Small intestine

The small intestine provides the final digestion of food, the absorption of all nutrients, as well as the mechanical movement of food towards the large intestine and some evacuation function. There are several divisions in the small intestine. The structural plan of these departments is the same, but there are some differences. The relief of the mucous membrane forms circular folds, intestinal villi and intestinal crypts. The folds are formed by the mucous membrane and submucosa. The villi are finger-like outgrowths of the lamina propria, covered with epithelium on top. Crypts are depressions of the epithelium in the lamina propria of the mucous membrane. The epithelium lining the small intestine is a single-layered prismatic. This epithelium is distinguished:

• Columnar enterocytes
• Goblet cells
• M cells
• Paneth cells (with acidophobic granularity)
• Endocrine cells
• Undifferentiated cells

The villi are mostly covered with columnar epithelium. These are the main cells that support the digestion process. On their apical surface there are microvilli, which significantly increase the surface area, and contain enzymes on their membranes. It is the columnar enterocytes that provide parietal digestion and absorb split nutrients. Goblet cells are scattered between columnar cells. These cells are glass-shaped. Their cytoplasm is filled with mucous secretions. In a small amount on the villi there are M cells- a kind of columnar enterocytes. There are few microvilli on its apical surface, and the plasmolemma forms deep folds. These cells produce antigens and carry them to the lymphatic cells. Under the epithelium of the villi, there is a loose connective tissue with single smooth muscle cells and well-developed plexuses. The capillaries in the villi are fenestrated, which ensures easier absorption. Crypts are essentially the intestines' own glands. At the bottom of the crypts are poorly differentiated cells. Their division ensures the regeneration of the crypt epithelium and villi. The higher to the surface, the more differentiated the crypt cells will be. Goblet cells, M cells and Paneth cells are involved in the formation of intestinal juice, since they contain granules secreted into the intestinal lumen. Granules contain dipeptidases and lysozyme. Crypts contain endocrine cells:

1. EC cells that produce serotonin
2. ECL cells that produce histamine
3. P cells that produce bambazine
4. And cells that synthesize enteroglucagon
5. K cells that produce pancreatosinin

The length of the crypts is limited by the muscle plate of the mucous membrane. It is formed by two layers of smooth muscle cells (inner circular, outer longitudinal). They are part of the villi, providing their movement. The submucosa is well developed. Contain the neuromuscular plexus, and areas of muscle tissue. Moreover, the closer to the large intestine, the more lymphoid tissue. It merges into plaques (Player's plaques). The muscular layer is formed:

1. Inner circular layer
2. Outer longitudinal layer

Nerve and vascular plexuses are located between them. Outside, the small intestine is covered with a serous membrane. In the duodenum, the ducts of the pancreas and gallbladder open. This also includes the acidic contents of the stomach. Here it is neutralized and the chyme is mixed with the digestive juice. The villi of the duodenum are shorter and wider, and the duodenal glands are located in the submucosa. These are alveolar branched glands that secrete mucus and enzymes. The main enzyme is enterokinase. As one approaches the large intestine, the crypts become larger, the number of goblet cells and lymphoid plaques increases. In order not to miss new interesting articles - subscribe to

Up to 2 liters of secretion ( intestinal juice) with a pH of 7.5 to 8.0. The sources of the secretion are the duodenal submucosa glands (Brunner's glands) and part of the epithelial cells of the villi and crypts.

· Brunner's glands secrete mucus and bicarbonates. The mucus secreted by the Brunner's glands protects the duodenal wall from the action of gastric juice and neutralizes the hydrochloric acid coming from the stomach.

· Epithelial cells of villi and crypts(Fig. 22-8). Their goblet cells secrete mucus, and their enterocytes secrete water, electrolytes and enzymes into the intestinal lumen.

· Enzymes... On the surface of enterocytes in the villi small intestine are peptidases(cleave peptides to amino acids), disaccharidases sucrase, maltase, isomaltase and lactase (break down disaccharides into monosaccharides) and intestinal lipase(breaks down neutral fats to glycerin and fatty acids).

· Regulation of secretion... Secretion stimulate mechanical and chemical irritation of the mucous membrane (local reflexes), agitation vagus nerve, gastrointestinal hormones (especially cholecystokinin and secretin). Secretion is inhibited by influences from the sympathetic nervous system.

Colon secretory function... Colon crypts secrete mucus and bicarbonates. The amount of secretion is regulated by mechanical and chemical irritation of the mucous membrane and local reflexes of the enteric nervous system. Excitation of the parasympathetic fibers of the pelvic nerves causes an increase in the secretion of mucus with a simultaneous activation of the motility of the colon. Strong emotional factors can stimulate bowel movements with intermittent production of mucus without fecal matter (bear disease).

The small intestine contains the duodenum, the jejunum, and the ileum. The duodenum is not only involved in the secretion of intestinal juice with a high content of bicarbonate ions, but is also the dominant zone in the regulation of digestion. It is the duodenum that sets a certain rhythm for the distal parts of the digestive tract through the nervous, humoral and intracavitary mechanisms.

Together with the antrum of the stomach, the duodenum, jejunum and ileum constitute an important single endocrine organ. The duodenum is part of the contractile (motor) complex, which generally consists of the antrum of the stomach, the pyloric canal, the duodenum and the sphincter of Oddi. It takes in the acidic contents of the stomach, secretes its secretions, changes the pH of the chyme to the alkaline side. The contents of the stomach act on the endocrine cells and nerve endings of the mucous membrane of the duodenum, which ensures the coordinating role of the antrum of the stomach and duodenum, as well as the relationship between the stomach, pancreas, liver, small intestine.

Outside of digestion, on an empty stomach, the contents of the duodenum have a slightly alkaline reaction (pH 7.2–8.0). When portions of acidic contents from the stomach pass into it, the reaction of the duodenal contents also becomes acidic, but then it changes rapidly, since the hydrochloric acid of the gastric juice is neutralized here by bile, pancreatic juice, as well as duodenal (Brunner's) glands and intestinal crypts (Lieberkun's glands ). In this case, the action of gastric pepsin is terminated. The higher the acidity of the duodenal contents, the more pancreatic juice and bile are secreted and the more the evacuation of stomach contents into the duodenum slows down. In the hydrolysis of nutrients in the duodenum, the role of pancreatic juice and bile enzymes is especially important.

Digestion in the small intestine is the most important step in the overall digestive process. It provides depolymerization of nutrients to the stage of monomers, which are absorbed from the intestine into the blood and lymph. Digestion in the small intestine occurs first in its cavity (cavity digestion), and then in the area of ​​the brush border of the intestinal epithelium with the help of enzymes built into the membrane of intestinal microvilli, and also fixed in the glycocalyx (membrane digestion). Cavity and membrane digestion is carried out by enzymes coming with pancreatic juice, as well as by intestinal enzymes proper (membrane, or transmembrane) (see Table 2.1). Bile plays an important role in lipid breakdown.

For humans, a combination of cavity and membrane digestion is most characteristic. The initial stages of hydrolysis are carried out due to cavity digestion. Most supramolecular complexes and large molecules (proteins and products of their incomplete hydrolysis, carbohydrates, fats) are degraded in the cavity of the small intestine in neutral and slightly alkaline media, mainly under the action of endohydrolases secreted by pancreatic cells. Some of these enzymes can be adsorbed on mucus structures or mucous deposits. Peptides formed in the proximal part of the intestine and consisting of 2-6 amino acid residues give 60-70% -amino-nitrogen, and in the distal part of the intestine - up to 50%.

Carbohydrates (polysaccharides, starch, glycogen) are broken down by pancreatic amylase to dextrins, tri- and disaccharides without significant accumulation of glucose. Fats undergo hydrolysis in the small intestine cavity by pancreatic lipase, which gradually cleaves fatty acids, which leads to the formation of di- and monoglycerides, free fatty acids and glycerol. Bile plays an essential role in the hydrolysis of fats.

The products of partial hydrolysis formed in the cavity of the small intestine, due to intestinal motility, come from the cavity of the small intestine to the zone of the brush border, which is facilitated by their transfer in the flows of the solvent (water) arising from the absorption of sodium and water ions. It is on the structures of the brush border that membrane digestion takes place. In this case, the intermediate stages of the hydrolysis of biopolymers are realized by pancreatic enzymes adsorbed on the structures of the apical surface of enterocytes (glycocalyx), and the final stages - by the intestinal membrane enzymes proper (maltase, sucrase, α-amylase, isomaltase, trehalase, aminopeptidase and others)> embedded in the enterocyte membrane covering the microvilli of the brush border. Some enzymes (α-amylase and aminopeptidase) also hydrolyze highly polymerized products.

Peptides entering the area of ​​the brush border of intestinal cells are broken down to oligopeptides, dipeptides and amino acids capable of absorption. Peptides consisting of more than three amino acid residues are hydrolyzed predominantly by brush border enzymes, and three and dipeptides are hydrolyzed by both brush border enzymes and intracellularly by cytoplasmic enzymes. Glycylglycine and some dipeptides containing proline and hydroxyproline residues and not having a significant nutritional value are absorbed partially or completely in an undigested form. Disaccharides from food (for example, sucrose), as well as those formed during the breakdown of starch and glycogen, are hydrolyzed by intestinal glycosidases themselves to monosaccharides, which are transported through the intestinal barrier into the internal environment of the body. Triglycerides are cleaved not only under the action of pancreatic lipase, but also under the influence of intestinal monoglyceride lipase.

Secretion

In the mucous membrane of the small intestine, there are glandular cells located on the villi that produce digestive secretions that are secreted into the intestine. These are Brunner's glands of the duodenum, Lieberkun's crypts of the jejunum, goblet cells. Endocrine cells produce hormones that enter the intercellular space, and from where they are transported to the lymph and blood. The cells secreting protein secretion with acidophilic granules in the cytoplasm (Paneth cells) are also located here. The volume of intestinal juice (normally up to 2.5 liters) can increase with local exposure to certain food or toxic substances on the intestinal mucosa. Progressive dystrophy and atrophy of the mucous membrane of the small intestine are accompanied by a decrease in the secretion of intestinal juice.

The glandular cells form and accumulate a secret and at a certain stage of their activity are rejected into the lumen of the intestine, where, decaying, they give this secret into the surrounding fluid. The juice can be divided into liquid and solid parts, the ratio between which varies depending on the strength and nature of the irritation of the intestinal cells. The liquid part of the juice contains about 20 g / l of dry matter, which consists partly of the contents of desquamated cells coming from organic blood (mucus, proteins, urea, etc.) and inorganic substances - about 10 g / l (such as bicarbonates, chlorides, phosphates). The dense part of the intestinal juice looks like mucous lumps and consists of intact desquamated epithelial cells, their fragments and mucus (goblet cell secretion).

Have healthy people periodic secretion is characterized by relative qualitative and quantitative stability, contributing to the maintenance of homeostasis of the enteric environment, which is primarily the chyme.

According to some calculations, an adult with digestive juices enters food up to 140 g of protein per day, another 25 g of protein substrates is formed as a result of desquamation of the intestinal epithelium. It is not difficult to imagine the significance of protein losses that can occur with prolonged and severe diarrhea, with any form of indigestion, pathological conditions associated with enteric insufficiency - increased intestinal secretion and impaired reabsorption (reabsorption).

The mucus synthesized by the goblet cells of the small intestine is an important component of secretory activity. The number of goblet cells in the villi is greater than in crypts (up to approximately 70%), and increases in the distal small intestine. This appears to reflect the importance of the non-digestive functions of mucus. It was found that the cell epithelium of the small intestine is covered with a continuous heterogeneous layer up to 50 times the height of the enterocyte. This supraepithelial layer of mucous overlays contains a significant amount of adsorbed pancreatic and a small amount of intestinal enzymes that implement the digestive function of mucus. The mucous secretion is rich in acidic and neutral mucopolysaccharides, but poor in proteins. This ensures the cytoprotective consistency of the mucous gel, mechanical, chemical protection of the mucous membrane, prevention of penetration of large molecular compounds and antigenic aggressors into the deep tissue structures.

Suction

Absorption is understood as a set of processes as a result of which food components contained in the digestive cavities are transferred through the cell layers and intercellular pathways into the internal circulatory environments of the body - blood and lymph. The main organ of absorption is the small intestine, although some food components can be absorbed in the large intestine, stomach, and even the mouth. Nutrients coming from the small intestine, with the flow of blood and lymph, are carried throughout the body and then participate in intermediate (intermediate) metabolism. Up to 8-9 liters of liquid are absorbed in the gastrointestinal tract per day. Of these, approximately 2.5 liters comes from food and drink, the rest is the liquid of the secretions of the digestive system.

The absorption of most nutrients occurs after their enzymatic processing and depolymerization, which occur both in the cavity of the small intestine and on its surface due to membrane digestion. Within 3–7 hours after a meal, all its main components disappear from the cavity of the small intestine. The intensity of absorption of nutrients in different parts of the small intestine is not the same and depends on the topography of the corresponding enzymatic and transport activities along the intestinal tube (Fig. 2.4).

There are two types of transport across the intestinal barrier into the internal environment of the body. These are transmembrane (transcellular, through the cell) and paracellular (shunting, going through the intercellular spaces).

The main type of transport is transmembrane. Conventionally, two types of transmembrane transport of substances through biological membranes can be distinguished - these are macromolecular and micromolecular. Under macromolecular transport the transfer of large molecules and molecular aggregates through the cell layers is understood. This transport is intermittent and is realized mainly through pino- and phagocytosis, collectively called "endocytosis". Due to this mechanism, proteins can enter the body, including antibodies, allergens and some other compounds that are important for the body.

Micromolecular transport serves as the main type, as a result of which the products of hydrolysis of food substances, mainly monomers, various ions, are transferred from the intestinal environment to the internal environment of the body, medications and other compounds with low molecular weight. The transport of carbohydrates through the plasma membrane of intestinal cells occurs in the form of monosaccharides (glucose, galactose, fructose, etc.), proteins - mainly in the form of amino acids, fats - in the form of glycerol and fatty acids.

During transmembrane movement, the substance crosses the membrane of the microvilli of the brush border of intestinal cells, enters the cytoplasm, then through the basolateral membrane - into the lymphatic and blood vessels intestinal villi and further into common system circulation. The cytoplasm of intestinal cells serves as a compartment that forms a gradient between the brush border and the basolateral membrane.

Rice. 2.4. Distribution of resorptive functions along the small intestine (after: S. D. Booth, 1967, with changes).

In micromolecular transport, in turn, it is customary to distinguish passive and active transport. Passive transport can occur due to the diffusion of substances through a membrane or water pores along a concentration gradient, osmotic or hydrostatic pressure. It is accelerated by water flows moving through the pores, changes in the pH gradient, as well as transporters in the membrane (in the case of facilitated diffusion, their work is carried out without energy consumption). Exchange diffusion provides microcirculation of ions between the cell periphery and the microenvironment surrounding it. Facilitated diffusion is realized with the help of special transporters - special protein molecules (specific transport proteins) that facilitate the penetration of substances through the cell membrane without energy consumption due to the concentration gradient.

Actively transported substance moves through the apical membrane of the intestinal cell against its electromechanical gradient with the participation of special transport systems functioning as mobile or conformational transporters (carriers) with the expenditure of energy. In this way, active transport differs sharply from facilitated diffusion.

The transport of most organic monomers across the brush border membrane of intestinal cells depends on sodium ions. This is true for glucose, galactose, lactate, most amino acids, some conjugated bile acids, and a number of other compounds. The driving force of such transport is the Na + concentration gradient. However, in the cells of the small intestine, there is not only a Ma + -dependent transport system, but also a Ma + -independent transport system, which is characteristic of some amino acids.

Water is absorbed from the intestine into the blood and comes back according to the laws of osmosis, but most of it is from isotonic solutions of intestinal chyme, since hyper- and hypotonic solutions are rapidly diluted or concentrated in the intestine.

Suction sodium ions in the intestine, it occurs both through the basolateral membrane into the intercellular space and further into the blood, and through the transcellular route. During the day, 5–8 g of sodium enters the human digestive tract with food, 20–30 g of this ion is secreted with the digestive juices (ie, only 25–35 g). Part of sodium ions are absorbed together with chlorine ions, as well as during the oppositely directed transport of potassium ions due to Na +, K + -ATPase.

Absorption of divalent ions(Ca2 +, Mg2 +, Zn2 +, Fe2 +) occurs along the entire length of the gastrointestinal tract, and Cu2 + - mainly in the stomach. Divalent ions are absorbed very slowly. The absorption of Ca2 + occurs most actively in the duodenum and jejunum with the participation of mechanisms of simple and facilitated diffusion; it is activated by vitamin D, pancreatic juice, bile and a number of other compounds.

Carbohydrates absorbed in the small intestine in the form of monosaccharides (glucose, fructose, galactose). Absorption of glucose occurs actively with the expenditure of energy. At present, the molecular structure of the N + -dependent glucose transporter is already known. It is a high molecular weight protein oligomer with extracellular loops with glucose and sodium binding sites.

Protein absorbed through the apical membrane of intestinal cells mainly in the form of amino acids and to a much lesser extent in the form of dipeptides and tripeptides. As with monosaccharides, the sodium cotransporter provides the energy for amino acid transport.

In the brush border of enterocytes, there are at least six Na + -dependent transport systems for various amino acids and three - independent of sodium. A peptide (or amino acid) transporter, like a glucose transporter, is an oligomeric glycosylated protein with an extracellular loop.

As for the absorption of peptides, or the so-called peptide transport, in the early stages of postnatal development in the small intestine absorption of intact proteins takes place. It is now accepted that, in general, the absorption of intact proteins is a physiological process necessary for the selection of antigens by subepithelial structures. However, against the background of the general intake of food proteins mainly in the form of amino acids, this process has very little nutritional value. A number of dipeptides can enter the cytoplasm by the transmembrane pathway, like some tripeptides, and are cleaved intracellularly.

Lipid transport done differently. Long-chain fatty acids and glycerol formed during the hydrolysis of food fats are practically passively transferred through the apical membrane into the enterocyte, where they are resynthesized into triglycerides and are enclosed in a lipoprotein membrane, the protein component of which is synthesized in the enterocyte. Thus, a chylomicron is formed, which is transported to the central lymphatic vessel of the intestinal villi and then enters the blood through the thoracic lymphatic duct system. Medium-chain and short-chain fatty acids enter the bloodstream immediately, without triglyceride resynthesis.

The rate of absorption in the small intestine depends on the level of its blood supply (affects the processes of active transport), the level of intraintestinal pressure (affects the processes of filtration from the lumen of the intestine) and the topography of absorption. Information about this topography makes it possible to imagine the peculiarities of absorption deficit in case of enteral pathology, with post-resection syndromes and other disorders of the gastrointestinal tract. In fig. 2.5 shows a scheme for monitoring the processes occurring in the gastrointestinal tract.

Rice. 2.5. Factors affecting the processes of secretion and absorption in the small intestine (after: R. J. Levin, 1982, with changes).

Motor skills

Motor-evacuation activity is essential for digestion processes in the small intestine, which ensures mixing of food contents with digestive secretions, movement of the chyme through the intestine, change of the chyme layer on the surface of the mucous membrane, increased intraintestinal pressure, which helps to filter some components of the chyme from the intestinal cavity into the blood. and lymph. The motor activity of the small intestine consists of non-propulsive stirring movements and propulsive peristalsis. It depends on the intrinsic activity of smooth muscle cells and on the influence of the autonomic nervous system and numerous hormones, mainly of gastrointestinal origin.

So, the contractions of the small intestine occur as a result of coordinated movements of the longitudinal (outer) and transverse (circulatory) layers of fibers. These abbreviations can be of several types. According to the functional principle, all abbreviations are divided into two groups:

1) local, which provide mixing and grinding of the contents of the small intestine (non-propulsive);

2) aimed at moving the contents of the intestine (propulsive). There are several types of contractions: rhythmic segmentation, pendulum, peristaltic (very slow, slow, fast, rapid), antiperistaltic and tonic.

Rhythmic segmentation provided mainly by the contraction of the circulatory muscle layer. In this case, the contents of the intestine are divided into parts. The next contraction forms a new segment of the intestine, the contents of which consists of parts of the former segment. This achieves mixing of the chyme and an increase in pressure in each of the forming segments of the intestine. Pendulum contractions provided by contractions of the longitudinal muscle layer with the participation of the circulatory. With these contractions, the chyme moves back and forth and a weak forward movement in the aboral direction. In the proximal parts of the small intestine, the frequency of rhythmic contractions, or cycles, is 9-12, in the distal - 6-8 per minute.

Peristalsis consists in the fact that above the chyme, due to the contraction of the circulatory layer of the muscles, an interception is formed, and below, as a result of contraction of the longitudinal muscles, an expansion of the intestinal cavity is formed. This interception and expansion moves along the intestine, moving the chyme portion in front of the interception. Several peristaltic waves simultaneously move along the length of the intestine. At antiperistaltic contractions the wave moves in the opposite (oral) direction. Normally, the small intestine does not contract antiperistaltically. Tonic contractions can have a low speed, and sometimes do not spread at all, significantly narrowing the intestinal lumen over a large extent.

A definite role of motility in the elimination of digestive secretions was revealed - peristalsis of the ducts, changes in their tone, closure and opening of their sphincters, contraction and relaxation of the gallbladder. To this should be added changes in the folding of the mucous membrane, the micromotor of the intestinal villi and microvilli of the small intestine - very important phenomena that optimize membrane digestion, the absorption of nutrients and other substances from the intestine into the blood and lymph.

Small intestine motility is regulated by nervous and humoral mechanisms. Intramural (in the intestinal wall) nervous formations, as well as the central nervous system, exert a coordinating influence. Intramural neurons provide coordinated contractions of the intestine. Their role is especially great in peristaltic contractions. Intramural mechanisms are influenced by extramural, parasympathetic and sympathetic nervous mechanisms, as well as humoral factors.

The motor activity of the intestine depends, among other things, on physical and chemical properties chyme. Coarse food (black bread, vegetables, coarse fiber foods) and fats increase its activity. At an average speed of movement of 1–4 cm / min, food reaches the cecum in 2–4 hours. The duration of movement of food is influenced by its composition, depending on it, the speed of movement decreases in the following order: carbohydrates, proteins, fats.

Humoral substances alter intestinal motility, acting directly on muscle fibers and through receptors on neurons of the intramural nervous system. Vasopressin, oxytocin, bradykinin, serotonin, histamine, gastrin, motilin, cholecystokinin-pancreosimin, substance P and a number of other substances (acids, alkalis, salts, digestion products of food substances, especially fats) increase the motility of the small intestine.

Protective systems

The intake of food in the W CT should be considered not only as a way of replenishing energy and plastic materials, but also as an allergic and toxic aggression. Nutrition is associated with the danger of penetration into the internal environment of the body of various kinds of antigens and toxic substances... Foreign proteins are especially dangerous. Only thanks to a sophisticated protection system negative sides food is effectively neutralized. In these processes, a particularly important role is played by the small intestine, which carries out several vital functions - digestive, transport and barrier. It is in the small intestine that food undergoes multi-stage enzymatic processing, which is necessary for the subsequent absorption and assimilation of the resulting hydrolysis products of nutrients that have no species specificity. By this, the body protects itself to a certain extent from the effects of foreign substances.

Barrier, or protective, the function of the small intestine depends on its macro- and microstructure, enzyme spectrum, immune properties, mucus, permeability, etc. The mucous membrane of the small intestine is involved in mechanical, or passive, as well as in active protection of the body from harmful substances. Non-immune and immune defense mechanisms of the small intestine protect the internal environment of the body from foreign substances, antigens and toxins. Acidic gastric juice, digestive enzymes, including proteases of the gastrointestinal tract, small intestine motility, microflora, mucus, brush border and glycocalyx of the apical part of intestinal cells belong to nonspecific protective barriers.

Due to the ultrastructure of the surface of the small intestine, that is, the brush border and glycocalyx, as well as the lipoprotein membrane, intestinal cells serve as a mechanical barrier that prevents the entry of antigens, toxic substances and other high-molecular compounds from the enteric medium into the internal one. Exceptions are molecules that undergo hydrolysis by enzymes adsorbed on glycocalyx structures. Large molecules and supramolecular complexes cannot penetrate into the area of ​​the brush border, since its pores, or intermicrovillous spaces, are extremely small. Thus, the smallest distance between microvilli is on average 1–2 µm, and the size of the cells of the glycocalyx network is hundreds of times smaller. Thus, the glycocalyx serves as a barrier that determines the permeability of food substances, and the apical membrane of intestinal cells due to the glycocalyx is practically inaccessible (or little accessible) for macromolecules.

Another mechanical, or passive, defense system includes the limited permeability of the small intestine mucosa for water-soluble molecules with a relatively low molecular weight and impermeability to polymers, which include proteins, mucopolysaccharides and other substances with antigenic properties. However, endocytosis is characteristic of the cells of the digestive apparatus during the period of early postnatal development, which contributes to the entry of macromolecules and foreign antigens into the internal environment of the body. The intestinal cells of adult organisms are also capable, in certain cases, of absorbing large molecules, including uncleaved ones. In addition, when food passes through the small intestine, a significant amount of volatile fatty acids is formed, some of which, when absorbed, cause a toxic effect, and others - a local irritant effect. As for xenobiotics, their formation and absorption in the small intestine varies depending on the composition, properties and contamination of food.

The immunocompetent lymphatic tissue of the small intestine makes up about 25% of its entire mucous membrane. Anatomically and functionally, this tissue of the small intestine is divided into three sections:

1) Peyer's patches - clusters of lymphatic follicles, in which antigens are collected and antibodies to them are produced;

2) lymphocytes and plasma cells that produce secretory IgA;

3) intraepithelial lymphocytes, mainly T-lymphocytes.

Peyer's patches (about 200-300 in an adult) are composed of organized clusters of lymphatic follicles, which contain the precursors of the lymphocyte population. These lymphocytes colonize other areas of the intestinal mucosa and take part in its local immune activity. In this regard, Peyer's patches can be considered as a region that initiates immune activity in the small intestine. Peyer's patches contain B and T cells, and a small number of M cells, or membrane cells, are localized in the epithelium above the plaques. It is assumed that these cells are involved in creating favorable conditions for the access of luminal antigens to subepithelial lymphocytes.

Interepithelial cells of the small intestine are located between intestinal cells in the basal part of the epithelium, closer to the basement membrane. Their ratio to other intestinal cells is approximately 1: 6. About 25% of interepithelial lymphocytes have T-cell markers.

In the mucous membrane of the human small intestine there are more than 400 000 plasma cells per 1 mm2, as well as about 1 million lymphocytes per 1 cm2. Normally, the jejunum contains 6 to 40 lymphocytes per 100 epithelial cells. This means that in the small intestine, in addition to the epithelial layer that separates the enteral and internal environments of the body, there is also a powerful leukocyte layer.

As noted above, the gut immune system is exposed to an enormous amount of exogenous food antigens. The cells of the small and large intestines produce a number of immunoglobulins (Ig A, Ig E, Ig G, Ig M), but mainly Ig A (Table 2.2). Immunoglobulins A and E, secreted into the intestinal cavity, seem to be adsorbed on the structures of the intestinal mucosa, creating an additional protective layer in the glycocalyx area.

Table 2.2 The number of cells of the small and large intestines that produce immunoglobulins

The functions of a specific protective barrier are also performed by mucus, which covers most of the epithelial surface of the small intestine. It is a complex mixture of various macromolecules, including glycoproteins, water, electrolytes, microorganisms, desquamated intestinal cells, etc. Mucin, a component of mucus that makes it gel-like, contributes to the mechanical protection of the apical surface of intestinal cells.

There is another important barrier that prevents the entry of toxic substances and antigens from the enteric into the internal environment of the body. This barrier can be called transformational, or enzymatic, since it is caused by enzymatic systems of the small intestine that carry out sequential depolymerization (transformation) of food poly- and oligomers to monomers capable of utilization. The enzymatic barrier consists of a number of separate spatially separated barriers, but as a whole forms a single interconnected system.

Pathophysiology

In medical practice, violations of the functions of the small intestine are quite common. They are not always accompanied by distinct clinical symptoms and are sometimes masked by extraintestinal disorders.

By analogy with the accepted terms ("heart failure", " renal failure"," Liver failure ", etc.), according to many authors, it is advisable to dysfunctions of the small intestine, its insufficiency, denote the term Enteric insufficiency"(" Failure of the small intestine "). Enteric insufficiency is usually understood as clinical syndrome caused by dysfunctions of the small intestine with all their intestinal and extraintestinal manifestations. Enteral insufficiency occurs with pathology of the small intestine itself, as well as with various diseases other organs and systems. In congenital primary forms of small intestine insufficiency, an isolated selective digestive or transport defect is most often inherited. In acquired forms, multiple defects in digestion and absorption prevail.

Large portions of gastric contents entering the duodenum are less impregnated with duodenal juice and neutralized more slowly. Duodenal digestion suffers also because in the absence of free of hydrochloric acid or with its deficiency, the synthesis of secretin and cholecystokinin, which regulate the secretory activity of the pancreas, is significantly inhibited. A decrease in the formation of pancreatic juice, in turn, leads to disorders of intestinal digestion. This is the reason that the chyme, in a form not prepared for absorption, enters the lower parts of the small intestine and irritates the receptors of the intestinal wall. There is an increase in peristalsis and water secretion into the lumen of the intestinal tube, diarrhea and enteral insufficiency develop as a manifestation of severe digestive disorders.

In conditions of hypochlorhydria and especially achilia, the absorption function of the intestine sharply deteriorates. Disorders of protein metabolism occur, leading to dystrophic processes in many internal organs, especially in the heart, kidneys, liver, muscle tissue. Disorders may develop immune system... Gastrogenic enteral insufficiency early leads to hypovitaminosis, deficiency in the body of mineral salts, disorders of homeostasis and blood coagulation system.

In the formation of enteric insufficiency, violations of the secretory function of the intestine are of certain importance. Mechanical irritation of the mucous membrane of the small intestine sharply increases the release of the liquid part of the juice. In the small intestine, not only water and low molecular weight substances are intensively secreted, but also proteins, glycoproteins, lipids. The described phenomena, as a rule, develop with sharply suppressed acid formation in the stomach and inadequate intragastric digestion in connection with this: undigested components of the food bolus cause a sharp irritation of the receptors of the mucous membrane of the small intestine, initiating an increase in secretion. Similar processes take place in patients who have undergone gastric resection, including the pyloric sphincter. Loss of gastric reservoir function, depression gastric secretion, some other postoperative disorders contribute to the development of the so-called "dumping" syndrome (dumping syndrome). One of the manifestations of this postoperative disorder is an increase in the secretory activity of the small intestine, its hypermotility, manifested by diarrhea of ​​the small intestine type. Inhibition of intestinal juice production, which develops in a number of pathological conditions (dystrophy, inflammation, atrophy of the mucous membrane of the small intestine, ischemic disease digestive organs, protein-energy deficiency of the body, etc.), a decrease in enzymes in it constitute the pathophysiological basis of disorders of the intestinal secretory function. With a decrease in the efficiency of intestinal digestion, the hydrolysis of fats and proteins in the cavity of the small intestine changes little, since the secretion of lipase and proteases with pancreatic juice increases compensatory.

The most important defects in the digestive and transport processes are in people with congenital or acquired fermentopathy due to a lack of certain enzymes. So, as a result of lactase deficiency in the cells of the intestinal mucosa, membrane hydrolysis and assimilation of milk sugar are disturbed (milk intolerance, lactase deficiency). Insufficient production of sucrase, α-amylase, maltase and isomaltase by cells of the mucous membrane of the small intestine leads to the development of intolerance by patients, respectively, to sucrose and starch. In all cases of intestinal enzymatic deficiency with incomplete hydrolysis of food substrates, toxic metabolites are formed, provoking the development of severe clinical symptoms, not only characterizing an increase in the manifestations of enteric insufficiency, but also extraintestinal disorders.

With various diseases of the gastrointestinal tract, there are violations of cavity and membrane digestion, as well as absorption. Disorders can have an infectious and non-infectious etiology, be acquired or hereditary. Defects of membrane digestion and absorption occur when the distribution of enzymatic and transport activities along the small intestine is disturbed after, for example, surgical interventions, in particular after resection of the small intestine. The pathology of membrane digestion can be caused by atrophy of the villi and microvilli, disruption of the structure and ultrastructure of intestinal cells, changes in the spectrum of the enzyme layer and the sorption properties of the structures of the intestinal mucosa, disorders of intestinal motility, in which the transfer of nutrients from the intestinal cavity to its surface is disturbed, in case of dysbacteriosis, etc. ... etc.

Disorders of membrane digestion occur in a fairly wide range of diseases, as well as after intensive antibiotic therapy, various surgical interventions on the gastrointestinal tract. With many viral diseases(poliomyelitis, mumps, adenovirus influenza, hepatitis, measles) there are severe digestive and absorption disorders with symptoms of diarrhea and steatorrhea. In these diseases, there is a pronounced atrophy of the villi, violations of the ultrastructure of the brush border, insufficiency of the enzymatic layer of the intestinal mucosa, which leads to disorders of membrane digestion.

Often, violations of the ultrastructure of the brush border are combined with a sharp decrease in the enzymatic activity of enterocytes. Numerous cases are known in which the ultrastructure of the brush border remains practically normal, but nevertheless, one or more digestive intestinal enzymes are deficient. Many food intolerances are due to these specific disorders of the enzyme layer of the intestinal cells. Currently, partial enzyme deficiencies of the small intestine are widely known.

Disaccharidase deficiencies (including sucrose deficiency) can be primary, that is, due to the corresponding genetic defects, and secondary, developing against the background of various diseases (sprue, enteritis, after surgery, with infectious diarrhea, etc.). Isolated sucrase deficiency is rare and in most cases is combined with changes in the activity of other disaccharides, most often isomaltase. Lactase deficiency is especially widespread, as a result of which milk sugar (lactose) is not absorbed and intolerance to milk arises. Lactase deficiency is determined by a genetically recessive pathway. It is assumed that the degree of repression of the lactase gene is associated with the history of this ethnic group.

Enzyme deficiencies of the intestinal mucosa can be associated both with a violation of the synthesis of enzymes in the intestinal cells, and with a violation of their integration into the apical membrane, where they perform their digestive functions... In addition, they can be caused by the acceleration of the degradation of the corresponding intestinal enzymes. Thus, for the correct interpretation of a number of diseases, it is necessary to take into account the disorders of membrane digestion. Defects in this mechanism lead to changes in the intake of essential nutrients into the body with far-reaching consequences.

The cause of impaired assimilation of proteins can be changes in the gastric phase of their hydrolysis, however, defects in the intestinal phase due to insufficiency of pancreatic and intestinal membrane enzymes are more serious. Rare genetic disorders include enteropeptidase and trypsin deficiencies. A decrease in peptidase activities in the small intestine is observed in a number of diseases, for example, an incurable form of celiac disease, Crohn's disease, duodenal ulcer, with radio- and chemotherapy (for example, 5-fluorouracil), etc. Aminopeptiduria should also be mentioned, which is associated with a decrease in the activity of dipeptidases cleaving proline peptides inside intestinal cells.

Many bowel dysfunctions in different forms pathologies may depend on the state of the glycocalyx and the digestive enzymes it contains. Disturbances in the adsorption of pancreatic enzymes on the structures of the mucous membrane of the small intestine can cause malnutrition (malnutrition), and atrophy of the glycocalyx can contribute to the damaging effect of toxic agents on the enterocyte membrane.

Violations of absorption processes are manifested in their slowdown or pathological enhancement. The slowdown in absorption by the intestinal mucosa may be due to the following reasons:

1) insufficient splitting of food masses in the cavities of the stomach and small intestine (abnormalities of cavity digestion);

2) disorders of membrane digestion;

3) congestive hyperemia of the intestinal wall (vascular paresis, shock);

4) ischemia of the intestinal wall (atherosclerosis of the vessels of the mesentery, cicatricial postoperative occlusion of the vessels of the intestinal wall, etc.);

5) inflammation of the tissue structures of the wall of the small intestine (enteritis);

6) resection of most of the small intestine (short bowel syndrome);

7) obstruction in the upper parts of the intestine, when food masses do not enter its distal parts.

Pathological enhancement of absorption is associated with an increase in the permeability of the intestinal wall, which can often be observed in patients with thermoregulation disorders (thermal lesions of the body), infectious and toxic processes in a number of diseases, food allergies, etc. Under the influence of some factors, the threshold of permeability of the mucous membrane of the small intestine for large-molecular compounds, including products of incomplete breakdown of food substances, proteins and peptides, allergens, metabolites. The appearance of foreign substances in the blood, in the internal environment of the body, contributes to the development of general phenomena of intoxication, sensitization of the body, and the occurrence of allergic reactions.

It is impossible not to mention such diseases in which the absorption of neutral amino acids in the small intestine is impaired, as well as cystinuria. In cystinuria, there are combined disturbances in the transport of diaminomonocarboxylic acids and cystine in the small intestine. In addition to these diseases, there are such as isolated malabsorption of methionine, tryptophan and a number of other amino acids.

The development of enteric insufficiency and its chronic course contribute (due to the disruption of the processes of membrane digestion and absorption) the emergence of disorders of protein, energy, vitamin, electrolyte and other types of metabolism with appropriate clinical symptoms. The noted mechanisms of the development of digestive insufficiency are ultimately realized in a multi-organ, multisyndromic picture of the disease.

In the formation of the pathogenetic mechanisms of enteric pathology, the acceleration of peristalsis is one of the typical disorders that accompany most organic diseases... Most common reasons acceleration of peristalsis - inflammatory changes in the gastrointestinal mucosa. In this case, the chyme moves through the intestines faster and diarrhea develops. Diarrhea also occurs when unusual irritants act on the intestinal wall: undigested food (for example, with achilia), fermentation and decay products, toxic substances. An increase in the excitability of the center of the vagus nerve leads to an acceleration of peristalsis, since it activates intestinal motility. Diarrhea, which helps rid the body of indigestible or toxic substances, is protective. But with prolonged diarrhea, deep digestive disorders occur, associated with impaired secretion of intestinal juice, digestion and absorption of nutrients in the intestine. Slowing down of the peristalsis of the small intestine is one of the rare pathophysiological mechanisms of the formation of diseases. At the same time, the movement of food gruel through the intestines is inhibited and constipation develops. This clinical syndrome, as a rule, is a consequence of the pathology of the colon.

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Chinese sages said that if a person has a healthy intestine, then he can overcome any disease. Delving into the work of this body, you never cease to be amazed at how complex it is, how many degrees of protection it has. And how easy it is, knowing the basic principles of its work, to help the intestines to maintain our health. I hope that this article, written on the basis of the latest medical research by Russian and foreign scientists, will help you understand how the small intestine works and what functions it performs.

The intestine is the longest organ in the digestive system and is divided into two sections. The small intestine, or small intestine, forms a large number of loops and passes into the large intestine. The human small intestine is approximately 2.6 meters long and is a long, tapering tube. Its diameter decreases from 3-4 cm at the beginning to 2-2.5 cm at the end.

At the junction of the small and large intestine is the ileocecal valve with the muscular sphincter. It closes the exit from the small intestine and prevents the contents of the large intestine from entering the small intestine. From 4-5 kg ​​of food gruel passing through the small intestine, 200 grams of feces are formed.

The anatomy of the small intestine has a number of features in accordance with the functions performed. So the inner surface consists of many folds in a semicircular
forms. Thanks to this, its suction surface is increased by 3 times.

In the upper part of the small intestine, the folds are higher and are located closely to each other, with distance from the stomach, their height decreases. They can completely
be absent in the area of ​​transition to the colon.

Small intestine

There are 3 sections in the small intestine:

• jejunum
• ileum.

The initial section of the small intestine is the duodenum.
It distinguishes between the upper, descending, horizontal and ascending parts. The small intestine and the ileum do not have a clear boundary between themselves.

The beginning and end of the small intestine are attached to the back wall of the abdominal cavity. On
for the rest of the length, it is fixed by the mesentery. The mesentery of the small intestine is the part of the peritoneum in which blood vessels, lymphatic vessels and nerves pass, and which allows the intestines to move.

Blood supply

The abdominal part of the aorta is divided into 3 branches, two mesenteric arteries and the celiac trunk, through which the blood supply to the gastrointestinal tract and abdominal organs is carried out. The ends of the mesenteric arteries narrow with distance from the mesenteric edge of the intestine. Therefore, the blood supply to the free edge of the small intestine is much worse than that of the mesenteric.

The venous capillaries of the intestinal villi combine into venules, then into small veins and into the superior and inferior mesenteric veins, which enter the portal vein. Venous blood first enters the liver through the portal vein and only then into the inferior vena cava.

Lymphatic vessels

The lymphatic vessels of the small intestine begin in the villi of the mucous membrane, upon exiting the wall of the small intestine, they enter the mesentery. In the mesentery zone, they form transport vessels that are capable of contracting and pumping lymph. The vessels contain a white liquid similar to milk. Therefore, they are called milky. At the root of the mesentery are central The lymph nodes.

Some of the lymphatic vessels can drain into the thoracic stream, bypassing the lymph nodes. This explains the possibility of the rapid spread of toxins and microbes by the lymphatic pathway.

Mucous membrane

The mucous membrane of the small intestine is lined with a single-layer prismatic epithelium.

Renewal of the epithelium occurs in different parts of the small intestine within 3-6 days.

The cavity of the small intestine is lined with villi and microvilli. The microvilli form the so-called brush border, which provides the protective function of the small intestine. It, like a sieve, weeds out high molecular weight toxic substances and does not allow them to penetrate into the blood supply system and into the lymphatic system.

Absorption of nutrients is carried out through the epithelium of the small intestine. The absorption of water, carbohydrates and amino acids occurs through the blood capillaries located in the centers of the villi. Fats are absorbed by the lymphatic capillaries.

In the small intestine, the formation of mucus lining the intestinal cavity also occurs. It has been proven that mucus has a protective function and promotes the regulation of intestinal microflora.

Functions

The small intestine performs the most important functions for the body, such as

• digestion
• immune function
• endocrine function
• barrier function.

Digestion

It is in the small intestine that the processes of food digestion take place most intensively. In humans, the process of digestion practically ends in the small intestine. In response to mechanical and chemical irritations, the intestinal glands secrete up to 2.5 liters of intestinal juice per day. Intestinal juice is secreted only in those parts of the intestine in which the food lump is located. It contains 22 digestive enzymes. The medium in the small intestine is close to neutral.

Fright, angry emotions, fear, and intense pain can slow down the digestive glands.

Rare diseases - eosinophilic enteritis, general variable hypogammaglobulinemia, lymphangiectasia, tuberculosis, amyloidosis, malrotation, endocrine enteropathies, carcinoid, mesenteric ischemia, lymphoma.

A quick overview of the functioning of the digestive system

The food we consume cannot be digested in this form. To begin with, food must be processed mechanically, transferred to an aqueous solution, and chemically degraded. Unused residues must be removed from the body. Since our gastrointestinal tract is made up of the same constituents as food, its inner surface must be protected from the effects of digestive enzymes. Since we eat food more often than it is digested and the breakdown products are absorbed, and in addition, the elimination of toxins is carried out once a day, the gastrointestinal tract should be able to store food for a certain time. The coordination of all these processes is carried out primarily: (1) the autonomous or gastroenteric (internal) nervous system (nerve plexuses of the gastrointestinal tract); (2) from outside the nerves of the autonomic nervous system and visceral afferents, and (3) numerous hormones of the gastrointestinal tract.

Finally, the thin epithelium of the digestive tube is a giant gateway through which pathogens can enter the body. There are a number of specific and non-specific mechanisms protecting this border between the external environment and the internal world of the body.

In the gastrointestinal tract, the liquid internal environment of the body and the external environment are separated from each other only by a very thin (20-40 μm), but huge epithelial layer (about 10 m 2), through which substances necessary for the body can be absorbed.

The gastrointestinal tract consists of the following sections: mouth, pharynx, esophagus, stomach, small intestine, large intestine, rectum, and anus. Numerous exocrine glands are attached to them: salivary glands

oral cavity, Ebner's glands, gastric glands, pancreas, bile system of the liver and crypts of the small and large intestine.

Motor activity includes chewing in the mouth, swallowing (pharynx and esophagus), crushing and mixing food with gastric juice in the distal stomach, mixing (mouth, stomach, small intestine) with digestive juices, moving in all parts of the gastrointestinal tract and temporary storage (proximal stomach , cecum, ascending part of the colon, rectum). The transit time of food through each of the sections of the gastrointestinal tract is shown in Fig. 10-1. Secretion occurs along the entire length of the digestive tract. On the one hand, secretions serve as lubricating and protective films, and on the other hand, they contain enzymes and other substances that ensure digestion. Secretion involves the transport of salts and water from the interstitium into the lumen of the gastrointestinal tract, as well as the synthesis of proteins in the secretory cells of the epithelium and their transport through the apical (luminal) plasma membrane into the lumen of the digestive tube. Although secretion can occur spontaneously, most of the glandular tissue is under the control of the nervous system and hormones.

Digestion(enzymatic hydrolysis of proteins, fats and carbohydrates) that occurs in the mouth, stomach and small intestine is one of the main functions of the digestive tract. It is based on the work of enzymes.

Reabsorption(or in Russian version suction) involves the transport of salts, water and organic matter (for example, glucose and amino acids from the lumen of the gastrointestinal tract into the blood). In contrast to secretion, the extent of reabsorption is determined rather by the supply of reabsorbable substances. Reabsorption is limited to specific areas of the digestive tract: the small intestine (nutrients, ions, and water) and the large intestine (ions and water).

Rice. 10-1. Gastrointestinal tract: general structure diagram and food transit time.

Food is processed mechanically, mixed with digestive juices and chemically broken down. Cleavage products, as well as water, electrolytes, vitamins and trace elements are reabsorbed. The glands secrete mucus, enzymes, H + and HCO 3 - ions. The liver supplies the bile needed to digest fats and also contains foods that must be eliminated from the body. In all parts of the gastrointestinal tract, the contents move in the proximal-distal direction, while intermediate storage sites make it possible to discrete food intake and emptying of the intestinal tract. The emptying time has individual characteristics and depends primarily on the composition of the food.

Functions and composition of saliva

Saliva is formed in three large paired salivary glands: the parotid (Glandula parotis), submandibular (Glandula submandibularis) and sublingual (Glandula sublingualis). In addition, there are many mucus-producing glands in the mucous membranes of the cheeks, palate and pharynx. Serous fluid is also secreted Ebner's glands, located at the base of the tongue.

Saliva is primarily needed for sensing gustatory stimuli, for sucking (in newborns), for oral hygiene, and for wetting hard food pieces (in preparation for swallowing). The digestive enzymes in saliva are also needed to remove food debris from the mouth.

Functions human saliva are as follows: (1) solvent for nutrients that only in dissolved form can be perceived by taste buds. In addition, saliva contains mucins - lubricants,- which make it easier to chew and swallow solid food particles. (2) Moisturizes the mouth and prevents the spread of infectious agents by keeping lysozyme, peroxidase and immunoglobulin A (IgA), those. substances with nonspecific or, in the case of IgA, specific antibacterial and antiviral properties. (3) Contains digestive enzymes.(4) Contains various growth factors, such as NGF (nerve growth factor) and EGF (epidermal growth factor).(5) Babies need saliva to firmly suck the lips to the nipple.

It has a slightly alkaline reaction. The osmolality of saliva depends on the rate of flow of saliva through the ducts of the salivary glands (Fig. 10-2 A).

Saliva is formed in two stages (Figure 10-2 B). First, the lobules of the salivary glands produce isotonic primary saliva, which is modified a second time during its passage through the excretory ducts of the gland. Na + and Cl - are reabsorbed, while K + and bicarbonate are secreted. Usually more ions are reabsorbed than released, so saliva becomes hypotonic.

Primary saliva occurs as a result of secretion. In most salivary glands a carrier protein that ensures the transfer of Na + -K + -2Cl - into the cell (cotransport), built into the basolateral membrane

wound of acinus cells. With the help of this carrier protein, the secondary-active accumulation of Cl - ions in the cell is ensured, which then passively exit into the lumen of the gland ducts.

On second stage in the excretory ducts from saliva Na + and Cl - are reabsorbed. Since the epithelium of the duct is relatively impervious to water, the saliva in it becomes hypotonic. Simultaneously (small quantities) K + and HCO 3 - stand out epithelium of the duct into its lumen. In comparison with blood plasma, saliva is poor in Na + and Cl - ions, but rich in K + and HCO 3 - ions. At a high speed of saliva flow, the transport mechanisms of the excretory ducts cannot cope with the load, therefore the concentration of K + decreases, and NaCl - increases (Fig. 10-2). The concentration of HCO 3 - practically does not depend on the rate of flow of saliva through the ducts of the glands.

Saliva Enzymes - (1)α -amylase(also called ptyalin). This enzyme is secreted almost exclusively by the parotid salivary gland. (2) Nonspecific lipases, which are secreted by the Ebner glands located at the base of the tongue are especially important for the infant, since they can digest the fat of milk already in the stomach thanks to the saliva enzyme swallowed at the same time as the milk.

The secretion of saliva is regulated exclusively by the central nervous system. Stimulation is provided reflexively under the influence smell and taste of food. All large human salivary glands are innervated as sympathetic, so and parasympathetic nervous system. Depending on the amount of mediators, acetylcholine (M 1 -cholinoreceptors) and norepinephrine (β 2 -adrenergic receptors), the composition of saliva changes near the acinus cells. In humans, sympathetic fibers cause the secretion of more viscous saliva, poor water, than when stimulated parasympathetic system... The physiological meaning of such double innervation, as well as differences in the composition of saliva, are not yet known. Acetylcholine also induces (via M 3 -cholinergic receptors) contraction myoepithelial cells around the acinus (Fig. 10-2 B), as a result of which the contents of the acinus are squeezed out into the duct of the gland. Also, acetylcholine promotes the formation of kallikreins, which release bradykinin from blood plasma kininogen. Bradykinin possesses vasodilating action... Expansion of blood vessels enhances the secretion of saliva.

Rice. 10-2. Saliva and its formation.

A- the osmolality and composition of saliva depend on the speed of saliva flow. B- two stages of saliva formation. V- myoepithelial cells in the salivary gland. It can be assumed that myoepithelial cells protect the lobules from expansion and rupture, which can be caused high pressure in them as a result of secretion. In the duct system, they can perform a function aimed at reducing or expanding the lumen of the duct.

Stomach

The wall of the stomach, shown on its section (Fig. 10-3 B) is formed by four membranes: mucosa, submucosa, muscular, serous. Mucous membrane forms longitudinal folds and consists of three layers: epithelial layer, lamina propria, muscle lamina. Consider all shells and layers.

Epithelial layer of the mucous membrane represented by a single-layer columnar glandular epithelium. It is formed by glandular epithelial cells - mucocytes, secreting mucus. The mucus forms a continuous layer up to 0.5 microns thick, being an important factor in the protection of the gastric mucosa.

Own lamina of the mucous membrane formed by loose fibrous connective tissue. It contains small blood and lymphatic vessels, nerve trunks, lymph nodes. The main structures of the lamina propria are the glands.

Muscle plate of the mucous membrane consists of three layers of smooth muscle tissue: internal and external circular; middle longitudinal.

Submucosa formed by loose fibrous loose connective tissue, contains arterial and venous plexuses, ganglia of Meissner's submucosal nerve plexus. In some cases, large lymphoid follicles can be located here.

Muscular membrane formed by three layers of smooth muscle tissue: internal oblique, middle circular, external longitudinal. In the pyloric part of the stomach, the circular layer reaches its maximum development, forming the pyloric sphincter.

Serous membrane formed by two layers: a layer of loose fibrous unformed connective tissue and the mesothelium lying on it.

All the glands of the stomach which are the main structures of its own plate - simple tubular glands. They open into the gastric fossa and are composed of three parts: bottom, body and necks (Figure 10-3 B). Depending on localization glands divide on cardiac, main(or fundamental) and pyloric. The structure and cellular composition of these glands are not the same. In quantitative terms, prevail major glands. They are the most weakly branched of all the glands in the stomach. In fig. 10-3 B shows a simple tubular gland of the body of the stomach. The cellular composition of these glands includes (1) superficial epithelial cells, (2) mucous cells of the neck of the gland (or accessory), (3) regenerative cells,

(4) parietal cells (or parietal cells),

(5) main cells; and (6) endocrine cells. Thus, the main surface of the stomach is covered with a single-layer highly prismatic epithelium, which is interrupted by numerous pits - the places where the ducts exit stomach glands(Fig. 10-3 B).

Arteries, pass through the serous and muscular membranes, giving them small branches that decay to capillaries. The main trunks form plexuses. The most powerful plexus is the submucosa. Small arteries branch off from it into its own plate, where they form a mucous plexus. From the latter, there are capillaries that encircle the glands and feed the integumentary epithelium. The capillaries merge into large stellate veins. Veins form a plexus of the mucous membrane and then the submucosal venous plexus

(Fig. 10-3 B).

Lymphatic system the stomach originates from the lymphocapillaries of the mucous membrane that blindly begin right under the epithelium and around the glands. The capillaries merge into the submucous lymphatic plexus. The lymphatic vessels departing from it pass through the muscular membrane, taking into themselves the vessels from the plexuses lying between the muscle layers.

Rice. 10-3. Anatomical and functional parts of the stomach.

A- functionally the stomach is divided into a proximal section (tonic contraction: food storage function) and distal(mixing and processing function). Peristaltic waves of the distal stomach begin in the region of the stomach containing smooth muscle cells, the membrane potential of which fluctuates with the greatest frequency. The cells in this area are the pacemakers of the stomach. The diagram of the anatomical structure of the stomach, to which the esophagus fits, is shown in Fig. 10-3 А. Then the duodenum begins. The stomach can also be divided into a proximal stomach and a distal stomach.B- an incision in the stomach wall. V- tubular gland of the body of the stomach

Cells of the tubular gland of the stomach

In fig. 10-4 B shows the tubular gland of the body of the stomach, and the insert (Fig. 10-4 A) shows its layers, indicated on the panel. Rice. 10-4 B demonstrates the cells that make up the simple tubular gland of the body of the stomach. Among these cells, we pay attention to the main ones, which play a pronounced role in the physiology of the stomach. This is, first of all, parietal cells, or parietal cells(Figure 10-4 B). The main role of these cells is the release of hydrochloric acid.

Activated parietal cells release large amounts of isotonic liquid, which contains hydrochloric acid in a concentration of up to 150 mmol; activation is accompanied by pronounced morphological changes in the parietal cells (Fig. 10-4 C). A weakly activated cell has a network of narrow, branched tubules(the diameter of the lumen is about 1 micron), which open into the lumen of the gland. In addition, in the cytoplasmic layer adjacent to the lumen of the tubule, a large number tubulovesicles. The tubulovesicles membrane contains K + / H + -AT Phase and ionic K + - and Cl - - channels. With strong cell activation, tubulovesicles are embedded in the tubular membrane. Thus, the surface of the tubular membrane is significantly increased and transport proteins (K + / H + -ATPase) and ion channels for K + and Cl - necessary for the secretion of HCl are built into it (Fig. 10-4 D). With a decrease in the level of cell activation, the tubulovesicular membrane is cleaved from the tubular membrane and remains in the vesicles.

The mechanism of HCl-secretion itself is unusual (Fig. 10-4 D), since it is carried out by H + - (and K +) - transporting ATPase in the luminal (tubular) membrane, and not as it is often found throughout the body - with using Na + / K + -AT Phase of the basolateral membrane. Na + / K + -AT Phase of the parietal cells ensures the constancy of the internal environment of the cell: in particular, it promotes cellular accumulation of K +.

Hydrochloric acid is neutralized by so-called antacids. In addition, the secretion of HCl can be inhibited due to the blockade of H 2 receptors by ranitidine (Histamine 2 -receptors) parietal cells or inhibition of the activity of H + / K + -AT Phase omeprazole.

Main cells secrete endopeptidases. Pepsin, a proteolytic enzyme, is secreted by the main cells of the glands of the human stomach in an inactive form (pepsinogen). Pepsinogen is activated autocatalytically: first, from a pepsinogen molecule in the presence of hydrochloric acid (pH<3) отщепляется пептидная цепочка длиной около 45 аминокислот и образуется активный пепсин, который способствует активации других молекул. Активация пепсиногена поддерживает стимуляцию обкладочных клеток, выделяющих HCl. Встречающийся в желудочном соке маленького ребенка gastrixin (= pepsin C) corresponds to labferment(chymosin, rennin) calf. It cleaves a specific molecular bond between phenylalanine and methioninone (Phe-Met bond) into caseinogen(soluble milk protein), so that this protein is converted into insoluble, but better digestible casein ("clotting" of milk).

Rice. 10-4. The cellular structure of the simple tubular gland of the body of the stomach and the functions of the main cells that determine its structure.

A- the tubular gland of the body of the stomach. Usually 5-7 of these glands flow into the fossa on the surface of the gastric mucosa.B- the cells that make up the simple tubular gland of the body of the stomach. V- parietal cells at rest (1) and upon activation (2). G- secretion of HCl by the parietal cells. Two components can be found in the secretion of HCl: the first component (not subject to stimulation) is associated with the activity of Na + / K + -ATPase, localized in the basolateral membrane; the second component (subject to stimulation) is provided by H + / K + -ATPase. 1. Na + / K + -ATPase maintains a high concentration of K + ions in the cell, which can leave the cell through the channels into the gastric cavity. Simultaneously, Na + / K + -ATPase promotes the elimination of Na + from the cell, which accumulates in the cell as a result of the work of the carrier protein, which provides the exchange of Na + / H + (antiport) by the mechanism of secondary active transport. For each removed H + ion, one OH-ion remains in the cell, which interacts with CO 2 to form HCO 3 -. The catalyst for this reaction is carbonic anhydrase. HCO 3 - leaves the cell through the basolateral membrane in exchange for Cl -, which is then secreted into the gastric cavity (through the Cl - channels of the apical membrane). 2. On the luminal membrane H + / K + -ATPase provides the exchange of K + ions for H + ions, which go into the stomach cavity, which is enriched with HCl. For each H + ion released, and in this case from the opposite side (through the basolateral membrane), one HCO 3 - anion leaves the cell. K + ions accumulate in the cell, enter the stomach cavity through the K + -channels of the apical membrane and then enter the cell again as a result of the work of H + / K + -ATPase (circulation of K + through the apical membrane)

Protection against self-digestion of the stomach wall

The integrity of the gastric epithelium is primarily threatened by the proteolytic action of pepsin in the presence of hydrochloric acid. The stomach protects against such self-digestion thick layer of stringy mucus, which is secreted by the epithelium of the stomach wall, additional cells of the glands of the fundus and body of the stomach, as well as the cardiac and pyloric glands (Fig. 10-5 A). Although pepsin can break down mucus mucins in the presence of hydrochloric acid, most of this is limited to the topmost mucus layer, since the deeper layers contain bicarbonate, which-

rye is secreted by epithelial cells and helps to neutralize hydrochloric acid. Thus, through the mucus layer there is an H + -gradient: from more acidic in the stomach cavity to alkaline on the surface of the epithelium (Fig. 10-5 B).

Damage to the epithelium of the stomach does not necessarily lead to serious consequences, provided that the defect is quickly repaired. In fact, such damage to the epithelium is quite common; however, they are quickly eliminated due to the fact that neighboring cells spread out, migrate laterally and close the defect. Following this, new cells are incorporated, which are formed as a result of mitotic division.

Rice. 10-5. Self-defense of the stomach wall from digestion due to secretion of mucus and bicarbonate

Small intestine wall structure

Small intestine consists of three departments - duodenum, jejunum and ileum.

The wall of the small intestine is composed of various layers (Figure 10-6). In general, outside under serous membrane passes external muscular layer, which consists of outer longitudinal muscle layer and inner annular muscle layer, and the innermost is muscle plate of the mucous membrane, which separates submucous layer from mucous. bundles gap junctions)

The muscles of the outer layer of the longitudinal musculature provide contraction of the intestinal wall. As a result, the intestinal wall is displaced relative to the chyme (food gruel), which contributes to better mixing of the chyme with digestive juices. The annular muscles narrow the intestinal lumen, and the muscle plate of the mucous membrane (Lamina muscularis mucosae) provides the movement of the villi. The nervous system of the gastrointestinal tract (gastroenteric nervous system) is formed by two plexuses: the intermuscular plexus and the submucosal plexus. The central nervous system is able to influence the functioning of the nervous system of the gastrointestinal tract through the sympathetic and parasympathetic nerves that approach the nerve plexuses of the food tube. In the nerve plexuses, afferent visceral fibers begin, which

transmit nerve impulses to the central nervous system. (A similar wall arrangement is also observed in the esophagus, stomach, large intestine and rectum). To accelerate reabsorption, the surface of the mucous membrane of the small intestine is increased due to folds, villi and brush border.

The inner surface of the small intestine has a characteristic relief due to the presence of a number of formations - circular folds of Kerkring, villi and crypt(intestinal glands of Lieberkühn). These structures increase the overall surface of the small intestine, which contributes to its basic functions of digestion. Intestinal villi and crypts are the main structural and functional units of the mucous membrane of the small intestine.

Mucous(or mucous membrane) consists of three layers - epithelial, lamina propria and muscle lamina of the mucous membrane (Fig. 10-6 A). The epithelial layer is represented by a single-layer columnar edged epithelium. In villi and crypts, it is represented by different types of cells. Villus epithelium composed of four types of cells - main cells, goblet cells, endocrine cells and Paneth cells.Crypt epithelium- five types

(Fig. 10-6 C, D).

In limbed enterocytes

Goblet enterocytes

Rice. 10-6. The structure of the wall of the small intestine.

A- the structure of the duodenum. B- the structure of the large duodenal papilla:

1. Large papilla of the duodenum. 2. Ampula of the duct. 3. Sphincters of ducts. 4. Pancreatic duct. 5. Common bile duct. V- the structure of various parts of the small intestine: 6. Duodenal glands (Brunner's glands). 7. Serous membrane. 8. Outer longitudinal and inner circular layers of the muscular membrane. 9. Submucous base. 10. Mucous membrane.

11. Own mucosal lamina with smooth muscle cells. 12. Group lymphoid nodules (lymphoid plaques, Peyer's patches). 13. Villi. 14. Folds. G - the structure of the wall of the small intestine: 15. Villi. 16. Circular fold.D- villi and crypts of the mucous membrane of the small intestine: 17. Mucous membrane. 18. Own lamina of the mucous membrane with smooth muscle cells. 19. Submucosa. 20. Outer longitudinal and inner circular layers of the muscular membrane. 21. Serous membrane. 22. Villi. 23. Central lactiferous sinus. 24. Solitary lymphoid nodule. 25. Intestinal gland (Lieberkunov's gland). 26. Lymphatic vessel. 27. Submucous nerve plexus. 28. The inner circular layer of the muscular membrane. 29. Muscular nerve plexus. 30. Outer longitudinal layer of the muscular membrane. 31. Artery (red) and vein (blue) of the submucosal layer

Functional morphology of the mucous membrane of the small intestine

Three sections of the small intestine have the following differences: the duodenum has large papillae - duodenal glands, the height of the villi, which grows from the duodenum to the ileum, is different, their width is different (wider - in the duodenum), and the number (the largest number in the duodenum ). These differences are shown in Fig. 10-7 B. Further, in the ileum there are group lymphoid follicles (Peyer's patches). But they can sometimes be found in the duodenum.

Villi- finger-like protrusions of the mucous membrane into the intestinal lumen. They contain blood and lymphatic capillaries. The villi are able to actively contract due to the components of the muscle plate. This promotes the absorption of the chyme (the pumping function of the villi).

Kerkring folds(Fig. 10-7 D) are formed due to protrusion of the mucous and submucous membranes into the intestinal lumen.

Crypts- These are deepening of the epithelium in the proper lamina of the mucous membrane. They are often referred to as glands (Lieberkühn's glands) (Figure 10-7 B).

The small intestine is the main site for digestion and reabsorption. Most of the enzymes found in the intestinal lumen are synthesized in the pancreas. The small intestine itself secretes about 3 liters of mucin-rich fluid.

The intestinal mucosa is characterized by the presence of intestinal villi (Villi intestinalis), which increase the surface of the mucous membrane by 7-14 times. The epithelium of the villi passes into the secretory crypts of Lieberkühn. The crypts lie at the base of the villi and open towards the intestinal lumen. Finally, each epithelial cell on the apical membrane bears a brush border (microvilli), which

paradise increases the surface of the intestinal mucosa by 15-40 times.

Mitotic division occurs deep in the crypts; daughter cells migrate to the apex of the villi. All cells, with the exception of Paneth cells (which provide antibacterial protection), take part in this migration. The entire epithelium is completely renewed within 5-6 days.

The epithelium of the small intestine is covered a layer of gelatinous mucus, which is formed by the goblet cells of crypts and villi. When the pyloric sphincter opens, the release of the chyme into the duodenum triggers an increased secretion of mucus Brunner's glands. The transition of the chyme into the duodenum causes the release of hormones into the blood. secretina and cholecystokinin. Secretin triggers the secretion of alkaline juice in the epithelium of the pancreatic duct, which is also necessary to protect the duodenal mucosa from aggressive stomach juice.

About 95% of the villus epithelium is occupied by columnar main cells. Although their main task is reabsorption, they represent the most important sources of digestive enzymes, which are localized either in the cytoplasm (amino and dipeptidases) or in the membrane of the brush border: lactase, sucrase-isomaltase, amino and endopeptidase. These brush border enzymes are integral proteins of the membrane, and part of their polypeptide chain, together with the catalytic center, is directed into the intestinal lumen, therefore enzymes can hydrolyze substances in the cavity of the digestive tube. Their secretion into the lumen in this case turns out to be unnecessary (parietal digestion). Cytosolic enzymes epithelial cells take part in the digestion processes when they break down proteins reabsorbed by the cell (intracellular digestion), or when the epithelial cells containing them die, are rejected into the lumen and are destroyed there, releasing enzymes (cavity digestion).

Rice. 10-7. Histology of various parts of the small intestine - duodenum, jejunum and ileum.

A- villi and crypts of the mucous membrane of the small intestine: 1. Mucous membrane. 2. Own lamina of the mucous membrane with smooth muscle cells. 3. Submucous base. 4. Outer longitudinal and inner circular layers of the muscular membrane. 5. Serous membrane. 6. Villi. 7. Central lactiferous sinus. 8. Single lymphoid nodule. 9. Intestinal gland (Lieberkunov's gland). 10. Lymphatic vessel. 11. Submucous nerve plexus. 12. The inner circular layer of the muscular membrane. 13. Muscular nerve plexus. 14. Outer longitudinal layer of the muscular membrane.

15. Artery (red) and vein (blue) of the submucosal layer.B, C - the structure of the villi:

16. Goblet cell (unicellular gland). 17. Cells of prismatic epithelium. 18. Nerve fiber. 19. Central milky sinus. 20. Microhemacirculatory bed of the villi, the network of blood capillaries. 21. Own lamina of the mucous membrane. 22. Lymphatic vessel. 23. Venula. 24. Arteriole

Small intestine

Mucous(or mucous membrane) consists of three layers - epithelial, lamina propria and muscle lamina of the mucous membrane (Fig. 10-8). The epithelial layer is represented by a single-layer columnar edged epithelium. The epithelium contains five main cell populations: columnar epithelial cells, goblet exocrinocytes, Paneth cells, or exocrinocytes with acidophilic granules, endocrinocytes or K cells (Kulchitsky cells), as well as M cells (with microfolds), which are a modification of columnar epithelial cells.

Epithelium covered villi and neighboring crypts. It mostly consists of reabsorbing cells, which bear a brush border on the luminal membrane. Scattered between them are goblet cells that form mucus, as well as Paneth cells and various endocrine cells. Epithelial cells are formed as a result of the division of the crypt epithelium,

from where they migrate for 1-2 days towards the tip of the villi and are rejected there.

In villi and crypts, it is represented by different types of cells. Villus epithelium composed of four types of cells - head cells, goblet cells, endocrine cells, and Paneth cells. Crypt epithelium- five types.

The main type of villous epithelium cells is limbed enterocytes. In limbed enterocytes

the epithelium of the villi membrane forms microvilli covered with glycocalyx, and it adsorbs enzymes involved in parietal digestion. Due to the microvilli, the suction surface is increased 40 times.

M cells(cells with microfolds) are a type of enterocytes.

Goblet enterocytes villus epithelium - unicellular mucous glands. They produce carbohydrate-protein complexes - mucins, which perform a protective function and promote the movement of food components in the intestine.

Rice. 10-8. Morphohistological structure of the villi and crypts of the small intestine

Colon

Colon consists of mucosa, submucosa, muscular and serous membranes.

The mucous membrane forms the relief of the colon - folds and crypts. There are no villi in the colon. The epithelium of the mucous membrane is single-layer cylindrical limb, and contains the same cells as the epithelium of the crypts of the small intestine - limb, goblet endocrine, borderless, Paneth cells (Fig. 10-9).

The submucosa is formed by loose fibrous connective tissue.

The muscular layer has two layers. Inner circular layer and outer longitudinal layer. The longitudinal layer is not continuous, but forms

three longitudinal ribbons. They are shorter than the intestine and therefore the intestine is collected in an "accordion".

The serous membrane consists of loose fibrous connective tissue and mesothelium and has protrusions containing adipose tissue.

The main differences between the colon wall (Fig. 10-9) and the thin one (Fig. 10-8) are: 1) the absence of villi in the relief of the mucous membrane. Moreover, crypts have a greater depth than in the small intestine; 2) the presence in the epithelium of a large number of goblet cells and lymphocytes; 3) the presence of a large number of solitary lymphoid nodules and the absence of Peyer's patches in the lamina propria; 4) the longitudinal layer is not continuous, but forms three ribbons; 5) the presence of protrusions; 6) the presence of fatty appendages in the serous membrane.

Rice. 10-9. Morphohistological structure of the large intestine

Electrical activity of muscle cells in the stomach and intestines

The intestinal smooth muscle consists of small, spindle-shaped cells that form bundles and forming cross-links with adjacent beams. Within one bundle, cells are connected to each other both mechanically and electrically. Thanks to such electrical contacts, action potentials propagate (through intercellular gap junctions: gap junctions) for the entire bundle (and not just for individual muscle cells).

The muscle cells of the antrum of the stomach and intestines are usually characterized by rhythmic fluctuations in the membrane potential. (slow waves) with an amplitude of 10-20 mV and a frequency of 3-15 / min (Fig. 10-10). At the time of the appearance of slow waves, the muscle bundles are partially reduced, therefore, the wall of these parts of the gastrointestinal tract is in good shape; this occurs in the absence of action potentials. When the membrane potential reaches the threshold value and exceeds it, action potentials are generated, following with a small interval one after another (spike sequence). The generation of action potentials is due to the Ca 2+ -current (Ca 2+ -channels of the L-type). An increase in the concentration of Ca 2+ in the cytosol triggers phasic contractions, which are especially pronounced in the distal stomach. If the value of the resting membrane potential approaches the value of the threshold potential (but does not reach it; the resting membrane potential shifts towards depolarization), then the potential of slow oscillations begins

regularly exceed the threshold potential. In this case, there is a periodicity in the occurrence of spike sequences. The smooth muscle contracts each time a spike sequence is generated. The frequency of rhythmic contractions corresponds to the frequency of slow oscillations of the membrane potential. If the resting membrane potential of smooth muscle cells approaches the threshold potential even more, then the duration of the spike sequences increases. Is developing spasm smooth muscles. If the resting membrane potential shifts towards more negative values ​​(towards hyperpolarization), then the spike activity stops, and with it the rhythmic contractions stop. If the membrane hyperpolarizes even more, then the amplitude of slow waves and muscle tone decrease, which ultimately leads to paralysis of smooth muscles (atony). Due to what ionic currents there are fluctuations in the membrane potential is not yet clear; one thing is obvious that the nervous system has no effect on fluctuations in the membrane potential. The cells of each muscle bundle have one, only their characteristic frequency of slow waves. Since neighboring beams are connected to each other through electrical intercellular contacts, a beam with a higher frequency of waves (pacemaker) will force this frequency onto an adjacent lower frequency beam. Tonic contraction of smooth muscles for example, the proximal stomach, due to the opening of another type of Ca 2+ channels, which are chemically dependent rather than voltage-dependent.

Rice. 10-10. Membrane potential of smooth muscle cells of the gastrointestinal tract.

1. As long as the wavelike oscillating membrane potential of smooth muscle cells (oscillation frequency: 10 min -1) remains below the threshold potential (40 mV), there are no action potentials (adhesions). 2. When induced (eg, by stretching or acetylcholine) depolarization, a sequence of spikes is generated each time the peak of the membrane potential wave exceeds the threshold potential value. These spike sequences are followed by rhythmic smooth muscle contractions. 3. Adhesions are generated continuously if the minimum values ​​of fluctuations in the membrane potential are above the threshold value. Prolonged contraction develops. 4. Action potentials are not generated at strong shifts of the membrane potential towards depolarization. 5. Hyperpolarization of the membrane potential causes attenuation of slow potential fluctuations, and smooth muscles completely relax: atony

Reflexes of the gastroenteric nervous system

Some of the reflexes of the gastrointestinal tract are own gastroenteric (local) reflexes, in which a sensory sensitive afferent neuron activates a nerve plexus cell, which innervates the smooth muscle cells located next to it. The effect on smooth muscle cells can be excitatory or inhibitory, depending on which type of plexus neuron is activated (Fig. 10-11 2, 3). The implementation of other reflexes involves motor neurons located proximal or distal to the site of stimulation. At peristaltic reflex(for example, as a result of stretching the wall of the digestive tube) a sensory neuron is excited

(Fig. 10-11 1), which through an inhibitory interneuron exerts an inhibitory effect on the longitudinal muscles of the parts of the digestive tube, lying proximally, and a disinhibition effect on the annular muscles (Fig. 10-11 4). At the same time, distally through the excitatory interneuron, the longitudinal musculature is activated (shortening of the alimentary tube occurs), and the annular musculature relaxes (Fig. 10-11 5). The peristaltic reflex triggers a complex series of motor events caused by stretching of the muscular wall of the digestive tube (eg, the esophagus; Fig. 10-11).

The movement of the food bolus shifts the place of activation of the reflex more distally, which again moves the food bolt, resulting in almost continuous transport in the distal direction.

Rice. 10-11. Reflex arcs of reflexes of the gastroenteric nervous system.

Excitation of an afferent neuron (light green) due to a chemical or, as shown in the picture (1), mechanical stimulus (stretching the wall of the food tube due to the food bolus) activates in the simplest case only one excitatory (2) or only one inhibitory motor or secretory neuron (3). Reflexes of the gastroenteric nervous system usually proceed according to more complex switching patterns. With a peristaltic reflex, for example, a neuron that is excited by stretching (light green), excites in an ascending direction (4) an inhibitory interneuron (purple), which in turn inhibits an excitatory motor neuron (dark green) that innervates the longitudinal muscles, and relieves inhibition from inhibitory motor neuron (red) of the annular muscle (contraction). At the same time, in the downward direction (5), an excitatory interneuron (blue) is activated, which, through excitatory or, respectively, inhibitory motor neurons in the distal part of the intestine, causes contraction of the longitudinal muscles and relaxation of the annular muscles

Parasympathetic innervation of the gastrointestinal tract

The innervation of the gastrointestinal tract is carried out with the help of the autonomic nervous system (parasympathetic(fig. 10-12) and sympathetic innervation - efferent nerves), as well as visceral afferents(afferent innervation). Parasympathetic preganglionic fibers, which innervate most of the digestive tract, come as part of the vagus nerves (N. vagus) from the medulla oblongata and as part of the pelvic nerves (Nn. Pelvici) from the sacral spinal cord. The parasympathetic system sends fibers to excitatory (cholinergic) and inhibitory (peptidergic) cells of the intermuscular plexus. Preganglionic sympathetic fibers originate from cells lying in the lateral horns of the sterno-lumbar spinal cord. Their axons innervate the blood vessels of the intestine or approach the cells of the nerve plexuses, exerting an inhibitory effect on their excitatory neurons. Visceral afferents originating in the wall of the gastrointestinal tract pass through the vagus nerves (N. vagus), as part of the visceral nerves (Nn. Splanchnici) and pelvic nerves (Nn. Pelvici) to the medulla oblongata, sympathetic ganglia and to the spinal cord. With the participation of the sympathetic and parasympathetic nervous systems, many reflexes of the gastrointestinal tract occur, including the reflex expansion during filling and intestinal paresis.

Although reflex acts carried out by the nerve plexuses of the gastrointestinal tract can proceed independently of the influence of the central nervous system (CNS), they are controlled by the central nervous system, which provides certain advantages: (1) parts of the digestive tract located far from each other can quickly exchange information through the central nervous system and thereby coordinate their own functions, (2) the functions of the digestive tract can be subordinated to the more important interests of the body, (3) information from the gastrointestinal tract can be integrated at different levels of the brain; which, for example in the case of abdominal pain, can even cause conscious sensations.

The innervation of the gastrointestinal tract is provided by autonomic nerves: parasympathetic and sympathetic fibers and, in addition, afferent fibers, the so-called visceral afferents.

Parasymaptic nerves the gastrointestinal tract emerges from two independent divisions of the central nervous system (Fig. 10-12). The nerves that serve the esophagus, stomach, small intestine, and the ascending colon (as well as the pancreas, gallbladder, and liver) originate from neurons in the medulla oblongata (Medulla oblongata), whose axons form the vagus nerve (N. vagus), while the innervation of the rest of the gastrointestinal tract starts from neurons sacral spinal cord, axons of which form the pelvic nerves (Nn. Pelvici).

Rice. 10-12. Parasympathetic innervation of the gastrointestinal tract

Influence of the parasympathetic nervous system on the neurons of the muscular plexus

Throughout the digestive tract, parasympathetic fibers activate target cells through nicotinic cholinergic receptors: one type of fiber forms synapses on cholinergic excitatory, and the other type is on peptidergic (NCNA) inhibitory cells of the nerve plexus (Fig. 10-13).

The axons of the preganglionic fibers of the parasympathetic nervous system are switched in the intermuscular plexus to excitatory cholinergic or inhibitory non-cholinergic-non-adrenergic (NCNA-ergic) neurons. Postganglionic adrenergic neurons of the sympathetic system act, in most cases, inhibiting plexus neurons, which stimulate motor and secretory activity.

Rice. 10-13. Innervation of the gastrointestinal tract by the autonomic nervous system

Sympathetic innervation of the gastrointestinal tract

Preganglionic cholinergic neurons sympathetic nervous system lie in the intermediolateral pillars thoracic and lumbar spinal cord(Fig. 10-14). The axons of the neurons of the sympathetic nervous system leave the thoracic spinal cord through the anterior

roots and are part of the visceral nerves (Nn. splanchnici) To superior cervical ganglion and to prevertebral ganglia. There, a switch occurs to postganglionic noradrenergic neurons, the axons of which form synapses on the cholinergic excitatory cells of the intermuscular plexus and through α-receptors exert inhibitory impact on these cells (see Fig. 10-13).

Rice. 10-14. Sympathetic innervation of the gastrointestinal tract

Afferent innervation of the gastrointestinal tract

In the nerves that provide the innervation of the gastrointestinal tract, as a percentage, there are more afferent fibers than efferent ones. Sensory nerve endings are non-specialized receptors. One group of nerve endings is localized in the connective tissue of the mucous membrane next to its muscle layer. It is assumed that they function as chemoreceptors, but it is not yet clear which of the substances reabsorbed in the intestine activate these receptors. It is possible that a peptide hormone (paracrine action) is involved in their activation. Another group of nerve endings lies inside the muscle layer and has the properties of mechanoreceptors. They respond to mechanical changes that are associated with contraction and stretching of the wall of the digestive tube. Afferent nerve fibers come from the gastrointestinal tract or as part of the nerves of the sympathetic or parasympathetic nervous system. Some afferent fibers that are part of the sympathetic

nerves, form synapses in the prevertebral ganglia. Most of the afferents pass through the pre- and paravertebral ganglia without switching (Fig. 10-15). The neurons of the afferent fibers lie in the sensitive

spinal ganglia of the posterior roots of the spinal cord, and their fibers enter the spinal cord through the dorsal roots. Afferent fibers, which are part of the vagus nerve, form an afferent link reflexes of the gastrointestinal tract, proceeding with the participation of the vagus parasympathetic nerve. These reflexes are especially important for the coordination of the motor function of the esophagus and the proximal stomach. Sensory neurons, the axons of which are part of the vagus nerve, are localized in Ganglion nodosum. They form connections with the neurons of the nucleus of a single path (Tractus solitarius). The information they transmit reaches the preganglionic parasympathetic cells located in the dorsal nucleus of the vagus nerve (Nucleus dorsalis n. Vagi). Afferent fibers, which also pass through the pelvic nerves (Nn. Pelvici), take part in the defecation reflex.

Rice. 10-15. Short and long visceral afferents.

Long afferent fibers (green), whose cell bodies lie in the posterior roots of the spinal ganglion, pass through the pre- and paravertebral ganglia without switching and enter the spinal cord, where they either switch to neurons of the ascending or descending pathways, or in the same segment of the spinal cord switch to preganglionic autonomic neurons, as in the lateral gray matter intermediate (Substantia intermediolateralis) thoracic spinal cord. In short afferents, the reflex arc is closed due to the fact that switching to efferent sympathetic neurons occurs already in the sympathetic ganglia.

Basic mechanisms of transepithelial secretion

The carrier proteins built into the luminal and basolateral membranes, as well as the composition of the lipids of these membranes, determine the polarity of the epithelium. Perhaps the most important factor determining the polarity of the epithelium is the presence of secreting epithelium in the basolateral membrane of cells. Na + / K + -AT Phases (Na + / K + - "pump"), sensitive to oubain. Na + / K + -ATPase converts the chemical energy of ATP into electrochemical gradients of Na + and K + directed into or out of the cell, respectively (primary active transport). The energy of these gradients can be reused in order to transport other molecules and ions actively across the cell membrane against their electrochemical gradient. (secondary active transport). This requires specialized transport proteins, the so-called carriers, which either provide the simultaneous transfer of Na + into the cell together with other molecules or ions (cotransport), or exchange Na + for

other molecules or ions (antiport). The secretion of ions into the lumen of the digestive tube generates osmotic gradients, so the water follows the ions.

Active secretion of potassium

In epithelial cells, K + is actively accumulated with the help of the Na + -K + -pump located in the basolateral membrane, and Na + is pumped out of the cell (Fig. 10-16). In the epithelium, in which K + secretion does not occur, K + channels are located in the same place where the pump is located (secondary use of K + on the basolateral membrane, see Fig. 10-17 and Fig. 10-19). A simple mechanism of K + secretion can be provided by the incorporation of numerous K + channels into the luminal membrane (instead of the basolateral membrane), i.e. into the membrane of the epithelial cell from the side of the lumen of the digestive tube. In this case, the K + accumulated in the cell enters the lumen of the digestive tube (passively; Fig. 10-16), and the anions follow the K +, resulting in an osmotic gradient, so water is released into the lumen of the digestive tube.

Rice. 10-16. Transepithelial secretion of KCl.

Na +/ K + -ATPase, localized in the basolateral cell membrane, when using 1 mol of ATP "pumps out" 3 moles of Na + ions from the cell and "pumps" 2 moles of K + into the cell. While Na + enters the cell throughNa +-channels located in the basolateral membrane, K + -ions leave the cell through K + -channels localized in the luminal membrane. As a result of the movement of K + through the epithelium, a positive transepithelial potential is established in the lumen of the digestive tube, as a result of which Cl - ions intercellularly (through tight contacts between epithelial cells) also rush into the lumen of the digestive tube. As shown by the stoichiometric values ​​in the figure, 2 moles of K + are released per 1 mole of ATP.

Transepithelial secretion of NaHCO 3

Most secreting epithelial cells first secrete an anion (eg, HCO 3 -). The driving force of this transport is the electrochemical Na + gradient directed from the extracellular space into the cell, which is established due to the mechanism of primary active transport carried out by Na + -K + -pumps. The potential energy of the Na + gradient is used by carrier proteins, with Na + being transported across the cell membrane into the cell along with another ion or molecule (cotransport) or exchanged for another ion or molecule (antiport).

For secretion of HCO 3 -(for example, in the ducts of the pancreas, in Brunner's glands or in the bile ducts), a Na + / H + exchanger is required in the basolateral cell membrane (Fig. 10-17). H + ions are removed from the cell with the help of secondary active transport, as a result OH - ions remain in it, which interact with CO 2 to form HCO 3 -. Carbonic anhydrase acts as a catalyst in this process. The formed HCO 3 - leaves the cell in the direction of the lumen of the gastrointestinal tract either through the canal (Fig. 10-17), or with the help of a carrier protein that exchanges C1 - / HCO 3 -. In all likelihood, both mechanisms are active in the pancreatic duct.

Rice. 10-17. Transepithelial secretion of NaHCO 3 becomes possible when H + ions are actively removed from the cell through the basolateral membrane. This is the responsibility of the carrier protein, which, through the mechanism of secondary active transport, ensures the transfer of H + ions. The driving force behind this process is the Na + chemical gradient supported by the Na + / K + -AT Phase. (Unlike Fig. 10-16, K + ions leave the cell through the K + channels through the basolateral membrane and enter the cell as a result of the work of Na + / K + -ATPase). For each H + ion that leaves the cell, one OH - ion remains, which binds to CO 2 to form HCO 3 -. This reaction is catalyzed by carbonic anhydrase. HCO 3 - diffuses through the anion channels into the lumen of the duct, which leads to the appearance of a transepithelial potential, at which the contents of the lumen of the duct are negatively charged with respect to the interstitium. Under the influence of such a transepithelial potential, Na + ions rush into the duct lumen through tight contacts between cells. The quantitative balance shows that the secretion of 3 mol of NaHCO 3 requires 1 mol of ATP.

Transepithelial secretion of NaCl

Most secreting epithelial cells first secrete an anion (eg, Cl -). The driving force of this transport is the electrochemical Na + gradient directed from the extracellular space into the cell, which is established due to the mechanism of primary active transport carried out by Na + -K + -pumps. The potential energy of the Na + gradient is used by carrier proteins, with Na + being transported across the cell membrane into the cell along with another ion or molecule (cotransport) or exchanged for another ion or molecule (antiport).

A similar mechanism is responsible for the primary secretion of Cl -, which provides the driving forces for the process of fluid secretion in the terminal

parts of the salivary glands of the mouth, in the acini of the pancreas, as well as in the lacrimal glands. Instead of a Na + / H + exchanger in basolateral membrane epithelial cells of these organs, a carrier is localized, providing the conjugated transfer of Na + -K + -2Сl - (co-transport; rice. 10-18). This transporter uses a Na + gradient for the (secondary active) accumulation of Cl - in the cell. Cl - can passively leave the cell through the ion channels of the luminal membrane into the lumen of the gland duct. In this case, a negative transepithelial potential arises in the lumen of the duct, and Na + rushes into the lumen of the duct: in this case, through tight contacts between cells (intercellular transport). The high concentration of NaCl in the lumen of the duct stimulates the flow of water along the osmotic gradient.

Rice. 10-18. A variant of transepithelial NaCl secretion, which requires active accumulation of Cl - in the cell. In the gastrointestinal tract, at least two mechanisms are responsible for this (see also Fig. 10-19), one of which requires a carrier localized in the basolateral membrane, which ensures the simultaneous transfer of Na + -2Cl - -K + across the membrane (cotransport ). It works under the influence of a Na + chemical gradient, which in turn is supported by the Na + / K + -AT phase. K + ions enter the cell both through the cotransport mechanism and through the Na + / K + -ATPase and leave the cell through the basolateral membrane, and Cl - leaves the cell through the channels localized in the luminal membrane. The likelihood of their opening increases due to cAMP (small intestine) or cytosolic Ca 2+ (terminal glands, acini). There is a negative transepithelial potential in the duct lumen, providing intercellular Na + secretion. The quantitative balance shows that 6 mol of NaCl is released per 1 mol of ATP.

Transepithelial secretion of NaCl (option 2)

This, a different mechanism of secretion is observed in the cells of the acinus of the pancreas, which

possess two carriers localized in the basolateral membrane and providing ion exchanges Na + / H + and C1 - / HCO 3 - (antiport; Fig. 10-19).

Rice. 10-19. A variant of transepithelial NaCl secretion (see also Fig. 10-18), which begins with the fact that with the help of the basolateral Na + / H + -exchanger (as in Fig. 10-17) HCO 3 - ions accumulate in the cell. However, later this HCO 3 - (unlike Fig. 10-17) leaves the cell with the help of the Cl - - HCO 3 - transporter (antiport) located on the basolateral membrane. As a consequence, Cl - as a result of ("tertiary") active transport enters the cell. Through Cl - channels located in the luminal membrane, Cl - leaves the cell into the lumen of the duct. As a result, a transepithelial potential is established in the duct lumen, at which the contents of the duct lumen bear a negative charge. Na + under the influence of transepithelial potential rushes into the lumen of the duct. Energy balance: here, 3 mol of NaCl is released per 1 mol of used ATP, i.e. 2 times less than in the case of the mechanism described in Fig. 10-18 (DPC = diphenylamine carboxylate; SITS = 4-acetamino-4 "-isothiocyan-2,2" -disulfontilbene)

Synthesis of secreted proteins in the gastrointestinal tract

Certain cells synthesize proteins not only for their own needs, but also for secretion. Messenger RNA (mRNA) for the synthesis of export proteins carries not only information about the amino acid sequence of the protein, but also about the signal sequence of amino acids included in the beginning. The signal sequence allows the protein synthesized on the ribosome to enter the cavity of the rough endoplasmic reticulum (RER). After cleavage of the signal sequence of amino acids, the protein enters the Golgi complex and, finally, into condensing vacuoles and mature storage granules. If necessary, it is released from the cell as a result of exocytosis.

The first stage of any protein synthesis is the entry of amino acids into the basolateral part of the cell. With the help of aminoacyl tRNA synthetase, amino acids are attached to the corresponding transport RNA (tRNA), which delivers them to the site of protein synthesis. Protein synthesis is carried out

hangs on ribosomes, which "read" from messenger RNA information about the sequence of amino acids in the protein (broadcast). mRNA for a protein intended for export (or for insertion into the cell membrane) carries not only information about the amino acid sequence of the peptide chain, but also information about signal sequence of amino acids (signal peptide). The signal peptide is about 20 amino acid residues in length. After the signal peptide is ready, it immediately binds to a cytosolic molecule that recognizes signal sequences - SRP(signal recognition particle). SRP blocks protein synthesis until the entire ribosomal complex is attached to SRP receptor(mooring protein) rough cytoplasmic reticulum (RER). After that, the synthesis begins again, while the protein is not released into the cytosol and through the pore enters the RER cavity (Fig. 10-20). After the end of translation, the signal peptide is cleaved by a peptidase located in the RER membrane, and the new protein chain is ready.

Rice. 10-20. Synthesis of protein for export in a protein-secreting cell.

1. The ribosome binds to the mRNA chain, and the end of the synthesized peptide chain begins to exit the ribosome. The amino acid signal sequence (signal peptide) of the export protein binds to a signal sequence recognition molecule (SRP, signal recognition particle). SRP blocks a position in the ribosome (site A), which is approached by tRNA with an attached amino acid during protein synthesis. 2. As a result, translation is suspended, and (3) SRP, together with the ribosome, binds to the SRP receptor located on the membrane of the rough endoplasmic reticulum (RER), so that the end of the peptide chain is in the (hypothetical) pore of the RER membrane. 4. SRP is cleaved 5. Translation can continue and the peptide chain grows in the RER cavity: translocation

Secretion of proteins in the gastrointestinal tract

concentrates. Such vacuoles turn into mature secretory granules, which are collected in the luminal (apical) part of the cell (Fig. 10-21 A). From these granules, the protein is released into the extracellular space (for example, into the lumen of the acinus) due to the fact that the granule membrane merges with the cell membrane and at the same time ruptures: exocytosis(Fig. 10-21 B). Exocytosis is a constantly ongoing process, however, the influence of the nervous system or humoral stimulation can significantly accelerate it.

Rice. 10-21. Secretion of protein for export in a protein-secreting cell.

A- typical exocrine protein-secreting cellcontains in the basal part of the cell densely packed layers of rough endoplasmic reticulum (RER), on the ribosomes of which exported proteins are synthesized (see Fig. 10-20). At the smooth ends of the RER, vesicles containing proteins are separated, which are transferred to cis-areas of the Golgi apparatus (post-translational modification), from the trans-areas of which condensing vacuoles are separated. Finally, on the apical side of the cell, there are numerous mature secretory granules that are ready for exocytosis (panel B). B- the figure shows exocytosis. The three lower, membrane-surrounded vesicles (secretory granule; panel A) are still free in the cytosol, while the vesicle on the upper left is adjacent to the inner side of the plasma membrane. The membrane of the vesicle in the upper right has already merged with the plasma membrane, and the contents of the vesicle are poured into the lumen of the duct

The protein synthesized in the RER cavity is packed into small vesicles that are detached from the RER. Protein-containing vesicles are suitable for the Golgi complex and merge with its membrane. In the Golgi complex, the peptide is modified (post-translational modification), for example, it is glycolyzed and then leaves the Golgi complex inside condensing vacuoles. In them, the protein is again modified and

Regulation of the secretion process in the gastrointestinal tract

The exocrine glands of the digestive tract, which lie outside the walls of the esophagus, stomach and intestines, are innervated by efferents of both the sympathetic and parasympathetic nervous systems. The glands in the wall of the digestive tube are innervated by the nerves of the submucosal plexus. The epithelium of the mucous membrane and the glands built into it contain endocrine cells that release gastrin, cholecystokinin, secretin, GIP (glucose-dependent insuli-releasing peptide) and histamine. Once released into the bloodstream, these substances regulate and coordinate motility, secretion, and digestion in the gastrointestinal tract.

Many, perhaps all, secretory cells at rest secrete small amounts of fluid, salt, and protein. In contrast to reabsorbing epithelium, in which the transport of substances depends on the Na + gradient provided by the activity of Na + / K + -ATPase of the basolateral membrane, the level of secretion can be significantly increased if necessary. Stimulation of secretion can be done as nervous system, so and humoral.

Throughout the gastrointestinal tract, hormone-synthesizing cells are scattered between epithelial cells. They release a number of signaling substances: some of which are transported through the bloodstream to their target cells. (endocrine action), others - parahormones - act on neighboring cells (paracrine action). Hormones affect not only the cells involved in the secretion of various substances, but also the smooth muscles of the gastrointestinal tract (stimulate its activity or inhibit it). In addition, hormones can have a trophic or antitrophic effect on the cells of the gastrointestinal tract.

Endocrine cells the gastrointestinal tract has the shape of a bottle, while the narrow part is supplied with microvilli and is directed towards the intestinal lumen (Fig. 10-22 A). Unlike epithelial cells, which provide transport of substances, granules with proteins can be found near the basolateral membrane of endocrine cells, which are involved in the processes of transport into the cell and decarboxylation of amine precursor substances. Endocrine cells synthesize, including biologically active 5-hydroxytrimptamine. Such

endocrine cells are called APUD (amine precursor uptake and decarboxylation) cells, since they all contain carriers necessary for the capture of tryptophan (and histidine), and enzymes that provide decarboxylation of tryptophan (and histidine) to tryptamine (and histamine). In total, there are at least 20 signaling substances produced in the endocrine cells of the stomach and small intestine.

Gastrin, taken as an example, synthesized and released WITH(astrin)-cells. Two thirds of the G cells are found in the epithelium lining the antrum of the stomach, and one third in the mucosal layer of the duodenum. Gastrin exists in two active forms G34 and G17(the numbers in the name mean the number of amino acid residues that make up the molecule). Both forms differ from each other in the place of synthesis in the digestive tract and in the biological half-life. The biological activity of both forms of gastrin is due to The C-terminus of the peptide,-Try-Met-Asp-Phe (NH2). This sequence of amino acid residues is also found in the synthetic pentagastrin, BOC-β-Ala-TryMet-Asp-Phe (NH 2), which is administered to the body to diagnose gastric secretory function.

An incentive for release gastrin in the blood is primarily the presence of protein breakdown products in the stomach or in the lumen of the duodenum. Vagus efferent fibers also stimulate gastrin release. The fibers of the parasympathetic nervous system activate G-cells not directly, but through intermediate neurons that release GPR(Gastrin-Releasing Peptide). The release of gastrin in the antrum is inhibited when the pH of the gastric juice drops to less than 3; thus, a negative feedback loop arises, with the help of which too strong or too long secretion of gastric juice is stopped. On the one hand, low pH directly inhibits G cells antrum of the stomach, and on the other hand, stimulates the adjacent D-cells, which release somatostatin (SIH). Subsequently, somatostatin has an inhibitory effect on G cells (paracrine effect). Another possibility for inhibition of gastrin secretion is that vagus nerve fibers can stimulate the secretion of somatostatin from D cells through CGRP(calcitonin gene-related peptide) - ergic interneurons (Fig. 10-22 B).

Rice. 10-22. Regulation of secretion.

A- an endocrine cell of the gastrointestinal tract. B- regulation of gastrin secretion in the antrum of the stomach

Reabsorption of sodium in the small intestine

The main departments where the processes take place reabsorption(or in Russian terminology suction) in the gastrointestinal tract, are the jejunum, ileum and upper colon. The specificity of the jejunum and ileum is that the surface of their luminal membrane is increased by more than 100 times due to intestinal villi and high brush border

The mechanisms by which salts, water and nutrients are reabsorbed are similar to those of the kidneys. The transport of substances through the epithelial cells of the gastrointestinal tract depends on the activity of Na + / K + -ATPase or H + / K + -ATPase. The different incorporation of carriers and ion channels into the luminal and / or basolateral cell membrane determines which substance will be reabsorbed from the lumen of the digestive tube or secreted into it.

Several absorption mechanisms are known for the small and large intestine.

For the small intestine, the absorption mechanisms shown in Fig. 10-23 A and

rice. 10-23 V.

Mechanism 1(Fig. 10-23 A) is localized primarily in the jejunum. Na+ -ions cross the brush border here with the help of various carrier proteins, which use the energy of an (electrochemical) Na + gradient directed into the cell for reabsorption glucose, galactose, amino acids, phosphate, vitamins and other substances, so these substances enter the cell as a result of (secondary) active transport (cotransport).

Mechanism 2(Fig. 10-23 B) is inherent in the jejunum and gallbladder. It is based on the simultaneous localization of two carriers in the luminal membrane, providing ion exchange Na + / H + and Cl - / HCO 3 - (antiport), which allows you to reabsorb NaCl.

Rice. 10-23. Reabsorption (absorption) of Na + in the small intestine.

A- conjugate reabsorption of Na +, Cl - and glucose in the small intestine (primarily in the jejunum). Cell-directed Na + electrochemical gradient supported by Na +/ K + -ATPase, serves as a driving force for the luminal transporter (SGLT1), with the help of which, through the mechanism of secondary active transport, Na + and glucose enter the cell (cotransport). Since Na + has a charge and glucose is neutral, the luminal membrane is depolarized (electrogenic transport). The contents of the digestive tube acquire a negative charge, which promotes the reabsorption of Cl - through tight intercellular contacts. Glucose leaves the cell through the basolateral membrane through a facilitated diffusion mechanism (glucose transporter GLUT2). As a result, 3 moles of NaCl and 3 moles of glucose are reabsorbed for one spent mole of ATP. The mechanisms of reabsorption of neutral amino acids and a number of organic substances are similar to those described for glucose.B- reabsorption of NaCl due to the parallel activity of two carriers of the luminal membrane (jejunum, gallbladder). If a carrier carrying out the Na + / H + exchange (antiport) and a carrier providing the exchange of Cl - / HCO 3 - (antiport) are built next to the mebran of the cell, then as a result of their work, Na + and Cl - ions will accumulate in the cell. Unlike NaCl secretion, when both transporters are located on the basolateral membrane, in this case both transporters are localized in the luminal membrane (NaCl reabsorption). The Na + chemical gradient is the driving force behind H + secretion. H + ions leave the lumen of the digestive tube, and OH - ions remain in the cell, which react with CO 2 (the reaction is catalyzed by carbonic anhydrase). HCO 3 - anions accumulate in the cell, the chemical gradient of which provides a driving force for the carrier that transports Cl - into the cell. Cl - leaves the cell through the basolateral Cl - channels. (in the lumen of the digestive tube H + and HCO 3 - react with each other to form H 2 O and CO 2). In this case, 3 mol of NaCl is reabsorbed per 1 mol of ATP.

Reabsorption of sodium in the large intestine

The mechanisms by which absorption occurs in the large intestine are somewhat different from those in the small intestine. It is also possible to consider here two mechanisms prevailing in this department, which is illustrated in Fig. 10-23 as Mechanism 1 (Figure 10-24 A) and Mechanism 2 (Figure 10-24 B).

Mechanism 1(Fig. 10-24 A) predominates in the proximal region large intestine. Its essence lies in the fact that Na + enters the cell through luminal Na + channels.

Mechanism 2(Fig. 10-24 B) is presented in the large intestine due to K + / H + -ATPase located on the luminal membrane, K + ions are reabsorbed primarily.

Rice. 10-24. Reabsorption (absorption) of Na + in the large intestine.

A- reabsorption of Na + through luminal Na +-channels (primarily in the proximal large intestine). According to the gradient of ions directed into the cell Na +can be reabsorbed, participating in the mechanisms of secondary active transport using carriers (cotransport or antiport), and enter the cell passively throughNa +-channels (ENaC = Epithelial Na +Channel), localized in the luminal cell membrane. The same as in fig. 10-23 A, this mechanism of Na + entry into the cell is electrogenic, therefore, in this case, the contents of the lumen of the alimentary tube are charged negatively, which contributes to the reabsorption of Cl - through tight intercellular contacts. The energy balance is, as in Fig. 10-23 A, 3 moles of NaCl per 1 mole of ATP.B- the work of H + / K + -ATPase promotes the secretion of H + ions and reabsorptionK + ions by the mechanism of primary active transport (stomach, large intestine). Due to this "pump" of the membrane of the gastric parietal cells, which requires ATP energy, H + ions accumulate in the lumen of the digestive tube in very high concentrations (this process is inhibited by omeprazole). H + / K + -ATPase in the large intestine promotes the reabsorption of KHCO 3 (inhibited by oubain). For each H + ion secreted in the cell, an OH - ion remains, which reacts with CO 2 (the reaction is catalyzed by carbonic anhydrase) to form HCO 3 -. HCO 3 - leaves the parietal cell through the basolateral membrane with the help of a carrier that provides the exchange of Cl - / HCO 3 - (antiport; not shown here), the release of HCO 3 - from the epithelial cell of the large intestine is carried out through the HCO ^ -channel. For 1 mole of reabsorbed KHCO 3, 1 mole of ATP is spent, i.e. we are talking about a rather "expensive" process. In this caseNa +The / K + -ATPase does not play a significant role in this mechanism; therefore, it is impossible to reveal a stoichiometric relationship between the amount of ATP consumed and the amount of transferred substances.

Exocrine pancreatic function

Pancreas possesses exocrine apparatus(as well as endocrine part), which consists of cluster-like end sections - acini(lobules). They are located at the ends of a branched system of ducts, the epithelium of which looks relatively uniform (Fig. 10-25). Compared with other exocrine glands in the pancreas, the complete absence of myoepithelial cells is especially noticeable. The latter in other glands support the end regions during secretion, when the pressure in the excretory ducts increases. The absence of myoepithelial cells in the pancreas means that acinar cells burst easily during secretion, so that certain enzymes destined for export to the intestine enter the pancreatic interstitium.

Exocrine pancreas

digestive enzymes are released from the cells of the lobules, which are dissolved in a liquid with a neutral pH and enriched with Cl - ions, and from

cells of the excretory ducts - an alkaline liquid free of proteins. Digestive enzymes include amylases, lipases, and proteases. Bicarbonate in the secretion of the cells of the excretory ducts is necessary to neutralize hydrochloric acid, which enters with the chyme from the stomach into the duodenum. Acetylcholine from the endings of the vagus nerve activates secretion in the cells of the lobules, while the secretion of cells in the excretory ducts is stimulated primarily by secretin synthesized in S-cells of the mucous membrane of the small intestine. Due to the modulatory effect on cholinergic stimulation, cholecystokinin (CCK) acts on acinar cells, as a result of which their secretory activity is enhanced. Cholecystokinin also has a stimulating effect on the level of secretion of cells of the epithelium of the pancreatic duct.

If the outflow of secretion is difficult, as in cystic fibrosis (cystic fibrosis); if the pancreatic juice is especially viscous; or when the excretory duct is narrowed by inflammation or deposits, it can lead to inflammation of the pancreas (pancreatitis).

Rice. 10-25. The structure of the exocrine pancreas.

The lower part of the figure schematically shows the concept of a branched system of ducts, at the ends of which acini (end portions) are located, which existed until now. The enlarged image shows that in reality the acinus is a network of secretory tubules connected to each other. The extralobular duct is connected through a thin intralobular duct with such secretory tubules

Mechanism of secretion of bicarbonate by cells of the pancreas

The pancreas secretes about 2 liters of fluid per day. During digestion, the level of secretion increases many times compared to the state of rest. At rest, on an empty stomach, the level of secretion is 0.2-0.3 ml / min. After a meal, the secretion level rises to 4-4.5 ml / min. Such an increase in the rate of secretion in humans is primarily the achievement of the epithelial cells of the excretory ducts. While acini secretes a neutral chloride-rich juice with digestive enzymes dissolved in it, the epithelium of the excretory ducts supplies an alkaline fluid with a high concentration of bicarbonate (Fig. 10-26), which in humans is more than 100 mmol. As a result of mixing this secretion with the chyme containing HC1, the pH rises to values ​​at which the digestive enzymes are maximally activated.

The higher the rate of secretion of the pancreas, the higher bicarbonate concentration v

pancreatic juice. Wherein chloride concentration behaves like a mirror image of the concentration of bicarbonate, so the sum of the concentrations of both anions at all levels of secretion remains the same; it is equal to the sum of K + and Na + ions, the concentrations of which change as insignificantly as the isotonicity of pancreatic juice. Such ratios of the concentrations of substances in the juice of the pancreas can be explained by the fact that two isotonic fluids are secreted in the pancreas: one rich in NaCl (acini), and the other rich in NaHCO 3 (excretory ducts) (Fig. 10-26). At rest, both acini and pancreatic ducts secrete a small amount of secretion. However, at rest, the secretion of acini predominates, as a result of which the final secret is rich in C1 -. When stimulating the gland secretin the level of secretion of the duct epithelium increases. In this regard, the concentration of chloride is simultaneously reduced, since the sum of anions cannot exceed the (unchanged) sum of cations.

Rice. 10-26. The mechanism of NaHCO 3 secretion in cells of the pancreatic duct is similar to NaHCO 3 secretion in the intestine, since it also depends on Na + / K + -ATPase localized on the basolateral membrane and a carrier protein that exchanges Na + / H + ions (antiport) through basolateral membrane. However, in this case, HCO 3 - enters the gland duct not through the ion channel, but with the help of a carrier protein that provides anion exchange. To maintain its operation, the Cl - channel connected in parallel must provide recirculation of Cl - ions. This Сl - -channel (CFTR = Cystic Fibrosis Transmembrane Conductance Regulator) defective in patients with cystic fibrosis (=Cystic Fibrosis), which makes the secret of the pancreas more viscous and poor in HCO 3 -. The fluid in the duct of the gland is charged negatively with respect to the interstitial as a result of the release of Cl - from the cell into the lumen of the duct (and penetration of K + into the cell through the basolateral membrane), which promotes passive diffusion of Na + into the duct of the gland along tight intercellular contacts. A high level of secretion of HCO 3 - is possible, most likely, because HCO 3 - is secondarily actively transported into the cell using a carrier protein that carries out conjugated transport of Na + -HCO 3 - (symptom; NBC carrier protein, in the figure not depicted; SITS transporter)

Composition and properties of pancreatic enzymes

Unlike duct cells, acinar cells secrete digestive enzymes(Table 10-1). In addition, acini supply non-enzymatic proteins, such as immunoglobulins and glycoproteins. Digestive enzymes (amylases, lipases, proteases, DNases) are necessary for the normal digestion of food constituents. There is data

that the set of enzymes changes depending on the composition of the food taken. The pancreas, in order to protect itself from self-digestion by its own proteolytic enzymes, secretes them in the form of inactive precursors. So trypsin, for example, is secreted as trypsinogen. As additional protection, pancreatic juice contains a trypsin inhibitor that prevents its activation within secretory cells.

Rice. 10-27. Properties of the most important digestive enzymes of the pancreas, secreted by acinar cells, and acinar non-enzymatic proteins (Table 10-1)

Table 10-1. Pancreatic enzymes

* Many digestive enzymes of the pancreas exist in two or more forms, which differ from each other in relative molecular weights, optimal pH values ​​and isoelectric points

** Classification system Enzyme Commission, International Union of Biochemistry

Pancreatic endocrine function

Islet apparatus presents endocrine pancreas and makes up only 1-2% of the tissue, predominantly of its exocrine part. Of these, about 20% - α -cells, in which glucagon is formed, 60-70% are β -cells, which produce insulin and amylin, 10-15% - δ -cells, which synthesize somatostatin, which inhibits the secretion of insulin and glucagon. Another type of cells - F cells produces a pancreatic polypeptide (also called PP cells), which is possibly a cholecystokinin antagonist. Finally, there are G cells that produce gastrin. Rapid modulation of the release of hormones into the blood is provided by the localization of these endocrine active cells in alliance with the islets of Langerhans (named

so in honor of the discoverer - the German student of medicine), which allows paracrine control and additional direct intracellular transport of substances-transmitters and substrates through numerous Gap Junctions(tight intercellular contacts). Insofar as V. pancreatica flows into the portal vein, the concentration of all pancreatic hormones in the liver, the most important organ for metabolism, is 2-3 times higher than in the rest of the vascular system. With stimulation, this ratio increases 5-10 times.

In general, endocrine cells distinguish two key for the regulation of hydrocarbon metabolism hormone: insulin and glucagon. The secretion of these hormones mainly depends on blood glucose concentration and modulated somatostatin, the third most important hormone of the islets, together with gastrointestinal hormones and the autonomic nervous system.

Rice. 10-28. Islet of Langerhans

Glucagon and Pancreatic Insulin Hormones

Glucagon synthesized into α -cells. Glucagon consists of a single chain of 29 amino acids and has a molecular weight of 3500 Da (Fig. 10-29 A, B). Its amino acid sequence is homologous to certain gastrointestinal hormones such as secretin, vasoactive intestinal peptide (VIP) and GIP. From an evolutionary point of view, this is a very old peptide that has retained not only its shape, but also some important functions. Glucagon is synthesized via preprohormone in the α-cells of the islets of the pancreas. Peptides similar to glucagon in humans are also additionally formed in various intestinal cells (enteroglucagon or GLP 1). Post-translational cleavage of proglucagon in different cells of the intestine and pancreas occurs in different ways, so that a number of peptides are formed, the functions of which have not yet been elucidated. Glucagon circulating in the blood is approximately 50% bound to plasma proteins; this so called large plasma glucagon, biologically inactive.

Insulin synthesized in β -cells. Insulin consists of two peptide chains, an A-chain of 21 and a B-chain of 30 amino acids; its molecular weight is about 6000 Da. Both chains are linked by disulfide bridges (Fig. 10-29 B) and are formed from a precursor, proinsulin as a result of proteolytic cleavage of the C-chain (binding peptide). The gene for the synthesis of insulin is localized on the 11th human chromosome (Fig. 10-29 D). With the help of the corresponding mRNA in the endoplasmic reticulum (ER) is synthesized preproinsulin with a molecular weight of 11,500 Da. As a result of the separation of the signal sequence and the formation of disulfide bridges between chains A, B, and C, proinsulin appears,

kulakh is transported to the Golgi apparatus. There, the cleavage of the C-chain from proinsulin and the formation of zinc-insulin-hexamers - a storage form in the "mature" secretory granules, takes place. Let us clarify that the insulin of different animals and humans differs not only in amino acid composition, but also in the α-helix, which determines the secondary structure of the hormone. More complex is the tertiary structure, which forms areas (centers) responsible for the biological activity and antigenic properties of the hormone. The tertiary structure of monomeric insulin includes a hydrophobic core, which forms styloid processes on its surface that have hydrophilic properties, with the exception of two non-polar regions that provide the aggregation properties of the insulin molecule. The internal structure of the insulin molecule is important for interaction with its receptor and the manifestation of biological action. In the study using X-ray structural analysis, it was found that one hexameric unit of crystalline zinc-insulin consists of three dimers rolled around an axis on which two zinc atoms are located. Proinsulin, like insulin, forms dimers and zinc-containing hexamers.

During exocytosis, insulin (A- and B-chains) and C-peptide are released in equimolar amounts, with about 15% more insulin remaining in the form of proinsulin. Proinsulin itself has only a very limited biological effect; there is still no reliable information about the biological effect of C-peptide. Insulin has a very short half-life, on the order of 5-8 minutes, while C-peptide has a 4 times longer. In the clinic, the measurement of C-peptide in plasma is used as a parameter of the functional state of β-cells, and even with insulin therapy it makes it possible to assess the residual secretory capacity of the endocrine pancreas.

Rice. 10-29. The structure of glucagon, proinsulin and insulin.

A- glucagon is synthesized inα -cells and its structure is presented in the panel. B- insulin is synthesized inβ -cells. V- in the pancreasβ - the cells that produce insulin are evenly distributed, while The α cells that produce glucagon are concentrated in the tail of the pancreas. As a result of the cleavage of the C-peptide in these areas, insulin appears, consisting of two chains:Aand V. G- insulin synthesis scheme

The cellular mechanism of insulin secretion

Pancreatic β-cells increase the level of intracellular glucose due to its entry through the GLUT2-transporter and metabolize glucose, as well as galactose and mannose, and each of these substances can cause insulin secretion by the islets. Other hexoses (for example, 3-O-methylglucose or 2-deoxyglucose), which are transported to β-cells, but cannot be metabolized there, and do not stimulate insulin secretion. Certain amino acids (especially arginine and leucine) and small keto acids (α-ketoisocaproate) as well as ketohexoses(fructose) can weakly stimulate insulin secretion. Amino acids and keto acids do not share any metabolic pathway with hexoses other than oxidation through the citric acid cycle. These data have led to the suggestion that ATP synthesized from the metabolism of these various substances may be involved in insulin secretion. Based on this, 6 steps of insulin secretion by β-cells were proposed, which are set out in the caption to Fig. 10-30.

Let's consider the whole process in more detail. Insulin secretion is mainly controlled by blood glucose concentration, this means that food intake stimulates secretion, and with a decrease in glucose concentration, for example, during fasting (fasting, diet), the release is inhibited. Usually insulin is secreted at intervals of 15-20 minutes. Such pulsating secretion, appears to be important for the effectiveness of insulin and provides adequate insulin receptor function. After stimulation of insulin secretion by intravenous administration of glucose, biphasic secretory response. In the first phase, the maximum release of insulin occurs within minutes, which weakens again after a few minutes. After about 10 minutes, the second phase begins with persistent increased insulin secretion. It is believed that different phases are responsible for both phases.

storage forms of insulin. It is also possible that a variety of islet cell paracrine and autoregulatory mechanisms are responsible for such biphasic secretion.

Stimulation mechanism insulin secretion by glucose or hormones is largely elucidated (Fig. 10-30). Increased concentration is crucial ATF as a result of the oxidation of glucose, which, with an increase in plasma glucose concentration, by means of carrier-mediated transport in an increased amount enters the β-cells. As a result, the ATP- (or on the ATP / ADP ratio) dependent K + -channel is inhibited and the membrane is depolarized. As a result, voltage-dependent Ca 2+ channels open, extracellular Ca 2+ rushes inward and activates the process of exocytosis. The pulsatile release of insulin results from a typical pattern of β-cell discharging in "bursts".

Cellular mechanisms of insulin action very diverse and not yet fully understood. The insulin receptor is a tetradimer and consists of two extracellular α-subunits with specific binding sites for insulin and two β-subunits, which have a transmembrane and an intracellular part. The receptor belongs to the family tyrosine kinase receptors and is very similar in structure to the somatomedin-C- (IGF-1-) receptor. The β-subunits of the insulin receptor on the inner side of the cell contain a large number of tyrosine kinase domains, which at the first stage are activated by autophosphorylation. These reactions are essential for the activation of the following kinases (for example, phosphatidylinositol 3-kinase), which then induce various phosphorylation processes by which most of the enzymes involved in metabolism are activated in effector cells. Besides, internalization insulin, together with its receptor in the cell, is possibly also important for the expression of specific proteins.

Rice. 10-30. Insulin secretion mechanismβ -cells.

Increased extracellular glucose is a trigger for secretionβ-cell insulin, which occurs in seven stages. (1) Glucose enters the cell via the GLUT2 transporter, the work of which is mediated by the facilitated diffusion of glucose into the cell. (2) An increase in glucose uptake stimulates glucose metabolism in the cell and leads to an increase in [ATP] i or [ATP] i / [ADP] i. (3) Increasing [ATP] i or [ATP] i / [ADP] i inhibits ATP-sensitive K + channels. (4) Inhibition of ATP-sensitive K + channels causes depolarization, i.e. V m becomes more positive. (5) Depolarization activates voltage-gated Ca 2+ channels of the cell membrane. (6) Activation of these voltage-gated Ca 2+ channels increases the input of Ca 2+ ions and thus increases i, which also causes Ca 2+ -induced Ca 2+ release from the endoplasmic reticulum (ER). (7) The accumulation of i leads to exocytosis and the release of insulin contained in the secretory granules into the blood

Liver ultrastructure

The ultrastructure of the liver and biliary tract is shown in Fig. 10-31. Bile is secreted by liver cells into the bile ducts. Bile ducts, merging with each other at the periphery of the hepatic lobule, form larger bile ducts - perilobular bile ducts, lined with epithelium and hepatocytes. The perilobular bile ducts flow into the interlobular bile ducts lined with cubic epithelium. Anastomosing between

themselves and increasing in size, they form large septal ducts, surrounded by fibrous tissue of the portal tracts and merging into the lobar left and right hepatic ducts. On the lower surface of the liver, in the area of ​​the transverse groove, the left and right hepatic ducts join and form a common hepatic duct. The latter, merging with the cystic duct, flows into the common bile duct, which opens into the lumen of the duodenum in the region of the large duodenal papilla, or Vater's nipple.

Rice. 10-31. Liver ultrastructure.

The liver consists oflobules (diameter 1-1.5 mm), which are supplied with branches of the portal vein at the periphery(V.portae) and hepatic artery(A.hepatica). The blood from them flows through the sinusoids, which supply blood to the hepatocytes, and then enters the central vein. Between the hepatocytes are tubular, closed from the side with the help of tight contacts and not having a wall of their own, bile capillaries or tubules, Canaliculi biliferi. They release bile (see Fig. 10-32), which leaves the liver through the bile duct system. The epithelium containing hepatocytes corresponds to the end sections of the normal exocrine glands (for example, the salivary glands), the bile ducts to the lumen of the end section, the bile ducts to the excretory ducts of the gland, and the sinusoids to the blood capillaries. Unusually, the sinusoids receive a mixture of arterial blood (rich in O 2) and venous blood from the portal vein (poor in O 2, but rich in nutrients and other substances from the intestines). Kupffer's cells are macrophages

Composition and secretion of bile

Bile is an aqueous solution of various compounds with the properties of a colloidal solution. The main components of bile are bile acids (cholic and a small amount of deoxycholic), phospholipids, bile pigments, cholesterol. The composition of bile also includes fatty acids, protein, bicarbonates, sodium, potassium, calcium, chlorine, magnesium, iodine, a small amount of manganese, as well as vitamins, hormones, urea, uric acid, a number of enzymes, etc. The concentration of many components in the gallbladder 5-10 times higher than in the liver. However, the concentration of a number of components, for example sodium, chlorine, bicarbonates, is much lower due to their absorption in the gallbladder. Albumin, which is present in the hepatic bile, is not found at all in the gallbladder.

Bile is produced in hepatocytes. In the hepatocyte, two poles are distinguished: vascular, carrying out the capture of substances from the outside with the help of microvilli and introducing them into the cell, and biliary, where substances are released from the cell. Microvilli of the biliary pole of the hepatocyte form the origins of the bile ducts (capillaries), the walls of which are formed by membranes

two or more adjacent hepatocytes. Bile formation begins with the secretion of water, bilirubin, bile acids, cholesterol, phospholipids, electrolytes and other components by hepatocytes. The secretory apparatus of the hepatocyte is represented by lysosomes, lamellar complex, microvilli and bile ducts. Secretion is carried out in the area of ​​microvilli. Bilirubin, bile acids, cholesterol and phospholipids, mainly lecithin, are excreted in the form of a specific macromolecular complex - bile micelle. The ratio of these four main components, which is fairly constant in the norm, ensures the solubility of the complex. In addition, the low solubility of cholesterol is significantly increased in the presence of bile salts and lecithin.

The physiological role of bile is mainly associated with the digestion process. The most important for digestion are bile acids, which stimulate the secretion of the pancreas and have an emulsifying effect on fats, which is necessary for their digestion by pancreatic lipase. Bile neutralizes the acidic contents of the stomach entering the duodenum. Bile proteins are able to bind pepsin. Foreign substances are also excreted with bile.

Rice. 10-32. Bile secretion.

Hepatocytes release electrolytes and water into the bile ducts. In addition, hepatocytes secrete primary bile salts, which they synthesize from cholesterol, as well as secondary bile salts and primary bile salts, which they capture from sinusoids (intestinal-hepatic recirculation). The secretion of bile acids is accompanied by additional secretion of water. Bilirubin, steroid hormones, foreign substances and other substances bind with glutathione or glucuronic acid to increase their solubility in water, and in this conjugated form are excreted in bile

Synthesis of bile salts in the liver

Liver bile contains bile salts, cholesterol, phospholipids (primarily phosphatidylcholine = lecithin), steroids, as well as metabolic products such as bilirubin, and many foreign substances. Bile is isotonic to blood plasma, and its electrolyte composition is similar to the electrolyte composition of blood plasma. The pH of bile is neutral or slightly alkaline.

Bile salts are metabolites of cholesterol. Bile salts are captured by hepatocytes from the blood of the portal vein or synthesized intracellularly, after conjugation with glycine or taurine through the apical membrane into the bile ducts. Bile salts form micelles: in bile - with cholesterol and lecithin, and in the intestinal lumen - primarily with poorly soluble lipolysis products, for which the formation of micelles is a necessary prerequisite for reabsorption. When lipids are reabsorbed, bile salts are released again, reabsorbed in the end portions of the ileum, and so they re-enter the liver: the gastro-hepatic circulation. In the epithelium of the large intestine, bile salts increase the permeability of the epithelium to water. The secretion of both bile salts and other substances is accompanied by the movement of water along osmotic gradients. The secretion of water, due to the secretion of bile salts and other substances, is in each case 40% of the amount of primary bile. Remaining 20%

water falls on the fluids secreted by the cells of the epithelium of the bile duct.

The most common bile salts- salt cholic, chenode (s) oxycholic, de (h) oxycholic and lithocholic bile acids. They are captured by liver cells from the sinusoidal blood using the NTCP transporter (cotransport with Na +) and the OATP transporter (Na + independent transport; OATP = O rganic A nion -T ransporting P olypeptide) and in hepatocytes form a conjugate with an amino acid, glycine or taurine(Figure 10-33). Conjugation polarizes the molecule from the amino acid side, which facilitates its solubility in water, while the steroid skeleton is lipophilic, which facilitates interaction with other lipids. Thus, conjugated bile salts can function as detergents(substances providing solubility) for usually poorly soluble lipids: when the concentration of bile salts in bile or in the lumen of the small intestine exceeds a certain (so-called critical micellar) value, they spontaneously form tiny aggregates with lipids, micelles.

The evolution of various bile acids is associated with the need to keep lipids in solution in a wide range of pH values: at pH = 7 - in bile, at pH = 1-2 - in the chyme coming from the stomach, and at pH = 4-5 - after the chyme is mixed with pancreatic juice. This is possible due to the different pKa " -values ​​of individual bile acids (Fig. 10-33).

Rice. 10-33. Synthesis of bile salts in the liver.

Hepatocytes, using cholesterol as a starting substance, form bile salts, primarily chenodeoxycholate and cholate. Each of these (primary) bile salts can conjugate with an amino acid, primarily taurine or glycine, which reduces the pKa "value of the salt from 5 to 1.5 or 3.7, respectively. In addition, the part of the molecule shown in the figure on the right becomes hydrophilic (middle panel) Of the six different conjugated bile salts, both cholate conjugates are shown on the right with their full formulas. cholate, secondary bile salts, lithocholate (not shown in the figure) and deoxycholate, are formed, respectively.The latter enter the liver as a result of enterohepatic recirculation and form conjugates again, so that, after secretion with bile, they again take part in the reabsorption of fats

Intestinal hepatic circulation of bile salts

To digest and reabsorb 100 g of fat, you need about 20 g bile salts. Nevertheless, the total amount of bile salts in the body rarely exceeds 5 g, and only 0.5 g are synthesized again daily (cholate and chenodoxycholate = primary bile salts). Successful absorption of fats with the help of a small amount of bile salts is possible due to the fact that in the ileum 98% of bile salts excreted with bile are reabsorbed by the mechanism of secondary active transport together with Na + (cotransport), enters the bloodstream of the portal vein and returns to the liver: intestinal hepatic recirculation(Figure 10-34). On average, this cycle is repeated for one bile salt molecule up to 18 times before it is lost in the feces. In this case, conjugated bile salts are deconjugated

in the lower part of the duodenum with the help of bacteria and decarboxylated, in the case of primary bile salts (formation secondary bile salts; see fig. 10-33). In patients who have surgically removed the ileum or who suffer from chronic intestinal inflammation (Morbus Crohn), most of the bile salts are lost in the feces, therefore, the digestion and absorption of fats is impaired. Steatorrhea(fatty stools) and malabsorption are the consequences of such violations.

Interestingly, a small percentage of bile salts that enter the large intestine plays an important physiological role: bile salts interact with lipids in the luminal cell membrane and increase its permeability to water. If the concentration of bile salts in the large intestine decreases, then the reabsorption of water in the large intestine decreases and, as a result, develops diarrhea.

Rice. 10-34. Intestinal hepatic recirculation of bile salts.

How many times a day the pool of bile salts circulates between the intestines and the liver depends on the fat content of the food. When normal food is digested, a pool of bile salts circulates between the liver and intestines 2 times a day; with food rich in fats, circulation occurs 5 times or even more often. Therefore, the figures in the figure only give a rough idea.

Bile pigments

Bilirubin formed mainly by the breakdown of hemoglobin. After the destruction of aged erythrocytes by macrophages of the reticuloendothelial system, the heme ring is split off from hemoglobin, and after the destruction of the ring, hemoglobin is first converted into biliverdin and then into bilirubin. Bilirubin, due to its hydrophobicity, is transported by blood plasma in an albumin-bound state. From blood plasma, bilirubin is captured by liver cells and binds to intracellular proteins. Then bilirubin forms conjugates with the participation of the enzyme glucuronyl transferase, turning into water-soluble mono- and diglucuronides. Mono- and diglucuronides are released into the bile duct by means of a carrier (MRP2 = SMOAT), whose work requires the expenditure of energy ATP.

If the content of poorly soluble, unconjugated bilirubin (usually 1-2% micellar "solution") increases in bile, regardless of whether this occurs as a result of glucuronyl transferase overload (hemolysis, see below), or as a result of liver damage or bacterial deconjugation in bile, then so-called pigment stones(calcium bilirubinate, etc.).

Fine plasma bilirubin concentration less than 0.2 mmol. If it increases to a value exceeding 0.3-0.5 mmol, then the blood plasma looks yellow and the connective tissue (first the sclera, and then the skin) turns yellow, i.e. such an increase in the concentration of bilirubin leads to jaundice (icterus).

A high concentration of bilirubin in the blood can have several reasons: (1) Massive death of red blood cells for any reason, even with normal liver function, increases

plasma concentration of unconjugated ("indirect") bilirubin: hemolytic jaundice.(2) A defect in the enzyme glucuronyltransferase also leads to an increase in the amount of unconjugated bilirubin in the blood plasma: hepatocellular (hepatic) jaundice.(3) Post-hepatitis jaundice occurs when there is a blockage in the biliary tract. It can happen as in the liver (holostasis), and beyond (as a result of a tumor or stone in Ductus choleodochus):obstructive jaundice. Bile accumulates above the blockage; it is squeezed out together with conjugated bilirubin from the bile ducts through the desmosomes into the extracellular space, which is connected with the liver sinus and thus with the liver veins.

Bilirubin and its metabolites are reabsorbed in the intestine (about 15% of the excreted amount), but only after glucuronic acid is cleaved from them (by anaerobic intestinal bacteria) (Fig. 10-35). Free bilirubin is converted by bacteria to urobilinogen and stercobilinogen (both colorless). They oxidize to (colored, yellow-orange) final products urobilin and stercobilin, respectively. A small part of these substances enters the bloodstream of the circulatory system (primarily urobilinogen) and, after glomerular filtration in the kidney, appears in the urine, giving it a characteristic yellowish color. At the same time, the end products remaining in the feces, urobilin and stercobilin, stain it brown. With a rapid passage through the intestines, unchanged bilirubin stains the feces in a yellowish color. When in the feces, as in holostasis or blockage of the bile duct, neither bilirubin nor its decay products are found, then the result is a gray color of feces.

Rice. 10-35. Elimination of bilirubin.

Up to 230 mg of bilirubin, which is formed as a result of the breakdown of hemoglobin, is excreted per day. In blood plasma, bilirubin is bound to albumin. In liver cells, with the participation of glucurontransferase, bilirubin forms a conjugate with glucuronic acid. Such conjugated, much better water-soluble bilirubin is released into bile and with it enters the large intestine. There, bacteria break down the conjugate and convert free bilirubin into urobilinogen and stercobilinogen, from which, as a result of oxidation, urobilin and stercobilin are formed, which give the stool a brown color. About 85% of bilirubin and its metabolites are excreted in the stool, about 15% is reabsorbed again (intestinal-hepatic circulation), 2% enters the kidneys through the circulatory system and is excreted in the urine