Pathophysiology
Summary
Gastroparesis is characterized by delayed gastric emptying without mechanical obstruction, and often presents as nausea, vomiting, abdominal pain, & early satiety. The condition often arises from vagus nerve dysfunction, which leads to impaired peristalsis of the stomach. It is usually idiopathic, but is also associated with diabetes, drugs like calcium channel blockers and tricyclic antidepressants, as well as surgical injury. Menetrier’s disease involves hypertrophy of stomach rugal folds due to hyperplasia of mucus-secreting cells, resulting in impaired peristalsis and decreased protein digestion. It presents similarly to gastroparesis, but may additionally cause weight loss, muscle wasting, hypoalbuminemia, & peripheral edema. Both conditions can lead to symptoms of upper GI bleeding.
Gastric adenocarcinoma is the most common malignancy of the stomach, and primarily in exists in two forms: intestinal-type and diffuse-type. Risk factors for intestinal-type gastric adenocarcinoma include chronic atrophic metaplastic gastritis (most common), H. pylori-mediated chronic gastritis, autoimmune gastritis, and consumption of preserved foods. Tobacco and alcohol and EBV infection are also risk factors for intestinal-type tumors, which commonly present as bulky exophytic masses that can cause bleeding and ulcerations. Diffuse-type tumors are associated with a loss of E-cadherin, leading to disorganized cell growth and a fibrosing desmoplastic reaction known as linitis plastica. Both types frequently metastasize to the liver, lungs, & ovaries.
Gastric lymphomas may develop from T-cells or B-cells, with chronic atrophic metaplastic gastritis and H. pylori-mediated chronic gastritis as significant risk factors. Marginal zone B-cell or diffuse large B-cell lymphoma are the most common subtypes. GI stromal tumors (GISTs) are mesenchymal tumors originating from interstitial cells of Cajal, the ‘pacemaker’ cells responsible for peristalsis. GISTs are primarily caused by gain-of-function mutations in the c-KIT oncogene, which encodes a tyrosine kinase. These tumors typically form well-circumscribed, fleshy, submucosal masses.
Lesson Outline
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FAQs
Gastroparesis is characterized by delayed gastric emptying in the absence of mechanical obstruction. Symptoms often include nausea, vomiting, abdominal pain, and early satiety. The underlying cause is usually dysfunction of the vagus nerve, which impairs peristalsis, the coordinated contraction and relaxation of stomach muscles that propels food through the digestive tract. Gastroparesis is most commonly idiopathic, but may be contributed to diabetes, certain medications like calcium channel blockers and tricyclic antidepressants, and surgical injury to the vagus nerve. However, the condition is often idiopathic, meaning its cause is unknown.
Menetrier's disease is a rare gastrointestinal disorder characterized by hypertrophy of the stomach's rugal folds due to hyperplasia of mucus-secreting cells. This condition inhibits normal peristalsis and leads to decreased protein digestion, as the increased mucus production results in fewer acid-secreting gastric glands. Menetrier's disease is also termed a "protein-losing enteropathy" because the increased permeability of the stomach mucosa leads to protein loss, manifesting as weight loss, muscle wasting, and hypoalbuminemia. Menetrier's disease is a risk factor for the development of gastric adenocarcinoma.
Gastric adenocarcinoma is the most prevalent type of stomach cancer, with intestinal-type gastric adenocarcinoma being the most common subtype. The primary risk factor is chronic atrophic metaplastic gastritis. Other risk factors include H. pylori-mediated chronic gastritis, autoimmune gastritis, consumption of salt and nitrosamine-preserved foods, smoking, drinking, and Epstein-Barr virus (EBV) infection.
In diffuse-type gastric adenocarcinoma, the loss of normal E-cadherin, an intercellular adhesion molecule, interferes with the intercellular connections between cells, leading to disorganized cell growth and a diffuse invasion pattern throughout the stomach, often referred to as an ‘infiltrative growth pattern.’
Gastric lymphomas are primarily of two types: marginal zone B cell lymphoma and diffuse large B cell lymphoma. The main risk factors include chronic atrophic metaplastic gastritis and H. pylori-mediated chronic gastritis. In particular, H. pylori infection can induce the formation of mucosa-associated lymphoid tissue (MALT), which may progress to gastric lymphoma. Epstein-Barr virus (EBV) infection is another notable risk factor for this malignancy.
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