Morphology of the Human Pancreas During Development and Aging

  • Renu Gupta
  • Shubhi Saini
  • Saroj Sharma
  • Tony G. Jacob
  • T. S. Roy
Chapter

Abstract

Pancreas gets affected by fibrosis associated with aging. This study analyzed the age-related fibrotic changes in the ductular system of the pancreas. After obtaining necessary ethical clearances, twelve human fetal and thirty post-natal and adult pancreas were collected and processed to obtain resin-embedded sections for transmission electron microscopy and paraffin-embedded sections for H&E staining and light microscopy. The sections were analyzed qualitatively and quantitatively. The human pancreas had mature zymogen granules in the exocrine part and secretory granules in the endocrine part by 20th week of gestation. The amount of connective tissue and acini increased with age. After the 3rd decade, there was increased fibrosis. This began around small and medium sized ducts. Changes in the epithelium of ducts were seen in later decades. There was a direct correlation between area of the ducts and increasing age. There was increased fibrosis in and around the islets of Langerhans. The number of fibroblasts and stellate cells increased with age. The increased fibrosis with increasing age that first appears around the small and medium sized ducts may be due to increased number of pancreatic stellate cells.

Keywords

Stellate cells Zymogen granules Islets of langerhans Fibrosis Nucleator Transmission electron microscopy 

Supplementary material

385338_1_En_4_MOESM1_ESM.tif (297 kb)
Suppl. Fig. 1Electronmicrograph of a pancreatic ductal cell displaying a monocilium on its luminal surfaceSupplementary material 1 (TIFF 296 kb)

References

  1. Adelman RC (1989) Changes in pancreatic hormones during aging. Prog Clin Biol 287:163–166Google Scholar
  2. Allen-Mersh TG (1985) What is the significance of pancreatic ductal mucinous hyperplasia? Gut 26:825–833CrossRefPubMedPubMedCentralGoogle Scholar
  3. Ammann RW, Heitz PU, Klöppel G (1996) Course of alcoholic chronic pancreatitis: a prospective clinicomorphological long-term study. Gastroenterology 111:224–231CrossRefPubMedGoogle Scholar
  4. Andrew W (1994) Senile changes in the pancreas of Wistar institute rats and of man with special regard to similarity of locale and cavity formation. Am J Anat 74:97–127CrossRefGoogle Scholar
  5. Apte MV, Haber PS, Applegate TL, Norton ID, McCaughan GW, Korsten MA, Pirola RC, Wilson JS (1998) Periacinar stellate shaped cells in rat pancreas: identification, isolation, and culture. Gut 43:128–133CrossRefPubMedPubMedCentralGoogle Scholar
  6. Ashizawa N, Endoh H, Hidaka K, Watanabe M, Fukumoto S (1997) Three-dimensional structure of the rat pancreatic duct in normal and inflamed pancreas. Microsc Res Tech 37(5–6):543–556Google Scholar
  7. Bojan F, Brian C (1980) Fine structure of rat liver during chronic intoxication with two heterocyclic N- nitrosamine: N- nitrosopiperidine and the non- carcinogen, 2, 2′, 6, 6′ – tetramethyl- N- nitroso – piperidine. Carcinogenesis 1(12):961–974CrossRefGoogle Scholar
  8. Bonner Weir S, Baxter LA, Schuppin GT, Smith FE (1993) A second pathway for regeneration of adult exocrine and endocrine pancreas: a possible recapitulation of embryonic development. Diabetes 42:1715–1720Google Scholar
  9. Bouwens L, Lu WG, De Krijger (1997) Proliferation and differentiation in the human fetal endocrine pancreas. Diabetologia 40:398–404Google Scholar
  10. Bouwens L, Wang RN, De Baly E, Pipeleers DG, Klöppel G (1994) Cytokeratins as markers of ductal cell differentiation and islet neogenesis in the neonatal rat pancreas. Diabetes 43:1279–1283CrossRefPubMedGoogle Scholar
  11. Collins P (1995) Embryology and Development. In: Williams PL (ed) Gray’s Anatomy, 38th edi. Churchill Livingstone, New York, pp 186–187Google Scholar
  12. Collins P (2002). Embryology of pancreas. In: Howard ER, Stringer MD, Columbani PM (eds) Surgery of liver, bile duct and pancreas in children, part 8. London, Arnold, pp 479–492Google Scholar
  13. Cotran RS, Kumar V, Collins T (1999) In: Robbins Pathologic Basis of Disease. 6th ed. Harcourt Asia PTE Ltd, Singapore, pp 39–40Google Scholar
  14. Detlefsen S, Bence S, Bernd F, Klöppel G (2005) Pancreatic fibrosis associated with age and ductal papillary hyperplasia. Virchows Arch 447:800–805CrossRefPubMedGoogle Scholar
  15. Donath MY, Schumann DM, Faulenbach M, Ellingsgaard H, Perren A, Ehses JA (2008) Islet inflammation in type 2 diabetes: from metabolic stress to therapy. Diab Care 31: Suppl 2:161–164Google Scholar
  16. Feyrter F (2005) Uber Die Pripheren Endokrinen Drusen des Menschen. Are there any stem cells in the pancreas? Pancreas 31(2):108–118Google Scholar
  17. Geokas MC, Conteas CN, Majumdar PN (1985) The aging gastrointestinal tract, liver, and pancreas. Clin Geriatr Med 1:177–205PubMedGoogle Scholar
  18. Ghadially FN (1997) In: Ultrastructural pathology of the cell and matrix. 4th ed, vol 2. Butterworth–Heinemann, Oxford, pp. 1014–1037Google Scholar
  19. Githens S (1993) Differentiation and development of the pancreas in animals. In: Go VL, Dimagno EP, Gardner JD, Lebenthal E, Reber HA, Scheele GA (eds) The pancreas: biology, pathobiology, and disease. 2nd ed. Raven Press, New York, 21–55Google Scholar
  20. Hamilton WJ, Boyd JD, Mossaman HW (1957) In Human Embryology, 2nd ed. W Heffer and Son’s Ltd, Cambridge, pp 208–210Google Scholar
  21. Hayden MR, Karuparthi PR, Habibi J, Wasekar C, Lastra G, Manrique C, Stas S, Sowers JR (2007) Ultrastructural islet study of early fibrosis in the Ren2 rat model of hypertension. Emerging role of the islet pancreatic pericyte-stellate cell. JOP 8(6):725–738Google Scholar
  22. Hruban RH, Adsay NV, Albores-Saavedra J, Compton C, Garrett ES, Goodman SN, Kern SE, Klimstra DS, Klöppel G, Longnecker DS, Lüttges J (2001) Offerhaus GJA. Pancreatic intraepithelial neoplasia. A new nomenclature and classification system for pancreatic duct lesions. Am J Surg Pathol 25:579–586CrossRefPubMedGoogle Scholar
  23. Junqueira LC, Carneiro J (1995) Pancreas. In: LC Junqueira, J Carneiro (eds) Basic histology, 8th ed. Lange Medical Publications, Los AltosGoogle Scholar
  24. Kern HF (1971) Die Feinstruktur des exokrinen Pankreasgewebe. Zeitshrift fur Zellforschung 113:322–343CrossRefGoogle Scholar
  25. Kim JW, Ko SH, Cho JH, Sun C, Hong OK, Lee SH, Kim JH, Lee KW, Kwon HS, Lee JM, Song KH, Son HY, Yoon KH (2008) Loss of beta-cells with fibrotic islet destruction in type 2 diabetes mellitus. Front Biosci 13:6022–6033Google Scholar
  26. Klimstra DS (1997) Pancreas. In: Histology for pathologists. 2nd edn. Lippincott-Raven, Philadelphia, pp 613–647Google Scholar
  27. Klöppel G, Bommer G, Heitz PU (1980) Immunocytochemistry of the endocrine pancreas in chronic pancreatitis and pancreatic carcinoma. In: Podolsky S, Vishwanathan M (eds) The spectrum of the diabetic syndromes, secondary diabetes. Raven Press, New York, pp 147–151Google Scholar
  28. Klöppel G, Detlefsen S, Feyerabend B (2004) Fibrosis of the pancreas: the initial tissue damage and the resulting pattern. Virchows Arch 445:1–8CrossRefPubMedGoogle Scholar
  29. Kloppel G, Maillet B (1993) Pathology of acute and chronic pancreatitis. Pancreas 8:659–670CrossRefPubMedGoogle Scholar
  30. Klöppel G, Solcia E, Longnecker DS, Capella C, Sobin LH (1996) Histological typing of tumours of the exocrine pancreas. In: WHO International histological classification of tumours. 2nd ed. Springer, Berlin, Heidelberg, New YorkGoogle Scholar
  31. Larson WJ (2001) In: Human embryology. 3rd ed. Churchill Livingstone, New York, pp 240–244Google Scholar
  32. Laugier R, Bernard JP, Berthezene P, Dupuy P (1991) Changes in pancreatic exocrine secretion with age: pancreatic exocrine secretion does decrease in the elderly. Digestion 50:202–211CrossRefPubMedGoogle Scholar
  33. Lohr M, Lubbersmeyer J, Otremba B, Klapdor R, Grossner D, Klöppel G (1989) Increase of B-cells in the pancreatic remnant after partial pancreatectomy in pigs: an immunocytochemical and functional study. Virchows Arch B Cell Pathol Mol Pathol 56:277–286CrossRefGoogle Scholar
  34. Louis K, Brenda S (1973) Changes in pancreatic morphology associated with aging. Gut 14:962–970CrossRefGoogle Scholar
  35. Mandarim-de-Lacuda CA (1990) Foot length growth related to crown- rump length, gestational age and weight in human staged fresh fetuses: An index for anatomical and medical use. Surg Radiol Anat 12:103–107Google Scholar
  36. Mazhuga PM, Medvetskiĭ EB, Rodionova NV (1981) Ultrastructure of the ductal epithelium in the human pancreas in chronic pancreatitis. Tsitol Genet 15(5):15–24Google Scholar
  37. Movassat J, Saulnier C, Portha B (1995) Beta-cell mass depletion precedes the onset of hyperglycaemia in the GK rat, a genetic model of non-insulin-dependent diabetes mellitus. Diab Metab 21(5):365–370Google Scholar
  38. Nagata A, Monno S (1984) Ultrastructure of pancreatic duct and pancreatic ductal cell. Cell 16:397–402Google Scholar
  39. Pitchumoni CS, Glasser M, Saran RM, Panchacharam P, Thelmo W (1984) Pancreatic fibrosis in chronic alcoholics and nonalcoholics without clinical pancreatitis. Am J Gastroenterol 79:382–388PubMedGoogle Scholar
  40. Ross MH, Kaye GI, Pawlina W (2003) Histology a text and atlas, 4th ed. Lippincott Williams & Wilkins, Baltimore, pp 533–567Google Scholar
  41. Rutter WJ (1980) The development of the endocrine and exocrine pancreas. Fitzgerald, PJ, Morrison AB (eds) In the pancreas. Williams and Wilkins, Baltimore, pp 30–38Google Scholar
  42. Sadler TW (2006) Langman’s medical embryology, 10th ed. Lippincott Williams & Wilkins, Baltimore, pp 215–216Google Scholar
  43. Sailaja K, Ahuja RK, Gopinath G (1996) Biparital diameter: a useful measure for determining gestation age of human abort uses. Natl Med J India 9:165–167PubMedGoogle Scholar
  44. Schmitz- Moormann P, Hein J (1976) Changes of the pancreatic duct system associated with aging: their relations to parenchyma. Virchows Arch A Pathol Anat Histol 371(2):145–152Google Scholar
  45. Shimizu M, Hayashi T, Suitor Y, Itch H (1989) Interstitial fibrosis in the pancreas. Am J Clin Pathol 91:531–534CrossRefPubMedGoogle Scholar
  46. Stamm BH (1984) Incidence and diagnostic significance of minor pathologic changes in the adult pancreas at autopsy: a systematic study of 112 autopsies in patients without known pancreatic disease. Human Pathol 15:677–683CrossRefGoogle Scholar
  47. Valderrama R, Navarro S, Campo E, Camps J, Gimenez A, Pares A, Caballeria J (1991) Quantitative measurement of fibrosis in pancreatic tissue. Evaluation of a colorimetric method. Int J Pancreatol 10:23–29PubMedGoogle Scholar
  48. Whitcomb DC (2006) Clinical practice: Acute pancreatitis. N Engl J Med 354:2142–2150CrossRefPubMedGoogle Scholar
  49. Young B, Lowe JS, Stevens A, Heath HW (2006) Wheater’s functional histology—A text and colour atlas, 5th edi. Churchill Livingstone, New York, pp 288–302Google Scholar
  50. Zulewski H, Abraham EJ, Gerlach MJ, Daniel PB, Moritz W, Muller B, Vallejo M (2001) Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes 50:521–533CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Singapore 2017

Authors and Affiliations

  • Renu Gupta
    • 1
  • Shubhi Saini
    • 2
  • Saroj Sharma
    • 3
  • Tony G. Jacob
    • 2
  • T. S. Roy
    • 4
  1. 1.Department of AnatomyAll India Institute of Medical SciencesJodhpurIndia
  2. 2.Department of AnatomyAll India Institute of Medical SciencesNew DelhiIndia
  3. 3.Dr. B.S. Ambedkar Medical College and HospitalDelhiIndia
  4. 4.Department of AnatomyAll India Institute of Medical SciencesNew DelhiIndia

Personalised recommendations