6. Pathophysiology of skeletal muscle Flashcards

Question

Rhabdomyolysis

Answer 1

Rapid breakdown of skeletal muscle Risk of kidney failure Treatment: Intravenous fluids (to treat shock) possibly haemodialysis, etc

Answer 2

``` 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 3

``` Causes of rhab (ie when cell membrane loses integrity) Trauma: Crush injury Drugs adverse effects of: statins or fibrates Hyperthermia Ischaemia to the skeletal muscle Compartment syndrome, thrombosis ```

Answer 4

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

Answer 5

Creatine Phosphokinase CK or CPK abbreviations used interchangeably The enzyme, not creatine phosphate 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 6

``` “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 in serum K = cause of rhabdo, Increase in K= result of rhabdo

Answer 7

ATP depleted after death Muscle cell does not resequester Ca2+ into SR Increase in 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

Answer 8

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

Answer 9

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

Answer 10

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 11

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 ```

Answer 12

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 13

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

Answer 14

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 15

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

Answer 16

``` 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 ```