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Figure 14.1 Malnutrition clinical presentations according to inflammation intensity; low‐ to medium‐grade inflammation is not considered malnutrition.
Cachexia
Cachexia syndromes associate anorexia, fatigue/asthenia, hypercatabolism/antianabolism, and weight loss in the long term. Cachexia is the cytokine‐associated wasting of protein and energy stores due to the effects of disease. Systemic inflammation mediated through cell injury or activation of the immune system triggers an inflammatory response. People with cachexia lose roughly equal amounts of fat and fat‐free mass while maintaining extracellular water and intracellular potassium. The loss of fat‐free mass is mainly from the skeletal muscle.
Cytokines are related to a number of disease conditions, including organ failure (heart, lung, kidney), neurodegenerative diseases, cancer, rheumatoid arthritis, and AIDS50 (Figure 14.1). For each pathology, a different cytokines profile is shown.51,52 Cardiac cachexia due to heart failure–associated inflammation is particularly frequent in NYHA stage III.51 Cancer cachexia is defined as an weight loss >5% in the last six months not due to simple starvation, BMI <20 kg/m2 and any degree of weight loss >2%, or appendicular muscle mass consistent with sarcopenia.53 During chemotherapy, very low intake of protein and weight loss induce impairment in quality of life, particularly fatigue.54 Decreased food intake and low calf circumference (a hallmark of sarcopenia) are independent risk factors for one‐year mortality.55
Cytokines have a direct negative effect on muscle mass, and increased concentrations of inflammatory markers have been associated with a reduced lean mass.56‐58 This direct effect also has been associated with a decline in muscle strength in older adults.
Increasingly, a consensus on the differential effects of starvation and cachexia is developing.59 Starvation can frequently be distinguished from cachexia (Table 14.2). However, in later stages, this distinction is more difficult. The hallmark of starvation is a rapid response to refeeding.
Table 14.2 Distinguishing starvation from cachexia.
Source: Thomas,50 © 2002 Elsevier.
| Starvation | Cachexia | |
|---|---|---|
| Appetite | Suppressed in late phase | Suppressed in early phase |
| Body mass index | Not predictive of mortality | Predictive of mortality |
| Serum albumin | Low in late phase | Low in early phase |
| Transthyretin | Low in late phase | Low in early phase |
| Transferrin | Low | Low |
| Retinol‐binding protein | Low | Low |
| Cholesterol | May remain normal | Low |
| Total lymphocyte count | Low, responds to refeeding | Low, unresponsive to refeeding |
| C‐reactive protein | Few data | Elevated |
| Inflammatory disease | Usually not present | Present |
| Response to refeeding | Reversible | Resistant |
Anorexia
A direct effect of systemic inflammation is appetite suppression. Cytokines directly result in feeding suppression and a lower intake of nutrients, and cachexia is nearly always accompanied by anorexia. IL‐1β and TNF‐α act on the glucose‐sensitive neurons in the ventromedial hypothalamic nucleus (a ‘satiety’ site) and the lateral hypothalamic area (a ‘hunger’ site).60
Acute illness is characterized by a spontaneous decrease in food intake despite an increased need for energy and nutrients.61 Although seemingly paradoxical, the voluntary suppression of food intake during illness is common to most species. Starvation induces autophagy as an adaptive and protective response to nutrient deprivation. Sickness‐associated anorexia appears to upregulate hepatic autophagy, improving the clearance of products such as lipopolysaccharides.62 Autophagy enhances the clearance of pathogens through actions in immune and non‐immune cells. However, underfeeding in acute disease may be detrimental, even in the early stages, depending on the exact mechanism of aggression against the body.62 The data suggest that cytokine levels are commonly associated with disease conditions characterized by cachexia and may play a role in mortality, weight loss, and appetite suppression. In contrast to starvation, cachexia is remarkably resistant to hypercaloric feeding.
The use of the Mini‐Nutritional Assessment (MNA) to explore weight loss
The evaluation of unintended weight loss begins with identifying people at risk. Several assessment instruments have proven validity in the assessment of weight loss or subsequent mortality. The Mini‐Nutritional Assessment (MNA) was developed to assess malnutrition in elderly populations. The full MNA is a multidimensional tool that identifies malnourished older subjects or those at risk for malnutrition, whatever the cause.63 A shorter form has been developed with similar performance64 (Figure 14.2). The MNA assesses body mass with either BMI or calf circumference.
Subjects with a normal baseline score had a lower mortality risk (0.35; 95% CI 0.18–0.66) than subjects with an abnormal MNA score. Subjects judged to be at risk for undernutrition by the MNA had more frequent acute illness, need for more assistance, and more weight loss. The MNA was found to be 96% sensitive and 60% specific for body weight loss. A subsequent analysis found that a six‐item version of the MNA has equivalent predictive value.
The MNA can be used to assess cancer cachexia.65 MNA is a powerful prognostic factor for several pathologies, particularly in cancer.55,66
Interventions
The treatment of undernutrition in the elderly begins with a careful differential diagnostic approach aimed at finding reversible medical causes. Medical conditions that may be associated with anorexia, decreased food intake, or increased metabolic requirements should be assessed. Anorexia may be associated with illness, drugs, dementia, or mood disorders. Decreased food intake may result from dysphagia, chewing problems, nausea, vomiting, diarrhoea, pain, or faecal impaction. Increased metabolic requirements may be precipitated by fever, infection, or the presence of chronic skin wounds.
