Flashcards in Exam #4: Adrenal Physiology Deck (34):
Outline the HPA axis & the control mechanisms of the HPA axis.
The HPA axis regulates GLUCOCORTICOID production, which in humans is 95% cortisol
What are the zones of the adrenal cortex?
From outer to inner:
1) Zona glomerulosa
2) Zona fasciculata=
3) Zona reticularis
What are the main steroid hormones that are secreted by each of the zones of the adrenal cortex?
1) Zona glomerulosa= aldosterone (minercorticoid)
2) Zona fasciculata= primarily glucocorticoids
3) Zona reticularis= primarily androgens
- Dehydroepiandosterone (DHEA)
Outline the pathways of cortisol, aldosterone, and the adrenal androgen synthesis.
What is the function of 17a-hydroxylase? What is the clinical outcome of a deficiency in 17a-hydroxylase?
What is the function of 3B-hydroxysteroid dehydrogenase? What is the clinical outcome of a deficiency in 3B-hydroxysteroid dehydrogenase?
What is the function of 21-hydroxylase? What is the clinical outcome of a deficiency in 21-hydroxlase?
What is the function of 11B-hydroxylase? What is the clinical outcome of a deficiency in 11B-hydroxylase?
How does ACTH increase adrenal steroid synthesis?
Generally, ACTH stimulates the rate-limiting steps in cortisol synthesis. Specifically,
1) MC2R-->Gas-->cAMP-->PKA-->phosphorylation of cholesterol ester hydrolase, increasing availability of free cholesterol
2) Increased synthesis of StAR (Steroid Acute Regulatory Protein)
3) Increases activity of cholesterol desmolase
What are the physiological effects of cortisol?
1) Metabolic= increased blood glucose
- Increased gluconeogensis
- Degradation of muscle & prevention of protein synthesis
- Lipolysis in fat cells
- Stimulation of hepatic glycogen synthesis
2) Anti-inflammatory= decreased synthesis of the precursor to prostaglandins & leukotrienes
3) Immunosuppressive= decreased lymphocyte production
4) Vascular reactivity= maintains the responsiveness of vascular smooth muscle to catecholamines
*****Note that in fetal development, glucocorticoids promote lung development
What are the physiological effects of aldosterone?
Generally, aldosterone functions to increase Na+ & H20 REABSORPTION & K+ SECRETION in the distal convoluted tubule & collecting ducts of the kidney
How does cortisol increase plasma glucose levels?
Cortisol increases plasma glucose by a variety of mechanisms including:
1) Increased gluconeogenesis
2) Muscle degradation and decreased amino acid uptake (shunted into gluconeogenesis)
3) Lipolysis of fat (shunted into gluconeogenesis)
How does aldosterone increase water and Na+ reabsorption?
1) Expression of the amiloride sensitive epithelial sodium channel (ENaC)
2) Expression of the basolateral Na+/ K+ ATPase pump
List the catcholamines released by the adrenal medulla.
How does cortisol regulate synthesis of epinephrine?
The catecholamines are synthesized from tyrosine. Eventually, DA is packaged into secretory vesicles, and in the vesicles, DA can be converted to NE. NE leaks into the cytoplasm.
*****The cytoplasmic enzyme, PNMT converts NE into Epi.
- Cortisol increases the expression of PNMT, and thus increases concentrations of Epi.
How does cortisol facilitate the effects of NE & epinephrine?
Cortisol maintains the responsiveness of the vascular smooth muscle to NE & Epi
What causes Cushing's Syndrome?
Chronic glucocorticoid excess i.e. excess cortisol, leads to Cushing's Syndrome
What are the symptoms of Cushing's Syndrome?
Increased susceptibility to infection
Virilization & hirsutism from excess androgens
Outline the pathophysiology of Cushing's Syndrome.
1) Pituitary tumor hypersecreting ACTH
2) Chronic glucocorticoid therapy
3) Ectopic hypersecretion of ACTH
4) Hypersecretion of CRH
5) Adrenal tumor hypersecreting cortisol
6) Iatrogenic from exogenous glucocorticoid administration
What is the general difference between primary and secondary adrenal insufficiency?
Adrenal insufficiency refers to a dysfunction of the adrenal cortex & deficient secretion of cortisol & aldosterone
- Primary= damage to the adrenal cortex
- Secondary= suppression of ACTH induced cortisol production
What causes primary adrenal insufficiency?
Primary adrenal insufficiency is caused by autoimmune destruction of the adrenal cortex, infection, and cancer
What causes secondary adrenal insufficiency?
Secondary adrenal insufficiency is caused by suppression of ACTH- induced cortisol production
- Hypothalmic or pituitary disorder
- Chronic exogenous glucocorticoid administration
What are the symptoms of primary adrenal insufficiency?
- Postural hypotension
What are the symptoms of secondary adrenal insufficiency?
- Postural hypotension
****Note that these can be life-threatening in the abrupt cessation of exogenous glucocorticoid administration
What are the symptoms of 21-hydroxylase deficiency?
This is a steroid hormone biosynthesis disorder that called "congenital adrenal hyperplasia." Symptoms include:
1) Increased growth of the adrenal cortex
2) Females born with male sex characteristics/ males with early development of adult characteristics
3) "Salt Wasting" leading to:
Outline the pathophysiology of 21-hydroxylase deficiency..
Without 21-hydroxylase, aldosterone and cortisol cannot be produced; rather, the androgens are synthesized.
- Decreased cortisol leads to increased ACTH
- Elevated ACTH leads to growth of the adrenal cortex & increased production of the androgens (again b/c aldosterone & cortisol cannot be produced)
Where is the receptor for CRH?
Corticotroph cells of the anterior pituitary
What is pro-opiomelanocortin?
The large precursor protein of ACTH, which is also called POMC for short
List the POMC cleavage products.
2) Melanocyte-stimulating hormones
3) Endogenous opioid peptide
What is the receptor for ACTH? Where is this receptor located?
Melanocortin 2 Receptor (MC2R), which is located on the surface of the adrenal cortex
Describe the fluctuations of cortisol throughout the day. What is the clinical significance?
- ACTH release follows a circadian rhythm and is higher just before and after waking
- Consequently, cortisol levels are highest in the morning
*****If glucocorticoid deficiency is suspected, cortisol levels should be measured early in the morning,
How does cortisol exert negative feedback on the anterior pituitary and hypothalamus.
Binding to the glucocorticoid receptor (GR)
What is the function of StAR?
This the Steroid Acute Regulatory Protein, it transports cholesterol into the inner mitochondrial membrane