First Aid GI Physiology Peyer?s Patches Unencapsulated lymphoid tissue found in the lamina propria & submucosa of small intestine Contain M cells that take up antigen Contains B cells that differentiate into plasma cells to secrete IgA Salivary Secretions Source Serous on the sides Mucinous in the middleParotid glands (most serous) Submandibular glands Submaxillary glands Sublingual gland (most mucinous) Functions ?-amylase Hydrolyzes ?-1,4 linkages to yield disaccharides (maltose, maltotriose, and ?-limit dextrans) Low flow rate ? hypotonic High flow rate ? isotonicInactivated by low pH in stomach Bicarbonate Neutralizes oral bacterial acids Maintains dental health Mucins lubricate food Stimulated by? Sympathetic activity ? T1-T3 superior cervical ganglion Parasympathetic activity ? facial and glossopharyngeal nerves Brunner?s Glands Located in duodenal submucosa (the only GI submucosal glands) Secrete alkaline mucus to neutralize acid from the stomach Hypertrophy is seen in peptic ulcer disease Secretory Products Autoimmune destruction of parietal cells causes chronic gastritis and pernicious anemiaIntrinsic Factor Secreted by parietal cells in the stomach Binds Vit B12 to aid absorption in the ileum K + & Cl - H +Gastric Acid Secreted by parietal cells in the stomach Stimulated by histamine, ACh, and gastrin Inhibited by somatostatin, GIP, prostaglandins, and secretin K + H+/K+ ATPase pumps H+ out of the cell and K+ into the cell (K+ gradient is maintained by K+/Cl- cotransporters) Gastrinoma ? gastrin secreting tumor causing continuous ? levels of acid Pepsin Secreted by chief cells in the stomach Stimulated by vagal stimulation and local acid H+ converts pepsinogen ? pepsin Digests proteins Bicarbonate (within mucus) Secreted by mucosal cells in the stomach and duodenum Stimulated by secretin Neutralizes acid and prevents autodigestion Especially phenylalanine and tryptophanHormones Gastrin Secreted by G cells in the stomach antrum Stimulated by stomach distention, amino acids, vagal stimulation Inhibited by stomach pH < 1.5 Action ? gastric H+ secretion ? growth of gastric mucosa ? gastric motility ?? in Zollinger-Ellison syndrome Cholecystokinin (CCK) Secreted by I cells in the duodenum and jejunum Stimulated by fatty acids and amino acids Action ? pancreatic secretions ? gallbladder contraction ? gastric emptying ? CCK in cholelithiasis causes pain that worsens after fatty meals Secretin Secreted by S cells in the duodenum Stimulated by acid, fatty acids Pancreatic enzymes do not function in acidic environmentsAction ? bile and pancreatic HCO3- secretion ? gastric acid secretion Somatostatin Secreted by D cells in the pancreatic islets and GI mucosa Stimulated by acid Inhibited by vagal stimulation Somatostatin stops all secretionsAction ? gastric acid and pepsinogen secretion ? pancreatic and small intestine fluid secretion Nitric Oxide is also found in the gut. Deficiency is implicated in achalasia (? lower esophageal sphincter tone)? gallbladder contraction ? insulin and glucagon release Antigrowth hormone effects Used to treat VIPomas and carcinoid tumors Gastric Inhibitory Peptide (GIP) Secreted by K cells in the duodenum and jejunum Stimulated by fatty acids, amino acids, oral glucose Action Exocrine: ? gastric H+ secretion Endocrine: ? insulin release Vasoactive Intestinal Polypeptide (VIP) Secreted by parasympathetic ganglia in sphincters, gallbladder, and small intestine Stimulated by distention, vagal stimulation Inhibited by adrenergic input Action ? intestinal water and electrolyte secretion ? relaxation of intestinal smooth muscle and sphincters VIPoma ? islet cell tumor that secretes VIP causing copious diarrhea Motilin Secreted by the small intestine (stimulated by fasting state) Action ? produces migrating motor complexes to clean out gut Pancreatic Enzymes ?-amylase ? hydrolyzes starch to oligosaccharides and disaccharides Lipase, phospholipase A, and colipase ? fat digestion Proteases (trypsin, chymotrypsin, elastase, carboxypeptides) ? protein digestion Enterokinase/Enteropeptidase (secreted by duodenal mucosa) converts trypsinogen ? trypsin Trypsin activates other proenzymes and more trypsinogen Carbohydrate Digestion/Absorption Hydrolyzed by salivary and pancreatic amylase ? oligo and disaccharides Oligosaccharide hydrolases Located at brush boarder of intestine Rate limiting step in carbohydrate digestion Produces monosaccharides from oligo- and disaccharides Absorption Monosaccharides (glucose, galactose, fructose) are absorbed by enterocytes Glucose and galactose via SGLT1 (Na+ dependent) Fructose via GLUT-5 facilitated diffusion Transported to blood via GLUT-2 Bile Composition Bile salts ? conjugated bile acids (with glycine or taurine) making them H2O soluble Phospholipids Cholesterol Bilirubin Water and ions Bile salts are actively absorbed in the distal ileum Bile acids (unconjugated) are passively absorbed in the colon Heme Metabolism Carried out in the reticuloendothelial system Heme ? biliverdin ? bilirubin (indirect/unconjugated) Bilirubin binds albumin and is shuttled to the liver Liver conjugates bilirubin with glucuronic acid to make it water soluble Direct/Conjugated bilirubin is excreted in bile GI bacteria convert bilirubin ? urobilinogen Urobilinogen is excreted in feces as stercobilin (gives stools their dark color) Urobilinogen is reabsorbed into enterohepatic circulation and excreted in the urine Pathology Esophageal Pathologies Achalasia Scleroderma (CREST syndrome) is associated with esophageal dysmotility involving low pressure proximal to the LESConstant contraction of lower esophageal sphincter due to loss of myenteric (Auerbach?s) plexus Symptoms Progressive dysphagia Dilated esophagus with distal stenosis on barium swallow (?birds beak?) ? Risk of esophageal carcinoma Mallory-Weiss Syndrome Painful mucosal lacerations at the gastroesophageal junction due to severe vomiting (presents with hematemesis) Seen in alcoholics and bulimics Boerhaave Syndrome ? transmural esophageal rupture due to violent retching Esphageal Stricture ? associated with lye ingestion Esophagitis Reflux Infection (HSV-1, CMV, Candida) Chemical ingestion Plummer-Vinson Syndrome Dysphagia (due to esophageal webs) Glossitis Iron deficiency anemia Barrett?s Esophagus BARRett?s ? B ecomes A denocarcinoma , R esults from R efluxGlandular metaplasia (replacement of nonkeratinized stratified squamous epithelium with intestinal columnar epithelium in the distal esophagus) Due to chronic acid reflux (GERD) ? Risk for adenocarcinoma Esophageal Cancer Squamous Cell Most common world wide Affects upper and middle 1/3 of esophagus Highly associated with achalasia, alcohol, smoking Adenocarcinoma Tied for most common in the Affects lower 1/3 of esophagus Highly associated with Barrett?s esophagus Tracheoesophageal Fistula Abnormal connection between the esophagus and trachea Most often ? blind upper esophagus with lower esophagus connected to the trachea Presentation Cyanosis Choking and vomiting with feeding Air bubble on chest x-ray Polyhydramnios (too much amniotic fluid) Congenital Pyloric Stenosis Hypertrophy of the pyloris causing obstruction Presentation Palpable ?olive? mass in epigastric region Nonbilious (no bile) projectile vomiting at ~ 2 wks old Treatment ? surgical incision Malabsorption Syndromes Celiac Sprue Autoantibodies against gluten (gliadin) in wheat Microscopic appearance ? flattening of intestinal villi and inflammation Affects the proximal small bowel (jejunum) Associated with dermatitis herpetiformis (chronic itchy rash of papules and vesicles on pressure points) ? Risk of malignancy (T-cell lymphoma) Screen for with serum transglutaminase Tropical Sprue Infectious cause (responds to antibiotics) Microscopic appearance ? flattening of intestinal villi and inflammation Affects entire small bowel Whipple?s Disease Caused by Tropheryma whippelii (gram positive bacteria) infection Microscopic presentation ? PAS-positive macrophages in lamina propria and mesenteric nodes Affects older males Associated with arthralgias, cardiac, and neurologic symptoms Bacterial lactose fermentation results in H + and short chain fatty acid productionDisaccharide Deficiency Lactase deficiency is most common Presents with osmotic diarrhea, gas, ? breath hydrogen Villi appear normal Pancreatic Insufficiency Etiology Cystic fibrosis Obstructing cancer Chronic pancreatitis Causes fat and protein malabsorption Gastritis Acute (erosive) Disruption of the mucosal barrier leading to inflammation Etiology Stress NSAIDs Alcohol Uricemia Burns Brain injury Chronic (nonerosive) Type A (within fundus/body of stomach) Autoimmune disorder against parietal cells Causes pernicious anemia and achlorhydria Type B (within antrum of stomach) Caused by H. pylori infection ? Risk of MALT lymphoma Ménétrier?s Disease ? Precancerous gastric hypertrophy with protein loss, parietal cell atrophy and ? mucous cells Stomach Cancer (Adenocarcinoma) Risk Factors Dietary nitrosamines (smoked foods) Achlohydria Chronic gastritis Type A blood Microscopic appearance ? signet ring cells Linitis Plastica = diffusely infiltrative (?leather bottle?) adenocarcinoma May cause acanthosis nigricans (velvety hyperpigmentation of skin folds) Metastasizes early and aggressively Virchow?s Node ? involvement of left supraclavicular node by metastases from the stomach Krukenberg?s Tumor ? bilateral metastases to the ovaries (abundant mucus + signet ring cells) Peptic Ulcer Disease Gastric Ulcer Caused by ? mucosal protection against gastric acid Ulcer margins are usually clean (unlike margins of carcinoma)70% due to H. pylori infection (chronic NSAID use is also implicated) Often occurs in older pts Pain ? with meals (leads to weight loss) Duodenal Ulcer Caused by ? gastric acid secretion or ? mucosal protection 100% due to H. pylori infection Pain ? with meals (leads to weight gain) Hypertrophy of Brunner?s glands (alkaline mucus secreting submucosal glands of the duodenum) Inflammatory Bowel Disease Crohn?s Disease Ulcerative Colitis Possible Etiology Post infectious (? activity of NF-?B so less cytokine production) Autoimmune Location Entire GI tract (especially terminal ileum) Skip lesions and rectal sparing with rectal involvement Continuous lesions Gross Morphology Transmural inflammation, cobblestone mucosa, creeping fat, linear ulcers, fissures Mucosal & submucosal inflammation, pseudopolyps Imaging ?String sign? on barium swallow x-ray ?Lead pipe? Microscopic Morphology Noncaseating granulomas and lymphoid aggregates Crypt abscesses & ulcers, bleeding Complications Strictures, fistulas, perianal disease, malabsorption Stenosis, toxic megacolon, colorectal carcinoma Intestinal Manifestations Diarrhea (± blood) Bloody diarrhea Extraintestinal Manifestations Migratory polyarthritis, erythema nodosum, ankylosing spondylitis, uvetitis, immunologic disorders Pyoderma gangrenosum, 1° sclerosing cholangitis Treatment Corticosteroids Sulfasalazine Mneumonic Creepy fat crone granny skipping down a cobblestone road away from the wreck (rectal skipping) Ulcerative colitis runs up continuously
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