Pathophysiology and Risk Factors in Peptic Ulcer Disease



Understanding peptic ulcer disease (PUD) pathophysiology and risk factors influencing PUD course poses a great challenge. In this chapter the role of noxious and protective factors in pathophysiology of PUD are discussed. The impact of obesity, alcohol consumption, smoking, as well as genetic factors and use of NSAIDs are also presented. Nowadays, the effective therapies based on inhibition of gastric acid production and Helicobacter pylori eradication provide a gold standard in PUD treatment. Nonetheless, the role of all the abovementioned factors on PUD course should be considered during diagnosis and therapy. Thus, it is important to remember that PUD is a multifactorial disease, and its management should not be based on a simple cause-effect relationship but be tailored for an individual patient.


Gastric acid Obesity Smoking Pathophysiology Peptic ulcer disease Risk factors 



Epidermal growth factor receptor

H. pylori

Helicobacter pylori


Nitric oxide


Nonsteroidal anti-inflammatory drugs




Peptic ulcer disease


Transforming growth factor-α



Hubert Zatorski is the recipient of the Diamentowy Grant Program of the Polish Ministry of Science and Higher Education (No.0202/DIA/2015/44).


  1. 1.
    Allen A, Flemström G. Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin. Am J Phys Cell Physiol. 2005;288(1):C1–19.CrossRefGoogle Scholar
  2. 2.
    Brzozowski T, Konturek PC, Konturek SJ, Brzozowska I, Pawlik T. Role of prostaglandins in gastroprotection and gastric adaptation. J Physiol Pharmacol. 2005;56(Suppl. 5):33–55.PubMedGoogle Scholar
  3. 3.
    Yang YH, Wu WKK, Tai EKK, Wong HPS, Lam EKY, So WHL, et al. The cationic host defense peptide rCRAMP promotes gastric ulcer healing in rats. J Pharmacol Exp Ther. 2006;318(2):547LP–554.CrossRefGoogle Scholar
  4. 4.
    Laine L, Takeuchi K, Tarnawski A. Gastric mucosal defense and cytoprotection: bench to bedside. Gastroenterology. 2008;135(1):41–60.CrossRefPubMedGoogle Scholar
  5. 5.
    Pai R, Soreghan B, Szabo IL, Pavelka M, Baatar D, Tarnawski AS. Prostaglandin E2 transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy. Nat Med. 2002;8(3):289–93.CrossRefPubMedGoogle Scholar
  6. 6.
    Fornai M, Antonioli L, Colucci R, Tuccori M, Blandizzi C. Pathophysiology of gastric ulcer development and healing: molecular mechanisms and novel therapeutic options, peptic ulcer disease, Dr. Jianyuan Chai (Ed.), InTech; 2011, DOI: 10.5772/17640. European Union: Rijeka, Croatia.
  7. 7.
    Hunt RH, Bazzoli F. Review article: should NSAID/low-dose aspirin takers be tested routinely for H. pylori infection and treated if positive? Implications for primary risk of ulcer and ulcer relapse after initial healing. Aliment Pharmacol Ther. 2004;19(Suppl 1):9–16.CrossRefPubMedGoogle Scholar
  8. 8.
    Aalykke C, Lauritsen JM, Hallas J, Reinholdt S, Krogfelt K, Lauritsen K. Helicobacter pylori and risk of ulcer bleeding among users of nonsteroidal anti-inflammatory drugs: a case-control study. Gastroenterology. 1999;116(6):1305–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Voutilainen M, Mantynen T, Farkkila M, Juhola M, Sipponen P. Impact of non-steroidal anti-inflammatory drug and aspirin use on the prevalence of dyspepsia and uncomplicated peptic ulcer disease. Scand J Gastroenterol. 2001;36(8):817–21.CrossRefPubMedGoogle Scholar
  10. 10.
    Rotter JI. Peptic ulcer. In: AEH E, Rimoin DL, editors. The principles and practice of medical genetics. New York: Churchill Livingstone; 1983. p. 863.Google Scholar
  11. 11.
    Zhang BB, Wang J, Bian DL, Chen XY. No association between IL-1β −31 C/T polymorphism and the risk of duodenal ulcer: a meta-analysis of 3793 subjects. Hum Immunol. 2012;73(11):1200–6.CrossRefPubMedGoogle Scholar
  12. 12.
    Yin YW, Hu AM, Sun QQ, Zhang BB, Wang Q, Liu HL, et al. Association between interleukin-8 gene −251 T/A polymorphism and the risk of peptic ulcer disease: a meta-analysis. Hum Immunol. 2013;74(1):125–30.CrossRefPubMedGoogle Scholar
  13. 13.
    Sugimoto M, Furuta T, Shirai N, Nakamura A, Xiao F, Kajimura M, et al. Different effects of polymorphisms of tumor necrosis factor-alpha and interleukin-1 beta on development of peptic ulcer and gastric cancer. J Gastroenterol Hepatol. 2007 Jan;22(1):51–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Sugimoto M, Yamaoka Y, Furuta T. Influence of interleukin polymorphisms on development of gastric cancer and peptic ulcer. World J Gastroenterol. 2010;16:1188–200.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Malaty HM, Graham DY, Isaksson I, Engstrand L, Pedersen NL. Are genetic influences on peptic ulcer dependent or independent of genetic influences for Helicobacter pylori infection? Arch Intern Med. 2000;160(1):105–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Nakajima T. Studies on factors affecting healing of gastric ulcer. A prospective, cooperative study in Japan. Am J Gastroenterol. 1976;66(2):150–4.PubMedGoogle Scholar
  17. 17.
    Edgren G, Hjalgrim H, Rostgaard K, Norda R, Wikman A, Melbye M, et al. Risk of gastric cancer and peptic ulcers in relation to ABO blood type: a cohort study. Am J Epidemiol. 2010;172(11):1280–5.CrossRefPubMedGoogle Scholar
  18. 18.
    Umlauft F, Keeffe EB, Offner F, Weiss G, Feichtinger H, Lehmann E, et al. Helicobacter pylori infection and blood group antigens: lack of clinical association. Am J Gastroenterol. 1996;91(10):2135–8.Google Scholar
  19. 19.
    Keller R, Dinkel KC, Christl SU, Fischbach W. Interrelation between ABH blood group 0, Lewis(B) blood group antigen, Helicobacter pylori infection, and occurrence of peptic ulcer. Z Gastroenterol. 2002;40(5):273–6.CrossRefPubMedGoogle Scholar
  20. 20.
    Aro P, Storskrubb T, Ronkainen J, Bolling-Sternevald E, Engstrand L, Vieth M, et al. Peptic ulcer disease in a general adult population: the kalixanda study: a random population-based study. Am J Epidemiol. 2006;163(11):1025–34.CrossRefPubMedGoogle Scholar
  21. 21.
    Fujimoto A, Hoteya S, Iizuka T, Ogawa O, Mitani T, Kuroki Y, et al. Obesity and gastrointestinal diseases. Gastroenterol Res Pract. 2013;2013:1–7.CrossRefGoogle Scholar
  22. 22.
    Csendes A, Burgos AM, Smok G, Beltran M. Endoscopic and histologic findings of the foregut in 426 patients with morbid obesity. Obes Surg. 2007;17(1):28–34.CrossRefPubMedGoogle Scholar
  23. 23.
    Dutta SK, Arora M, Kireet A, Bashandy H, Gandsas A. Upper gastrointestinal symptoms and associated disorders in morbidly obese patients: a prospective study. Dig Dis Sci. 2009;54(6):1243–6.CrossRefPubMedGoogle Scholar
  24. 24.
    Yamamoto S, Watabe K, Takehara T. Is obesity a new risk factor for gastritis? Digestion. 2012;85(2):108–10.CrossRefPubMedGoogle Scholar
  25. 25.
    Li LF, Chan RLY, Lu L, Shen J, Zhang L, Wu WKK, et al. Cigarette smoking and gastrointestinal diseases: the causal relationship and underlying molecular mechanisms (review). Int J Mol Med. 2014;34(2):372–80.Google Scholar
  26. 26.
    Zhang L, Ren JW, Wong CCM, Wu WKK, Ren SX, Shen J, et al. Effects of cigarette smoke and its active components on ulcer formation and healing in the gastrointestinal mucosa. Curr Med Chem. 2012;19(1):63–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Hecht SS. Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nat Rev. Cancer. 2003;3(10):733–44.CrossRefPubMedGoogle Scholar
  28. 28.
    Garrow D, Delegge MH. Risk factors for gastrointestinal ulcer disease in the US population. Dig Dis Sci. 2010;55(1):66–72.CrossRefPubMedGoogle Scholar
  29. 29.
    Parasher G, Eastwood GL. Smoking and peptic ulcer in the Helicobacter pylori era. Eur J Gastroenterol Hepatol. 2000;12(8):843–53.CrossRefPubMedGoogle Scholar
  30. 30.
    Kato I, Nomura AMY, Stemmermann GN, Chyou P. A prospective study of gastric and duodenal ulcer and its relation to smoking. Alcohol Diet. 1992;135(5):521–30.Google Scholar
  31. 31.
    Cohen S, Booth GH. Gastric acid secretion and lower-esophageal-sphincter pressure in response to coffee and caffeine. N Engl J Med. 1975;293(18):897–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Eisig JN, Zaterka S, Massuda HK, Bettarello A. Coffee drinking in patients with duodenal ulcer and a control population. Scand J Gastroenterol. 1989 Sep;24(7):796–8.CrossRefPubMedGoogle Scholar
  33. 33.
    Shimamoto T, Yamamichi N, Kodashima S, Takahashi Y, Fujishiro M. No association of coffee consumption with gastric ulcer, duodenal ulcer, reflux esophagitis, and non- erosive reflux disease: a cross-sectional study of 8013 healthy subjects in Japan. PLoS One. 2013;8(6):1–9.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Biochemistry, Faculty of MedicineMedical University of LodzLodzPoland

Personalised recommendations