EXMD

509B: INTESTINAL MALABSORPTION AND

DIARRHEA: Winter 2015.
Gary E. Wild, MD

G.I. Secretion & Absorption: the Balance Sheet

8.9 L
Total absorbed
by intestine

Intestinal Morphology

Intestinal Villus and Microvilli

Stem
cells

Secretory
cells

The Large Intestine

Malabsorption and Maldigestion

Maldigestion is a defect in the hydrolysis of
nutrients.
Malabsorption is a defect in the mucosal
absorption of nutrients and can occur in
multiple phases:
Luminal phase contact with digestive enzymes.
Mucosal phase absorption in the required
constituent form.
Delivery phase uptake into the cytoplasm and
delivery to lymphatics or portal venous system

Carbohydrate Malabsorption
Starch, sucrose and lactose comprise 85% of
ingested carbs.
Carbohydrate malabsorption caused by (1)
absolute or functional decreased mucosal
surface area, or, (2) decreased disaccharidases
or transporters.
Non-absorbed carbs increase osmolality in the
lumen and water enters lumen to maintain
isosmotic state. Non absorbed carbs are
fermented by colonic bacteria.

Carbohydrate Malabsorption
Lactase deciency is most common cause of
carb malabsorption.
Congenital lactase is rare. Primary lactase
deciency has delayed onset and is common in
North America, Africa and Asia.
Acquired lactase deciency can occur after
mucosal resection, mucosal disease or in the
post infectious state following gastroenteritis.

Symptoms and Diagnosis

Symptoms: Gas, bloating and osmotic diarrhea.
Diagnosis:
Dietary history.
Increased stool osmotic gap.
Stool pH < 6
Hydrogen BT showing an increase of 20 ppm above
baseline which is indicative of colonic fermentation
of unabsorbed carb. False +ve from bascterial
overgrowth and False ves from recent treatment
with antibiotics or from non H producers

Fat Malabsorption
Fat absorption requires competent pancreas, liver, small bowel
and lymphatics.
Triglycerides are the major form of dietary fat.
Pancreatic lipase is the major hydrolytic enzyme and breaks down
TG into fatty acids and beta monoglycerol. The pH optimal is 8. It
can be inactivated by overproduction of acid.
Hepatic derived conjugated bile salts combine with these
constituents to form micelles which enter enterocytes.
TG are re-esteried and synthesized into chylomicrons which are
exported into lymphatics.

Fat Malabsorption
Medium chain TG do not require micellar formation and pass
directly into portal blood.
Clinical features: Steatorrhea, weight loss and complications
from fat soluble vitamin deciencies A,D, E and K.
Diagnosis: > 14 g of fat in a 3 day stool collection on a 100 g/d
fat diet.
Need to determine cause of fat malabsorption
Small bowel (D-xylose testing)
Pancreatic (imaging, lab, endoscopic)

Protein Malabsorption
Dietary proteins are cleaved initially by gastric
pepsin (active at pH 1-3; inactive at pH > 5).
Pancreatic trypsin is activated by duodenal
derived enterokinase. Trypsin further activates
a series of pancreatic proteases which cleave
proteins into peptides and AAs.
Brush border oligopeptidases cleave small
peptides and subsequent OPD and free AAs
are transported into the enterocyte.

Protein Losing Enteropathy

Loss of protein from intestinal tract.
Liver attempts to compensate.
Three categories
Diseases with increased mucosal permeability
without erosions.
Diseases with mucosal erosions.
Diseases with increased lymphatic pressure.

Clinical Features
Diarrhea, edema, ascites, possible concomitant
CHO and fat malabsorption.
Low serum protein, albumin and Igs (except
IgE).
Lymphopenia in setting lymphangiectasia.
Diagnosed by measuring absorption of
marker alpha-1-antitrypsin.

Causes of Protein Losing Enteropathy

Mechanisms of Malabsorption

Mechanisms of Malabsorption

Diarrhea
Mechanisms
Decreased absorption (Villous function)
Increased secretion (Crypt function)
Both

Inammatory vs Non-Inammatory
Inammatory diarrhea (IBD, invasive pathogens, ischemia,
radiation)

Abdominal pain
Fever
Tenesmus (urgency to defecate)
Small volume mucoid stool with variable amounts of blood
and leukocytes

Non-Inammatory diarrhea (Toxin producing infections).

Watery diarrhea

Stool Osmotic Gap

Osmotic diarrhea
290 2(Na + K) = > 100

Secretory diarrhea
290 -2 (Na + K) = < 50

Osmotic vs Secretory Diarrhea

Osmotic vs Secretory Diarrhea

Small Intestinal Resection and Short

Bowel Syndrome
Diarrhea and malabsorption can result from
any process that shortens the intestine (eg.
Surgery, underlying disease).
Determining factors:
Length resected.
What region resection (eg. Proximal vs ileum)
o Concept of intestinal adaptation

Integrity of the remaining intestine

Presence of colon

Ileal Resection and Bile Salt Reabsorption

< 100 cm Ileal Resection.
Liver compensates by up regulating production.
Increased bile salts enter colon an elicit secretory
diarrhea.
Treated with cholestyramine

> 100 cm Ileal Resection.

Liver can no longer compensate
Bile salt deciency ensues leading to steatorrhea
Treatment with MCTs

Consequences of Ileal Resection

Diarrhea with either excess or deciency of bile
salts.
B12 deciency
Small intestinal bacterial overgrowth from loss
of ileao-cecal valve.
Gallstones from disruption of cholesterol pool
Calcium oxalate renal stones

Small Intestinal Diseases

Celiac disease
Whipples disease
Eosinophilic gastroenteritis.
Intestinal lymphangiectasia
Amyloidosis

Celiac Disease
Immune response to dietary gliadins (wheat, barley, rye).
Prevalence highest amongst people of European descent.
Prevalence of 1:100 in North America, 1:56 in symptomatic
patients, 1:22 in FDR of patients.
Occurs at all ages; 20% over 60.
95% HLA DQ2, 5%HLA DQ8 however 30 to 40% of general
population are DQ2 or DQ8.

Diagnosis
Presence of symptoms congruent with the
disease. These range from classic
malabsorption to more atypical extraintestinal
signs and symptoms. Atypical form is now the
most common form of disease presentation.
Supportive serological studies.
Characteristic small intestinal biopsy ndings.
There are proxy endoscopic markers.
Clinical response to gluten free diet (GFD).

Clinical Features of Celiac Disease

Clinical Features

Diseases Associated with Celiac Disease

IgA Based Serologic Tests for Celiac

Histology of Celiac

Normal small intestine

Celiac Disease

Normal villi

Villous atrophy

Spectrum of Histologic Findings

Causes of Villus Atrophy

Dermatitis Herpetiformis

Evaluation for Celiac

Disease

Patient presents with symptoms of celiac disease

Perform serologic IgA tTG

antibody testing

Positive

Negative

Small bowel biopsy

Positive
Dx confirmed,
Gluten-free diet

High clinical suspicion?

No

Yes

Negative

Small bowel biopsy

F/U and consider

Other dx, consider
Repeat bx

Positive

Negative

Tx and monitor
Improvement?
Yes
Dx confirmed

Low probability of celiac

disease; consider total
IgA test to R/O IgA
deficiency

Celiac ruled out,

Look for other cause

No
Evaluate for possible secondary
cause of symptoms

Treatment and Potential Complications

Life long gluten-free diet.
Potential complications:
Ulcerative jejunitis.
Refractory disease.
Enteropathy associated T cell lymphoma
Non-Hodgkins lymphoma.
Adenocarcinoma of intestine
Esophageal cancer

Whipples Disease
Multisystem disease.
Diarrhea
Weight loss
Arthritis
CNS ndings.
Gram +ve Tropheryma whippelii.
PAS +ve macrophages on small bowel biopsy. +ve PCR reaction.
Treatment with long term antibiotics