Chronic Diarrhea

Prof. Dr Haider Zaigham Baqai

Professor Medicine
Case Scenario
 A 40 year old male presents with 04 month
history of loose motions and bloating 3-4 days
especially after meals with no fever and blood in
stools. Recently he is complaining of generalized
body weakness, easy fatigue, aches and pain.
 On examination a middle aged man with pallor

and his vitals are normal.

 He has angular cheilosis, balled tongue and

edema feet.
 Abdomen is distended with no free fluid or

viceromegally.
Labs:
 Hb: 9.5 Gm/dL Macrocytosis
 TLC: 6.500 Hyper Segmented nuclei of
WBCs.
 Stool: undigested food particles, cysts of

giardia lamblia
Chronic Diarrhea
 Diarrhea is defined as passage of abnormally
liquid or unformed stools at an increased
frequency.
 For adults on a typical Western diet, stool

weight >200 g/d can generally be considered

diarrheal.
 Diarrhea may be further defined

◦ acute if <2 weeks,

◦ persistent if 2–4 weeks,
◦ chronic if >4 weeks
Causes of Chronic Diarrhea
 Giardiasis  Hyperthyroidism
 Intestinal TB  Diabetic neuropathy
 Celiac disease
 Lactose intolerance
 Drugs
 Cystic fibrosis
 Carcinoid tumors
 IBD  Bacterial overgrowth
 IBS  Short gut syndrome
 GI malignancies  HIV gastropathy
 Tropical sprue
Causes of chronic diarrhea

Secretory Osmotic Steatorrheal

causes causes causes

Inflammatory Dysmotile Factitial

causes causes causes

Iatrogenic
causes
 Secretory Causes
◦ due to derangements in fluid and electrolyte
transport across the enterocolonic mucosa.
◦ characterized clinically by watery, large-volume
fecal outputs
◦ typically painless
◦ persist with fasting
◦ Causes are bowl resection, carcinoids, medications,
 Osmotic Causes
◦ poorly absorbable, osmotically active solutes draw
enough fluid into the lumen to exceed the
reabsorptive capacity of the colon.
◦ characteristically ceases with fasting or with
discontinuation of the causative agent.
◦ Causes laxative intake, carbohydrate
malabsorption,
 Steatorrheal Causes
◦ Fat malabsorption
◦ greasy, foul-smelling, difficult-to-flush diarrhea
often associated with weight loss and nutritional
deficiencies due to concomitant malabsorption of
amino acids and vitamins
◦ Quantitatively, defined as stool fat exceeding the
normal 7 g/d
 Inflammatory Causes
◦ accompanied by pain, fever, bleeding, or other
manifestations of inflammation
◦ The unifying feature on stool analysis is the
presence of leukocytes or leukocyte-derived
proteins such as calprotectin
◦ Any middle-aged or older person with chronic
inflammatory-type diarrhea, especially with blood,
should be carefully evaluated to exclude a
colorectal tumour
Approach to the Patient:
Chronic Diarrhea
HISTORY
 The characteristics of the onset of diarrhea:
Whether it was congenital, abrupt, or gradual
in onset.
 The pattern of diarrhea : continuous or
intermittent?
 The duration of symptoms should be
identified clearly.
HISTORY
 Travel before the onset of illness
 Exposure to potentially contaminated food or

water
 Illness in other family members should be

elicited
 Stool characteristics: watery, bloody, or fatty
HISTORY

 Risk factors for HIV infection

 Weight loss
 Occurrence of diarrhea during fasting or at

night (suggesting a secretory diarrhea)

 Family history of IBD
HISTORY
 The volume of the diarrhea
 The presence of systemic symptoms, which
may indicate inflammatory bowel disease
(such as fevers, joint pains, mouth ulcers, eye
redness)
 All medications (including over-the-counter
drugs and supplements)
 History of diarrhea alternating with
constipation
 Timing of diarrhea: nocturnal diarrhea is

always pathological
HISTORY
 The presence or absence of fecal
incontinence. Some individuals complain of
diarrhea when their major difficulty is
disordered continence.
 ASSOCIATED SYMPTOMS
 Abdominal pain
 Alternating constipation
 Tenesmus
 Unintentional wt. loss
 Fever
PAST MEDICAL HISTORY
 Childhood diarrhea-resolves-re-emergence
in adulthood– celiac disease

 Uncontrolled diabetes

 Pelvic radiotherapy
PAST SURGICAL HISTORY
 Jejunoileal bypass

 Gastrectomy with vagotomy

 Bowel resection

 Cholecystectomy
RED FLAGS-suggestive of organic
causes
 Recent onset in an older patient
 Nocturnal diarrhea (especially if wakes patient)
 Weight loss
 Blood in stool
 Large stool volumes: >400 grams stool per day
 Anemia
 Hypoalbuminemia
 increased ESR
PHYSICAL EXAMINATION
GPE
 General appearance and mental status

 Vital signs

 Body weight

 Orthostasis- volume depletion,autonomic

dysfunction
 exophthalmos (hyperthyroidism)
 aphthous ulcers (IBD and celiac disease)
 lymphadenopathy (malignancy, infection or
Whipple's disease)
 enlarged or tender thyroid (thyroiditis,
medullary carcinoma of the thyroid)
 clubbing (liver disease, IBD, laxative abuse,
malignancy)
SKIN LESIONS
 dermatitis herpetiformis (celiac disease)
 erythema nodosum and pyoderma
gangrenosum (IBD)
 hyperpigmentation (Addison's disease)
 flushing (carcinoid syndrome)
 migratory necrotizing erythema
(glucagonoma).
ABDOMINAL EXAMINATION
 Surgical scars

 abdominal tenderness

 Masses

 Hepatosplenomegaly

 Hyperactive bowl sounds on

auscultation
◦ malabsorption
◦ bacterial overgrowth
◦ obstruction, or rapid
intestinal transit.
 PERINEAL AND RECTAL
EXAMINATION
 Signs of incontinence –
◦ skin changes from chronic irritation,
◦ gaping anus,
◦ weak sphincter tone.
 Crohn's disease
◦ perianal skin tags
◦ Ulcers
◦ fissures
◦ abscesses
◦ Fistulas
◦ stenoses.
 Fecal impaction or masses might be noted.
SYSTEMIC EXAMINATION
 wheezing and right-sided heart murmurs
(carcinoid syndrome)

 arthritis (IBD, Whipple's disease)

INVESTIGATIONS
ROUTINE LABORATORY TESTS
 Blood CP
 Anemia (MCV)
 Leukocytosis suggests the presence of
inflammation
 Eosinophilia is seen with neoplasm, allergy,
collagen-vascular diseases, parasitic infestation,
and eosinophilic gastroenteritis or colitis.
 Serum electrlytes
 Serum albumin
 Serum calcium
 Serum ferritin
STOOL ANALYSIS
 Ova, cysts and parasites
 PH
 Occult blood
 White blood cells
 Sudan stain for fat
 Fecal cultures
 pH, electrolytes and minerals, and laxatives
 Total fats
Radiological investigations
 USG abdomen
 Barium studies
 CT scan abdomen
Endoscopy
 Upper and lower GI endoscopy with biopsy
depending upon the differential diagnosis
Specific investigations
 According to differential diagnosis
 Anti smooth muscle, anti endomysial, Anti

TTG antibodies
 Antibodies to HIV, Entamoeba histolytica
 Stool antigen for giardia
 TSH
 Duodenal biopsy
 Serum gastrin and other hormones
-It is a state arising from abnormality in
absorption of food nutrients across the
gastrointestinal tract(GIT).

-Impairment can be of single or multiple

nutrients depending on the abnormality.

-This may lead to malnutrition and a variety

of anaemias. 3
5
 Malabsorption constitutes the
pathological interference with the
normal physiological sequence of
body such as:
Digestion(intraluminal process),
 Absorption (mucosal process) and
Transport (postmucosal events) of
nutrients. 3
6
 Normal Digestion and Absorption
Luminal Mucosal processes
processes
PANCREAS LIVER JEJUNAL MUCOSA LYMPHATICS BLOOD

1) Digestion 2) Micellar 3)BrushBorder 4) Delivery

Solubilization Digest,Absorpt
Triglyceride Fatty acids Mixed micelle Triglyceride Chylomicrons
Monoglycerides with bile acids synthesis
Chylomicron
formation

Protein Peptides Amino Acids

Amino Acids

Carbohydrate Oligosaccharides Monosaccharides

Disaccharides

These phases of digestion are reviewed and defined in the textbook.

Normal digestion:
a play in 3 acts

 Luminal digestion (pancreatic enzymes)

 Mucosal digestion (small bowel brush

border enzymes)

 Mucosal absorption (small bowel

mucosa, lymphatics)
Luminal Digestion of Fat
 Requires pancreatic lipases

 Requires conjugated bile acids (salts) from

the liver

 No small intestinal back-up available

Efficiency of Small Bowel Absorption:
not perfect
 Nutrients
◦ Fat 93-95% of triglyceride
◦ Starch 80-95% depending on
type
◦ Disaccharides 96-98%
◦ Protein 95-99%
 Minerals
◦ Iron 6-20% depending on
body iron status
Causes of
malabsorption:
 Intestinal malabsorption can be due
to:
1.digestive failure caused by enzyme
deficiencies
2.structural defects
3.mucosal abnormality
4.infective agents
5.systemic diseases affecting GIT
4
1
1.Due to digestive failure:
Pancreatic insufficiencies:
• cystic fibrosis
• chronic pancreatitis
• carcinoma of pancreas

Bile salt insufficiency:

• obstructive jaundice
• bacterial overgrowth

4
2
2. Due to structural defects:
•Inflammatory bowel diseases commonly:
Crohn's Disease
• Gastrectomy and gastro-jejunostomy
• Fistulae, diverticulae and strictures.
• Infiltrative conditions such as amyloidosis,
lymphoma.
•Short bowel syndrome.
•Eosinophilic gastroenteropathy etc.

4
3
3. Due to mucosal
abnormality:
-Coeliac disease

4. Due to enzyme
deficiencies:
-Lactase deficiency inducing lactose intolerance
- Disaccharidase deficiency
- Enteropeptidase deficiency

4
4
5.Due to infective agents:
-Whipple's disease
-Intestinal tuberculosis
-Tropical sprue
-Parasites e.g. Giardia lamblia.

6.Due to other systemic diseases affecting

GI tract:
-Hypothyroidism and hyperthyroidism
-Diabetes mellitus
-Hyperparathyroidism and
Hypoparathyroidism
-Carcinoid syndrome
4
5
Relationship between Diarrhea
and Malabsorption

DIARRHEA

MALABSORPTION
 Input

Malabsorption
= input –
absorption

Absorption

Output
Symptoms of
malabsorption
Diarrhoea, often
-steatorrhoea
- Weight loss
-Growth retardation
-Swelling or edema
-Anaemias
-Muscle cramps and
bleeding tendencies.

4
8
Steatorrhea
Angular Cheilosis
Deficiencies:

Vitamin B-12
Iron
Folate
B vitamins
Glossitis

Deficiencies of:
Vitamin B-12
Iron
Folate
Niacin
Red tongue with burning sensation

B-12 deficiency with hypersegmented PMNs

Zinc Deficiency

Acrodermatitis
54
Celiac disease

Celiac disease is an immune-mediated

enteropathy caused by a permanent sensitivity
to gluten in genetically susceptible individuals.

It occurs in symptomatic subjects with

gastrointestinal and non-gastrointestinal
symptoms, and in some asymptomatic
individuals

55
Incidence
 Age of onset from 6 months to 90+ years
 Affects up to 1%, mostly Caucasians,

Middle Eastern and West Asians

(Indian/Pakistani)
 Long-term risks include

◦ Osteoporosis
◦ 2x overall mortality rate
◦ 2x risk GI tumours

56
The Celiac Iceberg
Symptomatic
Celiac Disease Manifest
mucosal lesion

Silent Celiac
Disease

Latent Celiac Disease Normal

Mucosa

Genetic susceptibility: - DQ2, DQ8

Positive serology

57
 Pathogenesis of celiac

HLA-DQ2
E
Digestion Deamidation

E T-cell

IFN Injury

Gluten Resistant
proteins peptides

Villous atrophy 58
HLA-DQ in Celiac Disease

European Genetics Cluster on Celiac Disease; n=1007

0.4%
6.0%
5.7%
DQA1*05 & DQB1*02
(HLA-DQ2)
DQA1*05 or DQB1*02

DQ1*03 & DQB1*0302

(HLA-DQ8)
Other

88.0%

59
Gastrointestinal Manifestations (“Classic”)

 Most common age of presentation: 6-24

months
• Abdominal pain
 Chronic or recurrent diarrhea• Vomiting
 Abdominal distension • Constipation
 Anorexia • Irritability
 Failure to thrive or weight loss

60
Non Gastrointestinal Manifestations

Most common age of presentation: older child to adult

 Dermatitis Herpetiformis • Iron-deficient anemia

 Dental enamel hypoplasia resistant to oral Fe
of permanent teeth • Hepatitis
 Osteopenia/Osteoporosis
• Arthritis
• Epilepsy with occipital
 Short Stature calcifications
 Delayed Puberty

61
Celiac Disease Occurs with

The Big Three

 Anemia, Iron, Folate,   B deficiency
12
 Frequent tiredness or chronic fatigue;
  Ongoing GI upset

◦ Diarrhea &/or  constipation

◦ Abdominal pain, indigestion, bloating, gas

62
Major Complications of Celiac Disease

 Short stature  Osteoporosis

 Dermatitis  Gluten ataxia and

herpetiformis other neurological

 Dental enamel disturbances
hypoplasia  Refractory celiac
 Recurrent stomatitis disease and related
 Fertility problems disorders
 Intestinal lymphoma

63
 Clinical Associations:
“Clinical syndromes” Disease Associations
Anemia (all comers) 3-12% Dermatitis herpetiformis 100%
Steatorrhea 8% Diabetes mellitus (Type 1) 2-16%
Irritable bowel syndrome 0-7% Thyroiditis 3-5%
Fatigue 2% Selective IgA deficiency 8-29%
Osteoporosis 3% Addison’s disease 1%
Infertility (unexplained) 2-8% Primary biliary cirrhosis 6-7%
Sero-negative rheumatoid arthritis ? Liver failure (transplant) 4%
Depression ? Sjogren’s syndrome 15%
Fractured NOF ? Idiopathic ataxia or neuropathy 17%
Impaired memory ? Idiopathic ataxia 13%
Epilepsy 2%
Family History: Cerebral calcification and epilepsy 77%
1st degree relative 4-18% Down syndrome 4-19%
Identical twin 70-95% Turner syndrome 4-8%

64
Conclusion
 Celiac disease is
 common: 1% community
 GI symptoms are often absent or mild
 Fatigue, anaemia, headaches are common
 Celiac serology is a cheap and effective screen
 Gene testing can exclude celiac disease
 Gastroscopy and duodenal biopsy are essential
 Family testing is important
 Gluten free diet is complex - a skilled dietician is
essential

65
2.Tropical
Sprue
- Caused by infectious agents including
Giardia lamblia, Yersinia
enterocolitica, Clostridum difficile.
-it tends to involve the distal small
bowel.
-total villous atrophy is uncommon.

66
3.Crohn’s Disease
 I t is an inflammatory bowel disease

 Marked by patchy areas of

inflammation anywhere in GIT from
mouth to anus .
 Body’s immune system attacks GT I
leading to chronic inflammation.
67
4. Short Bowel
Syndrome
-Following resection, diarrhea and/or
steatorrhea can appear due to decrease
in the area of the absorptive surface
area.
-Other symptoms include
cramping, bloating and
heartburn.
68
5.Bacterial Overgrowth Syndrome

- There is proliferation of colonic-

type bacteria within the small
intestine.
- Due to stasis caused by impaired
peristalsis . This lead to diarrhea
and malabsorption.

69
Pathophysiology:
* Bacterial over growth leads to:
1.Metabolize bile salt resulting in deconjugation of
bile salts;
  Bile Salt and malabsorption of
fat.
2.Damage of the intestinal villi by:
 Bacterial invasion
 Toxin/.
 Metabolic products
 Damaged villi  cause total villous atrophy.

70
6. Whipple's
Disease
 Cause: by the bacteria Tropheryma whipplei.
Effect:

 Chronic multisystem disease associated with diarrhea,

steatorrhea, weight loss, arthralgia, and central nervous

system (CNS) and cardiac problems .
 Diagnosis:

- identification of T. whipplei by polymerase chain

reaction (PCR).
 - PAS-positive macrophages in the small intestine and

other organs with evidence of disease.

71
 INVESTIGATION OF MALABSORPTION

1. Consider possibility of malabsorption based

on clinical clues

2. Identify nutrient deficiencies

3. Document impaired digestion and/or

absorption of nutrients

4. Identify causative process and treat

appropriately
 Approach to Thinking about Malabsorption

1. How many nutrients?

Single nutrient (i.e., Vitamin B-12)
Subset of nutrients (i.e., fats)
Generalized malabsorption (i.e., several nutrients)

2. What type of nutrient?

Fat, carbohydrate, protein, vitamins,
minerals or combinations

3. Pathophysiologic process likely to be involved?

Luminal maldigestion
Mucosal maldigestion
Mucosal malabsorption
Tests of Malabsorption:
what types are available?

 Screening tests

 Quantitate nutrient malabsorption

 Specific diagnostic tests

Tests of Malabsorption
 Screening tests – simple, cheap, fast
◦ Stool smear with fat stain
◦ CBC for evidence of anemia
◦ Cholesterol/carotene blood levels
◦ Stool osmotic gap for carbohydrates
◦ Weight loss/clinical clues
Tests of Malabsorption
 Quantitate nutrient malabsorption: messy,
take time, accurate and quantitative
◦ 72-hour fecal fat
◦ D-xylose excretion (monosaccharide)
◦ Schilling’s test for B-12 absorption (no longer
available)
◦ Breath hydrogen test (carbohydrate)
 72-hour Fecal Fat Test
Fat input = 100 g/day

Fat
Absorption

Malabsorbed fat:
Normal < 7 g/day
 100 Gram Fat Diet
Average US diet =
~30-40 grams fat/day
Add ~ 1/2 stick butter/
margarine per day to
make a ~100 gram fat diet

Butter/Margarine
1 pound = 453 grams
1 stick = 113 grams

72 hour
Eat the equivalent of ~1/2 stick of butter/
margarine per day for 4-6 days

Fecal Fat
Collect stool for the last 3 days in tightly
sealed container

Test
Assay for total stool weight, fat content
Hydrogen Breath Test for
Carbohydrate Malabsorption
 Principle:
◦ malabsorbed sugar passes into colon
◦ bacteria produce hydrogen gas
◦ H2 diffuses into blood and is excreted by lungs
 Practice:
◦ Administer 25-50 grams of glucose or other
sugar orally
◦ Measure hydrogen in exhaled breath at 2-4
hours
 Variants:
◦ Other sugars can be employed to test for
specific disaccharidase or transporter defects
 lactase deficiency
 glucose-galactose malabsorption
American Gastroenterological Association
Examples: INTERPRETATION OF TESTS OF MALABSORPTION

Fat malabsorption only: Luminal maldigestion

pancreatic insufficiency
bile salt deficiency

Fat and B-12 malabsorption:Luminal maldigestion due to

(have to involve terminal ileum) ileal loss of bile salts and bile salt deficiency
Bacterial overgrowth:
deconjugation of bile acids
and bacterial uptake of B-12

Specific disaccharide
malabsorption: Mucosal maldigestion
disaccharidase deficiency

Fat and d-xylose malabsorption: Mucosal malabsorption

(+/- B-12 malabsorption Celiac sprue
depending on involvement of TI) Tropical sprue
Bacterial overgrowth
Severe Crohn’s disease
Whipple’s disease
Tools for Evaluation of Malabsorption:
diagnosis of underlying disease
once you have identified a small group of possible diseases.

 Radiographs of the small bowel to delineate

anatomy
 Endoscopic retrograde cholangiopancreatography
(ERCP) to define the anatomy of biliary and
pancreatic ducts
 Pancreatic secretory function tests
 Small bowel biopsy and/or antibody tests for
celiac sprue
 Quantitative small bowel bacterial culture, bile
acid or glucose breath tests for bacterial
overgrowth
American Gastroenterological Association
Bile duct

Pancreatic duct
 ERCP view
of Chronic
Pancreatitis

Endoscopic Retrograde
CholangioPancreatography

Single arrow points to bile

duct compressed by fibrotic
pancreas

Double arrow points to dilated

pancreatic duct with short
stubby side branches
Serological Tests

Role of serological tests:

 Identify symptomatic individuals who
need a biopsy
 Screening of asymptomatic “at risk”
individuals
 Supportive evidence for the diagnosis

 Monitoring dietary compliance

86
Serologic Tests

SERUM
SENSITIVITY SPECIFICITY
TESTS
IgA EMA 85-98% 97-100%
IgA tTG 90-98% 94-99%
IgA AGA 75-90% 82-95%
IgG AGA 69-85% 73-90%
87
Endoscopy with biopsy
 Normal Celiac

Gluten

Wheat
Rye
Barley

88
Histological Features

Normal 0 Infiltrative 1 Hyperplastic 2

Partial atrophy 3a Subtotal atrophy 3b Total atrophy 3c

Horvath K. Recent Advances in Pediatrics, 2002. 89

* Management of malabsorption
syndrome
Replacement of nutrients, electrolytes and fluid
: may be necessary.
 I n severe deficiency, hospital admission may b
e
required for parenteral administration.
Pancreatic enzymes are supplemented orally ni
pancreatic insufficiency.
 Dietary modification is important in some
conditions:
 Gluten-free diet in coeliac disease.
90
Lactose avoidance in lactose intolerance.
Treatment

 Only treatment for

celiac disease is a
gluten-free diet
Celiac disease
(GFD)
◦ Strict, lifelong diet
◦ Avoid:
 Wheat
 Rye
 Barley

91
Treatment – 6 Elements in RX
 Consultation with a skilled dietitian
 Education about the disease
 Lifelong adherence to a gluten-free diet
 Identification and treatment of
nutritional deficiencies
 Access to an advocacy group
 Continuous long-term follow-up by a
multidisciplinary team

92
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h a i o n
T u e s t
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