bubble_chart Overview

Normally, people have one bowel movement per day, while some individuals may have 2–3 bowel movements daily or once every 2–3 days, with normal stool consistency. The average daily stool output is 150–200 grams, containing 60–75% water. Diarrhea is a common symptom characterized by a significant increase in bowel movement frequency compared to usual habits, with loose or watery stools, daily stool output exceeding 200 grams, or the presence of undigested food, pus, blood, or mucus. Diarrhea is often accompanied by urgency, anal discomfort, or incontinence. It is classified into acute and chronic types. Acute diarrhea has a sudden onset and lasts within 2–3 weeks. Chronic diarrhea refers to symptoms persisting for more than two months or recurring with intervals of 2–4 weeks.

bubble_chart Etiology

(1) Acute diarrhea usually lasts no more than 3 weeks, with infection being the most common cause.

1. Food poisoning: Caused by toxins from Staphylococcus aureus, Bacillus cereus, Clostridium perfringens, Clostridium botulinum, etc., often presenting as non-inflammatory watery diarrhea.

2. Intestinal infections

(1) Viral infections: Rotavirus, Norwalk virus, and enteric adenovirus can cause non-inflammatory diarrhea in the small intestine.

(2) Bacterial infections: Vibrio cholerae and enterotoxigenic Escherichia coli can lead to non-inflammatory watery diarrhea in the small intestine. Salmonella, Shigella, Campylobacter, Yersinia enterocolitica, invasive E. coli, Staphylococcus aureus, Vibrio parahaemolyticus, and Clostridium difficile can cause colitis, resulting in bloody or purulent diarrhea.

(3) Parasitic infections: Giardia lamblia and Cryptosporidium can cause non-inflammatory watery diarrhea in the small intestine. Entamoeba histolytica invades the colon, causing inflammation, ulcers, and bloody or purulent diarrhea.

(4) Traveler's diarrhea: Diarrhea occurring during or after travel, often caused by infections such as enterotoxigenic E. coli, Salmonella, Giardia lamblia, or Entamoeba histolytica.

(5) Drug-induced diarrhea: Laxatives, hyperosmotic agents, cholinergic drugs, antibiotics, and certain antihypertensive or antiarrhythmic drugs may cause diarrhea during use.

(2) Chronic diarrhea persists for more than 2 months, with causes more complex than acute diarrhea, making diagnosis and treatment sometimes challenging. This is the focus of this chapter.

1. Chronic infectious intestinal diseases: ① Chronic amebic dysentery; ② Chronic bacterial dysentery; ③ Intestinal tuberculosis; ④ Giardiasis, schistosomiasis; ⑤ Intestinal candidiasis.

2. Non-infectious intestinal inflammation: ① Inflammatory bowel disease (Crohn's disease and ulcerative colitis); ② Radiation enteritis; ③ Ischemic colitis; ④ Diverticulitis; ⑤ Uremic enteritis.

3. Tumors: ① Colorectal cancer; ② Colonic adenomatous polyps; ③ Small intestinal malignancies with cachexia; ④ APUDomas (e.g., gastrinoma, carcinoid, VIPoma).

4. Small intestinal malabsorption

(1) Primary small intestinal malabsorption.

(2) Secondary small intestinal malabsorption.

1) Digestive disorders: ① Pancreatic enzyme deficiency (e.g., chronic pancreatitis, pancreatic cancer, pancreatic fistula); ② Disaccharidase deficiency (e.g., lactose intolerance); ③ Impaired bile secretion or bile salt deficiency (e.g., extrahepatic biliary obstruction, intrahepatic cholestasis, small intestinal bacterial overgrowth).

2) Reduced absorptive surface: ① Excessive small intestinal resection (short bowel syndrome); ② Small intestine-colon anastomosis or fistula.

3) Small intestinal infiltrative diseases: Whipple’s disease, alpha-heavy chain disease, systemic sclerosis, etc.

5. Motility-related diarrhea: Caused by intestinal motility disorders (often accelerated), such as irritable bowel syndrome, post-gastrectomy, vagotomy, partial intestinal obstruction, hyperthyroidism, or adrenal insufficiency.

6. Drug-induced diarrhea: ① Laxatives (e.g., phenolphthalein, senna); ② Antibiotics (e.g., lincomycin, clindamycin, neomycin); ③ Antihypertensives (e.g., reserpine, guanethidine); ④ Hepatic encephalopathy medications (e.g., lactulose, lactitol).

bubble_chart Pathogenesis

A normal person has a large amount of fluids and electrolytes entering the small intestine every 24 hours, approximately 2L from dietary intake and about 7L from secretions by the salivary glands, stomach, intestines, liver, and pancreas, totaling over 9L. The majority is absorbed by the small intestine. Daily, around 2L of fluid passes through the ileocecal valve into the colon, 90% of which is absorbed by the colon, with less than 200ml of water excreted in feces. This is the result of a dynamic balance in the secretion and absorption of water in the gastrointestinal tract. If this balance is disrupted, an increase of just a few hundred milliliters of fluid in the intestines daily can be enough to cause diarrhea.

(1) Osmotic diarrhea In normal individuals, after chyme passes through the duodenum into the jejunum, its breakdown products are either absorbed or diluted, and the electrolyte composition stabilizes, so the contents of the jejunum and ileum become isotonic, with their osmotic pressure primarily determined by electrolytes. If ingested food (mainly carbohydrates) or medications (primarily divalent ions like Mg²⁺

or SO₂^-4) are concentrated, hypertonic, and difficult to digest or absorb, the osmotic gradient between plasma and the intestinal lumen increases. Plasma water rapidly moves across the intestinal mucosa into the lumen until the contents become isotonic. The large volume of fluid retained in the lumen can stimulate intestinal motility, leading to diarrhea.

1. Causes of osmotic diarrhea

(1) Hypertonic medications: Laxatives such as magnesium sulfate and sodium sulfate; antacids like magnesium oxide and magnesium hydroxide; dehydrating agents like mannitol and sorbitol; ammonia-lowering drugs like lactulose.

(2) Hypertonic foods: Mainly certain carbohydrates that are not absorbed by the intestinal mucosa due to a lack of hydrolytic enzymes or other reasons, creating hypertonic intestinal contents that cause diarrhea. A common cause is insufficient digestive enzymes for food sugars, with congenital lactase deficiency being the most prevalent. Lactose malabsorption is widespread in China, with an incidence of 78–88% among healthy Han individuals. Among them, 55–65% experience watery diarrhea, colicky abdominal pain, abdominal distension and fullness, and increased flatulence after consuming milk or dairy products, a condition known as lactose intolerance. This occurs because undigested lactose accumulates, increasing intestinal osmotic pressure and drawing in large amounts of water, leading to diarrhea.

2. Characteristics of osmotic diarrhea: ① Diarrhea stops after fasting or discontinuing the medication; ② Intraluminal osmotic pressure exceeds plasma osmotic pressure; ③ Stool contains large amounts of undigested or unabsorbed food or drugs.

(2) Malabsorptive diarrhea Many diseases cause diffuse intestinal mucosal injury and functional changes, leading to malabsorptive diarrhea.

1. Common causes

(1) Impaired mucosal absorption: Conditions like tropical sprue and adult celiac disease involve mucosal lesions, with visible villous abnormalities such as blunting, shortening, or atrophy, and disorganized or absent microvilli. Adult celiac disease is extremely rare in China and is a congenital intestinal absorption disorder, also known as gluten-induced enteropathy. It may result from a defect in certain intestinal enzymes, leading to incomplete digestion of gluten and the production of toxic alcohol-soluble α-gliadin that damages the mucosa.

(2) Reduced mucosal surface area: Surgical resection of more than 75% of the small intestine or leaving less than 120cm of residual bowel can cause short bowel syndrome, impairing the absorption of various nutrients. Resection or damage to the distal ileum disrupts bile salt reabsorption, reducing total bile salts and leading to fat malabsorption.

(3) Bacterial overgrowth in the small intestine: This is also characteristic of blind loop syndrome. Bacteria deconjugate bile salts, impairing micelle formation and causing steatorrhea.

(4) Mucosal obstructive congestion: Commonly seen in portal hypertension and right heart failure, mucosal congestion and edema can cause malabsorption and diarrhea.

(5) Congenital selective absorption disorders: The most typical example is congenital chloridorrhea, but this condition is rare.

2. Characteristics of malabsorptive diarrhea ① Fasting can alleviate diarrhea; ② The intestinal contents consist of unabsorbed electrolytes and food components, with a higher osmotic pressure.

(3) Secretory diarrhea Intestinal secretion is primarily the function of mucosal crypt cells, while absorption relies on the epithelial cells on the surface of intestinal villi. Diarrhea occurs when secretion exceeds absorption capacity.

Factors that stimulate intestinal mucosal secretion can be divided into four categories: ① Bacterial enterotoxins, such as toxins from Vibrio cholerae, Escherichia coli, Salmonella, etc.; ② Neurohumoral factors, such as vasoactive intestinal peptide (VIP), serotonin, calcitonin, etc.; ③ Immune-inflammatory mediators, such as prostaglandins, leukotrienes, platelet-activating factor, tumor necrosis factor, interleukins, etc.; ④ Detergents, such as bile salts and long-chain fatty acids, which cause secretory diarrhea by stimulating anion secretion and increasing mucosal epithelial permeability. Various laxatives like castor oil, phenolphthalein, bisacodyl, aloes, and senna leaf also fall into this category.

The mechanism of intestinal secretion of large amounts of electrolytes and water is quite complex. Recent studies have found that the increase in second messengers such as cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), and calcium ions in intestinal mucosal crypt cells is a key factor in inducing mucosal secretion. Taking Vibrio cholerae and VIP as examples, both first bind to receptors on the brush border of epithelial cells, activating the adenylate cyclase-cAMP system, leading to an increase in cAMP concentration and causing massive intestinal fluid secretion. Not all factors that stimulate intestinal mucosal secretion act through cAMP; for instance, Clostridium difficile induces secretory diarrhea by increasing calcium ions.

(4) Exudative diarrhea Inflammation of the intestinal mucosa can lead to the exudation of large amounts of mucus, pus, and blood, resulting in diarrhea. The pathophysiology of exudative diarrhea is complex because inflammatory exudates can increase intestinal osmotic pressure; if the intestinal mucosa is extensively injured, the absorption of electrolytes, solutes, and water can be impaired; mucosal inflammation can produce prostaglandins, which further stimulate secretion, increase intestinal motility, and cause diarrhea.

1. Causes of intestinal inflammation ① Idiopathic, such as Crohn's disease and ulcerative colitis. ② Infectious inflammation: caused by invasive pathogens and cytotoxins, such as infections by Shigella, Salmonella, Helicobacter, Yersinia, Mycobacterium tuberculosis, Entamoeba histolytica, Clostridium difficile, etc.; ③ Ischemic inflammation; ④ Radiation injury to the intestine; ⑤ Abscess formation, such as diverticulitis and tumor infection.

2. Characteristics of exudative diarrhea ① Stool contains exudate and blood. Inflammation of the colon, especially the left colon, often presents with visible mucopurulent stool. If there are ulcers or erosions, blood is often present. In cases of small intestine inflammation, visible pus or blood in the stool is usually absent. ② The severity of diarrhea and systemic symptoms and signs depends on the extent of intestinal damage.

(5) Motility-related diarrhea Many drugs, diseases, and gastrointestinal surgeries can alter the normal motility of the intestines, accelerating peristalsis. This causes intestinal contents to pass through the lumen too quickly, reducing contact time with the mucosa and thereby impairing digestion and absorption, leading to diarrhea.

1. Common causes of motility-related diarrhea ① Drug-induced diarrhea, such as propranolol and quinidine, which can alter normal intestinal myoelectric control; ② Neurogenic diarrhea, such as diarrhea caused by diabetes, hyperthyroidism, or vagotomy; ③ Post-gastrointestinal resection diarrhea, such as partial or total gastrectomy or ileocecal resection, which can eliminate the valve functions of the pylorus and ileocecal region, leading to diarrhea. Extensive small intestine resection can also cause diarrhea; ④ Carcinoid syndrome; ⑤ Partial intestinal obstruction; ⑥ Irritable bowel syndrome.

2. Characteristics of motility-related diarrhea ① Loose or watery stool without exudate. ② Diarrhea is accompanied by hyperactive borborygmi and abdominal pain.

bubble_chart Auxiliary Examination

(I) Laboratory Tests

1. Routine Tests Blood tests and generation and transformation tests can assess the presence of anemia, leukocytosis, diabetes, as well as electrolyte and acid-base balance. Fresh stool examination is the most crucial step in diagnosing acute or chronic diarrhea disease causes, revealing bleeding, pus cells, protozoa, eggs, lipomas, undigested food, etc. The occult blood test can detect hidden bleeding. Stool culture can identify pathogenic microorganisms. To differentiate between secretory diarrhea and osmotic diarrhea, stool electrolyte and osmotic pressure tests may sometimes be required.

2. Small Intestine Absorption Function Tests

(1) Fecal Fat Measurement: Staining fecal smears with Sudan III and observing fat droplets under a microscope is the simplest qualitative method. A fecal fat content above 15% is often positive. The fat balance test, which chemically measures daily fecal fat content, yields the most accurate results. ¹³¹Iodine-triglyceride and ¹³¹iodine-oleic acid absorption tests are simpler but less accurate than the balance test. Elevated fecal fat levels indicate fat malabsorption, which may result from small intestine mucosal lesions, bacterial overgrowth, or pancreatic exocrine insufficiency.

(2) D-Xylose Absorption Test: A positive result reflects malabsorption due to jejunal disease or small intestine bacterial overgrowth. In cases of isolated pancreatic exocrine insufficiency or diseases affecting only the ileum, the xylose test remains normal.

(3) Vitamin B12 Absorption Test (Schilling Test): In cases of ileal dysfunction, excessive resection, bacterial overgrowth, or pernicious anemia, urinary excretion of vitamin B12 is below normal.

(4) Pancreatic Function Test: Abnormal results indicate that small intestine malabsorption is caused by pancreatic disease. Refer to the "Chronic Pancreatitis" section.

(5) Breath Tests: ① 14C-Glycine Breath Test: In cases of ileal dysfunction or excessive resection with bacterial overgrowth, pulmonary excretion of 14CO₂ and fecal excretion of 14CO₂ significantly increase. ② Hydrogen Breath Test: Useful for diagnosing lactose or other disaccharide malabsorption, small intestine bacterial overgrowth, or rapid small intestine transit.

(II) Imaging Diagnosis

1. X-ray Examination X-ray barium meal, barium enema, and abdominal plain films can reveal gastrointestinal lesions, motility status, gallstones, or calcifications in the pancreas or lymph nodes. Selective angiography and CT are particularly valuable for diagnosing digestive system tumors.

2. Endoscopy Proctoscopy and sigmoidoscopy with biopsy are simple procedures and valuable for early diagnosis of cancer in corresponding intestinal segments. Colonoscopy and biopsy can observe and diagnose lesions throughout the colon and terminal ileum. Small intestine endoscopy is challenging but can visualize duodenal and proximal jejunal lesions and perform biopsies. ERCP is highly valuable for suspected biliary or pancreatic diseases.

3. B-mode Ultrasound Scanning A non-invasive and non-radioactive method, it should be prioritized.

4. Small Intestine Mucosal Biopsy For diffuse small intestine mucosal lesions, such as tropical sprue, celiac disease, Whipple's disease, or diffuse small intestine lymphoma (alpha heavy chain disease), a small intestine biopsy tube can be orally inserted to obtain mucosal tissue for pathological diagnosis.

bubble_chart Diagnosis

The diagnosis of the primary disease or cause of diarrhea mainly relies on medical history, symptoms, signs, and routine laboratory tests, particularly stool examinations. Many cases can often be accurately diagnosed through careful analysis of the medical history and preliminary results of the aforementioned tests. If the diagnosis remains unclear, further examinations such as X-ray barium enema and barium meal studies, and/or colonoscopy may be performed. If still no definitive conclusion is reached, imaging diagnostic methods such as ultrasound, CT, or endoscopic retrograde cholangiopancreatography (ERCP) can be selected based on different conditions to examine biliary or pancreatic diseases. Alternatively, small intestine absorption function tests, breath tests, or small intestine mucosal biopsies may be conducted to investigate malabsorption. When highly suspected conditions like intestinal tuberculosis or intestinal amebiasis—which have specific treatments—cannot be confirmed despite efforts, a therapeutic trial may be conducted within a certain timeframe.

bubble_chart Treatment Measures

Diarrhea is a symptom, and the fundamental treatment should target the disease cause. Understanding the mechanism of disease behind diarrhea helps in grasping the treatment principles.

(1) Disease Cause Treatment It goes without saying that diarrhea caused by intestinal infections requires anti-infective treatment, with antibacterial therapy targeting the pathogens being the most ideal. Compound formulas such as co-trimoxazole, norfloxacin, ciprofloxacin, and ofloxacin are effective against bacterial dysentery, Salmonella, or toxigenic Escherichia coli and Helicobacter infections. Metronidazole is effective against Entamoeba histolytica and Giardia infections, making these drugs commonly used for acute infectious diarrhea, including the prevention and treatment of so-called traveler's diarrhea. For diarrhea caused by lactose intolerance or celiac disease, the treatment involves eliminating lactose or gluten from the diet, respectively. The principle for treating osmotic diarrhea is to discontinue the consumption of foods or medications that cause hyperosmolarity. Secretory diarrhea can easily lead to severe dehydration and electrolyte loss; in addition to addressing the disease cause, active oral or intravenous supplementation of salts and glucose solutions is necessary to correct dehydration. Colonic diarrhea caused by impaired bile salt reabsorption can be treated with cholestyramine to adsorb bile acids and stop diarrhea. For steatorrhea due to bile acid deficiency, medium-chain fats can replace long-chain fats in the daily diet, as the former can be directly absorbed via the portal venous system without requiring bile salt conjugation, hydrolysis, or micelle formation.

(2) Symptomatic Treatment When selecting medications, addictive drugs should be avoided, and if necessary, they should only be used for a short period. Disease cause treatment is primary. For cases where the disease cause is unknown, even if symptoms improve after symptomatic treatment, essential diagnostic steps should not be relaxed or omitted, especially for cases where malignant diseases have not been ruled out.

1. Antidiarrheal Drugs Commonly used agents include activated charcoal, tannin albumin, bismuth subcarbonate, and aluminum hydroxide gel, taken 3–4 times daily. Stronger-acting compound formulas such as camphor tincture (3–5 ml) and codeine (0.03 g) can be taken 2–3 times daily. Due to the risk of addiction with prolonged use, these are only suitable for short-term treatment of cases with excessively frequent diarrhea. The compound formula diphenoxylate (each tablet contains 2.5 mg of diphenoxylate and 0.025 mg of atropine), taken 1–2 tablets 2–4 times daily, has an additive central depressant effect and should not be combined with barbiturates or opioids. Loperamide is more potent and longer-lasting than diphenoxylate, does not contain atropine, and has fewer central effects. An initial dose of 4 mg is followed by adjustments to reduce bowel movements to 1–2 times daily, with a maximum daily dose of 8 mg. Probiotics can help regulate intestinal function.

2. Antispasmodic and Analgesic Agents Options include atropine, propantheline, scopolamine, and procaine.

3. Sedatives Options include diazepam, chlordiazepoxide, and phenobarbital-class drugs.