The silent reflux: esophagus and diabetes GERD is caused by - - PDF document

The silent reflux: esophagus and diabetes

GERD is caused by compromised esophageal defense mechanisms, including reduced bicarbonate production, and an abnormality of the lower esophageal sphincter, that produce a reflux of gastric contents from the stomach into the esophagus

What is silent/extra-esophageal reflux

• GERD is among the most common diseases encountered by primary

care physicians and gastroenterologists.

• The

predominant symptoms

• f

GERD are heartburn and regurgitation; however, patients may also present with atypical symptoms.

• These are often referred to as extraesophageal manifestations of

GERD.

• Extraesophageal reflux (EER) symptoms can occur with or without

typical GERD symptoms, which, in the latter setting, may delay the diagnosis of reflux

Yuksel ES, et al. New developments in extraesophageal reflux disease. Gastroenterol Hepatol (N Y). 2012 Sep; 8(9): 590–599.

Typical laryngopharyngeal reflux (LPR) symptoms

• Hoarseness / dysphonia (71%)
• Cough (51%)
• Globus pharyngeus (throat lump sensation) (47%)
• Frequent throat clearing (42%)
• Mild dysphagia / posterior pharynx edema (35%)
• Wheezing
• Sore throat
• Excessive throat mucus
• Post-nasal drip
• Post-prandial rhinorrhea

Laryngoscope 1991;101:1 Am J Gastroenterol 1990;85:38-40 Ear, Nose & Throat Journal 2002;81(Suppl 2):14-18

The Montreal definition of constituent syndromes of extraesophageal reflux

Yuksel ES, et al. New developments in extraesophageal reflux disease. Gastroenterol Hepatol (N Y). 2012 Sep; 8(9): 590–599.

Uncommon symptom in LPR

• HEARTBURN

− Hence, 'silent reflux'

• Only 35% of patients with LPR have heartburn;

− Only 25% with esophagitis

• Up to 38% have normal esophageal pH test

Laryngoscope 1991;101:1 Am J Gastroenterol 1990;85:38-40 Ear, Nose & Throat Journal 2002;81(Suppl 2):14-18

LPR complications

• Adult-onset asthma
• Interstitial lung disease
• Recurrent bronchitis
• Recurrent pneumonia
• Recurrent sinusitis
• Accelerated loss of tooth enamel
• Paradoxical vocal cord dysfunction
• Laryngeal spasm
• Subglottic stenosis
• Vocal cord granulomas and polyps
• Laryngeal CA (without history of smoking or alcohol use)

Laryngoscope 1991;101:1 Am J Gastroenterol 1990;85:38-40 Ear, Nose & Throat Journal 2002;81(Suppl 2):14-18

Gastroesophageal reflux disease (GERD) is the third most common cause of chronic cough (after postnasal drip syndrome [PNDS] and asthma). These 3 causes account for 86% of all cases of chronic cough, and there are

• ften multiple causes for each case.

Yuksel ES, et al. New developments in extraesophageal reflux disease. Gastroenterol Hepatol (N Y). 2012 Sep; 8(9): 590–599.

Asthma and GERD may exacerbate each other, as GERD may induce bronchospasm, and asthma may induce GERD. Treating both conditions may break this cycle and improve patients’ symptoms.

Yuksel ES, et al. New developments in extraesophageal reflux disease. Gastroenterol Hepatol (N Y). 2012 Sep; 8(9): 590–599.

Pathophysiology

• Direct mechanism: caustic acid and pepsin irritation

− Dense neural blanket in larynx protects against aspiration − Sensory deficit in those with laryngeal edema (reversible)

• Indirect

mechanism: irritation

• f

esophagus evoking laryngeal reflexes that causes vagally-mediated change (bronchoconstriction/cough and mucus accumulation/throat clearing)

Yuksel ES, et al. New developments in extraesophageal reflux disease. Gastroenterol Hepatol (N Y). 2012 Sep; 8(9): 590–599.

How does LPR cause damage

• Larynx has no intrinsic defense or clearance mechanisms.
• Gastric acid exposure.
• Pepsin activation at pH < 6.5
• pH < 4 – mucosal damage
• Pepsin inactivated at pH of 8
• Lingering pepsin can be reactivated within 24 hours

Laryngoscope 1991;101:1 Am J Gastroenterol 1990;85:38-40 Ear, Nose & Throat Journal 2002;81(Suppl 2):14-18

Risk factors

• Obesity or acute weight gain: increase intra-abdominal pressure
• Gastroparesis: diabetes, pre-diabetes, narcotics use, hypothyroidism,

idiopathic

• Habitual and volitional excessive gastric distension syndrome
• Aerophagia and carbonated beverages: delivery of gastric acid and

enzymes to LP with each burp or belch

• Hiatal hernia, alcohol, caffeine, peppermints, and chocolates: lowers

resting tone of the upper and lower esophageal sphincters

Laryngoscope 1991;101:1 Am J Gastroenterol 1990;85:38-40 Ear, Nose & Throat Journal 2002;81(Suppl 2):14-18

Risk factors

• Acidic and spicy foods: causes direct irritation and inflammation
• Nicotine: stimulates acid production
• Singing, heavy lifting, exercise, and bending over: prolonged duration

and high magnitude of increases in intra-abdominal pressure

• Gastric outlet obstruction / malignancy
• Sleep apnea

Laryngoscope 1991;101:1 Am J Gastroenterol 1990;85:38-40 Ear, Nose & Throat Journal 2002;81(Suppl 2):14-18

Diagnosis of LPR

Yuksel ES, et al. New developments in extraesophageal reflux disease. Gastroenterol Hepatol (N Y). 2012 Sep; 8(9): 590–599.

Treatment of LPR

• PPI therapy is the standard of care when GERD is suspected to be

the etiology of chronic throat symptoms.

• Patients who are unresponsive to PPI therapy may have either non-

reflux-related causes or a functional component to their symptoms.

• Continued acid and/or pepsin-related injury to the larynx is the cause
• f symptoms, despite a lack of response to PPI therapy.

Yuksel ES, et al. New developments in extraesophageal reflux disease. Gastroenterol Hepatol (N Y). 2012 Sep; 8(9): 590–599.

Non-response to PPI therapy

• Proton pumps in laryngeal seromucinous glands and duct cells may

play a role in the pathogenesis of LPR signs and symptoms.

• Laryngeal proton pumps may activate in response to reflux or other

causes of inflammation or infection in order to preserve intracellular pH and, thus, viability.

• An alternative explanation for the lack of response to PPI therapy in

LPR patients is that reflux may be intermittent and/or may occur in low volumes.

Yuksel ES, et al. New developments in extraesophageal reflux disease. Gastroenterol Hepatol (N Y). 2012 Sep; 8(9): 590–599.

Non-response to PPI therapy (Contd..)

• Therefore, patients who are suspected of having LPR but who do not

have any warning symptoms or signs should initially be treated with empiric PPI therapy for 1–2 months.

• If symptoms improve, the therapy may need to be prolonged for up to

6 months to allow healing of laryngeal tissue.

• After this time, the dosage should be tapered to the smallest amount

that still results in continued response.

• In unresponsive patients, impedance and/or pH monitoring may be

the best alternative to rule out reflux as the cause of continued symptoms and to move forward by considering other causes.

Yuksel ES, et al. New developments in extraesophageal reflux disease. Gastroenterol Hepatol (N Y). 2012 Sep; 8(9): 590–599.

Silent reflux in diabetes

Differences in individual upper (A) and lower (B) gastrointestinal symptoms between diabetic patients and control groups

Diabetic patients have a higher frequency of globus, heartburn and dysmotility like dyspepsia than the controls There was no difference for any item of the lower GI symptoms between the two groups

Kim JH, et al. World J Gastroenterol 2010 April 14; 16(14): 1782-1787

Prevalence of esophageal motor dysfunction in diabetics

• Mandelstam and Lieber were the first to survey a group of diabetics

for evidence of esophageal involvement.

• They reported that the emptying of barium from the esophagus was

delayed in nearly all diabetics with peripheral neuropathy.

• Later, they found that this group also exhibited a decrease in the

frequency of peristaltic contractions after swallowing.

• 80 percent of diabetics with peripheral neuropathy have abnormal

esophageal motility.

• Only 20 percent of diabetics without neuropathy have abnormal

esophageal motility

Ippoliti A. Esophageal disorders in diabetes mellitus. The yale journal of biology and medicine 56 (1983), 267-270

Esophageal changes in diabetes

• In general, the esophageal changes in diabetes can be described as

a loss of motility.

− Pressures are lower in the smooth muscle portion of the esophagus.

The amplitude of esophageal body contractions tends to be low, as does the lower esophageal sphincter pressure.

− The velocity of esophageal body contraction is reduced. The time

required for peristalsis to sweep down the esophagus is prolonged.

− The

pattern

• f

esophageal body contractions may show the following: absence of contraction after swallowing, and simultaneous

• r repetitive body contractions.

Ippoliti A. Esophageal disorders in diabetes mellitus. The yale journal of biology and medicine 56 (1983), 267-270

Clinical features of esophageal motor dysfunction in diabetes

• The esophageal motility changes of loss of peristalsis and delayed

transit would be likely to produce dysphagia or esophagitis.

• The latter is theorized, since impaired clearance of acid is an

important feature of reflux esophagitis.

• However, most studies agree that esophageal symptoms are quite

uncommon in diabetics.

Ippoliti A. Esophageal disorders in diabetes mellitus. The yale journal of biology and medicine 56 (1983), 267-270

Pathogenesis of esophageal motility abnormalities in diabetes

• Esophageal motility disturbances are common in diabetics in general

and are most prevalent in these with peripheral neuropathy or autonomic neuropathy.

• The usual findings are

− a decrease in the amplitude of esophageal contractions in the

smooth muscle portion of the body

− frequent absence of primary peristalsis − simultaneous or repetitive body contractions − decrease in the velocity of peristalsis

Ippoliti A. Esophageal disorders in diabetes mellitus. The yale journal of biology and medicine 56 (1983), 267-270

Pathogenesis of esophageal motility abnormalities in diabetes (Contd...)

• Radiographically, this may be manifested as delayed esophageal

emptying.

• Dysphagia and chest pain should be thoroughly evaluated and not

ascribed to the diabetes

Ippoliti A. Esophageal disorders in diabetes mellitus. The yale journal of biology and medicine 56 (1983), 267-270

Schematic representation of pathogenesis of DAN

Since transit of nutrients through the esophagus in most cases is rapid, gastric emptying is the major determinant of nutrient delivery to the small intestine Indeed, variation in the rate of gastric emptying accounts for ~35% of the variance in peak blood glucose concentrations after ingestion of oral glucose (75 g) in both healthy volunteers and patients with type 2 diabetes

Figure — Relationship between glycemic response (area under blood glucose concentration curve [AUC] between 0 and 30 min after ingestion) and gastric emptying of 75 g glucose in healthy subjects

Rayner CK, et al. Diabetes Care. 2001 Feb;24(2):371-81.

How does diabetes influence the clinical manifestations of reflux esophagitis?

• Diabetic autonomic neuropathy is a common complication of diabetes

and affects every segment of the GIT.

• GI problems tend to be more common and severe in diabetics.
• Reflux esophagitis is common in diabetic patients with a prevalence
• f 40.7%

Antwi C, et al. Does diabetic autonomic neuropathy influence the clinical manifestations of reflux esophagitis. Bratisl Lek Listy. 2003; 104(4-5): 139-142.

Parameters of diabetes in patients with reflux esophagitis

Antwi C, et al. Does diabetic autonomic neuropathy influence the clinical manifestations of reflux esophagitis. Bratisl Lek Listy. 2003; 104(4-5): 139-142.

Parameters of diabetes in patients with reflux symptoms indicative of possible reflux esophagitis

Antwi C, et al. Does diabetic autonomic neuropathy influence the clinical manifestations of reflux esophagitis. Bratisl Lek Listy. 2003; 104(4-5): 139-142.