Muscle in health and disease

Question 1

main component in muscle

Answer 1

water -80%

Question 2

what is muscle a store for

Answer 2

water + glycogen + intracellular ions (ex: K+)

Question 3

4 functions of skeletal muscle

Answer 3

1. movement
2. maintain posture
3. joint stability
4. generate heat (S.E heat production)

Question 4

Can skeletal muscle repair itself?

Answer 4

YES - has stem cells -able to regenerate muscle fibres- last lifetime - get less efficient with age

Question 5

What are the 2 different types of muscle fibres?

Answer 5

type 1 - slow twitch - RED
type 2- fast twitch - pale pink/WHITE

identify different muscle fibres in a muscle biopsy by ATPase staining

Question 6

What are the different types of type 2 muscle fibres?

Answer 6

type 2a = fastest rate of contraction - AEROBIC - WHITE
type 2b(x)= fast rate of contraction - ANAEROBIC - PINK

Question 7

Name an example of a muscle high in type 1 fibres?

Answer 7

soleus - calf muscle- maintains posture

Question 8

Name a muscle high in type 2a fibres

Answer 8

extraocular eye muscles

Question 9

Name a muscle high in type 2b(x) fibres

Answer 9

GASTROCNEMIUS- calf muscle - knee flexion + plantarflexion = walking/running/posture

Question 10

Review histology of skeletal muscle

1. nuclei
2. size of fibres
3. sarcomere arrangement
4. cell type

Answer 10

1. peripheral nuclei
2. muscle fibre size are all equal
3. sarcomere aligned (striations match up from sacromere-to-sacromere)
4. multinucleate cell- several muscle cells-fuse to 1 - 1 muscle cell runs length of muscle fibre - synchronorous + powerful contraction

Question 11

what is a sarcomere

Answer 11

contractile unit of muscle fibre - made up from contractile filamnetous proteins - ACTIN + MYOISN

Question 12

what is the relation of connective tissue to muscle

Answer 12

C.T is closely related to muscle - forms sheaths around muscle

Question 13

3 places disease can affect in muscle

Answer 13

1. muscle
2. associated C.T sheath
3. NMJ

Question 14

what is epimysium

Answer 14

C.T sheath surrounding muscle (organ)

Question 15

what is perimysium

Answer 15

C.T sheath surrounding FASICLE (group of muscle fibres)

Question 16

what is endomysium

Answer 16

C.T sheath surrounding individual muscle fibre

Question 17

what is a motor unit (MU)

Answer 17

MN + all the muscle fibres it innervates

Question 18

what is the result of loss innervation of a single MN

Answer 18

• loss of innervation to all muscle fibres supplied by the MN
• muscle fibres ATRPOHY + SMALLER + ANGULATED

Question 19

How can muscle fibres be re-innervation following loss of its MN innervation

Answer 19

Remaining, healthy MN sprout to innervate DE-INNERVATED fibres

• MU enlarges
• fibre type grouping
• group atrophy

Question 20

Infantile hypertonia

1. define
2. another name
3. cause - 2 types
4. histological changes
5. prognois

Answer 20

1. decreased muscle tone
2. floppy baby syndrome (test-baby on back- cannot lift head)
3. type 1 fibres larger +small type 2 fibres or vice versa - muscle unable to function properly
4. abnormally small +round muscle fibres & groups of hypertrophic muscle fibres
5. normal LE + QOL + only issue is inability to EXERCISE

Question 21

why is it hard to find a definitive cause for muscular disorders

Answer 21

• symptoms of muscle disorders are vague - muscle pain,weakness, tenderness, twitching fasiculations
• these are symptoms with many differential diangosis

Question 22

4 possible causes for muscular problem

Answer 22

1. neurological problem - MN de-innervation
2. C.T disease
3. drug exposure - statins -rhabdomyolesis -10%patients
4. endocrine disorders - high levels thyroxine/testosterone

Question 23

Name the 3 types of inflammatory myopathies

Answer 23

• polymyositis
• dermatomyositis
• inclusion body myositisi

myo = muscle
itis = inflammation
poly=many
derma=skin

Question 24

INFLAMMATORY MYOPATHIES

• ass with which type of infection?
• 2:1 prevelance females why?
• onset?
• affects which muscle

Answer 24

• microbial
• autoimmune disease more common in females
• 40-60s
• proximal muscles -quads/shoulders/biceps/hip flexors

Question 25

INFLAMMATORY MYOPATHIES - clinical features - 3 diagnostic tests

Answer 25

- symmetrical muscle weakness + pain 1. blood test - elevated creatine kinase levels 2. EMG- spontaneous muscle activity - 90% cases 3. BIOPSY

Question 26

why can serum creatine kinase be used as a marker for muscle disease?

Answer 26

CK - metabolic enzyme in muscles - ATP - normal cond- remains in muscle fibres - pathology-MUSCLE DAMAGE- CK leaks-muscle-blood

Question 27

what is the gold standard test for diagnosis of muscle disorders

Answer 27

BIOPSY

Question 28

What 4 histological changes can be seen on a biopsy in an inflammatory myopathy?

Answer 28

1. variability in muscle fibre size 2. central nuclei 3. immune cell infiltration *indicate necrosis + regeneration*

Question 29

what is the difference between polymyositis and dermatomyositis

Answer 29

``` polymyositis = many muscles inflammed dematomyositis= inflammation of muscles and skin ```

Question 30

which immune cells are seen in POLYMYOSITIS biopsy?

Answer 30

CD8+ T lymphocytes

Question 31

3 features of the rash asssociated with dermatomyositis 1. location 2. colour 3. pattern

Answer 31

1. eyelids + back 2. helitrope (pink/purple) 3. streaky pattern

Question 32

what complication can be found in patients with dermatomyositis, visible on X-ray

Answer 32

SUBCUTANEOUS CALCIFICATION | calcifications in muscle and skin

Question 33

what can be detected specifically in a blood test for dermatomyositis patients

Answer 33

- ANA -autonuclear antibodies - 90% cases * 40% cases will have ANTI-JO1 ANTIBODY*= CYTOPLASMIC PROTEIN NOT NUCLEAR Anti-jo1 patients - more severe disease progression -death

Question 34

What treatment is used for poly/dermatomyositis and for how long

Answer 34

CORTICOSTERIODS - high dose-1mg/kg per day - given until CK levels return to normal >2wks (prednisolone)

Question 35

What adjunctive therapy is given for poly/dermatomyositis

Answer 35

Methotroxate + Azathioprine = steroid sparing drugs (reduce dose of steroid needed - fewer SE)

Question 36

What is inclusion body myositis?

Answer 36

- inflammatory muscle disease - most apparent in legs + arms - symmterical muscle weakness + pain

Question 37

which INFLAMMATORY MYOPATHY is more common in MEN?

Answer 37

inclusion body myositis (ibm)

Question 38

Clinical features of inclusion body myositis (IBM)

Answer 38

1. dysphagia | 2. loss of quadricep reflex

Question 39

what features are visible on a biopsy in IBM

Answer 39

VACUOLES containing abnormally folded proteins | CK levels are only slightly elevated in blood test

Question 40

what is the most common myopathy in the elderly

Answer 40

INCLUSION BODY MYOSITIS

Question 41

Name proteins that can be found in the vacuoles of IBM

Answer 41

- B-amyloid - hyperphosphorylated tau - apo E

Question 42

What is a muscular dystrophy (MD)?

Answer 42

PROGRESSIVE , GENETIC determined DEGENERATIVE MYOPATHIES

Question 43

What causes myopathy in MD

Answer 43

mutations in muscle protein genes

Question 44

3 groups of mutations which can cause MD and examples

Answer 44

X-linked = Duchenne + Becker MD AR=limb girdle MD AD=oculopharngeal MD

Question 45

DUCHENNE MD 1. incidence 2. onset 3. pathology 4. clinical features 5. prognosis

Answer 45

1.20-30 per 100,000 2.once child starts to walk 3.DYSTROPHIN - muscle protein absent - reduction in sarcoglycans (glycoproteins) -loss ability to links cell membrane - laminin =loss of cell membrane STABILITY -muscle fibre degeneartion 4.SHOULDER + THIGH weakness ONLY 5. - wheelchair bound by age 12 -death in 20s - heart failure *only MEN*

Question 46

Histological features seen in Duchenne MD biopsy

Answer 46

1. variable muscle fibres (repeated degeneration + regeneration) 2. endomysial fibrosis 3. myophagocytosis

Question 47

How do patients with Duchenne MD die?

Answer 47

heart failure - dystrophin - cardiomyoctes

Question 48

What histological change occurs to muscle fibres in DMD?

Answer 48

Muscle fibers - necrosis- ADIPOSE + FIBROTIC material

Question 49

``` DRUG INDUCED MYOPATHIES Effect of: 1.corticosteroids 2.statins 3.alcohol ```

Answer 49

1. type 2 atrophy 2. rhabdomylosis -damaged skeletal muscle breaks down 3. chronic slow progressive PROXIMAL muscle weakness

Question 50

FIBROMYALGIA 1. define 2. specifics 3. comorbities 4. gender 5. onset 6. autoimmune- blood test? 7. treatment

Answer 50

1. widespread + symmetrical muscle pain + axial skeleton 2. >11/18 tender points 3. chronic fatigue syndrone + LBP + headaches + arthritis + SLEEP DISTURBANCES 4. female =90% 5. 30-60s 6. ANTIPOLYMER ANITBODIES - 50% patients 7. TCAs + SSRIs + exercise

Question 51

what is the relationship between fibromyalgia and sleep distubances

Answer 51

fibromyalgia - increases CSF level of sub P sub P = NT - increases pain sensitivity loss of sleep - increased sub P stores