Chap 27- Peripheral nerves and skeletal muscles Flashcards
structure of skeletal muscles
bundle of muscle fibers -> muscle fiber -> myofibril -> actin and myosin
fascia
- CT covering entire muscle
- located over layer of epimysium
epimysium
- CT that wraps around whole muscle
- continuation of tendon
perimysium
- covers each bundle of muscle fibers
endomysium
- CT that wraps each individual muscle fiber
sarcolemma
- cell membrane of muscle fibers
excitation contraction coupling
- electrical impulse triggers release of Ca from SR
- ACh is released at NMJ
- muscle contraction occurs
common characteristics of NMJ diseases
- painless
- weakness
myasthenia gravis
- autoantibodies against ACh receptors causes aggregation and degradation of receptors
- bimodal age distribution young females or older males
- leads to reduced muscle contractions
myasthenia gravis clinical features
- progressive generalized weakness exacerbated by exertion
- weakness starts at eyes
- can have focal muscle weakness if anitbodies against different parts
- highly linked to thymic disorders
lambert-eaton myasthenic syndrome
- antibodies against presynaptic Ca channel
- causes repetitive stimulation of muscles
- weakness in lower extremities then moves up
- usually have underlying malignancies
why is LEM associated with cancer?
- antibodies are formed against cancer cells
- antibodies are similar to Ca channels
neurogenic disease atrophy
- clusters or groups of fibers are atrophied
perifascicular atrophy
- atrophy on periphery of muscle bundle
- seen in dermatomyositis
type II fiber atrophy
- seen in prolonged corticosteroid use
dermatomyositis
- autoimmune disease
- proximal muscle weakness and skin changes
- can also affect joints, esophagus, lungs
- happens in children and older adults
clinical features of dermatomyositis
- proximal muscle weakness
- myalgia
- elevated CK
- heliotrope rash
- gottron papules
- dysphagia
- lung disease
what are gottron papules?
- scaling eruptions on knuckles, elbows and knees
- characteristic of dermatomyositis
pathogenesis of dermatomyositis
- autoimmune attack against endothelium of capillaries
- activates complement system -> MAC formation
- endothelial necrosis -> cytokine recruitment
- adhesion molecules expressed
- CD4 cells and macrophages bind to adhesion molecules
- ischemia
polymyositis
- dx of exclusion
- lacks distinctive cutaneous features
- adult onset
- proximal muscle weakness and myalgia
- can involve other systems
what are the main inflammatory . mediators of polymyositis?
CD8+
inclusion body myositis
- disease of late adulthood
- slowly progressing muscle weakness of distal muscles
- no autoantibodies
- debate on if it is primary or secondary disease
what are inclusion bodies?
abnormal protein aggregates inside muscle cells
chloroquine toxic myopathy
- drug induced lysosomal storage myopathy
- inhibits autophagy
- presents with slowly progressive muscle weakness
ICU myopathy
- degredation of sarcomeric myosin thick filaments
- produces profound weakness
- commonly occurs due to corticosteroid use
thyrotoxic myopathy
- acute or chronic proximal muscle weakness
- excess thyroid hormone inhibits AChI
- causes muscle fatigue due to too much activity
hypothyroidism myopathy
- cramping or aching muscles
- decreased movement
- slowed reflexes
alcohol myopathy
- binge drinking can cause rhabdo, myoglobinuria, renal failure
- causes direct muscle fiber lysis
congenital myopathy
- defect in excitation- contraction coupling unit
- seen at birth
- mostly nonprogressive
- normal CK levels
muscular dystrophy
- sx present typically later in life
- membrane damage causes necrosis
- progressive weakness
- elevated CK levels
muscular dystrophies with defects in extracellular matrix
- ullrich congenital MD
- merosin deficiency
duchene MD
- mutation in dystrophin
- x-linked
- severe progressive phenotype
- no inflammation except myophagocytosis
what does dystrophin typically do?
- mechanical stability to myofiber and cell membrane during contraction
- defects causes influx of Ca
clinical features of DMD
- normal at birth
- pseudohypertrophy
- weakness begins in pelvic girdle then extends to shoulders
- joint contractures, scoliosis, worsening respiratory reserve, sleep hypoventilation
- heart and brain problems
limb girdle muscular dystrophy
- muscle weakness that preferentially involves proximal muscle groups
- age and severity highly variable
myotonic dystrophy
- autosomal dominant
- myotonia
- muscle weakness, cataracts, endocrinopathy, cardiomyopathy
pathogenesis of myotonic dystrophy
- expansion of CTG triplet repeats in DMPK gene
- DMPK is important in RNA splicing leading to defective chloride channels
- muscle cannot easily relax
spinal muscular atrophy
- loss of motor neurons
- causes weakness and atrophy of voluntary muscles
- autosomal recessive
- affects muscles closest to center of the body
what causes spinal muscular atrophy?
- loss of function mutation in SMN1 gene
what is the hallmark of spinal muscular atrophy
- generalized hypotonia -> floppy infant
classifications of diseases of lipid/glycogen metabolism
- exercise or fasting -> muscle cramping/pain and rhabdo
- slowly progressive muscle damage
carnitine palmitoyltransferase II deficiency
- most common disorder or lipid metabolism
- causes episodic muscle damage when exercising or fasting
- impairs transport of FFA into mitochondria
myophosphorylase deficiency
- aka McArdle disease
- common glycogen storage diseases affecting skeletal muscle
- causes episodic muscle damage with exercise
Acid maltase deficiency
- impaired lysosomal conversion of glycogen to glucose
- causes glycogen to accumulate in lysosomes
- tx with enzyme replacement therapy
types of acid maltase deficiency
- severe= Pompe disease
- mild = adult onset myopathy
mitochondrial myopathies manifestations
- weakness
- elevated serum creatine kinase levels
- rhabdo
- chronic progressive external opthalmoplegia common- clue for dx
- maternally inherited
pathologic change seen in mitochondrial myopathies
- abnormal aggregates of mitochondria
- found in subsarcolemmal area of affected myofibers
- looks like ragged red fibers
ion channel myopathies
- affects fn of ion channel proteins
- manifestation depends on channel affected`
broad classifications of ion channel myopathies
- increase excitability -> hypertonia
- decreased excitability -> hypotonia -> hyperk/hypok/ normok -> periodic paralysis
KCNJ2
- potassium channel mutation -> hypokalemia
- causes andersen-twail syndrome
- period paralysis
- heart arryhthmias
- skeletal abnormalities
SCN4A
- Na channel mutation
- presents as many differet disorders i.e. myotonia or hyperk periodic paralysis
CACNA1S
- Ca channel mutation
- most common cause of hypokalemic paralysis
CLC1
- Cl channel mutation
- causes myotonia congenita
RYR1
- mutation affecting Ca sensitive Ca channels
- RYR causes release of Ca into cytoplasm from SR
- causes malignant hyperthermia
Axons
projection that transmits impulses away from cell body
dendrites
projection that transmits impulses toward cell body
terminal boutons
bulges at end of axon that communicate with neurons, muscle fibers, or glands
myelin sheath
surrounds axons and increases rate of impulse transmission
schwann cells
produce myelin sheath
nodes of ranvier
separate schwann cells
synapes
- gap between neurons
- made up of presynaptic terminal, synaptic cleft, and postsynaptic cell membrane
some causes of peripheral nerve damage
- inflammatory diseases
- infections
- metabolic changes
- toxic injury
- trauma
- paraneoplastic disease
- inherited gene defects
Guillain- Barre Syndrome (GBS)
- demyelinating peripheral neuropathy
- ascending paralysis
- can affect respiratory muscles
GBS pathogenesis
- associated with certain infections or prior vaccination
- T cell mediated immune response causes segmental demyelination that is induced by macrophages
- circulating Ig react with peripheral nerves
GBS clinical features
- ascending paralysis
- areflexia
- sensory involvement- loss of pain sensation
- slowed nerve conduction
- elevated CSF due to increased permeability of microcirculation
what is the most common cause of peripheral neuropathies?
diabetes
pathogenesis of diabetic neuropathy
- hyperglycemia -> glycosyation -> decreased protein fn and activated inflammatory signaling
- excess glucose -> conv to sorbitol -> increased ROS -> nerve damage
clinical features of diabetic polyneuropathy
- numbness, loss of pain sensation, paresthesia, dysestheisa
- difficulty with balance
- ANS dysfunction
- postural hypotension
- sexual dysfunction
- incomplete bladder emptying
