SKELETAL MUSCLE SKELETAL MUSCLE PATHOLOGYPATHOLOGY

Normal skeletal muscleNormal skeletal muscle

Atrophy and Atrophy and hypertrophy of hypertrophy of

musclemuscless

Pathophysiological Pathophysiological changes of muscleschanges of muscles

Atrophy and hypertrophy of Atrophy and hypertrophy of musclesmuscles

Muscle atrophiesMuscle atrophies Muscle atrophyMuscle atrophy is defined as a decrease in the is defined as a decrease in the

mass of the musclemass of the muscle

Physiologically: Physiologically: Muscle mass, muscle strength, Muscle mass, muscle strength, and bone density decrease in the elderlyand bone density decrease in the elderly

Disuse atrophy of muscles can occur after Disuse atrophy of muscles can occur after prolonged immobility such as extended bed-rest, prolonged immobility such as extended bed-rest, or having a body part in a cast. or having a body part in a cast. – This type of atrophy can usually be reversed This type of atrophy can usually be reversed

with exercise.with exercise.

Disuse Atrophy Of Muscles

There are many diseases and conditions There are many diseases and conditions which cause atrophy of muscle mass. which cause atrophy of muscle mass.

For example diseases such as For example diseases such as cancer and cancer and AIDSAIDS induce a body wasting syndrome called induce a body wasting syndrome called "cachexia”"cachexia”

Other conditions which can induce skeletal Other conditions which can induce skeletal muscle atrophy are muscle atrophy are congestive heart failure congestive heart failure and liver diseaseand liver disease..

Severe generalized muscle atrophy

Body wasting syndrome called "Cachexia”

Muscle hypertrophyMuscle hypertrophy Muscle hypertrophyMuscle hypertrophy is an increase in the is an increase in the

size of a musclesize of a muscle

Hypertrophy is an increase in mass of a Hypertrophy is an increase in mass of a muscle that can be induced by a number of muscle that can be induced by a number of stimuli. The most familiar of these is exercise.stimuli. The most familiar of these is exercise.

Pathologically in Pathologically in Acromegaly diseaseAcromegaly disease there is there is pathological muscle hypertrophy affecting pathological muscle hypertrophy affecting mainly the type (1) skeletal fibersmainly the type (1) skeletal fibers

ExerciseExercise Muscle HypertrophyMuscle Hypertrophy

Acromegaly DiseaseAcromegaly Disease

Muscle Diseases

Inflammatory MyopathiesInflammatory Myopathies– Infectious MyositisInfectious Myositis– Non-Infectious Myositis (Auto-immune )Non-Infectious Myositis (Auto-immune )

1-Polymyositis1-Polymyositis

2-Dermatomyositis2-Dermatomyositis

3-Inclusion body myositis3-Inclusion body myositis

Diseases of the Neuromuscular JunctionDiseases of the Neuromuscular Junction-Myasthenia Gravis-Myasthenia Gravis

-Lambert-Eaton Syndrome-Lambert-Eaton Syndrome

Classification of Muscle Classification of Muscle DiseaseDisease

DystrophiesDystrophies– Duchenne’s Muscular DystrophyDuchenne’s Muscular Dystrophy– Becker’s Muscular DystrophyBecker’s Muscular Dystrophy– Myotonic DystrophyMyotonic Dystrophy

Metabolic MyopathiesMetabolic Myopathies -Glycogen Storage Diseases -Glycogen Storage Diseases

-Mitochondrial Myopathies-Mitochondrial Myopathies

Toxic MyopathiesToxic Myopathies

Inflammatory Myopathies

Inflammatory myositisInflammatory myositis

1. Polymyositis 2. Dermatomyositis3. Inclusion body myositis Are of auto-immune origin

Polymyositis (PM)Polymyositis (PM)

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

Clinical presentation:Clinical presentation:– AdultsAdults– Bilateral proximal muscle weaknessBilateral proximal muscle weakness

Microscopic:Microscopic:– Endomysial lymphocytic inflammationEndomysial lymphocytic inflammation– Skeletal muscle fiber degeneration and Skeletal muscle fiber degeneration and

regenerationregeneration

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

PolymyositisPolymyositis

Endomysial lymphocyticEndomysial lymphocytic inflammationinflammation

DermatomyositisDermatomyositis

DermatomyositisDermatomyositis (DM) is a connective- (DM) is a connective-tissue disease related to polymyositis tissue disease related to polymyositis (PM) that is characterized by (PM) that is characterized by inflammation of the muscles and the skin. inflammation of the muscles and the skin.

The disease may also affect the joints, The disease may also affect the joints, the esophagus, the lungs, and, less the esophagus, the lungs, and, less commonly, the heart.commonly, the heart.

DermatomyositisDermatomyositis

Clinical presentation:Clinical presentation:1.1. Children and adultsChildren and adults

2.2. Bilateral proximal muscle weaknessBilateral proximal muscle weakness

3.3. Skin rashes (upper eyelids)Skin rashes (upper eyelids)

4.4. Peri-orbital edemaPeri-orbital edema

Microscopic:Microscopic:1.1. Perimysial and vascular lymphocytic Perimysial and vascular lymphocytic

inflammationinflammation

2.2. Skeletal muscle fiber degeneration and Skeletal muscle fiber degeneration and regenerationregeneration

Grotton lesions: scaly erythematous Grotton lesions: scaly erythematous eruptions or red patches overlying eruptions or red patches overlying the knuckles, elbows, and kneesthe knuckles, elbows, and knees

X-ray findings sometimes include X-ray findings sometimes include dystrophic calcifications in the dystrophic calcifications in the muscles, and patients may or may muscles, and patients may or may not notice small calcium deposits not notice small calcium deposits under the skin 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 presentationClinical presentation

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

The "lilac" rash is a violaceous The "lilac" rash is a violaceous eruption on the upper eyelids and in eruption on the upper eyelids and in rare cases on the lower eyelids as rare cases on the lower eyelids as well, often with itching and swellingwell, often with itching and swelling

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

DiagnosisDiagnosis::

The diagnosis of dermatomyositis is The diagnosis of dermatomyositis is usually confirmed by muscle biopsy, usually confirmed by muscle biopsy, EMG and blood tests. EMG and blood tests.

Liver enzymes, specifically creatin Liver enzymes, specifically creatin phosphokinase (CPK), are the major phosphokinase (CPK), are the major tool in assessing the progress of the tool in assessing the progress of the disease and/or the efficacy of disease and/or the efficacy of treatmenttreatment

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Perimysial and Perimysial and vascular vascular

lymphocytic lymphocytic inflammationinflammation

Inclusion body myositisInclusion body myositis

IBM causes progressive weakness of the IBM causes progressive weakness of the muscles of the wrists and fingers, the muscles muscles of the wrists and fingers, the muscles of the front of the thigh and the muscles that of the front of the thigh and the muscles that lift the front of the foot.lift the front of the foot.

IBM is generally a slowly progressive disease, IBM is generally a slowly progressive disease, and life expectancy isn’t significantly and life expectancy isn’t significantly affected. Most people with IBM remain able to affected. Most people with IBM remain able to walk, although they may require a cane or walk, although they may require a cane or wheelchair for long distances.wheelchair for long distances.

Clinical presentation:Clinical presentation: Adults> age 50Adults> age 50 Asymmetrical distal muscle weaknessAsymmetrical distal muscle weakness

MicroscopicallyMicroscopically– Cytoplasmic vacuoles with Cytoplasmic vacuoles with

basophilic granules and amyloidbasophilic 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

DiagnosisDiagnosis:: Elevated creatine kinase CK levelsElevated creatine kinase CK levels

Electromyography (EMG) studies usually Electromyography (EMG) studies usually display abnormalities. display abnormalities.

Muscle biopsy display several findings Muscle biopsy display several findings including; inflammatory cells invading including; inflammatory cells invading muscle cells, vacuolar degeneration, muscle cells, vacuolar degeneration, inclusions or plaques of abnormal proteins. inclusions or plaques of abnormal proteins.

Inclusion body myositisInclusion body myositis

Cytoplasmic vacuoles

Diseases of the Diseases of the Neuromuscular JunctionNeuromuscular Junction

1.1. Myasthenia GravisMyasthenia Gravis

2.2. Lambert-Eaton SyndromeLambert-Eaton Syndrome

Myasthenia gravisMyasthenia gravis

Myasthenia gravisMyasthenia gravis

Definition:Definition:– Autoimmune disease characterized by auto Autoimmune disease characterized by auto

antibodies against the neuromuscular junction, antibodies against the neuromuscular junction, causing a defect in the transmission of nerve causing a defect in the transmission of nerve impulses to muscles resulting in muscular weaknessimpulses to muscles resulting in muscular weakness

Pathogenesis:Pathogenesis: – Auto antibodies against the acetylcholine (Ach) Auto antibodies against the acetylcholine (Ach)

receptorreceptor– Associated with thymus gland hyperplasia and Associated with thymus gland hyperplasia and

thymomasthymomas

Neuromuscular junction in myasthenia gravis, reduced number of acetylcholine receptors

Clinical presentationClinical presentation1.1. Female> malesFemale> males2.2. Muscular weakness predominantly Muscular weakness predominantly

affecting the facial musclesaffecting the facial muscles3.3. Extra-ocular muscle weakness may Extra-ocular muscle weakness may

lead to ptosis and diplopialead to ptosis and diplopia4.4. Weakness worsens with repeated Weakness worsens with repeated

contractionscontractions5.5. Respiratory muscle involvement may Respiratory muscle involvement may

lead to deathlead 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:Diagnosis: Medical history and physical and neurological Medical history and physical and neurological

examinations.examinations.

Detection of acetylcholine receptor antibodies in Detection of acetylcholine receptor antibodies in bloodblood

Electromyography (EMG) can also detect Electromyography (EMG) can also detect impaired nerve-to-muscle transmissionimpaired nerve-to-muscle transmission

Other methods as nerve conduction studies Other methods as nerve conduction studies The The Edrophonium Test Edrophonium Test uses intra-venous uses intra-venous

administration of edrophonium chloride to block administration of edrophonium chloride to block the breakdown of acetylcholine and temporarily the breakdown of acetylcholine and temporarily increases the levels of acetylcholine at the increases the levels of acetylcholine at the neuromuscular junction.neuromuscular junction.

Associated with some type of cancer in Associated with some type of cancer in about 60 percent of cases (mostly about 60 percent of cases (mostly bronchial small cell carcinoma)bronchial small cell carcinoma)

The attack occurs at the junction between The attack occurs at the junction between nerve and muscle and interferes with the nerve and muscle and interferes with the ability of nerve cells to send signals to ability of nerve cells to send signals to muscle cellsmuscle cells

Eaton – Lambert SyndromeEaton – Lambert Syndrome

Distribution of affected muscles

Eaton – Lambert Eaton – Lambert SyndromeSyndrome

Cause:Cause: LES appears in association with cancer; LES appears in association with cancer;

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

Symptoms:Symptoms: Initially, leg weakness and difficulty walking; weakness of Initially, leg weakness and difficulty walking; weakness of

the eye muscles and those involved in talking, chewing the eye muscles and those involved in talking, chewing and swallowing may occur laterand swallowing may occur later

Dry mouth, constipation and bladder urgency sometimes Dry mouth, constipation and bladder urgency sometimes

occur occur

Males are more commonly affectedMales are more commonly affected

Repeated stimulation to the muscle lead to improved Repeated stimulation to the muscle lead to improved neurotransmission.neurotransmission.

Eaton – Lambert SyndromeEaton – Lambert SyndromeBronchial cancer

Weak nerve ending

How Is LEMS Diagnosed?

The autonomic The autonomic symptomssymptoms and predominant and predominant leg leg weakness weakness of LEMS help to distinguish it from MG. of LEMS help to distinguish it from MG.

ElectrodiagnosticElectrodiagnostic testing that shows an testing that shows an increased muscle response to repeated increased muscle response to repeated stimulation also favors LEMS rather than MG (in stimulation also favors LEMS rather than MG (in which the response decreases). which the response decreases).

In most cases, LEMS can be confirmed by In most cases, LEMS can be confirmed by detection of detection of anti-VGCC anti-VGCC antibodies antibodies ((voltage-voltage-gated calcium channel)gated calcium channel) in the blood. in the blood.

DYSTROPHIESDYSTROPHIES

DystrophiesDystrophies– Duchenne’s Muscular DystrophyDuchenne’s Muscular Dystrophy– Becker’s Muscular DystrophyBecker’s Muscular Dystrophy– Myotonic DystrophyMyotonic Dystrophy

Muscular dystrophyMuscular dystrophy

Definition:Definition:– Muscular dystrophy (MD) is the name for Muscular dystrophy (MD) is the name for

a group of disorders in which muscle a group of disorders in which muscle size and strength gradually decrease size and strength gradually decrease over time. over time.

– Most common types are:Most common types are: Duchene muscle dystrophyDuchene muscle dystrophy Becker muscle dystrophyBecker muscle dystrophy

Duchenne muscular Duchenne muscular dystrophydystrophy

Most common and severe form of Most common and severe form of muscular dystrophymuscular dystrophy

X-linked recessive inheritanceX-linked recessive inheritance Occurs in malesOccurs in males Three quarters of the patients die Three quarters of the patients die

before 25 years of agebefore 25 years of age

Clinical presentationClinical presentation1.1. Normal at birth with onset of symptoms by Normal at birth with onset of symptoms by

age of 5 yearsage of 5 years

2.2. Progressive muscle weaknessProgressive muscle weakness

3.3. Proximal weakness of shoulder and pelvic Proximal weakness of shoulder and pelvic girdlesgirdles

4.4. Calf pseudo hypertrophyCalf pseudo hypertrophy

5.5. Heart failure Heart failure

6.6. Respiratory insufficiencyRespiratory insufficiency

Laboratory: elevated serum creatinine Laboratory: elevated serum creatinine kinase (CK)kinase (CK)

Duchenne muscular dystrophyDuchenne muscular dystrophy

Microscopically:Microscopically:1.1. Muscle fibers of different sizesMuscle fibers of different sizes

2.2. Necrosis, degeneration and Necrosis, degeneration and regeneration of fibersregeneration of fibers

3.3. FibrosisFibrosis

4.4. Fatty infiltrationFatty infiltration

Duchenne muscular dystrophyDuchenne muscular dystrophy

Normal muscle fibers

Fiber NecrosisFiber Necrosis

FibrosisFatty

infiltration

Becker’s muscular Becker’s muscular dystrophydystrophy

Less common and not as severe as Less common and not as severe as Duchene muscular dystrophyDuchene muscular dystrophy

Later onset with variable progressionLater onset with variable progression Cardiac involvement is rareCardiac involvement is rare May have a relatively normal life May have a relatively normal life

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