Pathophysiology of muscle disease Flashcards
Types of muscle dz
- Exertional
- Non-exterional
Exertional muscle dz
Acquired:
- ‘tying-up’
Genetic:
- PSSM-1
- PSSM-2
- RER
- HYPP
- Myofibrillar myopathy
Non-exertional muscle dz
Acquired:
- Toxic: AM
- IMM
- Traumatic: atrophy
- Infectious: Clostridium spp
Genetic:
- MH
- Mitochondrial myopathies
- IMM
Other names for sporadic rhabdomyolysis
- tying-up
- monday-morning disease
- rhabdomyolysis
- azoturia
What is the most common muscular disorder in horses?
- Sporadic rhabdomyolysis
Sporadic rhabdomyolysis - CS
- stiff
- stilted gait
- excessive sweating
- increase respiratory rate after exercise
- firm painful muscles (hindquarters, back)
- reluctant to move
forward - occasional dark urine
Causes of sporadic rhabdomyolysis
- overexertion
- dietary imbalances
- exhaustion
Overexertion causing sporadic rhabdomyolysis
- increase in work intensity without a strong musculoskeletal foundation Z- disk instability
- overstretching of myofibers
- sarcolemma stretching
Dietary imbalance causing sporadic rhabdomyolysis
- Electrolytes (Na and Ca) both important in neural transmission and muscle contraction
- Low Vitamin E intake: poor antioxidant state
Exhaustion causing sporadic rhabdomyolysis
TB and endurance horses training in hot, humid weather: electrolytes loss in sweat and dehydration
What is RER
= recurrent exertion rhabdomyolysis
- intermittent form of rhabdomyolysis in horses likely linked to abnormal calcium regulation in myofibres
– SERCA receptor dysfunction?
Prevalence of RER
- 5% TB
- 6.5% SB
RER risk factors
➢ Fit horse with nervous temperament»epinephrin/adrenaline release?
➢ Young mares more at risk, but no associated with oestrus cycle
➢ Lack of turnout
➢ Held back during gallop: epinephrin and cortisol release?
What does the SERCA receptor do?
- allows removal Ca from sarcoplasm leading to relaxation
What does the RYR-1 receptor do?
- allows release of Ca to stimulate contraction
How does adrenaline affect the RYR-1 receptor?
- it increases it’s activity
What is PSSM-1?
= polysaccharide storage myopathy 1
➢Abnormal storage of glycogen in muscle fibres difficult to be metabolized by muscle cells
➢Genetic mutation in GY1: Glycogen synthase enzyme turn on constantly: PSSM-1
➢A subset of cases: amylase sensitive glycogen»>PSSM-2»>Myofibrillar myopathy & PSSM-2
Prevalence of PSSM-1
➢Highest in continental European draft breeds
➢Percheron Belgians
➢Shires and Claydesdales low in UK: Irish draft, Connemaras, Cobs present
➢Quarter horses (28%), Appaloosas (10%)
➢Very rare in light breeds: SB, TB, Arabians
PSSM-1 risk factors
➢breed and exercise of more than 20min in one session
➢Owner perception : high quality grass available
What do both PSSM-1&-2 cause?
- a myofibrillar myopathy (oxidative deficit)
PSSM-1 breeds & clinical presentation
➢Most draft horses are asymptomatic
– unless performance drafts
➢Stiffness after a short period of exercise
–reluctance to move forward, poor performance, sweating or more severe clinical signs: myoglobinuria
➢Mean age at diagnosis 4-8 years-old
What is PSSM-2?
➢Big box of muscle conditions with some accumulation of glycogen
– likely different aetiologies and/or mutations
Prevalence of PSSM-2
➢ 28% QH or American breeds
➢ Other light breeds such as Friesians, Selle francais, Morgans, Appaloosas, Arabs, occasional TB
PSSM-2 CS
- more subtle with poor performance mainly, milder elevation of muscle enzymes post exercise
Myofibrillar myopathy
➢ No always associated with severe increase in muscle enzymes (Arabs»»WB)
➢ Abnormal Desmin protein unable to support Z-disk: contractile apparatus dysfunction> fibrillar rupture
➢ Cysteine metabolism deficiency: core pathway for cytoplasmatic anti-oxidants
Myofibrillar myopathy presentation / presenting signs
➢ Poor performance
➢ Lack of hindlimb engagement
What is HYPP?
= hyperkalaemic periodic paralysis
➢ Na channels are ‘leaky’ : prolonged depolarization and abnormal action potentials
➢ High K might precipitate episodes: high sensitivity to small variations in K
Prevalence of HYPP
➢Quarter Horse and QH derived breeds: QH Impressive stallion lines»SCN-4A gene
HYPP CS
➢ Sporadic attacks of stiffness, muscle tremors, weakness and collapse
➢ Breathing difficulties: Paralysis of laryngeal muscles»stridor
➢ Prolapse of third eyelid
What is equine atypical myopathy?
❖Toxic rhabdomyolysis associated with Hypoglycin A ingestion (from sycamore)
❖Myofibrillar metabolic impairment of aerobic metabolism
– Postural muscles
– Intercostal muscles
– Myocardium
Outbreak presentation of equine atypical myopathy
- Autumn & Spring: toxic plant material on pastures
Mortality rate of equine atypical myopathy
- 68%
What do we know about Hypoglycin A?
➢Naturally occurring amino acid found in some trees of Sapindaceae family (including Acer) with unknown function in plants
– Deterrent to avoid herbivore consumption?
– Or Growth factor important for plant development?
➢Not believed to be toxic per se: clearance as free molecule by liver, however, becomes toxic once metabolised in the mitochondria:
– toxicity might be dose related?
Equine atypical myopathy CS
▪ Stiffness, muscle fasciculations, weakness, sweating and myoglobinuria (~90%)
▪ Colic, tachycardia, tachypnea, recumbency, distended bladder, reduced/Absent GI sounds
▪ Dysphagia (25%)
▪ Cardiorespiratory arrest -> euthanasia
Immune mediated myopathy causes
- Normally associated with previous respiratory infection (Strep. infections, viral (Flu and EHV), Corynebacterium)
- Purpura haemorrhagica
- Streptococcal myopathy
- QH immuno-mediated myopathy
Purpura haemorrhagica
- 10 days after S. equi infection» severe vasculitis with muscle infarction
Streptococcal myopathy
- occurs at the same time that classical strangles sings: stiffness and recumbency
QH immuno-mediated myopathy
- Precipitated by respiratory infection (Strepp +++)
- Lines predisposed genetically: MYI mutation makes myosin chaines (2Xa) similar to Strep prot M»_space; recgonised by immune system: molecular mimicry
- Lethargy, rapid muscle atrophy epaxial and rump muscles
Myonecrosis
➢ Most common due to Clostridium spp, but other anaerobic bacteria might be involved
– Clostridum perfringes
– Clostridium septicum
➢ IM injections or puncture wounds NSAIDs and Vitamins most common
➢ Occur 6-72 hours post injection: cervical musculature, gluteal and thigh muscles
Myonecrosis CS
- fever
- stiffness
- severe pain
- gangrene
- crepitation
