Cachexia

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Cachexia , or wasting syndrome , is weight loss, muscular atrophy, fatigue, weakness and significant loss of appetite in someone who is not actively trying to lose weight.

Cachexia is seen in people with cancer, AIDS, celiac disease, chronic obstructive pulmonary disease, multiple sclerosis, rheumatoid arthritis, congestive heart failure, tuberculosis, familial amyloid polyneuropathy, mercury poisoning (acrodynia), Crohn's disease, untreated type 1 diabetes mellitus/weight, anorexia nervosa and hormonal deficiency.

This is a positive risk factor for death, which means if the person has cachexia, the likelihood of death from underlying conditions increases dramatically. This could be a sign of various underlying disorders; when a patient comes with cachexia, the doctor will usually consider the possibility of adverse drug reactions, cancer, metabolic acidosis, certain infectious diseases (eg, tuberculosis, AIDS), chronic pancreatitis and some autoimmune disorders. Cachexia physically weakens the patient to a state of immobility that results from loss of appetite, asthenia and anemia, and response to standard treatments is usually poor. Cachexia includes sarcopenia as part of its pathology. This term comes from the Greek ????? kakos , "bad", and ???? hexis , "condition".

Video Cachexia

Cause

Cachexia is often seen in late-stage cancers, and in that context it is called cachexia cancer . Patients with congestive heart failure may have cachectic syndrome. Also, comorbid cachexia is seen in patients who have one of the various diseases classified as chronic obstructive pulmonary disease. Cachexia is also associated with advanced stage of chronic kidney disease, cystic fibrosis, multiple sclerosis, motor neurone disease, Parkinson's disease, dementia, HIV/AIDS and other progressive diseases.

Cancer

About 50% of all cancer patients suffer from cachexia. Those with gastrointestinal cancers and upper pancreas have the highest frequency of development of cachexic symptoms. This number increased to 80% in terminal cancer patients. In addition to increasing morbidity and mortality, exacerbating the side effects of chemotherapy, and reducing quality of life, cachexia is considered the direct cause of death of most cancer patients, ranging from 22% to 40% of patients.

Symptoms of cachexia cancer include progressive weight loss and depletion of adipose tissue host reserves and skeletal muscle. Cachexia should be suspected if weight loss is not realized more than 5% premorbid weight occurs within a period of six months. Traditional treatment approaches, such as appetite stimulants, 5-HT ₃ antibody, nutritional supplementation, and COX-2 inhibitors have failed to demonstrate success in reversing the metabolic abnormalities seen in cachexia cancers.

Maps Cachexia

Mechanism

The exact mechanisms in which this disease causes cachexia are poorly understood, but there may be roles for inflammatory cytokines, such as tumor necrosis factor-alpha (also dubbed 'cachexin' or 'cachectin'), interferon gamma and interleukin 6, and proteolysis-inducing factors tumors are secreted.

Associated syndromes include kwashiorkor and marasmus, although this does not always have an underlying cause disease and is most often a symptom of severe malnutrition.

Those who suffer from anorexia nervosa eating disorder appear to have high levels of ghrelin plasma. Ghrelin levels are also high in patients who have cachexia caused by cancer.

Cancer

Much of the current research focuses on determining the developmental mechanism of cachexia. The two main theories of cancer development cachexia are: Changes in control circles: High leptin levels, hormones secreted by adipocytes, block the release of Neuropeptide Y (NPY), which is the most potent stimulant-feeding peptide in hypothalamic or oxygenic tissue, leading to a decrease in energy intake, but a high metabolic demand for nutrients.

The cachectic syndrome is preserved by tumor-derived factors: Factors, such as lipid driving factors extracted from the urine of the cachectic patient, are suspected of inducing protein degradation in skeletal muscle by upregulating the ubiquitin-proteasome and lipolysis pathways in adipocytes. However, how they interact and whether they come into play early or in the late stages of uncertain disease.

Although the pathogenesis of cachexia cancer is poorly understood, several biological pathways are known to be involved, including proinflammatory cytokines such as TNF-alpha, neuroendocrine hormone, IGF-1, and tumor-specific factors such as proteolysis induced factors.

The inflammatory cytokines involved in wasting disease are interleukin 6, TNF-alpha, IL1B, and interferon-gamma. Although many tissues and different cell types may be responsible for increased circulation of cytokines during certain types of cancer, evidence suggests tumors are an important source. Cytokines alone are able to lose weight. TNF-alpha has been shown to have direct catabolic effects on skeletal muscle and adipose tissue and produce muscular atrophy through the proteolytic pathway of proteolytic ubiquitin. This mechanism involves the formation of reactive oxygen species leading to increased regulation of the transcription factor NF-? B. NF-? B is a gene regulator that encodes cytokines, and cytokine receptors. Increased production of cytokines induces proteolysis and breakdown of myofibrillar proteins.

src: cancerres.aacrjournals.org

Diagnosis

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Management

The treatment or management of cachexia depends on the underlying cause, the general prognosis and other related factors of the person. The causes of reversible, underlying disease and contributing factors are treated where feasible and acceptable. More evidence supports the effectiveness of ? - hydroxy? -methylbutyrate (HMB) as a treatment to reduce, or even reverse, loss of muscle mass, muscle function, and muscle strength occurring in hypercatabolic disease such as cachexia; consequently, in June 2016 it was recommended that both the prevention and treatment of muscle wasting conditions include supplementation with HMB, regular exercise resistance and high protein diet intake. Progestin such as megestrol acetate is a treatment option in refractory cachexia with anorexia as the main symptom.

Cachexia is now less common in HIV/AIDS than in the past due to the emergence of highly active antiretroviral therapy (ART). Treatments involving different combinations of cancer cachexia are recommended in Europe, as the combination of nutritional, medication and non-drug treatment may be more effective than monotherapy. Non-drug therapies that have proven effective in cancer-induced cachexia include nutrition counseling, psychotherapy interventions and physical training. Anabolic-androgenic steroids such as oxandrolone may be helpful in cachexia cancers but their use is recommended for up to 2 weeks because longer treatment duration increases the burden of side effects.

Other drugs that have been used or are being investigated in cachexia therapy, but do not have convincing evidence of efficacy or safety, and are generally not recommended including:

• Thalidomide and cytokine antagonist
• Cannabinoids
• Omega-3 fatty acids, including eicosapentaenoic acid (EPA)
• Non-steroidal anti-inflammatory drugs
• Prokinetics
• Ghrelin and ghrelin receptor agonist
• Anabolic catabolic transform agent such as MT-102
• Safe androgen receptor modulators
• Cyproheptadine
• Hydrazine

Medical cannabis has been allowed for cachexia treatment in several US states, such as Illinois, Maryland, Delaware, Nevada, Michigan, Washington, Oregon, California, Colorado, New Mexico, Arizona, Vermont, New Jersey, Rhode Island, Maine and New York Hawaii and Connecticut.

There is not enough evidence to support the use of oral fish oil for the management of cachexia associated with advanced cancer.

Cancer

There are only limited treatment options for patients with clinical cancer cachexia. The current strategy is to increase appetite by using appetite stimulants to ensure adequate nutritional intake. Pharmacological interventions with appetite stimulants, nutritional supplementation, 5-HT ₃ antagonists and Cox-2 inhibitors have been used to treat cachexia cancer, but with limited effects.

Studies using more dense calories (1.5 kcal/ml) and higher protein supplementation have suggested at least stabilization of body weight can be achieved, although an increase in lean body mass has not been observed in this study.

Therapeutic strategies have been based on blocking the synthesis of cytokines or their actions. Thalidomide has been shown to suppress TNF-alpha production in monocytes in vitro and to normalize high levels of TNF-alpha in vivo . A randomized, placebo-controlled trial in patients with cachexia cancer showed the drug was well tolerated and effective for weight loss and lean body mass (LBM) in patients with advanced stage pancreatic cancer. LBM enhancement and improved quality of life were also observed in a randomized, double-blind, protein-and-energy-dense, omega-3 fatty acids enriched oral supplement, provided the consumption was equal to or higher than 2.2 g of eicosapentaenoic acid per day. This is also through decreased production of TNF-alpha. However, data arising from a large, multicenter, double-blind, placebo-controlled trial showed that administration of EPA alone was not successful in treating weight loss in patients with advanced gastrointestinal or lung cancers.

Peripheral muscle proteolysis, as occurs in cancer cachexia, serves to mobilize the amino acids needed for the synthesis of liver and tumor proteins. Therefore, giving exogenous amino acids can theoretically serve as fuel-saving metabolism by providing substrates for muscle metabolism and gluconeogenesis. Studies have shown dietary supplementation with a specific combination of high protein, leucine and fish oils improves muscle function and daily activity and immune response in cachectic tumor-bearing rats. Other than that,? -hydroxy -? - methyl butyrate derived from leucine catabolism which is used as a supplement in mouse tumors prevents cachexia by modifying NF-B expression B.

A phase 2 study involving the administration of antioxidants, pharmaconutritional support, progestin (megestrol acetate and medroxyprogesterone acetate), and anticyclooxygenase-2 drugs, demonstrated efficacy and safety in the treatment of patients with advanced cancer from sites suffering from cachexia. This data reinforces the use of multidarget therapy (nutritional supplementation, appetite stimulation, and physical activity regimen) in the treatment of cachexia cancer.

The new study shows NSAIDS, such as Sulindac, found to significantly reduce cachexia.

Also studies have shown that branch-chain amino acids can restore the metabolism of cachectic patients from the weight of catabolic loss - to anabolic-increasing muscle, in more than 55% of patients. Branch amino acids consist mainly of leucine and valine. In a research paper published by J India Palliat Care, the effect of the findings concluded that bcaa interferes with brain serotonergic activity and inhibits excessive expression of critical proteolytic pathways. The potential role of branch-chain amino acids as antianorexia and anticachexia agents was proposed several years ago, but experimental and clinical trials have tested their ability to stimulate food intake and neutralize muscle wasting in anorectical patients, who lost weight. In the experimental model of cachexia cancer, BCAA was able to induce a significant emphasis in weight loss, resulting in a significant increase in skeletal muscle wet weight [30] as well as in muscle performance and total daily activity.

Essential glutamine amino acids have been used as a component of oral supplementation to reverse cachexia in patients with advanced cancer or HIV/AIDS.

src: erj.ersjournals.com

Epidemiology

According to the 2007 National Inpatient Sample of AHRQ, in the projection of 129,164 hospital meetings in the United States, cachexia was listed as at least one to 14 codes of diagnosis recorded based on a sample of 26,325 unbalance meetings. Samples of 32,778 unbalanced US outpatient visits collected by the National Ambulatory Medical Survey of CDC did not include visits where cachexia was one of the three diagnoses recorded during the visit.

src: erj.ersjournals.com

See also

• Progressive disease
• Terminal disease
• Cachexia Journal, Sarcopenia, and Muscle

src: www.biochemj.org

References

src: dmm.biologists.org

External links

• Scientists find the key to the "wasting syndrome" seen in cancer, AIDS (US Department of Veterans Affairs)

Source of the article : Wikipedia