Medical brain notes 44

  Treatment of Obesity Treatment of obesity depends on decreasing energy input below energy expenditure and creating a sus-tained negative energy balance until the desired weight loss is achieved. In other words, this means either reduc-ing energy intake or increasing energy expenditure. The current National Institutes of Health (NIH) guidelines recommend a decrease in caloric intake of 500 kilo-calories per day for overweight and moderately obese persons (BMI greater than 25 but less than 35 kg/m 2 ) to achieve a weight loss of approximately 1 pound each week. A more aggressive energy deficit of 500 to 1000 kilocalories per day is recommended for persons with BMIs greater than 35 kg/m 2 . Typically, such an energy deficit, if it can be achieved and sustained, will cause a weight loss of about 1 to 2 pounds per week, or about a 10 per cent weight loss after 6 months. For most people attempting to lose weight, increasing physical activity is also an important component of successful lon

  Inanition, Anorexia, and Cachexia Inanition  is the opposite of obesity and is characterizedby extreme weight loss. It can be caused by inadequate availability of food or by pathophysiologic conditions that greatly decrease the desire for food, including psy-chogenic disturbances, hypothalamic abnormalities, and factors released from peripheral tissues. In many instances, especially in those with serious diseases such as cancer, the reduced desire for food may be associated with increased energy expenditure, causing serious weight loss. Anorexia  can be defined as  a reduction in food intake caused primarily by diminished appetite , as opposed tothe literal definition of “not eating.” This definition emphasizes the important role of central neural mech-anisms in the pathophysiology of anorexia in diseases such as cancer, when other common problems, such as pain and nausea, may also cause a person to consume less food.  Anorexia nervosa  is an abnormal psychic state in which a person

  Starvation Depletion of Food Stores in the Body Tissues During Starvation. Even though the tissues preferentially use carbohydrate for energy over both fat and protein, the quantity of car-bohydrate normally stored in the entire body is only a few hundred grams (mainly glycogen in the liver and muscles), and it can supply the energy required for body functions for perhaps half a day. Therefore, except for the first few hours of starvation, the major effects are progressive depletion of tissue fat and protein. Because fat is the prime source of energy (100 times as much fat energy is stored in the normal person as carbohydrate energy), the rate of fat depletion continues unabated, as shown in Figure 71–3, until most of the fat stores in the body are gone. Protein undergoes three phases of depletion: rapid depletion at first, then greatly slowed depletion, and, finally, rapid depletion again shortly before death. The initial rapid depletion is caused by the use of easily mobilized prot

  Vitamins Daily Requirements of Vitamins.  A vitamin is an organiccompound needed in small quantities for normal metabolism that cannot be manufactured in the cells of the body. Lack of vitamins in the diet can cause impor-tant metabolic deficits. Table 71–3 lists the amounts of important vitamins required daily by the average person. These requirements vary considerably, depend-ing on such factors as body size, rate of growth, amount of exercise, and pregnancy. Storage of Vitamins in the Body.  Vitamins are stored to aslight extent in all cells. Some vitamins are stored to a  major extent in the liver. For instance, the quantity of vitamin A stored in the liver may be sufficient to main-tain a person for 5 to 10 months without any intake of vitamin A. The quantity of vitamin D stored in the liver is usually sufficient to maintain a person for 2 to 4 months without any additional intake of vitamin D. The storage of most water-soluble vitamins is rela-tively slight. This applies especi

  Vitamin A Vitamin A occurs in animal tissues as  retinol.  This vitamin does not occur in foods of vegetable origin, but  provitamins  for the formation of vitamin A do occur inabundance in many vegetable foods. These are the yellow and red  carotenoid pigments,  which, because their chemical structures are similar to that of vitamin A, can be changed into vitamin A in the liver. Vitamin A Deficiency Causes “Night Blindness” and Abnormal  Epithelial Cell Growth.  One basic function of vitamin A isits use in the formation of the retinal pigments of the eye. Vitamin A is needed to form the visual pigments and, therefore, to prevent night blindness. Vitamin A is also necessary for normal growth of most cells of the body and especially for normal growth and proliferation of the different types of epithelial cells. When vitamin A is lacking, the epithelial structures of the body tend to become stratified and keratinized. Vitamin A deficiency manifests itself by (1) scaliness of the skin a

  Thiamine (Vitamin B 1 ) Thiamine operates in the metabolic systems of the body principally as  thiamine pyrophosphate;  this compound functions as a  cocarboxylase,  operating mainly in con-junction with a protein decarboxylase for decarboxyla-tion of pyruvic acid and other a-keto acids. Thiamine deficiency  (beriberi)  causes decreased uti-lization of pyruvic acid and some amino acids by the tissues, but increased utilization of fats. Thus, thiamine is specifically needed for the final metabolism of carbo-hydrates and many amino acids. The decreased utiliza-tion of these nutrients is responsible for many debilities associated with thiamine deficiency. Thiamine Deficiency Causes Lesions of the Central and Peripheral Nervous Systems.  The central nervous system normallydepends almost entirely on the metabolism of carbohy-drates for its energy. In thiamine deficiency, the utiliza-tion of glucose by nervous tissue may be decreased 50 to 60 per cent and is replaced by the utilization of

  Niacin Niacin, also called  nicotinic acid,  functions in the body as coenzymes in the form of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinu-cleotide phosphate (NADP). These coenzymes are hydrogen acceptors; they combine with hydrogen atoms as they are removed from food substrates by many types of dehydrogenases. When a defi-ciency of niacin exists, the normal rate of dehydrogena-tion cannot be maintained; therefore, oxidative delivery of energy from the foodstuffs to the functioning ele-ments of all cells cannot occur at normal rates. In the early stages of niacin deficiency, simple phys-iologic changes such as muscle weakness and poor glan-dular secretion may occur, but in severe niacin deficiency, actual tissue death ensues. Pathological lesions appear in many parts of the central nervous system, and permanent dementia or many types of psy-choses may result. Also, the skin develops a cracked, pigmented scaliness in areas that are exposed to mechanical irrit

  Riboflavin (Vitamin B 2 ) Riboflavin normally combines in the tissues with phos-phoric acid to form two coenzymes,  flavin mononu-cleotide (FMN)  and  flavin adenine dinucleotide (FAD). They operate as hydrogen carriers in important oxida-tive systems of the mitochondria. NAD, operating in association with specific dehydrogenases, usually accepts hydrogen removed from various food substrates and then passes the hydrogen to FMN or FAD; finally, the hydrogen is released as an ion into the mitochon-drial matrix to become oxidized by oxygen. Deficiency of riboflavin in experimental animals causes severe dermatitis, vomiting, diarrhea, muscle spasticity that finally becomes muscle weakness, coma and decline in body temperature, and then death. Thus, severe riboflavin deficiency can cause many of the same effects as a lack of niacin in the diet; presumably, the debilities that result in each instance are due to gener-ally depressed oxidative processes within the cells. In the human being,

  Vitamin B 12 Several  cobalamin  compounds that possess the common prosthetic group shown next exhibit so-called vitamin B 12  activity. Note that this prosthetic group contains cobalt, which has bonds similar to those of iron in the hemoglobin molecule. It is likely that the cobalt atom functions in much the same way that the iron atom functions to combine reversibly with other substances. Vitamin B 12  Deficiency Causes Pernicious Anemia.  Vitamin B 12 performs several metabolic functions, acting as a hydro-gen acceptor coenzyme. Its most important function is to act as a coenzyme for reducing ribonucleotides to deoxyribonucleotides, a step that is necessary in the replication of genes. This could explain the major func-tions of vitamin B 12 : (1) promotion of growth and (2) promotion of red blood cell formation and maturation. This red cell function is described in detail in relation to pernicious anemia, a type of anemia caused by failure of red blood cell maturation when vitamin

  Folic Acid (Pteroylglutamic Acid) Several pteroylglutamic acids exhibit the “folic acid effect.” Folic acid functions as a carrier of hydroxy-methyl and formyl groups.  Perhaps its most importantuse in the body is in the synthesis of purines and thymine, which are required for formation of DNA.  Therefore,folic acid, like vitamin B 12 , is required for replication of the cellular genes. This may explain one of the most important functions of folic acid—to promote growth. Indeed, when it is absent from the diet, an animal grows very little. Folic acid is an even more potent growth promoter than vitamin B 12  and, like vitamin B 12 , is important for the maturation of red blood cells. However, vitamin B 12  and folic acid each perform specific and different chemical functions in promoting growth and maturation of red blood cells. One of the significant effects of folic acid deficiency is the development of  macrocytic anemia,  almost identical to that which occurs in pernicious anemia.

  Pyridoxine (Vitamin B 6 ) Pyridoxine exists in the form of  pyridoxal phosphate  in the cells and functions as a coenzyme for many chemi-cal reactions related to amino acid and protein metab-olism.  Its most important role is that of coenzyme in thetransamination process for the synthesis of amino acids. As a result, pyridoxine plays many key roles in metab-olism, especially protein metabolism. Also, it is believed to act in the transport of some amino acids across cell membranes. Dietary lack of pyridoxine in lower animals can cause dermatitis, decreased rate of growth, development of fatty liver, anemia, and evidence of mental deteriora-tion. Rarely, in children, pyridoxine deficiency has been known to cause seizures, dermatitis, and gastrointestinal disturbances such as nausea and vomiting.

  Pantothenic Acid Pantothenic acid mainly is incorporated in the body into  coenzyme A  (CoA), which has many metabolic roles inthe cells. Deficiency of pantothenic acid in lower animals can cause retarded growth, failure of reproduction, graying of the hair, dermatitis, fatty liver, and hemorrhagic adrenocortical necrosis. In the human being, no definite deficiency syndrome has been proved, presumably because of the wide occurrence of this vitamin in almost all foods and because small amounts can probably be synthesized in the body. This does not mean that pan-tothenic acid is not of value in the metabolic systems of the body; indeed, it is perhaps as necessary as any other vitamin.

  Ascorbic Acid (Vitamin C) Ascorbic Acid Deficiency Weakens Collagen Fibers Throughout  the Body.  Ascorbic acid is essential for activating theenzyme  prolyl hydroxylase,  which promotes the hydrox-ylation step in the formation of hydroxyproline, an inte-gral constituent of collagen. Without ascorbic acid, the collagen fibers that are formed in virtually all tissues of the body are defective and weak. Therefore, this vitamin is essential for the growth and strength of the fibers in subcutaneous tissue, cartilage, bone, and teeth. Ascorbic Acid Deficiency Causes Scurvy.  Deficiency of ascor-bic acid for 20 to 30 weeks, which occurred frequently during long ship voyages in the past, causes  scurvy.  One of the most important effects of scurvy is  failure ofwounds to heal.  This is caused by failure of the cells todeposit collagen fibrils and intercellular cement sub-stances. As a result, healing of a wound may require several months instead of the several days ordinarily necessary. Lac

  Vitamin D Vitamin D increases calcium absorption from the gas-trointestinal tract and helps control calcium deposition in the bone.  The mechanism by which vitamin D increasescalcium absorption is mainly to promote active trans-port of calcium through the epithelium of the ileum. In particular, it increases the formation of a calcium-binding protein in the intestinal epithelial cells that aids in calcium absorption. 

  Vitamin E Several related compounds exhibit so-called vitamin E activity. Only rare instances of proved vitamin E defi-ciency have occurred in human beings. In experimental animals, lack of vitamin E can cause degeneration of the germinal epithelium in the testis and, therefore, can cause male sterility. Lack of vitamin E can also cause resorption of a fetus after conception in the female. Because of these effects of vitamin E deficiency, vitamin E is sometimes called the “antisterility vitamin.” Defi-ciency of vitamin E prevents normal growth and some-times causes degeneration of the renal tubular cells and the muscle cells. Vitamin E is believed to play a protective role in the prevention of oxidation of unsaturated fats.  In the absence of vitamin E, the quantity of unsaturated fats in the cells becomes diminished, causing abnormal structure and function of such cellular organelles as the mitochondria, the lysosomes, and even the cell membrane.

  Vitamin K Vitamin K is necessary for the formation by the liver of prothrombin, Factor VII (proconvertin), Factor IX, and Factor X, all of which are important in blood coagulation. Therefore, when vitamin K deficiency occurs, blood clotting is retarded. Several compounds, both natural and synthetic, exhibit vitamin K activity. Because vitamin K is synthe-sized by bacteria in the colon, it is rare for a person to have a bleeding tendency because of vitamin K defi-ciency in the diet. However, when the bacteria of the colon are destroyed by the administration of large quan-tities of antibiotic drugs, vitamin K deficiency occurs rapidly because of the paucity of this compound in the normal diet.

  Mineral Metabolism The functions of many of the minerals, such as sodium, potassium, and chloride, are presented at appropriate points in the text. Only specific functions of minerals not covered elsewhere are mentioned here. The body content of the most important minerals is listed in Table 71–4, and the daily requirements of these are given in Table 71–5. Magnesium.  Magnesium is about one sixth as plentiful incells as potassium. Magnesium is required as a catalyst for many intracellular enzymatic reactions, particularly those related to carbohydrate metabolism. The extracellular fluid magnesium concentration is slight, only 1.8 to 2.5 mEq/L. Increased extracellular concentration of magnesium depresses nervous system activity as well as skeletal muscle contraction.This latter effect can be blocked by the administration of calcium. Low magnesium concentration causes increased irri-tability of the nervous system, peripheral vasodilation,  and cardiac arrhythmias, especially after acu

  Adenosine Triphosphate (ATP) Functions as an “Energy Currency” in Metabolism In the past, we have pointed out that car-bohydrates, fats, and proteins can all be used by cells to synthesize large quantities of adenosine triphosphate (ATP), which can be used as an energy source for almost all other cellular func-tions. For this reason, ATP has been called an energy “currency” in cell metabolism. Indeed, the transfer of energy from foodstuffs to most functional systems of the cells can be done only through this medium of ATP (or the similar nucleotide guanosine triphosphate, GTP).         An attribute of ATP that makes it highly valuable as an energy currency is the large quantity of free energy (about 7300 calories, or 7.3 Calories [kilocalories], per mole under standard conditions, but as much as 12,000 calories under physiologic conditions) vested in each of its two high-energy phosphate bonds. The amount of energy in each bond, when liberated by decomposition of ATP, is enough to ca