The main effects of the presence of unabsorbed substances in the gastrointestinal tract are indicated as follows:

• Diarrhea. Diarrhea appears as the most common malabsorption symptom [4][5][6][7][8]. It is the result of the presence of unabsorbed fluids in the gastrointestinal tract, that gives the stools a watery appearance. Diarrhea is worsened by the bacterial action, which produces hydroxyl fatty acids and increases the net fluid secretion. 
• Steatorrhea. The unabsorbed fats are then secreted giving the stools a classical fatty appearance, in a condition known as steatorrhea. Usually, the stools are pale, bulky, greasy, and foul-smelling. 
• Abdominal bloating and flatulence. The unabsorbed foods is digested through fermentation by the bacterial flora in the gastrointestinal tract, producing gaseous products such as hydrogen and methane which cause flatulence. This might also result in abdominal distention and cramps. 
• Weight loss. Weight loss is very common, although it can frequently be concealed by food consumption increase. 
• Nutritional deficiencies. Most common are the severe vitamin and mineral deficiencies, which appear especially in advanced cases of malabsorption. The related symptoms depend on the specific nutrient concerned. For example, iron deficiency might cause anemia, vitamin D deficiency might cause bone disorders, while calcium deficiency might cause hyperparathyroidism. In any case, the patient finds him/herself in a general status of weakness, where bone pain and fractures can also be observed. Other possible symptoms due to nutrient deficiencies include motor weakness (pantothenic acid), peripheral neuropathy (thiamine), a sense of loss (cobalamin), night blindness (vitamin A), seizure (biotin), and bleeding (vitamin K). Very severe might also be electrolyte deficiencies, like hypocalcemia and hypomagnesaemia, which frequently lead to tetany. Anemia also results from vitamin B-12 deficiency, and for this reason, it can be either microcytic (due to iron deficiency) and macrocytic (due to vitamin B-12 deficiency) [9].

The diagnostic tests used to identify malabsorption include the following:

• CBC count: used to detect microcytic and macrocytic anemia due to iron deficiency and vitamin B-12 respectively.
• Serum levels: the levels of electrolytes, minerals and vitamins are greatly affected during malabsorption, and can be used as useful diagnostic markers to detect impaired digestion and premucosal malabsorption. 
• Fecal fat excretion test: in addition to measuring the amount of fecal fats, this test can also be used to detect the presence of the pancreatic proteases, to distinguish between malabsorption with pancreatic origin from malabsorption with intestinal origin. A finding of more than 7 gram of fats per day is the hallmark of malabsorption. 
• Hydrogen breath test: The undigested carbohydrates are fermented by the bacterial flora resulting in a marked production and accumulation of hydrogen [10][11]. Carbohydrate absorption can also be measured by measuring the level of xylose excreted from the urine over a period of 5 hours, since this compound represents a not-metabolized carbohydrate form. 
• Endoscopy and histological examination: very useful to detect reduced absorptive areas due to surgical bowel resection or disease-induced absorptive capacity reduction. 
• Schilling test: employed with or without intrinsic factor, it is very useful to detect vitamin B12 deficiency, which later might lead to other gastric diseases such as gastritis and other inflammatory conditions. It is also very useful to determine if a deficiency is the result of other related conditions, such as pernicious anemia, pancreatic exocrine insufficiency, ileal disease, or bacterial overgrowth. 
• Barium studies: when applied to study the upper gastrointestinal tract, these tests might underline abnormal small bowel patterns revealing the etiological factors of a malabsorption episode.
• Ultrasound test: together with contrast radiography for fistulae, this test is used to detect postmucosal malabsorption resulting from impaired nutrient transport. 
• CT scan: CT scan can be employed to detect other related conditions, such as episodes of chronic pancreatitis and enlarged lymph nodes.
• Endoscopic retrograde cholangiopancreatogram (ERCP): this technique helps study malabsorption when this results from episodes of pancreatitis or biliary-related disorders. 
• Upper endoscopy: when combined with small-bowel biopsy, it is very useful to detect episodes of other mucosal diseases, usually due to bacterial overgrowth. The bacterial overgrowth can easily be revealed with 14C-xylose breath test, using the high level of CO2 produced by the marked catabolism of ingested xylose of the overgrown bacterial flora. Very useful is also the H2 breath test for the high H2 levels produced during bacterial carbohydrate degradation. The use of 14C-xylose breath test and H2 breath test is now become very common and has replaced the use of bacterial cultures to diagnose bacterial overgrowth-related syndromes. 
• X-ray: this test can reveal the presence of other anatomic conditions that might favor bacterial overgrowth, such as jejunal diverticula, fistulas, surgically created blind loops, or ulcerations. These pathological conditions can also include chronic pancreatitis which lead to pancreatic calcifications. The diagnosis of chronic pancreatitis can be confirmed by CT scan, magnetic resonance cholangiopancreatography (MRCP), and the already mentioned ERCP. Tests of pancreatic insufficiency might also be used to reveal the presence of other mild pancreatic diseases. 

The treatment of malabsorption depends on the etiological factors [10], and it is usually combined with an appropriate diet to enhance clinical outcome. There are two basic principles underlying the malabsorption management: (1) nutritional deficiency correction and (2) causative disease treatment.

Nutritional Support

• the nutrients in deficit, such as calcium, magnesium, iron and vitamins, must be supplemented through an appropriate diet;
• the supplementation of the proteins in deficit is also important;
• fats can be substituted by medium-chain triglycerides, since their transport route is portal rather than lymphatic and they do not required the formation of micelles to be absorbed;
• in certain clinical conditions, parental nutrition might become important, if not necessary. These conditions include massive resection or extensive local enteritis. 

Treatment of causative diseases

• celiac disease might be a causative factor for malabsorption, and can be easily treated with a gluten-free diet;
• in a similar way, lactose intolerance might also be treated, by following a lactose-free diet;
• the supplementation of proteases and lipases is one of the mainstays in the treatment of pancreatic insufficiency;
• in the case of pronounced bacterial overgrowth, an antibiotic therapy is also suggested;
• regional enteritis can be managed by following anti-inflammatory treatments, such as the use of corticosteroids and anti-inflammatory agents.

Malnutrition is the main consequence of malabsorption. For this reason, it should be identified as soon as possible and treated accordingly.

As previously mentioned, malabsorption is the consequence of several ethological factors which can be divided into three major groups, according to the three major phases of natural nutrient absorption [3].

Problems in the luminal phase: In this case maldigestion derives from problems involving the digestive mediators and interests patients who have undergone gastrectomy or those who have experienced deficiencies of pancreatic and intestinal enzymes and bile salts. Pancreatic insufficiency resulting from chronic pancreatitis, pancreatic resection, pancreatic cancer, or cystic fibrosis is the most common cause of impaired nutrient hydrolysis. The resulting lipase and proteases deficiency is then responsible for the subsequent malabsorption.

Problems in the mucosal phase: Mucosal and mural causes are very frequent ethological factors, and include conditions such as gluten-sensitive enteropathy, tropical sprue, autoimmune enteropathy, HIV/ AIDS-related enteropathy, and systemic sclerosis. Frequent are also the acquired disorders, as indicated below:

1. Decreased absorptive surface area (usually observed in intestinal resection)
2. Damaged absorbing surface (as observed in celiac sprue, AIDS enteropathy, or chemotherapy)
3. Intestinal wall infiltrating disease (such as lymphoma and amyloidosis)
4. Infections (such as bacterial overgrowth, giardiasis, and Whipple disease)

Problems in the postabsorptive phase: This includes the lymphatic system obstruction, both of congenital origin (like intestinal lymphangiectasia) and acquired origin (like tuberculosis), which then causes the impairment of chylomicron and lipoprotein absorption resulting in fat malabsorption or protein-losing enteropathy.

In Europe and the United States the prevalence of malabsorption ranges from 1 in 250 to 1 in 133 people, and appears to be higher in those with relatives affected by multiple sclerosis, with 1 in 22 people in the case of first-degree relatives and 1 in 39 people in the case of second-degree relatives. The disorder is very rarely reported in people with African, Caribbean, Chinese or Japanese origin. Malabsorption is far more frequent in women than men, while no age predilection has been reported.

It is paramount to understand the normal processes of digestion and absorption to comprehend the pathophysiology of malabsorption.

Digestion and absorption are generally divided in three major phases:

1. Luminal phase: the digestive enzymes and bile hydrolyze fats, proteins, and carbohydrates;
2. Mucosal phase: the digested products are carried inside the intestinal epithelial cells from the gastrointestinal lumen, by means of the special brush-border membrane of the epithelial cells themselves;
3. Postabsorptive phase: the nutrients are transported from the epithelial cell to the rest of the body through the lymphatic and portal circulation. 

Malabsoprtion occurs when any of these three phases is impaired. Instead, the term maldigestion is specifically used to refer to the impaired luminal phase.

Fats

While medium-chain triglycerides are directly absorbed by the gastrointestinal mucosa, long-chain triglycerides are split into fatty acids and monoglycerides by the pancreatic enzymes (lipase and colipase). These are then combined with bile acids and phospholipids to form micelles, which then pass through jejunal enterocytes and enter the body. The absorbed fatty acids are re-synthesized and turned into chylomicrons after being combined with proteins, cholesterol, and phospholipids. Chylomicrons are subsequently transported around the body through the lymphatic system. Fat deficiency occurs in three different occasions, when unabsorbed fats capture fat-soluble vitamins, when bacterial overgrowth causes bile salts deconjugation and dehydroxylation limiting the fat absorption itself, or when water secretion is stimulated by unabsorbed bile salts resulting in diarrhea.

Carbohydrates

Carbohydrates are split into monosaccharides by the amylase and the brush border enzymes present throughout the microvilli surface. Unabsorbed carbohydrates are fermented by gastrointestinal bacteria into CO2, methane, H2, and short fatty acids which in turn cause diarrhea. The remaining gases produced in the process cause the subsequent bloating and abdominal distension.

Proteins

Protein digestion is started in the stomach by gastrin pepsin, which also stimulates cholecystokinin release. Trypsinogen is then converted into trypsin by enterokinases, for the activation of pancreatic proteases and the subsequent hydrolysis of proteins into oligopeptides. These are finally absorbed directly or hydrolyzed as amino acids.

As for treatment, prevention too depends on the etiological factors concerned. Preventive malabsorption measures include lifestyle change, appropriate healthy diet, body cleansing, and daily physical exercise. Some traditional and natural therapies can also be useful.

The gastrointestinal tract (GI) is the site where ingested nutrients, such as vitamins, proteins, carbohydrates, and fats, can be absorbed and transported into the blood stream. Most of the absorption takes place in the small intestine (SI), thanks to the wide absorbing surface due to the great number of villi, numerous digestive enzymes, and the complex network of lymphatic and blood vessel which make sure the nutrients are properly carried into the blood. The digestive process is guaranteed by many factors working together, such as the activity and production of the enzymes involved the correct function of the digestive mucosa, the adequate and appropriate blood supply, the mobility of the intestine, as well as the presence of a proper bacterial flora. Therefore, any malfunction related to each of these aspects might potentially lead to a serious failure to absorb nutrients and cause malabsorption. The classical symptoms of this condition include diarrhea, steatorrhea, weight loss, and anemia.

Malabsorption occurs when the intestinal absorption capability falls under 85% of its full capability [1], is a situation in which the gastrointestinal tract is no longer capable to properly digest and absorb nutrients and maintain the mucosa integrity and fluid balance, a condition which results in an seriously impaired nutritional status and severely weakened physical conditions [2]. The intestinal malfunction can result from congenital defects which cause functional problems in the membrane transport system of the small intestine epithelium (primary malabsorption), or from acquired defects which might appear on the gastrointestinal surface when certain conditions occur (secondary malabsorption). Malabsorption should not be confused with maldigestion, which is due to an impaired nutrient digestion at the terminal digestive site of mucosal epithelial cells. Although their pathophysiology is different, digestion and absorption are strictly interdependent and their clinical presentations are very similar. For this reason, malabsorption usually indicates problems in both processes. In clinical practice, it is very important to find out the etiological factors underlying an episode of malabsorption, as the treatment depends on this evaluation.

The term “malabsorption” refers to a series of pathological conditions that originate from the impaired ability of the gastrointestinal tract to properly absorb nutrients. Conditions causing malabsorption include gastrointestinal infections and surgical procedures such as bowel resection.

The most common signs of malabsorption include diarrhea, steatorrhea, abdominal bloating, and nutritional deficiencies. Diarrhea is the consequence of the presence of unabsorbed water in the gastrointestinal tract, while steatorrhea, the production of light-colored, soft, bulky, greasy, and foul-smelling stools, is the consequence of the presence of large amounts of unabsorbed fats. In addition to diarrhea, the presence of unabsorbed carbohydrates leads to abdominal bloating and flatulence.

Nutritional deficiencies are responsible of a series of other malabsorption-related pathological conditions. For example, edema is the result of impaired protein absorption which in turn causes water accumulation in interstitial spaces throughout the body, while anemia is triggered by iron or vitamin deficiency.

Stool test is the most reliable tool to diagnose malabsorption, especially for detecting and measuring the quantity of stool fats. An amount of stool fats higher than 7 grams per day is usually the diagnostic hallmark which underlines the presence of malasborption. Very useful are also histological tests to detect the presence of parasitic infections, together with bowel biopsy to find possible abnormalities in the small intestine walls and pancreatic function tests to detect impaired pancreas functionality.

Frequently used as diagnostic tools are also blood and other laboratory tests, which reveal possible deficiencies in the levels of lactose and vitamin B12. Instead, imaging tests allow to reveal structural anomalies or episodes of bacterial overgrowth which might underline an episode of malabsorption. These include common techniques such as endoscopy, CT scan, and x-ray.

The prognosis of malabsorption depends on the etiological factors concerned.

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