ENDOCRINCE PATHOPHYSIOLOGY OVERVIEW, PART IV.docx

ENDOCRINCE PATHOPHYSIOLOGY OVERVIEW, PART IV.docx -...

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Endocrine Pathophysiology/NRHL 508/ M. Kipta 1 ENDOCRINE PATHOPHYSIOLOGY OVERVIEW: PART IV OVERVIEW OF ADRENAL FUNCTION MECHANSIM OF CORTISOL RELEASE o Corticosteroids (glucocorticosteroids, steroids)—hormones produced by the adrenal cortex o Necessary for life; change of secretion changes according to need & accelerates in response to stress o Corticosteroid secretion controlled by the HPA axis ↑Stress→the hypothalamus secretes CORTICOTROPIN RELEASING HORMONE that stimulates the anterior pituitary to secrete ADRENOCORTICOTROPIC HORMONE (ACTH), which stimulates the adrenal cortex to secrete corticosteroids Rate of corticosteroid secretion maintained within relatively narrow limits but changes according to need; when plasma corticosteroid levels rise to an adequate level, secretion of corticosteroids slows or stops— NEGATIVE FEEDBACK MECHANISM Adrenal storage of glucocortiocsteroids is minimal o Stress Responses Negative Feedback Mechanism does not work
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Endocrine Pathophysiology/NRHL 508/ M. Kipta 2 SNS is activated→↑ production of epinephrine/norepinephrine & the adrenal cortex produces 10 times the normal amount of cortisol→synergistic interaction of these hormones increases the person’s ability to respond to stress Basal production ranges between 5 and 10 mg/m 2 /day (equivalent of 20-30 mg/day of hydrocortisone or 5-7 mg/day of prednisone When severe stress occurs, production increases 5- to 10- fold-to a maximum of 100 mg/m 2 /day Increased SNS activity continues to stimulate cortisol production & overrules the negative feedback mechanism→excessive & prolonged secretion damages body tissues o Circadian Rhythm Basal stimulation follows a circadian rhythm: cortisol levels are lowest near bedtime, rise during sleep, reach a peak right before awakening, & then decline through the day—this pattern is linked to one’s sleep pattern Glucocorticosteroids secreted cyclically, with the largest amount being produced in the early in AM & the smallest amount during the evening hours—in people with a normal day- night schedule In people who work nightshift secretion peaks after arising & drop again before going to bed
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Endocrine Pathophysiology/NRHL 508/ M. Kipta 3 The hypothalamic-pituitary-adrenal (HPA) feedback system regulates and stimulates cortisol synthesis and release by the adrenal cortex. Each hormone in the HPA axis is influenced by a complex feedback loop because synthesis of one substance is regulated by plasma concentrations of the others. For instance, secretion of glucocorticoid, androgen, and estrogen depends on adrenocortical stimulation by adrenocorticotropic hormone (ACTH) from the anterior pituitary. Corticotropin-releasing factor, produced by the hypothalamus, controls ACTH release into the bloodstream. Circulating cortisol levels, stress, and circadian rhythms are also important in regulating ACTH secretion. ACTH in turn regulates cortisol release. The objectives of replacement and pharmacologic drug therapy involve maintaining balance in the HPA feedback system.
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