Skeletal muscle

Question 1

myopathy

Answer 1

disorder of muscle

Question 2

muscular dystrophy

Answer 2

inherited disorder

progressive muscle weakness and wasting

Question 3

Muscle regeneration

Answer 3

satellite cells reconstitute destroyed muscle

Question 4

fiber hypertrophy

Answer 4

response to increased load

Question 5

myotonia

Answer 5

tonic spasm of one or more muscle; also a condition characterized by such spasms

Question 6

hypotonia

Answer 6

deficient tone or tension

Question 7

arthrogryposis

Answer 7

fixation joints in an extended or flexed position

Question 8

creatine kinase (CK; CPK)

Answer 8

enzyme highly concentrated in muscle and brain

Question 9

Gower’s sign

Answer 9

weakness of proximal muscles

uses the hands and arms to walk up from a squatting position

Question 10

Type 1 fibers

Answer 10

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

Question 11

Type 2 fibers

Answer 11

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

Question 12

Innervating motor nuerons detrmines muscle types

Answer 12

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

Question 13

Denervation atrophy

Answer 13

disorder of motor neurons

breakdown of myosin and actin

resoption of myofibrils

Question 14

Spinal muscular atrophy (infantile motor neuron disease; SMA): description, types, and genetics

Answer 14

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

Question 15

Muscular dystrophy: description and pathology

Answer 15

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

Question 16

Duchenne MD (DMD): etiology, gene

Answer 16

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

Question 17

DMD clinical

Answer 17

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

Question 18

Becerk MD

Answer 18

defect in dystrophin quality/quantitiy of protein from abnormal gene at Xp21

less common than DMD

less severe than DMD

later onset than DMD

Question 19

Limb girdle muscular dystrophy

Answer 19

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

Question 20

facioscapulohumeral MD

Answer 20

facial weakness

wasting of the upper arm and shoulder msulces

the scapular bones look like wings when the arms are raised

Question 21

Emery dreifuss MD

Answer 21

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

Question 22

myotonic dystrophy: pathlogy and clinical features

Answer 22

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

Question 23

myotonic dystrophy: other clinical findings and genetics

Answer 23

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

Question 24

Ion channel myopahties types

Answer 24

channelopathies mutations in ion channels

familial

myotonia and or hypotonic paralysis

malignant hyperpyrexia

Question 25

Hypotonic channelopathies: hypokalemic periodic paralysis:

Answer 25

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

Question 26

Hypotonic channelopathies: other

Answer 26

hyperkalemic periodic paralysis normokalemic periodic paralysis

Question 27

malignant hyperpyrexia: etiology and trigger

Answer 27

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

Question 28

maliganant hyperpyrexia: pathology and tx

Answer 28

release C2+ from sarcoplasmic reticulum atp is depleted by muscle contraction anaerobic metabolism hyperthermia rhabdomyolysis hyperkalemia renal failure TX: dantrolene

Question 29

Congenital myopathies: age of discovery, presentation

Answer 29

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)

Question 30

Central core disease

Answer 30

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.

Question 31

nemaline myopathy

Answer 31

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

Question 32

centronuclear (myotubular) myopathy

Answer 32

various types: x linked, autosomal dominant, autosomal recessive central nuclei usually confied to type 1 fibers

Question 33

lipid myoapthies

Answer 33

accumulate lipid in myocytes defects in carnitine transport system defects in mitochondrial dehydrogenase enzyme system

Question 34

mitochondrial myopathies

Answer 34

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

Question 35

inflammatory myopathies

Answer 35

infectious: trichnella spiralis noninfectious: dermatomyositis, polymyositis, inclusion body myositis systemic inflammatory diseases: systemic sclerosis (scleroderma) and sarcoidosis

Question 36

Dermatomyositis: presentation. Other areas affected.

Answer 36

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

Question 37

dermatomyositis: associations. and juvenile version.

Answer 37

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.

Question 38

dermatomyositis vascular description and immune description

Answer 38

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

Question 39

polymyositis

Answer 39

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.

Question 40

inclusion body myositis: age, description of disease, and deposits

Answer 40

>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.

Question 41

inclusion body myositis other types and description

Answer 41

hereditary variants rimmed vacoles +/- amyloid deposits inflammation centered on myocytes

Question 42

thyrotoxic myoapthy

Answer 42

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.

Question 43

hypothyroidism myopathy

Answer 43

cramping/aching muscle; slow movements slow reflexes proximal weakness eg posterior neck elevated CK fiber atrophy

Question 44

ethanol myopathy

Answer 44

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

Question 45

drug induced myopathies (3 drugs)

Answer 45

steroid myopathy: proximal weakness: atrophy of predominately type 2 fibers chloroquine myopathy: proximal weakness. Vacuoles in myocytes Statins: 1.5% of users.

Question 46

ICU myopathy

Answer 46

profound weakness associated with corticosteroid therapy degraded myosin thick filaments

Question 47

myasthenia gravis: etiology and signs.

Answer 47

neuromusclar junction disease: immune mediated loss of acetylcholine receptors. Circulation anti AchR. decreased ACHrs thymic hyperplasia thymoma (an epithelial neoplasm)

Question 48

myasthenia gravis: clinical presentation

Answer 48

often begins with extraocular muscle weakness: drooping eyelids, diplopia. may present with generalized weakness weakness variable from minute to minute

Question 49

Myasthenia gravis: electrophysiology

Answer 49

decremental decrease in muscle response to repeated stimulus

Question 50

Myasthenia gravis: tx

Answer 50

thymectomy, anticholinesterase, predinisone, plasmapheresis

Question 51

myasthenia gravis: tenselon test

Answer 51

short acting anticholenestrase.

Question 52

lambert eaton myasthenic syndrome: etiology. associations. description.

Answer 52

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