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Flashcards in Lecture 8 Deck (43):

Functions of Stomach

Certain parts are more prone to certain conditions
Cardia: immediately inferior to gastro-oesophageal junction
Incisura: angle connecting Lesser curvature to antrum
-used to mark location of pathologies (e.g. inflammation/ulcers)


Pathologies in GO junction

Need to flip endoscope back on itself, so dont miss
e.g. gastricvarices


Major functions of the stomach

1. Reservoir for food (chamber)
2. Digests food (physical + chemical component) - antrum (distal) mixes and grinds up food (adequate consistency (large food chunks wont be well absorbed in SI. Needs to be liquid form - chyme)
3. Controls passage of food into small intestine
-Pylorus regulates size of particles and controls passage of food (chyme) into small intestine
4. Gastric Acid Secretion
5. Other secretion
-mucus, Hco3- (Bicarbonate) - Both protect stomach against gastric acid
-intrinsic factor, pepsinogen, prostaglandins


Gastric Motility

1. Relaxation of fundus (Vagovagal reflex)-elarges and allows food to be stored as reservoir
2. Contraction of body and antrum - co-ordinate together. allow food to be moved to distal stomach
3. Pylorus contracts (remains shut during physcial digestion. if relaxed food would spill into duodenum)
4. Mixing by retropulsion (in antrum)
Fundus acts as food store
Body and antrum mix food
Pylorus contracts to limit exit of chyme


Requirements of normal stomach function

1. Intact antrum (mixing), pylorus (need to hold things in stomach so can be digested) + Duodenum (controls chyme release into SI for late pancreatic digestion)
2. Normal vagal function to co-ordinate activity
3. Normal hormonal function


Abnormal gastric emptying

Abdnoraml is either too rapid or delayed
1. Rapid gastric emptying
-e.g. post-gastric surgery (antrum and pylorus removed)
--"dumping" syndrome -nausea, vomiting, (abdominal) cramping, diarrhoea
--food moves too quickly from stomach to duodenum and so are not completely digested (no antrum for mixing and no pylorus for controlled exiting)
--undigested (large) food particles result in a hyperosmolar chyme in small bowel ( rapidly draw fluid into SI)
--rapid fluid shift into gut causing intestinal distension = pain vomitting
--Diarrhoea due to osmotic effect (excess fluid in SI, not enough time to be reaborbed, therefore very high liquid stool)
2. Delayed gastric emptying
-mainly seen in people with diabetes
--e.g. diabetic gastroparesis caused by autonomic neuropathy (disease effecting autonomic nervous system)


Role of Gastric Acid

Acid secretion common to all mammals
Limited role of digestion (2 secondary to physical mixing)
Main role is to sterilise food -the food we eat isn't hostile. The stomach environment hostile to bacteria (because of gastric acid. prevents infections when absorbed in small intestine) except for Helicobacter pylori (can cause peptic ulcer disease)
Some help in absorption of iron and B12

Achlorhydria (absent or low gastric acid)
associated with condition of -pernicious anemia



(absent or low gastric acid)
associated with condition of -pernicious anemia


How is acid secreted in the stomach?- overview

Parietal cells
-located in body of stomach (middle portion, lesser and greater cruvature both) - important if removed in surgery
-have proton pumps to secrete HCL hydrochloric acid
Secrete approximately 2L/day daily of gastric acid


Parietal Cells relationship with Gastric Acid

H+/K+ ATPase pump
"proton" pump
requires ATP (energy for reaction)
Actively pumps H hydrogen ions Out of cell (into stomach) (in exchange for K+).
-because is shifting H+ against the Concentration gradient. Stomach has high Acid /H+ conc. Has to actively increase acid concentration from Low --> High
H2O + CO2 (both found within cell) H+ + HCO3-
Catalysed by Carbonic Anhydrase enzyme
In exchange K+ enters cell (counteracts change in ion shift 1:1 exchange)
HCO3- transported out of cell Into bloodstream
Cl- Chloride then enters cell
pH and osmolarity needs to stay in equilibrium
1. Rest: Parietal cells have Caniliculi which bind with Tuberovesicles.
2. Tuberovesicles fuse with Canaliculus.
3. Increase SA and numbers of H+/K+ ATPase
4. Increases acid secretion into lumen of gut actively
5. Acid secretion is against a 3 million x fold concentration gradient
[H+] inside = 4 x 10^2 M
[H+] outside = 0.1M
Excessive gradient therefore Needs energy


Protection of gastric mucosa from acid

Protective factors:
Mucus layer (thick. stops exposure)
Bicarbonate secretion (active release)
- protection is important.
- basis of why peptic ulcers form
- if layer of protection destroyed (e.g. via H bacter), ulcer occurs due to acid environment
-unique protection to stomach (Therefore people with reflux, acid entering outside of stomach (uniquely capable of being able to deal with acid environment) the oesophagus gets damaged)


Control of Gastric Acid Secretion

Gastric Acid Secretion my occur in co-ordinated fashion
-Secreted when eating, but low when not eating
-Parietal cell. ECL cell. G cell. D cell
Only parietal cell releases Gastric acid. Remaining influence the parietal cell.
ECL: Entrochremaffin-like cells. Body of stomach
Antrum= G cells = Gastrin cells + D cells



Molecule that transmits a signal from one neuron to another



Molecule released by a cell that targets itself
-acts on own receptor to promote own function



Molecule released by a cell that targets adjacent cells



Molecule (known as hormone) released by endocrine cells into circulation to target distant cells


ECL cells

Enterochromaffin-like (ECL) cells
-Body of stomach
-Secretes Histamine
-Histamine has Paracrine activity (neighbouring cell = parietal cell)
-H Directly stimulates acid secretion, by acting on parietal cells
-close as histamine doesnt have far to go


G cells

Gastrin Cells
-Antrum of stomach
-Secrete Gastrin
- Gastrin is hormone. Therefore has Endocrine activity
-INdirectly Stimulates acid secretion via ECL cells
--HAS to enter blood circulation
--binds to ECL cells in body. stimulating histamine release
--histamine stimulates parietal cells to secrete HCl


D cells

Antrum of stomach
Secretes Somatostatin
Somatostatin has Both endocrine (enter circulation) + Paracrine activity
-Inhibitory molecule (ensure regulation of secretion correclty)
-Inhibits Acid secretion, by acting on adjacent G cells --> therefore inhibiting Gastrin release
-switches of positive +ve feedback



Released by Vagus nerve AND Enteric Neurons (not a cell)
1. Parietal cells to release HCl
2. ECL cells to release histamine --> stimulates parietal cells
3. G cells to release gastrin --> stimulates parietal cells and ECL cells
-multiple manners of promoting acid release


Abnormal Gastric Acid secretion

Increased secretion:
-tumours that produce gastrin (gastrinoma).-- destruction of gastric mucosa. formation of multiple ulcers which are difficult to treat and manage

Decreased secretion:
-Pernicious anaemia: antibodies target/against parietal cells ( and intrinsic factor). Destroy. reduced acid secretion
-Gastric surgery: removal of parts of stomach that contain cells involved in HCl secretion (parietal cells)
-Vagotomy: loss of vagus nerve --> reduced ACh --> reduced Acid secretion (vagal trunk cut)
-Drugs: Receptors that block proton pump or histamine receptor (antagonists) on parietal cells. Therapeutic drugs e.g. for people with peptic ulcer disease



secreted from gastric Chief cells
Cleaved in acid to form pepsin (enzyme)
Pepsin degrades protein


Intrinsic Factor

Protein secreted by parietal cells
-B12 absorbption



Lipid molecules
Protection and repair of gastric mucosa (continuously, given acidic environment)


Cephalic Phase of Digestion

1. Initiated by thought, sight, smell of food (begins prior to eating)
2. Stimulates Vagus and Enteric nerves
3. Release of ACh from vagus nerve
4. ACh stimulates cells:
a) Parietal cell to release acid
b) ECL cell to release histamine --> stimulates parietal cells to release acid
c) G cells of antrum to release gastrin. Gastrin travels in blood stream --> stimulates ECL to release histamine --> Histamine stimulates parietal cells to release acid


Gastric Phase

5. Food enters Stomach.- gastric distension
6. Food broken into little pieces (Physical digestion) + release of aa Amino-acids
7. Gastric distension= stretching of stomach --> stimulates Enteric nerves --> more ACh release --> stimulates Parietal, ECL and G cells.
8. Presence of aa Amino acids in Antrum, Directly stimulate G cells. Gastrin travels in blood stream --> stimulates ECL to release histamine --> Histamine stimulates parietal cells to release acid


Intestinal Phase

1. Food starts to leave stomach to enter Duodenum
2. Stomach filled with HCl. -->low pH and lots of Acid floating around as no food. ==> need to switch of Acid secretion
a) Excess HCl in Antrum stimulates D cells -->
b) Inhibitory D cells release Somatostatin --> Inhibits G cells. --> prevent release of addition gastrin --> Gastric acid release decreased
3. Fats (from food) sitting in Duodenum + some HCl which has moved into Duodenum
a) stimulates 2x hormones - 1. Cholecystokinin 2. Secretin. v. important for inhibiting gastric acid.


What are the 3x phases of digestion?

1. Cephalic Phase
2. Intestinal Phase
3. Gastric Phase


Terminal Digestion in Duodenum

1. Secretin is released in duodenum in response to HCl
2. Cholecystokinin is released in duodenum in response to partially digested fats and proteins
3. Secretin and cholecystokinin inhibit gastric acid secretion and emptying (slows down digestion in stomach as duodenum is full w. fats/proteins + HCl)
4. Secretin also stimulates pancreas and bile ducts to release HCO3- (as content of chyme entering Duodenum is high in pH. SI small Intestine doesnt like acidic environment unlike stomach, therefore needs bicarbonate to counteract and neutralise the acidic chyme)
5. Cholecystokinin also stimulates release of pancreatic enzymes (for fat digestion) and gallbladder contraction to release bile (fat absorption)


Peptic ulcer disease

Disease of stomach and Duodenum
very common
historically limited treatment options
-mostly surgery due to complications re ulceration (in frequent not)
-now medications


Helicobacter pylori infection

most important organism re stomach diseases
causes multiple conditions:
1. Gastritis= "Non specific inflammatory response in stomach's gastric mucosa in response to the infection" Inflammation in stomach. May or may not be symptomatic.
2. Peptic Ulcer disease: Occurs if protective mucosal barrier is broken (gastric mucosa). Acidic environment starts destroying underlying mucosal layer of stomach. Causing ulceration or Crater to form.
-As ulcer becomes deeper --> can cause bleeding (invade underlying BV).
- Can also cause Perforation of stomach if ulcer goes extremely deep
-Hy.pylori most common cause (medications also cause NSAI + aspirin)
3. Gastric Cancer (tends to be high/mirror areas with large levels of H. pylori)
4. Gastric MALToma= Mucosa-Associated Lymphoid Tissue lymphOMA. -typically indirelent condition- not aggressive cancer/disease. Typically just defined to stomach(unlike other lymphomas which involve other parts of body)
-majority of maltoma's are treated successfully, not chemotherapy(like normal), but by eradicating H.pylori
-majority associated with H. Pylori, but not all
-Eradication of H. Pylori normally leads to remission or control of maltoma, but not always


Epidemiology of Helicobacter Pylori

H. pylori only infects humans and prefers the gastric Antrum
Person-to-person transmission must happen but route unclear (usually in childhood)
-arguments for both oral-oral (sharing of food -e.g. in families) and faecal-oral
Childhood infection (1-5 years) - doesn't tend to occur in adulthood
Childhood living conditions:
-household overcrowding
-running hot water
-some support of this but not definite
Ethnic group/country of birth- some have high prevalence of H pylori


Peptic ulcer Disease

1. Infection: H. Pylori infects the lower part of the stomach (antrum)
2. Inflammation: H. Pylori causes inflammation of the gastric mucosa (gastritis). This is often Asymptomatic. This inflammation tends to occur after a long period of time as people who present peptic ulcer diseases/ helicobacter related complications tend to be adults not children = Gastritis
3. Inflammatory cells cause destruction of protective barrier. Complications: Bleeding ulcer (either Antrum or Duodenum) or Perforated Ulcer. If occurs/progresses without detection.
4. Duodenal Ulcer: Inflammation and increased acid secretion
or Gastric Ulcer: Inflammation


Treatment of H. Pylori

Single antibiotic treatment does NOT work (one of few bacterias which cant be)
-despite being fully sensitive in the Laboratory
Treated with "Triple Therapy" -Emperic treatment (give standard treatment with a particular infection without determining its sensitivities)
-14 days of Omeprazole, Clarithromycin and Amoxycillin
1. Omeprazole: H. Pylori seems to like acidic environment. So omeprazole Lowers acidic environment to prevent repopulation/assist eradication of H. Pylori. Proton pump inhibitor, directly inhibits proton pump therefore directly inhibits H+ secretion
2. 2x Antibiotics:
a) Amoxycillin: commonly used for many infections.
b) Chlarithromycin
-after triple therapy, have stool test to confirm eradication
-esp if lived in another country, can have resistance to these antibiotics. After eradication havent gotten rid of H. pylori. = Then use Second-line-regimants when standard therapy isnt succesful
Low recurrence rate when successfully treated (most people who present with H.pylor infection, and adults dont tend to be suceeptible to re-infection)
-main risk of infection is during first 5 years of life


Empiric Treament

give standard treatment with a particular infection without determining its sensitivities


Detection of H Pylori

Blood test
Stool Test
-after triple therapy, have stool test to confirm eradication
(Endoscopy is one of the most common ways of diagnosing Peptic-Ulcer Disease)


What are the causes of Peptic Ulcer Disease?

1. H.Pylori is most common cause
2. Medication:
-NSAIDs (Non-Steroidal Anti-Inflammatory Drugs)
--e.g. voltarin, ibiprofin, neurofin, diclofinate
-ulceration in stomach or duodenum


History of Treatment of Ulcer Disease

1. Surgery: to reduce acid secretion (no effect medication previously)
-Gastrectomy: remove gastrin stimulus by removing the antrum (where gastrin in release, inhibiting g secretion)
-Vagotomy: remove part of vagus nerve to reduce acid secretion. (Sometimes performed w. Pyloroplasty)
-Pyloroplasty: cut pylorus and re-sutured to relax the pyloric sphincter (not as tight) (allows stomach to empty faster; food in stomach for less time and less stimulation of gastric acid) - particles go into small intestine partially digested, and can cause other symptoms due to its associated Hyper osmolarity)
2. 1986 H. pylori isolated
-Treatment was developed
-now surgery in infrequent


Symptoms of Peptic ulcer disease

-can be asymptomatic to begin with/intially
1. Pain (non-specific epigastric pain/pain in stomach)
2. Bleeding (if ulcerate BV)
3. Perforation (goes through entire gastric wall)
4. Obstruction (in pylorus or duodenum) from:
-Swelling (can obstruct pylorus = symptoms of outlet obstruction w. vomiting)
-Scarring causing stricture (if ulcer heals spontaneously --> scarring can cause stricture --> can lead to Obstruction)
-"Kissing ulcers" - ulcers close to eachother


What is the most common way of diagnosing Peptic Ulcer Disease?

Endoscopy : Bleeding from ulcer. Persistent pain that does Not respond to treatment
-alot of times just Clinical diagnosis


Gastric Adenocarcinoma

2x major types:
1. Intestinal:
-Well differentiated (tissue has well differentiated structures:)
-cells arranged in a tubular/glandular pattern
2. Diffuse:
-Poorly differentiated
-Lack glandular formation (host of cells w/o any significant structures)
-Can infiltrate gastric wall - Linitis plastica


Linitis Plastica

Diffuse Gastric Adenocarcinoma that has infiltrated gastric wall


H. pylori and Gastric cancer association

Is Association between gastric cancer and H. Pylori
-Stronger effect for intestinal type (increased risk of intestinal adenocarcinoma for people with h. pylori infection)
H. Pylori may produce widespread inflammation(non-specific) in gastric mucosa and destruction of parietal cells to reduce gastric acid secretion
--> Leads to low acid (achlorydria) --> Bacterial overgrowth --> bacteria can produce carincogens