Anda di halaman 1dari 67

MALABSORPTION SYNDROME

by DURRIYA RAZA House officer Medicine unit IV, CHK Death sits in the bowels . . . Bad digestion is the root of all evil. Hippocrates, 400 B.C.

Case
37-year-old man 32-year history of type 1 diabetes. presented with nausea, vomiting, abdominal pain, and watery diarrhea for last 1 week. His wife and two young children had similar symptoms that had lasted 45 days and resolved. Two weeks earlier, he had been treated with azithromycin (Zithromax) for sinusitis. No fevers, chills, hematochezia, and melana..

Bowel sounds were present. soft, flat abdomen with mild diffuse tenderness but no rebound or guarding. Stools for fecal leukocytes, ova and parasites, and c-difficile were all negative. He was treated symptomatically with Imodium and promethazine with gradual resolution of his symptoms

Over the subsequent year and a half, the patient had seven similar episodes. During these episodes, he was afebrile but had vomiting and liquid bowel movements with mucus. The episodes generally lasted for 2 weeks and resolved. Between episodes, he generally had one formed bowel movement per day but had alternating periods of constipation and diarrhea.

Differentials?
This patient's history of spouse and young children with similar symptoms certainly raises the possibility of viral gastroenteritis and bacterial and parasitic enteric pathogens. In addition, his previous treatment with a broad-spectrum antibiotic for sinusitis raises the possibility of pseudomembranous colitis. Appropriate testing ruled out these possibilities and the recurrence of symptoms made these diagnoses less likely. Nausea and vomiting in a patient with long-standing type 1 diabetes may represent gastroparesis, a manifestation of diabetic autonomic neuropathy.

Medication-induced diarrhea, enteric pathogens, pseudomembranous colitis, primary intestinal diseases, such as inflammatory bowel disease and celiac disease, and pancreatic exocrine insufficiency.

What is Malabsorption? The integrated processes of digestion and absorption have 3 phases: Luminal phase Mucosal phase Transport phase Disturbances of these processes lead to malabsorption

1. Luminal phase (processing defect) Digestive enzyme deficiency / inactivation bile salt synthesis; Excretion; loss; bile salt de-conjugation gastric acid; intrinsic factor (p. anemia) Bacterial consumption of nutrients

Mechanism

Postgastrectomy steatorrhea. Exocrine Pancreatic insufficiency. Reduced bile salt concentration in intestine: I.) Liver Disease II.) Cholestasis III.) Bacterial over growth IV.) Interruption of enterohepatic circulation of bile salt.

Mucosal phase Epithelial transport defect inflammations infections Brush border hydrolysis defect congenital/acquired disacharidase deficiency

Crohns disease Coeliac disease Tropical Sprue Disaccharide Deficiency Lymphoma TB

Post-absorptive phase(transport phase) Enterocyte processing Abetalipoproteinemia Lymphocytic obstruction intestinal

lymphangectasia

Signs & symptoms


Calori Fat Protein carbohydrate B12 Folic acid Vit B (general) Iron Ca & Vit D Vit A VIt K Weight loss with normal appetite Pale,voluminous,greasy offensive diarrhea Edema, muscle atrophy, amenorrhea Abdominal bloating, flatus, w. diarrhea Macrocytic anemia Subacut combined degeneration of sp.cord Macrocytic anemia Cheliosis, glossitis,A.stomatitis, Acrodermatitis Microcytic anemia Osteomalacea (bone pain,pathologic#), Tetany Follicular hyperkeratosis, Night blindness Bleeding diathesis, Hematoma

Malabsorption of fats
Digestive Less time to mix- gastric resection, autonomic neuropathy, amyloidosis Dec micelle formationDecreased bile acid synthesis/secretionCirrhosis, Biliary obstruction, CCK deficiency, Small intestinal bacterial overgrowth, Decreased Lipolysis- Chronic pancreatitis, Cystic fibrosis, Pancreatic/ampullar y tumors, Low luminal pH ,Excessive calcium ingestion, Lipase/co-lipase deficiency (rare)

Absorptive

Decreased Chylomicron Formation and/or Mucosal Absorption Celiac Disease, Abetalipoproteinemia (AR) ,Hypobetalipoproteinemia (incomplete AD), Chylomicron Retention Disease Defective Lymphatic Transport-Primary Intestinal Lymphangiectasia,Lymphoma, Whipple Disease, Trauma, Retroperitoneal Fibrosis

Post absorptive

Malabsorption of carbohydrates
Digestive Severe pancreatic insufficiency (amylase deficiency)

absorptive

Primary or Acquired Lactase Deficiency Post-infectious Lactase Deficiency Celiac Disease Crohn Disease Sucrase-isomaltase deficiency Trehalase deficiency

Malabsorption of proteins
Digestive
Ppartial or total gastrectomy (poor mixing) Eexocrine pancreatic insufficiency Ttrypsinogen deficiency Ccongenital deficiency of intestinal enterokinase

absorptive

Celiac Disease and Tropical Sprue Methionine Malabsorption Syndrome and Blue Diaper Syndrome (tryptophan) Short Bowel Syndrome

Jejunoileal bypass
Defects in neutral AA transporters (Hartsnup Disease) Cystinuria I-III (Cystine and bibasic amino acids) Oculocerebral Syndrome of Lowe (Lysine/arginine)

Malabsorption of vitamins
Vitamin B12 (Cobalamin) Atrophic gastritis (impaired peptin/acid secretion) Deficiency of gastric intrinsic factor (pernicious anemia / antrectomy ) Pancreatic insufficiency/Z-E Syndrome (reduced release of B12 from R-binding protein) Helminth Infection/SI BO Ileal Crohn Disease/Resection

Folic acid

Caused by diseases affecting the proximal small bowel Celiac disease/Whipple/Tropical Sprue Alcoholism

Fat Soluble Vitamins (ADEK)

Anything that disrupts fat absorption will result in one/more deficiency

Malabsorption of minerals
Calcium #Selective deficiency can occur. Renal disease/hypoparathyroidism Inborn defect in the vitamin D receptor or 1,25-dihydroxy vitamin D formation #Diseases that reduce intestinal surface area and/or cause formation of insoluble calcium soaps with long-chain fatty acids. Celiac Disease Bile acid deficiency Usually caused by loss of mucosal surface area and/or luminal binding by malabsorbed fatty acids.

Magnesium

Iron
Zinc: Copper

Caused by reduced mucosal surface area, but most often caused by GI bleeding.
Acrodermatitis enteropathica (defect in the Zinc transport protein hZIP4) Menkes Disease (kinky hair disease) is caused by an inherited disorder of cellular copper transport.

Approach to diagnosis-history
Steatorrhea
Bloody diarrhea

Chronic diarrhea + pain, fever Large volume Radiation

Osmotic + low pH

Surgery

Cholecystecto my, resection Lactase def

Chronic pancreatitis
Cystic fibrosis Crohns IBD, eosinophilic gastroenteritis, immunodef

Arsenic, drugs, bowel resection, crohns, carcinoid, gastrinoma

Clinical examination
1)anemia, dermatitis herpetiformis, edema 4)mucocutane ous manifestations 2)abdominal mass or tenderness

3)Flatus

undigested CHO

IBD Flushing dermatitis herpetiformis celiac disease Edema

erythema nodosum

ulcerative colitis

Carcinoid 5)Manifestations of vitamin and mineral deficiencies

ptn losing enteropathy 6)amenorrhea , infertility, Xeropthalmia, glossitis, and purpura, tetany, peripheral impotence neuropathy etc due to malnutrition

Investigations: General: - CBC - Blood film - Ca. - B12, folate - Iron study - LFT, PT, APTT

Specific Tests of fat absorption: Quantitative fecal fat Patient should be on daily diet containing 80-100 grams of fat. Fecal fat estimated on 72 H collection. 6 grams or more of fat/day is abnormal. May be due to: - Pancreatic - Small intestinal - Hepatobiliary disease

Tests for pancreatic function: 1) Bentiromide test: A test of

pancreatic exocrine function in which orally administered bentiromide is cleaved by chymotrypsin within the lumen of the small intestine, releasing paminobenzoic acid. Diminished urinary excretion of p-aminobenzoic acid may indicate pancreatic insufficiency.
2) Schilling test

The Schilling Test determine the cause for cobalamin malabsorption. Since cobalamin absorption requires multiple steps, including gastric, pancreatic, and ileal processes, the Schilling test can also be used to assess the integrity of these other organs Achlorhydria, Bacterial overgrowth syndromes administering 58Co-labeled cobalamin orally and collecting urine for 24 h. Urinary excretion of cobalamin will reflect cobalamin absorption

3) Pancreatic stimulation test Secretin stimulation 4) Radiographic techniques: - Plain abdominal X-ray - U/S abdomen - ERCP - CT abdomen

Carbohydrate absorption test

1) Hydrogen breath test the patient takes a base reading of hydrogen levels in his/her breath. The patient is then given a small amount of fructose, and then required to take readings every 15, 30 or 60 minutes for two to three hours. If the level of hydrogen rises above 20 ppm (parts per million) over the lowest preceding value within the test period, the patient is typically diagnosed as a fructose malabsorber. Hydrogen excretion in bacterial overgrowth small intestinal malabsorption

2) D-xylose test

5-carbon sugar excreted unchanged in urine 25 grams given Urine collected for 5 hours Normally 25% is excreted In patients with fat malabsorption, this test differentiates pancreatic from small intestinal malabsorpton. D-xylose is normal in pancreatic disease Serum level of D-xylose at 1-2 hours after ingestion can be measured. An abnormal test (<4.5 g excretion) primarily reects the presence of duodenal/jejunal mucosal disease.

Test for bacterial overgrowth:


1) Intestinal aspiration and culture 2) Breath test 3) C-D xylose breath test

1) Radiography of small intestine: Barium swallow and follow-through to see - Blind loop - Stricture - J. diverticular

2) Intestinal mucosal biopsy: - using crossby capsule - endoscopy Coeliac disease: - Villous atrophy Tropical spure: - short villi and increased lymphocyte

Coeliac Disease (gluten-free diet results in eventual restoration)

Normal mucosa Villi( V) , Small crypts (C)

Coeliac disease Inflammatory cells (L) Loss of villi Elongated crypts (C)

Coeliac disease

(dissecting microscope)

Normal jejunal mucosa series of ridges and finger-like projections

Coeliac disease surface becomes fiattened, developing a mosaic-like pattem

Selection of tests in evaluation malabsorption


Quantitaive fecal fat
Normal Abnormal D-xylose test

Normal

Abnormal

Abd. Radiograph Bentiromide test


CT-abd. Normal

14 C-D-xylose test

Abnormal Jej culture Tetracyclin Then repeat breath test

Small intestinal Bx

Radiologic Examination

A. Normal individual. B. Celiac sprue. C. Jejunal diverticulosis( blind loop) D. Crohn's disease.

Endoscopy

Gross morphology gives diagnostic clue


Cobblestone appearance crohn's D. Reduced duodenal folds and scalloping of duodenal mucosa celiac disease
Use of vital dyes to identify villous atrophy

Biopsy to establish Dx
For pts with documented steatorrhea or ch. Diarrhea

Lesions seen classifid in to three


Diffuse,specific e.g. whippls Disease Patchy, specific crohns D., lymphoma infectious causes Diffuse,non-specific celiac sprue, Tropical sprue autoimmune enteropathy

Suspected distal pathology - push enteroscopy wireless capsule endoscopy

Biopsy of Small-Intestinal Mucosa


Diffuse, specific

Whipples disease
Agammaglobulinemia Intestinal lymphoma Intestinal lymphangiectasia Eosinophilic gastroenteritis Amyloidosis Crohns disease Mastocytosis Celiac and tropical sprue Bacterial overgrowth Folate, B12 deficiency, Radiation Zollinger-Ellison syndrome Protein-calorie malnutrition

Macrophages containing PAS+ material


No plasma cells, no villi Patchy, specific Malignant cells in lamina propria Dilated lymphatics Eosinophil infiltration Amyloid deposits Noncaseating granulomas Mast cell infiltration Diffuse, nonspecific Short or absent villi; mononuclear infiltrate; Patchy damage to villi; Short villi Mucosal ulceration Villous atrophy

RESULTS OF DIAGNOSTIC STUDIES IN DIFFERENT CAUSES OF STEATORRHEA

Second line tests


Sigmoidoscopy, colonoscopy, ERCP Esophagogastroduodenoscopy with small intestinal biopsies Abdominal ultrasound Capsule endoscopy immunoglobulins, human immunodeficiency virus antibodies, antinuclear antibodies, ferritin, food allergen-specific IgE, adrenocorticotropic hormone, cortisol, chromogranin A, gastrin, urinary 5-HIAA Quantitative fecal fat

Third line tests


MRI Abdominal angiogram PET Somatostatin (octreotide) scan Endoscopic ultrasound Enteroscopy, including biopsies Spiral CT of the pancreas for tumor Tests for bile acid malabsorption Glucagon, somatostatin in serum/plasma

Back to our case


CBC, electrolytes, blood urine nitrogen, creatinine, liver function studies, and thyroid-stimulating hormone were all within normal limits. Treatment with metaclopramide (Reglan) and domperidone did not prevent the episodes, nor did treatment with tetracycline 250 mg 3 times per day for 14 days. A hydrogen breath test was negative. Colonoscopy was normal. Upper GI endoscopy revealed a normal esophagus, stomach, pylorus, and duodenum.

Multiple biopsy specimens were obtained from the post-bulbar duodenum and sweep. Biopsies from the small intestine revealed blunting of the villae consistent with celiac disease. In addition, IgA anti-endomysial antibodies were performed. These were positive in a titer of 1 to 640. The patient began a gluten-free diet with complete resolution of his symptoms and a 10-lb weight gain within 2 months.

Celiac disease and type 1 diabetes are autoimmune diseases with a common genetic predisposition. Both celiac disease and type 1 diabetes are associated with a high frequency of HLA-DR3 genotypes. As a result, celiac disease is more frequent in type 1 diabetes than in type 2 diabetes or in the general population. Studies that have screened patients with type 1 diabetes for celiac disease have found rates of celiac disease between 1% and 8%. These rates are 411 times higher than rates of celiac disease in the general population.

CELIAC DISEASE

Celiac disease (CD) is an immunemediated disorder that develops in genetically susceptible persons when gluten, a major protein found in wheat, barley, and rye is ingested in the diet. Also called nontropical sprue, celiac sprue, or gluten-sensitive enteropathy, CD is primarily an enteropathy characterized by inflammation of the small bowel mucosa and atrophy of the villi, resulting in nutrient malabsorption, wasting, and diarrhea.

Any organ system may be involved in CD, and patients can develop extraintestinal manifestationsalso called atypical manifestationssuch as anemia, bone disease, infertility, unfavorable outcomes of pregnancy, lymphoma, and liver disease.

Prevalence and epidemiology

Women are affected more commonly than men, but there is no age predilection.

Patients Who Are at Risk for Celiac Disease and Should Be Tested
Patients with gastrointestinal and classic symptoms: diarrhea, weight loss, abdominal distention, failure to thrive Patients with autoimmune diseases, type 1 diabetes, thyroid disorders, Sjgren's syndrome, microscopic colitis, inflammatory bowel disease First-degree relatives Patients with elevated liver enzymes

Patients with Down syndrome Patients with iron deficiency anemia Patients with osteoporosis Patients with delayed puberty Infertile patients Patients with irritable bowel syndrome

Pathophysiology Celiac disease is a multifactorial and a multisystem disorder involving a genetic predisposition, environmental exposure of the small bowel mucosa to gluten, and an immunologic response to gluten.

Genetic susceptibility defines persons who possess the gene pair encoding the major histocompatibility complex class II HLA DQ2 or DQ8. These genes are virtually required for CD to occur, and lack of these genes makes CD very unlikely.

The majority (>90%) of persons with CD possess the HLA DQ2 haplotype, and 5% to 10% possess the DQ8 haplotype, conferring a negative predictive value greater than 98%. These haplotypes are encoded within the HLA class II region of the major histocompatibility complex on chromosome 6p. However, about 40% of the general population carry these haplotypes without having the disease, which makes their presence necessary but not sufficient for its development. Intestinal antigen-presenting cells in people expressing HLA-DQ2, or HLA-DQ8, bind with dietary gluten peptides in their antigenbinding grooves activate specific mucosal T lymphocytes cytokines mucosal damage.

Clinical manifestations
Celiac disease exhibits a spectrum of clinical and pathologic manifestations. Symptoms can manifest in infancy and as early as cereals are introduced in the diet. Crampy abdominal pain, steatorrhea, failure to thrive, apathy and irritability, muscle wasting, and hypotonia are described. Any of these symptoms should trigger a diagnostic workup. Catch-up growth is well documented once a gluten free-diet is introduced.

In adults, the clinical symptoms are variable and not specific. The classic symptoms of malabsorption are less encountered. On the other hand, atypical presentations are increasingly recognized and becoming more common.

Patients with CD can exhibit weakness, fatigue, and dyspnea as a result of vitamin B12, folate, and iron deficiency; bone fractures, muscular atrophy, and tetany as a result of osteoporosis and osteopenia due to vitamin D and calcium deficiencies; peripheral neuropathy and ataxia as a result of cerebellar and posterior column inflammatory damage; and secondary hyperparathyroidism, edema, petechiae, and dermatitis herpetiformis. Infertility is observed in men and women. Amenorrhea, intrauterine growth retardation, and unfavorable outcomes of pregnancy have been reported.

Essentials of diagnosis
Weight loss Distention, flatulence, greasy stools Increased fecal fat (>7g/24h) Abnormal small bowel biopsy Clinical improvement on gluten-free diet

Diagnosis
Once the clinical suspicion in patients at risk factors is raised, the initial step toward a diagnosis is to obtain celiac serology antibody testing. This should be followed by a small bowel biopsy. The patient should be tested while following a gluten-containing diet. The most sensitive and specific serologic tests are endomysial antibody IgA EMA and tissue transglutaminase antibody IgA tTG. Sensitivities and specificities are higher than 85% and 97%, respectively, for EMA and 90% and 97%, respectively, for tTG. Gliadin antibodies have lower sensitivities and specificities and are not recommended for screening; however, gliadin antibodies may have a role in monitoring adherence to a gluten-free diet.

Pathologic changes on small-bowel biopsy are characterized by a spectrum of abnormalities described by Marsh and known as the Marsh criteria. The hallmark of CD is Marsh 3 or villous atrophy; however, this may be patchy or present in other disorders as in hypogammaglobulinemia, acute infectious gastroenteritis, or milk intolerance. Additionally, there is growing evidence that CD may be diagnosed when changes of earlier phase on biopsy such as Marsh 1 or Marsh 2 are seen.

Establishing Diagnosis in the Absence of Typical Symptoms The wide range of clinical manifestations of the disease coupled with less than Marsh 3 on biopsy makes the diagnosis of CD challenging for the clinician. In these situations, genetic testing or gluten challenge may be necessary for a definite diagnosis. A few scenarios may be encountered in a clinical setting and their proposed diagnostic workups include:

Positive serology and villous atrophy: Diagnosis established. Patient should be treated. Positive serology and normal small bowel mucosa biopsy: Disease is considered latent and biopsy should be repeated after a gluten challenge or a few months later on a normal diet.

Positive serology and increased intraepithelial lymphocytes: Potential celiac disease; repeat biopsy after a gluten challenge or in a few months on a normal diet, or obtain HLA typing. If any is positive, start a gluten-free diet. Normal serology and normal biopsy: Look for other causes of the patient's symptoms. Normal serology and villous atrophy: Exclude other causes of villous atrophy, immunodeficiency, IgA deficiency.

TREATMENT
Treatment consists of withdrawing gluten from the diet for life. It entails eliminating wheat, barley, and rye. This allows healing of the small bowel mucosa and restitution of nutritional status.

Deficiencies of vitamins D and B12, folic acid, calcium, and iron and nutritional deficiencies should be replaced as necessary. Prevention of bone loss and pneumococcal vaccination due to hyposplenism are necessary.

Response to the gluten-free diet is assessed by clinical and serologic improvement. There is no clear consensus on whether a repeat small bowel biopsy is necessary. However, repeat biopsy may be indicated in cases where adherence to diet is proved but response to diet is equivocal or lacking.

Foods That Are Safe in Celiac Disease


Plain meat (no bread or bread crumbs) Poultry Fish Shellfish Milk Vegetables Fruit Fats and oils Butter

References
Harrisons internal medicine Current diagnosis and treatment in gastroenterology Pubmed.com Emedicine.com

THANK YOU

Anda mungkin juga menyukai