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, [10] 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. [11] 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. [12, 13] 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. [14]
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. [15]
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. [16]
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. [16]
The adaptation phase generally begins 2-4 days after bowel resection and may last up to 12-
18 months. [16] 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. [16]
In the maintenance phase, the absorptive capacity of the GI tract is at its maximum. [16]
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. [16]

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. [17, 18] 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%). [19]
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. [20]
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
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. [21]
Byrne et al estimated that in the United States, approximately 10,000-20,000 patients receive
home-delivered TPN for short-bowel syndrome. [22]
Moreno and coworkers published data derived from the 2002 registry of patients receiving
home-based parenteral nutrition in Spain. [19] The program had an enrollment of 74

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%. [17, 23]
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. [24]
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.patients, making the prevalence in Spain
1.8 patients per 1 million population.

History
Patients with short-bowel syndrome invariably present with a history of several intestinal
resections, as occurs with Crohn disease, or with a history of a major abdominal catastrophe
or vascular accident, such as midgut volvulus or embolus to the superior mesenteric vessels.
Pursuant to the resultant malabsorption, diarrhea (with or without steatorrhea) is an almost
constant clinical finding.
Patients with short-bowel syndrome may describe significant weight loss, fatigue, malaise,
and lethargy. These symptoms are protean but consistent with the diarrheic diathesis and
resultant dehydration, electrolyte imbalance, protein-calorie malnutrition, and loss of critical
vitamins and minerals.
Vitamin and mineral deficiencies can lead to some specific symptoms, as follows:
 Patients with vitamin A deficiencies may report night blindness and xerophthalmia
 Vitamin D depletion can be associated with paresthesias and tetany
 Loss of vitamin E can cause paresthesias, ataxic gait, and visual disturbances because
of retinopathy
 A history of easy bruisability or prolonged bleeding might suggest vitamin K
depletion
 Patients reporting dyspnea on exertion or lethargy may be anemic from vitamin B12,
folic acid, or iron deficiency
 Calcium and magnesium losses can cause paresthesias and tetany
 Patients with critically low zinc levels may describe anorexia and diarrhea

Physical Examination
Physical examination of the patient with short-bowel syndrome can reveal many clues to the
diagnosis, depending on the duration and severity of the malabsorption.
Patients who are severely protein- and energy-malnourished may present with temporal
wasting, loss of digital muscle mass, and peripheral edema. The skin may be dry and flaky.
The nails can feature prominent ridges, and the lingual papillae are blunted or atrophic. In
children, poor growth performance is a telling feature.
The essential fatty acids are linoleic and linolenic acids. Patients with essential fatty acid
deficiency experience growth retardation, dermatitis, and alopecia.
The physical features of vitamin A deficiency include corneal ulcerations and growth delays.
Patients with low levels of the B complex vitamins in general can present with stomatitis,
cheilosis, and glossitis. Vitamin B1 deficiency is associated with edema, tachycardia,
ophthalmoplegia, and depressed deep tendon reflexes. Vitamin B6 deficiency can cause
peripheral neuropathies and seizures. Peripheral neuropathy can be a feature of B12
deficiency also.
Vitamin D depletion is associated with poor growth and bowed extremities.
Severe vitamin E deficiencies can result in ataxia, edema, and depressed deep tendon
reflexes.
The physical hallmarks of vitamin K deficiency are related to derangements in hemostasis.
These include petechiae, ecchymoses, purpura, or outright bleeding diatheses.
Physical clues to the presence of iron deficiency include pallor, spooned nails, and glossitis.
Zinc deficiency causes angular stomatitis, poor wound healing, and alopecia. Also, a scaly
erythematous rash can erupt around the mouth, eyes, nose, and perineum.
Laboratory Studies
The complete blood count (CBC) is an important laboratory test in the workup of the patient
with short-bowel syndrome. The primary reason to order this test is to determine if the patient
is anemic. The type of anemia can correlate with specific nutritional deficiencies. These
include the hypochromic microcytic anemia typical of depleted iron stores and the
megaloblastic anemia associated with vitamin B12 deficiency.
The plasma albumin level is an important indicator of overall nutritional status. This protein
has a half-life of approximately 21 days. Evidence is accumulating that severely depressed
albumin levels, especially below 2.5 g/dL, are associated with increased rates of major
morbidity and mortality in surgical patients. In addition, albumin is a good indicator of
hepatic protein synthesis. Note that during periods of stress or infection, the liver produces
acute-phase reactants (eg, C-reactive protein [CRP]) in preference to albumin.
In contrast to the above, an abnormally elevated albumin level may be observed rarely and is
consistent with dehydration.
Prealbumin is a good indicator of acute nutritional status. Its half-life is approximately 3-5
days. Many nutrition support practitioners use this protein to monitor the efficacy of nutrition
support regimens in their patients. Because of the relatively short half-life, it is not a good
nutritional screening tool; albumin is better for this purpose. Prealbumin levels can also be
skewed by hydration status and renal function.
Hepatocellular enzymes (eg, aspartate aminotransferase [AST], alanine aminotransferase
[ALT]) are important to monitor, especially in patients receiving long-term parenteral
nutritional support. Many patients on long-term parenteral nutritional support have transient
elevations of these enzymes that subsequently normalize, especially as they begin or increase
oral food intake.
Concern should be raised when patients have persistent elevation of the enzymes, especially
when they continue to increase. This is the group of patients that may progress to true
histologic hepatocellular damage, cirrhosis, and liver failure.
Serum bilirubin is a good indicator of liver function, but its sensitivity for early liver damage
probably is less than that of the hepatocellular enzymes.
Measure standard serum chemistries, including sodium, potassium, chloride, and carbon
dioxide–combining power, frequently in patients on long-term parenteral nutrition. Total
parenteral nutrition (TPN) is commonly associated with disturbances in these values, and
simple adjustments in the concentration of these are usually sufficient to correct the problem.
Blood urea nitrogen (BUN) determinations are important because they provide an indication
of renal reserve or function. More important, in this patient group, rising BUN levels may
indicate that the patient is being overfed with protein. Alternately, if BUN levels are
disproportionately elevated in relation to creatinine (>20:1), the patient may be dehydrated.
Serum creatinine is a good indicator of renal function. Rising creatinine should raise concern
about deteriorating renal function and may necessitate changes in the nutrition support
regimen.
The divalent cations calcium and magnesium and the anion phosphorus are important in
several cellular processes. Calcium and magnesium facilitate functioning of many enzyme
systems, regulate membrane stabilization and excitation, and serve important functions in
cardiac conduction and elsewhere. Phosphorus (as phosphates) and proteins are the major
intracellular anions. Phosphorus is also involved in the generation of adenosine triphosphate
(ATP), the major energy substrate of aerobic cells. Suspect loss of these ions in patients with
severe diarrhea, especially steatorrhea.
Calculation of nitrogen balance allows the clinician to investigate whether adequate amounts
of protein are being supplied to a particular patient. To perform this test, a 24-hour urine
collection is obtained, and the amount of urinary urea nitrogen (UUN) is measured. The
amount of protein (Pr) the patient is being fed is a known variable (g Pr). These values are
applied to the following equation:
 Nitrogen balance = g Pr/6.25 – (UUN + 4 g)
For every 6 g of protein, 1 g of nitrogen is present. The figure 4 g is for fecal losses. The fecal
protein loss can be much higher in patients with short-bowel syndrome, malabsorption, and
diarrhea.
Attaining positive nitrogen balance is important. It is associated with proper immune
function, good wound healing, replenishment of lean body mass in previously catabolic
patients, and growth in children.
Vitamin levels can be measured in serum. This is achieved best when a specific abnormality
that can be attributed to a vitamin deficiency is suspected on clinical grounds. The findings
associated with various vitamin deficiencies are discussed elsewhere (see Presentation). Treat
vitamin deficiency by supplementation of that vitamin.
Serum levels of zinc, chromium, selenium, and other important minerals and trace elements
can also be measured. Most of these elements serve as cofactors in various metalloenzyme
systems. Their depletion leads to degradation in enzyme function and, sometimes, serious
clinical sequelae, some of which have been described (see Presentation). Treat a deficiency in
one of these elements by replenishment, especially if a related clinical disorder (eg, glucose
intolerance and chromium deficiency) is present.
Hepatic synthesis of the proteins of the coagulation cascade is a highly conserved function.
Deficient hepatic production of coagulation factors is usually a sign of advanced liver
disease. Assess the international normalized ratio (INR), prothrombin time (PT), and
activated partial thromboplastin time (aPTT) in all patients who are considered candidates for
surgery, especially those with any evidence of liver dysfunction. Identification of a defect
should lead to replacement therapy (eg, vitamin K, fresh frozen plasma [FFP]).
Imaging Studies
Obtain a chest radiograph routinely in all patients who undergo placement of a temporary or
durable central venous catheter for hyperalimentation or other purposes. The chest radiograph
is obtained to ensure that no complications (eg, pneumothorax) have occurred. In addition, it
allows documentation of proper placement of the catheter tip (ie, in the vicinity of the
superior vena cava–right atrial junction).
A plain abdominal radiograph allows a preliminary assessment of bowel status. Signs of ileus
or obstruction, such as greatly dilated bowel, can be looked for.
Contrast studies are a more sensitive imaging choice than the plain radiograph. An upper
gastrointestinal (GI) series with small bowel follow-through can be useful. The small bowel
should appear somewhat dilated because this is one of the major mechanisms of small-bowel
adaptation. Areas of stricturing appear as significant narrowing. Look for these especially at
areas of known previous anastomoses. Overall, the bowel mucosal pattern should remain
relatively unchanged.
Abdominal computed tomography (CT) with contrast can be used to identify enteric
problems, such as bowel obstruction. It also is useful for imaging the liver and can
demonstrate changes consistent with cirrhosis. Other earlier signs of liver dysfunction, such
as fatty change, can be demonstrated as well.
Many patients with short-bowel syndrome develop biliary sludge or gallstones. Symptoms
consistent with biliary colic or cholelithiasis can be investigated with abdominal
ultrasonography. This study provides important information, such as indicating the presence
or absence of stones, gall bladder wall thickness, and common bile duct diameter.
Choledocholithiasis and fatty change of the liver may be demonstrated as well.
Other Tests
Patients with short-bowel syndrome, especially those on prolonged courses of TPN, can
develop metabolic bone disease. The major mechanism is calcium and vitamin D
malabsorption. Bone can become decalcified (less dense) and more prone to fracture. In this
situation it is useful to obtain an estimate of bone density.
Bone density is estimated by dual radiographic absorptiometry. Bone mineral density is
measured in terms of g/cm2. The patient's bone density is measured and compared to
reference values. A determination is made as to whether or not the patient is osteopenic.
Patients deemed osteopenic could be treated with estrogen; calcitonin; bisphosphonates; or
supplementation of calcium, vitamin D, and magnesium. Patients may be advised to increase
their activity level as well.