Gastroenteropancreatic endocrine system

The term and concept of the APUD system (“APUD” is an acronym derived from the first letters of English words a mine — amines, p recursor — predecessor, u ptake — digestion, absorption; d ecarboxylation — decarboxylation) was proposed by E. Pierce ( English AGE Pearse ) in 1969, based on the ability of cells of the APUD system to assimilate the precursors of amines (monoamines L-dihydroxy phenylalanine and 5-HTP ), decarboxylate them and synthesize the amines necessary for the formation of regulatory peptides. ^[2]

Recently, instead of the term APUD-system, the previously adopted synonym for the diffuse endocrine system has come into use again, while derivative terms such as apudocytes - cells that make up the APUD-system, apudoma - tumors resulting from apudocyte hyperplasia , are actively used in modern medical vocabulary.

There are two main types of apudocytes - sources of hormones of the digestive tract: the digestive tract neurons and endocrine cells scattered through the digestive tract.

Most of the gastrointestinal apudocytes are located in the stomach , small intestine, and pancreas . Also, some of them are present in the esophagus, colon. Liver apudocytes do not belong to the gastroenteropancreatic endocrine system. Apudocytes perform the functions of synthesis and secretion of regulatory polypeptides that have a hormonal effect on various aspects of the activity of the digestive organs. Due to the short time of existence and rather rapid inactivation of these polypeptides in the liver or directly in the bloodstream, their effect on organs outside the digestive system is noticeably less. ^[one]

Stomach endocrine cells

The main endocrine cells of the stomach are enterochromaffin-like cells (ECL-cells), which make up 35% of the neuroendocrine cells of the stomach of a healthy person , G-cells (26%) and D-cells . ECL cells secrete histamine , G-cells - gastrin , D-cells - somatostatin .

In the acid-producing zone of the stomach : in the body of the stomach, the bottom area and the intermediate zone, ECL- and D-cells are located next to parietal cells secreting hydrochloric acid and, thus, provide paracrine regulation of their histamine and somatostatin. ^[3] G-cells in this area of ​​the stomach are absent. ^[four]

G-cells are located in the antrum of the stomach. From G-cells to acid-producing parietal cells, gastrin is transported by blood through the portal vessels and the general systemic circulation. Next to G-cells are D-cells and, thus, the latter have the ability to paracrinely inhibit histamine secretion by G-cells. ^[3] At the same time, the number of G-cells in the antrum of the stomach is approximately 220–490 cells per 1 mm² ^[5] and exceeds the number of D-cells by 4 times. ^[3] G-cells are open cells; they have membrane receptors that are open through the lumen of the gastrointestinal tract. D-cells of the antrum are also open (unlike D-cells of the acid-producing zone, they are closed there, that is, they do not have direct contact with the lumen of the gastrointestinal tract). ^[four]

The secretion of open cells of the stomach significantly depends on the acidity of gastric contents . pH from 5 to 7 stimulates gastrin secretion, pH values ​​below 5 inhibit it, and at pH below 1.7, it is completely suppressed. Antral D cells also respond to acidity: the maximum secretion of somatostatin, which is an inhibitor of hydrochloric acid secretion, occurs at pH = 1, and is suppressed at pH values ​​above 3. ^[4]

Endocrine cells of the duodenum and jejunum

In the small intestine most of the endocrine cells are located in the crypts of the duodenum , the smaller - in the proximal part of the jejunum and even smaller in the distal part of the jejunum and in the ileum .

The endocrine and enterochromine cells of the intestine, as well as epithelial cells, develop from polypotent stem cells . Intestinal neurons originate from neuroectoderm . Endocrine cells differentiate all the time, complicate their structure and migrate from the crypts to the tops of the villi. Endocrine cells and peptidergic neurons share biochemical mechanisms necessary for the synthesis and production of polypeptides. Intestinal endocrinocytes are located among the superficial epithelium of the intestine. For all of them, the presence of a membrane with a thickness of 100 to 500 nm is typical, the thickness of which depends on the substance being produced. Endocrinocyte groups can form complexes that have intercellular gaps or tubules containing the produced agents. ^[one]

In the proximal small intestine, the largest among other organs of the gastrointestinal tract is a set of endocrine cells: I-cells producing cholecystokinin , S-cells - secretin , K-cells - glucose-dependent insulinotropic polypeptide , M-cells - motilin , D-cells - somatostatin , G cells — gastrin , etc. In the duodenal and jejunum there is an absolute majority of all the body's I, S, and K cells. ^[1] The number of G-cells in 1 mm² of duodenal ulcer 6 - 76 in contrast to 220-490 pyloric stomach. ^[five]

Ileal and colon endocrine cells

In the mucous membrane of the distal part of the ileum and in the large intestine are L-cells - cells that produce peptide hormones glucagon-like peptide-1 and peptide YY . ^[1] L-cells are the most numerous intestinal endocrine cells .. ^[6]

Pancreatic endocrine cells

Cells of the endocrine portion of the pancreas can either be found in the islets of Langerhans or be located alone or form small aggregations in the exocrine gland ^[7] .

Among apudocytes of the pancreas emit

• A-cells (closed-type cells) are contained in the endocrine pancreas and gastric mucosa, glucagon , endorphins , gastroinhibitory peptide (HIP) and cholecystokinin (CCK) are isolated;
• B-cells (cells of a closed type) are located in the endocrine part of the pancreas and secrete insulin ;
• D-cells (cells of the closed type) are located in the pancreatic islets, the mucous membrane of the stomach, small and large intestines. They secrete somatostatin ;
• D1-cells are contained in the pancreas, stomach, small and large intestine. They allocate VIP ;
• EC cells (open cells) are the most abundant species. They are found in the pancreas, mucous membrane of the gastrointestinal tract, airways and lungs. These cells secrete serotonin and substance P ;
• PP cells are found in the pancreas, mucous membrane of the pyloric stomach, small and large intestine. They secrete a pancreatic polypeptide ^[8] .

For many apudocytes , the principle is true: “one hormone - one cell”. Most of them produce one predominant hormone. However, there are cells secreting a whole spectrum of biologically active substances. The enterochromaffin cell , for example, can produce serotonin , substance P , enkephalin , motilin . All regulatory peptides (hormones and neurotransmitters) are single-stranded oligopeptides with hydrophilic properties and stable and strong bonds between amino acid residues. ^[one]

Hormones of the digestive system are classified by localization in the gastrointestinal tract; apudocytes secreting them; on the speed of action; on the similarity of their structure. The table lists the main regulatory peptides of the gastroenteropancreatic endocrine system: ^[1]

Incretins

Hormones that are produced after a meal and that stimulate insulin secretion are called incretin. Glue -dependent insulinotropic polypeptide and glucagon-like peptide-1 (enteroglucagon) are among the incretins. ^[9]

Apudomas are tumors emanating from cellular elements located in various organs and tissues (mainly islet (incretory) cells of the pancreas, cells of other parts of the gastrointestinal tract, thyroid gland C-cells) producing polypeptide hormones. The following types are described nowadays: ^[10]

• VIPoma ;
• Gastrinoma ;
• Glucagonom ;
• Carcinoid;
• Neurotensinomine;
• Ppoma ;
• Somatostatinoma ;
• Insulinoma

Vipoma

Vipom (Werner-Morrison syndrome, pancreatic cholera, aquatic diarrhea-hypokalemia-achlorhydria syndrome) is characterized by the presence of aquatic diarrhea and hypokalemia due to islet cell hyperplasia or a tumor, often malignant, originating from the islet cells of the pancreas (more than a body or a tail), a white adipose tissue is more common than the body, the body, the body, and the body. vasoactive intestinal polypeptide (VIP). In rare cases, VIPoma may occur in ganglioneuroblastomas that are localized in the retroperitoneal space, lungs, liver, small intestine, and adrenal glands, occur in childhood, and are usually benign. The size of pancreatic VIP is 1 ... 6 cm. In 60% of cases of malignant tumors at the time of diagnosis there are metastases. ^[11] The incidence of VIPomas is very low (1 case per year per 10 million people) or 2% of all endocrine tumors of the gastrointestinal tract . In half of the cases, the tumor is malignant. The prognosis is often unfavorable. ^[12]

Gastrinoma

With hyperplasia of G-cells , a gastrinoma is formed - a benign or malignant tumor localized in the pancreas, duodenal or jejunum, or even in the peripancreatic lymph nodes , in the gate of the spleen or in the wall of the stomach. This tumor produces a greater amount of gastrin, hypergastrine appears, which, through the mechanism of stimulation of parietal cells, causes excessive production of hydrochloric acid and pepsin . In a normal situation, G-cells under the influence of hydrochloric acid inhibit the production of gastrin, but G-cells are not affected by gastrinous factor. As a result, multiple peptic ulcers of the stomach, duodenum or jejunum develop. Gastrin secretion by gastrinomas is especially sharply increased after a meal.

Clinical manifestation of hypergastrinimia - Zollinger – Ellison syndrome (type 1) .. ^[13]

Glucagonom

Glucagonome is a tumor, often malignant, originating from Alpha cells of the pancreatic islets. It is characterized by migrating erosive dermatosis, angular cheilitis, stomatitis, glossitis, hyperglycemia, normochromic anemia. It grows slowly, metastasizes to the liver. There is 1 case for 20 million at the age of 48 to 70 years, more often in women. ^[ten]

Carcinoid

Neurotensinome

PPM

PPom is a pancreatic tumor secreting pancreatic polypeptide (PP). Clinical manifestations are practically absent. More often diagnosed after metastasis to the liver. ^[10] Treatment: surgical, chemotherapy and symptomatic. The prognosis depends on the start of treatment.

Somatostatinoma

Somatostatinoma is a malignant, slowly growing tumor, characterized by an increase in the level of somatostatin. This is a rare disease that occurs in people over 45 years old - 1 case per 40 million. ^[10]

There are:

• somatostatinoma from delta pancreatic cells and
• Somatostatin secreting drug is a tumor of the duodenum .

Diagnosis based on the clinic and increase the level of somatostatin in the blood. Treatment is prompt, chemotherapy and symptomatic. The prognosis depends on the timeliness of treatment.

Insulinoma