal Age o Below 40 s mostly women o Elderly same prevalence Underlying diseases o 65% - Thymic Hyperplasia o 15% - Thymoma It is often associated with Paraneoplastic syndrome o 60% of ELS patients have Small Cell Carcinoma of the Lung Very rare patients develop ELS without underlaying carcinoma Begins with extraocular muscles o Ptosis (dropping of eyelids) o Diplopia Muscle following physical activity o But improve after rest Significant improvement after admin of AchE inhibitor Death commonly due to Respiratory arrest Common affecting muscles of o Facial expression o Swallowing o Chewing o Talking Proximal muscle of the limbs o DOES NOT aggravate upon repetitive muscle movement Symptoms DO NOT improve after giving AchE inhibitor Develops autonomic dysfunction Autoantibodies attacking the Acetylcholine receptors through o Complement fixation that lead to direct injury to postsynaptic membrane o Increase internalization and degradation of Acetylcholine receptors o Inhibit the binding of Acetylcholine to its receptors At the end, the is reduce number of Ach receptorsa and reduced Ach activity Autoantibodies attacking Ca 2+ gated channels of presynaptic terminal Ca 2+ is needed for the release of Ach from the vesicles inside the presynaptic terminal This will therefore lead to reduce in the release of Ach without any impact on the number of Ach receptors
3 Disease Thyrotoxic Acute or chronic proximal muscle wekaness Before the sign and symptoms of thyroid dysfunction appear Ethanol Myopathy Exopthalmic Opthalmoplegia Thyrotoxic Periodic Paralysis Hyperthyroidism Drug Induced Disease of Muscle Toxic Clinical Features Swelling of eyelids Edema of the conjunctiva Diplopia Episodic muscle Accompanied by Hypokalaemia Muscle ache and cramp Slow movements and reflex Muscles are o Atrophy o Increased number of nuclei o Aggregation of collagen Excessive alcoholism will lead to an acute toxic syndrome that can lead to o Rhabdomyolysis with accompanied myoglobinuria which can lead to an acute renal failure Patients presented with an acute pain which can be either o Generalized o Localized Morphologically, its characterized by o Swollen myocytes o Fiber necrosis o Myophagocytosis o Muscle regerenation Cushing Syndrome (Steroid Therapy) o It is not directly related to Therapeutic range Steroid level in the body o Muscles appeared Atrophic Chloroquine o Presence of vacoules in the Myocytes
4 Disease of Muscle Inflammatory (Non-Infectious/Autoimmune Disorders) Dermatomyositis Inflammatory disorder of o Skin o Skeletal muscles Polymyositis Autoimmune disorder characterized by destruction of myofibers by o T cells o Macrophages Without/ lack of cutaneous lesion Inclusion Body Myositis Affecting both o Children o Adults 40% of patients have already developed cancer Predominantly happens in adults Commonly occurs in old people Most cases are sporadic Insidious onset Bilateral proximal muscle o Difficult to Climb stairs Getting up from chair o Accampanied Myalgia Skin develops rash at o Face o Extensors surface Dysphagia Extramuscular manifestations (in children) o Interstitial Lung Disease o Vasculitis o Myocarditis o Subcutaneous Calcification o Contracture Subacute to chronic Proximal muscle No apparent skin rash Elevated Creatinine Kinase is the most prominent features Distal muscle o Extensor of the knee o Flexor of Wrist Fingers Myofibers are containing vacoules with basophilic granules Circulating autoantibodies produced by B cells that attack endothelium o Begins with endothelial swelling and followed by necrosis o Leading to vasculitis of artery and vein in the Epimysium Perimysium Ultimately leads to ischemia and infarction Distal portion of muscles affect severely There is an increase expression of HLA1 and HLA2 molecules in the Sarcolemma CD8+, T-cells and Macrophages are seen surrounding the lesion Remain unclear CD8+ and T cells were found in the muscle fibers Immunosuppression therapy is not beneficial
5 Disease of Muscle Denervation Atrophy Spinal Muscular Atrophy (Infantile Motor Neuron Disease) Progressive neurological illnesses due to o Selective loss in the Anterior Horn of the Spinal Cord and Cranial Nerves nuclei Types Type 1 o Onset at birth o Death ensure within 3 years of life Type 2 o Onset later in childhood o Survive into adulthood Weakness in voluntary muscle movement o Swallow o Crawl o Walk Autosomal Recessive Disorder o Happens on Chromosome 5 that controls the survival of motor neuron Can be either o Homozygous deletion o Contangious deletion Neuronal Apoptosis Inhibitory Protein (NAIP) gene Muscular Dystrophy Duchenne Muscular Dystrophy Histology Muscle fibers were replaced by o Connective tissues o Fatty tissues Pseudohypertrophy o Enlargedment of the calf muscle by a complete replacement by fatty tissues Affects mostly boys rather than girls o Due to its X- linked recessive type of inheritance Close relatives may present the same problem Early signs o Difficulty in getting up from the ground o Usually walks with thighs and hands The full-fledged signs appear at the age of 3-5 years old o Clumsy o Walk tip-toe (cant flatten the feet) o Runs strangely o Falls often The signs are progressively worsen Muscles that involved o First affect the feet, extensor of the thigh, shoulders, elbows and ribs o Later hands, face, and neck muscles Completely unable to walk at the age of 10 Develops severe veterbral curve leading to heart and respiratory difficulties Dies at the age of 20 due to o Heart failure o Pneumonia Inherited through X-linked recessive Abnormalities on gene Xp21 region o Encodes for Dystrophin protein Absence in Dystrophin protein can lead to o Poor muscle fiber integrity during contraction o Manifested as muscle
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