Key points

The longer I live, the more I am convinced that…half the unhappiness in the world proceeds from little stoppages, from a duct choked up, from food pressing in the wrong place, from a vexed duodenum or an agitated pylorus.

Introduction

Gastroparesis is often defined as a chronic symptomatic disorder of the stomach manifested by delayed emptying without evidence of mechanical obstruction. This classic motility disorder of the stomach can lead to symptoms in patients that reduce the quality of life. Although in many patients symptoms can be controlled with dietary and medical therapy, some patients remain markedly symptomatic with progressive weight loss. This article provides an overview of the definitions and diagnosis of gastroparesis and updates the present status of the understanding of this disorder.

Introduction

Gastroparesis is often defined as a chronic symptomatic disorder of the stomach manifested by delayed emptying without evidence of mechanical obstruction. This classic motility disorder of the stomach can lead to symptoms in patients that reduce the quality of life. Although in many patients symptoms can be controlled with dietary and medical therapy, some patients remain markedly symptomatic with progressive weight loss. This article provides an overview of the definitions and diagnosis of gastroparesis and updates the present status of the understanding of this disorder.

Symptoms

Common symptoms of gastroparesis include nausea (>90% of patients), vomiting (84% of patients), and early satiety (60% of patients). Other symptoms include postprandial fullness and abdominal pain. Symptoms can be persistent or can manifest as episodic flares. Weight loss, malnutrition, and dehydration may be prominent in severe cases. In diabetic patients, gastroparesis may adversely affect glycemic control. In addition, poor glycemic control can worsen the delayed gastric emptying and symptoms.

Symptom profile is established and symptom severity assessed with the Gastroparesis Cardinal Symptom Index (GCSI), a subset of the Patient Assessment of Upper Gastrointestinal Symptoms. The GCSI comprises 3 subscales (nausea and vomiting, postprandial fullness and early satiety, and bloating) that the patient scores from no symptom to very severe symptoms with reference to the preceding 2 weeks. The GCSI daily diary, assessing nausea, vomiting, early satiety, postprandial fullness, and upper abdominal pain, is used to record symptoms on a daily basis and may be more accurate in recording symptoms.

Although it has been a common assumption that the gastrointestinal symptoms can be attributed to delay in gastric emptying, most investigations have observed only weak correlations between symptom severity and the degree of gastric stasis. In general, the symptoms that seem to be best correlated with a delay in gastric emptying include nausea, vomiting, early satiety, and postprandial fullness. Some symptoms that have been present in patients with gastroparesis, such as bloating and upper abdominal pain, are not correlated with delayed gastric emptying and might be related to sensory alterations that might also be present in patients with gastroparesis. There is an overlap of symptoms of gastroparesis and functional dyspepsia. Abdominal pain or discomfort may be present to varying degrees in patients with gastroparesis, but it is not usually the predominant symptom, as it can be in functional dyspepsia.

Etiology

Major causes of gastroparesis are diabetic, postsurgical, and idiopathic. Less common causes of gastroparesis include connective tissue disease, neurologic disease such as Parkinson disease, eating disorders, metabolic or endocrine conditions (hypothyroidism), critical illness, and medications such as opiate narcotic analgesics and anticholinergic agents. In addition, glucagon-like peptide-1 analogues, such as exenatide, used for treatment of type 2 diabetes mellitus can delay gastric empting.

Gastroparesis is a common complication of diabetes; delayed gastric emptying has been found to occur in approximately 40% of patients with longstanding type 1 diabetes and approximately 20% of patients with type 2 diabetes. These estimates are from academic medical centers, and true estimates may be lower in the general population in patients seeing primary care physicians. Diabetic gastroparesis is often attributed to chronic hyperglycemia-induced damage to the vagus nerve and is frequently observed in association with other diabetic complications such as neuropathy, retinopathy, and nephropathy. Glucose can modify gastric emptying tests and symptoms; hyperglycemia can delay gastric emptying and worsen symptoms of gastroparesis, whereas hypoglycemia may accelerate gastric emptying.

Postsurgical gastroparesis can occur with many types of operations but is most often observed after upper abdominal procedures because of injury to or sectioning of the vagus nerve. In the past, surgery for peptic ulcer disease, such as antrectomy with vagotomy, was associated with the development of gastroparesis. However, this type of surgery is being performed less often because of the use of proton pump inhibitor treatments of ulcers and treatment of Helicobacter pylori . Nisson fundoplication is probably the more common surgical procedure associated with gastroparesis. Bariatric surgeries and pancreatic surgery have also been associated with gastroparesis.

Idiopathic gastroparesis, with no obvious cause for the gastroparesis, is a common classification for gastroparesis. Characteristics of 243 patients with idiopathic gastroparesis enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium Registry were reported. Patients’ mean age was 41 years, and most (88%) were women. The most common presenting symptoms were nausea (34%), vomiting (19%), and abdominal pain (23%). Severe delay in gastric emptying (>35% retention at 4 hours) was present in 28% of patients. Severe delay in gastric emptying was associated with more severe symptoms of nausea and vomiting and loss of appetite compared with patients with mild or moderate delay. About 86% met criteria for functional dyspepsia, predominately postprandial distress syndrome. Thus, idiopathic gastroparesis is a heterogeneous syndrome that primarily affects young women and can occur even in overweight or obese individuals. Half of the patients had acute onset of symptoms, with a minority of patients with idiopathic gastroparesis (19%) reporting an initial infectious prodrome such as gastroenteritis or respiratory infection. It has been suggested that idiopathic gastroparesis of acute onset with infectious prodrome could constitute postviral or viral injury to the neural innervation of the stomach or the interstitial cells of Cajal in the stomach. In some series, patients with postviral gastroparesis improve over time, generally several years.

Pathophysiology

Gastric emptying is mediated by the vagus nerve, which helps regulate fundic accommodation, antral contraction, and pyloric relaxation. These regional gastric motility changes with food ingestion are then mediated through smooth muscle cells, which control stomach contractions; interstitial cells of Cajal, which regulate gastric pacemaker activity; and enteric neurons, which initiate smooth muscle cell activity. The pathophysiology of gastroparesis has not been fully elucidated but seems to involve abnormalities in functioning of several elements, including autonomic nervous system, smooth muscle cells, enteric neurons, and interstitial cells of Cajal. Histologic studies demonstrate defects in the morphology of enteric neurons, smooth muscle cells, and interstitial cells of Cajal and increased concentrations of inflammatory cells in gastric tissue.