Skeletal muscle Flashcards
myopathy
disorder of muscle
muscular dystrophy
inherited disorder
progressive muscle weakness and wasting
Muscle regeneration
satellite cells reconstitute destroyed muscle
fiber hypertrophy
response to increased load
myotonia
tonic spasm of one or more muscle; also a condition characterized by such spasms
hypotonia
deficient tone or tension
arthrogryposis
fixation joints in an extended or flexed position
creatine kinase (CK; CPK)
enzyme highly concentrated in muscle and brain
Gower’s sign
weakness of proximal muscles
uses the hands and arms to walk up from a squatting position
Type 1 fibers
action: sustained
use: endurance standing
color: red
metabolism: oxidative
glycogen: scant
lipids: abundant
mitochondria: many
z band: wide
NADH stain: dark
ATP ase Ph4.2: dark
One slow fat red ox
Type 2 fibers
action: sudden
use: short bursts speed. purposeful motion
color: white
metabolism: oxidative and anaerobic
glycogen: abundant
lipids: scant
mitochondria: few
z band: narrow
NADH stain: light
ATP ase Ph4.2: light
Innervating motor nuerons detrmines muscle types
fiber type grouping: neuron/axon drop out leads to larger motor units (muscle fibers per neuron)
grouped atrophy: loss of a motor neuron leads to atrophy of associated muscle
Denervation atrophy
disorder of motor neurons
breakdown of myosin and actin
resoption of myofibrils
Spinal muscular atrophy (infantile motor neuron disease; SMA): description, types, and genetics
progressive destruction of anterior horn cells and cranial nerve motor neurons.
Type 1: 0.4 months onset with severe hypotonia
type 2: 3 months to 2 years onset
type 3 > 2 years onset, can survive to adult
autosomal recessive: survival motor neuron 1
Muscular dystrophy: description and pathology
inherited disorders
often begin in childhood
progressive muscle weakness and wasting: may affect heart
pathology: variation in fiber size, internal nuclei, degeneration, necrosis, phagocytosis of fibers, later replaced by fibrofatty tissue
Duchenne MD (DMD): etiology, gene
Dystrophin protein defect from abnormal gene at Xp21 (deletion > frame shift or point mutation)
Huge gene (2.3 x 10^6). X linked
most common type of MD: 1/3500 male births
manifest before 5 and in wheel chair by 12
death in 20s
2/3 familial; 1/3 new mutations
DMD clinical
normal at birth
delayed walking then clumsy
weak pelvic then shoulder girlde
pseudohypertrophy of calves as fibers increase size
increased CK; later returns to normal with muscle loss
impaired cognition
death: respiratory failure, cardiac decompenstation, or lung infection
female carriers may have increased CK; risk for cardiomyopathy
Becerk MD
defect in dystrophin quality/quantitiy of protein from abnormal gene at Xp21
less common than DMD
less severe than DMD
later onset than DMD
Limb girdle muscular dystrophy
proximal muscles affected
AD, AR
begin to walk with a waddling gait because of weak hip and leg muscles
trouble getting out of chairs or climbing stairs
weakness in the shoulder make reaching over the head, holding arms, outstretched or carrying heavy objects difficult
many related to dystrophyn glycoprotein complex
facioscapulohumeral MD
facial weakness
wasting of the upper arm and shoulder msulces
the scapular bones look like wings when the arms are raised
Emery dreifuss MD
onset 10-20; triad
early on humeroperoneal weakness (proximal in the upper limbs and distal in the lower limbs)
prominent contractures, especially elbows and ankles
cardiomyopathy
myotonic dystrophy: pathlogy and clinical features
myotonia (sustained involuntary contraction). Stiffness, difficulty releasing grip, can be elicited by percussion of thenar eminence
onset in childhood
other muscle features: abnormal gait from weak foot dorsiflexion, weakness of intrinsic hand and wrist extension, facial muscle atrphy and ptosis
myotonic dystrophy: other clinical findings and genetics
cataracts, endocrinopathy, cardiomyopathy
autosomal dominant: dystrophilia myotonia-protein kinase. CTG repeat expain on 19q. has thousands of repeats and number of repeats expands with generations
anticipation: onset at younger age in succeeding generations
Ion channel myopahties types
channelopathies mutations in ion channels
familial
myotonia and or hypotonic paralysis
malignant hyperpyrexia
Hypotonic channelopathies: hypokalemic periodic paralysis:
most common 1/100,000, Ca2+ channel mutations most common,
Onset: first second decade.
Attacks of flaccid weakness provoked by carbohydrate rich meal, exercise, heat, cold, stress, medications
Hypotonic channelopathies: other
hyperkalemic periodic paralysis
normokalemic periodic paralysis
malignant hyperpyrexia: etiology and trigger
malignant hyperthermia
many identified genes: Ca2+, Ryanodine receptor RyR1 (RYR1)
sudden hypermetabolic state with tachypnea and general muscle contraction
triggered by anesthesia: halogen containg gases or succinylcholine
maliganant hyperpyrexia: pathology and tx
release C2+ from sarcoplasmic reticulum
atp is depleted by muscle contraction
anaerobic metabolism
hyperthermia
rhabdomyolysis
hyperkalemia
renal failure
TX: dantrolene
Congenital myopathies: age of discovery, presentation
defined by pathologic findings on biopsy
onset early in life
nonprogressive or slowly progressive
proximal or generalized weakness
may present as hypotonia (floppy baby) and arthrogryposis (congenital fixation of a joint in an extended or flexed position)
Central core disease
autosomal dominant
hyotonia
ryanodine receptor (RYR1) gene defect
risk for malignant hyperthermia
centrally light area in type 1 fibers
pay attention to histo. Core in center.
nemaline myopathy
NEM various types: autosomal dom and rec.
nonprogressive hyoptonia, weakness
delayed development in kinds
involves proximal limb muscle
subsarcolemmal spindle shaped particles from Z band (alpha actin) material
centronuclear (myotubular) myopathy
various types: x linked, autosomal dominant, autosomal recessive
central nuclei usually confied to type 1 fibers
lipid myoapthies
accumulate lipid in myocytes
defects in carnitine transport system
defects in mitochondrial dehydrogenase enzyme system
mitochondrial myopathies
oxidative phosphorylation disease
defect may be mtDNA or nuclear DNA
many manifestations can present as young adult
ragged red fibers from aggregated mitochondria
mitochondria “parking lot” paracrystalline inclusions
inflammatory myopathies
infectious: trichnella spiralis
noninfectious: dermatomyositis, polymyositis, inclusion body myositis
systemic inflammatory diseases: systemic sclerosis (scleroderma) and sarcoidosis
Dermatomyositis: presentation. Other areas affected.
skin rash precedes or begins with myositis. Lilac or heliotrope discoloration of upper eyelids with periorobital edema. Scaling erythematous eruption or dusky red pathces over knuckles, elbows, knees (grotten lesions)
muscle weakness +/- myalgias. Slow and symmetrical, early proximal muscles; late distal muscles. Dysphagia in 1/3
other: lung disease, vasculitis, myocarditis
dermatomyositis: associations. and juvenile version.
up to 25% have cancer. Paraneoplastic dsyndrome with breast and lung cancer
juvenile DM: in addition GI involved causing abdominal pain. GI vasculopathy leads to ulceration, hemorrhage, and perforation. Calcinosis.
dermatomyositis vascular description and immune description
microvasculature attacked by antibodies and compliment creating ischemia.
Decrease in muscle capillaries.
Telangiectasisas in nail folds, eyelids, gums.
Perifascuicular atrophy: atrophy prominent at periphery of fascicles.
Inflammation in perimysial connective tissue not muscle.
CD4 T cells and B cells
polymyositis
systemic inflammatory myopathy
muscle weakness +/- myalgias. early proximal muscles; late distal muscles. often dysphagia
other: lung disease, vasculitis, myocarditis.
autoantibodies against tRNA synthetases
+/- ANA positive
cytotoxic CD8 t cells in endomysium destroy muscle.
inclusion body myositis: age, description of disease, and deposits
> 50 years begins insidiously: some hereditary
begins with distal muscles: begins quadriceps, wrist and finger flexors. May be asymmetric.
CD8 cytotoxic t cells
intracellular depositis of B amyloid protein, B pleated sheet fibrils, and hyperphosphorylated Tau protein.
inclusion body myositis other types and description
hereditary variants
rimmed vacoles
+/- amyloid deposits
inflammation centered on myocytes
thyrotoxic myoapthy
acute or chronic proximal muscle weakness
may precede signs of thyroid dysfunction
exophthalmic opthalmoplegia: protrusion of the eyballs and diplopia due to orbital edema and contracture of the ocular muscles.
hypothyroidism myopathy
cramping/aching muscle; slow movements
slow reflexes
proximal weakness eg posterior neck
elevated CK
fiber atrophy
ethanol myopathy
acute rhabdomyolysis after a drinking binge
painful
myoglobinuria can lead to renal failure
may be generalized or limited to a group of muscles
may be with alcoholic neuropathy
drug induced myopathies (3 drugs)
steroid myopathy: proximal weakness: atrophy of predominately type 2 fibers
chloroquine myopathy: proximal weakness. Vacuoles in myocytes
Statins: 1.5% of users.
ICU myopathy
profound weakness
associated with corticosteroid therapy
degraded myosin thick filaments
myasthenia gravis: etiology and signs.
neuromusclar junction disease: immune mediated loss of acetylcholine receptors.
Circulation anti AchR.
decreased ACHrs
thymic hyperplasia
thymoma (an epithelial neoplasm)
myasthenia gravis: clinical presentation
often begins with extraocular muscle weakness: drooping eyelids, diplopia.
may present with generalized weakness
weakness variable from minute to minute
Myasthenia gravis: electrophysiology
decremental decrease in muscle response to repeated stimulus
Myasthenia gravis: tx
thymectomy, anticholinesterase, predinisone, plasmapheresis
myasthenia gravis: tenselon test
short acting anticholenestrase.
lambert eaton myasthenic syndrome: etiology. associations. description.
neuromuscular jjunction disorder
usually paraneoplastic, most commonly from small cell carcinoma of the lung
proximal weakness and autonomic dysfunction
antibodies inhibit presynaptic calcium channel and block acetylcholine release
enhanced neurotrasmission with repetatie stimualation
