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Chronic diarrhea and

malabsorption syndrome

Pisaln Mairiang, MD.
Department of Medicine,
Faculty of Medicine,
Khon Kaen University, Thailand
Daily fluid intake and endogenous secretion are
efficiently absorbed by the gastrointestinal tract
Oral intake 2000
Salivary glands 1500
Stomach 2500
Bile 500
Pancreas 1500
Intestine 1000 % Absorbed 8800 =98%
•Total fluid into 9000
GIT lumen
= 9000 ml
•Total fluid Net balance 2000-200=1800
absorbed
200 ml
= 8800 ml
Intestinal epithelial cell turnover time

Cell death
and sloughing
Villus
Region
Turnover time 48-72 hr

Crypt Dividing cells
Region
Paneth cells
The intestinal surface area
for absorption
Type of amplification surface area
surface factor (cm2)

Mucosal cylinder 1 3,300
Fold of kerkring 3 10,000
Villi 10 100,000
Microvilli 20 2,000,000

Total surface area = 200 m2
Chronic diarrhea

Functional Organic
Mucosal enterochromaffin cell
Mechanical or chemical
stimulation

5-HT4R: increas
and motility
Symptom Rome
- Based Diagnostic
III Diagnostic Algorithm
Criteria for IBS for IBS
At least 3 months, with onset at least 6 months previously of recurrent abdominal
pain or discomfort** associated with 2 or more of the following :
Improvement with defecation; and/or
Onset associated with a change in frequency of stool; and/or
Onset associated with a change in form (appearance) of stool

Felling of incomplete evacuation
Passing mucus during bowel movements Supportive symptoms
Abdominal fullness, bloating
Constipation Diarrhea
< 3 bowel movements/wk > 3 bowel movements
Hard lumpy stools Loose or watery stools
Straining during bowel movement Urgency

Assess for alarm features Yes
History : Unintended weight loss, nocturnal symptoms, rectal bleeding, patient age > 50 yr, Additional
family history Diagnostic testing
Laboratory results : anemia, leukocytosis, high ESR, abnormal blood chemistries,
abnormal thyroid function
Physical examination : relevant abnormalities (eg, abdominal mass, arthritis)
No
Make a positive diagnosis of IBS

Treat according to primary symptom
Assess response in 4-6 wk No response

Response Investigate further
Continue therapy
Chronic organic
diarrhea

HIV Non HIV
HIV

Watery Inflammatory Malabsorption
HIV watery diarrhea
Protozoa
• Cryptosporidium
• Microspordium
• Isospora belli
• Cyclospora
Viral
• HIV
Drug
• Protease inhibitors : nelfinorvir
Organisms Morphology/diagnosis Treatment
Cryptosporidium HAART

AFB staining in stool
Cyclospora Trimethoprim/sulfa
Or
Ciprofloxacin
AFB staining in stool 2-4 wks
Isospora Trimethoprim/sulfa
Or
Ciproflox or
pyramethamine
Stool/duodenal content 2-4 wks

Microspora Albendazole
Or
Biopsy/EM Metronidazole
HIV-associated chronic inflammatory diarrhea
A. Infectious
Protosoa
• E.histolytica
Bacteria
• Clostridium diffieile
• Salmonella
• Shigella
• Campylobacter
• MAC/M tuberculosis
Viral
• CMV
• Herpes simplex
Fungus
• Histoplasmosis
B. Neoplasm
• Lymphoma
• Kaposi sarcoma
Organism Diganosis Treatment

CMV Ganciclovir,
Foscarnet

MAC Amikacim,Ethabutal,
Rifampin,
Clarithromycin,
Ciprofloxacin

M.TB Anti-TB
HIV associated malabsorption
syndrome

• Giardia
• Lymphoma
• TB
• AIDS enteropathy
• Chronic pancreatitis
• Bacterial overgrowth
Chronic organic diarrhea (non-HIV)

Malabsorption
Watery Inflammatory Syndrome
Chronic watery diarrhea

Osmotic Secretory

• Ingestion of non absorbable solutes
• Carbohydrate malabsorption
Chronic secretory diarrhea

• Watery diarrhea/large volume
• Narrow osmotic gap
290-2 (Na + K) < 50
• Fasting has no (or only slightly)
effect on stool volume
Stool osmotic gap

290-2 (Na + K) > 100 = osmotic diarrhea
290-2 (Na + K) < 50 = secretory diarrhea
2 (Na + K) > 290 = ingestion of poorly absorpted
anion (PO4, sulfate) or
adding concentrated urine
Stool osmolality < 250 = adding water
Chronic secretory diarrhea

Endocrine Infection
• ZE syndrome • Aeromanas/pleisiomanas
• Vipoma Inflammatory
• Glucagonoma • Microscopic colitis
• Carcinoid syndrome
Bile acid diarrhea
• Medullary CA of thyroid
Tumor
• Mastocytoma
• Villous adenoma
• Pheochromocytoma
Idiopathic
Motility
• Dumping syndrome Laxative abuse
• Diabetic autonomic neuropathy
Chronic secretory diarrhea
Diseases Manifestation Diagnosis
ZE syndrome • Secretory diarrhea • serum gastrin>
• Malabsorption 1,000 pg/ml
• Severe peptic ulcer with • increase serum
complications gastrin <50% after
test meal
Vipoma • Severe watery diarrhea • fasting plasma VIP
• Hypokalemia >190 pg/ml
• Achlorhydria
• Hypokalemia

Carcinoid • Flushing • 24 hr urine 5 HIAA
• Bronchospasm >25 mg/day
• Heart murmur • somatostatin
receptor scan
Chronic secretory diarrhea
Diseases Manifestation Diagnosis

Medullary CA. thyroid • Thyroid nodule • 25-50% associated
• Secretory diarrhea with MEN
• Hypercalcemia

Glucagonoma • Migratory necrolytic
erythema
• Thromboembolism

Mastocytosis • Urticaria pigmentosa
• Flashing
• Peptic ulcer
Microscopic colitis
Lymphocytic colitis Primary symptom is
watery diarrhea
F/M=9/1,associate
With autoimmune Dz
Normal colonoscope
Intraepithelial
lymphocytic
infiltration

Collagenous colitis As Lymphocytic
colitis+intra-
epithelial deposit of
collagen band
10-100 micron in
width
Bile acid diarrhea
• Primary bile acid diarrhea
• Secondary bile acid diarrhea
• Ileal resection < 100 cm
• Ileal disease (Crohn, TB, radiation)
• Ileal bypass
NB : If ileal resection > 100 cm cause
decrease bile acid pool  steatorrhea
Osmotic diarrhea

Stool analysis

Low pH High Mg output
Carbohydrate Inadvertent ingestion
malabsorption Laxative abuse

Dietary review
Breath H2 test
(lactose)
Lactase assay
Chronic organic diarrhea (Non
HIV)

Inflammatory Secretory

Malabsorption
Chronic inflammatory diarrhea

• Fever
• Abnormal pain
• Mucus / Bloody
• Stool leukocytes
• ESR
Chronic inflammatory diarrhea

• Inflammatory bowel disease : Crohn’s, UC
• Infection : TB
• Collagen vascular disease
• Lymphoma, cancer
• Eosinophilic gastroenteritis
• Radiation
• Ischemic
Inflammatory diarrhea Clinical sy

Exclude infection Exclude structural
disease

Small-bowel Radiography /
Capsule endoscopy
Standard Other pathogens
Bacterial Parasites :strongyloid Sigmoidoscopy
Pathogens: E histolytica, Or colonoscopy
Shigella Viruses: CMV With biopsy
C difficile
Salmonella
CT scan
Campylobacter
of abdomen
Tuberculosis

Small-bowel
biopsy
Chronic organic diarrhea (Non
HIV)

Inflammatory Secretory

Malabsorption
Malabsorption
syndrome
• Malnutrition
• Maldigestion or malabsorption
• Diarrhea
CARBOHYDRATE
DIGESTION AND
ABSORPTION
DIETARY CARBOHYDRATES
Starch
• Digestible: amylopectin,
glycogen, amylose
• Indigestable: cellulose
and beta linked forms
Disaccharides: sucrose,
Brush border enzymes
Enzyme Substrate Products
Lactase Lactose Glucose
Galactose

Maltase a - 1, 4-linked Glucose
oligosaccharides up
to 9 residues

Sucrase Glucose
Sucrose Fructose

Isomaltase a - limit dextrin Glucose
PROTEIN DIGESTION
AND ABSORPTION
FAT DIGESTION AND
ABSORPTION
MECHANISM OF FAT
ABSORPTION
BILE SALT ABSORPTION
Deficiency of Luminal Conjugated Bile Acids
Pathophysiology Diseases

Decreased synthesis and/or Parenchymal liver diseases (e.g. liver
secretion of conjugated bile cirrhosis)
acids Biliary obstruction (e.g. primary biliary
cirrhosis, tumors)
Biliary fistula
Intestinal loss of conjugated Ileal resection
bile acids Severe ileal mucosal disease
Luminal deconjucation of Bacterial overgrowth syndrome
bile acids
Binding of bile salts or Cholestyramine (binding)
Insolubilization of bile salts
Zollinger-Ellison syndrome (low pH)
by a low luminal pH
Exocrine pancreatic insufficiency (low pH)
Malabsorption syndrome
SYMPTOMS AND SIGNS IN MALABSORPTI
Symptom or sign Pathophysiology
General symptoms

-Weight loss Nutrient
hyperphagia malabsorption
- Anemia Iron, folate or
- Kidney stones vitamin B12
deficiency
-Amenorrhea, Increased colonic
impotence, oxalate absorption
infertility Multifactorial
(including protein
SYMPTOMS AND SIGNS IN MALABSORPTI
Symptom or sign Pathophysiology

Gastrointestinal symptoms
Diarrhea Osmotic activity of carbohydrates or short-chain fatty
acids
Secretory activity of bile acids, fatty acids
Decreased absorption surface
Abdominal distension, Bacterial gas production from carbohydrates in the
flatulence colon or small bowel bacterial over-growth
Foul smelling flatulence or Malabsorption of proteins or intestinal protein loss
stool
Pain Flatulence
Ascites Protein loss or malabsorption
Musculoskeletal symptoms
Tenany, muscle weakness, Malabsorption of vitamin D, calcium, magnesium and
paresthesias phosphate
Bone pain, osteomalacia, Protein, calcium or vitamin D deficiency, secondary
fractures hyperparathyroidism
SYMPTOM AND SIGN IN MALABSORPTIO
Symptom or sign Pathophysiologic background

Skin and mucous membranes
Easy bruisability, Vitamin K and C deficiency
ecchymoses, petechiae
Glossitis, cheilosis, Deficiency of vitamin B complex, B12, C, folate and
stomatitis iron
Edema Protein loss or malabsorption
Acrodermatitis, scaly Zinc and essential fatty acid deficiency
dermatitis
Follicular hyperkeratosis Vitamin A deficiency
Hyperpigmented dermatitis Niacin deficiency (pellagra)
Thin nails with spoon – Iron deficiency
shaped deformity
Finger clubbing Severe nutrient malabsorption
Site of nutrient abso
Consequence of
short bowel
• Resection of terminal ileum> 100 cms
cause bile acid malabsorption and
colonic secretory diarrhea.
• Resection of jejunum associate with
hypergastrinemia due to reduction of
GIP,enteroglucagon.
• Maldigestion or malabsorption
• Diarrhea
LABORATORY IN MALABSORPTION

Stool test
Stool fat :
Qualitative,
Quantitative
Stool pH<5.5
Fat Malabsorption Syndrome

• Steatorrhea
• Malnutrition
Mechanism of fat malabsorption
Mechanism Example
Intraluminal
• Bile acid deficiency • Hepatobiliary diseases
• Pancreatic insufficiency • Bacterial overgrowth
• Terminal ileal disease
• Chronic pancreatitis
• Pancreatic tumors
• Inactivation of pancreatic enzyme

Mucosal
• Reduced mucosal absorption • Sprue (Caeliac, Tropical)
• Parasite
(Giardia,C.phillipenesis,
Strongyloid, Isospora)
• Infectrative, (Lymphoma,
Eosinophilic)
• Inflammatory : Crohn’s disease
Mechanism of fat malabsorption continue

Mechanism Example

• Decreased transportation • Intestinal lymplengietasia
from the intestine • Lymphoma
• Abetalipoproteinemia
• Whipple’s disease
• Venous stasis

• Mixed • Fistula
Short bowel
Fecal fat test
• Qualitative test
diet 80-100 gm (72 hrs)
stool sample is placed on a glass + glacial
acetic acid and sudan III
boil
> 100 globules/high power field
• Quantitative test
diet 80-100 gm (72 hrs)
Collect stool 48-72 hrs

Fat > 7 gm/day
Small intestinal biopsy
Diagnostic histology, diffuse lesion
Whipple •Weight loss
•Diarrhea
•Fever
•Arthritis
•PAS positive
macrophage

Microbacterium MAC is common in AIDS
Fever,weight loss, abdominal cramp
anemia,hepato-splenomegaly
Positive hemoculture,AFB in tissue

Abetalipoprotein Autosomal recessive,absence ApoA
Triglycerride accumilation in
Cytoplasm of enterocyte and
Hepatocyte,
Steatorrhea and fat soluble vitamin
Defiency(anemia,bleeding tendency)
Small intestinal biopsy
Diagnostic histology, patchy

Lymphoma

Lymphagiectasia Primary or secondary
Dilation of lacteals
Intestinal lymph leak into
Intestinal lumen
Steatorrhea and lymphopenia

Eosinophilic DDX.Parasites
Autoimmune
gastroenteritis Food allergy
Small intestinal biopsy
Diagnostic histology, patchy

Mastocytosis Mucosal, submucosal
infiltrate with mast cells

Strongyloidiasis
Small intestinal biopsy
Abnormal but not diagnostic

Caeliac /
tropical sprue
Bacterial
overgrowth
Malabsorption test

Mucosal Pacreatic Bacterial
overgrowth

D-xylase + - +/-

Schilling - + +

H2 breath +/- - +
14C tricelcin breath + + +
Bile acid breath test
Hints for diagnosis chronic diarrhea (1)
• General history of diarrhea: onset and duration of diarrhea, stool
character, frequency, amount & volume of stool, relationship with meals
• Associated symptoms : nausea vomitting, tenesmus, abdominal pain,
constipation, etc.
• Symptoms of malnutrition : anemia, edema, bruise
• Social history: diet (lactose, food allergy), occupation, environment,
travelling, contact with diarrhea
• Past history & underlying illness : DM. PU, thyrotoxicosis,
autoimmune disease, unsafe sex, radiation, pancreatitis, etc.
• Family history : IBD, polyposis syndrome, MEN1, MEN2
• Systemic enquiry : fever, weight loss, amenorrhea, impotence, change
of voice, polyuria, polydipsia, arthralgia/arthritis, rashes, eye symptoms,
paresthesia, difficulty walking, sweating, tremor, proteinuria, bone pain,
etc.
• Drugs history : antibiotics, magnesium compounds, laxatives, etc.
Hints for diagnosis chronic diarrhea (2)
• Anemia, dry, grey hair
• Glossitis, cheilitis, angular stomatitis, oral
ulcer,
• Eczema, dermatitis herpetiformis,
pyoderma gangrenosum, vasculitis,
• Goiter, exophthalmos, uveitis, episcleritis
etc
• Edema, ascites, bruise, muscle wasting
• Peripheral neuropathy
• Arthritis, ankylosing spondylitis,
• Perianal lesions
Hints for diagnosis chronic diarrhea (3)
• Flushing carcinoid syndrome
• Tachycardia  thyrotoxicosis, carcinoid
syndrome
• Peripheral neuropathy  DM, amyloidosis
• Peptic ulcer  ZE syndrome
• Proteinuria  amyloidosis, SLE
• Postural hypotension  DM, Addison’s
disease
• Dermatitis herpetiformis  coeliac disease
• Ataxia  Abetalipoproteinemia