Approach to Malabsorption syndromes for undergraduates

1. Dr. Prasoon Rastogi
MD Med.(KGMU)

2.  Malabsorption: defective
mucosal uptake and transport
of adequately digested
nutrients including vitamins
and trace elements.

3. 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

4. Impaired nutrient hydrolysis
 The most common cause for impaired nutrient
hydrolysis is pancreatic insufficiency.
-cystic fibrosis
-chronic pancreatitis
-carcinoma of pancreas
Inactivation of pancreatic enzymes by gastric
hypersecretion : Zollinger-Ellison Syndrome

5.  Inadequate mixing of bile
causing impaired hydrolysis.
-obstructive jaundice
-bacterial overgrowth

6. • Rapid transit of food through gut
- Gastroenterostomy
- partial gastrectomy
• Increased bile salt loss in faeces
- Crohn’s disease
- terminal ileal resection
• Lack of intrinsic factor
- pernicious anaemia

7. • Defect in brush border hydrolysis
-lactase deficiency
• Defect in epithelial transport
-coeliac disease
-tropical sprue
-lymphoma
-Whipple’s disease

8. • Lymphatic obstruction
-abdominal lymphoma
-tuberculosis
-lymphangiectasia
• Defect in epithelial processing
-abetalipoproteinaemia

9.  Thyrotoxicosis
 Hypothyroidism
 Diabetes mellitus
 Collagen vascular disease

10. 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.

12.  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.

13. 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.

14. ◦ Weight loss is common.
◦ The chance of weight loss
increases in diffuse diseases
involving the intestine, such as
celiac disease and Whipple
disease.

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

16.  Edema
◦ Hypoalbuminemia from chronic protein
◦ Extensive obstruction of the lymphatic system, as seen
in intestinal lymphangiectasia, can cause protein loss.
◦ With severe protein depletion, ascites may develop.

17. 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.

18. 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.

20.  Quantitative test
◦72hr stool fat collection – gold standard
 > 6gm/day – pathologic
 Qualitative tests
◦ Sudan lll stain
◦ Acid steatocrit – a gravimetric assay
◦ NIRA (near infra reflectance analysis)

22. ◦ 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

23.  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

24. ◦ A. Normal individual. B. Celiac sprue. C. Jejunal diverticulosis. D. Crohn's disease

25.  Gross morphology – gives diagnostic clue
◦ Reduced duodenal folds and scalloping
of duodenal mucosa – celiac disease
 Biopsy – to establish Dx
Lesions seen – classified in to three
◦ Diffuse, specific e.g. whipple’s Disease
◦ Patchy, specific – crohn’s D., lymphoma
infectious causes
◦ Diffuse, non-specific – Celiac sprue, Tropical sprue
autoimmune enteropathy
 Suspected distal pathology -wireless capsule endoscopy

27.  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

29.  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

31.  Genetic factors play an important role-
there is significantly increased risk of celiac
among family members
 HLA-DQ2 is found in 98 percent of celiac
patients from Northern Europe.

32. 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
 Addison’s disease
 Lupus
 Thyroid disease
 Autoimmune liver disease
 Sjogren’s disease
 Down syndrome
 Turner syndrome

33. Malignant disease
Malignant diseases are
more frequent in patients
with long-term untreated
classical CD.
 Small-bowel
adenocarcinoma,
 esophageal and
oropharyngeal squamous-
cell carcinoma,
 Non -Hodgkin’s lymphoma.

34. Diagnosis of Celiac: Serologic
Testing
• Some of the serologic tests used to
diagnose celiac:
• IgA and IgG tissue
transglutaminase
antibodies(Anti TTG)
• IgA endomysial antibodies
• IgA and IgG antigliadin
antibodies

35. 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

36. 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.
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

37. 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

39. • 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.

40.  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.

41.  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.

42. Normal small intestine is bacterial sterile due
to:
Cause of bacterial growth.
e.g.
◦ Small intestinal diverticuli
◦ Blind loop
◦ Strictures
◦ DM/ Scleroderma

43. Diagnosis:
 xylose test
 Culture of aspiration (definitive)
Treatment: Antibiotic
 Tetracyclin
 Ciprofl0xacin
 Metronidazole
 Amoxicillin

44.  Whipple's disease is a rare bacterial infection that most
often affects gastrointestinal system.
 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.

45. Tropheryma whippelli
It is found both intracellularly and
extracellularly grow slowly in acidic
vacuoles of cells

46. 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

47.  The morphologic hallmark 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.

50.  A rare autosomal recessive
disease.
 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.

51.  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.

53.  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.

54.  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.

56. 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

57. 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)

58. 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

59. Secondary lactose malabsorption
Bacterial overgrowth or stasis syndromes
Mucosal injury
Villus flattening or damage to the intestinal epithelium
• Celiac disease
• Crohn’s disease
• Radiation enteritis
• HIV enteropathy
• Whipple’s disease

60. Long-term malabsorption can result in:
 Anemia
 Gallstones
 Kidney stones
 Osteoporosis and bone disease
 Malnutrition and vitamin deficiencies

61.  Wide spectrum of disorders
 Both local and systemic causes
are there.
 Various genetic, environmental
& pathogenic organisms
implicated
 History & HPE often diagnostic