Cachexia (tissue wasting), anorexia (lack of appetite), and asthenia (weakness) frequently arise in palliative care and often overlap. The pathophysiologic processes involved are complex and may vary from one disease process to another. Cancer-associated cachexia has been most researched. Many other diseases associated with wasting are less well studied. One thing is clear - is overly simplistic to extrapolate from starvation to the wasting syndromes of chronic illnesses. It is also dangerous to extrapolate from one disease to another, as different diseases may have very different pathophysiologies.
Because cancer-related cachexia is relatively well understood (compared to other diseases), I focus on this. The concern of many patients, families, and clinicians is that patients who are losing weight and energy in advanced stages of cancer are, in fact, starving to death. In most cases the process is very different from starvation.75 It may sound strange, but humans were designed for starvation. That is, we evolved over millennia to survive periodic episodes of starvation. True starvation responses are geared for enhanced survival. In starvation hunger is initially dramatically increased; later it fades. Initial gut cramping that is experienced with starvation milks the intestine, which prevents bacterial overgrowth. The body shifts its metabolism to a slow, catabolic mode, which minimizes energy expenditure while preserving critically needed lean body mass until no other calories remain to be burned. Upon refeeding, assuming this is not done too quickly, appetite grows, the body shifts to an anabolic metabolic mode, and lean body mass is soon replenished.76 Refeeding dramatically increases the chance of survival.
The situation could not be more different in cancer-related cachexia. (Here, I am assuming that reversible causes of not eating or gaining weight, such as dysphagia, depression, nausea, and malabsorption have been addressed.) Appetite is lost early in the process. Gut cramping tends not to occur. The body becomes catabolic, but in a dysfunctional way. Total body energy expenditures may be increased, normal, or decreased. Lean body mass is not necessarily preserved. Refeeding either by tube feeding or total parenteral nutrition (TPN) in advanced disease does not replenish lean body mass, as it would in starvation. Patients' functional statuses do not improve, nor is survival improved. The details of the biochemical changes associated with cancer-related cachexia are beginning to be understood. It appears that a variety of tumor-associated cytokines, such as tumor necrosis factor (TNF), IL-1, IL-6, and LIF, are involved in this pathologic response.77-79 It seems likely that future therapy to modulate or block these mediators will alter the currently inexorable course associated with cancer-related cachexia.
Although the details of how cancer-related cachexia differs from starvation are probably beyond the understanding of most patients and families, we often need to summarize this information for them. Many will not accept that cancer-related cachexia is not starvation. For most people it seems obvious that if a patient is not eating and is loosing weight, he or she needs to be re-fed. If the patient is unable to take food naturally, one simply needs to override the system and feed artificially. Although similar processes may be involved in cachexia related to other diseases, such as congestive heart failure and dementia (although these and other diseases with associated cachexia are poorly studied), a special cautionary note must be voiced relating to AIDS.80 Certain patients with AIDS have demonstrated functional improvement and increased lean body mass with artificial feeding, highlighting the fact that real differences exist among different illnesses.81
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Palliative Care Perspectives
James L. Hallenbeck, M.D.
Copyright © 2003 by Oxford University Press, Inc.
The online version of this book is used with permission of the publisher and author on web sites affiliated with the Inter-Institutional Collaborating Network on End-of-life Care (IICN), sponsored by Growth House, Inc.