T2 l6 :intro to pathophysiology of muscle

Question 1

difference between endurance exercise and resistance training

Answer 1

endurance: responds to total contractile activity

resistance training: responds to loading and stretch

Question 2

what are the muscle plasticity adaptations

Answer 2

• structural; size, capillarisation

- contractile properties: fibre type transitions

Question 3

if the total number of muscle fibres are fixed at birth how do they grow

Answer 3

Hypertrophy:
-synthesis of myofilaments

• addition of sacromeres
• satellite cell activation
• angiogenesis & vascularisation

Question 4

list the effects of endurance exercise

Answer 4

fibre diameter

blood supply

mitochondrial content: express an increase in oxidative enzymes

fibres become slower-2x and 2a and type 1 eventually

Question 5

describe the changes that occur to non-endurance exercise

Answer 5

conversion to type IIX

• from type IIA
• greater muscle force & strength

increase in type IIX fibre size due to increase in numbers of sarcomeres & myofilaments

results in much larger muscles (bulk) and leads to an increase in power

Question 6

what type of injuries is ice used to reduce

Answer 6

To reduce swelling
By reducing perfusion
After an acute injury
Sprain
After exercise in overuse injury

Question 7

what type of injury is heat used to reduce

Answer 7

To relax and loosen tissues
Use before activities that irritate chronic injuries
Strain
Increases blood flow

Question 8

describe the class, function and diseases that aspirin can be used on

Answer 8

Aspirin is an NSAID:

• Reduces pain
• Reduces inflammation

Mechanism:

• Inhibits COX
• Reduces synthesis of prostaglandins
• Part of arachidonic acid pathway

Used for musc-skel pain:

• Chronic diseases
• –Osteoarthritis
• Sports injuries
• –Combined with ice
• –Often after exercise

Question 9

Arachidonic acid and prostaglandins

Answer 9

Gastro-intestinal adverse effects of chronic aspirin
Stomach bleeding
Ulcers

Question 10

what are the effects of testosterone :

Answer 10

Anabolic effects of testosterone:

• Increases protein synthesis
• Decreases catabolism (by opposing cortisol & glucocorticoids)
• Reduces fat: increase BMR, increase differentiation to muscle (rather than fat cells)

Question 11

what occurs in anabolic steroid abuse

Answer 11

anabolic steroid abuse:
-used to increase muscle size and strength

- large doses required – leads to damaging  
  side effects (kidney, liver, heart, mood 
  changes)

-male – testes atrophy, sterility, baldness

• female – breast/uterus atrophy, menstrual
  changes, facial hair, deepening of voice

Question 12

what is the effect of spaceflight on humans

Answer 12

• Theres a decrease in weight bearing that the muscles have to undertake
• Humans transition from type 1 to 2A/X fibres
• decrease in the relative muscle mass- all muscles undergo some atrophy, but predominately weight-bearing muscles

Question 13

what is the effect of bed rest on muscle

Answer 13

transition of type I fibres to type 2a

this causes weight bearing muscle atrophy

• decrease in muscle protein synthesis
• myofibrillar breakdown
• decrease strength due to smaller size
• loss of type 1 fibres

Question 14

how do you treat the effect of bed rest

Answer 14

Add physiotherapy to prevent contractures.

Question 15

describe contracture

Answer 15

-if limb is immobilised for a long period of time

-process of growth is reversed
sarcomeres are removed in series from myofibrils

-resulting in shortening of muscle called a contracture

Question 16

describe the multinucleate nature of skeletal muscles

Answer 16

They develop as myoblasts:

• Which are mononucleate
• Then the myoblasts fuse

-The nuclei are peripheral

-The multinucleate cells do not divide
Mitosis with multiple nuclei usually impossible

• Skeletal muscles are enlarged by:
• Fibre enlargement
• Increased vascularisation

Question 17

how does muscular regeneration occur

Answer 17

previous quiescent myogenic cells, called satellite cells, are activated:

• These proliferate, differentiate and fuse onto extant fibres
• They contribute to forming multinucleate myofibers

Question 18

describe myosatellite cells

Answer 18

Progenitor cells in muscle

• Also called “satellite cells”
• NOT related glial satellite cells

activated by mechanical strain on muscle

activation leads to proliferation and differentiation

Question 19

what are the causes of muscle pain

Answer 19

injury
overuse
infections
auto-immune

associated with rhabdomyolysis

Question 20

describe the aetiology of myopathy

Answer 20

Muscular weakness due to muscular muscle fibre dysfunction:

• Cf. neuropathy & neurogenic disorders
• Failure to contract cause possibly muscle or nerve

can be systemic or familial

Question 21

describe dystrophies

Answer 21

Dystrophies: familial, progressive:

• Stuck in degeneration-regeneration cycle
• Eventually regenerative ability is lost

Question 22

describe paresis

Answer 22

weakness of voluntary movement, or
partial loss of voluntary movement or
impaired movement

Usually referring to a limb

Question 23

describe fasciculations

Answer 23

: involuntary visible twitches in single motor units (neurogenic), which commonly occur in lower motor neuron diseases such as damage to anterior horn cell bodies characteristic of ALS or polio

clinically appear as brief ripples under the skin

Question 24

describe fibrillations

Answer 24

: involuntary spontaneous contractions of individual muscle fibres (myogenic) invisible to the eye but identified by electromyography

Question 25

describe rhabdomyolysis

Answer 25

Rapid breakdown of skeletal muscle | -Not cardiac muscle, not myocardial infarct

Question 26

is there An organ risk with rhabdo

Answer 26

Risk of kidney failure: - Cellular proteins (esp myoglobin) released into blood can “clog” renal glomeruli - Urine is “tea coloured”, no urine produced 12 hours after injury - Leads to electrolyte changes: hyperkalaemia

Question 27

what is the treatment for rhabdo

Answer 27

- Intravenous fluids (to treat shock) | - possibly haemodialysis, etc

Question 28

what can cause rhabdomyolysis

Answer 28

- Trauma: Crush injury - Drugs - -adverse effects of: statins or fibrates - Hyperthermia - Ischaemia to the skeletal muscle - -Compartment syndrome, thrombosis

Question 29

what are the signs and symptoms of rhabdo

Answer 29

Symptoms & signs (depending on severity): - muscle pains - vomiting and confusion - Dark urine

Question 30

different forms of CPK

Answer 30

skeletal muscle CPK isoform is CK-MM cardiac muscle CPK isoform is CK-MB

Question 31

what occurs to CPK levels when tissue damage occurs

Answer 31

when tissue damaged and cells lyse there is a release of tissue specific CK from cells into blood Elevations in CK-MM occur after skeletal muscle trauma or necrosis - muscular dystrophies, polymyositis and rhabdomyolysis - Test = “Total CK” (CK-MM is not a clinical test)

Question 32

how can you use myoglobin as a diagnostic test

Answer 32

“Buffers O2” Protein + Haem group “tea coloured” In plasma indicates rhabdomyolysis or MI -Can lead to renal failure Urine tested for myoglobin Diagnostic: Hyperkalaemia When muscle cells lyse They release K+ This increases serum K+ Nb: decrease serum K = cause of rhabdo, increase K = result of rhabdo

Question 33

how is rigor mortis caused

Answer 33

ATP depleted after death Muscle cell does not resequester Ca2+ into SR increases Cytosolic Ca2+ Ca2+ allows crossbridge cycle contraction Until ATP & creatine-P run out W/o ATP ----myosin stops just after power stroke With myosin still bound to actin Rigor mortis ends when muscle tissue degrades after 3 days

Question 34

what occurs in myasthenia gravis

Answer 34

progressive muscle weakness and fatigability Often starts with eye muscles Caused by depletion of nAChR arises as the immune system inappropriately produces auto-antibodies against nAChR

Question 35

pathophysiology of myasthenia gravis

Answer 35

less depolarisation of muscle fibres many fibres do not reach threshold repeated stimulation  neuromuscular fatigue symptoms include ptosis, diplopia, with weakness in eyelid and extraocular muscles proximal muscle weakness

Question 36

what is the treatment for MG

Answer 36

AChE inhibitors Neostigmine Increase ACh activity at NMJ. ACh released from nerve terminals into synapse not rapidly catabolised but can bind to the remaining AChRs for longer time Edrophonium (a/k/a tensilon): short-lived AChE inhibitor for diagnosis, temporarily improves symptoms eg ptosis Other category of treatment is directed at immune system Thymectomy – reduces symptoms in 70% of patients. Exact mechanism unknown. Rebalance immune system? use of immunosuppressive drugs e.g. corticosteroids plasmapheresis = removal of anti AChR antibodies from blood stream

Question 37

what occurs in spinal muscular atrophy

Answer 37

a/k/a Floppy Baby Syndrome One of most common genetic causes of infant death Severity and time of onset can vary greatly death of lower motor neurons in anterior horn of spine Muscle atrophy —> hypotonia & muscle weakness Via apoptosis Fibre type grouping Sensory system is spared (b/c not in anterior horn) ``` Caused by genetic defect SMN1 gene Required for survival of anterior horn neurons Autosomal recessive Other genes cause similar syndromes ```

Question 38

what is fibre type grouping

Answer 38

During spinal muscular atrophy Cycles of denervation are followed by collateral reinnervation surviving axons innervate surrounding fibres resulting in fibre type grouping In healthy muscles (Figure A), motor units are intermingled. During reinnervation, nearby surviving neurons re-innervate the denervated fibres, resulting in clusters (Figure B) study slide 32

Question 39

what occurs in malignant hyperthermia

Answer 39

Genetic (rare) susceptibility to gas anaesthetics Eg sevoflurane Mutation in RyR means gas anaesthetic  Ca2+ release Autosomal Dominant Channel is susceptible if any of subunits are Result: SERCA works too hard (to pump Ca back into SR)  O2 consumption,  CO2, acidosis, tachypnea, muscles overheat, the body overheats, muscles are damaged (rhabdomyolysis), hyperkalaemia, muscles become rigid Muscle cells open and leak their contents Plasma CK-MM increases Kidney failure possible: urine red from myoglobin dantrolene sodium can stop the abnormal calcium release Inhibits ryanodine receptor

Question 40

what occurs in muscular dystrophies

Answer 40

``` group of inherited disorders severe and progressive wasting of muscle muscle weakness Due to myopathy, not neuropathy waddling gate contractures cardiorespiratory muscle involvement ```

Question 41

what occurs in Duchenne muscular dystrophy

Answer 41

x-linked disease affects 1:3500 live male births -one third of cases arise spontaneously progressive loss of muscle tissue replaced by fibrofatty connective tissue Mutation: gene for dystrophin protein

Question 42

what sign is associated with Duchenne muscular dystrophy

Answer 42

Gowers sign -is a medical sign that indicates weakness of hip and thigh muscles associated with muscular dystrophy. The patient that has to use his hands and arms to "walk" up his own body from a squatting position.