TUTORIAL A10

Pemicu
Seorang wanita, ibu G, pekerjaan ibu rumah tangga, 47 tahun, datang ke Puskesmas dengan keluhan nyeri pada perut hilang timbul selama 1 minggu terakhir. Rasanya seperti menghisap, perih, dan kadang-kadang seperti diiris-iris. Perasaan ini lebih dirasakannya sewaktu lapar dan berkurang saat perut kenyang. Dia juga megeluh rasa kembung, mual-mual, dan muntah. Apa yang terjadi pada ibu G?

 Gejala penyakit ini telah dialami ibu G lebih kurang 1 tahun. Gejala ini hilang setelah makan obat yang diberikan oleh dokter. Obat-obatan yang diberikan terdiri dari : antasida dalam bentuk sirup dan tablet/kapsul. Pemeriksaan fisik dijumpai pada abdomen : palpasi supel, tidak ada organomegali, peristaltik baik.

More info

Hasil pemeriksaan darah lengkap : - Hb 12gr/dl - Leukosit 7.000/mm - Trombosit 180.000/mm - LED 20 mm/jam - Hasil pemeriksaan fungsi hati dan ginjal normal.

Identifikasi masalah
Ibu G, 47 thn dengan keluhan nyeri pada perut hilang timbul selama 1 minggu terakhir. Rasa seperti menghisap, perih dan kadangkadang seperti diiris-iris. Lebih dirasakan sewaktu lapar dan kurang saat perut kenyang. Mengeluh rasa kembung, mual-mual dan muntah.

Hipotesa
Dispepsia Gastritis Ulkus peptikum

Learning issue
Anatomi (lambung) Histologi (lambung) Fisiologi (lambung) Biosintesa HCL (biokimia) Dispepsia Gastriris DD untuk kasus

REGION OF ANTERIOR ABDOMINAL WALL 1. 2. 3. 4. 5. 6. 7. 8. 9. Hypochondrium dekster Epigastrium Hypochondrium sinister Lumbalis dekster Umbilikalis Lumbalis sinister Iliaca dekster Hypogastrium Iliaca sinister

REGION OF ANTERIOR ABDOMINAL WALL 1. 2. 3. 4. 5. 6. 7. 8. 9. Hypochondrium dekster Epigastrium Hypochondrium sinister Lumbalis dekster Umbilikalis Lumbalis sinister Iliaca dekster Hypogastrium Iliaca sinister

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STOMACH (VENTRICULUS , GASTER) A saccular dilatation of the alimentary canal conecting above with oesophagus below with the duodenum The form of stomach depends particulary on the volume of its contents and on the position of the body when empty contracted when filled fundus and corpus distend Position : the main portion of the stomach lies on the left side of the body

PARTS OF STOMACH Curvatura ventriculi minor Cardia, Fundus ventriculi Corpus ventriculi Curvatura ventriculi major Curvatura ventriculi minor Pars pyloricum Muscularis of the stomach: Outer layer : longitudinal muscle fibres Second layer : circular muscle fibers Deepest layer : oblique muscle fibre with numerous fold

Plica mucosae

Histologi

Stomach
Mucosa Submucosa Muscularis Externa Serosa

Mucosa of Gaster
Epithelium: simple columnar ep
Mucus layer/visible mucus; bicarbonate ion Gastric pit/Foveola gastrica
Surface lining cells Regenerative/stem cells

Lamina propria
Loose, vascular >>> Houses gastric/fundic/oxyntic glands
Surface lining cells Mucous neck cells Regenerative (Stem) cells Parietal (Oxyntic) cells Chief (Zymogenic) Cells DNES Cells/APUD/Enteroendocrine/Argentaffin Cells

Muscularis mucosae
3 layers: inner circular; outer longitudinal; outermost circular (occasionally)

Submucosa of gaster
Dense, irregular CT Richly vascularized n lymphoid tissue Submucosal plexus

Muscularis externa of gaster

Innermost oblique layer, middle circular layer, outer longitudinal muscle layer Myenteric plexus

Serosa of gaster
Thin, lose CT covered by simple squamous ep

Distribution of Cell Type in Fundic Glands

REGION
ISTHMUS NECK BASE

CELL TYPES
Surface-lining cells and few DNES cells Mucous neck cells, Stem cells, parietal cells, and few DNES cells Chief cells, occasional parietal cells, and few DNES cells

Differences in Mucosa Cardiac and Pylorus

Cardiac
Gastric pit depth shallower Highly coiled glands Cell population: mostly surface-lining cell, some mucous neck cells, a few DNES and Parietal cell, but no chief cells

Pylorus
Gastric pit deeper Highly convoluted and tend to branch Same as cardiac; but mostly mucous neck cells

 Apical cell

Surface Lining Cells Produced thick mucus layer

Glycocalyx-covered, short, stubby microvili Secretory granules

Lateral cell
Zonula occludens n adherens

Basally nucleus

Mucous Neck Cells

Columnar, resemble surface-lining cells Produce soluble mucus and lysozyme to lubricate gastric contents Predominat in pyloric

Regenerative (Stem) Cells

In the base of pits but more numeous in the neck Columnar Have little heterochromatin and display large nucleolus

Parietal (Oxyntic) Cells

Large, round to pyramid-shaped Mainly in upper half of fundic glands Produce HCl and gastric intrinsic factor Eosinophilic cytoplasm Invaginations apical plasmalemma to form intracellular canaliculi Tubulovesicular system

Chief (Zymogen) Cells

Columnar with basophilic cytoplasm, basally located nuclei, apical secretory granules (pepsinogen) Rich RER, Golgi apparatus, but a few lysosomes Microvilli Secretion of pepsinogen is induced by both neural and hormonal, triggered by secretin binding to the receptor (in basal cell)

DNES/Argentaffin/APUD/Enteroendocrine Cells

Releases secretory granules to lamina propria

Paracrine Endocrine Neurocrine

13 different secretory granules types 2 types

Closed type Open type
Microvili monitor luminal contents

Fisiologi

Primary Functions of Digestive System

Activity necessary:

Motility Movement of food through tract ,includes ingestion, mastication (chewing food and mixing with saliva), deglutition (swallowing) and peristalsis (rhythmic contractions along GI tract that propel food) Secretion muscular contraction. Endocrine (secretion of hormones that regulate digestive process) Exocrine (secretion of water, enzymes, acid, bicarbonate, into GI tract enzyme & other digestive juices.

Digestion
Hydrolysis reactions that break ingested polymers (large molecules) into their smaller subunits (monomers) breakdown of substances. proteins into amino acids fats into glycerol and free fatty acids complex sugars into monosaccharides

Absorption
Transfer of monomer subunits across wall of small intestine into blood or lymph transport modified nutrients.

Secretion/Digestion
Stomach:
Temporary stores ingested food. sphincters prevent backward flow of materials into esophagus and regulate release of stomach contents into small intestine Churn, mixes food with gastric juice. Mechanical and chemical breakdown of ingested material Produces, mucus, HCl and pepsinogen. HCl converts pepsinogen into pepsin. Sterilization of stomach contents by acid Pepsin digests proteins into peptide fragments. Absorbs some water, alkohol, glucose.

 Stomach:
lower region of stomach (antrum) secretes the hormone gastrin. Additional secretions:
Histamine (ECL cell) Somatostatin

Mucous cell, secrete mucous protects mucosa (epithel) from acid & pepsin. Chief cells, secrete : - Gastric lipase. - Pepsinogen HCl Pepsin Parietal (oxyntic) cells, secrete : - HCl . - Intrinsic factor binds vit. Pyloric gland Alkaline B12 mucus.

HCl Gastrin Histamine Pepsinogen

Control of Acid Secretion

Secretion is dependent upon activity of H, KATPase pump. Gastrin, histamine and acetylcholine increase numbers of enzyme in plasma membrane. + + H K ATP-ase Somatostatin inhibits acid secretion.

Gastrin

Pepsinogen

Control of Acid Secretion

May be considered as three separate phases. 1. Cephalic phase. 2. Gastric phase. 3. Intestinal phase.

Digestion in the stomach

CHO digestion is halted because acidic pH of the stomach inactivates salivary amylase Little fat digestion occurs in the stomach Protein digestion begins in the stomach
Involves mechanical breakdown of proteins by the churning actions of the stomach Involves the chemical digestion of proteins by acid and hormones
Gastric (stomach) acid = hydrochloric acid (HCl) Pepsin

Protein Digestion in the Stomach

Parietal cells
secrete acid (hydrochloric acid = HCL) & intrinsic factor stimulated to produce acid by gastrin

Chief cells
secrete pepsinogen & gastric lipase
Pepsinogen = inactive hormone Pepsinogen converted to pepsin (active hormone) by acidic pH of the stomach Pepsin breaks large proteins down into smaller peptides

Protein Digestion in the Stomach

G cells
Secrete gastrin Gastrin = hormone
target tissues = chief cells and parietal cells in stomach stimulates gastric juice production
HCL from parietal cells Pepsinogen from chief cells

Decreases pH of stomach
Promotes conversion of pepsinogen to pepsin

Absorption in the Stomach

Almost all products of digestion are absorbed in the intestine Notable exceptions
alcohol and aspirin can be absorbed directly through stomach wall due to their lipid solubility absorption of aspirin through stomach wall associated with bleeding, may be related to peptic ulcers in people taking large dosages

Chyme
Food in stomach is liquified
mixed with stomach juices to form pasty liquid material = chyme

Chyme = material passed from stomach to small intestine

Biosintesis HCl
Plasma Sel parietal Karbonik anhidras H2CO CO2 e H2O HCO
3 3

Lumen lambun g

CO2

H+ H+-K+ ATPase K+ Cl-

Cl-

Cl-

Biosintesis HCl
Sel sel parietal (oksintik) merupakan sumber HCl asam lambung. CO2 dari plasma masuk ke sel parietal dan dengan bantuan enzim karbonik anhidrase ditambah H2O menjadi H2CO3 Selanjutnya H+ masuk kedalam lumen lambung dengan bantuan H+-K+ ATPase sedangkan HCO3- akan melintas ke dalam plasma melalui pertukaran Cl-

Dyspepsia
Occurrence discomfort or pain originate from the gastroduodenal region Divided to : -functional -structural / organic -non gastrointestinal

Functional
Cause : genetic, infections and psychological Alter enteric visceral perception : hyperalgesia Alter enteric motor function : impair reflex fundal relaxation, impair gastric receptive relaxation, weak postprandial antral contractions, delay gastric emptying, small bowel motor dysfunction Alter CNS function : anxiety, depression, sexual abuse, sleep deprivation, stresful events

Structural
GERD : lower esophageal sphincter opens spontaneously or doesnt close properly cause gastric juice and foos to rise up PUD : defect in gastricduodenal mucosa (protect from Hcl) Pancreatic disease gallstones

Non GI
Cardiac disease Muscular pain

Symptoms & Signs Because indigestion is nonspecific, it is important to ascertain patients description of symptoms, including :
Character of symptoms Timing Relationship to meals Alleviating/exacerbating factors

Symptoms
Heartburn Warmth or burning in the substernal/upper epigastric area May be worse after certain foods (e.g., citrus, alcoholic beverages, fatty foods) Often alleviated by antacids Salty, sour, or bitter taste in the mouth that comes from regurgitation of gastric contents and bile (often accompanies heartburn) Epigastric gnawing Fullness or pain that is aggravated by eating Nausea Eructation (belching) Dry cough Early satiety

diagnosis
Exclusion other possible causes by history taking and physical examination. Helicobacter pylori (H. pylori) Stomach Bacteria - urea breath test and stool antigen test. Upper Gastrointestinal Endoscopy Gastrointestinal or "Whole Gut" Transit Study Gastric Accommodation Test Satiety (Liquid Meal) Test

 Treatment depends on the underlying cause of indigestion. GERD

Discontinuation of drugs that exacerbate acid reflux Dietary changes Elevation of the head of the bed Acid-suppressing medications Reassurance and patient education Clearing H. pylori infection Acid-suppressing medications Prokinetic medications

Treatment

Functional dyspepsia

Lactase deficiency
Milk product consumption should be reduced or eliminated from the diet. Lactase enzymes can be added or taken with dairy products.

Functional dyspepsia Reassurance and patient education Gas and bloating

Dietary exclusion of gas-producing foods such as legumes Use of simethicone or activated charcoal benefits some patients

Treating H. pylori infection Acid-suppressing medications

Meta-analysis of 8 controlled trials calculated a risk ratio of 0.86 (95% confidence interval 0.780.95) favoring proton pump inhibitor therapy over placebo.
The benefits of less potent acid-reducing therapies such as H2 antagonists are unproved.

Prokinetic drugs Low-dose tricyclic antidepressants

For patients refractory to acid suppressants or prokinetic drugs Mechanism of action is unknown but may involve blunting of visceral pain processing in the brain.

Therapies that modify gut flora, including antibiotics and probiotic preparations containing active bacterial cultures, are useful for cases of bacterial overgrowth and functional lower GI disorders.
Utility in functional dyspepsia is unproved.

Psychological treatments may be offered for refractory functional dyspepsia, but no convincing data suggest efficacy.

 H. pylori eradication H. pylori eradication is indicated for peptic ulcer disease and gastric mucosaassociated lymphoid tissue lymphoma. The utility of eradication therapy in functional dyspepsia is less well established, but < 15% of cases relate to this infection.
Meta-analysis of 13 controlled trials calculated a risk ratio of 0.91 (95% confidence interval 0.870.96) favoring H. pylori eradication therapy over placebo.

Several drug combinations show efficacy; most include 1014 days of a proton pump inhibitor or bismuth subsalicylate in concert with 2 antibiotics. Examples include:
Amoxicillin 1 g PO bid and clarithromycin 500 mg PO bid + PPI (10 days with lansoprazole, omeprazole, pantoprazole, esomeprazole, 7 days with rabeprazole) May substitute metronidazole 400 mg po daily for amoxicillin in the above regimen

Differential Diagnosis

Epigastric pain Definisi Nyeri pada abdomen (epigastrium) daerah perut bagian tengah atas, dalam angulus infrasternal kolik abdomen - bedah peritonitis umum, baik luar /dalam abdomen -Lain : pankreatitis, appendisitis, kolik empedu, kolisistitis, divertikulitis, obstruksi usus, perforasi viskus, peritonitis, salpingitis, kolik renal.

Peptic ulcer Putusnya kontinuitas mukosa lambung yang meluas sampai di bawah epitel.

Etiologi

-Non bedah pankreatitis akut, ileus paralitik,-90% H. Pylory -Endogen (HCL, pepsinogen/pepsin, garam

empedu) - eksogen ( obat-obatan, alkohol, bakteri) - genetik -Stress

Gejala klinik - nyeri abdomen tiba-tiba timbul/sudah berlangsung lama - Nyeri dapat ditentukan lokasinya/sebaliknya oleh pasien -Nyeri akut abdomen cenderung tiba2 - nyeri viseral akut, TD, denyut jantung berubah, pucat, berkeringat - nyeri somatik otot/lapisan dinding perut

-Nyeri hilang/timbul bila di beri makanan - sering terjadi anoreksia, Berat badan

menurun - nyeri sewaktu malam dapat terjadi

Kolelitiasis Definisi Etiologi Penyakit batu empedu - Kasus ini banyak di USA 20%penduduk dewasa , 2 dekade pertama -ras, familial (banyak pd penduduk asli USA, kulit putih, afro-amerika) -DM, sirosis hati, pankreatitis, kanker kandung empedu, reseksi ileum - obesitas, multiparitas, usia tua, wanita - gangguan metabolisme

Kolesistitis Reaksi inflamasi pd kandung empedu

Pankreatitis Reaksi peradangan pada pankreas

-Alkohol - stasis cairan empedu - batu empedu - Infeksi kuman -Iskemia dinding kandung empedu - pasca bedah -- utamanya batu kandung empedu yang - trauma terletak di duktus sistiikus yang menyebabkan -Infeksi ( virus parotitis, stasis cairan empedu hepatitis, coksackie, askaris, mikoplasma) -Obat-obat (azatioprin, sulfonamid, tiazid, dll) -Metabolik (hipertrigliserida, hiperkalsemia, gagal ginjal)

Gejala klinik

-akut nyeri hebat mendadak -kolik perut disebelah kanan atas epigastrium, -nyeri epigastrium tiba2

pd epigastrium/abdomen, kuadran kanan atas -Nyeri dapat menyebar punggung, bahu kanan -Berkeringat banyak -Jalan mondarmandir/berguling ke kanan kiri -Nausea, muntah -Nyeri dpt berlangsung berjam2

nyeri tekan -Meningkatnya suhu tubuh -Rasa nyeri menyebar pundak.skapula kanan -Berat ringan tergantung dr adanya inflamasi -Ikterus 20% kasus -Nyeri bertahan selama 60 menit tanpa reda

-muntah kebanyakan minum alkohol -Nyeri mendadak secara terus menerus -Menyebar nyeri punggung -Nyeri mual, muntah, berkeringat, lemah -Berlangsung sekitar 24 jam