Skip to main content
SpringerLink
Log in

Tissue Hypoxia and the Production of Erythropoietin

  • Conference paper
Book cover Erythropoietin

  • 113 Accesses

Abstract

Tissue hypoxia is the major stimulus for the production of erythropoietin. The plasma level of the hormone may rise from a normal value of 5–20 mU/ml to 1000 mU/ml or more in severe anemia or during hypoxic hypoxia. The main functions of erythropoietin are to allow for compensation for the permanent loss of aged red blood cells and to increase erythropoiesis after hemorrhage.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abbrecht PH, Littell JK (1972) Plasma erythropoietin in men and mice during acclimatization to different altitudes. J Appl Physiol 32: 54–58

    PubMed  CAS  Google Scholar 

  2. Alexanian R (1973) Erythropoietin excretion in bone marrow failure and hemolytic anemia. J Lab Clin Med 82: 438–445

    PubMed  CAS  Google Scholar 

  3. Bacon BR, Rothman SA, Ricanati ES, Rashad FA (1980) Renal artery stenosis with erythrocytosis after renal transplantation. Arch Intern Med 140: 1206–1211

    Article  PubMed  CAS  Google Scholar 

  4. Barceló AC, Bozzini CE (1982) Erythropoietin formation during hypoxia in mice with impaired responsiveness to erythropoietin induced by irradiation or 5-fluorouracil injection. Experientia 38: 504–505

    Article  PubMed  Google Scholar 

  5. Bourgoignie JJ, Gallagher NI, Perry MH, Kurz L, Warnecke MA, Donati RM (1968) Renin and erythropoietin in normotensive and in hypertensive patients. J Lab Clin Med 71: 523–536

    PubMed  CAS  Google Scholar 

  6. Caro J, Erslev AJ (1984) Biologic and immunologic erythropoietin in extracts from hypoxic whole rat kidneys and in their glomerular and tubular fractions. J Lab Clin Med 103: 922–931

    PubMed  CAS  Google Scholar 

  7. Cooper GW, Nocenti MR (1961) Unilateral renal ischemia and erythropoietin. Proc Soc Exp Biol Med 108: 546–549

    Google Scholar 

  8. Cotes PM, Doré CJ, Liu Yin JA, Lewis SM, Messinezy M, Pearson TC, Reid C (1986) Determination of serum immunoreactive erythropoietin in the investigation of erythrocytosis. N Engl J Med 315: 283–287

    Article  PubMed  CAS  Google Scholar 

  9. De Klerk G, Rosengarten PCJ, Vet RJWM, Goudsmit R (1981) Serum erythropoietin (ESF) titers in anemia. Blood 58: 1164–1170

    PubMed  Google Scholar 

  10. De Klerk G, Rosengarten PCJ, Vet RJWM, Goudsmit R (1981) Serum erythropoietin (ESF) titers in polycythemia. Blood 58: 1171–1174

    PubMed  Google Scholar 

  11. De Klerk G, Wilmink JM, Rosengarten PCJ, Vet RJWM, Goudsmit R (1982) Serum erythropoietin (ESF) titers in anemia of chronic renal failure. J Lab Clin Med 100: 720–734

    PubMed  Google Scholar 

  12. Dunn CDR, Smith LN, Leonard JI, Andrews RB, Lange RD (1980) Animal & computer investigations into the murine erythroid response to chronic hypoxia. Exp Hematol 8 [Suppl 8]: 259–279

    PubMed  CAS  Google Scholar 

  13. Erslev AJ, Caro J (1984) Secondary polycythemia: a boon or a burden? Blood Cells 10: 177–191

    PubMed  CAS  Google Scholar 

  14. Erslev AJ, Caro J (1984) Pure erythrocytosis classified according to erythropoietin titers. Am J Med 76: 57–61

    Article  PubMed  CAS  Google Scholar 

  15. Erslev AJ, Caro J, Kansu E, Silver R (1980) Renal and extrarenal erythropoietin production in anaemic rats. Br J Haematol 45: 65–72

    Article  PubMed  CAS  Google Scholar 

  16. Erslev AJ, Caro J, Miller O, Silver R (1980) Plasma erythropoietin in health and disease. Ann Clin Lab Sci 10: 250–257

    PubMed  CAS  Google Scholar 

  17. Erslev AJ, Wilson J, Caro J (1987) Erythropoietin titers in anemic, nonuremic patients. J Lab Clin Med 109: 429–433

    PubMed  CAS  Google Scholar 

  18. Faura J, Ramos J, Reynafarje C, English E, Finne P, Finch CA (1969) Effect of altitude on erythropoiesis. Blood 33: 668–676

    PubMed  CAS  Google Scholar 

  19. Fisher JW (1988) Pharmacologie modulation of erythropoietin production. Annu Rev Pharmacol Toxicol 28: 101–122

    Article  PubMed  CAS  Google Scholar 

  20. Fisher JW, Samuels AI (1967) Relationship between renal blood flow and erythropoietin production in dogs. Proc Soc Exp Biol Med 125: 482–485

    PubMed  CAS  Google Scholar 

  21. Fisher JW, Schofield R, Porteous DD (1965) Effects of renal hypoxia on erythropoietin production. Br J Haematol 11: 382–388

    Article  PubMed  CAS  Google Scholar 

  22. Freedman BJ, Penington DG (1963) Erythrocytosis in emphysema. Br J Haematol 9: 425–430

    Article  PubMed  CAS  Google Scholar 

  23. Fried W (1975) Erythropoietin and the kidney, Nephron 15: 327–349

    Article  PubMed  CAS  Google Scholar 

  24. Fried W, Kilbridge T, Krantz S, McDonald TP, Lange RD (1969) Studies on extrarenal erythropoietin. J Lab Clin Med 73: 244–248

    PubMed  CAS  Google Scholar 

  25. Fried W, Johnson C, Heller P (1970) Observations on regulation of erythropoiesis during prolonged periods of hypoxia. Blood 36: 607–616

    PubMed  CAS  Google Scholar 

  26. Garcia JF, Ebbe SN, Hollander L, Cutting HO, Miller ME, Cronkite EP (1982) Radioimmunoassay of erythropoietin: circulating levels in normal and polycythemic human beings. J Lab Clin Med 99: 624–635

    PubMed  CAS  Google Scholar 

  27. Gidding SS, Stockman JA (1988) Erythropoietin in cyanotic heart disease. Am Heart J 116: 128–132

    Article  PubMed  CAS  Google Scholar 

  28. Guidet B, Offenstadt G, Boffa G, Najman A, Baillou C, Hatzfeld C, Amstutz P (1987) Polycythemia in chronic obstructive pulmonary disease. Chest 92: 867–870

    Article  PubMed  CAS  Google Scholar 

  29. Hågå P, Cotes PM, Till JA, Minty BD, Shinebourne EA (1987) Serum immunoreactive erythropoietin in children with cyanotic and acyanotic congenital heart disease. Blood 70: 822–826

    PubMed  Google Scholar 

  30. Hammond D, Shore N, Movassaghi N (1968) Production, utilization and excretion of erythropoietin: I. Chronic anemias. II. Aplastic crisis. III. Erythropoietic effects of normal plasma. Ann NY Acad Sci 149: 516–527

    Article  PubMed  CAS  Google Scholar 

  31. Hudgson P, Pearce JMS, Yeates WK (1967) Renal artery stenosis with hypertension and high haematocrit. Br Med J 1: 18–21

    Article  PubMed  CAS  Google Scholar 

  32. Jacobson LO, Marks EK, Gaston EO, Goldwasser E (1959) Studies on erythropoiesis. XI. Reticulocyte response of transfusion-induced polycythemic mice to anemic plasma from nephrectomized mice and to plasma from nephrectomized rats exposed to low oxygen. Blood 14: 635–643

    PubMed  CAS  Google Scholar 

  33. Jelkmann W (1982) Temporal pattern of erythropoietin titers in kidney tissue during hypoxic hypoxia. Pflügers Arch 393: 88–91

    Article  PubMed  CAS  Google Scholar 

  34. Jelkmann W (1986) Renal erythropoietin: properties and production. Rev Physiol Biochem Pharmacol 104: 139–215

    Article  PubMed  CAS  Google Scholar 

  35. Jelkmann W, Bauer C (1981) Demonstration of high levels of erythropoietin in rat kidney following hypoxic hypoxia. Pflügers Arch 392: 34–39

    Article  PubMed  CAS  Google Scholar 

  36. Jelkmann W, Seidl J (1987) Dependence of erythropoietin production on blood oxygen affinity and hemoglobin concentration in rats. Biomed Biochim Acta 46: S 304–S 308

    CAS  Google Scholar 

  37. Jindal SK, Gupta B, Mohanty D, Das KC, Bidwai PS, Wahi PL (1978) Study of erythropoiesis, erythropoietin and haematological adjustments in congenital cyanotic heart disease. Indian J Med Res 67: 1019–1028

    PubMed  CAS  Google Scholar 

  38. Johannsen H, Gross AJ, Jelkmann W (1989) Erythropoietin production in malignancy. In: Jelkmann W, Gross AJ (eds) Erythropoietin. Springer-Verlag Berlin Heidelberg New York, pp 80–91

    Chapter  Google Scholar 

  39. Koury ST, Bondurant MC, Koury MJ (1988) Localization of erythropoietin synthesizing cells in murine kidneys by in situ hybridization. Blood 71: 524–527

    PubMed  CAS  Google Scholar 

  40. Kramer K, Deetjen P (1960) Beziehungen des O2-Verbrauchs der Niere zu Durchblutung und Glomerulusfiltrat bei Änderung des arteriellen Druckes. Pflügers Arch 271: 782–796

    Article  CAS  Google Scholar 

  41. Lacombe C, Da Silva JL, Bruneval P, Fournier JG, Wendling F, Casadevall N, Camilleri JP, Bariety J, Varet B, Tambourin P (1988) Peritubular cells are the site of erythropoietin synthesis in the murine hypoxic kidney. J Clin Invest 81: 620–623

    Article  PubMed  CAS  Google Scholar 

  42. Lange RD, Gallagher NI (1962) Clinical and experimental observations on the relationship of the kidney to erythropoietin production. In: Jacobson L, Doyle M (eds) Erythropoiesis. Grune and Stratton, New York, pp 361–373

    Google Scholar 

  43. Lechermann B, Jelkmann W (1985) Erythropoietin production in normoxic and hypoxic rats with increased blood O2 affinity. Respir Physiol 60: 1–8

    Article  PubMed  CAS  Google Scholar 

  44. Luke RG, Kennedy AC, Barr Stirling WB, McDonald GA (1965) Renal artery stenosis, hypertension, and polycythaemia. Br Med J 1: 164–166

    Article  PubMed  CAS  Google Scholar 

  45. McGonigle RJS, Wallin JD, Shadduck RK, Fisher JW (1984) Erythropoietin deficiency and inhibition of erythropoiesis in renal insufficiency. Kidney Int 25: 437–444

    Article  PubMed  CAS  Google Scholar 

  46. McGonigle RJS, Ohene-Frempong K, Lewy JE, Fisher JW (1985) Erythropoietin response to anaemia in children with sickle cell disease and Fanconi’s hypoproliferative anaemia. Acta Haematol 74: 6–9

    Article  PubMed  CAS  Google Scholar 

  47. Merino CF, Reynafarje C (1952) Bone marrow studies in the polycythemia of high altitudes. J Lab Clin Med 142: 637–647

    Google Scholar 

  48. Milledge JS, Cotes PM (1985) Serum erythropoietin in humans at high altitude and its relation to plasma renin. J Appl Physiol 59: 360–364

    PubMed  CAS  Google Scholar 

  49. Miller ME, Howard D (1979) Modulation of erythropoietin concentrations by manipulation of hypercarbia. Blood Cells 5: 389–403

    PubMed  CAS  Google Scholar 

  50. Miller ME, Rørth M, Parving HH, Howard D, Reddington I, Valeri CR, Stohlman F (1973) pH effect on erythropoietin response to hypoxia. N Engl J Med 288: 706–710

    Article  PubMed  CAS  Google Scholar 

  51. Miller ME, Garcia JF, Cohen RA, Cronkite EP, Moccia G, Acevedo J (1981) Diurnal levels of immunoreactive erythropoietin in normal subjects and subjects with chronic lung disease. Br J Haematol 49: 189–200

    Article  PubMed  CAS  Google Scholar 

  52. Mujovic VM, Fisher JW (1974) The effects of indomethacin on erythropoietin production in dogs following renal artery constriction. I. The possible role of prostaglandins in the generation of erythropoietin by the kidney. J Pharmacol Exp Ther 191: 575–580

    PubMed  CAS  Google Scholar 

  53. Naets JP, Garcia JF, Tousaaint C, Buset M, Waks D (1986) Radioimmunoassay of erythropoietin in chronic uraemia or anephric patients. Scand J Haematol 37: 390–394

    Article  PubMed  CAS  Google Scholar 

  54. Napier JAF, Dunn CDR, Ford TW, Price V (1977) Pathophysiological changes in serum erythropoiesis stimulating activity. Br J Haematol 35: 403–409

    Article  PubMed  CAS  Google Scholar 

  55. Pagel H, Jelkmann W, Weiss C (1988) A comparison of the effects of renal artery constriction and anemia on the production of erythropoietin. Pflügers Arch 413: 62–66

    Article  PubMed  CAS  Google Scholar 

  56. Pavlovic-Kentera V, Milenković P, Ruvidić R, Jovanović V, Biljanović-Paunović L (1979) Erythropoietin in aplastic anemia. Blut 39: 345–350

    Article  PubMed  CAS  Google Scholar 

  57. Pavlović-Kentera V, Clemons GK, Djukanović L, Biljanocić-Paunović L (1987) Erythropoietin and anemia in chronic renal failure. Exp Hematol 15: 785–789

    PubMed  Google Scholar 

  58. Penington DG (1961) The role of the erythropoietic hormone in anaemia. Lancet i: 301–306

    Article  Google Scholar 

  59. Powell JS, Adamson JW (1985) Hematopoiesis and the kidney. In: Seldin DW, Giebisch G (eds) The kidney: physiology and pathophysiology. Raven, New York, pp 847–866

    Google Scholar 

  60. Scaro JL, Guidi EE (1970) Relationship between plasma erythropoietin activity and hematocrit ratio in high altitude residents. Acta Physiol Latinoam 20: 103–105

    Google Scholar 

  61. Schooley JC, Mahlmann LJ (1975) Hypoxia and the initiation of erythropoietin production. Blood Cells 1:429–448

    CAS  Google Scholar 

  62. Takaku F, Hirashima K, Nakao K (1962) Studies on the mechanism of erythropoietin production. I. Effect of unilateral constriction of the renal artery. J Lab Clin Med 59: 815–820

    PubMed  CAS  Google Scholar 

  63. Tarazi RC, Frohlich ED, Dustan HP, Gifford RW, Page IH (1966) Hypertension and high hematocrit. Am J Cardiol 18: 855–858

    Article  PubMed  CAS  Google Scholar 

  64. Thomas DJ, Du Boulay GH, Marshall J, Pearson TC, Ross Russell RW, Symon L, Wetherley-Mein G, Zilkha E (1977) Effect of haematocrit on cerebral blood-flow in man. Lancet ii: 941–943

    Article  Google Scholar 

  65. Thorling EB, Erslev AJ (1968) The “tissue” tension of oxygen and its relation to hematocrit and erythropoiesis. Blood 31: 332–343

    PubMed  CAS  Google Scholar 

  66. Thurau K (1961) Renal Na reabsorption and O2 uptake in dogs during hypoxia and hydrochlorothiazide infusion. Proc Soc Exp Biol Med 106: 714–717

    PubMed  CAS  Google Scholar 

  67. Tyndall MR, Teitel DF, Lutin WA, Clemons GK, Dallman PR (1987) Serum erythropoietin levels in patients with congenital heart disease. J Pediatr 110: 538–544

    Article  PubMed  CAS  Google Scholar 

  68. Urabe A, Saito T, Fukamachi H, Kubota M, Takaku F (1987) Serum erythropoietin titers in the anemia of chronic renal failure and other hematological states. Int J Cell Cloning 5: 202–208

    Article  PubMed  CAS  Google Scholar 

  69. Van Dyke DC, Layrisse M, Lawrence JH, Garcia JF, Pollycove M (1961) Relation between severity of anemia and erythropoietin titer in human beings. Blood 18: 187–201

    Google Scholar 

  70. Vichinsky EP, Pennathur-Das R, Nickerson B, Minor M, Kleman K, Higashino S, Lubin B (1984) Inadequate erythroid response to hypoxia in cystic fibrosis. J Pediatr 105: 15–21

    Article  PubMed  CAS  Google Scholar 

  71. Wedzicha JA, Cotes PM, Empey DW, Newland AC, Royston JP, Tarn RC (1985) Serum immunoreactive erythropoietin in hypoxic lung disease with and without polycythaemia. Clin Sci 69: 413–422

    PubMed  CAS  Google Scholar 

  72. Weiss C, Fleckenstein W (1986) Local tissue pO2 measured with “thick” needle probes. Funktionsanal Biol Syst 15: 155–166

    Google Scholar 

  73. Zaroulis CG, Hoffman BJ, Kourides IA (1981) Serum concentrations of erythropoietin measured by radioimmunoassay in hematologic disorders and chronic renal failure. Am J Hematol 11: 85–92

    Article  PubMed  CAS  Google Scholar 

  74. Živný J, Kolc J, Málek P, Neuwirt J (1972) Renal ischaemia, hypoxic hypoxia and erythropoietin production. Scand J Haematol 9: 470–476

    PubMed  Google Scholar 

Download references

Authors
  1. H. Pagel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. Jelkmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Weiss
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Physiologisches Institut, Medizinische Universität zu Lübeck, Ratzeburger Allee 160, 2400, Lübeck 1, Federal Republic of Germany

    Wolfgang Jelkmann  & Andreas J. Gross  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1989 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Pagel, H., Jelkmann, W., Weiss, C. (1989). Tissue Hypoxia and the Production of Erythropoietin. In: Jelkmann, W., Gross, A.J. (eds) Erythropoietin. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-83745-6_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-83745-6_5

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-83747-0

  • Online ISBN: 978-3-642-83745-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation