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Small intestine

The small intestine ensures the final digestion of food, the absorption of all nutrients, as well as the mechanical movement of food towards the large intestine and some evacuation function. The small intestine has several sections. The structure of these departments is the same, but there are some differences. The relief of the mucous membrane forms circular folds, intestinal villi and intestinal crypts. Folds are formed by the mucous membrane and submucosa. Villi are finger-shaped outgrowths of the lamina propria, covered with epithelium on top. Crypts are depressions of the epithelium in the lamina propria of the mucous membrane. The epithelium lining the small intestine is single-layer prismatic. In this epithelium there are:

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

The villi are mainly covered by columnar epithelium. These are the main cells that support the digestion process. On their apical surface there are microvilli, which significantly increase the surface area, and contain enzymes on their membranes. It is the columnar enterocytes that provide parietal digestion and absorb broken down nutrients. Goblet cells are scattered between columnar cells. These cells are shaped like a glass. Their cytoplasm is filled with mucous secretion. Found in small quantities on the villi M cells- a type of columnar enterocyte. There are few microvilli on its apical surface, and the plasmalemma forms deep folds. These cells produce antigens and transfer them to lymphocytes. Under the villous epithelium there is loose connective tissue with single smooth muscle cells and well-developed plexuses. The capillaries in the villi are fenestrated, which ensures easier absorption. The crypts are essentially the intestinal glands. At the bottom of the crypts lie poorly differentiated cells. Their division ensures the regeneration of the epithelium of the crypts and villi. The higher to the surface, the more differentiated the crypt cells will be. Goblet cells, M cells and Paneth cells are involved in the formation of intestinal juice, as they contain granules secreted into the intestinal lumen. The granules contain dipeptidases and lysozyme. The crypts contain endocrine cells:

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

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

1. Inner circular layer
2. Outer longitudinal layer

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

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), 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.

Enzymes of the pancreas and intestinal juice also participate in the digestion of carbohydrates: β- amylase, amylo-1,6-glucosidase, oligo-1,6-glucosidase, maltase (α-glucosidase), lactase, which break down polysaccharides and disaccharides into simple sugars (monosaccharides) - glucose, fructose, galactose, absorbed by intestinal epithelial cells and entering the blood.

Digestion of fats is carried out by pancreatic lipases, which break down triglycerides, and intestinal lipase, which ensures the hydrolytic breakdown of monoglycerides. The products of fat breakdown in the intestine are fatty acids, glycerol, and monoglycerides, which enter the blood vessels and, for the most part, lymphatic capillaries.

A process occurs in the small intestine suction products of the breakdown of proteins, fats and carbohydrates into blood and lymphatic vessels. 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.

Development. The small intestine begins to develop in the 5th week of embryogenesis. The epithelium of the villi, crypts and duodenal glands of the small intestine are formed from the intestinal endoderm. At the first stages of differentiation, the epithelium is single-row cubic, then it becomes double-row prismatic, and finally, at the 7-8th week, a single-layer prismatic epithelium is formed. At 8-10 weeks of development, villi and crypts appear. During the 20-24th week, circular folds form. By this time, duodenal glands also appear. Intestinal epithelial cells in a 4-week embryo are not differentiated and are characterized by high proliferative activity. Differentiation of epithelial cells begins at 6-12 weeks of development. Columnar (bordered) epithelial cells appear, which are characterized by intensive development of microvilli, increasing the resorption surface. The glycocalyx begins to form towards the end of the embryonic - beginning of the fetal period. At this time, ultrastructural signs of resorption are observed in epithelial cells - a large number of vesicles, lysosomes, multivesicular and meconium bodies. Goblet exocrinocytes differentiate at the 5th week of development, endocrinocytes at the 6th week. At this time, transitional cells with undifferentiated granules predominate among endocrinocytes, EC cells, G cells and S cells are detected. In the fetal period, EC cells predominate, most of which do not communicate with the crypt lumen (“closed” type); in the later fetal period, an “open” cell type appears. Exocrinocytes with acidophilic granules are poorly differentiated in human embryos and fetuses. The lamina propria and submucosa of the small intestine are formed from mesenchyme at the 7-8th week of embryogenesis. Smooth muscle tissue in the wall of the small intestine develops from mesenchyme non-simultaneously in different parts of the intestinal wall: at 7-8 weeks the internal circular layer of the muscular layer appears, then at 8-9 weeks - the outer longitudinal layer, and finally at 24 - In the 28th week of fetal development, a muscular plate of the mucous membrane appears. The serous membrane of the small intestine is formed in the 5th week of embryogenesis from the mesenchyme (its connective tissue part) and the visceral layer of mesoderm (its mesothelium).

Structure. 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.

Circular folds (plicae circulares) are formed by the mucous membrane and submucosa.

Intestinal villi (villi intestinales) are finger- or leaf-shaped protrusions of the mucous membrane, freely protruding into the lumen of the small intestine.

The shape of the villi in newborns and in the early postnatal period is finger-shaped, and in adults it is flattened - leaf-shaped. Flattened villi have two surfaces - cranial and caudal and two edges (ridges).

The number of villi in the small intestine is very large. Most of them are in the duodenum and jejunum (22-40 villi per 1 mm2), slightly less in the ileum (18-31 villi per 1 mm2). The villi are wide and short (their height is 0.2-0.5 mm), in the jejunum and ileum they are somewhat thinner, but higher (up to 0.5-1.5 mm). The formation of each villi involves the structural elements of all layers of the mucous membrane.

Intestinal crypts(glands of Lieberkühn) ( cryptae seu glandulae intestinales) are depressions of the epithelium in the form of numerous tubes lying in the lamina propria of the mucous membrane. Their mouths open into the gap between the villi. There are up to 100 crypts per 1 mm2 of intestinal surface, and in total there are more than 150 million crypts in the small intestine. Each crypt has a length of about 0.25-0.5 mm, a diameter of up to 0.07 mm. The total area of ​​crypts in the small intestine is about 14 m2.

Mucous membrane small intestine consists of single-layer prismatic bordered epithelium (epithelium simplex columnarum limbatum), own layer of mucous membrane ( lamina propria mucosae) and the muscular layer of the mucous membrane ( lamina muscularis mucosae).

The epithelial layer of the small intestine contains four main cell populations:

• columnar epithelial cells ( epitheliocyti columnares),
• goblet exocrinocytes ( exocrinocyti calciformes),
• Paneth cells, or exocrinocytes with acidophilic granules ( exocrinocyticum granulis acidophilis),
• endocrinocytes ( endocrinocyti), or K-cells (Kulchitsky cells),
• as well as M-cells (with microfolds), which are a modification of columnar epithelial cells.

The source of the development of these populations are stem cells located at the bottom of the crypts, from which committed progenitor cells are first formed, which divide by mitosis and differentiate into a specific type of epithelial cell. Precursor cells are also located in the crypts, and during the process of differentiation they move towards the apex of the villus, where differentiated cells that are unable to divide are located. Here they complete their life cycle and desquamate. The entire renewal cycle of epithelial cells in humans is 5…6 days.

Thus, the epithelium of crypts and villi represents a single system in which several can be distinguished cell compartments, are at various stages of differentiation, and each compartment consists of about 7...10 layers of cells. All cells of the intestinal crypt represent one clone, i.e. are descendants of a single stem cell. The first compartment is represented by 1...5 rows of cells in the basal part of the crypts - committed progenitor cells of all four types of cells - columnar, goblet, Paneth and endocrine. Paneth cells, differentiating from stem and progenitor cells, do not move, but remain at the bottom of the crypts. The remaining cells, after 3-4 divisions of precursor cells in the crypts (the dividing transit population constituting the 5-15th rows of cells) move to the villus, where they form a transit non-dividing population and a population of differentiated cells. Physiological regeneration(renewal) of the epithelium in the crypt-villus complex is ensured by the mitotic division of precursor cells. A similar mechanism underlies reparative regeneration, and the epithelial defect is eliminated by cell proliferation.

In addition to epithelial cells, the epithelial layer may contain lymphocytes located in the intercellular spaces and then migrating into l. propria and from here to the lymphocapillaries. Lymphocytes are stimulated by antigens entering the intestine and play an important role in the immunological defense of the intestine.

The structure of the intestinal villi

On the surface, each intestinal villi is lined with single-layer prismatic epithelium. There are three main types of cells in the epithelium: columnar epithelial cells (and their variety - M-cells), goblet exocrinocytes, endocrinocytes.

Columnar epithelial cells villi ( epitheliocyti columnares villi), or enterocytes, make up the bulk of the epithelial layer covering the villus. These are prismatic cells characterized by a pronounced polarity of structure, which reflects their functional specialization - ensuring the resorption and transport of substances supplied with food.

On the apical surface of cells there is striated border (limbus striatus), formed by many microvilli. The number of microvilli per 1 µm2 of cell surface ranges from 60 to 90. The height of each microvilli in humans is about 0.9-1.25 µm, the diameter is 0.08-0.11 µm, the spaces between microvilli are 0.01-0.02 µm. Thanks to the huge number of microvilli, the absorption surface of the intestine increases 30...40 times. Microvilli contain thin filaments and microtubules. Each microvillus has a central part where a bundle of actin microfilaments is located vertically, which are connected on one side to the plasmalemma of the apex of the villus, and at the base of the villus they are connected to the terminal network - horizontally oriented microfilaments in the apical part of the cytoplasm of the enterocyte. This complex ensures the reduction of microvilli during absorption. On the surface of the microvilli there is a glycocalyx, represented by lipoproteins and glycoproteins.

In the plasma membrane and glycocalyx of the microvilli of the striated border, a high content of enzymes involved in the breakdown and transport of absorbed substances was found: phosphatases, nucleoside diphosphatases, L-, D-glycosidases, aminopeptidases, etc. The content of phosphatases in the epithelium of the small intestine exceeds their level in the liver by almost 700 times , and 3/4 of their number is in the border. It has been established that the breakdown of nutrients and their absorption occur most intensively in the area of ​​the striated border. These processes are called wall And membrane digestion in contrast to cavitary, which occurs in the lumen of the intestinal tube, and intracellular.

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.

In the apical parts of enterocytes there are connecting complexes consisting of two types of tight insulating junctions ( zonula occludens) and adhesive belts, or tapes ( zonula adherens), connecting neighboring cells and closing the communication between the intestinal lumen and intercellular spaces.

With the participation of microfilaments of the terminal network, the closure of intercellular gaps between enterocytes is ensured, which prevents the entry of various substances into them during digestion. Under the terminal reticulum in the apical part of the enterocyte there are tubes and cisterns of the smooth endoplasmic reticulum, which are involved in the absorption of fats, as well as mitochondria, which provide energy for the processes of absorption and transport of metabolites.

In the basal part of the columnar epithelial cell there is an oval-shaped nucleus, a synthetic apparatus - ribosomes and a granular endoplasmic reticulum. The Golgi apparatus is located above the nucleus, with its cisterns lying vertically relative to the surface of the enterocyte. Lysosomes and secretory vesicles that form in the Golgi apparatus move to the apical part of the cell and are localized directly under the terminal network and along the lateral plasmalemma.

Characteristically, there are wide intercellular spaces between the basal parts of enterocytes, limited by their lateral plasmalemmas. The lateral plasmalemmas have folds and processes that connect to the spines of neighboring cells. With active absorption of fluid, the folds straighten and the volume of intercellular space increases. In the basal parts of enterocytes there are thin lateral basal processes that contact similar processes of neighboring cells and lie on the basement membrane. The basal processes are connected by simple contacts and provide closure of the intercellular space between enterocytes. The presence of intercellular spaces of this type is characteristic of epithelia involved in fluid transport; in this case, the epithelium functions as a selective barrier.

In the lateral plasmalemma of the enterocyte, ion transport enzymes (Na+, K+-APTase) are localized, which play an important role in the transfer of metabolites from the apical plasmalemma to the lateral one and into the intercellular space, and then through the basement membrane into l. propria and capillaries.

Enterocytes also perform a secretory function, producing metabolites and enzymes necessary for terminal digestion (parietal and membrane). The synthesis of secretory products occurs in the granular endoplasmic reticulum, and the formation of secretory granules occurs in the Golgi apparatus, from where secretory vesicles containing glycoproteins are transported to the cell surface and localized in the apical cytoplasm under the terminal reticulum and along the lateral plasmalemma.

M cells(microfold cells) are a type of enterocyte, they are located on the surface of group lymphatic follicles (Peyer's patches) and single lymphatic follicles. They have a flattened shape, a small number of microvilli and got their name due to the presence of microfolds on their apical surface. With the help of microfolds, they are able to capture macromolecules from the intestinal lumen and form endocytic vesicles transported to the basolateral plasmalemmas and further into the intercellular space. In this way, antigens can come from the intestinal cavity that attract lymphocytes, which stimulates the intestinal lymphoid tissue.

Goblet exocrinocytes (exocrinocyti caliciformes) in the villi are located singly among the columnar cells. Their number increases in the direction from the duodenum to the ileum. In their structure, these are typical mucous cells. They experience cyclical changes associated with the accumulation and subsequent secretion of mucus. In the phase of secretion accumulation, the nuclei of these cells are pressed to their base, while drops of mucus are visible in the cytoplasm of the cells above the nucleus. The Golgi apparatus and mitochondria are located near the nucleus. The formation of the secretion occurs in the area of ​​the Golgi apparatus. During the stage of mucus accumulation in the cell, a large number of greatly altered mitochondria are found. They are large, light, with short cristae. After secretion is released, the goblet cell becomes narrow, its nucleus becomes smaller, and the cytoplasm is freed from secretion granules. The mucus secreted by goblet exocrinocytes serves to moisturize the surface of the intestinal mucosa and thereby promotes the movement of food particles, and also participates in the processes of parietal digestion. Beneath the villous epithelium is a basement membrane, followed by loose fibrous connective tissue of the lamina propria. It contains blood and lymphatic vessels and nerves oriented along the villus. The stroma of the villi always contains individual smooth muscle cells - derivatives of the muscular layer of the mucous membrane. Bundles of smooth myocytes are entwined with a network of reticular fibers that connect them to the villous stroma and basement membrane. The contraction of myocytes helps push the absorbed products of food hydrolysis into the blood and lymph of the intestinal villi. Other bundles of smooth muscle cells penetrating the submucosa form circular layers around the vessels passing there. The contraction of these muscle groups regulates blood flow.

The structure of the intestinal crypt

The epithelial lining of the intestinal crypts contains stem cells, progenitor cells of columnar epithelial cells, goblet exocrinocytes, endocrinocytes and Paneth cells (exocrinocytes with acidophilic granules) at all stages of development.

Columnar epithelial cells make up the bulk of the crypt epithelium. Compared to similar cells of the villi, they are lower, have a thinner striated border and basophilic cytoplasm. Mitotic figures are often visible in the epithelial cells of the lower half of the crypts. These elements serve as a source of regeneration for both epithelial cells of the villi and crypt cells. Goblet exocrinocytes are constantly located in the crypts; their structure is similar to those described in the villus. Exocrinocytes with acidophilic granules ( exocrinocyti cum granulis acidophilis, s Paneth), or Paneth cells, are located in groups or singly at the bottom of the crypts. In their apical part, dense granules that refract light are visible. These granules are strongly acidophilic, stain bright red with eosin, dissolve in acids, but are resistant to alkalis. Cytochemically, a protein-polysaccharide complex, enzymes (dipeptidases), lysozyme. Significant basophilia is detected in the cytoplasm of the basal part. There are a few mitochondria around the large round nucleus, and the Golgi apparatus is located above the nucleus. Acidophilia of granules is due to the presence of arginine-rich protein. Paneth cells contain a large amount of zinc, as well as enzymes - acid phosphatase, dehydrogenases and dipeptidases. The presence of a number of enzymes in these cells indicates the participation of their secretions in the digestive processes - the breakdown of dipeptides into amino acids. No less important is the antibacterial function of the secretion, associated with the production of lysozyme, which destroys the cell walls of bacteria and protozoa. Thus, Paneth cells play an important role in the regulation of the bacterial flora of the small intestine.

Endocrinocytes in the crypt there is much more than in the villi.

The most numerous are EC cells, secreting serotonin, motilin and substance P. A cells, producing enteroglucagon are few in number. S cells, producing secretin, are distributed irregularly in different parts of the intestine. In addition, found in the intestines I-cells, secreting cholecystokinin And pancreozymin- biologically active substances that have a stimulating effect on the functions of the pancreas and liver. Also discovered G cells, producing gastrin, D- and D1-cells producing active peptides (somatostatin and vasoactive intestinal peptide - VIP).

The lamina propria of the mucous membrane is characterized by the content of a large number of reticular fibers. They form a dense network throughout the lamina propria and, approaching the epithelium, participate in the formation of the basement membrane. Process cells, similar in structure to reticular cells, are closely associated with reticular fibers. Eosinophils, lymphocytes, and plasma cells are constantly found in the lamina propria. It contains the vascular and nerve plexuses.

The muscular plate of the mucous membrane consists of two layers: the inner circular and the outer (more loose) longitudinal. The thickness of both layers is about 40 microns. They also contain oblique bundles of muscle cells. From the internal circular muscle layer, individual muscle cells extend into the lamina propria of the mucous membrane.

Submucosa often contains lobules. It contains blood vessels and the submucosal nerve plexus.

Muscularis The small intestine consists of two layers: the inner - circular (more powerful) and the outer - longitudinal. The direction of movement of the muscle cell bundles in both layers is not strictly circular and longitudinal, but spiral. In the outer layer, the spiral curls are more stretched compared to the inner layer. Between the muscle layers there is a layer of loose fibrous connective tissue, in which there are nodes of the myenteric nerve plexus and blood vessels.

The function of the muscularis mucosa is to mix and push chyme along the intestines. In the small intestine, there are two types of contractions. Contractions of a local nature are caused mainly by contractions of the inner layer of the muscular layer. They are performed rhythmically - 12-13 times per minute. Other contractions - peristaltic - are caused by the action of the muscular elements of both layers and spread sequentially along the entire length of the intestine. Peristaltic contractions cease after destruction of the myenteric nerve plexus. Increased peristalsis of the small intestine occurs when the sympathetic (?) nerves are excited, weakening occurs when the vagus nerve is excited.

Small intestinal cancer is a malignant neoplasm of a cell of the intestinal tissue.

Tumors of the small intestine are rare and account for 1% of all intestinal cancers. The length of the loop-shaped small intestine reaches 4.5 m. It consists of intestines: duodenum, jejunum and ileum. In each of these components, under favorable conditions, small intestinal cancer can degenerate from a normal cell.

Malignant tumor of the small intestine

The absence of obvious specific primary symptoms forces patients to seek help from a doctor in the later stages of the disease. In this case, metastasis begins, due to which secondary intestinal cancer develops.

Metastases reach regional lymph nodes and other distant parts of the intestine, so the following cancers can develop:

Causes of small intestine cancer

Specific direct causes of small intestinal cancer have not yet been discovered. Attention is always paid to chronic enzymatic or inflammatory bowel disease; cancer symptoms can be hidden behind signs of diseases such as diverticulitis, ulcerative colitis, enteritis, Crohn's disease, duodenal ulcer. Often the tumor develops against the background of adenomatous polyps, which are prone to degeneration into oncogenic ones.

The duodenum is often affected due to the irritating effect of bile. The initial part of the small intestine is due to the juice of the pancreas and active contact with carcinogenic substances from food, fried foods, alcohol and nicotine.

The first symptoms and signs of small intestine cancer in men and women

If duodenal cancer is suspected, the first symptoms will be similar to gastric and duodenal ulcers and will manifest as aversion to food, dull pain in the epigastric zone radiating to the back. At a late stage, duodenal cancer exhibits symptoms associated with poor patency of the bile ducts and intestines due to tumor growth. The patient will suffer from endless nausea and vomiting, flatulence and manifestations of jaundice.

The jejunum and ileum signal about oncology with the first local signs and general dyspeptic disorders:

• nausea and vomiting;
• bloating;
• pain in the intestines;
• spasms in the navel and/or epigastrium;
• frequent loose stools with mucus.

It has been proven that small intestinal cancer symptoms and manifestations occur more often in men than in women. This fact is associated with the lifestyle of men, nutrition and abuse of malicious habits: alcohol, smoking and drugs. In addition, small intestinal cancer develops; signs and symptoms manifest themselves somewhat differently due to the different structure of the genitourinary system.

Very often, with breast, cervical and ovarian cancer, signs of intestinal cancer appear in women. With metastases of a tumor of the prostate gland or testicle, symptoms of intestinal cancer in men may appear. If the tumor compresses neighboring organs, this leads to the development of pancreatitis, jaundice, ascites, and intestinal ischemia.

Small intestine cancer: symptoms and manifestations

The tumor grows, so the symptoms of oncology in the small intestine intensify:

• intestinal patency is impaired;
• obvious or hidden intestinal blood loss appears;
• perforation of the intestinal wall develops;
• the contents enter the peritoneal cavity and peritonitis begins;
• intoxication (poisoning) of the body increases due to the breakdown of tumor cells, ulcers and intestinal fistulas appear;
• iron deficiency increases;
• the functions of the pancreas and liver are impaired.

Cancer does not have a gender identity, so the symptoms of bowel cancer in women and men are largely the same: increasing weakness, weight loss, malaise, anemia and rapid and unexplained fatigue, nervousness, anorexia, difficulty defecating, accompanied by pain, itching , frequent urges.

Classification of stages of small intestinal cancer. Types and Types of Small Bowel Cancer

According to histological classification, oncological formations of the small intestine are:

• adenocarcinoma- develops from glandular tissue next to the major papilla of the duodenum. The tumor is ulcerated and covered with a fleecy surface;
• carcinoid– develops in any part of the intestine, most often in the appendix. Less often - in the ileum, very rarely - in the rectum. The structure is similar to the epithelial form of cancer.
• lymphoma– rare tumor formation (18%) and combines lymphosarcoma and lymphogranulomatosis (Hodgkin’s disease);
• leiomyosarcoma– large tumor formation, more than 5 cm in diameter, can be palpated through the peritoneal wall. The tumor creates intestinal obstruction and wall perforation.

Lymphoma of the small intestine can be primary or secondary. If primary lymphoma of the small intestine is confirmed, the symptoms are characterized by the absence of hepatosplenomegaly, enlarged lymph nodes, changes on the sternum x-ray, CT scan, in the blood and bone marrow. If the tumor is large, disturbances in the absorption of food will be observed.

If the retroperitoneal and mesenteric lymph nodes spread tumor cells, then a secondary lymphoma forms in the small intestine. Types of small intestinal cancer include signet ring cell, undifferentiated and unclassified. Growth form – exophytic and endophytic.

Stages of small intestine cancer:

1. Stage 1 cancer of the small intestine – tumor within the walls of the small intestine, no metastases;
2. Stage 2 of small intestine cancer – the tumor extends beyond the intestinal wall, begins to penetrate other organs, there are no metastases;
3. Stage 3 of small intestine cancer - metastasis to the nearest lymph nodes, germination to other organs, no distant metastases;
4. small intestine cancer stage 4 – metastasis in distant organs (liver, lungs, bones, etc.).

Diagnosis of small intestine cancer

How to recognize colon cancer at an early stage? This determines what treatment will be used, the patient’s condition and the prognosis for survival.

Diagnosis of small intestine cancer is carried out using popular methods:

• X-ray examination;
• fibrogastroscopy;
• angiography of the vessels of the peritoneal cavity;
• laparoscopy;
• colonoscopy;
• CT and MRI;
• biopsy examination: determine the type of cells and the degree of their malignancy;
• electrogastroenterography: detect disturbances in small intestinal motility characteristic of cancer.

How to identify intestinal cancer, the symptoms of which do not manifest themselves in anything specific? During this period, it is very important to confirm or refute the suspicion of cancer, because the sooner treatment begins, the easier it is for the patient to endure its stages, the greater the chance of a positive result. When symptoms appear, the oncological process can be considered advanced, and the moment of early treatment will be missed.

Important! Early symptoms include a “young” state, which should alert any person - this is a reluctance to work or do household chores due to increased weakness and fatigue. The skin becomes pale and “transparent”. The patient constantly has heaviness in his stomach, he does not feel like eating at all. Following this, dyspeptic disorders appear: nausea, vomiting, pain and heartburn even from water.

When visiting a doctor, a blood test for colon cancer is immediately prescribed and examined. A general basic blood test can reveal anemia, the patient's condition, and the presence of inflammation. According to the level of ESR and hemoglobin - problems in the liver, kidneys and blood. The composition of the blood may indicate certain diseases, including cancer.

Tumor markers for small intestinal cancer are detected in the blood. The most informative and common tumor markers are alpha-fetoprotein, total PSA/free PSA, CEA, CA-15.3, CA-125, CA-19.9, CA-72.4, CYFRA-21.1, hCG and cytokeratin .

For example, using the tumor markers CA 19.9 and CEA (carcinoembryonic antigen), screening diagnostics of colon cancer is carried out. If CEA is determined, then you can find out the staging before surgery and monitor the patient diagnosed with colorectal cancer after it. If the disease progresses, then the level of CEA in the serum will increase. Although it may grow not in connection with a tumor, in later stages colorectal cancer can be detected without an increase in CEA in the blood.

Endoscopic diagnosis and open intestinal biopsy are the main methods for confirming small intestinal oncology.

Treatment of small intestine cancer

Treatment of small intestinal cancer: duodenal, jejunal and ileal intestines is carried out depending on the type of tumor and stage. The main method is bowel resection and removal of tumor formation.

With a confirmed diagnosis of small intestinal cancer, surgery reduces symptoms and increases life expectancy. If it is not possible to remove malignant tumors of the small intestine at a late stage or it is determined that the tumor is sensitive to chemotherapy, drugs that prevent the growth of cancer cells are used.

After a palliative operation (alleviating the patient's suffering), treatment is carried out with chemotherapy (polychemotherapy), but without radiation.

After the operation, intestinal motility is additionally diagnosed using electrogastroenterography to prevent the development of a dangerous complication - intestinal paresis.

To alleviate the patient's condition after surgery and chemotherapy, traditional medicine for intestinal cancer is introduced into complex therapy: alcohol tinctures, infusions and decoctions of medicinal herbs, mushrooms and berries. Appropriate nutrition for intestinal cancer prevents paresis, nausea and vomiting, and improves gastrointestinal motility.

Forecast and prevention of small intestine (bowel) cancer

Prevention of small intestinal cancer consists of timely removal of benign tumors and polyps, constant monitoring by specialists of patients with chronic inflammatory processes of the gastrointestinal tract, switching to a healthy diet and lifestyle, and giving up bad habits.

If treatment was given and bowel cancer was removed, how long do people live? If there are no regional or distant metastases, the tumor is removed, survival in the subsequent 5-year period can be 35-40%.

Conclusions! If the tumor is operable, a wide resection of a section of the intestine with lymph nodes and mesentery is performed within the boundaries of healthy tissue. To restore the integrity of the gastrointestinal tract, enteroenteroanastomosis is performed - small intestine into the small intestine or enterocoloanastomosis - small intestine into the large intestine.

For cancer of the duodenum, as part of the small duodenum, duodenectomy and sometimes distal resection of the stomach or pancreas (pancreaticoduodenectomy) are performed. In case of advanced oncology of the small intestine, a bypass anastomosis is performed between loops that remain unaffected. Surgical treatment is supplemented with chemotherapy.

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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 secretion 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.

SMALL INTESTINE EPITHELIA

Epithelium (E) of the small intestine consists of two types of epithelial cells: absorptive and goblet cells, lying on the basement membrane (BM). The absorptive and goblet cells are connected by junctional complexes (JCs) and multiple lateral interdigitations (LIs). Intercellular gaps (IC) are often formed between the basal parts. Chylomicrons (X, a class of lipoproteins formed in the small intestine during the absorption of lipids) can circulate between these gaps; Lymphocytes (L) penetrate here. Absorbing cells live about 1.5-3.0 days.

Suction cells (AC)- tall prismatic cells with an elliptical, often with invaginations, nucleus (N), located in the lower part of the cell body. The nucleoli, Golgi complex (G) and mitochondria are well developed. The granular endoplasmic reticulum often continues into the granular one. The cytoplasm contains a certain amount of lysosomes and free ribosomes.

The apical pole of the cell is polygonal in shape. Microvilli (Mv) are covered with a thick layer of glycocalyx (Gk), in some places in the figure it is partially removed. Microvilli and glycocalyx form the brush border (BBC), which increases the intestinal absorption surface to 900 m2.

Goblet cells (GC)- basophilic cells scattered among absorptive cells. In active cells, the nucleus is cup-shaped and located at the basal pole of the cell. The cytoplasm contains mitochondria, a well-developed supranuclear Golgi complex, several cisternae of the granular endoplasmic reticulum oriented parallel to each other, and many free ribosomes.

The last two structures are responsible for goblet cell basophilia. From the Golgi complex, numerous mucous droplets (MDs) surrounded by a single-layer membrane arise, filling the entire supranuclear cytoplasm and giving the cells a goblet shape. Droplets are released from cells by fusion of the surrounding membranes with the apical plasmalemma. Once mucus droplets are released, the goblet cells become invisible under a light microscope. Goblet cells are capable of replenishing the cytoplasm with mucus droplets during 2-3 secretory cycles, since their life lasts about 2-4 days.

Products goblet cells CHIC-positive and metachromatic, as it consists of glycoproteins and glycosaminoglycans; it serves to lubricate and protect the absorption cells. Networks of capillaries (Cap) and reticular fibrils (RF) belonging to the lamina propria (LP) of the mucosa are located immediately below the epithelial basement membrane (BM). Reticular fibers serve, among other things, to attach thin, vertically oriented smooth muscle cells (SMCs) to the basement membrane. Their contractions shorten the intestinal villi. At some distance from the epithelium, blind dilations of the lacteal vessels (ML) begin. Numerous openings (O) are visible between the endothelial cells, through which chylomicrons enter the lymphatic circulation. Anchoring filaments (AF) are also noted, attaching the lacteal vessels to the network of collagen fibers.

A large number of collagen (KB) and elastic (EF) fibers pass through the lamina propria of the mucous membrane. In the network of these fibrils there are lymphocytes (L), plasma cells (PC), histiocytes (H) and eosinophilic granulocytes (EG). Fibroblasts, fibrocytes (F) and some reticular cells belong to the permanent cells of the lamina propria of the mucous membrane.

ABSORPTION (ABSORPTION) OF LIPIDS IN THE SMALL INTESTINE

The function of absorptive cells is to absorb nutrients from the intestinal cavity. Since the absorption of proteins and polysaccharides is difficult to detect morphologically, we will describe lipid absorption.

Mechanism lipid absorption is divided into the enzymatic breakdown of fats into fatty acids and monoglycerides and the entry of these products into absorptive cells, where the resynthesis of new lipid droplets - chylomicrons (X) occurs. They are then released into the basal intercellular clefts, cross the basal lamina and enter the lacteal vessel (ML).

Chylomicrons are emulsified droplets of fat that have a milky color, which is why all lymphatic intestinal vessels are called lacteal.

Colon contains a mucous membrane that does not form folds, with the exception of its distal (rectal) section. There are no villi in this part of the intestine. The intestinal glands are long and characterized by a large number of goblet and border cells and a low content of enteroendocrine cells.

Limb cells- columnar, with short microvilli of irregular shape. The large intestine is well adapted to perform its main functions: absorbing water, forming fecal matter and producing mucus. Mucus is a highly hydrated gel that not only acts as a lubricant on the surface of the intestine, but also coats bacteria and various particles. Water absorption occurs passively following the active transport of sodium through the basal surfaces of epithelial cells.

Colon histology

Own plate rich in lymphoid cells and nodules, which often continue into the submucosa. Such a powerful development of lymphoid tissue (KALT) is associated with a huge population of bacteria in the colon. The muscular layer includes longitudinal and circular layers.

This shell differs from that in the small intestine, because bundles of smooth muscle cells of the outer longitudinal layer are collected into three thick longitudinal belts - intestinal ribbons (lat. teniae coli). In the intraperitoneal areas of the colon, the serous membrane contains small hanging protrusions consisting of adipose tissue - fatty appendages (lat. appendices epiploicae).

Gland in the colon. Its bordered and mucous goblet cells are visible. Please note that the goblet cells secrete a secretion and begin to fill the lumen of the gland with it. Microvilli on the border cells are involved in the process of water absorption. Staining: pararosaniline-toluidine blue.

IN anal(anal) area, the mucous membrane forms a series of longitudinal folds - rectal columns of Morgagni. Approximately 2 cm above the anus, the intestinal mucosa is replaced by stratified squamous epithelium. In this area, the lamina propria contains a plexus formed by large veins, which, when excessively dilated and varicose, give rise to hemorrhoids.

Small intestine cancer: characteristic signs and symptoms

What are the signs and symptoms when diagnosed with small bowel cancer? What is the etiology of the disease and principles of treatment?

Small bowel cancer

The small intestine consists of several sections. Depending on which of them the cancer develops, there are:

The most common type of cancer is the duodenum.

Cancer develops from various intestinal tissues and can spread to other organs. Depending on the tissue from which the tumor developed, several histological types are distinguished:

1. Lymphoma that develops from tissues rich in immune cells.
2. Sarcoma developing from smooth muscles that provide peristalsis of the small intestine.
3. Adenocarcinoma developing from mucosal cells. This is the most common form.

Different types of cancer have different etiologies and clinical manifestations, require different treatment approaches and prognoses.

Clinical manifestations

Based on the degree of development of the disease, there are several stages of cancer development, which are manifested by certain symptoms:

1. The tumor develops in the tissue area of ​​the intestinal walls. There is no spread to other organs or metastases. At this stage, most often there are no symptoms that may cause concern to the patient.
2. The tumor begins to spread to neighboring organs. There are no metastases.
3. The appearance of metastases in the nearest lymph nodes and in organs is absent.
4. The presence of metastases in distant organs.

The first symptoms of the disease appear with the development of severe narrowing of the intestine or ulceration of the tumor, which are prolonged pain in the epigastric region. This is accompanied by the following symptoms:

• weight loss;
• anemia (a drop in hemoglobin levels), which causes weakness and dizziness;
• vomiting if the tumor is localized in the upper parts of the jejunum;
• loose stools with mucus;
• signs of intestinal obstruction;
• obvious or hidden blood loss, especially often manifested in sarcoma;
• increased bilirubin levels with liver metastases;
• yellow skin color;
• sclera of the eyes.

Causes of small intestinal cancer

The exact causes of small intestinal cancer have not been identified. Based on clinical studies and statistical data, it is known that the risk of developing the disease is highest in the following cases:

• in cases of small intestinal cancer observed in direct relatives;
• in the presence of chronic inflammatory diseases of the small intestine that destroy the mucous membrane (Crohn's disease, celiac disease);
• in the presence of polyps in the intestines;
• in the presence of cancer of other organs;
• when exposed to radiation;
• when smoking, alcohol abuse, regular consumption of dried, salted, smoked foods, with a high content of animal fat (fatty meats, lard).

Small bowel cancer is more common:

• in developing countries in Asia;
• in blacks;
• among men;
• among persons over 60 years of age.

Diagnosis and treatment methods

If you notice any unpleasant symptoms, you should contact a qualified specialist as soon as possible. In the presence of cancer, early diagnosis is the most important condition for a favorable prognosis.

Research methods that allow diagnosing the presence of cancer, the degree of its development and spread:

1. FGDS (fibrogastroduodenoscopy) is a method of instrumental examination of the inner surface of the esophagus, stomach and duodenum by inserting a probe through the nasal sinuses or mouth.
2. Colonoscopy is a method of instrumental examination of the inner surface of the large intestine by inserting a probe through the anus.
3. Laparoscopy is an examination or surgical procedure in which a skin incision is made in the desired area and a miniature camera and surgical instruments are inserted into the abdominal area.
4. Ultrasound (ultrasound examination) of the abdominal organs.
5. CT (computed tomography), MRI (magnetic resonance imaging) of the small intestine.
6. Blood chemistry.
7. X-ray examination of the chest organs.
8. Bone tissue centigraphy.

When conducting instrumental examinations such as FGDS, colonoscopy, laporoscopy, a biopsy is performed (taking a tissue sample for detailed laboratory testing) to examine the tissue in detail for the presence of cancer cells and determine the type of tumor.

Surgery is the most effective treatment for small intestinal cancer. The operation consists of removing (ectomy) the tumor and affected tissues and lymph nodes. Artificial restoration of removed tissue can also be carried out in several ways:

1. Enteroanastomosis is a surgical connection between intestinal loops.
2. Enterocoloanastomosis is a surgical connection between the loops of the large and small intestines.

Resection (excision) is prescribed only by a doctor in the absence of contraindications. The type of surgical intervention depends on the stage of development of the disease and the extent of spread.

In advanced stages of cancer, when extensive resection is not possible, surgical implantation of a bypass anastomosis in a healthy area of ​​the organ is prescribed.

The earlier the stage of cancer development, the pathological tissue is removed, the more favorable the prognosis for the patient.

Conservative treatment. An addition to surgical treatment for small intestinal cancer is chemotherapy or radiation therapy. Radiation therapy involves exposing malignant cells to high-frequency radiation. Chemotherapy is the intravenous or oral administration of drugs into the body.

The listed procedures cause many side effects, including general weakness and malaise, nausea, vomiting, diarrhea, headaches, hair loss, hematopoietic disorders, weakness, diarrhea, the appearance of ulcers on the oral mucosa, and disruption of the immune system.

An important condition for the treatment of small intestinal cancer is proper nutrition, which includes compliance with the following conditions:

1. Exclusion from the diet of foods containing animal fats.
2. Inclusion in the diet of foods with sufficient fiber content, fish oil, soy, indole-3 carbinol.
3. Quitting alcohol and cigarettes.

In advanced cancer cases, when surgery is not advisable due to its ineffectiveness, radiation and chemotherapy may be prescribed. Radiation therapy may be given to relieve symptoms.

Preventive actions

With early diagnosis and treatment, a complete cure is possible. Small intestinal cancer develops over a long period of time and does not metastasize for a long time due to the fact that it is poorly supplied with blood and cancer cells do not spread so quickly throughout the body.

Even after the operation, the patient must undergo regular examination by an oncologist and undergo the necessary tests. It is also necessary to closely monitor the health status of persons at risk.

These tumors are observed in all parts of the small intestine;

14% of malignant neoplasms are sarcomas. The incidence of sarcomas does not depend on gender, with a peak incidence in the sixth to eighth decades of life. Typically, mesenchymal tumors of this location develop in younger patients than cancer, and are more common than AK and carcinoid. A common complication of mesenchymal tumors of the small intestine is intussusception. The prognosis for sarcoma depends on the mitotic index, size, depth of invasion, and the presence or absence of metastases. The 5-year life expectancy of patients is 45% (for carcinoid - 92%; for AK - 63%). With sarcoma of the small intestine, the prognosis is worse than with similar tumors of the colon, stomach, and esophagus. The macroscopic appearance, histological structure and cytological diagnostic capabilities are given in Chapter. about the stomach.

Gastrointestinal stromal tumors (GISTs) are of significant importance; leiomyoma, leiomyosarcoma, Kaposi's sarcoma, angiosarcoma rarely found in the small intestine (the histological and cytological picture is similar to tumors of the esophagus and stomach, see Chapters IV and V). Leiomyoma is most often localized intramural, large tumors bulge into the lumen, ulcerate and bleed.

Genetic features. In small, especially malignant gastrointestinal tract tumors, as in similar stomach tumors, mutations of the c-kit gene in exon 11 are detected. Using comparative genomic hybridization, deletions were identified on chromosomes 14 and 22, which is also characteristic of gastric GI tract. The fundamental criterion for the diagnosis of AK is the presence of invasion of the muscular plate of the mucous membrane, which in practice is not always easy to determine, because well-differentiated AK mimics an adenoma. On the other hand, in some adenomas, acellular mucus penetrates the intestinal wall, mimicking invasion. If the wall of the appendix contains acellular mucus, then the diagnosis of adenoma is possible only if the muscular plate is intact. Sometimes AK is so highly differentiated that it is difficult to verify it as a malignant tumor. Well-differentiated AC of the appendix grows slowly, clinically creating a picture of pseudomyxoma peritonei. Most appendiceal AKs are mucous. If there are >50% signet ring cells, the tumor is called signet ring cell. Non-mucous tumors proceed in the same way as in the colon. Metastases in the lymph nodes are observed late.

The 5-year life expectancy rate for localized AK of the appendix is ​​95%, for mucinous cystadenocarcinoma - 80%; for distant metastases of these tumors - 0% and 51%, respectively. An advanced stage, a high degree of malignancy, and a non-mucous tumor are associated with a poor prognosis for AK of the appendix. With complete removal of the tumor, an extension of life expectancy is noted.

The histological and cytological picture of AK is similar to that of similar tumors of other locations.

Pseudomyxoma peritonei represented by mucus on the surface of the peritoneum. A clear picture is due to the highly differentiated mucous membrane of the AK (Fig. 175-182), with few cells, the cellular component grows slowly, and the mucus arrives quickly. The tumor is poorly manifested on the surface of the peritoneum, while large volumes of mucus are located in the omentum, on the right under the diaphragm, in the renal space, in the ligament of Treitz, in the left parts of the colon, in the pelvic cavity. Occasionally, mucous cysts are found in the spleen. In these cases, the tumor tends to remain in the abdominal cavity for many years.

Most cases of pseudomyxoma peritonei arise from primary cancer of the appendix, but occasionally it can spread from the ovary, gallbladder, stomach, PTC, pancreas, fallopian tubes, urachus, lung, and breast. With pseudomyxoma peritonei, weight loss, a high degree of malignancy on histological examination, and morphological invasion of underlying structures are factors for an unfavorable prognosis.

In half of the cases of pseudomyxoma peritonei, loss of heterozygosity for one or two polymorphic microsatellite loci was detected, which indicates the monoclonality of the tumor. If the clinical picture is consistent, the cytological diagnosis is established reliably: “pseudomyxoma”.

Carcinoid tumor is the most common (50-75%) primary tumor of the appendix; -19% of all gastrointestinal carcinoids are localized in the appendix, mainly in its distal part; The tumor is more often diagnosed in women. Tubular carcinoid is observed at a significantly younger age than goblet cell carcinoid (mean age 29 years and 53 years, respectively). Asymptomatic lesions are often observed (a single tumor nodule is discovered accidentally in the appendectomy material). Rarely, carcinoid can cause obstruction of the lumen of the appendix, leading to appendicitis. Carcinoid syndrome occurs extremely rarely, always with metastases in the liver and retroperitoneum.

EC cell carcinoid of the appendix is ​​a clearly demarcated dense nodule, matte, grayish-white on section, the size<1 см. Опухоли >2 cm are rare, most located at the apex of the appendix. Goblet cell carcinoid and carcinoid-AC are found in any part of the appendix in the form of a diffuse infiltrate, measuring 0.5-2.5 cm.

In most cases, appendiceal carcinoid has a favorable prognosis. Tumors and metastases often grow slowly. Clinically non-functioning lesions of the appendix that do not grow into blood vessels, size<2 см, обычно излечивают полной местной эксцизией, в то время как размеры >2 cm, invasion of the mesentery of the appendix and metastases indicate aggressiveness of the lesion. Localization of the tumor at the base of the appendix involving the edge of the incision or the cecum is prognostically unfavorable and requires at least partial resection of the cecum in order to avoid residual tumor and relapse. The frequency of regional metastases of appendiceal carcinoid is 27%, distant metastases - 8.5%. The 5-year life expectancy rates for local appendiceal carcinoid are 94%, for regional metastases 85%, and for distant metastases 34%. Goblet carcinoid is more aggressive than regular carcinoid but less aggressive than appendiceal carcinoid; tubular carcinoid, on the contrary, has a favorable prognosis.

Histological picture: Most appendiceal carcinoids are EC cell enterochromatin tumors; L-cell carcinoids and mixed endocrine-exocrine cancers are rare.

The structure of the EC-cell argentaffin carcinoid of the appendix is ​​similar to the structure of a similar carcinoid of the small intestine (see above). Most tumors invade the muscular layer, lymphatic vessels and perineurium, and in 2/3 cases - the mesentery of the appendix and the peritoneum, however, they rarely metastasize to the lymph nodes and distant organs, unlike ileal carcinoid. In appendix carcinoids, supporting cells are visible around nests of tumor cells; in contrast, supporting cells are absent in EC cell carcinoids of the ileum and colon.

L-cell carcinoid producing glucagon-like peptides (GLP-1 and GLP-2, enteroglucagon glycentin, oxyntomodulin) and PP/PYY is non-argentaffin; most often measures 2-3 mm; characterized by tubular structures made of small cylindrical cells and trabecular structures in the form of long cords (type B); similar carcinoids are often found in the rectum.

Goblet cell carcinoid, usually 2–3 mm in size, grows in the submucosal layer, concentrically invades the wall of the appendix, and consists of small, round nests of signet ring cells resembling normal intestinal goblet cells, except for the compressed nuclei. Some of the cells are located in isolation; Pannet cells with lysosomes and foci resembling Brunner's glands are visible. When individual goblet cells fuse, extracellular “lakes” of mucus are formed. The picture is difficult to distinguish from mucous AK, especially with tumor invasion into the wall and distant metastases. There are argentaffin and argyrophilic tumors. Immunohistochemically, the endocrine component gives a positive reaction to chromogranin A, serotonin, enteroglucagon, somatostatin and PP; goblet cells express carcinoembryonic antigen. With EM, dense endocrine granules, mucus droplets, and sometimes both components are visible in the cytoplasm of the same cell.

Tubular carcinoid is often misdiagnosed as AK metastases, because the tumor is represented by small discrete tubes, sometimes with mucus in the lumen. Short trabecular structures are common; Solid nests are usually absent. In isolated cells or in small groups of cells, a positive argentaffin and argyrophilic reaction is often detected. Unlike cancer, it is characterized by an intact mucous membrane, orderly structures, and the absence of cell atypia and mitoses. The tumor is positive for chromogranin A, glucagon, serotonin, IgA and negative for protein S 100. An exocrine-endocrine tumor consists of goblet cells and structures characteristic of carcinoid and AK.

Genetic features: In contrast to AK of the colon, mutations of the KRAS gene were not found in typical carcinoid and goblet cell carcinoid of the appendix; in the latter, TP53 mutations were found in 25% of cases (mainly G:C->A:T transitions).

Cytological diagnosis: on routine smears, EC-cell and L-cell carcinoids are cytologically diagnosed as typical carcinoid NOS. Goblet cell carcinoid, tubular carcinoid, and exocrine-endocrine carcinoid cannot be identified as such cytologically. Small cell cancer has properties similar to those of this tumor in other parts of the gastrointestinal tract.

Rare tumors of the appendix: In the mucosa and submucosa, a non-urinoma is found, and occasionally an axial neuroma, which causes obliteration of the appendix lumen. The histological structure is similar to neuron of other localizations. Gastrointestinal tract infections are rarely found in the appendix. Kaposi's sarcoma in this organ may be part of an acquired immunodeficiency syndrome. Primary PL of the appendix (Burkitt's PL) is very rare; more often, tumors of neighboring organs spread to the appendix.

Secondary tumors are not typical for the appendix: isolated cases of metastases from cancer of the gastrointestinal tract, gall bladder, genitourinary tract, breast, lungs, thymoma, melanoma have been published. Involvement of the serosa of the appendix is ​​often associated with transintestinal spread. The cytological picture of tumors is similar to that of tumors of other organs.

Stomach Secretory. The function is to produce gastric juice by the glands. Mechanical function

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In the large intestine, water is absorbed from the chyme and feces are formed. In the large intestine

In the small intestine, the process of absorption of the breakdown products of proteins, fats and carbohydrates into the blood and lymphatic vessels also occurs. The small intestine also performs a mechanical function: it pushes chyme in the caudal direction.

Structure. The wall of the small intestine consists of the mucosa, submucosa, muscular and serous membranes.

On the surface, each intestinal villi is lined with single-layer columnar epithelium. There are three types of cells in the epithelium: bordered, goblet and endocrine (argyrophilic).

Enterocytes with a striated border make up the bulk of the epithelial layer covering the villus. They are characterized by a pronounced polarity of structure, which reflects their functional specialization: ensuring the resorption and transport of substances supplied with food.

Intestinal goblet cells are typical mucous cells in structure. They experience cyclical changes associated with the accumulation and subsequent secretion of mucus.

The epithelial lining of the intestinal crypts contains the following types of cells: bordered, borderless intestinal cells, goblet, endocrine (argyrophilic) and intestinal cells with acidophilic granularity (Paneth cells).

The lamina propria of the mucous membrane of the small intestine mainly consists of a large number of reticular fibers. They form a dense network throughout the lamina propria and, approaching the epithelium, participate in the formation of the basement membrane.

The submucosa contains blood vessels and nerve plexuses.

The muscular layer is represented by two layers of smooth muscle tissue: internal (circular) and external (longitudinal).

The serous membrane covers the intestine on all sides, with the exception of the duodenum. The lymphatic vessels of the small intestine are represented by a very widely branched network. Each intestinal villi has a centrally located lymphatic capillary that blindly ends at its apex.

Innervation. The small intestine is innervated by sympathetic and parasympathetic nerves.

Afferent innervation is carried out by the sensitive myenteric plexus, formed by the sensory nerve fibers of the spinal ganglia and their receptor endings.

Efferent parasympathetic innervation is carried out through the musculo-intestinal and submucosal nerve plexuses.

Structure thin guts. Thin intestine(intestinum tenue) – the next section of the digestive system after the stomach.

Thin intestine. IN thin gut All types of nutrients are chemically processed: proteins, fats and carbohydrates.

If you have symptoms of bloat thin guts it is necessary to immediately perform the operation, without waiting for the full classical picture of the disease to appear.

Ileum intestine- continuation of the skinny, its loops lie in the lower right part of the abdominal cavity. The last loops lie in the pelvic cavity thin guts.

Practically thin intestine can be implemented in thin, thin to thick and thick to thick. The most common type is ileocecal intussusception.

Fat intestine. In thick gut water is absorbed from the chyme and feces are formed.

Crypts in the colon gut better developed than in thin.

Colon intestine located around the hinges thin guts, which are located in the middle of the bottom.

Colonic structure guts. Colon intestine located around the hinges thin guts, which are located in the middle of the lower floor of the abdominal cavity.

The structure of the thick and blind guts. Fat intestine(intestinym crassum) – continued thin guts; is the final section of the digestive tract.

Thin intestine(intestinum tenue) – the section of the digestive system next after the stomach; zakan.

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 branch off 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 tubule 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 spike activity stops, and with it 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 are 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 closes due to the fact that switching to efferent sympathetic neurons occurs 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 from the amino acid side, which facilitates its solubility in water, while the steroid skeleton is lipophilic, which facilitates interaction with other lipids. Thus, conjugated bile salts can 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.

Every day, up to 2 liters of secretion are formed in the small intestine ( intestinal juice) with a pH of 7.5 to 8.0. Sources of secretion are the glands of the submucosal membrane of the duodenum (Brunner's glands) and part of the epithelial cells of the villi and crypts.

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

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

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

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

Secretory function of the colon. The crypts of the colon secrete mucus and bicarbonates. The amount of secretion is regulated by mechanical and chemical irritation of the mucous membrane and local reflexes of the enteric nervous system. Excitation of the parasympathetic fibers of the pelvic nerves causes an increase in mucus secretion with simultaneous activation of colon peristalsis. Strong emotional factors can stimulate acts of defecation with periodic release of mucus without fecal contents (“bear disease”).