Gastrointestinal manifestations of amyloidosis
Introduction
Introduction to gastrointestinal manifestations of amyloidosis Amyloidosis refers to a disease caused by the deposition of -structured fibrin-based amyloid in extracellular tissues of organ tissues. Amyloid protein exhibits fine fiber agglomeration under electron microscopy and is reflected by X-ray diffraction as a protein of antiparallel hydrogen-bound polypeptide chain structure. basic knowledge Sickness ratio: 0.001%-0.005% Susceptible people: no specific people Mode of infection: non-infectious Complications: intestinal obstruction
Cause
Gastrointestinal manifestations of amyloidosis
(1) Causes of the disease
Amyloid deposition in the organ tissue extracellularly, causing multiple organ dysfunction in the body. In the past, it was generally divided into: primary causes; myeloma, secondary, focal, genetic Sex and other rare types.
Most of the amyloid proteins of primary and myeloma amyloidosis are derived from the L-chain immunoglobulin-AL protein. Secondary amyloidosis can be induced by many diseases. Local amyloidosis is a single organ starch. Deposition of the sample, does not affect the whole body, hereditary amyloidosis is mostly autosomal dominant, represented by familial amyloid polyneuropathy (FAP), but familial Mediterranean fever is autosomal recessive In addition to focal, all of the above types are multi-systemic lesions, which are collectively referred to as systemic amyloidosis, but in fact, the amyloid fibrosis of the digestive wall of FAP with high incidence of digestive tract symptoms is lighter than other types. According to the study, the degree of FAP digestive tract symptoms is not related to the degree of amyloid fibrosis deposition in biopsy. The lesions of the digestive tract autonomic nerve of FAP are severe. According to autopsy, the vagus trunk, the epicardium and the endometrium are all visible. The amyloid fibrils deposit, the myelinated nerve fibers disappear almost completely, and amyloid fibrils can also be found in the celiac ganglia. The plexus (Meissner plexus and Auerbach plexus) showed a significant decrease in amyloid fibrosis and ganglion cell count. The catecholamine fluorescence method was used to perform autonomic nerve fiber examination on the rectal mucosa. In the case of FAP, catecholamine-containing nerves were seen from the early stage. The severe shedding of the fibers shows the denervation state of the digestive tract, and the same autonomic neuropathy of the digestive tract is also seen in the primary and amyloidosis of the myeloma, the starch fiber of the digestive tract and a wide range. The autonomic dysfunction causes a variety of gastrointestinal symptoms of systemic amyloidosis.
In recent years, the classification of fibrin categories according to deposition has been gradually established because the difference in affinity of different types of fibrin to deposited tissues has been clarified.
1. AL protein has high affinity for amyloid protein in the digestive tract, causing systemic amyloidosis. The whole and part of the variable region of the immunoglobulin L chain is called AL protein. The onset of amyloidosis is more than 40 years old. The cause is unknown. It occurs in patients who have been completely healthy in the past, and has no disease-inducing disease. Amyloid protein with myeloma amyloidosis is also derived from the L-chain immunoglobulin-AL protein. It is formed by deformation of the L chain of the M protein in the serum of the patient or the decomposition product of the peri-protein in the urine.
2. AA protein in inflammation, infection, the clinical encounter is mostly increased serum amyloid A protein (SAA) as a precursor of amyloid A protein (AA protein), hydrolyzed by SAA It consists of 76 amino acids, independent of 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, fungal disease, etc.; also seen in tumors, such as Hodgkin disease, medullary thyroid carcinoma.
(two) pathogenesis
Regarding the mechanism of the occurrence of gastrointestinal symptoms in amyloidosis, it has been considered in the past two aspects:
1. Due to the amyloid fibrosis of blood vessels in the wall of the digestive tract, it causes ischemia in the digestive tract.
2. Muscle damage, motor function is weakened.
In the wall of the digestive tract with obvious amyloid fibril deposition, it can be seen by the naked eye that the whole tube wall becomes hard, thick and inelastic, and there are many small particle bulges on the serosal surface. The above changes sometimes do not necessarily affect the entire digestive tract, but present Segmental distribution, sometimes showing a part of the intestinal tube significantly expanded, histological observations are mostly limited to autopsy cases, amyloid fibrin deposition can be seen in all layers of the digestive tract, the most obvious vascular wall of the submucosal tissue, followed by the muscularis and mucosa In the layer, the wall of the amyloid fibrils is thickened, the cavity is narrow, and the connective tissue around the blood vessels can also be seen in the deposition of amyloid fibrils, especially in the areas where the mass formation and the wall hypertrophy are obvious, and the amyloid deposition of the muscularis propria is significant.
The degree of amyloid fibrosis deposition in the stomach, small intestine, and large intestine varies among the types and between individuals, and is obvious in primary and concomitant myeloid amyloidosis, but in patients with FAP. It is obvious that the amyloid deposition of the stomach and small intestine and the deposition of the lamina propria of the mucosa are also obvious. In the primary amyloidosis and FAP, the amyloid fibrils deposit in the gastric mucosa are severe.
Prevention
Prevention of gastrointestinal manifestations of amyloidosis
prevention:
1. Because the cause of amyloidosis is unclear, there is no way to prevent primary amyloidosis.
2. Secondary amyloidosis can only initiate inflammatory diseases of amyloidosis, such as tuberculosis and rheumatoid arthritis, by prophylactic or effective treatment. If drugs can be used to control rheumatoid arthritis, the likelihood of developing secondary amyloidosis is reduced.
Complication
Gastrointestinal manifestations of amyloidosis Complications, intestinal obstruction
1. Bleeding, infarction, perforation of amyloid to capillary deposition may cause ischemia, erosion, and even ulceration due to vascular disorders. Hemorrhage may occur in ulcer bleeding, blood in the stool, and infiltration of the sigmoid colon and ileum.
2. Intestinal obstruction A large number of amyloid deposits in the gastrointestinal smooth muscle, and then autonomic nervous disorders cause motor dysfunction, causing symptoms of digestive tract obstruction.
Symptom
Gastrointestinal symptoms of amyloidosis common symptoms nausea constipation mucosa dry diarrhea bloody abdominal pain giant tongue
Digestive symptoms are often the core symptoms of systemic amyloidosis. Primary amyloidosis is the most significant, and different lesions can present different clinical symptoms.
1. Nausea, vomiting, loss of appetite, and deposition of amyloid fibrils in the muscular layer of the digestive tract mucosa and the muscularis propria, leading to dysfunction of the digestive tract, difficulty in the esophagus, difficulty in the stomach, stagnation of the contents of the stomach, nausea, vomiting, loss of appetite And other symptoms.
2. Constipation, diarrhea, lowering of the amyloid fibrils in the digestive tract leads to constipation or diarrhea. Intractable constipation will turn into severe diarrhea after using laxatives, and then change to constipation and diarrhea. When there is severe diarrhea, there may be fecal incontinence, and there are complaints about abdominal pain. Amyloidosis should be suspected of long-lasting diarrhea that is resistant to treatment.
3. The incidence of malabsorption malabsorption is 4.0% to 5.8%. The deposition of amyloid fibrils in the small intestine leads to atrophy, erosion and vascular dysfunction of the mucosal epithelium. In a few cases, malabsorption syndrome can occur, which is characterized by steatorrhea and giant red blood cells. Anemia or protein leakage enteropathy.
4. Bleeding, infarction, perforation of amyloid to capillary deposition may cause ischemia, erosion, and even ulceration due to vascular disorders. Ulcer may occur in any part of the digestive tract. Ulceration may occur in hemorrhage, blood in the stool, and sigmoid colon. Case report of infarction and ileum perforation.
5. Intestinal obstruction A large number of amyloid deposits in gastrointestinal smooth muscle deposition, and then autonomic dysfunction causes motor dysfunction, the incidence rate is 6% to 8%. The so-called amyloid tumor occurs in the antral pylorus and distal colon. Like the malignant tumors in the same site, it can cause symptoms of digestive tract obstruction. Patients with no organic stenosis may sometimes have symptoms of acute intestinal obstruction. Iegge et al. refer to this state as pseudo-intestinal obstruction, amyloid tumor. Common in primary and concomitant myeloid amyloidosis, a large number of gas images can be seen in the abdomen during intestinal obstruction.
6. Other giant tongue is a characteristic local sign of amyloidosis. It is found in 20% of patients, often accompanied by submandibular gland, sublingual gland and other parotid gland enlargement, patient's taste loss, salivary secretion decreased, oral mucosa Dryness, gingival and oral mucosa are prone to hemorrhage, and can form a small hematoma of the tongue and buccal mucosa. The latter two are common in primary amyloidosis, and the pharyngeal muscle dyskinesia (lower brain due to amyloid fibrosis infiltration) Patients with severe neurological paralysis and local amyloid fibrosis) and esophageal lesions often complain of dysphagia but are not seen in FAP patients.
Examine
Examination of gastrointestinal manifestations of amyloidosis
There are no abnormalities in blood routine and erythrocyte sedimentation test. About 50% of patients may have elevated serum creatinine levels. About 80% of patients may have proteinuria. One third of patients with multiple myeloma may develop hypercalcemia. Globulin examination revealed a decrease in IgG levels, and 2/3 of AL-type amyloidosis patients showed monoclonal antibodies by serum immunoelectrophoresis, 45% were monoclonal immunoglobulin heavy chains, and 20% were light chains (Bence Jones proteinemia) ), concentrated urine for immunoelectrophoresis showed that about 2 / 3 patients can find monoclonal light chain ( / = 2 / 1).
1. X-ray examination of gastrointestinal sputum angiography is characterized by poor dilatation of the digestive tract and weakening of peristalsis. The lesions of the stomach are wide. From the stomach to the antrum of the stomach, often accompanied by food residues, the mucosal morphology of the small intestine is rough and visible. Local stenosis and dilatation, gastric emptying and small intestine transit time are significantly prolonged, the image of the large intestine is the colonic bag disappears, the whole colon is stiff, and other manifestations include duodenal ampulla or ileum terminal polypoid changes, but FAP is generally Lack of wall sclerosis, the stomach, small intestine sputum transit time can be delayed or hyperthyroidism.
2. Endoscopy The color of the gastric mucosa under endoscopy is yellow, often accompanied by scattered leukoplakia. Mucosal folds can be red, swollen and hypertrophic, but these manifestations are lack of specificity. Colonoscopy often observes ulcerative colitis. Similar manifestations, namely mucosal edema, erosion, diffuse mucosal redness and ulceration, and some may also have polypoid changes. When the lower digestive tract has obstructive symptoms, the sigmoid colon can sometimes see bulge that is difficult to distinguish from Borrmann type III cancer. ulcer.
3. Biopsy The only diagnostic method for this disease is to confirm the deposition of amyloid fibrils in biopsy tissues. The biopsy sites of systemic amyloidosis in the past were gums, tongue, small intestine, and rectum. Among them, rectal biopsy is the most common. It is simpler than the rectal biopsy and the diagnosis rate is high. If necessary, biopsy can be performed on the stomach and rectum. The biopsy should be taken with sufficient depth. For this reason, the endoscope should be inserted with less gas and the site with good vision should be selected. Use a larger biopsy forceps, after the pliers are in contact with the mucosa, a little pressure should be applied to make the material as deep as possible. The gastric biopsy should take the mucosal muscle layer. Generally, 5 to 6 tissues are needed from the stomach angle to the gastric antrum. It is necessary to take the submucosal tissue for biopsy. Generally, 5 to 6 pieces of tissue are taken from the posterior wall 10 to 15 cm away from the anus. After biopsy, attention should be paid to hemostasis. The biopsy tissue is observed by Congo red staining under a polarizing microscope to observe the unique green color of amyloid protein. Refraction can be diagnosed. It is difficult to determine the classification of amyloidosis based on the amyloid fibrin deposition type on biopsy specimens. Specific tissue observation requires confirmation by electron microscopy. Amyloid fibrils, and apply various types of immunohistochemical staining comprehensive determination amyloid.
Diagnosis
Diagnosis and differential diagnosis of gastrointestinal manifestations of amyloidosis
For the giant tongue and a variety of digestive symptoms should be thought of this disease, early endoscopic examination of parallel mucosal biopsy, to determine the diagnosis of biopsy-dependent tissue confirmed amyloid fibrosis.
Due to the occurrence of progressive systemic failure and various gastrointestinal symptoms, this disease needs to be differentiated from gastrointestinal malignant tumors. Due to abnormal movement of the digestive tract, especially in patients with alternating constipation and diarrhea, it is necessary to distinguish from gastrointestinal lesions of diabetes. At the same time, attention should be paid to the differentiation of ulcerative colitis, Crohn's disease and ischemic enteritis.
