Gluten enteropathy

　　This disease is closely related to the consumption of wheat flour. A large number of studies have confirmed that gluten may be a pathogenic factor for this disease. Therefore, the name of the disease has recently been directly changed to gluten enteropathy, and it is believed that the pathogenesis is the result of the interaction of genetics, immunity, and gluten diet.

　　1. Patients with the disease are abnormally sensitive to wheat flour food containing gluten (commonly known as gluten), and the gluten in barley, wheat, rye, and oats can be hydrolyzed into gluten protein (i.e., gliadin) by ethanol, which may be a pathogenic factor of the disease. Gliadin is rich in glutamic acid and proline and can be separated into α, β, γ, and δ four types of gliadin by electrophoresis technology. α-gliadin is toxic to the intestinal mucosa. The toxicity of gluten protein to the intestinal mucosa disappears after continuous hydrolysis. Normal small intestinal mucosal cells have polypeptide degrading enzymes that can decompose them into smaller molecules of non-toxic substances. However, in active celiac disease patients, the enzyme activity of intestinal mucosal cells is insufficient to decompose them and cause disease.

　　2. The immunopathological research of the disease has found that gluten-soluble gliadin antibodies can be detected in the blood, small intestinal secretions, and feces of active celiac disease patients. Recently, IgA antibodies against endomysium and reticulin can also be detected. After a period of fasting from gluten-containing diet, when gluten food is consumed again, the complement and C3 in the patient's serum decrease sharply, and immune complexes can be measured. Biopsy of the small intestinal mucosa shows an increase in interepithelial lymphocytes, in situ proliferation, mainly sensitized T cells. In vitro organ culture experiments show that T cell activation can cause atrophy of the small intestinal villi and hyperplasia of the gland crypts, all of which suggest that the disease is an immune disease caused by gluten.

　　3. The disease has a genetic predisposition and is closely related to MHC genes. It has been observed that many family members of patients have the disease, and asymptomatic carriers of gluten-soluble gliadin, reticulin, and endomysial proteins can be detected in asymptomatic family members.

　　4. Pathological changes: The main pathological changes are in the small intestinal mucosa, with a significant difference in the degree and scope of the lesions. The villi of the small intestinal mucosa atrophy, flatten, deform, and even disappear. The surface circular cells decrease, and there is an increase in inflammatory cells and gland hyperplasia in the subepithelial layer. The columnar epithelial cells of the mucosa become low and flat. The cytoplasm has vacuoles, nuclei of uneven size, and microvilli are unclear. Some cases have thickened mucosa,呈慢性炎变, with villi still present but disordered, and the intestinal lumen can be expanded to varying degrees.

　　The secretion of enzymes in intestinal mucosal cells is reduced, such as disaccharidase, dipeptidase, lipase, phosphatase, and dehydrogenase. The secretion of intestinal juice and intestinal hormones is also reduced. Therefore, not only is the absorption area of the intestinal mucosa reduced, but the absorption function is reduced, and the activity of enzymes also decreases, and the function of digesting food is also reduced. Patients lose a large amount of fat, protein, sugar, water, and salt every day, causing various corresponding clinical symptoms.

　　Patients with IgA nephropathy, infertility, stomatitis, cheilitis, beriberi, night blindness, anemia, even cachexia and other complications. Also known as cachexia. This name comes from the concept of humoral pathology. Humoral pathology believes that the essence of disease lies in the abnormality of body fluids. The original text is from Hippocrates and Galen. Now it refers to the systemic failure state that occurs in the late stage of diseases such as cancer, tuberculosis, hemophilia, etc. It can be regarded as a toxic state caused by the dysfunction of many organs in the body, with symptoms such as emaciation, anemia, fatigue, and skin呈污秽黄色.

　　The clinical manifestations of this disease are essentially a malnutrition syndrome caused by the impairment of digestion and absorption of nutrients. The clinical manifestations vary greatly, with a significant number of patients having mild symptoms that are not easy to detect. The manifestations in adult patients may not be typical. Common symptoms and signs are as follows:

　　1. Diarrhea and abdominal pain. 80％～97％ of patients have diarrhea, with typical cases presenting with steatorrhea. The feces are pale, in large quantities, greasy or foamy, often floating on the surface, with a strong odor. The number of bowel movements per day ranges from several to more than ten. Most patients have chronic or intermittent diarrhea; some early or mild cases may not have diarrhea, or even constipation, which can often be missed. Abdominal pain is less common than diarrhea, usually presenting as abdominal distension pain, often occurring before defecation. The abdomen may have mild tenderness, and some cases may have significant distension, nausea, and vomiting.

　　2. Weight loss and varying degrees of fatigue and weakness are almost inevitable, with emaciation and weakness mainly due to malabsorption of proteins, fats, and others. Dehydration, potassium deficiency, and decreased appetite are also important factors. In severe cases, cachexia may occur.

　　3. Manifestations of vitamin deficiency and electrolyte imbalance. Deficiency of calcium and vitamin D can lead to tetany, sensory abnormalities, osteoporosis, osteomalacia, and can cause bone pain. Deficiency of vitamin K can lead to bleeding tendency, while deficiency of vitamin B complex can cause tongue coating, stomatitis, cheilitis, beriberi, and hyperpigmentation similar to pellagra. Deficiency of vitamin A can lead to follicular keratosis, corneal dryness, night blindness, etc. More than half of the patients have anemia, and there are concave nails. Some patients may have muscle tenderness and clubbing (toes).

　　4. Edema, fever, and nocturnal edema are common, with fever often caused by secondary infection. During the onset, the amount of nocturnal urine is greater than that of daytime urine. IgA nephropathy, infertility, and bleeding tendency may occur.

　　The disease is closely related to the consumption of wheat flour, so for susceptible populations, it is recommended to minimize the consumption of wheat flour and avoid eating wheat gluten-containing foods (such as various wheat products). If the gluten in the flour is removed, the remaining starch can be consumed. The principle is to have a diet high in protein, high in calories, low in fat, non-irritating, and easy to digest. Exercise regularly, pay attention to the addition of other complementary foods, and improve immunity.

　　1. Blood examination:Most cases are macrocytic anemia, but there are also normal erythrocytic or mixed anemia. Serum potassium, calcium, sodium, and magnesium can all decrease, and plasma albumin, cholesterol, phospholipids, and prothrombin can also decrease. In severe cases, the levels of serum folic acid, carotene, and vitamin B12 are also reduced.

　　2. Quantitative determination of fecal fat and fat absorption test:Generally, the Vandekamer method is used. When normal individuals consume 50～100g of fat per day, the fecal fat content is usually less than 5g/d, and the fat absorption rate is greater than 95%. The calculation method for fat absorption rate is as follows:

　　Fat absorption rate = intake of fat - fecal fat content × 100 / intake of fat.

　　Test method: Consume a standardized test meal (containing 60 to 100g of fat per day) for 3 days, and simultaneously measure the fecal fat for 3 days. Take the average value per day, and if the fecal fat content is greater than 6g per day, or the fat absorption rate is less than 95%, it can be considered as malabsorption of fat.

　　The quantitative test of fecal lipids is a simple method, and most patients with steatorrhea can be diagnosed accordingly, but it is not sensitive enough. In mild cases or when the fat intake is less than 60g, the amount of fecal fat may not necessarily increase. The fat absorption test can accurately reflect the fat absorption status.

　　3. 131I-glycerol triester and 131I-oleic acid absorption test:Before the test, take a compound iodine solution (Lugol solution) to block the thyroid's absorption of 131I, and take 0.5ml/kg of 131I-glycerol triester (or 131I-oleic acid) and peanut oil and water, respectively, after 72 hours of collection of feces, and calculate the percentage of the radioactive dose excreted in the feces to the ingested radioactive dose. If the excretion rate of 131I-glycerol triester in the feces is greater than 5%, or 131I-oleic acid is greater than 3%, it suggests malabsorption of lipids. This test method is simple, but its accuracy is not as good as the chemical determination method of fecal lipids.

　　4. Serum beta-carotene concentration measurement:It is a valuable screening test with a normal value greater than 100IU/dl. It is often lower than normal in cases of malabsorption caused by small intestinal diseases, normal or slightly reduced in cases of pancreatic dyspepsia, and may also be reduced in malnutrition, insufficient food intake, high fever, or certain liver diseases.

　　5. Other small intestine absorption function tests:Water-soluble substances such as xylose, glucose, lactose, and folic acid can be used to determine the absorption function of the upper small intestine. In patients with primary malabsorption syndrome, there may be typical impairment, while in cases of pancreatic or secondary steatorrhea, it may be normal.

　　(1) D-xylose absorption test D-xylose is passively absorbed in the jejunum after oral administration, without metabolism in the body and mainly excreted by the kidneys. When renal function is normal, the D-xylose test is the most sensitive indicator of jejunal absorption function. The method is to take 25g of D-xylose (dissolved in 250ml of water) on an empty stomach, followed by drinking 250ml of water to promote urination. Normally, 4.5 to 5g of D-xylose can be excreted in the urine within 5 hours after administration. If the excretion amount is between 3 to 4.5g, it is considered可疑 abnormal; those less than 3g are definitely malabsorption of the small intestine. Alternatively, oral administration can be conducted 2 hours later, and the blood concentration is measured. Normally, it should be greater than 20mg/dl. In cases of renal insufficiency, the excretion of D-xylose in the urine decreases and presents as a false negative, but the blood concentration remains normal. In patients with a large number of bacteria in the intestines, delayed gastric emptying, and ascites, the excretion of xylose by the kidneys may also decrease and affect the test results. Due to the adverse reactions such as upper abdominal discomfort, vomiting, and diarrhea that some patients may experience after ingesting 25g of D-xylose, some people have switched to the method of taking 5g of D-xylose orally. The excretion amount in the urine of normal people within 5 hours should be greater than 1.0 to 1.2g, and its diagnostic value is similar to that of the 25g oral method, but the adverse reactions are reduced. In recent years, the D-xylose hydrogen breath test method has been adopted, which is not affected by renal function and is as effective as the urine xylose excretion test.

　　(2) Vitamin B12 absorption test: Radioactive cobalt-labeled vitamin B12 can be used to determine the absorption function of the distal ileum. First, 1mg of vitamin B12 is injected intramuscularly to saturate the body's inventory, and then 2μg of vitamin B12 labeled with 60Co or 57Co is orally administered, and the urinary radioactivity content within 48 hours is measured. Normally, it should be greater than 8-10%. In cases of poor ileal function or resection, when intestinal bacteria overproliferate (such as blind loop syndrome), the urinary excretion is all lower than normal.

　　(3) 14C-glycocholic acid breath test: 10 microcuries of 14C-glycocholic acid is orally administered. In normal individuals, the vast majority is absorbed in the distal ileum, circulates to the liver, and is excreted into the bile duct; only a very small part is excreted into the colon and excreted in feces; another part is metabolized into 14CO2 and exhaled through the lungs. After normal individuals take 14C-glycocholic acid, the excretion of 14CO2 in feces within 4 hours is less than 1% of the total amount, and the excretion within 24 hours is less than 8%. There is a large amount of bacterial proliferation in the small intestine. When the ileum is resected or functionally dysregulated, the excretion of 14CO2 from the lungs and 14C in feces increases significantly, reaching 10 times that of normal individuals.

　　6. Pancreatic function test:Abnormalities can be displayed in chronic pancreatitis, pancreatic cancer, and pancreatic cystic fibrosis, which can help diagnose pancreatic malabsorption.

　　7. Gastrointestinal X-ray examination:The small intestine often has functional changes, which are more common in the middle and distal segments of the jejunum, mainly manifested as dilatation of the intestinal lumen, fluid accumulation, and barium sedimentation; the intestinal loops are segmented in a snowflake-like distribution; the mucosal folds become thickened or the intestinal wall is smooth, showing the 'candelabra' sign; the barium passage time is delayed, etc. Gastrointestinal X-ray examination can also exclude other organic lesions of the gastrointestinal tract.

　　8. Endoscopic examination:The applicative enteroscopy can reach 60-100cm below Treitz ligament, with a probe-type enteroscope being 256cm long and the tip diameter about 5mm. After insertion into the jejunum, it can slowly enter the distal ileum and even reach the colon with the help of peristalsis, and the operation process requires 6-8 hours. Generally, 50%-70% of the jejunal mucosa can be seen, and biopsy can be performed under direct vision, which improves the diagnostic level of small intestinal lesions and basically replaces blind aspiration biopsy. Sometimes, colonoscopy can pass through the ileocecal valve to observe the terminal ileum lesions.

　　The appearance of normal small intestinal mucosa is similar to that of duodenal mucosa. The mucosa of the upper jejunum is annular folds, and the mucosal surface is velvety. Down to the end of the ileum, the folds gradually decrease and almost disappear, the villi are short and blunt. When the small intestine absorbs poorly, the basic feature of the mucosa is that the villi become shorter, thicker, inverted, and peeled, showing atrophic changes.

　　In addition, the detection of IgA antibodies against gluten-soluble gliadin, endomysial protein, and reticulin protein can help in the diagnosis of this disease.

　　1. The most critical issue in diet therapy is to avoid gluten-containing foods such as various wheat products such as barley, wheat, oats, and spelt. If the gluten is removed from the flour, the remaining starch has no 'toxicity', and patients can eat it. Products made from corn, rice, quinoa, legumes, potatoes, sweet potatoes, etc. can be consumed, and fruits, meats, and milk are unlimited. After diet therapy, symptoms generally begin to improve significantly in 3 to 6 weeks, with diarrhea decreasing and weight increasing. Diet therapy usually lasts for 0.5 to 1 year, and those who do not receive treatment or are ineffective often die of cancer, neurological complications, and jejunoileal ulceration.

　　2. Symptomatic treatment and supportive therapy should supplement various vitamins A, B group, C, D, K, and folic acid. Correct electrolyte and water balance disorders, and human albumin or blood transfusion can be administered if necessary.

　　After confirming the diagnosis, comprehensive substitution therapy should be carried out for the cause, with dietary therapy being the most important.

　　1. Diet therapy should avoid gluten-containing foods (such as various wheat products), such as removing the gluten from flour, the remaining starch can be consumed. The principle is to eat high-protein, high-calorie, low-fat, non-irritating and easily digestible food.

　　2. Symptomatic treatment and supportive therapy should supplement various vitamins A, B group, C, D, K, and folic acid. Correct electrolyte and water balance disorders, and human albumin or blood transfusion can be administered if necessary.

　　3. In severe cases of adrenal cortical hormone crisis, ACTH can be administered intravenously, or prednisone or prednisolone can be taken orally. Sometimes it can improve the absorption function of the small intestine, alleviate clinical symptoms, but recurrence is common after drug discontinuation, and long-term use can cause water and sodium retention, exacerbate hypokalemia and osteoporosis.