Physiology of GI Disorders Lecture Outline

Physiology of GI Disorders Lecture Outline I. Disorders along the GI tract II. Nausea and vomiting 1 Physiology of GI Disorders Objectives 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. Explain disorders of the esophagus Explain the etiology and consequences of gastritis Identify etiology and implications of pa...

Physiology of GI Disorders Lecture Outline I. Disorders along the GI tract II. Nausea and vomiting 1 Physiology of GI Disorders Objectives 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. Explain disorders of the esophagus Explain the etiology and consequences of gastritis Identify etiology and implications of pancreatitis Explain malabsorption related to gluten intolerance Explain the etiology and consequences of dumping syndrome List causes of nausea and vomiting Identify the vomiting centers of the brain and their involvement in vomiting Explain the physiology of vomiting List risk factors for PONV Identify the receptors targeted in PONV prophylaxis Identify the variations in bowel obstructions at different sites along the GI tract 2 References Assigned reading from your text: Hall Chapter 67 3 I. Disorders Along the GI Tract 4 Disorders of the Esophagus q Paralysis of swallowing mechanism- multiple etiologies – – – – Damage to cranial nerves V, IX, X Damage to swallowing center in brainstem- encephalitis Failure of neuromuscular transmission- eg myasthenia gravis Deep anesthesia inhibits swallowing reflex and puts patients as risk for aspiration q Achalasia- failure of LES to relax q Megaesophagus- dilation of esophagus q Abnormalities include: – Complete abrogation of the swallowing act – Failure of glottis to close- food into lungs – Failure of soft palate/uvula to close posterior nares- food into nose 5 Disorders of the Stomach- Gastritis q The gastric barrier maintains mucus barrier and cells have tight junctions- protects mucosa and also prevents absorption by the stomach q Gastritis- inflammation of gastric mucosa – Chronic gastritis may be due to chronic infection – Some irritant substances especially damaging to gastric mucosal barrier Alcohol and aspirin damage tight junctions between cells Allows back-leak of H+ ions which H+ ions damage mast cells and causes histamine release Histamine damages blood capillaries within the mucosa to produce ischemia – Chronic gastritis may lead to: Gastric atrophy and Loss of stomach secretions- achlorhydria- reduces functional pepsin Pernicious anemia – Intrinsic factor combines with Vit B12 in the stomach and protects it in the ileum, intrinsic factor binds with epithelial receptors allowing B12 absorption and facilitates maturation of RBCs – Mucosa susceptible to digestion by peptic enzymes- ulcer 6 Peptic Ulcers q Most frequently occur within a few centimeters of the pylorus q Normal feedback controls ensure neutralization of gastric acid: – Acid in the duodenum inhibits gastric secretion and peristalsis – Presence of acid in the small intestine liberates secretin from intestinal mucosa which promotes pancreatic secretion of sodium bicarbonate q Caused by: – Excess secretion of acid and pepsin by gastric mucosa – Diminished ability of the gastroduodenal mucosal barrier to protect 7 Disorders of the Small Intestine q Pancreatic pathophysiology Lack of pancreatic secretion occurs: – – – Implications of loss of pancreatic secretion: – – – In pancreatitis When pancreatic duct blocked by gallstones After the head of the pancreas has been removed due to malignancy Loss of digestive enzymes Large portions of ingested food cannot be absorbed- > ½ nutrients not absorbed Copious fatty feces Pancreatitis- acute and chronic – – – Most commonly from excessive alcohol intake Also from blockage of the papilla of Vater by a gallstone When gallstone blocks passage of pancreatic enzymes- so much trypsinogen accumulates that it becomes activated to form trypsin- cascade continues – Active digestive enzymes now digest portions of the pancreas 8 Malabsorption q Sprue – – – Malabsorption Tropical (infectious) and nontropical (gluten enteropathy) When large portions of small intestine removed Gluten enteropathy or celiac disease- A type of sprue – – – – – Gluten has a destructive effect on intestinal enterocytes Decreases absorptive surface twofold Villi become blunted or destroyed Enterocytes replaced q 5 days- eliminating gluten from diet cures within a week Steatorrhea- excess fats in the stools Lactose intolerance– Enterocytes covering villi of small intestine must have lactase present to digest lactose. – Exogenous enzymes allow these individuals to consume lactose With severe malabsorption– – – Nutritional deficiency results in wasting Osteomalacia due to lack of calcium Macrocytic pernicious anemia from diminished vitamin B 12 and folic acid absorption 9 Malabsorption q Sprue – – – Malabsorption Tropical (infectious) and nontropical (gluten enteropathy) When large portions of small intestine removed Gluten enteropathy or celiac disease- A type of sprue – – – – – Gluten has a destructive effect on intestinal enterocytes Decreases absorptive surface twofold Villi become blunted or destroyed Enterocytes replaced q 5 days- eliminating gluten from diet cures within a week Steatorrhea- excess fats in the stools Lactose intolerance– Enterocytes covering villi of small intestine must have lactase present to digest lactose. – Exogenous enzymes allow these individuals to consume lactose With severe malabsorption– – – Nutritional deficiency results in wasting Osteomalacia due to lack of calcium Macrocytic pernicious anemia from diminished vitamin B 12 and folic acid absorption 10 Dumping Syndrome q Rapid entry of hypertonic meals into the intestine produces dumping syndrome Etiology: – After gastric bypass surgery to reduce the size of the stomach Gastric reservoir lost Interference with GI hormone signaling Suitable for restricted small meals If a patient overeats, the rapid absorption of glucose produces rapid hypoglycemia Distressing syndrome includes weakness, dizziness, and sweating after feeding – With rapid entry of hypertonic meals into intestine Provokes movement of large amounts water into gut Hypovolemia and hypotension result 11 II. Nausea and Vomiting 12 Causes of Nausea and Vomiting q Nausea- a prodrome to vomiting Nausea is caused by: – – – Irritative impulses from the GI tract Impulses that originate in the lower brain r/t motion Impulses from the cerebral cortex q Vomiting- GI tract empties itself when upper tract becomes irritated, distended, excited A protective response- an example of central regulation of gut function Vomiting is caused by: – – – – Excessive Irritation or Distension of the Upper GI Tract- especially duodenum Noxious stimuli in the gut lumen (infected food) CNS stimulation Effects of drugs – – – Rapidly changing motion Psychic stimuli - eg disquieting scenes Noxious odors 13 Ganong FIGURE 27–7 Neural pathways leading to the initiation of vomiting in response to various stimuli. 14 Vomiting Centers of the Brain q Major anatomical elements of vomiting: Chemoreceptor trigger zone (CTZ): – CTZ is located in the area postrema on the wall of the 4th ventricle – Area postrema is a sensory circumventricular organ Highly vascular Lacks a blood-brain barrier Brainstem Vomiting Center is in the medulla Nucleus tractus solitarius receives information from gut and CTZ – Noxious gut stimuli – And non-gut stimuli- smell, motion sickness, emotion, direct stimulation 15 Neural Pathways of Vomiting q Sensory afferents via: Upper GI tract (pharynx to upper small intestine) sends vagal and sympathetic afferent impulses to multiple brainstem nuclei CTZ lacks BBB- detects noxious chemical stimuli Vestibular organs respond to noxious movements q Motor impulses are transmitted by: CNs V, VII, IX, X, XII – Larynx and pharynx – Upper GI tract Efferent visceral autonomic fibers – Vagal and sympathetic nerves to lower GI tract Spinal nerves – to Diaphragm, abdominal, and intercostal muscles 16 Mechanics of Vomiting q Antiperistalsis – Retrograde peristalsis up the GI tract from the small intestine and stomach – Can occur from as far down as the ileum q Vomiting – An initial deep breath – Raising the hyoid bone to pull UES open – Closing of the glottis prevents aspiration – Lifting the soft palate to close posterior nares – Breath held in mid-inspiration – LES and esophagus relax – Strong downward contraction of diaphragm and a simultaneous contraction of the abdominal wall muscles squeezes the stomach and builds intragastric pressure until vomitus expelled 17 PONV Prophylaxis q Sensory input from: GI tract (NTS) CTZ (area postrema) Vestibular system q Receptors related to vomiting: For severe PONV- block multiple receptors Serotonin from enterochromaffin cells in small intestine initiate impulses via 5-HT receptors Receptors in area postrema and adjacent NTS 5-HT3 D2 q Common antiemetics/ prophylaxis: Ondansetron inhibits serotonin receptor subtype 5HT-3 Aprepitant inhibits substance P at the NK-1 receptor Metoclopramide inhibits dopamine at the D2 receptor Promethazine and diphenhydramine inhibit H1 and M1 receptors Scopolamine inhibits acetylcholine at M1 receptors (72 hours) Dexamethasone targets intracellular steroid receptors Famotidine antagonizes H2 receptors, decreases HCL production 18 Risk Factors for PONV Risk factors for PONV: Patient factors: – – – – – Female gender Nonsmoker History of motion sickness History of PONV Young patients Anesthesia Implications: – – – Long surgical duration Gynecological procedures Laparoscopic procedures – – Breast procedures Peds- T&A, strabismus Opioids Halogenated gases Neostigmine Solutions – – – Surgical risk factors: – – – Anesthesia Opioids-Multimodal analgesia Opioids- Regional anesthesia (preop) TIVA Prophylaxis – – – – Scopolamine patch Metoclopramide Decadron Pepcid 19 Gastrointestinal Obstruction q Obstructions may be caused by: Cancer Ulcer Spasm of a segment of the gut Paralytic ileus Fibrotic constrictions – from ulcerations/adhesions q Consequence of obstruction depends on location of obstruction: Pyloric obstruction – acidic vomitus – Causes metabolic alkalosis Small intestinal obstruction causes dehydration from vomiting large amounts intestinal fluidequal loss of stomach acid and intestinal base - neutral or basic vomitus Prolonged obstruction of the large intestine can eventually cause severe vomiting – Can lead to rupture of the intestine 20 1. A patient who has undergone anastomosis of his jejunum to his stomach reports to his primary care physician that he has experienced several episodes of nausea, cramping, dizziness, sweating, and a rapid heart rate an hour or two after ingesting large volumes of sugary beverages. What is his likely diagnosis? A. B. C. D. Hirschprung disease Achalasia Peptic ulcer disease Dumping syndrome 2. Which mechanism is likely most responsible for gastric ulcer formation? A. B. C. D. E. Back-leak of hydrogen ions Mucus secretion Proton pump inhibition Tight junctions between cells Vagotomy 3. A patient has peptic ulcer disease. Which of the following will eliminate the secretion of acid during the gastric phase of digestion? A. B. C. D. E. Antacids (Rolaids) Antigastrin antibodies Atropine Histamine H2 blocker Propton pump inhibitor 4. A patient who has maintained a grain-free diet since she was a child begins adding high fiber wheat and bran to her diet to reduce her serum cholesterol. The result is a 25pound weight loss with frequent stomach cramps, gas, and diarrhea. Which of the following is most likely increased in this woman? A. Hemoglobin concentration B. Carbohydrate absorption C. Fecal fat D. Protein absorption E. Serum calcium 5. Rapid change in direction or rhythm of motion of the body can induce vomiting. Which of the following is the likely origin of the impulses to the CTZ? A. Vomiting center B. Vestibular nuclei C. Area postrema D. GI tract 21