After the provision of water, the body’s first requirement is for metabolic fuels—fats, carbohydrates, and amino acids from proteins (see Table 16–1). Food intake in excess of energy expenditure leads to obesity, while intake less than expenditure leads to emaciation and wasting, marasmus, and kwashiorkor. Both obesity and severe undernutrition are associated with increased mortality. The body mass index = weight (in kg)/height2 (in m) is commonly used as a way of expressing relative obesity; a desirable range is between 20 and 25.
Energy Requirements Are Estimated by Measurement of Energy Expenditure
Energy expenditure can be determined directly by measuring heat output from the body, but is normally estimated indirectly from the consumption of oxygen. There is an energy expenditure of ∼20 kJ/L of oxygen consumed, regardless of whether the fuel being metabolized is carbohydrate, fat, or protein (see Table 14–1).
Measurement of the ratio of the volume of carbon dioxide produced: volume of oxygen consumed (respiratory quotient, RQ) is an indication of the mixture of metabolic fuels being oxidized (see Table 14–1).
A more recent technique permits estimation of total energy expenditure over a period of 1 to 2 weeks, using dual isotopically labeled water, 2H218O. 2H is lost from the body only in water, while 18O is lost in both water and carbon dioxide; the difference in the rate of loss of the two labels permits estimation of total carbon dioxide production, and hence oxygen consumption and energy expenditure (Figure 43–4).
Dual isotopically labeled water for estimation of energy expenditure.
Basal metabolic rate (BMR) is the energy expenditure by the body when at rest, but not asleep, under controlled conditions of thermal neutrality, measured about 12 hours after the last meal, and depends on weight, age, and gender. Total energy expenditure depends on the BMR, the energy required for physical activity, and the energy cost of synthesizing reserves in the fed state. It is therefore possible to estimate an individual’s energy requirement from body weight, age, gender, and level of physical activity. Body weight affects BMR because there is a greater amount of active tissue in a larger body. The decrease in BMR with increasing age, even when body weight remains constant, is the result of muscle tissue replacement by adipose tissue, which is metabolically less active. Similarly, women have a significantly lower BMR than do men of the same body weight and age because women’s bodies contain proportionally more adipose tissue.
Energy Requirements Increase With Activity
The most useful way of expressing the energy cost of physical activities is as a multiple of BMR. This is known as the physical activity ratio (PAR) or metabolic equivalent of the task (MET). Sedentary activities use only about 1.1 to 1.2 × BMR. By contrast, vigorous exertion, such as climbing stairs, cross-country walking uphill, etc, may use 6 to 8 × BMR. The overall physical activity level (PAL) is the sum of the PAR of different activities, multiplied by the time taken for that activity, divided by 24 hours.
Ten Percent of the Energy Yield of a Meal May Be Expended in Forming Reserves
There is a considerable increase in metabolic rate after a meal (diet-induced thermogenesis). A small part of this is the energy cost of secreting digestive enzymes and of active transport of the products of digestion; the major part is the result of synthesizing reserves of glycogen, triacylglycerol, and protein.
There Are Two Extreme Forms of Undernutrition
Marasmus can occur in both adults and children and occurs in vulnerable groups of all populations. Kwashiorkor affects only children and has been reported only in developing countries. The distinguishing feature of kwashiorkor is that there is fluid retention, leading to edema, and fatty infiltration of the liver. Marasmus is a state of extreme emaciation; it is the outcome of prolonged negative energy balance. Not only have the body’s fat reserves been exhausted, but there is wastage of muscle as well, and as the condition progresses there is loss of protein from the heart, liver, and kidneys. The amino acids released by the catabolism of tissue proteins are used as a source of metabolic fuel and as substrates for gluconeogenesis to maintain a supply of glucose for the brain and red blood cells (see Chapter 20). As a result of the reduced synthesis of proteins, there is impaired immune response and more risk from infections. Impairment of cell proliferation in the intestinal mucosa occurs, resulting in reduction in the surface area of the intestinal mucosa, and reduction in the absorption of such nutrients as are available.
Patients With Advanced Cancer and AIDS Are Malnourished
Patients with advanced cancer, HIV infection and AIDS, and a number of other chronic diseases are frequently undernourished, a condition called cachexia. Physically, they show all the signs of marasmus, but there is considerably more loss of body protein than that occurs in starvation. The secretion of cytokines in response to infection and cancer increases the catabolism of tissue protein by the ATP-dependent ubiquitin-proteasome pathway, so increasing energy expenditure. This differs from marasmus, in which protein synthesis is reduced, but catabolism in unaffected. Patients are hypermetabolic, ie, they have a considerably increased BMR. In addition to activation of the ubiquitin-proteasome pathway of protein catabolism, three other factors are involved. Many tumors metabolize glucose anaerobically to release lactate. This is then used for gluconeogenesis in the liver, which is energy consuming with a net cost of six ATP for each mol of glucose cycled (see Figure 19–4). There is increased stimulation of mitochondrial uncoupling proteins by cytokines leading to thermogenesis and increased oxidation of metabolic fuels. Futile cycling of lipids occurs because hormone sensitive lipase is activated by a proteoglycan secreted by tumors, resulting in liberation of fatty acids from adipose tissue and ATP-expensive reesterification to triacylglycerols in the liver, which are exported in VLDL.
Kwashiorkor Affects Undernourished Children
In addition to the wasting of muscle tissue, loss of intestinal mucosa and impaired immune responses seen in marasmus, children with kwashiorkor show a number of characteristic features. The defining feature is edema, associated with a decreased concentration of plasma proteins. In addition, there is enlargement of the liver as a result of accumulation of fat. It was formerly believed that the cause of kwashiorkor was a lack of protein, with a more or less adequate energy intake; however, analysis of the diets of affected children shows that this is not so. Protein deficiency leads to stunting of growth, and children with kwashiorkor are less stunted than those with marasmus. Furthermore, the edema begins to improve early in treatment, when the child is still receiving a low protein diet.
Very commonly, an infection precipitates kwashiorkor. Superimposed on general food deficiency, there is probably a deficiency of antioxidant nutrients such as zinc, copper, carotene, and vitamins C and E. The respiratory burst in response to infection leads to the production of oxygen and halogen free radicals as part of the cytotoxic action of stimulated macrophages. This added oxidant stress triggers the development of kwashiorkor.