Malabsorption syndromes

1. Malabsorption Syndrome
Speaker : Dr. Saikat Mandal
Moderator : Prof(Dr.) Sarbani
Chattopadhyay

2. Malabsorption Syndrome Maldigestion: impaired
breakdown of nutrients
(carbohydrates, protein, fat) to
absorbable split-products
(mono-, di-, or
oligosaccharides; amino acids;
oligopeptides; fatty acids;
monoglycerides)
 Malabsorption: defective
mucosal uptake and transport
of adequately digested nutrients
including vitamins and trace
elements.

3. Malabsorption Syndrome Malabsorption, which presents
most commonly as chronic
diarrhea, is characterized by
defective absorption of fats, fat-
and water-soluble vitamins,
proteins, carbohydrates,
electrolytes and minerals, and
water
 Malabsorption Syndrome is a
clinical term that encompasses
defects occurring during the
digestion and absorption of food
nutrients by the gastrointestinal
tract.

4.  The digestion or absorption of a
single nutrient component may
be impaired, as in lactose
intolerance due to lactase
deficiency.
 However, when a diffusion
disorder, such as celiac disease or
Crohn's disease, affects the
intestine, the absorption of
almost all nutrients is impaired.

5. External Causes
 Diabetes mellitus
 Hyperthyroidism
 Hypothyroidism
 Addisons' disease
 Hyperparathyroidism
 Hypoparathyroidism
 Carcinoid syndrome
 Widespread skin disease
 Malnutrition.
 Collagen diseases.
 Eating disorders.

6. Pathophysiology
Malabsorption results from disturbance in at least one of the
four phases of nutrient absorption:
1. Intraluminal digestion
2. Terminal digestion
3. Transepithelial transport
4. Lymphatic transport

7. Defects in Malabosorptive and Diarrheal
Disease
Disease Intraluminal
Digestion
Terminal
Digestion
Terminal
Digestion
Lymphatic
Transport
Celiac disease + +
Tropical sprue + +
Chronic pancreatitis +
Cystic fibrosis +
Primary bile acid
malabsorption
+ +
Carcinoid syndrome +
Autoimmune enteropathy + +
Disaccharidase deficiency +
Whipple disease +
Abetalipoproteinemia +
Viral gastroenteritis + +
Bacterial gastroenteritis + +
Inflammatory bowel disease + + +

8. Causes of Malabsorption
Syndrome
The best way to classify the numerous causes of
malabsorption is to consider the aforesaid 4 phases of
digestion and absorption.

9. The Luminal Phase
Impaired nutrient hydrolysis
 The most common cause for impaired nutrient
hydrolysis is pancreatic insufficiency.
The resultant deficiencies in lipase and proteases lead
to lipid and protein malabsorption, respectively.
Inactivation of pancreatic enzymes by gastric
hypersecretion

10. The Luminal Phase
 Inadequate mixing of
nutrients, bile, and
pancreatic enzymes, also
causes impaired hydrolysis.
 Failure to convert a
proenzyme to active form,
cause protein maldigestion
and malabsorption.

11. Impaired micelle formation
Impaired micelle formation causes a
problem in fat solubilization and
subsequent fat malabsorption.
(1) Decreased bile salt synthesis
(2) Impaired bile secretion from biliary
obstruction or cholestatic jaundice
(3) Impaired enterohepatic bile circulation
(4) Bile salt deconjugation

12.  Stasis of intestinal content
caused by a motor abnormality
(eg, scleroderma, diabetic
neuropathy, intestinal
obstruction),
 an anatomic abnormality (eg,
small bowel syndrome,
stricture, ischemia, blind
loops),
 or small bowel contamination
from enterocolonic fistulas can
cause bacterial overgrowth.

13. Mucosal phase
 Disaccharidase deficiency can lead to disaccharide
malabsorption.
 Lactase deficiency, either primary or secondary, is the
most common form of disaccharidase deficiency.
Secondary lactase deficiency can be due to acute
gastroenteritis (rotavirus and giardia infection), chronic
alcoholism, celiac sprue, radiation enteritis, regional
enteritis, or AIDS enteropathy.

14. Mucosal phase
 Immunoglobulin A (IgA) deficiency (most common
immunodeficiency) is due to decreased or absent serum
and intestinal IgA, which clinically appears similar to
celiac disease and is unresponsive to a gluten-free diet.
 Acrodermatitis enteropathica is an autosomal recessive
disease with selective inability to absorb zinc, leading to
villous atrophy and acral dermatitis.

15. Mucosal phase
Impaired nutrient absorption
Nutrient malabsorption is due to inherited or acquired
defects.
Inherited defects include glucose-galactose
malabsorption, abetalipoproteinemia, cystinuria, and
Hartnup disease.

16. Acquired disorders are far more
common and are caused by the
following:
(1) Decreased absorptive surface
area,
(2) Damaged absorbing surface,;
(3) Infiltrating disease of the
intestinal wall,
(4) Infections,

17. Post - absorptive Phase
 Obstruction of the lymphatic
system, both congenital (eg,
intestinal lymphangiectasia,
Milroy disease) and acquired
(eg, Whipple disease,
neoplasm [including
lymphoma], tuberculosis),
impairs the absorption of
chylomicrons and lipoproteins

18. Risk Factors
Factors that may increase chance of
having
malabsorption include:
 Medical conditions affecting the
intestine
 Use of laxatives
 Excessive use of antibiotics
 Intestinal surgery
 Excessive use of alcohol
 Travel to countries with high incidence
of intestinal parasites.

19. Pathophysiology of Clinical Manifestations of
Malabsorption Disorders
Symptom or Sign Mechanism
Weight loss/malnutrition Anorexia, malabsorption of nutrients
Diarrhea Impaired absorption or secretion of water and electrolytes; colonic fluid
secretion secondary to unabsorbed dihydroxy bile acids and fatty acids
Flatus Bacterial fermentation of unabsorbed carbohydrate
Glossitis, cheilosis, stomatitis Deficiency of iron, vitamin B12, folate, and vitamin A
Abdominal pain Bowel distention or inflammation, pancreatitis
Bone pain Calcium, vitamin D malabsorption, protein deficiency, osteoporosis
Tetany, paresthesia Calcium and magnesium malabsorption
Weakness Anemia, electrolyte depletion (particularly K+)
Azotemia, hypotension Fluid and electrolyte depletion
Amenorrhea, decreased libido Protein depletion, decreased calories, secondary hypopituitarism
Anemia Impaired absorption of iron, folate, vitamin B12
Bleeding Vitamin K malabsorption, hypoprothrombinemia
Night blindness/xerophthalmia Vitamin A malabsorption
Peripheral neuropathy Vitamin B12 and thiamine deficiency

20. Diarrhea
Diarrhea is the most common
symptomatic complaint
Diarrhea is defined as an increase in
stool mass, frequency, or fluidity,
typically greater than 200 g per day. In
severe cases stool volume can exceed
14 L per day and, without fluid
resuscitation, result in death. Painful,
bloody, small-volume diarrhea is
known as dysentery.

21. . Diarrhea can be classified according to four major categories:
• Secretory diarrhea is characterized by isotonic stool
and persists during fasting.
• Osmotic diarrhea, due to the excessive osmotic forces
exerted by unabsorbed luminal solutes. The diarrhea fluid is
over 50 mOsm more concentrated than plasma and abates
with fasting.
• Malabsorptive diarrhea follows generalized failures of
nutrient absorption and is associated with steatorrhea and is
relieved by fasting.
• Exudative diarrhea is due to inflammatory disease and
characterized by purulent, bloody stools that continue during
fasting.

22. Steatorrhea
 Steatorrhea is the result of fat
malabsorption.
 The hallmark of steatorrhea is the
passage of pale, bulky, and
malodorous stools.
 Such stools often float on top of the
toilet water and are difficult to flush.
Also, patients find floating oil
droplets in the toilet following
defecation.

23. Weight loss and fatigue
 Weight loss is common and may
be pronounced; however,
patients may compensate by
increasing their caloric
consumption, masking weight
loss from malabsorption.
 The chance of weight loss
increases in diffuse diseases
involving the intestine, such as
celiac disease and Whipple
disease.

24. Flatulence and abdominal
distention
 Bacterial fermentation of
unabsorbed food substances
releases gaseous products,
such as hydrogen and
methane, causing flatulence.
 Flatulence often causes
uncomfortable abdominal
distention and cramps.

25.  Edema
 Hypoalbuminemia from chronic protein malabsorption or from
loss of protein into the intestinal lumen causes peripheral
edema.
 Extensive obstruction of the lymphatic system, as seen in
intestinal lymphangiectasia, can cause protein loss.
 With severe protein depletion, ascites may develop.

26.  Anemia
 Depending on the cause, anemia
resulting from malabsorption
can be either microcytic (iron
deficiency) or macrocytic
(vitamin B-12 deficiency).
 Iron deficiency anemia often is a
manifestation of celiac disease.
 Ileal involvement in Crohn
disease or ileal resection can
cause megaloblastic anemia due
to vitamin B-12 deficiency.

27. Metabolic defects of bones
 Vitamin D deficiency can cause bone disorders,
such as osteopenia or osteomalacia.
 Bone pain and pathologic fractures may be
observed.
 Malabsorption of calcium can lead to secondary
hyperparathyroidism.

28. Investigations

29. Tests for steatorrhea
 Quantitative test
 72hr stool fat collection – gold standard
 > 6gm/day – pathologic
 P’ts with steatorrhea - >20gm/day
 Modest elevation in diarrheal disease
(may not necessarily indicate Malabsorption)
 Qualitative tests
 Sudan lll stain
 Detect clinically significant steatorrhea in
>90% of cases
 Acid steatocrit – a gravimetric assay
 Sensitivity – 100%, specificity – 95% , PPV – 90%
 NIRA (near infra reflectance analysis)
 Equally accurate with 72hr stool fat test
 Allows simultaneous measurement of fecal fat, nitrogen, CHO

31. Schilling test
 To determine the cause of
cobalamine(B12) malabsorbtion
 Helps to asses the integrity of gastric,
pancreatic and ileal functions.
 Abnormal cobalamine absorbtion in:
pernicious anemia, ch. Pancreatitis,
Achlorohydria, Bacterial overgrowth, ileal
dysfunction
 The test
 Administering 58Co-labeled cobalamine
 Cobalamine 1mg i.m. 1hr after ingestion to
saturate hepatic
binding sites
 Collecting urine for 24 hr
(dependant on normal renal & bladder
function)
 Abnormal - <10% excretion in 24 hrs

32. Schilling test cont….
58Co-
Cbl
With
Intrinsic
factor
With
pancreatic
enzyme
5 Days
Of Ab
Pernicious
Anemia
 N  
Chronic
Pancreatitis
  N 
Bacterial
overgrowth
   N
Ileal
disease
   

33. D-xylose test
 D-xylose
 A Pentose monosacharide absorbed
exclusively at the proximal SB
 Used to asses proximal SB mucosal
function
 The test
 After overnight fast, 25gm D-xylose
 Urine collected for next 5 hrs
 Abnormal test - <4.5 gm excretion
 False +ve results:
 Renal dysfunction
 Inadequate urine sample
 Impaired gastric empyting,
 Ascitis
 Drugs(ASA,indometacin,Neomycin)

34. D-Xylose Test Helpful in Distinguishing
Maldigestion from Malabsorption
MALDIGESTION
(pancreatic insufficiency)
MALABSORPTION
(celiac sprue)
Fecal Fat
D-Xylose
Excretion Normal
Jejunal
Biopsy Normal Abnormal “flat”

35. Barium studies
 A. Normal individual. B. Celiac sprue. C. Jejunal diverticulosis. D. Crohn's disease

36. Endoscopy
 Gross morphology – gives diagnostic clue
 Reduced duodenal folds and scalloping
of duodenal mucosa – celiac disease
 Use of vital dyes to identify villous atrophy
 Biopsy – to establish Dx
 For p’ts with documented steatorrhea
or ch. Diarrhea
 Lesions seen – classified in to three
 Diffuse, specific e.g. whippl’s Disease
 Patchy, specific – crohn’s D., lymphoma
infectious causes
 Diffuse, non-specific – Celiac sprue, Tropical sprue
autoimmune enteropathy
 Suspected distal pathology - push enteroscopy
wireless capsule endoscopy

40. Cystic fibrosis (MUCOVISCIDOSIS) is a disorder of ion
transport in epithelial cells.
 It affects fluid secretion in
Exocrine glands
Respiratory,
Gastrointestinal, and
Reproductive tracts.

41. Cystic fibrosis transmembrane
conductance regulator (CFTR)

42. Pathophysiology
 Gastrointestinal
 Pancreas
 Absence of CFTR limits function of chloride-bicarbonate
exchanger to secrete bicarbonate
 Leads to retention of enzymes in the pancreas, destruction of
pancreatic tissue.
 Intestine
 Decrease in water secretion leads to thickened mucus and
dessicated intraluminal contents
 Obstruction of small and large intestines
 Biliary tree
 Retention of biliary secretion
 Focal biliary cirrhosis
 Bile duct proliferation
 Chronic cholecystitis, cholelithiasis

43.  Gastrointestinal
 Exocrine pancreatic insufficiency
 Found in >90% of CF patients
 Protein and fat malabsorption
 Frequent bulky, foul-smelling stools
 Vitamin A, D, E, K malabsorption
 Sparing of pancreatic beta cells
 Beta cell function decreases with age
 Increased incidence of GI malignancy

44. Diagnosis
 DNA analysis not useful due to large variety of CF mutations
 Sweat chloride test >70 mEq/L
 1-2% of patients with clinical manifestations of CF have a
normal sweat chloride test
 Nasal transepithelial potential difference

45.  Criteria
 One of the following
 Presence of typical clinical features
 History of CF in a sibling
 Positive newborn screening test
 Plus laboratory evidence for CFTR dysfunction
 Two elevated sweat chloride concentrations on two separate days
 Identification of two CF mutations
 Abnormal nasal potential difference measurement

46. Disease

47. History of Celiac
• Cereal grains were first domesticated from wild
grasses in the Fertile Crescent about 10,000
years ago
Simopoulos AP (ed): Evolutionary Aspects of Nutrition and Health. Diet, Exercise, Genetics and Chronic Disease.
World Rev Nutr Diet. Basel, Karger, 1999, vol 84, pp 19–73

48. History of Celiac
• Aretaeus from
Cappadochia (now
Turkey) in the 2nd
century AD described a
chronic malabsorptive
condition
• He named this disorder
"koiliakos” which is Greek
for "suffering in the
bowels.”
Booth, CC. History of celiac disease. BMJ 1989; 298:527.

49. History of Celiac
• During World War II, celiac
children improved during the
food shortages when bread was
unavailable.
• After the war, symptoms
reoccurred when bread and
cereals were reintroduced.
• Dutch pediatrician Willem K
Dicke recognized and
confirmed this association
between cereal grains and
malabsorption.
Dicke, WK. Simple dietary treatment for the syndrome of GheeHerter. Ned Tijdschr Geneeskd 1941; 85:1715.
DICKE, WK, WEIJERS, HA, VAN DE, KAMER JH. Coeliac disease. II. The presence in wheat of a factor having a deleterious effect in cases of coeliac disease.
Acta Paediatr 1953; 42:34.

50. Pathophysiology
 Celiac disease as an immune disorder
that is triggered by an environmental
agent (the gliadin component of
gluten) in genetically predisposed
individuals.
 Also known as-
Celiac sprue
Non - tropical sprue
Gluten intolerance
Gluten-sensitive enteropathy

51. Grain protein exists in four
general storage forms which
are categorized by their
solubility characteristics:
 Prolamins (soluble in
ethanol)
 Glutenins (partially soluble
in dilute acid or alkali
solutions)
 Globulins (soluble in 10
percent NaCl)
 Minor albumins (soluble in
water)
Glutens specifically are the
prolamins and the glutenins

53. Pathophysiology
 The pathophysiology of gliadin toxicity in
celiac patients is poorly understood
 Similarities between gliadin proteins and
certain enteral pathogens may result in the
immunologic response to antigens in gluten.
 The current hypotheses:
 Gliadin-sensitive T cells in genetically
predisposed individuals recognize
gluten-derived peptide epitopes and
develop an inflammatory response which
produces mucosal damage

54. Pathogenesis of Celiac Disease

55.  Genetic factors play an important role- there is
significantly increased risk of celiac among family
members
 A close association with the HLA-DQ2 and/or DQ8
gene locus has been recognized
 HLA-DQ2 is found in 98 percent of celiac patients
from Northern Europe.
 However, ~25% of “normal” individuals in this
population will also demonstrate HLA-DQ2

56.  HLA class II molecules are expressed on the surface of
antigen-presenting cells
 They can bind to and subsequently present “foreign” peptides
to populations of CD4 T cells that recognize the DQ2- or
DQ8-peptide complex.
 Role of Tissue Transglutaminase-
Tissue transglutaminase can deamidate glutamine,
converting glutamine to negatively charged glutamic acid
This renders these peptides better binders to the
disease relevant DQ2 or DQ8 molecules
Once bound to DQ2 or DQ8, the DQ-“gluten”
peptide complexes activate DQ2 or DQ8 restricted T cells

57. Risk Factors for Celiac Disease
People suffering from other immune diseases and certain genetic
disorders are more likely to have celiac disease. Some disorders
associated with celiac include:
 Rheumatoid arthritis
 Type 1 diabetes
 Thyroid disease
 Autoimmune liver disease
 Addison’s disease
 Sjogren’s disease
 Lupus
 Down syndrome
 Turner syndrome
 Lactose intolerance
 Intestinal lymphoma

58. Malignant disease
Malignant diseases are more
frequent in patients with
long-term untreated classical
CD. Small-bowel
adenocarcinoma, esophageal
and oropharyngeal squamous-
cell carcinoma, and non-
Hodgkin’s lymphoma occur
more often in CD patients
than in healthy control
individuals.

59. Diagnosis of Celiac: Serologic
Testing
• Some of the serologic tests used to
diagnose celiac:
• IgA and IgG antigliadin
antibodies
• IgA endomysial antibodies
• IgA and IgG tissue
transglutaminase antibodies
• Anti reticulin antibodies (no
longer used)

60. 2. Histopathology: The only
definitive test is small intestinal
biopsy taken endoscopically (the
proximal duodenum is maximally
affected) or by Crosby capsule. It
shows subtotal or total villous
atrophy with intense
inflammatory infiltration.
3. Genetic Testing: HLA‐DQ2
and HLA‐DQ8 markers in >90%
CD patients

61. Normal Pathology

63. Diagnosis: Small Bowel Endoscopy
Normal Celiac

64. Diagnosis of Celiac: Gluten
Rechallenge
• Gluten Rechallenge- improvement in
symptoms and histology with gluten avoidance
with a documented return of these features
upon gluten reintroduction.
• May be performed by consuming 10 g of gluten
per day (an amount contained in four slices of
regular bread) for four to six weeks.
• One hazard of rechallenge is development of
fulminant diarrhea, with dehydration,
acidosis, and other metabolic disturbances
("gliadin shock").
KRAINICK, HG, DEBATIN, F, GAUTIER, E, et al. [Additional research on the injurious effect of wheat flour in celiac disease.I. Acute gliadin reaction (gliadin
shock).]. Helv Paediatr Acta 1958; 13:432

65. Diagnosis of Celiac Disease
Positive Negative
Probability < 2 to 5 percent
Obtain IgA endomysial or tTG Ab
and serum IgA level
Small bowel biopsy Diagnosis excluded

66. Probability > 2 to 5 percent
IgA endomysial or tTG Ab + IgA
AND Small bowel biopsy
•Family history
•Unexplained iron deficiency anemia
•Steatorrhea or other GI symptoms
•Failure to thrive
•Type 1 diabetes mellitus or other
associated disorders
•Other symptoms
{
Both
positive
Histology -
Serology +
Histology +
Serology -
Both
negative
Review and/or
repeat biopsy
Diagnosis
excluded
Rule out
other
causes of
villous
atrophy
- ++
TREAT
-

67. Intolerance

68. Lactose Intolerance
 Lactose intolerance is the inability to break down a type
of natural sugar called lactose.
 Lactose is commonly found in dairy products, such as
milk and yogurt.

69. Lactose Intolerance
 A person becomes lactose intolerant when his or her
small intestine stops making enough of the enzyme
lactase to digest and break down the lactose.
 When this happens, the undigested lactose moves into
the large intestine. The bacteria that are normally
present in the large intestine interacts with the
undigested lactose. The condition may also be called
lactase deficiency.

71. Etiology of lactose
malabsorption
Primary lactose
malabsorption
• Racial or ethnic lactose
malabsorption
• Developmental lactase
deficiency
• Congenital lactase
deficiency
Secondary lactose
malabsorption
• Bacterial
overgrowth/stasis
• Mucosal injury of GIT
that causes villus
flattening

72. Racial or ethnic lactose malabsorption
• Genetically determined reduction of
lactase activity
• Most common form of lactose
malabsorption
• The great majority of the world’s
population develop low intestinal
lactase during mid-childhood
(approximately at age 5 yrs)
• This finding is most prominent in
Asian and African populations; rare in
Caucasians of Scandinavian
background
• Molecular basis remains unknown

73. Developmental lactase deficiency
• Low lactase levels as a
consequence of prematurity
• Lactase activity in the fetus
increases late in gestation
• Premature infants born at 28-
32 weeks of gestation have a
reduced lactase activity

74. Congenital lactase deficiency
• Rare autosomal recessive disorder
(Finnish population)
• Characterized by the absence of
lactase activity in the small
intestine, with normal histologic
findings
• A gene located on the same
chromosome of the lactase gene, is
responsible for CLD
• Affected infants have diarrhea from
birth, hypercalcemia and
nephrocalcinosis

75. Secondary lactose malabsorption
Bacterial overgrowth or stasis syndromes
• Increased fermentation of dietary lactose in the small bowel,
leading to symptoms of lactose intolerance.
• Suspected from clinical history and from a very early peak of
breath hydrogen during lactose challenge.
Mucosal injury
Villus flattening or damage to the intestinal epithelium
• Celiac disease
• Crohn’s disease
• Radiation enteritis, chemotherapy
• HIV enteropathy
• Whipple’s disease

76. The acidic and osmotic effects of undigested lactose
may cause:
 Loose watery stool - with a degree of urgency an hour or
two after ingestion of milk.
 Perianal itching due to acidic stools.
Symptoms occur from one to several hours after
ingestion of milk or dairy products. These symptoms
are very nonspecific and occur with other disorders
such as milk-protein sensitivity, allergic-type reactions
to other substances in the meal, or intolerance of other
saccharides.

77. Diagnosis
Lactose tolerance test
 Oral administration of 50 gram lactose
 Blood glucose levels 0, 60 and 120 min
 Increase of blood glucose by less than
20mg/dl + symptoms – diagnostic
 False negative – diabetes, bacterial
overgrowth, delayed gastric emptying
 Sensitivity of 75%, specificity of 96%

78. Lactose breath hydrogen test
 Oral lactose (2g/kg)
 Breath hydrogen sampled at baseline and at 30 min
intervals for three hours
 Breath hydrogen value of 10ppm – normal, 10-20ppm –
indeterminate unless symptomatic, >20ppm – diagnostic
 False positive – recent smoking,
 false negative – recent use of antibiotics, lung disorders,
1% non-hydrogen producers

79. Disease

80. Whipple’s Disease
 Whipple's disease is a rare bacterial infection that most often
affects gastrointestinal system. Whipple's disease interferes
with normal digestion by impairing the breakdown of foods,
such as fats and carbohydrates
 Whipple's disease also can infect other organs, including
brain, heart, joints and eyes.
 The cause of Whipple's disease is infection with the
bacterium Tropheryma whipplei.

81. Tropheryma whippelli
Isolated in a cell culture from a patient
with endocarditis aerobic, rod-shaped,
gram-positive, non- acid fast, periodic
acid-Schiff (PAS) positive bacillus member
of the Actinomycetes (placed between the
genus Cellulomonas and the Actinomycetes
clade)
It is found both intracellularly and
extracellularly grow slowly in acidic
vacuoles of cells

82.  The bacteria will lead to the development of internal
sores and cause body tissue to thicken.
 When the villi (finger-like tissues that absorb
nutrients in the small intestine) begin to thicken, their
natural shape begins to change. This damages the villi
and prevents them from effectively absorbing
nutrients. This, in turn, leads to many of the
symptoms connected with Whipple’s.

83. Risk factors
Because so little is known about the bacterium that
causes Whipple's disease, risk factors for the disease
haven't been clearly identified. Based on available
reports, it appears more likely to affect:
 Middle-age and older individuals.
 Males more than females.
 Caucasian patients.
 Family clusters (suggesting an immunogenetic
component).
 HLA-B27 antigen; HLA-DRB1*13 and DQB1*06 alleles.
 Sewage plant workers, farmers and agricultural workers.

84. Diagnosis
• Periodic acid schiff:
• PAS-positive, diastase-resistant inclusions on light
microscopy
• Confirmed by characteristic trilaminar cell wall
• Polymerase Chain reaction:
• PCR-sequenced bacterial 16sRNA
• PCR can be applied to duodenal tissue, lymph node,
pleural-fluid cells, and peripheral blood
• Abnormal Labs:
• ESR, CRP
• anaemia of chronic disease
• hypoalbuminaemia

85.  The morphologic hallmark of
Whipple disease is a dense
accumulation of distended,
foamy macrophages in the
small intestinal lamina propria.
 The macrophages contain
periodic acid–Schiff (PAS)-
positive, diastase-resistant
granules that represent
lysosomes stuffed with partially
digested bacteria.
 Intact rod-shaped bacilli can
also be identified by electron
microscopy

86. Whipple's Disease: showing macrophages in the
small intestine

87. Whipple's Disease

88. Complications
 Whipple's disease is a progressive and potentially fatal
disease. Although the infection is rare, associated
deaths continue to be reported, due in large part to late
diagnoses and delayed treatment. Death often is
caused by the spread of the infection to the central
nervous system, which can cause irreversible damage.

89. Sprue

90. Tropical Sprue
• Tropical sprue: is a malabsorption disease commonly
found in the tropical regions, marked with abnormal
flattening of the villi and inflammation of the small
intestinal mucosa.
• Unrelated to gluten ingestion.
 People with tropical sprue do not absorb nutrients
properly, especially vitamin B12 and folic acid.

91. Pathophysiology
 The exact pathogenesis poorly
understood.
 An acute intestinal infection leads to
jejunal and ileal mucosa injury; then
intestinal bacterial overgrowth and
increased plasma enteroglucagon
results in retardation of small-
intestinal transit.
 Central to this process is folate
deficiency, which probably
contributes to further mucosal injury.

92.  Hormone enteroglucagon and motilin
levels are elevated.
 Enteroglucagon causes intestinal stasis
 The upper small intestine is
predominantly affected;
 Klebsiella, E coli and Enterobacter species
,cyclospora are isolated and are the usual
organisms associated with tropical sprue.

93. Bacterial over growth of small bowel
Normal small intestine is bacterial sterile due
to:
 Acid
 Int. peristalsis (major)
 Immunoglobulin
Cause of bacterial growth.
e.g.
 Small intestinal diverticuli
 Blind loop
 Strictures
 DM/ Scleroderma

95. Pathophysiology
1) Bacterial over growth: Metabolize bile salt
resulting in deconjugation of bile salt
  Bile Salt
 Impaired intraluminal micelle formation
 Malabsorption of fat.
2) Intestinal mucosa is damaged by
 Bacterial invasion
 Toxin
 Metabolic products
 Damage villi  may cause total villous atrophy.

97. Clinically:
 Steatorrhea
 Anaemia
 B12 def.
Reversed of symptom after antibiotic
treatment.
Diagnosis:
 Breath test
 xylose test
 Culture of aspiration (definitive)
Treatment: Antibiotic
 Tetracyclin
 Ciprofl0xacin
 Metronidazole
 Amoxicillin

98. Enteropathy

99.  X-linked disorder characterized by severe persistent diarrhea
and autoimmune disease.
 Occurs most often in young children.
 Severe familial form, termed IPEX
Immune dysregulation,
Polyendocrinopathy,
Enteropathy,
X-linkage
 Due to a germline mutation in the FOXP3 gene, which is
located on the X chromosome.

100.  FOXP3 is a transcription factor
expressed in CD4+ regulatory T cells.
 Individuals with IPEX and FOXP3
mutations have defective T-regulatory
function.
 Autoantibodies to enterocytes and
goblet cells are common.
 Antibodies to parietal or islet cells.
 Within the small intestine
intraepithelial lymphocytes may be
increased.

102.  A rare autosomal recessive
disease characterized by an
inability to secrete triglyceride-
rich lipoproteins.
 Caused by a mutation in the
microsomal triglyceride transfer
protein (MTP) that catalyzes
transport of triglycerides,
cholesterol esters, and
phospholipids.
 MTP-deficient enterocytes are
unable to export lipoproteins
and free fatty acids.

103.  The malabsorption of is therefore a failure of transepithelial
transport.
 Lipid vacuolization of small intestinal epithelial cells is
evident and can be highlighted by special stains, such as oil
red-O, particularly after a fatty meal.
 Presents in infancy with failure to thrive, diarrhea, and
steatorrhea.
 Complete absence of all plasma lipoproteins containing
apolipoprotein B.
 Acanthocytic red cells (burr cells) in peripheral blood
smears.

104. Possible Complications
Long-term malabsorption can result in:
 Anemia
 Gallstones
 Kidney stones
 Osteoporosis and bone disease
 Malnutrition and vitamin deficiencies

105. Take Home Message
 Wide spectrum of disorders
 Both local and systemic causes
are there
 Various genetic, environmental &
pathogenic organisms implicated
 History & HPE often diagnostic