Malabsorption Syndromes

Malabsorption Syndromes
Presenter:
Dr. Melaku Y.(IMR3)
Moderator:
Dr.Fikadu G.(Internist, Gastroenterologist
and Hepatologist,Assistant Prof.)
April,2022

Outline
Celiac Disease
Tropical Sprue
Small Intestinal Bacterial Overgowth(SIBO)
Short Bowel Syndrome(SBS)
Whipple Disease
6/9/2022 2

Celiac Disease
 Definition
 Epidemiology
 Pathogenesis
 Clinical Features
 Diagnosis
 DDX
 Treatment
 Refractory Celiac Disease
6/9/2022 3

Celiac…
Definition:
Celiac disease is an immune-mediated
enteropathy
Induced by the ingestion of gluten (present in
wheat, barley, and rye) in genetically susceptible
individuals
Reverts to normal after the exclusion of gluten
from the diet.
6/9/2022 4

Celiac…
Epidemiology:
 Affects individuals from multiple and diverse ethnic
and racial backgrounds.
 The overall prevalence of celiac disease in Europe has
been estimated at 1%, with the highest reported
prevalence of 2.4% in Finland
 Some authors have noted a female to male ratio of 2:1,
whereas others have reported equal prevalences in men
and women.
6/9/2022 5

Celiac…
Pathogenesis:
 The interaction of the water-insoluble protein moiety
(gluten) of certain cereal grains with the mucosa of the
small intestine in susceptible persons is central to the
pathogenesis of celiac disease.
 Celiac disease is considered an immune disorder that is
triggered by an environmental agent (gliadin) in
genetically predisposed persons.
 The wide spectrum of clinical manifestations is the
result of a complex interplay of varying environmental,
genetic, and immune factors.
6/9/2022 6

Celiac…
Pathogenesis:
Gluten as antigen
 Model for autoimmune diseases with a defined
environmental trigger
 Wheat protein exists in a number of storage forms that can
be categorized into 4 general groups based on solubility
characteristics:
 Prolamins (soluble in ethanol),
 Glutenins (partially soluble in dilute acid or alkali solutions),
 Globulins (soluble in 10% NaCl), and
 Albumins (soluble in water)
 The term gluten encompasses both the prolamins
and the glutenins
6/9/2022 7

Celiac…
Pathogenesis:
 The prolamins of wheat are referred to as gliadins
 Gliadin can be separated electrophoretically into 4
major fractions and exist as single polypeptide chains
 A partially deamidated peptide, consisting of amino
acids 56 to 75 of α-gliadin as a dominant epitope,
responsible for activation of T cells in celiac disease
 The release of intracellular tTG leads to the
deamidation of gluten proteins and an enhancement of
T-cell responses to the resulting DGPs
6/9/2022 8

Celaic…
Pathogenesis:
Other environmental factors:
Recurrent rotavirus infection(increase risk)
H.Pylori infection( inversely related)
Cesarean delivery(increase risk)
Antibiotic use(increase risk)
6/9/2022 9

Celiac…
Pathogenesis:
Genetic factors
Concordance for celiac disease in first-degree
relatives ranges between 8% and 18% and
estimates for concordance in monozygotic twins
range from 49% to 83%
It is now known that after gluten is absorbed,
lamina propria antigen-presenting cells (probably
dendritic cells) that express HLA-DQ2 or HLA-
DQ8, present gliadin peptides to sensitized T
lymphocytes
6/9/2022 10

Celiac…
Pathogenesis:
These lymphocytes then activate B lymphocytes
to generate Igs and other T lymphocytes to secrete
cytokines, including interferon (IFN)-γ,as well as
interleukin (IL)-4, IL-5, IL-6, IL-10, TNF-α, and
transforming growth factor (TGF)-β
 These cytokines induce not only enterocyte
injury but also expression of aberrant HLA class
II cell-surface antigens on the luminal surface of
enterocytes, possibly facilitating additional direct
antigen presentation by these cells to the
sensitized lymphocytes
6/9/2022 11

Celiac…
Pathogenesis:
Immune factors
 Both humoral and cell mediated immune responses to gliadin and
related prolamins in the pathogenesis of celiac disease
 IgA antibodies to endomysium, a connective tissue structure
surrounding smooth muscle, are highly specific for celiac disease.
 It is now known that the target autoantigen contained within the
endomysium is the enzyme tTG-2.
 Gliadin is a preferred substrate for this ubiquitous calcium-
dependent intracellular enzyme, and it has been shown that tTG
deamidates key neutral glutamine residues in gliadin and converts
them into negatively charged glutamic acid residues
6/9/2022 12

Celiac…
Pathogenesis:
tTG-mediated modification of gliadin to generate
DGPs plays a pivotal role in eliciting a stronger
proliferative response by gliadin-specific T cells
Activated T lymphocytes, most of which are
CD4+ cells, are abundant in the lamina propria of
the small intestine.
 In contrast, IELs, which are present in large
numbers in untreated celiac disease, are
predominantly CD8+ T cells
6/9/2022 13

Celiac…
Pathogenesis:
IL-15 regulates IEL homeostasis
 Promoting migration, preventing apoptosis, and
 enhancing the capacity of dendritic cells to function
as antigen-presenting cells.
 In response to gliadin peptides,
 IL-15 triggers an adaptive CD4+ T-cell response in
the lamina propria and
 also is capable of inducing direct epithelial cell
injury by inducing IEL secretion of IFN-γ
6/9/2022 14

Celiac…
Clinical Features:
 Celiac disease has protean manifestations of variable
severity that are summarized according to the “celiac
iceberg” model as classical, atypical, silent, or latent
 “Classical celiac disease” refers to those patients with
the florid malabsorption syndrome (this group is at the
top of the iceberg).
 “Atypical celiac disease” refers to significant but
generally monosymptomatic extraintestinal
manifestations.
6/9/2022 16

Celiac…
Clinical…
“Silent celiac disease” refers to the presence of
disease-specific autoimmunity with villous
atrophy in the absence of any symptoms or
apparent consequences.
 Potential celiac disease denotes those with
normal small intestinal histology who are at
increased risk of developing celiac disease
(usually identified by positive celiac disease-
specific serology).
6/9/2022 17

Celiac…
Clinical…
 Nonresponsive celiac disease (NRCD) is defined as ongoing
or recurrent symptoms or signs that suggest active celiac
disease despite a strict GFD for more than 6 to 12 months.
 Refractory celiac disease (RCD, a subset of NRCD) is
defined as symptomatic, severe small intestinal villus
atrophy despite a strict GFD for more than 6 to 12 months.
 Nonceliac gluten sensitivity refers to symptoms or signs
that develop upon gluten ingestion in people in whom a
diagnosis of celiac disease has been excluded.
6/9/2022 18

Celiac…
Clinical…
In the iceberg model, some atypical cases, but
most especially silent and latent celiac disease,
are below the waterline .
 Currently, non-classical symptoms are the
clinical presentation in more than 50% of
American patients with celiac disease .
6/9/2022 19

Celiac…
Clinical…
Although some patients still present with
severe illness due to significant malabsorption,
many have few, subtle, or no symptoms at
diagnosis
The latter cases may be identified by screening
relatives of patients with celiac disease or from
screening patients with associated disorders,
6/9/2022 20

Celiac…
Clinical:
GI Features
Many adults present with GI symptoms including
diarrhea, steatorrhea, abdominal bloating,
flatulence, and weight loss similar to those seen in
childhood celiac disease.
Diarrhea often is episodic rather than continuous.
Nocturnal, early morning, and postprandial
diarrhea are common
6/9/2022 22

Celiac…
Clinical…
 Severe abdominal pain in celiac disease can suggest the
presence of complications such as intussusceptions,
ulcerative jejunitis, or intestinal lymphoma.
 Abdominal distention with excessive amounts of
malodorous flatus is a common symptom.
 Symptoms of GERD may be significantly more common in
untreated celiac disease and improve on a GFD.
 Recurrent, severe, aphthous stomatitis affects many celiac
patients, may be their sole presenting symptom, and often
resolves on a GFD.
6/9/2022 23

Celiac…
Diagnosis:
Serologic tests
 Tissue transglutaminase antibodies
 Endomysial Antibodies
Histopathology
Genetic testing
6/9/2022 27

Celiac…
Tissue transglutaminase antibodies:
Test by enzyme linked immunosorbent assay is
the screening test of choice for celiac disease
Overall, the tTGA sensitivity is in the range of
95–98% and the specificity >94%
The higher the titer of tissue transglutaminase IgA
antibodies, the greater the likelihood of celiac
disease.
6/9/2022 28

Celiac…
Endomysial Antibodies:
 EMAs can be measured using an immunofluorescence technique.
 The overall sensitivity and specificity using monkey esophagus
as substrate are 97 and 99%, respectively.
 The very high specificity makes EMA a very powerful
serologic test, there are some disadvantages:
 the test is time consuming
 resource-intensive,
 requires microscopy and monkey esophagus substrate,
 semiquantitative at best,
 Highly operator-dependent
6/9/2022 29

Celiac…
Histopathology:
 Small-bowel biopsy is the confirmatory test for celiac
disease.
 Multiple biopsies (ideally four biopsies from the second
part of the duodenum plus two additional biopsies from the
duodenal bulb) are recommended
 Histologic findings include:
 Increased number of intraepithelial lymphocytes (>25 for 100
epithelial cells),
 Villous atrophy,
 Crypt hyperplasia.
6/9/2022 31

Celiac…
Histopathology…
 Biopsies may be classified according to one of several scales
 The most common in use by clinicians is the modified Oberhuber–
Marsh scale
 Stage I: where there is infiltration of the surface layer by intraepithelial
lymphocytes
 Stage II: where in addition to intraepithelial lymphocytes there is
hyperplasia of the crypts
 Stage III: Villous atrophy in addition to the other changes.
 A sub typing of IIIA, IIIB, and IIIC represents mild villous blunting,
partial villous atrophy, and total villous atrophy.
6/9/2022 32

Celiac…
Genetic testing:
 Celiac disease is strongly associated with two HLA
haplotypes: DQ2 and DQ8 .
 Patients with celiac disease carry at least one of those
two gene pairs (90–95% have DQ2).
 Typing of DNA from patients with celiac disease can be
easily performed from whole blood using sequence-
specific primers or allele-specific oligonucleotide
probes
6/9/2022 34

Celiac…
Genetic testing…
 Though approximately 30–35% of the general
Caucasian population carries either the HLA-DQ2 or
the HLA-DQ8 haplotype,
 only a small subset of these subjects have celiac disease
 Thus, HLA genotyping in a clinical setting is useful to
practically exclude the diagnosis of celiac disease
especially when the diagnosis is uncertain
6/9/2022 35

Celiac…
Treatment:
The management of celiac disease is a lifelong,
medically supervised diet that is devoid of gluten
Voluntary or accidental ingestion of gluten may
occur as a result of
 lack of readily available gluten free foods,
 eating outside of the home,
 cross-contamination (trace amounts of gluten in other
non-gluten-containing foods),
 Hidden sources of gluten (e.g., some vitamins and
prescription OTC medications
6/9/2022 38

Celiac…
Treatment…
Other important components of the initial
management include the aggressive correction of
dehydration and nutritional deficiencies
 All patients require assessment of the Potential
metabolic osteopathy by densitometry.
Temporary restriction of lactose for a period of a
few weeks may be beneficial in some cases .
6/9/2022 40

Tropical Sprue
 Definition
 Epidemiology
 Pathogenesis
 Clinical features
 Diagnosis
 Treatment
6/9/2022 44

Tropical Sprue
Definition:
Tropical sprue is an acquired disease of unknown
etiology that affects residents and/or visitors of
certain tropical areas
As infectious agents are the most frequent cause
of chronic diarrhea in a tropical environment, the
diagnosis of tropical sprue requires the exclusion
of active infection, especially by protozoa
6/9/2022 45

Tropical…
Definition…
Tropical sprue is diagnosed with
 malabsorption of at least 2 unrelated nutrient groups
(e.g., fat, carbohydrate, vitamins),
 small bowel biopsy findings of mucosal inflammation
and villous shortening,
and
 exclusion of the common causes of malabsorption all
had to be present to confirm the diagnosis
6/9/2022 46

Tropical…
Epidemiology:
The prevalence of tropical sprue is unknown and
may be different in different locations (e.g., high
prevalence in South India and the Philippines and
very low prevalence in Africa)
The incidence of tropical sprue appears to have
decreased during the past decade,
 Improved hygiene and,
 Widespread empiric use of antibiotics for the
treatment of chronic diarrhea
6/9/2022 47

Tropical…
Pathogenesis:
 The etiology of tropical sprue is not known
 The favored hypothesis is that tropical sprue is either initiated or
sustained by complex interactions among as yet unidentified
infectious agents, the enterocyte, and the immune system of the host
 The host risk factors (e.g., immunologic status, genetics) remain
obscure, as does the specific environmental trigger.
 Bacterial overgrowth, disturbed motility, and mucosal injury
contribute to the manifestation of tropical sprue in a susceptible host
.
6/9/2022 48

Tropical…
Pathogenesis:
The epidemiology of tropical sprue suggests an
infectious etiology, but extensive investigations
have not yet identified or isolated any consistent
causal agent
“Tropical enteropathy” describes non-specific
changes in the intestine (usually mild
inflammation and partial villous atrophy) of
asymptomatic subjects residing in tropical areas
and should not be confused with tropical sprue.
6/9/2022 49

Tropical…
Pathogenesis…
Coliforms (Klebsiella spp., Enterobacter
cloacae, or E. coli) isolated from the small
intestine of patients with TS in Haiti and
Puerto Rico
have been shown to secrete enterotoxins that
damaged the intestinal epithelium in animal
models
6/9/2022 50

Tropical…
Clinical features:
 TS typically affects adults, although it is also known to
occur in children
 The typical presentation is with chronic diarrhea, soreness
of the tongue, and weight loss
 The stool may have evidence of steatorrhea, being pale,
bulky, frothy, and foul smelling.
 Abdominal distension and borborygmi are prominent
features
6/9/2022 52

Tropical…
Diagnosis:
 Histologically, small intestinal biopsy specimens in TS
show varying degrees of villous blunting (atrophy), and
crypt elongation.
 In addition to blunting, the villi sometimes appear fused.
 The normal villous-to-crypt ratio in the jejunal mucosa is
4:1 or 5:1 in the partial villous atrophy seen with TS, this
ratio is reduced to 2:1 or 1:1
 In TS, the ileal mucosa usually displays more severe villous
blunting than the duodenal mucosa
6/9/2022 55

Tropical…
Diagnosis:
 Tropical sprue should be considered in the differential diagnosis of
chronic diarrhea and especially steatorrhea in patients with a recent
history of travel to or residence in tropical areas
 The histologic findings are non-specific and may be
indistinguishable from those seen in celiac disease.
 The d- xylose test and folic acid levels are usually abnormally low.
 Other indirect markers of malabsorption such as
 hypoalbuminemia,
 prolonged prothrombin time, and a
 Low level of β-carotene.
6/9/2022 57

Tropical…
Treatment:
 Dehydration and electrolyte imbalance must be corrected with appropriate
IV fluids (e.g., full-strength lactated Ringer solution.
 In severely malnourished individuals, care must be taken during refeeding
to correct phosphate depletion and prevent the refeeding syndrome which is
caused by rapid refeeding after a long period of undernutrition
 The syndrome consists of cardiac (e.g., heart failure, arrhythmias) and
neurologic (e.g., delirium, seizures, neuropathy, ataxia) abnormalities.
 Refeeding should commence at 10 kcal/kg/day and increase to 40 kCal/kg/
day over a period of 4 to 7 days.
 Thiamine, vitamin B complex, and multi-vitamin supplements should be
started with refeeding
6/9/2022 61

Tropical…
Treatment…
 Broad-spectrum antibiotics and folic acid are the treatment
of choice
 The clinical response is usually rapid (within weeks)
and complete.
 Recurrence is uncommon, especially if the patient is
not a resident of or frequent traveler to tropical areas.
 Relapses are common in treated patients who return to, or
remain in, tropical areas.
6/9/2022 62

Tropical…
Treatment:
 Tetracycline is the antibiotic of choice and should be
used for 3–6 months, usually in conjunction with folic
acid
 Sulfonamide therapy may be an effective alternative in
patients with allergy or other absolute contraindications
for the use of tetracycline.
 A GFD does not result in either clinical or histologic
improvement in tropical sprue.
6/9/2022 63

Small Intestinal Bacterial
Overgrowth(SIBO)
 Definition
 Pathogenesis
 Causes
 Diagnosis
 Treatment
6/9/2022 64

SIBO…
Definition:
 SIBO has traditionally been defined by quantitative
culture of aspirated juice from the proximal jejunum.
 The most widely accepted definition of SIBO is >105
colony-forming units of bacteria per milliliter of
aspirate (CFU/ mL) aerobic Gram-negative or strict
anaerobic bacteria obtained from a jejunal aspirate
 SIBO is typically a byproduct of structural
abnormalities involving the GI tract or alterations in gut
motor, secretory, or immunological function.
6/9/2022 65

SIBO…
Pathophysiology:
 The quantity and species of bacterial flora vary from
the proximal to distal small intestine.
 Normal colony counts are 102 CFU/ mL in the
proximal small intestine, increasing to as high as 109
CFU/ mL in the terminal ileum.
 In the proximal small intestine, Gram-positive,
aerobic bacterial species are most common, while
Gram-negative, anaerobic bacteria are more common
distally
6/9/2022 66

SIBO…
Pathophysiology…
 The normal gut micro flora is maintained by five major
mechanisms:
 gastric acid secretion,
 pancreatic enzyme secretion,
 small-intestinal motility,
 structural integrity of the GI tract,
 and an intact gut immune system
 Disruption of any of these protective mechanisms can
result in the development of SIBO
6/9/2022 67

SIBO…
Clinical features:
 The clinical consequences of SIBO span a spectrum
ranging from asymptomatic to florid malabsorption.
 Most often, affected patients report non-specific
symptoms, including bloating, distension, abdominal
cramping, and diarrhea.
 Diarrhea is usually multifactorial, with contributions
from malabsorption, maldigestion,bile acid
deconjugation, protein-losing enteropathy, and co
morbid disease processes
6/9/2022 73

SIBO…
Diagnosis:
 Aspiration of jejunal fluid for quantitative culture has
been considered the gold standard for the diagnosis of
SIBO
 Drawbacks include the
 invasive nature of sample collection,
 The contamination of aspirated material by oral flora,
 The lack of sensitivity for detecting distal SIBO,
 the expense, and
 the need for infrastructure and trained personnel in order to
perform quantitative culture.
6/9/2022 75

SIBO…
DX…
 Nowadays, despite being less extensively validated,
endoscopic duodenal sampling has mostly replaced
jejunal aspirates due to its sampling convenience.
 During endoscopy,
 the appearance of the small bowel is often normal and non-
specific;
 villous blunting appears to be the only histopathological
feature seen more frequently in SIBO patients when
compared to controls
6/9/2022 76

SIBO…
DX…
 Carbohydrate breath tests are used as a surrogate means
of identifying SIBO.
 Breath tests rely upon the ability of intestinal bacteria
to metabolize various carbohydrate substrates to
hydrogen and/or methane gas.
 Rapid rise in breath hydrogen or methane excretion
may indicate the presence of SIBO
 The most commonly used substrates include lactulose
and glucose.
6/9/2022 77

SIBO…
DX…
 In the absence of SIBO, lactulose is not fermented or
absorbed within the small intestine.
 When exposed to bacteria within the small intestine,
lactulose is fermented to short-chain fatty acids and a
number of gases, including hydrogen and methane.
 Colonic bacteria will also ferment lactulose, making it
difficult to interpret whether a positive breath test result
truly represents SIBO or simply rapid orocecal transit
6/9/2022 78

SIBO…
DX…
 The other substrate commonly used to test for SIBO is glucose.
 Glucose is avidly absorbed in the proximal small intestine.
 Because glucose typically does not reach the distal small bowel,
GBT may be less sensitive than LBT.
 Approximately 15–20% of patients (particularly those with
constipation-predominant IBS) can have methanogenic bacteria that
convert hydrogen into methane, yielding a false negative if only
hydrogen breath levels are measured.
6/9/2022 79

SIBO…
Treatment…
There are 3 components to the treatment of SIBO:
1. Correcting the underlying potentially causative
disease
2. Addressing any associated nutritional
deficiencies
and
3. Modifying the altered microbiota.
6/9/2022 83

SIBO…
Treatment:
 Antibiotics are most commonly used to acutely
decontaminate the small intestine
 An ideal antibiotic for SIBO should possess activity
against both aerobic and anaerobic enteric bacteria.
 A variety of antibiotics have been used to treat SIBO,
including amoxicillin– clavulanic acid,cefoxitin,
ciprofloxacin, norfloxacin,metronidazole, neomycin,
and doxycyclin.
6/9/2022 84

SIBO
TX…
 Most reports in the literature have recommended courses of 7–14
days.
 If a correctable underlying etiology for SIBO can be identified, a
single course of antibiotics may result in a durable clinical response.
 When patients have frequent or very severe bouts of SIBO, using
rotating courses of antibiotics every 4–6 weeks can be very
effective.
 Concerns over such a strategy include the development of
Clostridium difficile colitis and multidrug-resistant bacterial flora.
6/9/2022 85

SIBO…
Treatment…
In a meta-analysis of 10 randomized, placebo-
controlled studies using different antibiotics to
treat SIBO,
 Overall breath test normalization rate, which was
the primary outcome measured, was 51.1% for
antibiotics compared with 9.8% for placebo.
 Symptom response tended to correlate with breath
test normalization
6/9/2022 86

Short Bowel Syndrome(SBS)
 Etiology
 Pathophysiology
 Intestinal Adaptation To Resection
 Medical Management
 Home Parenteral Nutrition
 Complications
 Surgical Management
 Pharmacologic Enhancement Of Bowel Adaptation
6/9/2022 91

SBS…
Definition:
 Short-bowel syndrome (SBS) is defined as
 malabsorption due to insufficient intestinal surface area,
 with an inability to sustain an adequate nutritional, electrolyte, or
hydration status
 in the absence of specialized nutritional support.
 In adults, it is typically the consequence of extensive bowel
resection, with loss of absorptive surface area.
 Over time, the intestine can adapt in order to ensure more
efficient absorption.
6/9/2022 92

SBS…
Definition:
 Intestinal failure is defined as an inability to sustain an adequate
nutritional, electrolyte, or hydration status in the absence of
specialized nutritional support,
 Often seen in patients with SBS,which typically occurs in adults
with less than 200 cm of functional intestine.
 The patients at highest risk generally have a
 Duodenostomy or jejunoileal anastamosis with less than35 cm of
residual intestine,
 jejunocolic or ileocolic anastamosis with less than 60 cm of residual
intestine,
 an end jejunostomy with less than 115 cm of residual intestine
6/9/2022 93

SBS…
Pathophysiology:
The major consequence of extensive bowel
resection is loss of absorptive surface area, which
results in malabsorption of macro and
micronutrients, electrolytes, and water
The degree of malabsorption is determined by
 the length and function of the remaining intestine
 the specific portions of small and large intestine
resected, including
 whether the colon remains in continuity.
6/9/2022 96

SBS…
Pathophysiology:
 The length of the small intestine is estimated at 3–8m in
the adult
 Nutrient absorption is preserved until more than one-
half of the small intestine is removed
 Nutrient absorption may take place at any level of the
small intestine, but crypt morphology and microvillus
enzyme and transporter activity predict a proximal to
distal gradient in absorptive capacity, and as such, most
macronutrients are absorbed in the proximal 100 cm
6/9/2022 98

SBS…
Pathophysiology:
 Patients with a proximal jejunostomy have rapid gastric
emptying of liquids and rapid intestinal transit
 In addition, these patients are net secretors of salt and
fluid, as jejeunal fluid secretion is stimulated by oral
intake and subsequent gastric emptying, so they excrete
more fluid than they ingest
 On unrestricted diets, these patients cannot absorb large
volumes of water and electrolytes, and at less than 100
cm of intact jejunum
6/9/2022 100

SBS…
Pathphysiology:
 The intestine can adapt after bowel resection in order to
ensure more efficient absorption.
 These changes are most pronounced in the ileum, which
attains the morphologic characteristics of the jejunum,
with increased villous density and height and an increase
in length.
 Conversely, the specialized cells of the terminal ileum,
in which vitamin B12 and intrinsic factor receptors are
located, and in which bile salts are absorbed, cannot be
replaced by jejunal compensation
6/9/2022 101

SBS…
Pathophysiology:
 These adaptive changes may take up to 2 years to develop
fully, and depend on the presence of food and
biliary/pancreatic secretions.
 Because of this, patients with SBS are encouraged to start
oral intake as soon as possible after surgery
 In addition, the colon becomes an important digestive organ
in those with SBS.
 It has a large reserve absorptive capacity for sodium and
water, and preservation of even part of the colon can
significantly reduce fecal electrolyte and water losses
6/9/2022 102

SBS…
Pathophysiology:
 Adaptive hyperplasia is the result of an increase in
crypt cell production rate, presumably mediated by
growth factors released by the presence of food and
secretions in the intestinal lumen.
 Pharmacologic interventions to accelerate intestinal
adaptation in patients with SBS.
 Patients with the highest GLP-2 concentration
following a meal are most likely to be successfully
weaned from PN
6/9/2022 103

SBS…
Pathophysiology:
 The presence of comorbid conditions and the health of
the residual bowel and its blood flow are important
prognostic factors for patients who have undergone
massive enterectomy.
 Plasma citrulline concentration, an indicator of bowel
mass, may be a useful predictor for nutrition autonomy.
 Individuals with a plasma citrulline concentration
greater than 20 μmol/L had a 92% sensitivity and 90%
specificity for distinguishing children who gained
independence from PN
6/9/2022 104

SBS…
Treatment(Medical)
The most important aspects in the management
of patients with SBS are provision of adequate
nutrition, provision of sufficient fluid and
electrolytes
In the immediate postoperative phase, most
patients with extensive intestinal resections are
kept fasting and are supported with TPN.
6/9/2022 107

SBS…
Treatment(Medical)…
Weight and volume status are carefully monitored,
and stomal, fecal, and urinary losses of water, Na+
and K+ are measured
Massive enterectomy is associated with gastric
hypersecretion for the initial 6 months
 High doses of oral H2-receptor antagonists,
proton pump inhibitors (PPIs), or IV preparations
due to medication malabsorption.
6/9/2022 108

SBS…
Treatment(Medical):
 The use of antimotility agents, such as high doses of
loperamide hydrochloride (4–16 mg/day) or diphenoxylate.
 If these agents are ineffective, codeine sulfate or tincture of
opium is often necessary.
 ORSs improve hydration and decrease PN fluid
requirements, especially in those patients with a proximal
jejunostomy or with less than 100 cm of jejunum remaining
 These solutions take advantage of the sodium–glucose Co-
transporter and the solvent drag that follows intracellular
transport of sodium and water
6/9/2022 110

SBS…
Treatment(Medical):
 Patients who have undergone massive enterectomy
typically require PN initially.
 Once they are hemodynamically stable, enteral
nutrition should be started as soon as possible, and
advanced gradually as tolerated.
 When patients are able to eat, they should be
encouraged to eat a regular diet and to eat substantially
more than was typical
6/9/2022 112

SBS…
Treatment(Medical):
 Patients with SBS whose colon is in continuity should
consume a high-complex-carbohydrate diet
 Bacteria ferment them into short-chain fatty acids
(SCFAs), including butyrate, proprionate, and acetate.
 SCFAs provide fuel for the colonocyte and
significantly reduce fecal energy losses.
 sodium and water absorption are stimulated by SCFAs,
6/9/2022 113

SBS…
Treatment(Medical)…
Lipid digestion may be impaired, as micelle
formation is limited due to ileal bile salt
malabsorption.
Cholestyramine may be useful in decreasing bile
salt-induced diarrhea in those less than 100 cm of
terminal ileum resected
Regardless of whether the colon is present or
absent, intact protein in a quantity of 1.0 to 1.5
g/kg/day is recommended
6/9/2022 114

SBS…
Treatment(Medical):
 It is important to assess the vitamin and mineral status
of at regular intervals.
 It is unusual for water-soluble vitamin deficiencies to
develop, except in those with duodenostomies or
proximal jejunostomies.
 However, folate deficiency may develop in patients with
proximal jejunal resection, and these patients should
receive daily folate.
 In addition, vitamin B12 deficiency is seen in patients
who have >60 cm of terminal ileum resected
6/9/2022 115

SBS…
Treatment(Medical):
 The length of remaining bowel necessary to prevent
dependence on PN is approximately 100 cm in the absence
of an intact colon or 60 cm in the presence of a colon
 For those who require long-term PN, gradual attempts
should be made to wean them from PN; approximately 50%
can discontinue PN and resume oral intake after 1–2 years
 In addition, treatment with a synthetic analogue of
glucagon-like peptide 2 (GLP 2), an intestinotrophic agent,
was shown to have benefit
6/9/2022 117

SBS…
Treatment(Surgical):
 Anastamosis of the small bowel to the colon is the most
important surgical procedure, enhancing the ability of the
colon to become an energy-absorptive organ
 Longitudinal intestinal lengthening and tailoring (Bianchi
procedure)
 The main indication for intestinal transplantation is
 PN dependent SBS complicated by progressive liver disease
 If patients are referred for evaluation for transplantation prior to
the development of advanced fibrosis,
 patients with significant fluid losses and refractory dehydration.
6/9/2022 120

SBS…
Prognosis:
 The prognosis for patients with SBS depends on the type
and extent of bowel resection, along with the underlying
disease and health of residual intestine.
 Patients with small bowel length<50 cm, including those
with high jejunostomies and severe malabsorption, have a
worse prognosis.
 Mesenteric infarction and radiation enteritis as a cause for
the bowel resection has a worse prognosis
 overall prognosis, including survival and quality of life, is
improving, largely because of increasing experience with
long-term TPN
6/9/2022 121

Whipple Disease
 Epidemiology
 Pathogenesis
 Diagnosis
 DDX
 Treatment and Prognosis
6/9/2022 122

Whipple…
Definition and Epidemiology:
Whipple’s disease is a rare, chronic, systemic
infection caused by Tropheryma whipplei
Whipple’s disease is most common between the
4th and 6th decades of life, with a male
predominance.
It occurs predominantly in Caucasians and is
more common in farmers
6/9/2022 123

Whipple…
Pathophysiology:
 The symptoms and clinical findings in Whipple’s disease are caused
by chronic infection of the small intestine and other extraintestinal
sites with T. whipplei.
 T. whipplei DNA has been found in gastric fluid, saliva, and stool
samples from asymptomatic patients, suggesting that T. whipplei
may be a ubiquitous, commensal organism in the environment.
 Immune evasion and host interaction are important in the
pathogenesis of infection.
 Defects of monocyte/macrophage function ,plays an important
pathophysiologic role, leading to an inability of the host response to
eliminate the bacteria
6/9/2022 124

Whipple…
Pathophysiology…
 T. whipplei is a commensal bacterium of humans,
transmitted between humans
 May cause acute primary disease followed by acquired
immunity and bacterial clearance
 In some people it is not cleared and leads to a healthy
asymptomatic carrier state
 It may go on to cause WD, but only in a small subset
of people who lack an adequate immune response
6/9/2022 125

Whipple…
Pathophysiology:
The lamina propria of the small-bowel mucosa is
 Infiltrated by large, foamy macrophages,
 Distort normal villous architecture,
 Blunted, club-like appearance.
The cytoplasm of these macrophages is filled with
large glycoprotein granules that stain with PAS.
 The lymphatic channels are dilated.
6/9/2022 126

Whipple…
Pathophysiology…
 Electron microscopy reveals rod-shaped bacillary
bodies in the lamina propria.
 The bacilli have a characteristic cell wall and pale
central nucleoid.
 The Whipple bacillus is acid-fast-negative.
 PAS-positive macrophages and the characteristic bacilli
have been identified in many extraintestinal tissues,
reflecting the systemic nature of the disease.
6/9/2022 127

Whipple…
Clinical features:
Some authors have proposed the existence of 3
distinct types of disease:
 classic (disseminated and/or intestinal) WD
 chronic localized infection, such
endocarditis,isolated CNS disease or uveitis,
without detectable intestinal involvement;
and
 Acute transient infections, such as gastroenteritis
or pneumonia.
6/9/2022 129

Whipple…
Clinical features:
GI Symptoms
Diarrhea or steatorrhea is the most common
presenting complaint
Other intestinal symptoms include abdominal
bloating, cramps, and anorexia.
 Weight loss is the second most common
presenting complaint
6/9/2022 130

Whipple…
Clinical features:
Extraintestinal Symptoms
 Arthritis is the most common extraintestinal symptom, affecting the
majority of patients
 It often develops before the initial diagnosis of Whipple’s disease
and is typically an intermittent, migratory arthritis of both the large
and small joints.
 Fever is usually low grade and intermittent
 Fatigue and generalized weakness are also common.
 T. whipplei is associated with culture-negative infective endocarditis
6/9/2022 131

Whipple…
Clinical features:
Neurological Symptoms
 Symptoms related to CNS Whipple’s disease are present in a
minority of patients.
 Neurological symptoms may occur with GI symptoms or as isolated
symptoms.
 The most common CNS symptoms are dementia, paralysis of gaze,
and myoclonus.
 Two signs that are indicative of CNS WD are oculomasticatory
myorhythmia and oculofacial skeletal myorhythmia
.
6/9/2022 132

Whipple…
Radiologic and Endoscopic Findings:
A small-bowel series typically reveals marked
thickening of the mucosal folds, most prominent
in the proximal small bowel
Abdominal CT often reveals small-bowel
thickening and massive para-aortic and
retroperitoneal adenopathy
On endoscopy, a characteristic finding of pale,
shaggy, yellow mucosa in the postbulbar
duodenum may be seen
6/9/2022 134

Whipple…
Laboratory Findings:
 Low serum carotene levels,
 Hypoalbuminemia,
 Electrolyte disturbances,
 Anemia is usually present secondary to chronic disease or iron
deficiency
 The erythrocyte sedimentation rate is often elevated
 Prothrombin time is frequently prolonged
6/9/2022 135

Whipple…
Diagnosis:
 Small-intestinal mucosal biopsy is the diagnostic test of
choice.
 Diagnostic of Whipple disease:
 Infiltration of the lamina propria of the small intestine by
 PAS-positive macrophages containing
 Gram-positive,
 acid-fast-negative bacilli
 accompanied by lymphatic dilation
 Rarely, the diagnosis of Whipple’s disease is established in
the absence of intestinal involvement by the identification
of bacilli in involved tissues.
6/9/2022 136

Whipple…
Treatment:
 Antibiotic therapy usually results in dramatic
improvement.
 Treatment with an antibiotic that readily crosses the
blood–brain barrier (BBB) is appropriate
 One double-strength tablet TMP–SMX given twice
daily for 1 year has been proposed to be the optimal
long-term option
 Initial therapy with parenteral penicillin G and
streptomycin, ceftriaxone, or meropenem for 10–14
days results in a lower relapse rate
6/9/2022 137

Whipple…
Treatment:
 Patients may also develop an immune reconstitution
inflammatory syndrome (IRIS), manifested by a high
fever in the first few weeks following initiation of
antibiotics.
 This is more common in patients with CNS involvement
and in those who were on extended immunosuppressive
therapy
 After 1 year of antibiotic therapy, a small-intestinal
mucosal biopsy should be repeated to document the
absence of residual bacilli.
6/9/2022 138

Whipple…
Prognosis:
 The prognosis for patients with Whipple’s disease who
receive effective antibiotic therapy is excellent, with
rapid improvement in GI and extraintestinal symptoms.
 Relapse of GI symptoms and arthritis may occur early
or late and may respond favorably to further antibiotic
treatment, whereas CNS relapses tend to occur late
 If relapse is suspected, small-intestinal biopsy should
be repeated to assess for the presence of free bacilli.
 The treatment of relapse of Whipple’s disease is a
repeat course of the initial antibiotic therapy.
6/9/2022 141

References
 Sleisenger and Fordtrans’ Gastrointestinal and Liver
Disease(11th edition)
 Harrison’s Principles of Internal Medicine(20th edition)
 Practical Gastroenterology and Hepatology(2nd edition)
 Uptodate,2018
 Guidelines for management of patients with a short bowel ,J
Nightingale, J M Woodward on behalf of the Small Bowel
and Nutrition Committee of the British Society of
Gastroenterology
 N engl j med 367;25 nejm.org December 20, 2012
 J Gastroenterol 2020;115:165–178.
https://doi.org/10.14309/ajg.0000000000000501; published
online January 8, 2020
6/9/2022 142

Malabsorption Syndromes

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