Gastrointestinal manifestations of amyloidosis

　　1. Etiology

　　Amyloid deposits in the extracellular space of organ tissue cells progressively accumulate, causing dysfunction of multiple organs in the body. In the past, amyloidosis was generally classified according to the cause of the disease as: primary; associated with multiple myeloma; secondary; focal; hereditary; and other rare types.

　　Most primary and secondary amyloidosis associated with myeloma originate from the L chain of immunoglobulins - AL protein. Secondary amyloidosis can be induced by many diseases. Focal amyloidosis is the deposition of amyloid material in a single organ without affecting the whole body. Hereditary amyloidosis is mostly autosomal dominant inheritance, represented by familial amyloid polyneuropathy (FAP), but familial Mediterranean fever is autosomal recessive inheritance. In addition to focal amyloidosis, the above types are all multi-systemic damage and are collectively known as systemic amyloidosis. However, the amyloid fibrin deposition in the gastrointestinal tract of FAP, which has a high incidence of gastrointestinal symptoms, is lighter than that of other types. According to research, there is no correlation between the degree of gastrointestinal symptoms in FAP and the degree of amyloid fibrin deposition observed in biopsies. The autonomic neuropathy in the gastrointestinal tract of FAP is severe. According to post-mortem examination, there is significant amyloid fibrin deposition in the main trunk of the vagus nerve, the perineurium, and the endoneurium. The medullary nerve fibers almost completely disappear, and amyloid fibrin deposition can also be found in the celiac plexus. Amyloid fibrin deposition and a significant reduction in the number of ganglion cells can be seen in the nerve plexuses of the gastrointestinal tract wall (Meissner's nerve plexus and Auerbach's nerve plexus). The examination of autonomic nerve fibers in the rectal mucosa using the catecholamine fluorescence method shows severe shedding of nerve fibers containing catecholamines in FAP cases from an early stage, indicating the denervation state of the gastrointestinal tract. The same autonomic neuropathy in the gastrointestinal tract is also observed in primary and secondary amyloidosis associated with myeloma. The amyloid fibrin deposition in the gastrointestinal tract and the extensive autonomic nerve disorders have caused a variety of gastrointestinal symptoms in systemic amyloidosis.

　　In recent years, due to the clarification of the differences in the affinity of different types of fibrin for deposited tissues, the classification according to the type of deposited fibrin has gradually been established.

　　1, Amyloid proteins with high affinity for the gastrointestinal tract, mainly caused by the variant region of the L chain of immunoglobulins, are often associated with systemic amyloidosis. The amyloid protein in primary amyloidosis usually occurs in people over 40 years old, with an unknown cause and occurs in previously healthy individuals without any precipitating diseases. The amyloid protein in amyloidosis associated with myeloma also comes from the L chain of immunoglobulins - AL protein, which is deformed from the L chain of M protein in the patient's serum or the decomposition products of Benigni protein in the urine.

　　2, AA protein, often encountered in clinical practice during inflammation and infection, is mainly the amyloid A protein (AA protein) as a precursor in the acute phase serum (serum amyloid A protein, SAA). It is hydrolyzed from SAA and consists of 76 amino acids and is unrelated to immunoglobulins. Secondary amyloidosis can be induced by many diseases, such as rheumatoid arthritis, chronic infections including tuberculosis, osteomyelitis, lung abscess, bronchiectasis, chronic pyelonephritis, inflammatory bowel disease, mycosis, and so on; it also occurs in tumors such as Hodgkin's disease and medullary thyroid carcinoma.

　　Second, pathogenesis

　　Regarding the pathogenesis of gastrointestinal symptoms in amyloidosis, it was previously believed that there were two aspects

　　1, Due to the amyloid deposition in the blood vessels within the gastrointestinal wall, gastrointestinal ischemia is caused.

　　2, Muscle layer destruction, weakened motor function.

　　In the wall of the digestive tract with obvious amyloid deposition, macroscopically, the entire wall can be seen to become hard, thickened, and lack elasticity, with many small granules on the serosal surface. These changes may not always affect the entire digestive tract but may present in a segmental distribution, and sometimes part of the intestinal tract may become significantly dilated. Histological observations are mostly limited to autopsy cases. Amyloid deposition can be seen in all layers of the digestive tract, with the vascular wall of the submucosal tissue being the most obvious, followed by the intrinsic muscular layer and mucosal layer. The vascular wall with amyloid deposition becomes thickened, the lumen narrows, and amyloid deposition can also be seen in the connective tissue around the blood vessels. Especially in areas with obvious mass formation and wall thickening, the amyloid deposition in the intrinsic muscular layer is significant.

　　The degree of amyloid deposition in the stomach, small intestine, and large intestine varies between different types and individuals, and is more obvious in primary and associated myeloma amyloidosis, while it is relatively mild in FAP patients. From the perspective of location, the amyloid deposition in the stomach and small intestine, as well as the mucosal intrinsic layer, is also more obvious. In primary amyloidosis and FAP, the amyloid deposition in the gastric mucosa is more severe than that in the large intestine.

　　1, Bleeding, infarction, perforation: Amyloid protein deposition in capillaries can cause ischemia, erosion, and even ulcers due to vascular obstruction, leading to hematemesis and hematochezia. There may also be infarction of the sigmoid colon and perforation of the ileum.

　　2, Intestinal obstruction: Large amounts of amyloid protein沉积 in the gastrointestinal smooth muscle can lead to autonomic nerve disorders and motor dysfunction, causing symptoms of gastrointestinal obstruction.

　　Since the etiology of amyloidosis is unclear, there is no method to prevent primary amyloidosis.

　　When gastrointestinal symptoms of amyloidosis appear, spicy and irritating foods should be avoided. Avoid eating fried and greasy foods such as fried dough sticks, butter, butter, chocolate, etc., as these foods have the effect of moistening and increasing heat, which can increase the secretion of leukorrhea and is not conducive to the treatment of the disease. Quit smoking, alcohol, and other stimulating beverages.

　　Routine blood tests and erythrocyte sedimentation rate (ESR) are usually normal, about 50% of patients may exhibit elevated serum creatinine levels, about 80% may present with proteinuria, one-third of multiple myeloma patients may have hypercalcemia, immunoglobulin tests may reveal decreased IgG levels, and approximately two-thirds of AL-type amyloidosis patients show monoclonal proteins in serum immunoelectrophoresis, 45% are monoclonal immunoglobulin heavy chains, and 20% are light chains (Bence Jones proteinemia). Concentrated urine immunoelectrophoresis shows that about two-thirds of patients may have monoclonal light chains (λ/κ=2/1).

　　1. X-ray examination:The typical manifestations of gastrointestinal barium enema are poor expansion of the digestive tract and reduced peristalsis. The range of gastric lesions is relatively wide, from the corpus to the antrum, often accompanied by food residue retention. The mucosal morphology of the small intestine appears rough, with local narrowing and dilation, and the gastric emptying and small intestinal transit time are significantly prolonged. The image of the large intestine shows the disappearance of the haustra, the entire colon is rigid. Other manifestations include polypoid changes at the ampulla of the duodenum or the terminal part of the ileum. However, FAP patients generally lack wall hardening. The barium passage time in the stomach and small intestine may be delayed or increased.

　　2. Endoscopy:Under endoscopy, the color of the gastric mucosa is yellow, often accompanied by scattered white spots. The mucosal folds can show redness, swelling, and hypertrophy, but these manifestations are all non-specific. Colonoscopy often observes manifestations similar to ulcerative colitis, that is, mucosal edema, erosion, diffuse mucosal erythema, and ulcers. Some may also appear polypoid changes. When there are obstructive symptoms in the lower gastrointestinal tract, an elevated ulcer that is difficult to differentiate from Borrmann III-type cancer can sometimes be seen in the sigmoid colon.

　　3. Biopsy:The only diagnostic method for this disease is to confirm the deposition of amyloid fibers in the biopsy tissue. In the past, the biopsy sites for systemic amyloidosis were gingiva, tongue, small intestine, rectum, among which rectal biopsy was the most common. In recent years, many reports have proposed that gastric biopsy is simpler and has a higher diagnostic rate than rectal biopsy. If necessary, biopsies of both the stomach and rectum can be performed. When biopsying, pay attention to take enough depth, so the endoscope should be inserted with less air, choose a good viewing area, use a larger biopsy forceps, and apply slight pressure after the forceps touch the mucosa to take deeper samples. Gastric biopsy should reach the muscular layer of the mucosa, usually taking 5 to 6 pieces of tissue from the angle of the stomach to the antrum. Rectal biopsy is necessary to reach the submucosal tissue, usually taking 5 to 6 pieces of tissue from the posterior wall 10 to 15 cm from the anus. After biopsy, attention should be paid to hemostasis. The biopsy tissue stained with Congo red can be observed under a polarizing microscope to confirm the unique green birefringence of amyloid protein, which can be diagnosed. It is difficult to determine the type of amyloidosis based on the amyloid fiber deposition pattern in the biopsy specimen. Specific tissue observation requires confirmation of amyloid fibers through an electron microscope and comprehensive determination of the immunohistochemical type of amyloid protein using various stains.

　　First, dietary therapy for gastrointestinal symptoms of amyloidosis (the following information is for reference only, and detailed information should be consulted with a doctor)

　　1. Osmanthus Heart Porridge:50 grams of glutinous rice, 2 grams of osmanthus heart, 2 grams of Poria cocos. Rinse the glutinous rice clean. Put the osmanthus heart and Poria cocos in the pot, add an appropriate amount of water, bring to a boil with strong fire, then simmer over low heat for 20 minutes, filter the residue, and keep the juice. Put the glutinous rice and the juice in the pot, add some water, bring to a boil with strong fire, then simmer over low heat until the rice is soft and forms a porridge. Take once a day, before and after meals.

　　2. Fresh lotus root porridge:An appropriate amount of fresh lotus root, 100 grams of glutinous rice, and a little brown sugar. Wash the fresh lotus root, cut it into thin slices, and clean the glutinous rice. Put the glutinous rice, lotus root slices, and brown sugar in a pot, add an appropriate amount of water, boil it with high heat, then simmer it over low heat until the rice is cooked into porridge. Take twice a day, for breakfast and dinner.

　　3. Orange honey drink:1 orange and 50 grams of honey. Soak the orange in water to remove the sour taste, then peel and cut it into 4 pieces. Put the orange and honey in a pot, add an appropriate amount of water, boil it with high heat, then simmer it for 20 or 25 minutes with low heat. Remove the orange and keep the juice.

　　4. Goji lotus root soup:25 grams of goji berries and 50 grams of lotus root starch. First, boil the lotus root starch with an appropriate amount of water over low heat, then add goji berries, and boil again. It can be eaten after boiling. Take twice a day, 100-150 grams each time.

　　5. Tangerine peel porridge:25 grams of fresh tangerine peel and 50 grams of glutinous rice. First, wash the fresh tangerine peel and cut it into pieces, then cook it with glutinous rice. Eat after the glutinous rice is cooked. Take once a day, for breakfast.

　　6. Honey peach juice drink:20 grams of honey and 1 fresh peach. First, peel and remove the pit of the fresh peach, then press it into juice, and add honey and an appropriate amount of warm water. Take 1 to 2 times a day, 100 milliliters each time.

　　Secondly, what are the gastrointestinal manifestations of amyloidosis and what foods are good for the body?

　　1. Supplement vitamin C:Vitamin C has a protective effect on the stomach. Maintaining a normal level of vitamin C in the gastric juice can effectively exert the function of the stomach, protect the stomach, and enhance the stomach's resistance to diseases. Therefore, it is recommended to eat more vegetables and fruits rich in vitamin C.

　　2. Pay attention to eating nutritious foods:Eat more high-protein and high-vitamin foods to ensure that the body has sufficient nutrients, prevent anemia and malnutrition. For those with anemia and malnutrition, it is recommended to increase the intake of foods rich in protein and heme iron in the diet, such as lean meat, chicken, fish, liver, kidneys, and other internal organs. High-vitamin foods include dark-colored fresh vegetables and fruits, such as green leafy vegetables, tomatoes, eggplants, jujubes, and so on. It is best to eat 2 to 3 fresh hawthorns per meal to stimulate the secretion of gastric juice.

　　3. Pay attention to the acid-base balance of food intake:When there is excessive secretion of gastric acid, drinking milk, soy milk, eating steamed buns or bread can neutralize the gastric acid. When the secretion of gastric acid decreases, concentrated broths, chicken soups, fruits with a sour taste, or fruit juices can be used to stimulate the secretion of gastric juice, aid digestion, and avoid foods that may cause abdominal bloating and those rich in fiber, such as beans, bean products, sucrose, celery, chive, and so on. When suffering from atrophic gastritis, it is advisable to drink yogurt, as the phospholipid substances in yogurt tightly adhere to the gastric wall, providing protection for the gastric mucosa, repairing the injured gastric mucosa. The lactic acid and glucuronic acid produced by the metabolism of the unique component lactose in yogurt can increase the acidity in the stomach, inhibit the decomposition of proteins by harmful bacteria to produce toxins, and at the same time, protect the stomach from the erosion of toxins.

　　Thirdly, what foods should be avoided for the gastrointestinal manifestations of amyloidosis?

　　1. Eat less fried foods:Because these foods are not easy to digest, they increase the burden on the digestive tract, and eating too much can cause indigestion and increase blood lipids, which is harmful to health.

　　2. Eat less preserved foods: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:Cold and strong刺激性 foods have a strong stimulating effect on the mucous membrane of the digestive tract, causing diarrhea or inflammation of the digestive tract easily.

　　4. Avoid stimulation:Do not smoke because smoking causes the constriction of gastric blood vessels, affecting the blood supply to the gastric wall cells, reducing the resistance of the gastric mucosa and triggering stomach diseases. It is advisable to drink less alcohol and eat less spicy foods such as chili and pepper.

　　5. Coffee, alcohol, meat broth, chili, mustard, pepper, etc.:These foods should be avoided as they can stimulate the secretion of gastric juice or damage the gastric mucosa.

　　6. Some foods:It is easy to produce gas, causing a feeling of fullness in patients, so it should be avoided to eat, but whether food will produce gas and cause discomfort varies from person to person, and it can be decided whether to eat according to personal experience. In addition, hard foods such as fried rice, grilled meat, glutinous rice products such as rice cakes and zongzi, various desserts, cakes, fried foods, and frozen food products often cause discomfort to patients and should be chosen with care.

　　1. Symptomatic treatment can be given for general loss of appetite, belching, etc., with exercise promoters. For severe diarrhea and pseudo-obstruction, intravenous hyperalimentation can achieve certain effects. For refractory constipation, tetracycline group antibiotics are effective, using minocycline (dimethyl aminotetracycline) 200mg daily can improve the abnormal defecation in early cases.

　　2. The drug dimethyl sulfoxide (DMSO) has the effect of decomposing amyloid protein and is currently being tested in clinical trials.

　　3. It should be avoided to perform surgery as much as possible because the wound is very difficult to heal.