Gastric Secretion

Dr.Gomathi Sivakumar
Assistant Professor
IPEM,
MMC.
William Beaumont
He was a surgeon  who became
known as the "Father of Gastric
physiology" 

He described many functions of

gastric juice by making studies
on his patient Alexis St.Martin
who had a gastric fistula

He also reported that fear and

anger inhibited secretion
Gastric Secretion
 Functional anatomy of stomach
 Gastric secretion
 Functions of stomach
 Gastric function tests
 Applied aspects
FUNCTIONAL ANATOMY
Gastric mucosa
rugae – infoldings of mucosa and submucosa

simple columnar epithelium

gastric pits
gastric glands
-Cardiac
-Oxyntic (Main)
-Antral (pyloric)
 Cells
Types Location, Secretion,stimuli
 Surface mucus cells
Insoluble mucus
gel like coat

 Mucus neck cells

- HCO3-
- Soluble mucus
- progenitor cells
 Parietal cells/ Oxyntic cells
upper half of main gastric glands
HCl & intrinsic factor
vagus, gastrin, histamine
 Chief cells/Peptic/ Zymogen cells
Lower half – main gastric
pepsinogen
vagus, gastrin, histamine
 G Cells
Antral glands
Gastrin (hormone) ---> HCl secretion
 D Cells
Antral glands
Somatostatin (Hormone)
 Enterochromaffin-like cell
Histamine ---> HCl secretion
Muscular layer
 Inner oblique
 Middle circular
 Outer Longitudinal
Blood supply
 Gastric arteries from celiac trunk
 Gastric veins to portal vein
Innervation
 Intrinsic
 Extrinsic
Sympathetics via celiac plexus
Parasympathetic via vagus
Composition
Mechanism of secretion
Phases of secretion
Regulation of secretion

GASTRIC SECRETION
 Exocrine – Gastric juice
 Endocrine - Gastrin
 Gastric juice
 2 to 2.5 litres
 pH 1 to 2 acidic
 Water 99.45 %
 Solids 0.45%
 Gastric juice
 Electrolytes HCL
 Enzymes Pepsinogen, gelatinase lipase,
lysozyme,carbonic anhydrase
 Intrinsic factor
 Mucus (mucus gel layer)

Chyme ingested food plus stomach secretions

 Cell
 Location
 Function
 Regulation
 Gastric juice

HCL Secretion
 Secreted by parietal cells
Fundus
Body
Mechanism of acid secretion
 HCL Secretion (cont)
 Mechanism of HCl production:
 H/K ATPase
 Inhibited by: omeprazole
 H/K pump depends on [K]out
 [HCl] drives water into gastric content to
maintain iso-osmolality
 During gastric acid secretion:
amount of HCO3- in blood = amount of HCl being
secreted
 Alkaline tide
Neural & Hormonal Control of Gastric
Secretion

 Vagus nerve (neural effector)

 Gastrin (hormonal effector)
 Enterochromaffin-like cellsHistamine ---
H2 receptor (parietal cells)  acid secretion

 Cimetidine (H2 receptor blocker) peptic ulcer and

gastroesophageal reflux
Gastric Acid Secretion
 Basolateral membrane of the parietal cell
contains specific receptors for the three major
stimulants of acid production
 Histamine
 Gastrin
 Acetylcholine
 Each stimulant has its own 2nd messenger
system which allows for stimulation of the
parietal cell
Gastrin
 Chemical nature
 Secreted by
 Stimuli / inhibitors
 Functions
 Heidenheins pouch
 Applied – APUDoma/Zollinger Ellison
Syndrome
 Phases of Acid Secretion
 Cephalic phase20%(Guyton) 1/3to ½(Ganong):
 Smelling, Chewing and swallowing
 Stimulates parietal G-Cells
 GRP

 Gastric phase (70%):

 gastric distention
 proteins
 Intestinal phase (5%)(Gastrin fom duodenal
mucosa)
 digested proteins
Cephalic phase
Stimulated acid secretion begins with
 Cephalic phase
 Thought, sight or smell of food stimulates acid secretion
 Mediated by Vagal stimulation
 Vagal discharge
 Directs the cholinergic mechanism for stimulation
 Can be inhibited by Atropine (anticholinergic)

 Inhibits release of somatostatin

 Vagal effects inhibit tonic inhibition that is provided
by somatostatin
Gastric Phase
 Gastric Phase
 Begins when food enters the stomach
 The following are responsible for stimulation of acid secretion
 Presence of partially hydrolyzed food constituents

 Gastric distention

 Gastrin is the most important mediator of this phase

 Ends when Antral muscosa is exposed to acid
 When luminal pH is <2.0 in the antrum, gastrin release stops
 Somatostatin release is increased
 Entry of digestive products into the intestine begins the
intestinal-phase inhibition of gastric acid secretion
Intestinal phase
 Intestinal Phase
 Also, releases HCl by way of Gastrin

 Releases secretin to inhibit Gastrin which

ultimately decreases Acid production

 Inhibition of Acid Secretion
 Inhibitory hormones (Enterogastrones):
 Somatostatin (D-cells) in antrum
 Secretin (S-cells) in duodenum
 Glucose-dependent insulinotropic peptide
(GIP) in duodenum
Release of Gastric Juice

Figure 23.16
Experiments on Gastric secretion
Sham feeding
Pavlov’s pouch
Heidenhein’s pouch
 Bickel’s pouch
 Ivy’s pouch
Other Factors
 Pepsin
 Secreted from gastric chief cells
 Contributes to the overall coordination of the
digestive process
 Main function is to initiate protein digestion,
usually is incomplete
 Partially hydrolyzed protein by pepsin are important
signals for release of
 Gastrin
 Cholecystokinin
Other Factors
 Intrinsic Factor (IF)
 Located in the parietal cells (oxyntic gland)
 Main function is to absorb cobalamin (Vitamin
B12) form ileal mucosa and then transported
to the liver
 Secretion of IF is similar to acid secretion
 stimulated
 Ach
 Histamine
 Gastrin
Other Factors
 Bicarbonate
 Secreted from the gastric
mucosa
 Theory is that bicarbonate is
secreted to maintain a
neutral pH at the mucosal
surface, even if acidic in
lumen
 Cholinergic agonist, vagal
nerve stimulation have been
shown to increase gastric
bicarbonate production
FUNCTIONS OF STOMACH
 Motor – Storage, mixing, emptying
 Secretory
 Digestive – Protein
 Absorptive Highly lipid soluble, non-
ionised – aspirin, alcohol
 Excretory - Uremia,morphine
 Reflex function
GASTRIC FUNCTION TESTS
 Hence to get complete data of gastric fn, the
contents of stomach should be examined
 During resting period
 During digestion after meals
 After stimulation
Gastric juice secreted in 24 hrs is
N about 1500 ml to 2000ml.
Indications of Gastric Function
Tests
 To diagnose Gastric Ulcers
 To exclude the diagnosis of Pernicious
Anaemia & Peptic ulcer in Pt with GU.
 For presumptive diagnosis of Zollinger
Ellison Syndrome
 To determine the completeness of
Surgical Vagotomy.
CLASSIFICATION OF GFTs
 Analysis of Resting contents(Gastric Residuum)
 Fractional Test Meal Analysis
 Analysis after Stimulation
# Alcohol stimulation
# Caffeine stimulation
# Histamine stimulation
CONTD……
# Augmented Histamine test
# Insulin stimulation
# Pentagastrin test
 Tubeless Gastric Analysis
 Other relevant tests are estimation of
Sr.Gastrin, Sr.Pepsinogen levels, Tests for
Occult blood and Tests for H.Pylori
 Analysis of resting contents:

1) Volume : N20-50ml after a night fast

> 100-120 ml….is abnormal
Volume..
- Hypersecretion of Gastric juice
- Retention due to delayed emptying
- Regurgitation of duodenal contents.
 N
2) Consistency : Fluid, should not contain
food residues.
N
3) Colour: Clear/ Colourless/ slight
yellow/green..
Bright red / dark red / brown…abnormal
dark brown seen in bleeding gastric ulcer,
coffee ground appearance seen in Ca
stomach.
4) Bile: Small amounts are insignificant, but
increased in Intestinal Obstruction / Ileal
Stasis.
N
5) Mucus: in small amounts, increased in
gastritis , Ca Stomach.
6) Free & Total Acidity: determined by
titrating a portion of the sample with a
standard solution of NaOH.
 Free acidity measures only HCl, Topfer’s
reagent is used as indicator.

 Total acidity includes HCl and other

organic acids , Phenolphthalein is used as
indicator
 Normal values
- Free Acid : 0-30 mEq / L
> 50 mEq / L indicates Hyperacidity
- Total Acid : 10-40 mEq / L

7) Organic Acids: like lactic acid & butyric acid

in large amounts indicate
achlorhydria/hypochlorhydria.
 Fractional Test Meal Analysis

-Ewald test meal (2 pieces toast+250

ml tea)
-Oatmeal porridge
-Riegel meal..not used normally
 Procedure: After removing residual contents,
meal is given. With intervals of 15 minutes
contents of stomach are removed ,strained &
analysed.

 Normally free acid rises steadily from 15 min

– ½ hr/45 min, and decreases.
 Abnormal responses are:
1) Hyperchlorhydria / Hyperacidity: when free
acid is > 50mEq / L
Seen in - Duodenal ulcer,
Gastric ulcer,
Gastric cell hyperplasia,
After Gastroenterostomy,
Contd…..
Gastric Neurosis,
Hyperirritability,
Pylorospasm ,
Pyloric Stenosis ,
Chr. Cholecystitis,
Zollinger Ellison Syndrome.
2) Hypochlorhydria / Hypoacidity:
Seen in Ca Stomach , Atonic Dyspepsia

3) Achlorhydria: No HCl is seen but pepsin is

present. Seen in Ca Stomach, Chr.Gastritis,
Partial Gastrectomy, Pernicious Anaemia,
Hyper thyroidism, Myxoedema.
Fractional Test Meal
 ACHYLIA GASTRICA : is a condition
where both enzymes and acids are absent
Seen in – Advanced Ca Stomach
-- Advanced cases of Gastritis
-- Pernicious Anaemia
-- Subacute combined
degeneration of spinal cord.
Analysis after Stimulation :

1) Alcohol Stimulation :
-stimulant used is 7% ethyl alcohol.
- the residual contents removed after
overnight fasting, 100ml alcohol is given,
samples are taken every 15 min &
analysed for free, total acidity,peptic
activity,blood, bile,mucus.
 Advantages :
- more easy to administer
- consumed better than porridge
- gastric response is rapid
- emptying of stomach is more rapid than
porridge.
 Disadvantages:
- stimulus with alcohol is not so strictly
physiological as with oatmeal.
- stimulus is more vigorous compared to
oatmeal
- rather high levels of free acidity seen.
 2) Caffeine Stimulation :
- Caffeine Sodium Benzoate,500mg dissolved in
200ml of water is given.
- Advantages are similar to that of alcohol
stimulation.
 3) Histamine Stimulation Test:

- it is a powerful stimulant for secretion of HCl,

acts on oxyntic cells(specific H2receptors )
 Indications : To differentiate “ True “
Achlorhydria from “ False “ Achlorhydria

 Types of Histamine test

- Standard Histamine test
- Augmented histamine test (Kays test).
 Standard Histamine test: SC injection of Histamine
0.01mg/kg bwt , is given.
# Results
- Absence of HCl…true achlorhydria, seen in
pernicious anemia.
- Increase in HCl…Duodenal Ulcer
 Augmented Histamine test (Kays) :

larger dose, 0.04mg/kg b wt of histamine acid

phosphate, SC.
 Indications: -to show inability to secrete
acid as in pernicious anemia & subacute
combined degeneration of cord.
- to assess max possible acid secretion in
diagnosis & Surg.Rx of Duodenal ulcer.
 Disadv : larger dose causes severe allergic
reactions,hence another antihistaminic
given to prevent.
 Procedure: After overnight fast, residual contents
are analysed and contents are collected every 20
min for an hr.
 Halfway through this period 4ml of mepyramine
maleate (anthisan), given IM, to block H1
receptors.
 At the end of hr histamine acid phosphate,0.04mg
/ kg bwt, SC given.and contents removed every
15 min for 1 hr.
 Recently, histamine analogue,called
“Histalog”(3 beta-amino ethyl pyrazole) is used
instead of histamine

 recommended dose –10-50mg

 No side effects seen hence no need to use an

antihistamine to block H1 receptors.
 4) Insulin Stimulation test (Hollander’s
test): Hypoglycemia produced by insulin is
a potent stimulus of gastric acid secretion.
 Indications: to see the effectiveness of
vagotomy in pts with duodenal ulcer.
 15units of soluble insulin given IV
 Disadv: Hypoglycemia
 Results: in pts with
DU , before operation
there is marked &
prolonged output of
acid in response to
insulin. After successful
vagotomy, there is no
response and acid level
is very low.
 5) Pentagastrin test: Pentagastrin,
synthetic peptide, having biologically
active sequence of gastrin.It is “Butyl oxy
carbonyl- beta alanine Trp-Met-Asp-Phe
CONH2”
 Dose— 6 microgram/kg bwt. SC
 It is a potent stimulator, causing max
stimulation after assessing basal secretion
rate, hence it is a measure of Total
Parietal Mass.
 Procedure: after removing the residual
contents , the gastric juice secreted for
next 1 hr is collected as a single sample,
which is called BASAL SECRETION.
 Then pentagastrin is given & 4 samples are
collected with 15 min intervals.
 Basal Acid Output (BAO) is output in mmol /
hr, in basal secretion.
 Maximal Acid Output(MAO) is output in
mmol/hr, given by sum of the 15 min acid
output after stimulation.
 Peak Acid output (PAO) is output of 2
 Consecutive 15 min samples having highest
acid content and the value is multiplied by 2.
N
 Result: basal secretion rate is 1-2.5mEq/hr,
after pentagastrin stimulus..it is 20-40mEq/hr.
- in DU…. 15-83mEq/hr
- in ZE syndrome..basal secretion is > 10 mEq /
hr
 Tube Less Gastric Analysis :
 it avoids discomfort of naso gastric tube
 Used only as a screening test.
 Fasting secretion is stimulated by
histalogue , after 1 hr dye bound resin
“Diagnex Blue” with “ Azure A” is given
orally.
 In the presence of HCl resin releases
dye,which is absorbed & later excreted in
urine
 The quantity of dye in urine provides
indication of presence /absence of HCl.
 It is not reliable in pts with renal diseases,
urinary retention,malabsorption,pyloric
obstruction etc.
OTHER TESTS:

 Serum Gastrin : is estimated by Radio Immuno

Assay.
N
level is < 10 pico moles/L,
in Zollinger Ellison Syndrome it is > 100
pmol/L.
 Serum Pepsinogen : level
N is 30-160units/ml
- in pernicious anaemia…very low/absent
- in DU…> 200 units/ml
CONCLUSION

 Gastric Function tests are of limited

but specific value in diagnosing and
assessing some disorders of Upper
GIT.
APPLIED ASPECTS
 Gastric mucosal barrier
 Pathophysiology of peptic ulcer
 Effects of gastrectomy
The mucosal defense system is a three-level barrier
composed of preepithelial, epithelial, and subepithelial
elements
Structure of mucin
Functional significance
 Mucus – bicarbonate forms first line defence
against acid – pepsin attack
 Neutralises back diffused H+ ions
 In injured epithelium, intact epithelial cells
migrate to restore epithelial integrity called
restitution
 Restitution is favoured by alkaline micro
environment
Prostaglandins
 Pgs are fatty acid derivatives derived from
arachidonic acid
 Inhibits gastric acid directly
 Stimulates synthesis and secretion of mucus,
phospholipid, and bicarbonate secretion
 Enhances mucous blood flow
 Reduction of mucosal H+ ion back diffusion
 Stimulation of mucosal cell turn over
Peptic ulcer
 Excavation of gastric and duodenal
mucosa by digestive action of acid and
pepsin

 Barrier lost
 Excessive acid
 Antacids
 H2 blockers
 M3 blockers
 Proton pump inhibitors
 Surgical- bilateral vagotomy and partial
gastrectomy
Gastrectomy
 Nutritional disturbances
Carbohydrate
Protein, fat
B12 and Iron absorption affected
 Dumping syndromes
weakness, dizziness and sweating after
meals
oscillation b/w hyper and hypoglycemia
rapid entry of hypertonic meals into
intestine