GI #1

Pharyngeal arches 4 and 6

(Unnamed) cartilage in the 4th and 6th arches give rise to the laryngeal cartilages (thyroid, cricoid, arytenoids, corniculate, and cuneiform). Arch 4 gives rise to the pharyngeal constrictor group, cricothyroid, and levator veli palatini as well as the base of the tongue. Arch 6 gives rise to all laryngeal muscles except the cricothyroid. All are innervated by CN10 (vagus). The 4th aortic arch on the right becomes the subclavian and on the left becomes the arch of the aorta. The 6th aortic arches become the pulmonary arteries.

Pharyngeal muscles

*All pharyngeal muscles are innervated by the vagus nerve except the stylopharyngeus, which is innervated by the glossopharyngeal nerve (CN IX).* The glossopharyngeal nerve is the afferent limb of the gag reflex and both the vagus nerve and glossopharyngeal nerve serve as the efferent limb. Circular muscles The superior, middle, and inferior circular muscles are pharyngeal constrictors that propel food downward to the esophagus. The cricopharyngeus is the lowest part of the inferior constrictor and forms the upper esophageal sphincter. Longitudinal muscles elevate the pharynx during swallowing: stylopharyngeus, salpingopharyngeus, and palatopharyngeus.

pharyngoesophageal disorders

*Extraesophageal reflux Causes reflux laryngitis (hoarseness, throat clearing, cough, dysphagia, increased phlegm, and globes sensation) with a lack of classic heartburn and regurgitation symptoms. It can lead to pharyngeal and laryngeal edema, ulceration, granulomas, and leukoplakia.* Oropharyngeal dysphagia causes difficulty in initiating swallowing and can be neural/muscular (ALS, parkinson's, myasthenia, tardive dyskinesia, stroke) or structural (osteophytes, tumors, postcricoid webs). The cause of oropharyngeal dysphagia is discerned using functional endoscopic evaluation of swallow (FEES) and modified barium swallow. Palate surgery may be performed. Upper esophageal sphincter dysfunction A cricopharyngeus bar can occur when the cricopharynxgeus muscle becomes enlarged. The muscle can also be hypertonic, causing difficult swallowing. UES dysfunction can be diagnosed with barium swallow, EMG, or manometry (high pressure inside muscle signifies failure to relax or hypertrophy). The cricopharnyngeus muscle can be dilated, injected with Botox, or cut to relax/open it (myotomy). Zenker's diverticulum is caused by incomplete relaxation of the UES, causing increased pressure that produces a hernia at Killian's triangle - a weak spot between the inferior constrictor and the cricopharyngeus. This can cause dysphagia, regurgitation of undigested food (stuck in hernia), halitosis, cough, and aspiration pneumonia. DISH - diffuse idiopathic skeletal hyperostosis the spine pushes against the esophagus causing pharyngeal stasis of food, aspiration, and large posterior pharyngeal bony mass. Causes progressive choking with liquids and solids.

Vasculature of the gut

(unpaired) Arteries of the gut run within mesenteries to reach organs. Celiac trunk/axis arises at the T12 level and supplies the foregut - esophagus (left gastric), stomach (left gastric, right gastric, gastroduodenal, gastroepiploic), liver (common hepatic), pancreas (common hepatic), biliary apparatus (common hepatic), first part of duodenum (common hepatic). The celiac trunk arises from the aorta just inferior to the diaphragm (T12) and immediately branches into the common hepatic, splenic, and left gastric arteries. The common hepatic artery runs along the upper border of the pancreas and branches into the proper hepatic artery (clamped by pringle maneuver within the portal triad), right gastric artery (anastomoses with the left gastric artery to supply the lesser curvature), and gastroduodenal artery (supplies duodenum and pancreas and anastomoses with the gastroepiploic artery - branch of the splenic artery supplying the greater curvature of the stomach). The common hepatic artery supplies the liver, gallbladder, stomach, pancreas, and part of the duodenum (all of foregut but spleen and esophagus). The splenic artery arising from the celiac trunk is tortuous and branches into the short gastric and left gastroepiploic arteries. The splenic artery supplies the pancreas body, spleen, and greater curvature of the stomach (anastomoses with the gastroduodenal artery - branch of the common hepatic). The left gastric artery is the smallest branch of the celiac trunk and supplies the lesser curvature, anastomosing with the right gastric artery (branch of the common hepatic). The left gastric artery supplies the distal esophagus and lesser curvature of the stomach. Superior mesenteric artery arises from the L1 level and supplies the midgut - later duodenum, jejunum, ilium, cecum, ascending colon and first 2/3 of transverse colon. The superior mesenteric artery branches into the inferior pancreaticoduodenal, jejunal and ileal branches, middle colic (first 2/3 transverse colon), right colic (ascending colon), Ileocolic (Ileum and cecum), and appendicular arteries. The marginal artery (artery of Drummond) runs along the border of the large intestine and travels from the midgut to the hindgut to vascularize either area if the superior or inferior mesenteric artery is compromised. Inferior mesenteric artery arises from the L3 level of the aorta and supplies the hindgut - last 1/3 of transverse, descending colon, sigmoid colon, and proximal rectum. Branches of the inferior mesenteric artery include the left colic (descending colon), sigmoid, and superior rectal arteries. The artery of Drummond (marginal artery) runs along the border of the colon.

Campylobacter jejuni

Campylobacter jejuni is and enteroinvasive and inflammatory gram-negative, motile, cork-screw rod, that requires special charcoal agar and is microaerophilic. It colonizes animals. Campylobacter is the most common cause of diarrheal disease in the US. It has a low infectious dose and occurs most often when cooking with raw meat. It causes inflammatory diarrhea that can be bloody, cramps and fever for 1 week. Treat with rehydration and sometimes antibiotics.

esophagitis

Esophageal inflammation can be caused by infection (candida, CMV, herpes), drug/pill, corrosive/chemical, eosinophilic, or reflux (GERD). Mucosal necrosis can cause erosion followed by regenerative healing or ulceration followed by fibrosis and sometimes stricture. A common symptoms is odynophagia - food grates painfully on the way down. It is most common in immunocompromised patients and in those with diabetes, alcohol abuse, old age, and on systemic antibiotics. Esophageal candidiasis Candida is the most common esophageal pathogen, causing superficial white plaques (pseudomembranes) that can be scraped off and are made of candida pseudohyphae, PMNs, and necrotic debris. PAS staining is used to visualize the candida - the hyphae are bright red rods and the spores are small dark balls. Herpetic esophagitis is caused by HSV I and causes erosion/ulcers, superficial vesicles, and plaques. Histologically, epithelial nuclei are infected, causing nuclear inclusions (ground glass), margination of chromatin, and multi nucleation. Cytomegalovirus esophagitis is caused by CMV (herpes) and cause a single erosion/ulcer. Histologically, endothelial cells and fibroblasts are infected, causing nuclear and cytomegaly and nuclear inclusions (large owl eye). Pill/drug esophagitis occurs when pills get caught in the mid-distal esophagus, injuring the mucosa and causing localized inflammation, possibly with erosion/ulceration. Chemical/corrosive esophagitis Alkaline solutions are worse than acids, which are worse than alkaline solids. Alkali solutions cause liquifactive necrosis while acids cause coagulative necrosis. Eosinophilic esophagitis GERD or an environmental/dietary allergen causes infiltration of eosinophils into the mucosa, causing dysphagia of solid food and sometimes pain/heartburn. Patients diagnosed with upper endoscopy and biopsy often present late because they have adapted their eating. Patients will have rings of edema and linear furrows with white plaques (eosinophilic abscesses). Eosinophils have neon pink granules and bilobed nuclei histologically.

GI histology

General organization of the GI tract from lumen outward The mucosa contains the epithelium, lamina propria (loose connective tissue with glands), and muscular mucosae. The submucosa is dense, irregular connective tissue. The muscularis externa has an inner circular layer and an outer longitudinal layer of smooth muscle. The external layer contains the adventitia/serosa (loose connective tissue/with mesothelial lining from peritoneum) Tongue Stratified squamous epithelium (keratinized on dorsal side), serous glands/acini (darker - have ducts with simple cuboidal epithelium), mucous glands/acini (light), skeletal muscle, peripheral nerve fascicles, taste buds (formed by 8 spindle-shaped cells). Esophagus Stratified squamous epithelium, submucosa has many blood vessels and lymphatics. Only one longitudinal layer of smooth muscle in the muscularis mucosae. Glands are usually only in the lamina propria in the GI tract but there are both cardiac glands in the lamina propria and *esophageal mucous glands that extend into the submucosa* in the esophagus. Stomach In the cardiac region, stratified squamous epithelium of the esophagus turns to simple columnar, and gastric glands arise. The superficial layer of the mucosa is the foveolar compartment (pits) and extends through the epithelium lined by columnar mucous cells and continues into the glandular compartment in the lamina propria, which contains pink parietal cells higher up and blue chief cells deeper in the body and fundus. The deep/glandular compartment in the antrum contains mucous cells and G cells. Esophageal mucous glands in the submucosa extend into the cardiac region of the stomach, which has a thick submucosa and simple cardiac glands. The fundus and body of the stomach have more complex fundus glands that extend deeper into the wall. Fundic glands have surface lining mucous cells at the surface, *parietal cells* (fried egg; make HCl; many mitochondria to power endocytosis of vesicles after release of HCl from them) deeper in, *chief cells* (only in fundic glands) near the base of the fundic gland (red zymogen granules with pepsinogen on lumen side of cell, lots of rough ER on EM), and enteroendocrine cells at the base and facing toward a capillary rather than the lumen (release hormones). In the pyloric/antrum region, there are *no chief or parietal cells* but many surface lining mucous cells and mucous neck cells as well as G cells that release gastrin. The muscularis mucosae has an inner circular, outer longitudinal, and sometimes an outermost circular layer. The muscularis externa has an inner oblique, middle circular, and outer longitudinal. Duodenum Simple columnar epithelium, *goblet cells* (start in duodenum and increase in number moving down), villi with lamina propria in core (including a lacteal that absorbs fats and empties into blood stream near the neck), crypts of Lieberkuhn (intestinal glands), *Brunner's glands in the submucosa* (neutralize stomach acid), Auerbach's myenteric plexus (between smooth muscle layers of muscularis externa), Meissner's submucosal plexus. (Plexuses are parasympathetic, postganglionic cell bodies) Jejunum Simple columnar epithelium with brush border and more goblet cells, lamina propria within each villus, *Paneth cells* (dark granules of lysozyme antimicrobial) at base of crypts of Lieberkuhn, Meissner's submucosal plexus, and Auerbach's myenteric plexus. Ileum Simple columnar epithelium with more goblet cells, villi with lamina propria in their cores, crypts of Lieberkuhn. *Peyer's patches* are triangular clusters of lymphocytes in the Ilium containing B cells, plasma cells, and M cells (microfold, antigen presenting cells). (GALT can be found all along the GI tract) Cecum Simple columnar epithelium, many goblet cells, *no villi*, crypts of Lieberkuhn with lamina propria in between. Large intestine Simple columnar epithelium, tons of goblet cells, *no villi,* crypts of Lieberkuhn with lamina propria in between. Appendix Similar to colon but with *large lymphoid nodules* in the lamina propria and submucosa that can obliterate the crypts. *Muscularis mucosae will be thinner and can be discontinuous*. Lumen is also filled with debris. Anal canal Moving down - simple columnar cuboidal then stratified squamous nonkeratinized, then stratified squamous keratinized (anus)

Colon neoplasms

Hyperplastic polyps are the most common polyp in large bowel and have no malignant potential or increased risk for colorectal carcinoma. They are benign epithelial lesions of colorectal mucosa that are usually <3mm in diameter. They are usually small sessile polyps that are paler than the mucosa. Histologically, crypts in the upper half of the polyp have a serrated/convoluted appearance (rather than circular) with decreased numbers of goblet cells. Colonic adenomas are dysplastic and premalignant, giving rise to most colon cancer. Histologically, most are tubular with epithelium arranged in closely-packed branching tubules (lacking normal amount of lamina propria) having a cerebriform appearance at low power. Adenomas can also be villous (more aggressive than tubular), with straight, elongated, finger-like fronds extending from the muscularis mucosa to the luminal surface (velvety appearance grossly). Adenomatous colonic epithelium has pleomorphic, hyperchromatic nuclei, nuclear pseudostratification, loss of cytoplasmic mucin, overlapping cells, and increase in apoptosis and mitotic divisions. Low grade dysplasia has spindle shaped nuclei and high grade dysplasia has round nuclei with prominent nucleoli. Malignant polyp/ adenocarcinoma Invasive carcinoma is found in 2-5% of adenomas removed at colonoscopy. Histologically you see high-grade dysplasia with irregular, infiltrative glands of early invasive carcinoma. Colon cancer is the 4th most common cancer. Presentation is usually asymptomatic or sometimes abdominal pain. Red flags are obstruction (cancer in iliocecal junction), bleeding, weight loss, pencil thin stool, *iron-deficiency anemia,* and evidence of metastases. *Those with new iron deficiency anemia over age 50 should receive a colonoscopy (fecal occult blood testing should not be performed* because a negative test is not enough to rule out colon cancer). Stool becomes more solid as it moves right to left so greater obstruction is needed on the right to present with obstruction. *Barium enema will show an apple core lesion* (but not done often today). Tumors in the right colon are usually polypoid or fun gating exophytic masses. Tumors in the left are usually annular lesions that produce an apple-core appearance and present with bowel obstruction. Colorectal carcinoma colorectal carcinoma is carcinoma with a desmoplastic stroma that invades bowel wall. Prognosis is related to degree of differentiation (grade), extent of bowel penetration, and nodal involvement (stage). Tumor cells have oval or round nuclei, clumped chromatin and nuclear pleomorphism, and nucleoli may be large or irregular. Mucin secretion varies from minimal to abundant (mucin pools). Colon cancer screening starts at age 50 and can include fecal occult blood tests yearly, barium enema, CT calligraphy, sigmoidoscopy (only sigmoid and descending colon), and fecal DNA (may replace colonoscopy in next 10 years). Before therapy and after tumor removal, tests are performed to look for KRAS or BRAF mutations which would signify anti-EGFR therapy resistance. Microsatellite instability would indicate resistance for 5-fluorouracil therapy (lynch syndrome).

gastroparesis

Lack of gastric motility or emptying in the absence of obstruction caused by *diabetes,* scleroderma, drugs (opioids), or idiopathic. Symptoms include nausea/vomiting, bloating, epigastric pain (several hours after eating when stomach is still full), and weight loss. Hypovolemia and succession splash may be seen (splashing several hours after eating with auscultation). Opiates can induce a motility disorder that is clinically indistinguishable from gastroparesis. Diagnose with upper endoscopy to rule out physical obstruction and then perform a gastric emptying study to quantify the emptying of the stomach (normal is >90% after 4hrs). manage by decreasing size of meals, drinking more liquids, eating fewer leafy greens and other foods requiring trituration (less fiber), decreasing fat intake, pro kinetic agents (metoclopramide), surgery, or neurostimulators (extreme cases).

Branchial/pharyngeal arches

Orofacial and neck structures develop during the embryonic period, weeks 4-8, so teratogen exposure during this time will cause severe deformities. In fetal alcohol syndrome, children have a small head, flat mid face, smooth philtrum, low nasal bridge, small eye openings, short nose, and thin upper lip - some of the facial features are due to neural crest cell injury or impaired migration. Week 4 begins as a flat embryo and then folding occurs. Transverse folding creates the GI tract, and branchial arches (branchial = gills) start developing cranial to caudal in the form of 6 pairs (5th disappears) of ventrolateral bulges between the brain and thorax. The branchial/pharyngeal apparatus consists of a series of arches, clefts/grooves (external invaginations lined with ectoderm), pouches (internal invaginations lined with endoderm), and membranes (tissue separating cleft and pouch). The external layer of the arches arises from the ectoderm, muscle and blood vessels arise from mesoderm, skeletal tissues arise from the neural crest (ectoderm - migrates into arches), and the GI tract lining is derived from endoderm. *The arch is innervated by CN5 (trigeminal), 2 by CN7 (facial), 3 by CN9 (glossopharyngeal), and 4 and 6 by CN10 (vagus).* Arch 1 Muscles of mastication (CNV), anterior 2/3 of tongue (CNV = touch/temp, CNVII = taste) Forms the auricle/pinna of the ear (external ear. Preauricular tag is a remnant from auricle formation and microtia is a malformed auricle). Maxillary process - no cartilage > middle 1/3 of face, lip and palate formation with frontonasal process Mandibular process - Meckel cartilage > mandible, malleus, incus Cleft/groove 1 gives rise to the external auditory/acoustic meatus. Pouch 1 forms the eustachian tube. Membrane 1 becomes the tympanic membrane. Arch 2 Muscles of facial expression, buccinator (CNVII) Reichert cartilage > lesser horn of hyoid, styoid process, stapes. Contributes to the auricle/pinna of the ear. (Preauricular tag is a remnant from auricle formation and microtia is a malformed auricle) Pharyngeal clefts and membranes 2-4 disappear as arch 2 overgrows and covers them up. This temporarily creates a cervical sinus/vesicle that, if it doesn't fill in, creates a branchial cleft cyst along the anterior border of the sternocleidomastoid muscle. Branchial cleft cysts can swell with infection and are treated with complete surgical excision. (cleft anomalies involving the 1st cleft go through the parotid and can wrap around the facial nerve) Pouch 2 becomes the palatine tonsil. Arch 3 Stylopharyngeus (CNIX) and posterior 1/3 of tongue (CNIX - sensation) Cartilage > body and greater horn of hyoid Pouch 3 becomes the thymus and inferior parathyroids. Arches 4, 6 4 (CNX) - pharyngeal constrictor group, cricothyroid, levator veli palatine, base of the tongue (CNX - sensation) 6 - laryngeal muscles except cricothyroid (CNX) Cartilage > laryngeal cartilages (thyroid, cricoid) Pouch 4 becomes the superior parathyroids. (DiGeorge syndrome - pharyngeal pouches 3 and 4 do not develop normally so thymus and parathyroids may be partial or absent, causing immune deficiencies and/or hypocalcemia) Each arch has one vessel - aortic arch. Arch 1 and 2 disappear while 3, 4, 6 form named vessels. 3 > common carotids and part of internal carotids 4 > right aortic arch becomes part of right subclavian and left becomes part of arch of aorta 6 > pulmonary arteries

Salivary gland problems

Sialolithiasis is formation of calcium (stones) in the ductal system of salivary glands and the most common cause of inflammation esp. in men 50+ yrs. 80-90% form in Wharton's duct (submandibular gland) because it is longer, more tortuous, and moves against gravity. Sialolithiasis is not related to serum Ca and Ph but to stasis of saliva. It causes recurrent episodes of *postprandial salivary colic with pain and swelling in the submandibular gland.* Mumps is a contagious, incurable systemic myxovirus that causes fever, malaise, and headache followed by painful swelling of one or both parotid glands with erythema of Stenson's duct orifice. Deafness, encephalitis, sterility, and pancreatitis can also occur. Sialoadentis Swelling of the salivary glands can be treated with antibiotics, warm compression, massage, sialogogues (sour candy), sialoendoscopy, and gland excision. Chronic Sialorrhea is an increase in salivary flow while drooling is a spillage of saliva over the lower lip from a disturbance in the oral phase of swallowing (poor synchronization of lip closure). Children with developmental delay in oral neuromuscular control can improve until age 6 (eg. cerebral palsy). *Sialorrhea can be treated with medications and/or botox. * Diabetes and hyperlipidemia can cause fatty infiltration of salivary glands and decrease salivary flow. Deficiencies in niacin (pellagra), protein (Kwashiorkor, cirrhosis), thiamine (Beriberi), and vitamin A can cause parotid enlargement. Idiopathic xerostomia (dry mouth) can be caused by radiation therapy, blood pressure meds, anti-histamines, anti-depressants, and muscle relaxants.

Deglutition

Swallowing stage 1/oral stage - voluntary Food is chewed and mixed with saliva to form a bolus. Tongue muscles move the bolus toward the back of the mouth. Stage 2/pharyngeal stage - involuntary Soft palate elevates, sealing off the nasopharynx from the oropharynx. Longitudinal muscles of the pharynx elevate the pharynx to accept the bolus as vocal folds close to keep food and liquids from entering the airway. Stage 3/esophageal stage - involuntary the 3 pharyngeal constrictors sequentially contract and propel the bolus into the esophagus.

Inguinal canal

The inguinal canal is a passageway through the inferior abdominal wall that allows structures to pass between the abdominopelvic cavity and perineum into the external genital region. The deep inguinal ring is inside the abdominal wall and the superficial inguinal ring opens into the medial aspect of the aponeurosis of the external oblique. In inguinal hernias, visceria (usually parietal peritoneum or small bowel) protrudes through the inguinal canal following the path of the processes vaginalis and emerging into the scrotum. Surgery is needed and bowel entrapment in the inguinal canal (incarcerated hernia) is a surgical emergency because the bowel can become ischemic and die. *Direct inguinal hernias occur in middle aged males and are caused by weakness of the anterior abdominal wall, allowing viscera to protrude through the superficial ring (through the inguinal/Hesselbach's triangle) such that contents are outside the spermatic cord. The inguinal/Hesselbach's triangle is bounded by the inguinal ligament inferiority, the epigastric vessels laterally, and the rectus abdominis medially. Indirect inguinal hernias are congenital defects where small bowel or peritoneum follows the path of the spermatic cord through the deep and superficial rings into the scrotum. Indirect inguinal hernias are lateral to the epigastric vessels (lateral to inguinal triangle)* The main structures traversing the inguinal canal are the spermatic cord in males and the round ligament of the uterus in females. The illioinguinal nerve that innervates the scrotum or labia majora also passes through. Spermatic cords include the testicular artery (branch of aorta vascularizing testicle), ductus deferens, pampiniform plexus of veins (thermoregulation), genital branch of the genitofemoral nerve (innervates middle spermatic "cremaster" fascia), lymphatics, and autonomic nerves. Testicles begin development in the abdominal cavity between the peritoneum and transversals fascia and descend into the scrotum, pulled by the gubernaculum. They are enveloped by all of the fascia/muscular layers of the wall except the transversus abdominis and the peritoneum. The external oblique becomes the external spermatic fascia, the internal oblique becomes the middle "cremasteric" spermatic fascia, and the transversals fascia becomes the internal spermatic fascia. The processes vaginalis is the out-pocketing of the peritoneum that protrudes into the scrotum along with the testicle and neurovasculature. Most of the processes vaginalis degenerates except surrounding the anterolateral aspect of the testicle, forming the tunica vaginalis. The outer layer is the parietal layer and the inner layer is the visceral layer. If parts of the processes vaginalis don't degenerate, peritoneal fluid can accumulate and form a hydrocele (not painful) and swelling in the scrotum (usually disappears in first year but older boys and men can develop hydrocele from inflammation or injury within the scrotum). Non-communicating hydroceles are confined to the scrotum, hydroceles of the cord are confined to the spermatic cord, and communicating hydroceles communicate with the abdominal cavity (can require surgery). the testicular artery (branch of the aorta) supplies the testes, and the pampiniform plexus of veins drains the testis and converge to form the testicular veins. the right testicular vein drains into the IVC while the left testicular vein drains into the left renal vein.

Autonomic NS

Visceral motor fibers are part of the ANS. Visceral sensory fibers are not technically part of the ANS but are often considered with it because they accompany autonomic visceral motor nerve fibers. They run from from mucous membranes, glands, smooth and cardiac muscle travels to the spinal cord (no ganglion/synapse before reaching the spinal cord) Parasympathetic innervation stimulates peristalsis, relaxes the anal sphincter, and stimulates glycogen production. Sympathetic activation reduces peristalsis and blood flow to the gut, contracts the anal sphincter, and induces glycogen breakdown. The foregut Sympathetic innervation is by the greater thoracic splanchnic nerve from T5-T9, which contains preganglionic visceral motor fibers that synapse with postganglionic visceral motor fibers at the celiac ganglion. Parasympathetic innervation is via the vagus nerve. Preganglionic visceral motor parasympathetic fibers synapse with postganglionic at a ganglion near the liver. The midgut The midgut is sympathetically innervated by the lesser thoracic splanchnic nerve that arises at T10-11. Preganglionic visceral motor sympathetic fibers synapse at the aoricorenal and superior mesentery ganglion with postganglionic. Parasympathetic innervation is from the vagus nerve, with preganglionic visceral motor parasympathetic fibers synapsing with postganglionic at a ganglia near the kidney. Hindgut The hindgut receives sympathetic innervation via the lumbar splanchnic nerves from L1-L2. Preganglionic visceral motor sympathetic fibers synapse at the inferior mesenteric ganglion with postganglionic fibers. Parasympathetic innervation comes from pelvic splanchnic nerves, with the preganglionic visceral motor fiber reaching to a ganglion close to the descending colon and synapsing with postganglionic fibers. A tumor in the descending colon will cause deferred pain in the pubic region. Pain is transmitted along the sympathetic pathway and the hindgut is innervated sympathetically by nerves from L1-L1, and the dermatome L1-L2 is the pubic region.

Peptic ulcer disease

An ulcer is a defect in the mucosal surface penetrating through the muscularis mucosa. Risk factors of PUD include H. pylori, NSAIDs, gastric acid (Zollinger-Ellison syndrome: gastrinoma, often in the pancreas, causing severe gastric HCl secretion), alcohol, and smoking. Defensive factors include mucus barrier, HCO3 secretion, prostaglandins, cellular resistance, and mucosal blood flow. The mucus layer produced by surface epithelial cells contains water and mucin glycoprotein as well as secreted HCO3- that increases the pH just above the cells. Pepsin activity decreases at pH >5 so pepsin is unable to reach and harm epithelial cells (pH at their surface is 7). Prostaglandins are produced from arachiconic acid by COX-1 (constitutive) and COX-2 (inducible - inflammation, pain) and decreases acid production and increases mucus and bicarb secretion. NSAIDs block COX 1 and 2, decreasing mucous protection. Selective COX-2 inhibitors permit COX-1 pathway to persist. Cellular resistance includes tight junctions, mucosal restitution (migration of mucosa within minutes of small breaks without requiring cell division), and regeneration (cell division over days in response to larger breaks). Mucosal blood flow delivers O2, nutrients, and bicarbonate; removes back diffused acid; must be >50% of normal amount to protect the mucosa. Duodenal ulcers are often in the bulb of the duodenum. Gastric ulcers are often in the pre-pyloric region and lesser curvature of the antrum. Ulcers are usually a single punched out/cookie cutter hole with a smooth base, perpendicular sides, and flat margins. Ulcers have 4 zones: A top layer of fibrinopurulent exudate representing the immune response with PMNs and fibrin. A deeper layer of necrotic tissue. A layer of granulation tissue (early phase of scarring with many new blood vessels). The deepest layer of fibrotic tissue/scar. Uncomplicated PUD presents with epigastric pain, nausea, bloating, fullness, and early satiety, or can be asymptomatic. Complicated PUD presents with melena, hematemesis, or hematochezia (bright red blood in the stool if there is lots of blood loss); shock or peritoneal signs from perforation; and/or vomiting or succession splash from obstruction in the distal stomach or proximal duodenum from edema, scar contraction, and muscle hypertrophy. PUD can be diagnosed with upper endoscopy or barium swallow (barium will pool in ulcers). Uncomplicated PUD is treated with PPI for 4-8 weeks and eradication of H pylori to prevent recurrence (triple therapy - omeprazole + amoxicillin + clarythromycin). NSAIDs should be discontinued (aspirin) and smoking stopped. Complicated PUD should be treated with endoscopic therapy for bleeding, nasogastric suction to decompress the stomach and prevent aspiration and dilation/surgery for obstruction, and emergency surgery for perforation. Surgical management for ulcers is not usually done, but includes Billroth I (distal antrum and proximal duodenum are removed and stomach and duodenum are reconnected) and Billroth II (antrectomy with connection of stomach to lateral aspect of jejunum). In truncal vagotomy + pyloroplasty, vagal nerves to the pylorus are severed and pyloroplasty is used to open the pylorus permanently. In highly selective vagotomy, vagal fibers to the pylorus are retained and only fibers to the proximal stomach where acid is produced are cut.

Pharyngeal arch 3

(Unnamed) cartilage of arch 3 becomes the body and greater horn/cornu of the hyoid. The stylopharyngeus is the only muscle derivative and is innervated by CNIX (glossopharyngeal). Arch 3 also gives rise to the posterior 1/3 of the tongue (CNIX - sensory) The 3rd aortic arches becomes the common carotids and part of the internal carotids.

Esophageal motility disorders

Achalasia is lack of peristalsis in the esophageal body as well as non-relaxation of the lower esophageal sphincter. LES basal pressure can be normal or high. Achalasia can cause dysphagia for solids and liquids, chest pain or fullness after eating, heartburn, regurgitation, malnutrition, aspiration, and squamous cell carcinoma. Manometry is used to diagnose but barium swallow is also performed and shows a dilated esophagus and bird beak smooth symmetric narrowing of the distal esophagus. Endoscopy can be used to rule out strictures and masses (tumor). Most cases in the US are caused by an idiopathic inflammatory infiltrate in Auerbach's myenteric plexus (muscularis externa) that leads to ganglionic drop-out and loss of LES relaxation. Chagas disease from Trypanosoma cruzi is a common cause in South America. Achalasia can be treated with botulinum toxin injection in the LES to block presynaptic ACh release (neuron can't cause contraction), which lasts 6 months (not best for young patients). Young, healthy patients can receive pneumatic dilation, where a balloon is inflated to rupture the LES muscles. In esophageal myotomy, musculature of the lower esophagus is cut to expose the mucosa and release the obstruction of the LES (later antireflux surgery may be needed). Diffuse/distal esophageal spasm (DES) is repetitive, simultaneous, abnormally long contractions of the esophagus in response to swallows, causing chest pain and dysphagia as well as corkscrew esophagus with barium swallow. Manometry shows repetitive, simultaneous, abnormally long contractions in response to swallows. Pressures may be normal but contraction speed too fast, or there can be high pressure over a long period of time and large segment of esophagus (jackhammer esophagus). Therapy includes smooth muscle antagonists (calcium channel blockers and nitrates) and occasionally long myotomy. Ineffective esophageal motility is characterized by weak peristalsis (reduced or broken amplitude) causing dysphagia for solids and liquids and is often seen in association with reflux disease. Diagnose with esophageal manometry.

acute gastritis

Acute inflammation of the mucosa with PMNs caused by drugs (NSAIDs, alcohol, chemo), infection (H. pylori or virus), disease complications (uremia, infections), or mucosal hypoxia (shock, trauma, burns, surgery). Any of these etiologies can cause direct gastric mucosal injury or interfere with normal gastric protective mechanisms by decreasing mucous production, prostaglandins, epithelial repair, or intramural pH, causing acid and pepsin to injure the unprotected mucosa. Necrosis/erosion and hemorrhage are possible complications of acute gastritis.

Aspiration and ingestion of foreign bodies

Airway foreign bodies Most foreign bodies are radiolucent and don't appear on X-ray. But, X-rays can show overinflation caused by obstruction (prevents deflation). Most airway foreign bodies are food (35% peanuts). Diagnose with history of choking followed by coughing, wheezing and decreased breath sounds, and chest X-ray showing air trapping, atelectasis, infiltrates, or consolidation. If there is any question, repeat exam and imaging after 24 hours. Most pass on their own, but bronchoscopy can be used. Complication rates rise with increased time to diagnose. Complications develop in 60% of those where diagnosis is delayed >30 days (25% get bronchiectasis) Esophageal foreign bodies Battery ingestion is an emergency because liquefaction necrosis can cause perforation in 6 hours. The most common places for esophageal foreign bodies to lodge are at level C6 (cricopharynxgeus), T4 (descending aortic arch and carina push against esophagus), and lower esophageal sphincter. Signs and symptoms include infants refusing to eat or drink, children complaining of dysphagia or odynophasia, drooling, trachea compression. most are radiopaque on chest Xray but barium swallow may show radiolucent object. Esophogoscopy should be performed if there is airway distress, complete obstruction (inability to handle secretions can lead to aspiration), chest X-ray with double lumen sign (battery), and needles. Caustic ingestion causes tissue injury by chemical reaction. Acidic liquids like toilet bowl cleaners, battery fluid, and rust removal products coagulate in the stomach and form an eschar (scab) that sits on top and does not cause perforation as quickly as *alkaline liquids (drain and oven cleaners, dishwasher detergent, hair relaxers) that cause liquefactive necrosis and rapid perforation*. Alkaline fluids cause severe injury in minutes, granulation at 2 weeks and then stricture formation (place stent for 6 weeks to prevent closure). Symptoms of perforation include dyspnea, dysphagia, odynophagia, chest pain, abdominal pain, and nausea and vomiting. Signs include hoarseness, stridor, tachycardia, oropharyngeal burns, drooling, subcutaneous air, peritonitis, and fever.

Congenital abnormalities of developing GI tract

As the GI tract develops, it is originally patent, then fills in, and then recanalizes. In Duodenal atresia, recanalization does not occur, causing *bilious vomiting* and double bubble on X-ray. In congenital pyloric stenosis (which is fairly common in males), pyloric wall hypertrophy prevents food passage from the stomach, creating palpable mass in newborns and causing projectile *non-bilious vomiting*. An umbilical hernia occurs when intestines return to the abdomen in week 10 but re-herniate through an imperfectly closed umbilicus. This causes a *midline* protrusion with a small amount of abdominal contents *covered by skin.* An omphalocele is the persistence of herniated intestines (don't return in week 10). This causes a *midline* protrusion at the naval containing varying amounts of intestines *covered by peritoneum-like transparent sac*. Gastroschisis occurs when the abdominal wall fails to close after the intestines return to the abdomen, causing protrusion *near the midline* containing variable amounts of *uncovered* GI tract. Meckel's diverticulum is the *most common congenital anomaly of the GI tract (2% of population)*. It is a 2-inch long remnant of the vitelline duct (temporarily joins yolk sac to developing midgut) 2 feet from the ileocecal junction. The diverticulum can be lined with gastric epithelium or pancreatic tissue, both of which make digestive enzymes/acid that can cause bleeding. Mickey's diverticulum causes bleeding, intussusception, volvulus, and obstruction in the first 2 years. Hirschsprung's disease is the absence of innervation (Meissner's in submucosa and Auerbach's gin the muscularis externa) in the wall of the distal GI tract caused by failure of neural crest cells to make it to the distal colon/rectum. The aganglionic area is constricted and lacks the ability to move food, causing the proximal area to become dilated (*congenital megacolon*). Can prevent passage of meconium or constipation, depending on severity.

Astrovirus Adenovirus Enteroviruses

Astrovirus Outbreaks occur more often in infants or the elderly and cause mild gastroenteritis that rarely needs treatment. 90% get it by age 10. Has a star-like appearance on EM. Adenovirus Enteric adenovirus has dsDNA, icosahedral nucleocapsid, and no envelope with 50 serotypes (other types of infection more common, esp. respiratory). Enteroviruses Picornaviruses (icosahedral virion, +ssRNA, no envelope) that include poliovirus and coxsackievirus. Most infections summer to fall. Viruses found in water supplies (like US sewage). Coxsackie A causes URI, herpangina, meningitis, hand-foot-mouth disease Coxsackie B causes myocarditis, pleurodynia, meningitis Echovirus causes meningitis, pleurotynia, rash Diagnose enteroviruses with PCR, treat with IVIG in some cases, no vaccines for non-polio enteroviruses

GI bacteria general

Bacterial overgrowth syndrome - endogenous microbes of the lower GI tract are allowed to move up the tract because of reduced acidity, leading to vitamin deficiencies, fat malabsorption, and malnutrition. Enteric bacterial pathogens are groups by mechanism of disease: Enteroinvasive - facultative intracellular pathogens cause disease by invading host cells. Enterotoxic - bacteria produce enterotoxin to cause disease (do not invade cells) Enteropathogenic - bacteria destroy epithelium but do not invade cells. Salmonella, shigella, EIEC, Listeria, and campylobacter are enteroinvasive and inflammatory (stool contains blood and pus). C. diff and EHEC are enterotoxic and inflammatory. Vibrio cholerae, and ETEC are enterotoxic and secretory. Enteropathogenic E.coli (EPEC), enterohemorrhagic (EHEC), and H pylori are enteropathogenic. Lactose MacConkey agar is selective for gram negatives and differential for lactose fermentation - Lac+ pink, Lac- beige.

Extrahepatic biliary system

Bile exits the liver via hepatic ducts that empty into the common hepatic duct. The common hepatic becomes the common bile duct as it passes the cystic duct opening that connects the gallbladder to the common hepatic duct (opening of the gall bladder into the cystic duct is maintained by the spiral valve). The common bile duct is in the portal triad and empties into the 2nd part of the duodenum via the sphincter of Oddi. The pancreatic duct also empties through the sphincter of Oddi. The gallbladder receives, concentrates, and stores bile from the liver, and its cystic duct has spiral valves of Hiester. The triangle created by the common hepatic duct, the cystic duct, and the liver is called the cystohepatic triangle of Calot.

Pancreatic secretions

CCK and ACh stimulate receptors on pancreatic acinar cells, leading to release of enzyme containing vesicles. Cl- is actively moved against it's [] gradient so that water and Na+ will follow when help make up the pancreatic juices. After enzymes are released by acinar cells deep within the pancreatic ducts, they must be moved into the duodenum by centroacinar/duct cells. Secretin activates cAMP within duct cells, which activates CFTR Cl- channels to move Cl- from the cell into the lumen. Cl- then travels back into the lumen down its [] gradient, powering an antiproton that moves bicarb from inside the cell to the lumen. Na+ and water follow, increasing pancreatic juice volume. Somatostatin (released by D cells in the stomach and pancreas) inhibits this process. The endocrine pancreas consists of islets of langerhans. Alpha cells secrete glucagon that increases serum glucose by stimulating gluconeognesis and glycogenolysis. Beta cells secrete insulin that decreases glucose levels. Delta cells secrete somatostatin in response to acid in the lumen that inhibits secretion of gastrin, VIP, GIP, secretin, and motilin, pancreatic exocrine and endocrine secretion, and absorption of glucose, amino acids, and triglycerides. Somatostatin also decreases the rate of gastric emptying, reduces smooth muscle contractions and blood flow in the intestine.

Chronic gastritis

Chronic inflammation of the gastric mucosa caused by H. pylori or autoimmunity and involving lymphocytes, plasma cells, and macrophages. Cell and humoral mediated immune response lead to epithelial cell necrosis and can cause atrophy of glands and eventually mucosa as well as intestinal metaplasia that can become dysplastic and cancerous. Grossly, chronic gastritis causes loss of rural folds. Histologically, normal mucosa with back-to-back glands changes so that glands become spaced out by lamina propria filled with chronic inflammatory cells and lose depth. Intestinal metaplasia (simple columnar epithelium with absorptive [dense pink] and goblet cells) can occur. Autoimmune chronic gastritis has AD inheritance and causes autoantibodies to parietal cells (IF, enzymes, or other proteins) in the fundus/body of the stomach, leading to destruction of parietal cells by lymphocytes and gland atrophy. Decreased acid production leads to hypochlorhidria or achlorhidria and decreased intrinsic factor decreases B12 absorption and leads to anemia (*pernicious anemia*).

Clostridium

Clostridium are gram-positive, spore-forming bacilli in the Firmicutes phylum. They can be strict anaerobes (C. difficile) or slightly aerotolerant (C. perfringens and septicum) and are a relatively minor component of normal flora. Clostridium ferment carbs, fatty acids, and amino acids (producing smelly products). Toxins produced by overgrowth play a big role in disease. C. perfringens - slightly aerotolerant. Secretes A-B toxin called alpha-toxin which contains lecithinase that degrades tissue and cell membranes. Can cause Clostridial myonecrosis/Traumatic gas gangrene when tissue damage allows anaerobic metabolism and C. perfringens spores contaminate the wound. The spores germinate, causing tissue destruction, septic shock, and gas production. 25% will die without antibiotics and surgical removal of infected tissue. C. septicum - slightly aerotolerant. Can cause clostridial myonecrosis/gas gangrene when breaks in GI mucosa allow C. septicum to enter the bloodstream and invade muscle tissue at multiple sites, causing tissue destruction, septic shock, and gas production. Almost all will die without surgical removal of infected tissue and antibiotics. C. botulinum - food poisoning and wound botulism. Secretes binary A-B toxin with independent binding and active proteins linked by a S-S bond. Botulinum toxin prevents release of stimulatory NT, causing paralysis. C. tetani - secretes binary A-B toxin with independent binding and active proteins linked by a S-S bond. Prevents release of inhibitor neurotransmitters, causing spasticity. C. difficile - antibiotic-associated diarrhea and colitis. Secretes A-B toxins that include Toxin B, Toxin A, and others that have binding and enzymatic domains in a single protein - glucosylate Rho GTPases are cytotoxic and inflammatory.

Diaphragmatic apertures Posterior side of anterior abdominal wall

Daiphragmatic apertures (I 8 10 eggs at 12) Caval opening - aperture for the IVC at the T8 level (respiration propels blood to heart). Esophageal hiatus - aperture for passage of the esophagus and vagus nerves at T10 level. Aortic hiatus - the aorta goes behind the diaphragm (so flow not affected by respiration) and enters from behind, passing between the crura (legs) at the T12 level. The round ligament of the liver (ligamentum teres) is a remnant of the obliterated umbilical vein (conveyed oxygenated blood from the placenta) that runs from the umbilicus to the liver and is covered by the falciform ligament (double layer of peritoneum that reflects between the liver and anterior abdominal wall). The median umbilical fold is a single midline fold created by the median umbilical ligament, a remnant of the urachus (fetal connection between the bladder and umbilicus). Two medial umbilical folds are created by the medial umbilical ligaments, remnants of the fetal umbilical arteries (conveyed deoxygenated blood from fetus to placenta). Two lateral umbilical folds are created by the underlying inferior epigastric vessels.

Dental plaque and associated bacteria

Dental plaque-associated biofilms are made of host and bacterial proteins, polysaccharides, and bacteria. Supragingival plaque-associatd biofilms contain aerobic or aerotolerant gram-positive species like Actinomycetes. Subgingival PAB contain gram-negative anaerobes like Bacteroides. Actinomyces are gram-positive, non-spore forming anaerobic (oxygen tolerant) bacilli that look like hyphae microscopically and are part of the normal oral flora but can cause dental carries and periodontal disease (opportunistic). Actinomycosis is usually odontogenous and follows *dental procedures* more often in adults than children. Poor oral hygiene, smoking, heavy alcohol use increase risk. Actinomyces israelii infection causes lumpy jaw, a chronic infection with swelling of soft tissue, abscess, or mass lesion and characteristic *sulfur granules* in drained fluid. Long term antibiotics are required because it is slow growing (4-6 weeks IV penicillin or up to 1 year of oral antibiotics). Bacteroides are gram negative, non-spore forming, anaerobic bacilli in the oropharynx, intestinal tract, and female genital tract. Bacteroides fragilis is the main bacteria in the GI tract. Bacteroides are beneficial in that they ferment complex carbs, aid in acquisition and utilization of nitrogen, recycle bile acid components, and resist colonization of pathogenic bacteria (compete for attachment and nutrients, produce volatile fatty acids that prevent growth of other bacteria, release free bile acids). But Bacteroides are the most common genus isolated from anaerobic infections outside the GI tract (requires breach of epithelial barrier). Peritonitis from following compromised intestinal barrier function often involves synergy between E. coli and Bacteroides fragilis, which has a capsular polysaccharide that protects it from PMN recruitment.

Dysphagia

Dysphagia is the sensation of food being hindered as it passes from mouth to stomach. Dysphagia can be oropharyngeal (transfer) or esophageal (transport) Esophageal dysphagia includes obstructive (mechanical) and motility (neuromuscular). An upper endoscopy is always performed to rule out malignancy. Barium swallow is also used, as well as esophageal manometry when neuromuscular causes are suspected. Oropharyngeal dysphagia Patients with difficulty initiating swallows, causing coughing, choking, and nasal regurgitation probably have OPD. Dry mouth may be present. OPD can be caused by stroke or radiotherapy. Identify structural lesions amenable to treatment, determine functional integrity of swallow (flexible endoscopic evaluation of swallowing, modified barium swallow, or manometry), evaluate aspiration risk, and determine if OPD is amenable to therapy. Those with intermittent difficulty swallowing steak or bread often have Schatzki's ring at the gastroesophageal junction often in the presence of a hiatal hernia. Those with *intermittent difficulty swallowing solids and liquids as well as chest pain can have diffuse esophageal spasm, which produces a corkscrew esophagus* with modified barium swallow. Eosinophilic esophagitis can cause chronic difficulty swallowing solids but can present as acute food obstruction because patients adapt their eating until the esophagus is very narrow.

Escherichia coli

E. coli are gram negative rods, facultative anaerobes, lactose-positive on MacConkey agar, that usually colonize animals (some only humans), and most are non-pathogenic colonizers of the colon. E. coli can cause gastroenteritis, UTIs (uropathogenic E. coli - UPEC), bacteremia, and meningitis. Enterotoxigenic ETEC E. coli attach to epithelial cells and deliver their enterotoxin into the cell, causing cholera-like illness. Toxins can be acid stable or acid sensitive. ETEC is human only Enteroinvasive EIEC invade epithelial cells via a phagosome, escape, and spread to adjacent cells. EIEC is human only. Enteropathogenic EPEC Adheres to and damages epithelium but doesn't invade. It creates an actin bundle/pedestal formation. EPEC is in humans and animals. Enterohemorrhagic EHEC Adheres to and damages epithelium but doesn't invade. It creates an actin bundle/pedestal formation. EHEC is in humans and animals and secretes shiga toxin into cells.

Layers of the abdominal wall Rectus sheath

From outside, in: Superficial fascia - composed of an outer superficial layer (Camper's fascia) of fat and an inner deep membranous layer (Scarpa's fascia) of tough fibers. External oblique muscle Internal oblique muscle Transversus abdominis muscle Endoabdominal/transversalis fascia Peritoneum - thin serous membrane lining the inside of the abdominal cavity Rectus Sheath Compartment formed by the aponeuroses of the external and internal oblique and transverses abdominis muscles and surrounding the rectus abdominis and pyramidalis. Above the arcuate line (1in below the umbilicus), the aponeuroses of the external and internal oblique muscles cover the rectus abdominis (anterior layer) and the aponeuroses of the internal oblique and transversus abdominis run under the rectus abdominis (posterior layer) (the transversalis fascia and peritoneum are below that). Below the arcuate line, all of the aponeuroses run over the rectus abdominis (thick anterior layer) so that only the transversals fascia and peritoneum run below the rectus abdominis.

EGFR pathway ACP-related polyposis Lynch syndrome

EGFR pathway Over activation of the Epidermal Growth Factor Receptor (EGFR) pathway through proto-oncogene mutations promotes cell proliferation, migration, and invasion. Stimulation of the EGFR receptor at the cell membrane activates two pathways: KRAS and PIK3CA. Only one member of a pathway needs to be constitutively activated to cause proliferation, so there is no selective pressure for other genes within the same pathway to gain a mutation. But there can be selective pressure for the genes in the other pathway to mutate. Immunotherapy against EGFR is a treatment for cancer, but it is ineffective if a gene down the pathway is constitutively active. APC-related polyposis APC is a tumor suppressor gene that regulates beta catenin-related cell growth pathways. Absence of APC allows beta catenin to accumulate and activate cell growth. APC is often somatically mutated in colon cancer and known as familial adenomatous polyposis. Those with FAP develop polyps starting at 7-36yrs so colonoscopy is recommended starting at age 10. Colon cancer is inevitable so colectomy is performed after 20-30 adenomas with advanced histology. APC germline activation can cause Gardner syndrome with osteomas and soft-tissue tumors; medulloblastoma; and congenital hypertrophy of the retinal pigment epithelium. Different manifestations of germline APC inactivation are an example of pleiotropy. Lynch syndrome (hereditary non-polyposis colorectal cancer) causes 4% of colon cancer and is autosomal dominant involving a loss of function of a DNA mismatch repair gene (MLH1, MSH2, MSH6, or PMS2). Those with lynch syndrome have a 70% lifetime risk for colon cancer and females are at risk for endometrial and ovarian cancer. Also increases risk for other GI cancers, so surveillance endoscopy is used. Colon cancer is evaluated for lynch syndrome gene variants to see if lynch syndrome could be a cause (functional testing) before doing further genetic testing on the person. Immunohistochemistry testing for lynch syndrome uses staining to see if lynch-related genes are expressing their protein products. *A positive test (presence of staining) is normal.* Microsatellite instability can also be used to test for lynch syndrome (signifies absence of mismatch repair). Normal results are reported as MSI-low or MSI-stable while abnormal results are reported as MSI-high or MSI-unstable.

Enteric viruses

Enteric viruses lack envelops and have sturdy capsids so that they can be ingested and survive the stomach acid. They infect and cause disease in other sites after GI replication, but mucosal antibody may protect from disease. Cell mediated immunity is important in recovery from infection. They cause viral gastroenteritis with vomiting and watery diarrhea. Rotavirus, norovirus, astrovirus, and adenovirus are examples (not influenza!).

Gastric tumors

Epithelial tumors can be benign polyps or malignant adenocarcinoma (95% of gastric malignancies) of the diffuse or intestinal type. Non-epithelial gastric tumors include benign leiomyoma and malignant lymphoma (4-5% of malignancies). Non-neoplastic/hyperplastic polyps are focal protrusions of the mucosa into the lumen that occur following injury (like gastritis). Polyps are made of aggregates of regenerating mucosal cells and inflammatory cells. Adenocarcinomas can be caused by diet, H. pylori, or chronic atrophic gastritis. Diffuse type arises from gastric mucous cells that become poorly differentiated and discohesive (don't form glands). Signet ring cells are seen histologically amongst desmoplasia (connective tissue). Adenocarcinomas of the diffuse type are infiltrating and cause linitis plastica when very severe - the stomach wall becomes thickened and tough. Intestinal type adenocarcinoma occurs from chronic gastritis with intestinal metaplasia leading to dysplasia and adenocarcinoma. Grossly, ulcerating malignancies reach beyond the submucosa (unlike peptic ulcers), have heaped up margins, irregular sides, and a shaggy base. Diffuse and intestinal types can make lakes of extracellular mucus that pools outside of cells. Gastric metastases can appear in local lymph nodes, left supraclavicular nodes (Virchow node), or periumbilical nodes (Sister Mary Joseph nodes). They can also metastasize to the pancreas, duodenum, and peritoneum as well as to the lungs, liver, brain, and ovary (Krukenberg tumor) via the blood. Significant prognostic features include depth of invasion (histologic stage) and extent of nodal and distal metastases (clinical stage). Intestinal vs. diffuse is not a significant prognostic feature. Gastric lymphoma/MALT lymphoma/MALToma is low grade B cell lymphoma caused by H. pylori leading to chronic inflammation and influx of B cells that leads to lymphoma. Lymphoma can present in younger people. Some lymphomas regress with H pylori eradication, or there can be indolent growth (good prognosis with surgical removal), or can transform into high grade lymphoma (poor survival). Gastric lymphoma can be exophytic, infiltrating, or ulcerating (looks same as adenocarcinoma) grossly. Histopathology will have small malignant lymphocytes that infiltrate the mucosa and destroy gastric glands.

Immune response to parasites

Eukaryotic parasites have evolved to avoid, suppress, and deflect human immune responses (especially the helminths). When there is a response, it's with eosinophils (innate immune cells responding to antigens on many parasites; produce pink granulocytes) that rarely eliminate the parasites. Hygeine hypothesis: Our lack of exposure to parasites makes us more prone to developing auto-immunity and an allergic response when we are exposed to parasites.

Reflux esophagitis/GERD

GastroEsophageal Reflux Disease movement of gastric contents into the esophagus causing mucosal injury to the distal esophagus, including erythema, erosion, ulcers, fibrosis, and strictures (solid dysphasia, treat with balloon dilation). Inflammation in the epithelia will include PMN and eosinophils. Esophageal GERD causes heartburn, acid regurgitation, chest pain. Extra esophageal GERD causes chronic cough, laryngitis, asthma, throat clearing, and tooth decay. GERD can be caused by loss of costal or crural parts of the diaphragm (at hiatus). Risk of reflux symptoms is increased if reflux is unable to reenter the stomach because of imapaired motility, if saliva and CHO3 are less able to neutralize acid, if there is delayed gastric emptying, if there is a hiatal hernia, or if there is *transient lower esophageal sphincter relaxation* (most common cause). Production of too much acid is not usually the cause. Diagnose with empiric therapy with proton pump inhibitors in those with low risk of complications (not in those with weight loss, vomiting, bleeding/anemia, anemia, dysphagia, jaundice, palpable abdominal mass, or old age). Then do an esophagogastroduodenoscopy (EGD) aka upper endoscopy (but most patients with GERD have normal upper endoscopy). pH testing is used for patients who have failed therapy, and it involves measuring how much time acid spends in the esophagus (pH<4). Barium swallow is not a good test for GERD. non-medical treatment involves avoiding refluxogenic foods and acidic foods, losing weight, stop smoking, raise head of bed, and avoid recumbency 2-3 hrs after meals. medication treatment includes antacids, H2 receptor antagonists, and proton pump inhibitors. Surgical treatment is fundoplication, where the proximal stomach is wrapped around the lower esophagus to restore the anti-reflux barrier, but solid food dysphagia can result. GERD can lead to Barrett metaplasia, which can lead to dysplasia and adenocarcinoma. Barrett's esophagus is metaplasia of normal esophageal stratified squamous epithelium to intestinal columnar epithelium (including goblet cells, absorbative cells, villi and crypts). Whether it turns to adenocarcinoma is related to the length of metaplastic segment and the presence and degree of dysplasia. Dysplasia is typified by nuclear changes: large nuclei, pleomorphic, hyper chromatic, prominent nucleoli, nuclei at multiple cell levels, and increased mitotic figures.

Neuronal control of gastrointestinal motility

Gastrointestinal motility is under autonomic control via an extrinsic NS (sympathetic and parasympathetic) and an intrinsic NS (enteric NS). Preganglionic efferent parasympathetic fibers project to the cholinergic neurons in the myenteric and sub mucous plexuses to cause smooth muscle contraction. The enteric NS from the esophagus to the colon is innervated by the vagus and the colon and rectum are innervated from the sacral spinal cord nerves. Whether vagal stimulation of the esophagus and stomach stimulates or inhibits muscle contraction depends on activation of enteric circuits, but vagal stimulation of the small and large intestine mainly activates excitatory motor neurons that cause contraction. Preganglionic sympathetic efferent fibers exit the thoracic and lumbar regions and go to the prevertebral sympathetic ganglia. Postganglionic effort fibers synapse with neurons in the enteric NS and innervate blood vessels and mucosa. Sympathetic stimulation shunts blood from splanchnic to systemic circulation and suppresses motility and secretion. NE increases sphincter tone to keep them closed. Auerbach's Myenteric plexus is between the outer longitudinal and inner circular layers of the muscularis externa and controls their motor function. Excitatory motor neurons stimulate contraction via ACh and inhibitor neurons stimulate relaxation with NO. Meissner's submucosal plexus lies in the submucosa adjacent to the muscularis mucosa and controls intestinal secretion by innervating glandular epithelium, intestinal endocrine cells, and submucosal blood vessels.

Anaerobic infections

Generally organisms in the upper GI tract are mainly aerobic while those in the lower GI tract are anaerobic. But anaerobic organisms can be found all along the tract (living under water surface) and outnumber aerobes 1000:1. Firmicutes (Staph, Strep, Clostridium, Enterococci) and Bacteroidetes are the predominant phyla of anaerobes. Anaerobic microbes give off CO2 during metabolism. Obligate aerobes - Bacillus Obligate anaerobes - Clostridium, Bacteroides Facultative anaerobes (best at atmospheric O2) - E. coli, Staph, Strep, Candida Microaerophiles - require less than atmospheric O2 (best below atmospheric O2) - Helicobacter Aerotolerant (unaffected by O2) Lactobacilli. 2/3 of anaerobic bacterial infections also involve aerobic bacteria (treat with antibiotics covering anaerobes and aerobes), and both anaerobes and aerobes may be required to create abscesses. Anaerobic infections are diagnosed with aspirates of abscesses, tissue, and blood. Specimens that have contacted the mucus membrane are not appropriate. Samples must be transported quickly and gram staining is used to identify mixed infections and sometimes characteristic cell morphologies. Usually infections are simply treated empirically with antibiotics. Necrotic tissue and pus is removed, wound vac may be used. *Effective antibiotics for anaerobes include metronidazole, carbapenems and beta-lactams+beta-lactamase inhibitors.* Antibiotics that are always ineffective include Aminoglycosides, Tmp-Smx, and Aztreonam.

greater and lesser sac

Greater Sac Most of the peritoneal cavity is the greater sac, which includes the infracolic compartment up to the transverse colon and the supracolic compartment from the transverse colon to the diaphragm. The subphrenic/suprahepatic recess is the potential space below the diaphragm and above the liver. The sub hepatic/hepatorenal recess (Morison's pouch - blood pools there with internal bleeding) is between the liver and kidney. The paracolic recesses (gutters) are were the ascending and descending colon are sitting. Lesser Sac/Omental Bursa The lesser sac is an irregular space behind the liver, lesser omentum, and stomach. It includes the superior recess, spleens recess, and inferior recess (under the pancreas). Peritoneal fluid usually moves freely between the lesser and greater sac, but pancreas irritation can cause enzymes to collect in the lesser sac, requiring surgical drainage. The omental foramen is a natural opening between the lesser sac and greater sac and is bounded by the caudate lobe of the liver, first part of duodenum, hepatoduodenal ligament, and interior vena cava. An omental hernia occurs when the jejunum pushes through the omental foramen and becomes strangulated, requiring surgery. The pringle maneuver involves sticking your fingers into the omental foramen to clamp down on the portal triad and cut off blood flow through the proper hepatic artery and portal vein.

GALT

Gut-Associated lymphoid tissue tolerates commensal microbes, dietary antigens, and self antigens (default setting favors tolerance) and protects from pathogenic organisms. It prevents intestinal disorders like food allergy, celiac disease, and IBD. Microfold (M) cells sample lumen contents and present them to dendritic cells in Peyer's patches that present them to T cells to generate tolerance. Tolerance is mediated by T cells - giving a mouse the T cells from a mouse that had been fed an antigen and developed tolerance will transfer the tolerance to the recipient mouse. While TH1 and TH17 cells release INFgamma and IL-17, which are pro-inflammatory, TReg cells release IL-10 in response to the specific antigen, inhibiting inflammation. 70-80% of plasma cells are in the GI tract, and IgA is synthesized at the highest rate and remains at mucosal surfaces (IgG is highest concentration in circualation). IgA+ plasma cells develop in the Peyer's patches germinal centers and IgA is secreted as a dimer that attaches to a poly-Ig receptor on the apical membrane of epithelial cells and is transported across to the lumen, remaining bound to the receptor such that the IgA Fc regions are touching and are at 180 degrees. This makes S-IgA resistant to proteolytic enzymes and prevents the Fc region from interacting with mast cells to cause an inflammatory/allergic reaction. IgA deficiency is the most common immunodeficiency and can cause chronic diarrhea, ulcerative colitis, Crohn's disease, or recurrent oral/mucosal. infections.

Acid-Peptic pharmacology

H2 receptor antagonists are chemically similar to histamine and include cimetidine, ranitidine, famotidine, and nizatidine. They compete with histamine at the H2 receptor on parietal cells, suppressing stimulated and basal production of acid. They work best if used regularly rather than as needed. Proton pump inhibitors are the drugs of choice for acid-peptic diseases like GERD and peptic ulcer disease and are best used regularly rather than as needed. They are prodrugs that are activated by the acidic environment of secretary canaliculi of parietal cells, binding to H/KATPase on the luminal surface of parietal cells and irreversibly inhibiting them. They include omeprazole, lansoprazole, rabeprazole, pantoprazole, esomeprazole, and dexlansoprazole (contains granules with different dissolution profiles so some is absorbed in proximal duodenum and some more distally). Antacids act rapidly and so can be used as needed (heartburn) but is not for those who require chronic therapy. Chemical buffers (Mg(OH)2, Al(OH)3, CaCO3) neutralize HCl immediately for 2-4 hours. Sucralfate is sulfated sucrose and aluminum hydroxide that polymerizes in acidic environments, covering epithelial cells and ulcers. It has limited usefulness but is still prescribed. Mysoprostal is a synthetic analogue of prostaglandin E1 that binds the EP3 receptor of parietal cells to decrease intracellular cAMP and acid production. It also stimulates mucus and bicarb production. it is helpful in those using NSAIDs but can cause diarrhea and cramping.

Cancer basics

Hallmarks of cancer required for tumors: sustaining proliferative signaling (growth in absence of external signals), evading growth suppressors, activating invasion and metastasis, enabling replicative immortality, inducing angiogenesis, resisting cell death, deregulating cellular energetics, avoiding immune destruction Genome instability and mutation, and tumor-promoting inflammation are enabling characteristics. In the developed world, death rate increases with the 6th power of age, suggesting cancer development requires 6-7 successive mutations in a population of cells. Germline genetic variants are ones we are born with while somatic variants occur during our life - cancer can be either. High penetrance diseases have strong mendelian risk and include lynch syndrome and familial adenomatous polyposis. Oncogenes can cause cancer by gain of function of a proto-oncogene to form an oncogene. Oncogenes can involve ectopic expression (in cell type where gene usually silenced) or heterochronic expression (at time in development when usually silent). Loss of function of a tumor suppressor gene can cause cancer. Cancer occurs through progression of steps, with additional mutations becoming more likely after replication becomes more error prone. Proto-Oncogenes are proteins involved in signaling pathways for cellular proliferation (transcription factors that control expression of growth factors or inhibitors of apoptotic pathways). Tumor supressor genes can be gatekeepers that serve as regulators of cell cycle checkpoints or mediators of apoptosis. They can also be caretakers that encode proteins that detect or repair mutation. The 2 hit model for tumor suppressor genes explains why hereditary cancers occur at a younger age and why they can take a variety of forms. Cancer predisposition syndromes associated with tumor supressor genes often have an AD inheritance pattern with reduced penetrance (not everyone gets second hit). Suspect a hereditary cancer in those with multiple cancers, patterns of cancer in a family, cancer occurring at a young age, unusual cancers that are pathognomonic for certain conditions.

Colonic motility

Haustration consists of contractile activity that is almost continuous to extract water and electrolytes from the stool for 36-48hrs. Segmental contraction of circular muscle divides intestine into pockets (haustra). Forward propulsion occurs with sequential migration of haustra along intestine. Power propulsion is triggered by increased delivery of ilial chyme in the ascending colon after a meal, triggering the gastrocolic reflex - increased segmental and propulsive movements after a meal (or in response to irritant laxatives, parasites, enterotoxins). Power propulsion begins in the mid transverse colon and is preceded by cessation of haustration (circular muscles downstream relax). Transverse colon is the main location of water and electrolyte absorption because food remains there longer.

Helicobacter pylori

Helicobacter pylori is part of our normal flora but causes gastric ulcer disease in some for unknown reasons. Strains are very genetically diverse and only some cause ulcers. Mobile cag pathogenicity islands containing Cytotoxin-associated genes (Cags) and type 4 secretion system genes correlated with development of peptic ulcers and gastric cancer. H. Pylori is a gram negative rod (spiral) that lives in the foveolar gastric mucus in the stomach. H. pylori uses flagellar motility to penetrate the mucus layer of the stomach. Urease then converts urea to ammonia and CO2 to raise the pH (neutralize gastric acid), allowing for replication. Cytotoxins and ammonia cause mucosal cell death and bacterial mucinases destroy the mucous layer so that acid can reach the epithelial cells. First acute inflammation occurs with PMNs signaling acute gastritis. Chronic inflammation produces chronic gastritis and can lead to gastric lymphomas and adenocarcinoma. Necrosis can occur, causing peptic ulcer disease. Helicobacter pylori infection is diagnosed with microscopy of gram-stained biopsy smears, rapid urease test, urea breath test (radio labeled urea is ingested and H. pylori produce radio labeled CO2 using urease), antigen detection test with stool, or serology (look for antibodies). If infection with ulcers is present, treat with combination antibiotics, proton pump inhibitors, and bismuth subsalicylate. Triple therapy = omeprazole + amoxicillin + clarythromycin.

Helminths

Helminths include cestodes (*tapeworms/Taenia*) that are ingested as cysts in raw, contaminated meat. Adult worms develop from the cysts and live in the small intestine (diarrhea or anorexia), and eggs are shed in the feces. When Taenia solium (pork) eggs are ingested via fecal-oral transmission, larvae can form cysticerci in the brain, eyes, and skin. Treat Tania with Praziquantel. Trematodes (flukes) and Schistosomiasis (flat worms) Their asexual stage lives on snails and is transmitted to humans in fresh water by penetrating the skin. S. mansoni and S. japonicum adult worms go to the mesenteric veins and GI tract and eggs are shed in the stool. S. haematobium adult worms go to the bladder and eggs are shed in the urine. S. haematobium eggs are very inflammatory and cause granulomas and tissue damage in the bladder (bloody urine) that can lead to bladder cancer and increase HIV transmission. Treat schistosomiasis with Praziquantel. Intestinal nematodes (round worms) include Enterobius vermicularis (pinworms) and Ascaris lumbercoides (large intestinal round worms). After eggs are ingested, larvae and adult pinworms remain in the GI tract while Ascaris larvae travel to the lungs and are coughed up and swallowed and adults live in the small intestine. Under the microscope, pinworm eggs are smooth and Ascaris eggs are bumpy. Treat Ascaris with Benzimidazoles. Necator americanus (hookworm) Larvae penetrate the skin (bare feet), pass through the lungs, and end in the small intestine. Adults attach to intestinal mucosa and cause bleeding and anemia. Diagnose with hookworm eggs in fecal sample. Treat with Benzimidazoles. Strongyloides stercoralis Larvae penetrate skin, pass through lungs, and end in small intestine. They can reinfect without leaving the host (autoinfection). They can cause a rash on the butt as the larvae migrate (larva currens). Diagnose with larvae in fecal sample. Treat with Ivermectin or benzimidazoles. Antihelminthis agents include praziquantel, benzimidazoles, and ivermectin.

Hiatal hernia

Hiatal hernia is the herniation of the stomach into the thorax though an enlarged diaphragmatic hiatus. 95% of the time it is a sliding hernia rather than a paraesophageal hernia. They are usually acquired and secondary to weakening of the hiatal opening or abdominal conditions (pregnancy) that push the stomach up. Can cause incompetent lower esophageal sphincter and reflux (GERD).

Neck masses

History and physical is the most important part of a workup for a neck mass. Masses in children are usually benign but in an adult they are cancer until prove otherwise. Proximal aerodigestive tract evaluation is essential. Ranula Blocked sublingual gland ducts cause saliva to pool in the neck, producing unilateral soft tissue lesions under the tongue that can be bluish. Plunging ranula is a mucosal extravasation that herniates the mylohyoid muscle and appears in the neck.

prokinetic agents and antiemetics

Interneurons that release ACh onto gastric smooth muscle (muscarinic receptors) are responsible for gastric motility. Serotonin binds to 5-HT4 receptors to stimulate ACh secretion, and dopamine binds to D2 receptors to inhibit ACh secretion. Bethanechol stimulates muscarinic receptors on smooth muscle directly. *Metoclopramide is a 5-HT4 receptor agonist and an antagonist of the D2 dopamine receptor, increasing GI motility but causing extrapyramidal effects (dyskinesia) because of dopamine inhibition.* Domperidone blocks dopamine release, increasing gastric motility. Not FDA approved. Macrolide antibiotics like erythromycin are motilin receptor agonists that increase gastric motility but exhibit tachyphylaxis (drug effect wanes) and cause diarrhea. 5-HT3 receptor antagonists like ondansetron block 5-HT3 at various sites in the nervous system to suppress nausea and vomiting. They are very effective for chemo-induced nausea and vomiting and have few side effects. Phenothiazines like promethazine are antipsychotics used for antiemetic and sedative properties. They inhibit dopamine and muscarinic receptors. Can cause sedation/drowsiness. Dronabinol (not first line agent for nausea) is a THC extract from the cannabis plant that acts as a motilin agonist by stimulating cannabinoid receptor around the vomiting center. Dronabinol stimulates appetite in cachet patients.

Peptides/hormones of the small intestine

Intestinal endocrine cells are spread throughout the GI tract as single cells rather than glands Cholecystokinin (CCK) Secreted by I-cells in the duodenum/jejunum in response to contact with peptides and fatty acids, CCK causes gallbladder contraction, stimulation of pancreatic enzyme secretion, and relaxes the sphincter of Oddi (so that pancreatic enzymes and bile can enter the duodenum and digest food). There is a positive feedback loop in that increased pancreatic enzymes increase the digestion of food and peptide/fatty acid contact with I-cells, increasing CCK release. Release ends when food moves into the lower GI tract. Secretin released by S cells deep in duodenum glands in response to protein digestion and acid and stimulates bicarb secretion by the pancreas, stimulates movement of pancreatic enzymes into the duodenum, and decreases gastric acid secretion. There is a negative feedback loop in that increased alkaline fluid into the duodenum leads to decreased secretin production. Vasoactive intestinal peptide (VIP) is a neurocrine made and released in the parasympathetic ganglia in the enteric NS in sphincters (pyloric) in response to local distention and vagal stimulation. VIP stimulates intestinal secretion of electrolytes and water to aid in motility, inhibits gastric acid secretion, and stimulates NO formation that relaxes sphincters. Motilin is secreted by enterochromaffin cells and Mo cells in the stomach, small intestine, and colon to stimulate the migrating motor complex. Gastric inhibitory polypeptide/glucose-dependent insulinotropic peptide (GIP) is secreted by K cells in the duodenum and jejunum in response to glucose and fatty acids and decreases gastric acid secretion and increases insulin release.

Listeria monocytogenes

Listeria monocytogenes is a gram positive, motile rod that can grow at 4 degrees celsius, uses actin-based motility to move between cells, and can colonize animals. Listeriosis is a foodborne illness and can be transmitted mother to child transplacentally or at birth (meningitis, encephalitis). Infection in pregnant women can cause miscarriage, stillbirth, or preterm labor. It's relatively rare but can be in dairy (soft cheese) and processed meats. Listeriosis causes fever, muscle aches, vomiting. Diarrhea is less common.

Mandible TMJ

Mandible The body of the mandible includes the alveolar portion that supports the teeth while the ramus includes the coronoid process where the temporalis muscle attaches and the condyle that articulates with the temporal bone to form the temporomandibular joint. A mandibular foramen is on the inside of each ramus and is where the inferior alveolar nerve (branch of V3 of trigeminal nerve) enters and innervates the mandible and lower teeth (its often blocked during dental procedures). The Inferior alveolar nerve becomes the mental nerve and exits from the body of the mandible via the mental foramen. TMJ Synovial articulation surrounded by loose joint capsule including the condyle of the mandible, the articular tubercle of the temporal bone, and the mandibular fossa (valley) of the temporal bone. The articular disk/meniscus divides the joint cavity into an upper synovial cavity where gliding occurs (protrusion and retrusion) and a lower synovial cavity where rotational movements occur (elevation and depression).

Poliovirus

Most poliovirus infections are asymptomatic and resolve quickly but a small number cause aseptic (culture-negative) meningitis that can result in poliomyelitis - inflammatory viral disease of gray matter in spinal cord. Poliovirus does not infect and replicate in muscle cells, but paralytic polio can lead to progressive post-polio syndrome years later with muscle atrophy (including inability to breathe). Before the 20th century, there were no epidemics because polio was endemic - infants were protected from maternal antibody, exposed as young infants, and became immune. Epidemics involving children <5yrs increased in the early 1900s because better hygiene led to less exposure as infants and in mothers so young children were susceptible to disease. In the 1950s, children 5-10yrs were most at risk and 30% of those infected were >15yrs. The inactivated poliovirus vaccine is a trivalent killed preparation given 3 times and produces good serum IgG response but no secretory IgA. Vaccine protects against paralytic polio but not infection that can be spread in feces. The oral polio vaccine was given for a while but is not anymore - it involves ingesting a trivalent live mixture of 3 attenuated serotypes that replicate in the oropharynx and gut to stimulate IgA as well as IgG, but the viruses could be shed in feces and the live poliovirus could mutate back to neurovirulence. Polio is now endemic in 3 countries (Afghanistan, Pakistan, Nigeria).

Muscles of facial expression

Muscles of facial expression develop from the 2nd pharyngeal arch and are all innervated by the facial nerve CN VII. Damage of CN VII can cause facial paralysis. Bell's palsy is the most common acute unilateral facial paralysis - characterized by abrupt onset (12-48hrs) and resolution within 6-8 weeks and possibly caused by local viral infections that cause inflammation of CNVII within the facial canal within the temporal bone. Orbicularis oculi - muscles that ring the eyes and allow you to close them. Orbicularis oris - allows you to keep food in your mouth and talk with assistance from the buccinator muscle

Muscles of mastication

Muscles of mastication are derived from the 1st pharyngeal arch and are innervated by the mandibular division of the trigeminal nerve (V3) Muscles that elevate the mandible include temporalis, masseter, and medial pterygoid muscles. The lateral pterygoid protrudes the mandible forward to allow the mouth to open. To open the mouth, the lateral pterygoid muscles contract first, which pulls the mandible and articular disk forward (moves the condyle from the mandibular fossa, over the ridge of the articular tubercle). When the condyle sits beneath the articular tubercle, the suprahyoid muscles can contract to fully open the mouth. Suprahyoid muscles The mylohyoid forms the floor of the mouth (and is innervated by Trigeminal V3)), the digastric muscle consists of two bellies united by a common tendon - the anterior belly attaches to the mandible (and is innervated by the trigeminal nerve V3) while the posterior belly attaches to the mastoid process (and is innervated by the facial CN VII). The stylohyoid connects the styloid process of the skull and the hyoid bone (and is innervated by the facial CN VII) and the geniohyoid is deep to the mylohyoid. Trigeminal nerve V3 - anterior belly of digastric and mylohyoid Facial CN VII - posterior belly of digastric and stylohyoid.

muscles of the abdominal wall

Muscles of the anterior abdominal wall are innervated by thoracoabdominal nerves (ventral rami T7-T12). The anterior abdominal wall is made up of the external oblique, internal oblique, transverses abdomens, rectus abdomens, and pyramidalis (small, tenses the linea alba). The rectus abdomens and pyramidalis are enclosed in the rectus sheath, which is made of the aponeuroses (sheet of tendons) of the external oblique, internal oblique, and transversus abdomens muscles. The external oblique is the largest and most superficial, running interomedially and transforming to aponeurosis at the mid-clavicular line (and attaching centrally to the linea alba). There is also a thickened aponeurosis inferior to the external oblique muscle that forms the inguinal ligament, which attaches to the anterior superior iliac spine (ASIS) and to the pubic tubercle (and forms the floor of the inguinal canal). The internal oblique is the next layer in, with fibers that fan out and become aponeurotic at the mid-clavicular line. The transverses abdomens is the innermost abdominal muscle, runs transversely, and has an aponeurosis. The rectus abdominis are long strap-like vertical muscles separated by the linea alba and enclosed in the rectus sheath. Tendinous intersections within the muscles are sights of attachment to the rectus sheath. The posterior abdominal wall is made of the psoas major, psoas minor (sometimes absent), iliacus, quadratus lumborum (QL - laterally flexes vertebral column and serves as hip hiker), diaphragm, and transversus abdominis. The Psoas major (medial) and the iliacus (lateral) muscles unite to form the iliopsoas muscle (hip flexor).

Norovirus

Norovirus is a calicivirus - a small spherical vision with no envelope and a ss+RNA genome. It is the most common cause of viral gastroenteritis in adolescents and adults. Outbreaks are common in closed settings (ships, military bases, restaurants, college campuses). Norovirus causes nausea, emesis, cramps, diarrhea, low grade fever, malaise, headache, and myalgia. Systemic symptoms are due to viremia rather than enterotoxin. Illness lasts 2-3 days. histolotically, there will be changes in jejunum villi. Diagnose with assays for enzyme or PCR (but don't really need to know because no specific treatment). Treat with rehydration.

Oral cavity and oropharyngeal cancer

Oral cavity cancer is squamous cell carcinoma >90% of the time, is common in the developing world (most common cancer in Sri Lanka, Pakistan, India, Bangladesh), and risk factors include tobacco, alcohol, betel, DNA repair gene defects, and immune defects. The oral cavity drains into lymphatics under the mandible, directly dorsal to the jaw, and down along the sternocleidomastoid first before spreading elsewhere in the neck (more advanced tumors). Oral cancer is treated surgically, with radiation or chemo added. Oropharyngeal cancer is caused by tobacco and alcohol in older patients and *HPV types 16 and 18* in younger patients. Biopsy the lesion and get CT and chest X ray for staging, when do radiation +/- chemo (usually don't do surgery in younger patients).

Pharyngeal/branchial arch 1

Pharyngeal arch 1 forms the lower 2/3 of the face, including muscle, skeleton, and blood vessels and is innervated by CN5. It divides around the oral cavity to form the maxillary process and mandibular process. Skeletal derivatives of the maxillary process include the middle 1/3 of the face - maxillary, palate, zygomatic, squamous portion of temporal bone. Skeletal derivatives of the mandibular process start from Meckel cartilage that becomes the mandible, sphenomandibular ligament, spine of sphenoid bone, anterior ligament of malleus, malleus, and incus. Arch 1 and 2 form the auricle/pinna of the ear, cleft 1 forms the external acoustic meatus, membrane 1 forms the tympanic membrane, and pouch 1 forms the eustachian tube. Preauricular tag is a remnant from auricle formation and microtia is a malformed auricle. Muscles derived from pharyngeal arch 1 include muscles of mastication - mylohyoid, anterior belly digastric, masseter, temporalis, tensor tympani, and tensor veli palatini. Arch 1 forms the anterior 2/3 of the tongue, with CNV for touch/temp and CNVII for taste. Formation of the lower lip and jaw is simple and abnormalities are rare - arch 1 mandibular processes fuse at the midline. Formation of the upper lip and jaw involves 2 fusion sites (3 areas fuse in Y shape) and commonly causes cleft lip/palate. The medial nasal processes (of the frontonasal process - not arch 1) on each side fuse at the midline, forming the median palatine process at the very front of the palate that is later known as the primary palate. The maxillary process on either side become lateral palatine processes that begin vertical but are pushed horizontally at weeks 8-9 by the developing tongue, and then fuse to create the secondary palate. Cleft lip arises in 1/1000 births and cleft palate in 1/2500 births and are usually caused by genetic and teratogenic factors (alcohol, anticonvulsants). A cleft lip is any amount of clefting anterior to the incisive foramen (the intersection of the Y where the primary and secondary palate meet). Cleft palate is any amount of clefting posterior to the incisive foramen. Partial cleft palate - cleft uvula Complete unilateral/bilateral cleft palate - one/both lateral palatine process does not fuse at the midline/nasal septum. Complete unilateral/bilateral cleft lip - lateral palatine process does not fuse with the primary palatine process on one or both sides. Can have a combination of cleft lip and palate

Patterns of GI motility

Propulsion/peristalsis is an organized reflex response to gut wall stretch and the prototypic pattern of propulsion from the esophagus to rectum. Wall stretch initiates contraction of circular muscle and relaxation of longitudinal muscle in the propulsive segment with simultaneous relaxation of the circular muscle and contraction of the longitudinal muscle in the receiving segment immediately adjacent distally. Peristalsis occurs independent of extrinsic innervation but can be increased/decreased by parasympathetic/sympathetic innervation. Trituration process of crushing and grinding ingested food by the stomach. Mixing movements blend pancreatic, biliary and intestinal secretions with food in the small intestine. Segmentation is the prototypic mixing movement and involves a repetitive pattern of bidirectional propulsion into relaxed receiving segments. Reservoir functions The gastric body stores ingested food, exerting steady mechanical forces that participate in the regulation of gastric emptying. The colon holds material during the time required for absorption of excess water and stores residue stool until defecation is convenient.

Protozoa parasites

Protozoa are unicellular eukaryotes that have two forms. Trophozoites (slightly elongated/tear shaped) are motile, feeding, and reproducing while cysts (round) are non-motile/feeding/reproducing and have thick walls to survive in the environment (transmission). Some protozoa have flagellated forms called mastigotes and some have sexual stage. Protozoa can infect blood and tissue, urogenital tract (schistosomiasis and trichomoniasis), or the GI tract. Entameoba histolytica are transmitted between humans only via fecal-oral transmission. Intestinal trophozoites cause amebic dysentery (bloody diarrhea) and can spread to liver, lung, and brain. Cyst are infectious and trophozoites are pathogenic. Both are shed in the feces and can be diagnostic. Sigmoidoscopic exam shows *multiple small hemorrhagic areas with ulcers in the colon and stained biopsy has flask shaped ulcers.* Treat Entamoeba with Nitroimidazoles (metronidazole, tinidazole, nitazoxanide), Aminoglycosides (paramomycin) or Iodoquinol. Giardia lamblia is spread between mammals via fecal-oral transmission (contaminated food/water). Trophozoites in the duodenum don't invade but cause malabsorption and steatorrhea (fatty stool). Cysts are infectious and trophozoites are pathogenic and both are shed in feces of symptomatic individuals with diarrhea and can be diagnostic (googly eyes histologically). Only cysts are shed by asymptomatic people. Treat with Nitroimidazoles (metronidazole, tinidazole, nitazoxanide) Cryptosporidium are usually only transmitted between humans (swimming pools) via fecal-oral transmission (contaminated food/water). Trophozoites in the small intestine don't invade but cause secretory diarrhea. Oocysts (meiosis) are infectious and trophozoites and sexual stages are pathogenic. Cysts are resistant to chlorine. Cryptosporidium is problematic for immunocompromised and is detected via acid-fast oocysts in fecal smears. Treat with Nitroimidazoles (metronidazole, tinidazole, nitazoxanide). Protozoa parasites (Giardia, Entamoeba, Cryptosopridia) are treated with nitroimidazoles (Metronidazole, Tinidazole, Nitazoxanide), which are prodrugs that are activated enzymatically inside the protozoa or bacterial cell to damage DNA. Resistance is developed via mutations in the converting enzymes. Folate synthesis inhibitors (TMP-SMX for Cyclospora and Isospora) and Aminoglycosides (paromomycin for entamoeba) are also effective.

Rotavirus

Rotavirus has a 2 day incubation period followed by flow grade fever, emesis, then 4-8 days of watery diarrhea with large amounts of virus in the stool (spreads quickly in daycares, nursing homes, hospitals). Serious illness/death can result from severe dehydration (mostly children 6mo-2yrs in India, Africa, Middle east). Most children are infected by age 5, and *infections in the US begin in fall in the south west and spread to the NE by spring.* Viral protein (NSP4) acts as an *enterotoxin* (unusual for a virus) in villous epithelium, affecting Ca++ flux in uninfected enterocytes. Rotavirus has a ds+RNA segmented genome that can be independently reassorted within cells. Rotavirus is diagnosed with stool enzyme immunoassay or PCR. Rehydration therapy is the treatment. Prevent with good hygiene, infection control, and *live, attenuated reassortant vaccine given orally* (replicating organisms can bypass tolerogenic responses to get immune response).

Peptides/hormones of the mouth and stomach

Salivary peptides Salivary amylase (pytalin) is responsible for 75% of starch digestion in the mouth and first part of the stomach. Lingual lipase aids in fat digestion. (saliva also has electrolytes to buffer acid, lysozyme to attack bacterial cell walls, lactoferrin to chelate iron so organisms that use it can't grow, and S-IgA against viruses and bacteria). Gastric glands in the stomach Parietal cells (oxyntic cells) near the surface secrete H+ and intrinsic factor (exocrine for B12 absorption in small intestine) in the body and fundus. In the resting state, parietal cells keep H+/K+ATPases (aka proton pumps) sequestered in tubulovessicles. The secreting phase is stimulated by ACh (from vagus nerve) binding to M3 receptors (elevates free calcium), Histamine binding to H2 receptors (cAMP), or Gastrin binding to gastrin/CCK-B receptors (elevates free calcium) on the basolateral side of the parietal cells. Tubulovesicles then fuse with the intracellular canaliculi, causing the SA of the microvilli to increase as they accommodate the pumps. Carbonic anhydrase catalyzes the reaction of water and CO2 to H+ and HCO3-. The protons are actively secreted by the apical H/KATPases (possible because of basolateral Na/KATPase). The secretion of protons is accompanied by an equal number of HCO3- exiting the basolateral side via Cl/HCO3antiporter. The flux of bicarb into the blood increases the pH of gastric venous blood (alkaline tide). Deeper enterochromaffin-like cells (ECL) secrete histamine that acts as a paracrine and binds to H2 receptors to stimulate acid release by parietal cells. ECL cells release histamine in response to ACh and Gastrin. Chief cells deep in the glands secrete pepsinogen (exocrine) that breaks down into pepsin that digests protein in the stomach. G cells in the antrum and pylorus secrete gastrin into systemic circulation that stimulates acid production by parietal cells, pepsinogen production by chief cells, and histamine production by ECL cells. Delta (D) cells near G cells secrete somatostatin (endocrine) in response to increased stomach acid, which suppresses gastrin release and the action of secretin on duct cells in the pancreas to release bicarbonate. During the interdigestive phase, stomach acid (pH<2) activates delta cells to release somatostatin that inhibits G cells' release of gastrin, which prevents overproduction of acid. The cephalic phase begins when receptors the pharynx are stimulated by eating or thinking about eating, activating the vagus to stimulate acid production by parietal cells. The vagus nerve also stimulates interneurons in the enteric NS of the stomach, which releases GRP, which stimulates G cells to release gastrin, which stimulates parietal cells to release H+. In the gastric phase, the rise in pH does not stimulate D cells and also activates the vagus nerve, which causes release of gastrin releasing peptide (GRP/Bombesin) from enteric nerves that stimulates G cells to release gastrin. Gastrin release is also stimulated by peptides, amino acids, and gastric distention. The pyloro-pyloric reflexes are short reflex pathways mediated locally int he stomach wall involving single neurons or intermediary neurons. Vasovagal reflexes are long reflex pathways with afferent signals carried from the stomach to the vagal nucleus and efferent signals to increase acid production are carried back to the stomach. Gastrin enters systemic circulation and stimulates ECL cells, parietal cells, and chief cells to induce acid and pepsinogen secretion. The intestinal phase is when protein breakdown products stimulate duodenal G cells to produce gastrin, which also acts on the stomach as a hormone.

Salmonella enterica

Salmonella enterica is a gram negative rod, facultative anaerobe, lactose-negative on MacConkey. It is enteroinvasive and inflammatory. It colonizes the lower intestine of many animals, is acid-tolerant, and has many flagella. Typhoid fever is caused by Salmonella enterica serovar Typhi, which is an obligate human pathogen that colonizes the biliary duct and causes systemic infection. Typhi is spread fecal to oral. Thyphoid fever causes gastroenteritis, slowly progressing fever, and profuse sweating. Salmonella typhi has a low infectious dose compared to other types of salmonella. Antibiotic treatment is recommended (fluoroquinolone/ciprofloxacin, cephalosporin/ceftriaxone) and typhoid vaccines are recommended for international travelers (there are live, attenuated oral forms and killed whole bacterial injections). Non-typhoid Salmonella enterica have animal reservoirs and require a large infectious dose. Symptoms include intestinal inflammation, diarrhea, cramping, vomiting, and fever. Antibiotics are not usually recommended and dissemination (blood stream) is rare.

H pylori diagnostic testing

Serology Blood test to detect circulating antibodies against H pylori. It is the most commonly used test but antibodies are elevated after cure, so it can't be used to document eradication after treatment. It is the only test that is not affected by concurrent use of proton pump inhibitors. Urea breath test Patient is given urea tagged with 13C or 14C and H pylori produces urease that converts it to ammonia and tagged carbon that is exhaled. It is an active test because it indicates present infection. Recent use of antibiotics or PPIs/H2 antagonists can decrease sensitivity. Stool antigen test Detects bacterial antigens in the stool of infected patients. It can be falsely negative with antibiotics of antisecretory medications. It's an active test and can be used to document eradication. Rapid urease test (aka CLOtest) A sample of gastric mucosa (endoscopy - invasive) is placed in a well with urea gel and a pH indicator that turns from yellow to pink when pH increases. Urease from H pylori will hydrolyze the urea to ammonia, increasing the pH and changing the color to pink. Antisecretory drugs and antibiotics can produce false negative. Histology Traditionally the gold standard for diagnosis, but test can be falsely negative. Affected by antibiotics and antisecretory drugs. Histology is invasive and is an active test.

Shigella

Shigella are gram-negative, non-motile rods, facultative anaerobes, and enteroinvasive and inflammatory. They are lactose-negative on MacConkey agar and colonize humans only. They are acid-resistant and require a very low infectious dose. Shigellosis is transmitted person-to-person only, causing symptoms in 1-7 days that range from mild diarrhea to dysentery (S. dysenteriae) with abdominal pain, fever, blood/mucus/pus in stool, nausea and vomiting, and watery diarrhea. Hemolytic Uremic Syndrome can occur. Treat with rehydration and sometimes antibiotics. Shiga toxin is released by S. dysenteriae and EHEC and blocks glucose, electrolyte, and amino acid absorption, causing bloody diarrhea. Shiga toxin is an A+B toxin that cleaves the 28S ribosomal subunit and inhibits protein synthesis. Receptors are expressed on endothelial cells of the intestine, kidney (HUS), and brain.

Oral cavity disorders

Sjogren syndrome is a systemic autoimmune disorder associated with inflammation of epithelial tissues, and the *most common disorder associated with xerostomia* (dry mouth) and salivary dysfunction. Primary sjogren syndrome is a salivary and lacrimal gland disorder (dry eye), while secondary sjogren syndrome occurs with other autoimmune diseases like RA, lupus, and scleroderma. Those with Sjogren will have T cell infiltrates in exocrine tissues, autoantibodies anti-Ro and anti-La and rheumatoid factor and will experience cracked lips, desiccated oral tissues, fungal infections, trouble speaking without fluids, and keratoconjunctivitis sicca. Diagnose with Schirmer's test (measures tear production), lip/salivary gland biopsy for T cell infiltrates. Treatment is symptomatic. Those with Sjogren have *increased incidence of non-Hodgkin's lymphoma.* Oral leukoplakia is associated with immunosuppression and occurs generally along the lateral tongue margins bilaterally. White patches/plaques can vary histologically from hyperkeratosis to dysplasia, to carcinoma. Moderate dysplasia or worse warrants treatment. Erythroplakia is a red plaque and has a *higher malignant potential*. Oral candidiasis also causes white patches (thrush) but is more diffuse and can be scraped off with a tongue blade. It's caused by Candida albicans. Smoking, foreign bodies, diabetes, and immunosuppression are risk factors. Lichen Planus is a relatively common immunologis disease where T cells react to antigens causing white striaform lesions that are bilateral and symmetric on the buccal mucosa. *Topical steroids* or nonsteroidals, or cyclosporine (for severe cases) may be used.

Small bowel tumors

Small bowel tumors are very uncommon. Carcinoid tumors are rare well-differentiated neuroendocrine tumors usually in the ileum (and stomach). Carcinoid tumors are often asymptomatic but can obstruct with desmoplasia (fibrotic response scars the lumen and causes obstruction) or intussusception (one part of bowel telescopes over another as tumor is caught by peristalsis and dragged). Metastases develop in the liver and can cause carcinoid syndrome from secretion of serotonin, which causes *flushing,* diaphoresis, diarrhea, wheezing, and hypotension. Histologically, carcinoid tumors have bland tumor cells, salt and pepper chromatin pattern, and no large nucleoli. They can be identified as synaptophysin+ (stain red). Appendiceal carcinoids usually occur in the tip.

Esophageal neoplasia

Squamous epithelia will produce squamous cell carcinoma while columnar/glandular epithelia and intestinal metaplasia will produce adenocarcinoma. Squamous cell carcinoma arises from squamous epithelium and is composed of solid nests/cords of squamous cells +/- keratin pearls in desmoplastic (fibrotic) stroma. Squamous cell carcinoma can be caused by tobacco, alcohol, caustic ingestion, HPV. Adenocarcinoma is composed of glands and arises from normal simple columnar glandular epithelium, exocrine glands, or metaplastic glandular epithelium (Barrett's). Adenocarcinoma is caused by GERD/Berrett's esophagus, obesity, and tobacco. Fungating/polypoid/exophytic malignancies grow up from the epithelium and then straight down through the layers. Infiltrating malignancies grow down through the layers and outward horizontally. Ulcerating malignancies grow straight down and create craters. Esophageal cancer is uncommon in the US (common in other parts of world) but incidence of adenocarcinoma is rising quickly and is now more common than squamous cell. esophageal cancer is diagnosed with endoscopty with biopsy and barium swallow (esophagram). Esophageal cancer in the upper 1/3 can travel to cervical and supraclavicular nodes. Cancer in the middle 1/3 can travel to hilar and tracheal nodes. Cancer in the lower 1/3 can travel to gastric and celiac nodes. Local infiltration can occur: hoarseness suggest recurrent laryngeal nerve is effected, cough suggests trachea, hemorrhage can occur if the aorta is involved. The pericardium and pleura can also become involved.

Pharyngeal/branchial arch 2 (hyoid arch)

The 2nd pharyngeal arch is innervated by CN7 (facial). The Reichert cartilage becomes the lesser horn/cornu of the hyoid, stylohyoid ligament, styloid process, and stapes. Muscles of facial expression migrate into the face and include the posterior belly digastric, stylohyoid, stapedius, orbicularis occult, frontal, buccinator, orbicularis Doris, auricularis, occipitals, and platysma.

Anal canal

The anal canal lies below the pelvic diaphragm and ends at the anus. Above the pectinate/dentate/mucocutaneous line, there is a mucous membrane lined with simple columnar/cuboidal epithelium, innervated with visceral sensory nerves (less sensitive), with venous drainage to the portal system and lymphatic drainage to the internal iliac nodes. There are vertical anal columns with spaces between them called anal sinuses. Below the pectinate line there is skin (stratified squamous epithelium) with general sensory innervation (sensitive), venous drainage to the canal/systemic system, and lymphatic drainage to the superficial inguinal nodes. The internal anal sphincter is a thickening of the inner circular layer of muscularis externa (smooth muscle). The external anal sphincter is skeletal muscle (voluntary), and has subcutaneous, superficial, and deep parts.

Small intestine

The duodenum is in the epigastric region, the jejunum is in the left upper quadrant, and the ileum is in the right lower quadrant. The small intestine is 21 feet long and secretes hormones, continues digestion, and absorbs metabolites. The ileocecal sphincter is a thickening of the inner circular layer of the muscularis externa. The lumen of the small intestine is lined with crypts (intestinal glands) and villi (contain lacteals, increase SA 10x) lined with enterocytes and secretory cells. Microvilli increase SA 20X. Glands are usually limited to the lamina propria in the GI tract but there are pronounced, deeply projecting Brunner's glands in the duodenum making alkaline substances that neutralize acid and inhibit further acid secretion. In the jejunum, there are place circulares (similar to rugae in the stomach, increase SA 2x). In the Ileum, there are peyer's patches. Luminal surface area is increased 400x by microvilli, villi, and plicae circulares. The duodenum is C-shaped and 8-10in long with four parts. The first and second part are superior and descending and are in the foregut. The third and fourth parts are inferior/transverse and ascending and are in the midgut. The first part of the duodenum is intraperitoneal, but parts 2-4 are retroperitoneal. The 1st/superior part of the duodenum is at L1 level, is intraperitoneal, and has a duodenal cap/bulb/ampulla where most duodenal ulcers occur. The 2nd/descending part is secondarily retroperitoneal and located at L2-3. It contains a major papilla (opening of common bile duct and main pancreatic duct at junction of foregut and midgut) and a minor papilla (opening of accessory pancreatic duct). The 3rd/inferior/transverse part is at L3, is secondarily retroperitoneal, and is the beginning of the midgut. *The 3rd part of the duodenum crosses over the aorta/IVC alongside (just below) the left renal vein and under the SMA that branches from the aorta just above the left renal vein (nutcracker).* (SMA syndrome occurs when the angle between the aorta and SMA becomes more acute and obstructs the duodenum.) The 4th/ascending part is at L2 and terminates at the duodenojejunal junction, which is held in place by the suspensory ligament of Treitz. The jejunum is 8 feet long and mostly in the LUQ, vascularized by long vasa recta (unique characteristic in addition to plicae circulares). The ileum is the distal 3/5 of small intestine and mostly in the RLQ, vascularized by short vasa recta but with more arterial arcades than the jejunum.

Emesis

The emetic center is in the medulla and receives input from there cerebellum (from inner ear) and higher centers (pain, smell, sight, memory, fear, dread). The chemo-receptor trigger zone (CTZ) also innervates the emetic center. The CTZ is located at the blood brain barrier in the medulla and senses toxins in the blood stream and also receives signals from the vagal and sympathetic afferents from the stomach and small intestine. Gagging occurs with stimulation of the glossopharyngeal afferent in the pharynx leading to the solitary tract nucleus in the CNS and finally to the emetic center. The emetic center in the medulla coordinates contraction of the diaphragm and abdominal muscles, relaxation of the LES, anti-peristaltic motion of the duodenum, and contraction of the stomach to expel noxious chemicals from the gut. The glottis and soft palate are closed and respiration temporarily stops to prevent aspiration. Acute vomiting can be caused by infection, toxin, obstruction, trauma, or pregnancy. Chronic vomiting is caused by a motility disorder, toxin (medication), endocrine disease, obstruction, space occupying lesion in the brain stem near the chemoreceptor trigger zone, or other chronic GI diseases.

Esophagus

The esophagus is innervated by sympathetic and parasympathetic nerves (anterior vagal trunk is from left vagus and posterior vagal trunk is from right vagus). The esophagus is supplied by esophageal arteries from the aorta, bronchial arteries, and left gastric artery (from celiac trunk). It's drained by small vessels returning mainly to the azygos system. The top 1/3 is skeletal muscle, the middle 1/3 is a mix, and the bottom 1/3 is smooth muscle. The upper esophageal/pharyngoesophageal/cardiac sphincter is made of the cricopharynxgeus part of the inferior pharyngeal constrictor. The lower esophageal/gastroesophageal sphincter is made by thickening of the muscularis externa. The esophagus has a stratified squamous epithelium.

Gastric motility

The functional reservoir of the stomach is the upper 2/3 that tonically contracts with periods of relaxation. The lower 1/3 (andral pump) contracts phasicly. Functional reservoir - accommodates food during a meal and provides compressive force to push material towards antral pump During receptive relaxation, the act of swallowing stimulates mechanoreceptors in the pharynx that stimulate motor neurons in the enteric NS via efferent vagal fibers. In adaptive relaxation, vago-vagal reflex is triggered by distention of the gastric reservoir sensed by mechanoreceptors in the gastric wall. Feedback relaxation is triggered by nutrients entering the small intestine and involves local reflex connections between receptors in the small intestine and stomach and hormonal signals from endocrine cells in the small intestine. Antral pump triturates food into smaller particles. During propulsion, gastric pacemaking cells generate APs that create a leading and trailing contraction. Once the leading contraction reaches the terminal antrum, it stimulates the pylorus to contract and close. In emptying, small amounts of gastric material are emptied into the duodenum before closure of the pylorus. During retropulsion, trailing contraction follows and pushes the food against the closed pylorus, forcing it backward though the contracted portion of grinding up the food. 3 cycles of this occur until emptying is achieved. The speed of gastric emptying is controlled by neuronal mechanisms that adjust for volume, composition, and physical state of the food. Carb rich food leaves fastest, then proteins, then fats. Liquids empty faster than solids.

Stomach

The greater curvature of the stomach is a point of attachment for the gastroepiploic ligament and greater omentum. The lesser curvature is a point of attachment for the lesser omentum. The cardinal notch is that created by the funds and esophagus, the angular incisure is created by the lower curve of the stomach between the pyloric canal and body, and the pyloric orifice is the outlet surrounded by the pyloric sphincter - thickening of the muscularis externa. The stomach has 3 smooth muscle layers in the muscularis externa - inner oblique, middle circular, and outer longitudinal. The inside of the stomach has rugae (ridges). Fundic glands exist in the fundus and body and are branched, tubular and deep. Parietal cells and chief cells are there. Glands in the pyloric antrum are less branched and deep and contain many mucus cells.

Infratemporal fossa

The infratemporal fossa/masticatory spaces contains muscles of mastication, TMJ, parotid gland, maxillary artery and branches, and the mandibular division (V3) of the trigeminal nerve. V3 is the only division of the trigeminal nerve with sensory and motor nerves (V1 and V2 are sensory only). V3 exists the foramen ovale at the skull base and gives rise to: muscular branches that innervate muscles of mastication, the lingual nerve that carries somatic sensation from the anterior 2/3rds of the tongue, the inferior alveolar nerve that enters the mandible (mandibular foramen) and supplies sensory innervation to the mandible/lower teeth (exits as mental nerve through mental foramen), and the auriculotemporal nerve that provides sensory innervation to the TMJ/temporal region. The lingual and auriculotemporal nerves serve as conduits for other nerves traveling in the head. The maxillary artery is a branch of the external carotid artery and divides into mandibular, pterygoid, and pterygopalatine parts. The middle meningeal artery ascends into the cranial cavity. The sphenopalatine artery vascularizes the nasal cavity.

Small intestine motility

The inter digestive phase begins 2-3 hours after digestion and absorption of nutrients is complete (2-3 hours after eating) and includes the migrating motor complex - large amplitude contractions arising from the distal part of the stomach through the duodenum to the terminal ilium. This moves indigestible debris from the intestine while fasting (prevents bacterial overgrowth) and allows food >7mm from the antrum to the duodenum. phase 1 - silent/no contractions phase 2 - irregularly occurring contraction phase 3 - regular contractions Activity front (phase 2 and 3) is faster in the duodenum than ilium and one front begins when the one before it ends in the ilium. Gall bladder contraction and delivery of bile is coordinated with onset of MMC. MMC occurs without external input. Digestive state Segmentation occurs along the entire small intestine, breaking up food and increasing time and contact with the small intestine wall. Power propulsion is strong, long-lasting contraction of circular muscle that moves along the small and large intestines (can be retrograde in small intestine during emesis). It is a defensive adaptation that clears noxious stimuli from the bowel quickly (cramping and diarrhea).

Large intestine (colon)

The large intestine absorbs electrolytes and fluids, produces feces and mucus, and houses bacteria that produce vitamin B12 and K. The cecum is the first part of the colon and is a blind-ended tube inferior to the ileocecal opening. The appendix is a hollow tube connected to the cecum with large aggregations of lymph tissue and us suspended by the mesoappendix. The ascending colon is secondarily retroperitoneal, the transverse colon is intraperitoneal, the descending colon is secondarily retroperitoneal, and the sigmoid colon is intraperitoneal. The transverse colon is suspended by the transverse mesocolon. 2/3 of the way across the transverse colon, the midgut changes to the hindgut and parasympathetic innervation (visceral nerves) switches from the vagus to S2-S4 and blood supply switches from the superior mesenteric artery to the inferior mesenteric artery. The rectum extends from the sigmoid colon to the anal canal, has a superior, middle, and inferior transverse fold, and is partially covered by peritoneum. The ampulla is the lower dilated part where the feces are stored. The rectum is vascularized by the superior, middle, and inferior rectal arteries and veins. The superior rectal veins drain into the portal system and the middle and inferior rectal veins drain into the IVC.

liver and pancreas development

The liver develops in the ventral mesentery, connected to the ventral wall by the falciform ligament and posteriorly to the stomach by the hepatogastric ligament. As it enlarges, it rotates into the right abdominal area, causing rotation of the stomach and spleen into their final locations. The pancreas arises from a ventral (small) and dorsal (larger) bud in the mesenteries just below the level of the bile duct. The ventral bud rotates and fuses with the dorsal bud, becoming the head of the pancreas and the main pancreatic duct (empties into bile duct). The dorsal bud becomes the head, body, and tail of the pancreas. The pancreas begins int eh mesentery but is pushed into the left posterior abdominal wall, fuses there, and becomes retroperitoneal.

Liver

The liver is the largest visceral organ (gland) in the body, located in the right hypochondriac and epigastric regions. Its anterior, superior, and posterior border the diaphragm and it's visceral surface is inferior. It sits below the subphrenic/suprahepatic recess and above the hepatorenal recess (aka *Morison's pouch - blood collects there with internal bleeding).* The liver produces and releases bile, urea, and plasma proteins; stores glucose as glycogen, lipid as triglycerides, and vitamins, Fe, and Cu; converts amino acids and lipids into glucose in gluconeogenesis; detoxifies drugs and alcohol; processes and transfers bilirubin; and produces RBCs in the fetus. The liver is covered by visceral peritoneum except at the fossa for the gallbladder, the porta hepatis, and the bare area against the diaphragm. The porta hepatis is the entry point for hepatic arteries and portal vein and exit point for the hepatic ducts. The liver has a right lobe and a left lobe that includes the quadrate lobe (anterior, bordered by the gall bladder, porta hepatis, and fissure for ligamentum teres) and the caudate lobe (posterior, bordered by the hepatic vein, porta hepatis, and fissure for ligamentum venosum. The falciform ligament attaches to the anterior abdominal wall and separates the right and left lobes. Triangular ligaments attach the left and right ends of the top of the liver to the diaphragm. Coronary ligaments attach the center of the top of the liver to the diaphragm. Hepatogastric ligament attaches to the stomach and is part of the lesser momentum. The hepatoduodenal ligament attaches to the duodenum, is part of the lesser momentum, and contains the portal triad (common bile duct, hepatic artery proper, hepatic portal vein). The liver has 8 segments. The liver is supplied oxygenated blood by the proper hepatic artery and blood from the GI tract enters through the larger hepatic portal vein, which branches and enters sinusoids for processing by hepatocytes before entering central veins, then sub lobular veins. Blood from the proper hepatic artery and hepatic portal vein exit the liver via the hepatic vein (different from the hepatic portal vein). Bile drains out of the liver via the common bile duct that is also within the portal triad. A portal tract consists of branches of the portal vein, hepatic artery, and bile duct that run together in the liver.

Salivary gland neoplasms

The most common salivary gland benign tumors are Pleomorphic adenoma, Warthin's tumor, and benign cysts. The most common malignant tumors are mucoepidermoid carcinoma, adenoid cystic carcinoma, and adenocarcinoma. *Pleomorphic adenoma is the most common benign salivary gland neoplasm* but has malignant potential and so is usually removed. it is slow growing, painless, firm, solitary, and mobile and is imaged with ultrasound, MRI, or CT and diagnosed with fine needle aspiration. Whartin's tumor is a benign papillary cyst adenoma associated with smoking that occurs in older people and is slow growing, painless, and sometimes bilateral. Histologically you see cystic spaces. *Mucoepidermoid carcinoma is the most common malignant salivary gland tumor* in children (and overall) and can be found in non salivary tissues (thyroid, bronchus, lacrimal sac). Mucoepidermoid carcinoma is slow growing, firm, hard, and painless. Histologically, they contain mucus-secreting cells. Adenoid cystic carcinoma is the second most common malignant salivary gland tumor (most common for those in submandibular gland), and can also be found in breast, lacrimal glands, eyes, lung, brain, trachea, and sinus tissues. Adenoid cystic carcinoma travels along nerve tracts, is very slow growing, and has longer survival than other cancers even with metastases.

Pancreas

The pancreas is secondarily retroperitoneal except for part of its tail (head, unciate process, neck, body all retroperitoneal). The pancreatic duct of Wirsung runs from the tail through the body to the head and joins the common bile duct to form the hepatopancreatic ampulla (surrounded by the sphincter of Oddi) at the major duodenal papilla. The accessory pancreatic duct of Santorini empties into the duodenum at the minor papilla. The pancreas secretes trypsin, peptidases, amylases, lipase, and nucleases (exocrines) as well as insulin and glucagon (endocrines). The pancreas is supplied by the anterior superior and posterior superior pancreaticoduodenal arteries (celiac artery), the dorsal pancreatic branches of the splenic artery (from celiac), and the anterior inferior and posterior inferior pancreaticoduodenal arteries (from SMA).

Peritoneum

The parietal peritoneum is supplied by abdominal wall blood vessels, innervated by general sensory fibers (painful), and drained by lymphatic vessels in the abdominal wall. Visceral peritoneum (serosa/mesothelium) is supplied by blood vessels of the viscera, innervated by visceral sensory fibers (dull, hard to localize pain), and is drained by lymphatic vessels from the viscera. Intraperitoneal organs include the stomach, 1st part of the duodenum, liver, tail of the pancreas, spleen, jejunum, ileum, transverse colon, and sigmoid colon. Retroperitoneal organs include urinary structures (kidneys, ureters, bladder), circulatory structures (aorta and inferior vena cava), part of the esophagus and lower 1/3 of rectum (extraperitoneal). The 2nd-4th parts of the duodenum, head/neck/body of the pancreas, ascending colon, and descending colon are secondarily retroperitoneal - they are intraperitoneal during development but came in contact with the body wall and moved retroperitoneal. The greater omentum is a reflection of the peritoneum suspended from the greater curvature of the stomach and attached to the transverse colon. It provides pathways for neurovascular structures and can wrap around inflamed organs to prevent peritonitis. The lesser omentum is another reflection of peritoneum from the lesser curvature of the stomach to the liver, providing a pathway for the portal triad (proper hepatic artery to patient's left, portal vein posterior, and common bile duct to patient's right). It is made up of the hepatogastric and hepatoduodenal ligament (containing portal triad). Mesentery suspends organs from the body wall or connects them to each other, containing blood vessels that travel in between the 2 peritoneal layers. Mesentery refers to mesentery of the small intestine, but there is also the transverse mesocolon, sigmoid mesocolon, and mesoappendix. The root of a mesentery is the location on the posterior body wall where the parietal peritoneum reflects. Peritoneal ligaments are double layers of peritoneum between organs. The gastrolienal connects the stomach and spleen, the lienorenal connects the spleen and pancreas/kidney, the ligamentum teres hepatis and ligamentum venosum contained structures that were active in embryo (left umbilical vein) but are now only remnants.

Salivary glands

The parotid gland is the largest salivary gland and is innervated by the glossopharyngeal nerve (CN IX). *It drains secretions via the parotid/Stensen's duct, which passes superficial to the masseter muscle and then pierces the buccinator muscle, entering the oral cavity near the 2nd maxillary molar*. The facial nerve (CN VII) exits the skull via the stylomastoid foramen and divides into its main terminal branches within the parotid gland: Temporal > forehead above eye Zygomatic > below eye Buccal > toward upper lip Mandibular > jaw/chin Cervical > neck The submandibular gland and sublingual gland are innervated by the facial CN VII. The submandibular gland opens via a duct behind the lower incisors via a papilla. The sublingual gland is a small almond shaped gland with numerous excretory ducts in the mouth floor. Salivary glands can be imaged with plain film to look for calcified or radio-opaque stones or sialendoscopy (stope into duct) or ultrasound. CT and MRI area also used. Submandibular glands originate as ectodermal ingrowths of oral epithelium and contain acini that are composed of serous (thin fluid) and mucous (thick fluid) cells. Contractile myoepithelial cells surround the acini and help push the saliva through the ductal system. Total saliva flow is about 1.5L/day. The parotid gland is mainly composed of serous acini while the submandibular gland has serous and mucinous acini. The parotid gland profiles 25% of daily saliva flow and must be stimulated, while submandibular glands provide 70% of the saliva (basal flow). Sublingual glands are mainly mutinous and provide 5% of daily flow. Stimulated flow is controlled by the parasympathetic NS.

The tongue

The pharyngeal portion of the tongue (back 1/3) is innervated by CN IX, which provides taste and somatic sensation. The glossopharyngeal nerve (CN IX) runs beneath the tonsillar bed and can be injured when tonsils are removed, disturbing taste/sensory perception in the posterior 1/3rd of the tongue. The oral portion of the tongue (anterior 2/3) has many taste buds and receives somatic innervation from the lingual nerve (branch of trigeminal V3) and taste innervation from the chorde tympani nerve (branch of facial CN VII). The oral and pharyngeal portions are divided by the V-shaped sulcus terminalis. (the vagus nerve provides taste and somatic innervation to the epiglottis) All tongue muscles are innervated by the hypoglossal nerve (CN XII), which emerges from the medulla and exits the skull via the hypoglossal canal. *Damage causes deviation of the tongue to that side.* Extrinsic tongue muscles originate outside the tongue and alter its position: hypoglossus (depresses the tongue), styloglossus (retracts the tongue), and genioglossus (protrudes the tongue). Intrinsic tongue muscles are small longitudinal, transverse, and vertical fibers that alter its shape.

Posterior abdominal wall

The posterior abdominal wall contains mainly retroperitoneal structures, including the aorta with its branches, IVC and branches, kidneys and ureters, suprarenal glands, lumbar plexus, autonomic nerve plexuses, and lymphatics. Kidneys are retroperitoneal and located at T12-L3 (ribs 11-12). The right kidney is lower because of the liver. Perirenal/perinephric fat is exztraperitoneal fat outside the renal capsule. The renal fascia is exztraperitoneal fascia outside the perirenal fat. Pararenal/paranephric fat is extraperitoneal fat outside of the renal fascia. i.e. the kidney is surrounded by perirenal fat, then renal fascia, and then pararenal fat. The left renal vein goes under the superior mesentaric artery but in front of the aorta, creating the nutcracker. Suprarenal (adrenal) glands are on the superior pole of each kidney and have a cortex and medulla. The right gland is pyramidal and the left is semilunar. Suprarenal glands receive their blood supply from the superior suprarenal artery (from inferior phrenic artery), middle suprarenal artery (from aorta) and inferior suprarenal artery (from renal arteries). The suprarenal glands drain into the right suprarenal vein (into IVC) and the left suprarenal vein (drains into left renal vein). The abdominal aorta runs from T12 (aortic hiatus) to L4 where it bifurcates into the common iliac arteries. Prevertebral plexus of autonomic nerves suits on its surface. The celiac trunk, SMA and IMA are unpaired branches to the alimentary canal. The middle suprarenal arteries, renal arteries, and gonadal arteries are branches to paired viscera. The inferior phrenic arteries, lumbar arteries, and median sacral artery are posterior branches to the body wall. The IVC is formed by uniting the two external iliac veins at L5 and it pierces the diaphragm at T8, returning blood from all structures below the diaphragm to the heart. It receives no blood from the abdominal GI, spleen, pancreas, or gallbladder (hepatic system).

Esophageal motility

The proximal 1/3 of the esophagus is striated muscle and the distal 2/3s is smooth muscle. The upper and lower sphincters are tonically contracted to prevent air influx and gastric content reflux. Primary peristalsis is initiated by the voluntary act of swallowing. Secondary peristalsis occurs when the primary peristaltic event fails to clear the bolus from the body of the esophagus and is reflexively initiated by activation of mechanoreceptors. At the onset of the swallow, the lower esophageal sphincter relaxes which corresponds to a fall in pressure across the sphincter that lasts throughout the swallow and until the esophagus empties its contents into the stomach. Coordination of the peristaltic wave and relaxation of the lower esophageal sphincter is mediated by vagal nerve signals.

Spleen

The spleen is located against the diaphragm at ribs 9-10 in the left upper quadrant and is connected to the stomach by the gastrosplenic (gastrolienal) ligament and to the left kidney by the splenorenal (lienorenal) ligament. The hilum is the entry point for splenic vessels. The spleen filters blood, stores RBCs, phagocytose damaged/aged RBCs, proliferates B and T lymphocytes, and produces antibodies.

Arterial supply and nerves to abdominal wall

The superior epigastrics from the internal thoracic artery and the inferior epigastric from the external iliac artery anastomose with each other within the rectus abdominis. The intercostal arteries, musculophrenics, and small branches from the femoral and iliac arteries also anastomose and vascularize the abdominal wall. Innervation to the muscle and skin The ventral rami of thoracic spinal nerves (and some lumbar) innervate the abdominal wall. T7-T12 are the thoracoabdominal nerves, and T12 is the subcostal nerve. L1 ventral ramus divides into the iliohypogastric and ilioinguinal nerve (through canal into scrotum or labia major).

Forming the GI tract

Transverse folding in week 4 creates the GI tract from the yolk sac and the coelom (peritoneal cavity) also forms. The dorsal mesentery containing vasculature from the ectoderm remains and suspends the GI tract while the mental mesentery disappears except in the upper abdomen with the round ligament of the liver (ligamentum teres). The GI tract is ultimately made up of mesoderm and endoderm (lines the yolk sac). The gut is divided into the: Foregut - pharynx, esophagus, stomach, duodenum, pancreas, and liver. The foregut is supplied by the celiac artery (except the pharynx) Midgut - duodenum, jejunum, ileum, cecum, ascending colon, and 2/3 transverse colon. In forming, the midgut herniates as a loop into the umbilical cord, and the cranial limb grows and folds into the small intestine, while the caudal limb doesn't grow long but becomes the proximal large intestine. They return to the abdominal cavity at week 10, cranial limb then caudal, and rotate as they return. The midgut is supplied by the superior mesenteric artery. Hindgut - 1/3 of transverse colon, descending colon, sigmoid colon, rectum, cranial anal canal. The hindgut is supplied by the inferior mesenteric artery.

GI sphincters

Upper esophageal sphincter - at the junction of the posterior oropharynx and the proximal esophagus, prevents retrograde flow of gastroesophageal contents and passage of air into the esophagus. Tonically contracted. Lower esophageal sphincter - located at the junction of the distal esophagus and proximal stomach, is the primary barrier to prevent reflux of gastric contents into the esophagus. In the absence of a hiatal hernia, the lower esophageal sphincter is located at the diaphragmatic hiatus. Tonically contracted. The pylorus - at junction of distal stomach and duodenal bulb, regulation of gastric emptying and prevents reflux of bile acid and pancreatic enzymes into the stomach Sphincter of oddi - at level of the duodenal ampulla where both the pancreatic and common bile ducts insert into the duodenum, prevents reflux of small bowel chyme into the bile and pancreatic ducts, and maintenance of sterility of the pancreatic and biliary trees. The ileocecal valve - junction of the terminal ileum and cecum prevents reflux of colonic contents into the small bowel and limits small bowel bacterial overgrowth Internal and external anal sphincters - proximal and distal aspects of the anal canal, maintaining fecal continence

Hepatic portal system

Venous drainage of the spleen, pancreas, gallbladder, and abdominal part of the GI tract is through the hepatic portal system that delivers blood to the liver. The portal vein is created by the union of the splenic vein, superior mesenteric vein, and inferior mesenteric vein and travels in the portal triad in the hepatoduodenal ligament, bringing nutrients from the gut to the liver. Portal-systemic/caval anastomoses Obstruction in the liver or portal vein (e.g.. cirrhosis) cause blood to be re-routed around the liver to systemic circulation (inferior vena cava). The left gastric vein is rerouted to the esophageal veins associated with the azygos vein. This can cause esophageal varices and rupture. The paraumbilical veins are re-routed to the superficial veins on the abdominal wall, causing a caput medusae. Superior rectal vein drains into the middle and inferior rectal veins, and this can cause hemorrhoids. The colic veins anastomose with retroperitoneal veins.

Vibrio cholerae

Vibrio cholerae are gram negative, highly motile, comma-shaped rods that are enterotoxigenic and facultative anaerobes. Vibrio cholerae live in water and on shells of shellfish but do not infect animals. Transmission is via contaminated water or food. Cholera toxin and E. coli LT toxin are A+B toxins that activate adenylate cyclase, resulting in secretion of Na+, K+, Cl-, and HCO3- out of cells with water following and causing rice water diarrhea. Cholera can be asymptomatic or cause abrupt onset of watery diarrhea (20L/day) that looks like rice water. Cholera toxin leads to loss of fluid and electrolytes, hypokalemia, cardiac arrhythmia and renal failure, and death from hypovolemic shock in 72hrs. Oral rehydration is the main treatment and greatly reduces mortality. Vaccines are available but not in the US.

GI bacteria and immunity

pH shifts from 2 in the stomach, to 4-5 in the small intestine, to 7 in the large intestine. In the stomach and proximal small intestine, Lactobacilli, Strep., Candida, and Helicobacter are the prominent bacterial populations. In the small intestine, Lactobacilli, E. coli, and Enterococci are prominent. In the colon, Lactobacilli, Bacteroides, Bifidobacteria, and Clostridia are prominent. Many gram-negative enteric bacteria have flagella that allow for locomotion (vs. pili/fimbriae that are smaller and for adherence). If you inject mice with flagellin protein from bacteria from an infected mouse, the recipient mice will be prepared to mount an immune response to rotavirus (immune). This still occurs in mice without Rag1, which is needed to rearrange T cell receptor and antibody genes, demonstrating that it is the innate immune system responsible for bacterial protection from viral infection (TLR signaling after recognizing pathogen associated molecular patterns)