1. Maldigestion and Malabsorption

2. ETIOLOGY AND PATHOPHYSIOLOGY
Classically, maldigestion is defined as defective hydrolysis of nutrients, and malabsorption is defined as defective mucosal absorption. Although this distinction may be useful on pathophysiologic grounds, the clinical presentation and complications of maldigestion and malabsorption are similar.
When the distinction between these terms is not of clinical relevance, only the terms absorption and malabsorption are used.
ETIOLOGY AND PATHOPHYSIOLOGY
From a pathophysiologic point of view, mechanisms causing malabsorption can be divided into premucosal (luminal) factors, mucosal factors, and postmucosal factors (vascular and lymphatic). For clinical purposes, this approach is of limited value, because the various clinical pictures caused by malabsorption syndromes are determined mainly by the nature of the malabsorbed substrates. We therefore discuss the mechanisms causing malabsorption on the basis of the malabsorbed substrate.

3. Diseases That Cause Nutrient Malabsorption
1-Gastric Diseases :
Atrophic gastritis , Autoimmune gastritis (pernicious anemia) , Gastric resection or bypass surgery.
2-Pancreatic Diseases :
Congenital pancreatic enzyme deficiencies(Colipase deficiency ,  Lipase deficiency,  Trypsinogen deficiency).
Pancreatic insufficiency  ( Chronic pancreatitis,Cystic fibrosis).
Pancreatic tumors
3-Liver Diseases :
 Inborn errors of bile acid biosynthesis and transport,  Cirrhosis and other liver diseases,Portal hypertension.
4-Obstructive Biliary Diseases :
 Biliary tumors, Primary and secondary sclerosing cholangitis.
5-Lymphatic Diseases :
 Primary intestinal lymphangiectasia, Secondary intestinal lymphangiectasia , Lymphoma,Solid tumors,Thoracic duct trauma, damage, or obstruction

4. 6-Intestinal Diseases :
 Amyloidosis   Autoimmune enteropathy   Celiac disease   Collagenous sprue   Congenital intestinal defects (see Table )   Crohn's disease   Enteroendocrine cell deficiency   Autoimmune polyglandular syndrome type 1   Enteric anendocrinosis   Enterokinase deficiency   Eosinophilic gastroenteritis   Fistulas   Food allergy   Graft-versus-host disease   Hypolactasia   Ileal bile acid malabsorption   Intestinal infections  
 AIDS (HIV infection): Cryptosporidiosis, Mycobacterium avium complex infection, viral infections   Giardiasis   Helminthic infections   Tuberculosis   Whipple's disease   Immunoproliferative small intestinal disease   Intestinal ischemia   Intestinal lymphoma   Intestinal resections or bypass   Mastocytosis   Nongranulomatous chronic idiopathic enterocolitis   Postinfection malabsorption   Primary immunodeficiency diseases   Radiation enteritis   Refractory sprue   Sarcoidosis   Small intestinal bacterial overgrowth   Tropical sprue

5. 7-Neuroendocrine Tumors : Carcinoid syndrome Glucagonoma Somatostatinoma Zollinger-Ellison syndrome 8-Cardiac and Vascular Diseases : Congestive heart failure Constrictive pericarditis 9-Endocrine Causes : Addison's disease Diabetes mellitus Hyperthyroidism 10-Systemic Diseases : Cronkhite-Canada syndrome Mixed connective tissue disease Neurofibromatosis type 1 Protein-calorie malnutrition Scleroderma Systemic lupus erythematosus

6. CLINICAL FEATURES AND EVALUATION
Diagnosis of malabsorption requires suspecting its presence, confirming its existence, and demonstrating its cause.
History and Physical Examination
Gastrointestinal :
Diarrhea (watery or steatorrhea), Abdominal distention, flatulence , Foul- smelling flatulence or stool , Pain , Ascites .
Musculoskeletal :
Tetany, muscle weakness, paresthesias , Bone pain, osteomalacia, fractures
Cutoneous and Mucosal :
Easy bruisability, ecchymoses, petechiae , Glossitis, cheilosis, stomatitis, Edema , Acrodermatitis, scaly dermatitis , Follicular hyperkeratosis , Hyperpigmented dermatitis , Thin nails with spoon-shaped deformity , Perifollicular hemorrhage , Spiral or curly hair .
Other :
Weight loss, hyperphagia , Growth and weight retardation, infantilism , Anemia , Kidney stones , Amenorrhea, impotence, infertility , Night blindness, xerophthalmia , Peripheral neuropathy , Fatigue, weakness , Neurologic symptoms, ataxia .

7. Laboratory Findings
Blood Cell Count: Hematocrit, hemoglobin(Decreased in iron, vitamin B12, and folate malabsorption or with blood loss)
Mean corpuscular hemoglobin or mean corpuscular volume(Decreased in iron malabsorption; increased in folate and vitamin B12 malabsorption )
White blood cells, differential(Decreased in vitamin B12 and folate malabsorption; low lymphocyte count in lymphangiectasia).
Biochemical Tests (Serum ): Triglycerides(Decreased in severe fat malabsorption)
Cholesterol(Decreased in bile acid malabsorption or severe fat malabsorption)
Albumin(Decreased in severe malnutrition, lymphangiectasia, protein-losing enteropathy)
Alkaline phosphatase(Increased in calcium and vitamin D malabsorption (severe steatorrhea); decreased in zinc deficiency)
Calcium, phosphorus, magnesium(Decreased in extensive small intestinal mucosal disease, after extensive intestinal resection, or in vitamin D deficiency)
Zinc(Decreased in extensive small intestinal mucosal disease or intestinal resection)
Iron, ferritin(Decreased in celiac disease, in other extensive small intestinal mucosal diseases, and with chronic blood loss)

8. Other Serum Tests :
Prothrombin time(Prolonged in vitamin K malabsorption)
β-Carotene(Decreased in fat malabsorption from hepatobiliary or intestinal diseases)
Immunoglobulins(Decreased in lymphangiectasia, diffuse lymphoma)
Folic acid(Decreased in extensive small intestinal mucosal diseases, with anticonvulsant use, in pregnancy; may be increased in small intestinal bacterial overgrowth )
Vitamin B12(Decreased after gastrectomy, in pernicious anemia, terminal ileal disease, and small intestinal bacterial overgrowth)
Methylmalonic acid(Markedly elevated in vitamin B12 deficiency) Homocysteine(Markedly elevated in vitamin B12 or folate deficiency)
Stool Tests :
Fat(Qualitative or quantitative increase in fat malabsorption)
Elastase, chymotrypsin(Decreased concentration and output in exocrine pancreatic insufficiency)
pH(Less than 5.5 in carbohydrate malabsorption)

9. NONINVASIVE EVALUATION OF GASTROINTESTINAL DIGESTIVE AND ABSORPTIVE FUNCTION
Lactose malabsorption:
 ( Lactose hydrogen breath test, Lactose tolerance test Tests do not differentiate between primary and secondary lactose malabsorption
Fructose malabsorption:
Fructose hydrogen breath test(Questionable clinical relevance)
Small intestinal bacterial overgrowth:
 14C-d-xylose breath test   Glucose hydrogen breath test   Schilling test with and without antibiotics (A predisposing factor should be sought if the result of any of the tests is positive)
Bile acid malabsorption:
SeHCAT test, 14C-TCA test (Does not differentiate between primary and secondary causes)
Exocrine pancreatic insufficiency:
Quantitative fecal fat determination(To establish malabsorption in chronic pancreatitis) Fecal elastase or chymotrypsin, tubeless tests (Variable sensitivity and specificity, depending on type of test and stage of the disease)
Vitamin B12 malabsorption :
Schilling test(Test is performed without intrinsic factor and, depending on result with intrinsic factor, with antibiotics or with pancreatic enzymes . Further tests are needed if small intestinal bacterial overgrowth, terminal ileal disease, or pancreatic disease is suspected)
SeHCAT, selenium-75-homotaurocholic acid test; TCA, taurocholic acid

10. Fat Malabsorption (Quantitative Fecal Fat Analysis ):
The van de Kamer method is the quantitative titration of fatty acid equivalents in which the results are expressed as fecal output of fat in grams per 24 hours. This method is considered the gold standard for fecal fat analysis. Fecal fat excretion of less than 7 g per day with a fat intake of 100 g per day usually is considered normal. it still requires a 48- to 72-hour collection to exclude the influence of day- to-day variability; the stool must be mixed before a sample is obtained for analysis.
The Schilling Test :
The Schilling test is performed by administering a small oral dose of radiolabeled vitamin B12 and, simultaneously or within one or two hours, a large intramuscular flushing dose of nonradiolabeled vitamin B12. The unlabeled B12 saturates vitamin B12 carriers; thus, any radioactive vitamin B12 absorbed by the intestine is excreted in the urine. If less than 7% to 10% of the administered dose is recovered in urine within 24 hours, vitamin B12 malabsorption is confirmed. To specify the site of vitamin B12 malabsorption, a second phase of the Schilling test is performed subsequently with oral administration of intrinsic factor. In patients with pernicious anemia, the results of the Schilling test normalize after oral administration of intrinsic factor.Patients with pancreatic exocrine insufficiency might have an abnormal result on the Schilling test, with or without added intrinsic factor, but results normalize with addition of pancreatic enzymes . In small bowel bacterial overgrowth the results of the Schilling test can improve after antibiotic therapy (Chapter 102). In ileal disease or following ileal resection, abnormal results of the Schilling test persist despite intrinsic factor. Schilling test results are normal in patients with dietary vitamin B12 deficiency,

11. ENDOSCOPY, BIOPSY, AND DUODENAL ASPIRATION
D-Xylose Test :
Absorption of the pentose d-xylose is facilitated by passive diffusion. Approximately 50% of the absorbed d-xylose is metabolized, and the remainder is excreted in urine. After an overnight fast, a 25-g dose of d-xylose is swallowed, and the patient is encouraged to drink sufficient volumes of fluid to maintain good urine output. Urine is collected for the next five hours. As an alternative, one hour after ingestion of d-xylose, a venous sample may be obtained. Less than 4 grams (16% excretion) of d-xylose in the urine collection or a serum xylose concentration below 20 mg/dL indicates abnormal intestinal absorption. The traditional urine test appears to be more reliable than the one-hour blood test. The test is of limited clinical value today and mostly has been replaced by small intestinal biopsy.
ENDOSCOPY, BIOPSY, AND DUODENAL ASPIRATION
Endoscopy
Endoscopic inspection of the duodenal mucosa can provide clues to some causes of malabsorption. Aphthae suggest Crohn's disease, and small, diffuse, white, punctate lesions can be seen in primary or secondary lymphangiectasia. Mosaic-like scalloping of duodenal folds and reduction in the number of duodenal folds are highly suggestive of villus atrophy in celiac disease, although these abnormalities may be seen in other diseases.

12. Biopsy :
Examination of endoscopic biopsy specimens from the duodenum may be diagnostic or highly suggestive of a variety of small bowel disorders resulting in malabsorption ; follow-up small intestinal biopsy can be used to assess treatment effects. two or three jumbo duodenal or jejunal biopsy specimens usually are sufficient to allow histologic sectioning parallel to the villi and crypts. Specimens also may be obtained with smaller forceps, although the number of specimens obtained must then be increased to four to six. Charaterstic histological feature of malabsorption is villous atrophy.
Aspiration :
Fluid aspirated from the descending part of the duodenum may be examined microscopically for Giardia lamblia or cultured to detect bacterial overgrowth in patients with diffuse small intestinal motility disorders .
ABDOMINAL IMAGING
Small Bowel Follow-through and Small Bowel Enteroclysis
Abdominal Computed Tomography
Magnetic Resonance Imaging of the Small Intestine

13. DDX of villous atrophy:
1- celiac disease
2- tropical sprue
3- Infection (due to Giardia lamblia, Cryptosporidium)
4-AIDS enteropathy
5- Whipple's disease
6-Drug-induced enteropathy (NSAIDs, colchicine, neomycin)
7-Food protein hypersensitivity (rye, barley, egg, fish, rice, poultry)
8-Immunodeficiency (hypogammaglobulinemia)
9-Lymphoma
10-Prolonged folate or cobalamin deficiency
11- Crohn's disease
12-Protein-calorie malnutrition
13- zollinger Ellison syndrome
14- Chronic radiation damage
15-Traumatic injury

14. GENERAL APPROACH TO MANAGEMENT
Treatment of malabsorptive diseases must be directed against the underlying condition, if possible. In addition, nutritional deficits must be corrected.
In pancreatic insufficiency, in disorders of intestinal fat absorption, and in short bowel syndrome, medium-chain triglycerides can be used as a source of dietary calories, these patients, therefore, should consume a diet rich in carbohydrates and medium-chain triglycerides. In bile acid malabsorption after extensive ileal resections, intestinal fat absorption can be improved markedly by oral administration of natural conjugated bile acids or of synthetic cholylsarcosine. Replacement of conjugated bile acids also reduces urinary oxalate excretion and therefore should protect against development of kidney stones. Patients with cystic fibrosis or short bowel syndrome who are unable to absorb vitamin D from their diet may benefit from treatment with an ultraviolet lamp, which emits ultraviolet radiation similar to sunlight.

15. In patients with malabsorption and an intact colon, fluid depletion must be avoided to prevent kidney stones associated with hyperoxaluria.[326] In patients with malabsorption syndrome, special care should be given to the replacement of vitamins, iron, calcium, and trace elements to avoid deficiency syndromes.
In patients with diarrhea, symptomatic treatment with opiates or loperamide can increase the time available for absorption of nutrients.