Case 2 Flashcards
intracellular buffering: macromolecules
weak acids and bases on proteins act as buffers helps minimise PH fluctuations
what do chief cells secrete
pepsinogen, acid turns to pepsin which breaks down proteins
what do parietal cells secrete
HCL and intrinsic factors which help to absorb vitamin b12
properties of GI tract mucus
Resistant barrier (physical & chemical)
Viscous highly hydrated layer
Prevents dehydration of mucosal surfaces, provides
lubrication for movement of luminal contents in the gut
Porous to large macromolecules up to very small
particulate matter (not cellular microbes)
Allows absorption and secretion to continue
Self organises around particulate matter and promotes
its clearance (mechanism is unclear)
what is mucus
Mucus is a viscoelastic material: it has the viscous
behaviour of a liquid and the elastic properties of
a solid.Mostly water and ions 90%
Proteins (glycoproteins) 5-10%
Mucus glycoproteins (mucins) 1-5%
whats the key structural components of mucus gels
mucins
how do pathogens escape the mucus barrier
Most mucosal bacterial pathogens are flagellated –
allows them to swim in mucus
Many mucosal pathogens produce enzymes to degrade
the mucins and thereby disassemble the mucus barrierBacteria produce soluble toxins which can kill epithelial
cells and/or arrest intestinal cell division
Many pathogens attach to the apical surface of
epithelial cells and inject bacterial toxins
Many mucosal toxins disable tight junctions between
adjacent epithelial cells
H. pylori infectioon
Adhesin genes (colonisation) SabA gene – sialic acid binding adhesin BabA gene – Lewis b binding adhesin CagA pathogenicity island (epithelial pathology) CagA gene – type IV secretion system, disabling of epithelial tight junctions VacA gene - cytotoxin
what do G cells secrete
Gastrin, which stimulates chief and parietal and contraction of the wall to mix contents
stimulation of parietal cell
G cells release gastrin which stimulates ECL cells which release histamine which stimulate parietal cells to release HCL.
stomach ulcer
10% UK population affected at some stage of life-cycle Complications (~2 %) • GI bleeding • Perforation = life threatening acid/enzyme damage to stomach or intestinal wall
causes of ulcers
Bacterial infection Helicobacter pylori • Non-Steroidal Anti-Inflammatory Drugs • Zollinger-Ellison syndrome (gastrinsecreting tumour) • Other factors – Smoking, alcohol, caffeine, etc.
somatostatin
inhibits acid secretion by inhibiting G and ECL cells.
nausea
the unpleasant sensation of the
imminent need to vomit
vomiting
the forceful expulsion of gastric
contents associated with contraction of
abdominal and chest wall muscles
retching
-repetitive contractions of abdominal
wall without expulsion of gastric contents
regurgitation
effortless return of food back
into the mouth
rumination
effortless regurgitation of
undigested food after every meal
dyspepsia
Chronic or recurrent pain or discomfort centered in the upper
abdomen
CLINICAL FEATURES
• Epigastric pain- central upper abdominal or lower retrosternal
discomfort related to eating
• Postprandial fullness, unease
• Heartburn or water brash more likely to indicate oesophageal disease
physiologically the stomach is divided into what 2 parts
- Orad portion – this is the first 2/3 of the ‘body’ of the stomach.
- Caudad portion – this is the last 1/3 of the ‘body’ of the stomach + antrum
alkaline tide
when gastric glands are activly secreting, enough bicarbinate ions inc pH of blood, sudden influx is alkaline tide.
functions of parietal cells: HCl
kills microorganisms, denatures proteins, inactivates enzymes. break down plant cell walls and connective tissue in meat. activate pepsin from pepsinogen.
D cells
secrete somatostatin which inhibits gastrin.
what pH in the stomach allows pepsin to start
until the pH falls below 4.5 enzymes from salivary amylase and lingual lipase continue to work on carbs and lipids. when pH nears 2 pepsin becomes active breaks down large polypeptide chains before chyme enters duodenum.
why are nutrients not absorbed in the stomach
epithelial cells are covered by alkaline mucus so not exposed to chyme, lack specialised transport mechanisms of cells in small intestine, impermeable to water and digestion isnt completed by the time chyme leaves the stomach
cephalic phase
when you see smell think of food. directed by CNS, prepares stomach for food. parasymp division of ANS. Vagus nerve innervates submucosal. Parasymp innervate mucosal chief parietal G cells. phase only lasts minutes
Gastric phase
arrival of food in S. continues for hours while acid and enzymes process ingested food. Stimulation by distention of stomach, inc pH, presence undigested food-proteins and peptides especially. Distention of gastric wall stim histamine in lamina propria bind parietal cells stim acid. Neural responce stim submucosal and myenteric plexus activate secretory cells and movement. Hormonal response, presence of peptides in chyme stim G cells release gastrin which stim P and C cells.
intestinal phase
when chyme enters small intestine. controls rate gastric emptying to ensure digestive and absorptive functions efficiently. neural response: chyme leaving dec the distention, reducing stim of stretch recept, but distention of duodenum stim enterogastric reflex, inhibits gastrin and contractions and closes pyloric sphincter. mucus protects from arival of acids and enzymes in chyme.
hormonal responce: lipids and carbs stim CCK and GIP, drop in pH stim secretin, Partially digested proteins stim G cells to speed gastric processing.
3 motor functions of the stomach
- Storage of large quantities of food until the food can be processed in the stomach, duodenum, and lower intestinal tract.
- Mixing of this food with gastric secretions until it forms a semifluid mixture called chyme.
- Slow emptying of the chyme from the stomach into the small intestine at a rate suitable for proper digestion and absorption by the small intestine.
storage function of the stomach
• Food entering forms concentric circles of food in the orad portion of the stomach.
• The newest food is closest to the oesophageal opening, whilst the old food lies nearest to the outer wall of the stomach.
• When this food stretches the stomach wall, a ‘vagovagal reflex’ occurs.
• Signals are sent from the stomach to the brainstem and back, thus reducing the muscle tone of the muscular wall of the body of the stomach so that the wall can expand outwards progressively.
• This accommodates for greater quantities of food entering the stomach.
The maximal stomach volume/ capacity is between 0.8-1.5 litres.
mixing and propulsion of food in the stomach
• As long as food is in the stomach, weak peristaltic constrictor waves, called mixing waves, begin in the mid- to upper portions of the stomach wall and move toward the antrum about once every 15 to 20 seconds.
• These waves are initiated by the gut wall basic electrical rhythm, consisting of electrical “slow waves” that occur spontaneously in the stomach wall.
• As the constrictor waves progress from the body of the stomach into the antrum, they become more intense.
• Some of these waves become extremely intense, providing powerful peristaltic action potential–driven constrictor rings that force the antral contents under higher and higher pressure toward the pylorus.
• These constrictor rings also play an important role in mixing the stomach contents in the following way:
Each time a peristaltic wave passes down the antral wall toward the pylorus, it digs deeply into the food contents in the antrum.
The opening of the pylorus is small - only a few millilitres or less of antral contents are expelled into the duodenum with each peristaltic wave.
Also, as each peristaltic wave approaches the pylorus, the pyloric muscle itself often contracts, which further impedes emptying through the pylorus.
Therefore, most of the antral contents are squeezed upstream through the peristaltic ring toward the body of the stomach, not through the pylorus.
Thus, the moving peristaltic constrictive ring, combined with this upstream squeezing action, called “retropulsion,” is an exceedingly important mixing mechanism in the stomach.
retropulsion
Each time a peristaltic wave passes down the antral wall toward the pylorus, it digs deeply into the food contents in the antrum.
The opening of the pylorus is small - only a few millilitres or less of antral contents are expelled into the duodenum with each peristaltic wave.
Also, as each peristaltic wave approaches the pylorus, the pyloric muscle itself often contracts, which further impedes emptying through the pylorus.
Therefore, most of the antral contents are squeezed upstream through the peristaltic ring toward the body of the stomach, not through the pylorus.
Thus, the moving peristaltic constrictive ring, combined with this upstream squeezing action, called “retropulsion,” is an exceedingly important mixing mechanism in the stomach.
chyme
- The mixture of food that passes down the gut, after it has been mixed with the stomach secretions, is called chyme.
- The degree of fluidity of the chyme leaving the stomach depends on the relative amounts of food, water, and stomach secretions and on the degree of digestion that has occurred.
- Chyme appears like a murky semifluid or paste.
hunger contractions
- Hunger contractions occur in the stomach when it is has been empty for several hours or more.
- They are rhythmical peristaltic contractions in the body of the stomach.
- Hunger contractions are most intense in young, healthy people who have high degrees of GI tonus (i.e. a constant low-level activity of a body tissue, especially muscle tone).
- They are also triggered by a hypoglycaemic state.
- When hunger contractions occur in the stomach, the person sometimes experiences mild pain in the pit of the stomach, called hunger pangs.
pyloric pump
• The stomach contractions are mainly involved in mixing the food as they are weak with regards to causing emptying of the stomach.
• However, for about 20%of the time while food is in the stomach, the contractions become intense, beginning in mid-stomach and spreading through the caudad stomach no longer as weak mixing contractions but as strong peristaltic, very tight ring-like constrictions that can cause stomach emptying.
• As the stomach becomes progressively more and more empty, these constrictions begin farther and farther up the body of the stomach, gradually pinching off the food in the body of the stomach and adding this food to the chyme in the antrum.
• When pyloric tone is normal, each strong peristaltic wave forces up to several milliliters of chyme into the duodenum.
• Thus, the peristaltic waves:
1. Cause mixing in the stomach.
2. Provide a pumping action called the “pyloric pump.”
role pylorus in controlling stomach emptying
- The distal opening of the stomach is the pylorus.
- Here the thickness of the circular wall muscle becomes 50 -100% greater than in the earlier portions of the stomach antrum, and it remains slightly tonically contracted.
- Therefore, the pyloric circular muscle is called the pyloric sphincter.
- Despite normal tonic contraction of the pyloric sphincter, the pylorus usually is open enough for water and other fluids to empty from the stomach into the duodenum with ease.
- Conversely, the constriction usually prevents passage of food particles until they have become mixed in the chyme to almost fluid consistency.
- The degree of constriction of the pylorus is increased or decreased under the influence of nervous and humoral reflex signals from both the stomach and the duodenum.
regulation of stomach emptying
- The rate at which the stomach empties is regulated by signals from both the stomach and the duodenum.
- However, the duodenum provides by far the more potent of the signals, controlling the emptying of chyme into the duodenum at a rate no greater than the rate at which the chyme can be digested and absorbed in the small intestine.
gastric factors that promote emptying-food volume
- Increased food volume in the stomach promotes increased emptying from the stomach.
- This increased emptying is not due to increased storage pressure of the food in the stomach, because in the usual normal range of volume, the increase in volume does not increase the pressure much.
- However, stretching of the stomach wall elicits local myenteric reflexes in the wall that greatly accentuate activity of the pyloric pump and at the same time inhibit the pylorus
effect of gastrin on stomach emptying
• Gastrin is released by G-cells of the antral mucosa as a result of:
Stretching of the stomach wall.
Presence of protein food contents in the stomach.
• Gastrin has a few functions:
1. It has potent effects to cause secretion highly acidic gastric juice by stomach glands:
Gastrin activates ECL cells, which release histamine, which is the primary initiator for parietal cell acid production.
2. It has some effects on the motor function of the stomach:
It enhances the activity of the pyloric pump, thus promoting stomach emptying.
inhibitory effect of enterogastric nervous reflexes from the duodenum
• Upon food entering the duodenum, multiple nervous reflexes are initiated from the duodenal wall that pass back to the stomach to slow or even stop stomach emptying if the volume of chyme in the duodenum becomes too much.
• These reflexes are mediated by three routes:
1. Directly from the duodenum to the stomach through the enteric nervous system in the gut wall.
2. Through extrinsic nerves that go to the prevertebral sympathetic ganglia and then back through inhibitory sympathetic nerve fibres to the stomach.
3. Through the vagus nerves to the brainstem, where they inhibit the normal excitatory signals transmitted to the stomach through the vagi. (this pathway only plays a minor role)
• These parallel pathways have two effects on the emptying of the stomach:
1. Strongly inhibit the pyloric pump propulsive contractions.
2. Increase the tone of the pyloric sphincter.
factors monitered in the duodenum that can initiate enterogastric inhibitory reflexes
- Degree of distention of the duodenum
- Degree of irritation of the duodenal mucosa (if any) – especially sensitive to this
- Degree of acidity of the duodenal enzyme – especially sensitive to this
When the pH of the chyme in the duodenum falls below about 3.5-4, the reflexes frequently block further release of acidic stomach contents into the duodenum until the duodenal chyme has been neutralised by pancreatic and other secretions. - Degree of osmolality of the chyme
Hypertonic and hypotonic (especially hypertonic) fluids elicit the inhibitory reflex.
Too rapid flow of non-isotonic fluids into the small intestine is prevented, thereby also preventing rapid changes in electrolyte concentrations in the whole body extracellular fluid during absorption of the intestinal contents. - Presence of certain breakdown products in the chyme, especially breakdown products of proteins and perhaps to lesser extent of fats
By slowing the rate of stomach emptying, sufficient time is ensured for adequate protein digestion in the duodenum and small intestine.
horminal feedback from the duodenum inhibits gastric emptying
• As well as the nervous reflexes inhibiting gastric emptying, hormones released from the upper intestine do so as well.
• The stimulus for the hormone release is fats entering the duodenum, although other foods can increase this hormone release to a lesser extent:
o Fats bind to receptors on the duodenal and jejunal epithelium, thus extracting different hormones from the epithelium.
o These hormones are then carried by blood to the stomach, where they inhibit the pyloric pump and at the same time increase the strength of contraction pyloric sphincter
CCK
- The hormone that has the most potent effect in regards to hormonal feedback to inhibit gastric emptying is cholecystokinin (CCK).
- CCK is released from the duodenal and jejunal mucosa in response to fatty substances in the chyme.
- CCK acts as an inhibitor to block increased stomach motility caused by gastrin.
secretin
o Released from duodenal mucosa (S cells in the crypts of Lieberkuhn).
o Released in response to gastric acid passed from the stomach through the pylorus.
GIP
o This has a general but weak effect of decreasing GI motility.
o Released from the duodenal and jejunal mucosa.
o Released in response to fat in the chyme, but to lesser extent carbohydrates as well.
o Although GIP weakly decreases the GI motility, its primary function is to stimulate secretion of insulin by the pancreas
summary of regulation of stomach emptying
• Emptying of the stomach is controlled only to a moderate degree by stomach factors such as the degree of filling in the stomach and the excitatory effect of gastrin on stomach peristalsis.
• Probably the more important control of stomach emptying resides in inhibitory feedback signals from the duodenum, including both enterogastric inhibitory nervous feedback reflexes and hormonal feedback by CCK.
• These feedback inhibitory mechanisms work together to slow the rate of emptying when
1. Too much chyme is already in the small intestine.
2. The chyme is excessively acidic, contains too much unprocessed protein or fat, is hypotonic or hypertonic, or is irritating.
• In this way, the rate of stomach emptying is limited to that amount of chyme that the small intestine can process.
inc stretching of the stomach wall
Nervous reflexes (via enteric nervous system, extrinsic nerves and vagus nerve) – inhibit pyloric pump + increase pyloric sphincter tone
The following factors affect the duodenal mucosa and initiate the nervous reflexes:
• Distention
• Irritation of mucosa
• Acidity of digestive enzymes
• Osmolality of chyme (hyper-/hypotonic)
• Protein breakdown products
gastrin -– enhanced pyloric pump + increased HCl production in parietal cells
Hormonal feedback - inhibit pyloric pump + increase pyloric sphincter tone
The hormones are secreted due to the presence of fat in the duodenum.
The hormones released are:
• Secretin (released from duodenal mucosa in response to gastric acid) – inhibit gastrin, thus lowering acid secretion
• Cholecystokinin/ CCK (released from jejunal mucosa in response to fat in chyme) – inhibit gastrin, thus lowering acid secretion
• Gastric inhibitory peptide/ GIP(released from jejunal mucosa in response to fat in chyme) – weakly decrease GI motility
oxyntic glands/gastric glands
- Oxyntic glands/ Gastric glands
Acid forming glands composed of three types of cells:
1) Mucous neck cells – secrete mucus
2) Peptic (chief) cells – large quantities of pepsinogen
3) Parietal (oxyntic) cells – HCl and intrinsic factor
These are located on the inside surfaces of the body and fundus of the stomach, constituting the proximal 80% of the stomach
pyloric glands
Secrete mainly mucus for protection of the pyloric mucosa from the stomach acid and they also secrete the hormone gastrin.
These are located in the antral portion of the stomach, the distal 20% of the stomach.