“ ... the shoulders, clavicles, chest and thighs melt away .... This illness is fatal"
- Hippocrates, 460-370 BC
The term "cachexia" is derived from the Greek kakos and hexis, meaning ‘bad condition’. It is a syndrome characterised by a loss of body weight and muscle tissue, which occurs in absence of starvation and is not associated with an adaptive decrease in catabolism. Question 2 from the second paper of 2011 asked about the definitions, causes and consequences of cachexia for the critically ill patient. There has never been a widely agreed-upon definition of cachexia (this article told me so). There was a Cachexia Consensus Conference in 2008 during which a new definition was proposed. This definition included only “cachexia proper”, excluding causes such as malnutrition (starvation), malabsorption, and hyperthyroidism. The experts were keen to make the distinction between this weird metabolic syndrome which occurs often in the presence of optimal nutrition, and all other forms of weight loss.
"Cachexia is a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle with or without loss of fat mass "
In the abovelinked article, Evans et al confess that the definition is not well tested in epidemiological studies; rather the definition is offered as a means of driving such studies.
This disease entity is encountered in several clinical settings. These are listed below alongside a link to a recent article discussing them in greater detail. In general, these syndromes tend to exhibit the cardinal features of cachexia: they are all cytokine-driven wasting diseases which cannot be cured by increasing the dietary intake.
These are "fake" cachexia syndromes, which resemble cachexia only insofar as they produce extreme muscle wasting or weight loss, and result in the appearance of severe malnutrition. Clinically, these may be indistinguishable from the "proper" cachexia and their effect on survival in intensive care is likely to be similar. The main distinction is that most of the below-listed disease entities have a convenient cure, which can reverse all of their adverse features. Cachexia "proper" is associated with a greater morbidity partly because there is no readily available solution to it.
The only sane thing that can be said here is "unclear mechanism; possible combination of multiple factors". A lucid article from 2006 (Morley et al) is the main source for the summarised information below.
The influence of inflammatory cytokines is probably central.
Testosterone deficiency (and thus leptin excess) contributes significantly.
Other hormonal contributors to poor muscle protein synthesis
These are very similar to the consequences of malnutrition in the critically ill patient, which are discussed in greater detail in a dedicated chapter. In brief:
Anker SD, Coats AJ. Cardiac cachexia: a syndrome with impaired survival and immune and neuroendocrine activation. Chest. 1999 Mar;115(3):836-47.
Steinborn W, Anker S.D., Cardiac Cachexia: Pathophysiology and Clinical Implications. Basic Appl Myol 13 (4): 191-201, 2003
The experts report that at least in cardiac failure cachexia is a strong independent risk factor for mortality.
Fearon, Kenneth. "Cachexia: Treat wasting illness on multiple fronts." Nature 529.7585 (2016): 156-156.
Kir, Serkan, et al. "Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia." Nature 513.7516 (2014): 100-104.
Laviano, Alessandro, Angela Koverech, and Alessia Mari. "Cachexia: clinical features when inflammation drives malnutrition." Proceedings of the Nutrition Society 74.04 (2015): 348-354.
Loncar, Goran, et al. "Cardiac cachexia: hic et nunc:“hic et nunc”—here and now." International journal of cardiology 201 (2015): e1-e12.
Wagner, P. D. "Possible mechanisms underlying the development of cachexia in COPD." European Respiratory Journal 31.3 (2008): 492-501.
Morley, John E., David R. Thomas, and Margaret-Mary G. Wilson. "Cachexia: pathophysiology and clinical relevance." The American journal of clinical nutrition 83.4 (2006): 735-743.
Engineer, Diana R., and Jose M. Garcia. "Leptin in anorexia and cachexia syndrome." International journal of peptides 2012 (2012).
Morissette, Michael R., et al. "Effects of myostatin deletion in aging mice." Aging cell 8.5 (2009): 573-583.
Baronzio, G., et al. "Proinflammatory and regulatory cytokine levels in AIDS cachexia." In vivo (Athens, Greece) 13.6 (1998): 499-502.
Fouque, D., et al. "A proposed nomenclature and diagnostic criteria for protein–energy wasting in acute and chronic kidney disease." Kidney international 73.4 (2008): 391-398.
Roubenoff, Ronenn, et al. "Rheumatoid cachexia: cytokine-driven hypermetabolism accompanying reduced body cell mass in chronic inflammation." Journal of Clinical Investigation 93.6 (1994): 2379.
Coletti, Dario, Laura Belli, and Sergio Adamo. "Cachexia: novel perspectives for an old syndrome." Basic Appl Myol 16.5&6 (2006): 131-139.