Malabsorption (malabsorption syndrome)

Malabsorption (malabsorption syndrome, syndrome of impaired intestinal absorption, chronic diarrhea syndrome, sprue) - inadequate absorption of nutrients due to disruption of digestion, absorption or transport processes.

Malabsorption affects macronutrients (eg, proteins, carbohydrates, fats) or micronutrients (eg vitamins, minerals), causing abundant fecal secretion, nutritional deficiencies and the appearance of gastrointestinal symptoms.

[1], [2], [3], [4], [5], [6]

What causes malabsorption?

Malabsorption is caused by many causes. Some changes in malabsorption (eg, celiac disease) impair the absorption of most nutrients, vitamins and trace elements (total malabsorption); others (eg, pernicious anemia) are more selective.

Insufficiency of the pancreas causes malabsorption if more than 90% of the gland function is disrupted. Increased acidity (eg, Zollinger-Ellison syndrome) inhibits lipase and fat digestion. With liver cirrhosis and cholestasis, the synthesis of bile by the liver and the flow of bile salts into the duodenum decrease, causing malabsorption.

Causes of malabsorption

Mechanism	Cause
Inadequate mixing in the stomach and / or rapid passage from the stomach	Resection of the stomach according to Billroth II Gastrointestinal fistula Gastroenterostomy
Lack of digestive factors	Biliary obstruction Chronic liver failure Chronic pancreatitis Cholestyramine- induced bile salt deficiency Cystic fibrosis of pancreas Lactase deficiency in small intestine Pancreatic cancer Pancreas resection Deficiency of sucrose isomaltase in the small intestine
Changing the environment	Secondary motor disorders in diabetes, scleroderma, hyperthyroidism Excessive growth of microflora - blind intestinal loop (deconjugation of bile salts) Diverticulum Zollinger-Ellison syndrome (low pH in the duodenum)
Acute damage to the intestinal epithelium	Acute intestinal infections Alcohol Neomycin
Chronic damage to the intestinal epithelium	Amyloidosis Diseases of the abdominal cavity Crohn's disease Ischemia Radiation enteritis Tropical malabsorption Whipple's disease
Short bowel	Ileoejunal anastomosis with obesity Resection of the intestine (eg, with Crohn's disease, curvature, invagination or gangrene)
Disruption of transport	Acanthocytosis Addison's disease Disturbance of lymphatic drainage - lymphoma, tuberculosis, lymphangiectasia

Pathophysiology of malabsorption

Digestion and absorption occur in three phases:

1. Within the lumen of the intestine hydrolysis of fats, proteins and carbohydrates under the action of enzymes occurs; bile salts increase solubilization of fat in this phase;
2. digestion by enzymes of cellular microvilli and absorption of final products;
3. lymphatic transport of nutrients.

Malabsorption develops in case of violation of any of these phases.

Fats

Pancreatic enzymes break down long chain triglycerides into fatty acids and monoglycerides that bind to bile acids and phospholipids, forming micelles that pass through the enterocytes of the jejunum. Absorbed fatty acids are resynthesized and combined with protein, cholesterol and phospholipid, forming chylomicrons, which are transported by the lymphatic system. Medium chain triglycerides can be absorbed directly.

Unabsorbed fats capture fat-soluble vitamins (A, D, E, K) and, possibly, some minerals, causing their deficiency. Excessive development of microflora leads to deconjugation and dehydroxylation of bile salts, limiting their absorption. Unabsorbed bile salts irritate the colon, causing diarrhea.

[7], [8], [9], [10], [11], [12], [13]

Carbohydrates

Enzymes on microvilli cleave carbohydrates and disaccharides into constituent monosaccharides. The microflora of the large intestine ferments unabsorbed carbohydrates in CO ₂, methane, H and short chain fatty acids (butyrate, propionate, acetate and lactate). These fatty acids cause diarrhea. Gases cause bloating and flatulence.

[14], [15], [16], [17], [18], [19], [20], [21], [22]

Proteins

Enterokinase, an enzyme of enterocyte microvilli, activates trypsinogen in trypsin, which converts many pancreatic proteases into their active forms. Active pancreatic enzymes hydrolyse proteins into oligopeptides that are directly absorbed or hydrolyzed into amino acids.

Diseases that occur with malabsorption syndrome

• Insufficiency of the exocrine function of the pancreas.
• Malformations of the pancreas (ectopia, anular and bifurcated gland, hypoplasia).
• Syndrome Shvakhmana-Diamond.
• Cystic fibrosis.
• Deficiency of trypsinogen.
• Lipase deficiency.
• Pancreatitis.
• Cholestasis syndrome of any etiology.
• Primary bowel disease.
• Primary disorders of digestion and absorption of protein and carbohydrates:
  • deficiency of enterokinase, duodenase, trypsinogen;
  • Lactase insufficiency (transient, primary adult, secondary);
  • deficiency of sucrose-isomaltase;
  • Congenital malabsorption of monosaccharides (glucose-galactose, fructose).
• Primary disorders of absorption of fat-soluble substances:
  • abetalipoproteinemia;
  • violation of absorption of bile salts.
• Violation of electrolyte absorption:
  • chloride diarrhea,
  • sodium diarrhea.
• Infringement of absorption of micronutrients:
  • vitamins: folate, vitamin B ₁₂;
  • amino acids: cystine, lysine, methionine; Hartnup disease, isolated violation of tryptophan absorption, Low syndrome;
  • mineral substances: enteropathic acrodermatitis, primary hypomagnesemia, familial hypophosphatemia; idiopathic primary hemochromatosis, Menkes disease (malabsorption of copper).
• Congenital malformations of the enterocyte structure:
  • congenital atrophy of microvilli (syndrome of microvillin inclusion);
  • intestinal epithelial dysplasia (tuffing enteropathy);
  • syndromic diarrhea.
• Inflammatory bowel disease.
• Intestinal infections.
• Crohn's disease.
• Allergic diseases of the intestine.
• Infectious and inflammatory bowel disease in congenital immunodeficiencies:
  • Bruton's disease;
  • IgA deficiency;
  • combined immunodeficiency;
  • neutropenia;
  • acquired immunodeficiency.
• Autoimmune enteropathy.
• Celiac disease.
• Reduction of the absorption surface.
• Syndrome of the small intestine.
• Syndrome of the blind loop.
• Protein-energy insufficiency.
• Pathology of the blood and lymph vessels (intestinal lymphangiectasia).
• Endocrinopathies and hormone-producing tumors (vipoma, gastrinoma, somatostatinoma, carcinoid, etc.).
• Parasitic lesions of the digestive tract.

[23], [24], [25], [26]

Symptoms of malabsorption

The violation of absorption of substances causes diarrhea, steatori, bloating and gas formation. Other symptoms of malabsorption are the result of nutritional deficiencies. Patients often lose weight despite adequate diet.

Chronic diarrhea is the main symptom. Steatorrhea - fatty stool, a sign of malabsorption, develops if it is excreted with feces more than 6 g / day of fat. Steatorea is characterized by a fetid, light color, abundant and fatty stool.

The pronounced deficiency of vitamins and minerals develops with the progression of malabsorption; symptoms of malabsorption are associated with a certain nutritional deficiency. Deficiency of vitamin B ₁₂ can be caused by the syndrome of the blind bag or after extensive resection of the distal segment of the ileum or stomach.

Symptoms of malabsorption

Symptoms	Malabsorption substance
Anemia (hypochromic, microcytic)	Iron
Anemia (macrocytic)	Vitamin B12, folate
Bleeding, hemorrhage, petechiae	Vitamins K and C
Cramps and muscle pains	Ca, Mg
Edema	Protein
Glossitis	Vitamins B2 and B12, folate, nicotinic acid, iron
Chicken blindness	Vitamin A
Pain in the extremities, bones, pathological fractures	K, Mg, Ca, vitamin D
Peripheral Neuropathy	Vitamins B1, B6

Amenorrhea can be the result of malnutrition and is an important symptom of celiac disease in young women.

Diagnosis of malabsorption

Malabsorption is suspected in patients with chronic diarrhea, weight loss and anemia. Etiology is sometimes obvious. Chronic pancreatitis may be preceded by episodes of acute pancreatitis. Patients with celiac disease usually experience prolonged diarrhea, which is worse with foods rich in gluten, and there may be signs of herpetiform dermatitis. Cirrhosis of the liver and pancreatic cancer usually cause jaundice. Bloating, excessive secretion of gases and watery diarrhea 30 to 90 minutes after taking carbohydrate food suggest a deficiency of the enzyme disaccharidase, usually lactase. Previous operations on the abdominal cavity suggest a syndrome of the small intestine.

If the history of the disease involves a specific cause, the research should be directed to its diagnosis. If there is no obvious cause, laboratory blood tests (eg, a general blood test, erythrocyte indices, ferritin, Ca, Md, albumin, cholesterol, PV) help in the diagnosis.
In detecting macrocytic anemia, it is necessary to determine the levels of folate and B12 in serum. Folate deficiency is characteristic of changes in the mucosa of the proximal small intestine (eg, celiac disease, tropical sprue, Whipple's disease). Low levels of B ₁₂ can be observed with pernicious anemia, chronic pancreatitis, microflora overgrowth syndrome and terminal ileitis. The combination of low B ₁₂ and high levels of folate may suggest a syndrome of excess microflora growth because intestinal bacteria use vitamin B and synthesize folate.

Microcytic anemia involves iron deficiency, which can occur with celiac disease. Albumin is the main indicator of nutritional status. Reduction in albumin content may be a consequence of reduced intake, reduced synthesis or protein loss. Low serum carotene (a precursor of vitamin A) suggests malabsorption if its intake with food is adequate.

[27], [28], [29], [30], [31], [32], [33]

Confirmation of malabsorption

Tests confirming malabsorption are appropriate if the symptoms are uncertain, and the etiology is not established. Most malabsorption tests evaluate fat malabsorption due to the ease of measurement. Confirmation of malabsorption of carbohydrates is not informative, if at first steatorrhea is detected. Tests for protein malabsorption are rarely used, since it is sufficient to determine the nitrogen mass of feces.

Direct determination of fat in the stool for 72 hours is the standard for establishing steatorrhoea, but the study is unnecessary with obvious steatorrhea and the identified cause. The chair is collected over a three-day period during which the patient consumes more than 100 grams of fat per day. The total fat content in the stool is measured. The fat content in the stool is more than 6 g / day is considered a violation. Although severe malabsorption of fat (fat in the stool more than 40 g / day) suggests pancreatic insufficiency or a disease of the small intestine mucosa, this test can not diagnose a certain cause of malabsorption. Because the test is unpleasant and time-consuming, it should not be performed in most patients.

Staining of Sudan III stool smear is a simple and direct method, but not quantitative, showing the fat content in the stool. The definition of steatocrit is a gravimetric study performed as a primary stool study; The sensitivity of the method, according to some reports, is 100% and the specificity is 95% (the use of a chair for 72 hours is the standard). Using infrared reflection coefficient analysis, you can simultaneously check the stool for fat, nitrogen and carbohydrates, and this study can become a leading test.

An absorbtion test for D-xylose should also be performed if no etiology is established. This is the best non-invasive test, allowing to assess the consistency of the intestinal mucosa and differentiate the mucosal lesion from pancreatic disease. This test has a specificity of up to 98% and a sensitivity of 91% for malabsorption of the small intestine.

D-xylose is absorbed by passive diffusion and does not require pancreatic enzymes for digestion. Normal test results for D-xylose in the presence of moderate or severe steatorrhoea indicate exocrine pancreatic insufficiency, and not the pathology of the small intestine mucosa. Syndrome of excessive growth of microflora can cause incorrect test results with D-xylose due to the intestinal bacteria metabolism of pentose, which reduces the conditions for the absorption of D-xylose.

On an empty stomach, the patient drinks 25 g of D-xylose in 200-300 ml of water. Urine is collected more than 5 hours, and a sample of venous blood after 1 hour. The serum D-xylose content of less than 20 mg / dl or less than 4 g in urine indicates an absorption disorder. False levels can be observed with kidney disease, portal hypertension, ascites or delayed evacuation from the stomach.

[34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44]

Diagnosis of the causes of malabsorption

Endoscopy with a biopsy of the small intestine mucosa is performed in case of suspected small bowel disease or if changes in the D-xylose test are detected with massive steatorrhea. The biopsy of the small intestine must be sent to the bacillus and colony count to determine the syndrome of excess microflora growth. Histological features in biopsies of the small intestinal mucosa can establish a certain mucosal disease.

X-ray examination of the small intestine can detect anatomical changes that predispose to excessive bacterial growth. These include diverticulum of the jejunum, fistula, blind intestinal loops and anastomoses after surgical interventions, ulceration and constriction. Radiography of the abdominal cavity can reveal calcification of the pancreas, characteristic of chronic pancreatitis. Contrast studies of the small intestine with barium (passage in the small intestine or enteroclasm) are not informative, but the data obtained can provide some information about the disease of the mucous membrane (eg, enlarged loops of the small intestine, thinned or thickened folds of the mucosa, rough fragmentation of the barium columns) .

Studies of pancreatic insufficiency (eg, stimulated secretin test, bentiromide test, pancreatolauril test, serum trypsinogen, elastase in the stool, chymotrypsin in the stool) are performed in case the anamnesis assumes the disease, but the tests are insensitive with moderate severity of the pancreatic disease.

The respiratory test with Xylose helps to diagnose excessive growth of microflora. The xylose is taken orally and the concentration in the exhaled air is measured. Catabolism of xylose with excessive growth of microflora causes it to appear in the exhaled air. The hydrogen breathing test allows one to determine hydrogen in the exhaled air, formed by the degradation of carbohydrates by microflora. In patients with a deficiency of disaccharidase, intestinal bacteria destroy unabsorbed carbohydrates in the colon, increasing the hydrogen content in the exhaled air. The respiratory hydrogen test with lactose only confirms the deficiency of lactase and is not used as the primary diagnostic test in the study of malabsorption.

The Schilling test allows you to evaluate the malabsorption of vitamin B12. Its four stages allow to determine whether the deficiency is a consequence of pernicious anemia, pancreatic exocrine insufficiency, excessive growth of microflora or ileum disease. The patient takes 1 μg of radiolabeled cyanocobalamin orally in parallel with 1000 μg of unlabeled cobalamin injected intramuscularly to saturate the bonds in the liver. Urine collected in 24 hours is analyzed for radioactivity; the excretion in the urine of less than 8% of the oral dose indicates the malabsorption of cobalamin (step 1). If changes are detected at this stage, the test is repeated with the addition of an internal factor (step 2). Pernicious anemia is diagnosed if this supplement normalizes absorption. Stage 3 is performed after the addition of pancreatic enzymes; the normalization of the indicator at this stage indicates a secondary malabsorption of cobalamin due to pancreatic insufficiency. Stage 4 is performed after antibiotic therapy, including in relation to anaerobes; the normalization of the indicator after antibiotic therapy suggests excessive growth of microflora. Deficiency of cobalamin as a result of ileal disease or after its resection leads to changes at all stages.

Studies of the more rare causes of malabsorption include the determination of serum gastrin (Zollinger-Ellison syndrome), internal factor and antibodies to parietal cells (pernicious anemia), chloride in sweat (cystic fibrosis), lipoprotein electrophoresis (abetalipoproteinemia) and plasma cortisol (Addison's disease).

[45], [46], [47], [48]