MALABSORPTION SYNDROMES

1. Introduction

Disorders of absorption are considered as malabsorption syndromes. These disorders constitute a wide range of conditions with multiple etiologies and varied clinical manifestations. Almost all of these clinical problems are associated with diminished intestinal absorption of one or more dietary nutrients and are often referred to as the malabsorption syndrome.

Hemochromatosis and Wilson’s disease are the only two conditions where absorption is increased, in which there is increased absorption of iron and copper, respectively. Most, but not all, of these malabsorption syndromes are associated with Steatorrhoea, an increase in stool fat excretion of 6% of dietary fat intake. Some disorders of absorption are not associated with steatorrhoea.

Virtually all the dietary substances can give rise to malabsorption syndromes. But protein, fat, carbohydrates and vitamin B12 are the commonest substances which cause malabsorption syndromes.

2. Nutrient digestion and absorption

Digestion is a process in which large particles of food are broken down into small particles, which are readily absorbable. Absorption depends on the particle size, surface area and presence of other competitive substances. Digestion is started from the mouth. But it mainly occurs in the stomach and the small intestine. Main sites of absorptions are small intestine and the colon. Presence of folds, villi and microvilli increase the functional surface area of absorption. The intestinal epithelia have several other functions as well;

• Barrier and immune defense.
• Fluid and electrolyte absorption and secretion.
• Synthesis and secretion of several proteins.
• Production of several bioactive amines and peptides.

I. Digestion and absorption of LIPIDS

Fat digestion mainly takes place in the small intestine. Pancreatic enzymes are the cornerstone for the fat digestion. Lipase is the most important enzyme in this respect Fat absorption is linear to dietary fat intake. The total load of fat presented to the small intestine is considerably greater, as substantial amounts of lipid are secreted in bile each day. Steatorrhoea is caused by one or more defects in the digestion and absorption of dietary fat.

Fats consist of three types of fatty acids; long chain fatty acids, medium chain fatty acids, and short chain fatty acids. Dietary fat is exclusively composed of long-chain triglycerides. Assimilation of dietary lipid requires several integrated processes that can be divided into an intraluminal, or digestive phase; a mucosal or absorptive phase; and a delivery, or post absorptive phase.

An abnormality at any site of this process can cause steatorrhoea Therefore, it is essential that any patient with steatorrhoea be evaluated to identify the specific physiologic defect in overall lipid digestion absorption as therapy will be determined by the specific cause responsible for the steatorrhoea.

II. Digestion and absorption of CARBOHYDRATES

Carbohydrates in the diet are present in the form of starch, disaccharides (sucrose and lactose) and glucose. Carbohydrates are absorbed only in the small intestine and only in the form of monosaccharide. Therefore, before their absorption, starch and disaccharides must first be digested by pancreatic amylase and intestinal brush border disaccharides to monosaccharides. Monosaccharide absorption occurs by a Na dependent process mediated by the brush border transport protein SGLT. Lactose malabsorption is the only clinically important disorder of carbohydrate absorption

III. Digestion and absorption of PROTEINS

Protein is present in food almost exclusively as polypeptides and requires extensive hydrolysis to di- and tripeptides and amino acids before absorption. Proteolysis occurs in both the stomach and small intestine; it is mediated by pepsin secreted as pepsinogen by gastric chief cells and trypsinogen and other peptidases from pancreatic acinar cells. These proenzymes, pepsinogen and trypsinogen, must be activated to pepsin. Proteins are absorbed by separate transport systems for di- and tripeptides and for different types of amino acids, e.g., neutral and dibasic.

Alterations in either protein or amino acid digestion and absorption are rarely observed clinically, even in the presence of extensive small-intestinal mucosal inflammation. However, three rare genetic disorders involve protein digestion-absorption: (1) enterokinase deficiency is due to an absence of the brush border enzyme that converts the proenzymes trypsinogen to trypsin and is associated with diarrhea, growth retardation, and hypoproteinemia; (2) Hartnup syndrome, a defect in neutral amino acid transport, is characterized by a pellagra-like rash and neuropsychiatric symptoms; and (3) cystinria, a defect in dibasic amino acid transport, is associated with renal calculi and chronic pancreatitis.

3. Evaluation of malabsorption

Irrespective of the disease entity in clinical practice, history, examination and investigations are the steps of patients’ evaluation. The clues provided by the history, symptoms, and initial preliminary observations will serve to limit extensive, ill-focused, and expensive laboratory and imaging studies. The classical presentations described in text books are hardly found in clinical practice therefore diseases with malabsorption must be suspected in individuals with less severe symptoms and signs and with subtle evidence of the altered absorption of only a single nutrient rather than obvious evidence of the malabsorption of multiple nutrients.

Diarrhea can be caused by changes in fluid and electrolyte movement in either the small or the large intestine, but dietary nutrients are absorbed almost exclusively in the small intestine. Therefore the demonstration of altered absorption of nutrients does not exclude colonic dysfunction.

4. Investigations of malabsorption syndromes

Tests to find evidence of malabsorption

i. Full blood count

ii. MCV, MCH

iii. Serum iron binding capacity/ serum iron

iv. Serum folate

v. Prothrombin time

vi. Plasma protein

Tests to find the cause of the malabsorption

i. C-reactive protein

ii. Immunoglobulin

iii. Endomysial and antigliadin antibodies (celiac disease)

iv. Small intestinal biopsy

v. Radiographs

specific investigations

A.Investigations of steatorrhoea

ii. Plasma carotene

iii. Plasma optical density

iv. Plasma triglycerides

v. Vitamin A absorption

vi. 14C labeled triglycerides test

vii. Fecal fat test

B. Investigations of protein malabsorption

i. Fecal nitrogen

C.Investigations of carbohydrates malabsorption

i. Xylose absorption test

ii. Lactose tolerance test

iii. Fecal pH and sugar

iv. Intestinal disaccharide assay

v. Hydrogen breath test

D.Investigations of vitamin malabsorption

i. Schilling test

5. Specific disease entities

1. Lactose intolerance
2. pernicious anemia
3. celiac sprue
4. tropical sprue
5. short bowel syndrome

I. lactose intolerance

This is the only significant disorder of carbohydrates malabsorption. Lactose is a disaccharide which mainly present in the milk and it requires digestion by brush border lactase to its two constituent monosaccharide, glucose and galactose. Lactase is present in almost all species in the postnatal period but then disappears throughout the animal kingdom, except in humans. Lactase activity persists in many individuals throughout life.

But there are two types of lactase deficiencies found in humans-primary and secondary lactase deficiency.

The primary lactase deficiency is a genetically determined condition in which the lactase is decreased or absence. Even though other brush border enzyme levels are normal. Digestion and brush border absorption are also normal. This condition is common among the North American and Northern European Caucasians.

Secondary lactase deficiency occurs in association with small-intestinal mucosal disease with abnormalities in both structure and function of other brush border enzymes and transport processes. Secondary lactase deficiency is often seen in celiac sprue.

Symptoms of lactose intolerance are diarrhea, abdominal pain, cramps, and flatus. Development of symptoms depends on several factors such as amount of lactose in the diet, rate of gastric emptying and small intestinal transit time. If the rate of gastric emptying is rapid, severity of symptoms will be more pronounce.

Only treatment available is the avoidance of the dietary lactose. Patients should be given lactose free diet. If the patient develops symptoms while he/she is on strict dietary control, other differential diagnosis like irritable bowel syndrome should be considered.

II. Pernicious anemia

Pernicious anemia is an autoimmune condition in which auto antibodies are present against intrinsic factor. Intrinsic factor is essential for the vitamin B12 absorption. Therefore absence of intrinsic factor leads to reduced absorption of vitamin B12.pernicious anemia is considered as the commonest cause of the cobalamin deficiency.

It is most frequently seen in individuals of northern European descent and African Americans and is much less common in southern Europeans and Asians. Men and women are equally affected. It is a disease of the elderly, the average patient presenting near age 60; it is rare under age 30, although typical pernicious anemia can be seen in children under age 10 (juvenile pernicious anemia).

Through appropriate replacement therapy, patients with pernicious anemia should experience complete and lifelong correction of all abnormalities that are due to cobalamin deficiency, except to the extent that irreversible change in the nervous system may have occurred before treatment.

III. Celiac sprue

Celiac sprue is a common cause of malabsorption of one or more nutrients in Caucasians, especially those of European descent. The etiology of celiac sprue is not known, but environmental, immunologic, and genetic factors are important. Celiac sprue has protean manifestations, almost all of which are secondary to nutrient malabsorption, and a varied natural history, with the onset of symptoms occurring at ages ranging from the first year of life through the eighth decade.

The hallmark of celiac sprue is the presence of an abnormal small intestinal Biopsy therefore a small-intestinal biopsy is required to establish a diagnosis of celiac sprue.

A patient with celiac sprue should be given gluten free diet. In addition to this these patients should be provided with vitamin supplements such as folic acid.

Celiac sprue is associated with dermatitis herpetiformis (DH), though the association has not been explained. Patients with DH have characteristic papulovesicular lesions that respond to dapsone. Almost all patients with DH have histopathologic changes in the small intestine consistent with celiac sprue.

The most important complication of celiac sprue is the development of cancer. An increased incidence of both gastrointestinal and nongastrointestinal neoplasms as well as intestinal lymphoma exists in patients with celiac sprue. For unexplained reasons the occurrence of lymphoma in patients with celiac sprue is higher.

IV.Tropical sprue

Tropical sprue is a poorly understood syndrome that affects both expatriates and natives in certain but not all tropical areas and is manifested by chronic diarrhea, steatorrhoea, weight loss, and nutritional deficiencies, including those of both folate and cobalamin.

The etiology of tropical sprue is not known, though because tropical sprue responds to antibiotics, the consensus is that tropical sprue may be caused by one or more infectious agents. Nonetheless, there are multiple uncertainties regarding the etiology and pathogenesis of tropical sprue. First, its occurrence is not evenly distributed in all tropical areas; rather, it is found in specific locations including South India, the Philippines, and several Caribbean islands.

Broad-spectrum antibiotics and folic acid are most often curative, especially if the patient leaves the tropical area and does not return. Tetracycline should be used for up to 6 months and may be associated with improvement within 1 to 2 weeks. Folic acid alone will induce a hematological remission as well as improvement in appetite, weight gain, and some morphologic changes in small intestinal biopsy.

V. Short bowel syndrome

This is a descriptive term for the myriad clinical problems that often occur following resection of varying lengths of small intestine. The factors that determine both the type and degree of symptoms include the specific segment (jejunum vs. ileum) resected, the length of the resected segment, the integrity of the ileocecal valve, whether any large intestine has also been removed, residual disease in the remaining small and/or large intestine, etc.

The symptoms and signs depend on the above factors .But invariably these patients develop diarrhea and steatorrhoea.

Treatment of short bowel syndrome depends on the severity of symptoms and whether the individual is able to maintain caloric and electrolyte balance with oral intake alone. Initial treatment includes judicious use of opiates (including codeine) to reduce stool output and to establish an effective diet. An initial diet should be low-fat and high carbohydrate to minimize the diarrhea from fatty acid stimulation of colonic fluid secretion.