Gastroparesis pathophysiology On the Web
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The exact pathogenesis of gastroparesis is not fully understood. However, gastric emptying process is the result of interaction of smooth muscles, extrinsic and enteric autonomic nervous system, and interstitial cells of Cajal (ICC). Loss of expression of neuronal nitric oxide synthase (nNOS) and loss of interstitial cells of Cajal (ICC) play pivotal role in the pathogenesis of gastroparesis. Recent studies suggest that the loss of antioxidant gene expression (NRF2 gene) can contribute to the development of gastroparesis. NRF2 regulates expression of phase II antioxidant genes such as HO-1, SOD1, SOD2, GCLC, GCLM, CAT, and GPX1. On microscopic histopathological analysis of full thickness biopsy of the gastric body. Decreased number of interstitial cells of Cajal (also called fibroblast like cells) in circular muscle layer, immune cells infiltration of gastric tissue especially myenteric plexus predominantly consisting of lymphocytes and macrophages showing CD45 and CD68 immunoreactivity, and enteric nerve fiber loss within the circular smooth muscle layer are characteristic findings of gastroparesis.
- The exact pathogenesis of gastroparesis is not fully understood. However, it is well known that gastric emptying process is the result of interaction of smooth muscles, extrinsic and enteric autonomic nervous system, and interstitial cells of Cajal (ICC).
- The final process for the development of delayed of gastric emptying is increased tone of pylorus.
- Gastric emptying is mediated by the vagus nerve. The process of gastric emptying involves the following sequential steps:
- Interstitial cells of Cajal generate the contractile rhythm within the gut and possess a unique ability to produce slow waves in gastrointestinal smooth muscles.
- This electrical slow wave activity is the determinant of the characteristic frequency of phasic contractions of the stomach, intestine and colon as well as the direction and velocity of propagation of peristaltic activity, in coordination with the enteric nervous system.
- Interstitial cells of Cajal regulate both gastric pacemaker activity and enteric neurons, which then initiate smooth muscle cell activity. Slow wave activity in human stomach originates from a pacemaker region at the mid/upper corpus on the greater curvature. From this pacemaker region, a band of activity is formed rapidly and propagated in an organized fashion towards the distal antrum. Hence, tone of pyloric sphincter plays an important role in the regulation of gastric emptying.
- Non-adrenergic, non-cholinergic (NANC) innervation to the pylorus is predominantly inhibitory and mediates relaxation of the sphincter.
- A high density of nitric oxide synthase-immunopositive nerve cells and fibres have been been demonstrated in the pylorus.
- They are called inhibitory nitrergic neurons. Expression of neuronal nitric oxide synthase (nNOS) activity from nitrergic neurons in gastric wall secrete nitric oxide (NO).
- Major function of NO from these nitrergic enteric nerves include accommodation of the fundus and relaxation of pylorus through smooth muscle relaxation.
- These enteric nerves also control the muscle tone of the lower esophageal sphincter, the sphincter of Oddi, and the anus. The most important mechanism behind the pathogenesis of gastroparesis appears to be:
- Recent studies suggest that the loss of antioxidant gene expression (NRF2 gene) can contribute to the development of gastroparesis. NRF2 regulates expression of phase II antioxidant genes such as HO-1, SOD1, SOD2, GCLC, GCLM, CAT, and GPX1.
- Elevated expression of the enzyme heme oxygenase-1 may mitigate the development of gastroparesis.
- High oxidative stress in interstitial cells of Cajal and nitrergic enteric nerves are the potential cause of injury and decrease in their numbers.
The following conditions may be associated with gastroparesis:
- Other motility disorders of gastrointestinal tract such as achalasia, irritable bowel syndrome and constipation.
- Neurological diseases eg. Parkinson's disease
- Collagen vascular disorders
On microscopic histopathological analysis of full thickness biopsy of the gastric body. Decreased number of interstitial cells of Cajal (also called fibroblast like cells) in circular muscle layer, immune cells infiltration of gastric tissue especially myenteric plexus predominantly consisting of lymphocytes and macrophages showing CD45 and CD68 immunoreactivity, and enteric nerve fiber loss within the circular smooth muscle layer are characteristic findings of gastroparesis.
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