Malabsorption syndrome is the failure of the gastrointestinal system to intake nutrients properly. The pathophysiology of malabsorption syndromes involves an alteration to the stages of digestion, including the intraluminal stage, absorptive stage, or postabsorptive stage. The causes of malabsorption syndromes distort one or more of the aforementioned stages.
Patients with malabsorption syndrome present with gastrointestinal symptomatology, as well as systemic symptoms of nutrient deficiencies.
Diagnostic measurements include laboratory studies assessing the nutritional status, immune markers, and overall organ function; imaging and endoscopic approaches; microbiological studies; and histopathology in some cases.
Treatment strategies might include dietary modification, nutritional replenishment, antimicrobial or antiparasitic therapy, and surgical management.
Malabsorption Syndromes – Introduction
Malabsorption syndrome is a wide term used to refer to the impaired intake of nutrients in the gastrointestinal tract caused by defects in either digestion (maldigestion), absorption, or transport (true malabsorption). (1, 2)
Malabsorption may be isolated, affecting micronutrients such as vitamins or minerals, or macronutrients like fats or proteins (specific malabsorption), or global, affecting almost all nutrients (global malabsorption). (2, 3)
Pathophysiology of Malabsorption Syndromes
The small intestine is covered in folds called plicae circulares that project finger-like protuberances known as villi and microvilli, which increase the surface area available for nutrient absorption within the lumen. Therefore, the intake of most nutrients happens in this area, specifically the jejunum. (4, 5)
However, additional factors that also play an important role in nutrient digestion and absorption include the gallbladder, pancreas, lymphatic vessels, and blood vessels.
Absorption of nutrients happens in three well-described stages: (3, 5, 6)
|Intraluminal Stage||Mechanical mixing and the hydrolysis of macronutrients by digestive enzymes take place. Bile salts are also involved in the solubilization of fat.|
|Absorptive (Mucosal) Stage||In this stage, mucosal integrity, and brush border enzymes are necessary to absorb the nutrients.|
|Postabsorptive Stage||The transport of nutrients through capillaries and fine lymphatic vessels happens during this stage.|
Malabsorption can happen when the digestion/absorption process gets disrupted in any of the aforementioned stages due to: (1, 5-7)
- Mucosal disease;
- Mucosa damage, either acquired or congenital;
- Impaired intestinal membrane transport systems;
- Impaired intestinal motility;
- Unbalanced microbial flora;
- Defects in the blood flow or lymphatic system.
Digestion and Absorption of Proteins
Digestion of proteins begins in the stomach in the presence of several gastric pepsins and is continued in the duodenum by several proteases, which in their active form, hydrolyze proteins into dipeptides, tripeptides, or amino acids that are readily absorbed. Enterokinase, a brush border enzyme, is released by the action of bile salts and converts trypsinogen to trypsin, which then converts all other pancreatic proteases into their active forms. (3, 5, 8)
Digestion and Absorption of Fats
Fat digestion and absorption is a complex process that involves numerous steps that occur throughout the digestive system. The initial step is lipid emulsification, which takes place in the mouth during the process of mastication aided by lingual lipase and is then continued by the action of gastric lipase in the stomach. However, most lipid absorption occurs in the proximal two-thirds of the jejunum after the pancreas has released lipolytic enzymes (lipase and colipase) that break down long-chain triglycerides into monoglycerides and free fatty acids. These compounds combine with bile salts and phospholipids to form micelles or liposomes, which are readily absorbed by the intestinal mucosa. The absorption of medium-chain triglycerides occurs directly, whereas the monoglycerides and absorbed fatty acids undergo re-esterification into triglycerides. These are then combined with protein, cholesterol, and phospholipid to create chylomicrons, which are transported to the liver via the lymphatic system for their metabolism. (3, 5, 8)
Digestion and Absorption of Carbohydrates
Carbohydrate digestion starts in the mouth with salivary amylase and continues in the duodenum with the release of pancreatic amylase to break down the ingested starch, lactose, and sucrose from the diet. The resulting carbohydrates and disaccharides get further processed at the microvillus membrane by brush border enzymes and hydrolyzed into constituent monosaccharides. (3, 8-10)
Digestion and Absorption of Vitamins and Minerals
Vitamins and minerals are absorbed throughout the small intestine through different mechanisms and in the presence of several enzymes and other contributing factors, as is the case with fat-soluble vitamins (A, D, E, and K), which are dependent on the adequate absorption of lipids, and vitamin B12 which depends on the appropriate secretion of intrinsic factor by parietal cells. Therefore, dysfunction at any point in digestion or absorption can result in the malabsorption of one or more vitamins and/or minerals. (5, 8)
Due to the wide arrange of specific physiologic processes involved in vitamin and mineral digestion and absorption, the description of each one of them is beyond the scope of this overview.
Etiology of Malabsorption Syndromes
Malabsorption syndromes can be transient or chronic and have a variety of causes, including genetic factors, infections, autoimmune disorders, and other conditions.
Here is a table that summarizes some of the most frequent malabsorption causes per nutrient: (1, 3, 8, 10, 11-19)
|Type of Malabsorption||Most Frequent Causes||Additional Information|
|Protein Malabsorption||Inflammatory bowel disease.|
|It has been suggested that proteolysis in the stomach is not an essential step for the digestion of proteins since achlorhydric patients or those who have rapid gastric emptying are still able to digest proteins.|
|Fat Malabsorption||Crohn’s disease.|
Small intestinal bacterial overgrowth (SIBO).
Increased luminal acidity, including Zollinger-Ellison syndrome.
Impaired synthesis of bile acids due to liver disease or cholestasis.
Pancreatic insufficiency, including chronic pancreatitis.
Shwachman-Diamond syndrome (SDS).
|Remaining unabsorbed fats can trap fat-soluble vitamins (A, D, E, K) and minerals, leading to deficiencies.
Bacterial overgrowth can also limit fat absorption.
|Carbohydrate Malabsorption||Disaccharidase deficiency, usually lactase.|
Pancreatic amylase deficiency.
Inflammatory bowel disease.
|Any remaining unabsorbed carbohydrates get fermented by colonic bacteria, resulting in abdominal distention, bloating, flatulence, and acidic stool. These fatty acids cause diarrhea. The gases cause abdominal distention and bloating.|
|Micronutrient Malabsorption||Fat malabsorption.|
Pathology of the stomach or intestine.
Blind loop syndrome.
|Common deficiencies include but are not limited to, vitamin B12, iron, calcium, folate, vitamin D, zinc, magnesium, selenium, copper, carotenoids, thiamine, and zinc, among others.|
Secondary to opportunistic infections (giardiasis, cryptosporidiosis, and microsporidiosis, among others).
|Panmalabsorption often occurs as a result of several overlapping factors.
Diarrhea, weight loss, and generalized malnutrition are commonly found.
Clinical Findings in Patients with Suspicion of Malabsorption Syndromes
The consequences of malabsorption can range from mild discomfort to severe malnutrition, depending on the severity, duration, and type of nutrient deficiency. Signs and symptoms may include:
- Chronic diarrhea;
- Abdominal bloating;
- Steatorrhea, often referred to as foul-smelling, bulky, greasy, and floating feces;
- Weight loss or poor weight gain;
- Failure to thrive;
- Abdominal pain;
- Peripheral neuropathy;
- Poor wound healing;
- Pathologic fractures;
- Night blindness (20).
A thorough medical history should include a review of systems, paying special attention to the onset of symptoms, frequency, duration, intensity, location, timing, stool appearance and odor, and the presence of associated symptoms. The patient’s past medical history (including previous surgeries, radiation exposure, allergies, medication use, etcetera), social history, and family history are also important to consider differential diagnoses. (18, 21)
A complete physical exam should be performed. Common findings may include abdominal distension, hyperactive or hypoactive bowel sounds, ecchymosis, petechiae, pallor, rashes, glossitis, edema, cardiac arrhythmia, carpopedal spasm, decreased visual acuity, muscle wasting, and auditory disturbances, among others.
Diagnosis of Malabsorption Syndromes
Diagnosis of malabsorption syndromes involves a thorough medical history and physical examination that will support the indication of appropriate tests to assess nutritional deficiencies. Furthermore, in some cases, the diagnosis and cause of malabsorption will be clear from the beginning; for instance, in patients who have undergone bowel resection or bariatric surgery; therefore, additional testing may be unnecessary or may be directed to the specific case of the patient.
If malabsorption is suspected, but no cause is apparent in a patient with unspecific signs such as weight loss and diarrhea and no relevant past medical history or family history, the initial workup should include the following tests: (3, 16)
- Blood tests:
Complete blood count (CBC) with red blood cell (RBC) indices;
Iron panel, including ferritin;
Comprehensive metabolic panel;
- Fecal tests:
72-hour fecal fat excretion (gold standard test to diagnose steatorrhea, which is defined as fecal fat > 7 g/day);
Sudan III staining;
Near-infrared reflectance analysis (NIRA), which tests stool for fat, nitrogen, and carbohydrates at the same time;
Elastase and chymotrypsin.
After the initial workup, further testing may be necessary to diagnose the cause of malabsorption. These tests may include: (10, 15, 17, 19, 22, 23)
- Upper endoscopy with biopsy:
Upper endoscopy allows visualization and helps direct biopsies to suspicious areas of the small bowel mucosa. Furthermore, an aspirate sample can be taken for bacterial culture and colony count evaluation.
- Jejunal aspirate culture:
SIBO (gold-standard test for diagnosis).
- Colonoscopy with biopsy:
- Hydrogen breath tests:
Carbohydrate malabsorption syndromes;
The glucose-hydrogen and lactulose-hydrogen breath tests aid in the diagnosis of bacterial overgrowth, and the latter is useful only to confirm lactase deficiency.
- Schilling test:
This test can be performed to assess malabsorption of vitamin B12 and identify its cause.
- Imaging studies:
Computed tomography enterography and magnetic resonance enterography can detect anatomic and/or mucosal abnormalities that can increase the risk of bacterial overgrowth, such as fistulas, strictures, jejunal diverticula, ulcerations, blind loops, and anastomoses.
While other tests like abdominal flat plate x-rays, computed tomography, magnetic resonance cholangiopancreatography (MRCP), and endoscopic retrograde cholangiopancreatography (ERCP) can establish the diagnosis of chronic pancreatitis.
- Other tests:
Sweat chloride (cystic fibrosis);
Cortisol (Addison’s disease);
Gastrin (Zollinger-Ellison syndrome);
Intrinsic factor and parietal cell antibodies (pernicious anemia);
Lipoprotein electrophoresis (abetalipoproteinemia).
Treatment of Malabsorption Syndromes
It is imperative to diagnose the specific cause of malabsorption syndromes because the success of the treatment will depend on it, and the main goal is to prevent complications and improve the quality of life in affected patients.
The treatment of malabsorption syndrome involves a multidisciplinary approach. Depending on the underlying cause and severity of the condition, dietary modifications, nutrient supplementation, medications, and/or surgery may be necessary to manage the patient’s symptoms. (9, 10, 14, 16, 18, 20, 23)
Eliminating certain foods can prove to be both a diagnostic and therapeutic method, especially in cases of carbohydrate malabsorption syndromes. For instance, patients with lactose intolerance must be instructed to avoid the ingestion of dairy products and their derivates.
In any case, to manage malabsorption syndromes, dietary changes must always be implemented to avoid the ingestion of foods that triggers the symptoms. An interdisciplinary approach with a registered dietitian is also warranted.
Vitamin and Mineral Supplementation
Depending on the malabsorption syndrome, supplementation with vitamins and/or minerals may be necessary. Such is the case in patients with vitamin B12 deficiency, who will need to get vitamin B12 injections periodically to prevent neurological signs and symptoms.
Certain drugs can help alleviate the signs and symptoms of malabsorption; for instance, antidiarrheal medications can be considered in cases of acute or chronic diarrhea, while antibiotics are indicated in cases of small intestinal bacterial overgrowth. Pancreatic enzyme replacement is indicated in cases of exocrine pancreatic insufficiency.
In some cases of extensive damage to the mucosa, surgery (resection or transplant) may be the only option to treat malabsorption syndromes and improve symptoms. This happens more frequently in patients with severe malabsorption syndrome that went undiagnosed or untreated for a prolonged period of time.
Besides being a diagnostic tool, ERCP can also be curative when an obstruction (like a stone) is removed from the biliary tree.
The author does not report any conflict of interest
This information is for educational purposes, not to treat disease or supplant professional medical judgment. Physicians should follow local policy regarding the diagnosis and management of medical conditions.
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Krystie Linares is a physician with 10 years of experience as a family practitioner and occupational health specialist. She has collaborated with several companies, startups, and individuals, by doing research, developing educational content, managing medical libraries, and working as a database curator.