Diagnosis of gastroesophageal acid reflux gerd

Diagnosis:

There is no standard criterion for the diagnosis of GERD. Heartburn and regurgitation, with or without dysphagia, comprise the clinical syndrome of GERD and are the basis for making a clinical diagnosis. In a study by Klauser et al. , symptoms of heartburn and acid regurgitation were reported to have a high specificity (more than 90%) for GERD, but a low sensitivity. It is also well accepted that some patients can present with atypical symptoms, which are listed in. As such, making an accurate diagnosis of GERD on the basis of a subjective evaluation of symptoms alone is extremely challenging. (Dent J, 2007)

gastroesophageal acid reflux and Oral Health

Oral Health

GERD has been shown to affect overall oral health. One study showed that children with GERD have increased dental erosion, salivary yeast, and salivary Mutans streptococci compared with healthy children. In addition, research indicates that children with GERD have more dental caries and more severe erosion compared with healthy children. .( Franco RA, et al , 2006)

 

 

gastroesophageal reflux and Respiratory Conditions

Respiratory Conditions

GERD is associated with numerous respiratory conditions. Approximately 10% of patients presenting to ENT specialists have conditions that may be attributed to GERD.23 One study revealed that GERD is present in 75% of individuals with refractory ENT symptoms, and PPI therapy provided symptom relief or reduction in the majority of these individuals. Asthma is associated with the presence of GERD symptoms, and although the relationship has not been well-studied. It is estimated that prevalence of GERD in people with asthma is between 60%– 80% in adults and 50%–60% in children. Although the direct correlation is unknown, researchers have suggested that reflux aggravates asthma, which in turn induces further reflux.( Poelmans J, et al ,2006)

GERD is associated with a chronic nonproductive cough in some individuals; the cough occurs primarily during the day and while these patients are in an upright position. One study demonstrated that chronic cough was caused by reflux in 21% of cases. In addition, the researchers showed that chronic cough was the sole presenting symptom in GERD 43% of the time.( Loehrl TA, et al , 2004)

Otitis media may also be linked to GERD. A study examining otitis media with effusion in adults demonstrated that pepsinogen concentration was higher in middle-ear effusion in patients who reported GERD symptoms. In addition, treatment for GERD with PPIs provided some patients with GERD symptom relief as well as decreasing the concentration of pepsinogen in the effusion. Additionally, research has indicated that patients with chronic rhinosinusitis have an increased prevalence of GERD. These chronic rhinosinusitis symptoms in many patients are reduced when their GERD is treated.28 Laryngeal symptoms may be associated with GERD. Often, they present as hoarseness, frequent throat clearing, a postnasal drip, excess phlegm, sore throat, dysphagia, a globus sensation, or cough. Chronic laryngitis and chronic sore throat are associated with GERD in as many as 60% of patients. In addition, one study showed that at least 50% of patients presenting with laryngeal and voice disorders had laryngopharyngeal reflux. Less-common GERD-related laryngopharyngeal disorders include paroxysmal laryngospasm, subglottic stenosis, vocal-cord granuloma, and laryngeal and pharyngeal carcinoma.( Franco RA, et al , 2006)

Pathophysiology And Associated Conditions gastroesophageal acid reflux

Pathophysiology And Associated Conditions

Transient LES relaxation is the primary mechanism of GERD. It results from a vaso-vagal reflex triggered by stretch receptors of the proximal stomach. Studies have indicated that most reflux episodes are acidic. However, according to one study, 28% of episodes were only weakly acidic and 10% of episodes were weakly alkaline. Numerous factors may influence the symptoms of GERD. Delayed gastric emptying, volume of gastric content, quantity and acidity of refluxed contents, ability of the esophagus to clear this material, LES function, and the resistance of the esophageal tissue can influence reflux symptoms. Some researchers have proposed that patients with GERD can be categorized further as having erosive esophagitis,nonerosive reflux disease, and Barrett’s esophagus.( Zerbib F, et al ,2005)

Gastritis 

There is conflicting evidence regarding the role that Helicobacter pylori may play in GERD pathology. There are various studies that have looked at treatment of gastritis by eradicating H. pylori and the effects of treatment on concurrent GERD symptoms. The results of these studies vary from showing improvement to showing worsening of GERD symptoms. Research regarding inflammation in the gastroesophageal junction, or cardia, has indicated that the presence of erosive GERD or H. pylori gastritis is associated with the inflammation. In addition, GERD and carditis are associated with intestinal metaplasia at the gastroesophageal junction.( Malfertheiner P,2005)

Esophagitis

Esophagitis is common with GERD and may be classified as erosive or nonerosive with the severity based on the number and location of mucosal breaks. Other types of esophagitis, such as eosinophilic esophagitis, present with similar symptoms as GERD and are commonly misdiagnosed. The common presentation of eosinophilic esophagitis is dysphagia and food impaction. Additional symptoms may include epigastric pain, emesis, weight loss, and failure to thrive. The diagnosis is based on a histologic finding of greater than 20 eosinophils per high-powered field in the esophageal squamous mucosa. This condition also presents with motor disturbances that may cause food impaction in the absence of strictures. Manometry shows high amplitude long-duration waves in the distal esophagus particularly at night. The symptoms often respond to elimination or elemental dietary regimens and antiallergy treatment. (Pasha SF,, et al ,2006)Standard skin-prick tests measure type 1 hypersensitivity reactions, which are typically  mediated by immunoglobulin E (IgE). (It is possible to have a positive skin test but normal blood levels of IgE on a radioallergosorbent test [RAST].) However, these tests do not diagnose many food-allergy reactions, which are frequently IgG-mediated. Thus, IgG testing can offer additional insights that are frequently missed with standard skin-prick tests.( Luis AL et al ,2006)

Perception of gastro-oesophageal acid reflux

Perception of gastro-oesophageal reflux

Peripheral mechanisms

Gastrointestinal pain is mediated by spinal visceral afferent fibres, with a probable importantcontribution from vagal afferent fibres [6]. When activated,mechanoreceptors and chemo-sensitive receptors (resident in mesentery, serosa and submucosa) epolarise Ad- and C-fibres. The ability to transduce noxious mechanical, chemical or thermal stimuli into generator currents able to depolarize such fibres is a property of transducer channels such as transient receptor potential (TRP) channels. TRPV1, TRPV4 and TRPA1 channels have been shown to have a role in GI nociception, as have acid sensing ion channels (ASICs) and P2x purinoceptors.( Knowles CH , et al ,2009)

In the presence of tissue inflammation or injury there is an up-regulation of pain transmission. The ability to enhance pain transmission to the brain in these situations is important as heightened bodily awareness can alter behaviour to aid in the protection of injured sites and the promotion of healing. Research in somatic pain has suggested that both peripheral and central mechanisms can increase nociceptive transmission following inflammation or injury to tissues. Peripheral mechanisms include peripheral sensitisation (PS), which is an inflammatory mediator-induced facilitation of nociceptor activity in peripheral tissues. Peripheral sensitisation causes pain hypersensitivity at the site of injury or inflammation, also known as primary hyperalgesia. Here inflammatory products including bradykinin, histamine, 5HT, prostanoids, proteases and cytokines permit nociceptor firing at reduced thresholds.( Hobson AR, et al , 2008)

Central mechanisms

Spinal mechanisms In normal circumstances, the presence of stimuli will activate the peripheral receptors as mentioned above. Action potentials would then be generated via activation of Na/K channels and impulses will be sent to the spinal cord via peripheral afferent nerves. Repetitive stimulation or high intensity stimuli can cause a constant firing of action potential to the spinal cord. Enhanced nociceptor input in turn activates intracellular signalling cascades within spinal dorsal horn neurones,

leading to central sensitisation and amplified responses to noxious and innocuous inputs due to facilitated excitatory synaptic responses and depressed inhibition This facilitation is triggered by the pre-synaptic release of neurotransmitters and neuromodulators such as glutamate .( Woolf CJ,,2000)

brain derived neurotrophic factor (BDNF) and prostaglandins . These neurotransmitters and neuromodulators activate ligand-gated ion channels (NMDA-receptor-glutamate), metabotrophic receptors (metabotrophic glutamate receptor (mGluR)–glutamate and NK1–substance P) and tyrosine kinase receptors (Tyrosine Kinase (Trk) B–BDNF) and increase intracellular calcium via release from intracellular stores and calcium inflow. Consequently, calcium-dependent enzymes such as protein kinase A [31], protein kinase C  and tyrosine kinases are activated, leading to phosphorylation of the NMDA receptors. (Siddiqui A, et al , 2005)This dramatically changes NMDA-receptor kinetics and reduces its voltage-dependent magnesium block, thus augmenting its subsequent responsiveness to glutamate and increasing synaptic strength, enabling previously subthreshold inputs to activate the cell. This increase in gain alters receptive field properties and pain sensitivity, causing tissue hypersensitivity far beyond the site of injury. In addition to producing central sensitisation, which occurs within seconds of appropriate activation of spinal dorsal horn neurones, nociceptive input also generates an activity-dependent change in transcription in dorsal root ganglion and dorsal horn neurones These changes occur in response to a complex mechanism involving both an increase and a modification of constitutively .( Woolf CJ,et al ,1991)

 

Cortical mechanisms

A major limitation of most visceral hypersensitivity studies is that they rely on subjective methods of reporting sensation intensity .To overcome this, a commonly used neurophysiological technique, cortical evoked potentials (CEP), has been adopted for use as a more objective correlate of oesophageal sensation. CEP allow recording of cortical neuronal electrical fields generated in response to a peripheral nerve stimulus. Signal averaging of cortical electrical activity of up to 200 oesophageal stimuli is conducted to generate an optimal signal to noise ratio and a temporal pattern of cortical activation is obtained. Because of the excellent temporal resolution of this technique (one ms) it is possible to study the conduction velocity of afferent neuronal transmission from the oesophagus to the cortex. Using this technique before and after oesophageal acid infusion a consistent reduction in CEP latency to oesophageal electrical stimulation has been described which demonstrates that facilitation of afferent pathway conduction accompanied the CS.( Sarkar S et al,2001)

In a recent study in NERD and functional heartburn patients there was a correlation between pain threshold and acid exposure,with increased oesophageal sensitivity being associated with lower DeMeester score . Thus reflux negative (functional heartburn) patients had lower pain thresholds when compared to both reflux positive patients and controls. Cortical evoked potentials were normal in reflux negative patients butsignificantly delayed in the reflux positive group. This suggests that increased oesophageal pain sensitivity in functional heartburn patients is associated with heightened afferent sensitivity as normal latency evoked potential responses could be elicited with reduced afferent input. Similar differentiation in the afferent response using cortical evoked potentials has also been shown in subgroups of patients with Non Cardiac Chest Pain .( Hobson AR, et al ,2006)

Functional Magnetic Resonance imaging has also been used to study the brain processing of acid induced oesophageal hypersensitivity. Lawal A et al studied the brain processing to mechanical stimulation of the proximal oesophagus following infusion of acid or control buffer solution into the distal oesophagus. Following distal oesophageal acid infusion, both subliminal and liminal levels of proximal oesophageal distentions, caused a significant increase in brain activity in both the  ingulate and the insular cortices in comparison to the control buffer solution . This suggests the development of acid-induced sensitisation of the oesophagus to mechanical distention and indicates that this sensitisation is accompanied by increased activity in brain areas processing both sensory (insular cortex) and cognitive (cingulated cortex) aspects of sensation. (Lawal A,et al ,2008)