Case 2 Flashcards
1
Q
intracellular buffering: macromolecules
A
weak acids and bases on proteins act as buffers helps minimise PH fluctuations
2
Q
what do chief cells secrete
A
pepsinogen, acid turns to pepsin which breaks down proteins
3
Q
what do parietal cells secrete
A
HCL and intrinsic factors which help to absorb vitamin b12
4
Q
properties of GI tract mucus
A
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)
5
Q
what is mucus
A
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%
6
Q
whats the key structural components of mucus gels
A
mucins
7
Q
how do pathogens escape the mucus barrier
A
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
8
Q
H. pylori infectioon
A
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
9
Q
what do G cells secrete
A
Gastrin, which stimulates chief and parietal and contraction of the wall to mix contents
10
Q
stimulation of parietal cell
A
G cells release gastrin which stimulates ECL cells which release histamine which stimulate parietal cells to release HCL.
11
Q
stomach ulcer
A
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
12
Q
causes of ulcers
A
Bacterial infection Helicobacter pylori • Non-Steroidal Anti-Inflammatory Drugs • Zollinger-Ellison syndrome (gastrinsecreting tumour) • Other factors – Smoking, alcohol, caffeine, etc.
13
Q
somatostatin
A
inhibits acid secretion by inhibiting G and ECL cells.
14
Q
nausea
A
the unpleasant sensation of the
imminent need to vomit
15
Q
vomiting
A
the forceful expulsion of gastric
contents associated with contraction of
abdominal and chest wall muscles
16
Q
retching
A
-repetitive contractions of abdominal
wall without expulsion of gastric contents
17
Q
regurgitation
A
effortless return of food back
into the mouth
18
Q
rumination
A
effortless regurgitation of
undigested food after every meal
19
Q
dyspepsia
A
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
20
Q
physiologically the stomach is divided into what 2 parts
A
- 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
21
Q
alkaline tide
A
when gastric glands are activly secreting, enough bicarbinate ions inc pH of blood, sudden influx is alkaline tide.
22
Q
functions of parietal cells: HCl
A
kills microorganisms, denatures proteins, inactivates enzymes. break down plant cell walls and connective tissue in meat. activate pepsin from pepsinogen.
23
Q
D cells
A
secrete somatostatin which inhibits gastrin.
24
Q
what pH in the stomach allows pepsin to start
A
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.
25
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
26
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
27
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.
28
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.
29
3 motor functions of the stomach
1. Storage of large quantities of food until the food can be processed in the stomach, duodenum, and lower intestinal tract.
2. Mixing of this food with gastric secretions until it forms a semifluid mixture called chyme.
3. 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.
30
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.
31
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.
32
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.
33
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.
34
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.
35
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.”
36
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.
37
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.
38
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
39
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.
40
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.
41
factors monitered in the duodenum that can initiate enterogastric inhibitory reflexes
1. Degree of distention of the duodenum
2. Degree of irritation of the duodenal mucosa (if any) – especially sensitive to this
3. 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.
4. 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.
5. 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.
42
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
43
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.
44
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.
45
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
46
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.
47
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
48
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
49
oxyntic glands/gastric glands
1. 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
50
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.
51
oxyntic/gastric glands-mechanism of HCL secretion
•The parietal (oxyntic) cell contains large branching intracellular canaliculi.
•The HCl is formed at the villus-like projections inside these canaliculi and is then conducted through the canaliculi to the secretory end of the cell (the apical end).
• Mechanism:
The movement and exchange of ions in and out of parietal cells is primarily powered by ATP from the numerous mitochondria present in the parietal cells.
1)Cl- ions are actively transported from parietal cell cytoplasm into the lumen of the canaliculus via a chloride pump. Na+ ions are actively transported out of the canaliculus into the cytoplasm of the parietal cell via a sodium pump. This creates a negative potential (-40 to -70 mV) in the canaliculus. This causes K+ ions (and some Na+ ions) to enter the canaliculus from the cytoplasm. Thus, in effect, mainly KCl and smaller amounts of NaCl enter the canaliculus.
2)Water dissociates into hydrogen ions (H+) and hydroxyl ions (OH-) in the cytoplasm. H+ ions are actively secreted into the canaliculus in exchange for K+ ions. This is catalysed by the H+/K+ ATPase (proton pump).
Also, Na+ ions are ions are actively reabsorbed by a separate sodium pump. Therefore, the Na+ ions and K+ ions that were initially secreted into the canaliculus have ben reabsorbed, whilst H+ ions have been added to the canaliculus. This gives us the HCl in the canaliculus.
3)Water passes into the canaliculus by osmosis because of the increased ionic concentration in the canaliculus. The final secretion from the canaliculus contains water, HCl (conc = 150-160mEq/L), KCl (conc = 15mEq/L) and small amounts of NaCl.
4)OH- combines with CO2 under the influence of carbonic anhydrase to form bicarbonate ions (HCO3-). These diffuse into the extracellular fluid in exchange for Cl- ions.
52
secretion and activation of pepsinogen
• Different types of pepsinogen are secreted by the peptic (chief) cells of the gastric/oxyntic gland.
• All pepsinogens have the same function:
It has no digestive activity.
As soon as it comes into contact with HCl, it is activated to form active pepsin.
Pepsin functions as an active proteolytic enzyme for protein digestion, in an acid medium.
Optimum pH is 1.8 - 3.5 but above a pH of 5 it has almost no proteolytic activity and becomes completely inactivated is a short time
53
regulation of pepsinogen secretion
• Regulation of pepsinogen secretion by the peptic cells in the oxyntic glands occurs in response to two types of signals:
1. Stimulation of peptic cells by acetylcholine released from the vagus nerves or from the gastric enteric nervous plexus.
2. Stimulation of peptic cell secretion in response to acid in the stomach.
Acid doesn’t stimulate the peptic cells directly, instead it elicits additional enteric nervous reflexes that support the original nervous signals to the peptic cells.
The rate of pepsinogen secretion is influenced by the amount of acid in the stomach.
54
secretion intrinsic factor
* Intrinsic factor is essential for the absorption of vitamin B12 in the ileum.
* It is secreted by parietal (oxyntic) cells along with the secretion of HCl.
* When the acid-producing parietal cells of the stomach are destroyed, which frequently occurs in chronic gastritis, the person develops not only achlorhydria (lack of stomach acid secretion) but often also pernicious anemia because of failure of maturation of the red blood cells in the absence of vitamin B12 stimulation of the bone marrow.
55
pyloric glands-secretion of mucus and gastrin
• The pyloric cells are structurally similar to oxyntic glands but contain few peptic cells and almost no parietal cells.
• Instead, they contain mainly mucous cells that are identical with the mucous neck cells of the oxyntic glands.
• These cells secrete:
Small amounts of pepsinogen.
Large amounts of thin mucus that helps lubricate food movement, as well as to protect the stomach wall from digestion by the gastric enzymes
56
surface mucous cells
* The entire surface of the stomach mucosa between glands has a continuous layer of a special type of mucous cells called simply “surface mucous cells.”
* They secrete large quantities of viscid mucus that coats the stomach mucosa, thus providing protection for the stomach and lubrication.
* This mucus is alkaline (presence of bicarbonate ions), therefore, the normal underlying stomach wall is not directly exposed to highly acidic, proteolytic stomach secretion.
* Even the slightest contact with food or any irritation of the mucosa directly stimulates the surface mucous cells to secrete additional quantities of this thick, alkaline, viscid mucus
57
enterochromaffin like cells
• Parietal cells are the only cells that secrete HCl.
• Secretion of HCl is controlled by endocrine and nervous signals.
• Parietal cells operate in close association with enterochromaffin-like cell (ECL cell).
ECL cells secrete histamine which binds to H2 histamine receptors on parietal cells.
This activates the parietal cells to form and secrete HCl.
Rate of formation and secretion of HCl is dependent on the amount of histamine secreted by ECL cells.
• ECL cells themselves are activated in a few ways:
1. Gastrin – when G-cells of the antral mucosa come into contact with amino acids, they pass gastrin to ECL cells through the digestive juices, which in turn secrete histamine.
2. Acetylcholine – this is released from stomach vagal nerve endings.
3. Hormonal substances secreted by the enteric nervous system of the stomach wall.
58
stimulation of acid secretion by gastrin
• Gastrin is secreted by gastrin cells (G-cells) located in the antral mucsoa (pyloric glands).
• Gastrin is secreted in two forms:
a. G-34 = this contains 34 amino acids
b. G-17 = this contains 17 amino acids (and is more abundant)
• When amino acids reach the antral end of the stomach, they have a stimulatory effects on the G-cells in the pyloric gland.
• This causes release of gastrin into the digestive juices of the stomach.
• The vigorous mixing of the digestive juices transports the gastrin rapidly to the ECL cells in the body of the stomach, causing release of histamine directly into the deep oxyntic glands, which stimulates the parietal cells to form and secrete HCl.
59
cephalic phase of gastric secretion
• This occurs before food enters the stomach, especially whilst in the mouth.
• It results from the sight, smell, thought, or taste of food.
• The greater the appetite, the more intense the stimulation.
• Neuronal signals from appetite centres of the amygdala and hypothalamus are transmitted through the dorsal motor nuclei of the vagi through the vagus nerves to the stomach.
• This phase has stimulatory effects on HCl secretion:
It stimulates the vagus nerve to release more Ach, thus activating more ECL and parietal cells.
It stimulates the vagus nerve to activate gastrin-releasing-peptide (GRP), which increases the secretion of gastrin, thus activating parietal cells.
• This phase accounts for about 20% of gastric secretion associated with eating a meal.
60
gastric phase
• This occurs once food has entered the stomach.
• This phase has both stimulatory and inhibitory effects:
Stimulatory effects on HCl secretion:
It stimulates the vagus nerve to release more Ach, thus activating more ECL and parietal cells.
It stimulates the vagus nerve to activate gastrin-releasing-peptide (GRP), which increases the secretion of gastrin, thus activating parietal cells.
It increases the pH of the food, thus causing an increase in gastrin secretion.
It stimulates secretagogues, which increase H+ secretion.
Inhibitory effects on HCl secretion:
It inhibits the G-cells (antrum), which decreases the secretion of gastrin and so increases the pH in the stomach.
• This phase accounts for about 70% of gastric secretion associated with eating a meal.
61
intestinal phase
• This occurs as a result of the presence of food in the upper portion of the small intestine, particularly in the duodenum.
• This phase has both stimulatory and inhibitory effects:
Stimulatory effect:
It stimulates the G-cells (duodenum), which secrete more gastrin, resulting in an increase in the secretion of H+.
Inhibitory effect:
It inhibits chemoreceptors, which cause a decrease in nerve reflexes, thus decreasing H+ secretion.
Secretin, CCK and GIP increase the secretion of somatostatin, thus decreasing H+ secretion.
• The presence of food will continue to cause stomach secretion of small amounts of gastric juice because small amounts of gastrin is released by the duodenal mucosa
62
inhibition of gastric secretion
* Chyme initially increases gastric secretion.
* However, later chyme inhibits gastric secretion.
• This results from two influences:
1. Presence of food in the small intestine initiates a reverse enterogastric reflex, transmitted through the myenteric nervous system and vagus nerves, that inhibits stomach secretion.
This reflex can be initiated by distending the small bowel, by the presence of acid in the upper intestine, by the presence of protein breakdown products, or by irritation of the mucosa.
2. The hormone secretin is secreted as a result of the presence of… (listed above). It is important in the control of pancreatic secretion. Secretin opposes stomach secretion.
Other hormones have a slight effects on inhibiting gastric secretion – GIP, vasoactive intestinal polypeptide and somatostatin.
• Inhibition of gastric secretion by intestinal factors is to slow passage of chyme from the stomach when the small intestine is already filled or already overactive.
Somatostatin
• Somatostatin inhibits G-cells, ECL cells and if there is an excess of acid in the duodenum, it inhibits the parietal cells
63
gastric secretion during the indigestive period
* The stomach secretes gastric juice in the indigestive period.
* This is non-oxyntic secretion, consisting mainly of mucus, but little pepsin and almost no acid.
* Emotional stimuli increase indigestive gastric secretion
64
digestion of carbohydrates in the mouth and stomach
* Food is mixed with saliva (ptyalin = a-amylase) in the mouth when it is being chewed, secreted mainly by the parotid glands.
* This enzyme hydrolyzes starch into the disaccharide maltose and other small polymers of glucose that contain three to nine glucose molecules.
* Only 5% of all starches are hydrolysed by the time the food has been chewed and is swallowed.
* By the time the food reaches the stomach, 30-40% of all starches have been hydrolysed mainly to form maltose.
* Starch digestion sometimes continues in the body and fundus of the stomach for as long as 1hour before the food becomes mixed with the stomach secretions.
* Then activity of the salivary amylase is blocked by acid of the gastric secretions because the amylase is essentially non-active as an enzyme once the pH of the medium falls below about 4.0.
65
digestion of proteins in the stomach
* Pepsin is most active at a pH of 2.0 to 3.0 and is inactive at a pH>5.0.
* For pepsin to cause digestive action on protein, the stomach juices must be acidic.
* The gastric glands (parietal cells) secrete a large quantity of HCl at a pH = 0.8, but by the time it is mixed with the stomach contents and with secretions from the non-oxyntic glandular cells of the stomach, the pH then averages around 2.0 to 3.0, a highly favorable range of acidity for pepsin activity.
* One of the important features of pepsin digestion is its ability to digest the protein collagen, an albuminoid type of protein that is affected little by other digestive enzymes.
* Collagen is a major constituent of the intercellular connective tissue of meats.
* In persons who lack pepsin in the stomach juices, the ingested meats are less well penetrated by the other digestive enzymes and, therefore, may be poorly digested.
* Pepsin only initiates the process of protein digestion, usually providing only 10-20% of the total protein digestion to convert the protein to proteoses, peptones, and a few polypeptides.
* This splitting of proteins occurs as a result of hydrolysis at the peptide linkages between amino acids.
66
gastritis
– inflammation of the gastric mucosa.
• The inflammation of gastritis may be only superficial and therefore not very harmful, or it can penetrate deeply into the gastric mucosa, in many long-standing cases causing almost complete atrophy of the gastric mucosa.
• In a few cases, gastritis can be acute and severe, with ulcerative excoriation of the stomach mucosa by the stomach’s own peptic secretions.
• Gastritis is caused by chronic bacterial infection of the gastric mucosa.
• This is treated by an intensive antibacterial therapy.
• In addition, certain ingested irritant substances can be especially damaging to the protective gastric mucosal barrier (mucous glands and the tight epithelial junctions between the gastric lining cells), often leading to severe acute or chronic gastritis.
Two of the most common of these substances are excesses of alcohol or aspirin.
67
gastric barrier and its penetration in gastritis
• The ‘gastric barrier’ comprises of:
1. Highly resistant mucous cells that secrete a viscid and adherent mucus.
2. Tight junctions between the adjacent epithelial cells.
• These two form a barrier against gastric absorption of food into the blood.
• The gastric barrier is resistant to diffusion of ions across it.
• In gastritis:
1. The permeability of the barrier is greatly increased.
Hydrogen ions can now diffuse into the stomach epithelium, leading to stomach mucosal damage and atrophy.
2. The mucosa becomes susceptible to digestion by the peptic digestive enzymes.
This causes gastric ulcers.
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gastric atrophy
* Gastric atrophy is the damage to the mucosal glands of the stomach, such that little or no gastric gland digestive secretion remains.
* Gastric atrophy can also occur as a result of an autoimmune response against the gastric mucosa.
* Loss of stomach secretions in gastric atrophy leads to ‘achlorydria’ and, occasionally, ‘pernicious anaemia’.
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achlorhydria (hypochlorhydria)
* Achlorhydria – this means that the stomach fails to secrete HCl.
* Hypochlorhydria – this literally means “decreased acid secretion”.
* It is diagnosed when the pH of the gastric secretions fails to decrease below 6.5 after maximal stimulation.
* When acid is not secreted, pepsin also usually is not secreted; even when it is, the lack of acid prevents it from functioning because pepsin requires an acid medium for activity
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pernicious anaemia
* Normal gastric secretions contain intrinsic factor, secreted by the parietal cells (which also secrete HCl).
* Intrinsic factor must be present for absorption of vitamin B12 from the ileum.
* The intrinsic factor binds with vitamin B12 in the stomach and protects it from being digested and destroyed as it passes into the small intestine.
* Then, when the intrinsic factor–vitamin B12 complex reaches the terminal ileum, the intrinsic factor binds with receptors on the ileal epithelial surface.
* This in turn makes it possible for the vitamin B12 to be absorbed.
* In the absence of intrinsic factor, only about 1/50 of the vitamin B12 is absorbed.
* Vitamin B12 is not made available from the foods to cause young, newly forming red blood cells to mature in the bone marrow.
* This is called pernicious anaemia.
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peptic ulcer
localised breach of the gastric or duodenal mucosa that extends through the mucosa into the submucosa or muscularis propria, caused by the digestive action of gastric juice or upper small intestinal secretions.
• Epidemiology – 10% of UK population during life
• Most common symptom is pain.
• Most serious complication is bleeding or perforation which are life threatening.
• Causes
1. Excess secretion of acid and pepsin by the gastric mucosa.
2. Diminished ability of the gastrodudenal mucosal barrier to protect against the digestive properties of the stomach acid-pepsin secretion
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protection from gastric juices
1. Any area exposed to gastric juices is well supplied by mucous glands to provide a viscid coating of alkaline mucus.
2. The duodenum is protected by intestinal secretions.
An important secretion is pancreatic secretion – this contains large amounts of sodium bicarbonate that neutralise the HCl of the gastric juice, thus also inactivating pepsin and preventing digestion of the mucosa.
3. Also, large amounts of bicarbonate ions are provided in:
The secretions of the large Brunner’s glands in the proximal duodenal wall. This gland also secretes mucus which helps provide an alkaline environment.
In bile coming from the liver.
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feedback mechanisms for neutralisation of gastric juices
1. When excess acid enters the duodenum, it reflexly inhibits gastric secretion and peristalsis in the stomach, both by nervous reflexes and by hormonal feedback from the duodenum, thereby decreasing the rate of gastric emptying.
2. The presence of acid in the small intestine liberates secretin from the intestinal mucosa, which then passes by way of the blood to the pancreas to promote rapid secretion of pancreatic juice. This juice causes neutralization of the acid.
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helicobacter pylori
H-pylori are flagellated gram negative bacillus found on the luminal surface of the gastric epithelium that induces chronic mucosal inflammation.
They contain high levels of the enzyme urease. These bacteria metabolise urea.
(This urease production is the basis for diagnostic tests.)
H-pylori is a bacteria that can live in low pH environments, such as the stomach.
It does this by metabolising urea which releases NH3 (alkali).
This causes local alkaline conditions around the bacteria, allowing it to withstand the acidic conditions of the stomach.
H-pylori is capable of penetrating the mucosal barrier by:
Its physical capability to burrow through the barrier.
Releasing bacterial digestive enzymes that liquefy the barrier, allowing the strong acidic digestive juices to penetrate the underlying epithelium and digesting the gastroduodenal wall, thus leading to peptic ulceration (in 15% of patients).
H-pylori also inhibits somatostatin release in the antrum, thus causing an increase in acid secretion.
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urea breath test
main test- This test is based on the ability of H.pylori to convert urea to NH3 and CO2.
Patients swallow a meal consisting of non-radioactive carbon-13 urea and citric acid.
Breath sample taken by direct exhalation into test tubes 15 minutes later.
Urea is split by urease into NH3 and CO2.
The detection of the labelled CO2 in the exhaled breath indicates that the urea was split; this indicated that the urease is present in the stomach, and so H.pylori is present.
Must stop PPI’s antibiotics and bismuth containing drugs for 4 weeks prior and fast 6 hours before test.
Sensitivity and specificity >95%
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helicobacter stool antigen test and serology
Based on amplification of H.pyloru RNA shed in stool
Sensitivity >90%; specificity 80-90%
o Serology:
IgG indicates previous exposure, poor value
Sensitivity 90%; specificity 70-80%
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invasive tests
o CLO or Urease Test:
2 gastric samples placed in a medium containing urea and a pH indicator.
Hydrolysis of urea by HP urease alters pH-pink colour develops in a few hours.
o Gastric Biopsy for histopathology
o Gastric Biopsy for culture of H.pylori
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NSAIDS
NSAIDs compromise mucosal protection.
There are three mechanisms that control protection against excess acid:
1. Vagal and local reflexes – increases secretion of mucus.
2. Secretin – increases secretion of bicarbonate ions
3. Prostaglandin E2 (PGE2
Normally, PGE2 inhibits HCl secretion and stimulates mucus cell secretion (mucus and bicarbonate ions).
NSAIDs block the Arachadonic acid pathway by blocking COX and therefore increase HCl secretion and decreasing bicarbonate secretion.
Example – Misoprostol – stimulates mucus secretion (surface mucous cells and intestinal goblet cells) and inhibits H+ secretion from parietal cells.
NSAIDs inhibit PGE2 synthesis, thus increasing acid secretion and causing ulcers.
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zollinger ellison syndrome
This is a condition where there is a gastrin-secreting tumour, thus leading to excess acid secretion.
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other causes of gastric ulcers
smoking-increased nervous stimulation of the stomach secretory glands.
alcohol-because it tends to break down the mucosal barrier
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histamine and PGE2 intracellular pathway
* Histamine works via the Gs intracellular protein pathway, causing an increase in acid secretion.
* PGE2 works via the Gi intracellular protein pathway, causing a decrease in acid secretion.
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standard triple therapy
2 antibiotics + 1 PPI.
“CAP” = Clarityromycin (500mg bd) + Amoxicillin (1g bd) + PPI (standard dose bd)
Metronidazole (400mg bd) can be used instead of Amoxicillin
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modern Bismiuth based regimens
2 antibiotics + 1 bismuth compound.
“CAR” = Clarithromycin (500 mg bd) + Amoxicillin (1 g bd) + Ranitidine bismuth citrate (400 mg bd)
Metronidazole (400 mg bd) can be used instead of Amoxicillin
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retreatment
Standard triple therapy
As above using a regimen different from that first employed
Quadruple Therapy
PPI (standard dose bd) + Tetracycline (4× 500 mg) + Metronidazole (3× 400 mg/ 500 mg) + Ranitidine Bismuth Citrate (400 mg bd).
Bismuth Subcitrate (4× 100 mg)/ Bismuth Subsalicylate (4× 600 mg) can be used instead of Ranitidine Bismuth Citrate
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H2 histamine recveptor antagonists
– cimetidine, ranitidine
These block the H2 histamine receptors on the parietal cells.
As a result, histamine secreted by ECL cells can no longer activate parietal cells, thus preventing the secretion of HCl into the stomach lumen
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Proton pump inhibitor
These comprise of thioamide compounds.
Examples – Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole sodium
These block the action of the H+,K+ -ATPase pump permanently in the gastric parietal cell by binding to its sulphydryl group.
Given in encapsulated formulation to avoid breakdown by stomach acid.
It is absorbed in the small intestine and travels to parietal cells in blood
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bismuth compounds
hese are “coating compounds” which potentiate the action of antibiotics
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antacids
Sodium Carbonate, Calcium Carbonate, Magnesium or Aluminium Hydroxide
These are weak bases which react with gastric HCl to form a salt and water, relieving dyspepsia and reflux pain, by neutralising the acid secreted in response to a meal.
Antacids can interact with several drugs - Tetracyclines, Fluoroquinolones, Itriconazole and Iron.
As the metal salts are absorbed by the kidneys, long term use of antacids is unsuitable for patients with serious renal disorders.
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1st generation PPIs
- Omeprazole
• Lipid soluble, weak base – enters & accumulates in acid spaces (canaliculi of parietal cell).
• Activated in acid - chemically altered by H+ to an active sulphenamide form.
• Sulphenamide = cationic so trapped in canaliculi.
• Forms irreversible S-S bond with H+,K+ ATPase, therefore blocks its action permanently
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2nd generation PPIs
– Esomeprazole / Nexium
• 1st generation PPIs (e.g. omeprazole) are a mixture of optical (R and S) isomers.
• The S-isomer is more active in humans.
• Purified S-isomer is ‘esomeprazole/nexium’
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gastroscopy
• A gastroscopy is a medical procedure where a thin, flexible tube called an endoscope is used to look inside the stomach.
• An endoscope has a light and a camera at one end. The camera sends images of the inside of your body to a television monitor.
• A gastroscopy is a very common procedure, with more than 600,000 carried out by the NHS in England each year.
• Gastroscopy is used a means of investigation and diagnosis:
o Oesophagitis
o Duodenal and stomach ulcers
o Duodenitis and gastritis
o Cancer of the stomach and oesophagus
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visceral sensation
* Normal visceral sensation, for the most part, is not perceived, except for sensations such as hunger and rectal distension.
* Abnormal visceral sensation, however, is perceived as diffuse pain.
* The pain fibres that originate in the viscera are transmitted via C fibres, which only transmit colicky/ cramping, poorly localized types of pain.
* The parietal peritoneum is innervated by extensions of the peripheral spinal nerves, which carry the same types of noxious pain sensations as those overlying the dermatomes. Therefore, parietal pain results in sharp, localized pain.
* If the pathologic process progresses from the visceral to the parietal region, the referred pain will become localized, corresponding to the dermatome overlying the affected organ
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referred pain
* Many organs have an embryonic origination in one location of the body and then migrate to another area, pulling their vascular and nervous supply with them.
* Thus, visceral pain is often referred to sites far removed from the location of the organ (indicating the site of embryonal origin of their respective innervation).
* Peritonitis (e.g. this case) can cause irritation of the diaphragm. This will cause referred pain into the right shoulder via the C3, 4, 5 dermatome
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dyspepsia
• Dyspepsia is the chronic or recurrent pain or discomfort centred in the upper abdomen.
• Clinical features:
Epigastric pain – central upper abdominal or lower retrosternal discomfort related to eating
Postprandial fullness, unease
Accompanying symptoms may include nausea and vomiting, bloating, belching and weight loss
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gastric cancer
* 4th most common cause of cancer death in Europe and USA.
* Three times more common in men.
* Most diagnosed >65 years of age
* Incidence of antral and body cancer declining – probably because of falling prevalence of Helicobacter.
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gastric cancer risk factors
Conditions associated with hypochlorhydria
Helicobacter pylori-associated gastritis
Autoimmune gastritis
Post-gastric surgery (>20 years)
Chronic atrophic gastritis
Barrett'so esophagus (adenocarcinoma of cardia and distal esophagus)
Gastric adenoma
Intestinal metaplasia
• Genetic Risk Factors:
Gastric cancer family history
Familial adenomatous polyposis coli (FAP)
Hereditary nonpolyposis coli
Germline E-cadherin (CDH1) mutations
Proinflammatory cytokine gene polymorphisms
• Possible Risk Factors:
Peutz-Jeghers syndrome
Ménétrier's disease
Smoking
Diets low in fresh fruit and vegetables
Diets high in preserved, pickled, or smoked items
Alcohol
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clinical presentation of gastric cancer
Upper abdominal discomfort or pain
New-onset dyspepsia
Anorexia and early satiety
Weight loss
Vomiting (may be unaltered food in gastric outlet obstruction)
Iron deficiency anaemia
Distant lymphadenopathy (Virchow's node, etc.)
Metastatic spread - hepatomegaly, malignant ascites, bone pain, pulmonary metastases
Early gastric cancer is often asymptomatic
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investigations of gastric cancer
```
Blood tests
ESTABLISHING A DIAGNOSIS:
Upper gastrointestinal endoscopy and biopsy
Barium meal?? •
METHODS MAINLY FOR STAGING:
Computed tomography
Ultrasonography
Endoscopic ultrasonography
Positron emission tomography (PET) scan
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staging of gastric cancer
Five-year survival correlates closely with staging, with true in situ carcinoma having a survival rate of nearly 100%, through to stage 4 disease with a 5-year survival rate of 2%.
TUMOUR NODE METASTASIS
T1:
Tumours are confined to the mucosa and submucosa. N0:
No nodes involved M0:
No metastasis
T2:
Tumours penetrate the muscularis propria but not the serosa. N1:
Involvement of perigastric nodes within 3cm of the primary tumour M1:
Distant metastasis
T3:
Tumours reach the serosa but without the involvement of other organs. N2:
Spread to more distant regional lymph nodes.
T4:
Tumours have spread beyond the serosa. N3:
Involvement of nodes is to more distant intra-abdominal lymph glands that are not removable with surgery
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management of gastric cancer
Surgery if no metastasis and patient in otherwise good health
(Radical surgery has mortality of 10%)
Endoscopic Mucosal Resection for early gastric lesions confined to mucosa
Most surgery is palliative for relief of obstruction - supportive-palliative in advanced cases
Adjuvant chemotherapy
Family member, home support, liaison with GP are vital aspects of care
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physiological response of stress
• In some instances, almost all portions of the sympathetic nervous system discharge simultaneously producing an effect known as mass discharge. This frequently happens when the hypothalamus is activated by fright, fear or severe pain. The result leads to the stress response.
• The sympathetic nervous system has small preganglionic nerves and long postganglionic nerves. The preganglionic nerves are in close proximity (thoracic and lumbar regions).They ‘talk’ to each other. When the SNS is activated, all of the preganglionic nerves are activated simultaneously.
• Any condition-physical or emotional-that threatens homeostasis is a form of stress.
• Upon exposure to a wide variety of stress-causing factor, the body undergoes the stress response; this can be divided into three phases:
1. The Alarm Phase
2. The Resistance Phase
3. The Exhaustion Phase.
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alarm phase
* During the alarm phase, an immediate response to the stress occurs.
* This response is directed by the sympathetic nervous system.
* Activation of the SNS causes increased secretion of adrenaline.
* Adrenaline is the dominant hormone of the alarm phase, and its secretion accompanies a generalized sympathetic activation.
• In the alarm phase:
1. Energy reserves are mobilized, mainly in the form of glucose
2. The body prepares to deal with the stress-causing factor by “fight or flight” responses
• The characteristics of the alarm phase include the following:
1. Increased mental alertness.
2. Increased energy use by all cells, especially skeletal muscles.
3. Mobilization of glycogen (Hepatocytes perform glycogenolysis) and lipid reserves (adipose tissue cells perform lipolysis).
4. Changes in circulation, including increased blood flow to skeletal muscles and decreased blood flow to the skin, kidneys, and digestive organs.
5. A drastic reduction in digestion and urine production.
6. Increased sweat gland secretion.
7. Increases in blood pressure, heart rate, respiratory rate and metabolic rate.
• Although the effects of adrenaline are most apparent during the alarm phase, other hormones play supporting roles.
• In this phase, there is increased production of adrenaline and noradrenaline so that both the alpha and beta adrenergic receptors are activated with better efficiency.
• For example, the reduction of water losses resulting from ADH production and aldosterone secretion can be very important if the stress involves a loss of blood.
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resistance phase
• If a stress lasts longer than a few hours, the individual enters the resistance phase of the stress response.
• Glucocorticoids (cortisol) are the dominant hormones of the resistance phase.
• Growth Hormone, ADH and glucagon are also involved.
• Energy demands in the resistance phase remain higher than normal.
• Neural tissue has a high demand for energy, and neurons must have a reliable supply of glucose. If blood glucose concentrations fall too far, neural function deteriorates.
• Glycogen reserves are adequate to maintain normal glucose concentrations during the alarm phase, but are nearly exhausted after several hours. Therefore, alternate energy sources are sought for in the resistance phase.
• The endocrine secretions of the resistance phase achieve four integrated results:
1. Mobilization of remaining lipid and protein reserves:
The hypothalamus produces GHRH, stimulating the release of GH and glucocorticoids.
o Adipose tissue responds to GH and glucocorticoids by releasing stored fatty acids.
o Skeletal muscles respond to glucocorticoids by breaking down proteins and releasing amino acids into the bloodstream.
2. Conservation of glucose for neural tissues:
Glucocorticoids (cortisol) and GH stimulate lipid metabolism in peripheral tissues.
o Peripheral tissue (except neural) breaks down lipids to obtain energy.
Neural tissues do not alter their metabolic activities, however, and they continue to use glucose as an energy source.
3. Elevation and stabilization of blood glucose concentrations:
As blood glucose levels decline, glucagon and glucocorticoids (cortisol) stimulate the liver to manufacture glucose from other carbohydrates (glycerol) and from amino acids provided by skeletal muscles.
4. Conservation of salts and water, and the loss of K+and H+:
Blood volume is conserved through the actions of ADH and aldosterone.
As Na+ is conserved, K+ and H+ are lost.
• The resistance phase cannot be sustained indefinitely.
If starvation is the primary stress, the resistance phase ends when lipid reserves are exhausted and structural proteins become the primary energy source.
If another factor is the cause, the resistance phase ends due to complications brought about by hormonal side effects.
• There may be side-effects experienced as a result of the hormones:
1. Glucocorticoids (cortisol): anti-inflammatory action slows wound healing and increases the body’s susceptibility to infection.
2. The continued conservation of fluids under the influence of ADH and aldosterone stresses the cardiovascular system by producing elevated blood volumes and higher-than-normal blood pressures.
3. The suprarenal cortex may become unable to continue producing glucocorticoids, eliminating acceptable blood glucose concentrations.
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exhaustion phase
• When the resistance phase ends, homeostatic regulation breaks down and the exhaustion phase begins.
• Unless corrective actions are taken almost immediately, the failure of one or more organ systems will prove fatal.
• Mineral imbalances contribute to the existing problems with major systems.
The production of aldosterone throughout the resistance phase results in a conservation of Na+ at the expense of K+.
As the body’s K+ content declines, a variety of cells—notably neurons and muscle fibers—begin to malfunction.
Although a single cause (such as heart failure) may be listed as the cause of death, the underlying problem is the inability to sustain the endocrine and metabolic adjustments of the resistance phase.
• Stress occurs when the perceived demands of a situation are appraised as exceeding a person’s perceived resources and ability to cope
• These situations are stressors and lead to the stress response
• The more control we perceive we have over a situation the less stressful it is
• If the stressor can be predicted, its effect is lessened
• Appraisal is central to whether a person feels stressed or not
• Severe or chronic stress is associated with psychological problems
• Severe or chronic stress is associated with a range of illness and mortality
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HPA Axis
• Exaggerated activity in the HPA (hypothalamic-pituitary-adrenal) system is associated with anxiety disorders.
• Anxiety and depression coexist.
• Hyperactivity of the HPA axis is associated with depression.
Chronic stress results in excessive release of glucocorticoids (Cortisol) in the blood. It released from the adrenal cortex in response to an elevation in the blood level of adrenocorticotropic hormone (ACTH).
ACTH is released by the anterior pituitary gland in response to corticotropin-releasing hormone (CRH).
CRH is released into the blood of the portal circulation by parvocellular neurosecretory neurons in the paraventricular nucleus of the hypothalamus
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psychological response
• The psychological appraisal of a stressor is central to the stress response;
Without appraisal physiological changes are absent or minimal.
The degree of appraisal also influences the extent of the physiological response.
• It is likely that the mind–body interactions illustrated by stress are dynamic and ongoing.
• Therefore, rather than appraisal causing a change in physiology which constitutes the response, appraisal probably triggers a change in physiology which is then detected and appraised causing a further response and so on.
• In addition, psychological factors such as control, personality, coping and social support will impact upon this ongoing process.
• Approach coping strategies try to deal with the situation pro-actively and thus share some overlap with problem-focused strategies.
• Avoidant coping strategies try to avoid the problem.
* Stress occurs when the perceived demands of a situation are appraised as exceeding a person’s perceived resources and ability to cope.
* These situations are stressors and lead to the stress response.
* The more control we perceive we have over a situation the less stressful it is.
* If the stressor can be predicted, its effect is lessened.
* Appraisal is central to whether a person feels stressed or not.
* Severe or chronic stress is associated with psychological problems.
* Severe or chronic stress is associated with a range of illness and mortality.
* Males tend to respond to stress with increased levels of cortisol relating to ah higher chance of the fight-or-flight behavior in males. In females, they discovered that instead of increased cortisol levels, an increase in the activity of the limbic system was initiated.
* Females’ increased limbic activity gave proof to the tend-and-befriend theory for female coping strategies and says that females are more likely to alleviate stressful situations by nurturing and running to acceptable social groups
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stress reactivity
* Changes in physiology are known as ‘stress reactivity’ and vary enormously between people.
* For example, some individuals respond to stressful events with high levels of sweating, raised blood pressure and heart rate while others show only a minimal response. research also shows that some people are simply more reactive to stress than others.
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stress recovery
* After reacting to stress, the body then recovers and levels of sympathetic activation return to baseline.
* However, there is great variability in the rate of recovery both between individuals, as some people recover more quickly than others, and within the same individual across the lifespan
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allostatic load
* Stress recovery is linked with allostatic load.
* The body’s physiological systems constantly fluctuate as the individual responds and recovers from stress – a state of allostasis – and that, as time progresses, recovery is less and less complete and the body is left increasingly depleted.
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transaction model of stress
The Role of Appraisal (Model of Appraisal)
• Lazarus argued that stress involved a transaction between the individual and their external world, and that a stress response was elicited if the individual appraised a potentially stressful event as actually being stressful.
• Lazarus’s “model of stress”:
Described individuals as psychological beings who appraised the outside world, not simply passively responding to it.
Lazarus defined two forms of appraisal: primary and secondary.
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primary appraisal
The individual initially appraises the event itself.
There are four possible ways that the event can be appraised:
1) Irrelevant
2) Benign (gentle) and Positive
3) Harmful and a Threat
4) Harmful and a Challenge
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secondary appraisal
The individual evaluating the pros and cons of their different coping strategies.
• Therefore primary appraisal involves an appraisal of the outside world and secondary appraisal involves an appraisal of the individual themselves.
• The form of the primary and secondary appraisals determines whether the individual shows a stress response or not.
• This stress response can take different forms:
Direct action
Seeking information
Doing nothing
Developing a means of coping with the stress in terms of relaxation or defense mechanisms
• Lazarus’s model of appraisal and the transaction between the individual and the environment indicated a novel way of looking at the stress response – the individual no longer passively responded to their external world, but interacted with it.
• It is not an event itself that elicits stress, but the individual’s interpretation or appraisal of those events.
• This appraisal can be modified by providing information or withholding information from the individual.
• An event needs to be appraised as stressful before it can elicit a stress response.
• It could be concluded from this that the nature of the event itself is irrelevant – it is all down to the individual’s own perception.
• Multitasking seems to result in more stress than the chance to focus on fewer tasks at any one time. Therefore a single stressor which adds to a background of other stressors will be apprised as more stressful than when the same stressor occurs in isolation.
• If a stressor can be predicted and controlled then it is usually appraised as less stressful than a more random uncontrollable event.
• A feeling of being in control reduces the stress of an event and contributes to the process of primary appraisal.
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cannons flight or fight
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• Acute:
Increased sympathetic activation
Increased cognitive performance
Increased muscular priming
Increased immune functioning
• Chronic:
Decreased immune functioning
Decreased cognitive performance
This eventually leads to exhaustion.
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hans selyes general adaptation syndrome
• This is broken down into three phases (see previous notes):
1. Alarm Phase
Shock (initial symptoms)
Flight-or-Fight response (sympathetic nervous system activated)
Hormones such as cortisol and adrenaline (epinephrine) released.
Counter-shock (homeostasis)
2. Resistance Phase
Adaption
Parasympathetic nervous system returns many physiological functions back to normal levels while body focuses resources against the stressor.
Blood glucose levels remain high (cortisol and adrenaline continue to circulate at elevated levels).
Increased heart rate, breathing and blood pressure.
3. Exhaustion Phase
Symptoms reappear
If stressor continues beyond body’s capacity, organism exhausts resources and becomes susceptible to diseases and death
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shared decision making
• This is the making of decisions/ coming to an agreement where there is a balance between physician directed decision making and strict autonomy (i.e. the patient making the decision).
• Most patients and family members prefer shared decision making over either strict autonomy or physician-directed decision making.
• The model for shared decision making is consistent with ethical principles and patient preferences and can be referred to as the “shared decision-making continuum” because shared decision making will necessarily take different forms in different situations.
At one end is patient- or agent-driven decision making.
At the opposite end is physician-driven decision making.
In the middle are many possible approaches.
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patient agent driven decision making
* In this, the physician presents all options and the patient makes his/her own choice.
* The physician provides expert knowledge only and makes no recommendations
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physician recommendation decision making
* The physician explains all the option and also makes a recommendation.
* The physicians must base their recommendations on the patient’s values rather than on their own.
* This can require time and advanced communication skills.
* When a patient asks the physician what he/she should do, the physician mist consider the patient’s perspective and ensure he/she is neither intentionally nor unintentionally coercive.
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shared decision making
* The patient and the physician work together to reach a mutual decision.
* This process often requires a longstanding relationship and both parties must understand the values and biases of the other.
* Mutual respect and understanding are essential.
* Because the patient and physician necessarily have different perspectives, the physician must ensure that it is the patient’s values, not his/her own, that guide decision making.
* In some cases it may be appropriate for the physician to bear the major burden of decision making.
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informed non dessent decision making
• With informed non-dissent decision making, the physician, guided by the patient’s values, determines the best course of action and fully informs the patient.
• The patient may either remain silent, thereby allowing the physician’s decision to stand, or veto the decision.
• In this approach the patient must understand all pertinent information.
• Furthermore, the patient must appreciate that silence will be construed as tactic agreement.
Patients must understand that they are welcome to veto the decision and if so, their wishes will be honoured and they will receive excellent care.
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consent
Why? Because non-consensual contact may be an assault
•How much detail? As much as the patient needs
•Who? Ideally the person who will do the procedure
To assess mental capacity:
•England and Wales – Mental Capacity Act 2005
•Scotland – Adults with Incapacity (Scotland) Act 2000
•N Ireland – no primary legislation – relies on common law using ‘Best Interests’ test
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assessing capacity using MCA
From p44 of MCA (2005) Code of Practice:
2 stage test:
1. Person has a disturbance of mind or brain
•Mental illness
•Longstanding learning disability
•Damage from brain injury
•Physical illness causing confusion/drowsiness
•Signs of drug or alcohol use
2. Does the impairment or disturbance mean that the person is unable to make a specific decision when they need to? i.e. are they able to:
•understand information about the decision to be made (the Act calls this ‘relevant information’)
•retain that information in their mind
•use or weigh that information as part of the decision-making
process, or
•communicate their decision(by talking, using sign language
or any other means)
Note: The MCA (2005) does not define best interests, so they must be established for each patient
individually and may change over time
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healthy lifestyle concept
Scientific basis of healthy lifestyle concept: Alameda County study
7 factors predictive of early disease and death:
•smoking;
•not maintaining ideal weight (being under or over);
•snacking between meals,
•not having breakfast each day;
•not sleeping 7-8 hours a day or more than 8 hours;
•taking more than 5 units of alcohol in a session;
•not taking regular exercise
These behaviors also predictive of future disability
More positive health behaviours reported the lower the risk Note: Lifestyle disease accounts for about 70-80% of all deaths. Most of the mortality can be explained by smoking related activity. 25-34 men smoke, 45-54 women. 2/3 smokers want to give up
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obesity
Obesity is calculated as BMI Wt (kg)/ height (M2) and is classified as:
•mild (20-40%) or Grade 1 (25.29.9 BMI),
•moderate (41-100%) Grade 2 (30-39.9 BMI),
•severe (100%+) Grade 3 (40+ BMI).
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motivational interviewing
A collaborative conversation that elicits and strengthens peoples ability to self-manage and make
lifestyle behaviour changes.
•Encourages careful listening allows communication ‘under the radar’
•Supports self-efficacy
•Allows us to work with ambivalence to change
•Identifies peoples own solutions to the problem – increasing intention to change
•Can be easily incorporated into 10 min consultations
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4 processes of motivational interviewing
1)Engage(summarizing and reflecting)
a.Types of reflective listening:
i.Repeating (repeat and element)
ii.Rephrasing (repeat in different words)
iii.Paraphrase (repeat best guess at meaning; saying the next sentence)
iv.Reflection of feeling (paraphrase that emphasizes the emotional dimension and gives a new perspective)
2)Focus(agenda setting) – yours and the patients; shared decision making
3)Evoke(change talk – identify and respond)
a.Recognizing change talk:
i.DARN: preparation
1.Desires:“I would...”
2.Abilities:“ I can, I could... “
3.Reasons: “because...”
4.Needs:“It’s very important to me...
ii.CAT: action
1.Commitment:“I’m going to...”
2.Activation:“ I’m ready to...”
3.Steps “I’ve already done...”
b.Responding to change talk:
i.EARS
1.Elaborate
2.Affirm
3.Reflect
4.Summarise
4)Plan
(goals and actions)
a.SMART goals
i.Specific
ii.Measurable
iii.Achievable
iv.Relevant
v.Time-bound
126
alginate
Alginate is a naturally occurring anionic polymer typically obtained from brown seaweed, and has been extensively investigated and used for many biomedical applications, due to its biocompatibility, low toxicity, relatively low cost, and mild gelation by addition of divalent cations such as Ca2+ [4]. Alginate hydrogels can be prepared by various cross-linking methods, and their structural similarity to extracellular matrices of living tissues allows wide applications in wound healing, delivery of bioactive agents such as small chemical drugs and proteins, and cell transplantation. Alginate wound dressings maintain a physiologically moist microenvironment, minimize bacterial infection at the wound site, and facilitate wound healing. Drug molecules, from small chemical drugs to macromolecular proteins, can be released from alginate gels in a controlled manner, depending on the cross-linker types and cross-linking methods. In addition, alginate gels can be orally administrated or injected into the body in a minimally invasive manner, which allows extensive applications in the pharmaceutical arena. Alginate gels are also promising for cell transplantation in tissue engineering. Tissue engineering aims to provide man-made tissue and organ replacements to patients who suffer the loss or failure of an organ or tissue [5]. In this approach, hydrogels are used to deliver cells to the desired site, provide a space for new tissue formation, and control the structure and function of the engineered tissue [6]. In this review, general properties of alginate and its current and potential applications in biomedical science and engineering will be discussed
Commercially available alginate is typically extracted from brown algae (Phaeophyceae), including Laminaria hyperborea, Laminaria digitata, Laminaria japonica, Ascophyllum nodosum, and Macrocystis pyrifera [7] by treatment with aqueous alkali solutions, typically with NaOH [8]. The extract is filtered, and either sodium or calcium chloride is added to the filtrate in order to precipitate alginate. This alginate salt can be transformed into alginic acid by treatment with dilute HCl. After further purification and conversion, water-soluble sodium alginate power is produced [9]. On a dry weight basis, the alginate contents are 22–30% for Ascophyllum nodosum and 25–44% for Laminaria digitata
127
simvastatin
Simvastatin is in a group of drugs called HMG CoA reductase inhibitors, or "statins." It reduces levels of "bad" cholesterol (low-density lipoprotein, or LDL) and triglycerides in the blood, while increasing levels of "good" cholesterol (high-density lipoprotein, or HDL).Simvastatin is used to lower cholesterol and triglycerides (types of fat) in the blood.Simvastatin is also used to lower the risk of stroke, heart attack, and other heart complications in people with diabetes, coronary heart disease, or other risk factors.Simvastatin is used in adults and children who are at least 10 years old
