The vestigiality of the human vermiform appendix

Digestive System Physiology

Upper Gastrointestinal Endoscopy
Vomiting may be severe enough to cause weight loss, electrolyte abnormalities, and acid—base disturbances requiring hospitalization. Lymph nodules may form longitudinal aggregations of nodules in the lamina propria of the ileum. New techniques for nonradiation ERCP during pregnancy. Influence on innate and acquired immunity". Clinical trials are part of the cancer research process. If symptoms persist H 2 blockers can be used.

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Digestive System

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. The natural history and duration of bacterial enteritis may not be influenced greatly with antibiotics and their use should be reserved for patients with prolonged or dramatic symptoms.

Metronidazole giardiasis, Clostridium difficile , fluoroquinolones effective for most enteric pathogens , erythromycin stearate Campylobacter jejuni , cephalosporins Shigella , and ampicillin Salmonella are effective and low-risk in pregnancy.

Pregnancy increases the risk of gallstones. Gallbladder emptying and motility are decreased during pregnancy, providing the necessary environment of biliary stasis for gallstone formation. Along with these functional changes, the chemical components of bile change during pregnancy. Bile is more saturated with cholesterol and has a decreased bile acid content. It is surprising that even though the gallbladder is altered in so many ways, cholelithiasis and its complications are still uncommon during pregnancy.

The incidence of gallbladder disease during pregnancy is approximately 0. Cholecystitis occurs in approximately 1 in pregnancies, and approximately one-third require surgical intervention.

Fortunately the diagnosis can be confirmed accurately and safely during pregnancy by abdominal ultrasound. Gallstones may also lead to pancreatitis, which occurs in approximately 1 in to 1 in 10, pregnancies. The diagnosis relies on the measurement of serum amylase and lipase in the context of the appropriate clinical scenario see section on Acute Pancreatitis.

Biliary colic rarely requires operative intervention and is usually controlled symptomatically with pain medications. Cholecystectomy is postponed until after delivery unless complications arise in which the risk of the disease is higher than the risk of surgery.

Early data suggested an increase in fetal loss with open cholecystectomy. McKeller reported nine cholecystectomies without perioperative fetal or maternal losses.

Cholecystectomy in the first trimester may be associated with fetal loss and in the third trimester with early labor. Pregnancy was at one time an absolute contraindication for laparoscopic cholecystectomy; however, this procedure is safe and may be the procedure of choice in treating cholecystitis in pregnancy. Pancreatitis is rare during pregnancy, usually occurring in the third trimester or postpartum. It is no more common than in the nonpregnant patient and has a similar clinical presentation.

Diagnosis relies on clinical presentation and elevation of serum amylase and lipase. The presentation is not altered significantly by pregnancy. Classically, the patients present with mid-epigastric pain, which radiates to the back.

Nausea and vomiting are usually prominent and may be the only symptoms. Serum amylase may be lowered during pregnancy secondary to increased renal clearance. Although the incidence of pancreatitis during pregnancy is small, it does create significant problems when present. The high mortality is related to the extreme fluid shifts that occur during acute pancreatitis and recent data have shown a decrease in mortality with improved intensive care treatment.

There are limited data showing an increase in secretion of pancreatic enzymes and bicarbonate. Enhanced exocrine secretion may exacerbate pancreatitis regardless of its etiology. Triglycerides increase during pregnancy and may cause pancreatitis in patients with a preexisting hypertriglyceridemia. Alcohol is a rare cause, probably related to abstinence, which is practiced during pregnancy. Management of pancreatitis during pregnancy is similar to the nonpregnant patient.

Therapy revolves around meticulous fluid replacement as hypovolemia is the most common cause of mortality. By making sure that the patient takes nothing by mouth and prescribing antiemetics and analgesics that are appropriate in pregnancy this will control symptoms of nausea, vomiting, and pain. There should be a very low threshold for ICU admission given the high mortality for both mother and fetus. Patients whose diseases fail to improve with standard care need more diagnostic testing.

Ultrasound, which is safe during pregnancy, is usually used in the initial workup and may help to rule out pseudocyst, abscess, or retained common bile duct stone. If cholangitis or biliary obstruction develops, endoscopic retrograde cholangiopancreatography ERCP has been shown to be safe during pregnancy and provides a favorable alternative to surgical common bile duct exploration, which has a high risk of fetal loss.

Multiple reports document the safety and efficacy of ERCP during pregnancy. Clinical endocannabinoid deficiency CECD revisited: Cannabinoids inhibit neurodegeneration in models of multiple sclerosis CB2 cannabinoid receptors as an emerging target for demyelinating diseases: A novel role of cannabidiol in the regulation of p22phox and Nox4 expression Cannabidiol for the Prevention of Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice Endocannabinoids in Liver Disease Exogenous hepatitis B virus envelope proteins induce endoplasmic reticulum stress: Extraction of cannabinoids from cannabis sativa L plant and its potential antimicrobial activity In vitro antibacterial activity of Cannabis sativa leaf extracts to some selective pathogenicbacterial strains.

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Cannabinoids inhibit human keratinocyte proliferation through a non-CB1-CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis. Cannabidiol decreases the "drug-seeking behavior". The opposite of a "gateway drug". This storage capacity allows the body to eat only a few times each day and to ingest more food than it can process at one time. In the course of a day, the digestive system secretes around 7 liters of fluids. These fluids include saliva, mucus, hydrochloric acid, enzymes, and bile.

Saliva moistens dry food and contains salivary amylase, a digestive enzyme that begins the digestion of carbohydrates. Mucus serves as a protective barrier and lubricant inside of the GI tract.

Hydrochloric acid helps to digest food chemically and protects the body by killing bacteria present in our food. Enzymes are like tiny biochemical machines that disassemble large macromolecules like proteins, carbohydrates, and lipids into their smaller components. Finally, bile is used to emulsify large masses of lipids into tiny globules for easy digestion. Digestion is the process of turning large pieces of food into its component chemicals. Mechanical digestion is the physical breakdown of large pieces of food into smaller pieces.

This mode of digestion begins with the chewing of food by the teeth and is continued through the muscular mixing of food by the stomach and intestines. Bile produced by the liver is also used to mechanically break fats into smaller globules.

While food is being mechanically digested it is also being chemically digested as larger and more complex molecules are being broken down into smaller molecules that are easier to absorb. Chemical digestion begins in the mouth with salivary amylase in saliva splitting complex carbohydrates into simple carbohydrates.

The enzymes and acid in the stomach continue chemical digestion, but the bulk of chemical digestion takes place in the small intestine thanks to the action of the pancreas. The pancreas secretes an incredibly strong digestive cocktail known as pancreatic juice, which is capable of digesting lipids, carbohydrates, proteins and nucleic acids.

By the time food has left the duodenum , it has been reduced to its chemical building blocks—fatty acids, amino acids, monosaccharides, and nucleotides.

Once food has been reduced to its building blocks, it is ready for the body to absorb. Absorption begins in the stomach with simple molecules like water and alcohol being absorbed directly into the bloodstream.

Most absorption takes place in the walls of the small intestine, which are densely folded to maximize the surface area in contact with digested food. Small blood and lymphatic vessels in the intestinal wall pick up the molecules and carry them to the rest of the body. The large intestine is also involved in the absorption of water and vitamins B and K before feces leave the body.

The final function of the digestive system is the excretion of waste in a process known as defecation.

The interstitium: Redefining an organ