Case 1

A patient has a vagotomy in order to lower gastric acid production. One of the side effects is that he isn't able to eat as large a meal as he used to. What is the reason for this?

2 factors affect the ability of the stomach to stretch while filling. Smooth muscle plasticity is an inherent property of the cells in the stomach and would be unaffected by the vagotomy. However, the stomach won't relax because it lacks the reflective relaxation of the fundus and body of the stomach as the reflex is mediated by the vagus nerve (neurotransmitters NO and VIP).

Cimetidine and ranitidine are both H2 blockers. How do they differ clinically?

Cimetidine has profound drug-drug interactions by way of CYP P450 enzymes. Cimetidine also has steroid-like properties and can influence hormones such as testosterone, estrogen, and prolactin. Ranitidine lacks these actions.

1. Which food in a patient's diet is least likely to be exacerbating their peptic ulcer pain? A. Orange Juice B. Cayenne Pepper C. Coffee D. Martini

A. Orange Juice

What are the goals of the Gut associated lymphoid tissue (GALT)?

Clear pathogens & maintain homeostasis.

You have a 42 year-old female who is diagnosed with a non bleeding gastric ulcer by EGD after presenting with epigastric pain, melena and a 20 weight loss over the past year. She has a PMH of asthma. She drinks 2-3 beers on the weekends and smokes about half a pack a day for 25 years. She has two children under 5 and is working. She is on flovent and albuterol and has taken prednisone for asthma exacerbations. She has not been on nonsteroidals or aspirin. What is the most important next step to identify and treat the etiology of her ulcer?

Biopsy with H. pylori testing. EGD was indicated in this patient with melena and weight loss to evaluate for stricture or a malignancy. A gastric ulcer can actually be an ulcerated gastric carcinoma and should be biopsied. Helicobacter pylori is the major cause of peptic ulcer disease. H. pylori testing can be done by biopsy and observation of the tissue under the microscope or by doing a test for urease.

How do Effector CD4+ and CD8+ T cells enter the gastrointestinal tract?

CD4+ T cells utilize specialized integrins to traffic to the GI tract α4:β7 which will bind to MadCAM and CCR9 which recruits them into the LP from the bloodstream. CD8+ T cells express αEβ7 which will bind to E-cadherin to grant them access to the LP.

In what setting should intussusception be suspected?

Colicky pain is seen in more than 80% of cases. It typically lasts 15 to 30 minutes and the baby usually sleeps between attacks. In about 1/3 of the cases there are currant jelly stools. Other presenting symptoms include lower GI bleeding, blood streaking on the stools. A right lower quadrant mass may be palpable and distention may accompany decreased bowel sounds.

Elevation of the tongue is a necessary step in normal swallowing, because it is responsible for what?

Elevation of the tongue presses the food bolus against the back of the throat initiating the swallowing reflex by activating the swallowing center.

What is the likely diagnosis for an infant with excessive secretions and choking episodes with their first feeding in whom a nasogastric tube cannot be passed into the stomach?

Esophageal atresia with tracheoesophageal fistula. This congenital anomaly is usually diagnosed during the newborn period, when a chest radiograph reveals the intended nasogastric tube coiled in the upper esophageal pouch with the stomach distended with air.

Describe the overall organization and the cells that comprise gastric glands in the fundus and body of the stomach.

Gastric glands in the fundus and body of the stomach originate at the base of gastric pits. Initial cells include mucus neck cells. The upper third of the glands are populated by a predominance of parietal cells, which make HCl and intrinsic factor (which binds vitamin B12). The middle third of the gland has a mix of parietal cells and chief cells (which make pepsinogen). The lower third of the gland is populated by a predominance of chief cells and also contains enteroendocrine cells and stem cells.

Certain pancreatic tumors elevate plasma gastrin levels. What would you expect to see in the stomach of this patient?

Gastrin is responsible for stimulating stomach acid production. If you have an uncontrolled release of gastrin you would expect stomach hyperacidity resulting in a low pH.

Compare and contrast the causes and microscopic appearance of gastropathy and acute gastritis.

Gastropathy: cell injury and regeneration are present but neutrophils are absent - Causes of gastropathy: chemical injury, including drugs (NSAIDs) and alcohol; bile reflux; increased gastric acidity Acute gastritis: neutrophils are present - Causes of acute gastritis: Helicobacter pylori (main causes), also chemical or other noxious substances

A 24 year-old male presents with burning epigastric pain for the past month. The pain is relieved by food and antacids. He has been awakened by the pain several times. He has no dysphagia, nausea, vomiting, diarrhea, weight loss, melena or hematochezia. He has no past medical or surgical history and his only medicine is ibuprofen 600 mg three times a day for the past two months. He is using this for left knee pain after an injury. He drinks 1 to 2 beers on the weekends and does not smoke or use illicit drugs. Physical exam is significant only for epigastric tenderness. CBC is normal. Helicobacter pyloris testing is negative. What is your next step?

Given NSAID use, he has a good reason for the ulcer. He can be empirically treated with a proton pump inhibitor and discontinuing NSAIDs. Therapy should stop as soon as possible or stepped down to an H2 antagonist.

Describe the gross and microscopic features found in Barrett esophagus.

Gross--red, slightly raised, mucosa in the distal esophagus extending a variable length proximally replacing the normal white, finely wrinkled squamous mucosa. Microscopic--metaplastic gastric foveolar epithelium with interspersed intestinal goblet cells

What are the phases of H. pylori infection?

H. pylori is found in almost all patients with gastritis, gastric ulcers, duodenal ulcer, and gastric adenocarcinomas/ lymphomas. There are largely 2 phases of infection - acute and chronic. Acute disease is associated with a feeling of fullness, nausea, vomiting, and hypochlorhydria. Chronic is associated with gastritis in the gastric antrum where acid secretion is suppressed spreads to the entire stomach. Approximately, 10-15% of patients with chronic gastritis will progress to develop peptic ulcers.

Compare and contrast the microscopic features and associated laboratory tests between Helicobacter pylori and autoimmune gastritis.

Helicobacter gastritis: Microscopic: - Antrum>fundus - Numerous plasma cells; lymphocytes, sometimes in aggregates, germinal centers - Neutrophils invading foveolar epithelium, microabscesses ("active" inflammation) - Organisms found in superficial mucous using special stains Laboratory diagnosis: - Gastric pH: Normal or slightly increased or decreased - Gastrin: Normal to markedly increased - Serology: Anti-Helicobacter antibodies Autoimmune gastritis: Microscopic: - Chronic gastritis composed of predominantly lymphocytes, macrophages - Loss of mucin in foveolar cells, - Atrophy of specialized/mucous glands, intestinal metaplasia Laboratory diagnosis: - Gastric pH: Increased - Gastrin: Markedly increased - Serology: Anti-parietal cell antibodies - Hemoglobin: decreased (anemia) - Vitamin B12: decreased

Which cytokines would you expect to be expressed at a higher amount in the tissue of a patient with IBD?

IFNg, TNFa, IL-1beta, and IL-17 these are all proinflammatory cytokines that will skew the environment away from the tolerogenic normal environment of the gastrointestinal tract (IL-4, TGF-beta, IL-10) and toward a more inflammatory environment.

What are the predominant cytokines normally expressed in a normal healthy gastrointestinal tract?

IL-10 and TGF-β these induce Tregs in the periphery and inhibit the differentiation of Th1, Th2, and Th17.

What is the classic presentation of an infant with pyloric stenosis and how is it diagnosed?

Infants have progressive non-bilious projectile vomiting leading to dehydration with hypochloremic hypokalemic metabolic alkalosis. On physical exam an "olive" may be palpable in the epigastric region and peristaltic waves may be visible. If the classic signs and symptoms are present in association with the typical blood chemistry findings and a mass is palpated the diagnosis can be made on clinical grounds. If the diagnosis is in doubt ultrasound can be used to visualize the hypertrophic musculature and an upper GI contrast studies will demonstrate pyloric obstruction.

What is the role of intraepithelial Lymphocytes (IELs) in gastrointestinal infection?

Intraepithelial Lymphocytes (IELs) are specialized lymphocytes present in the epithelium and not the lamina propria. They usually number 10-15 lymphocytes/100 epithelial cells, and are predominantly CD8+ T cells. They have an activated appearance and contain perforin and granzyme in intracellular granules. IELs will kill an infected, stressed, or damaged intestinal epithelial cells (IECs).

How does secretory IgA survive in the gastrointestinal tract? What is its importance in the gastrointestinal tract and how does it function?

It has secretory component which keeps it from being degraded by the enzymes of the gastrointestinal tract. IgA works by binding to pathogens neutralizing them so they are unable to bind to host cells.

What is the importance of M cells in normal surveillance of the gastrointestinal tract?

M cells contain no microvilli; a limited mucin layer, broader microfolds, and do not secrete lysosomes so are constantly exposed to antigen. M cells transport antigen from gut lumen to immune cells across the epithelial barrier by endocytosis and deliver it APCs essentially bypassing normal IECs transport.

Meckel diverticulum has been conveniently referred to by the "rule of 2s," which explains the classic presentation of this congenital anomaly. Name a few of the "rule of 2s."

Meckel diverticulum are found in 2% of the general population, are usually located 2 feet proximal to the ileocecal valve, are approximately 2 inches in length, can contain 2 types of ectopic tissue (pancreatic or gastric), generally presents before the age of 2.

What role does Misoprostol or Sucralfate play in the treatment of peptic ulcers?

Misoprostol is an analog of PGE1 and is considered a cryoprotective agent. It will assist in the repair of the GI tract by activation of prostaglandin receptors to produce more protective mucous, less cAMP, and less gastric acid. Sucralfate has a different mechanism, but is basically a polymer that attaches to damaged, ulcerated GI tissue and is cyto-protective.

What is the natural history of an umbilical hernia?

Most umbilical hernias spontaneously closed before a patient is 2 years. Unlike an inguinal hernia, incarceration and strangulation are rare with an umbilical hernia.

How are the granules produced from an Actinomyces granuloma described?

They are referred to as sulfur granules due to their bright yellow appearance. They can look like a beautiful sandy beach on macroscopic examination.

What is the MOA of omeprazole and how does it help in the treatment of peptic ulcers?

Omeprazole is a proton pump (H+/K+ pump) inhibitor (PPI). It reduces proton secretion into the GI lumen which increases the pH by reducing the number of protons. This reduces the aggravation experienced by those patients with peptic ulcer disease.

What is the main difference between an omphalocele and gastroschisis?

Omphalocele is a herniation or protrusion of the abdominal contents into the base of the umbilical cord secondary to failure of lateral fold closure in utero. The sac is covered with peritoneum without overlying skin. Gastroschisis is extrusion of abdominal contents through the lateral abdominal folds in utero. The abdominal content is not covered by peritoneum or overlying skin.

What are the main mechanisms for promoting gastrointestinal tolerance?

Oral tolerance is the active, antigen specific non-response to antigens administered orally. Oral tolerance is dependent on the dose of exposure and form of exposure. Proteins are the most immunogenic with carbohydrates and fat less so. Large antigen doses induce more tolerance than small. This process appears to be mediated through expansion of T regulatory cells (CD4+, CD25+, FoxP3) that promote the production of transforming factor- b (TGF-b). Bystander suppression is the phenomenon that an antigen with oral tolerance will still be tolerant if given in a different route. If you develop tolerance to something orally then when you are exposed to that antigen through a different route (dermally, injection, etc) you will also exhibit tolerance to the antigen. This shows that the effector arm of oral tolerance can be non-specific, in terms of administration route.

What is the mechanism of action of ranitidine and other H2 blockers?

Ranitidine and other H2 blockers antagonize the H2 receptors in the parietal cells. Blocking this receptor causes a reduction of Camp signaling ending with reduced secretion of protons (H+) into the gastric lumen. This in turn raises the pH producing a less acidic environment.

What property of the segmentation process is responsible for the propulsive action it produces?

Segmentation are the regular contractions of the circular muscle that occur in the small intestine. Its function is mainly used to mix chime but the frequency decreases in the aboral direction (orthograde; mouth to anus) giving it a small propulsive effect.

During gastric juice secretions, which of the ions Na+, K+, H+, Cl- or HCO3 would you expect to decrease in concentration with increased flow rate?

Sodium is the only ion to decrease in concentration when flow rate increases. High flow rate is virtually all HCl, but K+ concentration does increase slightly. HCO3- isn't secreted in gastric juice.

A 53-year-old woman was operated on for the treatment of a chronic gastric ulcer that had not responded to medical treatment. During operation for partial gastrectomy (removal of part of the stomach), it was found that the posterior body wall of the stomach was fixed to posteriorly related structures due to adhesions. The surgeon proceeded to mobilize the body of the stomach with great care to avoid damaging important neighboring structures. What structures are at greatest risk for iatrogenic injury in this partial gastrectomy operation? (Iatrogenic = relating to illness caused by medical examination or treatment.)

Structures at high risk include: Pancreas, lesser omentum, splenic artery, left kidney, and spleen.

Which of the salivary glands is a mixed serous-mucus gland and produces the majority of the saliva?

Submandibular gland is the largest and produces the most saliva.

How are H. pylori infections treated? What is the MOA of those drugs?

Tetracycline, metronidazole, clarithromycin, bismuth, and omeprazole have been used to treat these infections. H. pylori infections are treated with the following drugs in combination. Option #1: Bismuth subsalicylate (Pepto-Bismol), metronidazole, and tetracycline for 2 weeks. Bismuth subsalicylate (Pepto-Bismol) exact MOA is unknown; it is a salicylate (like aspirin) but demonstrates anti-GI motility, anti-secretory, and anti-inflammatory effects. Metronidazole is a free-radical producer which reduces ATP production and affects DNA stability for anaerobic and protozoal infections. Tetracycline is a protein synthesis inhibitor. Option #2: Omeprazole and clarithromycin for 2 weeks. Omeprazole is a proton pump inhibitor which reduces gastric acid secretion. Clarithromycin is a macrolide derivative binds to 23 S subunit (part of the 50S subunit) also inhibiting bacterial protein synthesis. Several other treatment options exist which utilize amoxicillin and levofloxacin; however, their use is limited and favored when other drugs are contraindicated (due to an allergy or resistance).

A 9-year-old boy was admitted to the hospital with a temperature of 102°F and pain in the right lower quadrant. On examination, the skin of the right lower quadrant was tender/sensitive to the touch, and the abdominal muscles contracted and rigid. Explain from an anatomical perspective how the physical exam findings may be related.

The abdominal muscles and the overlying skin are supplied by the same segmental spinal nerves from the lower thoracic spinal levels (e.g., thoracoabdominal nerve arise from T7-T11).

What is the classic radiographic finding of duodenal atresia?

The double bubble. Swallowed air distends the stomach in the proximal duodenum.

Compare and contrast the submucosal plexus and the myenteric plexus.

The enteric nervous system is a subdivision of the autonomic nervous system and is self-contained within the gut. It is comprised of numerous, repeating ganglia of Submucosal and Myenteric plexuses. Both plexuses have motor and sensory portions. The Submucosal plexus contains sensory fibers that are mainly sympathetic, parasympathetic ganglia (nerve cell bodies), as well as pre- and post-parasympathetic nerve fibers. The motor component controls mucosal and submucosal gland secretion and blood flow. The sensory component consists of mucosal mechanosensitive neurons which convey info regarding the luminal contents, secretory status. The Myenteric plexus contains parasympathetic ganglia (nerve cell bodies) of postganglionic neurons and nerve fibers of both sympathetic and parasympathetic origin. The motor component controls GI motility (contraction/relaxation of smooth muscle), and the sensory component consists of tension-sensitive neurons and chemosensitive neurons.

Why is the GALT an immunotolerant zone?

The lamina propria contains specialized cells to "sample" potential pathogens. It is also full of effector cells that are ready to respond. However; their responses are kept at bay by the largely tolerogenic environment established in the gut so that we are able to eat without inflammation.

List the regions of the large intestine and describe the features that distinguish it from the small intestine.

The large intestine has 5 regions: cecum, appendix, colon (the largest portion), rectum, and anal canal. In general, regions of the large intestine lack villi but have cryts. Crypts are mostly filled with goblet cells and absorptive cells (primarily for water resorption). The colon has an additional feature to distinguish it from the small intestinal regions: the teniae coli. These are the outer layer of the muscularis externa which is gathered into three band-like structures that are spaced around the circumference of the tube.

What are the clinical findings of malrotation of the intestine?

The lesion may display in utero as volvulus or it may be asymptomatic throughout life. Infants may display intermittent vomiting or exhibit signs compatible with complete obstruction. Any infant with bilious vomiting requires careful evaluation for volvulus and other surgical obstructions. Recurrent abdominal pain, distention or lower GI bleeding may result from intermittent volvulus.

List the components of the mucosal layer of the GI tract and describe the function of each component.

The mucosa is the innermost layer of the GI Tract adjacent to the lumen. It is comprised of the epithelium, the lamina propria and muscularis mucosa. The epithelial sheet has 2 basic conformations depending on the region: stratified squamous or simple columnar. In general, the epithelia serves a barrier function, separating the contents of the GI lumen from the underlying tissues. Regions with stratified squamous epithelia are also specialized for protection (from abrasion) at the beginning and the end of the tract. Regions with simple columnar epithelia serve functions such as secretion (via numerous exocrine glands), absorption and transport of immunologic antigens across the epithelia to antigen presenting cells (via microfold cells or M cells). The lamina propria underlies the epithelia and glands and serves several functions. It contains the vasculature that supplies the overlying tissue with nutrients and O2. It also contains a nerve fibers from the submucosal plexus for glandular and muscle control as well as sensory information regarding the mucosa. Lastly, it contains MALT, so it serves as the environment for immunological response to pathogens, allergens, etc. The muscularis mucosa is composed of 2 smooth muscle layers, inner circular and outer longitudinal. Its contraction produces localized movements in the mucosa which can separate villi, form ridges/valleys and dislodge particulate matter, all of which facilitates absorption and secretion. Contraction of muscularis mucosa is distinct form peristalsis.

Activation of sensory neurons by distension of the GI wall by luminal content leads to proximal contraction and distal relaxation of intestinal smooth muscle (law of intestine). Which neurotransmitters mediate this distal relaxation?

The neurotransmitters that cause the GI smooth muscle to relax are Vasoactive Intestinal Peptide and Nitric Oxide. Substance P and Acetylcholine cause contraction. The neurotransmitter that passes these through the enteric nervous system signals is Calcitonin Gene Related Peptide (CGRP).

Which of the components of normal defecation must a young child must learn?

The only aspect of defecation that is under somatic control is the external anal sphincter. A child has to know how to control its contractions in order to display continence.

Describe the three phases of swallowing.

The phases of swallowing are the buccal phase, the pharyngeal phase and the esophageal phase.

What is known as the acid tide?

The production of HCO3- by the pancreas causes a simultaneous release of H+ into the bloodstream that results in a local reduction in blood pH. This is what is known as the acid tide.

What are three modifications that can be made to increase ease of swallowing for patients with dysphagia?

The three modifications that can be made to increase ease of swallowing for patients with dysphagia are postural adjustments, swallowing maneuvers, and pureeing foods/thickening liquids for consumption.

A 32-year-old man presents to his primary care physician for a 1-month history of persistent heartburn and stomach pain. Over the past two weeks he has also experienced episodes of nausea, vomiting, and diarrhea. The vomit is often red or black in color, as are his stools. He has lost approximately 10 pounds over the past month and says he often feel full despite not eating. An upper endoscopy is conducted which reveals blood in the stomach, and a gastric mucosal biopsy is taken which identifies the presence of a spiral shaped gram negative motile rod. The organism is oxidase positive and catalase positive. How does this organism colonize the acidic environment of the stomach?

There are 4 strategies for H. pylori colonization of the stomach: 1. Blockage of acid production by bactericidal acid-inhibitor protein allows the bacterium to survive in the low pH of the stomach. 2. High production of urease neutralizes gastric acids with ammonia 3. Actively motile helicobacters then pass through the gastric mucus and adhere to the gastric epithelial cells using surface adhesion proteins. This helps the bacterium evade the immune response as it blankets itself in host proteins. 4. Localized tissue damage is mediated by urease byproducts and the activity of VacA, a protein that after penetration into the epithelial cells damages the cells by producing vacuoles.

A 3-week-old boy was admitted to the hospital with a mid-inguinal swelling in the right groin that extended into the upper part of his scrotum. When he cries, the swelling enlarges. What is the likely diagnosis for this patient (be specific)? Anatomically/embryologically, how did this patient's condition likely occur?

This patient likely has an indirect inguinal hernia based on the location of the mid-inguinal swelling. The processus vaginalis in its upper part failed to become obliterated before birth leaving a pathway for small bowel to follow; thereby causing a hernia.

How can Actinomyces israelii be differentiated from Nocardia?

While both are Filamentous gram positive rods, Nocardia is acid fast and Actinomyces is not.