malabsorption syndromes
TRANSCRIPT
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