Fig. 22.4C2 ). Atrophic myofibers can be reinnervated by axonal branches from adjacent motor units, increasing the size of these motor units and returning trophic input to the atrophic myofibers (
Fig. 22.4C3 ). Multiple rounds of denervation and reinnervation result in a dwindling number of motor units of increasingly larger size. In this setting loss of innervation will therefore produce large clusters of atrophic myofibers, grouped atrophy (
Fig. 22.4C5 ). Because
Fig. 22.3 Thedystrophin-glycoproteincomplex(DGC).Thiscomplexofglycoproteinsservestocouplethecellmembrane(thesarcolemma)toextracellularmatrixproteinssuchaslaminin-2andtheintracellularcytoskeleton.Akeysetofconnectionsismadebydystrophin,ascaffoldingproteinthattethersthemyofibrillarcytoskeletontothetransmembranedystroglycansandsarcoglycans,andalsobindssignalingcomplexescontainingdystrobrevin,syntrophin,neuronalnitricoxidesynthetase(nNOS),andcaveolin.MutationsindystrophinareassociatedwithX-linkedDuchenneandBeckermusculardystrophies;mutationsincaveolinandthesarcoglycanproteinswithautosomallimb-girdlemusculardystrophies;andmutationsinα2laminin(merosin)withaformofcongenitalmusculardystrophy.
Table 22.2 Muscle Fiber Types
EnergymetabolismLowglycolyticHighglycolyticcapacity,highcapacity,lowoxidativecapacityoxidativecapacity
MyosinheavychainMYH7 MYH2,MYH4,geneexpressed http://ebooksmedicine.net
Fig. 22.4 Patternsofskeletalmuscleinjury.(A)Normalskeletalmusclehasrelativelyuniformpolygonalmyofiberswithperipherallyplacednucleithataretightlypackedtogetherintofasciclesseparatedbyscantconnectivetissue.Aperimysialinterfascicularseptumcontainingabloodvesselispresent(top center).
(B)Myopathicconditionsoftenareassociatedwithsegmentalnecrosisandregenerationofindividualmyofibers.Necroticcells(B1–B3)areinfiltratedbyvariablenumbersofinflammatorycells.Regenerativemyofibers(B4,arrow)arecharacterizedbycytoplasmicbasophiliaandenlargednucleoli(notvisibleatthispower).(C)Neurogenicchanges.(C1)Thisdiagrammaticrepresentationoffournormalmotorunitsshowsacheckerboard-typeadmixtureoflightanddarkstainedfibersofoppositetype.(C2)Damagetoinnervatingaxonsleadstoalossoftrophicinputandtheatrophyofmyofibers.(C3)Reinnervationofmyofiberscanresultinaswitchinfibertypeandsegregationoffibersofliketype.Asillustratedhere,reinnervationisalsooftenassociatedwithanincreaseinmotorunitsize,withmoremyofibersinnervatedbyanindividualaxon.(C4)NormalmusclehasacheckerboarddistributionoftypeI(light) andtypeII(dark) fibersonthisATPasereaction(pH9.4),correspondingtofindingsin(A).(C5)Clusteredflattened“angulated”atrophicfibers(grouped atrophy) areatypicalfindingassociatedwithdisruptedinnervation.(C6)Withongoingdenervationandreinnervation,largeclustersoffibersappearthatallsharethesamefibertype(fiber type grouping).