Abstract
While symptoms of gastroparesis are defined, the pathogenesis of this condition is poorly understood. Furthermore, gastric emptying scintigraphy, the gold standard for diagnostic testing, does not correlate with symptom severity. Some patients with the classic constellation of symptoms for gastroparesis have normal or near-normal gastric emptying patterns. Uncertainty of underlying pathophysiology underscores the struggle to develop effective therapies. The inability of the stomach to effectively empty its solid and liquid contents into the duodenum in the absence of a mechanical obstruction defines gastroparesis. Gastric emptying is dependent on well-coordinated efforts by multiple components in the gastric wall. Different cells, structures, and mechanisms are hypothesized to be responsible for gastroparesis. Currently, however there is a lack of histopathologic evidence to substantiate most of these hypotheses.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Parkman HP, Hasler WL, Fisher RS. American gastroenterological association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology. 2004;127:1592–622.
Lartigue S et al. Inter- and intrasubject variability of solid and liquid gastric emptying parameters. A scintigraphy study in healthy subjects and diabetic patients. Dig Dis Sci. 1994;39:109–15.
Grundy G. Signaling the state of the digestive tract. Rev Auton Neurosci: Basic Clin. 2006;125:76–80.
Ördög T. Interstitial cells of Cajal in diabetic gastroenteropathy. Rev Article Neurogasteroenterol Motil. 2008;20:8–18.
Ward SM, Sanders KM, Hirst GDS. Role of interstitial cells of Cajal in neural control of gastrointestinal smooth muscles. Neurogasteroenterol Motility. 2004;16 Suppl 1:112–7.
Iwakiri R, Fujimoto K. Diabetic gastropathy and interstitial cells of Cajal: a clue for bringing understanding out of chaos? Editorial. J Gastroenterol. 2006;41:1128–30.
Shah V, Lyford G, Gores G, Farrugia G. Nitric Oxide in gastrointestinal health and disease. Gastroenterology. 2004;126:903–13.
Takahashi T et al. Impaired expression of nitric oxide synthase in the gastric myenteric plexus of spontaneously diabetic rats. Gastroenterology. 1997;113:1535–44.
Jenkinson KM, Reid JJ. Effect of diabetes on relaxations to non-adrenergic, non-cholinergic nerve stimulation in longitudinal muscle of the rat gastric fundus. Br J Pharmacol. 1995;116:1551–6.
Vittal H, Farrugia G, Gomez G, Pasricha PJ. Mechanisms of disease: the pathological basis of gastroparesis-a review of experimental and clinical studies. Nat Clin Pract Gastroenterol Hepatol. 2007;4:336–46.
Watkins CC et al. Insulin restores neuronal nitric oxide synthase expression and function that is lost in diabetic gastropathy. J Clin Invest. 2000;106:373–84.
Cellek S. Point of NO return for nitrergic nerves in diabetes: a new insight into diabetic complications. Curr Pharm Des. 2004;10:3683–95.
Ördög T, Takayama I, Cheung WK, Ward SM, Sanders KM. Remodeling of networks of interstitial cells of Cajal in a murine model of diabetic gastroparesis. Diabetes. 2000;49:1731–9.
Horvath VJ, Vittal H, Lorincz A, et al. Reduced stem cell factor links smooth myopathy and loss of interstitial cells of Cajal in murine diabetic gastroparesis. Gastroenterology. 2006;130:759–70.
Wang XY, Huizinga JD, Diamond J, Liu JWC. Loss of intramuscular interstitial cells of Cajal and enteric nerves in streptozotocin-induced diabetic rat stomach. Neurogastroenterol Motil. 2006;18:758.
Horvath VJ et al. Reduced insulin and IGF-1 signaling, not hyperglycemia underlies the diabetes-associated depletion of interstitial cells of Cajal in the murine stomach. Diabetes. 2005;54:1528–33.
Guo C et al. Diabetic autonomic neuropathy: evidence for apoptosis in situ in the rat. Neurogastroenterol Motil. 2004;16:335–45.
Tay SS, Wong WC. Short and long-term effects of streptozotocin-induced diabetes on the dorsal motor nucleus of the vagus nerve in the rat. Acta Anat. 1994;150:274–81.
Schmidt RE et al. Analysis of the Zucker diabetic fatty (ZDF) type 2 diabetic rat model suggests a neurotropic role for insulin/IGF-1 in diabetic autonomic neuropathy. Amer J Pathol. 2003;163:21–8.
Ordog T, Baldo M, Danko R, Sanders KM. Plasticity of electrical pacemaking by interstitial cells of Cajal and gastric dysrhythmias in W/W mutant mice. Gastroenterology. 2002;123:2028–40.
Harberson J, Thomas RM, Harbison SP, Parkman HP. Gastric neuromuscular pathology in gastroparesis: analysis of full-thickness antral biopsies. Dig Dis Sci. 2010;55(2):359–70.
McCallum RW, Lin Z, Damjanov I, Sarosiek I, Forster J. Interstitial cells of Cajal in the stomach of patients with gastroparesis. Neurogastroenterol Motil. 2006;18:758.
Iwasaki H, Kajimura M, Osawa S, et al. A deficiency of gastric interstitial cells of Cajal accompanied by decreased expression of neuronal nitric oxide synthase and substance P in patients with type 2 diabetes mellitus. J Gastroenterol. 2006;41:1076–87.
Parkman HP et al. American Gastroenterological Association medical position statement: diagnosis and treatment of gastroparesis. Gastroenterology. 2004;127:1589–91.
Maleki D et al. Gastrointestinal tract symptoms among persons with diabetes mellitus in the community. Arch Intern Med. 2000;160:2808–16.
Pasricha PJ, Pehlivanov ND, Gomez G, Vittal H. Changes in the gastric enteric nervous system and muscle: a case report on two patients with diabetic gastroparesis. BMC Gastroenterol. 2008;8:21–9.
Anvari M et al. Role of nitric oxide mechanisms in control of pyloric motility and transpyloric flow of liquids in conscious dogs. Dig Dis Sci. 1998;43:506–12.
Spiller RC. Infection, immune function and functional gut disorders. Clin Gastroenterol Hepatol. 2004;2:445–55.
De Giorgio R, Barbara G, Stanghallini V, et al. Idiopathic myenteric ganglionitis underlying intractable vomiting in a young man. Eur J Gastroent Hepatol. 2000;12:613–6.
Battaglia E, Bassotti G, Bellone G, Dughera L, Serra AM, Chiusa L, et al. Loss of interstitial cells of Cajal in severe idiopathic gastroparesis. W J Gastroenterol. 2006;12:6172–7.
Zarate N, Mearin F, Wang XY, Hewlett B, Huizinga JD, Malagelada JR. Severe idiopathic gastroparesis due to neuronal and interstitial cells of Cajal degeneration: pathological findings and management. Gut. 2003;52:966–70.
Pardi DS, Miller SM, Miller DL, et al. Paraneoplastic dysmotility: loss of interstitial cells of Cajal. Am J Gastroenterol. 2002;97:1828–33.
Sigurdsson L, Flores A, Putnam PE, Hyman PE, Di Lorenzo C. Post-viral gastroparesis: Âpresentation, treatment and outcome. J Pediatr. 1997;131:751–4.
Pande H, Lacy BE, Crowell MD. Inflammatory causes of gastroparesis. Report of 5 cases. Dig Dis Sci. 2002;47:2664–8.
Bush TG, Savidge TC, Freeman TC, et al. Fulminant jejuno-ileitis following ablation of enteric glia in adult transgenic mice. Cell. 1998;93:189–201.
Cornet A, Savidge TC, Cabarrocas J, et al. Enterocolitis induced by autoimmune targeting of enteric glial cells: a possible mechanism in Crohn’s disease? Proc Natl Acad Sci. 2001;98:13306–11.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Sharma, A., Thomas, R. (2012). Pathology of Gastroparesis. In: Parkman, H., McCallum, R. (eds) Gastroparesis. Clinical Gastroenterology. Humana Press. https://doi.org/10.1007/978-1-60761-552-1_7
Download citation
DOI: https://doi.org/10.1007/978-1-60761-552-1_7
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-60761-551-4
Online ISBN: 978-1-60761-552-1
eBook Packages: MedicineMedicine (R0)