3Digestion is the first stage of metabolism This system does secretory, motor, absorption, excretion and immune functions
4Anatomico-physiological bases Secretory function- formation and exudation of digestive juices into intestinal lumenDaily secretion:1,5 l saliva,2,5 l gastric juice,1,0 l pancreas juice,1,2 l bile,2,5 l intestinal juice
5Anatomico-physiological bases Motor function- food movement into intestinal pipe and its permanent mixing with digestive juicesAbsorbtion- absorption of some ingredients from undigested food and indigestible material
6Anatomico-physiological bases Excretion- moving off undigested food remainders and also some matters picked out in intestinal lumenImmune functionIn wall of large intestine there are accumulations of lymphoid tissue - “Peyer’s plaques”, where ripening of lymphocytes takes place
8Anatomico-physiological bases Basic stomach functions:physical and chemical processing of food, his depositing and evacuation;participation in metabolism;participation in hemostasis (synthesis of gastromucoprotein by parietal cells etc.);participation in water-salt metabolism;Synthesis of prostaglandines and gastrointestinal hormones
9Клиническая фармация в гастроэнтерологии Factors that play the great role of the development of inflammation diseases in the gastroduodenal areaProtective factorsmucusIonic gradientbicarbonatesprostaglandinsEpithelial cellsMucus membrane blood supplyAggression factorsDrugs and medicines (NSAIDs)hydrochloric acidPepsinHelicobacter pyloriКлиническая фармация в гастроэнтерологии
10Ways of examination: questioning The main complaints of GIT impairment:Pain (in epigastric area)Appetite disordersDysgeusiaEructationHeartburnNauseaVomittingConstipationDiarrheaMeteorismFatigueКлиническая фармация в гастроэнтерологии
11Laboratory and instrumental methods of examination Fiber-optic gastroduodenoscopyКлиническая фармация в гастроэнтерологии
12Laboratory and instrumental methods of examination Colonoscopy and biopsyКлиническая фармация в гастроэнтерологии
13Laboratory and instrumental methods of examination X-ray examination of GITКлиническая фармация в гастроэнтерологии
14Laboratory and instrumental methods of examination Bacteriologic, histologic and fast urea test of Н. PyloriКлиническая фармация в гастроэнтерологии
15Laboratory and instrumental methods of examination Non-invasive test : Breath test with ureaКлиническая фармация в гастроэнтерологии
16An algorithm approach to the diagnosis of GIT disorders Клиническая фармация в гастроэнтерологии
17Laboratory and instrumental methods of examination HematologyКлиническая фармация в гастроэнтерологии
18Laboratory and instrumental methods of examination Urinalysis and blood biochemistry testsКлиническая фармация в гастроэнтерологии
19Laboratory and instrumental methods of examination Faeces analysisКлиническая фармация в гастроэнтерологии
20Main syndromes in gastroenterology: Gastric dyspepsiaIntestinal dyspepsiaMaldigestion and malabsorptionHypovitaminosisGastrointestinal bleedingAsthenoneurotic syndromeAnemic syndromesPain syndrome
21Syndromes in GIT disorders Hypovitaminosis: skin dryness,angular cheilosis, stomatitis, hair loss,trophic changes of nails
22Basic stomach diseases Chronic gastritis - chronic inflammatory-dystrophyc process in stomach mucous, being attended with violation of cells regeneration processes and progressing atrophy of glandular epithelium
24Basic stomach diseases Chronic autoimmune gastritis (type A) - variant of chronic gastritis, conditioned by appearance of antibodies to parietal (acid-secretory) cells of stomach mucous
25Basic stomach diseases EtiologyAt the beginning of this disease there is fundamental importance of combination of the exogenic and endogenic factorsPathogenyAlong of antibodies making to parietal cells of mucous stomach takes place her damage.Hereinafter develops diffuse atrophy of stomach mucous, his secretory function lowers, up to significant secretory insufficiency.In part of cases there is a produce of auto-antibodies to gastromucoprotein (internal Castle’s factor) then which lead to the development of В12-deficiency anemia.
26Chronic autoimmune gastritis (type A) Clinical manifestations/ syndromes1.Pain syndrome: pain in epigastric area, temporary aching after food. Patients complaints about heaviness or sense of stomach enlargement, pressure in epigastric area and left subcostal area.2.Syndrome of gastric dyspepsia: lowering of appetite, disagreeable taste in mouth, eructation, nausea with possible vomiting.3.Syndrome of intestinal dyspepsia: rumbling sounds in abdomen, flatulency, leaning to diarrhea.
27Chronic autoimmune gastritis (type A) Clinical manifestations/ syndromes4.Maldigestion and malabsorption: dehydration due to diarrhea, hypovitaminosis, weight loss.5.Neurotic (asthenoneurotic) syndrome: weakness, irritability, paresthesias, cold sensations in the extremities, neurogenic, cardiogenic, vascular symptoms (angina like pains, hypotension).
28Chronic autoimmune gastritis (type A) Diagnostic criteria of chronic gastritis type АClinical manifestationsSpecial methods of investigationComplaints - blunt pains in epigastrium, appetite loss, disagreeable taste in mouth, nausea, heaviness after food, belch rotten, diarrheas.Examination - coated tongue, symptoms hypovitaminosis (skin dryness, hair loss, stomatitis and etc.), flatulency.X-ray examination- tone and peristalsis is weak, forced stomach evacuation.Gastroscopy faded mucous.Biopsy - stomach mucous atrophy and inflammation signs
29Chronic autoimmune gastritis (type A) Principles of medicinal therapy correction of gastric secretion violations (substitution therapy, forcing of gastric secretion).forcing of mucous regeneration process (anabolic hormones, biologic stimulants).correction of metabolic disturbances (aminoacids, vitamins, anabolic hormones).correction of motored violations (prokinetics).correction of intestinal digestion violations (polyenzymatic medications: festal, panzynormum).
30Basic stomach diseases Chronic gastritis (type B) - variant of chronic gastritis, induced by bacterium Нelicobacter pylori.
31Basic stomach diseases Etiologic factors may be EndogenousExogenous
32Basic stomach diseases Endogenous factorsGenetic predisposition:augmentation of parietal cells;surplus gastrin liberation;rise of pepsinogen level in blood;Violation in gastroduodenal movements;lack of pepsin inhibitors;violation of Ig A structure;blood group 0 (I);positive Rh-factor;Presence of antigenes HLA В5, В15, В35.
33Basic stomach diseases Exogenous factorsviolation of nutrition;harmful habits (smoking, alcohol, abuse of coffee);professional influences and mode of life;damaging action of medicinal preparations (anti-inflammatory drugs, corticosteroids, some antibiotics, iron preparations, potassium).To be infected by Helicobacter pylori
34Basic stomach diseases Clinical manifestations Pain syndrome: “hungry” pain (nighttime pain) in epigastric area, which can stop after food intake;Neurotic syndrome: irritability, fatiguability, bad sleep;Syndrome of gastric dyspepsia: heartburn, nausea, sour belch;Syndrome of intestinal dyspepsia: constipations.
35Basic stomach diseases Diagnostic criterions of chronic gastritis type ВClinical manifestationsSpecial methods of investigationComplaints - hungry epigastric pains, vomiting on pains height, heart-burn, belch sour, constipation.Examination - sickliness attached to epigastral palpationX-ray exam- raised tonus of stomach antral area, peristalsis is weakened, hypersecretion signs.Gastroscopy - edema and hyperemia of mucous, folds hypertrophy mucous stomach.Biopsy - signs of chronic inflamma-tion and hyperplasia mucous of stomach antral area.
36Symptoms of Dyspepsia Ulcer-like Dominant Dysmotility-like Dominant Nocturnal painLocalized epigastric burningBetter with foodHeartburnRetrosternalburningNauseaBloatingEarly satietyWorse with food
37Major Causes of Dyspepsia Williams 1988 Stanghellini 1996 Heikkinen (n=1386) (n=1057) (n=766)% of Patients with DiagnosisGastric Cancer Peptic Ulcer Esophagitis/ Functional
39Helicobacter pyloriA spiral shaped, Gram-negative, microaerophilic, and flagellated bacterium, living in the stomach and duodenumAbout 3 microns long with a diameter of about 0.5 micronCausing up to 80% of peptic ulcers, more than 90% of duodenal ulcers, and some types of gastritisRediscovered in 1982 by the laureates and made connection with stomach ulcers and gastritisHelicobacter pylori (blue bars, curved, 2-4 microns) localized in the mucus on the mucous surface, at the intercellular lines. Photo: tangential section of the gastric mucous
40EpidemiologyApproximately two-thirds of the world's population is infected with H. pylori.70% - 90% in developing countries25% - 50% in developed countriesOver half the population is infected in early childhood in China.Most of those infected never have symptoms.The bacteria are most likely spread from person to person through fecal-oral or oral-oral routes.Possible environmental reservoirs include contaminated water sources.The source of H.pylori is unknown yet .
42Pathogenicity Stomach acid Gastric epithelium H.pylori lives in the mucus lining to escape from the highly acidic gastric juice. (Its helical shape facilitates its penetration of the mucus layer.)It can fight the acid by excreting an enzyme called urease.The immune system responds to the infection by sending white cells, killer T cells, and other infection fighting agents.However, they cannot easily get through stomach lining to reach the infection.As the immune response grows, immune cells die and release destructive compounds on the stomach lining cells.Within a few days, gastritis and perhaps eventually a peptic ulcer results.Gastric epithelium
45SymptomsThe most common ulcer symptom is burning pain in the epigastrium (the upper middle region of the abdomen). The pain typically occurs when the stomach is empty.Less common symptoms include nausea, vomiting, and loss of appetite.Bleeding can also occur.Recent studies have shown an association between long-term infection and the development of gastric cancer, which is the most common cancer in China.
46Testing for H. pylori Test Sensitivity Specificity Cost Comments C13 or C14 90% to 100% 96% to 100% ++ Limited - requires urease breath nuclear medicine test departmentSerology 91% to 98% 75% to 80% + Widely available commercial labsCapillary % to 90% 75% to 80% + Office test, must purchased by doctor adminEndoscopic 99% 99% ++++ Requires biopsy specialist Invasive(Cutler A. Gastro 1995;109:136. Megraud F. Scand J Gastro 1996;215:57)
47Fundamental rules of anti-ulcer therapy Steady lowering of acid reaction (рН > 3 not less h/day):Proton pump ihibitorsН2-histaminoblockersAntacidsEradication of Helicobacter pylori:AntibioticsBismuthDerivative nitromidazoleRise cytoprotection (peculiarly attached to gastric ulcers ):SucralfateColloid bismuthSynthetic analogues prostaglandinsReparantsUse of medications with minimum side effectsOptimum compliance (observance by treatment program)
48H. pylori Eradication (All given for one week) Treatments of choiceRegimen PPI AntibioticsPPI - AC BID Amoxicillin 1 g bid Clarithromycin 500 mg bidPPI - MC BID Metronidazole 500 mg bid Clarithromycin 250 mg bidAlternatePPI - BMT BID Bismuth 2 tabs qid Metronidazole 250 mg qid Tetracycline 500 mg qid
49H. pylori Eradication cure by one medication does not adapt First line therapy:“triple therapy”: proton pump inhibitor (omeprazolum 20 mg twice/day or pantoprazolum 40 mg/ day) + antibiotics against Н. pylori (amoxicillin 1 g or metronidazol mg twice/day and clarithromycin (500 mg twice/day))First/Second line therapy: “cure standard” - “quadrotherapy therapy”proton pump inhibitor (omeprazolum 20 mg twice/day or pantoprazolum 40 mg/ day)metronidazol (500 mg triplicate/day)tetracycline (500 mg quadruplicate/day)bismuth (120 mg quadruplicate/day)Course of treatment -10 daysSecond line therapy:«tripletherapy» includesproton pump inhibitor (omeprazolum 20 mg twice/day or pantoprazolum 40 mg/day) from first to tenth dayclarithromycin (500 mg twice/day)levofloxacin (500 mg once/day)
50Acid Suppression Therapy for Ulcer-like Functional Dyspepsia H2-receptor antagonist for 4 weeksORProton pump inhibitor for 2 weeks
52Fundamental rules antihelicobacter therapy In the same patient it is not allowed to repeat the previously used therapy which turned to be ineffective oneIf two types of treatment regimens are not effective , and there id no significant eradication, then it is necessary to determine the sensitivity of Н.рylori strain to the whole spectrum of used antibioticsAdministration of back up “quadritherapy” regimen is desirable only after complete clarification of the failure of the different variants of “triple therapy”The presence of Н. рylori up to year after conducted therapy should be considered as an infection set-back, but and not einfection“Quadrotherapy” regimen must be used in case of infection set-back
53Management of Ulcer-like Functional Dyspepsia Ulcer-like Symptoms DominantEducation/lifestyle modificationTest Hp+-Trial of acid suppressionEradicate HpReassessSuccessFailureInvestigateTrial of prokinetic
54Lifestyle Modification for Patients with Functional Dyspepsia Small frequent mealsStop smokingReduce alcoholReduce caffeineAvoid irritating foodstuffsMaintain an ideal weightReview medications
55Risk Factors for Stomach Cancer Helicobacter pylori was the first bacterium to be officially recognized as a cancer-causing agent.Helicobacter pylori infection. Nitrates and nitrites are substances commonly found in cured meats, some drinking water, and certain vegetables, that can be converted by Helicobacter pylori, into compounds that have been found to cause stomach cancer in animals.
56Helicobacter pylori: associated pathology Gastritis B %Ulceration %Gastric Ca <1%Lymphoma (MALT) <1%De todas las patologías asociadas a la infección por Hp, la UGD es la que ha visto mas substancialmente modificado su manejo clínico por la irrupción de esta bacteria
57Gastro-oesophageal reflux disease chronic symptom of mucosal damage caused by stomach acid coming up from the stomach into the esophagus.GERD is usually caused by changes in the barrier between the stomach and the esophagus, including abnormal relaxation of the lower esophageal sphincter, which normally holds the top of the stomach closed, impaired expulsion of gastric reflux from the esophagus, or a hiatal hernia.
58Alginate-containing antacid Gastro-oesophageal reflux diseaseEndoscopic image of peptic stricture, or narrowing of the esophagus near the junction with the stomach: This is a complication of chronic gastroesophageal reflux disease and can be a cause of dysphagia or difficulty swallowing.Barrett’s oesophagusAlginate-containing antacid
59Undiagnosed dyspeptic patient Alginate-containing antacidHeart burn without “alarm symptoms”If symptoms persist after1 week of regular treatment then H2 antagonistIf symptoms persist after2 weeks of regular treatment the patient should be referred to the general practitioner