Cachexia: symptoms, causes and treatment.

A summary of the characteristics of cachexia, a metabolic disease.

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

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

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

What is cachexia?

Cachexia (from Greek "kakos" and "hexis" "bad constitution, bad condition") is a state of extreme malnutrition, fatigue and generalized weakness.. It is a metabolic disorder that is thought to affect as many as nine million people worldwide, including 80% of those diagnosed with advanced Cancer disease. It involves an extreme loss of weight and muscle mass, making it extremely difficult to carry out daily tasks and more prone to accidents and sedentary lifestyles.

Contrary to what one may think, cachexia cannot be reversed with a high-calorie diet (surplus diet) or with a high amount of proteins and fats (ketogenic diet). The person is losing muscle mass and fat due to metabolic problems, not due to malnutrition caused bynot due to malnutrition caused by not being able to consume all the nutrients they need. Likewise, it is not uncommon to find relatives and 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

Although it is only in the last two decades that this metabolic disorder has received the attention it deserves, it is believed that Hippocrates himself described the disease in the 4th century B.C. Even so, cachexia has been considered a medical condition and not a medical condition. has been considered a medical condition and not a mere symptom since the year 2000, when medical research gave it this name.when medical research gave it this name and began to study and formally define it.

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

Causes

Cachexia can be seen in the late 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. This condition is often overlooked by physicians because more attention is paid to the main disease for which the patient is being treated.

Cachexia is physically debilitating. The patient reaches such a state of deterioration that there is very little mobility. He has no strength because of his extreme thinness, asthenia and anemia.. The response to treatments to reverse these symptoms is usually low, so the person will hardly recover muscle mass and fat.

Physiopathology

Cachexia has special physiological characteristics, although it has traditionally gone largely unnoticed or has simply been considered just another symptom of the serious disease with which it was accompanied. Nowadays it is considered a metabolic disorder and different hypotheses have been put forward to explain it.These hypotheses have served to create drugs with the intention of reversing the effects of this medical condition.

According to the most recent investigations, in cachexia what would happen is that the white adipose tissue or white fat is replaced by brown or brownish 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 is due to the action of different mediators of the inflammatory process and the cytokine interleukin-6 (IL-6).

In studies with mice, a relationship has been observed with genes encoding E3 ubiquitin ligase enzymes.. These enzymes are responsible for labeling proteins to generate cell killing. 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 could explain their relationship with cancer, autoimmune diseases and inflammation.

A molecular link to white fat browning has also been found, which is the increased expression of UCP1 protein. expression of the UCP1 protein. This molecule is responsible for uncoupling mitochondrial respiration towards heat production or thermogenesis rather than ATP synthesis, which leads to increased lipid mobilization and increased energy expenditure.

Diagnosis

Despite the prevalence of cachexia, diagnostic criteria have been proposed relatively recently and are still provisional and await standardization. Even so, it is generally agreed that cachexia should be diagnosed when there is progressive loss of muscle mass and fat, reduced food intake, problems in carbohydrate, lipid and protein metabolism, reduced quality of life and physical deterioration. and physical deterioration.

Although until relatively recently a loss of 10% of the individual's original weight was considered a diagnostic criterion, this criterion alone has been considered too limited to even diagnose a case of malnutrition. A 5% weight loss in the last 12 months is considered an indicator, but testing and analysis of nutrient levels are considered more reliable and decisive indicators in the diagnosis of this medical condition.

With the intention of being able to classify the level of severity of cachexia, different evaluation systems have been proposed. Among them are 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, his or her degree of performance of different physical tasks, loss of appetite and biochemical changes. This scale allows to categorize the case in four types: non- cachexia, pre-cachexia, cachexia and refractory cachexia.. The CASCO evaluates weight loss, changes in body composition, inflammation, metabolic alterations, 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 overall prognosis and the needs of the affected person. The main therapeutic approach for cachexia is to treating the disease that causes cachexia. For example, in the case of a person with cachexia associated with AIDS, active antiretroviral therapy would be applied. In any case, it is usually not possible to reverse cachexia, since it usually appears in advanced diseases.

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

1. Exercise

Physical exercise is often recommended in therapy, as it activates and strengthens the skeletal muscles. activates and strengthens the skeletal musculature.. People suffering from cachexia often indicate that they do little exercise and few carry out a routine, either for lack of motivation or because they believe that exercise can worsen their symptoms or even harm them.

2. Medication

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

3. Nutrition

Among the diets that seem to be able to reduce the loss of muscle mass are those with a high amount of calories and proteins, although this is no 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.
• Dev R (2019). "Measuring cachexia-diagnostic criteria". Annals of Palliative Medicine. 8 (1): 24–32. doi:10.21037/apm.2018.08.07. PMID 30525765