Muscle disease Flashcards
Define rhadomyolysis
lysis of mm fibres
What is Equine Rhabdomyolysis Syndrome?
mm cramping/ pain that occurs usually during or following exercise
Other names - Equine Rhabdomyolysis Syndrome
- monday morning disease
- set-fast
- azoturia
- myoglobinuria
- tying up
Presentations of Equine Rhabdomyolysis Syndrome
- ACUTE; may require tx, possibly emergency
- BETWEEN EPISODES: in a horse that has had several / multiple episodes (requires investigation of cause)
CS - Equine Rhabdomyolysis Syndrome - during episode
- stiff movements
- pain
- sweating
- tachycardia
- myoglobinuria
- plasma CK and AST
- r/o other dz
What is CK?
Creatine Kinase (NOT creatinine kinase)
Urine appearance -Equine Rhabdomyolysis Syndrome
coke coloured (myoglobinuria) but doesn’t have to look like this
How do plasma CK and AST change during a bout of Equine Rhabdomyolysis Syndrome?
See graph
Tx - acute exertional rhabdomyolysis
- analgesics (NSAIDs, opiates)
- IV/oral fluids
- diuretics (to maintain urine output in attempts to prevent/minimise nephrotoxic effects of myoglobin.
- avoid NSAIDs in severe myoglobinuria as both cayse renal damage so risk of acute renal failure
How is myoglobin nephrotoxic?
causes epithelial cells in renal tubules to slough off –> renal tubular cast
Dx - exertional rhabdomyolysis b/w episodes
EXERCISE TEST: do 20 mins lunge exercise, trot and canter, take pre and post 6 hour exercise CK measurement. >100% rise in CK significant, some individuals may be significant if 20% rise, some vets also measure AST
Aetiology - exertional rhabdomyolysis
- ACQUIRED
- INHERITED
Outline acquired exertional rhabdomyolysis
- OVEREXERTION: eccentric contraction, metabolic exhaustion, oxidative injury
- electrolyte imbalance
- hormones?
- infxn
Outline inherited exertional rhabdomyolysis
- recurrent exertional rhabdomyolysis d/t defective Ca regulation
- polysaccharide storage myopathy
What to consider in horse that undergoes repeated episodes of tying up
- consider acquired cases and if possible rule ou
- inherited causes more likely (certain acquired causes ay precipitate an attack in a genetically susceptible animal)
2 forms of genetic repeated exertional rhabdomyolysis
- recurrent exertional rhabdomyolysis of TBs
- polysaccharide storage myopathy (PSSM1)
Outline recurrent exertional rhabdomyolysis (RER)
- defect in Ca regulation
- small group of (related) TBs in USA
- unknown is all TBs with RER have same defect
- unknown if similar disorder occurs in other breeds (likely)
- commonest in young nervous fillies
- approximately 5% TBs affected
Prevention - RER
- Oral dantrolene: a Ca release channel blocker, for TBs with presumed Ca homeostasis problem
- High fat/ low carbohydrate problem: rice bran, vegetable oil, commercial
- Regular exercise/ turnout
Outline PSSM1
- affects QH, warmbloods, drafts, cobs, others
- heritable (autosomal dominant)
–> exertional rhabdomyolysis - occasionally mm atrophy/ weakess in drafts
- high prevalence in some draft breeds (>50%)
- abnormality of glucose metabolsim
= mutation in glycogen synthase gene in skeletal mm - mostly subclinical
What is glycogen synthase?
enzyme to form 1-4 links b/w glucose monomers to form glycogen
Outline DNA test for PSSM1
- blood (in EDTA) or hair pluck
- some horses with characteristic pathology don’t have the mutation - ‘PSSM2’
Dx - PSSM1
- DNA test
- mm biopsy (internalised nuceli non-specific but suggestive of myopathy, polysaccharide inclusions detected by PAS stain which stains glycogen pink)
Tx = PSSM1
- high fat, low carbohydrate diet (as RER)
- daily/regular exercise
- if necessary start with just hand walking and increase gradually every day
What is exhausted horse syndrome?
- a type of exertional rhabdomyolysis syndrome
- usually associated with long rides, often in hot, humid conditions, especially relatively unfit animls
- endurance rides/ races
- 3 day eventing/ cross country
- hunting
What happens in an exhausted horse? 3
- glycogen depletion from mm
- electrolyte loss from sweat
- hypovolaemia
CS - exhausted horse
- depression
- dehydration, anorexia, decreased thirst
- increased RR and HR
- pyrexia
- poor sweating response
- poor jugular distension, increased CRT, decreased pulse pressure
- decreased gut sounds
- laminitis
- synchronous diaphragmatic flutter (‘thumps’)
- mm pain and stiffness
Describe synchronous diaphragmatic flutter/ thumps
- subtle
- abdominal mm contract regularly –> flank twitch (often in time with heart as phrenic nn picks up vibrations from heart mm contractions)
- associated with hypocalcaemia
Tx - exhausted horse
- IV/oral fluids, supplement with electrolytes if necessary
- rapid cooling, misting tents
- NSAIDs
- check for evidence of rhabdomyolysis (CK and AST)
Prevention - exhausted horse
- training, heat acclimatisation
- free access to water and administer electrolytes during ride
- frequent veterinary checks
Which dogs are affected by rhabdomyolysis?
- exercising Sled dogs and greyhounds (likely slighly different dz as endurance vs. sprint)
- CS: myoglobinuria, elevated CK, hyperthermia, renal failure
Other names - coccygeal mm injury
- limber tail
- cold tail
- rudder tailed
Breeds affected by coccygeal mm injury
working breeds - labs, pointers etc
What is coccygeal mm injury?
- pain at tail base
- mild CK eleveation
- recovery over severeal days
- cold, exercise, swimming,
- prolonged cage transportation
Tx - coccygeal mm injry
- rest
- NSAIDs
What does Ryanidine Receptor 1 (RYR1) do?
allows Ca to leave SR –> cytoplasm to allow mm contraction
Name 3 channelopathies
- Sarcolemmal sodium pump
- Ryanodine receptor (RYR1)
- Calcium ATPase
What does sarcolemmal sodium pump channelopathy affect??
–> hyperkalaemic periodic paralysis
What does RYR1 channelopathy do?
–> MH in:
- mixed breed dogs
- landrace pigs
- QHs
(mutation causes Ca to stay at high levels in cell –> cell membrane breaks down. Pork –> PSE = pale, soft and exudative)
What does Calcium ATPase channelopathy do?
–> congenital pseudomyotonia in Chianina cattle (mm remain contracted all the time)
What is myostatin?
important paracrine hormne that is inhibitory to mm growth. A TGF-b protein
What do mutations in myostatin cause?
- Belgian Blue and Piedmontese cattle (mutation in both myostatin alleles –> double mm appearance where the mm fibres are huge, not actually 2 of each mm)
- Bully Whippets (heterozygotes for myostatin and run faster so popular in racing)
- Baby superman (son of olympic athlete)
- racehorses (variations in myostatin gene make horses particularly well suited to either sprint or endurance racing, tests for this £1000)
What happens with a mm strain injury?
- overstretching of mm –> fibre disruption –> inflammation and healing with fibrosis
- mild ot severe (complete rupture)
- recovery rapid - low grade injuries
- fibrous tissue may predispose to reinjury or contracture
- Dx: palpation and US
What is fibrotic myopathy in horses?
- common in QH
- semitendinosus usually affected, sometimes semimembranosus or gracilis
- -> characteristic gait (affected HL smacks down on floor)
- CAUSES: mm tear, IM injection, neuropathy
Tx - fibrotic myopathy
- rest
- NSAIDs
- sx resection of fibrous tissue or tenotomy
What is atypical myopathy?
- acute onset severe myopathy in horses at pasture
- fat accumulation in cardiac and skeletal mm
- CK and AST massively increased
- mm biopsy pre or post-mortem (triceps, intercostal, diaphragm)
- v high mortality (cardiac arrhythmias, weak diaphragm)
What is acyl CoA dehydrogenase important for?
fat breakdown
Cause - atypical myopathy?
- associated with ingestion of hypoglycin A (found in seeds of box elder tree - USA, sycamore tree - UK).
- metabolite MCPA is a potent inhibitor of acyl-coA dehydrogenase (fat breakdown)
Tx - atypical myopathy
- all speculative
- riboflavin (vitamin B2 supplementation)
- carnitine supplementation (protein that helps shuttle fat into mitochondria)
- support carbohydrate metabolism (insulin, glucose)
Dx - atypical myopathy
- mm biopsy
- urine/plasma acyl carnitine, organic acids, hypoglycin measurement?
Which animals are affected by muscular dystrophies?
- DOGS - golden retrievers, others
- CATS - sphynx/ Devon Rex
- Humans - DMD
Dx - muscular dystrophies
- usually with IHC
Cause - mm dysrophies
- 65% DMD patient have out-of-frame deletions
- Becker MD have in frame deletions
- n.b. these are both human diseaes
