Gastroesophageal Reflux Disease: Causes

Pathogenesis (disease development)

Primary gastroesophageal reflux disease.

The following physiologic mechanisms may contribute to reflux disease:

  • Aggressive gastric juice
  • Impaired self-cleaning powers of the esophagus (food pipe).
  • Insufficiency (weakness) lower esophageal sphincter (lower sphincter of the esophagus) (about 20% of cases are due to anatomical and functional changes).
  • Delayed gastric emptying
  • Change in the anatomical location of the junction between the esophagus and the stomach, for example, due to axial hiatal hernia (hiatal hernia or sliding hernia) or due to a so-called brachyesophagus (congenital shortness of the esophagus). In brachyesophagus, the abdominal part of the esophagus as well as parts of the gastric dome are located in the thoracic cavity (chest cavity) instead of the abdomen (abdominal cavity).
  • Muscular insufficiency (weakness) of the diaphragm legs.

Secondary gastroesophageal reflux disease.

In the secondary form of reflux disease, there is an underlying disease or situation that leads to changes in the transition from the esophagus to the stomach. These include:

  • Stimulants such as nicotine, alcohol
  • Surgical damage to the lower esophageal sphincter, for example, in the surgical therapy of achalasia (dysfunction of those parts of the smooth muscle of hollow organs denotes, which perform an occlusive function).
  • Gastric outlet stenosis (narrowing of the gastric outlet).
  • Muscular dystrophy (muscle atrophy)
  • Esophagitis (inflammation of the esophagus)
  • Scleroderma – collagenosis, which is a disease of the connective tissue that leads to hardening of the connective tissue.
  • Risk factors for intra-abdominal pressure increase: obesity (overweight), ascites (abdominal dropsy), constipation (constipation; due toabdominal press), gravidity (pregnancy).
  • Taking medications that cause smooth muscle to relax, such as alpha-adrenergic agents, aminophylline, nitrates, calcium channel blockers, phosphodiesterase inhibitors including sildenafil (Viagra)

Etiology (causes)

Biographical causes

  • Genetic burden from parents, grandparents (concordance in monozygotic (identical) twins of 30-45%)
    • Genetic diseases
      • Cornelia de Lange syndrome (CdLS) – dysmorphic syndrome with autosomal dominant inheritance: multiple congenital malformations, short stature, characteristic facies and mental retardation.
      • Trisomy 21 (Down syndrome) – special genomic mutation in humans in which the entire 21st chromosome or parts of it are present in triplicate (trisomy). In addition to physical characteristics considered typical for this syndrome, the cognitive abilities of the affected person are usually impaired; furthermore, there is an increased risk of leukemia.
  • Prematurity (GERD then more common in infants).
  • Age – it is controversial whether heartburn is more common in older individuals
  • Hormonal factors

Behavioral causes

  • Nutrition
    • Malnutrition:
      • Large, high-fat meals
      • Drinks rich in sugar such as cocoa or too much sweets (especially chocolate).
      • Hot spices
    • Fruit juices (eg citrus juices / orange juice) with a lot of fruit acids).
    • Peppermint tea and peppermint lozenges (mint).
    • Eating too hastily
    • Last food intake late in the evening before bedtime
  • Pleasure food consumption
    • Alcohol
    • Coffee
    • Tobacco (smoking)
  • Psycho-social situation
    • Stress
  • Overweight (BMI ≥ 25; obesity).

Disease-related causes

  • Ascites (abdominal dropsy)
  • Increased production of gastric acid
  • Gastroparesis – paralysis of the stomach; can occur in diabetes mellitus, for example.
  • Helicobacter pylori infection (predisposing to endoscopic negative reflux disease (NERD; English : Non erosive reflux disease)).
  • Hiatal hernia (diaphragmatic hernia), axial (axial sliding hernia) – pathological passage of portions of the stomach through the diaphragm.
  • Irritable esophagus (synonym: visceral hypersensitivity) – in this case, the esophagus is the cause of the insensitivity.
  • Cow’s milk protein allergy (in infants).
  • Gastric outlet stenosis – narrowing of the gastric outlet.
  • Gastric emptying disorders – may be the cause of refractory reflux.
  • Gastric carcinoma (stomach cancer)
  • Gastric indwelling probe
  • Myocardial infarction (heart attack)
  • Constipation (constipation)
  • Obstructive sleep apnea syndrome – sleep disordered breathing (SBAS) due to partial obstruction of the upper airway.
  • Esophagitis (inflammation of the esophagus):
    • Eosinophilic esophagitis (EoE; young men with allergic diathesis; leading symptoms: Dysphagia (dysphagia), bolus obstruction (“occlusion by a bite” – usually meat bites), and chest pain [children, adolescents, adults]Note: At least six esophageal biopsies should be obtained from different heights for diagnosis.
    • Infectious esophagitis (most common form: thrush esophagitis; furthermore, viral (herpes simplex type 1 (rarely type 2): cytomegalovirus, HIV (in the context of acute HIV syndrome 2-3 weeks after infection), bacterial (tuberculosis, Mycobacterium avium, streptococci, lactobacilli) and parasitic (Pneumocystis, cryptosporidia, Leishmania)).
    • Physicochemical esophagitis; esp. acid and alkali burns and radiation therapy.
    • “Tablet esophagitis”; most common triggers are antibiotics (esp. doxycycline), bisphosphonates, non-steroidal anti-inflammatory drugs (NSAIDs) and potassium chloride.
    • Systemic diseases that may be associated with esophagitis (eg, collagenoses, Crohn’s disease, pemphigus)
  • Esophageal cancer (esophageal cancer).
  • Sjögren’s syndrome (group of sicca syndromes) – autoimmune disease from the group of collagenoses, which leads to a chronic inflammatory disease of the exocrine glands, most commonly the salivary and lacrimal glands; typical sequelae or complications of sicca syndrome are:
    • Keratoconjunctivitis sicca (dry eye syndrome) due to lack of wetting of the cornea and conjunctiva with tear fluid.
    • Increased susceptibility to caries due to xerostomia (dry mouth) due to reduced salivary secretion.
    • Rhinitis sicca (dry nasal mucous membranes), hoarseness and chronic cough irritation and impaired sexual function due to disruption of mucous gland production of the respiratory tract and genital organs.
  • Scleroderma – collagenosis, which is a disease of the connective tissue that leads to hardening of the connective tissue.
  • Soorösophagitis – esophagitis caused by Candida albicans.
  • Delayed gastric emptying
  • Zollinger-Ellison syndrome – neoplasm in the pancreas (pancreas) that may be benign or malignant and produces mainly gastrin (regulates gastric juice secretion)

Medication

Operations

  • Peroral endoscopic myotomy (POEM; transection of the lower esophageal sphincter/esophageal sphincter between the stomach and esophagus) – endoscopic procedure for the treatment of achalasia (esophageal dysfunction) and other hypercontractile esophageal motility disorders (esophageal motility disorders in which the esophagus spasms; nutcracker esophagus) → post-POEM GERD.

Other causes

  • Pregnancy