Corticoid Therapy Flashcards
What are mineralcorticoids?
Aldosterone which acts on the basolateral aspect of the DCT to increase the action of the Na+/H+ exchanger and Na+/K+ ATPase to cause increased Na+ reabsorption into enterocytes, which will draw water in. The side effects of mineralcorticoids includes fluid retention and congestive heart failure due to hypertensive effects.
Where is aldosterone produced?
From the zona glomerulosa of the Adrenal cortex, for the control of Na+, K+ and Cl- levels. They maintain fluid volume and blood pressure, which affects cardiac output. Action of this area is stimulated by angiotensin II.
How are mineralcorticoids synthesised?
It is an intermediate of cholesterol metabolism
Cholesterol -> pregnenolone -> progesterone -> corticosterone -> aldosterone via the enzyme 18-hydroxylase. This enzyme is stimulated by the action of b-hydroxylase.
What are glucocorticoids?
Released from the zonal fasiculata of the adrenal glands. For clinical use, they act intracellularly by binding to glucocorticoid response elements for transactivation of anti-inflammatory mediators and trans-repression of pro-inflammatory mediator transcription within the nucleus.
Glucocorticoids are transported by the serum protein transcortin to target cells.
What are the systemic effects of cortisol?
It has catabolic effects to cause increased proteolysis and lipolysis, in order to promote gluconeogenesis, leading to a high circulating blood glucose. They cause osteoporosis and inhibit fibroblast action on the skin for renewal and inhibit calcium absorption and increase excretion from the kidney.
->Osteoporosis
->Proteolysis
->Lipolysis
->Increases gluconeogenesis in the liver
How is cortisol synthesised?
From cholesterol precursor
Cholesterol -> pregnenolone -> progesterone -> 11-deoxycortisol -> cortisol
This is by the action of Beta-hydroxylase enzyme.
What are androgens?
Hormone that promote growth and synthesis, produced after puberty by the pulsatile bursts of GHRH. The most active androgen is testosterone, and androgens are produced in the zonal reticularis.
How are androgens synthesised?
Synthesised from cholesterol, from the intermediate dehydroepiandrosterone in the zona reticulata of the adrenal gland. ACTH stimualates the action of this zone.
Cholesterol -> pregnenolone -> dehydroepiandrosterone -> androgen.
What is congenital adrenal hyperplasia?
Defect in 21-hydroxylase enzyme reduces the production of mineralcorticoids and glucocorticoids, therefore the physiological response of the body is to increase the production of ACTH, despite dysfunction which leads to hyperplasia of the adrenal gland. There will be a compensatory increase in androgens like testosterone which will cause early pubertal changes in children, with beard growth and small testes.
What are the types of congenital adrenal hyperplasia?
Salt wasting: loss of Na+ in urine due to aldosterone deficiency leads to hypotension , shock and metabolic acidosis
Simple virilisation, which causes the development of male sex characteristics early, and ambiguity of the genitalia in female babies.
What are the clinical uses of glucocorticoids?
Treatment of rheumatoid arthritis
Organ transplantation
Cancer treatment
End of life care
How does the HPA axis work?
Hypothalamus releases CRH to act on the anterior pituitary gland and produce ACTH to act on the adrenal cortex and increase glucocorticoid and androgen synthesis.
What are the side effects of glucocorticosteroid use?
Immunosuppression that can lead to dysphonia
Cushing’s syndrome
Suppression of endogenous glucocorticosteroid production that leads to reduction in size of adrenal gland.
What is Cushing’s syndrome?
Excess production of glucocorticoid hormones which results in:
Obesity
Osteoporosis
High blood pressure
Diabetes due to excess gluconeogenesis, which increases circulating blood glucose.
Cardiac hypertrophy
Emotional disturbances
Vascular atherosclerosis
How does Cushing’s syndrome present in females?
Hirsuitism
Amenorrhoea
