Musculoskeletal Flashcards
Which muscle fibres are initially recruited with slow exercise and how does the fibre type change as exercise speed or intensity increases?
During slow exercise Type 1 fibres and a small number of Type 2a fibres predominate. As the speed or duration increases more fibres will be recruited in the order of Type 1, Type 2a and Type 2x.
What is percussion myotonia?
When a muscle holds its contraction for several seconds after percussion.
Regardless of the cause of rhabdomyolysis the final pathway is cell death due to what?
Aberrant calcium cycling
What are the general mechanisms by which aberrant calcium cycling/calcium accumulation occurs?
- Energy pathways that generate ATP for the Ca pump can be impaired
- Ca pump or channels aren’t functioning adequately
- Cell membranes becomes damaged.
Histologically how can you differentiate neurogenic from myogenic muscle atrophy?
Neurogenic: involves Type 1 and Type 2 fibres, characterised by small, angular atrophied fibres.
Myogenic: fast-twitch fibres predominantly, characterised by anguloid atrophy.
List differentials for muscle fasciculations.
- Nerve root irritation
- Electrolyte abnormalities
- Weakness
- Fatigue
- Anxiety
- Cold
- Ion channel defects within the sarcolemma causing abnormal propagation of muscle cell depolarisation
What is the normal time to peak concentration and half-life of CK, AST and LDH in cases of muscle damage?
CK: Peaks within 4-6 hours, declines to normal within 48 hours unless elevation is above 100,000 iu/L in which case it may take relatively longer to return to normal. Endurance rides may cause increase between 1000-4000iu/L and prolonged recumbency without myopathy can result in increase to 3000iu/L.
AST: Peaks within 24 hours, not muscle-specific, plasma half-life is 7-10 days (some sources say 7-8) so can take weeks to return to normal.
LDH: Peaks within 24 hours and half-life is intermediary between CK and AST - probably around 7 days. Not muscle specific.
What is a reasonable exercise response test in a fit and an unfit horse to provoke subclinical exertional rhabdomyolysis?
Fit horse: walk for 3 mins then trot for 12 mins
Unfit horse: alternate between 2 mins walking, 2 mins trotting. Should see less than 3 fold increase (most healthy horses show no change at this level).
Which electrolytes should be measured as part of examination for mod-severe rhabdomyolysis or disease with muscle fasciculations as a feature?
Na, K, Ca, Cl and P
In cases of atypical myopathy/hypoglycin A toxicity, what is the expected urine pH?
Acidic.
Specific muscle groups are indicated for biopsy as a diagnosis of certain diseases - which ones are these?
- EMND: Sacrocaudalis dorsalis medialis muscle
- Hypoglycin A: Diaphragm and deep postural muscles
- Recumbency from severe rhabdomyolysis: deep pelvic muscles such as iliopsoas
- Immune-mediated myositis (eg in QH): gluteal or lumbar biopsy or biopsy of an atrophied muscle.
What are the normal and abnormal findings on EMG (specifically denervation, electrical conduction defects, and myopathic changes)?
Normal muscle: regular wave patterns suggesting adjacent motor units are being recruited.
Denervation: abnormal spontaneous electrical activity in the form of fibrillation potentials and positive sharp waves.
Electrical conduction defects: complex repetitive discharges or myotonic discharges
Myopathic changes: decreased duration and amplitude of motor unit action potentials.
What are the typical histologic findings with repetitive overtraining?
Increased muscle fibre size variation and centrally displaced myonuclei in muscle biopsies.
What are the recommended provisions of dietary electrolytes for horses exercising in hot humid conditions or sweating excessively?
30-50gNaCl/day
15-25g light salt containing KCl/day
Ca : P ratio of 2:1
What treatments may be indicated for acute rhabdomyolysis?
- Rest (don’t transport for 24-48hrs) and increased susceptibility to re-injury for 2 weeks after an acute episode.
- IVFT and address electrolyte and A/B derangements (typically hypo Na & Cl and hyper K and often alkalotic)
- Anxiolytics such as ACP may help; also increases blood flow through vasodilation
- Analgesia with NSAIDs (caution if dehydrated due to risk of renal damage, particularly with concurrent pigmenturia), Dom/Torb may also be used as analgesics if required.
- IV or enteral DMSO may help as an antioxidant, anti-inflammatory and osmotic diuretic
- Methylprednisolone succinate once.
- Muscle relaxants such as methocarbamol may have variable results.
- Dantrolene may decrease release of Ca from the SR which may help reduce further aggravation of muscle contraction and necrosis but is contraindicated in HYPP due to increases in K concentration
List examples of chronic exertional myopathies
- RER
- Malignant hyperthermia
- PSSM (type 1 and type 2)
- Idiopathic exertional rhabdomyolysis
- Mitochondrial myopathy
- Myofibrillar myopathy
- Fibrotic Myopathy.
What is the classic signalment of horses with RER and during what kind of exercise are episodes most likely to occur?
- Typically nervous temperament, SB and TB over-represented, young females over-represented
- Often exercise is preceded by a day or two of rest
- Usually occurs when exercise is restricted/the horse is held back (rarely occurs in horses allowed to freely gallop, hence not associated with lactic acid)
True or false: 2yo fillies have bigger fluctuations in their CK values than 3yos?
True
True or false: Abnormal amylase resistant polysaccharide has not been identified in horses with RER but increased sub-sarcolemmal amylase sensitive glycogen has been?
True.
What are the rest recommendations with horses with ER?
If sporadic ER, rest until CK normalises
With RER daily exercise should continue to prevent further episodes (only when CK <3000iu/L).
If CK >3000iu/L then a brief period of rest may be indicated.
What are the exercise recommendations to minimise the risk of further episodes of ER?
Interval training and reduction of job miles to <15min/session will benefit SBs
For ridden horses a relaxed warm-up with intermittent long and low stretching and regular breaks to stretch.
What are the nutritional recommendations for horses with RER?
- Less than 20% of the DE should be supplied by NSC (low glycaemic diets help with a calmer demeanour and low pre-exercise HR)
- At least 20% of DE should be supplied by fat (high-fat diet is less about changing the muscle metabolism and probably more about reducing anxiety and excitability which are closely linked to RER).
- Low-quality hay is less of an issue with TBs than QH due to less pronounced insulinemic response to high NSC hay.
- As lactic acidosis is no longer thought to be associated with RER supplements that reduce lactic acidosis are not indicated.
What additional therapeutics can be used to reduce the impact/severity of RER?
- ACP pre-exercise to reduce excitement
- Reserpine and fluphenazine have longer effects although fluphenazine has been associated with extrapyramidal effects
- Dantrolene may reduce [Ca] and decrease signs of rhabdomyolysis (significantly lower CK 4 hrs post-exercise in horses given dantrolene 1 hr before exercise)
- Phenytoin may help prevent rhabdomyolysis by its effects on ion channels (including Na and Ca channels). However, can cause drowsiness and ataxia at high doses so therapeutic monitoring and maintenance of 8ug/mL in blood is advised. * is a monoaminoxidase activator so affects [plasma] other drugs.
What is the affected gene and mode of inheritance of malignant hyperthermia and which breeds are affected?
- Exon 46 of the skeletal muscle ryanodine receptor 1 gene (RYR1)
- Autosomal dominant mutation
- QH and paints
What does the RYR1 defect do in cases of malignant hyperthermia?
Lowers the activation and heightens the deactivation threshold of the ryanodine receptor which intermittently can result in a dramatic efflux of Ca from the sarcoplasmic reticulum, increasing cyotplasmic Ca and producting a contracture. Anaerobic glycogen metaboilsm is activated, lactate is produced and excessive heat is generated and massive muscle necrosis ensues.
What are the common triggers for malignant hyperthermia and what concurrent defect may exacerbate the signs?
Rhabdomyolysis may be induced by exercise or anaesthesia (typically halothane anaesthesia). Exacerbated by a concurrent mutation of the GYS1 gene causing PSSM1.
What are the clinical signs and cause of death in horses with malignant hyperthermia?
- Hyperthermia (if develops during anaesthesia discontinue immediately and begin active cooling)
- Hypercapnoea
- Acidosis (treat with NaHCO3 if develops)
- Haemoconcentration, increase Ca, P, glucose and creatinine
- Death from cardiopulmonary arrest
True or false: muscle biopsy is often not that useful in diagnosis of malignant hyperthermia
True.
What treatments may be useful in malignant hyperthermia, particularly if anaesthesia is necessary?
Dantrolene 30-60 minutes before anaesthesia (unless they concurrently have HYPP in which the increased K with dantrolene makes in contraindicated).
What is the GYS1 gene associated with, how is it inherited and which condition is this a feature of?
Associated with increased amylase-resistant polysaccharide in skeletal muscle.
It is an autosomal dominant misense mutation resulting in higher than normal activity of glycogen synthase both at basal states and when activated by glucose-6-phosphate.
The GYS1 gene has been associated with PSSM1
In which breeds is PSSM1 common?
- European drafts but less commonly Shires or Clydesdales
- Irish Draught, Cob and Connemara
- QH, particularly halter horses (Type 1 accounts for 72% of QH with PSSM)
- WB (Type 1 accounts for 18%)
- Low prevalence in light breeds
True or false: No temperament, body type or gender predilection exists for PSSM1?
True
True or false: Signs of PSSM1 most commonly occur after strenuous exercise, particularly if exercise occurs every day.
False.
Most common at walk and trot, particularly after several days of rest.
What are the distinctive features of PSSM1 on histology?
Numerous subsarcolemmal vacuoles and dense crystalline period acid-schiff (PAS) positive and amylase resistant inclusion in fast-twitch fibres.