Exam 4 Study Guide - Gastrointestinal Physiology PDF

Exam 4 Study Guide GASTROINTESTINAL PHYSIOLOGY Anatomy of the GI system – NOT ON STUDY GUIDE Digestive system – enteric nervous system (extrinsic and intrinsic) Autonomic (involuntary) and hormonal control [except chewing, swallowing, defecation] ▪Vagus nerve o Ingested substances trigger hormones t...

Exam 4 Study Guide GASTROINTESTINAL PHYSIOLOGY Anatomy of the GI system – NOT ON STUDY GUIDE Digestive system – enteric nervous system (extrinsic and intrinsic) Autonomic (involuntary) and hormonal control [except chewing, swallowing, defecation] ▪Vagus nerve o Ingested substances trigger hormones that stimulate or inhibit ▪Muscular contractions – GI motility; timely secretion of substances that aid in digestion o Located near the areas that they innervate and control o Mouth o Reservoir for chewing and mixing of food with saliva o Taste buds (chemoreceptors) and olfactory nerves are stimulated – initiates salivation and secretion of gastric juices in the stomach Salivary glands o Submandibular, sublingual, parotid (largest; secretes saliva) o Saliva is composed of water with mucus, sodium, chloride, bicarbonate, potassium and salivary a-amylase (carb digestion) and is controlled by ANS ▪Cholinergic parasympathetic fibers stimulate salivary glands Ex: anticholinergic meds inhibit salivation ▪Sympathetic beta-adrenergic stimulation decreases salivary secretion – none, little, or little with rich protein content ▪A pH of 7.4 which neutralizes bacterial acids aiding to prevent injection ▪Contains IgA – prevents orally ingested microorganisms Esophagus o Conducts substances from oropharynx to stomach o Upper esophageal sphincter prevents entry of air into the esophagus during respiration o Lower esophageal sphincter (cardiac sphincter) prevents regurgitation from the stomach Increase tone by cholinergic vagal stimulation and the digestive hormone gastrin Decrease tone/relax by non-adrenergic, non-cholinergic vagal impulse and the hormones progesterone, secretin, and glucagon o o Vagus nerve allows relaxation of esophagus during swallowing Swallowing: complex event mediated by the swallowing center in reticular formation of brainstem Phases: oropharyngeal (voluntary) and esophageal (involuntary) Must coordinate with respiratory center Respiration is inhibited – epiglottis slides downward to prevent food from entering larynx and trachea o Peristalsis: Primary: immediately follows oropharyngeal phase of swallowing Secondary: bolus of food becomes stuck – wave of contraction and relaxation occurs that is independent of voluntary swallowing Stomach o Hollow muscular organ – stores food, secretes digestive juices, mixes food with juices – propels chyme into duodenum o Muscle layers – outer (longitudinal), middle (circular), inner (oblique) o Sphincters – lower esophageal (chyme enters from esophagus into stomach), pyloric (chyme exits stomach into duodenum of small intestine o Functional portions – upper (fundus), middle (body), lower (antrum) o Blood supply via branch of celiac artery; drainage via splenic vein and tributaries o Few substances absorbed in stomach – can absorb alcohol, aspirin, NSAIDS o Innervated by sympathetic and parasympathetic o Gastric motility Swallowing causes fundus to relax Gastrin and cholecystokinin enhance relaxation of stomach Gastrin and motilin and low blood glucose enhance peristalsis Sympathetic activity, secretin, cholecystokinin inhibit peristalsis Vagus nerve (parasympathetic) stimulates gastric secretion and motility Gastric mixing enhanced by retropulsion Gastric emptying   Increased by larger volumes of food Delayed by solids, fats, and non-isotonic solutions - Fat – cholecystokinin – inhibits intake, gastric motility, decreases gastric emptying so that fats do not exceed rate of bile and enzyme secretion Basics of gastric secretion; what cells secrete what -Composition of gastric juice depends on volume and flow rate -Potassium levels higher in gastric secretions than in plasma – important in vomiting, suctioning, etc. -Rate of secretion varies with time of day – lower in AM, higher in PM -Products: mucus (protective), HCl acid, enzymes (pepsinogen), hormones (gastrin), intrinsic factor (vit B12), gastroferrin (iron absorption) - empty into gastric pits o Gastric hydrochloric acid ▪Secreted by parietal cells of the stomach ▪Dissolves food fibers ▪Acts as bactericidal agent ▪Converts pepsinogen to pepsin ▪Stimulated by: acetylcholine via vagus nerve, caffeine, calcium, gastrin, histamine ▪Inhibited by: prostaglandins (mucus), gastric inhibitory peptide, somatostatin, secretin o Pepsin ▪Breaks down protein-forming polypeptides in the stomach ▪Strongest stimulation: acetylcholine via vagal stimulation ▪Inactivation: alkaline environment of duodenum – needs HCl to be converted from pepsinogen o Mucus Prostaglandins and nitric oxide: protect the mucosal barrier by stimulation of mucous and bicarbonate to inhibit acids Protect against aspirin, NSAIDS, H. Pylori, ethanol, regurgitated bile, and ischemia to prevent inflammation and ulceration o Intrinsic factor (IF) Required for absorption of vitamin B12 in the ileum – combines with vit B12 in the stomach Gastritis and failure of absorption mechanisms of vit B12 can lead to pernicious anemia o Gastric glands: primary secretory units ▪Parietal cells: HCl acid and intrinsic factor, gastroferrin ▪Chief cells: pepsinogen – pepsin ▪G cells: gastrin (hormone) ▪Enterochromaffin-like cells: histamine ▪D cells: somatostatin Phases of gastric secretion: o Celiac phase (mouth) ▪Begins with smelling, seeing, tasting, chewing, swallowing ▪Mediated by vagus nerve ▪Acid, pepsinogen, gastrin secreted ▪Insulin secreted by pancreas to hyperglycemia and is strong stimulus to gastric secretion o Gastric phase (stomach) ▪Begins with arrival of food to stomach ▪2 major stimuli to secretory effect – distension of stomach and presence of digested protein   Vagus nerve stimulated by distention – contributes to secretion stimulus Mediated by acetylcholine and can be blocked by atropine o Intestinal phase ▪Begins with movement of chyme from stomach to duodenum ▪Decelerated gastric secretion – when chyme enters alkaline environment of duodenum – inhibitory vagal reflexes decrease gastric motility ▪Secretin and cholecystokinin stimulate pancreatic secretions and inhibit gastric secretions Basic function of small intestine, and large intestine Small intestine o Three segments: -Duodenum: begins at pylorus and ends where it joins the jejunum called the Treitz ligament -Jejunum -Ileum: ilecocecal valve controls the flow of digested material from the ileum into the large intestine and prevents reflux into the small intestine o Peritoneum: serous membrane surrounding the organs of the abdomen and pelvic cavity ▪Visceral: lies over the organs ▪Parietal: lines the wall of the abdominal cavity ▪Peritonitis: inflammation of the peritoneum – occurs with perforation of the intestine or after surgery ▪Peritoneal Cavity: space between the two layers of the peritoneum o Muscle layers: outer longitudinal and inner circular ▪Mucosal folds (plica): within the small intestine slow the passage of food providing more time for digestion and absorption More numerous in the jejunum and upper ileum o Blood flow provided by superior mesenteric artery o Myenteric plexus and mucosal plexus: site of intrinsic motor innervation mediation -Parasympathetic: secretion, motility, pain sensation, intestinal reflexes -Sympathetic: inhibits motility and produces vasoconstriction o Villi: cover the mucosal folds and are the functional units of the intestine ▪Where absorption occurs – villi and microvilli increase surface area for absorption ▪Secretes enzymes necessary for digestion and absorbs nutrients ▪Composed of absorptive columnar cells (enterocytes) and mucus secreting goblet cells of mucosal epithelium – contain microvilli ▪Water and electrolytes absorbed through intracellular spaces called tight junctions ▪Entire epithelial population of cells is replaced every 4-7 days -Suppress cell division and shorten villi: starvation, vit B12 deficiency, cytotoxic drugs, irradiation –> leads to diarrhea and malnutrition -Stimulate cell production: nutrient intake and intestinal resection Large intestine o Massages fecal mass; absorbs water and electrolytes o Parts: ▪Cecum: pouch that receives chyme from the ileum ▪Appendix: attached to the cecum ▪Colon: ascending, transverse, descending, sigmoid ▪Rectum and anus o Mucous secreting cells (goblet cells) in the mucosa but NO VILLI o Valves and sphincters: ▪Ileocecal valve: admits chyme from ileum to cecum ▪O’Beirne sphincter: controls movement of wastes from the sigmoid colon into the rectum ▪Internal anal sphincter: smooth muscle ▪External anal sphincter: striated skeletal muscle Basics of digestion and absorption; what happens where Mouth o Breaks down food, mixes with saliva – initiates digestive process with salivary amylase Esophageal sphincters o Upper sphincter prevents air from entering stomach o LES (cardiac sphincter) prevents regurgitation of food mass into esophagus Stomach o Secretes pepsinogen, gastrin, and HCl acid that mix with food to form chyme ▪Parietal cells secrete acid – pump H+ into stomach in exchange for K+ Stimulated by gastrin, histamine, acetylcholine; inhibited by somatostatin, prostaglandins, secretin, vasoactive intestinal peptide ▪Mucous cells secrete mucosal protective layer – secretion mediated by prostaglandins o Intrinsic factor secreted to absorb vitamin B12 in the small intestine o Nu nutrients are absorbed – only alcohol, aspirin, NSAIDS... Small intestine o Duodenum receives chyme from the stomach through the pyloric valve -Absorbs vitamins, minerals, fats and sugars o Chyme stimulates liver and gallbladder to deliver bile and the pancreas to deliver digestive enzymes and alkaline secretions -Bile and enzymes flow through opening guarded by sphincter of Oddi o Jejunum absorbs carbs and proteins across intestinal mucosa by active transport into the villus capillaries o Ileum absorbs bile salts, vitamin B12, and chloride o All nutrients are absorbed in the small intestines as well as 85% of the water and fluid intake Colon o Cecum pouch connects the large intestine to the small intestine which is where the appendix is o Serves as a reservoir for fecal mass and absorbs water and electrolytes – no nutrient absorption o Feces (excrement) enters sigmoid colon – consists of food residue, unabsorbed GI secretions, shed epithelial cells, bacteria ▪Defecation reflex (retrosphincteric reflex): rectal wall stretches and tonically constricted internal anal sphincter relaxes creating urge to defecate – can be voluntarily overridden Nutrients and absorption: o Carbohydrates digested into monosaccharaides and disaccharides ▪Salivary and pancreatic amylases break down starches ▪Sugars are primary absorbed in the duodenum and in the upper jejunum ▪Glucose transporter 2 (GLUT2) facilitates transfer from cytosol to bloodstream – secondary active cotransport with sodium (Na/K-ATPase pump) ▪Humans lack enzymes to digest cellulose o Proteins digested into amino acids and peptides ▪Pancreatic enzymes accomplish major protein hydrolysis in small intestine -Trypsin and chymotrypsin: hydrolyze the bonds of large molecules (endopeptidase) -Carboxypeptidase: breaks away the end amino acids (exopeptidase) ▪Sodium dependent carrier actively transports amino acids from cytosol to bloodstream ▪Free amino acids can be absorbed directed from the intestinal lumen using membrane transport protein – secondary active cotransport with sodium (Na/K-ATPase pump) o Fats digested into fatty acids and monoglycerides ▪1. Emulsification: emulsifying agents cover the small fat particles and prevent them from re- forming into fat droplets Ready for lipolysis – lipase breaks down triglycerides; phospholipase cleaves fatty acids from phospholipids; cholesterol esterase breaks cholesterol esters ▪2. Micelle formation: fatty acids and monoglycerides must be made water soluble to be absorbed – micelles ▪3. Fat absorption – passive via simple diffusion ▪4. Resynthesized triglycerides and phospholipids: absorbed as chylomicrons and eventually enter systemic circulation Excess bind with apoproteins and transfer to systemic circulation o Minerals and vitamins ▪Most minerals absorbed by passive diffusion or active transport – with carrier protein ▪Most water-soluble vitamins are passively absorbed or by sodium-dependent active transport Intestinal motility: o Peristalsis – contractions of circular muscles (segmentation) mixes chyme and promotes digestion o Ileogastric reflex inhibits gastric motility when the ileum is distended o Intestinointestinal reflex inhibits intestinal motility when one intestinal segment is overdistended o Gastroileal reflex increases intestinal motility when gastric motility increases -Three reflexes prevent overloading, backup – keep things moving forward Basic functions of accessory organs; liver, gallbladder, exocrine pancreas Liver o Structure:         Largest solid organ in the body; right (larger) and left lobes Glisson capsule – fibroelastic capsule - contains blood vessels, lymphatics, nerves Requires large amount of blood – receives from hepatic artery (oxygenated) and hepatic portal vein (deoxygenated) [70% of supply] Hepatocytes are the functional cells of the liver Synthesize 700-1200 mL of bile per day and secrete into bile canaliculi – small channels between hepatocytes that can drain bile into the common bile duct and then into the duodenum through sphincter of Oddi Lipocytes are star shaped cells that store lipids including vitamin A Kupffer cells (mononuclear phagocyte system) are phagocytic cells - central to innate immunity Stellate cells contain retinoids (vitamin A) - are contractile in liver injury, regulate sinusoidal blood flow, may proliferate into myofibroblasts, participate in liver fibrosis, remove foreign substances from the blood and trap bacteria Pit cells are natural killer cells - important in tumor defense o Function: ▪Enterohepatic circulation – choleresis -Recycling of bile salts -Choleretic agent: substance that stimulates the liver to secrete bile -High concentration of bile salts is a strong stimulus – as well as secretin, cholecystokinin, and vagal stimulation ▪Formation of bilirubin – see below ▪Vascular and hematologic functions -Stores blood, removes bacterial and foreign particles, synthesizes clotting factors ▪Metabolizes fats Bile absorbs fat-soluble vitamins; hydrolyzed triglycerides produce ATP or are secreted into blood stream bound to proteins (lipoproteins) ▪Synthesizes phospholipids and cholesterol ▪Metabolizes proteins Deamination: the removal of ammonia (converted to urea and secreted in urine) converts amino acids into carbohydrates ▪Metabolizes carbohydrates -Liver releases glucose during hypoglycemia; takes up glucose during hyperglycemia; stores glucose as glycogen (glyconeogenesis) or converts it to fat -When all glycogen stores are used, amino acids and glycerol are converted to glucose ▪Metabolic detoxification Biotransformation – makes toxic substances less harmful ▪Storage of minerals and vitamins – release as needed ▪Produces bile to absorb fat-soluble vitamins Vitamin K – essential for synthesis of clotting factors; absorption depends on adequate bile production – impairment results in decreased clotting factors and risk of bleeding Gallbladder o Structure: saclike organ that lies on the inferior surface of the liver o Function: to store and concentrate bile between meals ▪Holds 90 mL – ejected when food enters duodenum through sphincter of Oddi ▪Cholecystokinin: hormonal regulation of gallbladder contraction ▪Vasoactive intestinal peptide, pancreatic peptide, and sympathetic nerve stimulation relax the gallbladder Exocrine pancreas o Structure: ▪Head is tucked into the curve of the duodenum; tail touches the spleen; body lies behind stomach ▪Composed of acini and networks of ducts that secrete enzymes and alkaline fluids to assist in digestion (release of bicarb aids in duodenal absorption) ▪Pancreatic duct aka Wirsung duct o Function: secretion of enzymes ▪Trypsinogen, chymotrypsin, and procarboxypeptidase Inactivates proteases; is activated by enterokinase ▪Trypsin inhibitor Prevents the pancreas from eating itself ▪Pancreatic enzymes    Pancreatic a-amylase digests carbohydrates Pancreatic lipase digests fat Pancreatic protease digests protein Basic function of bile Produced by the liver (hepatocytes) and is necessary for the fat digestion and absorption o Contains bile salts, cholesterol, bilirubin, electrolytes, and water o Primary bile acids are synthesized from cholesterol by the hepatocytes and are required for intestinal emulsification and absorption of fats – conjugated to form bile salts o Bile salts are conjugated bile acids that are required for the emulsification and absorption of fats o Secondary bile acids are the product of bile salts deconjugation by bacteria in the intestine   Secreted when there is the presence of chyme in the small intestine into the bile canaliculi Bile's alkalinity helps neutralize chyme – creates pH that enables the pancreatic enzymes to digest proteins, carbohydrates, and sugars Basics of bilirubin By-product of the destruction of aged red blood cells in the liver and spleen o Macrophages in liver and spleen break down RBC’s - Kupffer cells separate hemoglobin – heme is converted into iron and stored in liver – by-product is converted to bilirubin ▪Unconjugated bilirubin is lipid soluble and can cross cell membrane – present in the circulation bound to plasma protein ▪Conjugated bilirubin is combined with sugar to make it water soluble so it can be excreted via bile ▪Urobilinogen is in the ileum and colon – is deconjugated by bacteria and then converted to be excreted via feces (gives brown color) o Gives bile a greenish black color and produces yellow tinge of jaundice Labs measure total bilirubin o Higher % unconjugated = heme breaking down, inability of liver to conjugate ▪Ex: missing enzyme (congenital), hemolytic anemia o Higher % conjugated bilirubin = problem with secretion into bile ▪Ex: biliary obstruction, hepatitis PATHOPHYSIOLOGY Anorexia, vomiting, diarrhea, constipation basics Anorexia o Lack of a desire to eat despite physiologic stimuli that would normally produce hunger o Nonspecific symptom that is often associated with nausea, abdominal pain, diarrhea, and psychologic distress Nausea o A subjective experience – common associated symptoms include hypersalivation and tachycardia Vomiting oThe forceful emptying of the stomach and intestinal contents through the mouth oVomiting center: medulla oblongata – stimulated by several types of stimuli -Brain stimulation of receptors in the chemoreceptor trigger zone of the area in the fourth ventricle and vestibular center via 8th cranial nerve (dizziness/vertigo) leads to vomiting oMetabolic consequences of vomiting are fluid, electrolyte, and acid-base balance disturbances -Hyponatremia, hypokalemia, hypochloremia, and metabolic alkalosis oRetching is nonproductive vomiting oProjectile vomiting is spontaneous vomiting that does not follow nausea or retching -Caused by direct stimulation of the vomiting center by neurologic lesions – increased ICP, tumors, brain stem aneurysms – neuro problems Constipation o Infrequent or difficult defecation o Patho: ▪Normal transit (functional) constipation: normal rate of stool passage but difficult evacuation from low-residue, low-fluid diet – need to increase fiber and water intake ▪Slow-transit constipation: impaired colonic motor activity with infrequent bowel movements and straining ▪Pelvic floor dysfunction (pelvic floor dyssynergia or animus): failure of the pelvic floor muscles or anal sphincter to relax with defecation ▪Secondary: from an actual disease process, condition, or meds o Clinical manifestations: Two of the following for at least 3 months -Straining with defecation 25% of the time; lumpy or hard stools at least 25% of the time; sensation of incomplete emptying 25% of the time; manual maneuvers to facilitate stool evacuation at least 25% of the time; fewer than 3 bowel movements per week o Fecal impaction: hard, dry stool retained in rectum Diarrhea o Increased frequency of bowel movements – increased volume, fluidity, weight of feces o Often a protective mechanism – can be acute or chronic o Large-volume diarrhea: volume of feces is increased – caused by excessive amounts of water or secretions or both in intestines o Small-volume diarrhea: volume of feces is not increased – result of increased intestinal motility o Systemic effects are dehydration, electrolyte imbalance, metabolic acidosis, and weight loss o Steatorrhea (fat in stools) and diarrhea are common signs of malabsorption syndromes o Types: ▪Osmotic   Nonabsorbable substance in the intestine draws water into the lumen by osmosis causing large volume diarrhea Ex: lactose deficiency, magnesium sulfate, magnesium phosphate ▪Secretory   Form of large volume diarrhea caused by excessive mucosal secretion of chloride or bicarbonate-rich fluid or the inhibition of net sodium absorption Ex: bacterial enterotoxins – E. coli, neoplasms ▪Motility   Excessive motility decreases transit time, mucosal surface contact, and opportunities for fluid absorption Ex: resection of small intestine, short bowel syndrome, abnormal fistula o Systemic manifestations ▪Acute bacterial or viral infection – fever with or without cramping pain ▪Inflammatory bowel disease – fever, cramping pain, bloody stools ▪Malabsorption syndromes – steatorrhea and diarrhea Fecal characteristics o Shape: narrow or ribbon like may reflect obstruction in lower GI tract o Bloody stools: lower GI bleed, inflammatory bowel disease, bacterial infection o Black, tarry: upper GI bleed, Pepto Bismol intake, increased iron intake o Blood with stool: lower GI problem, hemorrhoids, cancer, ruptured diverticulum o Clay-colored: gallbladder or liver disease (decrease in conjugated bilirubin) o Frothy, fatty (steatorrhea): problems with fat digestion, children with CF, adults with pancreatic disease or cholecystitis – indicates loss of bile (necessary for fat digestion) ABD pain, basic patho, types Patho: from stretching, inflammation or ischemia o Biochemical mediators of the inflammatory response: histamine, bradykinin, serotonin – stimulate pain nerve endings producing abdominal pain Types: o Parietal (somatic pain): in the peritoneum ▪Localized, intense o Visceral pain: in the organs themselves ▪Poorly localized, diffuse, vague o Referred pain: felt in another area, usually the back ▪Is visceral pain intensified – share afferent nerve pathway ▪Due to distant inflammation, ischemia Locations o RUQ: liver, gallbladder, bile duct o RLQ: appendix, right ovary/fallopian tube o LUQ: stomach, gastroesophageal junction, spleen o LLQ: desc. colon (diverticular site),left ovary/fallopian tube o Bilateral posterior: kidneys/ureters; bilateral anterior: ovaries o Midline posterior: aorta; upper midline posterior: pancreas, aorta o Lower midline anterior: uterus, bladder Dysphagia Difficulty swallowing  Types: o Mechanical obstruction of the esophagus ▪Intrinsic: in wall of the esophageal lumen (tumors, strictures, diverticular herniations ▪Extrinsic: outside esophageal lumen and narrow esophagus by pressing inward (tumors) o Functional disorder that impairs esophageal motility ▪Caused by neuronal or muscular disorders that interfere with voluntary swallowing or peristalsis – CVA, Parkinson’s *Clinical manifestations: depends on location o Distention and spasm cause stabbing pain at level of obstruction o Upper obstruction: discomfort 2-4 seconds after swallowing o Lower obstruction: discomfort 10-15 seconds after swallowing o Tumor: begins with difficulty swallowing solids and leads to difficulty swallowing liquids o Neuromotor function loss: difficulty beginning with both solids and liquids o All types: retrosternal pain, regurgitation of undigested food, unpleasant taste, vomiting, and weight loss – complication: aspiration pneumonia GERD     Acid and pepsin refluxes from the stomach into the esophagus causing esophagitis Resting tone of the lower sphincter tends to be lower than normal from transient relaxation or weakness Conditions that increase abdominal pressure can contribute – vomiting, coughing, lifting, bending, obesity Risk factors: obesity, H. Pylori Types: o Physiologic reflux: does not cause symptoms -LES relaxes and regurgitation of gastric contents into esophagus – acid is neutralized and cleared by peristaltic action in esophagus in 1-3 minutes and LES tone is restored o Nonerosive reflux (NERD): symptoms of reflux disease but no visible mucosal injury o Reflux esophagitis: combination of factors causes injury and inflammation Clinical manifestations: o Heartburn, regurgitation of acidic chyme, and upper abdominal pain within 1 hour of eating o S/Sx worsen if person lies down or if intra-abd pressure increases (vomiting, coughing) Association with GERD and: laryngitis, asthma, chronic cough Gastritis Inflammatory disorder of the gastric mucosa -Acute o Associated with H.Pylori, NSAIDS, drugs, chemicals o Clinical manifestations: vague abdominal discomfort, epigastric tenderness, bleeding -Chronic o Fundal (upper) gastritis ▪Immune, type A ▪Autoantibodies to parietal cells and intrinsic factor – gastric atrophy and pernicious anemia o Antral (lower) gastritis ▪Nonimmune, type B ▪Associated with H.Pylori and NSAIDS o Clinical manifestations: vague symptoms – anorexia, fullness, N/V, epigastric pain, bleeding o Increased risk for gastric carcinoma with chronic H.Pylori infection PUD; duodenal and gastric ulcers, stress ulcer   A break or ulceration in the protective mucosal lining of the lower esophagus, stomach, or duodenum Patho: o Decreased mucosal protection -NSAID use (block prostaglandins – mucous), stress ulcers, tobacco and alcohol use o Increased acid production -Zollinger-Ellison syndrome-gastronoma – increases gastrin which increases acid secretion o Superficial -“Erosions” – erode the mucosa but do not penetrate the muscularis mucosae o Deep -True ulcers extend through muscularis mucosae and damage blood vessels causing hemorrhage or perforate the GI wall Duodenal ulcers o Most common of the PUD’s - tend to develop in younger people - *H.Pylori infection o All cause acid and pepsin concentrations in the duodenum to penetrate eh mucosal barrier and lead to ulceration o Clinical manifestations: -Chronic intermittent pain in epigastric area – pain begins 30 mins-2 hrs after eating when stomach is empty – can occur in during the night, disappear by morning -Relieved by ingestion of food or antacids - “pain-food-relief" pattern Gastric ulcers o Tend to develop in the antral region of the stomach adjacent to acid-secreting mucosa of the body o Frequently caused by H.Pylori - primary defect is an increased mucosal permeability to hydrogen ions – gastric secretion tends to be normal or less than normal o Clinical manifestations: -Similar to duodenal – pain-food-relief pattern is common – pain also occurs immediately after eating - tends to be chronic rather than intermittent -Causes more anorexia, vomiting, and weight loss than duodenal ulcers Stress ulcers o Related to severe illness, neural injury, positive pressure ventilation, shock, or systemic trauma o Types: -Ischemic: within hours of trauma, hemorrhage, sepsis, burns (curling ulcers) -Cushing: as a result of head/brain injury – decreased mucosal blood flow and hypersecretion of acid caused by overstimulation of the vagal nerve o Primary clinical manifestation: bleeding Pyloric obstruction    “Gastric outlet obstruction” - the blocking or narrowing of the opening between the stomach and duodenum Acquired or congenital Clinical manifestations: -Epigastric pain and fullness, nausea -Succession splash: sloshing sound in abdomen -At this stage vomiting is cardinal sign – copious and occurs several hours after eating – contains undigested food but no bile -With prolonged obstruction – malnutrition, dehydration, electrolyte abnormalities, extreme debilitation Dumping syndrome -Rapid emptying of chyme from a surgically created residual stomach into the small intestine -Clinical complication of partial gastrectomy or pyloroplasty surgeries -Developmental factors of early dumping syndrome: o Loss of gastric capacity, emptying control, and feedback control by the duodenum when it’s removed o Plasma volume decreases – vasomotor responses – tachycardia, hypotension, weakness, pallor, diaphoresis, dizziness – rapid distention of the intestine produces feeling of epigastric fulness, cramping, N/V/D -Late dumping syndrome: less common o Occurs 1-3 hours after eating o Symptoms: weakness, diaphoresis, confusion GI bleeding, upper and lower, hematemesis, hematochezia, melena, occult bleeding Upper GI bleeding o Esophagus, stomach, or duodenum – causes: bleeding peptic ulcers o Frank, bright red blood in emesis (hematemesis) or digested blood (“coffee-grounds”) o Melena: dark, tarry stools Lower GI bleeding o Below ligament of Treitz, jejunum, ileum, colon, rectum – causes: polyps, diverticulosis, cancer, hemorrhoids o Hematochezia: bright red or burgundy blood from rectum o Occult bleeding: slow, nonobvious blood loss that results in iron-deficiency anemia Physiologic response: depends on amount and rate of blood loss o Accumulation of blood in intestinal tract leads to irritation – increased peristalsis – diarrhea o BUN will increase if blood as been digested – breakdown of RBC’s - proteins increase serum urea o Hbg/hct are not good indicators of immediate blood loss Maldigestion vs. Malabsorption   Interfere with nutrient absorption Maldigestion: failure of the chemical processes of digestion  Malabsorption: failure of the intestinal mucosa to absorb (transport) the digested nutrients o Common causes: bile salt deficiencies, enzyme deficiencies, bacterial infections, disruption of mucosal lining, disturbed lymphatic and vascular circulation, loss of gastric or intestinal surface area Examples: o Celiac disease: inborn error of metabolism affects absorption of glutens (wheat, barley, rye, oats) o Pancreatic insufficiency: insufficient enzyme production – lipase, amylase, trypsin, chymotrypsin -Causes: pancreatitis, pancreatic carcinoma, pancreatic resection and CF -Leads to fat maldigestion – fatty stools (steatorrhea), weight loss o Lactase deficiency: congenital defect in lactase gene – inability to breakdown lactose – fermentation of lactose by bacteria, causing gas (cramping pain, flatulence) and osmotic diarrhea o Bile salt deficiency: conjugated bile salts are needed to emulsify and absorb fats and are synthesized from cholesterol in the liver – result of liver disease and bile obstructions -Poor intestinal absorption causes fatty stools, diarrhea, loss of fat-soluble vitamins     Vitamin A – night blindness Vitamin D – decreased calcium absorption, bone pain, osteoporosis, fractures Vitamin K – prolonged PT time, purpura, petechiae Vitamin E – testicular atrophy, neuro defects in children Ileus types and basic patho and findings Ileus: obstruction of the intestines – more common in small intestine (narrower) o Acute: mechanical causes; chronic/partial: tumors, inflammatory disorders (large intestine) Small intestine obstruction: o Colicky pains caused by intestinal distention followed by nausea and vomiting Large intestine obstruction: o Hypogastric pain and abdominal distention -Ex: colon cancer, diverticular strictures, twisting o Consequences related to the competence of the ileocecal valve o Ischemia occurs when intraluminal pressure exceeds capillary pressure in the lumen o Ogilvie syndrome: acute colonic pseudo-obstruction – massive dilation of large bowel that occurs in critically ill patients and immobilized older adults – characterized by dilation of the cecum and absence of mechanical obstruction  Obstruction leads to accumulation of fluid and gas inside lumen proximal to obstruction – impair water and electrolyte absorption and enhanced secretion with net movement of fluid from vascular space into intestinal lumen – distention – decreased ability to absorb water and electrolytes – increases net secretion of gastric juice, bile, pancreatic juice and intestinal secretions  Location and type of vomit: o Pyloric: early, profuse vomiting of clear, gastric fluid o Proximal small intestine: mild distention and vomiting of bile-stained fluid o Lower in small intestine: more pronounced distention because a greater length of intestine is proximal to the obstruction; vomiting may or may not occur later and contain fecal matter Ulcerative colitis and Crohn’s disease Ulcerative colitis: chronic inflammatory disease the causes ulceration of the colonic mucosa of sigmoid colon and rectum o Causes: infectious, immunologic, dietary, genetic o Patho: lesions are continuous with no skipped lesions – limited to mucosa – not transmural o Clinical manifestations: diarrhea (10-20/day), bloody stools, crampy lower abd pain relieved by defecation – remissions and exacerbations Chron’s o Most commonly affects distal small intestine and proximal large colon o Similar risk factors and causation as UC – strong association with CARD12/NOD2 gene mutations o Patho: skip lesions – inflammation affects some segments but not others – ulcerations produce longitudinal and transverse inflammatory fissures that extend into lymphoid tissue - “cobblestone” o Clinical manifestations: abd pain and diarrhea (>5/day) with passage of blood and mucus; inflammation of ileum causes RLQ tenderness; weight loss -Anemia may result from vitamin B12 and folic acid; bone disease from malabsorption of calcium; protein loss leads to hypoalbuminemia disease: idiopathic inflammatory disorder affecting any part of the digestive tract Diverticular disease; types and basic clinical manifestations and patho Types o Diverticula: herniations of mucosa through muscle layers of the colon wall (esp. L sigmoid colon) o Diverticulosis: asymptomatic diverticular disease o Diverticulitis: inflammatory stage of diverticulosis; inflammation of the diverticula Patho o Habitual consumption of low-residue diet reduces fecal bulk – reduces diameter of the colon – pressure within the narrow lumen can increase enough to rupture the diverticula -Also decreases immune response in the colon and permits low-grade inflammation o Diverticulitis can cause abscess formation, peritonitis, or obstruction – risk of perforation Clinical manifestations o Usually vague or absent o Cramping pain of lower abd – exacerbated by eating, diarrhea, constipation, distention, flatulence o Incomplete relief of pain after defecation o Abscess – fever, leukocytosis, tenderness of LLQ o RLQ pain w/ complications – hemorrhage, perforation w/ peritonitis, bowel obstruction, and fistula IBS  Functional gastrointestinal disorder with no specific structural or biochemical alterations  Characterized by recurrent abdominal pain and discomfort associated with altered bowel habits that present as diarrhea or constipation or both  Clinical manifestations: o Can be diarrhea or constipation predominant; alternating diarrhea/constipation, gas, bloating, nausea o Symptoms relieved with defecation and don’t interfere with sleep o Associated with anxiety, depression, and chronic fatigue syndrome Cause: unknown – may be related to visceral hypersensitivity, abnormal intestinal motility and secretion, intestinal infection, overgrowth of small intestinal flora, food allergy/intolerance, psychosocial factors Obesity Increase in body fat mass o Overweight: BMI greater than 25 kg/m 2 o Obesity: BMI greater than 30 kg/ m2  Adipocyte: cellular basis of obesity  Orexins: molecules that stimulate eating – hypocretins from the hypothalamus.  Anorexins: molecules that inhibit eating Types: o Visceral: intrabdominal, central, apple shape o Peripheral: gluteal-femoral, subcutaneous, pear shape Appendicitis Inflammation of the vermiform appendix – most common surgical emergency of the abdomen  Patho: obstruction by inflammatory process, foreign body, or neoplasm -Normally polymicrobial process: Enterobacteriaceae, anaerobes, enterococcus -Obstruction of the lumen leads to increased pressure, ischemia, and inflammation of the appendix  Clinical manifestations o 96% of patients will exhibit epigastric and RLQ pain – begins vague and increases in intensity – followed by N/V, anorexia; fever is common; diarrhea in children o Rebound tenderness: RLQ pain is associated w/ extension of the inflammation to surrounding tissues; pain when releasing palpation **Without surgical resection – inflammation – gangrene, perforation, peritonitis Cholelithiasis and Cholecystitis Cholelithiasis: gallstone formation – cholesterol stone formation in bile that is supersaturated with cholesterol o Causes: enzyme defect causing increased cholesterol synthesis; decreased secretion of bile acids to emulsify fats; decreased resorption of bile salts from the ileum; gallbladder smooth muscle hypomotility, stasis; genetic predisposition o Types of stones: -Black pigmented stones: formed in sterile environment and primarily composed of calcium bilirubinate polymer from hyperbilirubinbilia -Brown stones: associated with bacterial infection of the bile ducts with formation of stone that is composed of calcium soaps, unconjugated bilirubin, cholesterol, fatty acids, mucin o Clinical manifestations: ▪Epigastric and RUQ pain ▪Intolerance to fatty foods ▪Biliary colic: lodging of stones in the cystic or common duct ▪Jaundice: stone in common bile duct ▪Abdominal tenderness and fever indicate cholecystitis ▪Complication – pancreatitis caused by back up of pancreatic enzymes Cholecystitis: inflammation of the gallbladder o Acute vs chronic o Clinical manifestations: -Fever, leukocytosis, rebound tenderness in RUQ (+Murphy’s sign), abdominal muscle guarding -Pain increases after fatty meal when bile is attempting to be secreted Pancreatitis acute and chronic   Inflammation of the pancreas Causes: o Injury or damage to the pancreatic cells and ducts causing a leakage of pancreatic tissue – leak into the bloodstream to cause injury to blood vessels and other organs o Enzymes cause autodigestion of pancreatic tissue and leak into the bloodstream to cause injury to blood vessels and other organs Acute vs chronic o Acute: resolves spontaneously -Clinical manifestations:     Epigastric or midabdominal pain, N/V, fever, leukocytosis Elevated amylase 3x normal (amylase P is more specific) Lipase elevated and remains high Ranson's criteria to assess mortality rate – assesses lab values, etc. o Chronic: repeated exacerbations of acute pancreatitis can lead to chronic changes -Destroys acinar cells and the islets of Langerhans – pancreatic parenchyma is destroyed and replaced by fibrous tissues, strictures, calcification, ductal obstruction, and pancreatic cysts. -Chronic alcohol abuse is the most common cause – is a risk factor for pancreatic cancer ▪Clinical manifestations: -Continuous or intermittent pain associated with increased intraductal pressure, increased tissue pressure, ischemia, neuritis, ongoing injury, and changes in central pain perception -Weight loss, steatorrhea, DM accompanies disease progression Acute liver failure – NOT ON STUDY GUIDE     Severe impairment or necrosis of liver cells without preexisting liver disease or cirrhosis Leading cause is acetaminophen overdose Patho: hepatocytes become edematous – patchy areas of necrosis and inflammatory cell infiltrates disrupt the parenchyma – hepatic necrosis is irreversible Clinical manifestations: (early) anorexia, vomiting, abdominal pain, progressive jaundice – (late) ascites, peripheral edema, hepatomegaly, hepatic encephalopathy Cirrhosis Irreversible inflammatory fibrotic disease that disrupts liver function and structure -Causes: alcohol abuses and viral hepatitis -Patho: o Decreased function from nodular ad fibrotic tissue synthesis (fibrosis) o Biliary channels become obstructed and cause portal hypertension – portal hypertension causes blood to be shunted away from the liver – hypoxic necrosis develops Types: o Alcoholic liver disease     Oxidation of alcohol causing damage to hepatocytes Stages: Steatosis (alcoholic fatty liver): mildest form, reversible with abstinence Alcoholic hepatitis (steatohepatitis): inflammation; degeneration/necrosis of hepatocytes Alcoholic cirrhosis (fibrosis): toxic effects of alcohol metabolism on the liver, immunologic alterations, oxidative stress from lipid peroxidation, malnutrition impairs the hepatocytes’ ability to oxidize fatty acids, synthesize enzymes and proteins, degrade hormones, and clear portal blood of ammonia and toxins Clinical manifestations: nausea, anorexia, fever, abdominal pain, jaundice o Nonalcoholic fatty liver disease -Infiltration of hepatocytes with fat that occurs in the absence of alcohol intake; associated with obesity o Biliary -Begins in bile canaliculi and ducts -Types:   Primary biliary cirrhosis (autoimmune): t-lymphocyte mediated and antibody mediated destruction of the small intrahepatic bile ducts Secondary biliary cirrhosis: common bile duct obstruction; resolved w/ removal Portal hypertension   Abnormally high blood pressure in the portal venous system caused by resistance to portal blood flow Three regions affected: o Prehepatic (portal vein): caused by thrombosis or narrowing of the portal vein o Intrahepatic (within the liver): from vascular remodeling with intrahepatic shunts, thrombosis, inflammation, or fibrosis of the sinusoids o Posthepatic (hepatic vein): occur from hepatic vein thrombosis or cardiac disorders (right sided heart failure or constrictive pericarditis) that impair the pumping ability of the right heart – blood backs up and increases pressure in portal system High blood pressure in the portal veins causes collateral vessels to open between the portal veins and systemic veins; blood bypasses the obstructed portal vessels because blood pressure is considerably lower o Activates RAAS – increase renin – increased fluid retention – overload heart and liver further -Positive feedback Consequences: o Varices: distended, tortuous, collateral veins caused by prolonged elevation in hepatic portal vein pressure causing veins to open and turn into varices ▪Most common in lower esophagus and stomach – can also occur in abd wall and rect ▪Rupture can cause life threatening hemorrhage o Splenomegaly: enlargement of the spleen – see below o Ascites: accumulation of fluid in the peritoneal cavity - see below o Hepatic encephalopathy: brain toxicity - see below Clinical manifestations: vomiting of blood from esophageal varices is most common; and ascites Splenomegaly Causes: portal HTN causes increased intrasplenic blood pressure   Clinical manifestations: most common is thrombocytopenia – increased bleeding tendency Can be predictive of esophageal varices severity Ascites Causes: cirrhosis – also by heart failure, constrictive pericarditis, abdominal malignancies, nephrotic syndrome, malnutrition  Contributing factors: portal HTN, splanchnic vasodilation, hepatocyte failure, sodium retention  Clinical manifestations: abdominal distention, increased girth, weight gain o Secondary: respiratory distress (displaced diaphragm), peripheral edema, dilutional hyponatremia o Complication: peritonitis – fever, chills, shock  Hepatic encephalopathy Accumulation of toxins related to liver failure causing a disruption of neurotransmission o Ammonia accumulates and is toxic to the brain Clinical manifestations: personality changes, confusion, memory loss, flapping tremor (asterixis), stupor, coma, death – may slowly occur over time with chronic liver disease Jaundice  “icterus”: yellow or greenish pigmentation of the skin caused by hyperbilirubiinemia (>2.5-3)  Causes: o Extrahepatic obstruction to bile flow (gallstones) o Intrahepatic obstruction (from cirrhosis or hepatitis) o Prehepatic obstruction (excessive production of bilirubin from excessive hemolysis of RBC’s) Clinical manifestations: dark urine, clay-colored stools, yellow discoloration in sclera and then skin, skin xanthomas (cholesterol deposits), pruritis Hepatitis, types and stages, basics of each type Hepatic necrosis, Kupffer cell hyperplasia, infiltration of liver tissue by mononuclear phagocytes o Causes obstruction of bile flow and impairment hepatocyte function Chronic active hepatitis: occurs with hepatitis B and C with a predisposition to cirrhosis and hepatocellular carcinoma  Fulminant hepatitis: complication of hepatitis B (with or without D) or hepatitis C – causes widespread hepatic necrosis – often fatal  Stages: o Incubation phase: varies depending on virus o Prodromal (pre-icteric) phase: begins approximately 2 weeks after expsoure; ends with appearance of jaundice -Clinical manifestations: fever, malaise, anorexia, hepatomegaly, tenderness; highly transmissible o Icteric phase: actual phase of illness -Clinical manifestations: jaundice, hyperbilirubinemia, fatigue and abdominal pain, increased bilirubin in serum, PT prolonged o Recovery phase: begins with resolution of jaundice -Symptoms resolve after several weeks – chronic or chronic active hepatitis may develop  Types: o Hepatitis A -Found in feces, bile, sera of infected individual – transmitted fecal-oral route -RNA hepatovirus – vaccine available o Hepatitis B -Transmitted through contact with infected blood, body fluids, contaminated needles -42-nm hepadnavirus with partially double stranded DNA genome -Maternal transmission during 3rd trimester if infected – vaccine available o Hepatitis C -Responsible for most cases of posttransfusion hepatitis; IV drug use, HIV -Single stranded RNA virus -Co-infection with hep B is common; 80% develop chronic liver disease; no vaccine o Hepatitis D -Dependent on hepatitis B for replication – defective RNA virus – blood borne o Hepatitis E -Fecal-oral transmission – most common in developing countries – vaccine only in China -RNA hepavirus o Hepatitis G -Percutaneous transmission (IV drug use, hemodialysis, hemophiliacs) and associated with chronic viremia lasting 10 years -Flavivirus Cancers of GI tract basics Esophageal carcinoma o Adenocarcinoma (GERD) and squamous cell carcinoma (tobacco + alcohol) o Risk factors: concurrent alcohol and tobacco use, reflux esophagitis, radiation exposure, nutritional deficiencies o Clinical manifestations: dysphagia and chest pain Gastric carcinoma o Associated with h.pylori, high salt intake, food preservative (nitrates/nitrites), atrophic gastritis o 50% located in prepyloric antrum (lower stomach) o Clinical manifestations: (develop only after tumor has penetrated wall) weight loss, upper abdominal pain, vomiting, hematemesis, anemia Colorectal cancer o Second most common cancer death in the US o Risk factors: familial adenomatous polyposis coli (inherited form), polyps, family history o Location of tumors:     Right ascending colon: large and bulky – pain, change in bowel habits Transverse colon: pain, change in bowel habits, anemia Left descending, sigmoid colon: small button-like masses – stool is pencil shaped, pain, change in bowel habits, bright red blood in stool Rectum: blood in stool, change in bowel habits, rectal discomfort Rectal carcinoma o Located up to 15cm from the opening of the anus o Tumor can spread transmurally to the vagina in women or prostate in men Primary liver cancer o Risk factors: infection with hep A, C, D particularly in conjunction with cirrhosis; chronic alcoholic liver disease and non-alcoholic liver disease associated with cirrhosis; exposure to mycotoxins (mold); long duration of heavy smoking; hepatic iron overload Cancer of the gallbladder o Rate yet lethal – tends to occur in women > 50 – adenocarcinoma is most common o Clinical manifestations occur late in disease, metastasis has often already occurred – poor prognosis Pancreatic cancer o 5th as cause of cancer deaths – found late in disease progression – mortality nearly 100% -Initial symptoms: vague abdominal or midback pain, jaundice o Risk factors: heavy cigarette smoking o Most tumors are exocrine (ductal) adenocarcinomas – cells of ducts in the head, body, or tail o Endocrine tumors from islets of Langerhans are rare ENDOCRINE PHYSIOLOGY Feedback systems and hormone release basics Hormones: chemical messengers; convey specific regulatory information among cells and organs o Mechanisms of communication: autocrine (within cell), paracrine (between local cells) and endocrine (between remote cells) o Endocrine glands respond to specific signals by synthesizing and releasing hormones in circulation -Specific rates and rhythms of secretion; operate within feedback systems to maintain optimal internal environment; affect only target ells with appropriate receptors to initiate specific cell functions; excreted by kidneys or deactivated by liver (makes water-soluble for excretion) o Types:    Steroids – cortisol (adrenal cortex); estrogen, progesterone (ovaries); testosterone (testes) Amino acids – tyrosine, thyroxine (thyroid); catecholamines (adrenal medulla) Proteins – peptides, insulin (pancreas) o Released: -In response to an alteration in the cellular environment to maintain a regulated level of certain substances or other hormones o Regulated by: -Chemical factors (blood sugar or calcium levels); endocrine factors (hormone from one endocrine gland controlling another endocrine gland); neural control -Feedback *most important way* Negative feedback: most common – plasma levels of one type influence the level of other types – lack of negative feedback inhibition leads to pathologic conditions o Transport: released by endocrine glands and distributed throughout body    Water-soluble: free, unbound; short acting response (catabolized by enzymes) Lipid-soluble: bound, small amt in free or active form; rapid and long lasting response (pass easily through lipid membrane of cells) Only free hormones can signal a target cell o Receptors: located in or on plasma membrane or in the intracellular compartment of the target cell -Target cells: recognize and bind to hormones, initiate signal; more receptors=more sensitive *Up-regulation: low concentration of hormones increases number of receptors *Down-regulation: high concentration of hormones decreases number of receptors Basics of HPA axis what comes from where Hypothalamic-pituitary axis forms the structural and functional bases for the central integration of the neurologic and endocrine systems – produces many releasing/inhibitory hormones and tropic hormones o Hypothalamus: base of the brain; connected to anterior pituitary by portal blood vessels; connected to posterior pituitary by nerve tract -Produces hormones:        Prolactin-inhibiting factor (PIF-dopamine): inhibition of prolactin Thyrotropin-releasing hormone (TRH): release of TSH Gonadotropin-releasing hormone (GnRH): release of LH/FSH Somatostatin: inhibits release of GH and TSH Growth hormone-releasing factor (GRF): release of GH Corticotropin-releasing hormone (CRH): release of ACTH Substance P: inhibition of ACTH o Posterior pituitary: stores and secretes hormones synthesized in the nuclei of the hypothalamus -Antidiuretic hormone (ADH) -Controls plasma osmolality; causes water reabsorption in the kidneys -Released when plasma osmolality is increased, or intravascular volume is decreased -Oxytocin -Causes uterine contractions and milk ejection in lactating women -Reduces brain’s responsiveness to stressful stimuli (esp. in pregnant/postpartum) *Mediated by cholinergic and adrenergic NT’s - glutamate (stimulus); GABA (inhibitory) o Anterior pituitary: hormones regulated by feedback of hypothalamic releasing-inhibitory hormones/factors, from target gland hormones (cortisol and estrogen), or direct effect of NT’s -Adrenocorticotropic hormone (ACTH) -Target organ: adrenal cortex/gland -Function: increase steroidogenesis (cortisol, androgenic hormones, aldosterone) -Melanocyte-stimulating hormone (MSH) -Target organ: pigment cells -Function: promotes secretion of melanin and lipotropin – makes skin darker -Luteinizing hormone -Target organ: granulosa cells (women); Leydig cells (men) -Function: ovulation, progesterone production (women); testicular growth, testosterone production (men) -Follicle-stimulating hormone -Target organ: granulosa cells (women); Sertoli cells (men) -Function: follicle maturation, estrogen production (women); spermatogenesis (men) -Thyroid-stimulating hormone -Target organ: thyroid -Function: increase production and secretion of thyroid hormone, increased iodine uptake, promotes hypertrophy and hyperplasia of thymocytes -Growth hormone -Target organ: muscle, bone, liver -Function: essential to normal tissue growth and maturation; affects aging, sleep, nutritional status, stress, and reproductive hormones o Controlled by two hormones from hypothalamus 1. Growth hormone-releasing hormone (GHRH): increases secretion 2. Somatostatin: inhibits growth hormone -Prolactin -Target organ: breast -Function: milk production; effects on reproductive and immune functions Pineal gland and thymus – NOT ON STUDY GUIDE Pineal gland located within brain – made up of photoreceptive cells that secrete melatonin o Plays important role in circadian rhythms, reproductive systems (GnRH and puberty), immune regulation Thymus – releases thymosin that stimulates T cell development in the immune system Thyroid and parathyroid gland; hormones; and basic physiology Thyroid gland o Function: produces hormones that control rates of metabolic processes within the body o Structure    Two lobes lie just below larynx on either side of trachea; isthmus joins the two lobes Composed of follicles (follicle cells) - synthesize and secrete some thyroid hormones Parafollicular cells (c-cells) - secrete calcitonin - lower serum calcium levels by inhibition of osteoclasts o Hormones ▪Regulation of thyroid hormone secretion is by TRH from hypothalamus – stimulates TSH from anterior pituitary – TSH increases release of thyroid hormones, iodine uptake and oxidation, thyroid hormone synthesis, and synthesis and secretion of prostaglandins by the thyroid gland TSH responds to low levels of circulating thyroxine through negative feedback ▪Thyroid hormone (TH)/thyroxine/T4: precursor to triiodothyronine (T3) ▪Triiodothyronine (T3): regulates metabolic rate of all cells and processes cell growth ▪Circulating levels of TSH are used to monitor thyroid conditions and hormone levels -TSH high: decrease or insufficient level of TH has occurred – hypothyroidism -TSH low: increase or excess level of TH has occurred – hyperthyroidism Parathyroid glands o Structure: small glands located behind the thyroid gland o Hormones ▪Parathyroid hormone -Regulates serum calcium, increases calcium concentration, decreases phosphate level, acts as co-factor w/ vitamin D to increase calcium absorption -Antagonist to calcitonin Endocrine pancreas, cells and what their function is - which cells release what    Pancreas is both an endocrine (glucagon and insulin) and exocrine (digestive enzymes) gland Islets of Langerhans: secretion of glucagon and insulin - help regulate carb metabolism Hormone secreting cells: o Alpha: secrete glucagon – see below o Beta: secrete insulin and amylin – see below o Delta: secrete somatostatin and gastrin ▪Somatostatin: essential in carb, fat, and protein metabolism; may prevent excess insulin secretion ▪Gastrin: controls secretion of glucagon ▪Ghrelin: stimulates GH secretion, controls appetite, regulation of insulin sensitivity o F cells/PP cells: secrete pancreatic polypeptide ▪PP: released in response to low blood glucose and protein rich meals and signals satiety; increases gastric acid secretion; increased in pancreatic tumors and diabetes ANS innervation of pancreatic islets what does the SNS and PSNS do? Sympathetic nervous system o Stimulates alpha cells of pancreas to release glucagon o Need glucose/energy for “fight or flight” Parasympathetic nervous system o Stimulates beta cells of pancreas to release insulin, secretion of pancreatic juice o “rest and digest” Insulin what is its function where does it come from Comes from beta cells and synthesized from proinsulin Function o Anabolic hormone that promotes synthesis of proteins, lipids, and nucleic acids o Facilitates rate of glucose uptake into cells of the body - controls blood glucose levels o Facilitates intracellular transport of potassium, phosphate, and magnesium into cells o Secretion is regulated by chemical, hormonal, and neural control ▪Promoted by increased blood glucose levels, increase amino acids, parasympathetic (vagal) stimulation of beta cells ▪Diminished in low blood glucose levels, high levels of insulin (negative feedback), sympathetic stimulation (catecholamines) of alpha cells, hypokalemia (negative feedback) o Other functions:      Transports glucose from breakdown of carbs, fats, protein to help regulate metabolism andstore excess glucose in the tissues for future energy Carries amino acids into muscle cells synthesizes them into protein Carries triglycerides into fat (adipose) cells for storage After meals insulin stores nutrients When glucose isn’t available, catecholamines, cortisol, and glucagon break down and store complex fuels for energy o In the liver: ▪Inhibits glycogenolysis, inhibits gluconeogenesis, inhibits ketogenesis o Effects on the muscle: ▪Promotes protein synthesis, increase AA transport into muscle cells, promotes glycogenesis o Effects on fat: ▪Increase fatty acid synthesis, promotes triglyceride storage into fat cells, decrease lipolysis o Brain and blood cells do not require insulin for glucose transport Amylin: co-secreted with insulin by beta cells o Antihyperglycemic effect by delaying nutrient uptake, suppressing glucagon secretion after meals, has satiety effect Glucagon what is its function, where does it come from, what activates its release     Produced by alpha cells and cells lining the GI tract Activated by low glucose levels and sympathetic stimulation; inhibited by high glucose levels Function: acts on the liver and increases blood glucose by stimulating glycogenolysis and gluconeogenesis; glycogen to glucose – glucose secreted into circulation – increased blood sugar Antagonist to insulin Adrenal glands, cortex and medulla; hormones and basic functions    Paired pyramid-shaped organs located behind the peritoneum and close to the upper pole of each kidney Consists of outer cortex and inner medulla Adrenal cortex: stimulated by adrenocorticotropic hormone (ACTH) o Three zones/layers ▪Outer – zona glomerulosa: aldosterone ▪Middle – zona fasciculata: glucocorticoids ▪Inner – zona reticularis: mineralocorticoids, adrenal androgens and estrogens, glucocorticoids o Not directly innervated by PSNS or SNS cholinergic fibers o Glucocorticoid hormones: ▪Cortisol, cortisone, corticosterone -Increases blood glucose, causes protein breakdown, anti-inflammatory and growth- suppressing effects, decrease immune response (infection risk, poor wound healing) -Cortisol: the most potent naturally occurring glucocorticoid hormone o Deactivated by the liver o Regulated by the hypothalamus and anterior pituitary gland (ACTH) and stimulated by CRH – ACTH binds with receptors of adrenal cortex to release cortisol o Mineralocorticoid hormones: ▪Aldosterone -Cause sodium retention and potassium and hydrogen loss (regulated by RAAS) -Activated by sodium and water depletion, increased potassium levels, diminished effective blood volume, and increased levels of ACTH -Angiotensin II is the primary stimulant of aldosterone synthesis and secretion (RAAS) o Adrenal estrogens and androgens: ▪Estrogen and weak androgen secretion – androgens made stronger by peripheral tissues Adrenal medulla: o Chromaffin cells (pheochromocytes) - cells of the medulla ▪Secretes catecholamines epinephrine/adrenaline (majority) norepinephrine; “fight or flight” ▪Promote hyperglycemia – interfere with usual glucose regulatory feedback mechanisms PATHOPHYSIOLOGY Mechanisms of hormonal alterations – NOT ON STUDY GUIDE      1. Failure of feedback systems 2. Dysfunction of an endocrine gland – excessive or inadequate production 3. Altered hormone – inactivation or degradation 4. Ectopic hormone release from non-endocrine sites or autonomous production 5. Failure of target cell to respond to its hormone – receptor disorder, intracellular disorder SIADH basic patho and causes, what happens in the body with SIADH? What type of hyponatremia is present? Clinical manifestations? Patho: o Levels of antidiuretic hormone (ADH) are abnormally high o Most common cause: ectopic secretion of ADH; also, after surgery and some cancers o Water retention: action of ADH on renal collecting ducts increases their permeability to water, thus increasing water reabsorption by the kidneys o For diagnosis, normal renal, adrenal, and thyroid function must exist o Nephrogenic form: excess free water; genetic form – mutation in arginine vasopressin AVP gene Clinical manifestations: o Characterized by euvolemic hypotonic (dilutional) hyponatremia -Total body water: increased -Total body sodium: unchanged -Extracellular fluid: increased -Edema: absent o Hyponatremia, serum hypoosmolality (300 mOsm), Hypopituitarism; panhypopituitarism; basic patho, what they are? What deficiencies do you see and basic results of the deficiencies? Patho: o The absence of selective pituitary hormones or the complete failure of all pituitary hormone functions (panhypopituitarism)   The pituitary is vascular and therefore vulnerable to ischemia and infarction Necrosis leads to edema with swelling of the gland – over time pituitary undergoes shrinkage and symptoms of hypopituitarism develop Hormones affected: o ACTH (adrenocorticotropic hormone) deficiency ▪Cortisol deficiency o TSH deficiency ▪Altered metabolism o FSH and LH deficiency ▪Lack of secondary sex characteristics o GH deficiency ▪Lack of growth in children Hyperpituitarism; acromegaly patho, what happens to the body (manifestations), gigantism what is it and which bones does it affect? Patho: o Commonly from benign, slow-growing pituitary adenoma Clinical manifestations: o Headache and fatigue, visual changes (close to optic chiasm), CN palsies, hypersecretion of pituitary from tumor, hyposecretion of neighboring anterior pituitary hormones (hypocortisol and hypothyroid) Giantism: o GH hypersecretion in children and adolescents – effects long bone growth Acromegaly: o GH hypersecretion in adulthood – mostly caused by slowly progressive pituitary adenoma o Mortality: cardiac hypertrophy, HTN, atherosclerosis, type 2 DM – CAD o Other malignancies common o Connective tissue proliferation -Enlarged tongue, interstitial edema, increase in size and function of sebaceous and sweat glands, coarse skin and body hair o Bony proliferation -Large joint arthropathy, kyphosis, enlargement of facial bones and hands and feet, protrusion of lower jaw and forehead, need for increasingly larger sized shoes, hats, rings, and gloves o Symptoms of diabetes -Polyuria and polydipsia o CNS symptoms -Headache, seizure activity, visual disturbances, papilledema hypersecretion of prolactin: most common hormonally active pituitary tumor o Women: amenorrhea, galactorrhea, hirsutism, osteoporosis o Men: hypogonadism, ED, impaired libido, decreased ejaculation volume with no sperm Hyperthyroidism; thyrotoxicosis, primary, secondary, manifestations, Graves' disease, thyroid storm Hyperthyroidism/thyrotoxicosis o A condition that results from any cause of increased level of thyroid hormone – excess secretion o Primary: -Dysfunction of disease of the thyroid gland or anything that alters TH production o Secondary: -Conditions that cause alterations in pituitary or hypothalamic functioning; alters TSH or thyrotropin-releasing hormone (TRH) production o Clinical manifestations: -Increased metabolic rate with heat intolerance and increased tissue sensitivity to stimulation by the sympathetic nervous system; enlargement of the thyroid gland (goiter) -Thin hair, normal or enlarged thyroid that may be warm on palpation or nodular, heart failure (tachycardia), weight loss, diarrhea, warm skin with sweaty palms, hyperreflexia Graves’ disease o Patho: ▪Autoimmune hyperthyroid condition that develops autoantibodies (type II hypersensitivity reaction) towards the thyroid – **most common cause o Clinical manifestations: ▪Ophthalmopathy – exophthalmos: increased secretion of hyaluronic acid, orbital fat accumulation, inflammation, and edema of the orbital contents; diplopia: double vision ▪Pretibial myxedema (Graves’ dermopathy): leg swelling “orange peel appearance” Thyrotoxic crisis (thyroid storm) o Rare but life threatening within 48 hours if not treated o Results from excessive stress on patients with hyperthyroidism that’s either undiagnosed or underdiagnosed – ex of stress: infection, trauma, burns, surgery ▪Increased action of thyroxine (T4) and triiodothyronine (T3) o Clinical manifestations: ▪Hyperthermia, tachycardia, atrial tachydysrhythmias, high output heart failure, agitation or delirium, N/V/D Hyperthyroidism resulting from nodular thyroid disease o Toxic multinodular goiter: several hyperfunctioning nodules secrete thyroid hormone o Solitary toxic adenoma: only one nodule becomes hyperfunctioning o Clinical manifestations: ▪Same as hyperthyroidism but occur slowly; exophthalmos & pretibial myxedema don’t occur Hypothyroidism; primary, secondary, clinical manifestations, myxedema coma Patho: o Deficient production of thyroid hormone by the thyroid gland o Primary: ▪Inability of the thyroid gland to produce TH ▪Iodine deficiency (endemic goiter): most common worldwide ▪Autoimmune thyroiditis (Hashimoto disease): most common in US o Secondary (central): ▪Conditions that cause either pituitary or hypothalamic failure with deficiency of thyrotropinreleasing hormone (TRH) and TSH ▪Drugs – lithium o Clinical manifestations: ▪Low basal metabolic rate, cold intolerance, lethargy, tiredness, lowered basal body temperature, possible diastolic HTN ▪Loss of hair, coarse brittle hair, periorbital edema, puffy face, normal enlarged or small thyroid, heart failure (bradycardia), constipation, cold intolerance, muscle weakness, osteoporosis, edema of extremities ▪Myxedema: nonpitting, boggy edema especially around the eyes, hands and feet; thickening of the tongue ▪Myxedema coma: uncompensated hypothyroidism – medical emergency – decreased LOC, hypothermia without shivering, hypoventilation, hypotension, hypoglycemia, lactic acidosis, coma Caused by any stress, forgetting to take medication, overuse of narcotics or sedatives, trauma, surgery Congenital hypothyroidism o Thyroid hormone deficiency present at birth o If not treated, cretinism develops: growth retardation, developmental delay, and other abnormal features o Neonatal screening has reduced incidences Thyroid cancer Most common endocrine malignancy but overall rare Most consistent risk factor: exposure to ionizing radiation especially during childhood or puberty o Also affected by iodine deficiency Most have normal T3 and T4 levels: euthyroid Clinical manifestations: changes in voice and swallowing, difficulty breathing Mets to regional lymph nodes, lungs, brain, bone   Hyperparathyroidism; basic differences between primary, secondary, and tertiary; clinical manifestations, basic patho Primary: o Excess secretion of TPH from one or more parathyroid glands and hypercalcemia o 80-85% caused by parathyroid adenomas o Normal feedback mechanisms: elevated serum levels of calcium fail to normally inhibit the release of PTH by the parathyroid gland Secondary: o Increase in PTH secondary to a chronic disease ▪Chronic renal failure, dietary deficiency of vitamin D, calcium Tertiary: o Excessive secretion of PTH and hypercalcemia from long-standing secondary hyperparathyroidism Clinical manifestations: o Most asymptomatic o Primary: hypercalcemia and hypophosphatemia, possible kidney stones from hypercalciuria, alkaline urine, pathologic fractures o Secondary: low serum calcium but elevated PTH Hypoparathyroidism: clinical manifestations, basic patho, causes    Patho: o Abnormally low PTH levels – depressed serum calcium level, increased serum phosphate level Causes: o Parathyroid damage in thyroid surgery, autoimmunity, genetic mechanisms; alcoholism (hypomagnesium can lead to decreased PTH) Clinical manifestations: o Hypocalcemia, lowering the threshold for nerve and muscle excitation – muscle spasms, hyperreflexia, tonic-colonic convulsions, laryngeal spasms, death from asphyxiation o Chvostek and Trousseau signs o Phosphate retention DM, categories (type 1 type 2 gestational) and clinical manifestations and patho of each Group of diseases marked by high blood glucose resulting from defects in insulin production, insulin action, or both – dysfunction of the beta cells of endocrine pancreas that affects metabolism of fat, carbs, and protein  Normal fasting blood glucose 126 on two separate occasions or random >200 with symptoms of polyuria, polydipsia, and weight loss of subsequent day plasma glucose >126 Categories:   o Type 1: pancreatic atrophy and loss of beta cells ▪Autoimmune Environmental and genetic factors trigger cell-mediated destruction of beta cells o Environmental: viral infection, h. pylori, exposure to cow’s milk proteins, relative lack of vitamin D o Genetic: first-degree relative with type 1 DM, association with MHC Autoantibody, t-cell and macrophage destruction of pancreatic beta cells occur with a loss of insulin production and relative excess of glucagon o 1. lymphocyte and macrophage infiltrate islets – inflammation and islet beta cell death o 2. autoantibodies are produced against islet cells, inulin, glutamic acid decarboxylase, and other cytoplasmic proteins o Both alpha and beta cell functions are abnormal, and both lack insulin and amylin and have relative excess of glucagon – hyperglycemia, hyperketonemia Human leukocyte antigens are associated ▪Non-immune Occurs secondary to other diseases – pancreatitis, idiopathic diabetes ▪Clinical manifestations: -80-90% loss of function of beta cells before hyperglycemia develops -Polydipsia, polyuria, polyphagia, weight loss, fatigue o Type 2: insulin resistance and decreased insulin secretion by beta cells       Beta cell dysfunction: beta cell mass is decreased; elevated FFA hyperglycemia, adipokines, and inflammatory cytokines promote apoptosis of beta cells Glucagon: pancreatic alpha cells are less responsive to glucose inhibition resulting in increased glucagon release – increase hepatic production of glucose – further contributing to hyperglycemia Amylin: decreased in type 1 and type 2 Ghrelin: decreased in type 2 Risk factors: age, obesity, HTN, physical inactivity, family history, metabolic syndrome  Metabolic syndrome: central obesity, dyslipidemia, prehypertension, elevated fasting blood glucose level  Genetic, epigenetic, and environmental interactions; must be genetically predisposed  More common than type 1, affecting both adults and children Clinical manifestations Fatigue, pruritis, recurrent infections, visual changes, neuropathy Other types--o Gestational: any degree of glycose intolerance with the onset or first recognition occurring during pregnancy   Recommended that if high risk women are found to have diabetes at first prenatal visit that they receive diagnosis of overt diabetes Contributing factors: insulin resistance and inadequate insulin secretion; gestational diabetes increases risk for development of type 2 diabetes Complications of DM hypoglycemia, DKA, HHNKS (know differences between DKA and HHNKS and how they present), Somogye effect, dawn phenomenon; basic patho of each Hypoglycemia o Lowered plasma glucose level – newborns