Wayne State University School of Medicine GI PBL Case PDF

# WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE ## M1 FUNDAMENTALS OF A HEALTHY PATIENT: HUMAN BODY FOUNDATIONS II COURSE ### Case: Mr. Pham's Heartburn #### Authors: Rod D. Braun, Ph.D. and Xue Jing Li, M.D. (WSU SOM, Class of 2019) ## RESOLUTION AND REVIEW ### GOAL To use your knowledge and understan...

# WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE ## M1 FUNDAMENTALS OF A HEALTHY PATIENT: HUMAN BODY FOUNDATIONS II COURSE ### Case: Mr. Pham's Heartburn #### Authors: Rod D. Braun, Ph.D. and Xue Jing Li, M.D. (WSU SOM, Class of 2019) ## RESOLUTION AND REVIEW ### GOAL To use your knowledge and understanding of normal body structure and function to investigate a case of heartburn. ### CASE RESOLUTION AND REVIEW **The diagnosis for this patient is achalasia**, a disease in which the ganglion cells of the myenteric plexus in the esophagus are decreased in number or totally absent, resulting in loss of peristalsis and impaired lower esophageal sphincter (LES) relaxation. If the LES does not open, swallowed food accumulates in the lower esophagus, which can cause heartburn. #### **Mr. Pham's Initial Visit** On his initial visit, Mr. Pham presents with persistent heartburn that is not effectively treated with antacids, which relieve heartburn by neutralizing stomach acid (hydrochloric acid). He has also had bouts of chest pain, especially after eating, has had trouble sleeping, and has irregular eating habits. A potential explanation, i.e., a differential diagnosis, for heartburn not responding to acid suppression includes gastroesophageal reflux disease (GERD) due to insufficient acid suppression, peptic ulcer disease, esophageal hypersensitivity, esophageal cancer, and esophageal motility disorders, e.g., achalasia. The initial diagnosis is GERD, which occurs when stomach acid moves into the lower esophagus, because the lower esophageal sphincter loses its tone. Mr. Pham's eating habits are problematic, since eating meals and snacks just before bedtime is associated with increased time of supine acid exposure. Mr. Pham is advised to eat three regular meals a day and is prescribed pantoprazole (Protonix). Pantoprazole is a drug that belongs to the drug class called proton pump inhibitors (PPIs), which bind irreversibly to the gastric proton pump (H*-K+ ATPase) to prevent the release of gastric acid (hydrochloric acid, HCI) from parietal cells. #### **Mr. Pham's Follow-Up Visit #1** After 10 weeks Mr. Pham returns early for his follow-up visit, and he is still in great discomfort. His symptoms now include a worsening chronic cough, difficulty swallowing (dysphagia), and occasional regurgitation of food. His wife also reports that he has lost 10 pounds over the last five months. These new symptoms should impact the differential. Since Mr. Pham's symptoms did not resolve with PPI therapy, his symptoms are most likely caused by something other than GERD. His new symptoms are consistent with achalasia. Mr. Pham is referred for an esophagogastroduodenoscopy (EGD) with biopsy. EGD is a procedure in which a small flexible endoscope (a flexible tube with a light and camera attached to it) is introduced through the mouth or nose and advanced through the pharynx, esophagus, stomach, and duodenum. The camera captures images of the surrounding tissue as the endoscope is advanced. If a biopsy is to be performed, the endoscope is also equipped with a small forceps that excises tissue samples from the wall of the gastrointestinal tract. Based on the EGD images, a diagnosis of achalasia or pseudoachalasia is most likely. Pseudoachalasia is characterized by achalasia-like symptoms caused by secondary etiologies, i.e., it results from causes other than primary denervation. To confirm achalasia and to rule out pseudoachalasia, high-resolution esophageal manometry and an X-ray (a barium swallow) are ordered. Usually if EGD is suggestive of achalasia, then esophageal manometry is performed to verify the diagnosis. Although it is not always required, some physicians will also order a barium swallow x-ray to further confirm the diagnosis. ### Figure A: Normal high-resolution esophageal manometry recording. - The pressure topography (Clouse) plot is shown on the left and the tracing mode recording is shown on the right. - The tracing mode is similar to the output of a traditional esophageal manometry recording. - Left: Normal Clouse plot starting at the upper esophageal sphincter (UES) following a wet (water) swallow. LES: lower esophageal sphincter. Esophagogastric junction relaxation is summarized by the integrated relaxation pressure (IRP). - Right: Traditional esophageal manometry recording. This figure shows pressure recordings at different locations along the esophagus following a wet (water) swallow (WS). - The recordings are taken from the proximal esophagus (top) down to the distal esophagus and lower esophageal sphincter (LES) (bottom). - The position of each recording is listed on the right as distance from nares (nostrils). - This is an example of normal esophageal peristalsis and LES relaxation. A peristaltic sequence is recorded in the sensors above the LES. - The asterisk and bracket identify the pressure in the bolus that precedes the peristaltic contraction (bolus pressure). - The beginning of the rapid upstroke of the pressure wave (vertical arrow) corresponds to closure of the esophageal lumen by the peristaltic contraction. ### High-resolution esophageal manometry - is an outpatient procedure that measures the pressures and the pattern of muscle contractions in the esophagus. - In the procedure, a thin catheter with high-resolution pressure sensors is passed through the nose, down the esophagus, and into the stomach. - Up to 36 sensors, spaced 1 centimeter apart, span the esophagus and measure the pressures and the pattern of muscle contractions during the swallow. - A typical measurement from a normal esophagus is shown in Figure A, in which the pressure topography (Clouse) plot is on the left and the tracing mode recording is on the right. - The tracing mode is similar to the output of a traditional esophageal manometry recording. ### **Mr. Pham's recording** - is shown in Dr. Komnenov's "Gastrointestinal Motility” lecture notes. - In the normal esophagus, a manometry recording shows clear evidence of peristalsis. - The primary peristaltic contraction, also mediated by the swallowing reflex, involves a series of coordinated sequential contractions along the length of the esophagus. - Both the inner circular and outer longitudinal muscle layers of the muscularis externa contract in a coordinated fashion. - As each segment of the esophagus contracts, the circular layer creates an area of high pressure just behind the bolus, pushing it down the esophagus. - As the food bolus moves down the esophagus, the lower esophageal sphincter (LES) relaxes, i.e., the pressure decreases (bottom of each panel, "LES", Figure A). - In contrast to the normal recording, the Clouse plot in Mr. Pham's recording indicates that the pressures are relatively uniform along the length of the esophagus, and there is no evidence of the high-pressure boluses seen in the normal plot. - Similarly, in the tracing mode recording for Mr. Pham, the top five traces are very similar to one another, showing similar uniform pressure readings along the length of the esophagus. - Thus, there is no evidence of significant peristalsis in the esophagus of Mr. Pham. In addition, in Mr. Pham's case, the LES does not relax, and the LES pressure stays elevated in both plots. - The lack of any evidence of a relaxation, i.e., a pressure decrease, in the LES, is a hallmark of achalasia. ### **A barium swallow** - is an x-ray test that uses barium sulfate as a contrast agent to help visualize abnormalities in the esophagus or the upper gastrointestinal (GI) tract (esophagus, stomach, and duodenum). - Mr. Pham's x-ray presents the typical appearance of the esophagus in a barium swallow x-ray image of a patient with achalasia. - The narrowing of the LES, a "bird-beak" feature at the junction, is readily visible in the lower portion of the image, and dilatation of the proximal esophagus above the LES is also visible. ### Figure B: Esophageal motor innervation by the vagus nerve. - Left: The striated muscle of the proximal (upper) esophagus is directly innervated by the somatic efferent cholinergic fibers of the vagus nerve originating from the nucleus ambiguus. - In contrast, the smooth muscle of the distal (lower) esophagus is innervated by the preganglionic vagus nerve fibers from the dorsal motor nucleus. - The preganglionic vagus fibers release acetylcholine, a neurotransmitter that affects two types of postganglionic neurons in the myenteric plexus, the excitatory cholinergic neurons and the inhibitory nitrinergic neurons. NO, nitric oxide; VIP, vasoactive intestinal polypeptide. ### Esophageal peristalsis and LES relaxation - are coordinated by ganglion cells of the myenteric plexus. - The LES relaxes by two mechanisms: reduction in activity of excitatory enteric ganglion cells and activation of inhibitory enteric ganglion cells. - If these mechanisms are absent, then myogenic mechanisms (intrinsic ability of musculature of the sphincter to resist distension) will tend to close the sphincter. - In achalasia the ganglion cells of the myenteric plexus, especially the inhibitory neurons, are decreased in number or totally absent, resulting in loss of peristalsis and impaired LES relaxation. - These changes explain the typical esophageal manometry recording seen in a patient with achalasia. - Most likely the ganglion cell loss is the result of chronic ganglionitis, i.e., inflammation of ganglia. - The causes of the ganglionitis are not fully understood. ### **Esophageal Biopsy Results** - The esophageal biopsy rules out pseudoachalasia, which is characterized by achalasia-like symptoms caused by secondary etiologies, i.e., it results from causes other than primary denervation. - One of the most common causes of pseudoachalasia is esophageal cancer or submucosal gastric cancer with extension into the lower esophagus. - In some cases, physicians will order an endoscopic ultrasound (EUS) with fine needle aspiration to definitively rule out pseudoachalasia and cancer. - In this case, although there was no evidence of any tumor from the endoscopic or x-ray imaging, the biopsy specimens obtained during the endoscopy provide the opportunity to check for any evidence of cancer. ### The appearance of the biopsy specimen shown in Figure 4 of the case - is consistent with the diagnosis of achalasia. - The two panels from Figure 4 are reproduced in the lower two panels. - The upper panel of Figure C shows a normal myenteric plexus from another part of the alimentary canal, the ileum. - In the middle image in Figure C (top panel in Figure 4), lymphocytic infiltration is present, including infiltration into ganglion cell cytoplasm (ganglionitis), as indicated by the thick black arrow. - The nervous tissue has also been invaded by blood vessels. - In the lower panel, there is evidence of a scarred myenteric nerve with a minimal amount of lymphocytic inflammation. - A blood vessel is evident within the tissue. - Ganglion cells are not readily visible. - This is clearly a later stage of the disease process than the middle panel, since most of the ganglion cells have been lost and there is significant scarring within the peripheral nerve. - These histological sections are consistent with the loss of ganglion cells from the myenteric plexus, which is the hallmark of classic achalasia. ### Laparoscopic Heller Myotomy - Mr. Pham's achalasia was treated with laparoscopic Heller myotomy, which is a common treatment for patients with achalasia who have low surgical risk. - Laparoscopic Heller myotomy is a minimally invasive procedure to open the lower esophageal sphincter (LES) by performing a myotomy, i.e., cutting the smooth muscle of the muscularis externa of the distal esophagus and the smooth muscle of the LES. - A Dor fundoplication is a partial wrapping of the stomach around the esophagus that forms a low-pressure valve. - It is performed to prevent reflux from the stomach into the esophagus following the myotomy. - The procedure usually results in a great relief of the symptoms. - This is the treatment chosen for Mr. Pham. ### References - Ates F and Vaezi MF. The pathogenesis and management of achalasia: current status and future directions. Gut and Liver, 9: 449-463, 2015. - Murray JA, Clouse RE, and Conklin JL. Components of the standard oesophageal manometry. Neurogastroenterol Motil, 15: 591-606, 2003. - Vaezi MF, Pandolfino JE, and Vela MF. ACG clinical guideline: diagnosis and management of achalasia. Am J Gastroenterol, 108:1238-1249, 2013.