immune med muscle disorders review Flashcards
one of primary infectious agents that incite acute rhabdomyolysis
Streptococcus equi
causing infarctive purpura hemorrhagica (IPH), and immune-mediated myositis (IMM)
Pathophysiology of infective purpura hemorrhagica
usually have had an infection within the past month, often with S. equi or a strangles vaccination.
often QH
In susceptible horses, the immune response results in high antibody titers to the SeM protein (>1:1600) and SeM-IgA immune complexes.
Equine immune-mediated myositis predominantly happens in
Quarter Horses and related breeds (Paints, Appendix horses, and Appaloosas)
How many horses have a history of infection when presenting with immune med myositis?
Of affected horses, 39% have a history of being recently exposed to a “triggering factor” such as S. equi infection, a respiratory virus
which muscles are affected with immune mediated myositis
rarely generalized, and there is a
predilection for the gluteal and epaxial muscles
while other muscles such as the semimembranosus and semitendinosus muscles are relatively unaffected.
which protein is specifically expressed with immune mediated myositis?
MHC histocomp complex on muscle cells
treatment and prognosis of IMM
Anti-inflammatory doses of corticosteroid for approximately 1 month
combined with antibiotics if infection is present are often successful in halting muscle atrophy.
Muscle mass will regenerate over weeks to months, and horses can make a full recovery.
Almost 50% of horses will have recurrent episodes of muscle atrophy.
A specific genetic defect and mode of inheritance have only been identified for which muscular diseases?
A specific genetic defect and mode of inheritance have only been identified in
hyperkalemic periodic paralysis [3],
glycogen branching enzyme deficiency [7], and
malignant hyperthermia
malignant hyperthermia - which gene?
malignant hyperthermia in Quarter Horses with a mutation in the calcium release channel of the skeletal muscle sarcoplasmic reticulum, RyR1 gene
hyperkalemic periodic paralysis -gene?
hyperkalemic periodic paralysis in Quarter Horses caused by a mutation in the a-subunit of the skeletal muscle sodium channel, SCN4A gene
glycogen branching enzyme 1 deficiency- gene?
glycogen branching enzyme 1 deficiency in Quarter Horse and Paint foals due to a mutation in the glycogen branching enzyme 1, GBE1 gene
Glycogen branching enzyme deficiency
fatal autosomal-recessive (only homozygot carriers affected) disease of Quarter Horses and Paint Horses caused by
Y34X missense mutation at codon 34 in exon 1 (C to A substitution at position 102 of coding sequence) of the glycogen branching enzyme 1 (GBE1) gene
How many horses carry glycogen branching enzyme…
Approximately 8% of Quarter Horses and Paint Horses are carriers of GBED
which part of dead foal provides diagnosis of GBED
Cardiac Purkinje fibers appear to consistently contain amorphous PAS-positive globular inclusions in affected foals
not always present in skeletal muscle
PSSM most affected breeds?
Quarter Horses and related breeds (Paints and Appaloosas), draught horses (mainly Belgians and Percherons), and Warmbloods
histopath diagnosis of PSSM?
presence of PAS-positive inclusions in muscle biopsies that are resistant to amylase digestion (
Treatment of PSSM
Studies by Valberg and collaborators have shown that affected horses benefit from a combination of
daily regular exercise,
free exercise on pasture, and
dietary modification: includes high-fat (13%) and low starch (<10%) content of daily digestible energy
when does malignant hyperthermia set off?
volatile anesthetics such as halothane,
depolarizing muscle relaxants such as succinylcholine,
and stress
pathophysiology of malignant hyperthermia
mutations in the RyR1 gene cause
dysfunction of the calcium release channel of the sarcoplasmic reticulum in skeletal muscle,
resulting in excessive release of calcium into the myoplasm and a hypermetabolic state characterized by
intense heat,
hypercapnea,
lactic acidosis, and
in many cases, death
diagnosis of malignant hyperthermia
difficult
muscle looks histolog normal
all ages and breeds
Recurrent exertional rhabdomyolysis (RER) is the most prevalent muscle disease in
TB horses
It has been estimated that 5–10% of racing Thoroughbreds develop exertional rhabdomyolysis during a racing season with recurrences of up to 17%
cause of RER
autosomal-dominant mode of inheritance with variable expression .
Recurrent Exertionl Rhabdo is believed to be caused by an abnormality in intracellular calcium regulation, and not by lactic acidosis
increased serum CK activity 4–6 h postexercise
Pathophysiology of HYPP and clinical signs
4% of the Quarter Horse population may be affected
SCN4A gene mutation
- increased resting membrane potential,
- failure of a subpopulation of sodium channels to inactivate following depolarization, and
- excessive inward flux of sodium and outward flux of potassium
>>>resulting in persistent depolarization of muscle cells
Muscle hyperexcitability results in muscle tremors, fasciculations, and weakness that can progress to paralysis when muscle cells become persistently depolarized
what triggers HYPP?
Diets high in potassium (>1.1%) such as alfalfa, soybean, molasses, electrolyte supplements, and kelp-based supplements commonly trigger episodes
Lab diagnostics in HYPP
hyperkalemia (6–9 mmol/L; reference 3–5.6 mmol/L), mild hyponatremia, and hemoconcentration [74]. Serum CK is within reference values or may be mildly elevated a few hours post-episode.
e no specific histopathological findings in skeletal muscle
