Diarrhea and Constipation

LEARNING OBJECTIVES

• BACKGROUND

Diarrhea and constipation are very common presentations in ambulatory and urgent care centers. In the United States, up to 27% of patients have experienced constipation. Similarly, 211 to 375 million cases of diarrhea are reported annually. While there are a variety of definitions for both conditions, normal frequency of bowel movements in most adults range from three times a day to every 3 days. Even though most causes are self-limiting, both can be a symptom of a serious or life-threatening disorder. Because both disorders are so common and generally self-limiting, patients frequently try treatment with nonprescription products prior to seeking medical care. Therefore, screening patients for those more serious forms of these disorders is critical before recommending from the multitude of products available for self-care.

• DIARRHEA

Etiology

Diarrhea, defined as three or more bowel movements within a 24-hour period, can be classified as acute, persistent, and chronic. Acute diarrhea lasts for less than 14 days; persistent diarrhea lasts for more than 14 days; and patients experiencing diarrhea for more than 30 days have chronic diarrhea. Dysentery is usually defined as acute diarrhea in which subjects have frequent watery stools, often with blood and mucous. The most common cause of acute diarrhea is infection with viral pathogens, such as norovirus and rotavirus. Common bacterial causes include Shigella and Salmonella species along with Campylobacter jejuni, Clostridium difficile, and Escherichia coli species. Giardia lamblia, Entamoeba histolytica, and Cryptosporidium species are the most common protozoal causes of diarrhea. Noninfectious causes of acute diarrhea include foods and medication. Inflammatory bowel diseases such as celiac disease, microcolitis, ulcerative colitis, and Crohn’s disease all cause chronic diarrhea. Irritable bowel syndrome is a noninflammatory condition that in two versions (diarrhea predominant and mixed) cause chronic diarrhea. Lastly, diabetic gastroparesis, acquired immunodeficiency syndrome (AIDS), and post-gastrointestinal (GI) tract surgery are uncommon causes for chronic diarrhea. While most viral diarrheas are self-limiting (typically lasting 24 to 48 hours) complications such as dehydration are uncommon, except in infants and the elderly. Some bacterial diarrheas produce toxins that result in more serious complications such as toxic megacolon, intestinal perforation, sepsis, and even death. Some parasitic infections can cause persistent diarrhea and some may migrate to other internal organs such as the liver. Unfortunately, causes of diarrhea cannot be easily differentiated by symptoms alone. Therefore, when patients present to the pharmacy for OTC antidiarrheal products, a general rule applies. Any acute diarrheal illness >48 hours in duration should usually be referred for medical evaluation and treatment as indicated. Obviously, any patients with persistent or chronic diarrhea should be referred. Other causes for referral will be discussed under specific disorders.

Diagnosis

Identifying the cause of acute, persistent, and chronic diarrhea requires a careful and complete history. Patients should be questioned about recent travel, hospitalization, antibiotic use, dietary changes, or contact with others with similar symptoms. A history of bloody diarrhea is a cause for emergency referral to medical care. Some disorders, such as irritable bowel syndrome, are generally a diagnosis of exclusion. Physical examination, especially for dehydration, is also important. Examination, culture, and other studies of fecal material are important for the diagnosis of more serious causes of infectious diarrhea. Diagnostic endoscopy and some blood tests can help differentiate among chronic causes of diarrhea. See specific disorders for further details.

Common Causes of Acute Diarrhea (Table 12.1)

Viral Gastroenteritis Viral gastroenteritis can occur as diarrhea alone, but is usually accompanied by nausea and vomiting, fever, cramping abdominal pain, and malaise. Patients have a history of recent travel, exposure to a sick family member, or exposure to other sick people around the patient (nursing home, cruise ship, dormitory), or recent attendance at a potluck, picnic, or other potential sources of spoiled food or contaminated water. Physical examination is usually negative for abdominal tenderness and bowel sounds are usually hyperactive on auscultation. Most viral disease is caused by norovirus or adenovirus, but rotavirus is common in children. Norovirus and adenovirus are also called the “24-hour stomach flu” because of the short duration of symptoms (usually less than 48 hours). The disease is self-limiting in most adults and children, but like all infectious diarrheal diseases, infants under 1 year of age, adults >65 years of age, and immunocompromised patients can rarely have complications such as dehydration or more prolonged diarrhea. Rotavirus usually lasts for up to 1 week, so preventive oral rehydration is recommended because of the greater risk of dehydration.

Usually Self-Limiting Bacterial Gastroenteritis The symptoms of these generally self-limiting bacterial diarrheal diseases are very similar to their viral counterparts, but tend to last up to 7 days, increasing the risk of dehydration and necessitating preventive oral rehydration. Campylobacter jejuni, nontyphoid Salmonella species, Shigella, and Staphylococcus aureus are the most common causes. While antibiotic therapy is unnecessary in most cases, patients who are immunocompromised are at risk for systemic spread, sepsis, and death. Patients with high fever >102°F (39°C), those who appear toxic or fail to respond to supportive therapy require further workup and appropriate antibiotic therapy.

Toxigenic Bacterial Diarrhea While most Salmonella, Shigella, and Escherichia coli species produce local toxins that cause “travelers’ diarrhea,” some such as Shiga toxin–producing strains of E. coli can cause systemic effects such as hemorrhagic colitis and hemolytic-uremic syndrome, which can be fatal. Bloody stools are a hallmark sign of this dangerous pathogen. Probably the most widespread toxigenic bacterial diarrhea is Clostridium difficile or C. diff. This organism is a slow-growing anaerobic bacteria that is normally held in check by normal GI tract flora. When the patient receives a broad spectrum antibiotic, those normal GI tract flora are killed and C. difficile is permitted to grow and cause diarrhea. Symptoms include fever, watery diarrhea with unusual odor, described by some to smell like “horse manure,” and some patients will experience abdominal cramping. If untreated, bowel perforation or toxic megacolon can occur, resulting in peritoneal infections and sepsis. One of the biggest problems is that it can be spread from person to person by health care providers. Once outside the body spores can survive on inanimate objects for prolonged periods. Stomach acid generally kills most spores, so patients on acid suppression therapy with PPIs are more susceptible to C. difficile transmission. These spores are hardy and can survive even after cleaning inanimate objects. Because of its characteristics, it can cause epidemics in wards, hospitals, and nursing homes.

Parasitic Diarrhea Cryptosporidiosis, giardiasis, and amebiasis are common parasitic-induced diarrheal diseases. These have a longer incubation period and the diarrhea generally lasts more than 1 week. Cryptosporidium hominis and other animal species can cause human diarrheal disease. Also known as crypto, cryptosporidiosis is contracted through outdoor water sources as in lakes, rivers, and streams. Patients should be questioned about recent camping trips and water skiing or swimming in recreational water. Because the spores have an outer protective shell, it can be resistant to chlorine disinfection and outbreaks have occurred from city water supplies. In people with normal immune systems complications other than dehydration are uncommon. Specific diagnosis can be made by microscopic stool examination for ova and parasites and a specific antigen test. Giardia lamblia is also found in recreational water like cryptosporidium. In addition, daycare centers are also sources for the transmission of Giardia species. Fecal matter in patients with giardiasis has been described as “greasy” and has a unique foul odor. Diagnosis is also established by microscopic stool examination, culture and/or organism specific serological testing. Both diseases have effective antimicrobial treatments and other than dehydration are usually without sequelae. Entamoeba histolytica is uncommon in this country but is common in developing countries especially those with tropical climates where poor sanitation and overcrowding are more common. Travel within a month to Africa, Latin America, or India usually raises suspicion for the potential of amebiasis as a cause of diarrhea. Entamoeba histolytica can live in the intestines without causing disease in patients with normal immune systems. However, sometimes even in the face of normal immunity, it becomes invasive and causes diarrhea. It can also spread to other organs to form abscesses, most commonly in the liver, but also in the lungs and brain. Accurate microscopic examination for fecal matter microscopically requires considerable experience and expertise. Tests for antibodies to the organism are accurate in 85% of patients in the United States and are used in addition to microscopic analysis of feces.

Dietary Causes Various changes in dietary habits may also be a cause of diarrhea. Patients with lactase deficiency can have episodic bouts of diarrhea after ingesting dairy products due to osmotic effect of undigested lactose. Bloating and flatulence are also common manifestations due to the lactose fermenting coliform bacteria in the colon, which convert the lactose to carbon dioxide. Milk products are the most common cause and the incidence of symptoms is dose related. In addition, most patients can tolerate fermented cheeses such as sharp cheddar because much of the lactose is converted to lactic acid in the cheese-making process. Some public water systems have high magnesium content, so moving to a new area with higher levels may induce mild diarrhea of several weeks’ duration. Eventually, the bowel adjusts to the higher magnesium levels. Spicy food (curry, Thai, Mexican) can also induce diarrhea due to the irritant properties of the spices. Finally, bariatric surgery induces gastric dumping syndrome, which includes diarrhea, in 20% of patients.

Medication Medication is another common cause of diarrhea. Drugs can be local irritants or have pharmacological effects. Overuse of both irritant and osmotic laxatives can be a cause of acute diarrhea. Antacids typically contain high quantities of magnesium salts and even one or two large doses can cause loose stools. Broad spectrum antibiotics can alter intestinal flora, which may cause diarrhea. However, clavulanic acid is a direct irritant and accounts for the higher incidence of diarrhea with amoxicillin/clavulanic acid combination than with amoxicillin alone. Similarly, macrolides, specifically erythromycin, are motilin agonists accounting for the high incidence of diarrhea with these agents. Minerals such as magnesium and occasionally iron salts can also cause diarrhea. Many drugs currently used to treat dementia are parasympathomimetic and diarrhea is a common side effect. Side effects of some oral agents used in the treatment of type 2 diabetes mellitus causes enough diarrhea to limit adherence in many patients. Acarbose and miglitol by their mechanism of action create flatulence and diarrhea, while metformin’s irritant effects on the intestine can limit its use in certain patients. While drugs used to treat AIDS have been listed as possible frequent causes of diarrhea, the high background incidence of diarrhea in patients infected with human immunodeficiency virus (HIV) casts doubt on many of the reported rates in the literature. Finally, cancer chemotherapy routinely causes episodes of diarrhea.

Miscellaneous Causes In the early stages of intestinal obstruction, the bowel tries to clear the obstruction by increasing peristalsis, which can temporarily cause diarrhea. However, it is very short lived and quickly followed by signs of intestinal obstruction, e.g., constipation, abdominal pain, bloating, nausea, and vomiting. See Chapter 10 for more detail.

Common Causes of Chronic Diarrhea

Continuous or episodic diarrhea that lasts for more than 30 days usually indicates a systemic disease that requires referral to appropriate medical care. Other than amebiasis and C. difficile, infectious causes of diarrhea rarely last for more than 2 weeks. Medications and food intolerances while primarily acute in onset and duration can last for longer than 30 days, but patients usually relate the ingestion of medication or particular foods to the diarrheal episodes. Therefore, patients who present with chronic diarrhea syndromes should be questioned about travel to developing countries, recent hospitalization or antibiotic therapy, and changes in medication or diet in addition to investigating the causes discussed below.

Inflammatory Bowel Disease Over three-fourths of patients with inflammatory bowel disease (IBD) present with chronic intermittent or episodic diarrhea. Microcolitis, ulcerative colitis, and Crohn’s disease are the most common forms of IBD. These disorders require endoscopy and biopsy of the intestine to confirm the diagnosis. Microcolitis has been viewed in the past as a precursor or mild form of IBD. Upon endoscopy, the gross appearance of the bowel is normal, but biopsy specimens reveal lymphocytic infiltration and increases in collagen content of the colon wall. Ulcerative colitis and Crohn disease cause gross visible changes in the bowel, are associated with an increased risk of colon cancer, and in the more severe forms can be life threatening. Ulcerative colitis symptoms vary with the extent of the colon affected. Diarrhea or loose stools are common and rectal function can be compromised if the rectum is involved. An urgent need to defecate is also common. Crohn’s disease can occur throughout the GI tract, so in addition to ileocolonoscopy, other imaging studies may be required. If Crohn disease is present in the small intestine, then the patient will present with watery diarrhea because of the greater loss of fluid that cannot be compensated for by the colon. Finally, acute exacerbations may mimic appendicitis without the diarrhea due to right lower quadrant pain.

Celiac Disease Celiac disease, also known as celiac sprue or gluten-sensitive enteropathy, is a T-cell-mediated autoimmune reaction to gluten that occurs in about 1% of the population. In one study, less than 21% of patients with celiac disease had been diagnosed. It is more frequent in women than men. The disease is associated with two specific human lymphocyte antigen (HLA) types. Unfortunately, while almost all patients with celiac disease have either or both, 30% to 40% of the general population carries those HLA types. Gluten peptides such as gliadin penetrate between the cells of the epithelium to be deamidated by transglutaminase (tTG). This form binds to HLA, which activates cytotoxic T cells which damage the epithelium and produce antibodies to gliadin and tTG. Manifestations include episodic diarrhea, weight loss, and abdominal distention. Some patients have very little diarrhea but may present with iron-deficiency anemia, osteopenia, or a myriad of other non-GI symptoms. If suspected, immunoglobulin A (IgA) antitissue transglutaminase antibody levels (IgA-anti-tTG antibodies) in the serum are measured. To verify the diagnosis, patients with a positive test for IgA anti-tTG antibodies require a biopsy of the intestinal wall while ingesting gluten to confirm the diagnosis. The condition is easily controlled with a low gluten or gluten-free diet.

HIV Patients with HIV are susceptible to opportunistic infectious diarrhea due to decreased immune system function. Like with other opportunistic infections, elevations of CD4 lymphocyte count with highly active antiretroviral therapy (HAART) restore immunity and reduce the incidence of infectious diarrhea. While the most common cause is parasitic diarrhea, viral and bacterial diarrhea may also occur. In patients with suppressed immune functions, some unusual organisms, not seen in uninfected patients can be involved, including cytomegalovirus (CMV), Mycobacterium avium complex (MAC), and Isospora belli. These can cause serious infections with serious consequences. In 15% to 46% of HIV patients with diarrhea, no pathogen can be found. HIV infection by itself is associated with HIV enteropathy, which has diarrhea as a predominant symptom. Finally, HAART medications themselves can cause diarrhea.

Irritable Bowel Syndrome Irritable bowel syndrome (IBS) occurs in 10% to 15% of the population. It comes in three major types. First, constipation-dominant IBS is more common in females. Second, diarrhea-dominant IBS is more common in men. Finally, mixed-features IBS presents with short bouts of diarrhea, alternating with longer periods of constipation. Patients experiencing abdominal pain and discomfort at least 3 days a month for the past 3 months accompanied by altered bowel function should be evaluated for IBS. IBS is a diagnosis of exclusion. Serologic tests screening for celiac disease should be done in patients with mixed or diarrhea-predominant IBS. A careful history should be done, looking for alarm signs and symptoms (weight loss, anemia, blood or mucous in the stools, family history of colon cancer). In some cases, the abdominal pain/discomfort is relieved by defecation. The cause of IBS is unknown and probably multifactorial. Postinfectious and small intestine bacterial overgrowth (SIBO), are commonly discussed as potential causes.

• BLOATING/ABDOMINAL DISTENTION

Bloating, abdominal distension, and a sense of fullness are common symptoms that can occur alone or in conjunction with other GI symptoms. They are frequently associated with inflammatory bowel diseases, constipation, food intolerances such as celiac disease and lactase deficiency, and intestinal obstruction. Diabetic gastroparesis is a specific entity that deserves special attention because of pharmacists’ frequent involvement in the management of diabetes.

Diabetic Gastroparesis

When managing patients with diabetes, one must screen for a late complication of diabetic neuropathy which is known as diabetic gastroparesis. Patients who develop gastroparesis already have peripheral diabetic neuropathy (numbness, tingling, and/or pain in the feet). The neuropathy then extends to the autonomic nervous system with resultant delay in stomach and bowel emptying. Symptoms include early fullness while eating, bloating, belching, abdominal distention, heartburn, nausea, vomiting, constipation, and in the early stages as the bowel tries to overcome the lack of autonomic control by other physiological means, brief periods of diarrhea.

• CONSTIPATION

Normal frequency of bowel movements ranges from three times a day to every 3 days. Intervals between bowel movement of equal to or greater than every 4 days is considered constipation. Patients over 70 years of age may consider not just frequency of bowel movement, but also straining during defecation and difficulty or incomplete evacuation to be symptoms of constipation. Fecal matter is usually soft, formed, and brown in color due to stercobilin, derived from bilirubin. Color can also vary with the type of food. Red meat darkens stool due to breakdown of heme protein and iron release. Iron tablets can impart a dark green or green black color and a large amount of red chili peppers can color the stool red. Pale or white stools may indicate common bile duct obstruction such as caused by gallbladder disease, or cancer, and may be accompanied by jaundice. Fecal volume varies by the amount of food ingested and the amount of fiber ingested. Men tend to produce larger fecal volumes probably due to greater food intake. Culture and generations can also alter patient’s perceptions of “normal.” Historically, bowel movements have been viewed as cleansing the body of toxins, so regular daily bowel movements were a sign of health. For that reason, patients over 70 years of age today tend to worry if they do not have a bowel movement every day. “An apple (fiber) a day keeps the doctor away” is a saying that supports that belief. These beliefs have made several older generations frequent laxative users. Those beliefs are declining rapidly with younger generations and subsequently laxative use is declining.

Acute or Rapid Onset Constipation

In the elderly, intestinal obstruction can cause sudden onset or rapidly progressive constipation, which is usually accompanied by associated symptoms such as abdominal pain, nausea, vomiting, and abdominal distention. Similarly, constipation can be a sign of colon cancer. Recent changes in medication such as opioid analgesics can be marked by the sudden appearance of constipation. Stimulation of the protective peritoneal reflex by recent abdominal surgery or inflammation of the intestine due to appendicitis or trauma may induce the effect, which can result in sudden constipation. One of the reasons post-abdominal surgery patients are encouraged to walk early and often is that walking internally indicates normality and helps disengage the reflex more quickly.

Chronic or Intermittent Constipation

There are multiple causes of chronic or intermittent constipation. Medication is a common cause. Opiates, drugs with anticholinergic properties, and calcium channel blockers are prescription medications commonly associated with constipation. Nonprescription drugs such as calcium salts taken for the prevention of osteoporosis and vitamin/mineral preparations are also common causes of constipation. Dehydration is also a common cause especially in patients who move to or visit areas of low humidity such as the Southwestern United States. During pregnancy, issues like calcium supplementation, using maternal fluid to maintain fetal well-being, and physical interference by the growing fetus can combine to make constipation a problem. Females over 50, should have thyroid function tests done since hypothyroidism, a cause of constipation, is more frequent in that population. Similarly, in older females the trauma of multiple childbirths may lead to constipation due to pelvic floor dysfunction. Dietary changes, such decreased fiber or fluid intake, and insufficient exercise can also negatively impact bowel movement frequency or consistency. Less common but potentially more serious is diabetic gastroparesis. Irritable bowel syndrome with constipation should be ruled out.

Patients should be asked about the frequency, color, and consistency. Hard stools may indicate dehydration. Changes in medication, eating, and drinking habits should be queried. Physical examination of the abdomen should be conducted looking for previous surgical scars, abdominal distension, masses, and alarm bowel sounds (high-pitched tinkling sounds found in intestinal obstruction). Associated symptoms are important keys to referral. In patients with constipation plus severe abdominal pain and abdominal distention, and who look sick, intestinal obstruction should be investigated. In patients with long-standing diabetes, constipation accompanied by bloating, belching, and early satiety may indicate diabetic gastroparesis. Elderly patients with cold intolerance, fatigue, loss of energy, and hair loss, plus constipation may be hypothyroid. Patients with any of the above alarm symptoms, failure of laxatives to relieve constipation, potential for drug- or surgery-induced disease, or constipation of 7 or more days duration should be referred for further evaluation.

• KEY REFERENCES

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CASE 12.1

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