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Hypothalamic-pituitary-adrenal axis dysfunction in critically ill foals

Dembek, Katarzyna Agnieszka
http://rave.ohiolink.edu/etdc/view?acc_num=osu1479220019340433

Abstract Details

2016, Doctor of Philosophy, Ohio State University, Comparative and Veterinary Medicine.
Sepsis and neonatal maladjustment syndrome (NMS) are the most common diseases of newborn foals. The hypothalamus-pituitary-adrenal gland axis (HPAA) regulates a multitude of physiological processes including energy metabolism, water and electrolyte balance, immune function, and organ maturation. The HPAA is also the key regulator of the stress response to pathological conditions. Hypothalamic factors including corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) control the pituitary gland to release adrenocorticotropic hormone (ACTH), which stimulates the adrenal gland to synthesize cortisol, aldosterone, as well as steroid precursors and sex steroids. Relative adrenal insufficiency (RAI) or critical illness related corticosteroid insufficiency (CIRCI), defined as an insufficient cortisol response to stress or inadequate cortisol activity for the existing degree of critical illness has been associated with mortality in human patients. Our group and others have shown that RAI is associated with mortality in septic foals. However, a more detailed investigation on the multiple adrenocortical steroid response in critically ill foals is necessary to better understand the pathogenesis of equine perinatal disorders and the contribution of adrenal dysfunction to equine perinatal diseases. The overall aim of the studies reported herein was to investigate the association of multiple adrenal steroids and steroid precursors (e.g. pregnenolone, progesterone) with disease severity and outcome in foals. First, a new scoring method (Foal Survival Score) was developed to predict severity of disease and survival in hospitalized foals (Chapter 2). The second study determined the association of AVP and aldosterone concentrations with clinical signs and laboratory findings of tissue hypoperfusion in hospitalized foals (Chapter 3). Next, the response of adrenal corticosteroids and steroid precursors to stressful events was evaluated in hospitalized foals on admission. In this study, in addition to a poor cortisol response to sepsis, we found that RAI was characterized by high progestogen concentration (progesterone, 17a-hydroxyprogesterone) that was associated with mortality (Chapter 4). Further, a low dose ACTH (10 µg) stimulation test was performed in healthy and sick foals. As expected, the response of multiple adrenal steroids to exogenous ACTH was lower in septic compared to healthy foals. The response of 17a-hydroxyprogesterone to ACTH was a good predictor of non-survival in foals (Chapter 5). Next, the longitudinal assessment of adrenal steroids and steroid precursor dynamics during hospitalization was carried out in septic, premature and healthy foals (Chapter 6). Persistently increased concentrations of multiple adrenal steroids were associated with severity of disease and prematurity in hospitalized foals. Progesterone was a good predictor of outcome. Finally, oxytocin and neurosteroids (e.g. progesterone, pregnenolone) were determined in hospitalized foals with NMS and sepsis (Chapter 7). High oxytocin concentrations were associated with increased likelihood of NMS; however, low concentrations of oxytocin were predictive of sepsis in hospitalized foals. Taken together, these finding indicate that the response of the HPAA to foal disorders is a complex process. We documented imbalances of multiple steroids, some of which were linked to the type of disease, disease severity, and mortality. Our research also supports a role for progesterone on equine neonatal physiology as abnormal concentrations were linked to disease.
Ramiro Toribio, DVM, MS, PhD, DACVIM (Advisor)
208 p.
Animal Diseases; Animal Sciences; Animals; Veterinary Services
sepsis, adrenal insufficiency, neurosteroids, neonates, horse, equine

Recommended Citations

Citations

  • Dembek, K. A. (2016). Hypothalamic-pituitary-adrenal axis dysfunction in critically ill foals [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1479220019340433

    APA Style (7th edition)

  • Dembek, Katarzyna. Hypothalamic-pituitary-adrenal axis dysfunction in critically ill foals. 2016. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1479220019340433.

    MLA Style (8th edition)

  • Dembek, Katarzyna. "Hypothalamic-pituitary-adrenal axis dysfunction in critically ill foals." Doctoral dissertation, Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1479220019340433

    Chicago Manual of Style (17th edition)

osu1479220019340433
413
© 2016, some rights reserved.Creative Commons License Hypothalamic-pituitary-adrenal axis dysfunction in critically ill foals by Katarzyna Agnieszka Dembek is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by The Ohio State University and OhioLINK.