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 39.5ºC, 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 ileum’s
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 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.

 Referral may be unnecessary in a young

patient with typical symptoms of IBS
while it may be considered early in a
patient in whom Crohn's disease is
suspected
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;
 Stool ova and parasites.
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  Irritable bowel syndrome
laxatives)  Neuroendocrine tumors
 Post-cholecystectomy ◦ Gastrinoma
 Congenital syndromes ◦ VIPoma
(chloridorrhea) ◦ Somatostatinoma
 Bacterial toxins  Mastocytosis
 Ileal bile acid malabsorption  Carcinoid syndrome
 Inflammatory bowel disease  Medullary carcinoma of thyroid
 Microscopic colitis  Neoplasia
 Diverticulitis ◦ Colon carcinoma
 Vasculitis ◦ Lymphoma
 Drugs and poisons ◦ Villous adenoma
 Disordered motility  Addison's disease
◦ Postvagotomy diarrhea  Epidemic secretory (Brainerd)
◦ Postsympathectomy diarrhea diarrhea
◦ Diabetic autonomic neuropathy  Idiopathic secretory diarrhea
 Hyperthyroidism
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/ melanosis coli.
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  Maldigestion
syndromes ◦ Pancreatic exocrine
◦ Mucosal diseases insufficiency
◦ Short bowel ◦ Inadequate luminal bile
syndrome acid
◦ Postresection diarrhea
◦ Small bowel bacterial
overgrowth
◦ Mesenteric ischemia
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 (on a diet containing 100 grams
of fat per day) 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
monosaccharides 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;
 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-4-
cholesten-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 following ingestion
of 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 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 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 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, gluten-
containing diet
◦ celiac disease was present before, usually in
childhood;
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.
Clinical manifestations
 celiac disease may represent a continuum
with variable degrees of severity

 oligosymptomatic patients with celiac

disease may have significant nutritional
deficiencies.
Non-gastrointestinal 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 gluten-
free 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
(enteropathy-associated T-cell 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 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
 Crohn’s 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,
octreotide)
 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 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 (TMP-
SMX, one double-strength tablet twice
daily) maintenance therapy for one year
TREATMENT

 Several reported cases of Jarisch-

Herxheimer reactions one to two hours
after initial therapy of Whipple's disease with
intravenous antibiotics, especially penicillin.

 The reaction consists of fever of 39º to

40ºC, 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
Secondary lactose malabsorption

 Lactose intolerance may persist for

months after healing starts; this effect is
unique to this enzyme and its biochemical
basis is unexplained.
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

 Maintenance of calcium and vitamin

D intake
TREATMENT
 Administration of a commercially available
enzyme substitute (beta-galactosidases)

 Live culture yogurt, which contains

endogenous beta-galactosidase, is an
alternative source of calories and calcium,
and may be well-tolerated by many lactose-
intolerant patients.
 However, yogurts that contain milk or milk
products added back after fermentation may
produce symptoms.