MindMap Gallery Internal Medicine—Digestive System—General Introduction
Master: physiological esophageal anti-reflux defense mechanism; gastrointestinal mucosal barrier; gastric acid secretion; diagnosis of HBV infection; liver function assessment; detection of Helicobacter pylori. Familiar with: digestive system endoscopy and imaging diagnosis. Understand: the digestion and absorption of main nutrients and the metabolism of the liver; the metabolism and detoxification functions of the liver; the synthesis and activation of pancreatic enzymes and the physiological mechanism of the pancreas to prevent its own digestion.
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General overview of digestive system
Section 1 Digestive physiology and biochemical functions related to common diseases
1. Physiological esophageal anti-reflux defense mechanism
Under physiological conditions, when swallowing, the lower esophageal sphincter (lower esophageal sphincter (LES) relaxes, allowing food to pass After entering the stomach, transient LES loosening may also occur without swallowing. Relaxation, a small amount of transient gastroesophageal reflux occurs, due to some antibiotics The existence of reflux mechanism avoids the occurrence of gastroesophageal reflux
antireflux mechanism 1. Esophageal-gastric anti-reflux barrier: the anatomical structure at the junction of the esophagus and the stomach, including the LES, diaphragm crura, diaphragmatic esophageal ligament, and the acute angle between the esophagus and the fundus of the stomach. LES end of esophagus, 3-4cm, circular muscle bundle, high-pressure belt, anti-reflux 2. Esophageal clearance: spontaneous or secondary, 1-2 times, saliva flushing 3. Esophageal mucosal barrier: saliva, stratified squamous epithelium, rich blood supply under the mucosa
2. Gastric mucosal barrier
Gastric glands: gastric mucosal epithelium is indented
Pyloric gland: secretes mucus and gastrin
Fundic gland: composed of chief cells, parietal cells, neck mucus cells and endocrine cells, secretes gastric acid, pepsin and intrinsic factor, also called oxyntic gland
chief cell pepsinogen
parietal cell hydrochloric acid and intrinsic factor
Cardiac glands: secrete mucus
The pH of gastric juice is about 0.9-1.5. Normal people The secretion amount is 1.5-2.5L/d, in acid Pepsinogen is activated in a sexual environment. In addition, the gastric mucosa is often associated with various pathogens Microorganisms and irritating and damaging substances material contact, but the gastric mucosa can maintain itself intact, making the gastric cavity and gastric mucosa The H concentration in the membrane is maintained at 1000 times Poor high gradient state, which is related to the gastric mucosa The barrier involves three levels.
1. Pre-epithelial: It is composed of a layer of mucus gel and bicarbonate layer about 0.5mm thick covering the surface of gastric mucosal epithelial cells, which can prevent high concentrations of hydrochloric acid, pepsin, pathogenic microorganisms and other irritants in the stomach. Even damaging substances can damage gastric epithelial cells and maintain a high pH gradient between acidic gastric juice and neutral mucosa.
2. Epithelial cells: The top membrane of epithelial cells and the tight junctions between cells have a barrier effect on counter-diffusion and harmful factors in the gastric cavity. They regenerate quickly and are replaced approximately every 2-3 days, allowing them to repair damage quickly. Epithelial cells can produce inflammatory mediators, among which there are interepithelial lymphocytes, which are an important component of mucosal immunity.
3. Post-epithelial: The glycogen reserves in the gastric mucosal cells are less, and the ability to produce energy under hypoxic conditions is also low. Therefore, to protect the integrity of the gastric mucosa, it must be supplied with sufficient oxygen and nutrients. The rich capillary network of the gastric mucosa provides sufficient nutrition for the vigorous secretory function of epithelial cells and their continuous renewal. It also transports local metabolites and hydrochloric acid that reverse osmose back to the mucosa in a timely manner. The healthy blood circulation of the gastric mucosa is even more important for maintaining the integrity of the mucosa. is important. In addition, inflammatory cells in the stroma play a positive role in injury healing.
Molecular groups such as prostaglandins, nitric oxide, epidermal growth factor, calcitonin gene-related peptide, protease-activated receptors, peroxidase proliferator-activated receptors, and capsaicin pathways are involved in the complex regulation of gastric mucosal barrier function. Prostaglandin E has a protective effect on gastric mucosal cells and can promote mucosal blood circulation and secretion of mucus and bicarbonate. It is a type of mucosal protective molecule that is currently well understood.
3. Secretion and Regulation of Gastric Acid
The information sensed from food in the gastric antrum prompts the G cells of the pyloric gland to secrete gastrin. Most of the gastrin circulates and acts on the enterochromaffin cells of the gastric body in an endocrine manner, stimulating them to secrete histamine, histamine and a small amount of Gastrin promotes the synthesis and secretion of hydrochloric acid by gastric parietal cells through histamine H2 or cholekinin-B receptors. Somatostatin secreted by D cells in the gastric antrum has a negative regulatory effect on all three types of cells involved in the above process.
The process of hydrochloric acid secretion by gastric parietal cells can be roughly divided into three main steps:
① Histamine, acetylcholine and gastrin stimulate their respective receptors on parietal cells;
②In parietal cells, hydrogen ions are generated under the mediation of cAMP or calcium ions;
③The H-K-ATPase located in the secretory tubules and vesicles of parietal cells, also known as the proton pump, pumps H from the parietal cells into the gastric cavity against the concentration gradient. In addition, acetylcholine from the enteric nervous system affects the functional status of parietal cells, G cells, and D cells through neuroendocrine means, and its comprehensive regulatory effect on gastric acid secretion varies greatly.
4. Intestinal mucosal barrier
In the process of the intestinal tract being exposed to a large amount of food and the symbiosis of microorganisms in the intestinal lumen, its barrier defense system plays an important role. It can effectively block more than 500 types of intestinal parasitic bacteria and bacteria in the intestinal tract at a concentration as high as 1011/ml. Its toxins are displaced to tissues and organs outside the intestinal lumen, preventing the body from being invaded by endogenous microorganisms and their toxins. The intestinal mucosal barrier is a structural and functional unity that isolates the substances in the intestinal lumen from the body's internal environment and maintains the stability of the body's internal environment. It is composed of mechanical barriers, chemical barriers, immune barriers, biological barriers and intestinal peristalsis.
1. Mechanical barrier: refers to the complete barrier composed of intestinal mucosal epithelial cells, intercellular tight junctions and bacterial membrane, which is the most important in performing intestinal barrier function.
2. Chemical barrier: Gastric acid and bile salts can inactivate a large number of bacteria that enter the intestine through the mouth. It is composed of mucus and digestive juice secreted by the intestinal mucosal epithelium and antibacterial substances produced by normal parasitic bacteria in the intestinal lumen.
3. Immune barrier: The intestine is an important peripheral immune organ of the human body. It is produced by intestinal-associated lymphoid tissue (interepithelial lymphocytes, lamina propria lymphocytes and Peyer's nodes), mesenteric lymph nodes, liver Kupffer cells and plasma cells. It consists of secreted antibodies (sIgA) and defensins secreted by immune cells. Plays an important role in natural immunity and acquired immunity.
4. Biological barrier
5. Intestinal motility: Intestinal motility is like the scavenger of the intestine. In the case of intestinal obstruction or intestinal paralysis, it is often accompanied by overgrowth of small intestinal bacteria.
The natural immunity of the intestinal mucosa is innate in the body. It acts quickly and has diverse defense mechanisms. However, it lacks immune memory and has the same response to multiple stimulations of the same pathogen. Participating effector cells include: intestinal mucosal epithelial cells, macrophages, dendritic cells, B cells, eosinophils, mast cells, natural killer cells, etc. After the structural recognition receptors on these cells recognize the antigen, they quickly initiate natural In immune response, nuclear factor-kB is an important hub molecule of inflammatory response. Acquired immunity in the intestine is initiated after specific lymphocytes recognize exogenous antigens, and then function after lymphocyte proliferation and differentiation into effector cells. Although it has a slow onset of action, it has the characteristics of immune memory and specificity, so it has the effect of expanding natural immunity and enhancing its function. Defensins are short cationic peptides rich in cysteine. They penetrate microbial cell membranes through their electron attraction and cause cytoplasm to leak out. Therefore, they have strong antibacterial, fungal and viral effects.
5. Intestinal microecology
The intestinal microecology is composed of bacteria, fungi, viruses, etc., and its number and number of genes are far greater than the number of cells and genes in the human body itself. It is called the second genome of the human body. Intestinal flora can be roughly divided into: ① Probiotics: mainly anaerobic bacteria such as various bifidobacteria and lactobacilli. They are often close to the mucus layer and are an indispensable element of human health. They can synthesize various vitamins and participate in food. Digestion, promote intestinal peristalsis, prevent contact between pathogenic bacteria and intestinal epithelial cells, decompose harmful and toxic substances, etc.; ② Opportunistic pathogenic bacteria: such as Escherichia coli, enterococci and other bacteria with dual effects, under normal circumstances It is beneficial to health. Once the proliferation is out of control or transferred from the intestine to other parts of the body, it may cause diseases; ③ Harmful bacteria: such as Shigella dysenteriae, Salmonella, etc., once they grow in large numbers, they can cause a variety of diseases or affect the function of the immune system. .
Microorganisms and humans have co-evolved and formed a symbiotic relationship of mutual dependence and interdependence. There is mutual influence and two-way regulation between the intestinal mucosal barrier and intestinal microecology. The intestinal microecology affects the body's nutrition, metabolism, immunity, development and aging, and is related to many chronic diseases such as metabolic diseases, neuropsychiatric diseases, immune-related diseases, and tumors.
Intestinal microorganisms have the following functions: 1. Metabolic function: It can secrete complex proteases, which have a redox effect, can promote the decomposition of components in food, and decompose, metabolize or transform endogenous and exogenous other substances. 2. Nutritional function: Synthesizes a variety of vitamins, amino acids, peptides, and short-chain fatty acids. The metabolites of microorganisms promote the absorption of minerals and nutrients, thus affecting the nutritional metabolism of the host. 3. Host immune function: regulates the development and maturation of the host's immune organs, and serves as a broad-spectrum antigen to stimulate the host's immune response, including humoral immunity and cellular immunity. 4. Intestinal defense function: It is an important part of the intestinal mucosal barrier. It can prevent the invasion or colonization of potential pathogenic bacteria and maintain the intestinal mucosal barrier function and structural integrity.
6. Gastrointestinal peptides
Endocrine cells scattered in the gastrointestinal tract can produce more than 50 kinds of gastrointestinal peptides, such as cholecystokinin, somatostatin, intestinal vasoactive peptides, substance P, etc. The digestive tract is therefore the largest endocrine organ in the body. These gastrointestinal peptides are important for The secretion, motility, material transport, immunity and intestinal epithelial cell repair of the gastrointestinal tract have important and complex regulatory effects, and also affect the functions of other organs in the body.
7. Digestion and absorption of main nutrients and metabolism of liver
1. Sugar: Starch in food - pancreatic amylase - disaccharide - small intestinal epithelial cell brush border disaccharidase - monosaccharide - absorbed into the blood Part of glycogen provides energy for the body, and the other part is stored in the muscles and liver in the form of glycogen. Muscle glycogen supplies muscle contraction, and liver glycogen stabilizes blood sugar, which is particularly important for the brain and red blood cells. When blood sugar concentration drops, liver glycogen is broken down into glucose and released into the blood to replenish blood sugar.
Gluconeogenesis: When fasting for more than 10 hours, most of the stored liver glycogen is consumed, and the liver can synthesize part of the protein and fat in the body into liver glycogen and glucose. Impaired absorption of nutrients in the small intestine can lead to malnutrition, while excessive absorption of sugar can lead to obesity. When the liver is damaged and the synthesis, decomposition and gluconeogenesis of liver glycogen are impaired, it is difficult to maintain normal blood sugar levels, so chronic liver disease is easily complicated by diabetes.
2. Fat Lipids are emulsified by bile salts in the small intestine, digested by pancreatic lipase into monoglycerides, fatty acids and cholesterol, and then absorbed into the portal vein in the upper jejunum. In the smooth endoplasmic reticulum of small intestinal epithelial cells, long-chain fatty acids and 2-monoglycerides can be synthesized into triglycerides, which are combined with apolipoproteins, phospholipids and cholesterol to form chylomicrons, which enter the blood circulation through lymphatic vessels. . True chyloperitoneum is caused by rupture of lymphatic vessels in the small intestine.
In addition to the small intestine, the liver and adipose tissue are also places where triglycerides are synthesized, with the liver being particularly important. Monoglycerides, fatty acids and cholesterol entering the liver can be decomposed through oxidation to generate heat for energy, or excess fat can be converted into glycogen and glucose through gluconeogenesis. Abnormal lipid absorption caused by various reasons, increased triglyceride synthesis in hepatocytes, and decreased triglyceride transport out of hepatocytes are important pathophysiological links leading to the occurrence of fatty liver.
3. Protein Under the hydrolysis of gastric juice and pancreatic juice proteases, 1/3 of the protein becomes amino acids and 2/3 becomes oligopeptides. The oligopeptides at the brush border of the small intestinal epithelial cells can finally hydrolyze the oligopeptides into amino acids, which are passed through the amino acid carrier proteins of the small intestinal epithelial cells. Active transport transports it into cells with Na, and the γ-glutamyl cycle promotes the transport process of amino acids into intestinal cells. The amino acids absorbed through digestion (exogenous) are mixed with the amino acids produced by protein degradation in the body (endogenous), and are distributed throughout the body. It is called the amino acid metabolic pool, and its main function is to synthesize amino acids and peptides.
In addition to synthesizing the proteins it needs, the liver also synthesizes albumin, some globulin, fibrinogen, prothrombin and coagulation factors. Amino acid metabolism mainly occurs through ① deamination, which can be carried out in most tissues in the body. The liver is rich in transaminase, and alanine aminotransferase is liver-specific; ② α-keto acid metabolism generates α-keto acid after deamination into Non-essential amino acids are converted into sugars and lipids or have oxidative functions; ③ Most ammonia is synthesized into urea in the liver and detoxified. Certain proteins that are not fully digested are antigenic and are one of the causes of allergic reactions or aggravation of intestinal mucosal immune diseases. Intestinal bacteria produce putrefactive effects on undigested proteins, and most of their products are harmful to the human body. When the liver is seriously damaged, the synthesis of albumin is significantly reduced, which is an important mechanism for the formation of edema or peritoneal effusion; when liver cells are damaged, blood alanine aminotransferase will be significantly increased; the ability to remove ammonia is reduced, Excessive ammonia content in the blood is an important mechanism for the occurrence of hepatic encephalopathy.
8. Metabolism and detoxification functions of liver 4 forms of biochemical reactions 1. Oxidation: The oxidation of ethanol into ether, ethylamine, carbon dioxide and water is also called oxidative detoxification. 2. Reduction: Trichloroacetaldehyde is reduced and converted into trichloroethanol, thus losing its hypnotic effect. 3. Hydrolysis: Hydrolase hydrolyzes a variety of drugs or poisons 4. Binding: an important way of biological transformation, combining drugs or poisons with glucuronic acid, acetyl coenzyme A, glycine, adenosine 3-phosphate-5-phosphate sulfate, glutathione, etc., to facilitate excretion from bile and urine . When you have severe liver disease or portal hypertension or portosystemic shunt, pay attention to drug selection and master the dosage to avoid liver damage.
9. Coordinated movement of the bile duct Bile: bile canaliculi - intercalated ducts - interlobular bile ducts - left and right hepatic ducts - common hepatic duct - common bile duct - duodenum Gallbladder Sphincter of Oddi
10. Pancreatic enzyme synthesis, activation, and the physiological mechanism of the pancreas to prevent its own digestion Under physiological conditions, a variety of inactive pancreatic enzymes (trypsinogen, amylaseogen, lipaseogen, elastaseogen, phospholipaseogen, chymotrypsinogen, kallikreinogen, hydroxypeptidaseogen, etc.) and Lysosomal hydrolases are synthesized in the rough endoplasmic reticulum of pancreatic cells and transported to the Golgi apparatus. After lysosomal hydrolase is glycosylated and phosphorylated, it specifically binds to mannan-6 phosphorylated receptors and is transported into lysosomes; trypsin does not bind to mannan-6 phosphorylated receptors in principle. . It is through these two different pathways that the digestive enzymes and lysosomal hydrolases synthesized in the rough endoplasmic reticulum are finally "sorted" into different secretory vesicles, forming digestive zymogen granules and lysosomes respectively. .
Under various physiological stimuli, glandular cells increase the intracellular calcium ion concentration, prompting the release of zymogen granules, which enter the duodenum through the pancreatic duct and duodenal papilla, where they are activated under the action of enterokinase and exert their ability to digest food. Function. Since trypsin can activate many other pancreatic enzymes, the activation of trypsinogen to trypsin is the most critical in the activation of multiple pancreatic enzyme cascades. Under physiological conditions, trypsinogen secreted from acinar cells can be slightly activated in the pancreas, but enzyme-specific inhibitors (a1-antitrypsin, a2-macroglobulin, etc.) produced by pancreatic interstitial cells can Quickly inactivate trypsin that is activated in advance in the pancreas to avoid autodigestion.
Section 2 Important Diagnostic and Treatment Techniques for the Digestive System
1. Endoscopic diagnosis
Gastroscopy, endoscopic ultrasound, duodenoscopy Colonoscopy capsule endoscopy Enteroscopy
Capsule endoscopy is a non-invasive examination method of the digestive tract that uses special equipment to observe the morphology of the digestive tract mucosa. 1. Capsule endoscopy is a device that is similar to the size of a capsule and contains a tiny camera. After swallowing, the mucosa on the inner wall of the digestive tract is recorded and photographed, and then the image is observed through a computer connected to it to determine whether there are lesions. 2. Capsule endoscopy is different from ordinary endoscopy. The intestines need to be cleaned in advance before the examination. If there are complications such as digestive tract obstruction, capsule endoscopy should not be used. In clinical practice, capsule endoscopy is specifically used to observe the stomach and small intestine.
2. Laboratory testing
(1) Diagnosis of hepatitis B virus infection The diagnosis of hepatitis B virus (HBV) infection includes the detection of 5 serum immune markers of HBV, serum virus detection and tissue virology detection.
Hepatitis B five items (two pairs and a half) (infection or not) HBsAg HBsAb Da Sanyang HBeAg Xiao Sanyang HB HBcAb
Serum virus detection (whether antiviral treatment and efficacy evaluation) HBV-DNA quantitative detection HBV genotyping Detection of HBV drug-resistant mutant strains
(2) Helicobacter pylori detection Helicobacter pylori (Hp) detection plays an important role in the diagnosis and treatment of gastric precancerous diseases and lesions, peptic ulcer, gastric mucosa-associated lymphoma and other diseases.
1. Non-invasive method: 13C- or 14C-urea breath test (Hp-urea breath test, Hp-UBT) is commonly used. It has good compliance and high accuracy, making it one of the golden methods. Monoclonal enzyme-linked immunoassay (ELISA) is used to detect Hp antigen in stool, and its sensitivity and accuracy are comparable to Hp-UBT. 2. Invasive methods: mainly include rapid urease test, gastric mucosal tissue section staining and bacterial culture. Staining of gastric mucosal tissue sections is also one of the golden methods.
(3) Liver function assessment
1. Liver synthesis function
(1) Serum albumin: Albumin is only synthesized by liver cells. When the liver's synthesis function is reduced, serum albumin will be significantly reduced. When the condition is stable, the serum albumin value of some patients is still within the normal range. After experiencing bleeding, infection, surgery and other events, the serum albumin will decrease significantly and even be difficult to return to normal.
(2) Plasma coagulation factors: Most of the coagulation factors are synthesized in the liver, and their half-lives are much shorter than albumin, especially vitamin K-dependent factors (I, VII, IX, X). Therefore, in the early stages of liver function impairment, while albumin is still at normal levels, vitamin K-dependent coagulation factors are significantly reduced. Prothrombin time measurement (prothrombin time, PT), partially activated prothrombin time measurement and thrombin time measurement are the most commonly used indicators.
(3) Cholesterol: About 70% of endogenous cholesterol is synthesized in the liver. When the liver synthesis function is impaired, blood cholesterol levels will decrease.
2. Liver cell damage
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) exist in the cytoplasm of liver cells. When the liver cell membrane ruptures, ALT and AST will increase significantly. Therefore, It is an important indicator reflecting liver cell damage. Since AST also exists in skeletal muscle, kidney, myocardium and other tissues, if AST is mainly elevated in the blood, it does not necessarily mean that liver cells are damaged. AST is mainly located on mitochondria in liver cells. When ALT increases, it is accompanied by an obvious increase in AST, indicating severe damage to liver cells. enzyme bile separation phenomenon
3. Bilirubin metabolism
Bilirubin is a product of the decomposition and destruction of aging red blood cells in the blood circulation in the mononuclear-phagocytic cell system of the liver, spleen, and bone marrow. Total bilirubin (TB) includes two forms: indirect bilirubin (indirect IB) and direct bilirubin (DB). Unconjugated bilirubin is a metabolite of hemoglobin. After ingestion by liver cells, it is combined with glucuronic acid to form water-soluble conjugated bilirubin and is excreted from the biliary tract. If there is any obstacle in any of the above links, jaundice may occur.
Serum bilirubin Urinary bilirubin
Comprehensive judgment based on symptoms, signs, imaging data, pathology, etc.
3. Imaging diagnosis
1. Ultrasound (ultrasonography, US) 2. Computed tomography (CT) 3. Magnetic resonance imaging (MRI) Magnetic resonance cholangiopancreatography (MRCP)