SKELETAL MUSCLE PATHOLOGY

Normal skeletal muscle

Atrophy and hypertrophy of muscle s Pathophysiological changes of muscles

Atrophy and hypertrophy of muscles

Muscle atrophies Muscle atrophy is defined as a decrease in the mass of the muscle 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 Physiologically: Muscle mass, muscle strength, and bone density decrease in the elderly Disuse atrophy of muscles can occur after prolonged immobility such as extended bed-rest, or having a body part in a cast. Disuse atrophy of muscles can occur after prolonged immobility such as extended bed-rest, or having a body part in a cast. –This type of atrophy can usually be reversed with exercise.

Disuse Atrophy Of Muscles

There are many diseases and conditions which cause atrophy of muscle mass. There are many diseases and conditions which cause atrophy of muscle mass. For example diseases such as cancer and AIDS induce a body wasting syndrome called "cachexia” For example diseases such as cancer and AIDS induce a body wasting syndrome called "cachexia” Other conditions which can induce skeletal muscle atrophy are congestive heart failure and liver disease. Other conditions which can induce skeletal muscle atrophy are congestive heart failure and liver disease.

Severe generalized muscle atrophy Body wasting syndrome called "Cachexia”

Muscle hypertrophy Muscle hypertrophy is an increase in the size of a muscle 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. 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 Pathologically in Acromegaly disease there is pathological muscle hypertrophy affecting mainly the type (1) skeletal fibers

Exercise Muscle Hypertrophy Acromegaly Disease

Muscle Diseases

Inflammatory Myopathies Inflammatory Myopathies –Infectious Myositis –Non-Infectious Myositis (Auto-immune ) 1-Polymyositis2-Dermatomyositis 3-Inclusion body myositis Diseases of the Neuromuscular Junction Diseases of the Neuromuscular Junction -Myasthenia Gravis -Lambert-Eaton Syndrome Classification of Muscle Disease

Dystrophies Dystrophies –Duchenne’s Muscular Dystrophy –Becker’s Muscular Dystrophy –Myotonic Dystrophy Metabolic Myopathies Metabolic Myopathies -Glycogen Storage Diseases -Glycogen Storage Diseases -Mitochondrial Myopathies -Mitochondrial Myopathies Toxic Myopathies Toxic Myopathies

Inflammatory Myopathies

Inflammatory myositis Polymyositis Dermatomyositis 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 It means "inflammation of many muscles"); it is a type of chronic inflammation of the muscles possibly due to autoimmune causes

Clinical presentation: Clinical presentation: –Adults –Bilateral proximal muscle weakness Microscopic: Microscopic: –Endomysial lymphocytic inflammation –Skeletal muscle fiber degeneration and regeneration

POLYMYOSITIS mostly affects the muscles of the hips and thighs, the upper arms, the top part of the back, the shoulder area and the neck

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.

Muscle weakness can cause difficulty in many daily activities

Diagnosis: History and physical examination Elevation of creatine kinase Electromyograph (EMG) alteration Positive muscle biopsy

Polymyositis Endomysial lymphocytic inflammation inflammation

Dermatomyositis Dermatomyositis (DM) is a connective-tissue disease related to polymyositis (PM) that is characterized by inflammation of the muscles and the skin. 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. The disease may also affect the joints, the esophagus, the lungs, and, less commonly, the heart.

Dermatomyositis Clinical presentation: Clinical presentation: 1.Children and adults 2.Bilateral proximal muscle weakness 3.Skin rashes (upper eyelids) 4.Peri-orbital edema Microscopic: Microscopic: 1.Perimysial and vascular lymphocytic inflammation 2.Skeletal muscle fiber degeneration and regeneration

Grotton lesions: scaly erythematous eruptions or red patches overlying the knuckles, elbows, and knees Grotton lesions: scaly erythematous eruptions or red patches overlying the knuckles, elbows, and knees X-ray findings sometimes include dystrophic calcifications in the muscles, and patients may or may not notice small calcium deposits under the skin X-ray findings sometimes include dystrophic calcifications in the muscles, and patients may or may not notice small calcium deposits under the skin

Gottron's lesions: Discrete erythematous papules overlying the metacarpal and interphalangeal joints in a patient with juvenile dermatomyositis

Gottron's sign. Confluent macular erythema with scale confined to the skin overlying the patellae in a juvenile dermatomyositis

Clinical presentation The main symptoms include skin rash and symmetric muscle weakness which may be accompanied by pain. The main symptoms include skin rash and symmetric muscle weakness which may be accompanied by pain. The "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 The "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

Eruption is associated with peri-orbital edema and telangiectasias of the both eyelids.

Diagnosis: The diagnosis of dermatomyositis is usually confirmed by muscle biopsy, EMG and blood tests. 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 Liver enzymes, specifically creatin phosphokinase (CPK), are the major tool in assessing the progress of the disease and/or the efficacy of treatment

Dermatomyositis Perimysial and vascular lymphocytic inflammation

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 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. 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: Clinical presentation:  Adults> age 50  Asymmetrical distal muscle weakness Microscopically Microscopically –Cytoplasmic vacuoles with basophilic granules and amyloid

The first muscles affected in inclusion-body myositis are usually those of the wrists and fingers, and the muscles at the front of the thigh. The muscles that lift the front of the foot also may be affected

Diagnosis: Elevated creatine kinase CK levels Elevated creatine kinase CK levels Electromyography (EMG) studies usually display abnormalities. 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. Muscle biopsy display several findings including; inflammatory cells invading muscle cells, vacuolar degeneration, inclusions or plaques of abnormal proteins.

Inclusion body myositis Cytoplasmic vacuoles

Diseases of the Neuromuscular Junction 1. Myasthenia Gravis 2. Lambert-Eaton Syndrome

Myasthenia gravis

Definition: Definition: –Autoimmune disease characterized by auto antibodies against the neuromuscular junction, causing a defect in the transmission of nerve impulses to muscles resulting in muscular weakness Pathogenesis: Pathogenesis: –Auto antibodies against the acetylcholine (Ach) receptor –Associated with thymus gland hyperplasia and thymomas

Neuromuscular junction in myasthenia gravis, reduced number of acetylcholine receptors

Clinical presentation Clinical presentation 1.Female> males 2.Muscular weakness predominantly affecting the facial muscles 3.Extra-ocular muscle weakness may lead to ptosis and diplopia 4.Weakness worsens with repeated contractions 5.Respiratory muscle involvement may lead to death

Extra ocular muscle weakness leads to ptosis

In myasthenia gravis, muscle weakness often first appears in the muscles of the face, neck and jaw. The arm and leg muscles are affected later

Diagnosis: Medical history and physical and neurological examinations. Medical history and physical and neurological examinations. Detection of acetylcholine receptor antibodies in blood Detection of acetylcholine receptor antibodies in blood Electromyography (EMG) can also detect impaired nerve- to-muscle transmission Electromyography (EMG) can also detect impaired nerve- to-muscle transmission Other methods as nerve conduction studies Other methods as nerve conduction studies The Edrophonium Test uses intra-venous administration of edrophonium chloride to block the breakdown of acetylcholine and temporarily increases the levels of acetylcholine at the neuromuscular junction. The Edrophonium Test uses intra-venous administration of edrophonium chloride to block the breakdown of acetylcholine and temporarily increases the levels of acetylcholine at the neuromuscular junction.

Associated with some type of cancer in about 60 percent of cases (mostly bronchial small cell carcinoma) Associated with some type of cancer in about 60 percent of cases (mostly bronchial small cell carcinoma) The attack occurs at the junction between nerve and muscle and interferes with the ability of nerve cells to send signals to muscle cells The attack occurs at the junction between nerve and muscle and interferes with the ability of nerve cells to send signals to muscle cells Eaton – Lambert Syndrome

Distribution of affected muscles Eaton – Lambert Syndrome

Cause: LES appears in association with cancer; the cause may be that the body’s attempt to fight the cancer inadvertently causes it to attack nerve fiber endings (specifically, the so-called voltage-gated calcium channels found there) (pre-synaptic calcium channels) LES appears in association with cancer; the cause may be that the body’s attempt to fight the cancer inadvertently causes it to attack nerve fiber endings (specifically, the so-called voltage-gated calcium channels found there) (pre-synaptic calcium channels)

Symptoms: Initially, leg weakness and difficulty walking; weakness of the eye muscles and those involved in talking, chewing and swallowing may occur later Initially, leg weakness and difficulty walking; weakness of the eye muscles and those involved in talking, chewing and swallowing may occur later Dry mouth, constipation and bladder urgency sometimes occur Dry mouth, constipation and bladder urgency sometimes occur Males are more commonly affected Males are more commonly affected Repeated stimulation to the muscle lead to improved neurotransmission. Repeated stimulation to the muscle lead to improved neurotransmission.

Eaton – Lambert Syndrome Bronchial cancer Weak nerve ending

How Is LEMS Diagnosed? The autonomic symptoms and predominant leg weakness of LEMS help to distinguish it from MG. The autonomic symptoms and predominant leg weakness of LEMS help to distinguish it from MG. Electrodiagnostic testing that shows an increased muscle response to repeated stimulation also favors LEMS rather than MG (in which the response decreases). Electrodiagnostic testing that shows an increased muscle response to repeated stimulation also favors LEMS rather than MG (in which the response decreases). In most cases, LEMS can be confirmed by detection of anti-VGCC antibodies (voltage-gated calcium channel) in the blood. In most cases, LEMS can be confirmed by detection of anti-VGCC antibodies (voltage-gated calcium channel) in the blood.

DYSTROPHIES DYSTROPHIES

Dystrophies Dystrophies –Duchenne’s Muscular Dystrophy –Becker’s Muscular Dystrophy –Myotonic Dystrophy

Muscular dystrophy Definition: Definition: –Muscular dystrophy (MD) is the name for a group of disorders in which muscle size and strength gradually decrease over time. –Most common types are:  Duchene muscle dystrophy  Becker muscle dystrophy

Duchenne muscular dystrophy Most common and severe form of muscular dystrophy Most common and severe form of muscular dystrophy X-linked recessive inheritance X-linked recessive inheritance Occurs in males Occurs in males Three quarters of the patients die before 25 years of age Three quarters of the patients die before 25 years of age

Clinical presentation Clinical presentation 1.Normal at birth with onset of symptoms by age of 5 years 2.Progressive muscle weakness 3.Proximal weakness of shoulder and pelvic girdles 4.Calf pseudo hypertrophy 5.Heart failure 6.Respiratory insufficiency Laboratory: elevated serum creatinine kinase (CK) Laboratory: elevated serum creatinine kinase (CK)

Duchenne muscular dystrophy

Microscopically: Microscopically: 1.Muscle fibers of different sizes 2.Necrosis, degeneration and regeneration of fibers 3.Fibrosis 4.Fatty infiltration

Duchenne muscular dystrophy Normal muscle fibers Fiber Necrosis Fibrosis Fatty infiltratio n

Becker’s muscular dystrophy Less common and not as severe as Duchene muscular dystrophy Less common and not as severe as Duchene muscular dystrophy Later onset with variable progression Later onset with variable progression Cardiac involvement is rare Cardiac involvement is rare May have a relatively normal life span May have a relatively normal life span