GASTROINTESTINAL Last edited: 3/4/2024

23. MALABSORPTION
I. PATHOPHYSIOLOGY III. DIAGNOSTIC APPROACH TO IV. TREATMENT OF MALABSORPTION AND
A. MALABSORPTION MALABSORPTION AND MALDIGESTION MALDIGESTION DISORDERS
B. MALDIGESTION DISORDERS A. EXOCRINE PANCREATIC INSUFFICIENCY (EPI)
II. COMPLICATIONS OF MALABSORPTION AND A. ASSESS FOR EVIDENCE OF MALABSORPTION OR B. BILE ACID DEFICIENCY
MALDIGESTION DISORDERS MALDIGESTION C. LACTOSE INTOLERANCE
A. GLOBAL MALABSORPTION B. ASSESS FOR THE CAUSE OF MALDIGESTION D. CELIACS DISEASE
B. PARTIAL MALABSORPTION C. ASSESS FOR THE CAUSE OF MALABSORPTION E. WHIPPLE’S DISEASE
F. TROPICAL SPRUE
G. MANAGEMENT OF ANEMIA

00:49
I. Pathophysiology
A. Malabsorption 00:49

1. Pathophysiology:
o Mucosal damage → Inability to absorb nutrients → Small Intestine
↑Nutrient loss into the intestinal lumen →
Loss of nutrients in the stool
 The digestive enzymes and bile acids are normally
functioning, which allows adequate digestion of nutrients, Enzyme function
but the damaged mucosa does not allow those nutrients to Mucosal injury +
be absorbed Absorption

Fat Protein Carb Micronutrients

loss loss loss
2. Causes of Malabsorption: 08:24

Celiac Disease
a) Celiac Disease
o Gluten Ingestion → Gliadin proteins form →
Antigen-presenting cells engulf and express the gliadin protein
on its surface → Activation of T-Helper cells, which cause
Gluten
activation of Plasma Cells → Plasma cells synthesize and release
IgA antibodies, causing an immune response and resulting in
injury to the mucosal lining in the small intestine → This leads
Gliadin
to the inability to absorb nutrients → ↑Nutrient loss into the
intestinal lumen → Loss of nutrients into the stool (e.g.
Proteins, Fats, Carbs, Vitamins, and Minerals)
Mucosal
 The Following IgA Antibodies are Crucial to Identify: injury
• Tissue Transglutaminase (tTG-IgA)
o Most sensitive and moderately specific → The primary
screening antibody
• Deaminated Gliadin Peptide (dGP-IgA)
o Useful in young children or IgA deficiency
• Endomysial Antibodies (EMA-IgA) APC TH cell
o Most specific antibody (~100%) → The confirmatory tTG-IgA
antibody dGP-IgA
 Celiac may also lead to cutaneous lesions:
Plasma EMA-IgA
• Dermatitis herpetiformis
cell
Malabsorption GASTROINTESTINAL : Note #23 1 of 9
 b) Whipple’s Disease c) Tropical Sprue
o Tropheryma whipplei → Triggers o Exposure to Tropical Areas (The
direct mucosal injury of the intestinal Caribbean, India, and Asia) →
lining → Activates macrophage Infectious pathogen acquired →
reactions that engulf the bacteria and Triggers direct mucosal injury of the
form foamy macrophages → Leads to intestinal lining → Leads to the
the inability to absorb nutrients → inability to absorb nutrients →
↑Nutrient loss into the intestinal ↑Nutrient loss into the intestinal
lumen → Loss of nutrients into the lumen → Loss of nutrients into the
stool (e.g. Proteins, Fats, Carbs, stool (e.g. Proteins, Fats, Carbs,
Vitamins, and Minerals) Vitamins, and Minerals)
 Systemic Involvement:  Tropical sprue may be due to a
• Joints → Arthralgias variety of bacteria
• Myocardium → Cardiomyopathy • Examples:
• Brain → Dementia, Movement o E.coli
disorders o Klebsiella

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 B. Maldigestion 04:26

1. Pathophysiology:
o Deficiency of Intraluminal Digestive Enzymes or Absence of Small Intestine
Bile Acids in the intestinal lumen → Leads to the inability to
digest nutrients via the enzymatic activity, and inability to
emulsify fats for aiding in digestion via the bile acid presence → Digestion Absor ption
This inability to digest nutrients leads to the inability to absorb -
nutrients → ↑Nutrient loss into the intestinal lumen → Loss of Enzyme dysfunction +
nutrients into the stool Mucosa intact
 The intestinal mucosa is intact, but is unable to absorb
nutrients given they are not adequately digested to enable
absorption

Fat Protein Carb Micronutrients

loss loss loss
2. Causes of Maldigestion: 14:27

a) Exocrine Pancreatic Insufficiency (EPI) b) Bile Acid Deficiency (Partial)

o Chronic Pancreatitis or Cystic Fibrosis → Progressive fibrosis o Cirrhosis → Hepatocytes are unable to synthesize bile into the
and calcification of the pancreas → Loss of function in the biliary system → Reduction in bile/bile acids into the small
exocrine portion of the pancreas → ↓Pancreatic proteases, intestine → Inability to emulsify fats → Loss of fat in stool
lipases, and amylases in the intestinal lumen → Leads to the o Biliary Obstruction → Bile flow is blocked from moving by the
inability to digest proteins, fats, and carbohydrates common bile duct and into the small intestine → Reduction in
 An enzyme deficiency that is diagnostically crucial to identify bile/bile acids into the small intestine → Inability to emulsify
in EPI is ↓Fecal Elastase fats → Loss of fat in stool
o Crohn's Disease → Ileum inflammation occurs → Inability to
absorb bile acids → Reduced bile acids recycled back to the
hepatocytes → Hepatocytes unable to synthesize enough bile
Proteases into the biliary system → Reduction in bile/bile acids into the
small intestine → Inability to emulsify fats → Loss of fat in stool

Fat globules
Amylases

Chronic
Pancreatitis
Lipases
- -
Cystic Fibrosis
Cirrhosis
Fat
droplets Biliary Obstruction

Ileal Disease
(Crohn’s Disease)

c) Lactose Intolerance (Partial)

o Genetic or Acquired (e.g. Gastroenteritis) Lactase Deficiency
→ Inability to digest lactose-containing carbohydrates → -
Inability to absorb lactose-containing carbohydrates → Loss of
lactose-containing carbohydrates in the stool Lactase Carb loss
Genetic
Acquired (Gastroenter itis)

Malabsorption GASTROINTESTINAL : Note #23 3 of 9

 24:37
II. Complications of Malabsorption and Maldigestion Disorders
A. Global Malabsorption
1. Pathophysiology:

a) Celiac, Whipple’s, Tropical Sprue b) Exocrine Pancreatic Insufficiency

o Mucosal damage → Inability to absorb nutrients → o Loss of function in the exocrine portion of the pancreas
↑Nutrient loss into the intestinal lumen → → ↓Pancreatic proteases, lipases, and amylases in the
Loss of nutrients in the stool (e.g. Proteins, Fats, Carbs, intestinal lumen → Leads to the inability to digest
Vitamins, and Minerals) proteins, fats, and carbohydrates

2. Presentation:

a) Weight Loss Muscle wasting

o Due to ↓Protein Absorption → Leads to muscle wasting
Weight loss
b) Chronic Diarrhea Protein
absorption
o Due to ↓Carbohydrate Absorption → this leads to water
being pulled into the bowel lumen → larger volumes of liquid H2O pulled into lumen

stool pass through the intestines

Diarrhea
 Associated with Abdominal pain from bowel distention from
Carbohydrate
increased fluid in the intestinal lumen absorption
Abdominal
 Associated with Flatulence from increased gas production as pain
a byproduct of carbohydrate breakdown by bacterial in the Bacteria
intestinal lumen Flatulence Gas
Fat
c) Steatorrhea absorption

o Due to ↓Fat Absorption → Leads to greasy and foul-smelling

Fecal fat
stools

Steatorrhea
Night Blindness
d) Vitamin A, D, E, K Deficiency
Vitamin A o Due to ↓Fat Absorption → Inability to assist in the co-
absorption of fat-soluble vitamins across the small intestines
 Vitamin A Deficiency:
Rickets/Osteomalacia • May present with night blindness
+
Fat Vitamin D  Vitamin D Deficiency:
absorption • May present with hypocalcemia, rickets, or osteomalacia
Ca++
 Vitamin E Deficiency:
• May present with hemolytic anemia or neuropathy
Folate Vitamin E Neuropathy
B12
 Vitamin K Deficiency:
Fe • May present with bleeding
Hemolytic
Anemia
e) Anemia
Vitamin K o Due to ↓B12, Folate, and Iron Absorption →
Bleeding
Inability of the bone marrow to mature and produce RBCs →
Anemia C, S, AT-III ↓RBCs enter the circulation
II  B12 and Folate deficiency → Macrocytic Anemia
VII  Iron deficiency → Microcytic Anemia
IX
X

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 B. Partial Malabsorption
1. Pathophysiology:

a) Bile Acid Deficiency b) Lactose Intolerance

 Absence of Bile Acids in the intestinal lumen → Leads to the  Lactase Deficiency → Inability to digest lactose-containing
inability to emulsify fats for aiding in digestion → Leads to carbohydrates → Inability to absorb lactose-containing
the inability to absorb fats → ↑Fat loss into the intestinal carbohydrates → Loss of lactose-containing
lumen → Loss of fats into the stool carbohydrates in the stool

2. Presentation:

a) Bile Acid Deficiency b) Lactose Intolerance

i) Steatorrhea Watery Diarrhea
o Due to ↓Fat Absorption → Greasy and foul-smelling o Due to ↓Carbohydrate Absorption → water pulled into
stools the bowel lumen → larger volumes of liquid stool pass
through the intestines
ii) Vitamin A, D, E, K Deficiency  Associated with Abdominal pain from bowel distention
o Due to ↓Fat Absorption → Inability to assist in the co-
from increased fluid in the intestinal lumen
absorption of fat-soluble vitamins across the small
 Associated with Flatulence from increased gas
intestines
production as a byproduct of carbohydrate breakdown
 Vitamin A Deficiency:
by bacterial in the intestinal lumen
• May present with night blindness
 Vitamin D Deficiency:
• May present with hypocalcemia, rickets, or
osteomalacia
 Vitamin E Deficiency:
• May present with hemolytic anemia or neuropathy
 Vitamin K Deficiency:
• May present with bleeding

Global Partial
vs. Malabsorption
Malabsorption

Bile Acid
Deficiency
Lactose
Intolerance
Celiac
Tropical sprue
Whipple's
EPI
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 39:16
III. Diagnostic Approach to Malabsorption and Maldigestion Disorders

A. Assess for evidence of Malabsorption or Maldigestion

1. Obtain D-Xylose Test
Indications: D-xylose Test
o Suspicion of Malabsorption/Maldigestion disorder
D-xylose (Does not require luminal enzymes)
Abnormal Findings:
o Normal or ↑Serum or Urine Xylose Levels:
 The absorption of ingested D-xylose, which does not
require enzymatic digestion, indicates an intact
mucosa, as it must reach the bloodstream to be +
filtered by the glomerulus
 Present in Maldigestion → Intact mucosa Mucosa Mucosa
o ↓Serum or Urine Xylose Levels: intact damaged
 The failure to absorb ingested D-xylose, which does
not require enzymatic digestion, suggests a non-
Serum Serum
intact mucosa, preventing its entry into the level level
bloodstream and subsequent filtration by the
glomerulus
 Present in Malabsorption → Non-Intact Mucosa

Urine Urine
level level

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 B. Assess for the cause of Maldigestion C. Assess for the cause of Malabsorption
1. Obtain Fecal Fat Test, Hydrogen Breath Test, 1. Obtain Fecal Fat Test and Obtain Antibody Testing
and Fecal Elastase Levels (e.g. tTG-IgA, dGP-IgA, EMA-IgA)
Indications: Indications:
o Suspicion of Maldigestion with a ↑Serum or Urine Xylose o Suspicion of Malabsorption with a ↓Serum or Urine Xylose
levels after D-xylose test levels after D-xylose test
Abnormal Findings: Abnormal Findings:
o Exocrine Pancreatic Insufficiency: o Celiac Disease:
 ↑Fecal fat  ↑Fecal fat
• Due to a lack of pancreatic lipase enzymes → Leads to the • Due to the lack of an intact intestinal mucosa → Leads to
inability to digest fats the inability to absorb fats
 ↓Fecal Elastase Levels  (+) tTG-IgA, dGP-IgA, EMA-IgA
• Recommended to assess for Chronic Pancreatitis • If tTG-IgA is (+) → Celiac Disease is likely
o Bile Acid Deficiency: • If tTG-IgA is (-) or inconclusive → Assess dGP-IgA → If (+)
 ↑Fecal fat test is revealed → Celiac Disease is highly likely
• Due to a lack of bile acids → Leads to the inability to o A biopsy should be considered for definitive diagnostic
emulsify and digest fats confirmation
 Normal Fecal Elastase Levels o Whipple’s Disease and Tropical Sprue:
• Recommended to assess for Cirrhosis, Choledocholithiasis,  ↑Fecal fat
or Crohn's Disease • Due to the lack of an intact intestinal mucosa → Leads to
o Lactose Intolerance: the inability to absorb fats
 (-) Fecal fat  (-) tTG-IgA, dGP-IgA, EMA-IgA
• A negative test as this will not affect fat absorption • Due to the absence of antibodies, a biopsy can be
 (+) Hydrogen Breath test obtained to definitively diagnose Whipple's vs Tropical
• Occurs when lactose is not metabolized by lactase → sprue vs Seronegative Celiac
Bacteria metabolize lactose and generate large amounts of o Whipple’s indicate the presence of Tropheryma
H+ gas that can be detected whipplei and Foamy Macrophages

Malabsorption GASTROINTESTINAL : Note #23 7 of 9

46:01
IV. Treatment of Malabsorption and Maldigestion Disorders

A. Exocrine Pancreatic Insufficiency (EPI) C. Lactose intolerance

Treatment: Treatment:
 Pancreatic Enzyme Replacement  Lactose restriction or Lactase enzyme replacement prior to
Indications: ingestion of lactose-containing foods
 Diagnosis of Chronic Pancreatitis or Cystic Fibrosis that is Indications:
causing EPI  Diarrhea, flatulence, and abdominal pain associated with
Purpose: lactose intolerance
 Provide exogenous pancreatic enzymes to ensure any Purpose:
nutrients being ingested are properly digested and  Provide exogenous lactase enzymes to ensure any lactose
subsequently absorbed being ingested is properly being digested and subsequently
Monitoring: absorbed
 Improvement in steatorrhea, weight gain, and resolution of Monitoring:
complications (e.g. anemia, vitamin deficiency, etc.)  Improvement/Resolution in diarrhea, flatulence, and
abdominal pain

B. Bile Acid Deficiency D. Celiac Disease

Treatment: Treatment:
 Treatment of the underlying cause is critical  Gluten-free diet
 In the interim, use of bile acid sequestrants may be utilized Indications:
(e.g. Cholestyramine)  Diagnosed Celiac or presence of Dermatitis Herpetiformis
Indications: Purpose:
 Bile acid deficiency-related diarrhea  Prevent gliadin from triggering an immune response and
Purpose: downstream cascade from IgA antibodies → This reduces
 Bile acid sequestrants help reduce the severity of diarrhea mucosal injury and allows for proper absorption
Monitoring: Monitoring:
 Improvement in diarrhea  Improvement in steatorrhea, weight gain, and resolution of
complications (e.g. anemia, vitamin deficiency, etc.)
 IgA antibodies should normalize with a gluten-free diet
 Mucosal healing on follow-up biopsy

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 E. Whipple’s Disease G. Management of Anemia
Treatment: Treatment:
 IV Ceftriaxone for 2 weeks followed by Trimethoprim- o Folate, B12, and Iron Replacement
Sulfamethoxazole (i.e. Bactrim) Indications:
Indications:  Anemia secondary to Global Malabsorption
 Biopsy confirming Whipple's Disease Purpose:
Purpose:  In addition to treating the underlying causes → The
 Eradicate Tropheryma whipplei administration of these supplements ensures the bone
Monitoring: marrow has the nutrients needed to synthesize RBCs
 Improvement in steatorrhea, weight gain, and resolution of Monitoring:
complications (e.g., anemia, vitamin deficiency, etc.)  Improvement in Hemoglobin and normalization of the MCV

F. Tropical Sprue
Treatment:
 Tetracycline
Indications:
 Persistent diarrhea after returning from a trip in a tropical
area (e.g. Caribbean, India, Asia)
 Biopsy confirming Tropical sprue
Purpose:
 Eradicate infectious agents causing diarrhea
Monitoring:
 Improvement in steatorrhea, weight gain, and resolution of
complications (e.g., anemia, vitamin deficiency, etc.)

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