The differential diagnosis of an acute abdomen is most appropriately considered by its anatomic location (see Table 7-1).
Common gynecologic causes of lower quadrant pain include mittelschmerz, ovarian cyst, endometriosis, fibroids, ovarian torsion, pelvic inflammatory disease, ovarian tumor, ectopic pregnancy, infection of the uterus, threatened abortion, and round ligament pain secondary to pregnancy.
Medical conditions that may present as acute abdomen are many. Common examples include lower lobe pneumonias, acute myocardial
infarction (MI), diabetic ketoacidosis (DKA), acute hepatitis, porphyria, adrenal hemorrhage, and musculoskeletal problems. Appendicitis is a clinical diagnosis. The triad of right lower quadrant pain, anorexia, and leukocytosis is the most sensitive diagnostic tool. Nausea and vomiting usually follow the onset of pain. The patient may have a low-grade fever and mild leukocytosis. Fevers with higher temperatures or increased WBC counts suggest perforation.
TABLE 7-1. Differential Diagnosis of the Acute Abdomen
Right Upper Quadrant Pain
Right Lower Quadrant Pain
Ruptured ovarian cyst
Peptic ulcer disease (PUD)
Urinary tract infection
Small bowel obstruction
Inflammatory bowel disease (IBD)
Pelvic inflammatory disease (PID)
Left Upper Quadrant Pain
Lower Left Quadrant Pain
Splenic disease (e.g., infarct, abscess, or rupture)
Gastroesophageal reflux disease
Urinary tract infection
Dissecting aortic aneurysm
Small bowel obstruction
Boerhaave syndrome (i.e., rupture of the esophagus)
Abdominal aortic aneurysm
Boerhaave syndrome (i.e., rupture of the esophagus)
Thirty percent of patients with appendicitis have an elevated WBC count, whereas 95% have a left shift.
The intensity of pain is somewhat in proportion to the degree of irritation to the parietal peritoneum. Therefore, a retrocecal appendix (which is the most common location) may cause only a dull ache, given the lack of contact with the parietal peritoneum.
Laboratory studies are undertaken to support a clinical hypothesis. The evaluation generally includes a complete blood count (CBC), liver chemistries, amylase and lipase, coagulation profile, urinalysis, and urine pregnancy test:
▼ Lactic acid level should be obtained for patients with suspected ischemic bowel. An elevated level is associated with tissue hypoperfusion.
▼ Beta-hCG levels must be obtained for all women of childbearing age to exclude the possibility of ectopic pregnancy.
▼ Chest radiograph should be obtained on all patients with acute abdomen to rule out free air. Pneumonia may present as an acute abdomen.
▼ Abdominal radiograph is most effective in detecting either bowel obstruction or pneumoperitoneum. An upright and supine view is necessary.
▼ Appendicolith can be seen in 15% of patients with appendicitis, whereas renal stones may also be visualized up to 85% of the time.
▼ Other radiographic findings of acute appendicitis include right lower quadrant ileus, loss of psoas shadow, deformity of the cecal outline, free air, and soft tissue density.
Abdominal ultrasound is the study of choice in patients with possible acute cholecystitis or ovarian cyst. A sonographic Murphy sign is more sensitive than a clinical Murphy sign for acute cholecystitis. An inflamed appendix can be visualized with compression ultrasound (sensitivity ranges from 80% to 90%).
CT can also be used to diagnose appendicitis in patients whose clinical symptoms are ambiguous.
▼ Air in the appendix or a normal-appearing contrast-filled appendix virtually rules out the diagnosis of appendicitis.
▼ CT will provide an alternate diagnosis in 15% of patients when assessing for appendicitis.
Arteriography is the test of choice for patients with suspected mesenteric ischemia.
A diagnosis of chronic gastritis depends on biopsy of gastric mucosa.
Gastric antrum is spared.
Parietal cell antibodies and intrinsic factor antibodies help identify those patients prone to pernicious anemia (PA).
Characteristics include the following:
▼ Vitamin B12-deficient megaloblastosis
▼ Hypergastrinemia (due to hyperplasia of gastrin-producing cells)
▼ Gastric carcinoids
▼ Low serum pepsinogen I concentrations
Laboratory findings may be due to other accompanying autoimmune diseases (e.g., Hashimoto thyroiditis, Addison disease, Graves disease, myasthenia gravis, hypoparathyroidism, type 1 DM).
Gastric antrum is involved.
Anemia is caused by iron deficiency, and malabsorption may occur.
Helicobacter pylori infection is detectable in approximately 80% of patients with peptic ulcer and chronic gastritis. Diagnosis is by biopsy, culture, direct Gram staining, urease breath test, and serologic tests.
Hypogastrinemia is caused by destruction of gastrin-producing cells in the antrum.
Chronic antral gastritis is consistently present in patients with benign gastric ulcer.
Gastric acid studies are of limited value. Severe hypochlorhydria or achlorhydria after maximal stimulation usually denotes mucosal atrophy.
Infections (other bacteria [syphilis], viral [e.g., CMV], parasitic [e.g., anisakiasis], fungal)
Chemical (e.g., nonsteroidal anti-inflammatory drugs [NSAIDs], bile reflux, other drugs)
Noninfectious granulomatous (e.g., sarcoidosis, Crohn disease)
duct. CEA level in bile (obtained by percutaneous transhepatic drainage) was reported increased in 76% of a small group of cases.
The abnormal pancreatic function tests and increased tumor markers that occur with carcinoma of the body of the pancreas may be evident.
Macroamylase may be found in approximately 1% of randomly selected patients and 2.5% of persons with increased serum amylase level. Same findings may also occur in patients with normal molecular weight hyperamylasemia in which excess amylase is principally salivary gland isoamylase types 2 and 3.
pancreatic duct; they tend to fall after several days; ≤19% of patients with acute pancreatitis (especially when seen more than 2 days after onset of symptoms) may have normal values, especially with an alcoholic etiology and longer duration of symptoms, even when dying of acute pancreatitis. It may also be normal in relapsing chronic pancreatitis and patients with hypertriglyceridemia (technical interference with test). It is frequently normal in acute alcoholic pancreatitis. Acute abdomen due to GI infarction or perforation rather than acute pancreatitis is suggested by only moderate increase in serum amylase and lipase (<3× URL) and evidence of bacteremia. Of patients with acute alcoholic intoxication, 10-40% have elevated serum amylase (about half are salivary type); they often present with abdominal pain, but increased serum amylase is usually <3× URL. Levels >25× URL indicate metastatic tumor rather than pancreatitis. Serum pancreatic isoamylase can distinguish elevations due to salivary amylase that may account for 25% of all elevated values. (In healthy persons, 40% of total serum amylase is pancreatic type and 60% is salivary type.) Only slight increase in serum amylase and lipase values suggests a different diagnosis than acute pancreatitis. Many drugs increase both amylase and lipase in serum.
Figure 7-1. Algorithm for increased serum amylase and lipase. ULN, upper limit of normal.
PaO2 < 60 µmol/L.
Creatinine >2 mg/dL after rehydration.
Blood glucose >250 mg/dL.
Hemoconcentration (Hct > 47% or failure to decrease in 24 hours after admission), but Hct may be decreased in severe hemorrhagic pancreatitis.
GI bleed >500 mL/24 hours.
Presence, volume, and color of peritoneal fluid.
Methemalbumin may be increased in serum and ascitic fluid (AF) in hemorrhagic (severe) but not edematous (mild) pancreatitis; may distinguish these two conditions but not useful in diagnosis of acute pancreatitis.
WBC is slightly to moderately increased (10,000-20,000/µL).
Glycosuria appears in 25% of patients.
Hypokalemia, metabolic alkalosis, or lactic acidosis may occur.
Alcohol abuse accounts for approximately 36% of cases.
Biliary tract disease accounts for 17% of cases.
Idiopathic accounts for >36% of cases.
Trauma and postoperative factors account for >8% of cases.
Drugs (e.g., steroids, thiazides, azathioprine, estrogens, sulfonamides; children taking valproic acid) account for >5% of cases.
Hypertriglyceridemia (hyperlipidemia—types V, I, IV) accounts for 7% of cases.
Hypercalcemia from any cause.
Tumors (pancreas, ampulla).
Anatomic abnormalities of the ampullary region causing obstruction (e.g., annular pancreas, Crohn disease, duodenal diverticulum).
Renal failure and renal transplantation.
Miscellaneous (e.g., collagen vascular disease, pregnancy, ischemia, scorpion bites, parasites obstructing the pancreatic duct [Ascaris, fluke], Reye syndrome, fulminant hepatitis, severe hypotension, cholesterol embolization).
Pseudocysts of the pancreas.
Pancreatic infection or abscess diagnosed by increased WBC count, Gram staining, and culture of aspirate.
Polyserositis (peritoneal, pleural, pericardial, synovial surfaces). Ascites may develop cloudy or bloody or “prune juice” fluid, 0.5-2.0 L in volume, containing increased amylase with a level higher than that of serum amylase. No bile is evident (unlike in perforated ulcer). Gram stain shows no bacteria (unlike infarct of the intestine). Protein >3 g/dL and marked increase in amylase.
Adult respiratory distress syndrome (with pleural effusion, alveolar exudate, or both) may occur in approximately 40% of patients; arterial hypoxemia is present.
Disseminated intravascular coagulation (DIC).
WBC > 16,000/µL
Blood glucose >200 mg/dL
Serum LD > 350 U/L
Serum AST > 250 U/L
Age >55 years
Within 48 hours
>10% decrease in Hct
Serum calcium <8.0 mg/dL
Increase in BUN > 5 mg/dL
Arterial pO2 < 60 mm Hg
Metabolic acidosis with base deficit >4 mEq/L
1%, if 3 signs are positive
15%, if 3-4 signs are positive
40%, if 5-6 signs are positive
100%, if ≥7 signs are positive
Degree of amylase elevation has no prognostic significance.
CT scan, MRI, and ultrasound are useful for confirming diagnosis or identifying causes or other conditions.
Normal duodenal contents:
▼ Volume: 95-235 mL/hour
▼ Bicarbonate concentration: 74-121 mEq/L
▼ Amylase output: 87,000-276,000 mg
Serum amylase and lipase increase after administration of cholecystokinin and secretin in approximately 20% of patients with chronic pancreatitis. They are more often abnormal when duodenal contents are normal. Normally, serum lipase and amylase do not rise above normal limits.
Fasting serum amylase and lipase are increased in 10% of patients with chronic pancreatitis.
Bentiromide test is usually abnormal with moderate to severe pancreatic insufficiency but often normal in early cases.
Schilling test may show mild malabsorption of vitamin B12 (no longer performed).
Xylose tolerance test and small bowel biopsy are not usually done but are normal.
Chemical determination of fecal fat demonstrates steatorrhea. It is more sensitive than tests using triolein-131I.
Triolein-131I is abnormal in one third of patients with chronic pancreatitis.
Starch tolerance test is abnormal in 25% of patients with chronic pancreatitis.
Alcohol in 60-70%
Idiopathic in 30-40%
Obstruction of pancreatic duct (e.g., trauma, pseudocyst, pancreas divisum, cancer, or obstruction of the duct or ampulla)
Others occasionally (e.g., CF, primary hyperparathyroidism, heredity, malnutrition, miscellaneous [Z-E syndrome, Shwachman syndrome, α1-antitrypsin deficiency, trypsinogen deficiency, enterokinase deficiency, hemochromatosis, parenteral hyperalimentation])
Dyspepsia encompasses any or all of a great variety of upper abdominal symptoms, including upper abdominal pain or discomfort, nausea, bloating, heartburn, early satiety, regurgitation, and belching.
Nonulcerative dyspepsia is defined as persistent or recurrent abdominal pain or discomfort centered in the upper abdomen without definite structural or biochemical explanation. By definition, nonulcerative dyspepsia is a diagnosis of exclusion. Possible mechanisms include dysmotility of the stomach or small intestine, heightened visceral sensitivity, altered intestinal or gastric reflexes, and psychological distress.
Peptic ulcer disease (PUD):
▼ Epigastric abdominal pain is the most common symptom. Pain is nonradiating and is described as a “gnawing” or “hunger pain.” Pain occurs 1-2 hours postprandially and is relieved characteristically by food or antacids.
▼ Nocturnal pain is more specific for PUD and is due to the physiologic increase in acid secretion, which occurs in the early morning hours.
Dyspepsia is typically a chronic relapsing condition. Between 65% and 86% of patients with dyspepsia will experience dyspeptic symptoms, at least intermittently, 2-3 years after the initial presentation. Long duration of symptoms and intermittent symptoms can also occur in PUD and esophagitis; therefore, these characteristics are not reassuring as to the absence of pathology.
Gastroesophageal reflux disease (GERD) and dyspepsia have similar symptoms. Gastroesophageal reflux is a normal physiologic process that occurs daily in all individuals. GERD (expressed clinically as heartburn).
Helicobacter pylori infection is clearly implicated in the etiology of recurrent PUD, yet its role in nonulcerative dyspepsia remains unclear. Between 30% and 60% of patients with nonulcerative dyspepsia have H. pylori. However, the background prevalence in the general population is also high.
Laboratory investigation may not be necessary in young patients (<45 years of age) who have a normal examination and no indicators for organic disease. The etiology of dyspepsia is presented in Table 7-2.
In older patients at increased risk, the minimal laboratory workup should include a CBC, electrolytes, calcium, and liver chemistries.
Thyroid tests, hCG, amylase, and stool studies should be ordered if specific features of the history or examination are suggestive.
TABLE 7-2. Differential Diagnosis of Dyspepsia
Structural Disease Involving the Stomach or Esophagus
Peptic ulcer disease (15-25% of cases)
Reflux esophagitis (5-15% of cases)
Gastric or esophageal cancer (<2% of cases)
Other Gastrointestinal-Related Diseases
Chronic pancreatitis or pancreatic cancer
Nonsteroidal anti-inflammatory drugs
Other Possible Causes
* Nonulcerative dyspepsia occurs in up to 60% of cases, but the diagnosis requires the exclusion of other diagnostic entities.
▼ Upper endoscopy (i.e., esophagogastroduodenoscopy [EGD]): In the majority of cases, this is the study of first choice when further evaluation of dyspepsia is required, including the ability to obtain biopsies. As many as two thirds of endoscopies are completely normal in younger patients (i.e., <45 years of age). Therefore, it is best applied to older patients and to younger patients with classic symptoms.
▼ Upper GI radiography: This test is less accurate than upper endoscopy and cannot provide tissue diagnosis. It is best reserved for situations where endoscopy expertise is unavailable, for patients who refuse endoscopy or have low pretest probability of disease, and in situations where endoscopy might be considered unsafe.
H. pylori testing
Gastric emptying studies: Gastric scintigraphy and gastroduodenal manometry studies generally do not influence medical management and are reserved for patients with normal laboratory tests and a normal EGD, yet who continue to have frequent or protracted vomiting suggestive of a motility disorder. Even in these cases, empiric treatment with prokinetic agents should probably be tried first.
Ascites is a collection of free fluid in the peritoneal cavity.
Chronic liver disease (infectious hepatitis and alcoholism) causes 80% of cases of ascites (see Hepatomegaly, Jaundice).
Multiple causes, including cirrhosis, peritoneal carcinomatosis, or tuberculous peritonitis, account for 3-5% of cases.
Carcinomatosis causes <10% of cases of ascites.
Heart failure is responsible for <3-5% of cases, and nephritic syndrome is a rare cause of ascites.
Cryptogenic cirrhosis may account for up to 10% of cases.
Ascites is currently classified as high gradient or low gradient, depending on the serum ascites albumin gradient (SAAG). Calculation of SAAG involves the difference (not the ratio) between serum values and AF values.
High-gradient ascites results from portal hypertension, whether on the basis of cirrhosis or noncirrhosis. Nephrotic syndrome is an exception and will usually cause low-gradient ascites due to marked hypoalbuminemia.
Low-gradient ascites usually occurs as the result of cardiac failure, malignant carcinomatosis of the peritoneum, infections (such as TB), perforation of the bowel, connective tissues diseases, systemic lupus erythematosus (SLE), and chemical inflammation as in pancreatitis.
Culture: Bedside inoculation of AF in blood culture bottles has increased the positive bacterial yield to be interpreted in concert with the cell count. A Gram stain should also be done.
▼ Imaging studies and CT scans are useful: Ultrasonography is useful for detecting the presence of ascites as well as for determining the etiology. It may reveal evidence of chronic liver disease, malignancy, hepatomegaly, and pancreatic disorder.
▼ Ascites fluid findings: AF examination is the principle diagnostic tool. Using abdominal paracentesis to obtain and study the fluid is crucial to making a diagnosis.
Figure 7-2. Algorithm for the workup of patients with ascites. AILD, alcohol-induced liver disease; CEA, carcinogenic embryonic antigen; NASH, nonalcoholic steatohepatitis; TB, tuberculosis; TNC, total neutrophil count.
Transparent to pale fluid: Is seen in cases of portal hypertension. Neutrophilia in excess of 1,000/mL results in opalescence. A concentration of RBCs in excess of 10,000/mL gives a faint pink tinge, and cell counts >20,000/mL color it red. A traumatic tap is evident by a streak of blood rather than homogeneously red fluid and the tendency to clot. Hepatocellular carcinoma (HCC) and, rarely, metastatic disease can cause a bloody tap. TB is only a rare cause of hemorrhagic ascites.
Chylous or milky ascites: Has a higher triglyceride concentration than serum and >200 mg/dL. It is rarely seen and is usually an indication of cirrhosis rather than lymphoma or TB as was previously thought. The triglycerides are >1,000 mg/dL in truly milky ascites. Dark-brown ascites may be seen in significant hyperbilirubinemia, biliary perforation (when ascitic bilirubin is higher than serum bilirubin), pancreatitis, and, rarely, malignant melanoma.
Bloody ascites fluid: Once a traumatic tap has been ruled out, 50% of cases are due to HCC. TB rarely causes bloody fluid.
Staining: Gram staining has low yield. Even with centrifugation, it has 10% sensitivity in spontaneous bacterial peritonitis (SBP). Acid-fast bacilli (AFB) smear for TB has very low sensitivity. In an appropriate clinical setting of low-grade fever, malaise, and weight loss, a high cell count with lymphocytic predominance and low SAAG is suggestive of TB ascites.
Protein concentration of AF categorized ascites into exudative (ascitic protein >2.5 g/dL) or transudative (ascitic protein <2.5 g/dL). The significance of this has never been evaluated adequately and objectively.
Cell count and differential: In uncomplicated cirrhosis, the total WBC count is <500 cells/µL with <250 neutrophils/µL. After diuresis, the total cell count may go up, but the neutrophil count remains below 250 cells/µL. In SBP, the total WBC count and neutrophil count are usually, but not always raised. In TB and carcinomatosis, the cell count rises but with a predominance of lymphocytes. In traumatic taps, for every 250 RBCs, one neutrophil is subtracted from the total WBC count.
Core laboratory: The serum and AF glucose concentrations are nearly the same in uncomplicated portal hypertension (large numbers of WBCs, bacteria, or tumor cells consume glucose and may lead to diminished levels). Amylase values may be about 3-5 times higher than the serum values. LD levels rise because of release of LD from the neutrophils. The rise occurs in cases of secondary peritonitis, TB, and pancreatitis.
Cytology: Has limitations in the diagnosis of malignant ascites and has been replaced largely laparoscopic examination of the peritoneum along with biopsy and culture.
Errors may occur if serum albumin is very low or when serum and ascitic samples are not obtained within a short space of time from each other.
A high globulin level in serum may also give a false result.
WBC count >250/µL: sensitivity = 85%, specificity = 93%, and neutrophils >50% are presumptive of bacterial peritonitis.
pH < 7.35 and arterial-AF pH difference >0.10; both these findings are virtually diagnostic of bacterial peritonitis and the absence of the above findings virtually excludes bacterial peritonitis.
Lactate >25 mg/dL and arterial-AF difference >20 mg/dL are often present. LD is markedly increased. Phosphate, potassium, and gamma-glutamyltransferase may also be increased. Glucose is unreliable for diagnosis. Total protein <1.0 g/dL indicates high risk for SBP.
This condition shows polymicrobial infection, total protein >1.0 g/dL, AF/LD greater than serum upper limit of normal, and glucose <50 mg/dL compared with SBP.
Prevalence of SBP 15%; due to Escherichia coli approximately 50%, Klebsiella, and other gram-negative bacteria; gram-positive bacteria approximately 25% (especially streptococci).
Infection: Peritonitis is defined as WBC count >100/µL, usually with >50% PMNs (normal is <50 WBC/µL, usually mononuclear cells), or positive Gram stain or culture (most prevalent: coagulase-negative staphylococci, Staphylococcus aureus, Streptococcus sp.; multiple organisms, especially mixed aerobes and anaerobes, occur with bowel perforation). Successful therapy causes a fall in WBC count within the first 2 days and a return to <100/µL in 4-5 days; differential returns to predominance of monocytes in 4-7 days with increased eosinophils in 10% of cases. Patients check outflow bags for turbidity. Turbid dialysate can occur occasionally without peritonitis during the first few months of placing catheter (due to catheter hypersensitivity) with WBC count 100-8,000/µL, 10-95% eosinophils, sometimes increased PMNs, and negative cultures. Occasional RBCs may be seen during menstruation or with ovulation at midcycle. Because of low WBC decision level, manual hemocytometer count rather than an automated instrument must be used.
Metabolic change: Assay dialysate for creatinine and glucose; calculate ultrafiltrate volume by weighing dialysate fluid after 4-hour dwell time and subtracting it from preinfusion weight using specific gravity of 1.0.
AF amylase level greater than serum amylase level is specific for pancreatic disease, but both levels are normal in 10% of cases.
Methemalbumin in serum or AF and total protein >4.5 g/dL indicates poor prognosis.
Increased fluid cholesterol (>45 mg/dL) and fibronectin (>10 mg/dL) have S/S 90%/82%.
Positive cytology has S/S 70%/100%.
Increased AF CEA (>2.5 mg/dL) has S/S 45%/100%.
Nonimmune (occurs in 1 in 3,000 pregnancies):
▼ Cardiovascular abnormalities causing congestive heart failure (CHF) (e.g., structural, arrhythmias) (40% of cases).
▼ Chromosomal (e.g., Turner and Down syndromes are most common; trisomies 13, 15, 16, and 18) (10-15% of cases).
▼ Hematologic disorders (any severe anemia) (10% of cases).
▼ Inherited (e.g., α-thalassemia, hemoglobinopathies, G6PD deficiency)
▼ Acquired (e.g., fetal-maternal hemorrhage, twin-to-twin transfusion, congenital infection [parvovirus B19], methemoglobinemia).
▼ Congenital defects of the chest and abdomen.
▼ Structural (e.g., diaphragmatic hernia, jejunal atresia, volvulus, intestinal malrotation).
Peritonitis caused by GI tract perforation, congenital infection (e.g., syphilis, TORCH [toxoplasmosis, other agents, rubella, CMV, and herpes simplex], hepatitis), and meconium peritonitis.
▼ Lymphatic duct obstruction
▼ Biliary atresia.
▼ Nonstructural (e.g., congenital nephrotic syndrome, cirrhosis, cholestasis, hepatic necrosis, GI tract obstruction).
▼ Lower GU tract obstruction (e.g., posterior urethral valves, urethral atresia, and ureterocele) is the most common cause.
▼ Inherited skeletal dysplasias (enlarged liver causing extramedullary hematopoiesis).
▼ Fetal tumors, most often teratomas and neuroblastomas.
▼ Vascular placental abnormalities.
▼ Genetic metabolic disorders (e.g., Hurler syndrome, Gaucher disease, Niemann-Pick disease, GM1 gangliosidosis type I, I-cell disease, β-glucuronidase deficiency).
Immune (maternal antibodies reacting to fetal antigens [e.g., Rh, C, E, Kell])
Figure 7-4. Algorithm for spontaneous bacterial peritonitis. PMN, polymorphonuclear leukocytes.
Diarrhea is defined as >200 g of stool or an increase in the frequency or fluidity of normal stools. It may be acute or chronic, and it is considered chronic when it lasts at least 4 weeks.
Osmosis: Molecules not normally present in the intestinal lumen increase the osmolality of chime, drawing water into the lumen (i.e., lactose).
Secretion: Substances can cause intestinal cells to secrete sodium and water (i.e., cholera toxin).
Inflammation results in denuding of the intestinal lining, which in turn disrupts normal absorption, thereby allowing compounds from the lining to leak into the lumen resulting in an increased osmosis.
Motility: Hypermotility leads to an increased stool volume. Hypomotility can lead to bacterial overgrowth, which causes diarrhea through several different mechanisms.
Anal sphincter dysfunction causes fecal incontinence, which can be interpreted by the patient as diarrhea.
Laxative abuse accounts for approximately 15% of all chronic causes. It should be suspected in patients with a mental health disorder.
Sorbitol can cause diarrhea. In one study, approximately 17% of people had diarrhea following the ingestion of 4-5 minutes containing sorbitol.
Both bile salts and fatty acids cause secretion of chloride followed by water into the colon. Excess bile salts also lead to a mild degree of fat malabsorption.
Bacterial overgrowth can occur secondary to diabetes, blind loop syndrome, amyloidosis, diverticulitis, and scleroderma, among other causes.
Irritable bowel syndrome classically presents with diarrhea alternating with constipation, but it can also occur in a diarrhea-predominant form.
Gastric surgery syndrome results in a decreased contact time with the luminal surface and decreased digestive juices mixing with the chyme.
Hyperthyroidism usually has increased frequency and amount of diarrhea but not fluidity. Diarrhea is present in approximately 25% of hyperthyroid cases.
Inflammatory bowel disease (IBD):
▼ Ulcerative colitis (UC) is a relapsing and remitting disease that leads to acute inflammation of the colorectal mucosa. The rectum is involved in 55% of cases. In severe cases, bloody diarrhea often leads to weight loss, anemia, and electrolyte imbalance.
▼ Crohn disease is a chronic relapsing disorder characterized by transmural, asymmetric, and segmental inflammation. It typically involves the ileum, colon, or perianal region; right lower quadrant pain associated with bloody diarrhea is present in 80% of patients.
▼ Villous adenoma produces prostaglandins, which stimulate chloride and water secretion from the colon.
▼ Serotonin from carcinoid cells stimulates gut motility and increases intestinal secretion.
▼ Tumor-associated calcitonin stimulates gut motility.
▼ Gastrinoma leads to increased gastric acid, which directly causes fluid secretion.
from 6% to 42%. Upper endoscopy is useful for making the diagnosis of sprue, Whipple disease, and other small bowel infiltrative processes.
Stool for osmolality gap: The osmolality gap is calculated by the following formula: 2 (stool Na + K). The accuracy is fair in distinguishing between osmotic (if gap is 50) and secretory (if gap is >50) diarrhea.
Stool for pH: For carbohydrate intolerance (e.g., lactose or sorbitol), one small study found the pH <5.6. For bile acid-induced diarrhea, the pH is usually over 6.8.
Stool for fecal fat: This test is used to detect steatorrhea on the basis of malabsorption.
Qualitative: Sensitivity is 97-100%, but the specificity varies from 56% to 86%.
Quantitative: Based upon a 72-hour collection, the patient should be on a 75- to 100-g fat diet. A nutritional consult is advised to maximize compliance.
Test(s) for infectious agents (e.g., stool culture, O&P examination, rotavirus detection) based on clinical presentation.
Nutrition indices: CBC, albumin, and potassium (sensitivity of hypokalemia is 100% for pancreatic cholera or [VIPoma]) are routine studies in the evaluation of chronic diarrhea.
Hormonal studies: TSH, fasting serum gastrin level, calcitonin level, and 24-hour urine collection for 5-hydroxyindoleacetic acid (5-HIAA) are recommended.
D-xylose testing: This tests for small bowel malabsorption syndromes (e.g., sprue, Crohn disease, amyloidosis). Twenty-five grams of D-xylose are administered. A 5-hour urine collection and a 1-hour serum sample are obtained. A decreased amount of D-xylose in the urine and serum indicates small bowel malabsorption. The sensitivity of the test is decreased in the following situations: creatinine clearance of <30 mg/dL, portal hypertension, ascites, delayed gastric emptying, fiber supplements, glucose load, aspirin, and glipizide.
Bentiromide test (to test for pancreatic exocrine insufficiency): N-benzoyl-L-tyrosyl para-aminobenzoic acid (NBT PABA) is administered orally. The molecule is cleaved by chymotrypsin; PABA is absorbed and then measured in a 6-hour urine collection. PABA alone is a somewhat inaccurate measure, so additional markers have been used to increase the accuracy.
Serum immune markers: Several serum immune markers performed by ELISA have been found to be valuable for the diagnosis, stratification, and management of IBD (see Celiac Disease):
▼ Deoxyribonuclease (DNAse)-sensitive perinuclear antineutrophil cytoplasmic antibody (P-ANCA) is positive in 60-80% of adults with ulcerative colitis (UC) and in 83% of children with UC. P-ANCA is positive in 10% of patients with Crohn disease.
▼ Anti-Saccharomyces cerevisiae antibody (ASCA) is present in 70% of patients with Crohn disease.
▼ Pancreatic antibody may be positive in 30-40% of patients with Crohn disease.
▼ Outer membrane porin from E. coli (OmpC) antibody: An immunoglobulin A (IgA) response to OmpC is seen in 55% of patients with Crohn disease.
▼ Lactoferrin, stool: A sensitive and specific marker for detecting inflammation or from IBS once infectious causes of inflammation and colorectal cancer are ruled out.
Osmotic diarrhea is diarrhea with a <3-week (upper limit 6-8 weeks) duration. There are increased osmotically active solutes in the bowel; diarrhea usually stops during fasting.
▼ Laxatives (e.g., magnesium sulfate, milk of magnesia, sodium sulfate [Glauber salt], sodium phosphate, polyethylene glycol/saline)
▼ Drugs (e.g., lactulose, colchicine, cholestyramine, neomycin, paraaminosalicylic acid [PAS])
▼ Foods (e.g., mannitol, sorbitol [in diet candy, chewing gum, soda])
▼ Congenital malabsorption
Specific (e.g., lactase deficiency, fructose malabsorption)
General (e.g., abetalipoproteinemia and hypobetalipoproteinemia, congenital lymphangiectasia, cystic fibrosis)
▼ Acquired malabsorption
Specific (e.g., pancreatic disease, celiac sprue, parasitic infestation, rotavirus enteritis, metabolic disorders [thyrotoxicosis, adrenal insufficiency], jejunoileal bypass, bacterial overgrowth, short bowel syndrome, inflammatory disease [e.g., mastocytosis, eosinophilic enteritis])
Diarrhea caused by increased water and chloride secretion; normal water and sodium absorption may be inhibited.
Laxatives (e.g., aloe, anthraquinones, bisacodyl, castor oil, dioctyl sodium sulfosuccinate, phenolphthalein, senna)
Diuretics (e.g., furosemide, thiazides), asthma (theophylline), thyroid drugs
Cholinergic drugs (cholinesterase inhibitors, quinidine, clozapine, angiotensin-converting enzyme [ACE] inhibitors)
▼ Toxins (e.g., arsenic, mushrooms, organophosphates, alcohol)
▼ Infectious agents (for a discussion of infectious causes of diarrhea, see the Infectious Gastrointestinal Diseases section in this chapter and Chapter 13)
▼ Hormones (serotonin, calcitonin, VIP)
▼ Gastric hypersecretion (Z-E syndrome, systemic mastocytosis, short bowel syndrome)
▼ Bile salts (e.g., disease or resection of the terminal ileum)
▼ Fatty acids (e.g., disease of small intestine mucosa, pancreatic insufficiency)
▼ Congenital (e.g., congenital chloridorrhea, congenital sodium diarrhea)
Infection, injury, ischemia, vasculitis, abscess, and/or idiopathic
Stool contains blood and pus.
Decreased small intestinal motility (e.g., hypothyroidism, DM, amyloidosis, scleroderma)
Increased small intestinal motility (e.g., hyperthyroidism, carcinoid syndrome)
Increased colonic motility (e.g., irritable bowel syndrome)
Ingestion of viable pathogenic microorganisms or toxins is responsible for a wide variety of GI complaints.
Disease is usually manifested by GI tract signs and symptoms but may be manifested by systemic or localized illness without significant GI symptoms (e.g., enteric fever, botulism).
Fecal-oral transmission of infectious agents is commonly mediated by contamination of food but may be mediated by contaminated environmental sources.
The major syndromes associated with GI infections include acute vomiting, acute watery diarrhea, inflammatory diarrhea/dysentery, or enteric fever. If a diarrheal syndrome persists for >2 weeks, it is considered persistent or chronic.
Patients with infectious gastroenteritis may present with a variety of symptoms including nausea, vomiting, abdominal pain, diarrhea, and anorexia. Enteric fever, however, may be associated with minimal GI symptoms, but have prominent systemic or localized symptoms.
When evaluating a patient with a diarrheal illness, a number of issues should be pursued:
▼ Does the patient have any medical conditions, like immune compromise or decreased gastric acidity that would predispose to acquisition or severity of GI infection?
▼ What are the prominent signs and symptoms of disease?
▼ Has the patient had recent travel to regions where transmission of GI illness is endemic?
▼ Has the patient eaten any unusual food? Eaten at any function with mass-produced meals? Eaten any raw or incompletely cooked or pasteurized food?
▼ Has the patient or a close contact worked or resided in a closed community, like a day care center, cruise, inpatient or long-term care facility, or other setting in which transmission of an agent may be facilitated?
▼ What is the interval between likely exposure and onset of symptoms?
▼ Do any of the patient’s recent contacts have similar illness?
▼ What is the duration of clinical symptoms in affected patients?
▼ Has there been new contact with animals: domesticated, farm, or wild?
Diarrheal illness may be noninflammatory or inflammatory.
▼ Noninflammatory diarrhea is usually caused by disease of the small intestine resulting in hypersecretion or decreased absorption. There is usually abrupt onset and resolution after a brief duration of illness.
Systemic symptoms are usually absent or mild. Dehydration may be a complication, especially in the young or elderly.
▼ Inflammatory diarrhea is characterized by mucosal invasion or cytotoxic damage by the pathogen. The large intestine is most commonly affected. The mucosal invasion typically results in bloody stools with many fecal leukocytes. Systemic symptoms are typical, including fever, abdominal pain and tenderness, nausea and vomiting, headache, and malaise.
Syndromes: Clinical manifestations of GI pathogens may be variable and nonspecific. Most infections are self-limited and may be managed symptomatically. Specific diagnostic testing is recommended for severe disease or patients at risk for complication of infection, for infections suspected as part of a local outbreak, or for other epidemiologic purposes.
Gastroenteritis with acute vomiting as the prominent symptom. Suspect:
▼ Enteric viruses (e.g., rotavirus, norovirus, enteric adenovirus)
▼ Preformed toxin ingestion/food poisoning (S. aureus, Bacillus cereus)
Acute onset of watery diarrhea. Patients may have some vomiting and mild systemic symptoms. Stool shows no increased WBCs or RBCs. Suspect:
▼ Enteric viruses (astrovirus, norovirus or other calicivirus, adenovirus, rotavirus) are most common.
▼ Toxins (e.g., Clostridium perfringens or B. cereus).
▼ Parasites (e.g., Cryptosporidium species, Cyclospora cayetanensis, Giardia lamblia).
▼ Bacterial pathogens (any enteric pathogen may cause mild symptoms.)
Inflammatory diarrhea is the prominent symptom (grossly bloody stool, pus or increased fecal WBCs, fever, and significant systemic signs and symptoms). Diagnostic testing is recommended. The syndrome is most commonly caused by bacterial pathogens. Suspect Campylobacter species; Clostridioides (formerly Clostridium) difficile; Escherichia coli; enteroinvasive, or enterohemorrhagic, Plesiomonas; Salmonella species; Shigella species; and Yersinia. Entamoeba histolytica can also cause dysentery.
▼ Enteric fever should be considered in patients with significant fever and recent travel to an endemic area or other epidemiologic risk, whether the patient has diarrhea or not. Stool culture for Salmonella and blood cultures are recommended.
Persistent diarrhea as the prominent symptom (2 weeks or longer). This syndrome may occur in immunocompromised patients. In addition to bacterial causes, suspect:
▼ Parasites (e.g., Cryptosporidium species, Cyclospora cayetanensis, G. lamblia, Cystoisospora belli, Entamoeba histolytica).
▼ Consider noninfectious causes, such as persistent compromise of the gut’s resorptive capability, IBD, laxative use, etc.
Bacteria: Stool culture is most commonly submitted. Bacterial pathogens are present in high concentrations during acute symptomatic infection. Therefore, submission of a single specimen is usually sensitive for detection of bacterial causes of diarrhea.
▼ For routine cultures, consider Salmonella, Salmonella, Campylobacter, and Shiga toxin or Shiga toxin producing E. coli. Consider culture for Yersinia for patients with abdominal pain consistent with mesenteric adenitis. Consider culture for Vibrio for patients with diarrhea consistent with cholera and possible exposure.
▼ Additional cultures or testing for epidemiologic/infection control purposes may be required for some pathogens. Such testing is typically performed at local department of health labs.
▼ Clostridioides (formerly Clostridium) difficile testing is recommended for patients who develop symptoms consistent with C. diff infection >3 days after admission to an inpatient facility. A single specimen is sufficient for diagnosis.
▼ Cultures of blood and other specimens are recommended for high-risk patients like those with sepsis, immunocompromised, or children younger than 3 years.
Enteric viruses: Most acute GI syndromes with diarrhea and/or vomiting are caused by viruses, usually norovirus. Viral gastroenteritis is most commonly mild and self-limited with few systemic symptoms and may be effectively treated symptomatically without a specific diagnosis. Four viral pathogens are responsible for most cases of viral gastroenteritis in the United States: norovirus, rotavirus, enteric adenoviruses, and astroviruses.
▼ Viral culture is of limited utility. Some clinical laboratories may provide viral culture testing to rule out enteric adenoviruses (serotypes 40 and 41). Antigen detection testing is available for several enteric viruses and provides reliable detection of rotavirus and enteric adenovirus in stool specimens. Molecular diagnostic tests now play an important role in the detection of enteric virus infections.
Parasites: O&P testing is not cost-effective for routine testing of patients with GI complaints, but should be considered in patients with persistent diarrhea and specific epidemiologic risks, especially travel to regions with a high endemic rate of enteric parasitic infections, diarrhea in men who have sex with men, patients with HIV infection, etc.
▼ Sensitive and specific stool antigen testing is available for Cryptosporidium, Giardia, and E. histolytica. Antigen testing may serve as cost-effective initial testing for patients who require testing to rule out parasitic infection. When other parasites are suspected, three specimens for O&P testing should be submitted, separated by at least 24 hours, over 3-6 days.
Molecular diagnostic testing: For bacterial pathogens diagnosed using amplified molecular test methods, confirmation using culture methods is recommended. Isolation of the pathogen in culture may be needed for susceptibility testing or for compliance with public health requirements.
Reporting: Many of the agents of infectious gastroenteritis are easily spread from person to person. Therefore, in addition to routine reporting to requesting clinicians, positive test results are often reported by labs to local departments of health and to infection prevention clinicians in hospitals, long-term care facilities, or other closed communities.
Consider the possibility of foodborne illness in evaluating a patient’s illness.
Realize that many, but not all, foodborne illnesses present with prominent GI tract illness. Patients may present with predominant systemic, neurologic, or other signs and symptoms.
Understand the testing required for likely pathogens. When specific diagnosis is required, ensure that appropriate specimens and cultures, or other tests, are submitted for testing.
Obtain a clinical history that may provide clues regarding the source of the illness as well as assessing the possibility of a larger outbreak.
Report suspect cases to public health officials, as appropriate. Be aware that a patient may be a part of a larger outbreak in the community.
Instruct patients about how to prevent further transmission of illness to contacts.
Infectious agents (for a discussion of infectious causes of diarrhea, see the Infectious Gastrointestinal Diseases section in this chapter and Chapter 11)
IBD (e.g., Crohn disease, UC, collagenous colitis)
Carbohydrate malabsorption (e.g., lactase or sucrase deficiency)
Foods (e.g., ethanol, caffeine, sweeteners such as sorbitol, fructose)
Drugs (e.g., antibiotics, antihypertensive, antiarrhythmic, antineoplastic, colchicine, cholestyramine; see the previous section on acute diarrhea)
Laxative abuse, factitious
Endocrine (e.g., DM, adrenal insufficiency, hyperthyroidism, hypothyroidism)
Hormone-producing tumors (e.g., gastrinoma, VIPoma, villous adenoma, medullary thyroid carcinoma, pheochromocytoma, ganglioneuroma, carcinoid tumor, mastocytosis, somatostatinoma, ectopic hormone production by lung or pancreas carcinoma)
Injury caused by radiation, ischemia, and so on
Infiltrations (e.g., scleroderma, amyloidosis, lymphoma)
Previous surgery (e.g., gastrectomy, vagotomy, intestinal resection)
Immune system disorders (e.g., systemic mastocytosis, eosinophilic gastroenteritis)
Intraluminal maldigestion (bile duct obstruction, pancreatic exocrine insufficiency)
Laboratory changes due to complications or sequelae (e.g., hemorrhage, carcinoma, electrolyte disorders, toxic megacolon with perforation).
The lower sensitivity of combined serologic tests only modestly influences pretest and posttest probability in IBD but is very useful in distinguishing Crohn disease from UC. Serial measurements are not useful and do not correlate with disease activity; titers are stable over time.
Inadequate mixing of food with bile salts and lipase (e.g., pyloroplasty, subtotal or total gastrectomy, gastrojejunostomy)
Inadequate lipolysis due to lack of lipase (e.g., CF of the pancreas, chronic pancreatitis, cancer of the pancreas or ampulla of Vater, pancreatic fistula, vagotomy)
Inadequate emulsification of fat due to lack of bile salts (e.g., obstructive jaundice, severe liver disease, bacterial overgrowth of the small intestine, disorders of the terminal ileum)
Primary absorptive defect in the small bowel
Inadequate absorptive surface due to extensive mucosal disease (e.g., regional enteritis, tumors, amyloid disease, scleroderma, irradiation)
Biochemical dysfunction of mucosal cells (e.g., celiac sprue syndrome, severe starvation, or administration of drugs such as neomycin sulfate, colchicine, or PAS)
Obstruction of mesenteric lymphatics (e.g., by lymphoma, carcinoma, intestinal TB)
Inadequate length of normal absorptive surface (e.g., surgical resection, fistula, shunt)
Miscellaneous (e.g., “blind loops” of the intestine and diverticula, Z-E syndrome, agammaglobulinemia, endocrine and metabolic disorders)
Infection (e.g., acute enteritis, tropical sprue, Whipple disease [Tropheryma whippelii]; in common variable hypogammaglobulinemia, 50-55% of patients have chronic diarrhea and malabsorption caused by a specific pathogen such as G. lamblia or overgrowth of bacteria in the small bowel)
Primary malabsorption (congenital or acquired) because of absence of specific disaccharidase in brush border of small intestine mucosa
Isolated lactase deficiency (also called milk allergy, milk intolerance, congenital familial lactose intolerance, lactase deficiency) (is most common of these defects; occurs in approximately 10% of whites and 60% of blacks; infantile type shows diarrhea, vomiting, failure to thrive, malabsorption, and so on; often appears first in adults; become asymptomatic when lactase is removed from diet)
Sucrose-isomaltose malabsorption (inherited recessive defect)
▼ Oral sucrose tolerance curve is flat, but glucose plus fructose tolerance test is normal. Occasionally, there is an associated malabsorption with increased stool fat and abnormal D-xylose tolerance test, although intestinal biopsy is normal.
▼ Hydrogen breath test after sucrose challenge.
▼ Intestinal biopsy with measurement of disaccharidase activities.
▼ Sucrose-free diet causes cessation of diarrhea.
Glucose-galactose malabsorption (inherited autosomal recessive defect that affects the kidney and intestine)
▼ Oral glucose or galactose tolerance curve is flat, but IV tolerance curves are normal.
▼ Glucosuria is common. Fructose tolerance test is normal.
▼ Resection of >50% of the colon disaccharidase activity. Lactose is most marked, but there may also be sucrose. Oral disaccharide tolerance (especially lactose) is abnormal, but intestinal histology and enzyme activity are normal.
Diffuse intestinal disease—especially celiac disease in which activity of all disaccharidases may be decreased, with later increase as the intestine becomes normal on gluten-free diet; cystic fibrosis of the pancreas, severe malnutrition, UC, severe Giardia infestation, blind loop syndrome, β-lipoprotein deficiency, and effect of drugs (e.g., colchicine, neomycin, birth control pills). Oral tolerance tests (especially lactose) are frequently abnormal, with later return to normal with gluten-free diet. Tolerance tests with monosaccharides may also be abnormal because of defect in absorption as well as digestion.
Small intestinal bacterial overgrowth (see Figure 7-4)
▼ Quantitative aerobic and anaerobic culture of aspirate of small bowel content showing >105 cfu/mL of anaerobic organisms is considered diagnostic. The utility of culture is limited, however, because it requires invasive collection; there may be sampling error due to limited regions of involvement within the small bowel, and culture techniques and interpretation are not standardized.
▼ 14C-D-xylose breath test has good specificity.
▼ Hydrogen breath tests (glucose-H2, lactulose-H2)—not recommended because of limited sensitivity and specificity.