Adrian Pratama – 405100018 – GI Tract Block

PROBLEM - 2A (ADULT)
LO 1

 Capable to explain
 Histology(stomach & duodenum),
 Anatomy (stomach – ileum),

 Physiology (stomach & duodenum),

 Biochemistry of GI tract (stomach & duodenum)

1ST LO (1)

 Histology (stomach & duodenum)

STOMACH

 Function:
 continue the digestion of carbohydrates
 add an acidic fluid to the ingested food

 produces a gastric lipase that digests triglycerides

 Regions:
 Cardia, fundus, corpus (body), pylorus
Rugae of stomach Gastroesophageal junction
Gastric pits & glands
FUNDUS & CORPUS

Mucous neck cells  mucus secretion; Parietal cells  HCl & Intrinsic factors
OTHER CELLS
 Chief (zymogenic) cells
 lower region of the tubular glands
 contain the inactive enzyme pepsinogen
 Enteroendocrine cells
 secrete a variety of hormones, almost all short polypeptides
 In the fundus enterochromaffin cells (EC cells) are found on
the basal lamina of gastric glands  serotonin (5-
hydroxytryptamine)
 Gcells which produce the polypeptide gastrin
 Stem cells
 found in the neck region of the glands (low columnar cells with
basal nuclei and divide asymmetrically)
SYNTHESIS OF HIDROCHOLRIC ACID

HCO3- Na+
PYLORUS

-. Funnel shaped region opening to small

intestine

-. The mucosa had pyloric glands

DUODENUM

 Lining of the small intestine shows a series of

permanent circular or semilunar folds (plicae
circulares)
 Intestinal villi are 0.5- to 1.5-mm-long mucosal
outgrowths (epithelium plus lamina propria) and
project into the lumen
 Villi
are covered by a simple columnar epithelium of
absorptive cells and goblet cells
 Paneth cells 

Intestinal crypts / (Lieberkuhn) glands/rypts

Duodenal (Brunner) glands
1ST LO (2)

 Anatomy (stomach – ileum)

MUSCLES OF THE ANTEROLATERAL ABDOMINAL WALL
NERVES OF THE ANTEROLATERAL ABDOMINAL WALL

 Thoracoabdominal nerves
 distal, abdominal parts of the anterior rami of the inferior six
thoracic spinal nerves (T7 – T11)
 the former inferior intercostal nerves distal to the costal
margin
 Lateral (thoracic) cutaneous branches
 of the thoracic spinal nerves T7 - T9 or T10
 Subcostal nerve
 the large anterior ramus of spinal nerve T12
 Iliohypogastric & ilioinguinal nerves
 terminal branches of the anterior ramus of spinal nerve L1
 Anterior abdominal cutaneous branches of
thoracoabdominal nerve
 T7 – T9  skin superior to the umbilicus
 T10  skin around the umbilicus

 T11 + cutaneous branches of the subcostal (T12),

iliohypogastric, and ilioinguinal (L1)  skin inferior to
the umbilicus
VESSELS OF ANTEROLATERAL ABDOMINAL WALL

 Superior epigastric vessels and branches of the

musculophrenic vessels from the internal thoracic
vessels
 Inferior epigastric and deep circumflex iliac vessels
from the external iliac vessels
 Superficial circumflex iliac and superficial epigastric
vessels from the femoral artery and greater
saphenous vein
 Posterior intercostal vessels of the 11th intercostal
space and the anterior branches of subcostal vessels
ARTERIES
LYMPHATIC DRAINAGE

 Superficial lymphatic vessels

 superior to the transumbilical plane drain mainly to
the axillary lymph nodes; a few drain to the
parasternal lymph nodes
 inferior to the transumbilical plane drain to the
superficial inguinal lymph nodes
 Deep lymphatic vessels
 drain to the external iliac, common iliac, and right
and left lumbar (caval and aortic) lymph nodes
VEINS & LYMPH NODE
PERITONEUM & PERITONEAL CAVITY
  A continuous, glistening and slippery transparent
serous membrane
 parietal peritoneum
 lines the internal surface of the abdominopelvic wall
 served by the same blood and lymphatic vasculature and
the same somatic nerve supply
 visceral peritoneum
 invests viscera such as the stomach and intestines
 served by the same blood and lymphatic vasculature and
visceral nerve supply
SUBDIVISIONS OF PERITONEAL CAVITY
OVERVIEW
STOMACH
 Cardia
 the part surrounding the cardial orifice
 Fundus
 dilated superior part that is related to the left dome of the
diaphragm and is limited inferiorly by the horizontal plane of
the cardial orifice
 Body
 major part of the stomach between the fundus and the pyloric
antrum
 Pylorus
 funnel-shaped outflow region of the stomach; its wide part,
the pyloric antrum, leads into the pyloric canal, its narrow part
BED OF STOMACH
 left dome of the diaphragm, spleen, left kidney and suprarenal
gland, splenic artery, pancreas, and transverse mesocolon and
colon
ARTERIES
VEINS
NERVES & LYMPHATIC DRAINAGE
DUODENUM
 Superior (L1)
 proximal part has the hepatoduodenal ligament (part of
the lesser omentum) attached superiorly, greater
omentum attached inferiorly
 Descending (L1 – L3)
 major duodenal papilla, located posteromedially in the
descending duodenum
 Horizontal (L3)
 Ascending (L3 – L2)
 curves anteriorly to join the jejunum at the
duodenojejunal junction, supported by the attachment of
a suspensory muscle of the duodenum (ligament of
Treitz)
ARTERIES, VEINS, & LYMPHATIC DRAINAGE
JEJUNUM & ILEUM

 jejunum,
 begins at the
duodenojejunal flexure
where the alimentary
tract resumes an
intraperitoneal course
 ileum,
 ends at the ileocecal
junction, the union of the
terminal ileum and the
cecum
ARTERIES & VEINS
LYMPH DRAINAGE
NERVES
1ST LO (3)

 Physiology & Biochemistry (stomach &

duodenum)
STOMACH
 3 main functions
 Store ingested food until it can be emptied into the
small intestine
 Secretes HCl & enzymes, begin protein digestion
 Stomach’s mixing movement  ingested food
pulverized & mixed with gastric secretions  thick
liquid mixture (chyme)

 Gastric’s motility
 Filling, storage, mixing, emptying
GASTRIC FILLING
 Volume about 50 ml; can expand to 1l during a
meal
 Folds of gastric get smaller & nearly flatten out as
stomach relaxes slightly (receptive relaxation) 
enhance stomach to accomodate the extra
volume of food with little rise in stomach
pressure
 Triggered
by the act of eating & mediated by the
vagus nerve
GASTRIC STORAGE (BODY OF STOMACH)

 Interstitial cells of Cajal  generates slow wave

potential (Basic electrical rhythm)  occurs
continuously with or without muscle contraction
 food is stored in the relatively quite body
without being mixed

 Fundus contains only pocket of gas

GASTRIC MIXING (ANTRUM OF STOMACH)

 Strong antral peristaltic  mix food & gastric

juice ( chyme)  propels the chyme towards
pyloric sphincter
 Tonic contraction of pyloric sphincter keeps it
almost closed  bulk of the antral chyme
tumbled back into the antrum  propeled
forward  tumbled back again as the new
peristaltic wave advances
GASTRIC EMPTYING

 Gastric factor
 Amount of chyme; stomach distention  strecth of
smooth muscle, intrinsic plexuses, vagus nerve,
gastrin  gastric motility >>
 Degree of fluidity

 Duodenum factor
 Fat, acid, hypertonicity, & distention
MECHANISM OF H & CL IONS SECRETION
Function of HCl:

-. Activate pepsiongen 
pepsin

-. Aids breakdown of
connective tissue & muscle
fibers, reducing food into
smaller particles

-. Denaturates protein

-. Along with lysozyme  kills

microorganism
PEPSINOGEN, ACTIVATED  PROTEIN DIGESTION

Pepsin’s autocatalytic activity

MUCUS

 Lubricating properties, protects gastric mucosa

 Protect the stomach wall from self-digestion
because of pepsin
 doesn’t affect pepsin activity in the lumen
 Being alkaline  neutralizing HCl
 Doesn’t interfere with the function of HCl in the
lumen
REGULATORY PATHWAYS  PARIETAL & CHIEF CELLS

 Acetylcholine  short local reflexes & vagal

stimulation  parietal & chief cells, G & ECL cells
 G cells  secrete gastrin
 Main factor for increased HCl secretion by stimulating ECL
cells to release histamine
 Enterochromaffin like cells  paracrine histamine
 Speed up HCl secretion, potentiates ACh & gastrin
 D cells  paracrine somatostatin
 Negative feedback fashion
CONTROL OF GASTRIC SECRETION
2ND LO

 Capable to explain dyspepsia

NAUSEA & VOMITING
 Nausea  the subjective feeling of a need to
vomit
 Vomiting (emesis)  the oral expulsion of
gastrointestinal contents resulting from
contractions of gut and thoracoabdominal wall
musculature
ACTIVATORS OF EMESIS
 unpleasant thoughts or smells  cerebral cortex;
 cranial nerves mediate vomiting after gag reflex activation
 Motion sickness and inner ear disorders  labyrinthine
apparatus;
 whereas gastric irritants and cytotoxic agents such as cisplatin
stimulate gastroduodenal vagal afferent nerves (serotonin 5-
HT3 receptors)
 Labyrinthine disorders  vestibular cholinergic muscarinic M1
and histaminergic H1 receptors
 Nongastric visceral afferents are activated by intestinal
and colonic obstruction and mesenteric ischemia
MECHANISM
 Initiation of emesis
 nucleus tractus solitarius, dorsal vagal and phrenic nuclei,
medullary nuclei  regulate respiration
 nuclei that control pharyngeal, facial, and tongue movements
 Neurotransmitters  neurokinin NK1, serotonin 5-HT3, and
vasopressin

 Inspiratory thoracic and abdominal wall muscles contract

 high intrathoracic and intraabdominal pressures that
facilitate expulsion of gastric contents  gastric cardia
herniates across the diaphragm and the larynx moves
upward to promote oral propulsion of the vomitus
PHYSICAL EXAMINATON
 Demonstration of orthostatic hypotension and reduced
skin turgor indicate intravascular fluid loss
 Pulmonary abnormalities raise concern for aspiration of
vomitus
 Auscultation
 may reveal absent bowel sounds with ileus
 High-pitched rushes suggest bowel obstruction,
 succussion splash upon abrupt lateral movement of the
patient is found with gastroparesis or pyloric obstruction
 Tenderness or involuntary guarding raises suspicion of
inflammation
 Fecal blood suggests mucosal injury from ulcer, ischemia,
or tumor.
DIFFERENTIAL DIAGNOSIS
TREATMENT
-. Hospitalization is considered for severe dehydration especially if oral fluid
replenishment cannot be sustained

-. Once oral intake is tolerated, nutrients are restarted with liquids that are low in fat
INDIGESTION
 Indigestion is a nonspecific term that
encompasses a variety of upper abdominal
complaints including nausea, vomiting,
heartburn, regurgitation, and dyspepsia (the
presence of symptoms thought to originate in
the gastroduodenal region)
 Dyspepsia
 Epigastricburning, gnawing discomfort, or pain
 postprandial fullness, early satiety, bloating, eructation
(belching), and anorexia
MECHANISM
 Gastroesophageal Acid Reflux
 Reduced lower esophageal sphincter (LES) tone is an
important cause of reflux in scleroderma and pregnancy
 frequent transient LES relaxations during which acid bathes
the esophagus
 Overeating and aerophagia can transiently override the barrier
function of the LES
 Gastric Motor Dysfunction
 Disturbed gastric motility  acid reflux in some cases of
indigestion
 Delayed gastric emptying is also found in 25–50% of functional
dyspeptics
 bloating, nausea, and early satiety
 Visceral Afferent Hypersensitivity
 dyspeptic patients experience discomfort with fundic
distention to lower pressures than healthy controls
 Some patients with heartburn exhibit normal esophageal acid
exposure
 Other Factors
 Helicobacter pylori has a clear etiologic role in peptic ulcer
disease, but ulcers cause a minority of cases of dyspepsia
 functional dyspepsia is associated with a reduced sense of
physical and mental well-being and is exacerbated by stress,
suggesting an important role for psychological factors
 Analgesics cause dyspepsia
 nitrates, calcium channel blockers, theophylline, and
progesterone promote acid reflux
 ethanol, tobacco, and caffeine  LES relaxation
DIFFERENTIAL DIAGNOSIS

 GERD
 Functional Dyspepsia

 Ulcer disease

 Malignancy
GASTROESOPHAGEAL REFLUX DISEASE

 Symptoms
 15%  heartburn &/ regurgitation at least once a
week; 7%  daily
 Caused by backflow of gastric acid and other gastric
contents into the esophagus due to incompetent
barriers at the gastroesophageal junction
PATHOPHYSIOLOGY
 LES incompetence / transient decrease in LES tone (tLESR),
caused by
 scleroderma-like diseases,
 myopathy associated with chronic intestinal pseudo-
obstruction,
 pregnancy,
 smoking,
 anticholinergic drugs,
 smooth-muscle relaxants (β-adrenergic agents, aminophylline,
nitrates, calcium channel blockers, and phosphodiesterase
inhibitors),
 surgical
 esophagitis
 Gastric contents are most likely to reflux when
 gastric volume is increased (after meals, in pyloric
obstruction, in gastric stasis, during acid
hypersecretion states)
 gastric contents are near the gastroesophageal
junction (in recumbency, bending down, hiatal
hernia)
 gastric pressure is increased (obesity, pregnancy,
ascites, tight clothes)
CLINICAL FEATURES
 Heartburn and regurgitation of sour material into the
mouth
 Angina-like or atypical chest pain occurs in some patients
 Persistent dysphagia suggests development of a peptic
stricture
 Rapidly progressive dysphagia and weight loss may indicate
the development of adenocarcinoma in Barrett's esophagus
 Bleeding occurs due to mucosal erosions or Barrett's ulcer

 reflux of gastric contents into the pharynx, larynx,

tracheobronchial tree, nose, and mouth  chronic cough,
laryngitis, and pharyngitis, morning hoarseness; chronic
bronchitis, asthma, pulmonary fibrosis, chronic obstructive
pulmonary disease, or pneumonia
DIAGNOSIS
 Documentation of mucosal injury
 barium swallow,
 esophageal peptic stricture, a deep ulcer, or adenocarcinoma suggests
Barrett's esophagus
 esophagoscopy,
 presence of erosions, ulcers, peptic strictures, or Barrett's metaplasia
with or without ulcer, peptic stricture, or adenocarcinoma
 mucosal biopsy
 performed at least 5 cm above the LES
 Documentation & quantition of reflux
 ambulatory long-term (24–48 h) esophageal pH recording
 Definiton of the pathophysiology
TREATMENT
 Mild cases
 weight reduction, sleeping with the head of the bed
elevated by about 4–6 in
 blocks, and elimination of factors that increase abdominal
pressure
 should not smoke and should avoid consuming fatty
foods, coffee, chocolate, alcohol, mint, orange juice, and
certain medications (such as anticholinergic drugs,
calcium channel blockers, and other smooth-muscle
relaxants)
 avoid ingesting large quantities of fluids with meals
MEDICATIONS
 lifestyle change and over-the-counter antisecretory
agents may be adequate.
 H2 receptor blocking agents (cimetidine, 300 mg qid;
ranitidine, 150 mg bid; famotidine, 20 mg bid; nizatidine,
150 mg bid) are effective in symptom relief
 PPIs are comparably effective (omeprazole (20 mg/d),
lansoprazole (30 mg/d), pantoprazole (40 mg/d),
esomeprazole (40 mg/d), or rabeprazole (20 mg/d) for 8
weeks can heal erosive esophagitis in up to 90% of
patients)
 taken 30 min before breakfast
 cholestyramine, aluminum hydroxide, or sucralfate(low or
no acid)
SURGERY

 Antireflux surgery
 the gastric fundus is wrapped around the esophagus
(fundoplication)  creates an antireflux barrier
 Idealcandidates for fundoplication are those who have
classical GERD with good response to PPI therapy and in
whom motility studies show poor LES pressures but normal
peristaltic contractions in the esophageal body
 Laparoscopic or endoscopic antireflux procedures
should be considered as alternatives in young
patients who require long-term, high-dose PPIs
PEPTIC ULCER DISEASE
 Burning epigastric pain exacerbated by fasting and
improved with meals is a symptom complex associated
with peptic ulcer disease
 Ulcer  disruption of the mucosal integrity of the
stomach and/or duodenum leading to a local defect or
excavation due to active inflammation

 Epidemiology
 Lifetime prevalence of PUD in the United States is ~12% in
men and 10% in women
 estimated 15,000 deaths per year occur as a consequence of
complicated PUD
GASTRODUODENAL MUCOSAL DEFENSE
PHYSIOLOGY OF GASTRIC SECRETION
PATHOLOGY
 Duodenal ulcers
 first portion of duodenum (>95%), with ~90% located within 3
cm of the pylorus
 1 cm in diameter but can occasionally reach 3–6 cm (giant
ulcer)
 base of the ulcer often consists of a zone of eosinophilic
necrosis with surrounding fibrosis
 Gastric ulcers
 can represent a malignancy
 most often found distal to the junction between the antrum
and the acid secretory mucosa
 Benign GUs associated with H. pylori are also associated with
antral gastritis
 NSAID-related GUs are not accompanied by chronic active
gastritis but may instead have evidence of a chemical
gastropathy
PATHOPHYSIOLOGY

 Duodenal ulcers
 H. pylori and NSAID-induced injury account for the
majority of Dus
 average basal and nocturnal gastric acid secretion
appears to be increased in DU patients as compared
to controls
 Bicarbonate secretion is significantly decreased in the
duodenal bulb of patients with an active DU as
compared to control subjects
 Gastric ulcers
 majority of GUs can be attributed to either H. pylori or NSAID-
induced mucosal damage
 occur in the prepyloric area or those in the body associated
with a DU or a duodenal scar are similar in pathogenesis to
Dus
 Gastric acid output (basal and stimulated) tends to be normal
or decreased in GU patients
 develop in the presence of minimal acid levels, impairment of
mucosal defense factors may be present
 Abnormalities in resting and stimulated pyloric sphincter
pressure with a concomitant increase in duodenal gastric
reflux
 Delayed gastric emptying of solids has been described in GU
patients but has not been reported consistently
H. PYLORI & ACID PEPTIC DISORDERS
 The bacterium
 initially
named Campylobacter pyloridis
 gram-negative microaerophilic rod found most
commonly in the deeper portions of the mucous gel
coating the gastric mucosa or between the mucous
layer and the gastric epithelium
 Virulency
 outer membrane protein (Hop proteins), urease, and the
vacuolating cytotoxin (Vac A)
 cag pathogenicity island (cag-PAI)  Cag A into host cells;
Cag A activates a series of cellular events important in cell
growth and cytokine production
 Risk factor for H. Pylori
 birthor residence in a developing country
 domestic crowding

 unsanitary living conditions

 unclean food or water

 exposure to gastric contents of an infected individual

PATHOPHYSIOLOGY
NATURAL HISTORY OF INFECTION
NSAID – INDUCED DISEASE
 Epidemiology
 NSAIDs represent a group of the most commonly used
medications in the United States
 in the year 2000, the number of prescriptions written for NSAIDs was
>111 million at a cost of $4.8 billion
 75 mg/d of aspirin may lead to serious gastrointestinal
ulceration; thus, no dose of NSAID is completely safe

 Risk factors
 advanced age, history of ulcer, concomitant use of
glucocorticoids, high-dose NSAIDs, multiple NSAIDs,
concomitant use of anticoagulants, and serious or multisystem
disease
 infection with H. pylori, cigarette smoking, and alcohol
consumption
PATHOPHYSIOLOGY
OTHERS ETIOLOGY OF PEPTIC ULCERS
CLINICAL FEATURES
 Abdominal pain
 Epigastric pain described as a burning or gnawing
discomfort can be present
 ill-defined, aching sensation or as hunger pain
 DU
 Pain that awakes the patient from sleep (between midnight
and 3 A.M.) is the most discriminating symptom
 typical pain pattern in DU occurs 90 min to 3 h after a meal
and is frequently relieved by antacids or food
 GU
 The pain pattern in GU patients  discomfort may actually be
precipitated by food
PHYSICAL EXAMINATION

 Epigastric tenderness is the most frequent finding in

patients with GU or DU (right of the midline in 20%
of patients)
 Tachycardia and orthostasis suggest dehydration
secondary to vomiting or active gastrointestinal
blood loss
 tender, boardlike abdomen suggests a perforation

 succussion splash indicates retained fluid in the

stomach, suggesting gastric outlet obstruction
COMPLICATIONS
 GI bleeding
 Perforation
 DUs tend to penetrate posteriorly into the pancreas, leading to
pancreatitis
 GUs tend to penetrate into the left hepatic lobe.
 Gastrocolic fistulas associated with GUs have also been
described
 Gastric outlet obstruction
 obstruction secondary to ulcer-related inflammation and
edema in the peripyloric region
 early satiety, nausea, vomiting, increase of postprandial
abdominal pain, and weight los
DIFFERENTIAL DIAGNOSIS
 NUD, also known as functional dyspepsia or essential
dyspepsia
 heterogeneous disorders typified by upper abdominal pain
without the presence of an ulcer
 The etiology of NUD is not established
 proximal gastrointestinal tumors,
 gastroesophageal reflux,
 vascular disease,
 pancreaticobiliary disease (biliary colic, chronic
pancreatitis), and
 gastroduodenal Crohn's disease
DIAGNOSTIC EVALUATION

 Barium study

 Endoscopy
 H. Pylori tests
TREATMENT
ERADICATION OF H. PYLORI
THERAPY OF NSAID-RELATED GASTRIC OR
DUODENAL INJURY
APPROACH & TREATMENT (SUMMARY)
REFERENCES
 Dalley, Arthur F. Keith L Moore. Clinically Oriented
Anatomy. 5th edition. Lippincott Williams & Wilcins;
2006
 Fauci. Braunwald. Dkk. Harrison’s Principles of
Internal Medicine. 17th edition. United State: The
McGraw-Hills; 2008
 L. Mescher, Anthony. Junquera’s Basic Histology Text
and Atlas. 20th edition. United State: The McGraw-
Hills; 2010
 Sherwood,Lauralee. Fisiologi Manusia dari Sel ke
Sistem. Cetakan pertama edisi 2. Jakarta: EGC; 2001