Cachexia: symptoms, causes and treatment

In many serious chronic diseases, especially in their later stages, it is common to find that the patient is very emaciated. It barely retains muscle and fat, it is found in the bones and has no strength.

Originally this was considered a symptom of any serious disease, however, it seems It could be that, although it accompanies the main disease, these symptoms would, in themselves, be another disease: cachexia.

Next we will discover what this disease is, in what other medical conditions it can appear, what are its causes, diagnosis and treatment.

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What is cachexia?

Cachexia (from the Greek "kakos" and "hexis" "bad constitution, bad condition") is a state of extreme malnutrition, fatigue and general weakness. It is a metabolic disorder that is thought to affect up to nine million people in everyone, including 80% of people diagnosed with some advanced cancer disease. It implies an extreme loss of weight and muscle mass, making it extremely difficult to carry out daily tasks and being more prone to accidents and being sedentary.

Contrary to what one might think, cachexia cannot be reversed with a diet high in calories (surplus diet) or with a high amount of protein and fat (ketogenic diet). The person is losing muscle mass and fat due to metabolic problems, not due to malnutrition caused by not being able to consume all the nutrients you need. Likewise, it is not uncommon to find relatives and close friends of the cachectic person who think that forcing them to eat will reverse or slow down the course of the disease.

History of the condition

Despite the fact that it has been in the last two decades that the deserved attention has been paid to this disorder metabolic, the truth is that it is believed that Hippocrates himself described the disease in the fourth century BC. c. Still, cachexia It has been considered a medical condition and not a mere symptom since the year 2000, when medical research gave it this name and began to study it and define it formally.

Currently cachexia is considered when a person has lost about 5% or more of their body weight over a 12-month period, accompanied by a significant reduction in muscle strength. Clinically it is still little recognized by oncologists, and there are still no standard guidelines to treat it, focusing more on treating the underlying disease that accompanies it, be it cancer, infection, inflammation, or disorder autoimmune.

Causes

Cachexia can be seen in the last stages of almost all serious chronic diseases, such as cancer, HIV-AIDS and infectious diseases such as tuberculosis. Between 16 and 42% of people with heart failure, 30% of patients with chronic obstructive pulmonary disease, and 60% of people with kidney disease have cachexia. Normally, this condition often goes unnoticed among doctors because more attention is paid to the main disease for which the patient is being treated.

Cachexia physically debilitates. The patient reaches such a state of deterioration that he has very reduced mobility. He has no strength because of his extreme thinness, asthenia and anemia. The response to treatments to reverse these symptoms is usually low, with which the person will barely recover muscle mass and fat.

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pathophysiology

Cachexia presents special physiological characteristics, despite the fact that traditionally it has been unnoticed or, simply, it has been considered one more symptom of the serious illness with which it came accompanied. It is currently considered a metabolic disorder and different hypotheses have been put forward to explain it., hypotheses which have served to create drugs with the intention of reversing the effects of this medical condition.

According to the most recent research, in cachexia what would happen is that white adipose tissue, or white fat, is replaced by brown or brown fat, in which there is an increase in energy expenditure. This phenomenon of browning of white fat occurs before muscle atrophy, a very characteristic symptom in advanced cachexia, and would be due to the action of different mediators of the inflammatory process and the cytokine interleukin-6 (IL-6).

Studies with mice have shown a relationship with genes encoding E3 ubiquitin ligase enzymes. These enzymes are responsible for tagging proteins to generate cell destruction. Mice lacking these enzymes were more resistant to muscle loss. It seems that when muscle cells receive a signal from an inflammatory process, tumor or immune cell, these cells begin to produce more E3 ubiquitin ligase enzymes, which would explain its relationship with cancer, autoimmune diseases and inflammation.

A molecular link has also been found with the browning of white fat, which is the increase in UCP1 protein expression. This molecule is responsible for uncoupling mitochondrial respiration towards heat production or thermogenesis instead of towards the synthesis of ATP, which implies an increase in the mobilization of lipids and an increase in the expenditure energetic.

Diagnosis

Despite the prevalence of cachexia, the diagnostic criteria have been proposed relatively recently, in addition to the fact that they are still provisional and still awaiting standardization. Even so, there is agreement in considering that cachexia should be diagnosed when there is a progressive loss of muscle and fat mass, reduced food intake, problems in the metabolism of carbohydrates, lipids and proteins, reduced quality of life and physical deterioration.

Although until relatively recently the loss of 10% of the original weight of the individual, this criterion alone has been considered too narrow to even diagnose a case of malnutrition. Yes, a 5% weight loss in the last 12 months is considered an indicator, but tests and analyzes of nutrient levels are considered more reliable and decisive indicators in the diagnosis of this condition medical.

With the intention of being able to classify the level of severity of cachexia, different evaluation systems have been proposed. Among them we find the “Cachexia Staging Score” (CSS) and the “Cachexia Score” (CASCO):

The CSS takes into account weight loss, in addition to the patient's perceived muscle function, their degree of performance of different physical tasks, loss of appetite, and biochemical changes. This scale allows categorizing the case into four types: non-cachexia, pre-cachexia, cachexia and refractory cachexia.. The CASCO assesses whether weight loss, changes in body composition, inflammation, metabolic disturbances, immunosuppression, physical performance, anorexia, and changes in quality of life.

Treatment

The treatment of cachexia depends on the underlying disease with which it is accompanied, the general prognosis and the needs of the affected person. The main therapeutic route for cachexia is treat the disease that causes it. For example, in the case of a person with cachexia associated with AIDS, active antiretroviral therapy would be applied. In any case, the usual thing is not being able to reverse cachexia, since it usually appears in diseases in an advanced state.

Despite this, there are different therapeutic options to achieve some reversal or, at least, slow down the progress of cachexia.

1. Exercise

In therapy, physical exercise is usually recommended, since activates and strengthens the skeletal muscles. People who suffer from cachexia usually indicate that they do little exercise and few carry out a routine, since either due to a lack of motivation or because they believe that exercise can worsen their symptoms or even make them sick. damage.

2. Medication

As one of the symptoms of cachexia is loss of appetite, drugs that stimulate it are often used as a therapeutic route. In any case, appetite stimulants do not work to stop muscle loss and can have side effects that further deteriorate the patient's condition. These drugs include glucocorticoids, cannabinoids, and progestins.. Antiemetics such as 5-HT3 antagonists are also used if nausea is a common symptom.

3. Nutrition

Among the diets that seem to reduce the loss of muscle mass, we have those that have a high amount of calories and protein, although this is not a guarantee that the patient will ever recover the lost muscle mass.

Bibliographic references:

• Fearon KC, Moses AG (2002). "Cancer cachexia". International Journal of Cardiology. 85 (1): 73–81. doi: 10.1016/S0167-5273(02)00235-8. PMID 12163211
• Kumar NB, Kazi A, Smith T, Crocker T, Yu D, Reich RR, Reddy K, Hastings S, Exterman M, Balducci L, Dalton K, Bepler G (2010). "Cancer cachexia: traditional therapies and novel molecular mechanism-based approaches to treatment". Current Treatment Options in Oncology. 11 (3–4): 107–17. doi: 10.1007/s11864-010-0127-z. PMC 3016925. PMID 21128029
• DevR (2019). "Measuring cachexia-diagnostic criteria". Annals of Palliative Medicine. 8 (1): 24–32. doi: 10.21037/apm.2018.08.07. PMID 30525765