bubble_chart Overview

Malabsorption syndrome is not a single disease but a group of disorders. Any condition that leads to impaired absorption of fats, proteins, carbohydrates, vitamins, electrolytes, minerals, and water can be classified under this syndrome. Its main clinical manifestations include diarrhea, abdominal pain, and others. Malabsorption is not only associated with celiac sprue, tropical sprue, and other small intestine diseases but can also result from pancreatic enzyme deficiency, bile salt deficiency, disaccharidase deficiency, post-gastrointestinal surgery abnormalities, endocrine disorders, and drug-induced conditions.

bubble_chart Etiology

It has been proposed that infants with celiac disease and patients with non-tropical sprue are abnormally sensitive to foods containing gluten (commonly known as wheat gluten). The gliadin in gluten from wheat, barley, oats, etc., may cause toxic damage to the intestinal mucosa. Whether this damage is due to a toxic reaction, an allergic reaction, or an enzyme deficiency remains unclear. Tropical sprue, on the other hand, is unrelated to gluten, but it is speculated that certain abnormal bacteria in the intestine may be the triggering factor for the disease.

According to reports by John et al., the causes of malabsorption syndrome are as follows:

(1) Pancreatic enzyme deficiency: chronic pancreatitis, pancreatic cancer, pancreatectomy, cystic fibrosis.

(2) Bile salt deficiency: biliary obstruction, reduced hepatic synthesis (e.g., chronic hepatitis, cirrhosis), Crohn's disease, ileum resection, jejunal bacterial overgrowth due to stasis (e.g., surgically created "blind loop," diabetic autonomic neuropathy).

(3) Disaccharidase deficiency: lactose and other disaccharidase deficiencies.

(4) Small intestine diseases: extensive surgical resection (e.g., jejunal bypass surgery for obesity, post-traumatic), radiation enteritis, intestinal ischemia, celiac sprue, Whipple's disease, primary intestinal lymphoma, hypogammaglobulinemia, dermatitis herpetiformis, eosinophilic gastroenteritis, amyloidosis, strongyloidiasis, intestinal lymphangiectasia, glucose-galactose malabsorption.

(5) Multiple defects in digestion and absorption: post-gastrectomy, diabetes mellitus, endocrine disorders (Addison's disease, hyperthyroidism, Zollinger-Ellison syndrome), carcinoid tumors, systemic mastocytosis, scleroderma.

(6) Drugs: laxatives, colchicine, cholestyramine, para-aminosalicylic acid (PAS), neomycin.

Classification:

The classification proposed by Johnson is introduced as follows:

(1) Intraluminal factors:

1. Reduced effective length:

(1) Resection of the stomach or small intestine.

(2) Intestinal stoma surgery.

(3) Motility disorders.

2. Reduced digestive activity:

(1) Pancreatic juice: ① pancreatitis, ② pancreatic cancer, ③ pancreatectomy, ④ cystic fibrosis, ⑤ pancreatic duct stones with obstruction. ⑥ Pancreatic cutaneous fistula.

(2) Bile: ① hepatitis, ② cirrhosis, ③ T-tube drainage, ④ bile duct obstruction, ⑤ insufficient bile salt absorption, ⑥ congenital bile salt deficiency.

3. Changes in microbial flora:

(1) Blind loop.

(2) Small intestine diverticula.

(3) Intestinal stasis: ① visceral neuropathy, ② primary neuropathy, ③ scleroderma, ④ partial obstruction.

(4) Oral antibiotics (neomycin).

(5) Giardiasis (including hookworm, whipworm).

(6) Acute infectious diarrhea.

(7) Achlorhydria.

(2) Changes in the intestinal wall:

1. Mucosal epithelial cells:

(1) Childhood celiac disease.

(2) Gluten-induced enteropathy.

(3) Tropical sprue.

(4) Disaccharidase deficiency.

(5) Radiation enteritis.

(6) Drug-induced enteritis.

(7) Triglyceride lipase deficiency.

2. Basal substances:

(1) Lymphoma, leukemia.

(2) Whipple's disease.

(3) Segmental enteritis.

(4) Systemic mastocytosis.

(5) Amyloidosis.

(6) Subcutaneous nodule disease.

(7) Cancer, fleshy tumor.

(3) Abnormalities in blood or lymphatic vessels:

1. Blood:

(1) Pulsatile flow or venous insufficiency.

(2) Congestive heart failure.

(3) Vasculitis.

2. Lymph:

(1) Intestinal lymphangiectasia.

(2) Lymphatic obstruction.

(4) Unclear causes:

1. Zollinger-Ellison syndrome.

2. Malignant carcinoid tumors.

3.A-beta-lipoproteinemia.

4. Protein-losing enteropathy.

5. Pernicious anemia.

6. Hyperthyroidism.

7. Hypothyroidism.

8. Pneumatosis cystoides intestinalis.

9. Hemochromatosis.

10. Kwashiorkor (malignant malnutrition).

11. Hypogammaglobulinemia.

12. Adrenal-pituitary insufficiency.

13. Mesenteric membrane lymph node subcutaneous node.

bubble_chart Pathological Changes

Since the absorption function of the human body mainly occurs in the small intestine, changes in the small intestinal mucosa are quite pronounced.

Due to the atrophy of small intestinal villi, the visible mucosa can change from the normal plush-like appearance to a flat velvet-like state. Microscopic biopsy may reveal: willow-leaf-shaped villi becoming shortened, irregular in shape, blunt at the tips, and sometimes fused together or even disappearing. The superficial columnar cells decrease, while the submucosal layer shows increased inflammatory cells and glandular hyperplasia. The columnar epithelial cells of the mucosa become flattened, with vacuoles in the cytoplasm and nuclei of varying sizes, and the microvilli appear indistinct. In some cases, the mucosa may appear thickened with chronic inflammation, and while the villi remain, they are disorganized. Additionally, the intestinal lumen may exhibit varying degrees of dilation, which is most pronounced in young children with celiac disease.

Developmental disorders of the small intestinal mucosal villi can significantly reduce the absorptive surface area of the mucosa, and the impaired intracellular resynthesis of triglycerides may be the underlying cause of malabsorption.

Following the onset of small intestinal malabsorption, secondary factors such as intestinal lumen dilation, reduced motility, excessive intestinal mucus, and bacterial infections can further hinder the passage of food through the mucosal layer.

Although patients can generally tolerate the resection of short segments of the small intestine, malabsorption remains a possibility. Compston et al. found that even the removal of a short segment of the small intestine could lead to chronic vitamin D and calcium malabsorption, resulting in osteomalacia. The more extensive the small intestine resection, the more severe the malabsorption becomes. When more than 50% of the small intestine is resected, malabsorption becomes a significant clinical issue.

bubble_chart Clinical Manifestations

The clinical manifestations of malabsorption syndrome, in addition to the specific symptoms and signs of the primary disease causing malabsorption, mainly consist of a series of pathophysiological changes resulting from the impaired absorption of various nutrients. Common symptoms and signs are as follows:

(1) Diarrhea and abdominal pain: Most patients experience frequent or intermittent diarrhea. Due to impaired fat absorption, steatorrhea may occur, characterized by pale, bulky, greasy, or foamy stools that often float on water and have a foul odor. In patients with impaired fatty acid and bile salt absorption, diarrhea may present as loose stools. However, clinically, 5–20% of cases may not exhibit diarrhea and may even show symptoms of constipation. Abdominal pain is mostly distending pain, rarely colicky pain, often occurring before defecation and may be accompanied by grade I tenderness and stomach distension with gas.

(2) Weight loss, lack of strength, and easy fatigue: These are caused by reduced caloric absorption due to impaired absorption of fats, proteins, and carbohydrates, but dehydration, hypokalemia, and loss of appetite are also contributing factors. Severe cases may present with cachexia, with weight loss exceeding 10–20 kg.

(3) Manifestations of impaired vitamin and mineral absorption: Impaired iron absorption can lead to iron-deficiency anemia. Impaired absorption of vitamin B₁₂ and folic acid can result in macrocytic anemia. Impaired absorption of calcium, magnesium, potassium, and vitamin D can cause paresthesia and convulsions of the hands and feet. Impaired vitamin K absorption may lead to bleeding tendencies, presenting as ecchymosis, melena, and hematuria. Deficiency of B vitamins can cause glossitis, stomatitis, angular cheilitis, beriberi, etc.

(4) Edema, ascites, nocturia, and fever: These mainly manifest as hypoalbuminemia, leading to peripheral edema and ascites, nocturia due to impaired water absorption, and fever due to decreased immune function from malabsorption, making patients prone to infections.

(5) Milk intolerance: Caused by lactose malabsorption, presenting as colicky pain, stomach distension with gas, and diarrhea. In such patients, mucosal lactase levels may be reduced, and a flat lactose tolerance test may be positive.

bubble_chart Auxiliary Examination

(1) Hematological examination: Most cases present as megaloblastic anemia, but normocytic or mixed types (macrocytic hypochromic) can also occur. Tropical sprue diarrhea is mostly associated with macrocytic anemia. Serum concentrations of iron, potassium, calcium, sodium, and magnesium may all be reduced. Serum carotene levels may decrease. Plasma albumin, lipids, and prothrombin can also be reduced. Prothrombin time may be prolonged.

(2) Fecal fat measurement:

1. Qualitative test: First, visually inspect for the presence of floating fat droplets, then examine under a microscope. Sudan III staining can be used. Patients with grade II and grade III steatorrhea may test positive, while those with daily fecal fat excretion below 6g will test negative.

2. Quantitative test: In healthy individuals on a normal diet, daily fecal fat excretion does not exceed 6g, or 5% of the ingested fat.

Internationally, the intake-excretion balance test is used. The method involves consuming a standard test meal containing 50–80g of fat for 4–5 days, followed by collecting a complete 3-day stool sample. The fecal fat content is chemically measured daily. If the average daily fecal fat exceeds 7g, malabsorptive steatorrhea can be diagnosed. This is a highly reliable traditional standard method.

In recent years, some have proposed using radioactive iodinated triolein to assess intestinal absorption of neutral fats. However, this method has certain limitations because ¹³¹I commercial preparations are relatively unstable. More recently, it has been suggested that a stable non-radioactive agent, ¹³C-trioctanoin, can be used for qualitative and quantitative measurement of fat malabsorption, with better results than ³¹I.

(3) Small intestine absorption function tests:

1. α-Xylose method: After oral administration of 25g α-xylose, a 5-hour urine collection is analyzed quantitatively. Normal excretion should be 5g or more. This method can serve as a screening test for diffuse small intestine diseases.

2. Radioisotope labeling techniques: For example, ¹³¹I-albumin, ¹³¹IPVP (polyvinylpyrrolidone), ⁵¹Cr-albumin, and ⁶⁷Cu-ceruloplasmin can be used to quantitatively measure protein absorption disorders. Additionally, ⁵⁷Co-labeled vitamin B₁₂ absorption tests, such as the Schilling test, can be performed. Radioisotopes can also be used to assess malabsorption of iron, calcium, amino acids, folate, pyridoxine, and vitamin D.

(4) X-ray examination: Includes gastrointestinal studies and skeletal imaging. Reports indicate that the positive rate of X-ray findings in malabsorption syndrome generally reaches 80–90%.

Barium meal radiography of the gastrointestinal tract often reveals functional changes in the small intestine, most prominently in the jejunum. Key radiographic findings include intestinal dilation, fluid accumulation, and barium precipitation. The intestinal loops may appear segmented with a "snowflake" distribution pattern, mucosal folds may thicken, or the intestinal wall may appear smooth, resembling a "wax tube" sign. Barium transit time is delayed. Imaging of painful bone areas may show osteoporosis, osteomalacia, or pathological

fractures. (5) Small intestine mucosal biopsy: Peroral small intestine mucosal biopsy can be used in selected patients to investigate malabsorption. This technique has significantly advanced the understanding of the histopathological basis of malabsorption.

(6) Special tests for primary diseases causing malabsorption: For example, liver function tests for hepatitis or cirrhosis, amylase tests for pancreatic diseases, and blood glucose tests for diabetes, among others.

bubble_chart Diagnosis

For patients with chronic diarrhea, weight loss, especially those with steatorrhea, the possibility of malabsorption should be considered. Additionally, patients who have undergone partial esophagectomy, esophagogastrectomy, total gastrectomy, partial gastrectomy, vagotomy, small intestine resection, or those with pancreatic insufficiency, hepatobiliary diseases, blind loop syndrome, and other small intestine conditions requiring surgery may also have malabsorption syndrome.

The key points in diagnosis involve clarifying the following three aspects through medical history collection and the aforementioned examination methods: ① The specific disease location and individual condition causing malabsorption; ② Whether it is malabsorption of a single nutrient or multiple nutrients; ③ If it is malabsorption of a single nutrient, which one exactly? If multiple, which ones are predominant?

bubble_chart Treatment Measures

The treatment of malabsorption syndrome should be tailored to individual difficulties. The primary focus should be on treating the underlying diseases, such as liver, biliary, pancreatic, and small intestine disorders. However, there are some general principles and methods that should be followed for these patients:

(1) Dietary control: A high-calorie, high-protein, high-vitamin, easily digestible, non-irritating, and low-fat diet is recommended. Particularly for patients with steatorrhea, fat intake should be strictly limited to no more than 40g per day.

(2) Supplementation control: The principle is to supplement what is deficient. In the early stages, intravenous or intramuscular injections are preferred, with higher doses, which can later be switched to oral maintenance doses once the condition improves. For example, iron supplements should be given for iron-deficiency anemia; vitamin K and C for those with bleeding tendencies; and vitamin D and calcium for those showing signs of osteoporosis or osteomalacia. Some foreign scholars advocate the use of multivitamin preparations, while domestic products such as high-efficacy Centrum capsules and 21-Super-Vita tablets are available.

(3) Symptomatic treatment: For patients with particularly severe symptoms, appropriate symptomatic treatment can be administered on the basis of treating the underlying disease, dietary control, and supplementation to alleviate symptoms.

(4) Anti-infection: For patients with secondary infections, antibiotics such as norfloxacin capsules can be used as appropriate, with a dosage of 0.2g per dose, four times a day, taken before meals.

(5) Surgical treatment: Patients with "blind loop syndrome," small intestine tumors, pancreatic tumors, etc., may undergo surgical treatment.

(6) Cautious use of hormones: Adrenal corticosteroids may have some therapeutic effect for certain severe patients, as they can increase the absorption of nitrogen, fats, and other nutrients in the digestive tract, have a non-specific effect in enhancing appetite, and may induce a grade I sense of euphoria and comfort. Hydrocortisone can be administered intravenously at a dose of 100–300mg/24 hours. However, due to the tendency for relapse after discontinuation and the risks of long-term use, such as water and sodium retention, exacerbation of hypokalemia, and the potential to cause osteoporosis, they should generally be used with caution. Only in extremely refractory cases should their use be considered under the guidance of a physician.