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-position-statements

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 the inciting infection.

Irritable bowel syndrome

large volume diarrhea
bloody stools
nocturnal diarrhea
greasy stools

are not associated 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 with
Giardia
chronic diarrhea
Amebae
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 last three months!

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 history

Risk factors for HIV infection

History

Weight loss;

Occurrence of diarrhea during fasting or

at night (suggesting a secretory diarrhea);

Family history of IBD;

The volume of the diarrhea (SB vs. colon);

History

The presence of systemic symptoms;

All medications;

Association of symptoms with specific

food ingestion;

A sexual history;

A 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

Neuroendocrine tumors
Gastrinoma
VIPoma
Somatostatinoma

Mastocytosis
Carcinoid syndrome
Medullary carcinoma of thyroid
Neoplasia
Colon carcinoma
Lymphoma
Villous adenoma

Addison's disease
Epidemic secretory (Brainerd)
diarrhea
Idiopathic secretory diarrhea

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 C-reactive
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 cotransporters 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;
Exception: vitamin B12.

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 disease.

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 (selenium-homotaurocholic
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
cholestyramine may 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
barium and 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
barium studies.

Celiac disease

gluten-sensitive enteropathy/nontropical
sprue

frequent intrafamilial occurrence;

remarkably close association with the HLADQ2 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 of 10 and 40 years.

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 glutencontaining 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 D and
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 herpetiformis (up to 24%)

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 gluten-rich 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 D and, 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 improve faster than histology;

Decline 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 T-cell monoclonality;

Clinical 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 highgrade 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 long-term
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 acidSchiff (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 massive accumulation of T.
whipplei at sites of infection.

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 ceftriaxone followed by oral

trimethoprim-sulfamethoxazole (TMPSMX, 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 PO thrice
daily).

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 lactase deficiency
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 (beta-galactosidases)
Maintenance of calcium and vitamin
D intake