520005

research-article2014
PENXXX10.1177/0148607113520005Journal of Parenteral and Enteral NutritionTappenden

Invited Review
Journal of Parenteral and Enteral
Nutrition
Pathophysiology of Short Bowel Syndrome: Considerations Volume 38 Supplement 1
May 2014 14S­–22S
of Resected and Residual Anatomy © 2014 American Society
for Parenteral and Enteral Nutrition
DOI: 10.1177/0148607113520005
jpen.sagepub.com
hosted at
online.sagepub.com
Kelly A. Tappenden, PhD, RD, FASPEN1

Abstract
The human small intestine is organized with a proximal-to-distal gradient of mucosal structure and nutrient processing capacity. However,
certain nutrients undergo site-specific digestion and absorption, such as iron and folate in the duodenum/jejunum vs vitamin B12 and bile
salts in the ileum. Intestinal resection can result in short bowel syndrome (SBS) due to reduction of total and/or site-specific nutrient
processing areas. Depending on the segment(s) of intestine resected, malabsorption can be nutrient specific (eg, vitamin B12 or fat) or
sweeping, with deficiencies in energy, protein, and various micronutrients. Jejunal resections are generally better tolerated than ileal
resections because of greater postresection adaptive capacity than that of the jejunum. Following intestinal resection, energy scavenging
and fluid absorption become particularly important in the colon owing to loss of digestive and absorptive surface area in the resection
portion. Resection-induced alterations in enteroendocrine cell abundance can further disrupt intestinal function. For example, patients
with end jejunostomy have depressed circulating peptide YY and glucagon-like peptide 2 concentrations, which likely contribute to
the rapid intestinal transit and blunted intestinal adaptation observed in this population. SBS-associated pathophysiology often extends
beyond the gastrointestinal tract, with hepatobiliary disease, metabolic bone disease, D-lactic acidosis, and kidney stone formation being
chronic complications. Clinical management of SBS must be individualized to account for the specific nutrient processing deficit within
the remnant bowel and to mitigate potential complications, both inside and outside the gastrointestinal tract. (JPEN J Parenter Enteral
Nutr. 2014;38(suppl 1):14S-22S)

Keywords
short bowel syndrome; pathophysiology; malabsorption; intestine

Short bowel syndrome (SBS) refers to a condition in which
patients exhibit malabsorption-induced diarrhea, dehydration,
electrolyte disturbances, and malnutrition due to poor nutrient
processing capability resulting from extensive surgical resec-
tion of the intestine (Table 1).1,2 Intestinal failure occurs
when intestinal function is insufficient to meet the body’s
nutrition and hydration needs, and supplementary parenteral
nutrition and/or intravenous fluid (PN/IV) support is required.3
The reported incidence and prevalence of SBS vary by country
(see Jeppesen,4 this issue), but overall, the estimated new inci-
dence of SBS is approximately 2 persons per million per year.5
Although most patients with SBS require PN/IV support, at
least in the immediate postoperative period, many patients are
able to wean off PN/IV because of the innate process of intes-
tinal adaptation that increases total intestinal digestive and
absorptive capacity.6-9
Intestinal pathophysiology following resection presents a
spectrum of dysfunction, even in individuals with enteral auton-
omy. The symptoms and severity of SBS can vary markedly and
are dependent on the anatomic sections of the intestine that were
resected, the length and absorptive capacity of the remnant bowel,
and the presence of active primary disease.2,17,18
Normal Intestinal Physiology
The intact digestive system exhibits a proximal-to-distal ana-
tomic absorptive gradient. That is, the absorptive surface area
of the duodenum and proximal jejunum is greater than that of
the ileum. The number, height, and thickness of the plicae
From the 1Department of Food Science and Human Nutrition, University
of Illinois at Urbana-Champaign, Urbana, Illinois.
Financial disclosure: The publication of the supplement in which
this article appears is supported by an educational grant from NPS
Pharmaceuticals, Inc (Bedminster, NJ). K.A.T. has served as a consultant
for NPS Pharmaceuticals, Inc. No financial compensation was provided to
K.A.T. for the preparation of this work. Funding for medical writing assis-
tance was provided by NPS Pharmaceuticals, Inc.
Received for publication October 26, 2013; accepted for publication
December 9, 2013.
Corresponding Author:
Kelly A. Tappenden, PhD, RD, FASPEN, Department of Food Science
and Human Nutrition, University of Illinois at Urbana-Champaign, 443
Bevier Hall, 905 South Goodwin Avenue, Urbana, IL 61801, USA.
E-mail: tappende@illinois.edu.
Tappenden 15S

Table 1.  Causes of Short Bowel Syndrome Among Adults in Recent Studies Including More Than 50 Patients.

Crenn et al, Lal et al, Pironi et al, Jeppesen et al, Thompson et al, Jeppesen et al, Amiot et al,
200010 200611 200612a 201113 201114 201215 201316
Cause (N = 57) (N = 134) (N = 688) (N = 83) (N = 300) (N = 86) (N = 268)
Mesenteric ischemia/ 37 13 27 30 21 34 43
vascular disease
Crohn’s disease 7 21 23 36 16 21 6
Malignancy/radiation 35 10 13 NR 21 4b 23
Surgical resection NR 32 8c NR 28 NR 12c
Trauma NR NR NR 7 8 9 5d
Dysmotility NR 14 NR NR NR NR NR
Other 21 10 29 26 6 33 11

Values are presented as percentages. NR, not reported.

a
Study includes patients with intestinal failure receiving home parenteral nutrition (75% had short bowel syndrome).
b
Includes malignancy only.
c
Includes only surgical complications.
d
Includes volvulus.

circulares, for example, are greater in the jejunum than in the
ileum.19,20 Similarly, the villi are longer in the more proximal
regions of the bowel.19-21 Furthermore, in the small intestine,
the diameter of the lumen decreases aborally from the duode-
num to the distal ileum.19 The development of this anatomic
gradient is likely a product of the higher concentration of nutri-
ents in the proximal vs the distal small bowel. Several lines of
evidence have established the trophic properties of luminal
nutrients on the intestinal mucosa. First, starvation decreases
villus height and mitotic index, whereas hyperphagia increases
villus height and width.22,23 Second, following intestinal resec-
tion, oral nutrition is associated with increased villus height,
whereas absence of oral nutrition results in decreased villus
height.24 Finally, complex nutrients stimulate a greater degree
of intestinal adaptation than do more hydrolyzed nutrients.25,26
The functional capacity of the gastrointestinal (GI) tract is
reflected by this anatomic gradient. Digestion occurs primarily
in the stomach and proximal small intestine. Mechanical forces
and acidic secretions in the stomach begin the process of nutri-
ent breakdown, which is furthered by digestive enzymes and
bile released by the stomach, pancreas, and gallbladder.27 Most
macronutrient digestion and absorption occurs in the proximal
small intestine28 because of the proximity of bile and pancre-
atic secretions, the higher concentration of nutrients present in
these regions, and expanded functional epithelium relative to
the distal intestine. However, nutrient digestion and absorption
do continue throughout the small and large intestine when
luminal substrate is present.
Carbohydrates are digested by the action of amylase
released by both the salivary glands and the pancreas. The
majority of released sugars are absorbed by the proximal small
intestine.20 However, some complex carbohydrates reach the
colon intact, where they can be fermented by intestinal
microbes into several products, including short-chain fatty
acids (SCFAs).2 Besides being a preferred oxidative substrate
for colonocytes, SCFAs enhance mineral absorption, provoke
enteroendocrine secretions, and stimulate epithelial cell growth
and differentiation in the small and large intestine.29,30 The
details of carbohydrate digestion and absorption are discussed
in more depth in a recent review by Goodman.31
Dietary proteins are initially denatured by the acidic envi-
ronment of the stomach, where parietal cells of the fundus
secrete hydrochloric acid, thus lowering the gastric pH.27
Denaturation renders proteins more susceptible to hydrolysis
and proteolytic cleavage. The presence of food also triggers
fundal chief cells to release precursor proteinases, the pep-
sinogens, which are cleaved to their active form, pepsins, at
low pH.31 Pepsin primarily cleaves proteins at the peptide
bonds of aromatic amino acids.32 In the duodenum, the chyme
is mixed with pancreatic secretions containing bicarbonate,
which neutralizes the local pH, and preproteases, including
trypsinogen and chymotrypsinogen. Membrane-bound
enteropeptidase (also known as enterokinase) at the apical
surface of intestinal epithelial cells converts trypsinogen to
its active form, trypsin. This initiates a cascade, whereby acti-
vated trypsin cleaves additional molecules of trypsinogen as
well as other preproteases into their active forms.33 The acti-
vated peptidases catalyze the hydrolysis of proteins into short
polypeptides and amino acids.31 Larger oligopeptides are fur-
ther broken down by enzymes in the brush border membranes
of the jejunal and ileal epithelia before absorption.34 Amino
acids, dipeptides, and tripeptides are then transported by spe-
cific carrier proteins, most commonly PepT1, into jejunal and
ileal epithelial cells, where the dipeptides and tripeptides are
hydrolyzed by cytoplasmic peptidases to free amino acids.31
For a comprehensive review on the topic of peptide digestion
and absorption, please refer to the recent article by Jahan-
Mihan and colleagues.32
Lingual and gastric lipases initiate the breakdown of lipids,
which are represented in greatest abundance in the human diet
as triglycerides.31,35 Emulsification occurs at first via mechani-
cal shearing in the stomach and at the pyloric sphincter and
16S Journal of Parenteral and Enteral Nutrition 38(Suppl 1)
Figure 1.  (A) Site-specific absorption of dietary nutrients.2,38 (B) Location of release and primary effects of the major humoral and
neural mediators of nutrient processing. SCFA, short-chain fatty acid.
later via the addition of emulsification agents, including phos-
pholipids and, in the duodenum, bile salts.36 The net effect is to
increase the exposed surface area of the lipids available for
digestion. The majority of lipid digestion is carried out by pan-
creatic lipases that are mixed with the emulsified fat droplets in
the latter part of the duodenum.31 This generates long-chain
fatty acids and monoglycerides, which, along with bile salts,
are then incorporated into smaller-diameter micelles that can
be absorbed through the mucosal brush border.27 Medium-
chain fatty acids and SCFAs are hydrophilic enough to remain
soluble in the aqueous environment of the intestinal lumen and
do not generally require assimilation into micelles before
absorption.2,36 The subject of lipid digestion and absorption is
given a more thorough treatment in the review by Phan and
Tso.37
Fluid and electrolyte absorption occurs throughout the GI
tract.38 In total, 8–9 L/d of fluid reaches the small intestine,
from a combination of oral intake and endogenous secretions.
Approximately 98% of this fluid is absorbed by the GI tract,
including 80% by the small intestine and 18% by the colon.2
Although carbohydrates, lipids, and proteins are capable of
being absorbed throughout the small intestine, certain nutrients
undergo more site-specific digestion or absorption (Figure 1).
In the duodenum and proximal jejunum, nonheme iron is
absorbed following reduction to the ferrous form and subse-
quent uptake by transporter proteins such as the divalent metal
cation transporter (DMT1).39 The primary intestinal transporter
for dietary folate in humans, proton-coupled folate transporter
(PCFT), is also expressed primarily in the duodenum, with
somewhat reduced expression in the jejunum.40 In the jejunum
and the proximal ileum, the majority of lactase is synthesized,
and it is here that most lactose digestion occurs.41 Bile salt
resorption occurs in the ileum as well, as part of the enterohe-
patic circulation.2 In the distal ileum, a specific receptor com-
plex consisting of the proteins cubilin and amnionless plays a
key role in mediating absorption of vitamin B12.42 In the colon,
a second folate transporter, reduced folate carrier (RFC-1), is
expressed and may be responsible for the limited uptake of
folate produced by colonic bacteria.43
Regulation of Intestinal Transit
Modulation of intestinal motility is an important regulator of
nutrient processing in the intact digestive system. The pyloric
sphincter, which connects the stomach and duodenum, titrates
chyme based on nutrient composition and concentration.44
This sphincter regulates the movement of liquids and small-
diameter nutrient particles into the duodenum, thereby permit-
ting adequate mixing with bicarbonate, pancreatic, and biliary
secretions.27 Within the small intestine, the chyme is then
churned locally via segmentation contractions and propagated
distally via peristaltic contractions.2 The ileocecal valve that
links the ileum and the colon likely plays a role in decreasing
intestinal motility and may help prevent reflux of colonic flora
into the small intestine.45
GI transit can be modulated by the action of a number of
humoral and neural mediators. The peptide hormone cholecys-
tokinin (CCK) is released from enteroendocrine cells lining the
Tappenden 17S

Table 2.  Mediators Regulating Nutrient Processing.

Gastrointestinal
Mediator Segment(s) Cellular Source(s) Signal Origin Effect
51
Gastrin Stomach and G cells Luminal nutrients ●  Increases gastric acid secretion
duodenum ●  Regulates iron homeostasis
Cholecystokinin46,52 Duodenum, I cells Luminal nutrients, ● Stimulates gallbladder
jejunum, and primarily lipid and contraction
proximal ileum protein ●  Enhances pancreatic secretions
●  Inhibits gastric emptying
●  Promotes satiety
Secretin53 Duodenum and S cells Gastric acid, lipids, ● Increases pancreatic
jejunum fasting bicarbonate secretion
●  Increases pepsinogen secretion
● Slows gastric emptying and
gastric motility
●  Inhibits gastric acid secretion
Glucose-dependent Duodenum and K cells Glucose and lipid ●  Incretin effects
insulinotropic jejunum ● Increases glucose transport
polypeptide54 across the intestinal epithelium
Motilin55 Duodenum and M cells Increases cyclically ● Regulator of the migrating
jejunum during fasting motor complex
●  Increases GI motility
Vasoactive intestinal Proximal small Enteric neurons Intraduodenal acid ●  Relaxes smooth muscle
peptide27,56 intestine and ●  Increases blood flow
colon ● Stimulates pancreatic
bicarbonate secretion
●  Increases intestinal secretions
●  Reduces gastric acid secretion
Neurotensin27,57,58 Jejunum and ileum N cells Luminal fats in the ●  Reduces gastric acid secretion
proximal small ●  Reduces GI motility
intestine ● Stimulates pancreatic
bicarbonate secretion
Peptide YY59 Ileum and colon L cells Lipids, proteins, fatty ●  Slows gastric emptying
acids (including ●  Slows small bowel transit
SCFAs), bile salts, ●  Promotes satiety
cholecystokinin, ●  Reduces gastric acid secretion
gastric acid ● Reduces intestinal fluid
secretion
Glucagon-like Ileum and colon L cells Luminal nutrients in ●  Incretin effects
peptide-147 ileum/colon ●  Inhibits gastric emptying
●  Slows intestinal transit
●  Promotes satiety
Glucagon-like Ileum and colon L cells Luminal nutrients in ● Enhances small and large
peptide-247 ileum/colon intestinal villus/crypt cell
growth
●  Maintains mucosal integrity
●  Increases nutrient absorption
GI, gastrointestinal; SCFA, short-chain fatty acid.

proximal small intestine following contact with lipid- or pro-
tein-rich chyme. CCK decreases the rate of gastric emptying to
maximize nutrient digestion.46 In the distal small intestine,
release of peptide YY (PYY) and glucagon-like peptide 1
(GLP-1) from ileal L cells in response to nutrient stimulation
slows gastric emptying and intestinal motility.47,48 These pep-
tides, and perhaps others, are thought to mediate the so-called
ileal and colonic brakes, by which the entry of nutrients into
the distal intestine slows transit time through the proximal
small intestine.47,49,50
Humoral and Neural Mediators of Nutrient
Processing
Nutrient processing in the healthy human bowel is regulated
through the coordinated actions of a variety of humoral and
18S Journal of Parenteral and Enteral Nutrition 38(Suppl 1)
Figure 2.  Types of intestinal resections: (A) jejunoileal anastomosis, (B) jejunocolic anastomosis, (C) jejunostomy, and (D) outcomes
associated with each type of resection.17,60,61 PN, parenteral nutrition.
neural mediators (Table 2 and Figure 1). The presence of spe-
cific nutrients in the GI tract stimulates the release of special-
ized hormones and neuromodulators, which act to optimize
digestion through coordinated regulation of gastric acid con-
centration, digestive secretions, and intestinal growth, in addi-
tion to modulation of gastric emptying rate and intestinal
motility, as described previously.27 Among those mediators
affecting GI pH and digestive enzyme release are gastrin,
CCK, and secretin. Gastrin is produced by the G cells of the
stomach and duodenum in response to the presence of luminal
nutrients and acts primarily to stimulate gastric acid release.51
As chyme moves into the duodenum, it promotes local produc-
tion of CCK and secretin. CCK triggers the release of digestive
enzymes from the pancreas and bile from the gallbladder,
thereby promoting maximal digestion as described earlier.27,46
One of the major functions of secretin is the stimulation of the
release of bicarbonate solution by the pancreas. Bicarbonate
raises the pH of the chyme and permits optimal function of
digestive enzymes.53
Other peptides function to regulate nutrient absorption and
intestinal motility. In the distal intestine, stimulation by lumi-
nal nutrients induces local release of mediators including PYY,
GLP-1, and GLP-2, among others. A primary function of PYY,
as discussed previously, is to increase small bowel transit
time.49,50 GLP-1 and GLP-2 are generated from the same pre-
cursor protein but possess unique functions. GLP-1 is an incre-
tin hormone and also slows gastric emptying and intestinal
transit time.47 Unlike GLP-1, GLP-2 does not function as an
incretin; instead, it acts to stimulate the growth of the intestinal
mucosa and to promote nutrient and fluid absorption.47
Pathophysiology and Implications of
Intestinal Resection
In patients with SBS, the disruption to the proximal-distal gra-
dient of digestion and absorption depends on the anatomy of
the resection and the remnant bowel. The 3 most common
types of intestinal resections in patients with SBS are jejunoil-
eal anastomosis, jejunocolic anastomosis, and jejunostomy
(Figure 2). In a jejunoileal anastomosis, a portion of the jeju-
num and sometimes part of the ileum are resected, and the
remaining sections are joined together. These patients retain
the terminal ileum, and the colon remains in continuity with
the small intestine. In a jejunocolic anastomosis, the jejunum is
joined to the colon following resection of the ileum and some-
times part of the colon. Patients with an end jejunostomy have
a stoma created in the abdomen that is connected to the rem-
nant of the jejunum. The ileum, colon, and part of the jejunum
are removed.60 Due to the altered anatomy and associated
pathophysiology, each of these resections is associated with a
different range and severity of SBS symptoms (Figure 2).
Jejunoileal Anastomosis
In general, resections of the proximal intestine are more man-
ageable than distal resections because the extent of structural
Tappenden 19S
and functional adaption exhibited by the ileum is greater than
that of the duodenum or jejunum.62,63 Therefore, patients with
jejunoileal anastomoses rarely exhibit major nutrient or elec-
trolyte imbalances because the remnant ileum and intact colon
can compensate for the absence of the resected tissues.
Furthermore, following resection, the colon is capable of
becoming a vital digestive organ that can contribute up to 4.2
mJ/d of additional energy through SCFA production from mal-
absorbed carbohydrates reaching the resident microbiota.64,65
Patients with jejunoileal anastomoses often maintain proper
hydration for 2 primary reasons. First, the tight junctions in the
ileum are less permeable than those in the jejunum, so less
water enters the ileal lumen than the jejunal lumen following
ingestion of a hyperosmotic meal.2 Second, the colon has a
large reserve capacity for fluid absorption. Although under
normal conditions, the colon absorbs only approximately 1.9 L
of fluid per day, it has the potential to absorb up to 5 L of fluid
per day.66
Because most patients with a jejunoileal anastomosis retain
the duodenum and part of the jejunum, development of a nutri-
ent deficiency due to decreased site-specific digestion and
absorption is relatively infrequent.38 However, jejunal resec-
tions can result in a decrease in the regulatory hormones pro-
duced by jejunal cells. For example, gastric hypersecretion
often occurs in the acute postresection phase because of loss of
CCK and secretin feedback inhibition mechanisms that nor-
mally regulate gastrin and gastric acid secretion. As a result,
the pH of the proximal small intestine increases, which can
denature pancreatic enzymes and impair digestion.27,67,68 The
gastric acid hypersecretion phase is usually transient, lasting a
few weeks or months, and patients can often be successfully
treated with proton pump inhibitors or H2 antagonists.69
Jejunocolic Anastomosis
Ileal resections typically result in more severe disease than
jejunal resection because of the decreased adaptive capacity of
the jejunum relative to the ileum.62,63 More extensive ileal
resections are associated with worse outcomes. Among patients
with jejunocolic anastomoses, those with a remnant intestine
shorter than 60 to 65 cm are at the greatest risk of PN depen-
dence.18,70 Patients with ileal resections are also more likely to
experience diarrhea than patients with jejunal resections
because decreased water reabsorption by the distal small intes-
tine puts extra strain on the water-absorbing capacity of the
colon.2 If the colon is partly resected in addition to the ileum,
diarrhea is often further exacerbated.71
Ileal resection results in loss of specialized absorptive pro-
teins such as vitamin B12 receptors and bile salt transporters.
Supplementation with vitamin B12 is typically required for
these patients because of the deficit of specific B12 receptors
normally localized to the distal ileum.72 In addition, bile salt
absorption is reduced following ileectomy, which can result in
fat malabsorption, deficiencies in fat-soluble vitamins, steator-
rhea, and choleretic diarrhea.2,72,73
Plasma concentrations of hormonal mediators of digestion
are also affected by ileal resection. In particular, levels of PYY,
GLP-1, and GLP-2, all of which are synthesized by enteroen-
docrine L cells in the distal ileum and colon, are upregulated
following ileectomy, as long as the colon remains in continu-
ity.49,74 GLP-1 and PYY both inhibit gastric emptying, gastric
acid secretion, and small bowel motility.27,47 As a result,
patients with ileal resections and colon-in-continuity exhibit
normal gastric emptying and intestinal transit times for solids,
and gastric acid hypersecretion is less severe after an ileal
resection than after a jejunal resection.75,76 The other mediator
whose expression is upregulated, GLP-2, is an intestinotrophic
peptide hormone that increases villus height and crypt cell pro-
liferation, among other effects, and thus plays a role in mediat-
ing intestinal adaptation following resection.9,77-79
Jejunostomy
Patients with an end jejunostomy have more serious malab-
sorptive issues than patients with jejunocolic or jejunoileal
anastomoses because they lack both the ileum and colon. Thus,
these patients face the same deficits in ileal site-specific
absorption and water recovery as do patients with jejunocolic
anastomosis but do not derive the fluid-absorbing and energy-
salvaging benefits of an intact colon. End-jejunostomy patients
with less than 100 cm of remnant bowel tend to be “net secre-
tors,” meaning that their stomal output of fluid and salt exceeds
their intake because gastric and intestinal secretions are not
resorbed. These patients typically require long-term PN.80
Magnesium is normally absorbed in the distal small intes-
tine and colon. As a result, magnesium deficiencies are com-
mon in patients with an end jejunostomy. In 1 study, 10 of
12 patients without a colon had low serum magnesium levels
despite receiving oral magnesium supplements.81 Like patients
with an ileal resection, patients with an end jejunostomy also
lose site-specific absorption of vitamin B12 and bile salts.
Unlike patients with jejunocolic anastomosis, patients with
an end jejunostomy exhibit accelerated gastric emptying and
intestinal transit.82 Changes in intestinal hormones following
jejunostomy likely contribute to this phenomenon. Because
patients with an end jejunostomy lack the distal ileal and
colonic L cells that produce PYY, levels of that hormone
decrease following resection.49 No studies have specifically
examined GLP-1 concentrations in patients with an end jeju-
nostomy. However, healthy subjects who underwent a glucose
infusion that was restricted to the proximal small intestine
showed no change in GLP-1, whereas plasma GLP-1 levels
increased when glucose was infused over the entire small
intestine.83 Patients with an end jejunostomy also exhibit lower
postprandial increases in GLP-2 than do healthy subjects.84
Because GLP-2 has been shown in some human studies to
20S Journal of Parenteral and Enteral Nutrition 38(Suppl 1)
inhibit gastric emptying, reduced GLP-2 levels may lead to
increased rates of gastric emptying in patients with an end jeju-
nostomy.78,85 In addition to these hormonal alterations, the
amplitude, velocity, and propagation distance of postprandial
contractions in the jejunum are significantly greater than in the
ileum among healthy subjects.86 Thus, the intrinsic transit
time of nutrients through the jejunum may be faster than
through the ileum, resulting in less contact time between the
nutrient and the mucosa for digestion and absorption.
Pathophysiology in the GI Tract and
Beyond
The varying degrees of malnutrition experienced by patients
with SBS give rise to a range of clinical outcomes that have a
significant impact on patients’ lives. In those patients who have
undergone more extensive resections, malabsorption and the
resulting undernutrition can lead to weight loss; neurocogni-
tive, musculoskeletal, and cardiovascular effects; and immu-
nologic deficits. Additional detail is provided in the companion
article by Jeppesen.4
Complications from the malabsorption of fluids and nutrients
in patients with SBS can extend to tissues and organs beyond the
GI tract. Symptomatic calcium oxalate kidney stones develop in
almost one-fourth of patients with jejunocolic anastomosis and
<200 cm of remnant intestine.81 Bile salt deficiency in these
patients prevents full solubilization and absorption of fatty acids,
which then bind preferentially to intraluminal calcium. Under
normal conditions, calcium binds to oxalate in the distal intes-
tine, forming a precipitate that is expelled in the stool. But when
calcium instead binds to malabsorbed fatty acids, excess free
oxalate is absorbed by the colonic mucosa and excreted by the
kidney, increasing the probability of oxalate kidney stone forma-
tion.87 To offset the risk of nephrolithiasis, patients with SBS and
colon-in-continuity should limit their intake of dietary oxalate
and increase calcium consumption.72
Gallstones occur in up to 25%−45% of patients with
SBS.81,88,89 Because patients with ileal resections have dimin-
ished bile acid pools, insufficiently solubilized cholesterol can
supersaturate the bile and promote gallstone formation. Other
factors contributing to gallstone development in SBS include
reduced gallbladder contractility; altered bilirubin metabolism;
and hypersecretion of mucin, a nucleation-promoting protein.90
Gallstones are more likely to develop in patients with shorter
intestinal remnants, Crohn’s disease etiology, an absent ileocecal
valve, and long-term total PN dependence.88,89 However, gall-
stone prevalence is the same among patients with and without
colon-in-continuity.81 Many gallstones detected in patients with
SBS are asymptomatic, but cholecystitis can develop in up to
10% of patients.89
There are a number of other chronic complications associ-
ated with SBS, including hepatic and biliary disease, metabolic
bone disease, small bowel bacterial overgrowth, enteric hyper-
oxaluria, and D-lactic acidosis. A detailed discussion of these
conditions is beyond the scope of this article, but the topics are
addressed in some detail by companion articles in this supple-
ment. For further information, the reader is encouraged to refer
to a recent review article by Thompson et al.91
Conclusions
Following intestinal resection, the remnant bowel should be
evaluated in functional terms of absorptive capacity, rather
than in structural measures such as remaining length. Of the
3 most common types of intestinal resection that result in
SBS, jejunoileal anastomosis may be the most manageable
for patients and clinicians because of the inherent adaptive
capacity of the ileum and the lack of site-specific nutrient
digestion and absorption localized to the jejunum.
Conversely, the specialized nutrient processing of the ileum
cannot be compensated for following ileectomy. Patients
with an end jejunostomy are at the highest risk of PN depen-
dence because the loss of both ileum and colon greatly
reduces the ability of the intestinal tract to absorb fluids and
nutrients. In addition, an end jejunostomy is associated with
decreased gastric emptying and intestinal transit times,
which decreases the contact time between nutrients and the
absorptive mucosa. Because patients with SBS vary widely
in terms of remnant bowel anatomy and absorptive ability,
individualized patient management plans are essential to
optimizing patient outcomes.
Acknowledgments
Medical writing assistance was provided by Heather Heerssen,
PhD, of Complete Healthcare Communications, Inc (Chadds Ford,
PA) under the direction of the author.
References
1. Vanderhoof JA, Langnas AN. Short-bowel syndrome in children and
adults. Gastroenterology. 1997;113:1767-1778.
2. Hollwarth ME. Short bowel syndrome: pathophysiological and clinical
aspects. Pathophysiology. 1999;6:1-19.
3. Nightingale J, Woodward JM; Small Bowel Nutrition Committee of
the British Society of Gastroenterology. Guidelines for management of
patients with a short bowel. Gut. 2006;55(suppl 4):iv1-12.
4. Jeppesen PB. Spectrum of short bowel syndrome in adults: intesti-
nal insufficiency to intestinal failure. JPEN J Parenter Enteral Nutr.
2014;38(suppl 1):8S-13S.
5. Buchman AL. Etiology and initial management of short bowel syndrome.
Gastroenterology. 2006;130:S5-S15.
6. Rowland KJ, Yao J, Wang L, et al. Immediate alterations in intestinal oxy-
gen saturation and blood flow after massive small bowel resection as mea-
sured by photoacoustic microscopy. J Pediatr Surg. 2012;47:1143-1149.
7. Ziegler TR, Fernandez-Estivariz C, Gu LH, et al. Distribution of the H+/
peptide transporter PepT1 in human intestine: up-regulated expression
in the colonic mucosa of patients with short-bowel syndrome. Am J Clin
Nutr. 2002;75:922-930.
8. Cisler JJ, Buchman AL. Intestinal adaptation in short bowel syndrome.
J Investig Med. 2005;53:402-413.
9. Tappenden KA. Intestinal adaptation following resection. JPEN J
Parenter Enteral Nutr. 2014;38(suppl 1):23S-31S.
Tappenden 21S
10. Crenn P, Coudray-Lucas C, Thuillier F, Cynober L, Messing B.
Postabsorptive plasma citrulline concentration is a marker of absorptive
enterocyte mass and intestinal failure in humans. Gastroenterology.
2000;119:1496-1505.
11. Lal S, Teubner A, Shaffer JL. Review article: intestinal failure. Aliment
Pharmacol Ther. 2006;24:19-31.
12. Pironi L, Hebuterne X, Van Gossum A, et al. Candidates for intestinal
transplantation: a multicenter survey in Europe. Am J Gastroenterol.
2006;101:1633-1643; quiz 1679.
13. Jeppesen PB, Gilroy R, Pertkiewicz M, Allard JP, Messing B, O’Keefe
SJ. Randomised placebo-controlled trial of teduglutide in reducing paren-
teral nutrition and/or intravenous fluid requirements in patients with short
bowel syndrome. Gut. 2011;60:902-914.
14. Thompson JS, Weseman R, Rochling FA, Mercer DF. Current manage-
ment of the short bowel syndrome. Surg Clin North Am. 2011;91:493-510.
15. Jeppesen PB, Pertkiewicz M, Messing B, et al. Teduglutide reduces need
for parenteral support among patients with short bowel syndrome with
intestinal failure. Gastroenterology. 2012;143:1473-1481.
16. Amiot A, Messing B, Corcos O, Panis Y, Joly F. Determinants of home
parenteral nutrition dependence and survival of 268 patients with non-
malignant short bowel syndrome. Clin Nutr. 2013;32:368-374.
17. Buchman AL, Scolapio J, Fryer J. AGA technical review on short
bowel syndrome and intestinal transplantation. Gastroenterology.
2003;124:1111-1134.
18. Messing B, Crenn P, Beau P, Boutron-Ruault MC, Rambaud JC,
Matuchansky C. Long-term survival and parenteral nutrition depen-
dence in adult patients with the short bowel syndrome. Gastroenterology.
1999;117:1043-1050.
19. Tappenden KA. Mechanisms of enteral nutrient-enhanced intestinal adap-
tation. Gastroenterology. 2006;130:S93-99.
20. DeSesso JM, Jacobson CF. Anatomical and physiological parameters
affecting gastrointestinal absorption in humans and rats. Food Chem
Toxicol. 2001;39:209-228.
21. Altmann GG, Leblond CP. Factors influencing villus size in the small
intestine of adult rats as revealed by transposition of intestinal segments.
Am J Anat. 1970;127:15-36.
22. Menge H, Grafe M, Lorenz-Meyer H, Riecken EO. The influence of food
intake on the development of structural and functional adaptation follow-
ing ileal resection in the rat. Gut. 1975;16:468-472.
23. Altmann GG. Influence of starvation and refeeding on mucosal size and
epithelial renewal in the rat small intestine. Am J Anat. 1972;133:391-400.
24. Feldman EJ, Dowling RH, McNaughton J, Peters TJ. Effects of oral ver-
sus intravenous nutrition on intestinal adaptation after small bowel resec-
tion in the dog. Gastroenterology. 1976;70:712-719.
25. Weser E, Babbitt J, Hoban M, Vandeventer A. Intestinal adaptation: dif-
ferent growth responses to disaccharides compared with monosaccharides
in rat small bowel. Gastroenterology. 1986;91:1521-1527.
26. Bines JE, Taylor RG, Justice F, et al. Influence of diet complexity on
intestinal adaptation following massive small bowel resection in a pre-
clinical model. J Gastroenterol Hepatol. 2002;17:1170-1179.
27. Nightingale J, Spiller R. Normal intestinal anatomy and physiology.
In: Nightingale JMD, ed. Intestinal Failure. London, UK: Greenwich
Medical Media; 2001:15-36.
28. Borgstrom B, Dahlqvist A, Lundh G, Sjovall J. Studies of intestinal diges-
tion and absorption in the human. J Clin Invest. 1957;36:1521-1536.
29. Guarner F, Malagelada JR. Gut flora in health and disease. Lancet.
2003;361:512-519.
30. Wang Y, Zeng T, Wang SE, Wang W, Wang Q, Yu HX. Fructo-
oligosaccharides enhance the mineral absorption and counteract the
adverse effects of phytic acid in mice. Nutrition. 2010;26:305-311.
31. Goodman BE. Insights into digestion and absorption of major nutrients in
humans. Adv Physiol Educ. 2010;34:44-53.
32. Jahan-Mihan A, Luhovyy BL, El Khoury D, Anderson GH. Dietary pro-
teins as determinants of metabolic and physiologic functions of the gastro-
intestinal tract. Nutrients. 2011;3:574-603.
33. Erickson RH, Kim YS. Digestion and absorption of dietary protein. Annu
Rev Med. 1990;41:133-139.
34. Semrad CE, Chang EB. Malabsorption syndromes. In: Goldman L, and
Bennett JC, eds. Cecil Textbook of Medicine. 21st ed. Philadelphia, PA:
W. B. Saunders; 2000:712-722.
35. Hamosh M. Lingual and gastric lipases. Nutrition. 1990;6:421-428.
36. Carey MC, Small DM, Bliss CM. Lipid digestion and absorption. Annu
Rev Physiol. 1983;45:651-677.
37. Phan CT, Tso P. Intestinal lipid absorption and transport. Front Biosci.
2001;6:D299-D319.
38. Buchman A. Short bowel syndrome. In: Feldman M, Friedman LS, and
Brandt LJ, eds. Sleisenger and Fordtran’s Gastrointestinal and Liver
Disease. 8th ed. Philadelphia, PA: W. B. Saunders; 2006:2257-2276.
39. Fuqua BK, Vulpe CD, Anderson GJ. Intestinal iron absorption. J Trace
Elem Med Biol. 2012;26:115-119.
40. Qiu A, Jansen M, Sakaris A, et al. Identification of an intestinal folate
transporter and the molecular basis for hereditary folate malabsorption.
Cell. 2006;127:917-928.
41. Torp N, Rossi M, Troelsen JT, Olsen J, Danielsen EM. Lactase-phlorizin
hydrolase and aminopeptidase N are differentially regulated in the small
intestine of the pig. Biochem J. 1993;295(pt 1):177-182.
42. Kozyraki R, Cases O. Vitamin B12 absorption: mammalian physiology
and acquired and inherited disorders. Biochimie. 2013;95:1002-1007.
43. Dudeja PK, Kode A, Alnounou M, et al. Mechanism of folate trans-
port across the human colonic basolateral membrane. Am J Physiol
Gastrointest Liver Physiol. 2001;281:G54-G60.
44. Keinke O, Schemann M, Ehrlein HJ. Mechanical factors regulating gastric
emptying of viscous nutrient meals in dogs. Q J Exp Physiol. 1984;69:
781-795.
45. Ricotta J, Zuidema GD, Gadacz TR, Sadri D. Construction of an ileocecal
valve and its role in massive resection of the small intestine. Surg Gynecol
Obstet. 1981;152:310-314.
46. Chandra R, Liddle RA. Cholecystokinin. Curr Opin Endocrinol Diabetes
Obes. 2007;14:63-67.
47. Janssen P, Rotondo A, Mule F, Tack J. Review article: a comparison
of glucagon-like peptides 1 and 2. Aliment Pharmacol Ther. 2013;37:18-36.
48. Ballantyne GH. Peptide YY(1-36) and peptide YY(3-36), part I: distribu-
tion, release and actions. Obes Surg. 2006;16:651-658.
49. Nightingale JM, Kamm MA, van der Sijp JR, Ghatei MA, Bloom SR,
Lennard-Jones JE. Gastrointestinal hormones in short bowel syndrome.
Peptide YY may be the ‘colonic brake’ to gastric emptying. Gut. 1996;
39:267-272.
50. Savage AP, Adrian TE, Carolan G, Chatterjee VK, Bloom SR. Effects of
peptide YY (PYY) on mouth to caecum intestinal transit time and on the
rate of gastric emptying in healthy volunteers. Gut. 1987;28:166-170.
51. Chu S, Schubert ML. Gastric secretion. Curr Opin Gastroenterol.
2012;28:587-593.
52. Liddle RA, Goldfine ID, Rosen MS, Taplitz RA, Williams JA.
Cholecystokinin bioactivity in human plasma. Molecular forms, responses
to feeding, and relationship to gallbladder contraction. J Clin Invest.
1985;75:1144-1152.
53. Chu JY, Yung WH, Chow BK. Secretin: a pleiotrophic hormone. Ann N Y
Acad Sci. 2006;1070:27-50.
54. Ugleholdt R. Glucose-dependent insulinotropic polypeptide (GIP): from
prohormone to actions in endocrine pancreas and adipose tissue. Dan Med
Bull. 2011;58:B4368.
55. Poitras P, Peeters TL. Motilin. Curr Opin Endocrinol Diabetes Obes.
2008;15:54-57.
56. Larsson LI, Fahrenkrug J, Schaffalitzky De Muckadell O, Sundler F,
Hakanson R, Rehfeld JR. Localization of vasoactive intestinal polypep-
tide (VIP) to central and peripheral neurons. Proc Natl Acad Sci U S A.
1976;73:3197-3200.
57. Thomas RP, Hellmich MR, Townsend CM Jr, Evers BM. Role of gastro-
intestinal hormones in the proliferation of normal and neoplastic tissues.
Endocr Rev. 2003;24:571-599.
22S Journal of Parenteral and Enteral Nutrition 38(Suppl 1)
58. Zhao D, Pothoulakis C. Effects of NT on gastrointestinal motility and secre-
tion, and role in intestinal inflammation. Peptides. 2006;27:2434-2444.
59. Holzer P, Reichmann F, Farzi A. Neuropeptide Y, peptide YY and pancre-
atic polypeptide in the gut-brain axis. Neuropeptides. 2012;46:261-274.
60. Nightingale JMD. The short bowel. In: Nightingale JMD, ed. Intestinal
Failure. London, UK: Greenwich Medical Media; 2001:177-198.
61. O’Keefe SJ, Buchman AL, Fishbein TM, Jeejeebhoy KN, Jeppesen PB,
Shaffer J. Short bowel syndrome and intestinal failure: consensus defini-
tions and overview. Clin Gastroenterol Hepatol. 2006;4:6-10.
62. Dowling RH, Booth CC. Structural and functional changes following
small intestinal resection in the rat. Clin Sci. 1967;32:139-149.
63. Thompson JS, Quigley EM, Adrian TE. Factors affecting outcome fol-
lowing proximal and distal intestinal resection in the dog: an examination
of the relative roles of mucosal adaptation, motility, luminal factors, and
enteric peptides. Dig Dis Sci. 1999;44:63-74.
64. Nordgaard I, Hansen BS, Mortensen PB. Importance of colonic support
for energy absorption as small-bowel failure proceeds. Am J Clin Nutr.
1996;64:222-231.
65. Royall D, Wolever TM, Jeejeebhoy KN. Evidence for colonic con-
servation of malabsorbed carbohydrate in short bowel syndrome. Am J
Gastroenterol. 1992;87:751-756.
66. Debongnie JC, Phillips SF. Capacity of the human colon to absorb fluid.
Gastroenterology. 1978;74:698-703.
67. Sundaram A, Koutkia P, Apovian CM. Nutritional management of short
bowel syndrome in adults. J Clin Gastroenterol. 2002;34:207-220.
68. Jin HO, Lee KY, Chang TM, Chey WY, Dubois A. Secretin: a physiologi-
cal regulator of gastric emptying and acid output in dogs. Am J Physiol.
1994;267:G702-G708.
69. Kumpf VJ. Pharmacological management of diarrhea in patients with short
bowel syndrome. JPEN J Parenter Enteral Nutr. 2014;38(suppl 1):38S-44S.
70. Carbonnel F, Cosnes J, Chevret S, et al. The role of anatomic factors
in nutritional autonomy after extensive small bowel resection. JPEN J
Parenter Enteral Nutr. 1996;20:275-280.
71. Mitchell JE, Breuer RI, Zuckerman L, Berlin J, Schilli R, Dunn JK. The
colon influences ileal resection diarrhea. Dig Dis Sci. 1980;25:33-41.
72. Matarese LE. Nutrition and fluid optimization for patients with short
bowel syndrome. JPEN J Parenter Enteral Nutr. 2013;37:161-170.
73. Eusufzai S. Bile acid malabsorption: mechanisms and treatment. Dig Dis.
1995;13:312-321.
74. Jeppesen PB, Hartmann B, Thulesen J, et al. Elevated plasma glucagon-
like peptide 1 and 2 concentrations in ileum resected short bowel patients
with a preserved colon. Gut. 2000;47:370-376.
75. Landor JH, Behringer BR, Wild RA. Postenterectomy gastric hypersecre-
tion in dogs: the relative importance of proximal versus distal resection. J
Surg Res. 1971;11:238-242.
76. Nightingale JM, Lennard-Jones JE. The short bowel syndrome: what’s
new and old? Dig Dis. 1993;11:12-31.
77. Jeppesen PB, Sanguinetti EL, Buchman A, et al. Teduglutide (ALX-
0600), a dipeptidyl peptidase IV resistant glucagon-like peptide 2 ana-
logue, improves intestinal function in short bowel syndrome patients. Gut.
2005;54:1224-1231.
78. Jeppesen PB, Hartmann B, Thulesen J, et al. Glucagon-like peptide 2
improves nutrient absorption and nutritional status in short-bowel patients
with no colon. Gastroenterology. 2001;120:806-815.
79. Tappenden KA, Edelman J, Joelsson B. Teduglutide enhances structural
adaptation of the small intestinal mucosa in patients with short bowel syn-
drome. J Clin Gastroenterol. 2013;47:602-607.
80. Nightingale JM, Lennard-Jones JE, Walker ER, Farthing MJ. Jejunal
efflux in short bowel syndrome. Lancet. 1990;336:765-768.
81. Nightingale JM, Lennard-Jones JE, Gertner DJ, Wood SR, Bartram CI.
Colonic preservation reduces need for parenteral therapy, increases inci-
dence of renal stones, but does not change high prevalence of gall stones
in patients with a short bowel. Gut. 1992;33:1493-1497.
82. Nightingale JM, Kamm MA, van der Sijp JR, et al. Disturbed gastric emp-
tying in the short bowel syndrome: evidence for a ‘colonic brake’. Gut.
1993;34:1171-1176.
83. Little TJ, Doran S, Meyer JH, et al. The release of GLP-1 and
ghrelin, but not GIP and CCK, by glucose is dependent upon the
length of small intestine exposed. Am J Physiol Endocrinol Metab.
2006;291:E647-E655.
84. Jeppesen PB, Hartmann B, Hansen BS, Thulesen J, Holst JJ, Mortensen
PB. Impaired meal stimulated glucagon-like peptide 2 response in ileal
resected short bowel patients with intestinal failure. Gut. 1999;45:
559-563.
85. Nagell CF, Wettergren A, Pedersen JF, Mortensen D, Holst JJ. Glucagon-
like peptide-2 inhibits antral emptying in man, but is not as potent as glu-
cagon-like peptide-1. Scand J Gastroenterol. 2004;39:353-358.
86. Seidl H, Gundling F, Pfeiffer A, Pehl C, Schepp W, Schmidt T.
Comparison of small-bowel motility of the human jejunum and ileum.
Neurogastroenterol Motil. 2012;24:e373-e380.
87. Parrish CR. The clinician’s guide to short bowel syndrome. Pract
Gastroenterol. 2005;29:67-106.
88. Hill GL, Mair WS, Goligher JC. Gallstones after ileostomy and ileal resec-
tion. Gut. 1975;16:932-936.
89. Thompson JS. The role of prophylactic cholecystectomy in the short-
bowel syndrome. Arch Surg. 1996;131:556-560.
90. Nightingale JM. Hepatobiliary, renal and bone complications of intestinal
failure. Best Pract Res Clin Gastroenterol. 2003;17:907-929.
91. Thompson JS, Rochling FA, Weseman RA, Mercer DF. Current manage-
ment of short bowel syndrome. Curr Probl Surg. 2012;49:52-115.