Noninflammatory & Congenital Myopathies Flashcards by Hannah Brule

Are the following examples of myopathic or neurogenic muscle weakness?

Non-inflammatory etiology
Congenital
Inflammatory etiology
Myasthenia gravis
Metabolic disorders

Myopathic

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Are the following examples of myopathic or neurogenic muscle weakness?

Spinal muscular atrophy
Type II fiber atrophy
Critical illness myopathy

Denervation (neurogenic)

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What is the nature of myopathic vs neurogenic symptoms that may accompany muscle weakness?

Myopathic: pain
Neurogenic: weakness, tingling

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What is the most common entrapment syndrome?

Carpal tunnel syndrome

compressive neuropathy of the median nerve

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___ is a common response to injury in primary muscle diseases.

Necrosis

muscles liquify

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Muscle necrosis can be widespread or segmental.
What is an example of widespread necrosis?
What is an example of segmental necrosis?

Widespread: Rhabdomyolysis
Segmental: within a localized area, e.g. hamstring strain

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Regeneration can restore normal structure and function of fibers within ___ of a single instance of injury.

a few weeks

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Fiber necrosis and regeneration of muscle may occur at the same time with which types of disorders?

acute
subacute
chronic

subacute
chronic

simultaneous necrosis and regneration leads to fiber atrophy and fibrosis

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What is the result of simultaneous fiber necrosis and regeneration on muscle quality?

Fiber atrophy and fibrosis

loss of muscle function

as seen in subacute and chronic muscle disorders

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What is the function of a satellite cell?

Maintenance of a muscle cell

in case of damage

satellite cells have pleuripotential and can convert to muscle cells, filling space

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In the case of muscle damage, satellite cells are activated to divide and convert to muscle cells.
Which cells are responsible for cleaning up sliding filaments in the meantime?

Macrophage

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segmental regeneration

Injury to the muscle fiber causes segmental disnintegration of the ___.

sarcoplasm

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segmental regeneration

The muscle has been injured causing segmental disintegration of the sarcoplasm.
___ accumulate and penetrate the basement membrane to phagocytose the sarcoplasmic contents.

Macrophages

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segmental regeneration

After macrophages have begun phagocytosing the disintegrated sarcoplasmic contents, ___ are activated and proliferate forming ___.

satellite cells are activated and proliferate forming myoblasts

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segmental regeneration

The muscle fiber is injured causing segmental disintegration of the sarcoplasm. Macrophages phagocytose sarcoplasmic contents. Satellite cells are activated and proliferate forming myoblasts. Macrophages will leave with the debris.
From here, how will the fiber regenerate to normal?

Myoblasts align in the center of the fiber and begin to fuse
Fiber continues to regenerate (around the fused myoblasts) until it appears normal

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Is rhabdomyolysis inflammatory?

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What is the etiology of rhabdomyolysis?

Skeletal muscle trauma

way over doing it

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A patient has some swelling, tenderness, profound weakness in muscles, pain in joints, and fatigue. A biopsy is done of their muscle fibers. There is diffuse, widespread necrosis at varying degrees of regeneration. There are clusters of macrophages in and around muscle fibers. Evidence shows that sarcoplasmic contents have poured into circulation.
What is the diagnosis?

Rhabdomyolysis

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Is rhabdomyolysis acute or chronic?

Can be acute, subacute, or chronic

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How does muscle necrosis present with rhabdomyolysis?

Diffuse, widespread necrosis of muscle fibers; varying degrees of necrosis and regeneration throughout affected area

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Those with rhabomyolysis will have increased ___ released into the blood stream by muscle necrosis, which can lead to ___ and possibly mortality.

increased myoglobin released into the blood stream by muscle necrosis, which can lead to renal failure and possibly mortality

myoglobinuria will damage kidneys

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A patient gets a muscle biopsy and is diagnosed with rhabdomyolysis.
What did this biopsy likely show?

Clusters of macrophages in and around muscle fibers
Sarcoplasmic contents poured into circulation

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What are some risk factors for rhabdomyolysis?

Influenza
Metabolic myopathies
Alcoholism
Heat intolerance/stroke
Muscle necrosis due to ischemia (arterial occlusion, DVT)
Drugs (statins, cocaine, amphetamines)
Trauma, severe exertion

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How might alcoholism be a risk for rhabdomyolysis?

Pancreatitis can lead to inflammation eventually affecting vascular system

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How might heat intolerance/stroke be a risk for rhabdomyolysis?

Thickened blood due to sweating

A patient presents fatigued with profound weakness in their muscles and diffuse pain which they describe as "joint pain". You know they struggle with alcoholism and are taking statins for their hypercholesterolemia. What diagnosis is likely?

Rhabdomyolysis

How does Hilton's law relate to the "joint pain" experienced by those with rhabdomyolysis?

Joint shares innervation with the problematic muscle

If a patient has rhabdomyolysis, what may be elevated in their blood?

* Creatine kinase (muscle breakdown) * Potassium * Creatine ## Footnote myoglobin in blood is filtered into urine

Why would a patient with rhabdomyolysis have dark urine with a tea-like appearance if no blood is present?

Myoglobinuria ## Footnote myoglobin from muscles released into blood then filtered through kidneys

Patient presents with profound weakness and tenderness in several muscles. They get a urinalysis and results determine myoglobinuria and high proteins within the urine. What is the immediate concern for this patient?

Acute renal failure and quick death possible ## Footnote patient most likely has rhabdomyolysis

A patient presents with muscle weakness and diffuse pain. Upon a blood test, creatine kinase, potassium, and creatine are elevated. What is the likely diagnosis relating to muscle pathology?

Rhabdomyolysis

What are some treatments for rhabdomyolysis?

Out of chiropractic scope: * Early and **aggressive hydration** (may prevent kidney damage) * Diuretics (flush hyperkalemia) * Address hyperkalemia and low blood calcium levels

The prognosis for rhabdomyolysis varies depending on the extent of ___.

kidney damage

Are muscular dystrophies inflammatory?

What is the most frequent etiology of muscular dystrophy?

Hereditary/genetic

Is muscular dystrophy cureable?

No, it's progressive

What are the general characteristics of muscular dystrophy?

* Fiber necrosis with regeneration (imbalance) * Progressive fibrosis (eventual decreased contractility) * Infiltration by fatty tissue (marbling) * No inflammation

What are two X-linked muscular dystrophies?

* Duchenne * Becker (less severe form of Duchenne)

Besides Duchenne and Becker, what is another hereditary muscular dystrophy causing progressive muscle wasting?

Myotonic dystrophy

Duchenne muscular dystrophy involves an X-linked recessive inheritance of Xp21 gene mutations on the X chromosome. Due to this mutation, those with Duchenne muscular dystrophy do not make ___.

dystrophin

How often is Duchenne muscular dystrophy spontaneous? How common is Duchenne muscular dystrophy?

30% spontaneous somatic mutation 1 in 3600 live births

Duchenne muscular dystrophy is passed through ___ carriers.

heterozygous (mother)

How might a female carrier of Duchenne muscular dystrophy present?

2.5-25% will have symptoms (small percentage)

Duchenne muscular dystrophy primarily affects which sex?

Males

What is the biggest known causative risk for Duchenne muscular dystrophy?

Incest | not spontaneous somatic mutation

Patients with Duchenne muscular dystrophy are lacking dystrophin. What is the function of dystrophin?

* Link the sarcolemma (muscle cell membrane) to muscle cell fibers (actin and myosin) * Transfer force from fibers to membrane * Influence excessive influx of calcium ions and release of soluble muscle enzymes (e.g. creatine kinase) into serum

Duchenne muscular dystrophy means little to no dystrophin available. How will cells and muscles respond?

Breakdown of sarcolemma leads to **cell necrosis** Necrosis and repair efforts lead to **muscle fibrosis**

With Duchenne muscular dystrophy, cell necrosis will eventually outpace muscle regenerative capacity. The number of muscle fibers progressively decreases and is replaced by ___.

fibrofatty connective tissue

In which myopathy do we see pseudohypertrophy of the calves?

Duchenne muscular dystrophy | made of fibrofatty connective tissue

# Duchenne muscular dystrophy Late stage, ___ fibers disappear almost completely, but ___ fibers are still numerous.

**extrafusal** fibers disappear almost completely, but **intrafusal** fibers (spindle fibers) are still numerous

Muscle weakness in children with Duchenne muscular dystrophy is detectable by ___ years of age.

3-4 ## Footnote pelvic and shoulder regions initially

What are some examples of lower limb involvement of Duchenne muscular dystrophy?

* Pseudohypertrophy of calf muscles * Toe walk or waddling gait

What are some clinical manifestations of Duchenne muscular dystrophy that occur in the spine?

* Hyperlordosis * Scoliosis

A 3-year-old male patient is brought in by their parents. They report he is falling frequently, and has difficulty running, jumping, climbing stairs, and rising from the floor. You notice when the patient walks that he seems to be on his toes. Upon questioning, parents report he's always had some gastrointestinal issues. What is the likely diagnosis?

Duchenne muscular dystrophy

Patients with Duchenne muscular dystrophy are generally ___ by age 10, and ___ by age 15.

wheelchair bound by age 10, and bedridden by age 15

Death in those with Duchenne muscular dystrophy usually occurs as a result of ___ or ___ by approximately age 20.

**respiratory insufficiency** (diaphragm involvement) or **cardiac arrhythmia**

What are some non-musculoskeletal clinical manifestations of Duchenne muscular dystrophy?

* GI issues (smooth muscle impairment decreases motility) * Mild to moderate intellectual impairment | dystrophin is important in intellectual development

If dystrophin presents as a truncated protein, as opposed to absent or nearly absent (as in Duchenne), what is the diagnosis?

Becker muscular dystrophy | dysfunctional dystrophin

How does Becker muscular dystrophy compare to Duchenne?

* Milder and later onset * Better neural function

A 13-year-old male presents with an exercise intolerance due to muscle cramping. He does not recall an injury before noticing these symptoms. Months ago, he was having difficulty jogging due to physical dyscomfort, but lately he's had the same diffuse muscular and joint pain just from walking up stairs. When asked, he reports that his urine has been becoming more cola-colored for a while now. What is the likely diagnosis? What would confirm this?

**Becker muscular dystrophy** Confirmed by truncated protein (decreased quality) form of dystrophin | rhabdomyolysis symptoms with myoglobinuria without initial injury ## Footnote slow progressive muscle weakness in young male, slower and older than that of Duchenne

Central core disease, rod myopathy, and central nuclear myopathy are all examples of ___.

congenital myopathies

How are congenital myopathies evident at birth?

"Floppy child" syndromes, lack of head control

How do muscles present if affected by a congenital myopathy?

Hypotonia: * decreased deep tendon reflexes * decreased muscle volume

# congenital myopathies Spinal muscular atrophy (Werdnig-Hoffman disease) usually results in ___.

death within first year of life (severe hypotonia)

What are some complications of congenital myopathies evident in other bodily systems?

Pulmonary complications/weak respiration

What is the condition with an autosomal dominant chromosome 19 mutation of the gene that codes for ryanodine receptors?

Central core disease

What sort of mutation is involved in central core disease?

Chromosome 19 mutation of gene that codes for ryanodine receptors

A patient has central core disease, meaning they have a chromosome 19 mutation of the gene that codes for ryanodine receptors. What is the normal function of ryanodine receptors?

Help control calcium release from sarcoplasmic reticulum

Is central core disease autosomal dominant or recessive?

Autosomal dominant

Which fibers are primarily affected by central core disease?

Type I fibers (slow twitch/postural)

Fibers involved in central core disease show a central area of degeneration. Is there associated denervation present?

Central lack of tissue, but no associated denervation present

Central core disease puts individuals at higher risk for ___. | (temperature tolerance)

malignant hyperthermia

# central core disease What is the treatment for malignant hyperthermia?

Treatment with dantrolene: binds to ryanodine receptors ## Footnote reduced mortality from 80% to 10%

Malignant hyperthermia occurs after ___ in susceptible individuals such as those with central core disease.

anesthesia (halothane)

What is the congenital myopathy where rod-like inclusions arise from the Z-band and accumulate in the sarcoplasm?

Rod myopathy

Rod myopathy involves various mutations most commonly affecting which protein?

Nebulin

Is rod myopathy inflammatory?

Is denervation present in rod myopathy?

Is rod myopathy progressive?

Non-progressive

What is the best blood indicator of a muscle injury?

Increased serum creatine kinase

What are some clinical manifestations of rod myopathy?

* Hypotonia * Delayed motor milestones * Secondary skeletal changes (kyphoscoliosis) * Muscles of face, pharynx, and neck may be involved (lack of expression) * Muscle degeneration (especially with later onset) * Increased serum creatine kinase

What is an example of a secondary skeletal change to the spine possible with rod myopathy?

Kyphoscoliosis

What are the mutations involved in central nuclear myopathy?

Autosomal recessive or dominant mutations of dynamin 2

# central nuclear myopathy Mutations of dynamin 2 influence which processes?

* Endocytosis * Membrane function * Actin assembly

How does central nuclear myopathy appear histologically?

Single, centrally located nucleus in skeletal muscle cells ## Footnote skeletal muscle cells are normally multinucleated

Where in the body does central nuclear myopathy have the most effects? What is one of those effects?

Facial and extraocular involvement Bilateral ptosis ## Footnote no ahydrosis or miosis and it's bilateral, so it's **not** Horner's

Which muscle fibers are predominantly affected by central nuclear myopathy?

Type I fibers