Malabsorption Syndrome

Speaker : Dr. Saikat Mandal

Moderator : Prof(Dr.) Sarbani

Chattopadhyay

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.

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.

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.

External Causes

Diabetes mellitus

Hyperthyroidism

Hypothyroidism

Addisons' disease

Hyperparathyroidism

Hypoparathyroidism

Carcinoid syndrome

Widespread skin disease

Malnutrition.

Collagen diseases.

Eating disorders.

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

Defects in Malabosorptive and Diarrheal

DiseaseDisease Intraluminal

DigestionTerminal 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 + + +

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.

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

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.

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

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.

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.

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.

Mucosal phase

Impaired nutrient absorption

Nutrient malabsorption is due to inherited or acquired defects.

Inherited defects include glucose-galactosemalabsorption, abetalipoproteinemia, cystinuria, and Hartnup disease.

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,

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

Risk FactorsFactors 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.

Pathophysiology of Clinical Manifestations of

Malabsorption DisordersSymptom 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

Dermatitis Deficiency of vitamin A, zinc, and essential fatty acid

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.

. 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.

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.

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.

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.

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.

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.

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.

Investigations

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

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, ilealdysfunction

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

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

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)

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”

Barium studies

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

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., lymphomainfectious causes

Diffuse, non-specific – Celiac sprue, Tropical sprueautoimmune enteropathy

Suspected distal pathology - push enteroscopywireless capsule endoscopy

Cystic fibrosis (MUCOVISCIDOSIS) is a disorder of ion transport in epithelial cells.

It affects fluid secretion in

Exocrine glands

Respiratory,

Gastrointestinal, and

Reproductive tracts.

Cystic fibrosis transmembrane

conductance regulator (CFTR)

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

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

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

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

Celiac Disease

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

History of Celiac

• Aretaeus from Cappadochia (now Turkey) in the 2nd century AD described a chronic malabsorptivecondition

• He named this disorder "koiliakos” which is Greek for "suffering in the bowels.”

Booth, CC. History of celiac disease. BMJ 1989; 298:527.

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.

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

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

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

Pathogenesis of Celiac Disease

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

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

Risk Factors for Celiac Disease People suffering from other immune diseases and certain geneticdisorders 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

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.

Diagnosis of Celiac: Serologic

Testing

• Some of the serologic tests used to diagnose celiac:

• IgA and IgG antigliadinantibodies

• IgA endomysial antibodies

• IgA and IgG tissue transglutaminase antibodies

• Anti reticulin antibodies (no longer used)

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

Normal Pathology

Diagnosis: Small Bowel Endoscopy

Normal Celiac

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

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

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 biopsyDiagnosis

excluded

Rule out

other

causes of

villous

atrophy

- ++TREAT

-

Lactose Intolerance

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.

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.

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

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

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

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

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

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.

DiagnosisLactose 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%

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

Whipple Disease

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.

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 Actinomycetesclade)

It is found both intracellularly and extracellularly grow slowly in acidic vacuoles of cells

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.

Risk factorsBecause 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.

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

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

Whipple's Disease: showing macrophages in the small intestine

Whipple's Disease

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.

Tropical Sprue

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.

Pathophysiology

The exact pathogenesis poorly understood.

An acute intestinal infection leads to jejunal and ileal mucosa injury; then intestinal bacterial overgrowth and increased plasma enteroglucagonresults in retardation of small-intestinal transit.

Central to this process is folatedeficiency, which probably contributes to further mucosal injury.

Hormone enteroglucagon and motilinlevels 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.

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

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.

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

Autoimmune Enteropathy

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.

FOXP3 is a transcription factor expressed in CD4+ regulatory T cells.

Individuals with IPEX and FOXP3mutations 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.

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.

The malabsorption of is therefore a failure of transepithelialtransport.

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.

Possible ComplicationsLong-term malabsorption can result in:

Anemia

Gallstones

Kidney stones

Osteoporosis and bone disease

Malnutrition and vitamin deficiencies

Take Home Message

Wide spectrum of disorders

Both local and systemic causes are there

Various genetic, environmental & pathogenic organisms implicated

History & HPE often diagnostic