EXAM #2: ADRENAL PHYSIOLOGY Flashcards
Identify the main steroid hormones produced and secreted by each of the zones of adrenal cortex.
Glomerulosa= Aldosterone Fasiculata= Cortisol Reticularis= Androgens
Recognize and describe the control mechanisms of the hypothalamus-pituitary-adrenal (HPA) axis.
Hypothalamus= CRH
Anterior Pituitary= ACTH
Adrenal Cortex= Cortisol and Androgen production
What increases CRH secretion?
1) Stress
2) Circadian rhythms
When is CRH synthesis the highest?
AM
What is the mechanism by which ACTH increases adrenal steroid synthesis.
- ACTH activates receptors on cortical cells, specifically Melanocortin-2 receptor
- Steroidogenic enzyme expression is INCREASED
What cleaves cholesterol in the synthesis of the cortical steroids? What is the product?
Cholesterol Desmolase– Pregnenolone
Pregnenolone is shunted down the Glucocorticoid and Androgen synthetic pathways by what enzyme i.e. what shunts this pathway to the left?
17 a-hydoxylase
After 3B hydroxysteroid dehydrogenase, what are the next two enzymes that continue the production of the Corticosteroids down their biosynthetic pathway?
21 hydroxylase and 11 B-hydroxylase
What converts adrostiendione to Testosterone?
17B-hydroxysteroid dehydrogenase
What enzymes are unique to producing Aldosterone?
Aldosterone synthase i.e. 18 hydroxylase and 18B-hydrox dehydrogenase
What is the major Glucocorticoid?
Cortisol
What is the rate limiting step of Cortisol/Glucocorticoid synthesis?
Cholesterol desmolase i.e. cholesterol to pregnenolone
What is the difference between the outcome of chronically low ACTH and elevated ACTH on the morphology of the adrenal gland?
Low= atrophy High= hyperplasia
What are the major effects of increased cortisol? What is the mnemonic to remember these effects?
Cortisol is a BIG FIB
1) Blood pressure increased
2) Insulin resistance
3) Gluconeogenesis, lipolysis, proteolysis
4) Fibroblast activity increased
5) Immune system decreased
6) Bone resorption
*Cortisol increases beta-adrenergic receptors
How does cortisol increase blood glucose?
1) Increases enzymes and substrates (amino acids and adipose) that drive gluconeogenesis
2) Decreased glucose utilization by most cells
What is the main mineralcorticoid?
Aldosterone
*Note that some of the intermediates in the mineralcorticoid pathway have activity e.g. DOC
What is the name of synthetic aldosterone?
Fludrocortisone
What are the two major regulators that increase Aldosterone?
1) Angiostenin II
2) Elevated K+
What sets off the RAAS to ultimately increase ANGII?
Decreased renal perfusion pressure
What are the major effects of Aldosterone?
1) Increase Na+ and water reabsorption
2) Excretion of K+
In an enzymatic deficiency of Aldosterone, what is the expected response of Renin?
Increased Renin production
What are the two major actions of Aldosterone outside fo the kidney?
1) Conserve Na+ in sweating
2) Conserve/prevent loss of Na+ in stool
Describe the functions and physiological significance of both 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD type I) and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD type II).
- Cortisol can bind mineralcorticoid receptor
- 11β-HSD type II inactivates cortisol to cortisone in mineralcorticoid rich tissues
- 11β-HSD type I activates cortisone to cortisol in glucocorticoid rich tissues
What are the physiologic effects of 17α-hydroxylase deficiency?
1) Increased mineralcorticoids
2) Hypokalemia
3) Increased blood pressure
4) Decreased cortisol
5) Decreased androgens
What is the clinical presentation of 17α-hydroxylase deficiency in males?
- Ambiguious genitalia
- Undescended testes
What is the clinical presentation of 17α-hydroxylase deficiency in females?
Lack of secondary sexual characteristics
What are the physiologic effects of 21-hydroxylase deficiency in males?
1) Decreased mineralcorticoids
- Increased K+
- Decreased BP
2) Decreased cortisol
3) Increased androgens
What is the clinical presentation of 21-hydroxylase deficiency in females?
- Salt wasting
- Females have male genitalia (virilization)
What lab is diagnostic for 21-hydroxylase deficiency?
17-OH progesterone
What are the physiologic effects of 11β-hydroxylase deficiency?
1) Decreased aldosterone but increased DOC (precursor mineralcorticoid)
- Increased K+
- BUT INCREASED BP
2) Decreased cortisol
3) Increased androgens
What is the clinical presentation of 11β-hydroxylase deficiency?
Virilization
What is the difference between Cushing’s Syndrome and Cushing’s Disease?
Disease= increased cortisol due to pituitary tumor Syndrome= excessive endogenous or exogenous cortisol not from the pituitary
In Cushing’s Disease, what is the expected result of a high dose dexamethasone suppression test?
50% reduction in ACTH and cortisol
In an adrenal adenoma, what is the expected result of a high dose dexamethasone suppression test?
No reduction in cortisol or ACTH
*ACTH will be low
In ectopic ACTH production, what is the expected result of a high dose dexamethasone suppression test?
No reduction in cortisol or ACTH
*ACTH will be high
In iatrogenic cushing’s syndrome, what is the expected result of a high dose dexamethasone suppression test?
No reduction in ATCH or cortisol
*ACTH will be low
What catecholamine is predominantly produced by the chromaffin cells of the adrenal medulla?
Epinephrine
What enzyme catalyzes the rate-limiting step of catcholamine synthesis?
Tyrosine hydroxylase
How does NE get converted to Epi?
PNMT
What is required for the activation of PNMT?
Cortisol
Draw the major catabolic pathways of the catecholamines.
N/A
Which catecholamines have a greater effect at alpha and beta receptors?
Alpha= NE Beta= Epi
