Porth's Essentials of Pathophysiology, 4e

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Integrative Body Functions

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used for muscle contraction is derived largely from energy sources that are stored in muscle cells and then released as the muscle contracts. Because most of our energy sources come from the nutrients in food that is eaten, the ability to store energy and control its release is important. Normally, energy utilization is balanced with energy expenditure. When the intake of food consistently exceeds energy expenditure, the excess energy is stored as fat, and the person becomes overweight. Conversely, when food intake does not meet energy expenditure, fat stores and other body tissues are broken down and the person loses weight. More than 90% of body energy is stored as triglycer- ides in the fat cells of the body. The body has a limited ability to store dietary carbohydrates and proteins as energy sources. Dietary carbohydrates are largely con- verted to glucose, which is stored as glycogen in liver and skeletal muscle cells. Liver glycogen stores reach a maximum of approximately 200 to 300 g after a high-carbohydrate meal, after which the liver begins to convert some of the excess glucose to triglycerides for storage in fat cells. The amino acids from protein in the diet are stored mainly in the form of structural proteins, enzymes, nucleoproteins, and other types of cellular proteins. After all the cells have reached their limits, the excess amino acids are converted to glucose and used for energy or stored in the liver as glycogen or in adipose tissue as triglycerides. Triglycerides, which contain no water, have the high- est caloric content of all nutrients and are an efficient form of energy storage. When calorie intake is restricted for any reason, the triglycerides in fat cells are broken down, and their fatty acids and glycerol released as energy sources. Fat cells synthesize triglycerides from glu- cose and fatty acids. Insulin is required for fat storage. It promotes glucose transport through the cell membrane of fat cells. Some of the glucose is used to synthesize fatty acids, but more importantly it forms large amounts of α -glycerol phosphate. This compound supplies the glyc- erol that combines with fatty acids to form triglycerides. Therefore, in the absence of insulin, the storage of tri- glycerides in adipose tissue is almost blocked. Fat cells, or adipocytes , are modified fibroblasts that store almost pure triglycerides in quantities as great as 80% to 95% of their total cell volume. 1 Adipocytes occur singly or in small groups in adipose connective tissue, entire regions of which are committed to triglyc- eride storage. Collectively, adipocytes constitute a large body organ that is metabolically active in the uptake, synthesis, storage, and mobilization of lipids. In addi- tion, adipose tissue provides insulation for the body, fills body crevices, and protects body organs. 2 Early studies suggested that fully differentiated adi- pocytes do not undergo further cell division, and thus that the number of fat cells is fixed in early childhood. This theory proposed that subsequent gains in adipose tissue represented increases in fat cell size. This is no longer considered to be true, since adipose tissue in adults is now known to contain preadipocytes , capable of forming new fat cells, and fat deposition can result from proliferation of these immature adipocytes. 3

Some medications can also increase fat cell numbers. For example, the thiazolidinedione (TZD) class of anti- diabetic drugs can stimulate the formation of new fat cells from the preadipocytes, allowing increased uptake of glucose into these cells (and storage as fat), resulting in the desired reduction in serum glucose levels but with unwanted weight gain. 4 In contrast, some drugs can cause loss of fat cells. This occurs in persons who are HIV-positive and are treated with highly active antiret- roviral therapy (see Chapter 16). The mechanism of fat loss is not known; however, it may be due to increased apoptosis (programmed cell death) of the adipocytes. There are two types of adipose tissue: white (unilocu- lar) and brown (multilocular). 2 White fat , which despite its name is cream colored or yellow, is the predominant form of adipose tissue in adults. The adipocytes of white fat are large spherical cells that become polyhedral or oval when crowded in adipose tissue. The functions of white fat include energy storage, endocrine and adipocytokine secretion, insulation, and cushioning of vital organs. In the connective tissue under the skin, the white fat layer has significant insulating functions. Concentrations are found under the skin of the abdomen, buttocks, axilla, and thigh. Sex differences in the thickness of this fatty layer in different parts of the body account, in part, for the differences in body composition between males and females. Internally, white adipose tissue is preferentially located in the greater omentum, mesentery, and retro- peritoneal space and is usually abundant around the kid- ney. It is also found in the orbits around the eyeballs, in the bone marrow, and between other tissues, where it fills spaces. It retains this structural function even during reduced caloric intake, when the lipid content of adipose tissue elsewhere has been depleted. 2 Brown fat differs from white fat in terms of its ther- mogenic capacity (its ability to produce heat). The color of brown fat reflects the presence of iron in its abundant mitochondria. Brown fat mitochondria produce a spe- cific protein called uncoupling protein-1 (UCP-1) that releases the energy generated from metabolism as heat. It is found abundantly in newborns, in whom thermo- genesis is critical because of their proportionally greater heat loss as compared to adults and their reduced ability to shiver. Historically, adults were thought to have only a small amount of brown fat; however, recent studies have confirmed that moderate deposits of brown fat are com- monly present in adults and can be stimulated by sev- eral factors including cold and the sympathetic nervous system. Nutritional Status The body obtains the energy needed to perform its vari- ous functions and maintain the integrity and health of its cells from the various foods that are consumed in the diet. Because different foods contain different proportions of proteins, carbohydrates, fats, minerals, and vitamins, appropriate balances must be maintained among these constituents so that all segments of the body’s metabolic systems can be supplied with the prerequisite materials.