Chronic diarrhea

Definition
Its

definition has traditionally

been based upon the frequency,
volume, and consistency of
stools.
BUT
the relationship between these
features and patients' perception
of diarrhea is variable.

Definition
Chronic

diarrhea should be defined

as a decrease in fecal consistency
lasting for four or more weeks.

The American Gastroenterological Association (AGA) technical review for the

evaluation and
management of chronic diarrhea:

www.gastro.org/practice/medical-positionstatements

Epidemiology
Based

upon a commonly used

definition (ie, the presence of
excessive stool frequency) a
reasonable approximation is that
chronic diarrhea affects
approximately 5 percent of the
population.

Chronic

diarrhea can decrease

quality of life.

Etiology
In

developing countries, chronic diarrhea

is frequently caused by chronic bacterial,
mycobacterial, and parasitic infections,
although functional disorders,
malabsorption, and inflammatory bowel
disease are also common.

In

developed countries, common causes

are irritable bowel syndrome (IBS),
inflammatory bowel disease, malabsorption
syndromes, and chronic infections
(particularly in patients who are
immunocompromised).

Irritable bowel syndrome

The

symptom complex of chronic

lower abdominal pain and altered
bowel habits;

Symptoms

of IBS often correlate

with episodes of psychologic
stress.

Irritable bowel syndrome

Patients

with IBS complain of

crampy lower quadrant pain with
diarrhea, alternating diarrhea and
constipation, or normal bowel
habits alternating with either
diarrhea and/or constipation.

Diarrhea

is usually characterized
as frequent loose stools of small
to moderate volume.

Irritable bowel syndrome

Stools

generally occur during

waking hours, most often in the
morning or after meals.

Most

bowel movements are

preceded by extreme urgency
and may be followed by a feeling
of incomplete evacuation.

Irritable bowel syndrome

Approximately

one-half of all patients

with IBS complain of mucus discharge
with stools.

Incontinence

of liquid stool may occur

during periods of disease activity.

Pain

may be relieved with defecation.

Post-infectious IBS
Following

recovery from C.
difficile and other bacterial
infections.
May mimic the symptoms of the
original infection with diarrhea
and crampy pain.
Patients

who develop this

condition are more likely to have
had mild symptoms of IBS prior to

Irritable bowel syndrome

large

volume diarrhea
bloody stools
nocturnal diarrhea
greasy stools
are notassociated with IBS and
suggest an organic disease.

Functional diarrhea
Continuous

or recurrent passage
of loose or watery stools without
abdominal pain or discomfort

Inflammatory bowel
disease
Primarily

refers to ulcerative
colitis and Crohn's disease.
Most cases have their onset
between ages 15 and 40.

Crohn's disease
May

involve the entire

gastrointestinal tract from mouth to
perianal area.

Diarrhea,

abdominal pain, weight

loss, and fever are the typical
clinical manifestations for most
patients with ileitis, ileocolitis, or
Crohn's colitis.

Crohn's disease
Patients

can have symptoms for

many years prior to diagnosis.

Although

Hemoccult positive
stools are common in Crohn's
disease, gross bleeding is much
less frequent than in ulcerative
colitis.

Ulcerative colitis
Mild disease
Patients present insidiously with
intermittent rectal bleeding
associated with the passage of
mucus, and the development of
mild diarrhea with fewer than
four small loose stools per day.
Mild crampy pain, tenesmus, and
periods of constipation are also
common.

Ulcerative colitis
Moderate disease
Involvement of more than the distal
colon, with the inflammatory
process extending to at least the
splenic flexure (left-sided colitis).
Frequent loose, bloody stools (up to
10 per day), mild anemia not
requiring blood transfusions,
abdominal pain that is not severe,
and low grade fever.

Ulcerative colitis
Severe disease
Usually extensive colonic involvement,
often but not always extending to the
cecum (pancolitis).
Typically have frequent loose stools
(greater than 10 per day) with severe
cramps, fever up to 39.5C, and
bleeding often necessitating blood
transfusion.
Patients may suffer rapid weight loss,
leading to a poor nutritional state.

Microscopic colitis
Characterized

by chronic watery
(secretory) diarrhea of up to two liters
daily without bleeding, with a mainly
intermittent clinical course.
Usually occurs in middle-aged patients.
Lymphocytic

colitis
Collagenous colitis
(the diagnosis is made by histology,
and biopsies obtained from the right
colon are optimal)

Malabsorption syndromes
Malabsorption

refers to impaired
absorption of nutrients.

The

clinical and laboratory

features of malabsorption depend
upon the cause and severity of
the disease

Malabsorption syndromes
The

CLASSIC MANIFESTATIONS of
malabsorption are pale, greasy,
voluminous, foul-smelling stools
and weight loss despite adequate
food intake.

However,

this spectrum of
findings is relatively uncommon,
even in generalized mucosal
disease.

Malabsorption syndromes
The

majority of patients with

malabsorption have relatively
mild gastrointestinal symptoms,
which often mimic more common
disorders such as irritable bowel
syndrome.

Malabsorption syndromes
In

some cases, anorexia,

flatulence, abdominal distension,
and borborygmi may be the only
complaints suggesting
malabsorption; other patients
may be asymptomatic.

Cholecystectomy
Diarrhea

following cholecystectomy has

been reported in 5 to 12 percent of
patients.
In many cases resolves or significantly
improves with time (weeks to months).
The

diarrhea is related to excessive bile

acids overcoming the terminal ileums
reabsorptive capacity and entering the
colon (cholerheic diarrhea).

Chronic infections
Some

persisting infections
C. Difficile
Aeromonas
Plesiomonas
Campylobacter
can be associated
Giardia
with chronic
Amebae
diarrhea
Cryptosporidium
Whipple's disease
Cyclospora

Chronic infections
These

diagnoses should be
considered in patients with
specific risk factors such as
travel, HIV infection, use of
antibiotics, and consumption of
potentially contaminated drinking
water.

All

patients should be asked

about use of antibiotics within the

Chronic infections
Chronic

diarrhea due to Candida

albicans infection has been
described in case reports.
Most patients immunosuppressed
(in some cases received antibiotics)
and malnourished.
Diagnosis established by detection
of large numbers of Candida in small
bowel aspirates and stool specimens
and response to antifungal therapy.

EVALUATION
Optimal

strategies for the

evaluation of patients with
chronic diarrhea have not been
established.

Recommendations

have been
derived mostly from expert
opinion and from experience in
individual clinical centers.

EVALUATION
However,

it is generally agreed upon

that a specific diagnosis can be
achieved in more than 90 percent of
patients.
The selection of specific tests, timing of
referral, and the extent to which testing
should be performed depend upon an
appraisal of the likelihood of a specific
diagnosis, the availability of treatment,
the severity of symptoms, patient
preference, and comorbidities.

Timing of referral
The

timing of referral to a
subspecialist depends upon the
severity of symptoms, the
diagnoses being considered and
the need for endoscopic
procedures.

History
A

thorough medical history can

guide appropriate evaluation.

History
A

clear understanding of what led

the patient to complain of diarrhea;

Stool

characteristics;

Duration

of symptoms, nature of
onset (sudden or gradual)

Travel
Risk

history

factors for HIV infection

History
Weight

loss;

Occurrence

of diarrhea during
fasting or at night (suggesting a
secretory diarrhea);

Family
The

history of IBD;

volume of the diarrhea (SB

vs. colon);

History
The
All

presence of systemic symptoms;

medications;

Association

of symptoms with
specific food ingestion;

A
A

sexual history;

history of recurrent bacterial

infections (eg, sinusitis, pneumonia).

Physical examination

The

physical examination rarely

provides a specific diagnosis.

Physical examination
CLUES:

findings suggestive of IBD (eg, mouth

ulcers, a skin rash, episcleritis, an anal
fissure or fistula, the presence of visible
blood on digital examination, abdominal
masses or abdominal pain);
evidence of malabsorption (such as
wasting, physical signs of anemia, scars
indicating prior abdominal surgery);

Physical examination
CLUES:

lymphadenopathy (possibly suggesting HIV

infection);
abnormal anal sphincter pressure or reflexes
(possibly suggesting fecal incontinence);
palpation of the thyroid and examination for
exophthalmos and lid retraction may provide
support for a diagnosis of hyperthyroidism.

Specific testing
A

large number of tests are

available for diagnosing specific
causes of diarrhea.
There is no firm rule as to what
testing should be done.
The history and physical
examination may point toward a
specific diagnosis for which
testing may be indicated.

Minimum evaluation
Complete

blood count and

differential;
Erythrocyte sedimentation rate;
Thyroid function tests;
Serum electrolytes;
Total protein and albumin;
Stool occult blood.

Minimum evaluation
In

addition, most patients require

some form of endoscopic
evaluation and mucosal biopsy,
depending upon the clinical
setting

CATEGORIZE THE
SYMPTOMS
Because

irritable bowel
syndrome is one of the most
common causes of chronic
diarrhea, it is frequently useful to
begin evaluation by attempting
to categorize the symptoms and
signs of the diarrhea as more
likely to be either
functional (related to IBS)
or organic (related to an identifiable
bowel pathology).

CATEGORIZE THE
SYMPTOMS
The

presence of:

significant weight loss,

anemia,
occult or overt gastrointestinal bleeding,
nocturnal awakening with pain or
diarrhea
are inconsistent with IBS and should
alert to other diagnoses.

CATEGORIZE THE
SYMPTOMS
Another

useful way to guide

specific testing is to attempt to
categorize diarrhea as:
Watery (secretory/osmotic);
Inflammatory;
or
Fatty.

Secretory/osmotic
diarrhea
In

contrast to osmotic diarrhea,

secretory diarrhea
characteristically:
continues despite fasting;
is associated with stool volumes >1
liter/day
occurs day and night.

Secretory/osmotic
diarrhea
Although

usually unnecessary, the

distinction between an osmotic and a
secretory diarrhea can also be
established by measuring stool
electrolytes and calculating an osmotic
gap:
290 - 2 ({Na+} + {K+})
>125 mOsm/kg suggests an osmotic
diarrhea ;
<50 mOsm/kg suggests a secretory
diarrhea.

Secretory diarrhea
Laxative

abuse (nonosmotic laxatives)

Post-cholecystectomy
Congenital syndromes (chloridorrhea)
Bacterial toxins
Ileal bile acid malabsorption
Inflammatory bowel disease
Microscopic colitis
Diverticulitis
Vasculitis
Drugs and poisons
Disordered motility
Postvagotomy diarrhea
Postsympathectomy diarrhea
Diabetic autonomic neuropathy
Hyperthyroidism
Irritable

bowel syndrome
tumors

Neuroendocrine

Gastrinoma
VIPoma
Somatostatinoma
Mastocytosis
Carcinoid
Medullary

syndrome
carcinoma of thyroid

Neoplasia

Colon carcinoma
Lymphoma
Villous adenoma
Addison's

disease
secretory (Brainerd) diarrhea
Idiopathic secretory diarrhea
Epidemic

Secretory diarrhea
Further

testing may include:

stool cultures to exclude chronic

infection;
imaging of the small and large bowel;
selective testing for secretagogues
(secretory diarrhea occurs in 80% of
patients with carcinoid syndrome);
testing for bile-acid malabsorption or
empiric treatment with a bile-acid
binding resin may also be helpful.

Osmotic diarrhea

Mg,

PO4, SO4 ingestion

Carbohydrate malabsorption

Osmotic diarrhea
Further

testing in patients may be

unnecessary if the osmotic agent
can be identified based upon the
history.
Testing the stool for laxatives may
occasionally be required if laxative
abuse is suspected.

Inflammatory/infectious
diarrhea
should

be suspected in patients
with clinical features suggesting:
inflammatory bowel disease;
C. difficile infection;
those at risk for opportunistic
infections;
or those with a pertinent travel
history.

Inflammatory/infectious
diarrhea
Inflammatory

bowel disease

Ulcerative colitis
Crohn's disease
Diverticulitis
Ulcerative

jejunoileitis
Ischemic colitis
Radiation colitis
Neoplasia
Colon cancer
Lymphoma
Infectious

diseases

Pseudomembranous colitis
Invasive bacterial infections
Tuberculosis, yersinosis, others
Ulcerating viral infections
Cytomegalovirus
Herpes simplex
Amebiasis/other invasive parasites

Inflammatory/infectious
diarrhea
Diagnosis

can usually be
established by sigmoidoscopy or
colonoscopy or by analysis of
stool specimens (ie, culture or
testing for C. difficile toxin).

Inflammatory/infectious
diarrhea
Serum

markers of acute inflammation

(such as the sedimentation rate and Creactive protein levels) have been
proposed markers of inflammatory
diarrhea.
However, their test-characteristics have
not been well validated for this purpose;
thus, their role in patients presenting
with chronic diarrhea is unclear.

Inflammatory/infectious
diarrhea
Several

stool studies have also

been evaluated for identifying
patients with inflammatory
diarrhea:
Fecal leukocytes(Se 70%, Sp only
50%);
Fecal calprotectin(Se 93%, Sp 96%
for IBD).

Fatty diarrhea
(steatorrhea)
should

be suspected:

in patients who report greasy,

malodorous stools
and those who are at risk for fat
malabsorption, such as patients with
chronic pancreatitis.

Fatty diarrhea
(steatorrhea)
Malabsorption

syndromes

Mucosal diseases
Short bowel syndrome
Postresection diarrhea
Small bowel bacterial overgrowth
Mesenteric ischemia

Maldigestion

Pancreatic exocrine insufficiency

Inadequate luminal bile acid

Fatty diarrhea
(steatorrhea)

The

gold standard for diagnosis

of steatorrhea is quantitative
estimation of stool fat.

Colonoscopy versus
sigmoidoscopy

An

endoscopic evaluation should

be considered if there are
persistent symptoms,
inconclusive diagnosis, or failure
to respond to therapy.

Colonoscopy versus
sigmoidoscopy
An

advantage of colonoscopy is that

it permits examination and biopsy of
the entire colon and the terminal
ileum (in many patients).

However,

flexible sigmoidoscopy (to

60 cm) is often sufficient for
establishing the diagnosis, is less
expensive, and is associated with
fewer risks.

Symptomatic therapy
Symptomatic

therapy is indicated
when the diagnosis has been
made but definitive treatment is
unavailable, when diagnosis has
eluded diagnostic evaluation, and
as a temporizing measure during
evaluation.
Loperamide;
Intraluminal adsorbents.

Intestinal malabsorption

FAT ABSORPTION
Most

dietary lipids are absorbed in

the proximal two thirds of the
jejunum.

Normally,

more than 94 percent of

dietary fat is absorbed. As a
result, the presence of >6 grams
of fecal fat in a 24-hour collection
indicates fat malabsorption.

FAT ABSORPTION
Central

to the mechanism of fat

absorption is the problem of
solubilizing lipids in an aqueous
environment.
Lipids must be emulsified to
expose a large surface area to
lipolytic enzymes
mastication
gastric mixing
bile salts

FAT ABSORPTION
Enzymes

salivary lipase
pancreatic lipase and colipase
2-monoglycerides

and fatty acids

are then absorbed across the
apical membrane of the
enterocyte.

FAT ABSORPTION
Disease,

or resection, of greater than

100 cm of terminal ileum commonly
results in severe impairment of the
enterohepatic circulation of bile salts
resulting in fat malabsorption.

Similarly,

deconjugation of bile acids by

florid small bowel bacterial overgrowth
defunctionalizes the bile acids, and can
also result in fat malabsorption.

CARBOHYDRATE ABSORPTION
Dietary

starch and disaccharides

must be broken down into their
constituent monosaccarides prior
to absorption.

Enzymes

salivary and pancreatic amylase

brush border enzymes
(disaccharidases)

CARBOHYDRATE ABSORPTION
Carbohydrates

that are not

digested and absorbed in the
small intestine undergo bacterial
degradation in the colon.

Excessive

bacterial fermentation
is the reason for acidic stools,
abdominal distension, and
flatulence in patients with
carbohydrate malabsorption.

PROTEIN ABSORPTION
Protein

digestion begins in the

stomach by the action of gastric
pepsins, which are released as
proenzymes (pepsinogen 1 and
2), and undergo autoactivation at
low pH.

PROTEIN ABSORPTION
In

the duodenum, several proteases

act together to digest proteins into
amino acids, or dipeptides and
tripeptides.

Central

to this process is enterokinase,

which converts trypsinogen to trypsin,
which then catalyzes the conversion of
all other pancreatic proteases to their
active forms.

PROTEIN ABSORPTION
Following

pancreatic enzyme
digestion, amino acids,
dipeptides, and tripeptides can
be absorbed through highly
efficient sodium-dependent
amino acid co-transporters at the
brush border membrane.

PROTEIN ABSORPTION
Impaired

digestion and absorption of

dietary protein occurs when
pancreatic protease secretion and/or
activity is impaired, as in chronic
pancreatitis or cystic fibrosis.

Protein

malabsorption can also occur

in diseases associated with a
generalized reduction of the intestinal
absorptive surface.

VITAMIN, MINERAL, AND TRACE

ELEMENT ABSORPTION
The

fat-soluble vitamins (A, D, E,

and K) require solubilization in a
mixed micellar phase in order to
be absorbed.

The

proximal half of the small

intestine is the predominant site
for the absorption of most
vitamins and minerals;

VITAMIN, MINERAL, AND TRACE

ELEMENT ABSORPTION
The

excess fatty acids present in the

intestinal lumen of patients with
untreated fat malabsorption bind
divalent cations, such as calcium and
magnesium, creating soaps and causing
undue losses of these minerals.

Clinically

significant deficiencies of these

minerals are common in untreated fat
malabsorption and create a substantial
risk for metabolic bone disease.

MALABSORPTION
Refers

to impaired absorption of
nutrients.

Results

from:

congenital defects in the membrane

transport systems;
acquired defects in the epithelial
absorptive surface.
Maldigestion

(due to impaired
digestion of nutrients).

CLINICAL FEATURES
The

clinical features of
malabsorption depend upon the
cause and severity of the
disease.

Malabsorption

may either be
global or partial (isolated).

CLINICAL FEATURES
The

classic manifestations of
global malabsorption are diarrhea
with pale, greasy, voluminous,
foul-smelling stools and weight
loss despite adequate food
intake.

However,

this spectrum of
findings is relatively uncommon,
even with generalized mucosal

CLINICAL FEATURES
Clinical

manifestations related to
a specific micronutrient
deficiency can predominate in
some patients.

CLINICAL FEATURES

Partial

or isolated malabsorption
results from diseases that
interfere with the absorption of
specific nutrients.

Signs and symptoms of

malabsorption

TESTS

Because

symptoms may be
absent or mimic other diseases, a
routine battery of blood tests is
often helpful as an initial step
when malabsorption is suspected.

TESTS
The

malabsorption of fat is the most

commonly used indicator of global
malabsorption for two reasons:
(1) among the macronutrients (fat,
carbohydrates, and protein), the process by
which fat is absorbed is the most complex and,
therefore, it tends to be the most sensitive to
interference from disease processes;
(2) it is the most calorically dense
macronutrient and, therefore, its
malabsorption is a critical factor in the weight
loss that often accompanies malabsorptive
disorders.

TESTS for fat

malabsorption
Qualitative

assessment of fecal
fat on a single specimen, since it
is easier to perform.

Quantitative

assessment of a 72
hour stool collection on a 100
gram fat/day diet if the
qualitative is negative and
clinical suspicion remains high.

TESTS for carbohydrate

malabsorption
D-xylose

test - measures the

absorptive capacity of the
proximal small intestine;
Low blood levels and urinary
excretion suggests mucosal disease
such as celiac sprue.
Absorption is usually normal in
pancreatic insufficiency since
pancreatic enzymes are not required
for xylose absorption.

TESTS for carbohydrate

malabsorption
Lactose

tolerance test

Following oral administration of a 50 g

test dose, blood glucose levels are
monitored at 0, 60, and 120 minutes.
An increase in blood glucose by less
than 20 mg/dL plus the development
of symptoms is diagnostic.
or
An increase in breath hydrogen by
more than 20 ppm is diagnostic.

TESTS for carbohydrate

malabsorption
Breath

tests using H2 or (13)CO2 can

be used to diagnose specific forms of
carbohydrate malabsorption
BUT
Rely on bacterial fermentation of
nonabsorbed carbohydrate (antibiotic
administration often alters the
results)

TESTS for protein malabsorption

Technically

difficult

Enteral protein loss should be

directly demonstrable by
measurement of the alpha-1
antitrypsin clearance.
Plasma citrulline and arginine
concentrations are highly correlated
to small bowel length

ADDITIONAL TESTS
Schilling

test- can also be used

to determine the restoration of
the functional integrity of the
ileal mucosa after treatment of
ileal Crohn's disease

ADDITIONAL TESTS
75SeHCAT

(seleniumhomotaurocholic acid) test

serum test for 7 alpha-hydroxy-4cholesten-3-one
BUT
quantitative measurement of bile
acids in stool in patients who did not
respond to cholestyraminemay be
the method of choice to diagnose
cholerheic enteropathy.

Tests for bacterial

overgrowth
The

gold standard for diagnosis of

bacterial overgrowth is the direct
quantitative measurement of
bacterial counts from aspirated
intestinal fluid.
BUT
Hydrogen breath tests carbohydrate
substrates have replaced bacterial
cultures for the diagnosis of small
bowel bacterial overgrowth.

Tests for pancreatic

insufficiency
DIRECT

(duodenal fluid is
collected and analyzed to
quantify normal pancreatic
secretory content (ie, enzymes,
and bicarbonate)
INDIRECT (measure the
consequences of pancreatic
insufficiency )

Endoscopy and pancreatic

imaging
A

cobblestone appearance of the

duodenal mucosa is seen in
Crohn's disease, while reduced
duodenal folds and scalloping of
the mucosa may be evident in
celiac disease.
The unusual finding of multiple
jejunal ulcers may indicate the
presence of jejunoileitis or
lymphoma

Endoscopy and pancreatic

imaging
Small

bowel biopsy is safe and

can help establish the diagnosis.
Tissue should be obtained distal
to the ampulla of Vater using
biopsy forceps passed through a
gastroduodenoscope or
enteroscope.
Obtaining four biopsies at
different sites optimizes the
likelihood of obtaining a diagnosis

Endoscopy and pancreatic

imaging
Imaging

of the pancreas by CT,

ERCP, MRCP, or ultrasonography
may be helpful in the diagnosis of
chronic pancreatitis and may be
critical for distinguishing benign
from malignant causes.

Barium studies
An

upper gastrointestinal series with

small bowel follow-through or
enteroclysis (a double contrast study
performed by passing a tube into the
proximal small bowel and injecting
bariumand methylcellulose) can
provide important information about
the gross morphology of the small
intestine.

Wireless capsule
endoscopy
Wireless

capsule endoscopy
allows for visualization of the
entire small bowel and allows for
much more detailed evaluation of
small bowel mucosal disease
than bariumstudies.

Celiac disease
gluten-sensitive

enteropathy/nontropical

sprue
frequent

intrafamilial occurrence;
remarkably close association with the
HLA-DQ2 and/or DQ8 gene loci;
immune

disorder that is triggered by an

environmental agent (the gliadin
component of gluten) in genetically
predisposed individuals

Epidemiology
Celiac

disease occurs primarily in

whites of northern European
ancestry.

Prevalences

of 1:300 to 1:500 in
most countries.

Although

classically a disease of
infants, celiac disease now often
presents later, between the ages

CLASSIFICATION
Classic

disease:

villous atrophy
symptoms of malabsorption such as
steatorrhea, weight loss, or other
signs of nutrient or vitamin
deficiency
resolution of the mucosal lesions and
symptoms upon withdrawal of
gluten-containing foods.

CLASSIFICATION
Atypical

celiac disease - patients

exhibit only minor
gastrointestinal complaints:

anemia,
dental enamel defects,
osteoporosis,
arthritis,
increased transaminases,
neurological symptoms,
or infertility.

CLASSIFICATION
Asymptomatic

(silent) celiac

disease
recognized incidentally based upon
screenings for antibodies against
gliadin or tissue transglutaminase

CLASSIFICATION
Latent

celiac disease

patients who have normal jejunal

mucosa and minor symptoms or no
symptoms at one or more time
points while on a normal, glutencontaining diet

Clinical manifestations
diarrhea

with bulky, foul-smelling,

floating stools due to steatorrhea and
flatulence

the

consequences of malabsorption:

growth failure in children,

weight loss,
severe anemia,
neurologic disorders from deficiencies of B
vitamins,
osteopenia from deficiency of vitamin Dand
calcium.

Nongastrointestinal
manifestations
Neuropsychiatric

disease(peripheral
neuropathy, ataxia, depression,
anxiety, or epilepsy)
Arthritis
Iron deficiency
Metabolic bone disease
Hyposplenism
Kidney disease-glomerular IgA
deposition
Idiopathic pulmonary hemosiderosis

ASSOCIATED CONDITIONS
Dermatitis

24%)

herpetiformis(up to

ASSOCIATED CONDITIONS
Diabetes

mellitus- type 1
Down syndrome
Liver disease
Autoimmune thyroid disease
Infertility
Myocarditis and cardiomyopathy
Atrophic glossitis
Pancreatitis

DIAGNOSTIC APPROACH
All

testing should be performed

while patients are on a glutenrich diet.

Serologic

evaluation(IgA anti
tissue transglutaminase and IgA
endomysial antibody)

DIAGNOSTIC APPROACH

Small

bowel biopsy

DIAGNOSTIC APPROACH

DIAGNOSTIC APPROACH

Symptoms

resolve subsequently
on a gluten-free diet

Principles of a gluten-free diet

Wheat,

rye, and barley avoided.

Soybean

or tapioca flours, rice,

corn, buckwheat, and potatoes
are safe.

Nutritional considerations
Specific

dietary deficiency such

as iron, folic acid, calcium,
vitamin Dand, rarely, vitamin
B12 deficiency should be
corrected.

Monitoring the response to a

gluten-free diet
The

rapidity of the response to a glutenfree diet is variable. Approximately 70

percent of patients have noticeable
clinical improvement within two weeks;

Symptoms
Decline

improve faster than histology;

in the titer of antiendomysial

antibodies.

Nonresponders
The

most common reasons for a

lack of response are poor
compliance or inadvertent gluten
ingestion

Other

disorders
Refractory sprue (type 1 and 2)
Ulcerative jejunitis or intestinal
lymphoma

Refractory sprue
Can

be severe and associated with

progressive malabsorption and death.
A subset of patients develops
subepithelial collagen deposition, a
condition referred to as "collagenous
sprue.
The

dose of glucocorticoids required

varies among patients, and not all
patients respond.

Ulcerative jejunitis and intestinal

lymphoma
Considered

in patients with refractory

sprue unresponsive to corticosteroids;

Aberrant
Clinical

T-cell monoclonality;

manifestations are similar to

severe celiac disease; lassitude,
anorexia, weight loss, abdominal pain,
diarrhea, and fever.
Intestinal stricturing can develop with
resulting small bowel obstruction.

Ulcerative jejunitis
Ulcerative

jejunitis responds poorly

to a gluten-free diet

Associated

with an unfavorable
prognosis. Up to one-third of
patients die from complications.

The

prognosis can be improved if

the ulcerated or strictured segment
can be resected.

Enteropathy-associated T-cell
lymphoma
Lymphomas

are almost always of

high-grade histology and the
prognosis is poor.
Five-year survival is
approximately 10%.

Other complications

Esophageal

cancer
Adenocarcinoma of the small
bowel

SHORT BOWEL
SYNDROME
Malabsorption

due to insufficient
intestinal surface area, such that
the affected person is unable to
absorb sufficient fluid, energy or
nutrients to sustain life in the
absence of specific nutritional
support
Less than 200 cm of SB present

Etiology
Crohns

disease
Mesenteric infarction
Massive enterectomies after
trauma, etc.
Intestinal

atresia, necrotisig
enterocolitis (pedriatic)

Consequences
The

degree of malabsorption is determined

by:
The length of the remaining intestine;
The adequacy of the adaptive process in the
residual intestine (up to 2 years to fully develop)
The presence of the ileo-cecal valve (brake to
slow the intestinal transit) and prevents bacterial
overgrowth
The presence of the colon (up to 1000 kcal/day)
Most

patients with a jejunal length of less

than 100 cm and no colon will require longterm parenteral nutrition

Consequences
The

ileum is able to compensate

for the jejunal loss
The jejunum is unable to
compensate for the ileal
absorption of bile salts and
vitamin B12

Consequences
The

proximal small bowel

receives 7-9 L daily of water and
electrolytes, of which 6-8 L is
reabsorbed in the small bowel
Hypovolemia
Hyponatremia
Hypokalemia

Medical managemet
Appropriate

fluid and electrolyte

management
Total parenteral nutrition
Wait

for ADAPTATION

Medical managemet
Antidiarrheal

drugs (loperamide,
codeine, octerotide)
Special diets (hypercaloric, in
small meals)
Vitamin supplementation
Medication malabsorbtion also!!!
Home

parenteral nutrition
(overnight; tunneled catheter)

Complications
Bile

stones (altered composition of bile)

Liver disease (after 5 y of TPN, frequent
grade 2 fibrosis or more, including liver
failure) due to malabsorbtion of
nutrients and shortcut of the portal route
Calcium oxalate kidney stones (fat
malabsorbtion)
Lactic acidosis (colon present)
Metabolic bone disease
Neurologic abnormalities

Survival
TPN

dependence:

86% at 2 years;
75% at 5 years.
Quality

of life!
In U.S. most of them can work
full-time!!

Surgical management
Anastomosis

with the remaining

colon
Intestinal lengthening procedures
Creation of intestinal valves
Intestinal

transplantation
(intestinal/liver transplant!)

Whipple's disease
etiologic

agent was identified in

1991
Tropheryma

whipplei
gram-positive, non-acid-fast,
periodic acid-Schiff (PAS) positive
bacillus

EPIDEMIOLOGY
The

spectrum of infections due to

T. whipplei is wide.

In

Europe, the prevalence of the

bacterium in fecal samples from
the healthy adult population is
estimated to be 1 to 11 percent.

EPIDEMIOLOGY
The

disorder has a predilection for

white males of European ancestry,
suggesting an underlying genetic
predisposition that leads to
colonization of T. whipplei throughout
the intestinal tract, lymphoreticular
system, and central nervous system
upon exposure to soil microbes
the annual incidence since 1980 has
been approximately 30 cases per year

PATHOGENESIS
Invasion

or uptake of the bacillus

is widespread throughout the
body.

All

of these sites show a

remarkable lack of inflammatory
response to the bacillus.
In addition, the organism exerts
no visible cytotoxic effects upon
host cells, thereby allowing

CLINICAL
MANIFESTATIONS
Arthralgias
Weight

loss
Diarrhea
Abdominal pain
progress to a severe wasting
syndrome

CLINICAL
MANIFESTATIONS
There

may also be symptoms or signs

related to cardiac disease (dyspnea,
pericarditis, culture-negative
endocarditis), pleuropulmonary (pleural
effusion), or mucocutaneous disease;

CNS

disease(cognitive dysfunction,
oculomasticatory or oculofacial
myorhythmia , cerebellar ataxia,
dementia, myoclonus, hemiparesis,
peripheral neuropathy, seizures, upper
motor neuron disorders)

EVALUATION
Endoscopy

with small bowel

biopsy(extensive PAS-positive
material in the lamina propria
and villous atrophy )

EVALUATION
Confirmatory

electron microscopy
to demonstrate T. whipplei should
be performed if the diagnosis is in
doubt
PCR techniques

TREATMENT

parenteral

ceftriaxonefollowed
by oral trimethoprimsulfamethoxazole(TMP-SMX, one
double-strength tablet twice
daily) maintenance therapy for
one year

TREATMENT
Several

reported cases of JarischHerxheimer reactions one to two

hours after initial therapy of
Whipple's disease with intravenous
antibiotics, especially penicillin.
The reaction consists of fever of
39 to 40C, chills, headache,
hypotension, and severe abdominal
pain or pleuritic chest pain

Relapse
Relapses

have been reported in

as many as 17 to 35 percent of
patients.

Relapses

should be treated with

initial ceftriaxone(2 g IV twice
daily for four weeks) followed by
one year or more of oral
doxycycline(100 mg twice daily)
plus hydroxychloroquine (200 mg

Lactose intolerance
Intolerance

to lactose-containing
foods (primarily dairy products) is
a common problem:
the prevalence is 7 to 20 percent in
Caucasian adults;
65 to 75 percent among Africans and
African Americans;
50 percent in Hispanics.

Clinical symptoms

diarrhea,

abdominal pain, and

flatulence after ingestion of milk
or milk-containing products

ETIOLOGY OF LACTOSE
MALABSORPTION

primary

lactasedeficiency
lactase deficiency induced by
underlying intestinal disease

Primary lactose
malabsorption
Racial

or ethnic lactose
malabsorption(lactase
nonpersistence)

Developmental

lactase
deficiency(a consequence of
prematurity)
Congenital lactase
deficiency(rare autosomal
recessive disorder)

Secondary lactose
malabsorption
Bacterial

overgrowth or stasis syndromes

Any

form of mucosal injury of the

gastrointestinal tract that causes villus
flattening or damage to the intestinal
epithelium

DIAGNOSIS
Lactose

tolerance test(sensitivity
of 75 percent and a specificity of
96 percent )

Has

largely been replaced by the

lactose breath hydrogen test measures lactose nonabsorption.
Values of breath hydrogen over
20 ppm are considered diagnostic
of lactose malabsorption

TREATMENT
focuses

on eliminating symptoms,
while helping the patient adapt to a
gradual increase in lactose intake.

correctable

underlying disease?

TREATMENT
Reduced

dietary lactose intake

Substitution of alternative nutrient
sources to maintain energy and
protein intake
Administration of a commercially
available enzyme substitute (betagalactosidases)
Maintenance of calcium and vitamin
Dintake