Path: Neuromuscular Flashcards
What are the major types of skeletal muscle?
type 1= slow twitch - higher oxidative enzyme and mitochondrial content, sustained action
type 2 = fast twitch (2 subtypes) - higher glycogen and glycolytic enzymes, short bursts
determined by ant spinal motor neuron that innervates
How does normal muscle activate?
depolarization spreads along sarcolemma and T tubules - Ca released from SR due to DHPR/ryanodin receptor rxn - Ca exposes myosin binding sites on actin and myosin binds - fueled by ATP, conformational change in myosin leads to myofilament contraction - binding of fresh ATP permits dissociation of myosin
What role do dystrophins have?
help with translation of myofilament shortening into movement
What are the basics of skeletal muscle biopsies?
can stain for enzyme activity or membrane associated proteins
fresh frozen section
can also paraffin fix or use EM
mostly quads, delt, biceps, gastrocnemius - avoid end stage or sites of injections
What are the two broad categories of muscle disorders?
skeletal muscle fiber atrophy (type 2 and denervation atrophies)
myopathies = intrinsic muscle abnormality
What is amyotrophic lateral sclerosis?
= Lou Gherigs dz
progressive destruction of both UMN and LMN, denervation atrophy, weakness accompanied by spasticity, sometimes cognitive abnormalities
What morphologic changers are seen with amyotrophic lateral sclerosis?
degeneration of corticospinal tracts (pallor here in myelin stain)
What are the basics of inflammatory myopathies and what are two examples?
non-inf immune mediated attack - autoantibodies
polymyositis, dermatomyositis
What are other muscle diseases that may be associated with inflammation and why is it important to distinguish them?
inclusion body myositis, some muscular dystrophies, infectious myopathies
don’t want to subject pts to unecessary immunosuppressives
What are some exogenous agents that can cause toxic myopathies?
therapeutic agents (STATINs!)
some herbal meds
illicit/recreational drugs
conventional toxins (CO)
What is the range of manifestations seen in toxic myopathies?
asymptomatic elevations in CK to life threatening rhabdo
What types of proteins are implicated in muscular dystrophies?
proteins linking contractile apparatus to ECM
proteins that stabilize myofiber cell membrane
What are the basics of dystrophin?
encoded by largest gene in genome Xp21
different isoforms expressed in different tissues
large size makes it vulnerable to mutations
What are dystrophin related muscle diseases and what causes their pathology?
mutations in dystrophin or promoter regions def likely leads to destabilization of cell membrane and myofiber injury (esp during contraction)
What are congenital myopathies and what is one example?
myopathies with specific prototypic morphological change and minimal fiber destruction - classification based on morphology
central core dz
