Review of Nerve & Muscle Structure & Basic Pathology of Neuromuscular Diseases Flashcards

1
Q

What are the three layers of connective tissue which group skeletal muscle? What do they group specifically?

A

Epimysium - encircles the muscle

Perimysium - encircles the fascicles of muscle via collagenous septae

Endomysium - encircles the the individual muscle cells via a matrix of Type I / III collagen

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2
Q

What is a triad vs a dyad and where do they exist in muscle?

A

Triad - T-tubule + 2 terminal cisternae (extensions of sarcoplasmic reticulum), exist at A/I junction in SKELETAL muscle, 2 per sarcomere

Dyad - T-tubule + 1 terminal cisternae, exist at Z line in CARDIAC muscle, 1 per sarcomere

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3
Q

What is a normal pattern of muscle fibers in a muscle?

A

Random admixture of the two types of muscle fibers: Type 1 and Type 2 with not one taking major predominance

Type 1: Dark

Type 2: Light

-> mixture = checkerboard appearance

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4
Q

What is the difference between a Type 1 / 2 muscle fiber and how do you account for their appearance?

A

Type 1: Think “1 slow red ox”
Slow-twitch fibers for sustained contraction, appear red due to high myoglobin and mitochondria for oxidative metabolism

Type 2: Opposite, fast-twitch fibers which fatigue easily and appear white due to lack of mitochondria and increased glycogen levels

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5
Q

What stain can be used to differentiate between Type 1 / 2 muscle fiber?

A

Myosin ATPase stain. At pH 9.4, the staining patterns are flipped and Type 2 fibers will stain dark while type 1 stains white

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6
Q

What are the H band and M line?

A

M line - myomesin line, where the thick filaments are attached in the center of the A band

H band - center area of the A band which gets smaller as the muscle contracts. I band also gets smaller, A band is Always the same length.

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7
Q

What is a motor neuron, what does it control, and what dictates its size?

A

It is a single neuron which controls fibers of a specific type (Type I/II) within a muscle, arranged in a motor unit.

Muscles with fine control (i.e. extraocular muscles) will have smaller motor neurons which innervate fewer muscle fibers per unit (tight control)

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8
Q

What reflex are intrafusal fibers involved in?

A

These are the muscle spindle fibers

  • > involved in primary myotatic reflex arc “stretch reflex”
  • > maintenance of muscle tone by alpha/gamma coactivation
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9
Q

What muscle fiber types will hypertrophy in aerobic vs strength training and what fiber type atrophies first?

A

Strength training - Type 2 hypertrophy

Aerobic training - increased Type 1 fiber oxidative capacity

Disuse leads to relative atrophy of Type 2 fibers

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10
Q

What is the sequence of events in upper motor neuron injury?

A

Damage -> paralysis of voluntary movement

Initial flaccid paralysis -> later spastic paralysis due to imbalance of central inhibition

Eventual muscle atrophy due to disuse (vs muscle atrophy due to denervation in LMN injury)

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11
Q

What is neurogenic atrophy and does it include NMJ disease?

A

Skeletal muscle dysfunction and ultimately atrophy due to abnormalities in its innervation

Does not include NMJ diseases

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12
Q

What histopathologic phenomenon is common in neurogenic atrophy? What will occur as the denervating process ultimately finishes?

A

Fiber type grouping - ability of adjacent nerve terminals to sprout and renervate denervated myocytes leads to homogeneity of fiber types in an area (all innervated by collaterals from one motor unit) -> loss of checker board appearance due to all muscle fibers becoming the same type.

Group atrophy - denervation leads to massive atrophy of muscle fascicles or muscles (loss of key motor units)

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13
Q

What are common drugs / toxins which can cause myopathies?

A

Statins, steroids, alcohol, cocaine

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14
Q

What are the clinical features of myopathies, including type of weakness and lab values?

A

Symmetrical weakness, affecting proximal > distal muscles
Fatiguability

Features of myonecrosis: myoglobinuria, elevated CK, hyperkalemia

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15
Q

How does myofiber regeneration occur and what does it look like under the microscope?

A

Satellite cells are the stem cells of muscle -> regeneration will follow necrosis in myopathies

Looks like basophilic fiberes in areas of necrosis

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16
Q

What pathology is characteristic of Duchenne / Becker muscular dystrophies in early and late stage?

A

Early - Myonecrosis due to loss of structural entegrity, leads to inflammation and fibrosis of endomysium

Late - Regeneration by satellite cells cannot keep up, leads to fibrofatty replacement of muscle

17
Q

What are the mechanisms of polymyositis vs dermatomyositis?

A

Polymyositis - autoinvasive CD8+ T cells with endomysial inflammation due to direct attack of muscles

Dermatomyositis - Antibody or immune-complex mediated microangiopathy (affects blood vessels) with secondary muscle damage

18
Q

What are some causes of steroid myopathy and how does it occur?

A
  1. Iatrogenic steroid
  2. Endocrinopathies i.e. Cushing’s disease

Steroids impair muscle protein / carbohydrate metabolism due to insulin resistance and protein catabolism -> selective atrophy of Type 2 fibers

19
Q

What dermatomes innervate the following?

  1. Posterior half of skull
  2. Nipple
  3. Xiphoid process
  4. Umbilicus
A
  1. Posterior half of skull (S2) - anterior half is trigeminal nerve
  2. Nipple - T4 = Teat pore
  3. Xiphoid process - T7
  4. Umbilicus = Belly ButTen = T10
20
Q

What dermatomes innervate the following?

  1. Inguinal ligament
  2. Knee
  3. Penis / anus
A

Inguinal Ligament: IL = L1

Knee: Down on all 4’s = L4

Penis: S2,3,4 keep your penis off the floor

21
Q

How does regeneration typically occur following Wallerian degeneration?

A

Denervated Schwann cells proliferate, forming cords of residual Schwann cells called Bands of Bungner
-> help guide re-growth of axon in unison with the endoneurial tube formed via the basal lamina

22
Q

What can happen if regeneration following Wallerian degeneration goes wrong?

A

Formation of traumatic neuroma -> abberent regeneration forms a tumor-like mass of nerve fibers, Schwann cells, and scar tissue

23
Q

Other than Wallerian degeneration, what are two other neuronal pathologies which can occur to peripheral nerves?

A
  1. Axonal dystrophy -> distal axonal degeneration, also called dying back neuropathy
  2. Segmental demyelination -> damage or loss of myelin internodes along length of axon, also called hypertrophic neuropathy (see later)
24
Q

What neurons are particularly affected in distal axon degeneration and how do they appear?

A

Particularly the longest axons

  • > distal ed will appear swollen
  • > will lead to a progressive loss of axons overtime
25
Q

What are the consequences of segmental demyelination?

A
  1. Remyelinated segments may not conduct as efficiently as normal segments (shorter internodal segments)
  2. Onion bulb formations -> concentric proliferation of Schwann cells and collagen around nerve fiber leads to enlargement of nerve fascicle called “hypertrophic neuropathy”
26
Q

How are peripheral neuropathies classified?

A
  1. Type of nerve involved - sensory/motor/autonomic
  2. Anatomic pattern of involvement
  3. Clinical time course
  4. Primary involvement of axon or myelin sheath
27
Q

What is polyneuropathy vs mononeuropathy multiplex?

A

Polyneuropathy - symmetric involvement of multiple nerves -> i.e. “stocking and glove” distal neuropathy

Mononeuropathy multiplex - asymmetric involvement of multiple nerves, usually involving different areas of the body