Musculoskeletal Flashcards
In healthy individuals, MHC Ag are not usually detected on the sarcolemma. In cases of immune mediated myositis, is MHC expressed?
MHC I and II expression occur in mature nondegenerate myofibers of horses with IMM in conjunction with a phase of active lymphocytic infiltration, findings that together support an immune‐mediated etiology for the disease. Unlike IMM, MHC expression in specific myofibers of PSSM horses occurs in the absence of lymphocytic infiltrates. Because the degree of MHC sarcolemmal expression varies in IMM‐affected horses and also is present in horses with PSSM, MHC staining alone is not diagnostic for IMM in horses.
10.1111/jvim.14371
Describe immune mediated myositis in horses, biochemical changes and histology changes.
Rapid and diffuse symmetrical muscle atrophy, predominately of gluteal and epaxial muscles. Lethargy and stiffness. Increases in CK and AST. Histology shows mononuclear cell infiltration of predominately CD4+, with lymphocytes and myonecrosis. May be an autoimmune disease, possibly related to bacterial or viral origins.
10.1111/jvim.14637
What is the prognosis of immune mediate myositis in horses?
IMM horses have a favorable prognosis, but those with concurrent disease and/or fever.
10.1111/jvim.14637
Research has shown that initiation of hypothermia before the onset of either sepsis or lameness provided some inhibition to inflammatory signaling in lamellar samples. Was the same true with initiation of hypothermia at the onset of lameness?
The lack of inhibition of inflammatory mediators in lamellar tissue samples in the current study, when evaluated in conjunction with the degree of lamellar protection provided by cryotherapy in the same study subject, indicates that the protective effects of digital hypothermia may not be mediated through inflammatory pathways.
10.1111/jvim.14633
What interleukin cytokine has consistently been shown to have the greatest increases in lamellae in different models of sepsis-related laminitis?
IL-6
10.1111/jvim.15027
What mutation has been strongly associated with immune mediate myositis in Quarter Horses?
An E321G mutation in MYH1 Subsequent sequencing of genes within the associated locus identified a missense mutation in a highly conserved region of MYH1 that segregated with disease status.
10.1111/jvim.15299
Is the E321G MYH1 mutation prevalent in horses presenting with nonexertional rhabdomyolysis (nonER) regardless of whether or not horses presented with or without muscle atrophy?
In conclusion, the E321G MYH1 mutation is strongly associated with nonER in QH‐related breeds whether or not generalized muscle atrophy is present. Because most nonER horses with the MYH1 mutation did not present with muscle atrophy or have lymphocytic infiltrates in muscle biopsy samples, we suggest that the term MYH1 myopathy (MYHM) be applied specifically to horses with atrophy or rhabdomyolysis that test positive for the MYH1 mutation. This term rather than IMM for horses with this genetic mutation eliminates the confusion about whether the underlying mechanism for rhabdomyolysis and atrophy is immune‐mediated and distinguishes those inflammatory or immune‐mediated myopathies that are not caused by the MYH1 mutation.
10.1111/jvim.15299
What is SERCA and how does it play a role muscle contraction?
SERCA is the sarcoplasmic reticulum calcium transporting ATPase. After contraction, SERCA induces muscle relaxation by catalyzing the transport of 2 Ca2+ ions into the lumen of the SR using the free energy from hydrolysis of 1 ATP molecule. Phospholamban (PLN) inhibits SERCA activity and is primarily expressed in cardiac and slow twitch muscle fibers.
10.1111/jvim.15425
What are some transmembrane regulators of SERCA? How might they play a role in recurrent exertional rhabdomyolysis?
Sarcolipin (SLN), first discovered in 1974 as a peptide that copurifies with SERCA, was subsequently found to decrease the Ca2+ affinity of SERCA and decrease the energetic coupling efficiency of SERCA (Ca2+/ATP transport ratio <2), thereby decreasing SR luminal Ca2+ stores.
Dwarf open reading frame has been shown to enhance SERCA activity in the mouse heart by displacing PLN.
A decrease in SLN and MRLN or increase in DWORF expression could increase SR Ca2+ stores by decreased SERCA inhibition (ie, decreased Ca2+ affinity), thereby acting to increase calcium release channel (RYR1) Ca2+ release and myoplasmic Ca2+ concentration during contraction and potentially leading to clinical manifestations of RER.
10.1111/jvim.15425
Do the coding sequences for several sarcoplasmic transmembrane regulators differ between recurrent exertional rhabodomyolysis and control horses?
Mutations in the coding sequences of SLN, MRLN, or DWORF were not identified in TB, STD, or QH horses with RER.
10.1111/jvim.15425
Discuss some differences between vitamin E-responsive myopathy (VEM) and EMND.
VEM - mitochondrial stains show “moth-eaten” staining pattern in muscle fibers and preponderance of anguloid rather than angular muscle fiber atrophy; anguloid are common with myogenic atrophy and characterized by concavity on >/= 1 side; horses can regain their muscle mass and return to previous level of performance within 3 months; could be a precursor to EMND
EMND - angular atrophy is smaller fiber size with pronounced triangular shape
10.1111/jvim.15643
