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?

More info• 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.

Hasil pemeriksaan darah lengkap :

- Hb 12gr/dl

- Leukosit 7.000/mm³

- Trombosit 180.000/mm³

- 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 kadang- kadang 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. Hypochondrium dekster

2. Epigastrium

3. Hypochondrium sinister

4. Lumbalis dekster

5. Umbilikalis

6. Lumbalis sinister

7. Iliaca dekster

8. Hypogastrium

9. Iliaca sinister

REGION OF ANTERIOR ABDOMINAL WALL

1. Hypochondrium dekster

2. Epigastrium

3. Hypochondrium sinister

4. Lumbalis dekster

5. Umbilikalis

6. Lumbalis sinister

7. Iliaca dekster

8. Hypogastrium

9. Iliaca sinister

1 2 3

4 5 6

7 8 9

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 CELL TYPES

ISTHMUS Surface-lining cells and few DNES cells

NECK Mucous neck cells, Stem cells, parietal cells, and few DNES cells

BASE 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

Surface Lining Cells

• Produced thick mucus layer• Apical cell

– 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

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) muscular contraction.muscular contraction.

Primary Functions of Digestive SystemActivity necessary:

MotilityMotility

SecretioSecretionn •Endocrine (secretion of hormones that

regulate digestive process)•Exocrine (secretion of water, enzymes, acid, bicarbonate, into GI tract enzyme & enzyme & other digestive juices.other digestive juices.

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

DigestioDigestionn

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

AbsorptioAbsorptionn

• 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.– Binds vit. B12 allows abs. in ileum

Secretion/Digestion

Pepsinogen

HCl

Gastrin

Histamine

• Stomach:– lower region of stomach (antrum) secretes the hormone

“gastrin”.– Additional secretions:

• Histamine (ECL cell)• Somatostatin Mucous cellMucous cell, secrete , secrete

mucous mucous protects mucosa protects mucosa (epithel) from acid & (epithel) from acid & pepsin.pepsin.Chief cellsChief cells, secrete :, secrete :- Gastric lipase.Gastric lipase.- Pepsinogen Pepsinogen Pepsin PepsinParietal (oxyntic) cellsParietal (oxyntic) cells, , secrete :secrete :- HCl .HCl .- Intrinsic factor Intrinsic factor binds binds vit. Bvit. B1212Pyloric gland Pyloric gland Alkaline Alkaline mucus.mucus.

HClHCl

Control of Acid Secretion

•Secretion is dependent upon activity of H, K-ATPase pump.

•Gastrin, histamine and acetylcholine increase numbers of enzyme in plasma membrane.

•Somatostatin inhibits acid secretion.

Pepsinogen

Gastrin

H+K+ ATP-ase

Control of Acid Secretion

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

Biosintesis HCl

Sel parietalPlasma Lumen

lambung

CO2 CO2

H2O

Karbonik anhidrase

H2CO3

HCO3-

Cl- Cl- Cl-

H+

K+H+-K+ ATPase

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

• Helicobacter pylori

Structural • GERD : lower esophageal sphincter opens

spontaneously or doesn’t 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

patient’s 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 • 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

• Functional dyspepsia – Reassurance and patient education – Clearing H. pylori infection – Acid-suppressing medications – Prokinetic medications

• 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 0.78–0.95) 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 mucosa–associated 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 0.87–0.96) favoring H. pylori eradication therapy over placebo.

• Several drug combinations show efficacy; most include 10–14 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 Peptic ulcer

Definisi Nyeri pada abdomen (epigastrium) daerah perut bagian tengah atas, dalam angulus infrasternal

Putusnya kontinuitas mukosa lambung yang meluas sampai di bawah epitel.

Etiologi -Non bedah pankreatitis akut, ileus paralitik, kolik abdomen- bedah peritonitis umum, baik luar /dalam abdomen-Lain : pankreatitis, appendisitis, kolik empedu, kolisistitis, divertikulitis, obstruksi usus, perforasi viskus, peritonitis, salpingitis, kolik renal.

-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 Kolesistitis Pankreatitis

Definisi Penyakit batu empedu Reaksi inflamasi pd kandung empedu Reaksi peradangan pada pankreas

Etiologi - 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

- stasis cairan empedu

- Infeksi kuman-Iskemia dinding kandung empedu-- utamanya batu kandung empedu yang terletak di duktus sistiikus yang menyebabkan stasis cairan empedu

-Alkohol- batu empedu- pasca bedah- trauma -Infeksi ( virus parotitis, hepatitis, coksackie, askaris, mikoplasma)-Obat-obat (azatioprin, sulfonamid, tiazid, dll)-Metabolik (hipertrigliserida, hiperkalsemia, gagal ginjal)

Gejala klinik

-akut nyeri hebat mendadak pd epigastrium/abdomen, kuadran kanan atas-Nyeri dapat menyebar punggung, bahu kanan-Berkeringat banyak-Jalan mondar-mandir/berguling ke kanan kiri-Nausea, muntah-Nyeri dpt berlangsung berjam2

-kolik perut disebelah kanan atas epigastrium, 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

-nyeri epigastrium tiba2

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