301 Dyspepsia, GORD & peptic ulcers Flashcards
What is gastro-oesophageal reflux (GOR)?
Condition affecting GI tract whereby the acidic contents of stomach are able to flow back into oesophagus
What is heartburn?
When stomach acid comes in contact with oesophagus lining, patient may experience burning sensation in chest or throat
What is the difference between GOR and GORD?
When symptoms become more frequent & affect person’s wellbeing
Symptoms occur two or more times a week
What is dyspepsia?
Pain or discomfort (including upper abdominal pain, heartburn, reflex, bloating/fullness, early satiety, bloating or nausea) centred in upper abdomen/GI tract
Symptoms >4 weeks
Oesophagus anatomy
Muscular tube about 25cm long
Tube collapsed when not involved in transporting food to stomach
Takes fairly straight course throughout thorax
Goes through oesophageal hiatus to enter abdomen
What is the lower oesophageal sphincter (LOS)?
Where oesophagus joins stomach, there is thickening of circular smooth muscle
Extends 3cm above juncture with stomach
How do LOS and diaphragm act together?
Acts as a valve to keep stomach contents out of oesophagus
Diaphragm muscle helps to ensure integrity of seal
What does LOS do whilst swallowing?
Receptive relaxation of LOS allows passage of food from oesophagus into stomach
Difference between LOS and oesophagus in terms or pressure
LOS normally constricted (pressure of 15-30mmHg) - oesophagus mid-point is relaxed
Why is the pressure of LOS important?
The tonic constriction of LOS prevents significant reflux of highly acidic contents of stomach into oesophagus
Why might presence of acidic stomach contents in oesophagus be an issue?
Reflux oesophagitis occurs in patients with GERD when toxic substances such as gastric acid, pepsin & bile salts come into contact with the oesophageal mucosa, resulting in damage to the distal oesophageal mucosa
What happens in GORD?
Reflux occurs when there is loss of LOS tone
Relaxation of sphincter naturally occur as vagal reflex when stomach distends
Allows small amount of acid into oesophagus after meals
Called transient lower oesophageal sphincter relaxations (TLOSRs)
GORD patients and TLOSRs
In GORD patients TLOSRs are more likely to be associated with acid reflux
When are gastric contents more likely to reflux?
Gastric volume increased
After meals, if gastric emptying is impaired, obstructions
Gastric contents are near junction
Posture (bending down, reclining)
Gastric pressure is increased
Obesity, ascites (fluid build-up in abdomen), pregnancy, tight clothes
Causes of GORD
Genetic - family history
Age - increased age
Gender - male or pregnancy
Dietary triggers - spicy, fatty, chocolate, mint, caffeine
Obesity - overweight, increased risk of hiatus hernia
Stress
Medication
Smoking
Which medications cause GORD?
NSAIDs (indomethacin vs ibuprofen)
Calcium channel blockers (nifedipine)
Nitrates
Antibiotics (doxycycline)
Bisphosphonates (alendronate) - sit up 30 mins after taking
Iron supplements (pregnancy)
Quinine
Potassium supplements
Anticholinergics
TCAs
Progesterone
BZDs
Theophylline
What is hiatus hernia?
Structural abnormality in which superior part of stomach protrudes slightly above diaphragm through diaphragmatic hiatus
Most often due to abnormal relaxation or weakening of sphincter
How does the diaphragm aid in maintaining anti-reflex barrier?
Retention of gastric contents and acid above diaphragm can result in increased volumes of gastric juice entering oesophagus
What is hiatus hernia caused by and risk factors?
Caused by sharp, physical exertions which increase abdominal pressure (coughing, vomiting, straining)
Obesity and pregnancy can increase risk, as can increasing age
80% of hiatus hernias are sliding
Why do symptoms occur in GORD?
Oesophageal epithelium is not able to handle gastric juices for extended periods of time
Level of damage depends on frequency of episodes & volume of gastric juice entering oesophagus
Patient experiences in GORD
Heartburn - feeling of burning rising up from stomach or lower chest towards neck
Regurgitation
Waterbrash - acidification of oesophagus causes sudden stimulation of salivation - mouth fills with saliva
Atypical symptoms of GORD
Chest pain (caution)
Cough
Asthma
Throat/voice changes
GORD complications: reflux oesophagitis
Complication of reflux where mucosal defences are unable to counteract damage caused by acid, pepsin and bile
GORD complications:
non erosive oesophagitis
Mucosa may be normal or mildly erythematous (redness due to dilated capillaries)
GORD complications: erosive oesophagitis
Clear mucosal damage with redness, friability (solid substance breaking into smaller pieces when stressed/rubbed) & ulcers, persistent damage can lead to stricture formation
GORD complications: Barrett’s oesophagus
Complication of long-standing reflux, distal squamous epithelium converted to columnar epithelium, increases relative risk of patient developing adenocarcinoma of oesophagus 30-125 fold, although lifetime risk still low (<2%)
GORD complications: Strictures
Adenocarcinoma of oesophagus
Abnormal narrowing of the oesophageal lumen
Type of oesophageal cancer that develops in the glandular cells of the oesophagus
GORD in babies
Common (~40% of infants)
Does not usually require investigation
If distressed behaviour, gagging, choking, faltering growth, chronic cough, single case of pneumonia then medical treatment needed
GORD in babies: breast-fed
Feeding assessment then add in alginate trial (1-2 weeks Gaviscon Infant Sachets maximum 6 in 24 hours)
GORD in babies: bottle-fed
More frequent smaller feeds, thickened formula such as Carobel, Enfamil AR
What can dyspepsia be caused by?
Can be caused by reflux or peptic ulcer disease (PUD)
Can be mild and self-limiting
Dyspepsia: alarm signs or RED flags
GI bleeding
Difficulty swallowing
Weight loss
Abdominal swelling
Vomiting
If >50-55 years with new onset - refer
<18 years - refer
Any alarm signs present - advise to see GP urgently
Endoscopy - what percentage have these disorders:
Functional dyspepsia (“non-ulcer”)
Oesophagitis
Peptic (GU/DU) ulcers
Barrett’s oesophagus
Gastric cancer
- 60%
- 20%
- 13%
- 1.4%
- 3%
Aims of dyspepsia treatment
Manage symptoms
Treat underlying causes of dyspepsia
Do not exacerbate co-morbidities
Dyspepsia lifestyle changes
Healthy eating, weight reduction and smoking cessation
Avoid fatty foods, spicy foods and onions, citrus fruits and juices, tomatoes
Obesity, smoking, coffee and chocolate can cause reduction in LOS
Fatty foods may delay gastric emptying
Raising bed head at night may also reduce acid regurgitation
Avoid eating large meals before bed
Consider withdrawal of precipitant medications
Dyspepsia: pharmacological measures
Antacids
- Neutralised HCl secreted by gastric parietal cells
- Can be used for dyspepsia, PUD, GORD
- Liquid preparations more effective but less convenient
E.g. aluminium hydroxide, calcium carbonate, magnesium salts
Why do we need to take care with these antacids?
Aluminium hydroxide
Calcium carbonate
Magnesium salts
Constipation - aluminium and calcium
Diarrhoea - magnesium salts
Avoid antacids with high Na content - heart failure, renal failure, cirrhosis (chronic liver disease) & oedema
Avoid aluminium in renal disease as this may accumulate
DIs with antacids
Phenytoin - can reduce absorption of phenytoin and cause loss of seizure control
Quinolones - reduced absorption causing loss of antibiotic efficacy
Antacids with alginates - rafting agents increases viscosity of stomach contents and protects oesophageal mucosa from acid contents
Antacids with simethicone - antifoaming agents to relieve flatulence (can be used to relieve hiccoughs (hiccups) in palliative care)
What should be done with DIs and antacids?
Antacids should not be taken at same time as other drugs
Take antacid 2 hours before or after other meds
Dyspepsia: H2 receptor antagonists
E.g. cimetidine, famotidine, nizatidine, ranitidine
Competitively block H2 receptors on parietal cell Reducing gastric acid secretion
Adverse effects: usually well tolerated, side effects reported in 1-2% cases
Dyspepsia: cimetidine and side effects
Slurred speech, confusion states (elderly), interacts with androgen receptors occasionally causing gynaecomastia & galactorrhoea, thrombocytopenia, granulocytopenia, neutropenia, reversible cholestatic jaundice with cimetidine
Dyspepsia: ranitidine side effect
Reversible hepatitis
DIs with H2 receptor antagonists
Phenytoin, carbamazepine - reduces anticonvulsant clearance causing possible toxic effects
Theophylline - reduced theophylline clearance causing possible toxic effects
Avoid effervescent tabs in Na+ restriction - heart failure, renal impairment
Why are ranitidine and cimetidine no longer in use?
Ranitidine withdrawn from UK market due to link to NDMA, a probable human carcinogen increase over time
Cimetidine also linked and no longer used due to side effects
Dyspepsia: proton pump inhibitors
E.g. Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole
Irreversibly inactivate hydrogen/potassium ATPase enzyme system thus suppressing both stimulated & basal acid secretion
Dyspepsia: proton pump inhibitors side effects
Generally well tolerated, occasional headache, tiredness, rarely - antiandrogenic effects, deranged LFTs, thrombocytopenia
Dyspepsia: other treatment agents
Sucralfate - adsorbs pepsin and decreases its concentration
Misoprostol - inhibits basal and nocturnal gastric acid secretion through direct stimulation of prostaglandin E1 receptors on parietal cells in the stomach
Dyspepsia: initial management
Uninvestigated dyspepsia
Functional dyspepsia
- PPI for 4 weeks
Test for H.Pylori and if positive, treat
(If high risk for H.Pylori, test first or in parallel with PPI) - Test for H.Pylori and if positive treat
If H.Pylori negative - PPI or H2 antagonist for 4 weeks
Dyspepsia: follow up treatment
1. Patients with refractory symptoms
2. If symptoms persist or recur after initial treatment
3. If uninvestigated dyspepsia taking NSAID (but NSAID can’t be stopped)
4. If uninvestigated dyspepsia taking aspirin (but aspirin can’t be stopped
- Assess for new alarm symptoms and consider alternative diagnoses
Check adherence to original management and lifestyle measures - PPI or H2 antagonist at lowest dose to control symptoms (PRN therapy may be considered)
- Consider reducing NSAID dose or (if possible) switch to paracetamol or COX-2-inhibitor, consider using long-term gastro-protection with acid suppression therapy
- Consider switching aspirin to alternative antiplatelet agent
Dyspepsia: general follow up management points
Patients given H.Pylori eradication so not need regular testing
Patients with dyspepsia should receive annual review of symptoms and treatment
(A “stepped down” approach should be encouraged)
Refer to specialist if patient has unexplained/unresponsive GO symptoms or if H.Pylori does not respond to 2nd line therapy
What is peptic ulcer disease (PUD)?
Disruption of mucosal integrity of stomach and/or duodenum leading to local defect or excavation due to active inflammation
What does PUD represent?
An imbalance between protective factors that normally maintain mucosal integrity and destructive factors (gastric acid, pepsin etc.)
What are ulcers?
Breaks in mucosal surface >5mm in size that reach sub-mucosa
They form when there is an imbalance between protective and destructive factors present in stomach and duodenum
3 protective measures of gastro-duodenal defence mechanisms
Mucous/bicarbonate layer
Surface epithelial cells
Prostaglandins
Gastro-duodenal defence mechanisms: mucous/bicarbonate layer
Produced by epithelial cells
Contains water & lipids and glycoproteins (mucin)
Layer impedes diffusion of ions & molecules - sets up pH gradient, pH 1-2 at luminal surface and 6-7 on epithelial surface
Gastro-duodenal defence mechanisms:
Surface epithelial cells
Cells not only produce mucus
Have tight junctions forming protective seal
Cells can be replaced quickly and undergo constant turnover
Gastro-duodenal defence mechanisms:
Prostaglandins
Gastric mucosa contains high levels of prostaglandins
Regulate mucosal bicarbonate and mucous release, inhibit parietal cell secretion & maintain blood flow and epithelial cell repair/replacement
PUD epidemiology:
Gastric ulcers (GU)
Duodenal ulcers (DU)
- Occur more frequently later in life (60s)
Less common than DU
Often silent (no symptoms)
Diagnosed when complications occur - Occur in 5-15% western population
Mortality & morbidity associated with disease has decreased >50% in last 30 years, may be due to H.Pylori eradication
PUD - pathology
DU
GU
- Located within 3cm of pylorus in 90% cases, rarely malignant
- Can represent malignancy
PUD - causes:
DU
GU
- H.Pylori & NSAID induced injury account for majority
Appears to be increase in average basal & nocturnal acid secretion in patients with DU
Bicarbonate secretion appears to be decreased - H.Pylori and NSAID also implicated in majority of cases
Increased acid reflux, delayed gastric emptying
PUD: Symptoms
Epigastric pain described as burning or gnawing can be present in both DU & GU
Discomfort also described as ill-defined aching or hunger pain
Typical pain pattern in DU is 90 mins to 3 hrs after meal, frequently relieved by antacids or food
Pain worsened by food
Nausea & weight loss also more common in GU
PUD: Causative factors
- NSAIDs (aspirin, ibuprofen, diclofenac)
Anything can interrupt prostaglandin synthesis can cause ulcer formation - Other factors
Mental stress
Smoking
Corticosteroids
Zollinger-Ellison syndrome (presence of gastric-secreting tumour)
Blood group O
What do prostaglandins maintain?
Gastro-duodenal integrity
What is Zollinger-Ellison syndrome?
Rare syndrome
Cells in pancreas release gastrin
Leads to high gastric acid production & severe ulcer disease
Extrapancreatic gastrinomas which release gastrin can occur (usually wall of duodenum) and surgery is indicated
Requires much higher doses of PPIs long term
Complications of PUD
Gastric outlet obstruction & intestinal perforation & haemorrhage (potentially life-threatening)
PUD: Patients at high risk of complication with NSAID are…
Those with history of complicated PU OR
TWO or more of the following
- >65 years of age
- High dose NSAIDs
- Other meds with increased risk of PU (SSRIs, anticholinergic, steroids)
- Serious co-morbidities (CVD, HTN, diabetes, renal or hepatic disease)
- Heavy smoker
- Excess alcohol intake
- Previous ADR to NSAIDs
- Prolonged need for NSAIDs
PUD: diagnosis
Endoscopy - invasive - direct exam of oesophagus, stomach & duodenum
H.Pylori can be diagnosed using urea breath test - non-invasive (other methods faecal antigen test, laboratory-based serology & biopsy-based methods)
What are the gold-standard tests for PUD diagnosis?
Stool antigen test or 13C urea breath test or endoscopy with biopsy, serology tests only if locally validated
What should patients do with medication before their endoscopy?
Patients free from meds with PPI for min. 2 weeks beforehand
H2 antagonist use is fine, no anti-bacterials 2 weeks before test
PUD: treatment aims
Promote ulcer healing
Manage symptoms
Treat H.Pylori infection if detected
Reduce risk of ulcer complications & recurrence
Not exacerbate co-morbidities
PUD: non-pharmacological management
Healthy eating, weight loss, avoid food triggers, eat smaller meals, eat evening meal 3-4 hours before bedtime & rise bedhead, smoking reduction and then cessation, avoid alcohol (reduction initially), avoid ulcerogenic drugs, avoid caffeine (gastric acid stimulant), stress/anxiety/depression management
When is an urgent endoscopy needed in suspected PUD?
If dysphagia present OR significant GI bleeding OR in those aged 55 yrs OR unexplained weight loss, upper abdominal pain, reflux or dyspepsia
PUD: Steps of initial management
- Stop meds and recreational drugs can induce ulcers if possible: NSAIDs, steroids, SSRIs, KCl, crack cocaine
- Antacids used short term but long-term not recommended
- Test for H.Pylori
PUD: pharmacological management, test results of H.Pylori
If positive without Hx of NSAIDs
Ulcer associated with NSAIDs
H.Pylori negative without Hx of NSAIDs
- H.Pylori eradication
- PPI for 8 weeks - followed by H.Pylori eradication if H.Pylori positive
- PPI or H2 antagonist for 4-8 weeks
PUD: follow up management, dependent on lesion size
Patient with PU who test positive for H.Pylori should:
- Be reviewed 6-8 weeks after eradication treatment and re-tested
- Repeat endoscopy to confirm healing after 6-8 weeks
If ulcer healed and NSAIDs still required - review NSAIDs every 6 months, consider PRN use, reduced dose, switching to paracetamol or alternative analgesic
What is acid suppression therapy?
Co-prescribed for gastro-protection, PPI preferred (alternatives - H2 antagonist or Misoprostol)
PUD: What happens if symptoms recur after initial treatment?
PPI may be used at lowest dose to control symptoms on “as needed” basis
PUD: What happens if symptoms persist or unhealed ulcer?
Check adherence, check other causes (Ca, H.Pylori, meds), switch to alternative acid suppression therapy
PUD: H.Pylori eradication regimens
Triple therapy for 1 week: high dose PPI, clarithromycin and either amoxicillin or metronidazole
Consider previous exposure to clarithromycin or metronidazole due to high resistance rates
PUD: H.Pylori eradication regimens
What if ulcer is large or complicated or perforated?
Continue PPI for at least another 3 weeks
1st line treatment of PUD (triple therapy)
Acid suppressant
Antibacterial
2nd antibacterial
- Lansoprazole 30mg BD or Omeprazole 20-40mg BD
- Amoxicillin 1g BD or if allergic to penicillin clarithromycin 500mg BD
- Either clarithromycin 500mg BD or metronidazole 400mg BD, if allergic to penicillin use metronidazole option
PUD: 2nd line treatment
Acid suppressant
Antibacterial
2nd antibacterial
- Same as first line with either clarithromycin or metronidazole (whichever was not used 1st line)
If allergic to penicillin and no previous exposure to quinolone - Lansoprazole 30mg BD or Omeprazole 20-40mg BD
- Metronidazole 400mg BD
- Levofloxacin 250mg BD
What should be prescribed with NSAIDs (including coxibs)?
PPIs for anyone with osteoarthritis or rheumatoid arthritis
Anyone 45 years + with chronic low back pain
High risk of GI side effects (65+ or using them long term)
History of GI bleed, dual antiplatelet therapy, concomitant oral anticoagulation/antiplatelet/NSAID
(Use the cheapest PPI)
NSAID usage and PUD risk:
If NSAID is clinically necessary
Consider low-dose ibuprofen (1200mg/day or less) or naproxen (1000mg/day or less) as 1st line
What do warfarin and NOACs increase risk of?
Bleeds not ulceration
What PPI should be used as cover with other medications in PUD (are they taking antiplatelets, SSRIs, corticosteroids, nicorandil?)
Consider lansoprazole 15mg (no difference with 30mg)
Co-prescribing omeprazole/esomeprazole with clopidogrel should be avoided
What are ulcer-inducing drug examples?
Antiplatelets, NSAIDs, anticoagulants, SSRIs, iron-containing therapies, corticosteroids
When is PPI usage licensed?
- Short-term treatment of PUD (gastric and duodenal)
- Eradication of H.Pylori (in combo with antibiotics)
- Prevention & treatment of NSAID-associated ulcers
- Gastro-protection in patients with Hx of dyspepsia & taking aspirin post CVA, MI
- Long-term in Barrett’s and Zollinger-Ellison syndrome
- Treating dyspepsia
Who is at higher risk of clostridium difficile infection?
Frequent PPIs more than doubled patient risk
Elderly & broad spectrum antibiotics
What does achlorhydria (stomach does not produce enough HCl) result in?
Malabsorption of calcium & vitamin B12
What is a rare complication and increased risk of PPI use?
- Interstitial nephritis
Severe cases of hypomagnesaemia rarely reported - Pneumonia
Dementia
PPI use: RAHS-rebound acid hypersecretion syndrome, how to avoid?
Try alternate day dosing before stopping
What is rare SCLE (subacute cutaneous lupus erythematosus)?
Non-scarring dermatosis can develop in sun-exposed areas
