Burn Induced Cachexia

For My steam project I chose to research Cachexia in association with burn victims. As shown in the ink drawing Above. A man is in a burning room and is exposed to flames. He is burned and is depicted and skinny and frail, relating to the effects of Cachexia.

This work is meant to Identify the effect of cachexia/Hypermetabolism on the Skeletal Muscle and bone tissues in response to burning wounds. It is also meant to identify the aforementioned tissues and their functions.

Victims who suffer burns from stage 4 and up face a lot of issues when beginning the healing process. Along with the lymphatic system, respiratory system, and nervous system, major tissues that are badly affected are the Skeletal and muscle tissues. Both of these are fairly regenerative tissues but muscle tissue more so, and while they do undergo a healing process, they are not the same on a cellular level after being damaged by burns. These two tissues are the focus of burn induced cachexia and hypermetabolism, which cause dysfunction in muscle and bone tissues.

Bones(Osseous tissue) are present throughout the body, supporting other tissues. When burned in an accident they can face a multitude of issues, the first of which being bone loss or loss of bone mineral content(BMC). This burn injury results in a rise of proinflammatory cytokines which are as the name states “Proinflammatory” and do not promote healing. Through a chain of cellular interactions, these cytokines stimulate osteoclast activity. Therefore hastening bone resorption into the bloodstream. Other factors also play a role in the stimulation of osteoclast activity, and inhibition of osteoblasts. This means that bone resorption or degradation is increased while bone production is lowered. 

It is also notable that Parathyroid hormone(PTH) is much lower than what is required to regulate the calcium and phosphorus in the body in burn victims. Thus the calcium metabolism is no longer in good condition to regulate our calcium levels in a productive way.

Our Skeletal muscle is all over the body with origins and insertions along our bones. These tissues are in charge of voluntary movement, locomotion, and environmental manipulation. These contractile tissues are adversely affected by burns, and the key term to understanding burn induced muscle cachexia is hypermetabolism. Hypermetabolism is an increase in resting metabolic activity, in this case in response to the burn wound. The now hyperactive metabolism sets off an increase of stress regulators, such as catecholamines and glucocorticoids. These induce hypercatabolic responses, particularly proteolysis, which is the breakdown of proteins and peptides. This breakdown of proteins in the muscle, as well as other miscellaneous tissues within the body, become the fuel source for the hyperactive metabolism, and are used to heal the wound. 

This degradation of tissues due to a disturbed calcium metabolism, and a hyperactive metabolism weakens the body in order to heal burn wounds, and continues to be catabolic after the wound has healed, even continuing three years after the injury takes place. This is costly to the body and can actually bring harm to the body in the form of sepsis, organ failure, early stages of osteoporosis, and other medical complications. 

Burns and wounds. Burns and Wounds | Johns Hopkins Medicine. (n.d.). Retrieved November 8, 2022, from https://www.hopkinsmedicine.org/health/conditions-and-diseases/burns#:~:text=Second%2Ddegree%20burns%20involve%20the,may%20be%20swollen%20and%20painful.&text=Third%2Ddegree%20burns%20destroy%20the,bones%2C%20muscles%2C%20and%20tendons 

Cherney, K. (2019, June 4). 4th degree burn and other degrees: Classification, healing, more. Healthline. Retrieved November 8, 2022, from https://www.healthline.com/health/4th-degree-burn  

Klein, G. L. (2006, August 8). Burn-induced bone loss: Importance, mechanisms, and management. Journal of burns and wounds. Retrieved November 8, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1687146/ 

Knuth, Carly M, et al. “Burn-Induced Hypermetabolism and Skeletal Muscle Dysfunction.” American Journal of Physiology. Cell Physiology, U.S. National Library of Medicine, 1 July 2021, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321793/ 

CA;, Dinarello. “Proinflammatory Cytokines.” Chest, U.S. National Library of Medicine, Aug. 2000, https://pubmed.ncbi.nlm.nih.gov/10936147/  

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Rhabdomyolysis and Compartment Syndrome

For my STEAM project I will be looking at exercise induced rhabdomyolysis (exRML) and compartment syndrome. Exercise induced rhabdomyolysis is a pathophysiological condition of the skeletal muscle system that can cause acute renal failure and in some cases death. The class objectives related to this are: 1.) know the different energy molecules in the cell and their use in anaerobic and aerobic exercise. 2.) describe how a muscle contraction is induced. These objectives pertain because exRML is caused by and increase of Ca2+  levels in cells because of the depletion of adenosine triphosphate (ATP).

Rhabdomyolysis and compartment syndrome was first recognized in1940-1941 in patients with crush injuries caused by building destruction during World War II. It is most commonly found in crush and burn injuries where the muscle has been directly injured but other causes of RML have also been recognized including toxins, endocrinopathies, malignant hyperthermia, the medical conditions and overexertion. I am going to be focusing specifically on overexertion or exercise induces RML for my steam project.

Ca2+ has an important role in the Pathogenesis of exRML. Numerous studies have shown an increased level of Ca2+  in patients with exRML. Increased Ca2+ has been reported in the sarcoplasm of exRML patients with deficiency or depletion of ATP due to intensity of exercise. ATP is continually produced during exercise and when ATP is depleted ATP-dependent ion transporters may be affected. The increase of Na+ and K+ that happen when there is an action potential is dependent of ATP so when there is not enough ATP it can cause a disfunction of the Na+ – K+ ATPase resulting in increased levels of Na+  which causes the cell to produce more Ca2+  and this disfunction of the Ca2+ pump is what they think causes RML. The increased level of Ca2+  damages the phospholipids of the cell membrane which causes toxicity to the cell and cell death. Death of muscular tissues may create additional space for increased accumulation of intravascular fluid which causes compartment syndrome. And the toxicity of the blood enters the circular system and can cause renal failure and death. 

I read a number of case studies one where a Soldier got fatal exRML with Compartment syndrome in both legs after an Army physical fitness test and another where a number of high school football players developed exRML and triceps compartment syndrome following an upper arm exercise. From 2008 to 2015 19 confirmed cases of exRML were reported in wildland firefighters with five of those cases developing into compartment syndrome. It became such an important issue in wildland fire that the U.S. Forest service issued an eighteen page report just on the issue.

For my STEAM project I made a model of a lower leg made of wet felted wool and yarn showing a leg with compartment syndrome. When a patient develops compartment syndrome, besides aggressive fluid therapy, the patient may require a deep fasciotomy to open the compartments and relieve the pressure that is reducing circulation in the leg. In my model you can see the fasciotomy and the swelling of the muscles that is caused by RML. Symptoms of exRML include muscle pain developing hours after exercise peaking between 24 to 48 hours post exercise, cramping, swelling, weakness, stiffness and decreased range-of-motion, nausea or vomiting, fever, rapid hear rate, confusion or lack of consciousness, and tea or Coca-Cola colored urine. I also included in my model a glass of dark urine to remind people of one of the most common sign of RML. Heat stress and heat stroke are possible contributing factors of RML as well as the use of dietary supplements such as creatine snd hydroxycut. Creatine in particular which is used by many weight lifters has been found to be a major risk factor.

Bibliography

Coban, Y. K. (2014). Rhabdomyolysis, compartment syndrome and thermal injury. World Journal of Critical Care Medicine, 3(1), 1–7. https://doi.org/10.5492/wjccm.v3.i1. 

Kim, J., Lee, J., Kim, S., Ryu, H. Y., Cha, K. S., & Sung, D. J. (2016). Exercise-induced rhabdomyolysis mechanisms and prevention: A literature review. Journal of Sport and Health Science, 5(3), 324–333. https://doi.org/10.1016/j.jshs.2015.01.012 

Kuklo, T. R., Tis, J. E., Moores, L. K., & Schaefer, R. A. (2000). Fatal rhabdomyolysis with bilateral gluteal, thigh, and leg compartment syndrome after the Army Physical Fitness Test. The American Journal of Sports Medicine, 28(1), 112–116. https://doi.org/10.1177/03635465000280010401 

Minnema, B. J., Neligan, P. C., Quraishi, N. A., Fehlings, M. G., & Prakash, S. (2008). A case of occult compartment syndrome and nonresolving rhabdomyolysis. Journal of General Internal Medicine, 23(6), 871–874. https://doi.org/10.1007/s11606-008-0569-1 

Oh, J. Y., Laidler, M., Fiala, S. C., & Hedberg, K. (2011). Acute exertional rhabdomyolysis and triceps compartment syndrome during a high school football camp. Sports Health: A Multidisciplinary Approach, 4(1), 57–62. https://doi.org/10.1177/1941738111413874 

West, M., Domitrovich, J., & Symonds, J. (2018). Rhabdomyolysis in Wildland Fire A review of reported cases. Wildfire Today. Retrieved November 22, 2022, from https://wildfiretoday.com/docs/Rhabdo_5_9_16.pdf 

rhabdomyolysis and compartment syndrome
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