Blind Loop Syndrome

Etiology

Anatomic Abnormalities (most prevalent)

• Afferent loop syndrome (most commonly from Billroth II, Roux-en-Y, Whipple procedure)[4]
• Surgical complications (fistulas, strictures, scarring)
• Anastomosis
• Jejunal diverticulosis

Motility Disorders 

• Scleroderma
• Parkinson disease
• Diabetic gastroparesis[5]

Inflammatory Disease 

• Crohn disease
• Radiation enteritis
• Diverticulitis
• Celiac disease[6]

Epidemiology

There is insufficient epidemiological data, as the patient presentation can be vague, and the diagnosis is infrequently worked up or mistaken for alternative diagnoses.

Pathophysiology

In this disease process, the etiologies, as mentioned above, can cause stasis in a segment of the proximal small intestine. This dysfunction impairs peristaltic motility and impedes luminal flow. Throughout digestion, food is diverted around the stagnant length of the bowel, suitably referred to as the “blind loop.” Naturally, particulate builds up, serving as a focal point for bacterial proliferation.

The consensus of current literature points to Bacteroides, E. coli, Streptococcus, and Lactobacillus as the implicating species in BLS.[7] However, there is debate on how these organisms disrupt cobalamin absorption to manifest this constellation of symptoms. One theory suggests that bacteria (i.e., Bacteroides) directly injure the alimentary tract through released toxins or harmful by-products of microbial metabolism.[8] Another theory proposes that microbes (i.e., E. coli, Streptococcus) remove the available supply of vitamin B12 from the lumen for use during replication.[9] 

In addition to restricting the absorption of B12, microbial overgrowth also impairs fat absorption. Under normal conditions, conjugated bile salts are transported into the duodenum to solubilize dietary lipids. As food passes through the gut, the intestinal flora deconjugates a small percentage of bile salts/acids, which exit the body through the stool. However, in stagnant conditions, the population of bacteria drastically increases. Accordingly, more bacteria (notoriously anaerobes) yield a larger number of unconjugated bile salts/acids, manifesting as steatorrhea and fat-soluble deficiencies.[10][11]

Histopathology

The blind loop histology exhibits patterns that deviate from the prototypical mucosa. Specifically, affected tissues display villous and crypt gland hypertrophy. Vesiculated columnar cells can also be seen in a fraction of the villi. Furthermore, affected segments display epithelial damage without evidence of direct bacterial infiltration.[12] In some cases, a loss of enzymatic activity at the brush border can result in acquired lactase deficiency.[13]

History and Physical

A comprehensive history and thorough physical exam are essential, as the presentation is often vague and variable amongst patients. Inquiring about recent surgical history or comorbidities may provide the insight needed to recognize this condition. Although it can be challenging to identify, listed below are the symptoms most commonly associated with BLS:

Megaloblastic Anemia

It typically results from vitamin B12 deficiency; sometimes multifactorial, seen in conjunction with low folate levels.[14]

Diarrhea/Steatorrhea

The specific presentation depends on the etiology, region, and extent of bowel involvement; diarrhea/steatorrhea also contributes to weight loss.[15]

Malnutrition

Patients can develop multiple micronutrient deficiencies due to intestinal damage and impaired fat absorption.[16] Unabsorbed fatty acids may also bind to dietary calcium, inducing hypocalcemia. Listed below are varying ways in which these deficiencies may present:

• Vitamin A deficiency: xeropthalmia, night blindness, hyperkeratosis
• Vitamin D deficiency: secondary hyperparathyroidism, muscle weakness, fractures
• Vitamin K deficiency: bruising, melena, hematuria, menorrhagia
• Vitamin E deficiency: neuropathy, nystagmus, skeletal myopathy
• Calcium deficiency: brittle bones, seizures, prolonged QT interval

Protein Loss

It can be seen as cachexia or edema on physical exam.[17]

Other non-specific symptoms include diffuse, crampy, and colicky abdominal pain, nausea, belching, bloating, and flatulence.

Evaluation

Radiologic Imaging

Diagnostic imaging is a practical method for evaluating a blind loop. Applicable radiologic studies include x-rays, computerized tomography (CT) scans, barium series, and CT enterography. Although abdominal films and CT scans are simple and cost-effective modalities, they have limited utility in the context of this syndrome. Accordingly, evidence of obstruction or dilatation on X-ray/CT should prompt further workup when BLS is suspected.

Barium studies are beneficial as they provide added information concerning the structure and motility of the bowel. In addition to assessing transit time, they can detect aberrations like jejunal diverticula, intestinal strictures, and fistulas. Ultimately, CT enterography is the superior test for identifying mechanical causes of overgrowth. Although similar to the barium series, it is more sensitive and provides greater detail.[7][18]

Breath Tests and Cultures

If there is high clinical suspicion for blind loop syndrome, it is valid to consider ordering additional testing. A sensible workup may include any of the following: a qualitative fecal fat test, hydrogen breath test, D-xylose absorption test, bile acid breath test, or small bowel aspiration.

Initially, testing for fecal fat is an appropriate first step, as it can confirm the presence of malabsorption; otherwise, it has limited diagnostic relevance in this condition. Next, the hydrogen breath test and its more accurate counterpart, the D-xylose absorption test, are applicable for detecting the presence of bacterial overgrowth. However, neither are notably useful for expressly identifying blind loop syndrome.[19]

Alternatively, the bile acid breath test is more specific, assessing for both bacterial overgrowth and bile acid malabsorption. Overall, it is a simple and effective test.[20][21] To establish a definitive diagnosis, it is necessary to quantify cultures from a small bowel aspirate. Regardless, this procedure is uncommon for diagnostic confirmation as acquiring these cultures can be invasive, costly, and time-consuming.[22]

The Schilling Test

Of note, the Schilling test was once widely used to confirm the presence of a blind loop. In this test, medical professionals would assess for urinary cobalamin. Excretory patterns mirrored that of pernicious anemia but would correct with the addition of antibiotics. Regardless of its benefit in BLS, most medical centers have deemed this test obsolete, and no substitute exists.

Treatment / Management

Medical Management

The primary objectives for managing blind loop syndrome are to reduce bacterial overload, correct related deficiencies, and manage unwanted symptoms. Historically, the standard of care for bacterial eradication has been a single course of empiric antibiotics. In the past, physicians routinely prescribed one of the tetracyclines, as they have strong anaerobic coverage. While effective, recent studies have shown improved efficacy in alternative therapies, namely rifaximin and metronidazole.[23][24] The recommended duration of therapy ranges from 7-10 days. While a single course is often sufficient, recurrence is not an uncommon phenomenon. In such cases, physicians may try switching treatments to prevent microbial resistance.(A1)

Surgical Management

Surgical intervention is an option for blind loops with anatomic etiologies. It can also benefit patients with refractory cases requiring multiple rounds of antibiotics. The intended goal of surgery is to address the underlying defect, resect blind loops with significant hypertrophy, and re-establish a functional gastrointestinal tract. If a stricture and non-functional loop are present, then stricturoplasty or resection is indicated. In the case of anastomotic blind loop syndrome, the blind loop should be resected, and the anastomosis remade. In patients who develop stagnancy after undergoing a Billroth II, there is evidence of success in converting it to a Billroth I; in this instance, the duodenum is involved and should not be resected.[7]

Nutritional Care

The purpose of nutritional care is to prevent negative outcomes by correcting underlying deficiencies. Nourishment is especially critical in those with considerable weight loss. While individual needs may vary, nutritionists generally recommend a high-calorie, low-fat diet. Depending on the extent of disease progression, patients may also require supplementation in the form of intramuscular B12, oral vitamins, or minerals. Ultimately, it is also the physician’s role to counsel patients with acquired lactase deficiencies.

Differential Diagnosis

Irritable bowel syndrome (IBS) is a functional condition with a poorly understood pathophysiology. Patients typically complain of abdominal pain that improves with defecation, changes in stool frequency, and altered stool consistency. Although it presents similarly, IBS does not have the accompanying deficiencies seen in BLS.[25]

Celiac disease is an autoimmune pathology marked by blunting of the duodenal villi. Symptoms include chronic diarrhea, bloating, weight loss, and vitamin B12 deficiency. Although comparable to blind loop syndrome, celiac disease has distinguished tissue transglutaminase antibodies elicited in response to gluten consumption.[26]

Tropical sprue is a malabsorptive illness with a suspected infectious etiology - as in BLS, patients present with diarrhea or steatorrhea and a vitamin B12 deficiency. However, Tropical Sprue has a unique geographical distribution and distinctive mucosal histology.[27]

Whipple disease is another malabsorptive illness resulting in weight loss, diarrhea, steatorrhea, and other non-specific symptoms of indigestion. On physical exam, patients may present with altered mental status, arthralgias, and lymphadenopathy. A mucosal biopsy exhibiting T. whipplei establishes a definitive diagnosis.[28]

Pancreatic insufficiency is a disorder where the pancreatic exocrine function is impaired. People with a history of pancreatitis may present with steatorrhea, weight loss, and fat-soluble deficiencies. A D-xylose test can help to differentiate Pancreatic Insufficiency from blind loop syndrome by assessing the integrity of the gastrointestinal mucosa.[29]

Crohn disease is an inflammatory bowel pathology characterized by non-caseating granulomas and transmural inflammation. It commonly involves the terminal ileum, resulting in watery diarrhea, steatorrhea, and vitamin B12 deficiency. In contrast to BLS, Crohn disease can also exhibit extra-intestinal manifestations, including uveitis and erythema nodosum. A colorectal biopsy is required to confirm this diagnosis.[30]

Prognosis

The prognosis of BLS depends on the etiology and extent of disease progression. 

Complications

Subacute Combined Degeneration

Subacute combined degeneration is a dangerous neurological complication of blind loop syndrome. As stated above, excessive intestinal overgrowth limits the capacity of cobalamin absorption. Over time, prolonged B12 deficiency leads to demyelination of the dorsal column-medial lemniscus pathway. This condition presents with paresthesia, ataxia, and a loss of positional sense. Left untreated, it may result in severe symptoms like spasticity or paraplegia.[31]

Osteomalacia

Osteomalacia is another reported sequela of blind loop syndrome. In this pathology, prolonged vitamin D deficiency from fat malabsorption results in bone demineralization. Symptoms can manifest as aching bone pain, arthralgias, or proximal muscle weakness. Recognizing and treating this disease is critical to preventing insufficiency fractures.[32][33] 

Retroperitoneal Hemorrhage

Retroperitoneal hemorrhage is a rare but potentially life-threatening surgical sequela of blind loop syndrome. Physiologically, fat malabsorption depletes vitamin K stores. This deficit stunts the production of prothrombin, resulting in a hypocoagulable state. During surgery, patients can develop uncontrolled intraoperative bleeding and eventual hemorrhagic shock. Considering this complication before surgical intervention is crucial, as the mortality rate is about 18%.[14][34]