Upper GI tract lecture Flashcards
Session plan
Disorders of oesophagus
Disorders of the stomach
Oesophageal anatomy
C5 to T10 (25cm long)
Start off at the upper oesophageal sphincter where we have the cervical oesophagus which goes down to the sternal notch, and that’s skeletal muscle. Below that we have the upper thoracic oesophagus and middle thoracic oesophagus, and they contain skeletal and smooth muscle. Below that we have the lower thoracic oesophagus, that is smooth muscle that goes down to the lower oesophageal spincter
LOS is a physiological mechansim in itself but has anatomical advantages:
- The last 3 to 4cm of the distal oesophagus is actually within the abdomen, so the advantage of that is that when you increase your abdominal pressure, that pressure will extrinsically compress the lower oesophageal sphincter.
- Right and left crux of diaphragm come around the oesophagus like a sling. The advantage of that is that when the diaphragm contracts it’s like a pair of scissors so it contracts and squeezes and compresses the distal oesophageal spincter.
- Phrenoesophageal ligament-this is the extension of fascia of the inferior surface of diaphragm, so it has 2 limbs, an upper limb which attaches itself to the lower part of the oesophagus within the thorax, and a lower limb which attaches itself to the cardia of stomach. The phrenoesophageal ligament anchors the distal esophagus to the crural diaphragm.
- Angle of His-this refers to the angle that exists between the distal oesophagus as it comes through into the abdomen, and then there’s usually an acute angle where the fundus joins it. So the advantage of that is that say you have a heavy meal, your stomach is full of food so it expands and compresses the distal oesophagus from lateral to medial.
His notes from slide:
- LOS pressure increased (from outside) in proportion to increase in intraabdo pressure
- In a scissor like manner – sphincter automatically clamped when diaphragm contracts
- phrenoesophageal ligament (phrenicoesophageal ligament, or phrenoesophageal membrane) is the ligament by which the esophagus is attached to the diaphragm. It is an extension of the inferior diaphragmatic fascia and is divided into an upper and lower limb which attach to the superior and inferior surfaces of the diaphragm respectively at the esophageal hiatus. The upper limb attaches the esophagus to the superior surface of the diaphragm and the lower limb attaches the cardia region of the stomach to the inferior surface of the diaphragm at the cardiac notch of stomach. The ligament allows independent movement of the diaphragm and esophagus during respiration and swallowing.
- “Angle of His” refers to the normally acute angle between the abdominal esophagus and the fundus of the stomach at the esophagogastric junction.
This angle is one of the elements that are important in the prevention of gastroesophageal reflux disease (GERD). When the fundus of the stomach gets expanded by air, because of the normal anatomy and relations of the esophageal hiatus, the esophagogastric junction structures are “pushed” from left to right, pushing close the gastroesophageal flap valve or “rosette”.
Swallowing
OPUL
Oral phase
Pharyngeal phase
Upper oesophageal phase
Lower oesophageal phase
How do we measure motility of oesophagus to work out if we have any disorders?
=We use pressure measurements ie manometry
Far to right where it says swallowing, can see pressure measurements between 0 and 40mmHg. So when the oesophagus is contracting, the peristaltic waves are about 40mmHg.
The LOS resting pressure is about 20mmHg. That decreases to less that 5mmHg during receptive relaxation to allow food to pass through the LOS into stomach. That is mediated by inhibitory noncholinergic nonadrenergic (aka nonadrenergic noncholinergic) neurons of the myenteric plexus. So essentially they inhibit the LOS, and they need to be intact for this process to work properly.
His notes from slide:
NCNA (also NANC & Neurocrine)
- secreted by postganglionic non-cholinergic neurons of the enteric nervous system
- hormone that affects ‘nerves’
- vasoactive intestinal peptide (VIP), gastrin release peptide (GRP), and enkephalins
What are the Functional disorders of oesophagus?
A functional disorder is a medical condition that impairs normal functioning of bodily processes that remains largely undetected under examination, dissection or even under a microscope.
-Make sure there isn’t a stricture that is causing the problem as most important symptom a pateint gets with difficulty swallowing is dysphagia.
Nomenclature:
- If taking a history localisation of dysphagia is important and what type it is.
- Regurgitation-return of oesophageal NOT gastric contents, from above an obstruction. So something is not letting the food you swallowed go down so it regurgitates, and that cen be functional or mechanical.
Reflux-passive return of gastroduodenal content to mouth aka water brash
BOTH these are different to vomiting
Hypermotility-give an example of high motility in the oesophagus
=syndrome called Achalasia
Mentioned before that the NCNA neurones inhibit the LOS. What happens here is you get loss of these sphincters, you get decreased activity of those neurones, so as a result, you can’t relax your oesophageal sphincter.
Aetiology unknown but proposed mechanism:
- A-suggested there’s an environmental trigger, chronic infections such as varicella, Zoster, HSV-1 etc.
- Some people think there is a genetic predisposition.
- Essentially the first stage once you’ve had your initial insult, is a non autoimmune inflammatory infiltrate.
- That inflammatory infiltrate then promotes wound repair, fibrosis, etc.
- You start getting loss of immunological tolerance, you then get an autoimmune inflammatory infiltrate, which causes apotosis of the neurons.
- You then get a humoral response
- Then you get your autoimmune myenteric plextitis, ganglionitis, vasculitis etc.
There are a number of conditions that can mimic primary achalasia, anything that causes oesophageal motor abnormalities, causing similar hypermotiluty problems.
There’s a chronic parasitic infection in south america called Chagas’ disease
Chagas’ Disease – South American chronic infection with parasite Trypanosoma Cruzi
What actually happens in Achalasia?
The main problem is increasing resting pressure of the LOS.
LOS should be resting pressure 20mmHg, but actualy its resting pressure is about 80, because it can’t relax.
And the problem starts that your receptive relaxation phase sets in to late and secondly it is too weak (so if you follow the red line from 80mmHg can see it dips, but it only dips to about 60, which is far higher than the resting pressure of the stomach)
So what happens then? =Your food collects in the oesophagus, increasing pressure throughout the oesophagus and overtime you get dilation of the oesophagus and then eventually propagation of peristaltic waves cease.
- symptoms of achalasia are dyspha- gia (trouble swallowing), regurgitation of food (not vomiting), retrosternal pain, and weight loss.
- Serious complications of achala- sia are esophagitis and pneumonia, caused by aspiration of esophageal contents (contain- ing bacteria).
Disease course
Big problem here is not only functional-people will lose weight, pain, aspiration pneumonia, dysphagia
-But also increases risk of eosophageal cancer (but having said that it isn’t common)
On the right here you can see a typical barium swallow. You can see a dilated oesophagus in figure A coming down to what looks like a birds beak, very tight. The one on the right just shows it as food contents, you’re not seeing lots of barium in there, that’s all food debris etc.
Whenever treating start most simply
First Treatment
=pneumatic dilatation
Wire in middle of oesophagus with deflated balloon, go to second diagram and see a little green arrows and wire has crossed the lower oesophageal spincter and balloon is still not inflated, then we go to the third diagram and the balloon is inflated, and what that’s doing is it’s stertching the muscles of the oesophageal sphincter and in some cases you actually get tearing of the muscle fibres. In far right you have restored flow.
X-ray on the right: top image shows where the stricture is, the balloon is not fully inflated because it’s working against pressure. If you go to B, you can then see the balloon is fully inflated, that shows that that stricture has been dealt with.
B-fully inflated
Surgical treatment, most people end up having surgery after pneumatic dilatation
Do procedure called Heller’s Myopathy (think it would be hell if someone cut into your oesophagus muscle). If go to top diagram, can see some laprascopic scissors, what you’re doing there is you’re cutting your myotomy so cutting muscle 6cm of the distal oesophagus going 3cm into the cardia of the stomach. So essentially what you’re seeing there is just the mucosa (looks like sausage). So you’ve cut the muscle to get rid of the stricture. Most people would then take the fundus of the stomach and then wrap it around the exposed mucosa and stitch it to the other side of the oesophagus, just to give it protection.
Risks: Can perforate mucosa as very tricky to cut through muscle and not mucosa.
Vagus nerve injury is rare as it is quite visible
Splenic injury, because most people take the fundus, which has short gastrics which go straight from the stomach to the spleen. So you’re right against the spleen and it’s very easy to make the spleen bleed so splenic injury is fairly common.
Heller’s myotomy and dor fundoplication
Suture fundus to RIGHT of myotomy
A Dor fundoplication (a partial wrapping of the stomach around the esophagus to make a low-pressure valve) is performed to prevent reflux from the stomach into the esophagus following the myotomy.
More recently people are describing endoscopic ways of treating this: POEM
PerOral Endoscopic Myotomy
If you look at A, that is an endoscope coming into the dilated oesophagus and A is a mucosal incision to get underneath the mucosa.
B, you’re then creating a submucosal tunnel.
C you are then doing a Myotopy, so you are essentially cutting muscle as much as you need.
D: You then wthdraw and have to close the mucosal incision, and that will be done endoscopically with clips.
So that’s a lesser procedure but not as effective as doing a surgical one.
Hypomotility
Hypermotility is caused secondary to neuronal defects, because there are neuronal defects, muscle isn’t working properly, get atrophy of smooth muscle in oesophagus.
Pressure is almost down to 0, so peristalsis just stops completely, also get lowering of the resting pressure of the LOS, so because of that, there is nothing to stop reflux into the distal oesophagus. So different from Achalasia where you are getting too tight a contraction, here there is no contraction at all below the LOS.
Treatment-make sure there isn’t an organic obstruction as with all of these conditions, can use prokinetics (if you are pro kinetic, you are cis a pride). If that all fails, can use dilatation, that can work, but once peristaltic failure occurs, that’s usually irreversible, an people may end up having their oesophagus’ taken out and replaced with the stomach itself.
CREST syndrome, also known as the limited cutaneous form of systemic sclerosis (lcSSc), is a multisystem connective tissue disorder. The acronym “CREST” refers to the five main features: calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia.
His notes:
- Calcinosis
- Raynauds phenomena
- Esophageal
- Sclerodactely
- Telangiectasia
Disordered coordination of peristalsis down the oesophagus
Hypertrophy of circular muscle of oesophagus giving corkscrew appearance.
Pressures should be 40mmHg
X-ray on right is barium swallow and looks like typical corkscrew. B-endoscopy, typical appearance, completely uncoordinated corkscrew
Treatment-may respond to forceful pneumatic dilitation of the cardia but results aren’t as predictable as they are for achlasia.
Dealt with functional causes.
Vascular anomalies causing dysphagia
Middle diagram-aberrant Right subclavian Artery which goes behind the oesophagus and constricts it against trachea, only way to solve this is to reconnect the subclavian artery where it should be.
Dysphagia lusoria (or Bayford-Autenrieth dysphagia) is an abnormal condition characterized by difficulty in swallowing caused by an aberrant right subclavian artery.
Double aortic arch is another vascular anomaly which can cause dysphagia.
Oesophageal perforation-very common clinically
3 areas of contriction, first is cricopharyngeal constriction, second is where the aorta and bronchus cross the oesophagus, 3rd is where oesophagus goes through the diaphragm.
Numerous causes-most common is iatrogenic. OGD has an incidence of injury to oesophagus
Effort rupture of the esophagus, or Boerhaave syndrome, is a spontaneous perforation of the esophagus that results from a sudden increase in intraesophageal pressure combined with negative intrathoracic pressure (eg, severe straining or vomiting).
Iatrogenic
Commonest
Sclerotherpay-is dealing with bleeding within oesophagus eg mallory tears and varices.
Dilatation of patients with achlasia is probably the highest incidence.
Middle diagram shows outline of endoscop poking through the cricopharyngeal muscle, that is the commonest place that it happens. Pictures on right show typical tear you see inside oesophagus when that happens.
Spontaneous
Commonest is left posterolateral aspect of distal oesophagus
Arrows shows leaking of barium out of oesophagus
Foreign bodies
Disk batteries get stuck in mucosa, this is a growing problem
Chest x-ray go to clavicles and then in middle is a razor blade.
Trauma-not so common
If in neck-usually been stabbed
Give away sign is surgical empysema, so perforation in the oesophagus, you get leakage of air and that can give very distinctive crepitations in skin of the chest wall.
Intraoperative
Hiatus hernia repair is top image, that’s the stomach going through the hiatus hernia, you have to mobilise the whole thing so is easy to make holes.
Hellers cardiomyotomy, you’re cutting through muscle and trying to keep mucosa in tact.
In chest doing thoracic surgery, it’s easier to damage oesophagus
Thyroid surgery in neck
Malignant causes
Primary management
First of all go on presentation, pain is biggest one. How do you investigate?- simplest is just to do a chest X-ray
Top left can see right chest is clear, left is full of oesophageal contents, so that will be fluids, gastric juices, reflux etc. The next diagram is showing some mediastinal air, so if you go along the right border, obviously there’s air inside the oesophagus, so air escapes causing medistinal changes and emphysema. Bottom left-black arrows point out fluid outside oesophagus, but that’s contained. Ct scan on bottom right-the arrow points to the oesophagus, the white in the middle is contrast and then if you go to the right of that can see a lot of that contrast is leaking freely outside, so that’s not contained and will cause serious problem for patient.
Primary management-swallow
Left is contained perforation so leaking but no leaking freely
Next one shows free contrast coming out of the oesophagus
Always have to do an OGD as well
Initial management
Nil By mouth
Always should be referred to tertiary centre
Tazocin is a broadspectrum antibiotic
Most important-is the leak contained and well defined or is it diffuse and non contained?
Definitive management
Only consider conservative if patient isn’t going to survive an operation and it is contained with minimal contamination. If only minimal contamination can put in oesopageal stent which can be removed.
Chest x-ray on right, within red circle is an oesophageal stent, that can be put in and removed.
Usually what you have to do is OPERATE:
Scissors are debriding tissue, once you’ve taken away all the tissue, you then cut into the oesophagus through the muscle, because you want to identify exactly where the mucosal tear goes up to and then do primary repair and stitch mucosa closed and then stitch the muscle closed.
Sometimes need pedicle flap (These flaps are called pedicle flaps, which mean they remain connected to the blood supply.), take a bit of intercostal muscle, still attached to artery, vein and nerve supply and place that over your repair if repair is not possible.
Sometimes as mentioned with achlasia, you take a bit of the fundus and you buttress it and stitch that over the top to make it stronger. All these needs lots of big chest drains as it’s when things collect that patients get unwell.
The get out clause and definitive solution is doing an oesophagectomy. Mobilising stomach and taking it into chest and joining it to first bit of viable oesophagus.
Stomach-protective mechanisms against reflux
Circle with blue-hormones, histamines, acetylcholine all increase pressure and inhibit reflux
Red box decrease LOS pressure and therfore increase reflux
Sudden unexpected pressure on stomach can lead to sporadic reflux. You get a little bit of reflux everytime you swallow, we also all get transient sphincter opening where pressure is decreasing (can see within green arrow.)
Sporadic reflux
- unexpected pressure on full stomach
- swallowing
- transient sphincter opening
Volume clearance – rapid return of reflux volume by oesophageal peristalsis reflex
pH clearance – residual gastric juice left behind – pH rises step by step with swallowed saliva buffers residual reflux volume
PROTECTIVE MECHANISMS FOLLOWING REFLUX
- bolus volume is 15ml of fluid regurgitates everytime and oesophageal peristalsis reflux can clear this.
- After you swallow the pH in your distal oesophagus goes down but then increases stepwise as you swallow saliva which buffers that
- Distal epithelium has barrier properties
Failure of protective mechanisms:
any one of these fails=GORD
If transient sphincter opening happens more frequently then going to have failure of protective mechanism.
Anything that decreases volume clearance essentially abnormal peristalsis, so reflux oesophageal peristalsis decreases=GORD
His notes from slide:
Factors that diminish the pressure in the LOS:
– increased frequency of transient sphincter opening (swallowing air, drinks containing CO2);
– decreased volume clearance (abnormal distal oesophageal peristalsis);
– slowed pH clearance, for example, due to decreased salivary flow (sleep, chronic saliva deficiency [xerostomia]), or de-creased buffering capacity of the saliva (smoking cigarettes);
– hiatus hernia, in which the abdominal part of the oesophagus is displaced into the thorax, so that an important mechanism of sphincter closure, increased intra-abdominal pressure, is absent;
– direct irritation and damage to the esophageal mucosa, for example, by citrus fruits, tomato-based foods, hot spices, high- proof alcohol, and nonsteroid anti-inflam- matory drugs (NSAIDs; → p. 142).
Sliding hiatus hernia
People with very severe disease almost always have a sliding hiatus hernia, however, lots of people have a sliding hiatus hernia and don’t have GORD and lots of people have GORD without sliding hiatus hernia.
Sliding hiatus hernia: essentially the whole stomach is squeezing through diaphragm.
CT scan on left shows extreme sliding hiatus hernia. On left is liver, right near top is stomach, if follow it down its all within chest, pancreas is actially in chest. Can see on right CT liver and below is kidney and following it up can see it is def above diaphragm and grey thing above the diaphragm is again the pancreas, so extreme example.
His Notes:
Sliding Hiatus Hernia
Variable association with GORD
- Most pts with severe stages of GORD have a hernia
- But most GORD pts don’t have a hernia & many with a hernia don’t have GORD
Rolling hiatus hernia
This is where gatrooesophageal junction is in place but a bit of stomach squeezes alongside the oesophagus.
That is actually a surgical or endoscopic emergency because if that happens you stomach can become ischaemic.
How do you investigate possible GORD?
First do a OGD and exclude other causes
-if patients have a normal OGD but still have symptoms that sound like GORD then move onto oesophageal manometry and 24hr oeosphageal pH recording to get diagnosis
Treatment
-very simple-lifestyle changes and PPIs, this pretty much covers it most of the time, unusual to have to precede to surgical intervention.
(Top right is endoscopy, and is typical benign peptic stricture from GORD on left is a swallow and this is a clear stricture)
Surgical or endoscopic intervention is with:
1) lapracopic Nissen’s fundoplication-stitches to tighten up right and left crux to tighten around oesophagus
2) Then take fundus of stomach, again dividing its connections, blood supply to spleen and then essentially wrap it round behind and then stitch it around the oesophagus.
Stomach functions
year 1
Stomach-what does it produce?
Year 1
Gastritis
People don’t realise this has lots of causes and it is important to know what time this is.
Erosive and haemorrhagic gastritis-shown of left of image, get acute ulcers that are prone to bleeding. Can be caused by ischaemic stomach and marathon runners can get these ulcers from stomach ischaemia as all the blood is diverted to muscles.
Nonerosive, chronic active gastritis-Occurs in antrum and is pretty much down to H.Pylori. It essentially not only weakens mucus covering stomach but it also increases gastrin which is responsible for chronic gastric and duodenal ulcers. Simple to treat with triple therapy (2 antibiotics and PPI)
Atrophic (fundal gland) gastritis-Very different. Look at diagram on right. Essentially you have autoantibodies which are against parts and products of the parietal cells so get parietal cell atrophy, so decaresed acid secretion which will result in G-cell hyperplasia and that will result in epithelial metaplasia and possibly cancer. The decrease in acid secretion and increase in gastrin, we’ve got ECL, essentially neuroendocrine hyperplasia, so it’s very common to see neuroendocrine tumours within the stomach are common. On top of that, as problems with IF secretion which decreases, you get decrease in cobalamine absorption and long term will lead to cobalamine deficiency and pernicious anaemia.
Reactive gastritis-because around an acute ulcer you’ll get a different type of gastritis, which is reactive for what’s going on in the acute erosive haemorrhagic gastritis.
His notes:
1. Erosive and hemorrhagic gastritis (→ A 1) can have many causes, for example:
– intake of nonsteroidal anti-inflammatory drugs (NSAIDs), whose local and systemic mucosa-damaging effect is described in greater detail on p. 146;
– ischemia (e.g., vasculitis or while running a marathon);
– stress (multi-organ failure, burns, surgery, central nervous system trauma), in which the gastritis is probably in part caused by ischemia;
– alcohol abuse, corrosive chemicals;
– trauma (gastroscope, swallowed foreign body, retching, vomiting, etc.);
– radiation trauma.
This type of gastritis can quickly produce an acute ulcer (e.g., through stress or NSAIDs; → p. 146), with the risk of massive gastric bleeding or perforation of the stomach wall (→A1).
2. Nonerosive, chronic active gastritis (type B; → A 2)
- is usually restricted to the antrum.
- cause is a bacterial colonization of the antrum with Helicobacter pylori, which can be effectively treated with antibiotics (see also ulcer; → p. 144 ff).
- Helicobacter colonization not only
- diminishes mucosal protection,
- but can also stimulate antral gastrin liberation and thus gastric juice secretion in the fundus, a constellation that favours the development of chronic ulcer.
3. Atrophic (fundal gland) gastritis (type A; → A 3), - most often limited to the fundus,
- has completely different causes - the gastric juice and plasma usually contain
- autoantibodies (mainly immunoglobulin G, infiltrates of plasma cells, and B lymphocytes)
- against parts and products of parietal cells (→ A, upper right), such as microsomal lipoproteins, gastrin receptors, carboanhydrase, H+/K+-ATPase, and intrinsic factor (IF).
- parietal cells atrophy with the effect that acid and IF secretion falls markedly (achlorhydria).
- IF antibodies also block the binding of cobalamines to IF or the uptake of IF–cobalamine complexes by cells in the ileum, ultimately resulting in cobalamine deficiency with pernicious anemia (→ blood, p. 34).
- In atrophic gastritis more gastrin is liberated in response to this, and the gastrin-forming cells hypertrophy.
- Hyperplasia of the enterochromaffin-like (ECL) cells occurs, probably as a consequence of the high level of gastin. These cells carry gastrin receptors and are responsible for producing histamine in the gastric wall. This ECL cell hyperplasia can sometimes progress to a carcinoid.
- main danger in atrophic gastritis is extensive metaplasia of the mucosa which, as a precancerous condition, may lead to carcinoma of the stomach.
4) Reactive gastritis, (→ A 4) occurs in the surroundings of erosive gastritis (see above), of ulcers or of operative wounds. The latter may partly be caused after operations on the antrum or pylorus by enterogastric reflux (reflux gastritis), result- ing in pancreatic and intestinal enzymes and bile salts attacking the gastric mucosa.
Regulation of gastric secretion
Green box-factors that stimulate gastric secretion
neural-Ach
endocrine-gastrin
paracrine-histamine
All these will stimulate parietal cells, cheif cells to produce hydrogen ions and pepsin.
Red box-inhibit gastric secretion-PROSTAGLANDINS inhibit gastric secretion!!!
His Notes:
Regulation of gastric secretion (→ A 1) is achieved through neural, endocrine, paracrine, and autocrine mechanisms.
parietal cells produce H+ ions in gastric juice - contain H+/K+-ATPase in their luminal membrane, chief cells enrich the glandular secretion with pepsinogen (→ A).
Stimulation is provided by: acetylcholine, the postganglionic transmitter of vagal parasympathetic fibers (muscarinic M1 receptors and via neurons stimulating gastrin release by gastrin-releasing peptide [GRP]), gastrin (endocrine) originating from the G cells of the antrum, and histamine (paracrine, H2 receptor), secreted by the ECL cells and mast cells of the gastric wall.
Inhibitors are secretin (endocrine) from the small intestine, somatostatin (SIH; paracrine) as well as prostaglandins (especially E2 and I2), transforming growth factor α (TGF-α) and adenosine (all paracrines and autocrines). The inhibition of gastric secretion by a high concentration of H+ ions in the gastric lumen is also an impor- tant regulatory mechanism (negative feed- back; → A 1, left).
If mucosal protection is defeated you get
Methods of mucosal protection
=ulcers
Epithelial cells produce bicarbonate and prostaglandins are responsible for this bicarbonate production
Epithelium itself has barrier properties, tight junctions, it’s all regulated by EGF
Epithelial cell membrane is strong and if anythng gets through, it can expel Hydeogen ions
Stomach has good blood perfusion means that H ions can be got rid of if they get through.
His notes:
a A gel-like mucus film, 0.1 – 0.5 mm thick, protects the surface of the gastric epithelium.
- The mucus is secreted by epithelial cells (and depolymerized by the pepsins so that it can then be dissolved).
b The epithelium secretes HCO3 – ions
- are enriched not only in the liquid layer directly over the epithelium, but also diffuse into the mucus film, where they buffer H+ ions that have penetrated from the gastric lu- men.
- Prostaglandins are important stimulants of this HCO – secretion.
c In addition, the epithelium itself (apical cell membrane, tight junctions) has barrier properties
- that largely prevent the penetration of H+ ions
- or can very effectively remove those H+ ions that have already penetrated (Na+/H+ exchange carrier only basolaterally).
- These properties are regulated, among others, by the epidermal growth factor (EGF) contained in saliva and bound to receptors of the apical epithelial membrane.
- Glutathione-dependent, antioxidative mechanisms are also part of this cytoprotection.
d Finally, good mucosal blood flow serves as the last “line of defense” that, among other actions, quickly removes H+ ions and provides a supply of HCO – and substrates of energy metabolism.
If anything happens, you have to repair it:
At defect in epithelium will get flatterning of epithelial cells to close gap and then sideways migration along the basement membrane. This all happens within about 30 mins.
You’ll also get epithelial cell gap closed by cell proliferation, so cover defect by cell division.
If basement membrane is destroyed then have to instigate acute wound healing. Then once that happens you get your epithelial closure by restitution and cell division.
His notes:
Epithelial repair and wound healing. The following mechanisms repair epithelial defects that occur despite the protective factors listed above (→ B, bottom left):
- The epithelial cells adjoining the defect are flattened and close the gap through sideward migration (→ p. 4) along the basal membrane. This restitution takes about 30 minutes.
- Closing the gap by cell growth takes longer (proliferation; → p. 4). EGF, TGF-α, insulin- like growth factor (IGF-1), gastrin-releasing peptide (GRP), and gastrin stimulate this process. When the epithelium is damaged, especially those cell types proliferate rapidly that secrete an EGF-like growth factor.
- If ultimately the basement membrane is also destroyed, acute wound healing pro- cesses are initiated: attraction of leukocytes and macrophages; phagocytosis of necrotic cell residua; revascularization (angiogen- esis); regeneration of extracellular matrix as well as, after repair of the basement mem- brane, epithelial closure by restitution and cell division.
Ulcer formation-what promote ulcers?
On right is things trying to heal it, to prevent ulcer formation
NSAIDs block cyclooxygenase so if get decreased prostaglandin synthesis which is important in production of bicarbonate which protects mucous layer in stomach so mucosal protection will decrease as not as much bicarbonate there. Similarly loss of bicarbonate means lost inhibition of hydrogen ions secretion and pepsinogen secretion so they increase, that’s why they’re ulcer producing.
His notes:
The danger of epithelial arrosion and sub- sequent ulcer formation exists whenever the protective and reparative mechanisms are weakened and/or the chemical attack by the acid–pepsin mixture is too strong and per- sists for too long (→ A 3 and B, top). Gastric and duodenal ulcers may thus have quite dif- ferent causes.
A further common cause of ulcer is the intake of NSAIDs, for example, indomethacin, diclofenac, aspirin (especially in high doses).
Their anti-inflammatory and analgesic action is based mainly on their inhibitory effect on cyclo-oxygenase, thus blocking prostaglandin synthesis (from arachidonic acid).
An undesirable effect of NSAIDs is that they systemically block prostaglandin synthesis also in gastric and duodenal epithelia. This decreases HCO – secretion, on the one hand (weakened mucosal protection; → B, eft), and stops inhibition of acid secretion, on the other (→ A 1). In addition, these drugs damage the mucosa locally by nonionic diffusion into the mucosal cells (pH of gastric juice<
NSAIDs an acute ulcer may thus develop after days or weeks, the inhibitory action of these drugs on platelet aggregation raising the danger of bleeding from the ulcer.
Acute ulcers also occur if there is very se- vere stress on the organism (stress ulcer), as after major surgery, extensive burns, and multi-organ failure (“shock”). The main cause here is probably impaired blood flow through the mucosa correlated with high plasma concentrations of cortisol.
Often psychogenic factors favor ulcer de- velopment. Strong emotional stress without an outward “safety valve” (high cortisol lev- els) and/or disturbed ability to cope with “normal” stress, for example, in one’s job, are the usual causes. Psychogenically raised secretion of gastric acid and pepsinogen, as well as stress-related bad habits (heavy smoking, antiheadache tablets [NSAIDs], high-proof alcohol) often play a part.
Smoking is a risk factor for ulcer develop- ment. A whole series of moderately effective single factors seem to add up here (→ B). Al- cohol in large quantities or in high concen- tration damages the mucosa, while moderate drinking of wine and beer increases gastric secretion through their nonalcoholic compo- nents.
Rare causes of ulcer are tumors that auto- nomically secrete gastrin (gastrinoma, Zol- linger–Ellison syndrome), systemic mastocy- tosis, or basophilia with a high plasma hista- mine concentration.
Apart from antibiotics (see above) and (rarely necessary) surgical intervention, the treatment of ulcer consists of lowering acid and pepsinogen secretion by blocking H2 and M1 receptors (→ A 1) and/or of H+/K+- ATPase. Treatment with antacids acts partly by buffering the pH in the lumen, but also has further, as yet not fully understood, ef- fects on the mucosa.
H.Pylori
Urease is what they produce and that neuralises gastric acid so can get defect in mucous barrier and can get mucosal damage not only be pepsin and h+ but H.pylori also secretes exotoxins and secretory enzymes causing direct gastric mucosal injury.
His Notes:
Infection with Helicobacter pylori (H. pylori) is the most common cause of ulcer. As a consequence, administration of antibiotics has been shown to be the most efficacious treatment in most ulcer patients not receiving nonsteroidal anti-inflammatory drugs (NSAIDs; see below).
- H. pylori probably survives the acidic environment of the mucus layer because it possesses a special urease. The bacterium uses this to produce CO2 and +NH3, and HCO3 and NH4 , respectively, and can thus itself buffer H+ ions in the surroundings.
- H. pylori is transmitted from person to person, causing inflammation of the gastric mucosa (gastritis, especially in the antrum; → p. 142).
- A gastic or duodenal ulcer is ten times more likely to develop in such cases than if a person does not suffer from gastritis of this kind.
- The primary cause of such an ulcer is a disorder in the epithelium’s barrier function, brought about by the infection (→ B).
It is likely that, together with this ulcer formation due to the infection, there is also an increased chemical attack, as by oxygen radicals that are formed by the bacteria themselves, as well as by the leukocytes and macrophages taking part in the immune re- sponse, or by pepsins, because H. pylori stim- ulates pepsinogen secretion.
The fact that infection of the gastric an- trum also frequently leads to duodenal ulcer is probably related to gastrin secretion being increased by the infection. As a result, acid and pepsinogen liberation is raised and the duodenal epithelium is exposed to an in- creased chemical attack. This causes meta- plasia of the epithelium, which in turn favors the embedding of H. pylori, leading to duode- nitis and increased metaplasia, etc.
H. Pyloi-clinical outcomes of infections
Ultimate complication of ulcers is perforational bleeding.
Ulcers less common due to triple therapy and PPi blockers
Ulcer treatment:
Session review:
