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Medicine Sem 4 > Case 2 > Flashcards

Case 2 Flashcards

1
Q

physiologically, what is the stomach divided into?

A

two parts:

  1. Orad portion – this is the first 2/3 of the ‘body’ of the stomach.
  2. Caudad portion – this is the last 1/3 of the ‘body’ of the stomach + antrum.
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2
Q

what are the three motor functions of the stomach?

A
  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.
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3
Q

storage function of the stomach

  • how does food sit in stomach
  • what does distention cause
  • maximal capacity
A

• 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.

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4
Q

what are digestive juices of the stomach secreted by and where are they found?

A
  • The digestive juices of the stomach are secreted by the gastric glands, which are present in almost the entire wall of the body of the stomach except along the lesser curvature of the stomach.
  • These come into direct contact with the food lying against the mucosal surface of the stomach.
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5
Q

as long as food is in the stomach, what happens?

A
  • The digestive juices of the stomach are secreted by the gastric glands, which are present in almost the entire wall of the body of the stomach except along the lesser curvature of the stomach.
  • These come into direct contact with the food lying against the mucosal surface of the stomach.
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6
Q

what are these mixing waves initiated by?

A

the gut wall basic electrical rhythm, consisting of electrical “slow waves” that occur spontaneously in the stomach wall.

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7
Q

what happens as these constrictor waves progress from the body of the stomach into the antrum?

A
  • 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.
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8
Q

how do these constrictor rings also play an important role in mixing the stomach contents?

A

 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.

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9
Q

what does the degree of fluidity of chyme leaving the stomach depend on?

A

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.

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10
Q

hunger contractions

  • when do they occur
  • what are they
  • who most intense in
  • what also triggered by
  • what also experienced with this
A
  • 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.
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11
Q

what is stomach emptying brought about by?

A

strong peristaltic contractions in the stomach antrum.

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12
Q

what are stomach contractions mainly involved in? how do they change and what do they become involved in? what happens as the stomach becomes more empty?

A
  • 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.
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13
Q

when pyloric tone is normal, how much can each strong peristaltic wave force into the duodenum?

A

up to several milliliters of chyme

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14
Q

thus, what do the peristaltic waves do?

A
  1. Cause mixing in the stomach.

2. Provide a pumping action called the “pyloric pump.”

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15
Q

what is the thickness of the circular wall muscle of the pylorus like compared to earlier portions of the stomach antrum? what state is it normally in? what is the pyloric circular muscle called? what does this allow and not allow through?

A
  • 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.
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16
Q

what is the degree of constriction of the pylorus affected by?

A

• 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.

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17
Q

what is regulation of stomach emptying controlled by?

A
  • 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.
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18
Q

describe and explain the effect of gastric food volume on rate of emptying

A
  • 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.
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19
Q

what is gastrin released by?

A

G cells of the antral mucosa

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20
Q

what is gastrin released as a result of?

A

 Stretching of the stomach wall.

 Presence of protein food contents in the stomach.

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21
Q

what are the functions of gastrin?

A
  1. It has potent effects to cause secretion highly acidic gastric juice by stomach glands:
     Gastrin activates ECL (enterochromaffin-like) 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.
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22
Q

what effect does the duodenum have on stomach emptying?

A

• 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.

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23
Q

what are the three routes that these reflexes from the duodenum are mediated through?

A
  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)
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24
Q

what effects do these enterogastric inhibitory reflexes have?

A

• 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.
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25
Q

what are the types of factors that are continually monitored in the duodenum and that can initiate enterogastric inhibitory reflexes?

A
  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.
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26
Q

what is the stimulus for hormone release from the upper intestine?

A

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.

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27
Q

what is the hormone that has the most potent effect in regards to hormonal feedback to inhibit gastric emtpying?

A

cholecystokinin (CCK)

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28
Q

where is CCK released from and what is the stimulus?

A

released from the duodenal and jejunal mucosa in response to fatty substances in the chyme.

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29
Q

what hormone does CCK act as an inhibitor against?

A

• CCK acts as an inhibitor to block increased stomach motility caused by gastrin.

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30
Q

what are other inhibitors of stomach emptying?

A

the hormones secretin (opposite - don’t secrete chyme) and gastric inhibitory peptide (GIP).

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31
Q

where is secretin released from?

A

duodenal mucosa (S cells in the crypts of Lieberkuhn).

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32
Q

what is secretin released in repsonse to?

A

gastric acid passed from the stomach through the pylorus.

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33
Q

GIP

  • what effect does it have
  • where released from
  • what released in response to
  • what’s its primary function
A

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.

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34
Q

summarise the regulation of stomach emptying

A

• 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.

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35
Q

what are the gastric factors that increase stomach emptying?

A

Increased stretching of the stomach wall – increased pressure in the stomach

Gastrin – enhanced pyloric pump + increased HCl production in parietal cells

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36
Q

what are the duodenal factors that decrease stomach emptying?

A

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

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

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37
Q

what are the two types of tubular glands that the stomach mucosa also has? what are they composed of? where are they located? how much of the stomach do they constitute?

A
  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.
  2. 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.
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38
Q

where si HCl formed?

A
  • 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).
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39
Q

what is the mechanism of HCl secretion in the gastric glands?

A

 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.

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40
Q

where is pepsinogen secreted by? what type of pepsinogen? what is their function?

A

• 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.

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41
Q

what is the optimum pH for pepsinogen? at what pH does it lose activity?

A

 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.

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42
Q

describe regulation of pepsinogen secretion

A

• 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.

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43
Q

what is intrinsic factor essential for?

A

the absorption of vitamin B12 in the ileum. (protein that binds to B12 and is required for B12 uptake in the ileum)

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44
Q

what is intrinsic factor secreted by?

A

parietal (oxyntic) cells along with the secretion of HCl.

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45
Q

what happens when the acid-producing parietal cells of the stomach are destroyed?

A

• 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.

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46
Q

describe the regulation of gastric acid

A

increase by histamine, ACh, gastrin

decrease by somatostatin, GIP, prostaglandin, secretin

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47
Q

where are bicarbonate ions produced? what is their action? how are they regulated?

A
  • mucosal cells (stomach, duodenum, salivary glands, pancreas) and Brunner’s glands (duodenum)
  • neutralises acid
  • increase pancreatic and biliary secretion with secretin
  • HCO3- is trapped in mucus that covers the gastric epithelium
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48
Q

how are pyloric glands different to parietal cells? what do cells of the gland secrete?

A
  • 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.

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49
Q

describe surface mucous cells

  • where are they
  • what do they secrete
  • what is the mucus like and why
  • what stimulates these cells
A
  • 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.
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50
Q

what are the only cells that secrete HCl?

A

parietal cells

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51
Q

which cells do parietal cells operate in close association with? describe this association

A

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.

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52
Q

how are ECL cells activated?

A
  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.
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53
Q

where is gastrin secreted from?

A

by gastrin cells (G-cells) located in the antral mucsoa (pyloric glands).

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54
Q

what are the two forms that gastrin is secreted in?

A

a. G-34 = this contains 34 amino acids

b. G-17 = this contains 17 amino acids (and is more abundant)

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55
Q

what stimulates gastrin release and what effect does this have?

A
  • 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.
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56
Q

what are the phases of gastric secretion?

A
  1. Cephalic phase
  2. Gastric phase
  3. Intestinal phase
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57
Q

cephalic phase

  • what is it
  • what stimulates it
  • what signals does this produce - from where to where
A
  • 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.
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58
Q

what are the stimulatory effects of the cephalic phase? how important for gastric secretion?

A

• 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.

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59
Q

gastric phase

  • when does this phase occur/what stimulates it
  • what are stimulatory and inhibitory effects
  • how important for gastric secretion
A

• 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 (I think this means if there is less acid):
 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.

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60
Q

intestinal phase

  • what does it occur as a result of
  • what are the stimulatory and inhibitory effects
A
  • 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: (bigger part of intestinal phase)
 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.

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61
Q

how does chyme influence gastric secretion? what causes these influences?

A
  • Chyme initially increases gastric secretion.
  • However, later chyme inhibits gastric secretion.
  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.
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62
Q

what is the purpose of intestinal factors inhibiting gastric secretion?

A

to slow passage of chyme from the stomach when the small intestine is already filled or already overactive.

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63
Q

what does somatostatin do?

A

inhibits G-cells, ECL cells and if there is an excess of acid in the duodenum, it inhibits the parietal cells.

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64
Q

is gastric juice secreted in the interdigestive period?

A

Yes
• This is non-oxyntic secretion, consisting mainly of mucus, but little pepsin and almost no acid.
• Emotional stimuli increase interdigestive gastric secretion.

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65
Q

what are the actions of gastrin?

A
  • increase gastric H+ secretion
  • increase growth of gastric mucosa
  • increase gastric motility
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66
Q

where is cholecystokinin released by?

A

I cells (duodenum, jejunum)

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67
Q

what is the action of cholecystokinin?

A
  • increase pancreatic secretion
  • increase gall bladder contraction
  • decrease gastric emptying
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68
Q

what is the action of secretin?

A
  • increase pancreatic HCO3- secretion
  • decrease gastric acid secretion
  • increase bile secretion
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69
Q

where is somatostatin produced?

A

D cells (pancreatic islets, GI mucosa)

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70
Q

what is the action of somatostatin?

A
  • decrease gastric acid and pepsinogen secretion
  • decrease pancreatic and small intestine fluid secretion
  • decrease gallbladder contraction
  • decrease insulin and glucagon release

(sommm, hoommm = relax, calm, less acid, less everything)

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71
Q

what enzyme in saliva breaks down carbohydrates? what does this enzyme do?

A

ptyalin = a-amylase
• This enzyme hydrolyzes starch into the disaccharide maltose and other small polymers of glucose that contain three to nine glucose molecules.

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72
Q

what percentage of all starches are hydrolysedby the time the food has been chewed and is swallowed? what about by the time it has reached the stomach?

A

5%
• 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.

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73
Q

what happens to salivary amylase in the stomach?

A

• 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.

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74
Q

at what pH is pepsin most active? when is it inactive?

A
  • 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.
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75
Q

how are gastric glands responsible for getting the optimum pH for pepsin?

A

• 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.

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76
Q

what is pepsin involved n the digestion of?

A
  • 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.
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77
Q

gastritis

  • what is it
  • is it serious
  • what caused by
  • treatment
  • what are common irritants that are especially damaging to the protective gastric mucosal barrier
A
  • 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.

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78
Q

what does the ‘gastric barrier’ consist of? what does form a barrier against?

A
  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.
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79
Q

what happens in gastritis due to resistant barrier being removed?

A
  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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80
Q

what is gastric atrophy? what does it lead to?

A
  • 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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81
Q

what is achlorhydria?when is it diagnosed? what does this cause?

A
  • 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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82
Q

describe how intrinsic factor is involved with B12 absorption

A
  • 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.
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83
Q

what is pernicious anaemia?

A
  • 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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84
Q

peptic ulcers

  • what are they
  • how common
  • most common symptom
  • most serious complicatino
A
  • 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.

ulcer = acid/enzyme damage to stomach or intestinal wall

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85
Q

what are the causes (not specific) of peptic ulcers?

A
  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.
  • Occur due to increase acid and/or decrease protection
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86
Q

what are the mechanisms for protection from gastric juices?

A
  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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87
Q

what are the feedback mechanisms for neutralisation of gastric juices?

A
  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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88
Q

what are specific causes of peptic ulcers in humans?

A

1) Bacterial Infection by Helicobacter Pylori (H-pylori)
2) NSAIDS (e.g. Aspirin)
3) Zollinger-Ellison Syndrome
4) Other Causes
- Smoking
- Alcohol
- Caffeine
- Stress ulcers (most likely occur when you are already under medical care for a major illness, surgical procedure, trauma, or injury – the presence of a stress ulcer adds another complication to your other medical conditions that lead to the ulcer)
- Steroids, Crohn’s, drugs…

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89
Q

what is H. pylori? how common?

A

are flagellated gram negative bacteria found on the luminal surface of the gastric epithelium that induces chronic mucosal inflammation.

  • 50% of people across world are colonised with H. Pylori, but only 0.5% in this country
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90
Q

what does H. pylori contain high levels of?

A

the enzyme urease - these bacteria metabolise urea

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91
Q

where is H. pylori capable of living and why?

A

 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.

it develops a mucous protective layer

92
Q

how is H. pylori capable of penetrating the mucosal barrier?

A

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).

  • ‘burrow’ through mucus (protected from acidity to some extent) and adhere to epithelium
93
Q

what does H. pylori inhibit? what effect does this have?

A

inhibits somatostatin release in the antrum, thus causing an increase in acid secretion.

94
Q

what are non-invasive methods for diagnosis of H. pylori? what are negatives of each test?

A

o Urea breath test: (MAIN ONE)
 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 (13C) 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%

o Heliobacter Stool Antigen Test:
 Based on amplification of H.pylori RNA shed in stool
 Sensitivity >90%; specificity 80-90%
o Serology:
 IgG indicates previous exposure, poor value
 Sensitivity 90%; specificity 70-80%

  • Stool antigen test - PPI will interfere with result
  • 13urea breath test - PPI will interfere with result
  • Serology - cannot distinguish active from previous infection
95
Q

what are invasive tests for the diagnosis of H. pylori?

A

o CLO (Campylobacter-like organism) 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

96
Q

what are the three mechanisms that control protection against excess acid?

A
  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).
97
Q

how do NSAIDS cause peptic ulcers?

A

 NSAIDs compromise mucosal protection.
 Normally, PGE2 inhibits HCl secretion and stimulates mucus cell secretion (mucus and bicarbonate ions).
 NSAIDs block the Arachadonic acid pathway by blocking COX1 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.

  • NSAIDs inhibit COX1 = decrease PGE2 in the mucosa of stomach & duodenum
  • Normal actions of PGE2:
  • stomach – parietal cells decrease H+
  • stomach & duo – increase mucosal protection
  • So NSAIDs = increase H+ & decrease protection
98
Q

what is Zollinger-Ellison syndrome?

A

 This is a condition where there is a gastrin-secreting tumour, thus leading to excess acid secretion.

99
Q

how do smoking and alcohol contribute to the formation of gastric ulcers?

A
  • Smoking - presumably because of increased nervous stimulation of the stomach secretory glands.
  • Alcohol - because it tends to break down the mucosal barrier.
100
Q

histamine and PGE2 intracellular pathways - what do both cause?

A
  • 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.
101
Q

what is treatment of H. pylori infection?

A

• Standard Triple Therapy (first line treatment)
 2 antibiotics + 1 PPI.
 “CAP” = Clarityromycin (500mg bd) + Amoxicillin (1g bd) + PPI (standard dose bd)
 Metronidazole (400mg bd) can be used instead of Amoxicillin

• 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.
• 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

102
Q

what are examples of antibiotics used to treat H. pylori?

A

clarithromycin, amoxicillin, metronidazole, tetracycline

103
Q

H2 histamine receptor antagonists

  • examples
  • what do they do
  • effect
A

 Examples – 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.

  • Identified by design, i.e. compounds with structural motives similar to histamine
104
Q

proton pump inhibitors

  • what do they comprise of
  • examples
  • what do they do
  • how are they given
  • where absorbed
A

 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

105
Q

what are bismuth compounds?

A

“coating compounds” which potentiate the action of antibiotics.

106
Q

antacids

  • examples
  • what are they
  • what do they do
  • what do they interact with
  • who unsuitable for
A

 Examples - 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.

107
Q

1st generation PPIs

  • example
  • what are they, what do they do
  • when activated - what happens to activated product
  • what formed
  • how given
  • onset
A
  • Example - Omeprazole
  • Lipid soluble, weak base – enters & accumulates in acid spaces (canaliculi and tubulovesicles 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. (until new pumps synthesised)

*given in encapsulated formulation to avoid breakdown by stomach acid – it’s absorbed in the small intestine and travels to parietal cells via the blood = ‘slow’ onset (1-2 h)

108
Q

2nd generation PPIs

  • example
  • what is difference between these and 1st generation
A

• Example – 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’
- Long-term side effects of PPIs = reduction in bone density

109
Q

what is gastroscopy? what used for?

A

• 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.
• 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

110
Q

is normal visceral sensation perceived?

A

for the most part no, except for sensations such as hunger and rectal distention

111
Q

how is abnormal visceral sensation perceived?

A

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.

112
Q

how is parietal pain perceived? why?

A
  • 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.
113
Q

what referred pain can peritonitis cause?

A

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.

114
Q

what is dyspepsia?

A

indigestion

• Dyspepsia is the chronic or recurrent pain or discomfort centred in the upper abdomen.

115
Q

what is rumination?

A

effortless regurgitation of undigested food after every meal

116
Q

what is the most common symptom as a result of gastrointestinal disease?

A

nausea and vomiting

117
Q

what are sulphonamides?

A

type of antibiotic

118
Q

what are clinical features of dyspepsia?

A

 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

119
Q

epidemiology of gastric cancer - age and sex

A
  • 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.
120
Q

what is the clinical presentation of gastric cancer?

A

 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

121
Q

what are the investigations for gastric cancer?

A 
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
122
Q

how does five year survival correlate with staging?

A

 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%.

123
Q

what is the staging of gastric cancer?

A

Tumour:
T1:
Tumours are confined to the mucosa and submucosa.
T2:
Tumours penetrate the muscularis propria but not the serosa.
T3:
Tumours reach the serosa but without the involvement of other organs.
T4:
Tumours have spread beyond the serosa.

Node:
N0:
No nodes involved
N1:
Involvement of perigastric nodes within 3cm of the primary tumour
N2:
Spread to more distant regional lymph nodes.
N3:
Involvement of nodes is to more distant intra-abdominal lymph glands that are not removable with surgery

Metastasis:
M0: 
No metastasis
M1: 
Distant metastasis
124
Q

what is the management of gastric cancer?

A

 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

125
Q

what is stress?

A

Any condition-physical or emotional-that threatens homeostasis

126
Q

what is stress? when does stress occur? when is stress lessened? what is central to whether a person feels stressed or not? what is severe or chronic stress associated with?

A

Any condition-physical or emotional-that threatens homeostasis
• 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

127
Q

what is the alarm phase?

A
  • 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.
128
Q

what is the resistance phase? what are side effects?

A
  • 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.
129
Q

describe the exhaustion phase

A

• 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.

130
Q

what is hyperactivity of the HPA axis associated with?

A

anxiety disorders and depression

131
Q

how does chronic stress affect the HPA axis?

A

 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.

132
Q

what is allostatic load? how linked to stress recovery?

A

allostatic load is ‘wear and tear on the body’
• 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.

133
Q

what is the transaction model of stress? model of appraisal?

A

• 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.
1. 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
2. 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.

primary appraisal = is this stressful?
secondary appraisal = can I cope with this?

134
Q

Cannon’s Fight/Flight reponse

A 
•	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.

135
Q

what is Hans Selye’s General Adaption Syndrome (GAS)?

A
  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.
136
Q

what is shared-decision making?

A

• 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.

  • 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.
137
Q

what is shared-decision making?

A

‘Involving patients in decisions to the extent that they desire’

• 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.

  • 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.
138
Q

what is physician-recommendation decision making?

A
  • 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.
139
Q

what is informed non-dissent decision making?

A
  • 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.
140
Q

where does absorption take place? and of what?

A

mostly small intestine, very little in stomach, relatively little in colon

Duodenum: 
-	Iron 
-	Carbohydrates 
-	Proteins, lipids, sodium, and water  
-	Bile acids (little)
Jejunum:
-	Carbohydrates (bit less) 
-	Protein, lipids, sodium, and water (less) 
-	Bile acids (little) 
Ileum:
-	Carbohydrates (lot less) 
-	Protein, lipids, sodium, and water (less) 
-	Cobalamin (vitamin B12) 
-	Bile acids (lots)
141
Q

what is absorbed in the GI tract?

A
  • 80% ingested water
  • Electrolytes
  • Vitamins
  • Minerals
  • Carbohydrates
  • active/facilitated transport
  • monosaccharides
  • Proteins
  • di-/tripeptides
  • amino acids
  • Lipids
  • monoglycerides
  • fatty acids
  • micelles
  • chylomicrons
142
Q

what digestive enzymes are secreted?

A
  • Peptidases
  • amino-
  • di-
  • tri-
  • Sucrases
  • Maltase
  • Lactase
  • Saccharidases
  • di-
  • tri-
  • lipase
  • Nucleases

Requires pancreatic enzymes & bile to complete digestion

143
Q

small intestine - how suited for absorption? how enzymes released into lumen?

A
  • Huge surface area for absorption
  • SI epithelium is rapidly turned over (chemotherapy targets rapidly dividing cells = digestive problems)
  • Loss of cells at villi tips releases enzymes into lumen
144
Q

how much fluid do crypt cells secrete each day?

A

about 2-3 litres isotonic fluid/day

145
Q

how does glucose uptake take place in the small intestine? into the blood

A
  • Coupled transport process
  • Sodium-potassium ATPase pumps sodium out of the basolateral membrane
  • This in turn drives the sodium-glucose symporter in the apical membrane
  • Glucose transported by a transporter protein out the basolateral membrane
146
Q

describe fat absorption in the small intestine

A
  1. Large fat globules are emulsified by bile salts in the duodenum
  2. Digestion of fat by pancreatic enzyme lipase yields free fatty acids and monoglycerides, which then form micelles
  3. Fatty acids and monoglycerides leave micelles and enter epithelial cells by diffusion
  4. Chylomicrons containing fatty substances are transporter out of the epithelial cells and into lacteals, where they are carried away from the intestine by lymph
147
Q

what is a weight loss drug?

A

Orlistat

148
Q

how does Orlistat work? what are side effects?

A
  • The pancreatic lipase is a good target in the treatment of obesity
  • Orlistat inhibits this enzyme and significantly reduces fat absorption
  • Alli (a low dose orlistat preparation) is available over the counter/online in the UK
  • Response depends on the patient’s diet and undesired effects include an increase in the number and nature of bowel movements, abdominal discomfort, oily stools, flatulence, and oily spotting in underwear (patients started to eat less fat to minimise the side effects)
  • Not very common anymore
149
Q

short bowel syndrome

  • what is it
  • what does it result in
  • what causes it
  • treatment
A
  • Most CHO, protein, and fat are absorbed in the first 100-150cm of jejunum (normal SI length = 600cm)
  • Problems may occur at less than 200cm of functional SI
  • SBS results in a malabsorptive state
  • Due to insufficient absorptive surface area
  • Can result in fluid and electrolyte imbalances as well as poor nutritional status
  • May be congenital, as a result of surgical resection, or changes in blood supply to the SI
  • Prognosis improves with increasing length of remaining intestine
  • Treatment by diet supplementation, parenteral nutrition and increasingly intestinal transplant
150
Q

who is bariatric surgery for?

A
  • For severe obesity
  • BMI > 40 kg/m2
  • Failure to maintain weight loss by non-surgical means over a period of months/years
151
Q

what are different techniques for bariatric surgery?

A
  • gastric banding
  • gastric bypass: small stomach pouch, and shortening of intestine – without removal of intestine
  • biliopancreatic diversion: removal of portion of stomach, and diversion of bile and pancreatic juices (less time for digestion and absorption)
152
Q

what is odynophagia?

A

painful swallowing – pain can be felt in your mouth, throat, or oesophagus

153
Q

what is succession splash?

A

hen percuss abdomen you can hear and feel fluid sloshing around

154
Q

What is Virchow’s node?

A

node in left supraclavicular fossa = Troisier sign – gastric cancer (late sign)

155
Q

what does a BRAVO capsule do?

A

measures acid reflux in the oesophagus

156
Q

what tests do you do if you have a suspcision of malignant pathology?

A
  • Blood tests – FBC, UEs (urea & electrolytes), LFTs (liver function tests), iron studies
  • OGD (max. 8 biopsies)
  • CT scan (need fully functioning kidneys due to the contrast)
  • PET-CT scan
  • Laparoscopy (if someone has cancer of stomach that seen on endoscopy, but can’t see well on CT scan, will need to do laparoscopy – key hole operation done under general anaesthetic)
157
Q

what are benign gastric and duodenal disorders? (examples)

A
  • Gastritis
  • Peptic ulceration
  • GORD (gastro-oesophageal reflux disease) – more abnormality with gastroesophageal sphincter
  • Achalasia – more related to LES
  • Functional disorders = non-malignant conditions of the stomach – bloating, delayed gastric emptying
  • Crohn’s disease – inflammatory condition that can affect anywhere in your GI tract – mouth to anus
158
Q

what are complications of peptic ulceration?

A
  • Pain
  • Heartburn
  • Reflux
  • Bleeding
  • Perforation
  • Structure/obstruction
  • (malignancy)
159
Q

where does bleeding and perforation of ulcers tend to occur?

A

Ulcers that tend to bleed tend to be in the posterior part of the first part of the duodenum – due to the gastroduodenal artery running in that part
Ulcers on the anterior part of the duodenal wall tend to perforate (hole that can lose a lot of bile and gut content through it)
- Anterior ulcers perforate, posterior ulcers bleed

160
Q

what is HDGC? what gene is associated with it?

A

Hereditary diffuse gastric cancer = a rare inherited condition associated with an increased risk of gastric cancer

  • It tends to affect much of the stomach rather than staying in one area
  • The average age for someone with HDGC to be diagnosed with stomach cancer is 38
  • Gene mostly commonly associated with HDGC is CDH1 – mutation in this gene gives a person an increased risk of developing gastric cancer and other cancers associated with HDGC
161
Q

what is the gold standard for diagnosis of gastric and duodenal disorders?

A

OGD & biopsy

162
Q

what is the gold standard for diagnosis of gastric and duodenal disorders?

A

OGD & biopsy

oesophago-gastro-duodenoscopy

163
Q

how many waves per minute in the stomach?

A

3

164
Q

summarise gastric motility - what does fundus and antrum do?

A
  • Fundus: relaxes on feeding to accommodate food without rise in pressure – vagus nerve controls this
  • Antrum: pumps and churns (3 waves/minute) to emulsify contents
165
Q

what are gastric glands composed of?

A
  • Surface epithelial cells – HCO3- and mucus secretion
  • Mucous neck cells – mucous secretion
  • Parietal cells – HCl secretion
  • Chief cells – pepsinogen secretion
166
Q

what does a parietal cell have? (strucutre)

A
  • microvilli

- secretory canaliculi

167
Q

what are the morphological changes of the parietal cell?

A
  • Resting
  • Secreting
  • Early recycling
  • Late recycling
168
Q

what is the [H+] gradient like in the stomach?

A
  • pH of gastric juice about 0.8
    so [H+] about 0.16 M (approx. isotonic HCl)
  • pH of plasma about 7.4
    so [H+] about 4 x 10^-8 M
  • so [H+]juice/[H+]plasma about 4,000,000!!

= the biggest biological gradient in the human body

169
Q

what is the source of secreted H+?

A

CO2
CO2 (from blood) + H2O H2CO3 HCO3- (goes through basolateral membrane to blood) + H+ (goes through apical membrane to lumen)

Carbonic anhydrase catalyses CO2 + H2O H2CO3

170
Q

how does apical H+ secretion happen?

A
  • active transport of H+ by ‘proton pump’ H+, K+-ATPase
  • K+ recycles via K+ ion channels (channels move it out, ATPase moves it back in)
  • Cl- secreted via Cl- ion channels
171
Q

describe the proton pump

A
  • 100 kDa catalytic alpha subunit
  • Glycosylated beta subunit necessary for full function
  • 1H+:1K+:1ATP stoichiometry
  • similar mechanism to Na+, K+-ATPase
  • conformational change driven by phosphorylation and dephosphorylation

structure of the alpha subunit:

  • Nucleotide-binding
  • Phosphorylation
  • Actuator domains
172
Q

what happens as the basolateral membrane of the parietal cell?

A
  • HCO3- leaves the cell passively by 1:1 exchange for Cl-
  • Exactly balances Cl- secretion at apical membrane
  • Basolateral Na+, K+-ATPase maintains intracellular [Na+] and [K+]
173
Q

how is gastric acid secretion regulated?

A

Amino acids -> G-cell -> gastrin (+ ACH - vagus nerve) -> ECL -> histamine -> parietal -> H+ into lumen

H+ (pH <3.5) -> D-cell -> somatostatin -> G-cell -> gastrin etc.

174
Q

describe transepithelial signalling to gut endocrine cells

A
  • Gut epithelium senses the chemical content of the lumen
  • Luminal signal = nutrients
  • Basolateral signal = gut hormones
  • Nutrients -> signal transduction -> gut hormones
175
Q

what does CCK target in the pancreas?

A

acini cells

176
Q

what does secretin target in the pancreas? what does it lead to?

A

duct cells

pancreatic ductal bicarbonate secretion

Ducts secrete up to 140 mM HCO3-

177
Q

what moves through acini cells into duct?

A

NaCl & H2O go through acini cells into duct

178
Q

what moves through duct cells into duct?

A

NaHCO3 & H2O go through duct cells into duct

179
Q

what do chief cells secrete?

A
  • pepsinogen

- gastric lipase

180
Q

which two cells secrete pepsinogen?

A
  • chief cells

- mucous cells

181
Q

what do endocrine cells of the stomach secrete? what do these do?

A

ghrelin and leptin
ghrelin - stimulates appetite
leptin - inhibits appetite

182
Q

what does acid do in terms of iron?

A

reduces dietary iron (Fe3+ -> Fe2+) for absorption in duodenum

183
Q

how do nutrients affect gastric emptying and what do they induce?

A

they delay gastric emptying and induce satiety
Nutrients -> gut hormones
Nutrients -> vagal afferent -> satiety

184
Q

what are key nutrient sensors?

A

enteroendocrine cells

  • Gut epithelium is the largest endocrine and sensory organ in the body
  • Functionally akin to taste buds?
  • oral taste receptors present on EEC (enteroendocrine cells)!
  • sweet, bitter etc.
185
Q

where is the main area for acid secretion?

A

Lower part of the stomach, antrum & pylorus

186
Q

where do gastric glands contain parietal cells?

A

fundus and corpus

187
Q

where are chief cells found in stomach?

A

bit lower down in corpus

188
Q

where are G cells found in stomach?

A

in antrum

189
Q

what are secretagogues?

A

substances which promote secretion

190
Q

control of parietal cells? main way and other way?

A
  • G-cell & nerve -> gastrin & ACh -> ECL cell -> histamine -> parietal cell -> H+
  • This is the main way, rather than gastrin and ACh directly binding to parietal cells
191
Q

what happens when histamine, gastrin, ACh binds to parietal cells?

A
  • when histamine, gastrin, ACh bind to parietal cells -> intercellular messengers, increase in intracellular calcium with gastrin & ACh, increase in cAMP with histamine
  • tubulovesicles insert themselves into the membrane, producing a microvillus-like appearance – packed full of proton pumps
  • 6 – 10 x increase in number of proton pumps at surface
192
Q

where are ulcers most common?

A

duodenum

193
Q

where is H. pylori mainly found/where does H. pylori mainly cause inflammation? (?) what cytotoxins produced? what coating?

A
  • Predominantly in the gastric antrum
  • Cytotoxin-associated gene protein A (CagA) – injected cytotoxin by H. pylori
  • Vacuolating toxin (VacA) – secreted cytotoxin by H. pylori
  • Peptidoglycan, lipopolysaccharide coating (PGN, LPS)
194
Q

how does an infection in the antrum cause duodenal ulcers?

A
  • Antrum is the site of gastrin release which is inhibited by somatostatin
  • Inflammation in the antrum inhibits somatostatin release, therefore increase H+ secretion
195
Q

what does somatostatin usually do? what happens in the gastric phase and intestinal phase that stimulate this?

A
  • Somatostatin works on/inhibits G cells (in antrum), ECL cells, and parietal cells (to some extent)
  • Gastric inhibitory phase – acidity in the antrum stimulates delta-cells to produce somatostatin and inhibit the G cells
  • In intestinal phase, secretin, CCK, GIP all work on delta-cells to increase somatostatin production and reduce acid secretion
196
Q

why is NSAIDs now the number one cause of ulcers rather than H. pylori?

A

triple therapy has been so effecive

197
Q

what do bismuth and P-CABS do?

A
  • Potassium competitive acid blockers (P-CABs) in development (& use in the Far East)
    =faster onset and longer lasting but more reversible
  • It’s all to do with pH!
  • H. pylori tolerates very acid pH but only grows/divides at less acid pH (>5.5)
  • Clarithromycin, amoxicillin & tetracycline all work best in dividing cells
  • PPIs reduce acidity, enhancing antibiotic action (new P-CABs may give a longer lasting high pH)
  • Bismuth blocks H+ influx into H. pylori so enhance antibiotic action even as the effects of PPIs are diminishing with time
198
Q

what do H2 antagonists and PPIs do actually to the ulcer?

A

don’t cure the ulcer, they reduce the effect of the acid and let the ulcer cure, but as soon as you go off drugs, you develop ulcers again

199
Q

what are mucins?

A

mucus glycoproteins

they are extrememly large glycoprotein polymers

200
Q

what are the main molecules of mucus? what is allowed to move through?how can it stop things moving through? what other mucins are there?

A
  • Main molecules are enormous thread-like glycoproteins = mucins
  • Allows things to move through – e.g. oxygen and digested food products
  • Also has particular mechanisms that bind to things, e.g. viruses and bacteria, that stop them gaining access to the underlying epithelial cells
  • Also have membrane-associated mucins – they can report and signal to the cell that things are changing – act as a last line of defence, like a receptor
201
Q

what is the mucus layer a barrier for?

A
  • Particulates
  • Acid/pepsin
  • Toxins
  • Pathogens
  • Sperm – allow or block depending on time of cycle
  • Pharmaceuticals/gene therapies (problem for gene therapies for cystic fibrosis)
202
Q

which disease result from compromised barrier?

A
  • Gastric/duodenal ulcers
  • Ulcerative colitis
  • Crohn’s disease
  • Dry eye
  • Xerostomia (dry mouth)
    (all the above due to a loss of a barrier/loss of mucus)
203
Q

what is mucus thickness like along the GI tract? how does the firmess fo the mucus change from lumen to epithelium?

A
  • Antrum – more than corpus, duodenum and jejunum
  • Ileum – thickness increases a lot
  • Colon – thickness increases even more
  • Firmly adherent mucous layer increases bit in antrum and colon
  • Loosely adherent mucus layer causes the biggest changes
  • Nearer the epithelium you are, the firmer the mucus is and the nearer the lumen, the looser the mucus is
204
Q

what are the two zones of the intestinal mucus barrier?

A
  • Adherent layer (molecules tight and compact – small pore size – stops things from physically getting through)
  • Loose layer (nearer the lumen)
205
Q

where do you find commensal bacteria and pathogens?

A

In the loose layer you have the beneficial bacteria and pathogens (commensal bacteria can become pathogenic if its not in the environment it should be – e.g. if it doesn’t stay in the loose layer of the mucus)

206
Q

what are the properties of GI tract mucus?

A
  • Resistant barrier (physical & chemical) – as well as pathogens and commensal bacteria
  • Viscous highly hydrated layer
  • Prevents dehydration of mucosal surfaces (by binding a lot of water), 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)
207
Q

what is mucus? what is it made up of?

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% (what gives it its physical form)
208
Q

describe mucins

  • how much of mass due to sugars
  • what is loose and tight gel due to
A
  • Protein rope with many sugars attached, repeated over and over again
  • Up to 80% of mass of one of molecules due to these sugars
  • The middle part of molecule with all the sugar has receptors that different bacteria can bind to
  • The long ropes take up lots of space, so when you get many of these together they intertwine with one another and they form gels
  • When you have a low concentration of these molecules, you have a loose gel, when you have a high concentration you form a gel that’s very tight
209
Q

what are the different members of a family of gel-forming mucins? where are they found?

A
  • 5 identified members
  • MUC 2, 5AC, 5B, 6 and 19
  • Share some generic structure
  • Corpus and antrum = MUC5AC & MUC6
  • Small intestine & colon = MUC 2
  • Both genes make different types of gel
210
Q

what is the role of mucins?

A
  • Space filling – gel formation
  • Protease resistance (host, viral or bacterial)
  • Pathogen binding/evasion/killing
211
Q

how do mucins form mucus?

A
  • Entanglement

- Cross links

212
Q

how do mucins provide protease resistance?

A
  • If most of the molecule is covered in sugars, protease can’t damage it
  • There are sites (at the beginning and end of each monomer) that can be cleaved, but it takes a lot longer to dismantle this barrier
213
Q

describe pathogen subversion of the epithelial mucosal 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 barrier (enzymes that chop up the proteins and sugars)
  • Bacteria 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
214
Q

what is another line of defence against pathogens?

A

MECHANISM OF HOST DEFENCE: ‘SUGAR-COATED CELLS’

  • All cells have their own sugar coat as well
  • So closer to the surface you have another line of defense
215
Q

what is the last line of defence?

A

EPITHELIAL CELL SURFACE TRANSMEMBRANE (Tm) MUCINS

  • Important as a last line of defence
  • Outer part of the molecule (extracellular portion) can become detached, which sends signals to the cell that something’s happening and that it might need to replenish its mucous barrier
216
Q

describe pathogen binding/evasion - sugars

A
  • Sugars on the outside of mucus gel – binds bacteria
  • The mucus gel has 100s/1000s of sugars that it can bind to
  • If there’s some disruption in mucus gel, the bacteria can get through and bind to sugars on the epithelial cell surface, so that it can try and get in
  • However, the sugars on the cell surface get shed and go through the mucus and out of it with the bacteria
217
Q

H. pylori infection

  • are symptoms normally shown
  • how common is development of chronic inflammation with persistent infection
  • what are serious resulting pathologies from chronic gastritis
A
  • Majority of people are asymptomatic or have very mild symptoms
  • 90% of infected individuals develop chronic inflammation with persistent infection (gastritis)
  • Serious resulting pathologies from chronic gastritis:
  • gastric and duodenal ulcers
  • gastric carcinoma (5% of world cancer burden)
218
Q

what are adhesin genes?

A
  • Adhesin genes (colonisation) (sugar-binding proteins on Helicobacter)
  • SabA gene – sialic acid (sugar) binding adhesin
  • BabA gene – Lewis b binding adhesin
219
Q

what are CagA and VacA genes?

A
  • CagA pathogenicity island (epithelial pathology)
  • CagA gene – type IV secretion system, disabling of epithelial tight junctions
  • VacA gene – cytotoxin
220
Q

what are the two mucins in the stomach and what layers do they form?

A
  • MUC5AC
  • MUC6
  • Closer to the lumen there’s more MUC5AC, whereas MUC6 seems to be much closer to the epithelial surface
221
Q

describe the functions of mcuins in defence against H. pylori

A

H. pylori has adhesins for glycan structures on cell surface glycoproteins and glycolipids found on the gastric epithelial surface – BabA (Le^b) and SabA (Le^a and sialyl-Le^x)
- MUC5AC – binding – has many sugars that these bacteria lectins are able to bind to
- MUC6 – growth inhibition (if MUC5AC is ineffective at blocking bacteria)
= mucus layer (both of them)
- Glycans on MUC5AC (Le^b and Sialyl Le^x) are shared with cell surface MUC1
- Glycans on MUC6 (alpha 1-4 GlcNAc) inhibit cell wall synthesis of H. pylori and prevent infection
- MUC1 is shed from the cell surface (epithelial) when H. pylori binds

So, there is a system of binding, then killing, and then binding

222
Q

what is self determination?

A
  • The process by which a person controls their own life
223
Q

what are some symptoms that are different between gastric and duodenal ulcers?

A 
Gastric ulcers
-	Increase pain when eating – presence of food, HCl production 
-	Associated with weight loss 
Duodenal ulcers
-	Decrease pain when eating 
-	Associated with weight gain
224
Q

what is malaena?

A

production of dark sticky faeces containing partly digested blood, as a result of internal bleeding or the swallowing of blood

225
Q

what are alginates?

A
  • Forms a gel in the highly-acidic stomach and protects the stomach mucosa
  • Antacids work by counteracting (neutralising) the acid in your stomach
  • Most alginates work by forming a gel which floats on top of the stomach contents
  • The get acts as a protective barrier, preventing stomach acid from irritating the oesophagus
  • some antacids also contain a medicine called an alginate, which produces a protective coating on the lining of your stomach
  • antacids should be taken when you experience symptoms or when you expect them, such as after meals or at bedtime
  • antacids containing alginates are best taken after meals

Medicine Sem 4 (23 decks)

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