A 45-year-old woman comes to the office for evaluation of dysphagia. The patient's symptoms first began 2 years ago with regurgitation and bloating after meals but have recently progressed to difficulty swallowing both solid foods and liquids. She has been using antacids without relief. The patient has no other medical history. She drinks 1 or 2 beers on weekends but does not smoke or use illicit drugs. Family history is unremarkable. Vital signs are within normal limits. BMI is 21 kg/m². The abdomen is nontender and soft with normal active bowel sounds. The patient undergoes upper endoscopy that shows a dilated esophagus and retained food. Esophageal manometry reveals increased lower esophageal sphincter (LES) tone and incomplete relaxation. Peristalsis is absent in the distal esophagus. Injection of which of the following into the patient's LES would most likely help relieve her symptoms?

Question

Quizplus · Accepted Answer

Achalasia is an esophageal motility disorder characterized by the absence of esophageal peristalsis in the distal esophagus and incomplete relaxation of a hypertonic lower esophageal sphincter (LES). Achalasia is caused by the immune-mediated destruction of inhibitory ganglion cells in the esophageal wall. Nitric oxide-producing neurons in the myenteric plexus that are responsible for esophageal smooth muscle relaxation are preferentially destroyed, whereas excitatory cholinergic neurons responsible for smooth muscle contraction are relatively spared. This imbalance results in increased lower esophageal tone and impaired sphincter relaxation. Botulinum toxin, a neurotoxin formed by Clostridium botulinum, prevents the fusion of acetylcholine-containing synaptic vesicles with the plasma membrane. This effectively prevents acetylcholine release into the neuromuscular synapse, resulting in muscle weakness and paralysis. In a patient with achalasia, injection of botulinum toxin into the LES causes cholinergic blockade, leading to sphincter relaxation and symptomatic improvement. (Choices B and D) In addition to the cholinergic neurons, there are multiple other hormones and neurotransmitters that modulate esophageal tone. Prostaglandins promote LES relaxation, whereas alpha-adrenergic agonists, such as phenylephrine, increase LES tone. Because corticosteroids inhibit prostaglandin synthesis, both corticosteroids and phenylephrine would worsen the patient's symptoms. (Choices C and E) Neostigmine is a cholinesterase inhibitor and pilocarpine is a cholinergic agonist. Both of these medications increase cholinergic stimuli at the LES and would worsen the patient's symptoms. Educational objective: Achalasia is caused by loss of inhibitory ganglion cells in the distal esophageal wall and is characterized by the absence of esophageal peristalsis and incomplete relaxation of a hypertonic lower esophageal sphincter. Botulinum toxin prevents acetylcholine release into the neuromuscular synapse, resulting in inhibition of cholinergic neurons and lower esophageal sphincter relaxation.

A 45-Year-Old Woman Comes to the Office for Evaluation of Dysphagia