14.6 POJA-L6342 Rhabdomyolysis
Rhabdomyolysis
Rhabdomyolysis: a case report
For educative purposes a report of the muscle biopsy of a patient with rhabdomyolysis is selected. Clinically, rhabdomyolysis is characterised by weakness, myalgia, and muscle swelling. Biochemically an elevation of creatine kinase (CK) which is proportionate to the extent of myonecrosis is always observed (ref. 1). Muscle regenerates rapidly following myonecrosis. It is postulated by Torres (ref. 2) when muscle injury occurs the result is an excessive intracellular influx of Na+ and Ca2+. Water is drawn into the cell due to the increase of intracellular Na+ with loss of integrity of the sarcoplasm. The prolonged presence of intracellular high Ca2+ levels leads to a sustained myofibrillar contraction resulting in depletion of ATP. The increase of Ca2+ activates Ca2+-dependent proteases and phospholipases and promotes lysis of the sarcolemma and further damage to the ion channels. The end result of these alterations is an inflammatory, self-sustaining myolytic cascade that causes necrosis of the muscle fibres and release of the muscle contents into the extracellular space/bloodstream.
The focus of this report is merely on the histopathologic process of myonecrosis and regeneration of skeletal muscle fibres also referred as muscle fibres, or myofibres or fibres (ref. 3).
The case report is illustrated with the following POJA-L numbers:
Summary
- After necrosis of pre-existing myofibres the satellite cells differentiate via myotubes into small maturing myofibres positive for Leu-19. Small clusters and files of Leu-19 positive myofibres indicate regeneration following failure of myofibres due to necrosis.
- Following rhabdomyolysis regenerating muscle fibres reveal intermediate ATPase activity (after preincubation at pH 4.2) like normal foetal myofibres. It is assumed that this activity is based on the presence of foetal myosin. Further development into mature fibres may occur eventually.
- Myophagy is validated by infiltrated macrophages that contain considerable amounts of hydrolytic enzymes. Following necrosis removal of degraded cellular constituents are accomplished in the clearing processes. As a rule, regenerations follow the aforementioned diffuse myolytic events.
Acknowledgements:
The report is in agreement with the former attending neurologist P. Poels MD, PhD (Dept. Neurology Radboud university medical center, Nijmegen, The Netherlands).
The histopathological base for the diagnosis is discussed in consultation with H. ter Laak PhD (Dept. Pathology, Radboud university medical center, Nijmegen, The Netherlands).
References:
Rhabdomyolysis: a case report
For educative purposes a report of the muscle biopsy of a patient with rhabdomyolysis is selected. Clinically, rhabdomyolysis is characterised by weakness, myalgia, and muscle swelling. Biochemically an elevation of creatine kinase (CK) which is proportionate to the extent of myonecrosis is always observed (ref. 1). Muscle regenerates rapidly following myonecrosis. It is postulated by Torres (ref. 2) when muscle injury occurs the result is an excessive intracellular influx of Na+ and Ca2+. Water is drawn into the cell due to the increase of intracellular Na+ with loss of integrity of the sarcoplasm. The prolonged presence of intracellular high Ca2+ levels leads to a sustained myofibrillar contraction resulting in depletion of ATP. The increase of Ca2+ activates Ca2+-dependent proteases and phospholipases and promotes lysis of the sarcolemma and further damage to the ion channels. The end result of these alterations is an inflammatory, self-sustaining myolytic cascade that causes necrosis of the muscle fibres and release of the muscle contents into the extracellular space/bloodstream.
The focus of this report is merely on the histopathologic process of myonecrosis and regeneration of skeletal muscle fibres also referred as muscle fibres, or myofibres or fibres (ref. 3).
The case report is illustrated with the following POJA-L numbers:
- (14.1.2. POJA-L6282+6280+6267+6265+6278+6272)
- (14.1.2. POJA-L6283+6271+6275+6274+6266+6270)
- (14.1.2. POJA-L6279+6273)
- (14.1.2. POJA-L6300+6300-CCC)
Summary
- After necrosis of pre-existing myofibres the satellite cells differentiate via myotubes into small maturing myofibres positive for Leu-19. Small clusters and files of Leu-19 positive myofibres indicate regeneration following failure of myofibres due to necrosis.
- Following rhabdomyolysis regenerating muscle fibres reveal intermediate ATPase activity (after preincubation at pH 4.2) like normal foetal myofibres. It is assumed that this activity is based on the presence of foetal myosin. Further development into mature fibres may occur eventually.
- Myophagy is validated by infiltrated macrophages that contain considerable amounts of hydrolytic enzymes. Following necrosis removal of degraded cellular constituents are accomplished in the clearing processes. As a rule, regenerations follow the aforementioned diffuse myolytic events.
Acknowledgements:
The report is in agreement with the former attending neurologist P. Poels MD, PhD (Dept. Neurology Radboud university medical center, Nijmegen, The Netherlands).
The histopathological base for the diagnosis is discussed in consultation with H. ter Laak PhD (Dept. Pathology, Radboud university medical center, Nijmegen, The Netherlands).
References:
- https://neuromuscular.wustl.edu/
- Rhabdomyolysis: pathogenesis, diagnosis, and treatment. Torres P.A., Helmstetter J.A., Kaye A.M., Kaye A.D. Ochsner J Spring 2015, 15, 58-69. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365849/)
- Muscle biopsy. A practical approach. Dubowitz V., Sewry C.A., Oldfors A. 2013, 4th edition, Elsevier Limited. (https://www.elsevier.com/books/muscle-biopsy/dubowitz/978-0-7020-7471-4)