Gastrointestinal System Lecture Notes PDF

GASTROINTESTINAL SYSTEM Copyright Pass NPLEX 2018 1  GASTROINTESTINAL SYSTEM ▪ Embryology & Anatomy ▪ Physiology ▪ Biochemistry ▪ Pathology SAMPLE CASE 1 A 22-year-old male has a history o...

GASTROINTESTINAL SYSTEM Copyright Pass NPLEX 2018 1  GASTROINTESTINAL SYSTEM ▪ Embryology & Anatomy ▪ Physiology ▪ Biochemistry ▪ Pathology SAMPLE CASE 1 A 22-year-old male has a history of mild, fluctuating, unconjugated hyperbilirubinemia. Lab test results indicate normal liver function. As there is no evidence of other disease processes, he is diagnosed with Gilbert syndrome. 1. What is the etiology of Gilbert syndrome? A. A genetic absence of UDP-glucouronosyltransferase B. A genetic decrease in hepatic levels of UDP-glucouronosyltransferase C. Immature hepatic processing, causing deficient conjugation of bilirubin D. A deficiency of canalicular membrane transporters of bilirubin glucuronide 4 Copyright Pass NPLEX 2018 2  ▪ Answer: B - A genetic decrease in hepatic levels of UDP-glucouronosyltransferase ▪ Genetic syndrome causing impairment to bilirubin conjugation resulting in slight buildup of bilirubin in the body. 5 SAMPLE CASE#2 A 42-year-old male presents with chronic nausea, emesis, and upper abdominal pain. Lab test results indicate normal serum gastrin and a normal CBC. He is diagnosed with chronic gastritis caused by Helicobacter pylori. 1. A gastric biopsy would most likely reveal the presence of H. pylori and the presence of _____________. A. Normal rugal folds with multiple hemorrhagic erosions of the gastric mucosa B. Intraepithelial neutrophils and subepithelial plasma cells of the stomach antrum C. Enlarged rugae and hyperplasia of the mucosal epithelium; no inflammation D. Mucosal atrophy with lymphocytes and macrophages present in the stomach body and fundus, and loss of parietal cells 6 Copyright Pass NPLEX 2018 3  ▪ Answer: B - Intraepithelial neutrophils and subepithelial plasma cells of the stomach antrum 7 EMBRYOLOGY & ANATOMY Copyright Pass NPLEX 2018 4  EMBRYOLOGY Foregut ▪ Endoderm ▪ Esophagus, stomach, pharynx, proximal portion of the duodenum Midgut ▪ Endoderm ▪ Distal portion of the duodenum, jejunum, ileum, cecum, and appendix, ascending colon, majority of transverse colon Hindgut ▪ Endoderm ▪ Distal transverse colon, descending colon, sigmoid colon, rectum, super anal canal ▪ Urethral and bladder epithelium Proctodeum ▪ Ectoderm ▪ Connects to hindgut and forms the pectinate line ANATOMY ▪ Oral cavity ▪ Pharynx ▪ Esophagus ▪ Mesenteries and associated structures ▪ Stomach ▪ Small intestine ▪ Liver ▪ Gallbladder ▪ Pancreas ▪ Large intestine ▪ Rectum ▪ Pelvic diaphragm ▪ Anus Copyright Pass NPLEX 2018 5  ORAL CAVITY ▪ General ▪ Teeth ▪ Tongue ▪ Salivary glands ORAL CAVITY ▪ Keratinized stratified squamous epithelium changes to nonkeratinized stratified squamous epithelium of the mucous membrane at the vermillon border ▪ Gums, hard palate, filiform papillae of the tongue are partially keratinized ▪ No muscular mucosa present Palate ▪ Composed of hard (anterior 2/3) and soft palate (posterior 1/3) ▪ Innervated by CN V2 ▪ Soft palate ▪ Contains 5 muscles: levator veli palatini, tensor veli palatini, palatoglossus, palatopharyngeus, musculus uvulae Copyright Pass NPLEX 2018 6  TEETH ▪ Composed of a crown, neck, root, and pulp cavity ▪ Sockets are made of alveolar bone and encased in gingiva ▪ Dentin, enamel, cementum layers ▪ Periodontal membrane/ligaments extends from the root to the periosteum of the alveolar wall Image: Wikimedia Commons – Author: BruceBlaus ▪ Deciduous teeth (20) – in children, eight incisors, four canines, eight premolars ▪ Permanent teeth (32) – adults, eight incisors, four canines, eight premolars, twelve molars ▪ Alveolar arteries supply blood. ▪ Superior alveolar nerve (CN V2) supplies the maxilla ▪ Inferior alveolar nerve (CN V3) supplies the mandible TONGUE Filiform papilla ▪ Most of the tongue surface; rough, keratinized tips Fungiform papilla ▪ Scattered among the filiform papillae; taste buds Circumvallate papillae ▪ Anterior to the terminal sulcus; large and surrounding trenches contain taste buds and serous von Ebner’s glands/ducts Foliate papillae ▪ Line the lateral aspect of the tongue and have taste buds Taste buds are innervated by the facial nerve in the anterior 2/3 of the tongue and the glossopharyngeal nerve in the posterior 1/3. Taste sensations = sweet (anterior), saltiness (anterolateral), sour (posterolateral), bitter (posterior) Copyright Pass NPLEX 2018 7  ▪ Terminal sulcus on the dorsal surface → divides the tongue into the anterior and posterior parts. ▪ Foramen cecum is the pit located on the dorsal surface ▪ Lingual septum is a fibrous septum under the median sulcus. ▪ Lingunal follicles are collectively called the lingual tonsils ▪ Sublingual caruncles are papillae on the base of the lingual frenulum which contain the opening of the submandibular duct from the submandibular salivary gland. ▪ Extrinsic muscles alter the position of the tongue ▪ genioglossus, hyoglossus, styloglossus, and palatoglossus muscles ▪ Intrinsic muscles alter the shape of the tongue ▪ Superior and inferior longitudinal, transverse, and vertical muscle ▪ Lingual artery supplies the tongue ▪ Branches include the dorsal lingual arteries (posterior portion), deep lingual artery (ventral portion), sublingual branch of the facial artery (sublingual gland and floor of the mouth) ▪ Dorsal lingual and deep lingual/ranine veins ▪ Deep lingual veins → sublingual vein (and dorsal lingual vein) → inferior jugular vein ▪ Superior deep cervical lymph nodes drain the posterior 1/3 of the tongue ▪ Inferior deep cervical lymph nodes drain the medial part of the anterior 2/3 of tongue ▪ Submandibular lymph nodes drain the lateral part of anterior 2/3 ▪ Submental lymph nodes drain the apex. Innervation ▪ CN V3 – touch and temperature sensation of anterior 2/3 ▪ CN VII – taste sensation of anterior 2/3 ▪ CN X – palatoglossus muscle ▪ CN IX – touch, temperature, and taste sensation of posterior 1/3 ▪ CN XII – all other muscles Copyright Pass NPLEX 2018 8  SALIVARY GLANDS Parotid gland ▪ Stenson’s duct is found in the inside of the cheek adjacent to the 2nd upper molar ▪ Branches of the external carotid and superficial temporal arteries supply blood ▪ Retromandibular veins drain the blood. ▪ Parasympathetic innervation via the CN IX and sympathetic innervation from the cervical ganglia. ▪ Superficial and deep cervical lymph nodes drains the lymph. Submandibular gland ▪ Sublingual and submental arteries from the lingual and facial arteries, respectively ▪ Presynaptic parasympathetic fibers from facial nerve, lingual nerve, and chorda tympani which synapse with the submandibular gland. Sublingual gland ▪ Wharton’s duct extends from posterior part of the gland and has 3 orifices on the sublingual papilla ▪ Submental branch of the facial artery ▪ Lingual nerve and presynaptic parasympathetic fibers from CN VII which synapse with the submandibular ganglion. ▪ Lymph drains into deep cervical lymph nodes Image: Wikimedia Commons – Author: BruceBlaus Copyright Pass NPLEX 2018 9  PHARYNX ▪ Nasopharynx ▪ Oropharynx ▪ Laryngopharynx NASOPHARYNX ▪ Superior to the soft palate; choanae open between the nasopharynx and nasal cavity ▪ Pharyngeal tonsil ▪ Salpingopharyngeal fold = mucous membrane flap that extends from the Eustachian tube ▪ Tubal tonsil is located near the pharyngeal orifice of the auditory tube ▪ Pharyngeal recess is the lateral projection of the pharynx which extends laterally and posteriorly. Copyright Pass NPLEX 2018 10  OROPHARYNX ▪ Palatine tonsil found between the palatine arches ▪ Internal pharyngeal muscles include stylopharyngeal (innervated by CN IX), palatopharyngeus, and salpingopharyngeus (both innervated by CN X via pharyngeal branch of CN X and pharyngeal plexus) ▪ The superior, middle, and inferior constrictor muscles coordinate movement of food during swallowing by aiding the epiglottis to direct food to the esophagus. ▪ Superior, middle, and inferior constrictor muscles innervated by pharyngeal plexus of nerves (pharyngeal branches of CN X and CN IX) and superior cervical ganglion LARYNGOPHARYNX ▪ Bordered by the larynx, epiglottis, pharyngoepiglottic folds, cricoid cartilage, and middle and inferior constrictor muscles. ▪ Piriform recess is a mucosal-lined depression on the side of the inlet of the larynx. ▪ Tonsillar artery supplies it with blood. ▪ External palatine vein drains it. ▪ Lymph drains to the jugulodigastric (tonsillar) node. Copyright Pass NPLEX 2018 11  Image: Wikimedia Commons – Author: OpenStax College ESOPHAGUS ▪ Starts posterior to cricoid cartilage at C6 level and passes through the diaphragm at T10 and enters the cardia of the stomach. ▪ Internal circular layer of muscle and external longitudinal layer of muscle. ▪ The cervical esophagus is supplied by the inferior thyroid artery and drains by the inferior thyroid vein. ▪ Lymph drains into paratracheal and inferior deep cervical lymph nodes ▪ The abdominal portion is supplied by the left gastric and left inferior phrenic arteries and drained by the left gastric vein. ▪ Lymph drains into the left gastric lymph nodes. Copyright Pass NPLEX 2018 12  ▪ Upper half receives somatic motor and sensory ▪ Somatic fibers from branches of recurrent laryngeal nerves ▪ Vasomotor fibers from cervical sympathetic trunk ▪ Lower half receives parasympathetic, sympathetic, and visceral sensory ▪ Upper esophageal sphincter formed by the cricopharyngeus muscle. ▪ Lower esophageal sphincter formed by diaphragmatic musculature that forms the esophageal hiatus ▪ Esophagogastric junction (Z-line) = where the mucosa changes from esophageal to gastric mucosa MESENTERIES ▪ Double layer of peritoneum with a loose connective tissue layer in the middle which attaches organs to the wall of the body. ▪ Mesentery proper contains the jejunum and ileum, mesogastrium, mesoappendix, transverse/sigmoid mesocolon Organs not enveloped in mesentery ▪ Duodenum (excluding proximal ⅓), ascending and descending colon, rectum, kidneys, pancreas, suprarenal glands, ureters, aorta, IVC Omentum is a double-layered peritoneal fold from the stomach and duodenum to the abdominal wall or organs. ▪ Lesser omentum connects the liver to lesser curve of stomach and duodenum ▪ Greater omentum hangs from the greater curve of the stomach and proximal duodenum to attach to the transverse colon. ▪ Epiploic foramen = opening between the greater and lesser peritoneal sacs Copyright Pass NPLEX 2018 13  Image: Wikimedia – Author: Henry Gray STOMACH ▪ Secretes gastric juices (mucus, HCl, pepsin) to create chyme ▪ Blood supply: ▪ Lesser curvature – right and left gastric arteries ▪ Greater curvature – right and left gastro-omental arteries ▪ Fundus and upper greater curvature – short gastric arteries ▪ Blood drained by the right and left gastric verins, right and left gastro-omental veins, and short gastric veins. ▪ Gastric lymphatic vessels drain into the gastric and gastro-omental lymph nodes ▪ Sympathetic innervation via the thoracic splanchnic nerves. ▪ Parasympathetic innervation via the vagus nerve (CN X) Copyright Pass NPLEX 2018 14  Image: Wikimedia Commons – Author: OpenStax College SMALL INTESTINE ▪ Duodenum ▪ Jejunum ▪ Ileum Copyright Pass NPLEX 2018 15  DUODENUM ▪ Proximal portion of the small intestine ▪ Bile and pancreatic enzymes enter via the duodenal papilla ▪ Ampulla is the only part of the duodenum that is intraperitoneal Descending portion ▪ Pancreatic and bile ducts form the hepatopancreatic ampulla Ascending portion ▪ Duodenojejunal flexure ▪ Ligament of Treitz = suspensory muscle that connects duodenum to diaphragm ▪ Blood is supplied by the celiac trunk and superior mesenteric artery ▪ Associated arteries = duodenal, gastroduodenal, superior and inferior pancreaticoduodenal ▪ Duodenal veins drain blood. ▪ Lymph is drained by the pancreaticoduodenal, superior mesenteric, pyloric, and celiac lymph nodes. ▪ Sympathetic innervation from the celiac and superior mesenteric plexuses. ▪ Parasympathetic innervation via the vagus nerve. Copyright Pass NPLEX 2018 16  Image: Wikimedia Commons – Author: Luke Guthmann JEJUNUM ▪ Blood supplied by the superior mesenteric artery ▪ Superior mesenteric vein drains blood. ▪ Mesenteric lymph nodes drain to the superior mesenteric lymph nodes. ▪ Lacteals are lymph vessels in the villi of the intestine which absorb fat ▪ Sympathetic innervation via the superior mesenteric plexus. ▪ Parasympathetic innervation via the vagus nerve (CN X) Copyright Pass NPLEX 2018 17  ILEUM ▪ Iliocecal junction ▪ Superior mesenteric artery supply blood. ▪ Superior mesenteric vein drains blood. ▪ Mesenteric lymph nodes drains into the superior mesenteric and ileocolic lymph nodes. ▪ Sympathetic innervation via the superior mesenteric plexus. ▪ Parasympathetic innervation via the vagus nerve (CN X) LIVER ▪ Round ligament attaches the liver to the abdominal wall. ▪ Porta hepatis ▪ Transverse fissure on the visceral surface between the caudate and quadrate lobes ▪ Portal vein, hepatic artery, bile duct, hepatic nerve plexus, and lymphatic vessel travel along this fissure. ▪ Portal triad = portal vein, hepatic artery, bile duct, hepatic nerve, and lymph vessels ▪ Portal vein and hepatic artery supply blood. ▪ Hepatic vein drains into the inferior vena cava. ▪ Superior and deep lymph vessels drain into the hepatic lymph nodes. ▪ Innervation via the hepatic nerve plexus. Copyright Pass NPLEX 2018 18  Right & left lobes ▪ Fossa of the gallbladder and inferior vena cava demarcate the two lobes on the visceral surface. ▪ Falciform ligament separates the two lobes on the diaphragmatic surface. Caudate lobe ▪ Considered part of the right liver ▪ Separated from the left lobe on the visceral surface by the fissure for ligamentum venosum Quadrate lobe ▪ Part of the right liver ▪ Separated from the left lobe on the visceral surface by the fissure for ligamentum teres Diaphragmatic surface ▪ Anterior, superior, posterior surfaces ▪ Subphrenic recesses = spaces between the anterior liver and diaphragm ▪ Right and left subphrenic recesses divided by the falciform ligament ▪ Hepatorenal recess is located on the right side ▪ Bare area = triangular area on the posterior aspect of the liver where it contacts the diaphragm and is not covered by visceral peritoneum ▪ Demarcated from the rest of the liver by the coronary ligament ▪ Enclosed where the areas meet at the right triangular ligament ▪ Formed by the left layers of the falciform ligament and lesser omentum Visceral surface is covered by peritoneum ▪ Except for the porta hepatis and gallbladder Copyright Pass NPLEX 2018 19  Image: Wikimedia Commons – Author: Henry Gray Image: Wikimedia Commons – Author: Henry Gray Copyright Pass NPLEX 2018 20  GALLBLADDER ▪ Located on the visceral side of the liver in the gallbladder fossa ▪ Common bile duct = cystic duct + common hepatic duct ▪ Cystic artery supplies blood. ▪ Cystic vein → portal vein ▪ Hepatic lymph nodes drain lymph. ▪ Sympathetic innervation from the celiac plexus. ▪ Parasympathetic via the vagus nerve. ▪ Sensory input from the right phrenic nerve. PANCREAS ▪ Accessory pancreatic duct opens into the duodenum at the minor duodenal papilla. ▪ Pancreatic arteries supply the body and tail and the inferior and superior pancreaticoduodenal arteries supply the head. ▪ Pancreatic veins → splenic vein ▪ Pancreaticosplenic lymph nodes → celiac, hepatic, and superior mesenteric lymph nodes ▪ Sympathetic innervation via vagus and thoracic splanchnic nerves. ▪ Parasympathetic innervation via the celiac and superior mesenteric plexuses Copyright Pass NPLEX 2018 21  LARGE INTESTINE ▪ Ascending colon ▪ Transverse colon ▪ Descending colon ▪ Sigmoid colon ASCENDING COLON ▪ Retroperitoneal portion of the colon located on the right side of the abdomen ▪ Starts at the cecum and ends at the hepatic flexure ▪ Cecum = blind pouch with no mesentery ▪ Appendix = blind intestinal diverticulum which contains lymphoid tissue ▪ Connected to the cecum via the mesoappendix ▪ Appendicular artery supplies blood ▪ Ileocecal vein drains into the superior mesenteric vein. ▪ Ileocolic artery supplies blood. ▪ Ileocolic vein drains the ascending colon ▪ Ileocolic lymph nodes drains lymph. ▪ Superior mesenteric plexus and vagus nerve innervate. Copyright Pass NPLEX 2018 22  TRANSVERSE COLON ▪ Begins at the hepatic flexure and terminates at the splenic flexure ▪ Teniae coli = 3 longitudinal bands of thickened smooth muscle ▪ Haustra = sacculations between teniae coli ▪ Omental appendices/epiploic appendices = fat lobules that extend from the omentum ▪ Transverse mesocolon = mesentery that loops down from the transverse colon ▪ Superior mesenteric artery supplies half of the transverse colon while the inferior mesenteric artery supplies the other half. ▪ Right and left colic arteries also supply blood. ▪ Superior mesenteric vein drains it. ▪ Middle colic lymph nodes → superior mesenteric lymph nodes ▪ Innervated by the superior and inferior mesenteric nerve plexus. DESCENDING COLON ▪ Retroperitoneal section that extends from the left colic flexure to the left iliac fossa ▪ Left colic artery and superior sigmoid arteries supply blood. ▪ Inferior mesenteric vein → splenic vein → portal vein ▪ Epicolic and paracolic lymph nodes → intermediate colic lymph nodes ▪ Sympathetic innervation from the lumbar trunk and superior hypogastric plexus. ▪ Parasympathetic innervation from the pelvic splanchnic nerves. Copyright Pass NPLEX 2018 23  SIGMOID COLON ▪ Connects the descending colon and the rectum ▪ Teniae coli terminate at the rectosigmoidal junction where the longitudinal muscle broadens. ▪ Left colic artery and superior sigmoid arteries supply this area. ▪ Inferior mesenteric veins → splenic vein → portal vein ▪ Sympathetic innervation from the lumbar trunk and superior hypogastric plexus. ▪ Parasympathetic innveration from the pelvic splanchnic nerves. RECTUM ▪ Sacral flexure due to the rectum following the shape of the sacrum and coccyx ▪ Anorectal flexure = where the rectum ends as it enter the pelvic diaphragm through the levator ani muscle to become the anal canal. ▪ Lateral flexure = 3 transverse folds which form the valves of Houston ▪ Ampulla of rectum = dilated terminal portion ▪ Supported by the pelvic diaphragm and anococcygeal ligament ▪ Rectovesical pouch (males) ▪ Reflected peritoneum which extends from the rectum to bladder ▪ Rectouterine pouch (females) ▪ Reflected peritoneum which extends from the rectum to fornix of the vagina ▪ Pararectal fossa = laterally reflected peritoneum ▪ Extends from the rectum and allows it to distend when filled with feces Copyright Pass NPLEX 2018 24  ▪ Superior rectal artery supplies the proximal portion ▪ Middle rectal arteries supply the middle and distal areas. ▪ Inferior rectal arteries supply the anorectal junction and anal canal. ▪ Superior, middle, and inferior rectal veins drain the rectum. ▪ Pararectal lymph nodes drain the proximal half while the internal iliac lymph nodes drain the distal half. ▪ Sympathetic innervation via the lumbar trunk and superior hypogastric plexus. ▪ Parasympathetic innervation via the pelvic splanchnic nerves. Image: Wikimedia Commons – Author: BruceBlaus Copyright Pass NPLEX 2018 25  PELVIC DIAPHRAGM ▪ Composed of the levator ani muscle, coccygeus muscle, and fascia above and below the muscles. ▪ Separates the pelvic cavity from the perineum ▪ Ischioanal fossa = space around the anal canal between the skin and pelvic diaphragm ▪ Anal triangle contains the anus ▪ Urogenital triangle contains the root of the scrotum and penis in males and external genitalia in female ▪ Internal pudendal artery supplies blood. ▪ Internal pudendal vein drains this area. ▪ Pudendal nerve innervates it. Image: Wikimedia Commons – Author: OpenStax Copyright Pass NPLEX 2018 26  ANUS ▪ Starts where the puborectalis muscle forms a U-shaped sling Internal sphincter ▪ Involuntary ▪ Smooth muscle that occupied the upper 2/3 of the anal canal ▪ Innervated by parasympathetic fibers from the pelvic splanchnic nerves External sphincter ▪ Voluntary ▪ Striated muscle along the distal 1/3 of the anal canal ▪ Innervated by the inferior rectal nerve which comes from the pudendal nerve ▪ Pectinate line = forms the intermuscular groove of the anus and marks the junction of the superior and inferior anal canals ▪ Superior rectal arteries supply the area superior to the pectinate line. ▪ Inferior rectal arteries supply the area inferior to the pectinate line. ▪ Internal rectal venous plexus drains the entire anal canal. ▪ Internal iliac and superficial inguinal lymph nodes drain the areas superior and inferior to the pectinate line, respectively. ▪ Sympathetic and parasympathetic fibers of the inferior hypogastric plexus innervates the area superior to the pectinate line. ▪ The inferior area is innervated from the inferior rectal nerves and branches of the pudenal nerve. Copyright Pass NPLEX 2018 27  PHYSIOLOGY PHYSIOLOGY ▪ Motility/Peristalsis ▪ Regulation of motor activity ▪ Digestion & absorption ▪ Macronutrient digestion Copyright Pass NPLEX 2018 28  MOTILITY/PERISTALSIS Chewing ▪ Involuntary chewing reflexes stimulates when food puts pressure on against the gums, palate, and tongue. Degluttination ▪ When pressure receptors found in the walls of the pharynx are stimulated by a bolus of food at the rear of the mouth the swallowing reflex is initiated. ▪ Receptors send signals to the swallowing center of the medulla ▪ Motor impulses are transmitted to the muscle of the pharynx, esophagus, and respiratory muscles via cranial nerves. ▪ Peristalsic contractions squeeze the food bolus into the esophagus. Esophageal propulsion ▪ Skeletal muscles surround the upper 1/3 of the esophagus ▪ Layers of circular and longitudinal smooth muscle create contractions. Stomach mixing, storage, and emptying Mixing ▪ Peristalsis starts near the cardiac sphincter and move toward the pylorus. ▪ Small amount of chyme is released into the duodenum with each wave of contraction. ▪ Pacemaker cells, found in the longitudinal smooth muscle layer, determine the rate of peristalsis. Storage ▪ Peristalsis closes the pyloric sphincters ▪ Chyme is broken down and mixed with gastric juices. Emptying ▪ Force and amount of gastric emptying per contraction are determined reflexively by neural and hormonal input to antral smooth muscle. ▪ Rate of gastric emptying depends on stomach and duodenal contents. Copyright Pass NPLEX 2018 29  Small intestine mixing and propulsion Mixing ▪ Mainly stationary contraction and relaxation ▪ Produces continuous division and subdivision of intestinal contents ▪ Pacemakers are found in the longitudinal smooth muscle layer Propulsion ▪ After absorption is nearly complete, migratory motility complex contractions occur ▪ Peristaltic waves are initiated in the duodenum ▪ Once new food arrives peristalsis stops and segmentation begins Colon mixing and mass movements Mixing ▪ Contraction of the colon’s circular smooth muscles = segmenting motion/haustal contractions ▪ Locally controlled – activated by distension Mass movements ▪ 3-4 times per day often following a meal ▪ Intense contraction that spreads over the transverse segment of the colon towards the rectum ▪ Sudden distention of the rectal walls produces mass movement of fecal material into the rectal causes a defecation reflex. Copyright Pass NPLEX 2018 30  MOTOR ACTIVITY REGULATION Neural regulation ▪ Cephalic, gastric, and intestinal phases Enteric nervous system ▪ Deep myenteric plexus – control motility ▪ Superficial submucosal plexus – regulates glands ▪ Stimulation at one point in the plexus can cause an impulses to be sent up and down the GI tract. ▪ Contains: ▪ Adrenergic and cholinergic neurons ▪ Nonadrenergic and noncholinergic neurons ▪ Chemical (ATP, small peptides, nitric oxide) Autonomic nervous system ▪ Extrinsic controls exerted by the autonomic fibers via long reflex arcs ▪ Enteric nervous system is connected to the CNS by afferent visceral fibers and fiber of the sympathetic and parasympathetic branches of the ANS. Cephalic phase ▪ Initiated when smell, sight, taste, chewing, and emotions stimulate receptors in the head ▪ Efferent nerves activate nerves in GI nerve plexuses Gastric phase ▪ Initiated by stretch and chemoreceptors in the stomach ▪ Causes increased gastric secretions and motility Intestinal phase ▪ Initiated by distension, acidity, osmolarity, and digestive products in the intestinal tract ▪ Stimulates gastrin and motility Copyright Pass NPLEX 2018 31  Local hormone regulation ▪ Hormones are secreted by endocrine cells in the gastric and small intestinal epithelium. ▪ Chemical substances in chyme stimulate the release of hormones. Gastrin ▪ Produced in the stomach ▪ Stimulates the secretion of HCl and gastric juice in response to peptides and amino acids ▪ Stimulates gastric emptying in response to the release of Ach from parasympathetic nerves. Somatostatin ▪ Produced in the stomach and duodenum and release in response to food in the stomach ▪ Inhibits all secretions, motility, and emptying of the stomach ▪ Inhibits secretion of insulin and glucagon from the pancreas ▪ Inhibits the contraction of the gallbladder and thus bile release Cholecystokinin (CCK) ▪ Produced in the duodenum ▪ Stimulates acinar cells to release pancreatic enzymes ▪ Stimulates the contraction of the gallbladder and release of bile Secretin ▪ Produced in the duodenum ▪ Stimulates duct cells of the pancreas to release bicarbonate ions ▪ Stimulates bile/bicarbonate secretion from the liver Gastric inhibitory peptide (GIP) ▪ Produced in the duodenum ▪ Inhibits gastric gland secretion and motility ▪ Stimulates insulin secretion from the pancreatic Copyright Pass NPLEX 2018 32  DIGESTION & ABSORPTION Oral cavity ▪ Mastication physically breaks down food and is aided by saliva ▪ Salivary amylase starts to break down starches into oligosaccharides ▪ Salivary lysozyme and IgA disinfects the foods ▪ Stomach acid denatures the salivary enzymes ▪ Parasympathetic nervous system is the primary control for salivation. ▪ Sympathetic nervous system stimulates the secretion of thick, mucous-rich saliva Stomach ▪ Gastrin and vagus nerve stimulation regulates the strength of peristalsis ▪ Hypertonic solution in the duodenum inhibits gastric emptying ▪ HCl denatures proteins and activates pepsinogen ▪ Pepsin cleaves proteins to form polypeptides ▪ Intrinsic factor is secreted by parietal cells ▪ HCl secreted by parietal cells when stimulated by Ach, gastrin, and histamine during a meal, especially if high in protein. Copyright Pass NPLEX 2018 33  Small intestine ▪ Pancreatic digestive enzymes and brush border enzymes complete digestion. ▪ Alkaline mucous from intestinal glands and bicarbonate help neutralize chyme and provide the ideal environment for enzymatic activity. ▪ Duodenal/Brunner’s glands secrete alkaline mucous into the duodenum helps neutralize acidic chyme ▪ Goblet cells secrete mucous ▪ Paneth cells, found deep in the crypts, secrete an antibacterial lysozyme ▪ Brush border enzymes include disaccharidases and peptidases ▪ Enterokinase = proteolytic enzyme Pancreas ▪ Acinar cells produce pancreatic juice which is enzyme-rich. ▪ Epithelial cells release bicarbonate ions. ▪ Secretin is released in response to HCl in the duodenum and stimulates the duct cells to secrete HCO3- ▪ Cholecystokinin (CCK) is released in response to proteins and fats in the duodenum and stimulates the acinar cell to secrete enzymes. ▪ Vagal stimulation causes the release of pancreatic juice during cephalic and gastric phases. Copyright Pass NPLEX 2018 34  Liver ▪ Bile release into the duodenum is regulated by the Sphincter of Oddi ▪ Between meal the sphincter closes and dilute bile from the liver is shunted into the gallbladder where it is concentrated. Large intestine ▪ Secretions lack digestive enzymes and are mainly composed of mucous and fluid containing bicarbonate and potassium ions ▪ Goblet cells secrete mucous in response to distention ▪ HCO3- neutralizes acids made by bacteria as they break down fiber and vitamins ▪ Digestion via bacteria ▪ Bile acids, fatty acids, and carbohydrate fermentation ▪ Water, electrolytes, toxins, and bacterial metabolites are absorbed. MACRONUTRIENT DIGESTION ▪ Carbohydrates ▪ Amino acid & proteins ▪ Lipids Copyright Pass NPLEX 2018 35  CARBOHYDRATES ▪ Acinar cells of exocrine cells produce: ▪ Salivary alpha-amylase, pancreatic alpha-amylase, alpha-glucosidase or maltase, alpha- dextrinase, sucrase, lactase ▪ Digestion begins in the mouth with salivary alpha-amylase ▪ Breaks down starch and glycogen by hydrolyzing alpha-1,4 glycosidic linkages ▪ Pancreatic alpha-amylase interacts with dietary starch and glycogen. ▪ Disaccharidases (alpha-glucosidase or maltase) and oligosaccharides (alpha- dextrinase) ▪ Remove glucose from non-reduced ends and complete conversion of starch/glycogen into usable forms of glucose. ▪ Indigestible polysaccharides = fiber that bulk up stool ▪ Absorbed in their monosaccharide form before entering the portal venous system ▪ Free glucose is transported into the blood via sodium-dependent hexose transporters AMINO ACIDS & PROTEINS ▪ Gastric juices break down proteins. ▪ Pepsin is a proteolytic enzyme that hydrolyzes peptide bonds within a protein. ▪ Other peptidases include: ▪ Trypsin, chymotrypsin, carboxypeptidase A/B, elastase ▪ Brush border has peptidases that aid in the shortening of amino acid chains. ▪ Amino acids, dipeptides, and tripeptides are absorbed by intestinal epithelial cells. Copyright Pass NPLEX 2018 36  ▪ Dipeptides and tripeptides are hydrolyzed to amino acids by cytosolic peptidases ▪ Amino acids are transported into the cell via sodium-amino acid cotransporters ▪ Amino acids stimulate insulin production to help muscle cells uptake branched chain amino acids ▪ Amino acid uptake stimulates production of albumin in the liver and contractile proteins in muscles. LIPIDS Mouth ▪ Lingual lipase starts lipid digestion Stomach ▪ Ligual lipase and gastric lipase are acid-resistant Pancreas ▪ Lipase, phospholipase, cholesterol esterases are required for lipolysis ▪ Colipase helps lipase attach to a lipid which allows fatty acids to be hydrolyzed into smaller glycerides. Small intestine ▪ Micelle contents diffuse through the lipid membrane of enterocytes ▪ Within the enterocytes cytoplasm the products of lipolysis are reesterified into triglycerides and phospholipids ▪ Chylomicrons enter lacteals and pass with lymph into the thoracic duct. Copyright Pass NPLEX 2018 37  Bile acids and salts ▪ Bile is composed of cholesterol, bilirubin, phospholipids, and bile salts ▪ Bile emulsifies fat making it more available to pancreatic lipase ▪ Micelles = free fatty acids and monoglycerides surrounded by bile salts and phospholipids ▪ Bile salts raise the pH of chyme ▪ Bile eliminates excess cholesterol and waste products from the body ▪ Bile acid produced in the liver = cholic acid and chenodeoxycholic acid Bile acid synthesis regulation ▪ Hydroxylation of cholesterol by 7-alpha-hydroxylase = rate-limiting step ▪ Requires oxygen, NADPH, cytochrome P450, vitamin C ▪ HMG-CoA reductase requires substrate Bile acids are recycled via enterohepatic circulation ▪ Cholesterol cannot be broken down and is thus excreted via bile ▪ Bile salts are deconjugated and dehydroxylated by normal flora ▪ Reabsorbed via the ileum and returned to the liver or excreted via feces Copyright Pass NPLEX 2018 38  BIOCHEMISTRY BIOCHEMISTRY ▪ Vitamins ▪ Macrominerals ▪ Microminerals ▪ Monosaccharides ▪ Disaccharides ▪ Polysaccharides ▪ Amino acids and proteins ▪ Metabolism ▪ Non-digestive glandular functions Copyright Pass NPLEX 2018 39  VITAMINS ▪ Water soluble = B1,B2, B3, B5, B6, B12, C, folate, biotin ▪ Fat soluble – A, D, E, K Deficiencies ▪ B1 = Beriberi, Wernicke’s ▪ B2 = cheilosis/glossitis ▪ B3 = Pellegra (dementia, diarrhea, dermatitis) ▪ B5 = burning feet, headache, nausea ▪ B6 = Neuropathy ▪ B9 (folate) = macrocytotis, glossitis, colitis, no neurological deficit, neural tube defects ▪ B12 = Pernicious anemia, neuropathy ▪ C = scurvy ▪ Biotin = seborrheic dermatitis, nervous disorders MACROMINERALS Calcium = most abundant cation in the body ▪ Muscle contraction, membrane permeability, nerve conduction, bone matrix Phosphorus = 2nd most abundant mineral ▪ Component of nucleic acids, cell membranes, energy reactions, bone matrix Magnesium ▪ Cofactor for many enzymatic reactions Sodium ▪ Maintains fluid balance, acid-base balance, nerve and muscle excitability Potassium ▪ Main intracellular cation, acid-base balance, nerve and muscle excitability Copyright Pass NPLEX 2018 40  MICROMINERALS Iron ▪ Most is found in hemoglobin ▪ Oxygen transport, energy production, activation of oxygen Zinc ▪ Important cofactor for enzymes, needed for normal reproduction, cell division, wound healing, vision Copper ▪ Needed for iron mobilization from the liver, cofactor for SOD, needed for blood clotting, energy production, estrogen breakdown, and collagen synthesis Selenium ▪ Component of glutathione peroxidase and involved in protecting against heavy metal toxicity Cobalt ▪ Part of vitamin B12 (cobalamin) Fluoride ▪ Part of calcified tissues Silicon ▪ Part of cartilage and bone Manganese ▪ Use in cartilage formation and cholesterol synthesis, and needed for brain chemistry and helps prevent fatty liver due to its interaction with choline Chromium ▪ Needed for proper insulin function and glucose metabolism Iodine ▪ Needed for thyroid hormone synthesis Copyright Pass NPLEX 2018 41  MONOSACCHARIDES Glucose ▪ Used to synthesize other carbohydrates ▪ Major fuel source for many tissues ▪ Insulin and glucagon keep blood glucose levels in a narrow range Fructose ▪ Similar to glucose and can be converted to glucose ▪ Ketose that forms furanose rings Galactose ▪ Can be converted to glucose Mannose ▪ Found in glycoproteins of plant gums DISACCHARIDES Two monosaccharides covalently bonded via a glycosidic linkage between anomeric carbon of one molecule and a different carbon on the second molecule Sucrose = glucose + fructose (α1,β2) ▪ Both anomeric carbons used in the glycosidic linkage (no alpha or beta ring structures) Lactose = glucose + galactose ((β1-4) ▪ Galactose uses its anomeric carbon ▪ Glucose can open to form alpha and beta ring structures Maltose = glucose + glucose (α1-4) ▪ One glucose uses its anomeric carbon in the alpha-1,4 linkage ▪ Both alpha and beta ring forms Isomaltose = glucose + glucose (α1-6) ▪ Bound by alpha-1,6 glycosidic linkage Copyright Pass NPLEX 2018 42  POLYSACCHARIDES > 6 monosaccharides in a chain Amylose ▪ Non-branching starch with alpha-1,4 glycosidic linkages Amylopectin ▪ Starch with alpha-1,4 glycosidic linkages with branch points involving apha-1,6 glycosidic linkages Glycogen (α1-4 and α1-6 linkages) ▪ Glucose storage molecule which is highly branched Inulin ▪ Starch made of repeating fructose molecules Cellulose ▪ Glucose molecules are bound by beta-1,4 glycosidic linkages AMINO ACIDS & PROTEINS 20 amino acids are used in protein synthesis ▪ Composed of a carboxyl group, amino group, side chain all attached to an alpha-carbon Essential amino acids - PVT TIM HALL ▪ Phenylalanine, valine, threnonine, tryptophan, isoleucine, methionine, histidine, leucine, arginine, and lysine Non-essential amino acids ▪ Alanine, arginine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, tyrosine Copyright Pass NPLEX 2018 43  AMINO ACID DERIVATIVES ▪ Phenylalanine → tyrosine ▪ Tyrosine ▪ → L-dopa → dopamine → NE → Epi ▪ → L-dopa → melanin ▪ → thyroxine ▪ Histadine → histamine ▪ Lysine → carnitine ▪ Tryptophan → serotonin or niacin or melatonin Oligopeptides ▪ Contains a small number of amino acids ▪ Reduced glutathione Polypeptides ▪ < 50 amino acids and therefore not considered a protein ▪ Primary structure = simple sequence of amino acids ▪ Secondary structure = alpha-helix and beta-pleated sheet folding patterns ▪ Tertiary structure = 3D structure involving electrostatic and hydrophobic interactions, hydrogen bond, and disulfide formation between amino acids along the primary chain ▪ Quaternary structure = interaction between tertiary proteins (> 2 polypeptide chains) Copyright Pass NPLEX 2018 44  Covalent bonds hold amino acids in their primary structure ▪ Can be broken via digestion (hydrolysis) Weak bonds = ionic interactions, hydrogen bonds ▪ Help maintain secondary, tertiary, and quaternary structures Globular proteins = tightly arranged tertiary structure with a hydrophilic surface and hydrophobic interior ▪ Ex: albumin Fibrous proteins = used for structures ▪ Ex: collagen Helix = group of proteins that twist on themselves to increase stability PROTEIN FUNCTIONS ▪ Growth, maintenance and structure of tissues ▪ Enzymes ▪ Hormones ▪ Antibodies ▪ Maintenance of volume and electrolyte balance ▪ Acid-base balance ▪ Transportation ▪ Energy ▪ Lubricants ▪ Blood clotting and vision Copyright Pass NPLEX 2018 45  AMINO ACID SYNTHESIS Non-essential amino acids synthesized via transaminases ▪ Muscle and liver have a large amount of transaminases Transamination ▪ Involves amino group transfer from one amino acid to form another ▪ Two amino acids and their corresponding alpha-keto acids ▪ Ex: glutamate and alpha-ketoglutarate ▪ Requires vitamin B6 (pyridoxal phosphate), biotin, THF, SAM α-ketoglutarate acts as the predominant amino group acceptor Glutamate + oxaloacetate ←→ alpha-ketoglutarate + aspartate TRANSAMINASES Aspartate transaminase (AST) ▪ Transfers amino group from glutamate to oxaloacetate to form aspartate ▪ Found in the liver, heart, skeletal muscle, and RBCs Alanine aminotransferase (ALT) ▪ Transfers amino group from alanine to alpha-ketoglutarate ▪ Largest amount found in the liver, can be found in the heart, skeletal muscles, and RBCs Alkaline phosphatase ▪ Hydrolyzes phosphate esters ▪ Found in the bone, placenta, liver, intestines, and kidneys Copyright Pass NPLEX 2018 46  AMINO ACID CATABOLISM ▪ Enterocytes preferentially absorb glutamine and other amino acids before they enter portal circulation following a protein-rich meal. ▪ Liver takes all amino acids EXCEPT branched chain amino acids which continue to muscles where insulin aids their absorption. Nitrogen metabolism ▪ Transamination reaction so the carbon structure can be used in muscle for energy or transported to the liver for glucose or ketone body production ▪ Nitrogen structures are converted to alanine or glutamine then transported to the liver to be transformed into urea. Nitrogen waste ▪ Ammonia (primarily in the form of urea), creatinine, uric acid METABOLISM ▪ Liver ▪ Hormones ▪ Glycolysis ▪ Krebs Cycle ▪ Electron transport chain & oxidative phosphorylation ▪ Gluconeogenesis ▪ Glycogenesis & glycogenolysis ▪ Hexose monophosphate shunt ▪ Other carbohydrate pathways ▪ Acetyl-Coenzyme A metabolism Copyright Pass NPLEX 2018 47  LIVER ▪ Converts glucose to glycogen via glycogenesis when glucose levels in the blood are high. ▪ Converts glycogen to glucose via glycogenolysis when blood glucose is low ▪ Converts galactose and fructose to glucose then glucose into fat ▪ When glycogen stores are depleted amino acids are converted into glucose via gluconeogenesis HORMONES Insulin ▪ Produced in beta cells within islets of Langerhans ▪ Increases glucose utilization rate via oxidation, glycogenesis, and lipogenesis ▪ Production and release is stimulated by an increase in glucose and certain amino acids in the blood. ▪ Lowers blood glucose by: ▪ Increased facilitated diffusion of glucose into muscle and adipose cells ▪ Promoting glucose storage and glycogen within the liver and muscle cells ▪ Increases glucose uptake by liver and adipose cells so it can be converted into fat Copyright Pass NPLEX 2018 48  Glucagon ▪ Produced by alpha cells within islets of Langerhans ▪ Increases blood glucose levels in response to hypoglycemia or elevated blood levels of amino acids ▪ Causes the liver to release glucose via: ▪ Stimulating glycogenolysis ▪ Activating hepatic gluconeogenesis ▪ Increasing lipolysis of triglycerides in adipose tissue ▪ Secretion inhibited by somatostatin and insulin Cortisol ▪ Increases and maintains normal blood glucose levels by: ▪ Stimulating gluconeogenesis within the liver ▪ Mobilizing amino acids from extrahepatic tissues ▪ Inhibiting muscle and adipose tissue glucose uptake ▪ Promoting fat breakdown in adipose tissue Epinephrine ▪ Promotes glycogenolysis within the liver and muscle via cAMP production in the liver and muscle cells ▪ Decreases insulin release Copyright Pass NPLEX 2018 49  GLYCOLYSIS ▪ Occurs in the cytoplasm of all body tissues ▪ Pyruvate is the end product in cells that have mitochondria ▪ Lactate is formed in cells without mitochondria (ex. RBCs) Anaerobic energy production = 2 lactate and 2 ATP molecules ▪ NADH is used to reduce pyruvate to lactate via lactate dehydrogenase Aerobic energy production = 2 ATP, 2 NADH, and 2 pyruvate ▪ Pyruvate enters Krebs cycle to generate more ATP via the production of NADH and FADH2 ▪ NADH enters the ETC to generate ATP ▪ Glucose 6-phosphate is important in: ▪ Glycolysis, gluconeogenesis, pentose phosphate pathway, glycogenesis, glycogenolysis Image: Wikimedia Commons – Author: YassineMrabet Copyright Pass NPLEX 2018 50  The following 3 reactions are irreversible and regulated: Hexokinase/glucokinase ▪ Hexokinase is inhibited glucose 6-phosphate ▪ Stimulated by high levels of insulin ▪ Glucokinase it NOT inhibited by glucose 6-phosphate Phosphofructokinase-1 (PFK-1) – rate limiting enzyme ▪ Activated by fructose 2,6-bisphosphate (product of PFK-2) ▪ Increased activity with insulin activation of PFK-2 and high levels of AMP ▪ Inhibited by ATP and citrate Pyruvate kinase ▪ Activated by fructose 1,6-bisphosphate and insulin-induced phosphatases ▪ Inhibited by ATP and alanine KREBS CYCLE ▪ Occurs in the mitochondria ▪ Liberates hydrogen ions for the production of ATP within the ETC Rate-limiting enzymes Citrate synthase ▪ Controlled by the availability of its substrates (acetyl-CoA and oxaloacetate) ▪ Inhibited by succinyl-CoA, NADH, ATP Isocitrate dehydrogenase ▪ Stimulated by isocitrate, ADP, NAD ▪ Inhibited by ATP and NADH Alpha-ketoglutarate dehydrogenase ▪ Inhibited by succinyl-CoA, NADH, ATP, GTP Copyright Pass NPLEX 2018 51  Image: Wikimedia Commons – Author: Narayanese, WikiUserPedia, YassineMrabet, TotoBaggins KREBS CYCLE KEY POINTS Energy production per one cycle ▪ ATP equivalents = 12 ▪ NADH x 3 = 9 ATP ▪ FADH2 x 1 = 2 ATP ▪ GTP x 1 = 1 ATP ▪ CO2 x 3 Kreb Cycle Intermediates ▪ Pyruvate from glycolysis ▪ Acetyl CoA from fatty acid oxidation (even carbon chains) ▪ Citrate is used for fatty acid synthesis ▪ Succinyl CoA from fatty acid oxidation (odd carbon chains) ▪ Malate is used in gluconeogenesis ▪ Succinate enters the electron transport chain Copyright Pass NPLEX 2018 52  ELECTRON TRANSPORT CHAIN & OXIDATIVE PHOSPHORYLATION ▪ Components are embedded in the mitochondrial cristae ▪ NADH and FADH2 are electron donors and are found in the interior matrix ▪ NADH donates its electron and hydrogen in complex I ▪ NADH dehydrogenase is attached to a FMN which contains an Fe-S molecule ▪ FMN passes electrons to coenzyme Q producing energy to pump H+ across the membrane ▪ FADH2 donates its electrons to CoQ via complex II ▪ Electrons on CoQ flows through a series of cytochromes in complex III and IV ▪ Each cytochrome contains a heme molecule where ferric iron is reduced to ferrous iron when it accepts an electron ▪ Cytochrome aa3 also contains copper ▪ Oxygen is the final electron acceptor and water is generated ▪ One ATP is generated for every 2 electrons (4 hydrogens) passed to oxygen ▪ 3 ATP are generated for every NADH ▪ 2 ATP for every FADH2 Oxidative phosphorylation ▪ Couples ATP production with respiration ▪ Water is created from respiratory O2 ▪ Hydrogen flows down its concentration gradient using ATP synthase which produces ATP Inhibitor/uncoupler examples ▪ 2,4-dinitrophenol causes the ETC to proceed without establishing a proton gradient ▪ Cyanide and carbon monoxide block electron flow in cyt c oxidoreductase Copyright Pass NPLEX 2018 53  Image: Wikimedia Commons – Author: OpenStax College GLUCONEOGENESIS ▪ Occurs primarily in liver cell cytosol ▪ Pyruvate → oxaloacetate → malate ▪ Forms glucose from lactate and pyruvate, Krebs cycle intermediates, and carbon skeletons of all amino acids EXCEPT leucine and lysine ▪ All non-carbohydrate precursors must be converted to oxaloacetate first. ▪ Glycerol, lactate, amino acids (alanine, aspartate, glutamine) ▪ Glucagon and cortisol stimulates. ▪ Insulin inhibits. ▪ Pyruvate carboxylase uses ATP, biotin, CO2 as cofactors. ▪ All other steps require ATP and NADH Copyright Pass NPLEX 2018 54  Rate-limiting enzymes ▪ Pyruvate dehydrogenase, pyruvate kinase, PFK-1, glucokinase/hexokinase must be inactive for gluconeogenesis to occur ▪ Pyruvate dehydrogenase is inhibited by acetyl-CoA ▪ Pyruvate carboxylase activated by acetyl-CoA, cortisol, and ATP ▪ PFK-1 is inhibited by high ATP and citrate levels ▪ Phosphorylation of liver enzymes by cAMP-dependent protein kinase stimulates gluconeogenesis ▪ Gluconeogenesis increases with lower levels of fructose-2,6- bisphosphate ▪ ATP inhibits phosphofructokinase ▪ AMP inhibits fructose-1,6-bisphosphatase ▪ Gluconeogenesis can use: ▪ Lactate, glycogenic amino acids and glycerol to make glucose ▪ alpha-ketoacids (pyruvate, oxaloacetate and alpha- ketoglutarate) Image: Wikimedia Commons – Author: Dwong527 GLYCOGENESIS & GLYCOGENOLYSIS Rate-limiting enzymes ▪ Glycogen synthase – regulates glycogen synthesis ▪ Inactivated by protein kinases and activated by protein phosphatase ▪ Glycogen phosphorylase A – regulates glycogen degradation ▪ Glucagon/epinephrine binds & activates adenylate cyclase → increase cAMP → activates protein kinase → phosphorylates phosphorylase kinase → phosphorylates glycogen phosphorylase B → glycogen phosphorylase A (active form) ▪ AMP and calcium stimulate muscle glycogen breakdown ▪ High glucagon and/or epinephrine → increased glycogen degradation ▪ Epinephrine stimulates glycolysis and glycogenolysis in muscle cells. ▪ UTP → UDP-glucose which is a good glucose donor for glycogen formation ▪ Inorganic phosphate → glucose-1-phosphate as glucose is removed from glycogen Copyright Pass NPLEX 2018 55  HEXOSE MONOPHOSPHATE SHUNT ▪ Glucose enters as glucose 6-phosphate ▪ Regulatory enzyme = glucose-6-phosphate dehydrogenase ▪ Occurs in the cytoplasm of cells ▪ Protects RBCs from oxidative damage (keeps glutathione reduced) ▪ Used in fatty acid and cholesterol synthesis in liver and adipose cells ▪ Used for steroid hormone synthesis in the adrenal cortex ▪ Oxidative portion produces ribulose-5-phosphate, CO2, and 2 NADPH molecules ▪ Non-oxidative portion produces ribose residues, fructose-6-phosphate, and glyceraldehyde-3-phosphate ▪ NADPH is used for: ▪ Reduction reactions of FA, cholesterol, and steroid synthesis ▪ Hepatic phase I detoxification reactions ▪ Synthesis of tyrosine from phenylalanine ADDITIONAL CARBOHYDRATE PATHWAYS ▪ Fructose → fructose-1-phosphate → dihydroxyacetone phosphate (DHAP) + glucose-3-phosophate ▪ Mannose and galactose go through 3 steps in order to form glucose-6-phosphate ▪ Both these pathways require ATP ▪ UDP-glucose is required for the galactose pathway Copyright Pass NPLEX 2018 56  ACETYL-COA METABOLISM ▪ Acetyl-CoA is completely oxidized by the Krebs cycle Synthesis ▪ Via degradation of carbohydrates, fatty acids, and most amino acids ▪ From pyruvate via pyruvate dehydrogenase (decarboxylation) ▪ Requires niacin (NAD), CoASH (from pantothenic acid), thiamine, riboflavin (FAD), lipoic acid Utilization ▪ Combines with oxaloacetate to form citrate ▪ Transported out of the mitochondria and used for fatty acid synthesis ▪ Ketone body synthesis in hepatic mitochondria ▪ Cholesterol synthesis pathway ▪ Pyruvate → acetyl-CoA is regulated by covalent modification via pyruvate dehydrogenase complex (PDC) ▪ Increased ATP inactivates PDC ▪ Increased ATP demand results in the PDC being regenerated via free Ca2+ NON-DIGESTIVE GLANDULAR FUNCTIONS Iron from hemoglobin is stored mainly in the liver Hepcidin is produced by the liver when iron levels are high Transferrin transports iron in the blood and is made in the liver Copyright Pass NPLEX 2018 57  DETOXIFICATION PROCESSES Cytochrome P450 ▪ Found in hepatocytes, intestines, kidneys, lungs, and blood-brain barrier ▪ Contains heme ▪ Aids phase II enzymes conjugate foreign and endogenous molecules so they can be excreted ▪ Various families ▪ Adds an oxygen atom to substrate and to water ▪ Catalyzes hydroxylation reactions ▪ Requires electrons from electron transfer chains Phase II enzymes ▪ Create water-soluble metabolites that can be removed by kidneys ▪ When molecule donors run out toxins can build up in tissues ▪ Transmethylases ▪ Utilize S-adenosylmethionine as a methyl donor in order to methylate molecules that have been activated by CYP450 ▪ Sulfotransferases ▪ Glucuronyl transferases Glutathione-related enzymes ▪ Glutathione S-transferases (GST) attaches reduced glutathione ▪ Doesn’t necessarily require prior activation by phase I enzymes ▪ Dependent on sufficient levels of reduce glutathione and NADPH ▪ Rate limiting product = cysteine Copyright Pass NPLEX 2018 58  PATHOLOGY ▪ Salivary gland diseases ▪ Pancreatic diseases ▪ Hepatic diseases ▪ Gallbladder diseases ▪ Deficiency and malabsorption conditions ▪ Obstructive gastrointestinal diseases ▪ Inflammatory gastrointestinal diseases ▪ Congenital gastrointestinal diseases ▪ Abdominal cavity conditions ▪ Vascular gastrointestinal diseases ▪ Gastrointestinal neoplasms ▪ Infectious gastrointestinal diseases Copyright Pass NPLEX 2018 59  PAROTITIS ▪ Inflammation of the parotid gland ▪ Typically caused by mumps but can be caused by Staphylococcus aureus ▪ Present in Sjogren’s syndrome ▪ Parotiditis due to mumps is generally bilateral and can involve the submaxillary and sublingual gland swelling which are tender during febrile stage (24-72 hours) PANCREATITIS Acute pancreatitis ▪ Premature activation of pancreatic enzymes resulting in autodigestion of the organ and hemorrhagic fat necrosis ▪ Severe abdominal pain, prostration, elevated serum amylase and hypocalcemia ▪ Associated with biliary tract disease, alcoholism, and abdominal trauma Chronic pancreatitis ▪ Progressive fibrosis, destruction, calcification, and formation of pseudocysts ▪ Steatorrhea, abdominal and back pain, progressive disability ▪ Strongly associated with alcoholism ▪ Complications include diabetes mellitus Copyright Pass NPLEX 2018 60  HEPATIC DISEASES ▪ Cholestasis ▪ Cirrhosis ▪ Hepatic failure ▪ Gilbert’s syndrome ▪ Viral hepatitis ▪ Alcoholic hepatitis ▪ Portal hypertension ▪ Jaundice CHOLESTASIS ▪ Decreased bile flow → build up bile in the liver causing hepatocyte damage ▪ Obstructive – from gallstones and liver or biliary tree tumors ▪ Metabolic – lack of synthesis or secretion ▪ Drugs and toxins ▪ Primary biliary cirrhosis and primary sclerosing cholangitis are common causes ▪ Intrahepatic cholestasis of pregnancy (ICP) – usually develops in the 3rd trimester and is related to high estrogen levels ▪ Pruritis, jaundice, fatigue ▪ Can be life-threatening and ICP can cause premature labour, abnormal clotting, stillbirth, and meconium aspiration Copyright Pass NPLEX 2018 61  CIRRHOSIS ▪ Liver fibrosis or sclerosis replaces hepatocyte mass ▪ Fatigue, palpably hard, shrunken liver, jaundice and potentially liver failure if progressive ▪ Usually secondary to hepatitis or chronic liver damage HEPATIC FAILURE Acute ▪ Caused by acute liver trauma such as acute fulminant hepatitis Chronic ▪ Caused by alcoholic cirrhosis and chronic viral hepatitis ▪ Jaundice, elevated liver enzymes, protein synthesis failure, detoxification failure, abnormal hormone catabolism, hepatorenal syndrome, portal hypertension Copyright Pass NPLEX 2018 62  GILBERT’S SYNDROME ▪ Slight buildup of bilirubin in the body ▪ Genetic syndrome causing impairment to bilirubin conjugation ▪ Reduce bilirubin uptake by the liver ▪ Decreased glucouronyl transferase activity ▪ Mild jaundice if present but generally asymptomatic and blood work can reveal mild unconjugated hyperbilirubinemia ALCOHOLIC HEPATITIS ▪ Acute form is a serious inflammatory condition ▪ Severe cholestasis develops major liver damage ▪ Neutrophil infiltrates, focal hepatocyte necrosis, Mallory bodies, and fatty liver changes ▪ Fibrosis of the area around the central veins ▪ Fever, hypotension, jaundice, ascites, tachycardia, hepatomegaly (tender), elevated serum transaminases (AST:ALT >2), leukocytosis, abnormal clotting status, hyperbilirubinemia ▪ Complications include hepatic encephalopathy and death if severe Copyright Pass NPLEX 2018 63  PORTAL HYPERTENSION ▪ Elevated pressure within the portal venous system ▪ Prehepatic – due to portal and splenic vein obstruction ▪ Portal vein thrombosis, congenital atresia of the portal vein ▪ Intrahepatic – due to intrahepatic vascular obstruction ▪ Liver cirrhosis, metastases, schistosomiasis ▪ Posthepatic – due to venous congestion ▪ CHF, IVC and hepatic vein thrombosis, constrictive pericarditis, IVC malformation ▪ Ascites, hepatic encephalopathy, splenomegaly, esophageal, gastric, and anorectal varices, caput medusae, mild pancytopenia ▪ Complications include hepatorenal syndrome, bacterial peritonitis, and variceal rupture JAUNDICE Type Causes Hyperbilirubinemia Hemolytic – intravascular Hemolytic anemia Unconjugated Hemolytic – extravascular Internal hemorrhage Unconjugated Obstructive Gallstones, pancreatic Conjugated carcinoma, ductal atresia Impaired conjugation Gilbert’s syndrome, neonatal Unconjugated jaundice, hepatitis, drugs, cirrhosis Impaired secretion from Jaundice of pregnancy, steroid Conjugated hepatocytes drugs, sepsis Impaired hepatic uptake Drugs, starvation Unconjugated Copyright Pass NPLEX 2018 64  GALLBLADDER DISEASES ▪ Cholecystitis ▪ Cholelithiasis CHOLECYSTITIS ▪ Inflammation of the gallbladder ▪ Usually due to chronic cholelithiasis and bile acid accumulation ▪ Can result from cholangitis or exogenous estrogen exposure as well ▪ Cholangitis ▪ Charcot’s triad = RUQ pain, jaundice, fever ▪ Potentially fatal ▪ Cholecystitis ▪ RUQ discomfort, fatty food intolerance, nausea, fever can occur if severe along with acute abdominal pain Copyright Pass NPLEX 2018 65  CHOLELITHIASIS ▪ Accumulation of bile resulting in gravel and stone formation within the gall bladder ▪ Associated with lack of exercise and fiber, and a diet high in saturated fat and sugar ▪ More common in women ▪ Strongly associated with with obesity and insulin resistance ▪ Often asymptomatic but can lead to cholecystitis or passage of a stone(s) ▪ Complications include cholecystitis, biliary colic (acute stone passage), cholangitis, obstructive jaundice acute pancreatitis DEFICIENCY & MALABSORPTION CONDITIONS ▪ Achlorhydria & hypochlorhydria ▪ Celiac disease ▪ Lactase deficiency Copyright Pass NPLEX 2018 66  ACHLORHYDRIA & HYPOCHLORHYDRIA ▪ Low or the absence of gastric acid secretion ▪ Usually asymptomatic but dyspepsia, nausea, reflux, and constipation can occur ▪ Causes include pernicious anemia, aging, and chronic stress ▪ Complications include infection, nutrient malabsorption, gastric dysbiosis, gastric cancer, esophageal candidiasis, small intestinal dysbiosis, food allergies, altered drug metabolism CELIAC DISEASE ▪ Autoimmune disease where gluten triggers systemic inflammation. ▪ Immune cells attack antibody-coated gluten antigens in mucosal villi of jejunum and results in damage and destruction of villi. ▪ Acute steatorrhea, weight loss, weakness, severe abdominal pain, vomiting, intermittent attacks, failure to thrive ▪ Other presentations include mild indigestion, malabsorption, chronic fatigue, recurrent abdominal pain, skin rash ▪ Complications include: ▪ Autoimmune thyroiditis, Sjorgren’s syndrome, Addison’s disease, IBD, iron-deficiency anemia, vitamin B12 deficiency, folate deficiency, osteoporosis, dermatitis herpetiformis, intestinal lymphoma Copyright Pass NPLEX 2018 67  LACTASE DEFICIENCY ▪ Absence of lactase in the brush border and therefore unable to digest lactose ▪ Digestive upset after eating dairy often associated with bloating, cramping, flatulence, and diarrhea. ▪ Congenital lactase deficiency = autosomal recessive ▪ Absence of lactase OBSTRUCTIVE GASTROINTESTINAL DISEASES ▪ Achalasia ▪ Adynamic ileus ▪ Hiatal hernia ▪ Intussusception ▪ Volvulus ▪ Megacolon Copyright Pass NPLEX 2018 68  ACHALASIA ▪ Loss of lower esophageal motility causing the LES to be unable to relax. ▪ Leads to esophagitis and an imbalance between inhibitory and excitatory impulses in the enteric nervous system ▪ Risk factors: amyloidosis, Parkinsonism, esophageal cancer, esophageal surgery ▪ Dysphagia (liquids and solids), chest pain, nighttime cough, regurgitation, aspiration ▪ Complications include esophageal cancer and pneumonia from aspiration ADYNAMIC ILEUS ▪ GI tract obstruction due to motor dysfunctional ▪ Due to abdominal surgery, hypothyroidism, opioids, spinal cord injury, peritonitis ▪ Constipation, nausea, vomiting, dyspepsia, excessive belching, bowel sounds are absent ▪ Complications include enteritis and fecal impaction Copyright Pass NPLEX 2018 69  HIATAL HERNIA ▪ Part of the stomach herniates through the esophageal hiatus of the diaphragm ▪ Correlated with GERD Sliding ▪ Esophagogastric junction is above the diaphragm Paraesophageal ▪ Esophagogastric junction is below the diaphragm INTUSSUSCEPTION ▪ Bowel obstruction due to the proximal segment of the bowel telescoping into a distal part. ▪ Most commonly occurs in childhood ▪ Nausea, vomiting, abdominal pain ▪ Fatal if not treated within 2-5 days Copyright Pass NPLEX 2018 70  VOLVULUS ▪ Portion of the gastrointestinal tract twists on itself causing an obstruction ▪ Abdominal pain, vomiting, distension, and acute mesenteric ischemia ▪ Occurs commonly in the mid-gut in infants and colon in adults ▪ Chronic constipation and laxative abuse are causes in adults MEGACOLON ▪ Enlargement of the colon ▪ Not due to an obstruction ▪ Hirschsprung’s disease = rare autosomal dominant ▪ Myenteric (Auerbach’s) plexus fails to develop ▪ Medications such as antidiarrheals can inhibit colon movement ▪ Ulcerative colitis or pseudomembranous colitis can result in toxic megacolon ▪ Constipation, abdominal pain, fecaloma, abdominal tympany, fever, bloating ▪ Complications include Chaga’s disease, colonic rupture, death Copyright Pass NPLEX 2018 71  INFLAMMATORY GASTROINTESTINAL DISEASES ▪ Appendicitis ▪ Barrett’s esophagus ▪ Diverticular disease ▪ Peptic ulcer disease ▪ Esophagitis ▪ Acute gastritis ▪ Chronic gastritis ▪ Gastroesophageal reflux disease ▪ Ulcerative colitis ▪ Crohn’s disease APPENDICITIS ▪ Inflammation of the appendix with peritonitis ▪ Due to obstruction of the appendix lumen ▪ Anorexia, nausea, severe abdominal pain (vague then localizes in the right lower quadrant), vomiting, guarding, bowel sounds are absent, fever ▪ Complications include peritoneal inflammation, rupture and death Copyright Pass NPLEX 2018 72  BARRETT’S ESOPHAGUS ▪ Stratified squamous epithelium of the lower esophagus changes to columnar epithelium ▪ Results from chronic influx esophagitis ▪ Heartburn occurs but it can be asymptomatic ▪ Complications include peptic ulceration, esophageal stricture with reflux, and esophageal cancer DIVERTICULAR DISEASE Diverticulosis ▪ Multiple diverticula without inflammation. ▪ May be asymptomatic or vague discomfort can be present Diverticulitis ▪ Inflammation of diverticula ▪ Can lead to perforation, peritonitis, abscess formation, and bowel stenosis ▪ Abdominal pain, diarrhea (can be bloody), and fever Copyright Pass NPLEX 2018 73  PEPTIC ULCER DISEASE ▪ Ulceration/erosion of the stomach or duodenal mucosa ▪ H. pylori infection causes chronic gastritis and weakens the stomach and/or duodenal defenses ▪ Abdominal pain and nausea, melena, abdominal tenderness and guarding over affected area, iron deficiency anemia ▪ Complications include bleeds, perforation, and death ESOPHAGITIS ▪ Esophageal inflammation in the lower portion resulting in GERD ▪ Can damage the myenteric plexus and interfere with peristalsis ▪ Caused by hiatal hernia, incompetent lower esophageal sphincter, pregnancy, and scleroderma. ▪ Chronic GERD can damage the epithelium causing hyperemia and metaplasia ▪ Substernal burning after eating, chest pain, chronic cough, chronic laryngitis ▪ Can lead to Barrett’s esophagus Copyright Pass NPLEX 2018 74  GASTRITIS Acute ▪ Focal damage to the gastric mucosa with inflammation resulting in chronic dyspepsia ▪ Significant increase in gastric acid production which can cause nausea, vomiting, pain, and potentially occult blood. ▪ Causes include smoking, alcohol, NSAIDs, brain injury Chronic Fundal (type A) ▪ Partietal cells are immobilized/destroyed by primary CD4-T cell-mediated autoimmunity (Ab) ▪ Associated with humoral autoantibodies against parietal cells, intrinsic factor, and vitamin B12 ▪ Complications include pernicious anemia, celiac disease, autoimmune thyroiditis, ulcer, gastric carcinoma Antral (type B) ▪ Due to infection with H. pylori ▪ Peptic ulcer, gastric lymphoma, thrombocytopenia purpura GASTROESOPHAGEAL REFLUX DISEASE (GERD) ▪ Reflux of gastric and/or duodenal contents into the esophagus resulting in inflammation of the esophageal mucosa. ▪ Caused by transient abnormal lowering of lower esophageal sphincter (LES) pressure. ▪ Pyrosis, retrosternal pain, worse lying down and after large meals, hypochlorhydria, gradually progressive dysphagia with solids, abdominal pain similar to PUD in the stomach and duodenum. Asthma, worse after eating spicy foods. ▪ Risk factors include smoking, food allergies, hyper- or hypochlorhydria, drugs, hiatal hernia, pregnancy, obesity. Copyright Pass NPLEX 2018 75  ULCERATIVE COLITIS (UC) ▪ Systemic autoimmune disease ▪ Results in continuous inflammatory ulceric lesions ▪ Limited to the mucosa and submucosa of the rectum and descending colon ▪ Pseudopolyps present ▪ Bloody, mucoid diarrhea (can be severe), fatigue, fever, arthralgias ▪ Complications include: ▪ Ankylosing spondylitis, uveitis, arthritis, erythema nodosum, pyroderma gangrenosum, sclerosing cholangitis, colorectal cancer, toxic megacolon, osteoporosis CROHN’S DISEASE ▪ Systemic autoimmune disease involving ulcers and non-caseous granulomas ▪ Skip lesions and transmural inflammation ▪ Lumen narrowing due to wall thickening ▪ Between acute attacks GI and systemic inflammation are present and the disease continues to progress. ▪ Waxing-waning course with episodes of acute GI pain, fatigue, diarrhea, fever, anal fistula, and aphthous stomatitis ▪ Complications include B12 and folate malabsorption, skin lesions, iron deficiency, uveitis, arthritis, autoimmune diseases, adhesions, strictures, obstruction, enteric fistula, osteoporosis, thromboembolism, colorectal cancer, intestinal lymphoma, urolithiasis Copyright Pass NPLEX 2018 76  CONGENITAL GASTROINTESTINAL DISEASES ▪ Esophageal atresia ▪ Esophageal webs & rings ▪ Meckel’s diverticulum ▪ Pyloric stenosis ESOPHAGEAL ATRESIA ▪ Failure of the esophagus to completely form and connect to the stomach resulting in fistulation with the trachea ▪ Drooling, choking, coughing, regurgitation of all food ▪ Aspiration pneumonia can result if there is a tracheoesophageal fistula Copyright Pass NPLEX 2018 77  ESOPHAGEAL WEBS & RINGS ▪ Membrane partially obstructs esophagus forms a mesh across the lumen or an annulus projecting into the lumen. ▪ Chest pain and dysphagia ▪ Congenital = lower 2/3 of the esophagus ▪ Acquired = upper 1/3 of the esophagus ▪ Can result in Plummer-Vinson syndrome, bullous diseases, celiac disease MECKEL’S DIVERTICULUM ▪ Out-pouching of the small intestinal layers generally the ileum due to the vitelline duct failing to degrade after birth ▪ Generally asymptomatic but can cause painless hematochezia before intestinal obstruction, volvulus, and intussusception ▪ Rule of 2s ▪ 2% of the population, 2’ from the ileocecal valve, 2” in length, 2% experience symptoms, 2 yoa is most common time of presentation, male:female = 2:1 Copyright Pass NPLEX 2018 78  PYLORIC STENOSIS ▪ Hypertrophy of the pylorus resulting in constriction or total obstruction of the stomach outlet ▪ Severe and progressive vomiting in a newborn, hunger, dehydration, low urine output, and metabolic alkalosis ▪ Complications include poor weight gain, electrolyte imbalance, and dehydration ABDOMINAL CAVITY CONDITIONS ▪ Ascites ▪ Peritonitis Copyright Pass NPLEX 2018 79  ASCITES ▪ Buildup up fluid within the peritoneal cavity ▪ High serum-ascites albumin gradient (SAAG)/transudative effusions ▪ Due to portal blood pressure pushing fluid out ▪ Normal glucose levels and few WBC ▪ Usually secondary to portal hypertension or liver disease ▪ Can occur with CHF and constrictive pericarditis ▪ Low SAAG/exudative effusions ▪ Due to inflammation or cancer resulting in protein-rich fluid ▪ Low level of glucose and pH, higher WBC levels than high SAAG form ▪ Seen in peritoneal cancer, TB, nephrotic syndrome ▪ Complications include pressure on other organs of the abdomen and infection PERITONITIS ▪ Inflammation of the peritoneum starting with the visceral layer of the peritoneum contacting an infected or inflamed organ ▪ Causes diffuse abdominal pain (visceral peritoneum), localized pain (parietal peritoneum), tenderness on palpation, rebound tenderness, guarding, nausea and vomiting, tachycardia, fever ▪ Severe inflammation causes paralysis of the intestines ▪ Complications include sepsis, shock, peritoneal abscess, and death Copyright Pass NPLEX 2018 80  VASCULAR GASTROINTESTINAL DISEASES ▪ Esophageal varies ▪ Hemorrhoids ▪ Infarction ▪ Vascular ectasias of the colon ESOPHAGEAL VARICES ▪ Dilated sub-mucosal veins in the lower third of the esophagus ▪ Due to portal hypertension most commonly due to cirrhosis. Copyright Pass NPLEX 2018 81  HEMORRHOIDS ▪ Dilated internal and/or external venous plexuses within the anal canal ▪ Often due to straining, pregnancy, low fiber diet ▪ Pain and itching can be present ▪ Can become thrombotic or inflamed and often bleed INFARCTION ▪ Transmural infarctions → ischemic enteritis ▪ Partial infarction ▪ Mucosal = mucosa only ▪ Mural = mucosa + submucosa ▪ Due to partial occlusions of the superior mesenteric artery or its branches due to arteriosclerosis, shock or heart failure Copyright Pass NPLEX 2018 82  VASCULAR ECTASIAS OF THE COLON ▪ Dilated, tortuous vessels that develop in the cecum and ascending colon ▪ Most common cause of lower GI bleeding in people over the age of 60 ▪ Occurs in association with renal failure, cirrhosis, CREST syndrome, and after radiation treatment to the bowel. GASTROINTESTINAL NEOPLASMS ▪ Esophageal cancer ▪ Gastric cancer ▪ Intestinal cancer ▪ Hepatocellular carcinoma ▪ Oral cancer ▪ Pancreatic cancer ▪ Cororectal cancer Copyright Pass NPLEX 2018 83  ESOPHAGEAL CANCER ▪ Primarily squamous cell cancer ▪ Arises from Barrett’s esophagus ▪ Dysphagia, cachexia, hoarseness, weight loss, pain, hematemesis ▪ Tumor can enter the esophageal lumen, trachea, bronchi, or aorta ▪ High mortality GASTRIC CANCER ▪ Adenocarcinoma ▪ Looks like an ulcer and can be found on the edge of an ulcer crater ▪ Diffuse ▪ Stiffened stomach, cancer found throughout the stomach wall ▪ Associated with high animal product intake and low vegetable intake ▪ Intestinal ▪ Discrete mass in the stomach ▪ Associated with high salt, grains, nitrosamines, chronic gastritis ▪ Vague GI upset, weight loss, fatigue, anorexia Copyright Pass NPLEX 2018 84  INTESTINAL CANCER ▪ Very rare ▪ Generally occurs as lymphoma secondary to IBD or chronic celiac disease HEPATOCELLULAR CARCINOMA ▪ Associated with chronic HBV and HCV infections, chronic alcoholism, chronic aflatoxin B consumption ▪ Asymptomatic until the disease has progressed ▪ May see jaundice, ascites, and/or easy bruising ▪ AFP is a common tumor marker Copyright Pass NPLEX 2018 85  ORAL CANCER ▪ Generally squamous cell cancer ▪ Often involves the tongue ▪ Any sore in the mouth that does not heal within 14 days should be consider cancer until proven otherwise Leukoplakia ▪ Irregular white mucosal patch due to hyperkeratosis secondary to chronic irritation ▪ Often benign but can be dysplasia or carcinoma in situ Erythroplakia ▪ Irregular red patches, usually precancerous ▪ Associated with chewing tobacco, smoking, alcohol, HPV PANCREATIC CANCER ▪ Adenocarcinoma that starts in the ductal epithelium in the pancreatic head causing the blockage of the common bile duct ▪ Abdominal pain (radiates to the back), weight loss, anorexia, migratory thrombophlebitis ▪ High mortality rate and often fatal within a year. Copyright Pass NPLEX 2018 86  COLORECTAL CANCER ▪ Common adenocarcinoma of the rectal or colonic epithelium ▪ Starts as a polyp which can cause microscopic bleeding ▪ Left-sided tumors → ring-shaped and can cause obstruction. ▪ Right-sided tumors → large masses that don’t cause obstruction ▪ Complication include GI obstruction, metastasis and death INFECTIOUS GASTROINTESTINAL DISEASES ▪ Dysentery, infectious diarrhea, and food poiso