Journey through the GI tract

1. Journey through the GI tract Barb Bancroft, RN, MSN www.barbbancroft.com BBancr9271@aol.com

2. Open wiiiiiiide… • Let’s take a journey through the GI tract with a few stops along the way…

3. The Teeth • Tooth loss and heart disease • Periodontal disease, subclinical vasculitis and coronary plaque development • State with the least teeth is the state with the most heart disease

4. Oral bacteria and coronary artery disease • Specific periodontal pathogens are implicated • Enter the bloodstream via small ulcers that develop in the gum tissue of patients with periodontal disease • Contribute to plaque formation via inflammation; induce platelet aggregation and clot formation • 4 bacteria are implicated—Tannerella forsythia, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Treponema denticola. • Depending on the bacterial concentration, the increased risk of heart attack in persons with one or another of these bacteria ranges from 200-300 percent, compared to people with no evidence of the bacteria

5. Floss • “Floss only the teeth you want to keep…” • MINUTIAE: On average, each person uses 54 feet of dental floss every month or about 1.5 feet of floss per day which equals 548 feet of floss in a year.

6. Meth mouth • 22 y.o. meth user; snorted and/or injected meth x 2 years • Denied use of any other drugs • Drank 2-3 liters of carbonated drinks each day because of a dry mouth • How addicting is methamphetamine? Dopamine and addiction • (British Journal of Medicine 2006;333:156)

7. Osteoporosis and tooth loss • Osteoporosis of the mandible and maxilla on dental X-rays—loss of trabecular bone • Women who do NOT take estrogen have fewer teeth

8. Bites • The bite scale. The King of the Jungle, the African lion, has a bite force of only 940 pounds (427 kg). Hyenas register a 1,000-pound (454 kg) bite which explains why they might get the best of the African lion. Dusky sharks manage only 300 pounds (136 kg) of force.

9. Bites • Labrador retrievers nip at your ankles with 125 pounds (57 kg) of force, only slightly surpassed by the infamous Mike Tyson, the heavyweight boxer, who chomped off Evander Holyfield’s ear with a force of 170 pounds (77 kg). • Had we lived in the day of the dinosaur, Tyrannosaurus Rex, the bite would have registered 3,011 pounds (1369 kg). • What about Petey the pit bull? Endorphins, L-tyrosine and dopamine

10. Other human bites • Self-inflicted bites • Thumb-sucking • Seizures (can you swallow your tongue?) • Child abuse

11. Gingival hypertrophy • Drugs—phenytoin (Dilantin), nifedipine (Procardia), cyclosporine • Leukemias—acute and chronic

12. The immunocompromised patient • Candida albicans (inhaled steroids in asthmatics) • Diabetics with hyperglycemia • Fungal infections and TNF-α antagonists (infliximab/Remicade; adalimumab/Humira; certolizumab/Cemzia etanercept/Enbrel) • HSV-1, HSV-2 • Kaposi’s sarcoma • HPV • HIV (TB)

13. OPEN Wide • Aphthous ulcers and celiac disease • Mouth clues to vitamin deficiencies • Vitamin C—gingivitis, dental erosion • Vitamin B2 (riboflavin)—stomatitis, cheilosis, geographic tongue • Vitamin B3 (niacin), B6 (pyridoxine), B12 (cobalamin), folic acid (B9)—glossitis • Calcium (hypocalcemia)—numbness and tingling around the mouth**; tetany; Chvostek’s sign; Trusseau’s sign

14. Say “ah”… • Soft palate and the uvula • Relationship of the pharyngeal musculature with CN IX (Glossopharyngeal) and X (Vagus) • Stroke patients • Swallowing • What is the hardest thing to swallow?

15. Water… • Ya’ can’t size it, ya’ can’t shape it…

16. Back to CN IX and X • The gag reflex • CN IX and X close off the nasopharynx • Head injured patients lose their gag reflex and have a high risk of aspiration pneumonia • Open your mouth and pant like a dog • “K, K, K, K, K” • uvula midline

17. Causes of nasal speech • Cleft palate (folic acid!!) • Lou Gehrig’s (ALS) disease • Glossopharyngeal nerve palsy—(viral) • Guillain-Barré syndrome with bulbar onset (cranial nerve onset vs. ascending paralysis beginning with the longest nerves first—ie. the feet) • #1 cause of Guillain-Barré

18. The “PRILS” Muffled speech Swollen lips, pharyngeal edema Hives around the mouth Highest risk patients? Don’t forget the cough… Drugs discovered because of a bite—Brazilian pit viper Captopril (Capoten) Enalapril (Vasotec) Lisinopril (Prinivil, Zestril) Perindopril (Aceon) Moxepril (Univasc) Benazepril (Lotensin) Quinapril (Accupril) Trandolapril (Mavik) Ramipril (Altace) Etc… Diabetics, HBP, CHF, post-MI) ACE inhibitors and angioedema

19. Hoarseness • Vocal cords supplied by a branch of the vagus--recurrent laryngeal nerve • Causes of hoarseness? increased vocal cord thickness--testosterone, hypothyroidism, acromegaly, aneurysm of the thoracic aorta, lung cancer, and GERD—just to name a few • Hypothyroidism, large tongue, teeth indentations--♀ > ♂ • Amyloidosis

20. Salivary glands—parotid, sublingual, submandibular • Parotid gland—MUMPS (kids and vaccines) • Hypertrophy of the parotid gland in women with eating disorders (serum amylase will be elevated) • Acetylcholine innervates the salivary glands to produce saliva • Drugs to boost acetylcholine for patients w/ dry mouths—5 mg QID pilocarpine; cevimeline (Evoxac) • Artificial saliva?

21. More on saliva • Sjögren’s syndrome (sicca)—autoimmune disease; may be primary or secondary to another autoimmune disease such as lupus • Saliva as innate defense--IgA • Taste and saliva—the elderly and anticholinergic drugs; stop the flow of saliva

22. Drugs with anti-cholinergic properties • Amitryptyline (Elavil) • Doxepin (Sinequan) • oxybutynin (Ditropan) • Meclizine (Antivert) • Theophylline • Captopril (Capoten), nifedipine (Procardia) • Prednisolone • digoxin • dipyridamole (Persantine) • warfarin • Furosemide (Lasix) • isosorbide dinitrate (Isordil)

23. More anticholinergic drugs • Codeine • Oxycodone • Fexofenadine (Allegra) • thioridazine (Mellaril) • Hydroxyzine (Atarax) • Loratadine (Claritin) • dicyclomine (Bentyl) • Cimetidine (Tagamet), ranitidine (Zantac) • benztropine (Cogentin) • trihexyphenidyl (Artane) • Diphenhydramine (Benadryl) • haloperidol (Haldol)

24. Sublingual • Saliva and sublingual drugs—you need saliva to absorb sublingual drugs • NTG under the tongue to vasodilate the coronary arteries in patients with anginal chest pain • Jaundice and soft palate/sublingual mucosa

25. How much saliva do you make a day? about 1 liter of saliva per day How many times do you swallow in an hour? (70/200/10) Swallowing is something we take for granted…spit in a cup! Swappin’ saliva…chemistry? MHC complex Speaking of saliva…

26. Neurologic conditions • Parkinson disease • Low dopamine with a relative increase in acetylcholine • Relative increase in acetylcholine results in excess saliva and drooling

27. You take swallowing for granted--until you have this sore throat… • Say ahhhhh… • Can you say “ouch”? • Can you say “I have a sore throat, and I can’t swallow…” • Group A beta hemolytic strep • Peritonsillar abscesses

28. Enlarged tonsils • EBV infection of tonsils • Waldeyer’s ring (tonsils and adenoids) • Kids and sleep apnea; kids, lack of sleep and growth hormon • Adults and sleep apnea? (hypertension, CAD in adults) • Behavior disorders? ADHD? In kids? • Non-Hodgkin’s lymphoma

29. Oral signs of an eating disorder • The frequent vomiting and nutritional deficiencies often associated with eating disorders can severely affect health • 89% of bulimic patients have signs of tooth erosion; over time, loss of tooth enamel can be considerable • Change in color, shape, length • Brittle, translucent, and sensitive to temperature • Swelling of salivary glands • Dry and cracked lips • Chronic dry mouth

30. Oral cancers • Causes? The usual suspects… • Tobacco, smoked, chewed, pipes, cigars, cigarettes, cigarillos • Alcohol?

31. Cut back on the booze… • Alcohol is on the list of “probable cause” for cancers of the colon, rectum and breast; “convincing cause” of cancers of the mouth and pharynx, larynx, esophagus, liver, and “possible cause” for lung cancer.

32. The big surprise…Oral cancers and HPV • HPV-16 and oral sex • mouth/throat cancer • Will the HPV vaccine (Gardisil) prevent this type of cancer if given early?

33. Let’s move into the esophagus • Hollow, highly distensible muscular tube that extends from the pharynx to the gastroesophageal junction at the level of T11 or T12 vertebra. • 10 to 11 cm in the newborn • 23 to 25 cm in the adult • A 2-4 cm segment just proximal to the anatomic esophagogastric junction, at the level of the diaphragm, is the LES, or lower esophageal sphincter

34. GERD (gastroesophageal reflux disease) • ACID is the bad guy • The Lower Esophageal Sphincter (LES) pressure • With GERD--decreased pressure in the lower esophageal sphincter due to drugs, nicotine, alcohol, fatty foods, peppermint, chocolate, citrus fruits and juices, increased pressure in stomach (late evening meal) • So, how about a pizza, cold beer and a cigarette before bedtime? • What drugs? Bronchodilators, NTG, tetracycline, quinidine, KCl, NSAIDS, Iron salts, bisphosphonates, Viagra and other ED drugs • Obesity

35. What are non-drug ways to reduce GERD? • Dietary changes? • A meta-analysis in the Archives of Internal Medicine revealed support for 2 measures: • Weight loss and head-of-bed elevation • Avoiding tobacco, alcohol, high-fat foods, and carbonated beverages was NOT shown to alleviate symptoms of GERD—even tho’ there is substantial evidence that consumption of these substances has an adverse impact on GERD

36. Pharmacology of GERD • Classic reflux sx (heartburn, reflux) have a + predictive value of 80% • Empiric therapy can be started without endoscopy, but endoscopy can only tell whether or not erosive esophagitis is present • PPIs (Proton Pump Inhibitors)—the “prazoles” are the mainstay of therapy in healing erosive esophagitis and treating symptoms of GERD • Omeprazole (Prilosec), lansoprazole (Prevacid), pantoprazole (Protonix), rabeprazole (Aciphex), and “the purple pill”—esomeprazole (Nexium) • Fastest acting—esomeprazole, rabeprazole, omeprazole, lansoprazole, pantoprazole

37. Drugs to treat GERD • MOA—Inhibition of the proton pump at the luminal surface of the stomach…especiallyafter a meal—work best when taken 30-60 minutes before breakfast or dinner H+, Intrinsic Factor-B12 PPIs work here Luminal surface Parietal cell Basilar surface H2 H2 receptors H2 blockers work here

38. H2 blockers • Work by blocking H2 receptors on basal surface of the parietal cell; work best when taken at night to reduce nocturnal histamine secretion and acid production • Cimetidine (Tagamet)* • Ranitidine (Zantac) • Famotidine (Pepcid)** • *drug interactions and side effects • **least drug interactions and side effects and most effective

39. Has your patient been on the “prazoles” for longer than 5 years? • Check B12 levels in your patients… • The parietal cell that pumps acid also pumps out intrinsic factor (IF) • Intrinsic Factor is necessary for the absorption of B12 from food • If you stop pumping the acid into the stomach, you also stop pumping intrinsic factor for B12 absorption • Combine that with a decreased absorption of B12 over the age of 50 and you may have a B12 deficiency; • May also be caused by an autoimmune disease with antibodies against IF (pernicious anemia) • No acid, no calcium (elderly and patients on PPIs need to take calcium citrate for absorption) • No acid, no iron (check for iron deficiency anemia)

40. Hematologic and neurologic symptoms of B12 deficiency • Hematologic—megaloblastic anemia (big, immature RBCs)—MCV is greater than 120; also known as a macrocytic anemia • Neurologic—Cognitive dysfunction; Spinal cord dysfunction; peripheral neuropathy • The number 1 nutritional cause of dementia is B12 deficiency—is it reversible? Yes. • How can you supplement with B12?

41. B12 supplementation • Pill • Sublingual • Nasal • Injection • Need 6 mcg per day; take 1000 mcg by mouth/sublingual/nasal daily (1% via passive diffusion in stomach if you take B12 by mouth) • 1000 mcg/month via injection • Do not take over 3,000 mcg per day…the one dreaded side effect is:

42. Barrett’s esophagus • Complication of acid reflux (GERD) • Metaplasia of the lower third of the esophagus • What is metaplasia? The substitution of one adult cell for another adult cell • Usually a protective mechanism • Gastric epithelial cells have replaced squamous epithelial cells of the esophagus • Gastric epithelial cells are “used to” acid

43. What do we know about Barrett’s esophagus? • Patients with at least weekly symptoms of GERD—3-15% are found to have Barrett’s • May be a gross underestimate—autopsy findings were 20-fold higher than clinical studies • Caucasian males greater than 55; 2:1 ratio; big bellies contribute…Body fat increases intraabdominal pressure; fatty foods decrease LES pressure; high dietary intake of nitrates • Increased insulin resistance results in high serum levels of insulin-like growth factor-1 • Adenocarcinoma of the esophagus (10% in 1960; 50% in 2005); • One of fastest rising cancers in U.S.

44. What do we know about Barrett’s esophagus? • Progression to dysplasia is an ominous histologic finding—precursor to invasive adenocarcinoma • Annual risk is 0.5% per year • 30x to 40 x greater risk of adenocarcinoma w/ Barrett’s if greater than 2 cm of Barrett mucosa on endoscopy • Does ultra-aggressive anti-secretory therapy have anti-proliferative effects on intestinal metaplasia? Recent studies say yes…higher than conventional PPI doses • BID dosing if QD doesn’t relieve symptoms of GERD (35% of patients are on BID dosing) • Add H2 blocker at HS—double the OTC dose (Zantac 300 po hs) • Nocturnal symptoms are more often associated with severe disease—esophageal cancer, otolaryngologic and pulmonary disorders

45. Esophageal candidiasis/rupture • HIV patients—dysphagia in AIDS patients—also consider Herpes simplex and CMV esophagitis • Irritation and possible rupture in postmenopausal females taking bisphosphonates (Fosamax and friends) • Other pills “stick” • Lye, acids, and detergents

46. Esophageal dysmotility syndromes • Achalasia--LES is too tight, lack of peristalsis in lower third of esophagus; LES needs to be dilated frequently • Viagra has been used to open the LES (nitric oxide relaxes the sphincter) • Esophageal spasms (women and other spastic disorders)

47. Esophageal varices • How do you develop esophageal varices? • Due to increased pressure in the portal system of the liver • Primarily due to cirrhosis of the liver; 90% of patients with cirrhosis will develop varices • Worldwide, hepatic schistosomiasis is the second most common cause of variceal bleeding • Beta blockers to reduce portal pressure • 40% die with first episode, rebleeding occurs in more than half within one year

48. Major causes of cirrhosis of the liver today are… • Hepatitis C (15% clear on own; 85% develop chronic hepatitis; chronic hepatitis can lead to cirrhosis and hepatocellular carcinoma) • Hepatitis B (10% develop chronic hepatitis, 90% clear on own as adults; opposite percentages with infants and vertical transmission) • Alcohol (fatty liver) • Diabetes (fatty liver) • Obesity (fatty liver) • NASH (Non-alcoholic steato-hepatitis, also known as non-alcoholic fatty liver disease--NAFLD)

49. Hepatitis C virus--1989 • Cirrhosis with progression to hepatocellular cirrhosis

50. Hepatitis C virus—identified in 1989 HIGH RISK GROUPS—primary factors • IV drug user (even 1 time experimental drug use) • Blood transfusions prior to July1992 —or organ transplant recipients • Persons who have ever received hemodialysis • Hemophiliacs who received clotting factor concentrates prior to 1987 • Children born to HCV-infected moms (screen at age 1 or older)