Muscle
mitochondrial myopathy - what is affected, sx, findings on microscope
"OX phos" diseases mtDNA or nuclear DNA eye weakness ragged red fibers due to agg of mt appear like a parking lot structural abnormalities
Perifascicular atrophy - seen in
Dermatomyositis
creatine kinase - where is it found; elevated levels associated with
muscle enzyme found in skeletal and cardiac muscle and brain; elevated blood levels associated with heart attack, muscular dystrophy, and other skeletal muscle pathologies (muscle damage)
ICU myopathy - what is deficient, assoc w this drug, area of mm weakness (p or d)
myosin-deficient myopathy; usually with corticosteroid therapy; proximal > distal weakness with flaccid mm
dermatomyositis - where are telangiectasias found
nail folds, eyelids, gums
Fiber type grouping
neuron/axon drop out; fewer nerves innervate fibers leading to larger motor units (fibers per neuron)
are muscle fibers grouped by type normally?
no
Statin-induced myopathy (Toxic myopathy) - Ab, sx
no autoantibodies; flu-like sx that are worse at PM
type 1 muscle fiber mnemonic
one (1) slow, fat (lipid rich), red (high Mb) ox (oxidative)
dermatomyositis - can be a _____ syndrome
paraneoplastic (breast and lung)
when would you see type II fiber atrophy sparing type I fibers (what drug)
prolonged corticosteroid use
inclusion body myositis - loss of muscle in
quads (calves are bigger)
hypotonia
reduced muscle tone or tension
Epimysium
surrounds entire muscle
dystrophin glycoprotein complex
this complex provides scaffolding for sarcomeres; important to muscular dystrophies
can myasthenic syndromes be congenital
yes
fasicle
bundle of muscle fibers
fiber hypertrophy
an increase in the size of existing individual muscle fibers; response due to inc load
Botulism mechanism of action
blocks Ach release from presynaptic neurons
muscle fasicle
bundle of muscle fibers
dermatomyositis - common x ray finding in kids
calcinosis: Ca++ depositis in subq tissue
besides statins, what other drugs can cause toxic myopathies; EM presentation
chloroquine and hydroxychloroquine; curvilinear bodies on EM
botulism - nerves affected and sx
cranial except I and II (no muscles); blurred vision, ptosis
Ullrich congenital muscular dystrophy
defect in collagen VI (ECM defect)
merosin deficiency (CMD)
defect in merosin (ECM defect)
lipid or glycogen myopathies - defects in what 2 systems
defects in carnitine system and mtDH enzyme system
most common inflammatory myopathy in kids
dermatomyositis
segmental muscle necrosis
destruction of a portion of the fiber length
MD female carrier
dilated cardiomyopathy (not in BMD), LV dilation by echo, elevated CK, weakness
CMD - ECM receptor abnormalities - what is defective
dystroglycan
Arthrogryposis
fixation of many joints in a flexed or contracted position
Dystroglycan
forms a large complex with dystrophin, other adapter proteins, and signaling molecules that links the actin cytoskeleton to the surrounding matrix
floppy baby differential dx
generalized hypotonia congenital myotonia/myopathy encephalopathy (brain) spinal muscular atrophy
Spinal Muscular Atrophy on histology
genetic disorder characterized by severe muscle weakness in infancy and progressive respiratory failure enlarged fibers have retained motor innervation
muscle regeneration - what cells are involved
*Satellite cells* reconstitute destroyed muscle
Malignant hyperthermia - triggers, inheritance, genes, treatment, etiology
Autosomal-dominant trait characterized by often fatal hyperthermia in affected people exposed to certain anesthetic agents (succinylcholine) (releases too much Ca from SR, ATP is made with nowhere to go, so heat is generated) RYR1 gene treatment: dantrolene
Ethanol myopathy: binge drinking leads to acute ______ with accompanying ________, which may lead to ______ failure
Binge drinking of alcohol produces an acute toxic syndrome of rhabdomyolysis with accompanying myoglobinuria, which may lead to renal failure
congenital myopathies vs MD vs congenital MD - which has CNS involvement, which has distinct structural abnormalities
Congenital myopathies: • Typically present in infancy • Often associated with distinct structural abnormalities Muscular dystrophies: • Progressive muscle weakness • Often comes to attention after infancy Congenital muscular dystrophies • Present in infancy • often have CNS involvement
Perimysium
Connective tissue surrounding a fascicle
Endomysium
Connective tissue surrounding a muscle fiber
Gower's sign
Difficulty rising to standing position; has to walk up legs using hands; occurs in Muscular dystrophy; weakness of *proximal muscles*
muscular dystrophy
group of hereditary diseases characterized by degeneration of muscle and weakness
immune-mediated necrotizing myopathy (IMNM) - often associated with this auto-Ab, this drug
HMGCR Ab (HMG CoA reductase) many cases associated with statin drug exposure (NOT the same as statin toxic myopathy)
Dystrophin
Links thin filaments to proteins of sarcolemma (surrounds fibers of muscle)
SMA genetics, inheritance
LoF of SMN1 (AR)
grouped atrophy - what it is; suggestive of
Loss of a *motor neuron* leads to *atrophy* of associated muscle. Suggestive of neurogenic disease
hypothyroidism myopathy - presentation, CK, atrophy of
head ptosis due to proximal mm weakness; elevated CK; fiber atrophy
Inclusion body myositis - age, muscles affected, classic histology, lymphs, antibodies associated, protein inclusion types, injury site, CK levels
Mainly seen in people 50+. Begins with weakness of distal muscles (extensors of the knee and flexors of the wrist and fingers) and presents with *rimmed vacuoles* (lysosomes), β-amyloid & tau protein inclusions. It's also CD8+ and anti-cN1A+. injury site: endomysium, myocyte CK: modest increase
Thyrotoxic myopathy - presentation, classic findings
Presents most commonly as an acute or chronic proximal muscle weakness that may precede the onset of other signs of thyroid dysfunction note goiter and EO
Limb Girdle Muscular Dystrophy
Proximal muscles of pelvis and shoulder initially affected. Difficult to get out of chairs, climb stairs, waddling gait, reaching over head, carry heavy things, outstretched arms = difficult AD, AR many due to DGC
Hypotonic Channelopathies ________, _________, and ___________ periodic paralysis
hypokalemic, hyperkalemic, and normokalemic periodic paralysis (K levels)
hyperplasia
increase in number of cells
Ion channel myopathies - features (2), also includes this disease
This group of familial diseases feature myotonia, relapsing episodes of hypotonic paralysis (induced by vigorous exercise, cold, or a high-carbohydrate meal), or both. also include malignant hyperthermia (hyperpyrexia)
Hypokalemic periodic paralysis - triggers, example
Triggers: carbohydrate rich meals, rest after exercise, rarely cold temperatures goats that just drop randomly
myotonia
a neuromuscular disorder characterized by the slow relaxation of the muscles after a voluntary contraction
muscle fiber
a single, multinucleated muscle cell with repeating sarcomere units
Facioscapulohumeral muscular dystrophy - areas and clinical findings
affects the face, upper arms, and scapular region. winged scapula