Case 2b(Child)Zazillah405110087

ANATOMY OF GIT(GASTRIC-ILLEUM)

GastricGastric most wide part of the digestive tract that serves as shelter to digest food into the chyme and manage streaming into the small intestine digestibility. Gastric has two holes (os cardiacum and pylorus), two arches (curvatura major and curvatura minor), and two surface (facies anterior and posterior).

Small Intestinesmall intestine comprises the duodenum, jejunum, and ileum .

Small IntestineDuodenum:Duodenum approximately 25 cm in length C-shaped surrounding the pancreatic caput Divided into four parts, namely pars superior, pars deccendens, pars horizontalis (inferior) and the pars ascendens

Pars ascendens duodeni:duodenum to jejunum with an indentation that called flexura duodenojejunal. This curve was detained by a band called the musculus suspensory fibromuscularis duodeni (Treitz ligament) Pars Descendens duodeni:there is a protrusion of the papilla major duodeni have anpullae hepatopancreaticae musculus sphincter (sphincter Oddi) that functions regulate expenditures of bile and pancreas.

PancreasPancreas is an exocrine and endocrine glands.Consisting of:Caput overwhelmed by the shape of the duodenal CNeck on the left caputCorpus in the upper left neckCauda at the left end of the pancreas

Hepar

HISTOLOGY OF GIT(GASTRIC-ILLEUM)

GasterCardiacCorpusFundus:T. MucosaeColumnar surface epitheliumGastric foveolaeT.propria+fundus glandsElastic membranT. M. MucosaeT. Submucosae

PyloricT. MucosaeColumnar surface epitheliumGastric foveolae (wide and deep)T.propria+pyloric glandsElastic membranT. M. MucosaeT. SubmucosaeT.muscularis

The glandsgastric glands start from the base of gastric pit, up to tunica muscularis mucosa*Fundus1. mucous neck cellthe apical site got zymogen granule which is constist of pepsinogen2. parietal cellproducing HCL& intrinsic factor3. chief cell4. argentaffin cell

Neck mucous cells. These are small columnar or triangular shape cells with a basal nucleus, larger granules that stain light purple, and more ribosoms than the surface mucous cells.

Parietal cells have a broad pyramidal base with central nuclei, clear cytoplasm and abundant mitochondria. concentrated in the upper and middle portions of the gastric glands. Parietal cells have an apical membrane invagination, called a secretory or intracellular canaliculy, where HCl is released through a unique H+/K+ ATPase. Parietal cells also secrete intrinsic factor, a glycoprotein that aids in Vitamin B12 absorption. Bicarbonate is released at the basal surface into the capillary blood flow to neutralize hydrogen ions.

Chief cells are large, cubodial cells with basophilic cytoplasm and a basally located nucleus. The cells are concentrated in the middle to lower portions of the gastric glands. They have abundant RER, well developed Golgi and numerous apical secretory granules which release pepsinogen I and II. These precursors are activated by the stomach's low luminal pH into the proteolytic enzyme pepsin.

DuodenumT. mucosaeViliColumnar surface epithelium+goblet cellCrypt/of lieberkuhnT.M. MucosaeT. submucosaeT.muscularis

Duodenum Lieberkhun glandTunica mucosaBrunner glandTunica submucosaTunica muscularis

Jejunum T. mucosaeViliColumnar surface epithelium+goblet cellCrypt/of lieberkuhnT.M. MucosaeT. submucosaeKerckrings folds (T/mucosae+T.submucosae)T.muscularis

Jejunum VilliPlica kerckringiTunica muscularis mucosaTunica submucosaTunica muscularis

Ileum VilliLymphonodus aggregatiTunica muscularis mucosaTunica submucosaTunica muscularis

Liberkhun glandGoblet cellPaneth cell

PHYSIOLOGY AND BIOCHEMISTRYOF GIT (GASTRIC-ILLEUM)

Physiology - Digestive SystemThe functions of the digestive system are:Ingestion - eating foodDigestion - breakdown of the foodAbsorption - extraction of nutrients from the foodDefecation - removal of waste productsThe digestive system is a group of organs that breakdown the chemical components of food, with digestive juices, into micromolecul nutrients which can be absorbed to generate energy for the body

Stomach Adding and grinding bolus chymeThe peristaltic waves push chyme to duodenum

Gastric emptiying and mixing process:Peristalic in the upper fundus pyloric sphincter propels chyme fowardA small portion of chyme is pushed throgh the partially open sphincter into duodenumWhen the peristaltic contraction reaches pyloric sphincter, the sphincter tightly closed Chyme hit the closed sphincter ad tossed back into the antrum(retropultion)

The StomachIt is the widest part of the alimentary canal and acts as a reservoir for the food where it may remain for between 2 and 6 hours.Here the food is churned over and mixed with various hormones, enzymes including pepsinogen which begins the digestion of protein, hydrochloric acid, and other chemicalsThe stomach has an average capacity of 1 liter, varies in shape, and is capable of considerable distension.At regular intervals a circular muscle at the lower end of the stomach, the pylorus opens allowing small amounts of food, now known as chyme to enter the small intestine.

Duodenum

Small IntestineThe small intestine measures about 7m in an average adult and consists of the duodenum, jejunum, and ileum.Both the bile and pancreatic ducts open into the duodenum together. The small intestine, because of its structure, provides a vast lining through which further absorption takes place.

BIOCHEMISTRYDigestion & Absorption of CarbohydratesThe digestion of carbohydrates is by hydrolysis to liberate oligosaccharides, then free mono- and disaccharides. Points in carbohydrate digestion :Amylases Catalyze the Hydrolysis of Starchcatalyzed by salivary and pancreatic amylases, which catalyze random hydrolysis of (14) glycoside bonds, yielding dextrins, then a mixture of glucose, maltose, and isomaltose

Disaccharidases Are Brush Border EnzymesThe disaccharidases, maltase, sucrase-isomaltase, lactase, and trehalase are located on the brush border of the intestinal mucosal cells, where the resultant monosaccharides and others arising from the diet are absorbed. lactase is gradually lost through adolescence, leading to lactose intolerance. Lactose remains in the intestinal lumen, where it is a substrate for bacterial fermentation to lactate, resulting in discomfort and diarrhea.

There Are Two Separate Mechanisms for the Absorption of Monosaccharides in the Small IntestineGlucose and galactose are absorbed by a sodium-dependent process. They are carried by the same transport protein and compete with each other for intestinal absorption .Other monosaccharides are absorbed by carrier-mediated diffusion. Because they are not actively transported, fructose and sugar alcohols are only absorbed down their concentration gradient, and after a moderately high intake, some may remain in the intestinal lumen, acting as a substrate for bacterial fermentation.

Transport of glucose, fructose, and galactose across the intestinal epithelium. The SGLT 1 transporter is coupled to the Na+-K+ pump, allowing glucose and galactose to be transported against their concentration gradients. The GLUT 5 Na+-independent facilitative transporter allows fructose, as well as glucose and galactose, to be transported down their concentration gradients. Exit from the cell for all sugars is via the GLUT 2 facilitative transporter

Digestion & Absorption of LipidsThe major lipids in the diet are triacylglycerols and, to a lesser extent, phospholipids. These are hydrophobic molecules, and have to be hydrolyzed and emulsified to very small droplets (micelles) before they can be absorbed. The fat-soluble vitamins, A, D, E, and K, and a variety of other lipids (including cholesterol) are absorbed dissolved in the lipid micelles. Absorption of the fat-soluble vitamins is impaired on a very low fat diet.

Hydrolysis of triacylglycerols is initiated by lingual and gastric lipases forming 1,2-diacylglycerols and free fatty acids.

Pancreatic lipase is secreted into the small intestine, and requires a further pancreatic protein, colipase, for activity. Major end products of luminal tricyglycerol digestion are : 2-monoacylglycerols and free fatty acids

Monoacylglycerols are poor substrates for hydrolysis, so that less than 25% of ingested triacylglycerol is completely hydrolyzed to glycerol and fatty acids.

Bile salts, formed in the liver and secreted in the bile, permit emulsification of the products of lipid digestion into micelles together with phospholipids and cholesterol from the bile.

The bile salts pass on to the ileum, where most are absorbed into the enterohepatic circulation. Glycerol released in the intestinal lumen is not reutilized but passes into the portal vein; glycerol released within the epithelium is reutilized for triacylglycerol synthesis via the normal phosphatidic acid pathway. Long-chain fatty acids are esterified to yield to triacylglycerol in the mucosal cells and together with the other products of lipid digestion, secreted as chylomicrons into the lymphatics, entering the bloodstream via the thoracic duct. Short- and medium-chain fatty acids are mainly absorbed into the hepatic portal vein as free fatty acids.

Digestion & Absorption of ProteinsSeveral Groups of Enzymes Catalyze the Digestion of ProteinsThere are two main classes of proteolytic digestive enzymes (proteases), with different specificities for the amino acids forming the peptide bond to be hydrolyzed. Endopeptidases hydrolyze peptide bonds between specific amino acids throughout the molecule. They are the first enzymes to act, yielding a larger number of smaller fragments: eg, pepsin in the gastric juice; trypsin, chymotrypsin, and elastase secreted into the small intestine by the pancreas.Exopeptidases catalyze the hydrolysis of peptide bonds, one at a time, from the ends of peptides. Carboxypeptidases, secreted in the pancreatic juice, release amino acids from the free carboxyl terminal;

aminopeptidases, secreted by the intestinal mucosal cells, release amino acids from the amino terminal. Dipeptidases in the brush border of intestinal mucosal cells catalyze the hydrolysis of dipeptides, which are not substrates for amino- and carboxypeptidases.

The proteases are secreted as inactive zymogens; such as :Pepsinogen is activated to pepsin by gastric acid and by activated pepsin (autocatalysis). In the small intestine, trypsinogen, the precursor of trypsin, is activated by enteropeptidase, which is secreted by the duodenal epithelial cells; trypsin can then activate chymotrypsinogen to chymotrypsin, proelastase to elastase, procarboxypeptidase to carboxypeptidase, and proaminopeptidase to aminopeptidase.

Free Amino Acids & Small Peptides Are Absorbed by Different Mechanisms

The end product of the action of endopeptidases and exopeptidases is a mixture of free amino acids, di- and tripeptides, and oligopeptides, all of which are absorbed. Free amino acids are absorbed across the intestinal mucosa by sodium-dependent active transport.). Dipeptides and tripeptides enter the brush border of the intestinal mucosal cells, where they are hydrolyzed to free amino acids, which are then transported into the hepatic portal vein. Relatively large peptides may be absorbed intact, either by uptake into mucosal epithelial cells (transcellular) or by passing between epithelial cells (paracellular). Many such peptides are large enough to stimulate antibody formationthis is the basis of allergic reactions to foods.

Digestion & Absorption of Vitamins & MineralsThe fat-soluble vitamins (A, D, E ,K) are absorbed in the lipid micelles that are the result of fat digestion; water-soluble vitamins and most mineral salts are absorbed from the small intestine either by active transport or by carrier-mediated diffusion. Vitamin B12 absorption requires a specific transport protein, intrinsic factor; calcium absorption is dependent on vitamin D; (via binding protein calbindin which is induced by vitamin D)zinc absorption probably requires a zinc-binding ligand secreted by the exocrine pancreas, and the absorption of iron is limited.Iron Absorption Is Limited and Strictly Controlled, But Enhanced by Vitamin C and Alcohol

Small IntestineThe site where most digestion and absorbtion take place.Divided into 3 segments: duodenum, jejunum and ileumIts motility includes:SegmentationMigrating motility complex

SegmentationSegmentation consists of oscillating, ring-like contraction of the circular smooth muscle along the small intestines length; between the contracted segments are relaxed areas containing a small bolus of chyme.After a brief period of time, the contracted segments relax, and ring-like contraction appear in the previously relaxed area.The new contraction forces the chyme in a previously relaxed segment to move in both direction into the now relaxed adjacent segments, shortly thereafter, the areas of contraction and relaxation is alternate again.In this way, the chyme is chopped, churned and thoroughly mixedFunctions: mixing the chyme with digestive juices secreted in small-intestine lumen and exposing the chyme to the absorbtive surface of the small intestines mucosa

Segmentation

Migrating Motility ComplexWhen most meal has been absorbed, segmentation cease and are replaced between meals by the migrating motility complex. This between meal motility consists of weak, repetitive peristaltic waves that move a short distance down the intestine before dying out.Each contraction will sweep any remnants of the preceding meal plus mucosal debris and bacteria forward toward the colon

SecretionsExocrine gland cells of small intestine mucosa secrete about 1.5 liters of an aqueous salt and mucus solution called succus entericus.Functions: provides protection and lubrication also provides plenty of H2O to participate in the digestion of foodNo digestive enzymes are secreted inti the intestinal juice.

DigestionDigestion within the small intestine lumen is accomplished by pancreatic enzymes with fat digestion being enhanced by bile secretion.This digestion is completed by special hairlike projections of luminal surface of small instine epithelial cell, microvilli

AbsorptionAll products of carbohydrate, protein and fat digestion, as well as electrolytes, vitamin and water are absorbed by small intestine indiscriminately. Only absorption calcium and iron is adjusted by body needs.Most absorption occurs in duodenum and jejunum, very little in ileum (normally only B12 and bile salt are absorbed by ileum)

SYNDROME OF DYSPEPSIApersistent or recurrent upper abdominal pain or discomfort characterized by postprandial fullness, early satiety, nausea, and bloating.

SYNDROME OF DYSPEPSIAEpidemiology: Each year 10-20% of US population seeks medical attention. NUD 2-3 x peptic ulcer disease.Etiology & Pathogenesis: Imbalance of the aggravating factors and defensive factors. The aggravating factor increased and the defensive factors decrease will cause functional and organic /ulcer dyspepsia.

AGGRAVATING FACTORS OF SYNDROME DYSPEPSIA:Gastric acid PepsinHelicobacter pylori infectionGastric motor activity: 25-50% patients exhibit postprandial antral hypomotility or delayed gastric emptyingPsychological factors: anxiety and depressionDiet: foods: spicy/hot, sour, vinnegar, drinks: coffee, smoking/tobacco, alcohol Drugs: non-steroidal anti-inflammatory drugs(nsaid), traditional pain killer drugs, steroids, antibiotics(erythromycin, ampicillin), iron, potassium, digoxin, theophylline.Metabolic diseases: diabetes mellitus, hypothoroidismHypopotassemia.Free radicals

DEFENSIVE FACTORS OF SYNDROME DYSPEPSIA:ProstaglandinMucusMucosal blood flowSurfactantBicarbonatHeat shock proteinEpitel/preepithelial factorsetc

CLINICAL FEATURES IN SYNDROME DYSPEPSIANon Ulcer Disease: Ulcer like: dominant epigastric pain, relieved by antacids or foodDysmotility like: epigastric discomfort aggravated by food or associated with early satiety, fullness, nausea, retching, vomiting, or bloating.Nonspecific: symptoms does not fit the other categoriesReflux like: heartburn and regurgitationUlcer: the same with NUD

PHYSICAL EXAMINATION IN SYNDROME DYSPEPSIAnot specificepigastric tenderness some timesabdominal mass if advanced gastric carcinoma

Nausea is the subjective feeling of need to vomit.Vomiting(emesis) is the oral expulsion of gastrointestinal contents resulting from contractions of gut and thoracoabdominal wall musculature.Nausea and Vomit

Cause of nausea and vomiting

IntraperitonealExtraperitonealMedication/Metabolic DisordersObstructing disorders: Pyloric obstruction Small bowel obstruction Colonic obstruction Superior mesenteric artery syndromeCardiopulmonary disease : Cardiomyopathy Myocardial infarctionDrugsCancer chemotheraphyAntibioticsCardiac antiarrhytmicsDigoxinOral hypoglicemicsOral contraceptivesEnteric infection ; viralBacterialLabyrinthine disease:Motion sicknessLabyrinhtitisMalignancyEndocrene/metabolic diseasePregnancyUremiaKetoacidosisThyroid and parathyroid diseaseAdrenal insufficiencyBiliary colicAbdominal irradiationPosoperative vomiting

Inflammatory diseases: Cholecystitis PancreatitisAppendicitisHepatitisIntracerebral disorders :MalignancyHemorrhageAbscesshydrocephalusToxinsLiver failureethanolAltered sensorimotor functionGastrioparesisIntestinal pseudoobstructionFunctional dyspepsiaGERChronic idiopathic nauseaFunctional vomitingCyclic vomiting syndromePsychiatric ilnessAnorexia and bulimia nervosaDepressionBiliary colicAbdominal irradiationPosoperative vomiting

Emesis mechanism

Emesis mechanism

Vomiting is controlled by two brainstem areas, the vomiting center and chemoreceptor trigger zone.Activation of the chemoreceptor trigger zone result in impulses to the vomiting center, which controls the physical act of vomiting.PathophysiologyCoordinated by several brain stem nuclei, neurotransmitters, smell orginate in the cereebral cortexEffected by neuromuscular responses in the gut, pharynx and thoracoabdominal wallExpulsion of gastric contentsProducing high intrathoracic and intra abdominal pressureInspiratory thoracic and abdominal wall muscle contractMovement of the material to the mouthReflex elevation of the soft palate and closure of the glotis

The history: drug history, the timing, and character of the vomitus.

Diagnostic testingRadiographs suggest intestinal obstructionElectrolyte replenishment indicated for hypokalemia or metabolic alkalosisDetection of iron-deficiency anemia mucosal injurySerology testing abnormal pancreatic enzymesCT intraperitoneal inflamatory processesGastrointestinal motility testing detect a motor disorder

ComplicationRupture of esophagus (Boerhaaves syndrome), hematemesis from a mucosal tear (Mallory-Weiss syndrome), dehydration, malnutrition, dental caries and erosions, metabolic alkalosis, hypokalemia and aspirasi pneumonitisEvaluation

Treatment

Treatment Mechanism Examples Clinical indicationAntiemetic agentsAntihistaminergic

Anticholinergic

Antidopaminergic

5-HT3 antagonist

NK1 antagonist

Tricyclic antidepressantDimenhydrinate, meclizineScopolamine

Prochlorperazine, thiethylperazineOndansetron, granisetron

Aprepitant

Amitriptyline, nortriptylineMotion sickness, inner ear diseaseMotion sickness, inner ear diseaseMedication-,toxin-, or metabolic-induced emesisChemotherapy- and radiation-induced emesis, postoperative emesisChemotherapy-induced nausea and vomitingChronic idiopathic nause, functional vomiting, cyclic vomiting syndrome

Treatment Mechanism Examples Clinical indicationProkinetic agents5-HT4 agonist and antidopaminergicMotilin agonist

Peripheral antidopaminergic5-HT4 agonist

Somatostatin analogueMetoclopramide

Erythromycin

Domperidone

Tegaserod

OctreotideGastroparesis

Gastroparesis, ?intestinal pseudoobstructionGastroparesis

?Gastroparesis,?intestinal pseudoobstructionIntestinal pseudoobstructionSpecial settingsBenzodiazepines

Glucocorticoids

CannabinoidsLorazepam

Methylprednisolone, dexamethasoneTetrahydrocannabinolAnticipatory nausea and vomiting with chemotherapyChemotherapy-induced emesis?Chemotherapy-induced emesis

Cyclic Vomiting Syndrome

Clinical FindingsCharacterized by recurrent episodes of stereotypical vomiting in children usually older than 1 year of age.Forceful and frequent up to 6 times/hour for up to 72 hours or more.Episode frequency 2-3/month to < 1/yearPatients experience abdominal pain, anorexia, and rarely, diarrhea.The episodes end suddenly, often after a period of sleep.Family history is positive for migraine in 50-70% of cases (develop migraine headaches as adults).Research suggests that abnormalities of neurotransmitters and hormones provoke CVS.

Clinical Findings (continued)About one quarter of patients have typical migraine symptoms during episodes :premonitory sensationheadachephotophobiaphonophobiaIdentifiable triggers include :infectionpositive or negative emotional stressdiet (chocolate, cheese, MSG)mensesmotion sickness

Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders

DDDrug toxicityICP SeizuresBrain tumorChiari malformationRecurrent sinusitisCholedocal cystGallstonesRecurrent small obsructionIBDFamial pancreatitisObstructive uropathyRecurrent urinary infectionDiabetesMitochondrial diseasesDisorders of fatty and organic acid metabolismAdrenal insufficiencyMnchausen syndrome by proxy

TreatmentAvoidance of triggers prevents spells in some patients.Sleep can also end a spell although some children awaken and resume vomiting.Diphenhydramine or lorazepam are used at the onset of spells in some children to reduce nausea and induce sleep.Early use of antimigraine medications (sumatriptan), antiemetics (ondansetron), or antihistamines can abort spells in some patients.Once a spell is well established, intravenous fluids are often required to end it.Preventing spells with prophylactic propanolol, amitriptyline, or antihistamines is effective in some patients with frequent or disabling spells.Some patients have been successfully treated with anticonvulsants.

Gastritis

What is Gastritis?An inflammation, irritation or erosion of the stomach lining. Can be of acute or a chronic complaint.Acute gastritis often due to chemical injury (alcohol/drugs) Chronic gastritis: H. Pylori infection, chemical, autoimmune.

Etiology Bile reflux Drugs NSAIDs, such as aspirin, ibuprofen, and naproxen Cocaine Iron Colchicine, when at toxic levels, as in patients with failing renal or hepatic function Kayexalate Chemotherapeutic agents, such as mitomycin C, 5-fluoro-2-deoxyuridine, and floxuridinePotent alcoholic beverages, such as whisky, vodka, and gin Bacterial infections H pylori (most frequent) H heilmanii (rare) Streptococci (rare)

Etiology Fungal infections Candidiasis Histoplasmosis PhycomycosisParasitic infection (eg, anisakidosis) Acute stress (shock) Radiation Allergy and food poisoningSpicy food SmokingViral infections (eg, CMV)

CLASSIFICATION OF GASTRITISAcute gastritisAcute H. pylori infectionOther acute infectious gastritisChronic atrophic gastritisType A : Autoimmune, body predominantType B : H. pylori related, antral predominantIndeterminantUncommon forms of gastritisLymphocyticEosinophilicCrohns diseaseSarcoidosisIsolated granulomatous gastritis

Typesof gastritis:a)Acute Gastritis:(acute hemoragic gastritis or acute erosive gastropathies) Bleeding from side mucose and lossing integrity which is characteristic of gastric mucosal lesion accompanying inflammation Macroscopic examination:Oedemmucosal friability ErotionThe bleeding side with blood extravation into the mucose

Mostly there is often linear at the peak of the mucosa folds

Acute GastritisAcute gastritis can be broken down into 2 categories: erosive (eg, superficial erosions, deep erosions, hemorrhagic erosions) nonerosive (generally caused by Helicobacter pylori).

Erosive GastritisAcute erosive gastritis can result from the exposure to a variety of agents or factors. This is referred to as reactive gastritis. These agents/factors include nonsteroidal anti-inflammatory medications (NSAIDs), alcohol, cocaine, stress, radiation, bile reflux, and ischemia. This results from oral or systemic administration of these agents either in therapeutic doses or in supratherapeutic doses.

Chronic GastritisAutoimmuneBacterial (H. Pylori)Chemical (NSAIDs)Chronic noninfectious granulomatous gastritisLymphocytic gastritisEosinophilic gastritisIschemic gastritisRadiation gastritis

ULKUS PEPTIKUM

Peptic UlcerAn ulcer is defined as disruption of the mucosal integrity of the stomach and or duodenum --- local defect / excavation due to active inflammation.Burning epigastric pain excacrbated by fasting and improved with meals symptom --- PUD

ULKUS PEPTIKSuatu daerah ekskoriasi mukosa lambung atau usus yang terutama disebabkan kerja pencernaan getah lambung atau sekresi usus halus bagian atas

EPIDEMIOLOGI ULKUS PEPTIK DI AMERIKA SERIKAT4 juta pasien (baru & kambuh) terkena ulkus peptik per tahun12% pria & 10% wanita15.000 kematian per tahun terjadi akibat ulkus peptik yang terkomplikasi

ETIOLOGI & FAKTOR RISIKO ULKUS PEPTIKKetidakseimbangan antara kecepatan sekresi getah lambung & derajat yang diberikan sawar mukosa gastroduodenal & netralisasi asam lambung oleh getah duodenumKandungan asam dan peptik IritasiSuplai darah yang burukSekresi mukus yang burulInfeksi H pyloriMerokokAlkoholAspirin & OAINS

PATOFISIOLOGI ULKUS PEPTIKNormal : jika asam >> duodenum refleks saraf & umpan balik hormon hambat sekresi & peristaltik lambung m kecepatan pengosongan lambungAdanya asam pada usus halus sekretin (melalui darah) pankreas sekresi getah pankreas lebih cepat (mengandung NaCO3 ) netralisir asam

PATOFISIOLOGI ULKUS PEPTIKPatogenesis :H pylori penetrasi (kemampuan fisik atau lepaskan enzim-enzim pencernaan bakterial yang mencairkan sawar) sawar mukosa lambung getah asam kuat pencernaan penetrasi jaringan epitelium & cerna dinding GI ulkus peptikumMerokok p rangsangan saraf pada kelenjar penyekresi di lambungAlkohol merusak sawar mukosaAspirin & OAINS merusak sawar mukosa

KLASIFIKASI ULKUS PEPTIKUlkus duodenalUlkus gaster

ULKUS DUODENALKerusakan permukaan mukosa > 5 mm dengan kedalaman sampai ke submukosa pada duodenum

EPIDEMIOLOGI ULKUS DUODENAL6-15% populasi barat100% H pylori berkolonisasi pada mukosa antral gasterMortalitas, kebutuhan pembedahan, kunjungan paramedis >50% setelah 30 tahun yang lalu

PATOLOGI ULKUS DUODENALSering terjadi pada bagian pertama duodenum (>95%) dengan kedalaman 3 cm dari pilorus, D = 1 cm tapi dapat mencapai 3-6 cm (ulkus raksasa)Ulkus dibatasi dengan kedalaman yang mencapai propria muskularisDasar ulkus terdiri dar zona nekrosis eosinofilik dengan fibrosis di sekitarnyaKeganasan UD jarang

PATOFISIOLOGI ULKUS DUODENALH pylori & NSAID yang menginduksi patologis penyebab paling umumTerdapat abnormalitas sekretori asamRata-rata terjadi p sekresi sekresi asam gastrik nokturnal & basalPengosongan gaster pada cairan dipercepatSekresi bikarbonat pada bulbus duodenal berhubungan dengan infeksi H pylori

ULKUS GASTERKerusakan permukaan mukosa > 5 mm dengan kedalaman sampai ke submukosa pada gaster

EPIDEMIOLOGI ULKUS GASTERLebih dari separuh pada priaInsidens puncak pada dekade ke-6Terjadi lebih lambat daripada lesi duodenal

PATOLOGI ULKUS GASTERPerlihatkan keganasanUG jinak sering ditemukan di distal pada junction antara antrum & mukosa sekretori asam, jarang pada fundusSecara histologi UDUG yang berhubungan dengan H pylori antral gastritisOAINS yang berhubungan dengan UG tidak disertai gastritis kronik aktif, tidak adanya H pyloriEkstensi fibrin otot polos ke dalam mukosa bagian atas juga ditemukan

PATOFISIOLOGI ULKUS GASTERDapat disebabkan oleh H pylori dan/atau OAINS yang menginduksi kerusakan mukosaTerjadi pada area prepilorik atau bagian tubuh lainnya yang berhubungan dengan UD atau bekas luka duodenal yang mirip dengan patogenesis UDOutput asam gastrik (basal & yang distimulasi) bisa normal atau b

PATOFISIOLOGI ULKUS GASTERBila ada level asam yang minimal faktor kerusakan pertahanan mukosa adaAda abnormalitas tekanan sfingter pilorik yang istirahat dan distimulasi dengan samanya dalam p refluks gastrik duodenal Meskipun asam empedu, lysolesitin dan enzim pankreas mempatologis mukosa gastrik pada UG tidak terbuktiPengosongan lambung yang terlambat dari solid ada pada UG, tapi belum pernah dilaporkan

GEJALA ULKUS PEPTIKSakit perutKomplikasi 10% pasien dengan OAINS yang induksi penyakit mukosa : Pendarahan, perforasi, & obstruksiNyeri epigastrium (terbakar, gelisah/ketidaknyamanan) UG & UDPola nyeri UD 90 menit s.d. 3 jam setelah makan dan dapat disembuhkan dengan antasid atau makanan, Nyeri yang membangunkan pasien dari tidur (tengah malam s.d. 3 pagi) 2/3 pasien UD mengeluhkannya & 1/3 pada NUDPola nyeri UG ketidaknyamanan berhubungan dengan kondisi makanan, nausea, & BBDispepsia 30% dengan ulkus pada endoskopi

GU vs DUGUDUBurning epigastric pain exacerbated by with mealsDefined as breaks in the mucosal surface >5 mm in size, with depth to the submucosaNausea and weight loss occur more commonlyH. pylori and NSAID-induced injury account for the majorityGastric acid output tends to be normal or decreased in the presence of minimal acid levels, impairment of mucosal defense factors may be presentDelayed gastric emptying of solidsMalignancy is frequentBenign GU: discrete crater with radiating mucosal folds originating from the ulcer marginUlcers >3 cm in size or those associated with a mass especially of the body and fundus are often malignant (70%)Burning epigastric pain frequently relieved by foods or antacid; pain awakens Px from sleep most discriminating symptomUsually

ETIOLOGY: H. pylori and NSAIDH. pyloriNSAIDFirst step in infection is dependent on the bacterias motility and its ability to produce UREASE capable of producing ammonia from urea which can damage the epithelial cells; also it produces proteases and phospholipases that breakdown the glycoprotein lipid complex of the mucus gel, thus reducing the efficacy of this first-line of mucosal defense2 factors that predispose to higher colonization rates: poor economic status and less educationRisk factors for infection: 1. birth of residence in a developing country, 2. domestic crowding, 3 unsanitary living conditions, 4. unclean food or water, and 5. exposure to gastric contents of an infected individualTransmission: Person-to-person oral-oral or fecal-oral routeBacterial and host factors important in determining H. pylori-induced GI disease: BACTERIAL FACTORS 1. Structure, 2. Adhesins, 3. Porins, 4. Enzymes (urease, vac A, cag A)HOST FACTORS 1. Duration, 2. Location, 3. Inflammatory response, 4. Genetic? Risk factors: 1. advanced age, 2. Hx of ulcers, 3. concomitant use of glucocorticoids, 4. high-dose NSAIDs, 5. multiple NSAIDs, 6. concomitant use of anticoagulants, 7. serious or multisystem diseasePROSTAGLANDINS play a critical role in maintaining gastroduodenal mucosa integrity and repair interruption of prostaglandin synthesis can impair mucosal defense and repair, thus facilitating mucosal injury via a systemic mechanismEPITHELIAL EFFECTS (due to prostaglandin depletion): 1. inc HCl secretion, 2. dec mucin secretion, 3. dec HCO3 secretion, 4. dec surface active phospholipids secretion, 5. dec epithelial cell proliferation

Clinical featuresHistoryAbdominal pain Acid --- activation chemical reseptors --- enhanced sensitivity / altered gastroduodenal motilityEpigastric pain (burning and gnawing discomfort)Ill defined (aching sensation - hunger pain)Pain pattern discomfort precipitated by foodNauseaWeight loss

Physical ExaminationPain may be found to the right of the midline (20% ps)Epigastric tenderness the most frequent findingTachycardia and orthostasis dehydration because of vomiting or blood lossSeverely tender or boardlike abdomen perforationSuccussion splash gastric outlet obstrution

PEMERIKSAAN FISIK ULKUS PEPTIKKekenyalan epigastrik UG & UDNyeri ditemukan pada garis tengah kanan 20% pasienTakikardia & ortostasis dehidrasi sekunder u/ vomitus atau kehilangan darah GI aktifKekenyalan berat perforasiAdanya succussion splash mengindikasikan cairan yang ada pada perut obstruksi outlet gastrik

Diagnostic EvaluationDocumentation of an ulcer requires either a radiographic (barium study) / endoscopic procedure.Barium studies GU discrete crater with radiating mucosal folds originating from mucosal the ulcer margin.Ulcers > 3cm / associated with a mass malignantBarium studies must be followed by endoscpy and biopsi ( 8% BS benign malignant if used endoscopy / surgery)

EndoscopyProvides the most sensitive and spesific approach for examining the upper GIT.Facilitate photographic documentation of a mucosal defect and biposy to role out malignancy GU.Helpful in identifying lesions too small to detect by radipgraphic, determine if an ulcer is a source of blood loss.

Complication1. Gastrointestinal bleedingThe most commonOccurs in 15% ps often in individuals >60 yo increase use of NSAID20% ps ulcer with related hemorrhage bleed without any SS. 2. PerforationThe second most commonAppears because increased use of NSAIDPenetration is a form of perforation which ulcer bed tunnels into an adjacent organ. GUs left hepatic lobe 3. Gastric outlet obstructionLeast common Ps may have relative obstruction related in inflammation and edema peripyloricResolve with ulcer healing but secondary obtrustion because of scar formation is possibleEarly satiety, nausea, vomiting, postprandial abdominal pain and weigth loss gastric outlet obstruction Dx

Differential DiagnosisProximal GI tumoursGERVascular diseaseBiliary cholicChronis pancreatitisChronic diseases

PENATALAKSANAAN MEDIKAMENTOSA ULKUS PEPTIKObat penekan asamAntasidAntagonis reseptor H2Inhibitor pompa proton (H+, K+-ATPase)Agen protektif mukosalSukralfat membantu sebagai barier fisikokimiawi yang mengeluarkan akso trofik dengan mengikat faktor pertumbuhan (EGF), menambah sintesis prostaglandin, stimulasi mukus dan sekresi bikarbonat dan menambah pertahanan & perbaikan mukosa Analog prostaglandin penambahan pertahanan & perbaikan mukosa, menambah sekresi bikarbonat, stimulasi aliran darah mukosa, & m jumlah sel mukosaBismuth-containing preparations ulcer coating, prevensi pepsin/HCl yang menginduksi kerusakan, mengikat pepsin, menstimulasi prostaglandin, bikarbonat, & sekresi mukus

TreatmentAcid Neutralizing / Inhibitory DrugsAntacidNeutralization of secreted acid with antacids constituted the main form of therapy for peptic ulcers.The most commonly used agents : mixture aluminium hydroxide and magnesium hydroxide (avoid these side effect)Calcium carbonate and sodium bicarbonateSide effect : aluminium hydroxide constipationMagnesium hydroxide loose stoolsLong term, calcium carbonate milk alkali syndromeSodium bocarbonate systemic alkalosisContraindication :Magnesium - containing preparation # chronic renal failure

H2 receptors antagonistsCimetidine, ranitidine, famotidine and nizatidineHomology of histamineInhibit basal and stimulated acid secretion when used at therapeutic doses.Now, drug is often used for treatment of active ulcers (4-6 weeks) in combination with antibiotics eradicating H. pyloriCimetidine was the first H2 receptor antagonists used to treatment of acid peptic disordersRanitidine, famotidine and nizatidine ulcer prevention (once a day)Side effect :Cimetidine Weak antiandrogenic : reversible gynecomastia and impotenceCimetidine and ranitidine : inhibit cytokrom P450Systemic toxicities : pancitopenia, neutropenia,anemia,thrombocytopenia

PPI Omeprazole, esomeprazol, iansoprazol, rabeprazol, pantoprazol substituted benzimidazole derivatives.These agents potently inhibit all phases of gastric acid secretion.Esomeprazol most potent acid inhibitroy agentsOmperazol and Iansoprazol administered as enteric-coated granules dissolves within the small intestine.Iansoprazol orally disintegrating tablet advantage for dysphagiaOmeprazol mixed with sodium bicarbonate admnistered orally / via gastric tubeTenatoprazol containing imidazopyridine benzimidazole irreversible PPI inhibiting nocturnal acid secretion

Onset action id rapid ; maximum acid inhibitory effect 2-6 hours after administration ; duration of inhibition lasting up 72-96 hours.Their efficacy is maximized if they are administered before a mealsSide effect :Omeprazole and lansoprazol inhibit hepatic cytochrome P450

Cytoprotective agentsSucralfateInsoluble in water viscous paste within the stomcah and duodenumBinding to sites of active ulcerationAct by several mechanism :Physicochemical barrierEnhancing mucosal Promoting a trophic action by binding growth factorsStimulate mucous and bicarbonate secretion and enhancing mucosal defense and repairToxicity :ConstipationContraindication :Chronic renal insufficiency

Bismuth containing preparationsBismuth-containing compounds the DOC for treating PUD against H. PyloriColloidal bismuth subcitrate and bismuth-subsalicylate widely usedPotential mechanism :Ulcer coatingPrevention of pepsin / HCl induced damageBinding of pepsinSide effect :Short term : black stools, constipation, darkening of toungeLong term (high doses, avidly absorbed) : neurotoxicity

Prostaglandin analoguesmaintaining mucosal integrity and repair treatment PUDMechanism : rapidly absorbed enhancement of mucosal defense and repair through enhance mucous bicarbonate secretion, stimulate mucosal blood flow.Side effect : diarrheaContraindication :Misoprostol # pregnant womenMiscellaneous drugsA number of drugs aimed at treating acid peptic disordersAnticholinergic inhibit activation of the muscarinic receptor in parietal cells Tricyclic antidepressants

THERAPY OF H. pylori

Regimens Recommended for Eradication of H. pylori InfectionDrugDose (respectively)Triple TherapyBSS + Metronidazole + TetracyclineRanitidine bismuth citrate + Tetracycline + Clarithromycin or MetronidazoleOmeprazole (lansoprazole) + Clarithromycin + Metronidazole or Amoxicillin2 tablets qid, 250 mg qid, 500 qid400 mg bid, 500 mg bid, 500 mg bid20 mg bid, 250/500 mg bid, 500 mg bid, or 1 g bidQuadruple TherapyOmeprazole (Lansoprazole) Bismuth subsalicylateMetronidazoleTetracycline20 mg (30 mg) daily2 tablets qid250 mg qid500 mg qid

THERAPY OF H. pyloriTriple therapy has a poor Px complianceSimpler (dual therapy) and shorter regimens (7-10 days) are not as effective as triple therapy for 14 days2 anti H. pylori regimens are available in prepack formulation1. PREVAC (Lansoprazole, clarithromycin, and amoxicillin)2. HELIDAC (BSS, tetracycline, and metronidazole)

Most feared cxn of amoxicillin is pseudomembranous colitis

GER and GERDDefinition :any condition noted clinically or histopathologically that results from gastroesophageal reflux, ranging in seriousness from mild to life-threatening; principle characteristics are heartburn and regurgitation. When there is damage to the esophageal epithelium, it is known as reflux esophagitis. (Dorland)

Etiology :Decreased efficacy of esophageal antireflux mechanisms, particularly LES tone.Central nervous system depressantsHypothyroidismPregnancysystemic sclerosing disorders, alcohol or tobacco exposurethe presence of a nasogastric tube may be contributing causes

However, in most instances no antecedent etiology is identified.Inadequate or slowed esophageal clearance of refluxed material Delayed gastric emptying and increased gastric volume, contributing to the volume of refluxed materialReduction in the reparative capacity of the esophageal mucosa by protracted exposure to gastric juices.

The action of gastric juices is critical to the development of esophageal mucosal injury; in severe cases refluxed bile from the duodenum also may contribute to the mucosal disruption.

Morphology. The anatomic changes depend on the causative agent and on the duration and severity of the exposure: Simple hyperemia ("redness") may be the only alterationthree histologic features are characteristic The presence of inflammatory cells, including eosinophils, neutrophils, and excessive numbers of lymphocytes, in the squamous epithelial layerBasal zone hyperplasia exceeding 20% of the epithelial thicknessElongation of lamina propria papillae with capillary congestion, extending into the top third of the epithelial layer.

Clinical Features. Although largely limited to adults over age 40, reflux esophagitis is occasionally seen in infants and children. dysphagia, heartburn, and sometimes regurgitation of a sour brashhematemesis, or melena. most people experience reflux symptoms without damage to the distal esophageal mucosa, due to the short duration of the reflux. Anatomic damage appears best correlated with prolonged exposure of the lower esophagus to refluxed material.Rarely, chronic symptoms are punctuated by attacks of severe chest pain that may be mistaken for a "heart attack.The potential consequences of severe reflux esophagitis are bleeding, ulceration, development of stricture, and a tendency to develop Barrett esophagus, with its attendant risks.

Incompetent barriersScleroderma-like disease, myopathy associated with chronic intestinal pseudoobstruction, pregnancy, smoking, anti-cholinergic drugs, smooth muscle relaxants , surgical damage of LES, esophagitisGastric volume increaseAfter meals, pyloric obstruction, gastric stasis, during acid hypersecretion stateGastric content are near gastroesophageal junctionRecumbency, bending down, hiatal herniaGastric pressure increasesObesity, pregnancy, ascites, tight clothes

Gatroesophageal Reflux Disease (GERD)Causes

THERAPY OF NSAID-RELATED GASTRIC AND DUODENAL INJURY

Recommendations for Treatment of NSAID-Related Mucosal InjuryClinical SettingRecommendationActive UlcerNSAID discontinuedNSAID continuedProphylactic therapyH. pylori infetionH2 receptor antagonist or PPIPPI only agents that can heal GU and DUs independent of whether NSAID are discontinuedMisoprostol, PPI, Selective COX-2 inhibitorEradication if active ulcer present or there is a past history of PUD

Esophageal exposure to refluxed gastric content depends on the amount of refluxed material per episodes, the frequency of refluxed episodes, and the rate of clearing esophagusPeristaltic contraction impaired esophageal clearance impairedImpaired salivary secretion increase esophageal exposure timePathophysiology

Heartburn and regurgitation of sour material into the mouth characteristic symptomsPersistent dysphagia peptic strictureRapidly progressive dysphagia and weight loss adenocarcinoma in Barretts esophagusExtraesophageal manifestationChronic cough, laryngitis, pharyngitis, morning hoarsenessRecurrent pulmonary aspiration aggravate chronic bronchitis, asthma, pulmonary fibrosis, chronic obstructive pulmonary disease, pneumoniaChronic sinusitis, dental decay Clinical features

History Therapautic trial with PPI (omeprazole) for 1 weekDiagnosis studiesIndicated in patient with persistent symptoms, symptoms while on therapy, or those with complicationDivided into 3 categories:Documentation of mucosal injuryDocumentation and quantitation of refluxDefinition of phatophysiologyDiagnosis

Documentation if mucosal injuryBarrium swallowNormal but may reveal an ulcer or a strictureEsophagoscopyReveal presence of erosions, ulcers, peptic strictures, or adenocarcinomaMucosal biopsiesShow early changes of esophagitisPerformed at least 5cm above the LESBernstein testSymptomatic esophagitis heartburnDocumentation and quantitation of refluxAmulatory long term (24-28 hours) esophageal pH recordingOnly when the role of reflux is unclearDetermination of pathophysiologic factors in GERDIndicated for management decisions antireflux surgery

Goals symptom relief, heal errosive esophagia, prevent complicationMild casesWeight reductionSleeping with the head of bed elevated about 4-6 inch with blocksElimination factors that increase adominal pressurePatient sould not smoke, avoid consuming fatty food, coffee, chocolate, alcohol, mint, orange juice, certain medication (anticholinergic drugs, calcium channel blocker, etc), avoid ingesting large quantities of fluids with mealsH2 receptors blocking agents symptom reliefTreatment

PPI8 weeks heal errosive esophagitisTaken 30 minutes before breakfastPreventing recurrentsAssociated peptic stricture endoscopic dilation (relief dysphagia)Esophagoscopy patient suspected bleeding or development of cancerAntireflux surgeryFundoplication

Reflux esophagitisMucosal defenses are unable to counteract the damage cause by acid, pepsin, and bilePeptic strictureResults from fibrosis that cause luminal constrictionComplication

90% patient experience a good result after surgery80-85% of cases of esophagitis heal after treatment with a PPIDifferential diagnosisPrognosisCholelithiasisDiverticulitisPeptic ulcer diseaseAchalasiaCoronary artery disease

***************************************************Discrete : terdiri dari unsur yang berbeda atau tidak terkait ; margin : batas*Bed tunnels : terowongan ; adjacent : berdekatan*Calcium carbonate converts to calcium chloride in the stomach. Milk alkali syndrome : hypercalcemia, hyperphosphatemia, renal calcinosis renal insufficiency.*