книги студ / color atlas of physiology 5th ed[1]. (a. despopoulos et al, thieme 2003)

Energy Metabolism and Calorimetry

The chemical energy of foodstuffs is first converted into energy-rich substances such as creatine phosphate and adenosine triphosphate (ATP). Energy, work and amount of heat are expressed in joules (J) or calories (cal) (!p. 374). The energy produced by hydrolysis of ATP (!p. 41) is then used to fuel muscle activity, to synthesize many substances, and to create concentration gradients (e.g., Na+ or Ca2+ gradients; !p. 26ff.). During all these energy conversion processes, part of the energy is always converted to heat (!p. 38ff.).

In oxidative (aerobic) metabolism (!p. 39 C), carbohydrates and fat combine with O2 to yield CO2, water, high-energy compounds (ATP etc.) and heat. When a foodstuff is completely oxidized, its biologically useable energy content is therefore equivalent to its physical caloric value (CV).

The bomb calorimeter (!A), a device consisting of an insulated combustion chamber in a tank of water, is used to measure the CV of foodstuffs. A known quantity of a foodstuff is placed in the combustion chamber of the device and incinerated in pure O2. The surrounding water heats up as it absorbs the heat of combustion. The degree of warming is equal to the caloric value of the foodstuff.

Fats and carbohydrates are completely oxidized to CO2 and H2O in the body. Thus, their physiological fuel value (PFV) is identical to their CV. The mean PFV is 38.9 kJ/g (= 9.3 kcal/ g) for fats and 17.2 kJ/g (= 4.1 kcal/g) for digestible carbohydrates (!p. 227 A). In contrast, proteins are not completely broken down to CO2 and water in the human body but yield urea, which provides additional energy when it is oxidized in the bomb calorimeter. The CV of proteins (ca. 23 kJ/g) is therefore greater than their PFV, which is a mean of about 17.2 kJ/g or 4.1 kcal/g (!p. 227 A).

At rest, most of the energy supplied by the diet is converted to heat, since hardly any external mechanical work is being performed. The heat produced is equivalent to the internal energy turnover (e.g., the work performed by the heart and respiratory muscles or expended for active transport or synthesis of substances).

In direct calorimetry (!B), the amount of heat produced is measured directly. The test subject, usually an experimental animal, is placed in a small chamber immersed in a known volume of ice. The amount of heat produced is equivalent to the amount of heat absorbed by the surrounding water or ice. This is respectively calculated as the rise in water temperature or the amount of ice that melts.

In indirect calorimetry, the amount of heat produced is determined indirectly by measur. - ing the amount of O2 consumed (VO2;

!p. 120). This method is used in humans. To determine the total. metabolic rate (or TEE;

!p. 226) from VO2, the caloric equivalent (CE) of a foodstuff oxidized in the subject’s metabolism during the measurement must be known. The CE is calculated from the PFV and the amount of O2 needed to oxidize the food. The

180 g of glucose therefore generates 2827 kJ of heat and consumes 134.4 L of O2 resulting in a CE of 21 kJ/L. This value represents the CE for glucose under standard conditions (O"C; !C). The mean CE of the basic nutrients at 37"C is 18.8 kJ/L O2 (carbohydrates), 17.6 kJ/L O2 (fats) and 16.8 kJ/L O2 (proteins).

The oxidized nutrients must be known in order to calculate the metabolic rate from the CE. The respiratory quotient (RQ) is a rough. measure. of the nutrients oxidized. RQ = VCO2/ VO2 (!p. 120). For pure carbohydrates oxidized, RQ = 1.0. This can be illustrated for glucose as follows:

The oxidation of the fat tripalmitin yields:

2 C51H98O6 + 145 O2 102 CO2 + 98 H2O [10.2]

The RQ of tripalmitin is therefore 102/145 = 0.7. Since the protein fraction of the diet stays relatively constant, each RQ between 1 and 0.7 can be assigned a CE (!D). Using the. known CE, the TEE can be calculated as CE · VO2.

Food increases the TEE (diet–induced thermogenesis, DIT) because energy must be consumed to absorb and store the nutrients. The DIT of protein is higher than that of other substances, e.g., glucose.

Gastrointestinal (GI) Tract: Overview,

Immune Defense, Blood Flow

Food covering the body’s energy and nutrient requirements (!p. 228ff.) must be swallowed, processed and broken down (digestion) before it can be absorbed from the intestines. The three-layered GI musculature ensures that the GI contents are properly mixed and transported. The passage time through the different GI segments varies and is largely dependent on the composition of the food (see A for mean passage times).

Solid food is chewed and mixed with saliva, which lubricates it and contains immunocompetent substances (see below) and enzymes. The esophagus rapidly transports the food bolus to the stomach. The lower esophageal sphincter opens only briefly to allow the food to pass. The proximal stomach mainly serves as a food reservoir. Its tone determines the rate at which food passes to the distal stomach, where it is further processed (chyme formation) and its proteins are partly broken down. The distal stomach (including the pylorus) is also responsible for portioning chyme delivery to the small intestine. The stomach also secretes intrinsic factor (!p. 90).

In the small intestine, enzymes from the pancreas and small intestinal mucosa break down the nutrients into absorbable components. HCO3– in pancreatic juices neutralizes the acidic chyme. Bile salts in bile are essential for fat digestion. The products of digestion (monosaccharides, amino acids, dipeptides, monoglycerides and free fatty acids) as well as water and vitamins are absorbed in the small intestine.

Waste products (e.g. bilirubin) to be excreted reach the feces via bile secreted by the liver. The liver has various other metabolic functions. It serves, for example, as an obligatory relay station for metabolism and distribution of substances reabsorbed from the intestine (via the portal vein, see below), synthesizes plasma proteins (incl. albumin, globulins, clotting factors, apolipoproteins etc.) and detoxifies foreign substances (biotransformation) and metabolic products (e.g., ammonia) before they are excreted.

The large intestine is the last stop for water and ion absorption. It is colonized by bacteria and contains storage areas for feces (cecum, rectum).

Immune defense. The large internal surface area of the GI tract (roughly 100 m2) requires a very effective immune defense system. Saliva contains mucins, immunoglobulin A (IgA) and lysozyme that prevent the penetration of pathogens. Gastric juice has a bactericidal effect. Peyer’s patches supply the GI tract with immunocompetent lymph tissue. M cells (special membranous cells) in the mucosal epithelium allow antigens to enter Peyer’s patches. Together with macrophages, the Peyer’s patches can elicit immune responses by secreting IgA (!p. 98). IgA is transported to the intestinal lumen by transcytosis (!p. 30). In the epithelium, IgA binds to a secretory component, thereby protecting it from digestive enzymes. Mucosal epithelium also contains intraepithelial lymphocytes (IEL) that function like T killer cells (!p. 98). Transmitter substances permit reciprocal communication between IEL and neighboring enterocytes. Macrophages of the hepatic sinusoids (Kupffer’s cells) are additional bastions of immune defense. The physiological colonies of intestinal flora in the large intestine prevent the spread of pathogens. IgA from breast milk protects the GI mucosa of neonates.

Blood flow to the stomach, gut, liver, pancreas and spleen (roughly 30% of cardiac output) is supplied by the three main branches of the abdominal aorta. The intestinal circulation is regulated by local reflexes, the autonomic nervous system, and hormones. Moreover, it is autoregulatory, i.e., largely independent of systemic blood pressure fluctuations. Blood flow to the intestines rises sharply after meals (acetylcholine, vasoactive intestinal peptide VIP, etc. function as vasodilatory transmitters) and falls during physical activity (transmitters: norepinephrine, etc.). The venous blood carries substances reabsorbed from the intestinal tract and enters the liver via the portal vein. Some components of reabsorbed fat are absorbed by the intestinal lymph, which transports them to the greater circulation while bypassing the liver.

Saliva

The functions of saliva are reflected by its constituents. Mucins serve to lubricate the food, making it easier to swallow, and to keep the mouth moist to facilitate masticatory and speech-related movement. Saliva dissolves compounds in food, which is a prerequisite for taste buds stimulation (!p. 338) and for dental and oral hygiene. Saliva has a low NaCl concentration and is hypotonic, making it suitable for rinsing of the taste receptors (NaCl) while eating. Infants need saliva to seal the lips when suckling. Saliva also contains α-amylase, which starts the digestion of starches in the mouth, while immunoglobulin A and lysozyme are part of the immune defense system (!p. 94ff.). The high HCO3– concentration in saliva results in a pH of around 7, which is optimal for α-amylase-catalyzed digestion. Swallowed saliva is also important for buffering the acidic gastric juices refluxed into the esophagus (!p. 238). The secretion of profuse amounts of saliva before vomiting also prevents gastric acid from damaging the enamel on the teeth. Saliva secretion is very dependent on the body water content. A low content results in decreased saliva secretion—the mouth and throat become dry, thereby evoking the sensation of thirst. This is an important mechanism for maintaining the fluid balance (!pp. 168 and 184).

Secretion rate. The rate of saliva secretion varies from 0.1 to 4 mL/min (10–250 µL/min per gram gland tissue), depending on the degree of stimulation (!B). This adds up to about 0.5 to 1.5 L per day. At 0.5 mL/min, 95% of this rate is secreted by the parotid gland (serous saliva) and submandibular gland (mucinrich saliva). The rest comes from the sublingual glands and glands in the buccal mucosa.

Saliva secretion occurs in two steps: The acini (end pieces) produce primary saliva (!A, C) which has an electrolyte composition similar to that of plasma (!B). Primary saliva secretion in the acinar cells is the result of transcellular Cl– transport: Cl– is actively taken up into the cells (secondary active transport) from the blood by means of a Na+-K+-2Cl– cotransport carrier and is released into the lumen (together with HCO3–) via anion chan-

nels, resulting in a lumen-negative transepithelial potential (LNTP) that drives Na+ paracellularly into the lumen. Water also follows passively (osmotic effect). Primary saliva is modified in excretory ducts, yielding secondary saliva. As the saliva passes through the excretory ducts, Na+ and Cl– are reabsorbed and K+ and (carbonic anhydrase-dependent) HCO3– is secreted into the lumen. The saliva becomes hypotonic (far below 100 mOsm/kg H2O; !B) because Na+ and Cl- reabsorption is greater than K+ and HCO3– secretion and the ducts are relatively impermeable to water (!B). If the secretion rate rises to values much higher than 100µL/(min · g), these processes lag behind and the composition of secondary saliva becomes similar to that of primary saliva (!B).

Salivant stimuli. Reflex stimulation of saliva secretion occurs in the larger salivary glands (!D). Salivant stimuli include the smell and taste of food, tactile stimulation of the buccal mucosa, mastication and nausea. Conditioned reflexes also play a role. For instance, the routine clattering of dishes when preparing a meal can later elicit a salivant response. Sleep and dehydration inhibit saliva secretion. Saliva secretion is stimulated via the sympathetic and parasympathetic nervous systems (!C2):

Norepinephrine triggers the secretion of highly viscous saliva with a high concentration of mucin via

"2 adrenoreceptors and cAMP. VIP also increases the cAMP concentration of acinar cells.

Acetylcholine: (a) With the aid of M1 cholinoceptors and IP3 (!pp. 82 and 274), acetylcholine mediates an increase in the cytosolic Ca2+ concentration of acinar cells. This, in turn, increases the conductivity of luminal anion channels, resulting in the production of watery saliva and increased exocytosis of

salivary enzymes. (b) With the aid of M3 cholinergic receptors, ACh mediates the contraction of myoepithelial cells around the acini, leading to emptying of the acini. (c) ACh enhances the production of kallikreins, which cleave bradykinin from plasma kininogen. Bradykinin and VIP (!p. 234) dilate the vessels of the salivary glands. This is necessary because maximum saliva secretion far exceeds resting blood flow.