Malabsorption

diminished intestinal absorption of one or more

dietary nutrients
Steatorrhea - increase in stool fat excretion of 6% of
dietary fat intake
Diarrhea

Malabsorption
Diarrhea as a symptom
decrease in stool consistency
increase in stool volume
increase in number of bowel movements
any combination of these three changes
Diarrhea as a sign quantitative increase in stool water
Increase weight of 200 to 225 mL, or g per 24 h

Malabsorption
Osmotic diarrhea
diarrhea is secondary to diminished absorption of one
or more dietary nutrients
e.g., lactose intolerance

Secretory diarrhea
diarrhea that is due to small- and/or large-intestinal
fluid and electrolyte secretion
e.g., E. coli enterotoxin

NUTRIENT DIGESTION AND ABSORPTION

Other functions of the intestines:

Barrier and immune defense

Fluid and electrolyte absorption and secretion
Synthesis and secretion of several proteins
Production of several bioactive amines and
peptides

Enterohepatic circulation:
Liver

Portal vein

Bile ducts

Small intestines

Primary functions of bile acids

(1) to promote bile flow
(2) to solubilize cholesterol and phospholipid in the gall
bladder by mixed micelle formation
(3) to enhance dietary lipid digestion and absorption by
forming mixed micelles in the proximal small intestine

LIPIDS
Steatorrhea is caused by one or more defects in
the digestion and absorption of dietary fat .
Three types of fatty acids compose fats:
long-chain fatty acids (LCFAs)
medium-chain fatty acids (MCFAs)
short-chain fatty acids (SCFAs)

Assimilation of dietary lipid requires several

integrated processes that can be divided into:
(1) intraluminal, or digestive, phase
(2) mucosal, or absorptive, phase
(3) delivery, or postabsorptive, phase

The digestive phase has two components:

lipolysis
micellar formation

 The initial step in lipid digestion is the formation

of emulsions of finely dispersed lipid, which is
accomplished by mastication and gastric
contractions.
Lipolysis, the hydrolysis of triglycerides to free
fatty acids, monoglycerides, and glycerol by
lipase, is initiated in the stomach by a gastric
lipase
impaired lipolysis can lead to steatorrhea and can
occur in the presence of pancreatic insufficiency
due to chronic pancreatitis in adults or cystic
fibrosis in children and adolescents

Carbohydrate malabsorption
Forms of carbohydrate:
starch, disaccharides (sucrose and lactose), and
glucose

Digestion and absorption

Carbohydrates are absorbed only in the small
intestine and only in the form of monosaccharides
starch and disaccharides must first be digested by
pancreatic amylase and intestinal brush border
disaccharidases to monosaccharides.

 Types of carbohydrate malabsorption

Lactose malabsorption is the only clinically important
disorder of carbohydrate absorption.
Lactose, the disaccharide present in milk, requires
digestion by brush border lactase to its two constituent
monosaccharides, glucose and galactose.
Lactase is present in almost all species in the
postnatal period but then disappears throughout the
animal kingdom, except in humans
lactase deficiency is associated with significant lactose
malabsorption

 Clinical manifestations of Lactase

deficiency
Diarrhea
Abdominal pain
Cramps
Flatus

 Factors in the development of Lactose

intolerance:
Amount of lactose in the diet.
Rate of gastric emptying
Small-intestinal transit time
Colonic compensation by production of
SCFAs from nonabsorbed lactose

Proteins
Three rare genetic disorders involve protein
digestion-absorption:
(1) Enterokinase deficiency is due to an absence of
the brush border enzyme that converts the
proenzyme trypsinogen to trypsin and is associated
with diarrhea, growth retardation, and
hypoproteinemia;
(2) Hartnup syndrome, a defect in neutral amino
acid transport, is characterized by a pellagra-like rash
and neuropsychiatric symptoms; and
(3) Cystinuria, a defect in dibasic amino acid
transport, is associated with renal calculi and chronic
pancreatitis

Evaluation of Malabsorption

History and PE
Stool exam
Schillings test
Urinary D-Xylose test
Radiography
Small intestinal mucosal biopsy

 Schillings test
performed by administering 58Co-labeled cobalamin
and collecting urine for 24 h
dependent upon normal renal and bladder function.
Urinary excretion of cobalamin will reflect cobalamin
absorption provided that intrahepatic binding sites for
cobalamin are fully occupied.
1 mg cobalamin is administered intramuscularly 1 h
following ingestion of the radiolabeled cobalamin.
Abnormal Schilling test - defined as 10% cobalamin
excretion in 24 h

 Abnormal Schillings test

1. Pernicious anemia - absence of both gastric acid and
intrinsic factor secretion.
2. Chronic pancreatitis as a result of deficiency of pancreatic
proteases to split the cobalamin-R binder complex
3. Achlorhydria or absence of another factor secreted with
acid that is responsible for splitting cobalamin away from the
proteins in food to which it is bound can lead to vitamin B12
malabsorption
4. Bacterial overgrowth syndromes, produce cobalamin
deficiency from bacterial utilization of cobalamin (often
referred to as stagnant bowel syndrome).
5. Ileal dysfunction (either as a result of inflammation or prior
intestinal resection) due to impaired function of the
mechanism of cobalamin-intrinsic factor uptake by ileal
intestinal epithelial cell.

 D- Xylose test
test for carbohydrate absorption that provides an assessment of
proximal small-intestinal mucosal function
25 g D-xylose is administered and urine collected for 5 h
abnormal test - 4.5 g excretion
reflects duodenal/jejunal mucosal disease

Specific malabsorption syndromes

1. Celiac Sprue
Etiology - unknown
Environmental - gluten
Immune
presence of IgA antigliadin and antiendomysial antibodies
treatment with prednisolone for 4 weeks of a patient with celiac
sprue who continues to eat gluten will induce a remission and
convert the "flat" abnormal duodenal biopsy to a more normal
appearing one
gliadin peptides may interact with gliadin-specific T cells that may
either mediate tissue injury or induce the release of one or more
cytokines that are responsible for the tissue injury.

Genetic -

 Diagnosis
A biopsy should be performed in patients with symptoms and
laboratory findings suggestive of nutrient malabsorption and/or
deficiency
(1) absence or reduced height of villi, resulting in a "flat"
appearance
(2) increased loss of villus cells in association with increased
crypt cell proliferation resulting in crypt hyperplasia and loss
of villus structure, with consequent villus, but not mucosal,
atrophy
(3) cuboidal appearance and nuclei that are no longer
oriented basally in surface epithelial cells and increased
intraepithelial lymphocytes.
(4) increased lymphocytes and plasma cells in the lamina
propria.

Mechanism of Diarrhea:
(1) steatorrhea, which is primarily a result of the changes in
jejunal mucosal function
(2) secondary lactase deficiency, a consequence of changes in
jejunal brush border enzymatic function
(3) bile acid malabsorption resulting in bile acid-induced fluid
secretion in the colon, in cases with more extensive disease
involving the ileum
(4) endogenous fluid secretion resulting from the crypt
hyperplasia

Associated disorders

Dermatitis heptiformis
Insulin dependent Diabetes mellitus
IgA globulin deficiency

Complications

Development of malignancy

2. Tropical Sprue
- poorly understood syndrome that affects both expatriates
and natives in certain but not all tropical areas
manifested by:
chronic diarrhea
steatorrhea
weight loss
nutritional deficiencies:
folate and cobalamin

Causative agents

G. lamblia
Yersinia enterocolitica
C. difficile
Cryptosporidium parvum
Cyclospora cayetanensis

 Diagnosis
presence of an abnormal small-intestinal mucosal biopsy in an individual
with chronic diarrhea and evidence of malabsorption who is either
residing or has recently lived in a tropic country
the histopathologic features of tropical sprue are present with a similar
degree of severity throughout the small intestine
and a gluten-free diet does not result in either clinical or histopathologic
improvement in tropical sprue

Treatment
Broad-spectrum antibiotics and folic acid are most often curative,
especially if the patient leaves the tropical area and does not return.
Tetracycline should be used for up to 6 months and may be associated
with improvement within 1 to 2 weeks.
Folic acid alone will induce a hematologic remission as well as
improvement in appetite, weight gain, and some morphologic changes
in small intestinal biopsy.

3. Short Bowel Syndrome

- a descriptive term for the myriad clinical problems that often occur
following resection of varying lengths of small intestine

factors that determine the type and degree of symptoms:

(1)
(2)
(3)
(4)
(5)

The specific segment (jejunum vs. Ileum) resected

The length of the resected segment
The integrity of the ileocecal valve
Whether any large intestine has also been removed
Presence of residual disease in the remaining small and/or large
intestine (e.G., Crohn's disease, mesenteric artery disease)
(6) The degree of adaptation in the remaining intestine.

Causes
Three different situations in adults that demand intestinal resections:
(1) mesenteric vascular disease including both atherosclerosis,
thrombotic phenomena, and vasculitidies
(2) primary mucosal and submucosal disease, e.g., Crohn's
disease
(3) operations without preexisting small intestinal disease, such
as trauma and jejunoileal bypass for obesity

Treatment
Judicious use of opiates to reduce stool output
Diet should be low-fat, high-carbohydrate to minimize the
diarrhea from fatty acid stimulation of colonic fluid secretion
Replacement therapy of vitamin and minerals
Fat-soluble vitamins, folate, cobalamin, calcium, iron, magnesium, and zinc

Home TPN (total parenteral nutrition) if above approaches are not

successful

4. Bacterial Overgrowth Syndrome

group of disorders with diarrhea, steatorrhea, and macrocytic

anemia whose common feature is the proliferation of colon-type
bacteria within the small intestine

bacterial proliferation is due to :

stasis caused by impaired peristalsis (i.e., functional stasis)

changes in intestinal anatomy (i.e., anatomic stasis)
or direct communication between the small and large intestine
also been referred to as stagnant bowel syndrome or blind loop
syndrome

Bacterial Overgrowth Syndrome

Macrocytic anemia is due to cobalamin, not folate,
deficiency.
Bacteria use up the relatively small amounts of dietary
cobalamin

Steatorrhea is due to impaired micelle formation

a consequence of a reduced intraduodenal concentration of bile
acids and the presence of unconjugated bile acids

Diarrhea is due to the steatorrhea

colonic-type bacteria in these patients are producing one or
more bacterial enterotoxins that are responsible for fluid
secretion and diarrhea.

Bacterial Overgrowth Syndrome

Diagnosis

Low serum cobalamin

High serum folate
Abnormal Schilling test
Demonstration of increased levels of aerobic and/or anaerobic
colonic-type bacteria in a jejunal aspirate obtained by intubation

Treatment
Correction of the anatomic abnormality
Antibiotics for 3 weeks
Tetracycline
Clavulanic-amoxicillin
Cephlosporin

Whipples Disease
a chronic multisystem disease associated with :
Diarrhea
steatorrhea
weight loss
arthralgia
central nervous system problem
cardiac problems
caused by the bacteria Tropheryma whippelii

Whipples Disease
Clinical presentation

Diarrhea
steatorrhea
abdominal pain
weight loss
migratory large-joint arthropathy,
fever
ophthalmologic symptoms
central nervous system symptoms.
Late development of dementia
an extremely poor prognostic sign

Whipples Disease
Diagnosis
A multisystem disease in a 50-year-old Caucasian
male with diarrhea and steatorrhea
Demonstration of PAS-positive macrophages
containing the characteristic small T. whippelii in
jejunal biopsies
Culture of T. whippelii

Treatment
Co-trimoxazole for 1 year
Chloamphenicol 2nd choice

Protein-Losing Enteropathy
Non-specific group of gastrointestinal and
nongastrointestinal disorders with hypoproteinemia
and edema in the absence of either proteinuria or
defects in protein synthesis
characterized by excess protein loss into the
gastrointestinal tract

Protein-Losing Enteropathy
Classification
(1) mucosal ulceration such that the protein loss primarily
represents exudation across damaged mucosa, e.g., ulcerative colitis,
gastrointestinal carcinomas, peptic ulcer

(2) nonulcerated mucosa but with evidence of mucosal damage

so that the protein loss represents loss across epithelia with
altered permeability, e.g., celiac sprue and Menetrier's disease in the small
intestine and stomach, respectively

(3) lymphatic dysfunction, either representing primary lymphatic

disease or secondary to partial lymphatic obstruction that may
occur as a result of enlarged lymph nodes or cardiac disease

Pathophysiologic Classification of Malabsorption

Inadequate digestion
Postgastrectomy
Deficiency or
inactivation of
pancreatic lipase
Exocrine pancreatic
insufficiency
Chronic pancreatitis
Pancreatic carcinoma

Cystic fibrosis
Pancreatic
insufficiency congeni
tal or acquired
Gastrinoma acid
inactivation of lipase
Drugs orlistat

Reduced intraduodenal bile acid

concentration/impaired micelle
formation
Liver disease
Parenchymal liver disease
Cholestatic liver disease

Bacterial overgrowth in
small intestine:
Anatomic stasis
Afferent loop stasis/blind
loop/strictures/fistulae

Functional stasis
Diabetes
Scleroderma
Intestinal
pseudoobstruction

Interrupted
enterohepatic
circulation of bile salts
Ileal resection
Crohn's disease

Drugs
(bind or precipitate bile
salts) neomycin,
cholestyramine,
calcium carbonate

Impaired mucosal
absorption/mucosal loss or
defect
Collagenous sprue
Intestinal resection or

bypass
Inflammation,
infiltration, or
infection:

Crohn's disease
Amyloidosis
Scleroderma
Lymphoma
Eosinophilic enteritis
Mastocytosis
Tropical sprue
Celiac disease

Whipple's disease
Radiation enteritis
Folate and vitamin B12
deficiency
Infections salmonellosis,
giardiasis
Graft-vs.-host disease

Genetic disorders

Disaccharidase deficiency
Agammaglobulinemia
Abetalipoproteinemia
Hartnup disease
Cystinuria

Impaired nutrient delivery to

and/or from intestine
Lymphatic obstruction
Lymphoma
Lymphangiectasia

Circulatory disorders
Congestive heart failure
Constrictive pericarditis
Mesenteric artery
atherosclerosis
Vasculitis

Endocrine and
metabolic disorders
Diabetes
Hypoparathyroidism
Adrenal
insufficiency
Hyperthyroidism
Carcinoid syndrome