Lecture 107 Flashcards by Taylor Hall

Type 1 muscle fibers are used in:

Endurance

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Type 2 muscle fibers are used in:

Rapid/power movements

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In normal muscle, motor units have a ____ pattern

Checkerboard

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Histological cross section views of normal muscle

Large polygonal cells with peripheral nuclei

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Histological longitudinal views of normal muscle

Visible striations

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What happens during segmental myofiber degeneration?

A portion of the muscle fiber undergoes necrosis, releasing creatine kinase (CK) into the blood.

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In myogenic injury, which marker is often elevated in the bloodstream when muscle fibers are damaged?

Creatine kinase (CK) is released into the blood from damaged muscle fibers

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What cell type fuses with damaged myofiber segments to enable myofiber regeneration?

Satellite cells fuse with the damaged segments, leading to regenerating myofibers that appear more basophilic initially.

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Why do regenerated myofibers sometimes have a basophilic appearance on histology?

They contain high levels of RNA, giving them a more basophilic (blue) tint under standard stains.

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What is the limitation of myofiber regeneration in chronic disease?

Ongoing or severe disease can outpace the regenerative capacity, resulting in incomplete or failed repairs over time.

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When is myofiber hypertrophy typically seen?

Hypertrophy generally appears with exercise as a physiologic adaptation, but it can also develop pathologically

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What are cytoplasmic inclusions within muscle fibers, and what might they consist of?

Abnormal accumulations such as vacuoles, protein aggregates, or clusters of organelles that can form during certain muscle diseases or injuries.

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What is a neurogenic injury to muscle, in simple terms?

Muscle atrophy and dysfunction caused by a loss or disruption of innervation, affecting the group of fibers supplied by that neuron.

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How does a motor neuron influence the fiber type of a muscle?

Each motor neuron determines the fiber type (Type 1 vs. Type 2) of the muscle fibers it innervates.

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What happens to muscle fibers during denervation?

The affected group of fibers becomes atrophic, typically appearing angular and flattened on histology.

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Define reinnervation and its impact on muscle fiber type.

Surviving axons can sprout to reinnervate denervated fibers; once reinnervated, those fibers switch to the fiber type of the “rescuing” axon

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What distinguishes a myopathic disorder in terms of fiber necrosis?

Myopathic processes feature single-fiber necrosis

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Which gene is mutated in Spinal Muscular Atrophy (SMA) and how does it affect muscle?

A loss-of-function mutation in the SMN1 gene leads to defective snRNP assembly and destruction of anterior horn cells

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What is a characteristic presentation of SMA Type I (Werdnig-Hoffmann disease)?

Floppy infant presentation by 4 months of age

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How does SMA Type I commonly progress?

Typically fatal by 2–3 years of age due to extensive denervation and respiratory failure.

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Histologically marked grouping of atrophic, angular fibers with some normal/hypertrophied fibers is indicative of:

Spinal muscular atrophy

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What is the function of dystrophin?

Dystrophin anchors the intracellular cytoskeleton to the ECM

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What happens if dystrophin is absent or abnormal?

If absent or abnormal, muscle fibers are prone to mechanical stress damage, leading to progressive degeneration.

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What is the genetic cause of Duchenne Muscular Dystrophy?

An X-linked recessive frameshift or nonsense mutation in the dystrophin gene (Xp21) results in absent dystrophin.

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Typical clinical onset of Duchenne MD

Age 5 with progressive proximal muscle weakness (pelvic girdle first), Gower’s sign, and calf pseudohypertrophy.

What is pseudohypertrophy of the calves?

Muscle enlargement caused by replacement of normal muscle fibers with fat and connective tissue.

What are the leading causes of death in Duchenne MD patients?

Respiratory insufficiency and cardiac complications

Why is serum CK elevated in Duchenne MD, especially in early stages?

Damaged muscle fibers leak CK into the bloodstream

How does the genetic defect differ between Duchenne and Becker Muscular Dystrophy?

Becker MD involves a partially functional (truncated) dystrophin

How does disease severity differ between Duchenne and Becker MD?

Becker MD typically has a later onset and milder progression; many patients have near-normal life expectancy.

A CTG repeat expansion in the DMPK gene leads to abnormal RNA splicing and reduced chloride channel function in what condition?

Myotonic dystrophy

Define myotonia in Myotonic Dystrophy.

Myotonia is prolonged muscle contraction with delayed relaxation

Clinical features commonly seen in Myotonic Dystrophy.

Frontal balding, cataracts, testicular atrophy, and sometimes cardiac conduction defects (arrhythmias).

What general defect characterizes an ion channel myopathy?

An inherited mutation in an ion channel (calcium, sodium, potassium, or chloride) that alters muscle cell excitability.

A defect in the CACNA1S calcium channel gene is associated with what condition?

Hypokalemic periodic paralysis

Which conditions are linked to RYR1 mutations?

Malignant hyperthermia and some congenital myopathies (like central core disease).

CLC1 mutation can cause what condition?

Myotonia congenita

Which agents typically trigger malignant hyperthermia?

Halogenated inhaled anesthetics (like halothane) or succinylcholine

Hypermetabolic crisis with severe muscle rigidity, very high fever, tachycardia, and tachypnea are signs of?

Malignant hyperthermia

What is the treatment of choice for malignant hyperthermia?

Dantrolene

In Central Core Disease, which gene is typically mutated, and what major risk is increased?

RYR1 gene is affected, and these patients have a higher risk of malignant hyperthermia.

Which histologic feature is characteristic of Central Core Disease?

“Core” areas in the muscle fiber with reduced oxidative and glycolytic enzyme activity

What are the key biopsy findings in Nemaline Myopathy?

Rod-shaped (thread-like) nemaline bodies (aggregates) in Type 1 fibers

What condition can be autosomal dominant or recessive, involving genes encoding components of the thin filament (NEM1–7)?

Nemaline myopathy

What is the clinical presentation of nemaline myopathy?

Childhood weakness, "floppy baby"

Two general patterns of muscle dysfunction in lipid/glycogen metabolism disorders.

1. Exercise- or fasting-induced episodes (cramping, rhabdomyolysis) 2. Slowly progressive form of muscle damage without acute crises.

Why does Carnitine Palmitoyltransferase II (CPT II) deficiency impair muscle function?

It blocks the transport of fatty acids into mitochondria, causing toxic buildup of fatty acids in muscle and episodic damage under stress or fasting.

Clinical manifestations of CPT II deficiency

Muscle weakness (especially with prolonged exercise or fasting), hypoketotic hypoglycemia, and possibly dilated cardiomyopathy

In McArdle disease (Type V), which enzyme is deficient?

Myophosphorylase (muscle glycogen phosphorylase)

What symptom typically occurs in McArdle disease during intense exercise?

Painful muscle cramps and potential myoglobinuria

Which blood test result is characteristically flat in McArdle disease during exercise?

The venous lactate curve remains flat

In Pompe disease (Type II), which enzyme is deficient?

Acid maltase (lysosomal α-1,4-glucosidase)

What is the result of acid maltase deficiency in Pompe disease?

Lysosomal glycogen build-up

Clinical signs of Pompe diease

Cardiomegaly, exercise intolerance, hypotonia

How does infantile-onset Pompe disease typically present?

Severe hypertrophic cardiomyopathy, marked hypotonia (“floppy baby”), and early death if untreated.

What defines MERRF (Myoclonic Epilepsy with Ragged Red Fibers)?

Patients have myoclonus, seizures, and ragged red fibers on muscle biopsy

What mutation is often associated with MERRF?

Mitochondrial MT-TK gene

What is chronic progressive external ophthalmoplegia?

Progressive weakness of extraocular muscles (eyes and eyelids)

Leber hereditary optic neuropathy is caused by:

Degeneration of retinal ganglion cells resulting is subacute loss of central vision

What are the three major inflammatory myopathies

Dermatomyositis, Polymyositis, and Inclusion Body Myositis

What skin findings are characteristic of dermatomyositis?

A heliotrope rash and Gottron’s papules

Immune attack on small blood vessels (capillaries), often with complement deposition (C5b–9), leading to perifascicular muscle fiber ischemia describes what condition?

Dermatomyositis

Patients with dermatomyositis are at an increased risk for:

Malignancies

What common antibodies are seen in dermatomyositis?

Anti-M12 (classic rash) and Anti-Jo1 (interstital lung disease and "mechanics hands")

Perifascicular atrophy, inflammation (CD4+ T cells, B cells) around small vessels in perimysium, and complement deposition (C5b–9) are all found in biopsy of:

Dermatomyositis

How does polymyositis differ from dermatomyositis?

Symmertrical proximal muscle weakness but no skin findings

Which inflammatory cells predominate in polymyositis, and where are they located histologically?

CD8+ T lymphocytes infiltrate within the endomysium, attacking muscle fibers directly.

Which age group most commonly presents with Inclusion Body Myositis?

It often affects those over 65

What pattern of weakness is typical in inclusion body myositis?

Distal muscle involvement (e.g., finger flexors) that may be asymmetric.

What are the hallmark histological features of Inclusion Body Myositis?

Rimmed vacuoles (autophagic vacuoles) in myofibers and a CD8+ T-cell inflammatory infiltrate.

Why is Inclusion Body Myositis often resistant to immunosuppressive treatment?

It has degenerative aspects in addition to inflammation

Which receptors are targeted by autoantibodies in Myasthenia Gravis?

Antibodies target post-synaptic acetylcholine receptors

What thymic abnormalities are commonly associated with Myasthenia Gravis?

Thymoma or thymic hyperplasia, especially in younger adults.

How does the weakness in Myasthenia Gravis typically present?

Extraocular muscles are often affected first (ptosis, diplopia), weakness worsens with repeated use

Which class of drug typically improves Myasthenic symptoms?

Acetylcholinesterase inhibitors

In Lambert-Eaton syndrome, which presynaptic channel is targeted by autoantibodies?

Antibodies target P/Q-type voltage-gated calcium channels

Which malignancy is Lambert-Eaton syndrome most strongly associated with?

Small cell lung carcinoma (SCLC)

What key clinical feature distinguishes Lambert-Eaton syndrome from Myasthenia Gravis in terms of muscle strength?

In Lambert-Eaton, muscle strength improves with repeated activity, because more calcium accumulates presynaptically over time

What autonomic symptoms are found in Lambert-Eaton syndrome?

Dry mouth, constipation, erectile dysfunction

How is Lambert-Eaton syndrome diagnosed?

EMG with repetitive stimulation

How is Lambert-Eaton treated?

Agents that enhance ACh release (e.g. amifampridine)