Cachexia / Wasting Syndrome

Cachexia is a condition which denotes the excessive loss of weight. It occurs because of the depletion of adipose tissue and muscle mass in people who are not trying to lose weight.

It is also known as “wasting syndrome”, and causes disproportionate muscle wasting, weakness, fatigue, and loss of appetite in affected individuals. The word “cachexia” originates from two Greek terms “kakos” which means “bad” and “hexis” which means “condition.”

Cachexia is seen in a number of patients with conditions such as:

  • AIDS
  • cancer
  • celiac disease
  • rheumatoid arthritis
  • multiple sclerosis
  • congestive heart failure
  • tuberculosis
  • mercury poisoning
  • severe sepsis
  • malabsorption

It usually sets in during the late stages of chronic illnesses.

Cachexia affects about an estimated 16–42% of heart failure patients, and nearly 60% of patients with kidney disease. It affects over 5 million people in the US. This condition remained overlooked for several years, as doctors and researchers tended to focus on the major illness that had been diagnosed in the patients.

Differentiating cachexia from other syndromes that cause weight loss is crucial for prompt diagnosis and effective management of this condition.

Causes of Cachexia

Although the exact cause of cachexia is not yet clearly understood, several studies have shown that inflammatory cytokines such as tumor necrosis factor-alpha (TNF- α), interleukin 6 (IL-6), and interferon-gamma (IFN-γ) may play a role in the development of cachexia.

Studies focusing on the weight loss mechanism in rabbits showed that TNF-α administration in lab rabbits induces cachexia, with anorexia and adipose tissue depletion. TNF-α has also been shown to trigger muscle protein degradation, though there was no proof of direct action. According to one study, TNF-α administration in healthy rats increase degradation of muscle protein, though weight loss was not evident in the rats. Other studies have shown that TNF-α has the ability to cause catabolism of human adipose tissue and muscles.

Various animal studies have proved that IL-6 has the potential to play a role in the development of cachexia, along with other factors. In one particular study in mice, infusion of IL-6 did not cause weight loss in mice harboring a tumor clone that does not induce weight loss. This was taken as indication that IL-6 alone was not responsible for cachexia induction.

Weight loss in Starvation and Cachexia

Weight loss in cachexia is different from the weight loss that results from starvation. The latter is a direct result of inadequate calorie intake.

During the initial stages of starvation, the body supplies the brain and erythrocytes with glucose by two compensatory mechanisms:

  • It breaks down the glycogen reserves in liver and muscle
  • It increases the production of glucose in the liver, using gluconeogenic amino acids formed as a result of muscle catabolism.

However, in long-term starvation, the body starts to use fat as a fuel. That is, it converts fatty acids from adipose tissue to ketone bodies, which provide the required energy to brain and peripheral tissues. This results in muscle mass conservation. Therefore, in prolonged starvation, the major share of weight loss is because of burning fat and only a minor portion is from muscle.

In contrast, weight loss in cachexia involves loss of equal amounts of fat and muscle. Hence, for a given percentage of weight loss, a cachectic person loses more muscle than a starving person. Also, the weight loss or change in body composition in the case of cachexia is not reversible by ensuring adequate calorie ingestion, unlike cases of simple starvation. This is because of profound metabolic changes taking place in cachexia, which lead to a higher basal rate of energy expenditure, as well as to the increased degradation of fat and muscle.

The altered body composition of the patient at presentation helps to differentiate cachexia from other syndromes such as anorexia causing weight loss. However, anorexia may be a contributing factor to the muscle wasting seen in patients with cachexia. This is because the loss of appetite and reduced intake of food interferes with the psychological and physical quality of life of the patient.


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