Non-Inflammatory Muscle Pathology Flashcards
Widespread muscular necrosis is called ____
rhabdomyolysis
In terms of location, muscular necrosis can be ____ or ____
widespread or segmental (localized)
Cells around the outside of muscle cells that maintain the muscle cell are called ____
satellite cells
Explain the steps of segmental regeneration of muscle
- injury to m. fiber causes segmental disintegration of sarcoplasm
- macrophages accumulate & penetrate the basement membrane to phagocytose sarcoplasmic contents
- activated satellite cells proliferate forming myoblasts
- macrophages leave w/ debris
- myoblasts align in center of fiber and begin to fuse
- fiber continues to regenerate until normal (up to 6mo)
Name 3 non-inflammatory muscle pathologies
- Rhabdomyolysis
- Duchenne muscular dystrophy
- Becker muscular dystrophy
What is the etiology of Rhabdomyolysis?
skeletal muscle trauma
(also side effect of statin drugs)
What happens to muscle in Rhabdomyolysis?
diffuse, widespread, varying degrees of necrosis & regeneration of muscle fibers
How long can Rhabdomyolysis last?
can be acute, subacute, or chronic (eg. exercise induced compartment syndrome)
What will a biopsy of Rhabdomyolysis show?
clusters of macrophages in and around muscle fibers
(sarcoplasmic contents poured into circulation)
What are the risk factors for Rhabdomyolysis?
- Drugs: statins (eg. for hypercholesterolemia), cocaine, amphetamines
- trauma (crushing inj), severe exertion
- metabolic myopathies
- alcoholism
- heat intolerance/stroke
- influenza (muscle soreness = cell lysis)
What are the clinical manifestations of Rhabdomyolysis?
- swelling, tenderness, & ++ weakness in mm
- fatigue
- joint pain
- diffuse muscular pain
- ^creatinine kinase, K+, creatine in blood
- myoglobinuria –> acute renal failure
Why might patients with Rhabdomyolysis present with joint pain?
Hilton’s law
not a joint problem, but shared innervation with involved muscles
How would Rhabdomyolysis affect urine?
Myoglobinuria (myoglobin dumped into urine) causing tea-coloured urine
What causes acute renal failure in patients with Rhabdomyolysis?
myoglobin dumped into urine damages kidneys
What are the possible treatments for Rhabdomyolysis?
- early & aggressive hydration to prevent kidney damage
- diuretics
- address hyperkalemia & low blood Ca2+ levels
- prognosis varies depending on extent of kidney damage
Are muscular dystrophies cureable?
No, they are progressive
What are the general muscle characteristics of muscular dystrophies?
- fiber necrosis w/ regeneration (imbalanced)
- progressive fibrosis (eventual loss of contractility)
- infiltration by fatty tissue (marbling)
- no inflammation
What form(s) of muscular dystrophy is/are seen in pediatric patients?
X-linked: Duchenne & Becker
What form(s) of muscular dystrophy is/are seen in adults?
Myotonic dystrophy
What is the etiology of Duchenne muscular dystrophy?
- X-linked recessive inheritance (passed by mother)
- Xp21 gene mutation = no dystrophin produced
What sex is primarily affected by Duchenne muscular dystrophy?
males
(only 1 X chromosome to mutate; not likely to survive to reproduce)
What is the function of dystrophin?
- links sarcolemma (m. cell mem.)to muscle cell fibers
- transfers force from fibers to membrane
Describe the pathogenesis of Duchenne muscular dystrophy
- lack of dystrophin influences ^influx of Ca2+ (hypercontraction) & release of soluble m. enzymes (eg. creatine kinase) into serum
- breakdown of sarcolemma –> necrosis & repair
- progressive m. fibrosis
- necrosis > repair
- m. fibers replaced by fibrofatty CT
- late stage: extrafusal fibers disappear
Duchenne muscular dystrophy primarily affects ____ fibers, but ____ fibers are still numerous
extrafusal; intrafusal/spindle
What are the clinical manifestations of Duchenne muscular dystrophy?
- pseudohypertrophy of calves
- ^serum creatine kinase
- abnormal m. morphology in utero
- developmental/intellectual delays by 2-3yrs of age
- m. weakness by 3-4yrs (hips & shoulders initially)
- toe walk; waddling gait
- hyperlordosis & scoliosis
- falling, difficulty running/jumping/stairclimbing & getting up from floor
- GI issues (less motility; smooth m)
What is pseudohypertrophy of the calves?
muscle fibers replaced by fibrofatty CT in calves, causing appearance of hypertrophied calf muscles
(Duchenne MD)
Where does muscle weakness begin in Duchenne muscular dystrophy?
Pelvic (hip) and shoulder regions
What are the typical outcomes of Duchenne muscular dystrophy?
- wheelchair bound by age 10
- bedridden by age 15
- death occurs due to respiratory insufficiency (diaphragm) or cardiac arrhythmia by age 20
What is the etiology of Becker muscular dystrophy?
truncated dystrophin protein
How does Becker MD compare to Duchenne MD?
- lower quality rather than absent dystrophin
- milder & later onset (better neural function)
What are the clinical manifestations of Becker muscular dystrophy?
- exercise intolerance (m. cramping)
- rhabdomyolysis
- myoglobinuria
Name 3 congenital myopathies
- central core dz
- rod myopathy
- central nuclear myopathy
Congenital myopathies are also called ____
“floppy baby/child syndromes”
(don’t develop head control)
What is the primary symptom of congenital myopathies?
hypotonia
- decreased DTRs
- decreased m. volume
Name an example of a condition with severe hypotonia that results in death within the first year of life
Spinal muscular atrophy (Werdnig-Hoffman Dz)
What is the 2nd most common lethal autosomal recessive condition?
Spinal muscular atrophy
What is the most common lethal autosomal recessive condition?
cystic fibrosis
What is the etiology of Central core disease?
chromosome 19 mutation of gene coding for ryanodine receptors
(autosomal dominant)
What is the function of ryanodine receptors (RyR)?
help control Ca2+ release from SR
Central core disease primarily affects ____ fibers
type I (slow twitch)
How do biopsied muscle fibers appear in Central core disease?
- involved fibers show central area of degeneration
- may resemble fibers in denervating conditions, but no associated denervation present
Central core disease puts individuals at higher risk for ____
malignant hyperthermia
What are the clinical manifestations of Central core disease?
children will become ambulatory but have less than normal muscle strength
What is malignant hyperthermia?
- spike in body temperature occurs after anesthesia
- Rhabdomyolysis or m. damage results from ^Ca2+ release through mutated RyR in SR
How is Malignant hyperthermia treated in patients with Central core disease?
dantrolene (binds to RyR)
What is the etiology of Rod myopathy?
- various mutations, most commonly affecting Nebulin (connects z-line to actin)
Describe the pathogenesis of Rod myopathy
- rod-like inclusions arise from Z-band and accumulate in sarcoplasm
- inflammation & denervation not present
- non-progressive
What are the clinical manifestations of Rod myopathy?
- hypotonia
- delayed motor milestones
- secondary skeletal changes (kyphoscoliosis)
- may involve mm of face, pharynx, neck
- m. degeneration (late onset)
- ^serum creatine kinase
What causes scoliosis in congenital myopathies?
lack of postural tone
What is the best indicator of muscular breakdown on lab findings?
^serum creatine kinase
What is the etiology of Central nuclear myopathy?
autosomal recessive or dominant mutations of dynamin 2
What are the clinical manifestations of Central nuclear myopathy?
facial & extraocular involvement (bilateral ptosis)
What is ptosis?
drooping of upper eyelid
What is the function of dynamin 2?
endocytosis, membrane function & actin assembly
Describe the histologic appearance of Central nuclear myopathy?
single, centrally located nucleus in skeletal m cells
Central nuclear myopathy primarily affects ____ fibers
type I
