What do small intestinal cells secrete? Small intestine (small intestine). Classification of stages of small intestine cancer. Types and Types of Small Bowel Cancer

Tone The intestine is conventionally divided into 3 sections: duodenum, jejunum and ileum. The length of the small intestine is 6 meters, and in people who eat mainly plant foods, it can reach 12 meters.

The wall of the small intestine consists of 4 shells: mucous, submucosal, muscular and serous.

The mucous membrane of the small intestine has own relief, including intestinal folds, intestinal villi and intestinal crypts.

Intestinal folds formed by the mucous and submucous membranes and are circular in nature. Circular folds are highest in the duodenum. As the small intestine progresses, the height of the circular folds decreases.

Intestinal villi They are finger-shaped outgrowths of the mucous membrane. In the duodenum, the intestinal villi are short and wide, and then along the small intestine they become tall and thin. The height of the villi in different parts of the intestine reaches 0.2 - 1.5 mm. Between the villi, 3-4 intestinal crypts open.

Intestinal crypts represent depressions of the epithelium into the own layer of the mucous membrane, which increase along the small intestine.

The most characteristic formations of the small intestine are intestinal villi and intestinal crypts, which increase the surface many times over.

On the surface, the mucous membrane of the small intestine (including the surface of the villi and crypts) is covered with single-layer prismatic epithelium. The lifespan of the intestinal epithelium ranges from 24 to 72 hours. Solid food accelerates the death of cells that produce crypts, which causes an increase in the proliferative activity of crypt epithelial cells. According to modern ideas, generative zone The intestinal epithelium is the bottom of the crypts, where 12-14% of all epithelial cells are in the synthetic period. During their life, epithelial cells gradually move from the depths of the crypt to the top of the villus and, at the same time, perform numerous functions: they multiply, absorb substances digested in the intestine, and secrete mucus and enzymes into the intestinal lumen. The separation of enzymes in the intestine occurs mainly along with the death of glandular cells. The cells, rising to the top of the villi, are rejected and disintegrate in the intestinal lumen, where they release their enzymes into the digestive chyme.

Among the intestinal enterocytes, intraepithelial lymphocytes are always present, which penetrate here from the lamina propria and belong to T-lymphocytes (cytotoxic, memory T-cells and natural killer cells). The content of intraepithelial lymphocytes increases in various diseases and immune disorders. Intestinal epithelium includes several types of cellular elements (enterocytes): bordered, goblet, borderless, tufted, endocrine, M-cells, Paneth cells.

Limb cells(columnar) constitute the main population of intestinal epithelial cells. These cells are prismatic in shape; on the apical surface there are numerous microvilli, which have the ability to contract slowly. The fact is that microvilli contain thin filaments and microtubules. In each microvillus, in the center there is a bundle of actin microfilaments, which are connected on one side to the plasmalemma of the apex of the villus, and at the base they are connected to the terminal network - horizontally oriented microfilaments. This complex ensures the reduction of microvilli during absorption. On the surface of the border cells of the villi there are from 800 to 1800 microvilli, and on the surface of the border cells of the crypts there are only 225 microvilli. These microvilli form a striated border. The surface of the microvilli is covered with a thick layer of glycocalyx. Border cells are characterized by a polar arrangement of organelles. The nucleus lies in the basal part, above it is the Golgi apparatus. Mitochondria are also localized at the apical pole. They have a well-developed granular and agranular endoplasmic reticulum. Between the cells lie endplates that close the intercellular space. In the apical part of the cell there is a well-defined terminal layer, which consists of a network of filaments located parallel to the cell surface. The terminal network contains actin and myosin microfilaments and is connected to intercellular contacts on the lateral surfaces of the apical parts of enterocytes. With the participation of microfilaments in the terminal network, the closure of intercellular gaps between enterocytes is ensured, which prevents the entry of various substances into them during digestion. The presence of microvilli increases the surface of cells by 40 times, due to which the total surface of the small intestine increases and reaches 500 m. On the surface of the microvilli there are numerous enzymes that provide hydrolytic cleavage of molecules not destroyed by enzymes of gastric and intestinal juice (phosphatases, nucleoside diphosphatases, aminopeptidases, etc.). This mechanism is called membrane or parietal digestion.

Membrane digestion not only a very efficient mechanism for the breakdown of small molecules, but also the most advanced mechanism that combines the processes of hydrolysis and transport. Enzymes located on the membranes of microvilli have a dual origin: partly they are adsorbed from the chyme, partly they are synthesized in the granular endoplasmic reticulum of the border cells. During membrane digestion, 80-90% of peptide and glucosidic bonds and 55-60% of triglycerides are broken down. The presence of microvilli turns the surface of the intestine into a kind of porous catalyst. It is believed that microvilli are able to contract and relax, which affects the processes of membrane digestion. The presence of the glycocalyx and very small spaces between the microvilli (15-20 microns) ensures sterility of digestion.

After cleavage, hydrolysis products penetrate the microvilli membrane, which has the ability of active and passive transport.

When fats are absorbed, they are first broken down into low-molecular compounds, and then resynthesis of fats occurs inside the Golgi apparatus and in the tubules of the granular endoplasmic reticulum. This entire complex is transported to the lateral surface of the cell. By exocytosis, fats are removed into the intercellular space.

The cleavage of polypeptide and polysaccharide chains occurs under the action of hydrolytic enzymes localized in the plasma membrane of microvilli. Amino acids and carbohydrates enter the cell using active transport mechanisms, that is, using energy. They are then released into the intercellular space.

Thus, the main functions of the border cells, which are located on the villi and crypts, are parietal digestion, which proceeds several times more intensely than intracavitary, and is accompanied by the breakdown of organic compounds to final products and the absorption of hydrolysis products.

Goblet cells located singly between the bordered enterocytes. Their content increases in the direction from the duodenum to the large intestine. There are slightly more goblet cells in the crypt epithelium than in the villous epithelium. These are typical mucous cells. They experience cyclical changes associated with the accumulation and secretion of mucus. In the phase of mucus accumulation, the nuclei of these cells are located at the base of the cells and have an irregular or even triangular shape. Organelles (Golgi apparatus, mitochondria) are located near the nucleus and are well developed. At the same time, the cytoplasm is filled with drops of mucus. After secretion is released, the cell decreases in size, the nucleus becomes smaller, and the cytoplasm is freed from mucus. These cells produce mucus necessary to moisturize the surface of the mucous membrane, which, on the one hand, protects the mucous membrane from mechanical damage, and on the other, promotes the movement of food particles. In addition, mucus protects against infectious damage and regulates the bacterial flora of the intestines.

M cells located in the epithelium in the area of ​​localization of lymphoid follicles (both group and single). These cells have a flattened shape, a small number of microvilli. At the apical end of these cells there are numerous microfolds, which is why they are called “microfolded cells.” With the help of microfolds, they are able to capture macromolecules from the intestinal lumen and form endocytic vesicles, which are transported to the plasma membrane and released into the intercellular space, and then into the lamina propria of the mucous membrane. After which, lymphocytes t. propria, stimulated by the antigen, migrate to the lymph nodes, where they proliferate and enter the blood. After circulating in the peripheral blood, they repopulate the lamina propria, where B lymphocytes transform into plasma cells that secrete IgA. Thus, antigens coming from the intestinal cavity attract lymphocytes, which stimulates an immune response in the intestinal lymphoid tissue. M cells have a very poorly developed cytoskeleton, so they are easily deformed under the influence of interepithelial lymphocytes. These cells do not have lysosomes, so they transport various antigens using vesicles without modification. They lack glycocalyx. The pockets formed by the folds contain lymphocytes.

Tufted cells on their surface they have long microvilli protruding into the intestinal lumen. The cytoplasm of these cells contains many mitochondria and tubules of the smooth endoplasmic reticulum. Their apical part is very narrow. It is assumed that these cells perform the function of chemoreceptors and, possibly, carry out selective absorption.

Paneth cells(exocrinocytes with acidophilic granulation) lie at the bottom of the crypts in groups or singly. In their apical part there are dense oxyphilic-staining granules. These granules are easily stained with eosin in a bright red color, dissolve in acids, but are resistant to alkalis. These cells contain large amounts of zinc, as well as enzymes (acid phosphatase, dehydrogenases and dipeptidases. The organelles are moderately developed (the Golgi apparatus is best developed). The cells Paneth perform an antibacterial function, which is associated with the production of lysozyme by these cells, which destroys the cell walls of bacteria and protozoa. These cells are capable of active phagocytosis of microorganisms. Thanks to these properties, Paneth cells regulate the intestinal microflora. In a number of diseases, the number of these cells decreases. In recent years IgA and IgG are detected in these cells. In addition, these cells produce dipeptidases that break down dipeptides into amino acids. It is assumed that their secretion neutralizes hydrochloric acid contained in chyme.

Endocrine cells belong to the diffuse endocrine system. All endocrine cells are characterized by

o the presence of secretory granules in the basal part under the nucleus, which is why they are called basal granular. On the apical surface there are microvilli, which apparently contain receptors that respond to changes in pH or to the absence of amino acids in the gastric chyme. Endocrine cells are primarily paracrine. They secrete their secretion through the basal and basal-lateral surfaces of cells into the intercellular space, directly influencing neighboring cells, nerve endings, smooth muscle cells, and vascular walls. Partially the hormones of these cells are released into the blood.

In the small intestine, the most common endocrine cells are: EC cells (secreting serotonin, motilin and substance P), A cells (producing enteroglucagon), S cells (producing secretin), I cells (producing cholecystokinin), G cells (producing gastrin), D-cells (producing somatostatin), D1-cells (secreting vasoactive intestinal polypeptide). Cells of the diffuse endocrine system are distributed unevenly in the small intestine: the largest number of them is contained in the wall of the duodenum. Thus, in the duodenum there are 150 endocrine cells per 100 crypts, and in the jejunum and ileum there are only 60 cells.

Borderless or borderless cells lie in the lower sections of the crypts. They often show mitoses. According to modern concepts, borderless cells are poorly differentiated cells and act as stem cells for the intestinal epithelium.

Proprietary layer of mucous membrane constructed of loose, unformed connective tissue. This layer makes up the bulk of the villi; between the crypts it lies in the form of thin layers. The connective tissue here contains many reticular fibers and reticular cells and is very loose. In this layer, in the villi under the epithelium lies a plexus of blood vessels, and in the center of the villi there is a lymphatic capillary. These vessels receive substances that are absorbed in the intestine and transported through the epithelium and connective tissue t.propria and through the capillary wall. The hydrolysis products of proteins and carbohydrates are absorbed into the blood capillaries, and fats into the lymphatic capillaries.

In the proper layer of the mucous membrane there are numerous lymphocytes, which lie either singly or form clusters in the form of single solitary or grouped lymphoid follicles. Large lymphoid accumulations are called Peyre's patches. Lymphoid follicles can even penetrate the submucosa. Peyre's patches are mainly located in the ileum, less often in other parts of the small intestine. The highest content of Peyre's patches is found during puberty (about 250); in adults, their number stabilizes and sharply decreases during old age (50-100). All lymphocytes lying in the t.propria (singly and grouped) form an intestinal-associated lymphoid system containing up to 40% of immune cells (effectors). In addition, the lymphoid tissue of the wall of the small intestine is currently equated to the bursa of Fabricius. Eosinophils, neutrophils, plasma cells and other cellular elements are constantly found in the lamina propria.

Muscular plate (muscular layer) of the mucous membrane consists of two layers of smooth muscle cells: internal circular and external longitudinal. From the inner layer, single muscle cells penetrate into the thickness of the villi and contribute to the contraction of the villi and the squeezing out of blood and lymph, rich in absorbed products from the intestine. Such contractions occur several times per minute.

Submucosa constructed from loose, unformed connective tissue containing a large number of elastic fibers. There is a powerful vascular (venous) plexus and a nerve plexus (submucosal or Meissnerian) located here. In the duodenum in the submucosa there are numerous duodenal (Brunner's) glands. These glands are complex, branched and alveolar-tubular in structure. Their terminal sections are lined with cubic or cylindrical cells with a flattened basal nucleus, a developed secretory apparatus and secretory granules at the apical end. Their excretory ducts open into the crypts, or at the base of the villi directly into the intestinal cavity. Mucocytes contain endocrine cells belonging to the diffuse endocrine system: Ec, G, D, S – cells. Cambial cells lie at the mouth of the ducts, so renewal of gland cells occurs from the ducts towards the terminal sections. The secretion of the duodenal glands contains mucus, which has an alkaline reaction and thereby protects the mucous membrane from mechanical and chemical damage. The secretion of these glands contains lysozyme, which has a bactericidal effect, urogastrone, which stimulates the proliferation of epithelial cells and inhibits the secretion of hydrochloric acid in the stomach, and enzymes (dipeptidases, amylase, enterokinase, which converts trypsinogen into trypsin). In general, the secretion of the duodenal glands performs a digestive function, participating in the processes of hydrolysis and absorption.

Muscularis built of smooth muscle tissue, forming two layers: internal circular and external longitudinal. These layers are separated by a thin layer of loose, unformed connective tissue, where the intermuscular (Auerbach) nerve plexus lies. Due to the muscular membrane, local and peristaltic contractions of the wall of the small intestine along the length are carried out.

Serosa It is a visceral layer of the peritoneum and consists of a thin layer of loose, unformed connective tissue, covered with mesothelium on top. A large number of elastic fibers are always present in the serous membrane.

Features of the structural organization of the small intestine in childhood. The mucous membrane of a newborn baby is thinned, and the relief is smoothed (the number of villi and crypts is small). By the period of puberty, the number of villi and folds increases and reaches its maximum value. The crypts are deeper than those of an adult. The surface of the mucous membrane is covered with epithelium, a distinctive feature of which is the high content of cells with acidophilic granules, lying not only at the bottom of the crypts, but also on the surface of the villi. The mucous membrane is characterized by abundant vascularization and high permeability, which creates favorable conditions for the absorption of toxins and microorganisms into the blood and the development of intoxication. Lymphoid follicles with reactive centers are formed only towards the end of the neonatal period. The submucosal nerve plexus is immature and contains neuroblasts. In the duodenum, the glands are few in number, small and unbranched. The muscle membrane of a newborn is thinned. The final structural formation of the small intestine occurs only by 4-5 years.

Brief overview of the functioning of the digestive system

The foods we consume cannot be digested in this form. To begin with, food must be processed mechanically, transferred into an aqueous solution and chemically broken down. Unused residues must be eliminated from the body. Since our gastrointestinal tract consists of the same components 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, waste removal is carried out once a day, the gastrointestinal tract must be able to store food for a certain time. The coordination of all these processes is carried out primarily by: (1) the autonomic or gastroenteric (internal) nervous system (nerve plexuses of the gastrointestinal tract); (2) externally transmitted 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 gate through which pathogens can enter the body. There are a number of specific and nonspecific mechanisms for protecting this boundary 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 microns) but huge layer of epithelium (about 10 m2), 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. They are joined by numerous exocrine glands: salivary glands

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

Motor activity includes chewing in the mouth, swallowing (pharynx and esophagus), crushing and mixing food with gastric juices in the distal stomach, mixing (mouth, stomach, small intestine) with digestive juices, movement in all parts of the gastrointestinal tract and temporary storage (proximal stomach , cecum, ascending colon, rectum). The transit time of food through each section 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 may occur spontaneously, most glandular tissue is under the control of the nervous system and hormones.

Digestion(enzymatic hydrolysis of proteins, fats and carbohydrates) occurring 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 substances (for example, glucose and amino acids from the lumen of the gastrointestinal tract into the blood). Unlike secretion, the extent of reabsorption is determined rather by the supply of reabsorbed substances. Reabsorption is limited to certain 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 and transit time of food.

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

Functions and composition of saliva

Saliva is produced 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 the sensation of taste stimuli, for sucking (in newborns), for oral hygiene, and for wetting solid pieces of food (in preparation for swallowing). Digestive enzymes in saliva are also necessary to remove food debris from the mouth.

Functions human saliva is as follows: (1) solvent for nutrients that can only be perceived by taste buds in dissolved form. In addition, saliva contains mucins - lubricants,- which facilitate chewing and swallowing solid food particles. (2) Moisturizes the oral cavity and prevents the spread of infectious agents by containing lysozyme, peroxidase and immunoglobulin A (IgA), those. substances that have 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) Infants need saliva to ensure that their lips attach tightly to the nipple.

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

Saliva is formed in two stages (Fig. 10-2 B). First, the lobules of the salivary glands produce isotonic primary saliva, which is secondarily modified during passage through the excretory ducts of the gland. Na + and Cl - are reabsorbed, and K + and bicarbonate are secreted. Typically, more ions are reabsorbed than excreted, causing the saliva to become 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), embedded in the basolateral membrane

acini cell wound. With the help of this carrier protein, 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 of saliva Na+ and Cl - are reabsorbed. Since the epithelium of the duct is relatively impermeable to water, the saliva in it becomes hypotonic. Simultaneously (small quantities) K+ and HCO 3 - are released the epithelium of the duct into its lumen. Compared to blood plasma, saliva is poor in Na+ and Cl - ions, but rich in K + and HCO 3 - ions. At high saliva flow rates, the transport mechanisms of the excretory ducts cannot cope with the load, so the concentration of K + falls and NaCl increases (Fig. 10-2). The concentration of HCO 3 is practically independent of the speed of saliva flow through the gland ducts.

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 baby, since they can digest the fat of milk already in the stomach thanks to the salivary enzyme swallowed at the same time as the milk.

Saliva secretion is regulated exclusively by the central nervous system. Its stimulation is provided reflexively influenced smell and taste of food. All major salivary glands in humans are innervated by sympathetic, so and parasympathetic nervous system. Depending on the amounts of mediators, acetylcholine (M 1 -cholinergic receptors) and norepinephrine (β 2 -adrenergic receptors), the composition of saliva changes near the acinar cells. In humans, sympathetic fibers cause the secretion of more viscous saliva, poor in water, than when stimulating the parasympathetic system. The physiological meaning of this double innervation, as well as the differences in the composition of saliva, are not yet known. Acetylcholine also causes (through 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 into the glandular duct. Acetylcholine also promotes the formation of kallikreins, which release bradykinin from blood plasma kininogen. Bradykinin has a vasodilating effect. Vasodilation increases the secretion of saliva.

Rice. 10-2. Saliva and its formation.

A- osmolality and composition of saliva depend on the speed of saliva flow. B- two stages of saliva formation. IN- myoepithelial cells in the salivary gland. It can be assumed that myoepithelial cells protect the lobules from expansion and rupture, which can be caused by 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

stomach wall, shown on its section (Fig. 10-3 B) is formed by four membranes: mucous, submucosal, muscular, serous. Mucous membrane forms longitudinal folds and consists of three layers: the epithelial layer, the lamina propria, and the muscular lamina. Let's look at all the shells and layers.

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

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

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

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

Muscularis 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.

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

All gastric glands which are the main structures of the lamina propria - simple tubular glands. They open into the gastric pits and consist of three parts: bottom, body And cervix (Fig. 10-3 B). Depending on location glands divide on cardiac, main(or fundamental) And pyloric. The structure and cellular composition of these glands are not the same. Quantitatively predominant main glands. They are the most poorly branched of all the gastric glands. In Fig. 10-3 B represents 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 gland neck (or accessory), (3) regenerative cells,

(4) parietal cells (or parietal cells),

(5) chief 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 - places where the ducts exit stomach glands(Fig. 10-3 B).

Arteries, pass through the serous and muscular membranes, giving them small branches that disintegrate into capillaries. The main trunks form plexuses. The most powerful plexus is the submucosal one. Small arteries extend from it into the lamina propria, where they form the mucous plexus. Capillaries depart from the latter, entwining the glands and feeding the integumentary epithelium. The capillaries merge into large stellate veins. The veins form the mucosal plexus and then the submucosal venous plexus

(Fig. 10-3 B).

Lymphatic system The stomach originates from blindly starting directly under the epithelium and around the glands of the lymphocapillaries of the mucous membrane. The capillaries merge into the submucosal lymphatic plexus. The lymphatic vessels extending from it pass through the muscular layer, receiving vessels from the plexuses lying between the muscular 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 a distal section (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 highest frequency. The cells in this area are the pacemakers of the stomach. A diagram of the anatomical structure of the stomach, to which the esophagus approaches, is shown in Fig. 10-3 A. The stomach includes several sections - the cardiac part of the stomach, the fundus of the stomach, the body of the stomach with the pacemaker zone, the antrum of the stomach, the pylorus. Next begins the duodenum. The stomach can also be divided into the proximal stomach and the distal stomach.B- incision in the wall of the stomach. IN- tubular gland of the body of the stomach

Tubular gland cells of the stomach

In Fig. Figure 10-4 B shows the tubular gland of the body of the stomach, and the inset (Figure 10-4 A) shows its layers, indicated on the panel. Rice. 10-4 B shows 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 that play a pronounced role in the physiology of the stomach. This is, first of all, parietal cells, or parietal cells(Fig. 10-4 B). The main role of these cells is to secrete hydrochloric acid.

Activated parietal cells secrete large quantities of isotonic liquid, which contains hydrochloric acid in a concentration of up to 150 mmol; activation is accompanied by pronounced morphological changes in parietal cells (Fig. 10-4 B). A weakly activated cell has a network of narrow, branched tubules(lumen diameter is about 1 micron), which open into the lumen of the gland. In addition, in the layer of cytoplasm bordering the lumen of the tubule, a large amount of tubulovesicle. Tubulovesicles are embedded in the membrane K+/H+-ATPhase and ionic K+- And Cl - - channels. When cells are strongly activated, tubulovesicles are embedded in the tubular membrane. Thus, the surface of the tubular membrane increases significantly and the transport proteins necessary for the secretion of HCl (K + /H + -ATPase) and ion channels for K + and Cl - are built into it (Fig. 10-4 D). When the level of cell activation decreases, the tubulovesicular membrane splits off from the tubule membrane and is stored in vesicles.

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

Hydrochloric acid is neutralized by so-called antacids. In addition, HCl secretion can be inhibited due to blockade of H2 receptors by ranitidine (Histamine 2 receptors) parietal cells or inhibition of H + /K + -ATPase activity omeprazole.

Chief cells secrete endopeptidases. Pepsin - a proteolytic enzyme - is secreted by the main cells of the human gastric glands in an inactive form (pepsinogen). Activation of pepsinogen is carried out autocatalytically: first from the 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 labenzyme(chymosin, rennin) calf. It cleaves a specific molecular bond between phenylalanine and methionine (Phe-Met bond) into caseinogen(soluble milk protein), due to which 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- tubular gland of the body of the stomach. Usually 5-7 of these glands flow into the pit on the surface of the gastric mucosa.B- cells that make up the simple tubular gland of the body of the stomach. IN- parietal cells at rest (1) and during activation (2). G- secretion of HCl by parietal cells. Two components can be detected 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 exit the cell through channels into the stomach cavity. At the same time, Na + /K + -ATPase promotes the removal of Na + from the cell, which accumulates in the cell as a result of the work of the carrier protein, which provides Na + /H + exchange (antiport) through the mechanism of secondary active transport. For every H+ ion removed, one OH-ion remains in the cell, which reacts 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 ensures the exchange of K + ions for H + ions, which exit into the gastric 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, exit into the gastric 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 (K + circulation 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 a thick layer of viscous mucus, which is secreted by the epithelium of the stomach wall, accessory cells of the glands of the fundus and body of the stomach, as well as cardiac and pyloric glands (Fig. 10-5 A). Although pepsin can break down mucus mucins in the presence of hydrochloric acid, this is mostly limited to the uppermost layer of mucus, since the deeper layers contain bicarbonate, who-

It is secreted by epithelial cells and helps 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 gastric epithelium does not necessarily lead to serious consequences, provided that the defect is quickly corrected. In fact, such epithelial damage 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 inserted, resulting from mitotic division.

Rice. 10-5. Self-protection of the stomach wall from digestion through the secretion of mucus and bicarbonate

Structure of the wall of the small intestine

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

The wall of the small intestine consists of various layers (Fig. 10-6). Overall, outside serosa passes outer muscular layer, which consists of outer longitudinal muscle layer And inner annular muscle layer, and the innermost is muscular plate of the mucous membrane, which separates submucosal layer from mucosal. bunches gap junctions)

The muscles of the outer layer of longitudinal muscles provide contraction of the intestinal wall. As a result, the intestinal wall shifts relative to the chyme (food gruel), which facilitates better mixing of the chyme with digestive juices. The ring muscles narrow the intestinal lumen, and the muscular plate of the mucous membrane (Lamina muscularis mucosae) ensures the movement of villi. The nervous system of the gastrointestinal tract (gastroenteric nervous system) is formed by two nerve 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. Afferent visceral fibers begin in the nerve plexuses, which

transmit nerve impulses to the central nervous system. (A similar wall structure is also observed in the esophagus, stomach, large intestine and rectum). To speed up reabsorption, the surface of the mucous membrane of the small intestine is increased due to folds, villi and a 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 area of ​​the small intestine, which facilitates its basic digestive functions. 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 muscular lamina of the mucous membrane (Fig. 10-6 A). The epithelial layer is represented by a single-layer cylindrical bordered epithelium. In the villi and crypts it is represented by different types of cells. Villous epithelium composed of four types of cells - chief cells, goblet cells, endocrine cells And Paneth cells.Crypt epithelium- five types

(Fig. 10-6 C, D).

In bordered enterocytes

Goblet enterocytes

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

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

1. Major duodenal papilla. 2. Duct ampulla. 3. Sphincters of the ducts. 4. Pancreatic duct. 5. Common bile duct. IN- structure of various parts of the small intestine: 6. Glands of the duodenum (Brunner's glands). 7. Serous membrane. 8. Outer longitudinal and inner circular layers of the muscularis propria. 9. Submucosa. 10. Mucous membrane.

11. The lamina propria with smooth muscle cells. 12. Group lymphoid nodules (lymphoid plaques, Peyer's patches). 13. Villi. 14. Folds. G - 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. Mucosa. 18. The lamina propria of the mucous membrane with smooth muscle cells. 19. Submucosa. 20. Outer longitudinal and inner circular layers of the muscularis propria. 21. Serous membrane. 22. Villi. 23. Central lacteal sinus. 24. Single lymphoid nodule. 25. Intestinal gland (Lieberkühn's gland). 26. Lymphatic vessel. 27. Submucosal nerve plexus. 28. Inner circular layer of the muscularis propria. 29. Muscular nerve plexus. 30. Outer longitudinal layer of the muscularis propria. 31. Artery (red) and vein (blue) of the submucosal layer

Functional morphology of the small intestinal mucosa

The three sections of the small intestine have the following differences: the duodenum has large papillae - duodenal glands, the height of the villi is different, which grows from the duodenum to the ileum, their width is different (wider in the duodenum), and 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 capable of actively contracting due to the components of the muscle plate. This promotes the absorption of chyme (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 indentations of the epithelium into the lamina propria of the mucosa. They are often regarded as glands (glands of Lieberkühn) (Fig. 10-7 B).

The small intestine is the main site of 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 villous epithelium 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 tip of the villus. All cells, with the exception of Paneth cells (providing 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 gel-like mucus, which is formed by goblet cells of the crypts and villi. When the pyloric sphincter opens, the release of chyme into the duodenum triggers increased secretion of mucus Brunner's glands. The passage of chyme into the duodenum causes the release of hormones into the blood secretin and cholecystokinin. Secretin triggers the secretion of alkaline juice in the epithelium of the pancreatic duct, which is also necessary to protect the mucous membrane of the duodenum from aggressive gastric juice.

About 95% of the villous epithelium is occupied by columnar chief cells. Although their main task is reabsorption, they are important sources of digestive enzymes that are localized either in the cytoplasm (amino- and dipeptidases) or in the brush border membrane: lactase, sucrase-isomaltase, amino- and endopeptidases. These brush border enzymes are integral membrane proteins, and part of their polypeptide chain, together with the catalytic center, is directed into the intestinal lumen, so 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 (cavitary 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. Mucosa. 2. The lamina propria with smooth muscle cells. 3. Submucosa. 4. Outer longitudinal and inner circular layers of the muscularis propria. 5. Serous membrane. 6. Villi. 7. Central lacteal sinus. 8. Single lymphoid nodule. 9. Intestinal gland (Lieberkühn's gland). 10. Lymphatic vessel. 11. Submucosal nerve plexus. 12. Inner circular layer of the muscularis propria. 13. Muscular nerve plexus. 14. Outer longitudinal layer of the muscularis mucosa.

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

16. Goblet cell (unicellular gland). 17. Prismatic epithelial cells. 18. Nerve fiber. 19. Central lacteal sinus. 20. Microhemacirculatory bed of the villi, network of blood capillaries. 21. Lamina propria 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 muscular lamina of the mucous membrane (Fig. 10-8). The epithelial layer is represented by a single-layer cylindrical bordered 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), and M cells (with microfolds), which are a modification of columnar epithelial cells.

Epithelium covered villi and those adjacent to them crypts. It mostly consists of reabsorbing cells that 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 division of the crypt epithelium,

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

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

The main type of villous epithelial cells is bordered enterocytes. In bordered enterocytes

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

M cells(microfold cells) are a type of enterocyte.

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

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

Colon

Colon consists of mucous, submucosal, 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-layered, cylindrical, bordered, and contains the same cells as the epithelium of the crypts of the small intestine - bordered, goblet-shaped endocrine, borderless, Paneth cells (Fig. 10-9).

The submucosa is formed by loose fibrous connective tissue.

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

three longitudinal strips. They are shorter than the intestine and therefore the intestine is assembled into an “accordion”.

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

The main differences between the wall of the large intestine (Fig. 10-9) and the thin wall (Fig. 10-8) are: 1) the absence of villi in the relief of the mucous membrane. Moreover, the crypts have a greater depth than in the small intestine; 2) the presence of a large number of goblet cells and lymphocytes in the epithelium; 3) the presence of a large number of single 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 deposits in the serous membrane.

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

Electrical activity of muscle cells of the stomach and intestines

The smooth muscle of the intestine is made up of small, spindle-shaped cells that form bunches and forming cross-links with neighboring bundles. 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).

Muscle cells of the antrum of the stomach and intestines are usually characterized by rhythmic fluctuations in membrane potential (slow waves) amplitude 10-20 mV and frequency 3-15/min (Fig. 10-10). At the moment of slow waves, the muscle bundles are partially contracted, so the wall of these sections of the gastrointestinal tract is in good shape; this occurs in the absence of action potentials. When the membrane potential reaches a threshold value and exceeds it, action potentials are generated, following each other at a short interval (spike sequence). The generation of action potentials is caused by Ca 2+ current (L-type Ca 2+ channels). An increase in Ca 2+ concentration 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 slow oscillation potential begins

regularly exceed the potential threshold. In this case, periodicity in the occurrence of spike sequences is observed. Smooth muscle contracts each time a spike train is generated. The frequency of rhythmic contractions corresponds to the frequency of slow oscillations of 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. 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 is hyperpolarized even more, then the amplitude of slow waves and muscle tone decrease, which ultimately leads to smooth muscle paralysis (atony). Due to what ionic currents oscillations in membrane potential occur is not yet clear; One thing is clear: the nervous system does not influence fluctuations in membrane potential. The cells of each muscle bundle have one, unique frequency of slow waves. Since neighboring bundles are connected to each other through electrical intercellular contacts, a bundle with a higher wave frequency (pacemaker) will impose this frequency on an adjacent beam with a lower frequency. Tonic contraction of smooth muscle for example, the proximal stomach, is due to the opening of Ca 2+ channels of a different type, which are chemo-dependent rather than voltage-dependent.

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

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

Reflexes of the gastroenteric nervous system

Some reflexes of the gastrointestinal tract are intrinsic gastroenteric (local) reflexes, in which a sensory afferent neuron activates a nerve plexus cell that innervates adjacent smooth muscle cells. The effect on smooth muscle cells can be excitatory or inhibitory, depending on what type of plexus neuron is activated (Fig. 10-11 2, 3). Other reflexes involve 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 the inhibitory interneuron, has an inhibitory effect on the longitudinal muscles of the sections of the digestive tube lying proximally, and a disinhibitory effect on the circular muscles (Fig. 10-11 4). At the same time, the longitudinal muscles are activated distally through the excitatory interneuron (the food tube is shortened), and the circular muscles relax (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).

Movement of the bolus moves the site of reflex activation more distally, which again moves the bolus, resulting in virtually 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 a bolus of food) 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. In the peristaltic reflex, for example, a neuron that is excited by stretching (light green) excites in the ascending direction (4) an inhibitory interneuron (purple), which in turn inhibits the excitatory motor neuron (dark green) innervating the longitudinal muscles and removes inhibition from inhibitory motor neuron (red) circular muscle (contraction). At the same time, in the descending direction (5), the excitatory interneuron (blue) is activated, which, through excitatory or inhibitory motor neurons in the distal part of the intestine, causes contraction of the longitudinal muscles and relaxation of the circular muscles

Parasympathetic innervation of the gastrointestinal tract

The gastrointestinal tract is innervated by 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 the excitatory (cholinergic) and inhibitory (peptidergic) cells of the intermuscular nerve plexus. Preganglionic sympathetic fibers begin from cells lying in the lateral horns of the sternolumbar 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 as part of the vagus nerves (N. vagus), as part of the splanchnic nerves (Nn. splanchnici) and pelvic nerves (Nn. pelvici) to the medulla oblongata, sympathetic ganglia and to the spinal cord. The sympathetic and parasympathetic nervous systems are involved in many gastrointestinal reflexes, including the dilation reflex and intestinal paresis.

Although reflex acts carried out by the nerve plexuses of the gastrointestinal tract can occur independently of the influence of the central nervous system (CNS), they are under the control of 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 its 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.

Parasymptotic nerves the gastrointestinal tract emerge from two independent sections of the central nervous system (Fig. 10-12). Nerves serving the esophagus, stomach, small intestine, and ascending colon (as well as the pancreas, gallbladder, and liver) originate from neurons in the medulla oblongata. (Medulla oblongata), the axons of which form the vagus nerve (N. vagus), whereas the innervation of the remaining parts of the gastrointestinal tract begins from neurons sacral spinal cord, the axons of which form the pelvic nerves (Nn. pelvici).

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

The 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 stimulants, and the other type - on peptidergic (NCNA) inhibitory nerve plexus cells (Fig. 10-13).

Axons of preganglionic fibers of the parasympathetic nervous system switch in the myenteric plexus to excitatory cholinergic or inhibitory non-cholinergic-non-adrenergic (NCNA-ergic) neurons. Postganglionic adrenergic neurons of the sympathetic system act in most cases inhibitory on 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 columns thoracic and lumbar spinal cord(Fig. 10-14). The axons of the neurons of the sympathetic nervous system exit the thoracic spinal cord through the anterior

roots and pass as part of the splanchnic 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 innervation to the gastrointestinal tract, there are more afferent fibers than efferent fibers in percentage terms. Sensory nerve endings are unspecialized 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. Perhaps a peptide hormone is involved in their activation (paracrine action). 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 coming as 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). Neurons of afferent fibers lie in sensory

spinal ganglia of the dorsal roots of the spinal cord, and their fibers enter the spinal cord through the dorsal roots. Afferent fibers that pass as part of the vagus nerve form the afferent link reflexes of the gastrointestinal tract, occurring with the participation of the vagus parasympathetic nerve. These reflexes are especially important for coordinating the motor function of the esophagus and proximal stomach. Sensory neurons, the axons of which go as part of the vagus nerve, are localized in Ganglion nodosum. They form connections with neurons of the nucleus of the solitary tract (Tractus solitarius). The information they transmit reaches preganglionic parasympathetic cells localized 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), the cell bodies of which lie in the dorsal roots of the spinal ganglion, pass through the pre- and paravertebral ganglia without switching and enter the spinal cord, where they are either switched to neurons of the ascending or descending tracts, or in the same segment of the spinal cord switch to preganglionic autonomic neurons, as in the lateral intermediate gray matter (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 lipid composition 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 epithelial cells in the basolateral membrane Na + /K + -ATPase (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 from these gradients can be reused 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 simultaneous transfer of Na + into the cell along 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 water follows the ions.

Active potassium secretion

In epithelial cells, K + actively accumulates 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 epithelium that does not secrete K + , 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 for K+ secretion can be achieved by inserting 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 mole of ATP, “pumps” 3 moles of Na + ions out of 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 junctions between epithelial cells) also rush into the lumen of the digestive tube. As the stoichiometric values ​​in the figure show, 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 the Na + -K + pump. The potential energy of the Na+ gradient is used by carrier proteins, with Na+ being transferred 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 -(eg, pancreatic ducts, Brunner's glands, or bile ducts) require a Na + /H + exchanger in the basolateral cell membrane (Fig. 10-17). H + ions are removed from the cell using secondary active transport, leaving OH - ions in it, which interact with CO 2 to form HCO 3 - . Carbonic anhydrase acts as a catalyst in this process. The resulting HCO 3 - leaves the cell in the direction of the lumen of the gastrointestinal tract either through a channel (Fig. 10-17) or with the help of a carrier protein that carries out the C1 - / HCO 3 - exchange. 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. A carrier protein is responsible for this, which, through the mechanism of secondary active transport, ensures the transfer of H+ ions. The driving force for this process is the Na + chemical gradient maintained by the Na + /K + -ATPase. (In contrast to Fig. 10-16, K + ions exit the cell through the basolateral membrane through K + channels, entering the cell as a result of the work of Na + /K + -ATPase). For every H + ion that leaves the cell, one OH - ion remains, which binds to CO 2, forming HCO 3 -. This reaction is catalyzed by carbonic anhydrase. HCO 3 - diffuses through anion channels into the lumen of the duct, which leads to the emergence of transepithelial potential, in which the contents of the duct lumen are charged negatively with respect to the interstitium. Under the influence of such transepithelial potential, Na + ions rush into the lumen of the duct through tight junctions between cells. The quantitative balance shows that the secretion of 3 moles of NaHCO 3 requires 1 mole 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 the Na + -K + pump. The potential energy of the Na+ gradient is used by carrier proteins, with Na+ being transferred 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

sections of the salivary glands of the mouth, in the acini of the pancreas, as well as in the lacrimal glands. Instead of the Na + /H + exchanger in basolateral membrane epithelial cells of these organs, a transporter is localized, providing conjugate transfer of Na + -K + -2Cl - (cotransport; rice. 10-18). This transporter uses the Na + gradient to (secondary active) accumulate Cl - in the cell. From the cell, Cl - can passively exit 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 junctions between cells (intercellular transport). A 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 transporter localized in the basolateral membrane to ensure simultaneous transfer of Na + -2Cl - -K + across the membrane (cotransport ). It operates under a Na+ chemical gradient, which in turn is maintained by the Na+/K+ -ATPase. K + ions enter the cell both through the cotransport mechanism and through Na + / K + -ATPase and exit the cell through the basolateral membrane, and Cl - leaves the cell through channels localized in the luminal membrane. The likelihood of their opening increases due to cAMP (small intestine) or cytosolic Ca 2+ (terminal sections of glands, acini). A negative transepithelial potential arises in the lumen of the duct, providing intercellular secretion of Na +. The quantitative balance shows that 6 moles of NaCl are released per 1 mole of ATP

Transepithelial secretion of NaCl (option 2)

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

have 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 secretion of NaCl (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 using the Cl - -HCO 3 - transporter (antiport) located on the basolateral membrane. As a result, 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 lumen of the duct, at which the contents of the lumen of the duct carry a negative charge. Na +, under the influence of the transepithelial potential, rushes into the lumen of the duct. Energy balance: here, per 1 mole of ATP used, 3 moles of NaCl are released, 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"-disulfonestilbene)

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 at the beginning. The signal sequence ensures that the protein synthesized on the ribosome enters the cavities of the rough endoplasmic reticulum (RER). After cleavage of the amino acid signal sequence, 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 transfer RNA (tRNA), which delivers them to the site of protein synthesis. Protein synthesis is carried out

falls on ribosomes, which “read” information about the sequence of amino acids in a protein from messenger RNA (broadcast). mRNA for a protein intended for export (or for integration into the cell membrane) carries not only information about the sequence of amino acids of the peptide chain, but also information about signal sequence of amino acids (signal peptide). The length of the signal peptide is about 20 amino acid residues. Once 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 this, synthesis begins again, and the protein is not released into the cytosol and enters the RER cavities through a pore (Fig. 10-20). After the end of translation, the signal peptide is cleaved off by a peptidase located in the RER membrane, and a new protein chain is ready.

Rice. 10-20. Synthesis of a protein intended 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 signal sequence of amino acids (signal peptide) of the protein intended for export binds to a molecule that recognizes signal sequences (SRP, signal recognition particle). SRP blocks the position in the ribosome (site A) to which a tRNA with an attached amino acid approaches 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 rough endoplasmic reticulum (RER) membrane, so that the end of the peptide chain ends up in a (hypothetical) pore of the RER membrane. 4. SRP is cleaved off 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 collect 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 fuses with the cell membrane and ruptures: exocytosis(Fig. 10-21 B). Exocytosis is a constantly ongoing process, but the influence of the nervous system or humoral stimulation can significantly accelerate it.

Rice. 10-21. Secretion of a protein intended 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 released and transported to cis-regions of the Golgi apparatus (post-translational modification), from the trans-regions of which condensing vacuoles are separated. Finally, on the apical side of the cell lie numerous mature secretory granules that are ready for exocytosis (panel B). B- The figure demonstrates exocytosis. The three lower membrane-enclosed 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 vesicle membrane at the top 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 packaged into small vesicles, which are separated from the RER. Vesicles containing protein approach Golgi complex and merge with its membrane. The peptide is modified in the Golgi complex (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 embedded in it contain endocrine cells that release gastrin, cholecystokinin, secretin, GIP (glucose-dependent insulin-releasing peptide) and histamine. Once released into the blood, these substances regulate and coordinate motility, secretion, and digestion in the gastrointestinal tract.

Many, perhaps even all, secretory cells at rest secrete small amounts of fluid, salts and proteins. Unlike the reabsorbing epithelium, in which the transport of substances depends on the Na + gradient provided by the activity of the Na + /K + -ATPase of the basolateral membrane, the level of secretion can be significantly increased if necessary. Secretion stimulation can be carried out as nervous system so and humoral.

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

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

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

Gastrin, taken as an example, is synthesized and released WITH(astrin)-cells. Two thirds of G cells are found in the epithelium lining the antrum of the stomach, and one third is found in the mucosal layer of the duodenum. Gastrin exists in two active forms G34 And G17(the numbers in the name indicate 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 biological half-life. The biological activity of both forms of gastrin is due to 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 introduced into the body to diagnose gastric secretory function.

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. Efferent fibers of the vagus nerve also stimulate the release of gastrin. The fibers of the parasympathetic nervous system activate G cells not directly, but through interneurons that release GPR(Gastrin-Releasing Peptide). The release of gastrin in the antrum of the stomach is inhibited when the pH value of gastric juice decreases to a level less than 3; Thus, a negative feedback loop arises, with the help of which the secretion of gastric juice is stopped too much or for too long. On the one hand, low pH levels directly inhibit 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 may stimulate somatostatin secretion from D cells through CGRP(calcitonin gene-related peptide)- ergic interneurons (Fig. 10-22 B).

Rice. 10-22. Regulation of secretion.

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

Sodium reabsorption in the small intestine

The main departments where 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 a high brush border

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

Several mechanisms of absorption are known for the small and large intestines.

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 the (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 gall bladder. 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 NaCl to be reabsorbed.

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

A- coupled reabsorption of Na +, Cl - and glucose in the small intestine (primarily in the jejunum). An electrochemical gradient of Na+ directed into the cell, which is maintained by Na+/ K+ -ATPase, serves as the 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 junctions. Glucose leaves the cell through the basolateral membrane via the facilitated diffusion mechanism (glucose transporter GLUT2). As a result, per mole of ATP expended, 3 moles of NaCl and 3 moles of glucose are reabsorbed. The mechanisms of reabsorption of neutral amino acids and a number of organic substances are similar to those described for glucose.B- NaCl reabsorption due to the parallel activity of two luminal membrane transporters (jejunum, gall bladder). If a carrier that carries out the exchange of Na + /H + (antiport) and a transporter that ensures the exchange of Cl - /HCO 3 - (antiport) are built nearby into the cell membrane, then as a result of their work, Na + and Cl - ions will accumulate in the cell. Unlike NaCl secretion, where 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 for H+ secretion. H + ions enter the lumen of the digestive tube, and OH - ions remain in the cell, which react with CO 2 (the reaction catalyst is carbonic anhydrase). HCO 3 - anions accumulate in the cell, the chemical gradient of which provides the driving force for the carrier that transports Cl - into the cell. Cl - leaves the cell through 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 per 1 mol of ATP is reabsorbed

Sodium reabsorption in the large intestine

The mechanisms by which absorption occurs in the large intestine are somewhat different from those in the small intestine. Here we can also consider two mechanisms that predominate in this section, as illustrated in Fig. 10-23 as mechanism 1 (Fig. 10-24 A) and mechanism 2 (Fig. 10-24 B).

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

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

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

A- Na+ reabsorption through luminal Na+-channels (primarily in the proximal colon). Along the gradient of ions directed into the cell Na+can be reabsorbed by 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. 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 food tube are charged negatively, which promotes the reabsorption of Cl - through intercellular tight junctions. 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 parietal cells of the stomach, 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 every H+ ion secreted, an OH - ion remains in the cell, which reacts with CO 2 (the reaction catalyst is carbonic anhydrase) to form HCO 3 - . HCO 3 - leaves the parietal cell through the basolateral membrane using a transporter that ensures the exchange of Cl - /HCO 3 - (antiport; not shown here), the exit of HCO 3 - from the colon epithelial cell occurs through the HCO^ channel. For 1 mole of reabsorbed KHCO 3, 1 mole of ATP is consumed, i.e. We are talking about a rather “expensive” process. In this caseNa+/K + -ATPase does not play a significant role in this mechanism, therefore it is impossible to identify a stoichiometric relationship between the amount of ATP expended and the amounts of transferred substances

Exocrine function of the pancreas

Pancreas has exocrine apparatus(along with endocrine part), which consists of cluster-shaped end sections - acini(lobes). They are located at the ends of a branched system of ducts, the epithelium of which looks relatively uniform (Fig. 10-25). Compared to other exocrine glands, the pancreas is particularly noticeable in its complete absence of myoepithelial cells. The latter in other glands support the terminal sections 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 certain enzymes destined for export to the intestine end up in the pancreatic interstitium.

Exocrine pancreas

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

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

If the outflow of secretions is difficult, as in cystic fibrosis (cystic fibrosis); if pancreatic juice is especially viscous; or when the excretory duct is narrowed as a result of 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 hitherto existing idea of ​​a branched system of ducts, at the ends of which acini (end sections) are located. The enlarged image shows that the acini is actually a network of secretory tubules connected to each other. The extralobular duct is connected through a thin intralobular duct to such secretory tubules

The mechanism of bicarbonate secretion by pancreatic cells

The pancreas secretes about 2 liters of fluid per day. During digestion, the level of secretion increases many times compared to the resting state. At rest, on an empty stomach, the secretion level is 0.2-0.3 ml/min. After eating, the secretion level increases to 4-4.5 ml/min. This increase in the rate of secretion in humans is achieved primarily by the epithelial cells of the excretory ducts. While the acini secrete 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 HC1-containing chyme, the pH rises to values ​​at which digestive enzymes are maximally activated.

The higher the rate of pancreatic secretion, the higher bicarbonate concentration V

pancreatic juice. Wherein chloride concentration behaves as a mirror image of the bicarbonate concentration, 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 vary as little as the isotonicity of pancreatic juice. Such ratios of concentrations of substances in pancreatic juice 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 the acini and the pancreatic ducts secrete a small amount of secretion. However, at rest, acini secretion predominates, as a result of which the final secretion is rich in C1 -. When stimulating the gland secretin the level of secretion of the duct epithelium increases. In this regard, the chloride concentration simultaneously decreases, since the sum of anions cannot exceed the (constant) sum of cations.

Rice. 10-26. The mechanism of NaHCO 3 secretion in pancreatic duct cells is similar to NaHC0 3 secretion in the intestine, since it also depends on Na + /K + -ATPase localized on the basolateral membrane and a transport 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, a Cl - channel connected in parallel must ensure recycling of Cl - ions. This Cl - channel (CFTR = Cystic Fibrosis Transmembrane Conductance Regulator) defective in patients with cystic fibrosis (=Cystic Fibrosis), which makes pancreatic secretion more viscous and poor in HCO 3 -. The fluid in the gland duct is charged negatively relative to the interstitial fluid as a result of the release of Cl - from the cell into the lumen of the duct (and the penetration of K + into the cell through the basolateral membrane), which promotes passive diffusion of Na + into the gland duct along intercellular tight junctions. A high level of HCO 3 - secretion is possible, apparently, because HCO 3 - is secondarily actively transported into the cell using a carrier protein that carries out the coupled transport of Na + -HCO 3 - (symport; NBC carrier protein, not shown in the figure pictured; SITS transporter protein)

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 components. 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 an additional protection, pancreatic juice contains a trypsin inhibitor, which prevents its activation inside the 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 pancreatic digestive enzymes exist in two or more forms that differ in relative molecular weights, optimal pH values, and isoelectric points

** Classification system Enzyme Commission, International Union of Biochemistry

Endocrine function of the pancreas

Insular apparatus is endocrine pancreas and makes up only 1-2% of the tissue, predominantly its exocrine part. Of these, about 20% are 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 cell is F cells produces pancreatic polypeptide (otherwise known as PP cells), which may be an antagonist of cholecystokinin. Finally, there are also G cells that produce gastrin. Rapid modulation of the release of hormones into the blood is ensured by the localization of these endocrine active cells in alliance with the islets of Langerhans (called

so in honor of the discoverer - a German medical student), allowing paracrine control and additional direct intracellular transport of transmitter substances and substrates through numerous Gap Junctions(tight intercellular junctions). Because the 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 secrete two key to regulate 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 insulin hormones of the pancreas

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 several 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 a preprohormone in the α-cells of the pancreatic islets. Peptides similar to glucagon in humans are also additionally produced in various intestinal cells (enteroglucagon or GLP 1). Post-translational cleavage of proglucagon occurs differently in different cells of the intestine and pancreas, so that a variety 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, not biologically active.

Insulin synthesized into 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 interconnected 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 insulin synthesis is localized on human chromosome 11 (Fig. 10-29 D). With the help of the corresponding mRNA in the endoplasmic reticulum (ER) it 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, which in microvesicles

culah is transported to the Golgi apparatus. There, the C-chain is cleaved from proinsulin and zinc-insulin hexamers are formed - a storage form in “mature” secretory granules. Let us clarify that insulin from 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 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. X-ray diffraction analysis revealed that one hexameric unit of crystalline zinc insulin consists of three dimers folded 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 quantities, with about 15% of the insulin remaining as 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, about 5-8 minutes, while C-peptide has a 4 times longer half-life. In the clinic, measurement of C-peptide in plasma is used as a parameter of the functional state of β-cells, and even with insulin therapy allows one to assess the residual secretory capacity of the endocrine pancreas.

Rice. 10-29. 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. IN- in the pancreasβ -cells that produce insulin are evenly distributed, whereasα-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- scheme of insulin synthesis

Cellular mechanism of insulin secretion

Pancreatic β-cells increase intracellular glucose levels by entering through the GLUT2 transporter and metabolize glucose as well as galactose and mannose, each of which can induce islet secretion of insulin. Other hexoses (eg, 3-O-methylglucose or 2-deoxyglucose), which are transported into β-cells but cannot be metabolized there and do not stimulate insulin secretion. Some amino acids (especially arginine and leucine) and small keto acids (α-ketoisocaproate) as well as ketohexoses(fructose) may weakly stimulate insulin secretion. Amino acids and keto acids do not share any metabolic pathway with hexoses except 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 stages of insulin secretion by β-cells were proposed, which are outlined in the caption to Fig. 10-30.

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

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

Stimulation mechanism The secretion of insulin by glucose or hormones is largely understood (Fig. 10-30). The key is to increase concentration ATP as a result of the oxidation of glucose, which, with increasing plasma glucose concentration, enters β-cells in increased quantities using carrier-mediated transport. As a result, the ATP- (or 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 in and activates the process of exocytosis. The pulsatile release of insulin results from the typical β-cell discharge pattern 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 inside 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 downstream kinases (eg phosphatidylinositol 3-kinase), which then induce various phosphorylation processes through which most enzymes involved in metabolism are activated in effector cells. Besides, internalization insulin together with its receptor into the cell may also be important for the expression of specific proteins.

Rice. 10-30. Mechanism of insulin secretionβ -cells.

An increase in extracellular glucose levels is a trigger for secretionβ-cells produce insulin, which occurs in seven steps. (1) Glucose enters the cell through the GLUT2 transporter, whose operation is mediated by facilitated diffusion of glucose into the cell. (2) Increased glucose input stimulates cellular glucose metabolism and leads to an increase in [ATP]i or [ATP]i/[ADP]i. (3) An increase in [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 takes on more positive values. (5) Depolarization activates voltage-gated Ca 2+ channels in the cell membrane. (6) Activation of these voltage-gated Ca 2+ channels increases the influx of Ca 2+ ions and thus increases i , which also causes Ca 2+ -induced Ca 2+ release from the endoplasmic reticulum (ER). (7) Accumulation of i leads to exocytosis and release of insulin contained in secretory granules into the blood

Ultrastructure of the liver

The ultrastructure of the liver and biliary tract is shown in Fig. 10-31. Bile is secreted by liver cells into bile canaliculi. Bile canaliculi, 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 empty into the interlobular bile ducts, which are lined with cuboidal 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 the 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 major duodenal papilla, or papilla of Vater.

Rice. 10-31. Ultrastructure of the liver.

The liver consists oflobes (diameter 1-1.5 mm), which are supplied at the periphery by branches of the portal vein(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 lie tube-shaped bile capillaries or canaliculi, closed laterally by tight junctions and not having their own wall, Canaliculi biliferi. They secrete bile (see Fig. 10-32), which leaves the liver through the bile duct system. The epithelium containing hepatocytes corresponds to the terminal sections of ordinary exocrine glands (for example, salivary glands), the bile canaliculi correspond to the lumen of the terminal section, the bile ducts correspond to the excretory ducts of the gland, and the sinusoids correspond to blood capillaries. What is unusual is that the sinusoids receive a mixture of arterial (rich in O2) and venous blood from the portal vein (poor in O2, but rich in nutrients and other substances coming from the intestines). Kupffer cells are macrophages

Composition and secretion of bile

Bile is an aqueous solution of various compounds that has the properties of a colloidal solution. The main components of bile are bile acids (cholic and in small quantities 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, due to their absorption in the gallbladder, is much lower. Albumin, present in hepatic bile, is not detected at all in cystic bile.

Bile is produced in hepatocytes. In a hepatocyte, two poles are distinguished: vascular, which, with the help of microvilli, captures substances from the outside and introduces 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 bile canaliculi (capillaries), the walls of which are formed by membranes

two or more adjacent hepatocytes. The formation of bile begins with the secretion of water, bilirubin, bile acids, cholesterol, phospholipids, electrolytes and other components by hepatocytes. The secreting apparatus of the hepatocyte is represented by lysosomes, lamellar complex, microvilli and bile canaliculi. Secretion occurs in the microvilli zone. Bilirubin, bile acids, cholesterol and phospholipids, mainly lecithin, are secreted in the form of a specific macromolecular complex - bile micelle. The ratio of these four main components, which is fairly constant under normal conditions, ensures the solubility of the complex. In addition, the low solubility of cholesterol increases significantly in the presence of bile salts and lecithin.

The physiological role of bile is associated mainly with the digestive process. The most important for digestion are bile acids, which stimulate pancreatic secretion 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 capable of binding pepsin. Foreign substances are also excreted with bile.

Rice. 10-32. Secretion of bile.

Hepatocytes secrete electrolytes and water into the bile canaliculi. Additionally, hepatocytes secrete primary bile salts, which they synthesize from cholesterol, as well as secondary bile salts and primary bile salts, which they take up from the sinusoids (enterohepatic recirculation). The secretion of bile acids is accompanied by additional secretion of water. Bilirubin, steroid hormones, foreign substances and other substances bind to glutathione or glucuronic acid to increase their solubility in water, and in such a conjugated form are released into bile

Synthesis of bile salts in the liver

Liver bile contains bile salts, cholesterol, phospholipids (primarily phosphatidylcholine = lecithin), steroids, as well as waste 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 value of bile is neutral or slightly alkaline.

Bile salts are cholesterol metabolites. Bile salts are taken up 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 canaliculi. 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. During lipid reabsorption, bile salts are released again, reabsorbed in the terminal ileum and thus return to the liver: the gastrohepatic 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 movements 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 comes from fluids secreted by the epithelial cells of the bile duct.

Most common bile salts- salt cholic, chenode(h)oxycholic, de(h)oxycholic and lithocholic bile acids. They are taken up by liver cells from sinusoidal blood via the NTCP transporter (Na+ cotransport) and the OATP transporter (Na+ independent transport; OATP = O organic A nion -T transporting P olypeptide) and in hepatocytes form a conjugate with an amino acid, glycine or taurine(Fig. 10-33). Conjugation polarizes the molecule on 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 perform the function 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 (the 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 chyme coming from the stomach and at pH = 4-5 - after the chyme is mixed with pancreatic juice. This is possible due to 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 material, form bile salts, primarily chenodeoxycholate and cholate. Each of these (primary) bile salts can conjugate to an amino acid, most notably 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 part of the figure).Of the six different conjugated bile salts, both cholate conjugates are shown on the right with their complete formulas.The conjugated bile salts are partially deconjugated by bacteria in the lower small intestine and then dehydroxylated at the C-atom, thus from the primary bile salts chenodeoxycholate and 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 again form conjugates so that after secretion with bile they again take part in the reabsorption of fats

Enterohepatic circulation of bile salts

To digest and reabsorb 100 g of fat you need about 20 g bile salts. However, the total amount of bile salts in the body rarely exceeds 5 g, and only 0.5 g are synthesized anew 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 secreted with bile are reabsorbed again through the mechanism of secondary active transport together with Na + (cotransport), enters the blood of the portal vein and returns to the liver: enterohepatic recirculation(Fig. 10-34). On average, this cycle is repeated for one molecule of bile salt 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 are decarboxylated, in the case of primary bile salts (formation secondary bile salts; see fig. 10-33). In patients who have had their ileum surgically removed or who suffer from chronic intestinal inflammation Morbus Crohn Most of the bile salts are lost in the feces, so the digestion and absorption of fats is impaired. Steatorrhea(fat stool) and malabsorption are the consequences of such violations.

Interestingly, the small percentage of bile salts that enter the large intestine plays an important physiological role: bile salts interact with the lipids of 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. Enterohepatic 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 digesting normal food, the pool of bile salts circulates between the liver and intestines 2 times a day; with fat-rich foods, circulation occurs 5 times or even more often. Therefore, the figures in the figure give only an approximate idea

Bile pigments

Bilirubin formed mainly during the breakdown of hemoglobin. After the destruction of aged red blood cells by macrophages of the reticuloendothelial system, the heme ring is split off from hemoglobin, and after the destruction of the ring, hemoglobin is converted first into biliverdin and then into bilirubin. Bilirubin, due to its hydrophobicity, is transported by blood plasma in a state bound to albumin. From blood plasma, bilirubin is taken up by liver cells and binds to intracellular proteins. Bilirubin then forms conjugates with the participation of the enzyme glucuronyltransferase, turning into water-soluble mono- and diglucuronides. Mono- and diglucuronides are released into the bile canaliculus via a transporter (MRP2 = sMOAT), the operation of which requires ATP energy.

If the content of poorly soluble, unconjugated bilirubin increases in the bile (usually 1-2% micellar “solution”), 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 the 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. This increase in bilirubin concentration 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 in

blood plasma concentration of unconjugated (“indirect”) bilirubin: hemolytic jaundice.(2) A defect in the glucuronyl transferase enzyme also leads to an increase in the amount of unconjugated bilirubin in the blood plasma: hepatocellular (hepatic) jaundice.(3) Posthepatitis jaundice occurs when there is a blockage in the bile ducts. This can occur both 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 extruded along with conjugated bilirubin from the bile canaliculi through desmosomes into the extracellular space, which is connected to the hepatic sinus and thus to the hepatic 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 into urobilinogen and stercobilinogen (both colorless). They oxidize to (colored, yellow-orange) end products urobilin And stercobilin, respectively. A small part of these substances enters the blood of the circulatory system (primarily urobilinogen) and, after glomerular filtration in the kidney, ends up in the urine, giving it a characteristic yellowish color. At the same time, the end products remaining in the feces, urobilin and stercobilin, color it brown. When quickly passing through the intestines, unchanged bilirubin turns the stool yellowish. When neither bilirubin nor its breakdown products are found in the stool, as in the case of holostasis or blockage of the bile duct, the consequence of this is the gray color of the stool.

Rice. 10-35. Removal of bilirubin.

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

The wall of the small intestine is composed of mucous membrane, submucosa, muscular and serous membranes.

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

The mucous membrane of the small intestine consists of a single-layer prismatic bordered epithelium of the own layer of the mucous membrane and the muscular layer of the mucous membrane.

The epithelial layer of the small intestine contains four 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.

The small intestine includes three sections: duodenum, jejunum and ileum.

In the small intestine, all types of nutrients are chemically processed - proteins, fats and carbohydrates.

Enzymes of pancreatic juice (trypsin, chymotrypsin, collagenase, elastase, carboxylase) and intestinal juice (aminopeptidase, leucine aminopeptidase, alanine aminopeptidase, tripeptidase, dipeptidase, enterokinase) are involved in the digestion of proteins.

Enterokinase is produced by cells of the intestinal mucosa in an inactive form (kinazogen) and ensures the conversion of the inactive enzyme trypsinogen into active trypsin. Peptidases provide further sequential hydrolysis of peptides, which began in the stomach, to free amino acids, which are absorbed by intestinal epithelial cells and enter the blood.

In the small intestine, the process of absorption of the breakdown products of proteins, fats and carbohydrates into the blood and lymphatic vessels occurs. In addition, the intestine performs a mechanical function: it pushes chyme in the caudal direction. This function is carried out due to peristaltic contractions of the muscular lining of the intestine. The endocrine function performed by special secretory cells is the production of biologically active substances - serotonin, histamine, motilin, secretin, enteroglucagon, cholecystokinin, pancreozymin, gastrin and gastrin inhibitor.

Intestinal juice is a cloudy, viscous liquid, a product of the activity of the entire mucous membrane of the small intestine, has a complex composition and different origins. A person secretes up to 2.5 liters of intestinal juice per day. (Potyrev S.S.)

The crypts of the mucous membrane of the upper part of the duodenum contain duodenal, or Brunner's, glands. The cells of these glands contain secretory granules of mucin and zymogen. The structure and function of Brunner's glands are similar to the pyloric glands. The juice of Brunner's glands is a thick, colorless liquid of a slightly alkaline reaction, which has little proteolytic, amylolytic and lipolytic activity. Intestinal crypts, or Lieberkühn's glands, are located in the mucous membrane of the duodenum and the entire small intestine and surround each villi.

Many epithelial cells of the crypts of the small intestine have secretory ability. Mature intestinal epithelial cells develop from undifferentiated borderless enterocytes, which predominate in the crypts. These cells have proliferative activity and replenish intestinal cells that are desquamated from the tips of the villi. As they move toward the apex, the borderless enterocytes differentiate into absorptive villous cells and goblet cells.

Intestinal epithelial cells with striated borders, or absorptive cells, cover the villus. Their apical surface is formed by microvilli with outgrowths of the cell membrane, thin filaments that form the glycocalyx, and also contains many intestinal enzymes translocated from the cell where they were synthesized. Lysosomes located in the apical part of cells are also rich in enzymes.

Goblet cells are called unicellular glands. The cell overflowing with mucus has the characteristic appearance of a glass. Mucus secretion occurs through breaks in the apical plasma membrane. The secretion has enzymatic, including proteolytic, activity. (Potyrev S.S.)

Enterocytes with acidophilic granules, or Paneth cells, in a mature state also have morphological signs of secretion. Their granules are heterogeneous and are released into the lumen of the crypts according to the type of merocrine and apocrine secretion. The secretion contains hydrolytic enzymes. The crypts also contain argentaffin cells that perform endocrine functions.

Even in the cavity of the small intestinal loop, isolated from the rest of the intestine, the contents are the product of many processes (including desquamation of enterocytes) and two-way transport of high- and low-molecular substances. This, in fact, is intestinal juice.

Properties and composition of intestinal juice. During centrifugation, intestinal juice is divided into liquid and dense parts. The ratio between them varies depending on the strength and type of irritation of the mucous membrane of the small intestine.

The liquid part of the juice is formed by secretions, solutions of inorganic and organic substances transported from the blood, and partly by the contents of destroyed intestinal epithelial cells. The liquid part of the juice contains about 20 g/l of dry matter. Inorganic substances (about 10 g/l) include chlorides, bicarbonates and phosphates of sodium, potassium, and calcium. The pH of the juice is 7.2-7.5, with increased secretion it reaches 8.6. The organic substances of the liquid part of the juice are represented by mucus, proteins, amino acids, urea and other metabolic products.

The dense part of the juice is a yellowish-gray mass that looks like mucous lumps and includes undestroyed epithelial cells, their fragments and mucus - the secretion of goblet cells has a higher enzymatic activity than the liquid part of the juice (G.K. Shlygin).

In the mucous membrane of the small intestine, a continuous change in the layer of surface epithelial cells occurs. They are formed in the crypts, then move along the villi and are exfoliated from their tips (morphokinetic, or morphonecrotic, secretion). Complete renewal of these cells in humans occurs in 1-4-6 days. Such a high rate of formation and rejection of cells ensures a fairly large number of them in the intestinal juice (about 250 g of epithelial cells are rejected per day in a person).

Mucus forms a protective layer that prevents excessive mechanical and chemical effects of chyme on the intestinal mucosa. The activity of digestive enzymes is high in mucus.

The dense part of the juice has significantly greater enzymatic activity than the liquid part. The bulk of enzymes are synthesized in the intestinal mucosa, but some of them are transported from the blood. Intestinal juice contains more than 20 different enzymes that take part in digestion.

The main part of intestinal enzymes takes part in parietal digestion. Carbohydrates are hydrolyzed by b-glucosidases, b-galactasidase (lactase), glucoamylase (g-amylase). β-glucosidases include maltase and trehalase. Maltase hydrolyzes maltose, and trehalase hydrolyzes trehalose into 2 glucose molecules. b-Glucosidases are represented by another group of disaccharidases, which includes 2-3 enzymes with isomaltase activity and invertase, or sucrase; with their participation, monosaccharides are formed. (Briefly T.F.)

The high substrate specificity of intestinal disaccharidases when they are deficient causes intolerance to the corresponding disaccharide. Genetically fixed and acquired lactase, trehalase, sucrase and combined deficiencies are known. A significant population of people, especially the peoples of Asia and Africa, have been diagnosed with lactase deficiency.

In the small intestine, the hydrolysis of peptides continues and is completed. Aminopeptidases constitute the bulk of enterocyte brush border peptidase activity and cleave the peptide bond between two specific amino acids. Aminopeptidases complete membrane hydrolysis of peptides, resulting in the formation of amino acids - the main absorbable monomers.

Intestinal juice has lipolytic activity. Intestinal monoglyceride lipase is of particular importance in the parietal hydrolysis of lipids. It hydrolyzes monoglycerides of any hydrocarbon chain length, as well as short-chain di- and triglycerides, and to a lesser extent medium-chain triglycerides and cholesteryl esters. (Potyrev S.S.)

A number of food products contain nucleoproteins. Their initial hydrolysis is carried out by proteases, then the RNA and DNA cleaved from the protein part are hydrolyzed by RNA and DNases, respectively, to oligonucleotides, which, with the participation of nucleases and esterases, are degraded to nucleotides. The latter are attacked by alkaline phosphatases and more specific nucleotidases, releasing nucleosides that are then absorbed. The phosphatase activity of intestinal juice is very high.

The enzyme spectrum of the mucous membrane of the small intestine and its juice changes under the influence of certain long-term diets.

Regulation of intestinal secretion. Food intake, local mechanical and chemical irritation of the intestine increase the secretion of its glands using cholinergic and peptidergic mechanisms.

In the regulation of intestinal secretion, local mechanisms play a leading role. Mechanical irritation of the mucous membrane of the small intestine causes an increase in the secretion of the liquid part of the juice. Chemical stimulators of secretion of the small intestine are products of the digestion of proteins, fats, pancreatic juice, hydrochloric and other acids. Local exposure to nutrient digestion products causes the release of intestinal juice rich in enzymes. (Briefly T.F.)

The act of eating does not significantly affect intestinal secretion, at the same time, there is evidence of the inhibitory effects on it of irritation of the antrum of the stomach, the modulating effects of the central nervous system, the stimulating effect on the secretion of cholinomimetic substances and the inhibitory effect of anticholinergic and sympathomimetic substances. Stimulates intestinal secretion of GIP, VIP, motilin, inhibits somatostatin. The hormones enterocrinin and duocrinin, produced in the mucous membrane of the small intestine, stimulate the secretion of intestinal crypts (Lieberkühn's glands) and duodenal (Brunner's) glands, respectively. These hormones are not isolated in purified form.

The small intestine consists of 3 parts: 1) duodenum (intestinum duodenum), 2) jejunum (Intestinum jejunum) and 3) ileum (intestinum lleum). The wall of the small intestine consists of 4 membranes: 1) mucosa, including a layer of epithelium, the lamina propria and the muscular plate; 2) submucosa; 3) the muscular layer, consisting of the inner circular and outer longitudinal layers of smooth myocytes. and 4) serious. SOURCES OF DEVELOPMENT of epithelium - intestinal endoderm, loose connective and smooth muscle tissue - mesenchyme, mesothelium of the serous membrane - visceral layer of the splanchnotome.

RELIEF (SURFACE) of the mucous membrane is represented by folds, villi and crypts (simple tubular glands). Folds of the mucous membrane are formed by the mucosa and submucosa, have a circular direction and are called semilunar (plica semilunalls), or circular (plica circularls). VILLI (Villi Intestinalls) are protrusions of the mucous membrane, which include loose connective tissue of the lamina propria, smooth myocytes of the muscular plate and single-layer prismatic (intestinal) epithelium covering the villi. The villi also include an arteriole, which branches into capillaries, a venule and a lymphatic capillary. The height of the villi in the duodenum is 0.3-0.5 mm; jejunum and ileum - up to 1.5 mm. The thickness of the villi in the duodenum is greater than that of the jejunum or ileum. There are up to 40 villi per 1 sq.mm in the duodenum, and no more than 30 in the jejunum and ileum.

The epithelium covering the villi is called columnar (epthelium colmnarae). It consists of 4 types of cells: 1) columnar epithelial cells with a striated border (epitheliocytus columnar is cum limbus striatus); 2) M-cells (cells with microfolds): 3) goblet exocrinocytes (exocrinocyts caliciformis) and 4) endocrine, or basal granular cells (endocrinocytus). Columnar epithelial cells with a striated border are so called because there are microvilli on their apical surface. The average height of microvilli is about 1 µm, the diameter is 0.01 µm, the distance between microvilli is from 0.01 to 0.02 µm. Between the microvilli there is a highly active alkaline phosphatase, nucleoside diphosphatase, L-glycosidase, O-glycosidase, aminopeptidase. Microvilli contains microtubules and actin filaments. Thanks to these ultrastructures, microvilli carry out movement and suction. The surface of microvilli is covered with glycocalyx. Digestion in the striated border is called parietal. The cytoplasm of columnar epithelial cells has a well-developed ER, Golgi complex, mitochondria, lysosomes and multivesicular bodies (a vesicle or vesicle containing smaller vesicles) and microfilaments, which form the cortical layer in the apical part. The nucleus is oval-shaped, active, located closer to the basal part. On the lateral surface of columnar epithelial cells in the apical part of the cells there are intercellular connections: 1) tight insulating junctions (zonula occludens) and 2) adhesive bands (zonula adherens), which close the intercellular gaps. Closer to the basal part of the cells, there are desmosomes and interdigitations between them. The lateral surface of the cell cytolemma contains Na-ATPase and K-ATPase. which are involved in the transport of Na and K through the cytolemma. The functions of columnar epithelial cells with a striated border: 1) produce digestive enzymes involved in parietal digestion, 2) participation in parietal digestion and 3) absorption of cleavage products. M-CELLS are located in those places of the intestine where there are lymph nodes in the lamina propria of the mucous membrane. These cells belong to a type of columnar epithelial cells and have a flattened shape. There are few microvilli on the apical surface of these cells, but the cytolemma here forms microfolds. With the help of these microfolds, M cells capture macromolecules (antigens) from the intestinal lumen, endocytic vesicles are formed here, which then enter the lamina propria of the mucous membrane through the basal and lateral plasmalemma, come into contact with lymphocytes and stimulate them to differentiate. GOBLET EXOCRINODITES are mucous cells (mucocytes), have a synthetic apparatus (smooth ER, Golgi complex, mitochondria), a flattened inactive nucleus is located closer to the basal part. A mucous secretion is synthesized on the smooth ER, the granules of which accumulate in the apical part of the cell. As a result of the accumulation of secretion granules, the apical part expands and the cell takes on the shape of a glass. After secretion is released from the apical part, the cell again acquires a prismatic shape.

ENDOCRINE (ENTEROCHROPHILOUS) CELLS are represented by 7 varieties. These cells are contained not only on the surface of the villi, but also in the crypts. Crypts are tubular depressions located in the lamina propria of the mucous membrane. In fact, these are simple tubular glands. Their length does not exceed 0.5 mm. The crypts include 5 types of epithelial cells; 1) columnar epithelial cells (enterocytes), differ from the same cells of the villi by a thinner striated border: 2) goblet ecocrinocytes are the same as in the villi:

3.) epithelial cells without a striated border are undifferentiated cells, due to which the epithelium of the crypts and villi occurs every 5-6 days; 4) cells with acidophilic granules (Paneth cells) and 5) endocrine cells. CELLS WITH ACIDOPHILIC GRANULARITY are located singly or in groups in the area of ​​the body and bottom of the crypts. These cells have a well-developed Golgi complex, granular ER, and mitochondria. located around a round core. In the apical part of the cells there are acidophilic granules containing a protein-carbohydrate complex. Acidophilia of granules is explained by the presence of the alkaline protein arginine in them. The cytoplasm of cells with acidophilic granularity (Paneth cells) contains zinc and enzymes: acid phosphate, dehydrogenases and dipephydases, which break down dipeptides into amino acids, in addition there is lysozyme, which kills bacteria. Functions of Paneth cells; cleavage of dipetidases to amino acids. antibacterial and HC1 neutralization. CRYPTS AND VILLI of the small intestine represent a single complex due to: 1) anatomical proximity (crypts open between the villi); 2) crypt cells produce enzymes involved in parietal digestion and 3) due to undifferentiated crypt cells, crypt cells and villi are renewed every 5-6 days. ENDOCRINE CELLS of villi and creep of the small intestine are represented by 1) EU cells that produce serotonin, motilin and substance P; 2) A-cells that secrete enteroglucagon, which breaks down glycogen into simple sugars; 3) S-cells that produce secretin, which stimulates the secretion of pancreatic juice; 4) 1-cells secreting cholecystokinin. stimulating liver function, and pancreozymin. activating the function of the pancreas; 5) G cells. producing gastrin; 0) D-cells secreting somatostatin; 7) D1 cells that produce VIL (vasoactive intestinal peptide). The lamina propria of the mucous membrane is represented by loose connective tissue, which contains many reticular fibers and reticular-like cells. In addition, in the lamina propria there are single lymph nodes (nodull lymphatlcl solita-rl), the diameter of which reaches 3 mm. and grouped lymph nodes (nodull lyinphatlcl aggregati), the width of which is 1 cm and the length is up to 12 cm. Most single lymph nodes (up to 15,000) and grouped lymph nodes C up to 100) are observed in children from 3 to 13 years, then their number begins to decrease. Functions of lymph nodes: hematopoietic and protective.

THE MUSCULAR PLATE of the mucous membrane of the small intestine consists of 2 layers of smooth myocytes: internal circular and external longitudinal. Between these layers there is a layer of loose connective tissue. THE SUBMUCOUS BASE consists of loose connective tissue, which contains all the plexuses: nervous, arterial, venous and lymphatic. In the submucosa of the duodenum there are complex branched tubular glands (giandulae submucosae). The terminal sections of these glands are lined mainly with mucocytes with light cytoplasm and a flattened inactive nucleus. The cytoplasm contains the Golgi complex, smooth ER and mitochondria, and in the apical part there are granules of mucous secretion. In addition, apical granular, goblet, undifferentiated and sometimes parietal cells are found in the terminal sections. The small ducts of the duodenum are lined with cubic epithelium, the larger ones, opening into the intestinal lumen, are lined with columnar bordered epithelium. The secretion of submucosal glands has an alkaline reaction and contains dipeptidases. The meaning of the secretion: breaks down dipeptides into amino acids and alkalizes the acidic contents coming from the stomach into the duodenum. The MUSCULAR TUNER of the wall of the small intestine consists of 2 layers of smooth myocytes: the inner circular and the outer longitudinal. Between these layers there is a layer of loose connective tissue in which 2 nerve plexuses are located: 1) the myenteric nerve plexus and 2) the myenteric sensory nerve plexus. Due to the local contraction of the myocytes of the inner layer, the contents of the intestine are mixed, and due to the conjugal contraction of the inner and outer layers, peristaltic waves arise, promoting the pushing of food in the caudal direction. The serosa of the small intestine consists of a connective tissue base covered with mesothelium. The duplication of the serous membrane forms the mesentery of the intestine, which is attached to the dorsal wall of the abdominal cavity. In animals whose body occupies a horizontal position, the intestine is suspended on the mesentery. Therefore, the intestines of animals always occupy the correct position, i.e. it does not rotate around the mesentery. In humans, the body is in a vertical position, so conditions are created for the intestines to rotate around the mesentery. With a significant rotation of the intestine around the mesentery, partial or complete obstruction occurs, which is accompanied by pain. In addition, the blood supply to the intestinal wall is disrupted and necrosis occurs. At the first signs of intestinal obstruction, a person needs to give the body a horizontal position so that the intestines are suspended on the mesentery. This is sometimes enough for the intestines to take the correct position and its patency to be restored without surgical intervention. BLOOD SUPPLY TO THE SMALL INTESTINE is carried out due to those arterial plexuses: 1) submucosal, located in the submucosal base; 2) intermuscular, located in the layer of connective tissue between the outer and inner muscular layers of the muscular layer and 3) mucous, located in the lamina propria of the mucous membrane. Arterioles branch from these plexuses, branching into cacillaries in all membranes and layers of the intestinal wall. Atrerioles extending from the mucous plexus penetrate each intestinal villi and branch into capillaries that flow into the villi venule. Venules carry blood to the venous plexus of the mucous membrane, and from there to the plexus of the submucosa. THE OUTFLOW OF LYMPH from the intestine begins with lymphatic capillaries located in the villi of the intestine and in all its layers and membranes. Lymphatic capillaries flow into larger lymphatic vessels. through which lymph enters a well-developed plexus of lymphatic vessels located in the submucosa. INNERVATION OF THE SMALL INTESTINE is carried out by two intermuscular plexuses: 1) the muscular-intestinal plexus and 2) the sensitive musculo-intestinal plexus. The SENSITIVE MUSCULAR-INTESTINAL nerve plexus is represented by afferent nerve fibers, which are dendrites of neurons coming from 3 sources: a) neurons of the spinal ganglia, b) sensory neurons of the intramural ganglia (type II Dogel cells) and c) sensory neurons of the vagus nerve ganglion. The musculo-intestinal nerve plexus is represented by various nerve fibers, including axons of sympathetic ganglion neurons (sympathetic nerve fibers) and ascons of efferent neurons (type II Dogel cells) located in the intramural ganglia. Efferent (sympathetic and parasympathetic) nerve fibers end with motor effectors on smooth muscle tissue and secretory ones on crypts. Thus, in the intestine there are sympathetic and parasympathetic reflex arcs, which are already well known. In the intestine there are not only three-membered, but also four-membered reflex sympathetic arcs. The first neuron of the four-member reflex arc is the neuron of the spinal ganglion, the second is the neuron of the lateral intermedius nucleus of the spinal cord, the third neuron is in the sympathetic nervous ganglion and the fourth is in the intramural ganglion. There are local reflex arcs in the small intestine. They are located in the intramural ganglia and consist of type II Dogel cells, the depdrites of which end in receptors, and the axons end in synapses on type I Dogel cells, which are the second neurons of the reflex arc. Their axons end in effector nerve endings. FUNCTIONS OF THE SMALL INTESTINE: 1) chemical processing of food; 2) suction; 3) mechanical (motor); 4) endocrine. CHEMICAL PROCESSING OF FOOD is carried out due to 1) intracavitary digestion; 2) parietal digestion and 3) near-membrane digestion. Intracavitary digestion is carried out due to the enzymes of pancreatic juice entering the duodenum. Intracavitary digestion ensures the breakdown of complex proteins into simpler ones. Parietal digestion occurs on the surface of the villi due to enzymes produced in the crypts. These enzymes break down simple proteins into amino acids. Premembrane digestion occurs on the surface of epithelial mucous membranes due to intracavitary enzymes and enzymes produced in the crypts. What are epithelial mucous membranes 7 The epithelium of the villi and crypts of the small intestine is renewed every 5 days. The rejected epithelial cells of the crypts and villi are the mucous epithelial deposits.

PROTEINS are broken down in the small intestine using trypsin, kinasegen, and erypsin. THE DISSOLUTION OF NUCLEIC ACIDS occurs under the influence of nuclease. THE BREAKDOWN OF CARBOHYDRATES is carried out using amylase, maltava, sucrose, lactase, and glucosidases. LIPIDS are broken down by lipases. The absorptive function of the small intestine is carried out through the striated border of columnar epithelial cells covering the villi. These villi constantly contract and relax. At the height of digestion, these contractions are repeated 4-6 times per minute. Contractions of the villi are carried out by smooth myocytes located in the stroma of the villi. Myocytes are located radially and obliquely in relation to the longitudinal axis of the villi. The ends of these myocytes are braided with reticular fibers. The peripheral ends of the reticular fibers are woven into the basement membrane of the villous epithelium, the central ends into the stroma surrounding the vessels located inside the villi. With the contraction of smooth myocytes, there is a decrease in the volume of the stroma located between the vessels and the epithelium of the villi, and a decrease in the volume of the villi themselves. The diameter of the vessels around which the stroma layer becomes thinner does not decrease. Changes in the villi during their contraction create conditions for the entry of breakdown products into the blood and lymphatic capillaries of the villi. At the moment when smooth myocytes relax, the volume of the villi increases, intravillous pressure decreases, which has a beneficial effect on the absorption of breakdown products into the stroma of the villi. Thus, it seems that the villi are increasing in size. then decreasing, they act like an eye dropper; when you squeeze the rubber cap of the pipette, its contents are released, and when you relax, the next portion of the substance is sucked in. In 1 minute, about 40 ml of nutrients are absorbed in the intestine. ABSORPTION OF PROTEINS occurs through the brush border after they are broken down into amino acids. ABSORPTION OF LIPIDS IS CARRIED OUT IN 2 WAYS. 1. On the surface of the striated border, with the help of lipase, lipids are broken down into glycerol and fatty acids. Glycerol is absorbed into the cytoplasm of epithelial cells. Fatty acids undergo esterification, i.e. with the help of cholinesterol and cholinesterase, they are converted into fatty acid esters, which are absorbed into the cytoplasm of columnar epithelial cells through the striated border. In the cytoplasm, esters decompose to release fatty acids, which are combined with glycerol with the help of kinasegen. As a result, lipid droplets with a diameter of up to 1 micron, called chylomicrons, are formed. Chylomicrons then enter the stroma of the villi, then into the lymphatic capillaries. 2nd PATH of lipid absorption is carried out as follows. On the surface of the striated border, lipids are emulsified and combined with protein, resulting in the formation of droplets (chylomicrons), which enter the cytoplasm of the cells and intercellular spaces, then into the stroma of the villi and the lymphatic capillary. The MECHANICAL FUNCTION of the small intestine is to mix and push the chyme in a caudal direction. The ENDOCRINE function of the small intestine is carried out due to the secretory activity of endocrine cells located in the epithelium of the villi and crypts.

Columnar epithelial cells- the most numerous cells of the intestinal epithelium, performing the main absorption function of the intestine. These cells make up about 90% of the total number of intestinal epithelial cells. A characteristic feature of their differentiation is the formation of a brush border of densely located microvilli on the apical surface of the cells. The length of microvilli is about 1 µm, the diameter is approximately 0.1 µm.

Total number of microvilli per surfaces per cell varies widely - from 500 to 3000. Microvilli are covered on the outside with glycocalyx, which adsorbs enzymes involved in parietal (contact) digestion. Due to microvilli, the active absorption surface of the intestine increases 30-40 times.

Between epithelial cells in their apical part, contacts such as adhesive bands and tight junctions are well developed. The basal parts of the cells contact the lateral surfaces of neighboring cells through interdigitations and desmosomes, and the base of the cells is attached to the basement membrane by hemidesmosomes. Thanks to the presence of this system of intercellular contacts, the intestinal epithelium performs an important barrier function, protecting the body from the penetration of microbes and foreign substances.

Goblet exocrinocytes- These are essentially unicellular mucous glands located among columnar epithelial cells. They produce carbohydrate-protein complexes - mucins, which perform a protective function and promote the movement of food in the intestines. The number of cells increases towards the distal intestine. The shape of the cells changes in different phases of the secretory cycle from prismatic to goblet. In the cytoplasm of cells, the Golgi complex and the granular endoplasmic reticulum are developed - centers for the synthesis of glycosaminoglycans and proteins.

Paneth cells, or exocrinocytes with acidophilic granules, are constantly located in the crypts (6-8 cells each) of the jejunum and ileum. Their total number is approximately 200 million. In the apical part of these cells, acidophilic secretory granules are detected. Zinc and a well-developed granular endoplasmic reticulum are also detected in the cytoplasm. The cells secrete a secret rich in the enzyme peptidase, lysozyme, etc. It is believed that the secretion of the cells neutralizes the hydrochloric acid of the intestinal contents, participates in the breakdown of dipeptides into amino acids, and has antibacterial properties.

Endocrinocytes(enterochromaffinocytes, argentaffin cells, Kulchitsky cells) - basal granular cells located at the bottom of the crypts. They are well impregnated with silver salts and have an affinity for chromium salts. Among endocrine cells, there are several types that secrete various hormones: EC cells produce melatonin, serotonin and substance P; S cells - secretin; ECL cells - enteroglucagon; I-cells - cholecystokinin; D-cells - produce somatostatin, VIP - vasoactive intestinal peptides. Endocrinocytes make up about 0.5% of the total number of intestinal epithelial cells.

These cells renew themselves much more slowly than epithelial cells. Using historadioautography methods, a very rapid renewal of the cellular composition of the intestinal epithelium was established. This occurs within 4-5 days in the duodenum and somewhat more slowly (5-6 days) in the ileum.

lamina propria of the mucous membrane The small intestine consists of loose fibrous connective tissue, which contains macrophages, plasma cells and lymphocytes. There are also both single (solitary) lymph nodes and larger accumulations of lymphoid tissue - aggregates, or group lymph nodes (Peyer's patches). The epithelium covering the latter has a number of structural features. It contains epithelial cells with microfolds on the apical surface (M-cells). They form endocytotic vesicles with antigen and exocytosis transfer it into the intercellular space where lymphocytes are located.

Subsequent development and plasma cell formation, their production of immunoglobulins neutralizes antigens and microorganisms in the intestinal contents. The muscular plate of the mucous membrane is represented by smooth muscle tissue.

In the submucosa base of the duodenum There are duodenal (Brunner's) glands. These are complex branched tubular mucous glands. The main type of cells in the epithelium of these glands are mucous glandulocytes. The excretory ducts of these glands are lined with border cells. In addition, Paneth cells, goblet exocrinocytes and endocrinocytes are found in the epithelium of the duodenal glands. The secretion of these glands is involved in the breakdown of carbohydrates and neutralization of hydrochloric acid coming from the stomach, mechanical protection of the epithelium.

Muscular lining of the small intestine consists of inner (circular) and outer (longitudinal) layers of smooth muscle tissue. In the duodenum, the muscular layer is thin and, due to the vertical position of the intestine, practically does not participate in peristalsis and the movement of chyme. On the outside, the small intestine is covered with a serous membrane.