Pathophysiology of muscular disorders Flashcards
what are the general categories of muscular disease?
exertional - aquired or genetic
non-exertional - genertic or aquired
What is the most common muscular disorder of horses? what type of disorder is this?
what are the common names for this?
how does it present?
Sporadic Rhabdomyolysis - Exertional
- Other terminology: tying-up, monday-morning disease, rhabdomyolysis, azoturia
- Stiff, stilted gait, excessive sweating, increase respiratory rate after exercise»»firm painful muscles (hindquarters, back), reluctant to move forward, occasional dark urine
What are the causes of exertional sporadic rhabdomyolysis?
- Overexertion: increase in work intensity without a strong musculoskeletal foundation Z-disk instability, overstretching of myofibers, sarcolemma stretching
- Dietary imbalances: Electrolytes (Na and Ca) both important in neural transmission and muscle contraction. Low Vitamin E intake: Poor antioxidant state
- Exhaustion: TB and endurance horses training in hot, humid weather : electrolytes loss in sweat and dehydration
what are the risk factors for Exertional recurrent extertional rhabdomyolysis?
what is this condioton linked to?
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?
Intermittent form of rhabdomyolysis in horses likely linked to abnormal calcium regulation in myofibers –> SERCA receptor dysfunction?
what is the fucntion of the SERCA receptor and the RYR-1 receptor in muscles?
Both have a role in Ca regulation in the muscle
SERCA receptor: allows removal Ca from sarcoplasm leading to relaxation
RYR-1 receptor: allows release of Ca to stimulate contraction - adrenaline further increases RYR-1 activity
What breeds have a higher prevalance of Polysaccharide storage myopathy? why?
what are the risk factors?
what is the pathophysiology?
Prevalence: highest in continental European draft breeds
* Percheron Belgians
* Shires and Claydesdales low in UK: Irish draft, Connemaras, Cobs
* Quarter horses (28%), Appaloosas (10%)
- Very rare in light breeds: SB, TB, Arabians
Genetic mutation in GY1: Glycogen synthase enzyme turn on constantly: PSSM-1
Risk factors: breed and exercise of more than 20min in one session
Owner perception : high quality grass available
pathophysiology: Abnormal storage of glycogen in muscle fibres difficult to be metabolized by muscle cells
There are 2 types of Polysaccharide storage myopathy, 1 and 2? what is the difference?
What are the clinical signs of PSSM 2?
- PSSM-1 is genetic
- Genetic mutation in GY1: Glycogen synthase enzyme turn on constantly: PSSM-1
- PSSM-2 the cause is unknown, and has been renamed to Myofibrillar myopathy: oxidative deficit
- A subset of cases: amylase sensitive glycogen –> PSSM-2 –>Myofibrillar myopathy & PSSM-2
PSSM 2- quatre horse and american breeds (light breeds)
Clinical signs: more subtle with poor performance mainly, milder elevation of muscle enzymes post exercise
what is the clinical presentation of Polysaccharide storage myopathy (PSSM-1)?
- 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 are the clinical signs of Myofibrillar myopathy?
What is it caused by?
How can it be managed?
- No always associated with severe increase in muscle enzymes (Arabs»»WB)
- Poor performance, lack of hindlimb engagement
- Abnormal Desmin protein unable to support Z-disk: contractile apparatus dysfunction> fibrillar rupture
- Cysteine metabolism deficiency: core pathway for cytoplasmatic anti-oxidants
management: provide horse with antioxidants
What horse get hyperkalemic periodic paralysis (HYPP)?
What causes the diease?
what are the clinical signs?
Quarter Horse and QH derived breeds: QH Impressive stallion lines passed genetic mutation, SCN-4A gen
* Na channels are ‘leaky’ : prolonged depolarization and abnormal action potentials
* High K might precipitate episodes: high sensitivity to small variations in K
Clinical signs:
* Sporadic attacks of stiffness, muscle tremors, weakness and collapse
* Breathing difficulties: Paralysis of laryngeal muscles»stridor
* Prolapse of third eyelid
*
What toxic plants can cause non-exertional muscular disorder?
- Eppatorium spp
- Malva parviflora
- Haploppapus spp
- Cassia spp
- box elder (USA and australia)
- Sycamore
What is Equine atypical myopathy accociated with?
what occurs within the body to cause myopathy?
what are the clinicla sizs?
Toxic rhabdomyolysis associated with Hypoglycin A ingestion
Compound is metabolised in mitochondira, the muscle in horses is rich in mitochondia therefore clinical signs in mitochondria - Myofibrillar Metabolic impairment of Aerobic metabolism, Postural muscles, Intercostal muscles, Myocardium
Outbreak presentation: Autumn & Spring: toxic plant material on pastures
Still high mortality rates (68%) ( cardio-respiratory arrest or euthanasia)
Clincial signs: tachycardia, resp diatress, muscle tremors, weakness, low head carriage, sweating, colic (GI stasis), recumbancy
Give three examples of immune mediated non-exertional myopathies that are caused by infection? what pathogens cause these?
Normally Associated with previous respiratory infection : Strep. infections, viral (Flu and EHV), Corynebacterium
Purpura haemorragica: 10 days after S. equi infection» severe vasculitis with muscle infarction
Streptococcal myopathy: occurs at the same time that classical strangles (S. equi) 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; regonised my immune system : molecular mimicry
Lethargy, rapid muscle atrophy epaxial and rump muscles
What fungus is associated with myonecrosis?
How is myonecrosis caused?
what are the clinical signs?
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
Clinical signs: fever, stiffness, severe pain, gangrene, crepitation
