Gastro-oesophageal reflux disease

(Notes from Companion FRCS)

Typical symptoms: heartburn, regurgitation, dysphagia (atypically cough, hoarseness, chest pain).

Response to PPI

Smoking and alcohol

BMI

OGD – oesophagitis and complications of it (Barrett’s, erosive oesophagitis LA grade C/D, stricture, ulceration), exclude other disease (eg. gastritis, PUD), exclude neoplasia

<2/3^rd will have evidence of reflux at OGD

Los Angeles classification:

Grade A           1 or more mucosal breaks <5mm and not covering more than 2 mucosal folds

Grade B           1 or more mucosal breaks >5mm and not covering more than 2 mucosal folds

Grade C           1 or more mucosal breaks continuous between 2 or more mucosal folds but less than 75% of circumference

Grade D           1 or more mucosal breaks that involves more than 75% of the circumference

24 hour ambulatory pH monitoring

–       High specificity and sensitivity

–       Important predictor of response to surgery

–       PPIs should be withheld for 7 days

–       Results should be correlated with symptoms

DeMeester score

–       Score calculated using six parameters to indicate severity of GORD

–       >14.72 indicates significant reflux

Barium swallow to exclude anatomical abnormalities and achalasia

Manometry

–       Very important to exclude achalasia and other dysmotility (eg scleroderma)

–       Also allows confirmation of lower oesophageal sphincter and therefore accurate positioning of the pH catheter           

–       Involves a trans-nasal water-perfused catheter which has 8 pressure sensing side holes at 3cm intervals. Pressure changes are recorded by impendence due to contractions within the oesophagus

–       The ‘pull-through’ technique involves withdrawing the catheter at 1cm intervals until the high pressure zone (>20mmHg)

–       The amplitude and duration of the waves are assessed as well as the percentage of wet swallows that produce a peristaltic response

Partial vs total fundoplication

–       Ann Surg 2013: RCT = 14 year follow-up, after anterior fundoplication the recurrence of reflux was higher but dysphagia was lower than with Nissen’s

–       Conclusion was that both provide good long-term outcomes with similar rates of reflux and dysphagia

Notes from Companion Series

One third of patients (32-38%) with GORD symptoms will have normal endoscopy

Upto 20% of patients with oesophagitis or Barrett’s don’t experience heartburn

Although 24-hr pH monitoring is the gold standard, it can be normal in upto 25% with symptoms and/or oesophagitis

Typical symptoms: hearburn, regurgitation (volume reflux) and intermittent dysphagia

Atypical symptoms: voice change, throat clearing, sore mouth, dental decay, pharyngitis, tonsillitis, sinusitis, chronic cough.

Anatomy of oesophagus

–       Pharynx to stomach

–       25cm

–       3 sections:

o   Cervical: starts at cricopharyngeus for 5cm

o   Thoracic: starts at thoracic inlet at T1 to hiatal opening in diaphragm – 18cm

o   Abdominal: variable depending on presence of HH but normal 1-2cm

–       Outer layer is longitudinal, inner layer is circular muscle

–       Proximally, including the cricopharyngeus its composed of striated muscle only

–       Over next 4-5cm there’s striated and smooth

–       Distally, its mostly smooth muscle

–       Down to the GOJ, the inside is lined by squamous mucosa which changes abruptly to glandular mucosa at the z-junction

–       Blood vessels, nerves and glands form the submucosa

–       Nerve supply is mostly vagal (from recurrent laryngeal proximally, and vagus proper to the main body)

–       Sympathetic nerves arise from middle cervical and upper four thoracic ganglia

Motility

–       Primary contractions are initiated by swallowing

–       Secondary contractions occur if a food bolus is stuck in the oesophagus and distends the lumen

–       Tertiary contractions (non-peristaltic) are usually only seen in 24-hr manometry

–       Peristalsis occurs through slight delay in the contraction of circular muscle compared to the longitudinal

–       Dry swallows often fail to produce a peristaltic wave whereas a wet swallow will produce a longer and greater amplitude wave.

–       Stronger waves are produced with hot substances (ice cream can show complete absence)

–       Only 25% of patients with mild oesophagitis will have peristaltic dysfunction, 48% with severe oesophagitis

–       If there’s stricture, 64% will have a dysmotility

–       Patients with Barret’s will have more severe dysmotility than other reflux diseases, with correlation to the segment length

–       Its unclear if dysmotility occurs secondary to acid-induced mucosal damage.

–       Some improvement in dysmotlity occurs after successful antireflux surgery, although others found no improvement in peristaltic actions after healing of oesophagitis after surgery.

–       There is also no correlation between severity of oesophagitis and delayed transit times (only with incidence of peristaltic dysfunction)

–       Several studies have shown a lack of relationship between motility and dysphagia after anti-reflux surgery (ie patients with dysphagia are just as likely to have normal motility)

–       DeMeester found that patients with oesophagitis were more likely to have prolonged reflux episodes at night compared with shorter daytime episodes (ie poor oesophageal clearance during sleep accounts for greater oesophageal damage). There are fewer primary and secondary peristaltic waves at night, therefore much decreased acid clearance

–       Sleeping with the head of the bed elevated improves nocturnal acid clearance and heals microscopic oesophagitis

Antireflux barrier

In theory, gastric contents should be able to freely flow from the positive pressure environment of the abdomen (+5mmHg) to the slight negative environment of the thorax (-5mmHg). This is prevented by 4 mechanisms

1.     Sling and clasp fibres of the gastric cardia

Oblique sling fibres in the muscular coat of the stomach holds the cardio-oesophageal angle at an acute position. This is said to cause a flap like mechanism. (However, this angle disappears in sliding hernias and yet not all patients will have reflux, so it questions how important this mechanism is)

2.     Diaphragmatic crura

The right crura in particular is thought to contribute to the LOS pressure when there isn’t a sliding hernia. They may be the reason why respiration, coughing and straining all show on manometry. A type of buttressing effect.

3.     Distal oesophageal compression

Phreno-oesophageal ligament – there’s an upper and lower halfs of which the upper part is the only one of significance. It’s a continuation of the fascia from the undersurface of the diaphragm that connects with the submucosa and intramuscular septae of the lower oesophagus. This anchors the GOJ within the abdomen to prevent herniation. The height of insertion determines the length maintained in the positive pressure environment of the abdomen. Even in sliding hiatus hernias, a proportion of the oesophagus in the chest will be enveloped in the fascia which will transmit pressure within the abdomen to that portion.

4.     Lower oesophageal sphincter

This can’t be demonstrated anatomically, only on manometry there is a high-pressure zone that has a raised basal tone and relaxes during swallowing, belching and vomiting. It extends over the terminal 1-4cm, where there is significant asymmetry in pressure, with the highest pressures in the posterior and right directions. The pressures vary throughout the day, with posture, with meals and with activities such as bending and coughing.

It is regulated by myogenic, neural and humoral factors. Atropine and vagal interruption reduces the pressure. Acetylcholine receptors act on post-ganglionic neurones by nicotinic and muscarinic receptors. But nitric oxide may be the mediator between the nerves and the muscles.

Transient lower oesophageal sphincter relaxation (TLOSR) last between 5-40 seconds, are increased after meals and their frequency correlates with severity of reflux (although spontaneous reflux across a low pressure sphincter also increases in these patients). TLOSRs may be a variant of the belch reflex or be initiated by gastric distension. Studies show they are a vagally mediated reflex triggered by mechanoreceptors located in proximal stomach.

–       While not all patients with sliding hernias have GORD, a significant proportion of patients with GORD will have a hiatus hernia (32% endoscopic/90% radiological vs 5.8% normal prevalence)

–       Post-prandial acid-rich contents can reside in the hernia pocket above the crura and can more easily reflux into the oesophagus.

–       Saliva contributes to neutralise the acid left behind after a swallow takes place (production correlates with frequency of swallowing – average 1/minute), mainly due to its high bicarbonate content. At night, when saliva production ceases, the secretion of bicarbonate from submucosal glands within the oesophagus may be an important defence mechanism.

–       Conditions that cause gastric outlet obstruction can cause reflux and severe oesophagitis

–       Zollinger-Ellison is associate with severe oesophagitis

–       H Pylori infection in the distal stomach (antral gastritis) increases gastric acid production and its treatment can improve reflux. However, proximal gastric involvement can cause atrophic gastritis which decreases acid production and in these cases, eradication of H Pylori can worsen reflux. Clinically however eradication seems to have little effect on GORD.

–       Duodenal contents normally reflux through pylorus into stomach. It is thought that bile and pancreatic juices contribute to oesophagitis, metaplasia and dysplasia. However, it is acid reflux (rather than bile in itself) that has the greatest effect, as acid suppression leads to resolution of oesophagitis even in the presence of continuing bile reflux.

Investigations

Endoscopy – mucosal visualisation, histology/cytology, interventions. Can also identify motility abnormalities

Contrast radiology – structural abnormalities as well as peristalsis may be shown but can often be missed.

pH studies – uses miniature pH catheters and computer software to analyse prolonged recordings. Combines occurrences of patient symptoms with acid reflux episodes. Software then produces a standardised table of results which include number of reflux episodes, number lasting more than 5 minutes, total acid reflux time (% of total). The latter is the most robust reproducible measurement – in most centres its measured as the time when pH is <4 at 5cm above a monometrically defined LOS. It should be less than 5% over 24 hours in normal individuals. The variables can be divided into day, night and postprandial variables.

It’s important to correlate the patient’s symptomatic periods with the variables (traditionally in the 2 minutes before onset of symptoms).

SI (symptom index) = number of symptom episodes associated with actual reflux / total number of symptom episodes x 100%

An SI >50% is considered significant

These patients are more likely to respond to conservative or surgical management

Placement of the probe at 5cm above manometrically determined LOS is important to avoid slippage into the stomach or under-measurement of reflux episodes.

Multiple levels of measurements can be taken to investigate chronic cough, hoarseness, dental erosions

PH monitoring is normally done off acid suppression therapy but can be done during if they have symptoms refractory to medical management

Keeping a food diary is important to exclude acidic foods or drinks as causative to measurements. Patients should however, have their “normal” diet

Disadvantages: 5-10% are intolerant, many don’t eat their normal diet with tube in and due to social awkwardness don’t lead their normal lives during measurement

Wireless pH monitors aim to overcome this (Bravo). Must be placed with same care as above. Usually placed 6cm above z-line. (HPZ normally 1-1.5cm above z-line) Data is collected on a portable receiver attached to belt. More expensive, licensed if “patient can’t tolerate nasal intubation”

Manometry – to identify motility disorders, particularly in those being considered for surgery (anti-reflux and myotomy).

The normal swallow: pharynx contracts and pushes bolus to upper oesophageal sphincter which quickly relaxes, a peristaltic wave progresses it down the oesphags and the relaxation of LOS permits it to enter stomach. Normal amplitude varies from 30mmHg proximally to 180 mmHg distally. Contractions are usually upto 6 seconds and peristaltic velocity about 5cm/s. Manometry catheters are passed into stomach and then withdrawn to identify HPZ. At least 3 catheters 5cm apart are needed to assess motility.

Traditionally, 10 wet swallows are done to assess number of peristaltic contractions, amplitude and velocity and abnormal contractions. Furthermore, LOS relaxation is assessed with a sleeve device which straddles the LOS.

The criticism is that these studies are not physiological as they are done in a laboratory. Hence abnormalities that occur during normal daily activities may not be identified. Its really only good for identifying achalasia and nutcracker oesophagus, not for dysmotility syndromes.

Also, symptoms of GORD are rarely triggered by small wet swallows in fasted patients. With only few sensors, the ability to propel food bolus is not really detected well, focal abnormalities can be missed, variations in anatomy eg hiatus hernia are poorly accounted for.

High-resolution manometry – can detect focal oesophageal dysmotility and measure the oesophago-gastric pressure gradient. Upto 36 sensors can be used to create a 3D image that captures the functional anatomy of the oesophagus. Effectively, it makes it easier to predict bolus transport. HRM also allows swallows with solids and multiple repeated swallows of large volumes of liquids.

Oesophageal impedance measurement – detect flow of gas and liquid by measuring the voltage in the lumen. Can determine direction of bolus movement as well as velocity, proximal extent of reflux and recurrent refluxes during same period of pH drop. It can be combined with pH studies to see if the antegrade movement of bolus is acidic or alkaline. This makes it the most sensitive method for reflux detection (MII-pH); important in detecting post-prandial reflux which is often non-acidic and to get an SI in patients having symptoms refractory to acid-suppression.