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An acid is any substance that in water solution tastes sour, changes blue litmus paper to red, reacts with some metals to liberate hydrogen, reacts with bases to form salts, and promotes chemical reactions (acid catalysis).
1692: Viridet was probably first to identify ‘acid’ in various animals’ stomachs including humans.
1823: William Prout presented, ‘On nature of Acid and Saline Matters Usually Existing in Stomachs of Animals’ – confirmed hydrochloric acid in many species (man, dog, rabbit, horse, calf.)
1868: Kussmaul suggested a Bismuth compound to treat ‘peptic ulcers’.
1905: Reigel suggests ulcers are caused by excess acid
1915: Dr Bertram Sippy – proposed a diet to control acid (hourly feedings of milk, eggs, and sodium bicarb)
1957: Jens Skou ‘discovered’ the first Ion pump- Na/K pump (digitalis)
1960-70s: Studies on frogs and identified H/K pumps- and developed the proton pump inhibitors (PPIs)
1981: Marshall and Warren treat peptic ulcers with antibiotics.
What does stomach acid do?
The average human secretes up to 1.5 litres of hydrochloric acid per day. This activates digestive enzymes, which split up the proteins. The acidic gastric juice also kills bacteria.
Control of gastric acid
Gastric acid production is mainly controlled by the central nervous system’s vagus nerve (which controls sight, smell, taste, thoughts and emotional state). Ultimately the vagus nerve sends signals using acetylcholine to the hydrogen potassium adenosine triphosphatase pumps in the stomach to produce acid. This is also triggered by the hormone gastrin, and histamine.
Zollinger Ellison syndrome is a condition where there are one or more gastrinomas in the pancreas, producing gastrin. 1: 1 000 000 (about 10 medical aid patients in SA). Twenty-five per cent have MEN 1 syndrome (tumours of pancreas, pituitary and parathyroid).
To confirm a gastrinoma we measure fasting gastrin or chromogranin A. Not recommended as screening tests, because of rarity of these diseases. Patients are more likely here to have false positives, especially if the patient has been on PPIs, is inadequately fasted, have atrophic gastritis, and even hypercalcaemia.
Peptic ulcer disease causes
NSAIDS/ Aspirin – their inhibition of prostaglandin, which weakens the mucous lining of the stomach, which then allows the acid to burn through. Steroids themselves don’t cause peptic ulcers, but combined with NSAIDs or aspirin, you increase the risk.
Patients on SSRIs using NSAIDs have a much higher risk of bleeding or duodenal ulcers.
Potassium chloride has also been linked with NSAIDs to increase risk.
H. pylori’s effect has been proven. Hypercalcaemia is often forgotten as a cause.
How do we test for H pylori?
Serology is no longer recommended. Stool antigen testing seems to be the simplest. At the same time, that you test for faecal immunofluorescence you can add faecal calprotectin, a biochemical measurement of the protein calprotectin in the stool.
Breath testing is available but needs to be pre-booked and can be cumbersome.
The role of endoscopy is really to look for colon cancer and polyps. Biopsies are taken and then assessed with rapid urease tests. If there is a pH change, that means a urease-splitting organism is present, confirming the presence of H. Pylori. It can also be seen on white light endoscopy (special stains). We use this for PCR- resistance testing, through a culture.
First-line treatment is two antibiotics and PPI for 14 days: amoxicillin and clarithromycin; amoxicillin and levofloxacin; or clarithromycin and metronidazole.
Quadruple therapy: Bismuth (not readily available), tetracycline, metronidazole and a PPI.
This involves troubling symptoms related to reflux of gastric contents. These can be oesophageal symptoms (GORD) or extra-oesophageal symptoms.
Erosive and nonerosive oesophagitis include Barrett’s oesophagus. This is columnar lined mucosa in the distal oesophagus with goblet cells/ intestinal metaplasia. This can be without or with dysplasia.
Lifestyle and dietary modification
If the patient is overweight, consider weight loss (and perhaps sleep studies). Elevation of head of bed can help (avoid sleeping three hours after eating). The Nurses’ health study II: 48 308 nurses (42-62 years old), showed intake of coffee (more than two a day), tea, or fizzy drinks (more than two a week) was associated with an increased risk of GORD symptoms.
Raaj et al. looked at 42 955 females, who ate whole grains, vegetables, and fruit daily; had normal body weight, didn’t smoke, exercised for 30 minutes per day; and had no more than two cups of soda, tea, or coffee per day, had 80% reduction of risk of reflux.
- Elimination of possible dietary triggers (wheat, dairy, spicy food – individual triggers)
- Avoidance of tight-fitting garments
- Promotion of salivation (oral lozenges or chewing gum)
- Abdominal breathing exercises.
GORD and PPIs
About 71 000 000 Americans report reflux symptoms and 30 000 000 are using regular PPIs. PPIs are most potent inhibitors of acid. They are most effective if taken 30-60 minutes before first meal of the day.
Use for initial treatment for eight weeks. For maintenance, use at the lowest dose to control symptoms.
Side effects of PPIs
- Magnesium and Vitamin B12, iron and vitamin D might be affected
- It affects the microbiome so there might be an increased risk of C. difficle and other enteric infections
- Microscopic colitis
- Increased risk of colonisation with multi-drug-resistant organisms
- Could possibly increase the risk of contracting Covid-19 and severe Covid-19.
- Dementia has not been shown prospectively, but epidemiologically there is a concern about log-term use, as with community-acquired pneumonia.
Functional disorders of the gut
These are defined by the Rome Criteria. Rome IV includes:
- Oesophageal Disorders
- Functional chest pain
- Functional heart burn
- Functional dysphagia
- Gastro-duodenal disorders
- Nausea and vomiting.
An approach to functional disorders
Exclude alarm symptoms:
- Loss of weight
- Evidence of gastrointestinal bleeding
- Family history of cancer
- New onset of symptoms >45.
Pain is not normally an alarm symptom. Don’t forget about gallstones. Pancreatic cancer typically has pain radiating to the back and is persistent.
Treatment of functional disorders
- Acknowledge symptoms are real
- Good drug history (NSAIDS, aspirin, cannabis, opioids etc)
- Exclude H. pylori (stool test)
- Empiric PPI
- Muscle relaxants, prokinetics
- Neuromodulators (eg amitriptyline, mirtazapine)
- Chromogranin and fasting gastrin should not be used as screening tests
- H. pylori serology is no longer recommended
- Discuss effective lifestyle changes with patients
- PPIs are safe (but there are side effects): use lowest dose
- Exclude alarm symptoms.
Acid-related disorders have plagued human (and animal) kind throughout recorded history. In the third millennium we have finally learnt to control acid and cure gastric and duodenal ulcers. However, we still have more to learn.