SKELETAL MUSCLE PATHOLOGY. Pathophysiological changes of muscles Atrophy and hypertrophy of muscles
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1 SKELETAL MUSCLE PATHOLOGY Pathophysiological changes of muscles Atrophy and hypertrophy of muscles Muscle atrophies Muscle atrophy is defined as a decrease in the mass of the muscle Physiologically: Muscle mass, muscle strength, and bone density decrease in the elderly Disuse atrophy of muscles can occur after prolonged immobility such as extended bedrest, or having a body part in a cast.
2 Muscle hypertrophy Muscle hypertrophy is an increase in the size of a muscle Hypertrophy is an increase in mass of a muscle that can be induced by a number of stimuli. The most familiar of these is exercise. Pathologically in Acromegaly disease there is pathological muscle hypertrophy affecting mainly the type (1) skeletal fibers Classification of Muscle Disease Muscle Diseases Inflammatory Myopathies Infectious Myositis Non-Infectious Myositis (Auto-immune ) 1-Polymyositis 2-Dermatomyositis 3-Inclusion body myositis Diseases of the Neuromuscular Junction -Myasthenia Gravis -Lambert-Eaton Syndrome Dystrophies Becker s Muscular Dystrophy 3. Myotonic Dystrophy Metabolic Myopathies -Glycogen Storage Diseases -Mitochondrial Myopathies Toxic Myopathies 1. Polymyositis Inflammatory Myopathies
3 2. Dermatomyositis 3. Inclusion body myositis Are of auto-immune origin Polymyositis (PM) It means "inflammation of many muscles"); it is a type of chronic inflammation of the muscles possibly due to autoimmune causes Clinical presentation: 1. Adults 2. Bilateral proximal muscle weakness Microscopic: 1. Endomysial lymphocytic inflammation 2. Skeletal muscle fiber degeneration and regeneration Signs and symptoms Symptoms include pain with marked weakness and loss of muscle mass in the proximal musculature particularly in the shoulder and pelvic girdle. The hip extensors are often severely affected leading to particular difficulty in ascending stairs and rising from a seated position. Dysphagia (difficulty in swallowing) occurs in 1/3 of patients. Low grade fever and peripheral lymphadenopathy may be present.
4 Diagnosis: History and physical examination Elevation of creatine kinase Electromyograph (EMG) alteration Positive muscle biopsy Dermatomyositis Dermatomyositis (DM) is a connective-tissue disease related to polymyositis (PM) that is characterized by inflammation of the muscles and the skin. The disease may also affect the joints, the esophagus, the lungs, and, less commonly, the heart. Clinical presentation The main symptoms include skin rash and symmetric muscle weakness which may be accompanied by pain. The heliotrope or "lilac" rash is a violaceous eruption on the upper eyelids and in rare cases on the lower eyelids as well, often with itching and swelling
5 Diagnosis: The diagnosis of dermatomyositis is usually confirmed by muscle biopsy, EMG and blood tests. Liver enzymes, specifically creatin phosphokinase (CPK), are the major tool in assessing the progress of the disease and/or the efficacy of treatment Inclusion body myositis IBM causes progressive weakness of the muscles of the wrists and fingers, the muscles of the front of the thigh and the muscles that lift the front of the foot. IBM is generally a slowly progressive disease, and life expectancy isn t significantly affected. Most people with IBM remain able to walk, although they may require a cane or wheelchair for long distances. Clinical presentation: Adults> age 50 Asymmetrical distal muscle weakness Microscopically Cytoplasmic vacuoles with basophilic granules and amyloid
6 Elevated creatine kinase CK levels Diagnosis: Electromyography (EMG) studies usually display abnormalities. Muscle biopsy display several findings including; inflammatory cells invading muscle cells, vacuolar degeneration, inclusions or plaques of abnormal proteins. Muscular Dystrophies A group of primary muscle disorders that have a heriditary basis. They occur at all ages with varying degrees of severity. Muscular dystrophy refers to a group of hereditary progressive diseases each with unique phenotypic and genetic features Becker s Muscular Dystrophy Emery- Dreifuss Dystrophy Facioscapulohumeral Dystrophy Scapuloperoneal Syndrome Oculopharyngeal Dystrophy Congenital Muscular Dystrophies Kearns-Sayre Syndrome Myotonic Dystrophy
7 Limb-Girdle Muscular Dystrophies Also called Pseudohypertrophic muscular dystrophy. X linked recessive disorder Incidence : 30 per 1,00,000 live born males No abnormality is usually obvious at birth During 2 nd year, when boys begin walking, the early clumsiness is seen. Soon, the child needs to place one hand on the knee to assume an upright position when rising from the floor( GOWER S MANEUVER ) The iliotibial bands & heel cords are the first to become tight. By 5-6 yrs of age, stair climbing becomes labored,and children use railing to pull themselves upward. At the age of 6-7 yrs, the boys often complain of sudden spontaneous falls. At 8-10 yrs of age, affected children cease to be able to climb stairs or stand up from floor and it is almost this time by which they begin to use wheel chair. Contractures of hips,knees & ankles become severe when relatively untreated child spends much of the day in wheelchair. Hips & Knees are locked at 90 degrees & feet turn downward & inward in an exaggerated position of equinovarus. With, development of severe scoliosis, resp fn becomes compromised. Cardiac inv : degeneration & fibrosis of posterolateral wall of lt.ventricle Mental impairment is common. IQ is 1 SD below the mean. By yrs, pts are predisposed to fatal pulmonary infections. Affected children die either from resp.failure or cardiomyopathy that is resistant to treatment. Other causes : aspiration & acute gastric dilatation.
8 Duchenne dystrophy is caused by a mutation of the gene that encodes dystrophin, a 427-kDa protein localized to the inner surface of the sarcolemma of the muscle fiber. It is localized to the short arm of the X chromosome at Xp21. The most common gene mutation is a deletion. Diagnosis DNA studies looking for deletion in dystrophin gene - the least invasive test to confirm the diagnosis. 30 % of pts in whom deletion is not found, Muscle Biopsy is required to establish absence of dystrophin. Serum.CK levels markedly elevated (>10000 mu/ml ) EMG myopathic changes Muscle Biopsy : variation in the size of the fibres, fibrosis, groups of basophilic fibres & opaque / hypercontracted fibres (hyaline fibres) Western blot analysis of muscle biopsy specimens, revealing abnormalities on the quantity and molecular weight of dystrophin protein. Immunocytochemical staining of muscle with dystrophin antibodies can be used to demonstrate absence or deficiency of dystrophin localizing to the sarcolemmal membrane. Treatment Physical Therapy : aim : to keep joints as loose as possible. Commenced at 3-4 yrs of age, when parents are taught to stretch child s heel cords, hip flexors, iliotibial bands on daily basis. Night splints can be considered Bracing : appropriate use of bracing delay child s progression to wheelchair by approx 2yrs Surgery : Reconstructive surgery of the leg often accompanies bracing. The purpose : to keep leg extended & prevent contractures of iliotibial bands & hip flexors. Percutaneous tenotomies of Achilles tendon, knee flexors, hip flexors and iliotibial bands. Pharmacological : Prednisolone improves muscle strength & fn ( 3 yrs. Deflazacort synthetic steroid. Becker s Muscular Dystrophy
9 Less severe form of X-linked recessive muscular dystrophy results from allelic defects of the same gene responsible for Duchenne dystrophy Incidence : 3 per 1,00,000 live born males. The pattern of muscle wasting in Becker muscular dystrophy closely resembles that seen in Duchenne. Proximal muscles, especially of the lower extremities, are prominently involved. As the disease progresses, weakness becomes more generalized Hypertrophy of muscles, particularly in the calves, is an early and prominent finding. Becker s Muscular Dystrophy Pts first experience difficulties b/w age 5-15 yrs Onset can also occur in 3 rd or 4 th decade or even later. Pts with Becker dystrophy walk beyond age 15, while patients with Duchenne dystrophy are typically in a wheelchair by the age of 12. Frequent complaint in teenagers with BMD is leg cramps & muscle pains Significant proportion of these pts have cardiomyopathy. Some present with heart failure only. Others : hyper CK emia, myalgia without weakness & myoglobinuria. Diagnosis & Treatment Western blot analysis of muscle biopsy: reduced amount or abnormal size of dystrophin Mutation analysis of DNA from peripheral blood leukocytes Quantification of dystrophin in muscle as in BMD, dystrophin may not be absent but reduced in amount / abnormal in size. Treatment : less aggressive physiotherapy, corticosteroids, bracing genetic counscelling Thank you
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