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fat‐free mass index (kg/m2) by dual‐energy absorptiometry or corresponding standard using body composition methods such as bioelectrical impedance analysis, computed tomography, or magnetic resonance imaging. When not available by regional preference, physical examination or standard anthropometric measures such as mid –arm muscle or calf circumferences may be used. Thresholds for reduced muscle mass need to be adapted to race (Asia). Functional assessment such as hand grip strength may be considered as a supportive measure.

      c Consider gastrointestinal symptoms as supportive indicators that can impair food intake or absorption (e.g., dysphagia nausea, vomiting, diarrhea, constipation, or abdominal pain). Uses clinical judgement to discern severity based on the degree to which intake or absorption is impaired. Symptom intensity, frequency, and duration should be noted.

      d Reduced assimilation of food /nutrients is associated with malabsorptive disorders such as short bowel syndrome, pancreatic insufficiency, and after bariatric surgery. It is also associated with disorders such as esophageal strictures, gastroparesis, and intestinal pseudo‐obstruction. Malabsorption is a clinical diagnosis manifest as chronic diarrhea or steatorrhea. Malabsorption in those with ostomies is evidenced by elevated volumes of output. Use clinical judgement or additional evaluation to discern severity based on frequency, duration, and quantitation of fecal fact and/or volumes of losses.

      e Acute disease‐/injury‐related. Severe inflammation is likely to be associated with major infection, burns, trauma, or closed head injury. Other acute disease‐/injury‐related conditions are likely to be associated with mild to moderate inflammation.

      f Chronic disease‐related. Severe inflammation is not generally associated with chronic disease conditions. Chronic disease conditions. Chronic or recurrent mild to moderate inflammation is likely to be associated with malignant disease, chronic obstructive pulmonary disease, congestive heart failure, chronic renal disease, or any disease with chronic or recurrent Inflammation. Note that transient inflammation of a mild degree does not meet the threshold for this etiologic criterion.

      g C‐reactive protein may be used as a supportive laboratory measure.

Schematic illustration of malnutrition clinical presentations according to inflammation intensity; low- to medium-grade inflammation is not considered malnutrition.

      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.

      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

      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

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