Lecture 10: Diseases of Muscle Flashcards
(95 cards)
1
Q
What two muscle enzymes are evaluated in rhabdomyolysis muscle diseases and what disease are they elevated in
A
Creatinine Kinase (CK)
Aspartame Aminotransferase (AST)
Elevated in rhabdomyolysis
2
Q
How long is plasma half life for CK and how long does it take to return to normal
A
Plasma half life: <2hrs
Returns to normal 2-3 days later
3
Q
What is the plasma half life of AST and how long does it take to return to normal
A
Plasma half life: 24hrs
Takes 2 weeks to return to normal
4
Q
What disease is also known as “typing up”
A
Rhabdomyolysis
5
Q
What are some clinical signs of Rhabdomyolysis
A
- Stiff, unwilling to move
- Muscle tremors
- Sweating, tachypnea, tachycardia
- Pawing
- Can progress to recumbency
- Wine color urine- myoglobinuria
6
Q
What muscle is good for biopsy
A
Semimembranosus
7
Q
Horse presents as very stiff and muscle biopsy shows amylase resistant glycogen accumulation in muscle fibers. What is likely cause
A
Polysaccharide Storage Myopathy type 1 (PSSM1)
8
Q
Horse presents with muscle stiffness, short stride, muscle fasciculations. What tests do you want to run
A
- CK and AST- baseline
- Exercise tolerance test- to compare CK and AST
- Muscle biopsy
- Genetic testing
- Vitamin E and Selenium levels
9
Q
What is the 5+ panel test for muscle diseases
A
- Polysaccharide storage myopathy type 1
- Malignant hyperthermia
- Hyperkalemic periodic paralysis
- Glycogen branching enzyme deficiency
- Myosin heavy chain myopathy
- Hereditary equine regional dermal asthenia
10
Q
What does the histo for PSSM type 1 look like
A
Increased concentrations of glycogen within the muscle tissue
11
Q
What breeds are predisposed to PSSM1
A
- Stock breeds- quarter horses, paints, Appaloosa
- Drafts and their crosses
12
Q
What pathophysiology of PSSM type 1
A
- Base pair mutation in GYS1 gene
- Gain of function in glycogen synthase combined with increased insulin sensitivity
- Result of large stores of glycogen that are amylase resistant so muscle cells can’t contract
13
Q
What are the diagnostic tests for PSSM1
A
- Genetic test for GYS1 mutation
- Muscle biopsy semimebranosus
14
Q
What is tx for PSSM1
A
- Daily exercise
- Low starch <14%
- High fat >6%
15
Q
What is prognosis for PSSM1
A
Varies from reasonable to excellent
16
Q
What are some signs of PSSM type 2
A
Poor performance, undiagnosed gait abnormality, sore muscles, drop in energy levels
Doesn’t have a typing up appearance like type 1
17
Q
What is the mean onset of PSSM type 2 and what breeds
A
8-11yrs old
Warmbloods >80%
Arabians 100%
18
Q
How do you diagnose PSSM type 2
A
- Abnormal aggregates of periodic acid schiffs positive glycogen within muscle
- Negative for GYS1 mutation
19
Q
Arabian between age of 11-15 years that is extremely fit, ties up mildly. Test muscle enzymes and there is none to minimal elevation. What is likely disease
A
Myofibrillar myopathy
20
Q
Warmblood between 8-10 years old with extremely vague lameness/soreness issues. There are no changes in muscle enzyme elevation. What muscle disease is likely
A
Myofibrillar myopathy
21
Q
How do you dx myofibrillar myopathy
A
Muscle biopsy, semimebranosus or middle gluteal
22
Q
What causes myofibrillar myopathy
A
- Weakness in Z-discs and resulting in proliferation of cytoskeletal proteins
- Desmin is a cytoskeletal intermediate that maintains parallel alignment of the sarcomeres of the Z discs
23
Q
What disease was thought to be PSSM type 2 due to pools of glycogen within the disrupted myofibrils but is actually ___, caused by weakness in Z-discs
A
Myofibrillar myopathy
24
Q
What is tx for myofibrillar myopathy
A
- Exercise
- Amino acid supplements: purina supersport, progressive nutrition topline xtreme
- Feed < 12% NSC
25
What causes over exertion induced rhabdomyolysis
History of increase in work intensity without foundation of consistent training
26
What does light microscopy vs electron microscopy show for overexertion induced rhabdomyolysis
Light microscopy: normal
Electron microscopy: disruption of muscle contractile proteins
27
How much volume do horses lose in sweat
15L/hr
28
What are some clinical signs of exhaustion
Dull, depressed, muscle group spasms, clinically dehydrated, elevated heart and respiratory rate, elevated temperature the thumps
29
What is thumps and what causes it
Hypocalcemia, easily excited muscles so heart and muscles are beating at same time
30
What is the clinical pathology for exhaustion
Hypocalcemia, hypomagnesemia, hypokalemia, hypochloremic metabolic alkalosis, normal CK/AST, but can progress to rhabdomyolysis and multiple organ failure
31
What causes malignant hyperthermia
Autosomal dominant mutation in ryanodine receptor (RYR1) and results in abnormal calcium release within muscles
32
What are some signs of malignant hyperthermia
Increase in body temperature and rhabdomyolysis
33
What can trigger malignant hyperthermia
Exercise or anesthesia
34
How do you dx malignant hyperthermia
Genetic testing
35
What is tx for malignant hyperthermia
Supportive care, avoid anesthesia or pretreat with dantrolene
36
What is prognosis for malignant hyperthermia
Not good
37
What causes recurrent equine rhabdomyolysis
Abnormalities in the regulation of muscle contraction and relaxation
38
What breeds commonly get recurrent equine rhabdomyolysis
Thoroughbreds and Standardbreds
39
How do horses with recurrent equine rhabdomyolysis present
Anxious, lame
40
T or F: fillies are more likely to havre recurrent equine rhabdomyolysis
True
41
What diet to horses with recurrent equine rhabdomyolysis tend to be on
>10lb of sweet feed
42
What is pathophysiology for recurrent equine rhabdomyolysis
Enhanced storage of intracellular calcium in sarcoplasmic reticulum with excessive release during muscle contraction resulting in prolonged depolarization
43
How do you dx recurrent equine rhabdomyolysis
Disease rule out
1. Muscle biopsy normal
2. No genetic test
44
What is tx for recurrent equine rhabdomyolysis
1. Daily exercise
2. Low stress (acepromazine)
3. Low starch <20% calories and high fat >20% calories
4. Muscle relaxants: dantrolene, phenytoin
45
What is a nutritional cause of non-exertional rhabdomyolysis
Vitamin E or selenium deficiency “white muscle disease”
46
How do you dx white muscle disease
1. Test whole blood selenium or glutathione perioxidase
2. Test levels of vitamin E
47
What is tx for white muscle disease
1. Supplement natural source alpha tocopherol 2000 IU/day
2. Supplement selenium 1-3mg/day
48
What causes myosin heavy chain myopathy
Autosomal codominant genetic disorder/ mutation in MYH1
49
What two syndromes does myosin heavy chain myopathy cause
1. Nonexertional rhabdomyolysis
2. Immune mediated myositis
50
__% of quarter horses test positive for myosin heavy chain myopathy
7%
51
__% of reining, working cow, halter horses test positive for myosin heavy chain myopathy
16-22%
52
What is MYHM: immune mediated myositis characterized by
Episodes of severe muscle atrophy following autoimmune event
53
What are some triggering factors for MYHM: immune mediates myositis
1. S. Equi
2. Respiratory disease
3. Vaccination
54
What are some clinical signs for MYHM: immune mediated myositis
Rapid onset muscle atrophy of epaxials and gluteals
55
How do you dx MYHM: immune mediated myositis
Biopsy of muscles reveal lymphocytic vasculitis
56
How do you tx MYHM: immune mediated myositis
Corticosteroids
57
What is prognosis for MYHM: immune mediated myositis
Depends on response but down and unable to stand is grave prognosis
58
What signs are seen with MYHM: non-exertional rhabdomyolysis
Stiffness, swelling of muscles along back and haunches, difficulty rising
59
What causes toxic rhabdomyolysis
1. Hypoglycemia A ingested from Box Elder (acre negunda) trees
2. Ionophores
60
How does hypoglycin A cause toxic rhabdomyolysis
Metabolized to become inhibitor of multiple acyl-CoA dehydrogenases which damages mitochondria and impairs lipid metabolism, results in cell death
61
What are some clinical signs of toxic rhabdomyolysis
Sweating, fasciculations, weakness, recumbency, myoglobinuria, colic, myocardial damage, dysphasia and rhabdomyolysis
62
What is elevated in toxic rhabdomyolysis caused by hypoglycin A
CK/AST/ troponin
63
What is tx for toxic rhabdomyolysis from hypoglycin A
Supportive care
64
What is prognosis for hypoglycin A toxic rhabdomyolysis
Grave, >90% die
65
What is commonly added to ruminant feeds to increase growth, but is very toxic to horses
Ionophores
66
How do ionophores cause rhabdomyolysis
Form lipid soluble complexes with cations to facilitate cation transport across cell walls, excessive influx of calcium and sodium cause swelling and cell death
67
What are some clinical signs of Ionophores toxicity
1. Sudden death within 24hrs
2. Inappetance
3. Tremors
4. Ataxia
5. Stumbling
6. Tachycardia
68
What is prognosis for toxic rhabdomyolysis caused by ionophores
1. If horse survives acute intoxication the damage myocardial and skeletal cells are replaced with fibrosis resulting in permanent dysfunction and will lead to cardiac failure
2. Typically fatal
69
How do you tx acute rhabdomyolysis
1. IV fluids to prevent pigment nephropathy
2. Anti-inflammatories (NSAIDS, steroids)
3. Anxiolytics/muscle relaxation- acepromazine
4. Muscle relaxants: dantrolene, methocarbamol phenytoin
5. Analgesics: butorphanol, alpha 2 agonists
6. Limit exercise
7. Address inciting cause
70
What do you need to use cautiously when tx acute rhabdomyolysis due to renal insult
NSAIDS
71
What disease are steroids absolutely indicated for tx of acute rhabdomyolysis
MYHC causing immune mediated myositis
72
How does dantrolene work
Exhibits muscle relaxation by activity ryanadine R1 receptor antagonist that decrease release of calcium from sarcoplasmic reticulum
73
How does methocarbamol work
Acts on the neurons of the spinal cord and reduce acute skeletal muscle spasm
74
How does phenytoin work
Anticonvulsant action from promotion of sodium effluent from neurons and thereby inhibiting spread of seizure activity
75
What typically causes Clostridial myositis
Intramuscular injection or penetrating wound
76
__environment is essential for Clostridial myositis
Anaerobic
77
What are the toxins for clostridial myositis
Lecithinase, hemolysin, Neuroamindases
78
What are the clinical signs associated with clostridial myositis
Pain, swelling, crepitus, depression, fever, found dead, rapid progression of signs
79
What are the most common bacterial causes of clostridial myositis
1. C. Perfringens type A- most common in horses
2. C. Sordellii- fatal
80
What is prognosis for C. Myositis
Guarded
81
What is the pathophysiology of myotonia
Delayed relaxation of muscle after mechanical stimulation or voluntary contraction, abnormal muscle excitability
82
What are nondystophic myotonas result of
Sarcolemmal ion channel dysfunction
83
What myotonia typically appears in first year of life and doesn’t progress
Myotonia congenital
84
What causes myotonia congenita
Mutation in the gene for the skeletal muscle chloride channel 1 protein (CLCN1)
85
Which myotonia is severe, progressive, and rare
Myotonia dystrophica
86
How do you dx myotonia
1. Electromyographic examinations that show repetitive and high frequency
2. Muscle biopsy in myotonia dystrophica but not congenita
87
What dystrophic changes on muscle biopsy are seen with myotonia dystrophica
Ringed fibers, numerous centrally displayed myonucleis, sarcoplasmic masses, increased endometrial and peri trial connective tissue
Fiber type grouping and atrophy of bot type I and II muscle fibers
88
How do you dx myotonia
1. Genetic testing for new forest ponies
2. PE
3. Clinical pathology- muscle enzymes normal because no rhabdomyolysis
89
How do the muscle enzymes change in myotonia
They dont because this is not rhabdomyolysis
90
What breeds are predisposed to HYPP
Quarter horse, Appaloosa’s, paints and crosses
91
What causes HYPP
Mutation in defective sodium channel genes SCN4A that results in failure to close following depolarization leading to abnormal muscle contraction and paralysis
92
What are some clinical signs of HYPP
Myotonia, muscle fasciculations, muscle cramping, third eyelid prolapse, weakness, recumbency, pharyngeal paralysis
93
What are some clinical pathologies associated with HYPP
1. CSK/AST not elevated- not rhabdomyolysis
2. Hyperkalemia acutely
3. Genetic testing
94
What is tx for HYPP
1. Clients have Karo syrup at home
2. Dextrose IV, Calcium IV
3. Sometimes tracheostomy
4. Reduce potassium diet- avoid alfalfa, orchard, brome, boy bean meal
5. Feed Timothy, Bermuda, oats, corn, wheat, barely, beet pulp, pasture
6. Increase renal potassium excretion with Acetazolamide
95
How does acetazolamide work is what is dose
Potent carbonic anhydrase inhibitor that promotes potassium wasting in urine
Dose: 2-2mg/kg PO q8-12
