GI systems 2006

1、Physiology of the Esophagus and StomachGERD Patho PhysiologyBarriers to Gastroesophageal Reflux LES Tone Transient Relaxation of LES unrelated to swallingEsophageal Clearance Decreased esophageal PeristalsisGastrodudenal Factors GastroparesisMucosal Resistance Defensive Factors in MucosaNormal Acid

2、ProductionGastroesophageal Reflux DiseasePathophysiology Hiatus Hernia Predisposes to more severe esophagitis Kasapidis P Dig Dis & Sci 1995 Visceral Hypersensitivity Role in NCAAP Mayer EA Gastro 1994 Alkaline Reflux Is not important Champion G Gastro 1994 Helicobacter Pylori Not important in t

3、he pathophysiology of GERD NIH Consensus Conference 1994Conditions and Factors that Increase the presence of Acid in the Esophagus Transient relaxation of the LES Decreased LES resting tone Impaired esophageal clearance Diminished salivation Delayed gastric emptying Hiatus hernia Lifestyle and dietG

4、astroesophagealPathophysiology Nitric Oxide Important in the control of : Esophageal peristalsis LES sphincter TLESRArand. NAMJ. Physio 1994TLESRFundic distension appears to be major stimulantDepends on the release of Nitric OxideBoulant. JGastro 1994Epidemiology of GERDChronic persistent symptoms a

5、nd complicationFrequent SymptomsMild recurrent symptomsGastroenterologistFamily physicianOTC / Self medicationAdapted from Castell et al, 1985Typical Symptoms of GERD1.Pyrosis (Heartburn)2.RegurgitationAtypical Symptoms of GERDPulmonary and ENT symptoms Asthma, intermittent wheezing, chronic cough S

6、ore throat, vocal chord inflamation with hoarseness Posterior laryngitis Globus sensation, polyps on vocal chords Chronic bronchitis, aspiration pneumonia Chronic intertitial pulmonary fibrosis EaracheOther Noncardiac chest pain Waterbrash, gingivitis, dental enamel erosion Hiccups, halitosis Nausea

7、 / VomitingAlarm Symptoms of GERD Dysphagia Odynophagia GI bleeding Chronic anemia Weight loss Non cardiac angina-like chest pain Failure to respond to 4 to 8 weeks of medical therapyLifestyle and Dietary Factors that Aggravate Symptoms of GERD Eating very large meals Eating spicy or fatty foods Smo

8、king / tobacco Obesity and tight clothing Laying down 2 hours after eating Certain medicationFoods that Exacerbate GERD Coffee ( even decaffeinated) Alcoholic beverages Chocolate and peppermint Fatty foods Caffeine Tomato products Citrus fruit and juices Certain spices like pepper Raw OnionsTable 1.

9、 Diagnostic tests in GREDTests to determine the presence of refluxAmbulatory 24-hour pH recordingBarium mealRadionuclide scintigraphyTests to determine whether symptoms are due to reflux24-hour pH recordingBernstein (acid perfusion) testTests to determine the presence of mucosal damageEndoscopyMucos

10、al biopsyBarium mealTests Available for Diagnosis of GERDEndoscopyBarium meal /Upper GI seriesEsophageal motility study (manometry)24-hour ambulatorypH monitoringBernstein testSavary-Miller Classification of Reflux EsophagitisGrade 1 One or more erosions with erythema, with or without exudateGrade 3

11、Multiple circumferential erosionsGrade 2Confluent exudative erosions notcovering the entire circumferenceof the esophagusGrade 4Chronic mucosal lesions : Ulcers, stricture, scarring, Columnar epitheliumReflux oesophagitis : Savary & Miller stage 11. Samll tongue-shaped erosion2. Z-line: transiti

12、on from squamous epithelium to columnar epithelium3. Inflammatory vascular alteration of the squamous epithelium Reflux oesophagitis: Savary & Miller stage 21.Aphthous longitudinal erosions with surrounding mucosal oedema2.Early confluent erosionsReflux oesophagitis: Savary & Miller Stage 31

13、. Longitudinal erosion, party scabbed2. Circular confluent erosive lesionReflux oesophagitis Savary & Miller Stage 41. Circular, partly flame-shaped erosions with hyperaemic halo2. Constricted lumen of the oesophagusEsophageal Manometry and 24-Hour pH MonitoringEsophageal ManometryLESHypotensive

14、Transient LES relaxationEsophageal body:Low amplitude esophageal wavesDisordered peristalsis24-Hour pH Monitoring:Time with pH 5 minLongest reflux episodeIndications for Use of Barium Meal and H. pylori TestingBarium Meal:RingsHiatal herniaCancerH. Pylori Testing:Controversial best not to testInvest

15、igate ? One in a life time Endoscopy looking for Barretts Esophagus. Alarm Symptoms Atypical Patients Symptoms Failure to respond to a PPIInvestigation of GERD Barium Swallow Endoscopy ( + Biopsy) 24 hr Ambulatory pH Esophgeal ManometryGERDNERD Traditional concept: Milder: NERD New concept: More sev

16、ere: Erosive esophagitisBarretts esophagusNERDErosive esophagitisBarretts esophagusAdapted from Chey WD. Am J Med 2004;117(suppl 5A):36SGastroesophageal reflux diseaseFunctional heartburnNonerosive reflux diseaseErosive esophagitisEndoscopy-negative reflux diseaseA heterogeneous group of disorders p

17、resenting as typical symptoms of gastroesophageal reflux in the absence of visible esophageal injury at endoscopyA recent study (n = 543) found: NERD in 55% of women, 38% of men Women have significantly higher symptom severity scores for: Heartburn Regurgitation Belching Nocturnal symptomsLin M, et

18、al. Am J Gastroenterol 2004;99:1442GERDGASTROPARESISTreatment for GASTROPARESIS Diet Drugs Botulism Toxin Gastric Pacing SurgeryTREATMENT FOR GASTROPARESISDIET Small Frequent meals Low fat Low residue Liquids tolerated better than solids Good Glycaemic control Jejunal Feeding Tube (80 ml/hr over nit

19、e) TPNGASTROPARESIS - DrugsTHE PRESENT Metoclopramide Erythromycin Domperidone Cisapride TegaserodTHE FUTURE Clonidine Sildenafil Tadafil MosaprideTHE PAST Motilin Agonists (Motiloids)GASTROPARESISCombination TherapyDopamineAntagonism5HT4AgonismMetoclopramideDomperidoneCisaprideTegaserodDose: hour A

20、/C meals and HSANTI-EMETIC/ANTI- NAUSEANTS Treatment Gravol Metoclopramide Domperidone Prochloperazine (Stemetil) P.O or Suppository Ondansetron (Zofran)Treatment for GASTROPARESIS Diet Drugs Botulism Toxin Gastric Pacing SurgeryGoals for the Treatment of GERD Eliminate symptomsHeal esophagitis, if

21、presentPrevent ComplicationsPrevent recurrence (maintenance therapy)Improve quality of lifePharmacological Treatment of GERD Over-the-counter medications H2-receptor antagonists Prokinetic agents Proton pump inhibitors (PPIs)Treatment of GERD Step Up vs Step DownManagement of the First Encounter and

22、 Maintenance Therapy of Uncomplicated GERD Lifestyle Modifications OTC Antacids H2 Receptor Antagonists Step-Up ApproachFoods that decrease LES pressure Fatty foods Caffeine Chocolate Peppermint AlcoholMedications that Exacerbate GERDBy decreasing LES pressure or delaying Gastric emptying Beta adren

23、ergics Calcium channel blockers Anticholinergics Theophylline ProgesteroneGastroesophageal Reflux DiseasePathophysiology Hiatus Hernia Predisposes to more severe esophagitis Kasapidis P Dig Dis & Sci 1995 Visceral Hypersensitivity Role in NCAAP Mayer EA Gastro 1994 Alkaline Reflux Is not importa

24、nt Champion G Gastro 1994 Helicobacter Pylori Not important in the pathophysiology of GERD NIH Consensus Conference 1994Agents that Decrease LES Pressure and-or Slow Gastric EmptyingFoodsFatChocolateCoffeePeppermintsDrugsAnticholinergicsNitratesTheophyllinesNicotine (smoking)Alpha-blockersCalcium ch

25、annel blockersLevodopaNarcoticsHormones / MiscellaneousProgesteronesEstrogenCholecystokininSomatostatinBeta-agonistsProstaglandinsAntireflux Lifestyle & Dietary Modifications Limit consumption of fatty foods, cafeine, mint and chocolate Limit consumption of tomato-based foods, citrus juices and

26、spicy foods Avoid excess alcohol Avoid eating large meals Avoid reclining less than 2 hours after a meal Elevate head of the bed 10 to 15 cm Lose weight Avoid wearing tight clothing Discontinue drug therapies that worsen GERD, if possible Quit smokingH2 receptor antagonist in GERD Effective symptom

27、rellief in nonerosive disease Often ineffective in healing erosive esophagitis Probably no important difference among agents Bid-qid dosing necessary Safe in long-term use at standard dosingGERD H2 Receptor AntagonistsCimetidineTagmet600 mg BID or TIDRanitidineZantac150 mg BIDFamotidinePepcid 20 mg

28、BIDNizatidine Axid150 mg BIDGERDProton Pump InhibitorsOmeprazoleLosec20-40 mg ODLanzoprazolePrevacid30 mg ODPantoprazole Pantoloc40 mg OD(Esomeprazole)(Nexium)40 mg ODPharmacologic Traits of PPIs Require parietal cell activation Possess a plasma half-life of 1 to 2 hours Possess a duration of action

29、 of 24 hoursOxyntic GlandThe Binding Action of PPIsApo-Omeprazole20mgLosecOmeprazole20 mgPantolocPantoprazole40mgPrevacid Lanzopazole30mgNexiumEsomeprozole40mgParietRapebrazole20mg$1.60?Proton Pump Inhibitors 2005ParietRabeprazole10mg 20mg Apo-Omeprazole20mg$1.52LosecOmeprazole20 mg$2.20PantolocPant

30、oprazole40mg$1.95Prevacid Lanzopazole30mg$2.00NexiumEsomeprozole40mg$2.10ParietRapebrazole20mg$1.60?Proton Pump Inhibitors 2005ParietRabeprazole10mg $0.6520mg $1.65Apo-Omeprazole40mg$3.04LosecOmeprazole40 mg$4.40PantolocPantoprazole40mg$1.95Prevacid Lanzopazole30mg$2.00NexiumEsomeprozole40mg$2.10Par

31、ietRapebrazole20mg$1.60?Proton Pump Inhibitors 2005ParietRabeprazole10mg $0.6520mg $1.65Treatment of Gastroesophageal Reflux DiseaseCost for 28 Days TherapyCimetidine 600 mg BID $21.59*OTC Zantac 75 mg BID $29.96Ranitidine 150 mg BID $35.89*OTC Pepcid 10 mg BID $44.97Famotidine 20 mg BID $49.89*Niza

32、tidine 150 mg BID $62.68*Omeprazole 20 mg OD $78.75*Omeprazole 20 mg BID $146.51*Lanzoprazole 30 mg OD $72.59*Pantoprazole 40 mg OD $69.51*Includes prescription dispensing fee of $10.99Symptom Severity for GERDMildModerateSevereReflux symptoms less then 3x/weekSymptoms present for less than 6 months

33、Symptoms do not interfere with daily activityPain (heartburn) intensity in symptoms of the order of 1-3 out of a grading of 10Defined as mid-range between mild and severe symptomsDaily attacks of reflux painSymptoms present for longer than 6 monthsSymptoms regulary interfere with daily activity and

34、can awaken the patient at nightPain (heartburn) intensity in symptoms of the order of 7-10 out of a grading of 10 Proposed clinical classification of severity of disease. Note that this classification does not necessarily correspond to endoscopic severity. Severe complicated esophagitis or Barretts

35、may present clinically with mild symptoms.Treatment of GERDA patient who has responded poorly to PPI therapydespite: Regular and appropriate use of the PPI A trial of a different PPI A trial of an increased dose of the PPI Review lifestyle issues NSAIDs, OTC drugs, smoking, alcohol use Nocturnal sym

36、ptoms: raise head of bed, do not eat near bedtime, use a pre-dinner PPI dose Endoscopy ? CADET-PE: empirical treatment is safe in young, otherwise healthy patients H pylori: Test-and-treat favoured in Europe Going straight to empiric therapy generally favoured in North AmericaFollow-up and reassessm

37、ent are importantReview the diagnosis and consider Changing the PPI Ambulatory esophageal pH monitoring and motility study (impedance testing) Alternatives to acid suppression Prokinetic agents Tricyclic antidepressants (few data) Combination therapy with a prokinetic Surgical options (in rare cases

38、)GERDWho to consider for surgery: Younger patient 10 years. Barretts epithelium and low-grade dysplasia generally warrant surveillance. Risk factors for development of adenocarcinoma in patients with Barretts epithelium: white, male, longer duration, severity and frequency of GERD, size of hiatal he

39、rnia, obesity, smoking, dysplasia, diet low in fresh fruit Long-term PPI therapy has not been associated with any clinically significant adverse events.GERDConclusion Major Pathophysiology TRLES Look for alarm symptoms and investigate Treatment step up approach Treatment step down approach controver

40、sial Consider surgery in younger patients Complications of GERD Peptic Stricture Barretts Esophagus Respiratory Problems Asthma Cough ENT problems LaryngitisTumor of the oesophagus1. Barretts Syndrome2. Polypous Tumor Formation (adenocarcinoma)Sliding hiatal hernia : represented by inversion1. Shaft

41、 of the endoscope2. Schatzkis ring3. Hiatal lumenNon-Reflux Esophagitis Infectious Esophagitis Candida Esophagitis Herpes Esophagitis Pill Induced Exophagitis Doxyccycline NSAIDs KLC Fosamax Radiation induced EsophagitisGastroesophageal Reflux DiseasePathophysiology Hiatus Hernia Predisposes to more

42、 severe esophagitis Kasapidis P Dig Dis & Sci 1995 Visceral Hypersensitivity Role in NCAAP Mayer EA Gastro 1994 Alkaline Reflux Is not important Champion G Gastro 1994 Helicobacter Pylori Not important in the pathophysiology of GERD NIH Consensus Conference 1994Antireflux Lifestyle & Dietary

43、 Modifications Limit consumption of fatty foods, cafeine, mint and chocolate Limit consumption of tomato-based foods, citrus juices and spicy foods Avoid excess alcohol Avoid eating large meals Avoid reclining less than 2 hours after a meal Elevate head of the bed 10 to 15 cm Lose weight Avoid weari

44、ng tight clothing Discontinue drug therapies that worsen GERD, if possible Quit smokingAgents that Decrease LES Pressure and-or Slow Gastric EmptyingFoodsFatChocolateCoffeePeppermintsDrugsAnticholinergicsNitratesTheophyllinesNicotine (smoking)Alpha-blockersCalcium channel blockersLevodopaNarcoticsHo

45、rmones / MiscellaneousProgesteronesEstrogenCholecystokininSomatostatinBeta-agonistsProstaglandinsEsophagealMotorDisorderEsophageal Motor Disorders Oropharyngeal Esophagus and LES Nut Cracker Esophagus Diffuse Esophageal Spasm Achalasia Scleroderma Non Cardiac Angia Like Chest PainDysphagia Difficult

46、y in swallowingMechanical ObstructionIncoordinate motor activityOdynaphagia Painful SwallowingGERDCandidiasisHerpes EsophagitisOropharyngeal Dysfunction Patho Physiology Bulbar Palsy Pseudobulbar PalsyOropharyngeal Dysfunction Symptoms Dysphagia Globus Inhalation Investigations Video-Fluroscopy Bari

47、um Swallow ManometryOropharyngeal Dysfunction Treatment Eating Slowly Double swallow Cricopharyngeal MyolomyEsophageal Motor Disorders Primary Aetiology Unknown Secondary GERD Neuropathy Diabetes SclerodermaEsophageal Motor Disorders Symptoms Dysphagia Chest pain Associated with: Heartburn Regurgita

48、tion Investigation Barium Swallow (Solid Bolus) Endoscopy Esophageal ManometryAchalasiaPathophysiology Degeneration of inhibitory nitric oxide neurons in LES and body of esophagus Degeneration of vagal nerve Dorsal motor nucleiChagas Dislease Trypanosoma Cruzi destroys myenteric neuronsSecondary Ach

49、alsia Neoplasms Lung GastricAchalasiaManometryAperistalsis in lower esophagusHigh LES pressureAbsent or incomplete LES relaxation to swallowingAssociated DES a Vigorous AchalasiaBarium SwallowDilated EsophagusBeak Like Appearance at LesNo Gastric BubbleAchalasiaSymptoms Dysphagia Solids Liquids Rare

50、ly Heartburns Regurgitation Chest pain Weight lossTreatmentCalcium Channel BlockersPneumatic Balloon Dilatation60-80% effectiveBotox injectionHeller Myotomy + FundoplicationLaproscopic MyotomyAchalasiaComplications Malnutrition Pulmonary Aspiration Esophageal Diverticula Squamous Cell Carcinoma Esop

51、hageal RuptoriSclerodermaPathophysiologySmall blood vessel damageIntramural neuronal dysfunctionFibrosis and muscle damageManometryLax LESAperistaltic EsophagusSymptomsHeartburnDysphagiaTreatmentPPIEsophageal DilatationThe Esophagus as a cause of Angina-like Chest Pain 1/3 of patient with Angina-lik

52、e symptoms have normal cardiac exam Non cardiac chest pain GERD DES Pathophysiology ? Abnormal Visceral PerceptionThe Esophagus as a cause of Angina-like Chest PainInvestigation Endoscopy Manometry with provocative testing 24 hour ambulatory PH Tial of a PPITreatment Exclude cardiac cause PPI Nitrat

53、es Calcium Channel BlockerHypertensive LESManometry High LES Pressure Normal relaxationSymptoms Dysphagia Chest PainTreatment Acid Suppression Nitrates Calcium Channel Blockers Botox injectionZenkers Diverticulum Acquires Pulsion Diverticulum Posteriorly Midline Secondary to CPS Dysfunction Treatmen

54、t - SurgeryGERDGASTROPARESISTreatment for GASTROPARESIS Diet Drugs Botulism Toxin Gastric Pacing SurgeryTREATMENT FOR GASTROPARESISDIET Small Frequent meals Low fat Low residue Liquids tolerated better than solids Good Glycaemic control Jejunal Feeding Tube (80 ml/hr over nite) TPNGASTROPAESIS - Dru

55、gsTHE PRESENT Metoclopramide Erythromycin Domperidone Cisapride TegaserodTHE FUTURE Clonidine Sildenafil Tadafil MosaprideTHE PAST Motilin Agonists (Motiloids)GASTROPARESISCombination TherapyDopamineAntagonism5HT4AgonismMetoclopramideDomperidoneCisaprideTegaserodDose: hour A/C meals and HSANTI-EMETI

56、C/ANTI- NAUSEANTS Treatment Gravol Metoclopramide Domperidone Prochloperazine (Stemetil) P.O or Suppository Ondansetron (Zofran)TREATMENT OF GERDContinuous TherapyPulse TherapyPRN TherapyGERD Apo-Omeprazole20mgLosecOmeprazole20 mgPantolocPantoprazole40mgPrevacid Lanzopazole30mgNexiumEsomeprozole40mgParietRapebrazole20m