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