Introduction to pathophysiology of skeletal muscle Flashcards

Question

Give the side effects of anabolic steroid abuse

Answer 1

``` 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

Answer 2

Decreased weight bearing Transition of type I fibres to type IIA/X fibres Decreased relative muscle mass - all muscles undergo some atrophy - predominately weight bearing muscles

Answer 3

transition of type I fibres to type IIA weight-bearing muscle atrophy - decreased muscle protein synthesis - myofibrillar breakdown - Decreased strength (due to decreased size) - loss of type I fibres

Answer 4

treat by resuming minor activity early. Add physiotherapy to prevent contractures.

Answer 5

Shortening of muscle

Answer 6

if limb immobilised for long periods: process of growth is reversed sarcomeres are removed in series from myofibrils

Answer 7

patients with paralysed limbs must have physical therapy to prevent contractures occurring

Answer 8

Multinucleate

Answer 9

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

Answer 10

Fibre enlargement | Increased vascularisation

Answer 11

During inflammation and degeneration of damaged muscle tissue previous quiescent myogenic cells, called satellite cells, are activated These proliferate, differentiate and fuse onto extant fibres They contribute to forming multinucleate myofibers

Answer 12

``` Progenitor cells in muscle Also called “satellite cells” NOT related glial satellite cells Essential for regeneration & growth Most are quiescent Activated by mechanical strain Activation —> proliferation & differentiation ```

Answer 13

Muscle pain

Answer 14

Injury, overuse, infections, auto-immune

Answer 15

Rhabdomyolysis

Answer 16

Muscular weakness due to muscular muscle fibre dysfunction Cf. neuropathy & neurogenic disorders Failure to contract cause possibly muscle or nerve Systemic vs. familial

Answer 17

familial, progressive Stuck in degeneration-regeneration cycle Eventually regenerative ability is lost

Answer 18

weakness of voluntary movement, or partial loss of voluntary movement or impaired movement Usually referring to a limb From Greek “to let fall”

Answer 19

involuntary visible twitches in single motor units (neurogenic)

Answer 20

commonly occur in lower motor neuron diseases such as damage to anterior horn cell bodies characteristic of ALS or polio

Answer 21

clinically appear as brief ripples under the skin

Answer 22

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

Answer 23

Rapid breakdown of skeletal muscle

Answer 24

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

Answer 25

``` Intravenous fluids (to treat shock) possibly haemodialysis, etc ```

Answer 26

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

Answer 27

muscle pains vomiting and confusion Dark urine

Answer 28

The enzyme distinct forms of CPK found in different tissues skeletal muscle CPK isoform is CK-MM cardiac muscle CPK isoform is CK-MB 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)

Answer 29

``` “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: decreased serum K = cause of rhabdo, increased K = result of rhabdo

Answer 30

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

Answer 31

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

Answer 32

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)

Answer 33

``` Caused by genetic defect SMN1 gene Required for survival of anterior horn neurons Autosomal recessive Other genes cause similar syndromes ```

Answer 34

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, motor units are intermingled. During reinnervation, nearby surviving neurons re-innervate the denervated fibres, resulting in clusters

Answer 35

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) Increased O2 consumption, increased 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

Answer 36

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

Answer 37

``` 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 ```