Review of Nerve & Muscle Structure & Basic Pathology of Neuromuscular Diseases Flashcards
What are the three layers of connective tissue which group skeletal muscle? What do they group specifically?
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
What is a triad vs a dyad and where do they exist in muscle?
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
What is a normal pattern of muscle fibers in a muscle?
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
What is the difference between a Type 1 / 2 muscle fiber and how do you account for their appearance?
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
What stain can be used to differentiate between Type 1 / 2 muscle fiber?
Myosin ATPase stain. At pH 9.4, the staining patterns are flipped and Type 2 fibers will stain dark while type 1 stains white
What are the H band and M line?
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.
What is a motor neuron, what does it control, and what dictates its size?
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)
What reflex are intrafusal fibers involved in?
These are the muscle spindle fibers
- > involved in primary myotatic reflex arc “stretch reflex”
- > maintenance of muscle tone by alpha/gamma coactivation
What muscle fiber types will hypertrophy in aerobic vs strength training and what fiber type atrophies first?
Strength training - Type 2 hypertrophy
Aerobic training - increased Type 1 fiber oxidative capacity
Disuse leads to relative atrophy of Type 2 fibers
What is the sequence of events in upper motor neuron injury?
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)
What is neurogenic atrophy and does it include NMJ disease?
Skeletal muscle dysfunction and ultimately atrophy due to abnormalities in its innervation
Does not include NMJ diseases
What histopathologic phenomenon is common in neurogenic atrophy? What will occur as the denervating process ultimately finishes?
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)
What are common drugs / toxins which can cause myopathies?
Statins, steroids, alcohol, cocaine
What are the clinical features of myopathies, including type of weakness and lab values?
Symmetrical weakness, affecting proximal > distal muscles
Fatiguability
Features of myonecrosis: myoglobinuria, elevated CK, hyperkalemia
How does myofiber regeneration occur and what does it look like under the microscope?
Satellite cells are the stem cells of muscle -> regeneration will follow necrosis in myopathies
Looks like basophilic fiberes in areas of necrosis
What pathology is characteristic of Duchenne / Becker muscular dystrophies in early and late stage?
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
What are the mechanisms of polymyositis vs dermatomyositis?
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
What are some causes of steroid myopathy and how does it occur?
- Iatrogenic steroid
- 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
What dermatomes innervate the following?
- Posterior half of skull
- Nipple
- Xiphoid process
- Umbilicus
- Posterior half of skull (S2) - anterior half is trigeminal nerve
- Nipple - T4 = Teat pore
- Xiphoid process - T7
- Umbilicus = Belly ButTen = T10
What dermatomes innervate the following?
- Inguinal ligament
- Knee
- Penis / anus
Inguinal Ligament: IL = L1
Knee: Down on all 4’s = L4
Penis: S2,3,4 keep your penis off the floor
How does regeneration typically occur following Wallerian degeneration?
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
What can happen if regeneration following Wallerian degeneration goes wrong?
Formation of traumatic neuroma -> abberent regeneration forms a tumor-like mass of nerve fibers, Schwann cells, and scar tissue
Other than Wallerian degeneration, what are two other neuronal pathologies which can occur to peripheral nerves?
- Axonal dystrophy -> distal axonal degeneration, also called dying back neuropathy
- Segmental demyelination -> damage or loss of myelin internodes along length of axon, also called hypertrophic neuropathy (see later)
What neurons are particularly affected in distal axon degeneration and how do they appear?
Particularly the longest axons
- > distal ed will appear swollen
- > will lead to a progressive loss of axons overtime
