Overview of Malabsorption Syndromes and Clinical Presentations

1. Malabsorption syndrome Nady Semeda , MSc, M.D

2. Introduction -In general, malabsorption constitutes the pathological interference with the normal physiological sequence of digestion (intraluminal process), absorption (mucosal process) and transport (postmucosal events) of nutrients. -Most diseases producing malabsorption generate defective assimilation of many nutrients resulting in classical overt malabsorptive symptoms. -On the contrary, some rare diseases selectively affect one nutrient resulting in a disorder with a paucity of symptoms.

3. Clinical Aspects of Malabsorption • (1) clear features of overt malabsorption (usually in patients with severe and long-standing malabsorption). • (2) evidence of subclinical malabsorption (minor symptoms and signs are present, mostly extraintestinal features). • (3) circumstances in which classical malabsorption diseases can be present in cases with an asymptomatic clinical course and normal physical examination.

4. Classical Overt Malabsorption • Chronic diarrhea is a highly subjective symptom : Watery, diurnal and nocturnal, bulky, frequent stools are the clinical hallmark of overt malabsorption. • Stool color can be influenced by fat content. Patients with steatorrhea present pale, yellow, floating, spongish stools. • Other gastrointestinal features are anorexia, hyperphagia, nausea, vomiting, abdominal distention, borborygmis. • abdominal pain is unusual.

5. Subclinical malabsorption • is well recognized, especially in celiac disease. • Patients do not present gastrointestinal symptoms, rather they exhibit long-lasting and frequently missed extraintestinal features. • rather they exhibit long-lasting and frequently missed extraintestinal features that are rarely associated with intestinal problems (short stature, infertility, bone disease, hematological problems, etc.)

6. Common causes of malabsorption (1) Giardiasis • Giardia Intestinalis is a protozoan parasite that over the last years has been recognized as an important pathogen for human beings with a worldwide distribution. • Most patients are asymptomatic, but other can express acute or more frequently chronic diarrhea, malnutrition and growth retardation in children. • Giardiasis is associated with a wide repertoire of small intestinal mucosal abnormalities ranging from normal appearance at light microscopy (96% of cases) to subtotal villous atrophy with crypt hyperplasia and intraepithelial lymphocyte infiltration.

7. - the presence of malabsorption syndrome in giardasisis is closely related to the degree of enteropathy, however, Giardia also promote changes in a variety of luminal factors (bacterial overgrowth, bile salt deconjugation and uptake by the parasite, inhibition of host enzymes, etc.)

8. (2) Celiac disease • It is commonly assumed that chronic diarrhea and overt malabsorption are the classical clinical features of celiac disease. • It refers to a condition known as gluten hypersensitivity, which is present in wheat and oat. • several studies have demonstrated that most of the new cases are now individuals with milder gastrointestinal symptoms, features related to extraintestinal manifestations , or patients in whom the primary diagnosis is an autoimmune disorder such as primary biliary cirrhosis , thyroid diseases , insulin-dependent diabetes mellitus. • Despite manifestations of intestinal mucosal atrophy, the disease can be clinically asymptomatic as was observed among first-degree relatives. • Serological diagnosis in the form of anti endomyaseal antibody , anti tissue transglutaminase antibodies. • Treatment is by gluten withdrawal from food.

9. (3) Whipple’s Disease • Whipple’s disease is a chronic systemic disorder that has been suspected to be of infectious origin since its first description due to a pathogen known as T.whippellii . • The disease is characterized by multiorgan involvement with prominent compromise of the gastrointestinal tract, lymph nodes, endocardium, central nervous system, bone and joint and eye . • The disease is also characterized by the presence of foamy, large macrophages containing periodic acid-Schiff-positive diastaseresistant inclusions (PAS), with a typical rod shape generated from duodenal aspirates . • Treatment by antibiotics like ceftriaxone and cotrimoxazole .

10. (4) tropical sprue • There are a series of specific causes of chronic diarrhea and malabsorption that mostly affect populations of tropical and subtropical areas; these include intestinal tuberculosis, Mediterranean lymphomas, severe malnutrition, etc. • Patients must be suspected of tropical sprue if they are resident in or were visitors to tropical or subtropical areas and have chronic diarrhea and malabsorption of two unrelated substances such as xylose and vitamin B12. • Although the small intestinal biopsy is not characteristic (tropical enteropathy: villous enfacement, inflammatory infiltration of lamina propria and epithelium, minor enterocyte damage), it is useful to differentiate from other disorders where biopsy can be diagnostic (Whipple’s disease, strongyloidiasis, etc.).

11. (5) Bile Acid Malabsorption • Bile acids are necessary for the absorption of dietary fats and sterols from the intestine. They are synthesized in the liver.The gall bladder stores bile between meals that is excreted into the intestine during digestion. • More than 90% of bile acids are reabsorbed from distal intestine in the enterohepatic recirculation; most importantly, in the distal 100 cm of ileum there is an active uptake step. • Malabsorption of bile acids can produce diarrhea with some • special characteristics.

12. • These can be classified as primary or secondary bile acid malabsorption. • Primary malabsorption is also known as idiopathic diarrhea • Secondary bile acid malabsorption is associated with intestinal resection , disease of the distal ileum or other clinical conditions such as postcholecystectomy and post vagotomy. • bile acid metabolism assessment should be routinely performed in patients for which the cause of diarrhea is not obvious after full investigation. • If this disorder is confirmed, therapeutic strategy should include the use of bile acid chelators.

13. (6) Vitamin B12 Malabsorption • Often, macrocytic anemia is present in patients with primary gastrointestinal alterations. • Vitamin B12 has a complex intraluminal metabolic process starting with the salivary excretion (protein R) and including the participation of gastric secretion (intrinsic factor), a pancreatic factor (proteases) and an active uptake in the terminal ileum. • Several gastrointestinal conditions can be associated with malabsorption of vitamin B12. • Among others, small bowel bacterial overgrowth, tropical sprue, celiac disease, Crohn’s disease, Whipple’s disease are the most relevant gastrointestinal conditions associated with clinical evidences of vitamin deficiency.

14. • decreased intrinsic factor-receptor activity in ileal mucosa constitutes an important pathogenic mechanism. • Juvenile megaloblastic anemia caused by selective intestinal malabsorption of vitamin B12 has been considered a distinct condition displaying autosomal-recessive inheritance. • Ileal damage secondary to radiation side effects was also demonstrated as a cause of vitamin B12 malabsorption.