Protein-losing gastroenteropathy

　　9. Pathogenic cause

　　There are many gastrointestinal diseases that can cause protein loss. Physiological research has confirmed that only about 10% of the decomposition products of plasma albumin and globulin are excreted from the intestine, therefore, it is considered that the loss of gastrointestinal protein in normal people under physiological conditions can be ignored.

　　7. Pathogenesis

　　The pathogenesis of protein-losing enteropathy mainly has three aspects:

　　5. 1. Mucosal erosion or ulceration of the gastrointestinal mucosa leads to protein exudation or leakage.

　　4. Mucosal cell injury or deficiency, widened intercellular tight junctions, leading to increased mucosal permeability, and plasma protein leakage into the intestinal lumen.

　　3. Intestinal lymphatic obstruction, increased interstitial pressure between the intestines, causes the protein-rich interstitial fluid not only to remain in the interstitium or be absorbed into the blood circulation, but also to overflow into the intestinal lumen and be lost. The mechanism of protein loss in enteropathy caused by intestinal inflammation is not yet clear, and it may be due to the exudation of extracellular fluid and inflammatory fluid in the inflammatory area.

　　Under normal circumstances, the amount of plasma protein that leaks into the gastrointestinal tract is not much, it is estimated that these proteins are less than 6% of the blood circulation albumin, only equivalent to 10% to 20% of the daily decomposition rate of these plasma proteins, of which more than 90% are digested and reabsorbed, therefore, the decomposition metabolism of the gastrointestinal tract does not occupy an important position in the total decomposition metabolism of plasma proteins.

　　In protein-losing enteropathy, the loss of plasma proteins from the gastrointestinal tract is far beyond the normal loss. The daily degradation rate of protein in the gastrointestinal tract can reach 40% to 60% or more of the total circulating plasma protein. The loss of protein from the gastrointestinal tract in protein-losing enteropathy is unrelated to the molecular weight of the protein. A large amount of plasma protein leaks into the gastrointestinal tract, causing the half-life of plasma proteins to shorten and the turnover rate to accelerate. Studies have shown that in this disease, due to the leakage of plasma proteins from the gastrointestinal mucosa regardless of their molecular size, the plasma proteins with slower synthesis rate and/or longer half-life decrease more significantly. Albumin and IgG have a longer half-life, even if the body compensates for synthesis, its ability is limited; the rate of albumin synthesis in the liver can be increased by at most 1 times; while the synthesis of IgG and other immunoglobulins is not stimulated by the decrease in plasma concentration, so the plasma concentration of albumin and IgG decreases the most in this disease, causing patients with this disease to often have hypoalbuminemia. Plasma proteins with fast turnover rate and short half-life, such as transferrin, ceruloplasmin, and IgM, are not easily affected, and only slightly decreased in this disease. While fibrinogen has the shortest half-life and the fastest synthesis rate, so the plasma concentration is generally normal. Proteins lost into the gastrointestinal cavity are decomposed into amino acids and peptides in the intestinal lumen and reabsorbed into the blood circulation, serving as the nitrogen source of the body. If a large amount of protein is lost into the gastrointestinal tract, enters the intestine quickly, or the intestinal peristalsis is fast, then a large amount of protein will be excreted from the intestine. Those who lose protein from the intestine due to intestinal lymphatic obstruction may also have a decrease in blood lymphocytes due to the loss of lymphocytes from the intestine. In addition, other plasma components such as copper, calcium, iron, and lipids can also be lost from the gastrointestinal tract.

　　What complications can protein-losing enteropathy easily lead to

　　1. Mainly due to the decrease in plasma albumin and IgG, early symptoms often include fatigue, weight loss, weakness, and decreased sexual function. In severe deficiency, dry skin, desquamation, hyperpigmentation, and sometimes bedsores, dry and brittle hair, and easy hair loss may be seen. There may be inattention, decreased memory, excitability, and even apathy. Some patients, especially children, may have growth and development disorders, even death.

　　1. Clinical manifestations of the primary disease

　　Symptoms and signs vary due to the primary disease.

　　2. Hypoproteinemia

　　Decreased levels of plasma albumin, gamma globulin (IgG, IgM, IgA, but often without IgE), human fibrinogen, transferrin, lipoproteins, and serum ceruloplasmin.

　　3. Lower limb edema

　　Due to the decreased colloid osmotic pressure of plasma, there is an increased exudation of fluid from capillaries, although systemic edema is very rare, but edema of the upper limbs or face and/or unilateral edema can be seen in the expansion of lymphatics. If it is only a decrease in serum proteins but the reduction of albumin is not obvious, it is almost very rare to appear clinical symptoms.

　　4. Indigestion

　　Fat and/or carbohydrate malabsorption can cause diarrhea and clinical manifestations of fat-soluble vitamin deficiency.

　　5. Immune function decline

　　Lymphatic obstruction and lymphocytopenia can reduce the patient's cellular immune function.

　　1. Effective treatment for the etiopathology of protein-losing enteropathy is the key to prevention.

　　2. Provide adequate nutrition, increase the supply of animal protein, plant protein, and fresh vegetables. Avoid rough and刺激性食物, avoid hard, spicy, salty, hot, excessively rough, and strongly stimulating foods.

　　3. Relax, as stress is a promoting factor for chronic gastritis and should be avoided. Emotional unrest and impatience are easy to cause mucosal disorders and functional disorders of the stomach.

　　1. 51Cr-chloride琥珀胆碱

　　In the past, the diagnosis of protein-losing enteropathy relied on measuring the stool loss of radioactive macromolecules injected intravenously to determine the diagnosis of protein-losing enteropathy. Although this test is relatively precise, these experiments involve exposure to radioactive activity and are cumbersome, expensive, and inconvenient, and therefore are not suitable for routine clinical examinations in children.

　　2. α1-antitrypsin test

　　A glycoprotein synthesized by the liver, the main inhibitor of human serine kinases, this protein has a molecular weight similar to that of albumin and constitutes 5% of total serum protein. Due to its antiproteinase activity, α1-antitrypsin is rarely digested by intestinal kinases and is mainly excreted in its original form in stool. Its excretion, unlike other proteins or fecal nitrogen, can therefore be used as an indirect measure of albumin lost in the gastrointestinal tract. Researchers have used the concentration of α1-antitrypsin in randomly dried stool to measure the amount of protein lost in the gastrointestinal tract.

　　More recently, researchers have quantitatively measured α1-antitrypsin in plasma and collected stool at regular intervals to measure this protein, calculating the α1-antitrypsin clearance and expressing it as ml/d. The literature indicates that there is no correlation between the random stool concentration of α1-antitrypsin and the measurement of its clearance. It is currently considered that the plasma α1-antitrypsin clearance is the best method for detecting gastrointestinal protein loss (in adults or children), but this method is only suitable for detecting protein loss from the pylorus to the colon because this protein cannot be detected when the pH of gastric juice is less than 3, and at the same time, due to the significantly higher concentration of α1-antitrypsin in meconium than in stool, this test cannot be performed in infants under one week old.

　　In patients without diarrhea, the clearance value of α1-antitrypsin is greater than 24ml/d; in patients with diarrhea, the clearance of α1-antitrypsin is greater than 56ml/d, indicating abnormal gastrointestinal protein loss. There is a good negative correlation between α1-antitrypsin clearance and serum albumin concentration. When serum albumin is less than 30g/L and α1-antitrypsin is greater than 80ml/d, the diagnosis is clear. Positive occult blood in stool can cause abnormal α1-antitrypsin clearance because intestinal bleeding can significantly increase the clearance of the intestines, thus, it is easy to cause misdiagnosis. The sensitivity of α1-antitrypsin in the diagnosis of intestinal protein loss is 58%, and the specificity is 80%.

　　3. X-ray examination

　　Gastrointestinal X-ray examination is of great significance for differential diagnosis, especially the following X-ray signs: giant thickening of gastrointestinal mucosal folds (seen in hypertrophic secretory gastritis); X-ray signs of malabsorption (intestinal lumen dilation, snowy or feather-like barium sedimentation, barium distributed in segmented form, seen in various protein-losing enteropathies with malabsorption); general thickening of small intestinal mucosal folds (lymphoma, Crohn's disease, primary intestinal lymphangiectasis, or secondary intestinal lymphatic obstruction); nodular changes of small intestinal mucosa followed by pressure sign (lymphoma, Crohn's disease), abdominal CT scan helps to detect enlargement of mesenteric lymph nodes, etc.

　　4. Small intestinal mucosal biopsy

　　Multiple small intestinal mucosal biopsies are significant for the diagnosis of lymphoma, celiac disease, eosinophilic gastroenteritis, collagenous gastroenteritis, intestinal lymphangiectasis, Whipple's disease, etc.

　　5. Lymphangiography

　　Foot lymphangiography is very helpful in distinguishing congenital or secondary intestinal lymphangiectasis, the former showing poor development of surrounding lymphatics and thoracic duct lesions, with contrast medium retained in the para-peritoneal lymph nodes, but the mesenteric lymphatic system is not engorged; the latter, contrast medium can reflux into the dilated mesenteric lymphatics and overflow into the intestinal lumen or peritoneal cavity.

　　6. Ascites examination

　　Patients with ascites can undergo diagnostic puncture to examine ascitic cells, protein, chyle microparticles, enzymes, malignant cells, etc.

　　First, a therapeutic diet for protein-losing enteropathy (the following information is for reference only, detailed information needs to be consulted with a doctor)

　　1. Braised tofu with water chestnut meat:Fresh water chestnut meat (rubbed off the thin skin and washed) 200 grams, fresh mushrooms (cut off the stems, washed) 100 grams, soft tofu 350 grams, salt, monosodium glutamate, and sesame oil as needed. Cut each water chestnut into 4 pieces, cut the mushrooms into 4 sections, and set the tofu in small pieces aside. Place the wok over high heat, heat the oil to about 70 degrees Celsius, add the water chestnut meat to the pot, fry for a moment, then remove and drain the oil. Heat the wok again, add oil to about 70 degrees Celsius, add ginger slices, stir-fry until fragrant, add tofu, fry for a moment, add water, add the water chestnut meat, mushrooms, and salt, cover and cook for 10 minutes, add monosodium glutamate for seasoning, drizzle with sesame oil, and serve in a dish. It is suitable for eating with meals and is beneficial for invigorating the stomach and benefiting the middle.

　　2. Dried Red Date Duck:1 duck (about 750 grams in weight, slaughtered, plucked and cleaned of internal organs, with the beak and claws cut off, the duck is salted and scraped clean, the duck meat is washed with warm water, drained and set aside), dried red dates (cleaned, soaked in warm water for 2 hours) 60 grams, scallions, ginger, yellow wine, salt, and monosodium glutamate as needed. Place the wok over high heat, heat the oil to about 80 degrees Celsius, add the duck meat, dried red dates, ginger slices, scallion segments, yellow wine, salt, and simmer over low heat for 2 hours, then remove the duck meat, cut into pieces, arrange in the shape of a duck, place the dried red dates on top, remove the scallion segments and ginger slices from the pot, add monosodium glutamate, thicken with wet starch, pour over the duck meat, and it is ready to serve. It is suitable for eating with meals and is beneficial for nourishing the stomach, benefiting the heart and spleen, and replenishing Qi and producing body fluid.

　　3. Winter Melon Soup Ingredients:50 grams of ham, 250 grams of winter melon, appropriate amounts of salt and monosodium glutamate. Wash 50 grams of ham with warm water, place it in a bowl, steam for 30 minutes; peel, remove the seeds and flesh of the winter melon, and clean it. Cut the ham into slices 3 cm long and 1.5 cm wide, and cut the winter melon into strips 4 cm long and 1.5 cm wide. Place the winter melon pieces in the pot, add enough water, bring to a boil over high heat, then reduce to medium heat, cook until seven degrees of maturity, add the ham slices, and add salt, cook until the winter melon is tender, and season with monosodium glutamate. It is beneficial for nourishing the stomach, benefiting the spleen, and promoting diuresis.

　　4. Braised Carp with Ginseng:100 grams of fresh ginseng; 20 grams of prepared Radix Astragali, soaked in water for 1 hour; 1 carp (about 750 grams in weight), killed, with gills, scales, fins, and internal organs removed, cleaned; 30 grams of mushrooms soaked in water; appropriate amount of seasoning. Cut the fish body into a cross pattern on both sides; cut the fresh ginseng diagonally. Heat the wok over high heat, add peanut oil and heat to 160°C, fry the carp to a golden yellow, pour in cooking wine, and drain the oil. In the wok over high heat, add lard and sugar and stir-fry to a date red color, add scallions and garlic, then add clear soup, add the fried carp, and add ginseng slices and Astragalus slices, bring to a boil, then simmer over low heat until the soup thickens. Remove the fish and place it on a plate. Add the Astragalus slices, ginseng slices, and mushrooms to the pot, cook for a while, add salt, monosodium glutamate, and soy sauce, thicken with wet starch, pour in lard, and pour it over the fish. Eat the ginseng slices together. It is used for side dishes and is beneficial for replenishing middle qi and benefiting the spleen and stomach.

　　5. Astragalus and Chicken Gizzard Porridge:12 grams of raw Astragalus, 10 grams each of raw Coix Seed and red bean, 7 grams of chicken gizzard powder, 1 piece of golden pomelo cake, and 80 grams of glutinous rice. Boil the raw Astragalus in water for 20 minutes, strain the juice, add Coix Seed, red bean, and glutinous rice to cook into porridge, and then add the chicken gizzard powder. It is beneficial for stomach health and protein supplementation.

　　What foods are good for the body for protein-losing gastrointestinal disease?

　　1. Eat more vegetables and fruits rich in vitamin C.

　　2. Provide high-protein, high-fat, high-calorie, low-carbohydrate, low-fiber, and easily digestible foods. Pay attention to supplementing various vitamins and minerals such as iron, potassium, sodium, and chlorine, which can be obtained from foods such as lean meat, fish, liver, whole wheat bread, potatoes, and peanuts.

　　3. Consume nutritious and easily digestible soft foods, such as noodles, rice porridge, and milk for breakfast.

　　4. Meat, liver, kelp, mushrooms, spinach, and rapeseed can meet the daily iron requirement of 20 milligrams for adults under 50 years old.

　　What foods should be avoided for protein-losing gastrointestinal disease?

　　1. Eat less fried food, as these foods are difficult to digest and can increase the burden on the digestive tract. Eating too much can cause indigestion and increase blood lipids, which is harmful to health.

　　2. Eat less salted food, as these foods contain a lot of salt and certain carcinogens, which are not suitable for eating in large quantities.

　　3. Eat less cold and spicy foods, as these foods have a strong stimulating effect on the mucous membrane of the digestive tract, which can easily cause diarrhea or inflammation of the digestive tract.

　　4. Drink less alcohol and eat less spicy food such as chili and pepper.

　　5. Avoid acidic foods, fruits with high acidity, such as: pineapples, mandarins, oranges, etc.

　　1. Surgical Treatment

　　Protein-losing gastrointestinal disease is a clinical syndrome. Various effective treatment measures should be adopted according to different etiologies. Symptomatic treatment includes a low-salt diet, diuretics, etc., and intravenous administration of human serum albumin has only temporary effects.

　　1. Etiological Treatment: Identify the etiology and treat the primary disease. Only by completely curing the etiology that causes protein-losing gastrointestinal disease can the disease be cured. Once the etiology is clear, appropriate treatment should be given. It should be pointed out that some etiologies that cause this disease can only be cured by surgical treatment, such as malignant tumors, restrictive pericarditis, and giant hypertrophic gastritis, etc. Only when the etiology is not yet clear, or effective treatment cannot be taken for the etiology, can symptomatic supportive treatment be adopted.

　　2. Symptomatic supportive treatment for edema or serous cavity effusion caused by hypoproteinemia can be appropriately selected with diuretics, supplemented with human serum albumin; for those with steatorrhea and vitamin deficiency, pancreatic enzyme preparations and vitamins can be supplemented. (1) Diet: High-protein and high-calorie diet should be provided, and for those with severe edema, a low-salt diet should be given; for patients with lymphatic obstruction, low-fat or medium-chain triglycerides (MCT) treatment should be provided to reduce the burden on the intestinal lymphatics. (2) Diuretics: Potassium-sparing and potassium-wasting diuretics can be used together, such as spironolactone and thiazide drugs, and potent diuretics such as furosemide can be used when necessary to reduce edema and decrease ascites. (3) Correcting hypoproteinemia: As previously mentioned, intravenous administration of human serum albumin has only temporary effects and is generally not recommended to correct hypoproteinemia solely by transfusion of human serum albumin, but it is preferable to increase plasma protein concentration through etiological treatment and dietary regulation. (4) Antibiotics for infections: Vitamin deficiency should be supplemented with vitamin groups, and calcium, magnesium, and other supplements should be given if there are convulsions.

　　2. Surgical Treatment

　　For localized protein-losing gastrointestinal diseases, local resection surgery can be performed, such as partial small intestine resection for lymphangiectasis limited to a segment of the small intestine.