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The use of gastrointestinal drugs during pregnancy and lactation. This increased activity will likely reduce the chances of progressing with a normal term delivery unless medical therapy is intensified. As mentioned above, important differences exist in nearly all respects between the human and rabbit appendixes Dasso et al. However, for patients over 55, when symptoms persist despite Helicobacter pylori H. Endoscopic surveillance for gastric intestinal metaplasia has not been extensively studied in the U.
General Information About Gastrointestinal Carcinoid Tumors
Given the common symptoms of nausea, vomiting, and dyspepsia that occur, it is not surprising that the upper gastrointestinal tract is affected by pregnancy. The enlarging uterus displaces the stomach and may anatomically alter the pressure gradient between the abdomen and thorax. Increased pressure within the stomach allows for reflux of the gastric contents into the esophagus, which lies in the negative pressure of the intrathoracic cavity.
The pressure gradient may even accentuate a hiatal hernia contributing to gastroesophageal reflux. Contributing to the increased incidence of gastroesophageal reflux are the motility changes that also occur with pregnancy. Lower esophageal sphincter tone is decreased secondary to increased progesterone levels and a decrease in the peptide hormone motilin. Gastric emptying has been partially studied in pregnancy. Nondyspeptic asymptomatic women have normal solid gastric emptying in early pregnancy, and gastric emptying does not lengthen in the third trimester or postpartum.
Studies using gastric ultrasound and acetaminophen clearance in asymptomatic healthy pregnant women at term show normal gastric emptying. Although alterations in the physiology of the upper gastrointestinal tract increase reflux symptoms, it has been shown that symptoms of peptic ulcer disease may actually decrease. The small intestine exhibits decreased motility during pregnancy. This increased transit time is related to elevations in progesterone levels during normal pregnancy and may contribute to the increased symptoms of constipation in late pregnancy.
The many changes that pregnancy exerts on the colon lead to increased symptoms of constipation. The colon may be subject to the same decreases in motility that affect the other portions of the gastrointestinal tract. Progesterone has been shown to alter colonic transit time in rats. The functional changes that occur with the enlarging uterus may mechanically limit colonic emptying and probably is the main reason for symptomatic constipation in late term.
There is also a significant increase in water and sodium absorption secondary to the increased aldosterone levels during pregnancy, leading to reduced stool volume and prolonged colonic transit time. There is an increased risk of gallstone formation in pregnancy. The risk of gallstones is related to parity. Two pregnancies double the risk, and four quadruples the risk.
Bile stasis within the gallbladder leading to the supersaturation of cholesterol and the nucleation of cholesterol crystals are important factors in the formation of gallstones. Pregnancy has been shown to effect biliary motility and cholesterol secretion.
The fasting volume and residual volume in the gallbladder are increased during pregnancy, promoting bile stasis. These effects are most likely secondary to high levels of progesterone during pregnancy. Although estrogens have not been shown to alter biliary motility, they do have a role in promoting gallstone disease. In addition, pregnancy induces a down-regulation of contractile G proteins in gallbladder muscle, resulting in impaired gallbladder emptying.
Nausea and vomiting are common in the first trimester of pregnancy and may be the first sign of pregnancy. It usually peaks at approximately weeks 10 to 15 of gestation and resolves at approximately week In general, first trimester vomiting is not deleterious to mother or fetus. When vomiting is prolonged, intractable, and interferes with nutrition and fluid intake, it is termed hyperemesis gravidarum HG. Vomiting may be severe enough to cause weight loss, electrolyte abnormalities, and acid—base disturbances requiring hospitalization.
These disorders must not be overlooked because delay in diagnosis could be disastrous. The pathogenesis of nausea and vomiting in pregnancy is still undetermined, although many believe the hormonal changes that occur during pregnancy are most likely involved. However, nausea and vomiting are more prevalent in the first trimester when estrogen levels are lower compared with the third trimester when estrogen levels are higher. Progesterone has also been implicated in slowing transit time in the bowel.
Another hormone, human chorionic gonadotropin HCG , which is present in its highest concentrations during the first trimester, may be a more likely cause. The levels of HCG are increased during molar pregnancies, in which nausea and vomiting are common. There is, however, no clear relationship between levels of HCG in molar pregnancy and the presence of vomiting.
The relationship between Helicobacter pylori infection and hyperemesis has been extensively investigated in pregnancy, and results are inconclusive. Although some studies clearly indicate an increased seroprevalence of antibodies to H. The spread of this infection is clearly related to such factors as local levels of hygiene and public health support as well as socioeconomic status.
These factors and the lack of correlation of infection with severity, duration, or type of symptoms make the relationship between H. The treatment of nausea and vomiting of pregnancy depends on the severity of the symptoms and ranges from changes in dietary habits to hospitalization with hyperalimentation and fluid resuscitation. For mild nausea and vomiting, a change in diet may be all that is needed. Conventionally, antiemetics have been avoided in the first trimester.
Because of its relative safety, pyridoxine vitamin B 6 has been frequently used. Vitamin B 6 administered at a dose of 25 mg orally every 8 hours improved severe nausea and decreased vomiting significantly in a double-blind placebo-controlled study. Ginger and acupressure may be effective on occasion as well. Once dehydration is corrected, the patient should be started on small frequent water feedings with a gradual advancement to frequent small volume carbohydrate meals.
If symptoms are intractable, phenothiazines or metoclopramide may be used, because they have been shown to be safe in the second and third trimesters. Antihistamines such as promethazine, centrally acting serotonin blocking agents such as ondansetron, granisetron, and dolasetron are pregnancy category B agents and may be helpful and safe in pregnancy.
Continuous intravenous droperidol and bolus diphenhydramine have been reported to be beneficial. A short course of methylprednisolone at 16 mg three times daily for 2 weeks has been successful in terminating vomiting. It is the aggressive treatment of these disturbances that has greatly affected the decrease in mortality of hyperemesis gravidarum. Today, HG is rarely a cause of maternal mortality, compared with the s when mortality was approximately per million. Prolonged periods of hospitalization with total parenteral nutrition may be required when treatment with standard crystalloid solutions fail to maintain a normal metabolic state.
Psychosocial factors may play a role in the pathogenesis of hyperemesis gravidarum, and many have advocated various psychotherapeutic strategies with some success hypnotherapy, biofeedback.
The risk of symptomatic gastroesophageal reflux is related to increasing gestational age, presence of heartburn prepartum, and parity. Endoscopically, the esophagus may appear normal in a patient with severe pyrosis; this disparity has been explained by subtle histologic changes, perhaps allowing exposure of submucosal nerves to irritating gastric contents.
The pathophysiology of gastroesophageal reflux is a complex interplay between the lower esophageal sphincter LES , the esophagogastric angle, and the esophageal clearance of acid.
LES pressure decreases and remains low during pregnancy, reaching its nadir at 36 weeks, and returning to normal after delivery. The LES response to physiologic stimuli is also affected by pregnancy, and hormonal changes may be very important. The LES responses to stimulation by acetylcholine and gastrin are blunted by estrogen and progesterone in the experimental animal, 32 and the administration of estrogen and progesterone to normal menstruating women significantly decreases LES pressure.
Progesterone seems to mediate LES relaxation, but estrogen is a necessary primer. Although the expanding uterus may play some role in displacing or altering the esophagogastric angle, the role for increased abdominal pressure as an important factor in promoting reflux has been refuted. Studies in men with cirrhosis with tense ascites show that increased abdominal pressure actually causes a compensatory increase in LES pressure.
Reflux symptoms are limited to the duration of pregnancy and have no adverse effect on the mother or fetus. Complications caused by gastroesophageal reflux such as peptic stricture or bleeding are rare during and after pregnancy.
Although subtle histologic changes may be noted on esophageal biopsy, visible mucosal damage is rarely noted on endoscopy. Diagnosis of gastroesophageal reflux is based on clinical symptoms and endoscopy, although rarely necessary, is the diagnostic procedure of choice.
The safety of endoscopy is discussed more fully in a subsequent section of this chapter. Lifestyle modifications certainly have a role to play in treating gastroesophageal reflux. Dietary measures such as limiting oral intake within 3 hours of bedtime, increasing frequency and reducing volume of meals, reducing dietary fat, and eliminating caffeine, chocolate, and mints are measures that have some effect in controlling the symptoms of gastroesophageal reflux.
Alcohol and smoking should be eliminated. Elevation of the head of the bed and avoiding prolonged recumbency are additional lifestyle measures of some benefit.
If lifestyle modifications do not control symptoms, the next step would be the use of systemic oral antacids. These agents are safe in pregnancy and should be used in appropriate dosing e. Potential adverse effects are rare but do include reduced iron absorption, sodium and fluid retention, and the potential for metabolic alkalosis in the mother and fetus. Antacids containing sodium bicarbonate should be avoided because they could cause maternal or fetal metabolic alkalosis and fluid overload.
Sucralfate is not absorbed and appears to be quite safe in pregnancy, without any teratogenic or impaired reproductive effects in rodents, and has successfully controlled symptoms of gastroesophageal reflux in pregnant patients.
Histamine H 2 -receptor antagonists are the mainstay of treatment in gastroesophageal reflux in pregnant patients whose symptoms do not respond to lifestyle measures or oral antacids. No increase in congenital malformations was noted in a cohort of pregnant women who used H 2 -receptor antagonists during the first trimester of pregnancy.
H 2 -receptor antagonists do cross the placenta and are excreted in breast milk 40 , 41 but are probably safe to use during breastfeeding. Studies in rodents showed some antiandrogenic activity of cimetidine to male offspring. This effect was not seen with ranitidine. Nizatidine was associated with growth retardation in rat pups reared by lactating rats administered nizatidine. Proton pump inhibitors are very potent suppressors of gastric acid and have made a major impact in the treatment and healing of severe peptic esophagitis, but their use in pregnancy has not been as extensive as H 2 -receptor antagonists.
Omeprazole has some potential for teratogenicity, causing dose-related embryo toxicity used in doses 17—times the usual human dose! Many patients with gastroesophageal reflux will respond to standard antisecretory doses of H 2 -receptor antagonists, but some patients will continue to experience symptoms unless acid suppression is very substantial.
Acid suppression approaching the level achieved with proton pump inhibition can be achieved by increasing the dosage of an agent such as ranitidine e. Continued use of H2-receptor antagonists may induce tachyphylaxis and require progressive escalation of dosage to maintain therapeutic effect. Promotility agents may have a limited role to play in symptomatic gastroesophageal reflux and could be added if acid suppression alone does not work.
Metoclopramide does cross the placenta but does not harm the fetus 47 and probably can be used during pregnancy, although its therapeutic efficacy is modest. Peptic ulcer disease is no more common in pregnancy than in other normal populations and older epidemiologic studies suggest a decreased incidence in pregnancy. It is also believed that increased levels of histaminase produced by the placenta also contribute to the decreased acid secretion.
Gastric secretory data are scarce, however, and Van Thiel reported no difference in basal and peak acid production at various stages of pregnancy in four women with a previous history of peptic ulcer.
Now that it is clear that H. Overall, however, the incidence of H. This can be performed noninvasively through serologic testing, and stool antigen analysis, as well as through histology and rapid urease testing during endoscopy. Urea breath testing involves modest radiation risk and probably should be avoided in pregnancy.
Pregnant patients with peptic ulcer who test positive for H. These regimens consist of triple and double antibiotics in combination with proton pump inhibitors. Given the perceived risks of treatment eradication therapy probably should be postponed until after delivery.
Maintenance H 2 receptor antagonists or proton pump inhibitors will prevent recurrent ulcer in most patients until eradication therapy can be performed postpartum. If ulcer disease is complicated or unresponsive to antisecretory therapy, metronidazole and amoxicillin have been shown to be safe in pregnancy and are categorized as class B drugs in pregnancy and can be combined with a proton pump inhibitor for a day course to eradicate H. Other antibiotics effective in eradicating H.
Bismuth, a category C drug has been associated with fetal toxicity in animals and may increase the risk of closure of the fetal ductus arteriosus. The mainstay of treatment is lifestyle modification and avoidance of medical intervention. If the patient is infected with H. Dyspeptic symptoms may be caused by essential dyspepsia, peptic ulcer disease, or gastroesophageal reflux.
Aggressive diagnostic testing in uncomplicated cases is unwarranted and empiric therapy to control symptoms is the appropriate approach. As these symptoms may be difficult to differentiate from gastroesophageal reflux much of the same advice is given small meals, no late-night snacks, and avoidance of fatty foods, acidic citrus drinks, caffeine, chocolate.
The comments regarding treatment modalities in gastroesophageal reflux in pregnancy noted earlier apply to the treatment of peptic ulcer and dyspepsia as well. If symptoms fail to resolve with these conservative measures, antacids may be used safely.
Sucralfate, a sulfated polysaccharide complex with aluminum oxide is safe and effective in pregnancy. It binds to the proteinaceous surface of an ulcer. If symptoms persist H 2 blockers can be used. All H 2 receptor blockers cimetidine, ranitidine, famotidine, nizatidine are rated as category B drugs during pregnancy. Studies in rats suggest that cimetidine has some potential for fetal antiandrogenic effects. Five are available omeprazole, lansoprazole, pantoprazole, rabeprazole, and esomeprazole and all are category B in pregnancy except for omeprazole, which is rated C.
Misoprostol, a synthetic prostaglandin E 1 analogue with antisecretory and cytoprotective properties, is category X and is an abortifacient. If the symptoms are refractory to the aforementioned interventions, then upper endoscopy is warranted to establish the diagnosis and rule out complications.
Complications of PUD such as perforation and hemorrhage should be treated in the same fashion as those in a nonpregnant patient, because delays in diagnosis and treatment can pose an increased risk to the mother and fetus Fig. Algorithm for evaluation of dyspepsia. As noted in the section dealing with peptic ulcer, symptomatic peptic ulcer is rare in pregnancy and gastrointestinal bleeding from ulcer is also rare. Many diseases responsible for overt, symptomatic gastrointestinal bleeding in the general population e.
The most common form of upper gastrointestinal bleeding in the pregnant patient is the Mallory—Weiss syndrome. The most common cause of lower gastrointestinal bleeding is hemorrhoids.
Hemorrhoids may be caused by a prolapse of anal canal cushions, which are rich in blood vessels. The increased circulating blood volume, increased abdominal pressure, and venous stasis caused by the enlarging uterus during pregnancy are contributing factors.
It is not surprising that bleeding may occur with straining at defecation. Coupled with the frequent constipation of late pregnancy, this can be quite distressing. External hemorrhoids occur distal to the anal dentate line and rarely bleed unless thrombosed. Internal hemorrhoids are classified by degree: Inflammatory bowel disease, particularly ulcerative colitis, account for lower gastrointestinal bleeding in some women. Patients with mild ulcerative colitis often pass blood and mucous with normal stools.
As the colitis becomes more severe and spreads proximally, diarrhea occurs. Profuse hemorrhage is one of the complications of ulcerative or Crohn's colitis and may lead to emergency colectomy.
Regional enteritis of the small intestine rarely causes profuse hemorrhage but may cause iron deficiency anemia. In young people, hemorrhage from a Meckel's diverticulum in the small intestine can occur and may be diagnosed with a technetium-labeled nuclear scan if the bleeding is severe enough to justify this modest radiation exposure. The term inflammatory bowel disease IBD is frequently used to describe two entities, ulcerative colitis and Crohn's disease.
Ulcerative colitis is a chronic recurrent disease that is characterized by diffuse mucosal inflammation occurring in the colon. The disease usually begins in the rectum and spreads continuously throughout the colon. Crohn's disease is also a chronic recurrent inflammatory disease, which may affect the whole alimentary canal.
The peak age of onset for both is during the childbearing years ranging from approximately 15 to 30 years of age. Questions have been raised about infertility in women with IBD.
The role that fear plays cannot be discounted, because many patients are erroneously discouraged from becoming pregnant. The outcome of pregnancy in inflammatory bowel disease, as well as the influence of pregnancy on inflammatory bowel disease, has been extensively studied. Many large studies have shown that most women with ulcerative colitis and Crohn's disease will proceed to have normal, full-term pregnancies.
Some patients do face a higher risk of an adverse pregnancy outcome. Previous tertiary referral based studies on inflammatory bowel disease have suggested a higher rate of pre-term birth and low birth weight when inflammatory bowel disease was active at conception or during the course of the pregnancy.
When examined in a community population, there is no association between disease activity and adverse outcome. Although there is no clear evidence to show what constitutes an appropriately safe period of quiescent IBD before planned conception, most experienced physicians suggest that 3 months of inactive disease is good rule of thumb. Severe exacerbations that require surgery or intensification of medical therapy will lead to higher rates of fetal mortality.
It is for these reasons that patients should be counseled to attempt conception during remission. The main priority is to maintain IBD in remission.
A healthy mother will have a straightforward pregnancy and a healthy baby. Medical regimens that control and maintain IBD are for the most part safe in pregnancy and postpartum and should be continued without fear. Pregnant women will paradoxically stop medications that have kept them in remission. Physicians frequently will look at immunomodulators such as azathioprine and 6-mercaptopurine and their FDA D labeling and counsel their patients to stop although the evidence in the transplant and inflammatory bowel disease population suggests that their use in pregnancy is safe.
The effect of pregnancy on the course of IBD has also been well documented. Patients with inactive ulcerative colitis will most likely remain asymptomatic and proceed with a normal pregnancy.
This increased activity will likely reduce the chances of progressing with a normal term delivery unless medical therapy is intensified. Active Crohn's disease will remain active throughout pregnancy and may worsen, also decreasing the chances of a normal pregnancy. As stated previously, it is important for patients to plan their pregnancy during disease remission. The treatment of IBD should be broken down into treatment of quiescent disease and active disease. The critical factor needed to insure a good outcome for mother and fetus is maintenance of remission at conception and during pregnancy.
Active disease, not the medications used to treat IBD, poses the greatest threat. Medications that maintain IBD remission should be continued. A number of medicines for IBD have been given safely in pregnancy and this makes the decision to treat IBD quite palatable. All aminosalicylates sulfasalazine, mesalamine, balsalazide are pregnancy category B except olsalazine which is category C.
Sulfasalazine is composed of 5-aminosalicylic acid an azo-bonded to sulfapyridine. Breast feeding is also low risk with these agents and sulfasalazine, unlike other sulfonamides, does not displace bilirubin or cause kernicterus in the infant. Sulfasalazine has an excellent safety record in pregnancy. Supplemental folic acid 2 mg daily should be administered because sulfasalazine inhibits folate conjugase, interfering with folate absorption.
Mesalamine has been shown to be safe during pregnancy. Diav-Citrin reported on a prospective, controlled cohort study of pregnant women exposed to mesalamine during pregnancy without significant differences in rates of live births, miscarriages, terminations, or fetal distress. Corticosteroids are pregnancy category C. Although they are associated with a slightly increased risk of oral cleft in the newborn, a prospective study of women who received corticosteroids during the first trimester did not reveal an increased rate of any anomaly.
Patients in remission should have the dose tapered to the lowest possible dose that allows maintenance of inactivity. There are no clear data linking azathioprine or 6-MP with fetal abnormalities. If azathioprine is currently being used to maintain remission it might be prudent to stop it and alter therapy before conception.
If this is not possible, azathioprine can be continued, but the risks and benefits have to be discussed with the patient. Recent observations have raised the issue of the effects of immunomodulator therapy in fathers and the outcome of pregnancy. In a small and retrospective analysis, two spontaneous abortions and two congenital anomalies were noted in a group of 13 pregnancies when the father had used 6-MP within 3 months of conception.
Cyclosporine is generally considered to be dangerous for use during pregnancy; however, there have been recent case reports documenting its safety and efficacy in pregnancy.
The literature regarding its use in pregnancy comes mainly from the transplant literature in which there seems to be a low rate of neonatal complications. Other potent immunomodulators including tacrolimus and mycophenolate mofetil have been used in refractory IBD but there are no data on safety in pregnancy. The data on their use in pregnant transplant patients are favorable. Biologic agents such as the mouse chimeric antibody to tumor necrosis factor, infliximab have been very beneficial in Crohn's disease and ulcerative colitis.
Another tumor necrosis factor antibody, adalimumab has been released for use in Crohn's disease. Both agents are pregnancy category B. Pregnancy and fetal outcomes have been favorable with infliximab treatment during pregnancy.
Case reports suggest that breast feeding is safe with infliximab, but the data is limited. Adalimumab, a human recombinant monoclonal antibody to tumor necrosis factor has demonstrated safety and efficacy in Crohn's disease.
Its use in pregnancy is limited and restricted to several successful case reports. Metronidazole and ciprofloxacin are the most frequently used antibiotics in IBD. Short courses of these drugs are probably safe in pregnancy. Most exacerbations can be managed safely with careful monitoring, hydration, nutritional support, and medication. In mild or moderate ulcerative colitis, aminosalicylates, orally or rectally, can be used safely.
If the disease does not respond, or if disease is severe, corticosteroids should be used. Depending on the distribution of the disease, either oral or rectal corticosteroid preparations can be used. If the disease does not respond to oral steroids, or becomes severe, hospitalization is required.
All oral intake should be discontinued and aggressive hydration should be instituted. Steroids should be administered intravenously in four divided doses of solumedrol 60 mg. Plain films of the abdomen should be obtained to rule out toxic megacolon, and the surgical service should be consulted.
If disease does not respond, cyclosporine therapy may be attempted to avoid surgery. Surgery is associated with a significant risk of spontaneous abortion; however, in severe disease it may be the only option for maternal survival. Crohn's disease is also initially managed with supportive care.
Treatment for mild, moderate, and severe disease is similar to the aforementioned treatment for ulcerative colitis. There are some novel treatment options for disease that does not respond to antiinflammatory medications.
Elemental diets have been shown to be as effective as steroids in mild-to-moderate disease. Teahon reported successful treatment of four pregnant patients with active Crohn's disease. All four responded to treatment and delivered healthy infants.
Cesarean section should be considered for patients with active perianal disease, because some data suggest vaginal delivery, and episiotomy may exacerbate perianal disease and prevent healing. Endoscopic evaluations are safe in pregnancy and are indicated in the evaluation of IBD in pregnancy. Flexible sigmoidoscopy is usually all that is required and does not put the fetus at risk secondary to the need for sedation. If a full colonoscopy is required conscious sedation seems to be safe, although this is poorly studied.
It does seem that meperidine is safer than both diazepam and midazolam. Intestinal obstruction is relatively rare in pregnancy but is the second most common nonobstetric abdominal emergency. The incidence is 1 in pregnancies.
The peak incidence of bowel obstruction occurs in the eighth month when the fetal head descends in to the pelvis, but it may also occur during delivery or the puerperium when a sudden change in uterine size may shift abdominal anatomic relationships.
There is no relation between maternal age or parity and the risk of intestinal obstruction. Bowel obstruction must be considered in any patient with sever emesis, particularly when associated with cramping abdominal pain, distension, and the inability to defecate or pass flatus. Partial intestinal obstruction may cause intermittent cramping, which is relieved by borborygmi, passing flatus, or defecation.
The diagnosis is confirmed by plain abdominal film demonstrating distended bowel loops and air-fluid levels, often with uneven fluid levels in a single loop as a result of pressure. Despite the concern regarding x-rays during pregnancy, the identification of intestinal obstruction needs to be prompt and effective and radiological studies should not be delayed.
Colonic volvulus has been successfully treated with colonoscopy. Colonic pseudo-obstruction or Ogilivie's syndrome is adynamic ileus of the colon and may occur after delivery. Endoscopic colonic decompression may be needed if the colon dilates to more than 12 cm. Intravenous infusion of 2 mg of neostigmine results in prompt decompression in patients not responding to conservative measures, but should be restricted to use in the post-partum period. The most common gastrointestinal disorder is clearly irritable bowel syndrome.
The diagnosis of irritable bowel syndrome IBS depends on the presence of specific symptoms. The Rome II criteria have a high accuracy in diagnosing this disorder.
The presence of abdominal discomfort for 12 weeks or longer, which need not be continuous plus two of three of the following: Other manifestations included abdominal bloating, passage of rectal mucus, sense of incomplete evacuation, and temporary resolution of pain with bowel movements.
Fever, weight loss, and rectal bleeding are not manifestations of this disorder. There is often a close correlation with stress and symptoms are frequently exacerbated during menses. The pathophysiology of IBS is not clear, but disturbances in colonic motility and alteration in colonic emptying, although inconsistently related to symptoms, are noted frequently. Using positron emission tomography PET , patients with IBS demonstrate abnormal activation in various regions of the brain.
IBS rarely begins during pregnancy and typically has been present for years. Functional bowel disease usually improves during pregnancy, especially after the first trimester.
In those patients with dyspepsia and nausea, the hormonal changes creating nausea in pregnancy may trigger worsening of symptoms and even possibly lead to a picture resembling hyperemesis gravidarum. Abdominal bloating and constipation are frequent symptoms during pregnancy. The physiologic changes responsible for these symptoms are discussed in the section on gastrointestinal physiology.
The average frequency of bowel movements ranges from three times per day to once every three days. Unfortunately, common usage defines constipation as infrequent bowel movements; thus, patients become concerned when their bowel fails to move after a certain number of days.
A change in bowel habit often occurs in pregnancy and is usually within the accepted limits of normal. Distinction should be made between irritable bowel syndrome and functional constipation of pregnancy. Constipation related to irritable bowel syndrome is accompanied by a sense of abdominal distension, bloating, and lower abdominal pain.
Functional constipation relates to a number of factors, including both qualitative and quantitative changes in activity and diet.
The pregnant woman may rest more and eat less because of the pressure of the expanding fetus within the abdomen. In addition, there is a certain amount of pressure against the colon, particularly toward the end of pregnancy, with decreased ability to exert intraabdominal pressure in defecation. The concern over a change in bowel habit may lead to the use of laxatives, which could create problems for both IBS and functional constipation. Colonic contractions and spasm may be accentuated by the irritating effect of laxatives.
The best approach is the increased use of dietary fiber by regular use of bread, fruits, vegetables, and fruit juice. Nonstarch polysaccharide bulking agents such as psyllium, methylcellulose, or sterculia are quite safe in pregnancy because no systemic absorption occurs. Stool softeners containing docusate are safe but probably less effective than the bulking agents. Osmotic laxatives are recommended for constipation-predominant IBS patients whose symptoms do not respond to fiber.
Osmotic laxatives include milk of magnesia, poorly absorbable sugars such as lactulose and sorbitol, and polyethylene glycol in powdered form. Stimulant laxatives should be reserved for relatively intractable cases of constipation. Of the anthraquinone laxative, senna is safe and effective in pregnancy but is excreted in breast mil and should be used with caution during lactation.
Mineral oil has the potential for interfering with maternal absorption of fat-soluble vitamins, leading to coagulopathy in the neonate. Sodium phosphate may promote salt retention in the mother but probably is safe to use. Magnesium-based laxatives and bisacodyl, as well as saline-based enemas, are safe but may lead to salt and water retention and should not be used in the long-term, because dependency may lead to colonic atony and inertia.
Phenolphthalein was recently removed from the market, and bisacodyl is the only diphenylmethane laxative available and can be used orally or as a suppository. Glycerin suppositories are safe but should be used sparingly. Antispasmodic drugs are the most commonly prescribed medications for IBS.
Dicyclomine is rated category B and hyoscyamine is category C. Their use should be restricted for patients with refractory pain not responding to other measures. A metaanalysis of multiple randomized, controlled trials of peppermint oil reported some therapeutic success, 86 and this agent seems safe in pregnancy.
There are no epidemiologic data on diarrhea in pregnancy. It seems that pregnancy predisposes to constipation and not diarrhea. Diarrhea may occur in pregnant women and the differential diagnosis is probably identical to that in nonpregnant women.
Diarrhea may be a component of IBS. Peripherally-acting opioid agents such as loperamide are the agents of choice to treat noninfectious diarrhea in pregnancy. Loperamide is safe, 87 but diphenoxylate with atropine is associated with fetal anomalies in animals and is rated category C. Infectious diarrhea should be investigated with appropriate stool cultures.
Yeast infection in the mouth thrush is characterized by a thick white coating of the tongue and throat along with pain and burning. If the infection extends further, candida esophagitis results, which may cause intestinal bleeding, heartburn, and difficulty swallowing. Oral candida can readily be diagnosed by physical examination, but candida esophagitis will usually require endoscopy for accurate diagnosis. Treatment is highly effective and is focused on the eradication of the yeast infection with antifungal medications such as nystatin Mycostatin , ketocanazole Nizoral , or flucanazole Diflucan.
The Small Intestine in Diabetes In some cases of longstanding diabetes, the enteric nerves supplying the small intestine may be affected, leading to abnormal motility, secretion, or absorption. This leads to symptoms such as central abdominal pain, bloating, and diarrhea. Delayed emptying and stagnation of fluids in the small intestine may lead to bacterial overgrowth syndromes, resulting in diarrhea and abdominal pain.
Metclopropamide and cisapride may help to accelerate the passage of fluids through the small intestine, whereas broad-spectrum antibiotics will decrease bacterial levels. Diagnosis can be quite difficult and may require small-bowel intubation for quantitative small-bowel bacterial cultures.
Breath hydrogen testing and the [ 14 C]- D -xylose test may be helpful in diagnosing bacterial overgrowth as well.
All of these tests are somewhat cumbersome, and an empiric trial of antibiotics is often the most efficient means of diagnosing and treating this condition. Numerous antibiotic regimens have been shown to be effective, including 5- to day courses of tetracycline, ciprofloxin, amoxacillin, or tetracycline. A short course may provide prolonged relief, but typically, additional courses of antibiotics are required when symptoms recur in several weeks or months. At times, enteric neuropathy may lead to a chronic abdominal pain syndrome similar to the pain of peripheral neuropathy in the feet.
This condition may be very difficult to treat but will sometimes respond to pain medications and tricyclic antidepressant medications, such as amitryptilline Elavil. Unfortunately, narcotic addiction may be common in patients with chronic painful enteric neuropathy. Individuals with diabetes also have an increased risk of celiac sprue. In this condition, an allergy to wheat gluten develops, leading to inflammation and thinning of the mucosa of the small intestine. Why this association occurs is not clear.
However, sprue may lead to diarrhea, weight loss, and malabsorption of food. This condition responds well to a gluten-free diet, but patients may have difficulty adhering to such a diet. Diagnosis can be made with endoscopic biopsy of the small intestine or with serological evaluation for anti-endomysial and anti-gliadin antibodies.
The Colon in Diabetes Limited information is available regarding the effects of diabetes on the large intestine. We do know that enteric neuropathy may affect the nerves innervating the colon, leading to a decrease in colon motility and constipation. Anatomic abnormalities of the colon, such as structure, tumor, or diverticulitis, should be excluded with a barium enema or colonoscopy. Fiber supplementation with bran or psyllium products, as well as a high-fiber diet, increases the water content of the bowel movement and may relieve constipation.
Mild laxatives and stool softeners will often help as well. In addition, cisapride accelerates colonic movement and may increase the frequency of bowel movements. This may be related to problems in the small bowel or colon. Abnormally rapid transit of fluids may occur in the colon, leading to increased stool frequency and urgency.
In addition, abnormalities in the absorption and secretion of colonic fluid may develop, leading to increased stool volume, frequency, and water content. Diabetic diarrhea is a syndrome of unexplained persistent diarrhea in individuals with a longstanding history of diabetes.
This may be due to autonomic neuropathy leading to abnormal motility and secretion of fluid in the colon. There are also a multitude of intestinal problems that are not unique to people with diabetes but that can cause diarrhea. The most common is the irritable bowel syndrome. The workup and treatment of diarrhea is similar in patients with or without diabetes. If the basic medical evaluation of diarrhea is nondiagnostic, which it frequently is, then treatment is tailored toward providing symptomatic care with antidiarrheal agents such as diphenoxylate Lomotil or loperamide Immodium.
Fiber supplementation with bran, Citrucel, Metamucil, or high-fiber foods may also thicken the consistency of the bowel movement and decrease watery diarrhea. More recently, the 5HT3 receptor antagonist alosetron Lotronex has been used effectively for the treatment of diarrhea-predominant irritable bowel syndrome.
Tincture of opium and paregoric have also been used to improve the quality of daily life in some cases. Finally, in severe cases, injections of octreotide Sandostatin , a somatostatin-like hormone, have been shown to significantly decrease the frequency of diabetic diarrhea. Obviously, in these severe cases, referral to a gastroenterologist is indicated. The pancreas has a tremendous reserve, and a modest reduction in pancreatic enzyme secretion rarely leads to difficulty in digesting or absorbing carbohydrate, fat, or protein.
The exocrine pancreas may also be affected in some patients with type 2 diabetes but to a lesser extent. Individuals who have secondary diabetes because of severe pancreatitis or surgical removal of the pancreas usually have more severe symptoms of pancreatic exocrine insufficiency. Treatment with pancreatic enzyme replacement therapy is usually effective. A trial of oral enzyme replacement therapy can be done safely for diagnostic and therapeutic purposes.
The Liver in Diabetes Although liver function tests are commonly abnormal in patients with diabetes, it is unclear whether this is a reflection of the underlying obesity that is so common in patients with type 2 diabetes or whether it is an effect of poorly controlled diabetes. People with type 1 diabetes in very poor control may also develop this syndrome, although it is much less common. Fatty infiltration of the liver may lead to tender hepatomegally, elevated liver enzyme tests, and abdominal pain syndromes.
Occasionally, this may progress to fibrosis and cirrhosis of the liver. The diagnosis is usually suspected on the basis of the clinical presentation but can be confirmed with abdominal ultrasonography and, if needed, percutaneous liver biopsy. Metabolic abnormalities such as hemochromatosis and infectious etiologies such as viral hepatitis need to be excluded as part of the evaluation. Therapy is geared toward improving glycemic control and instituting a low-calorie, low-fat diet.
Caloric restriction will lead to weight loss, better glycemic control, lower serum triglycerides and cholesterol, and improvement in the fatty infiltration of the liver. Ursodiol Actigal may provide some benefit in the treatment of hepatic steatosis.
Diabetic patients seem to have an increased incidence of gallstones and gall bladder problems, but these, much like fatty infiltration of the liver, are primarily related to the obesity associated with type 2 diabetes and not to the diabetes itself.
Obesity leads to secretion of bile by the liver that is supersaturated with cholesterol, leading to crystallization and stone formation. Typical symptoms of biliary colic include intermittent right upper abdominal pain, jaundice, or pancreatitis. In the past, patients with diabetes have been instructed to have surgery for asymptotic gallstones because of a concern for an increased risk of complications from gallstones, such as infection, pancreatitis, or rupture of the gall bladder.
However, more recent experience with modern medical and surgical care indicates that this is no longer the case. Thus, patients with diabetes and gallstones should be managed in a fashion similar to nondiabetic patients.
Surgery is generally recommended only for those individuals whose gallstones are causing symptoms. Conclusions GI problems in diabetes are common but not commonly recognized in clinical practice. The duration of diabetes and the degree of glycemic control are major determinants in the incidence and severity of GI problems. The entire GI tract can be affected, including the mouth, esophagus, stomach, small intestine, colon, liver, and pancreas, leading to a variable symptom complex.
The workup starts with a thorough patient history and appropriate laboratory, radiographic, and GI testing. In addition to pharmacological therapy, glycemic control and dietary manipulation play an important role in managing GI disorders in people with diabetes.