Practice Essentials
Each year in the United States, many patients undergo resection of long segments of small intestine for various disorders, including inflammatory bowel disease (IBD), malignancy, mesenteric ischemia, and others. Juvenile survivors of necrotizing enterocolitis, midgut volvulus, and other abdominal catastrophes are becoming more common. Various nonoperative procedures can leave patients with a functional short-bowel syndrome. An example of this clinical scenario is radiation enteritis.
Those patients who are left with insufficient small bowel absorptive surface area develop malabsorption, malnutrition, diarrhea, and electrolyte abnormalities. The subset of patients with clinically significant malabsorption and malnutrition are said to have developed short-bowel syndrome.
The average length of the adult human small intestine is approximately 600 cm, as calculated from studies performed on cadavers. According to Lennard-Jones and to Weser, the range extends from 260 to 800 cm. [1] Any disease, traumatic injury, vascular accident, or other pathology that leaves less than 200 cm of viable small bowel or results in a loss of 50% or more of the small intestine places the patient at risk for developing short-bowel syndrome.
Short-bowel syndrome is a disorder clinically defined by malabsorption, diarrhea, steatorrhea, fluid and electrolyte disturbances, and malnutrition. The final common etiologic factor in all causes of short-bowel syndrome is the functional or anatomic loss of extensive segments of small intestine so that absorptive capacity is severely compromised. Although resection of the colon alone typically does not result in short-bowel syndrome, the condition's presence can be a critical factor in the management of patients who lose significant amounts of small intestine. [2, 3]
Massive small intestinal resection compromises digestive and absorptive processes. Adequate digestion and absorption cannot take place, and proper nutritional status cannot be maintained without supportive care. Today, the most common causes of short-bowel syndrome in adults include Crohn disease, [4] radiation enteritis, mesenteric vascular accidents, trauma, and recurrent intestinal obstruction. In the pediatric population, necrotizing enterocolitis, intestinal atresias, and intestinal volvulus are the most common etiologic factors.
Other conditions associated with short-bowel syndrome include congenital short small bowel, gastroschisis, and meconium peritonitis.
Not all patients with loss of significant amounts of small intestine develop short-bowel syndrome. Important cofactors that help to determine whether the syndrome will develop or not include the premorbid length of small bowel, the segment of intestine that is lost, the age of the patient at the time of bowel loss, the remaining length of small bowel and colon, and the presence or absence of the ileocecal valve.
Several operative or invasive procedures and therapies have been designed for and applied to the treatment of short-bowel syndrome. These include the establishment of central venous access for delivery of total parenteral nutrition (TPN), intestinal transplantation, and nontransplantation abdominal operations. The history of these various treatment strategies is discussed in this section.
TPN was developed successfully by Dudrick et al. [5] Their landmark paper included laboratory studies in a canine model and clinical results in 30 adult patients with a variety of gastrointestinal (GI) maladies ranging from achalasia to traumatic pancreatitis to regional enteritis. The animal model clearly demonstrated efficacy. Beagle puppies fed entirely intravenously surpassed their littermate controls in weight gain and were equal in terms of activity level, skeletal growth, and other developmental landmarks.
In the clinical arm of the study, [5] the 30 subjects receiving TPN were able to achieve positive nitrogen balance, maintain weight, heal wounds, and close fistulae. Wilmore and Dudrick reported positive nitrogen balance, growth, and development in an infant born with diffusely atretic small bowel who was fed entirely parenterally. [6]
After these initial successes, the new technique was introduced into the clinical mainstream, and indications for its use have expanded tremendously. Patients with short-bowel syndrome are now routinely treated with TPN, especially early in their course. [7] New therapeutic strategies that may allow patients to discontinue or curtail the use of TPN are discussed in subsequent sections.
Numerous nontransplant operative approaches have been used in the treatment of patients with short-bowel syndrome. The creation of reversed intestinal segments was popular in the 1960s and 1970s. The aim of this operation was to produce a sort of functional partial small-bowel obstruction that would slow intestinal transit time, thereby encouraging greater nutrient absorption and decreasing diarrhea and nutrient loss.
Around that time, recirculating small bowel loops were also being created, with the same idea in mind. The results were mixed to questionable, and these procedures are rarely used today. Intestinal lengthening (Bianchi procedure), the creation of artificial enteric valves, strictureplasty, and intestinal tapering procedures continue to be employed at some centers today.
Intestinal transplantation was first attempted in dogs in 1959. The procedures failed because of the great concentration of immune system cells associated with the gut. The discovery and clinical implementation of powerful immunosuppressive drugs, such as FK506 (tacrolimus) and cyclosporine A, made successful small bowel transplantation possible.
The first successful combined transplantation of small intestine and liver in a human was performed in 1990. Since that time, the technique of isolated small intestinal transplantation has been developed and applied. Better graft survival rates are achieved when patients receive their transplant before complications secondary to short-gut syndrome occur, especially that of cirrhosis. [8]
Anatomy
The duodenum extends from the pylorus to the duodenojejunal flexure and is about 25 cm in overall length. [9] At the upper left border of the second lumbar vertebra is the duodenojejunal flexure. Here the duodenum turns anteriorly and caudally to become the jejunum just distal to the ligament of Treitz.
The small bowel is divided relatively arbitrarily into the jejunum (the proximal two fifths) and ileum (the distal three fifths), though grossly the jejunum may appear to be of greater caliber, with a slightly thicker wall. It is fixed to the retroperitoneum by the root of the mesentery, which extends from the left upper quadrant of the abdomen to the right lower quadrant.
The terminal ileum is located in the right lower quadrant. The ileocecal valve marks the transition from small intestine to large intestine. The first portion of the colon is called the cecum. The ascending colon climbs along the right paracolic gutter and bends toward the midline at the hepatic flexure. Here, the transverse colon begins and makes its way to the splenic flexure, where the colon angles slightly medially and also inferiorly to become the descending colon.
As the descending colon crosses the pelvic brim, it becomes the sinuous sigmoid colon. This portion of the colon heads toward the midline and then proceeds inferiorly. Below the pelvic peritoneal reflection, the sigmoid colon becomes the rectum.
The blood supply to the duodenum is extensive and is derived from branches of both the celiac axis and the superior mesenteric artery. These include, but are not limited to, the gastroduodenal artery, the superior and inferior pancreaticoduodenal arteries, the right gastroepiploic artery, and the supraduodenal and retroduodenal arteries. This dual blood supply helps to preserve the duodenum in the event of sudden occlusion of the superior mesenteric artery.
Although their blood supply is rich, the jejunum, with the exception of its proximal few centimeters, and ileum depend solely on branches of the superior mesenteric artery. These are termed the jejunal and ileal, or intestinal, arteries. The ileocolic artery, a branch of the superior mesenteric artery, also supplies the terminal ileum.
The ileocolic artery and the right colic artery supply the cecum and the ascending colon. The dominant blood supply of the proximal two thirds of the transverse colon is the middle colic artery. All of these colic arteries are branches of the superior mesenteric artery. Thus, the entire midgut, from jejunum to mid transverse colon, is dependent on the superior mesenteric artery.
Branches of the left colic artery, which is derived from the inferior mesenteric artery, supply the distal transverse colon and the descending colon. The sigmoid arteries and the superior rectal artery are derived from the inferior mesenteric artery as well.
For an exhaustive exegesis on the anatomy and the techniques of multivisceral abdominal organ transplantation, see "The Many Faces of Multivisceral Transplantation" by Starzl et al. [10]
Pathophysiology
Physiologic derangements in short-bowel syndrome are the result of the loss of large amounts of intestinal absorptive surface area. The sequelae of this loss include malabsorption of water, electrolytes, macronutrients (ie, proteins, carbohydrates, fats), and micronutrients (ie, vitamins, minerals, trace elements).
The GI tract is a vital locus for water and electrolyte absorption and transport. In addition to managing exogenously obtained sources of these nutrients, such as daily water intake and the electrolytes found in liquid and solid foods, the GI tract must deal with its own considerable daily secretions.
The monumental nature and efficiency of this task was illustrated by Sellin, [11] who noted that the GI tract processes 8000-9000 mL of fluid per day, with the vast majority of this derived from endogenous secretions. Fluid reabsorption by the healthy GI tract is efficient (98%), and only 100-200 mL are lost in fecal matter each day. The great majority (80%) of this reabsorption occurs in the small intestine.
Disturbances in the major determinants of intestinal fluid absorption negatively impact the ability to reabsorb this large fluid load. The major determinants include intestinal mucosal surface area, the health or integrity of the mucosa, the status of small bowel motility, and the osmolarity of solutes in the intestinal lumen.
Clinically, these disturbances can manifest as major components of short-bowel syndrome, namely diarrhea, dehydration, and electrolyte imbalance. Thus, short-bowel syndrome can be produced by clinical entities that result in critical loss of mucosal surface area (eg, massive small-bowel resection) or degrade mucosal integrity (eg, radiation enteritis).
Macronutrients and micronutrients are absorbed along the length of the small intestine. However, the jejunum has taller villi, deeper crypts, and greater enzyme activity than the ileum. [12] Therefore, under normal conditions, about 90% of digestion and absorption of significant macronutrients and micronutrients are accomplished in the proximal 100-150 cm of the jejunum. [13, 14] This includes absorption of proteins; carbohydrates; fats; vitamins B, C, and folic acid; and the fat-soluble vitamins A, D, E, and K.
However, if a significant portion or all of the jejunum is resected, the absorption of proteins, carbohydrates, and most vitamins and minerals can be unaffected because of adaptation in the ileum. Unfortunately, enzymatic digestion suffers because of the irreplaceable loss of enteric hormones produced by the jejunum. Biliary and pancreatic secretions decrease. Gastrin levels rise, causing gastric hypersecretion. The resultant high acid output from the stomach may injure the small bowel mucosa.
Additionally, the low intraluminal pH creates unfavorable conditions for optimal activity of the pancreatic enzymes that are present. Diarrhea may then result if a large osmotically active solute load of unabsorbed nutrients is delivered to the ileum and colon.
Ileal resection severely decreases the capacity to absorb water and electrolytes. In addition, the terminal ileum is the site of absorption of bile salts and vitamin B12. Loss of significant lengths of ileum almost invariably results in diarrhea. Continued loss of bile salts following resection of the terminal ileum leads to fat malabsorption, steatorrhea, and loss of fat-soluble vitamins.
Retention of the ileocecal valve plays a pivotal role in massive small bowel resection. If the ileocecal valve can be preserved, intestinal transit is slowed, allowing more time for absorption. If the ileocecal valve is lost, transit time is faster, and loss of fluid and nutrients is greater. Furthermore, colonic bacteria can colonize the small bowel, worsening diarrhea and nutrient loss.
Preservation of the colon has positive and negative attributes. Philips and Giller demonstrated that colonic water absorption could be increased to as much as five times its normal capacity following small -bowel resection. [15]
Also, by virtue of its resident bacteria, the colon has the inherent capacity to metabolize undigested carbohydrates into short-chain fatty acids, such as butyrate, propionate, and acetate. These are a preferred fuel source for the colon. Interestingly, work by Pomare et al and Halverstad demonstrated that the colon can absorb up to 500 kcal daily of these metabolites, which then can be transported via the portal vein to be used as a somatic fuel source. [16]
In contrast, maintenance of the colon increases the incidence of urinary calcium oxalate stone formation. Oxalate is normally bound by calcium in the small bowel and thus is insoluble when it reaches the colon. After massive enterectomy, much of this calcium is bound by free intraluminal fats. Free oxalate is delivered to the colon, where it is absorbed. This can eventually lead to saturation of the urine with calcium oxalate crystals and result in stone formation. Retention of the colon in the absence of a competent ileocecal valve can lead to small intestinal bacterial overgrowth.
The physiologic changes and adaptation of patients with short-bowel syndrome can be viewed in three phases. [17]
The acute phase occurs immediately after massive bowel resection and may last up to 3-4 months. it is associated with malnutrition and fluid and electrolyte loss through the GI tract. Fluid and electrolyte loss through the GI tract may be as high as 6-8 L/day. Patients will have abnormal liver function test results and transient hyperbilirubinemia.
Enteral feedings may also be initiated, but it should be relatively slow. Patients with less than 100 cm of small intestine will require TPN. The presence of ileocecal valve or colon may play a significant role in the outcome of these patients. [17]
The adaptation phase generally begins 2-4 days after bowel resection and may last up to 12-18 months. [17] During this second phase, up to 90% of the bowel adaptation may occur. Villous hyperplasia, increased crypt depth, and intestinal dilatation occur. Early continuous feedings with a high viscosity elemental diet may reduce the duration of TPN. [17]
In the maintenance phase, the absorptive capacity of the GI tract is at its maximum. [17] Some patients may still require TPN. In other patients, nutritional and metabolic homeostasis can be achieved by small meals and supplemental nutritional support for life. These patients will also require vitamins and mineral supplements, including vitamins A, B12, and D, magnesium, and zinc. [17]
To summarize, the acute phase has the following characteristics:
-
Starts immediately after bowel resection and lasts 1-3 months
-
Ostomy output of greater than 5 L/day
-
Life-threatening dehydration and electrolyte imbalances
-
Extremely poor absorption of all nutrients
-
Development of hypergastrinemia and hyperbilirubinemia
The adaptation phase has the following characteristics:
-
Begins within 48 hours of resection and lasts up to 1-2 years
-
Approximately 90% of the bowel adaptation takes place during this phase
-
Enterocyte hyperplasia, villous hyperplasia, and increased crypt depth occur, resulting in increased surface area; intestinal dilatation and lengthening also occur
-
Luminal nutrition is essential for adaptation and should be initiated as early as possible; parenteral nutrition is also essential throughout this period
The maintenance phase has the following characteristics:
-
The absorptive capacity of the intestine is at its maximum
-
Nutritional and metabolic homeostasis can be achieved by oral feeding, or patients are committed to receiving supplemental or complete nutritional support for life
Etiology
In the first decades of the twentieth century, bowel strangulation and midgut volvulus were the most common etiologies resulting in short-bowel syndrome. By the 1950s and 1960s, mesenteric vascular accidents, including thrombosis and embolism of the superior mesenteric artery, had become the most common causes of short-bowel syndrome.
Jejunoileal bypass procedures once were popular for the treatment of morbid obesity. However, they produced an iatrogenic short-gut syndrome and the attendant metabolic and hepatic complications associated with chronic malabsorption. These procedures have since been abandoned.
Studies by Ladefoged et al and Nightingale and Lennard-Jones found that Crohn disease has become the most common etiology of short-bowel syndrome in adults, accounting for 50-60% of cases. [18, 19] Other important causative entities include mesenteric ischemia and radiation enteritis.
In contrast, the Spanish home parenteral nutrition registry data reported by Moreno et al described mesenteric ischemia as the leading cause of short-bowel syndrome (29.7%), followed by neoplastic diseases (16.2%), radiation enteritis (12.2%), motility disorders (8.1%), and Crohn disease (5.4%). [20]
Occasionally, trauma that involves one or more of the major mesenteric vessels results in extensive bowel necrosis and short-bowel syndrome.
Leading pediatric and neonatal etiologies of short-bowel syndrome include necrotizing enterocolitis, multilevel small-bowel atresia, and midgut volvulus with ischemic bowel infarction.
In a study of 114 infants with jejunoileal atresia, Stollman et al found that surgical treatment (which included resection with primary anastomosis in 69% of the children and temporary enterostomy in 26% of them) resulted in short-bowel syndrome in 15% of the patients. [21] This led the investigators to suggest that short-bowel syndrome is the chief factor behind longer hospital stays for and increased feeding problems and rates of morbidity and mortality in infants who are surgically treated for jejunoileal atresia.
Epidemiology
Estimates of the incidence and prevalence of short-bowel syndrome are difficult to make and, therefore, are rare. Most estimates are based on data describing patients requiring long-term home parenteral nutrition for short-bowel syndrome.
A report by Lennard-Jones estimated that in the United Kingdom, the incidence of short-bowel syndrome requiring such therapy was two patients per million population. [22]
Byrne et al estimated that in the United States, approximately 10,000-20,000 patients receive home-delivered TPN for short-bowel syndrome. [23]
Moreno and coworkers published data derived from the 2002 registry of patients receiving home-based parenteral nutrition in Spain. [20] The program had an enrollment of 74 patients, making the prevalence in Spain 1.8 patients per 1 million population.
Prognosis
At present, there is no reliable cure for short-bowel syndrome. Patients who are maintained on parenteral nutrition at home have reasonably good short-term outcomes. Data from Howard et al and Ladefoged et al revealed that the 4-year survival rate in patients who depend on parenteral nutrition is about 70%. [18, 24]
Eventually, many of these patients run out of venous access or have severe septic complications. Cost also is a major factor. Home parenteral nutrition costs range from about $50,000 to more than $200,000 per year. As mentioned before, the most common cause of death in these patients is liver failure.
The authors have reviewed the use and results of pharmacologic bowel compensation, including growth hormone, glutamine, and a high-carbohydrate diet. This may allow additional patients to be liberated from parenteral nutrition. The clinical results have been favorable, as described in earlier studies, but these results have not been reproduced at numerous medical centers. [25]
Nontransplant surgical procedures have been applied to short-bowel syndrome. Early results were mixed, but many of the procedures being performed then involved segment reversal. Subsequent series have demonstrated clinical improvement in more than 80% of patients. The most common operations performed in these series were intestinal tapering, intestinal lengthening, and strictureplasty. Even in these series, segment reversal and creation of artificial valves produced dubious results.
Organ transplantation is a promising therapeutic option but continues to be fraught with problems. Early postoperative mortality can be as high as 30%. Data from leading transplant centers have shown that the 1-year survival rates can be as high as 80-90%, and approximately 60% of patients are alive at 4 years.
