L73: Adrenal Gland Flashcards
What are mineralocorticoids?
Hormones secreted in the Zona Glomerulosa of the Adrenal Cortex that promotes sodium retention and water retention in the kidney
Aldosterone
What enzyme is found in Zona Glomerulosa cells that allow them to produce Aldosterone?
Aldosterone Synthase
What are the target tissues of Aldosterone?
MR highly expressed in: Distal Tubule Colon Salivary Ducts Sweat Ducts
What does Aldosterone do?
Stimulate sodium and water reabsorption
Increases potassium secretion
How does aldosterone cause its effects?
Increases transepithelial Na+ transport in distal tubule and collecting duct of nephron
Increases potassium excretion in collecting duct cells
What stimulates Aldosterone release?
Increases in EC fluid K+ conc.
How does the Renin-Angiotensin-Aldosteron System work?
Decreased BP stimulates renin release from kidney from JGA -> Renin cleaves angiotensinogen from liver to angiotensin I -> ACE converts angiotensin II -> Vasocontrictor and stimulates Aldosterone release
What is the net result of Aldosterone secretion?
Increased EC fuid volume and increased BP
What is the net result of AVP/ADH?
STimulate distal nephron water permeability -> increased water retention -> decreases plasma osmolality and decreases sodium concentration in blood
What does Mineralocorticoid receptor (MR) bind?
Binds with high affinity to both glucocorticoids and mineralocorticoids
Does Aldosterone have a specific binding protein?
No
What inactivates glucocorticoids in the kidney?
11B-HSD Type II converts cortisol to cortisone and thus inactivates it
What does Carbenoxolone do?
Inhibit 11B HSD2 -> excess MR activation
What produces similar results as Carbenoxolone?
Licorice: inhibit 11B HSD2 -> increased sodium and water retention with excessive consumption
What enzyme converts cortisone back to cortisol?
11B HSD1 : potential DM T2 drug target
What is produced in the Zona Reticularis of hte Adrenal Cortex?
Adrenal Androgens: DHEA
What is DHEA?
Precursor for testosterone and estrogen
Declines with age
Weak androgen due to low binding affinity for androgen receptors
What is the first step in steroid hormone biosyntehsis?
Conversion of cholesterol to pregnenolone
How are adrenal steroid hormones synthesized?
Cholesterol imported into cell as LDL or HDL -> STAR transports cholesterol form outer mitochondria to inner mitochondria (rate limiting step) -> Converted to pregnenolone by CYP11A1(P450scc)
What does cholesterol ester hydrolase do?
Esterifies cholesterol; Stimulated by ACTH
What are the common causes of congenital adrenal hyperplasia (CAH)?
21a hydroxylase deficiency
11B hydroxylase deficiency
Both lead to excess ACTH stimulation of cortex due to lack of negative feedback
What does 21ahydroxylase deficiency lead to?
Excess DHEA
No glucocorticoids or mineralocoritcoids
Sx: Virilization (masculinization), ambiguous genitalia, sodium loss
What does 11B hydroxylase deficiency lead to?
Salt and water retention due to excess mineralocorticoid activity
Where are 21a-hydroxylase found in the Adrenal Cortex? What is its gene code
CYP21A2
Z. Fasciculata and Z.Glomerulosa
Where are 11 hydroxylase found in the Adrenal Cortex? What is its gene code
CYP11B1/CYP11B2
Z. Fasciculata and Z.Glomerulosa
Where are 17a-hydroxylase found in the Adrenal Cortex? What is its gene code
CYP17
Z.Fasciculata and Z.Reticularis
Where are Aldosterone Synthase found in the Adrenal Cortex? What is its gene code
CYP11B2
ZGlomerulosa
Where are Desmolase/P450scc found in the Adrenal Cortex? What is its gene code
CYP11A1
All
What is the major cell type found in the adrenal medulla?
Chromaffin cells (Pheochromocytes)
What causes Epi/NE release from the adrenal medulla?
Sympathetic nerve stimulation (ACh)
What innervates the adrenal medulla?
Splanchnic nerve
Where is epinephrine synthesized?
Only in the adrenal medulla
When is epinephrine release?
As response to acute stress
Rapid activation and rapid return
How do peripheral nerves release NE
Convert dopamine to norepinephrine
What does cortisol do in the adrenal medulla?
Stimulate conversion of NE to epinephrine (only in adrenal medulla)
What are the physiological effects of Epi?
Act through adrenergic receptors (a and B)
Arousal: pupil dilation, sweating, GI and bronchial muscle relaxation
Metabolic: glucose release, inc metabolic rate
CV: vasoconstriction, tachycardia
What are the 3 main targets for the metabolic effects of Epinephrine?
Muscle:Increase glycogenolysis, dec glucose uptake
Fat: inc lipolysis, dec glucose uptake
Liver: inc gycogenolysis, inc gluconeogenesis,inc glucose release, inc ketogenesis
How does epinephrine affect pancreatic hormone secretio?
decrease insulin
increase glucagon
How do cortisol and Epi work together to deal with a stress response?
Cortisol: CRH ->Pituitary->ACTH ->Adrenal Cortex -> Cortisol
Epi: Sympathetic neurons in hypothalamus -> spinal cord-> adrenal medulla -> epinephrine
Result: Increase energy mobilization and redistribution, cardiovascular response inc, arousal, behavioral activaiton, aggression
How are catecholeamines metabolized?
Short half life
Degraded by COMT or MAO to produce VMA which is excreted in urine
How can VMA levels be clnically useful?
Metabolic byproduct of catecholeamines
Detect tumors producing excess Epi/NE
What are pheochromocytomas?
The 10% tumor
Tumors of chromaffin cells leading to catecholeamine overproduction
What are the symptoms of pheochromocytomas? How is it treated?
HTN wihtout response to medication
Headaches
Tachycardia
Treatment: surgery and alpha/beta blockers pre surgery
Where are the pheochromocytomas found?
Extra-adrenal sites (10%): Sympathetic nerve chain, distal aorta, ureter, urinary bladder
Adrenal Glands (90%)
Why are pheochromocytomas called the 10% tumor?
10% are: Malignant Bilateral In children Familial Recur MEN Syndrome Stroke presented with Extraadrenal
