Blind loop syndrome

　　One, etiology of the disease

　　Under normal circumstances, the stomach and the upper part of the small intestine contain only a small amount of bacteria, which is because the stomach acid and the propulsive movement of the small intestine can inhibit and clear bacteria. Any factor that leads to low stomach acid or causes a slowing down or interruption of intestinal motility can lead to excessive growth of bacteria in the small intestine.

　　1, Bacterial overgrowth in the stomach

　　Low acid or no acid, atrophy of gastric mucosa, post-gastric surgery motility or anatomical abnormalities (such as post-gastrectomy remnant stomach) where there is almost no acid-producing gastric fundic glands containing parietal cells, leading to no acid. In addition, Sachs's research has shown that omeprazole can inhibit the H-K-ATPase in parietal cells, rendering it inactive. The binding of this proton pump inhibitor to the enzyme is irreversible until new enzymes are synthesized and transported to the apical membrane, at which point enzyme activity is restored. This renewal process takes 48 hours, so taking omeprazole once can cause sustained low acid for 48 hours.

　　2, Intestinal stasis

　　(1) Anatomical causes: Billroth II surgery or jejunoileal anastomosis after gastric resection, duodenal jejunal diverticulum, blind loop caused by surgery, re-circulation loop surgery, intestinal stenosis, adhesions, obstruction caused by inflammation and lymphoma.

　　(2) Small intestinal motility disorders: Scleroderma, idiopathic small intestinal pseudo-obstruction, absent or impaired migrating motor complex, diabetic autonomic neuropathy, etc.

　　(3) Abnormal intestinal channels: Gastro-colonic or jejuno-colonic fistula, resection of ileocecal valve.

　　3, Others

　　Chronic pancreatitis, immune deficiency syndrome.

　　II. Pathogenesis

　　1, Overgrowth of bacteria in the small intestine can directly or indirectly affect the structure and function of the intestine, causing malabsorption. When bacteria overgrow in the small intestine, they can compete with the host for vitamin B12 in the diet. Although intrinsic factor can inhibit the competition of aerobic bacteria for vitamin B12, slowing down their uptake of vitamin B12, intestinal stasis can provide time for them to absorb it. Moreover, intrinsic factor cannot inhibit the uptake of vitamin B12 by Bacteroides, and although the intestinal bacteria themselves can synthesize vitamin B12, it is firmly bound within the bacterial body and cannot be utilized by the host. Therefore, vitamin B12 deficiency may occur, and it cannot be corrected by oral administration of intrinsic factor. However, since the folic acid synthesized by the intestinal bacteria can be released into the intestinal lumen and utilized by the host, folate deficiency does not occur.

　　2, Overgrowth of bacteria in the small intestine can interfere with the metabolism of bile salts, causing conjugated bile salts to be broken down into free bile salts, which are rapidly reabsorbed by the small intestine. The reduction in conjugated bile salts makes it difficult for micelles to form, leading to poor fat absorption and diarrhea. In addition, when the concentration of free bile acids in the intestinal lumen reaches a certain level, it can also damage the submicroscopic structure of the absorbing epithelial cells, affecting the absorption of sugars and proteins.

　　1, Anemia and gastrointestinal bleeding: Typical cases present with macrocytic hyperchromic anemia due to a lack of vitamin B12. Sometimes, due to mucosal injury leading to ulcer formation or vitamin K deficiency causing skin and mucosal bleeding, small cell hypochromic iron deficiency anemia or mixed anemia may occur due to bleeding. Occasionally, there may be massive gastrointestinal bleeding.

　　2, Hypoproteinemia: 70% to 90% of patients with hypoproteinemia, which is the main manifestation of the disease, mainly due to the influence of intestinal bacteria on amino acid absorption and protein loss. Nutritional edema may occur.

　　3. Weight loss is caused by malnutrition due to long-term malabsorption of nutrients such as fat, protein, and sugars.

　　1. Clinical manifestations vary greatly due to different causes, generally including symptoms of malabsorption and primary diseases. Mild cases may only have mild diarrhea, mild anemia, and weight loss, while severe cases may often have watery diarrhea, steatorrhea, bloating, anemia, weight loss, and in severe cases of fat malabsorption, rickets, night blindness, or hypocalcemic convulsions may occur. A lack of vitamin K may cause bleeding of the skin and mucous membranes.

　　2. Anemia is often due to a lack of vitamin B12, which belongs to macrocytic anemia. Sometimes, small cell anemia or mixed anemia may occur due to ulceration caused by retention in the intestinal loop.

　　3. Hypoproteinemia is common, which may lead to malnutrition edema.

　　4. Primary diseases such as blind loops formed by surgery or small intestinal stenosis may cause abdominal discomfort, bloating, diarrhea, accompanied by spasmodic pain around the umbilicus before diarrhea and anemia. Generally, there is a relatively long interval between the formation of blind loops and excessive bacterial overgrowth, ranging from a few months to several years. Sometimes, the primary disease may even mask the symptoms of excessive bacterial overgrowth, such as intestinal stenosis or fistula caused by Crohn's disease, weakened intestinal motility caused by scleroderma or pseudo-obstruction, and it is difficult to distinguish between malabsorption caused by primary diseases such as Crohn's disease, radiation enteritis, short bowel syndrome, and lymphoma. Intestinal diverticula are more common in the elderly, and there is a long interval between diverticula and excessive bacterial overgrowth. Initially, there may be no symptoms, and later, steatorrhea and anemia may appear.

　　Blind loop syndrome should inhibit excessive bacterial overgrowth in the small intestine and support treatment. Even if the overgrowth is satisfactorily controlled, nutritional support therapy is also necessary. Patients with steatorrhea can reduce the fat content in their diet or replace part of the fat with medium-chain triglycerides. Appropriate supplementation of vitamin B12, vitamin K, and calcium is also required. The use of prokinetic drugs may help clear excessive bacterial overgrowth, but whether it is effective for anatomical abnormalities such as blind loops and multiple diverticula is unknown, and it may also worsen malabsorption of the primary disease.

　　1. Bacterial culture of small intestinal contents

　　The collection of small intestinal contents should be done by multi-point sampling, with various specific methods. Direct vision small intestinal puncture for fluid extraction during abdominal surgery is the most accurate, but it has little practical value. Currently, the most commonly used method in China is to extract small intestinal fluid through endoscopic catheter or small intestinal catheter, which is relatively reliable with a low contamination rate. It is necessary to discontinue antibiotics for at least one week before the examination and fast for at least 8 hours. The specimen should be avoided from being contaminated or diluted by saliva, and must be obtained under anaerobic conditions. After serial dilution, it should be inoculated into several culture media and incubated under anaerobic conditions, which may result in different numbers of Bacteroides, anaerobic Lactobacillus, Escherichia coli, and Enterococcus. A bacterial count exceeding 10^5/ml is considered to have clinical significance and is often used as a control standard for other tests such as breath tests. This test is relatively complex and time-consuming, and the overgrowth of bacteria within the loop may lead to missed diagnoses. In addition, it is also difficult to extract the contents of the distal small intestine.

　　2. Urobilinogen determination

　　Urobilinogen is a product of the decomposition of tryptophan by intestinal bacteria, which is excreted in urine after absorption. In normal people, it is negative or light blue, and a deeper color suggests overgrowth of bacteria. The operation is simple but both sensitivity and specificity are poor, and it is now rarely used.

　　3. Measurement of jejunal fatty acids and jejunal bile acids

　　It has good diagnostic value, but obtaining samples and determining technology is difficult and complex.

　　4. Xylose breath test

　　Xylose is mostly decomposed by intestinal bacteria, only a small part is absorbed, and the main site of absorption is the proximal small intestine, which is rarely affected by bacteria in the distal small intestine and colon, or malabsorption. Overgrowth of intestinal bacteria increases the decomposition of 14C-labeled xylose and the production of CO2. The 14C xylose breath test has good sensitivity and specificity, with 85% of patients showing an increase in 14CO2 in the breath within the first 60 minutes after the test, with the 30-minute breath sample being the most reliable, and it is often used as the first choice for various breath tests.

　　5. Hydrogen breath test

　　Substrates include lactulose and glucose, which are decomposed by intestinal bacteria to produce hydrogen and are also used as a method to understand the time of intestinal movement and absorption status. Some people compared the hydrogen breath test of 10g lactulose and 80g glucose, with the sensitivity of the former being 68% and the specificity being 44%; and the latter being 62% and 85%, respectively. This method is non-radioactive, simple to operate, but has many conditions and individual differences, and even some bacterial populations do not produce hydrogen during metabolism. In China, the sensitivity of the mannitol hydrogen breath test is reported to be 71% and the specificity is 67%.

　　6. Glycine

　　Bile salts or 14C-glycocholic acid are separated from bile salts and absorbed in the ileum, metabolized into 14CO2, and the specificity of this method is not as good as that of the xylose breath test, with a false positive rate of up to 30% to 40%. The reason is that after ileal lesions or ileal resection, bile salts enter the colon for decomposition, and it is sometimes difficult to understand whether all bile acids are in the small intestine. It is often necessary to perform fecal 14C bile acid analysis at the same time when conducting this test.

      In addition to conventional treatment, attention should also be paid to the following aspects in diet for patients with blind loop syndrome: The diet should be light and healthy, attention should be paid to hygiene, and a reasonable diet should be arranged. Spicy and刺激性 food should be avoided.

　　1. Treatment

　　1. Eliminate the cause

　　Small intestinal diverticula, blind loops after surgery, intestinal fistulas, strictures, and other structural abnormalities can generally be corrected by surgery, but it is not practical for certain patients (such as multiple diverticula, scleroderma). Therefore, the indications for surgery should be strictly controlled, and efforts should be made to avoid the above situations during surgery, and establish the size and quantity of the circulation loops reasonably. Theoretically, the use of prokinetic drugs may help clear overgrown bacteria, but whether it is effective for anatomical abnormalities such as blind loops and multiple diverticula, and whether it may worsen malabsorption of the primary disease (such as short bowel syndrome) remains to be explored.

　　2. Antimicrobial Drug Treatment

　　In theory, the selection of antibacterial drugs should be based on the sensitivity of bacteria in the small intestinal lumen, but usually due to the existence of many different bacterial species and very different sensitivities, the selection in this case is very difficult. Generally, the following principles should be followed: try to select antibacterial drugs with high sensitivity, few adverse reactions, and effective for both anaerobic and aerobic bacteria; antibacterial drugs that are ineffective against anaerobic bacteria should not be selected, such as penicillin, ampicillin, oral aminoglycosides, kanamycin, neomycin, etc. Diagnose as clearly as possible before taking medication, and avoid empirical treatment.

　　(1) Tetracycline: The initial dose is 250mg, 4 times/day, taken orally. If effective, diarrhea improves, and the absorption of fat and vitamin B12 improves within a week. However, up to 60% of patients have no effect on tetracycline treatment at present.

　　(2) Amoxicillin/Clavulanate Potassium (Augmentin): Each tablet contains 250mg of amoxicillin and 125mg of clavulanate potassium, which can effectively inhibit aerobic and anaerobic flora, correct malabsorption, 1-2 tablets per time, 4 times/day.

　　(3) Cefradine 250mg, 4 times/day.

　　(4) Chloramphenicol 50mg/(kg·d) body weight, taken orally in 4 divided doses, often shows good efficacy when the above drugs are ineffective.

　　(5) Metronidazole 200mg, 3 times/day. Tinidazole 0.1g, 3 times/day.

　　The effects of most patients are significant after 1 course (7-10 days). For those with rapid recurrence of symptoms, cyclic treatment can be adopted, that is, treatment for 1 week per month, lasting for 1-2 months, which can also achieve satisfactory results, but attention should be paid to the adverse reactions of drugs.

　　3. Supportive Treatment

　　Even if the overgrowth of bacteria is satisfactorily controlled, nutritional support therapy is necessary. Fatigue patients can reduce the fat in food or use medium-chain triglycerides to replace part of the fat. Vitamin B12, vitamin K, and calcium should also be supplemented appropriately.

　　II. Prognosis

　　Due to the improvement of examination methods in recent years, timely diagnosis and treatment can be made as soon as possible when the disease has not reached severe malnutrition and mucosal injury, correcting the anatomical abnormalities, and the prognosis of most patients is generally good. Delayed treatment can have serious consequences. Patients with severe malnutrition or scleroderma, pseudo-obstruction of the small intestine often require long-term nutritional support, and the prognosis is poor.