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What receptor do principal cells in the cortical collecting duct express
Mineralocorticoid receptor
Which hormone normally activates MR in principal cells
Aldosterone
What is the primary effect of aldosterone on sodium in principal cells
Increased Na+ reabsorption
What potassium channel is upregulated by aldosterone in principal cells
ROMK
What ATPase is upregulated by MR activation in principal cells
Na+ K+ ATPase
Which glucocorticoid can also bind MR
Cortisol
Why does cortisol normally not activate MR in principal cells
Conversion to cortisone by 11β HSD2
What enzyme converts cortisol to cortisone in the kidney
11β HSD2
Is 11β HSD2 inducible or constitutive in principal cells
Constitutive
Can cortisone bind the mineralocorticoid receptor
No
What happens to cortisone after formation in principal cells
Exported and cleared
In normal physiology MR activation in principal cells reflects which hormone
Aldosterone
What happens when 11β HSD2 is inhibited or overwhelmed
Cortisol activates MR excessively
What sodium channel is increased when cortisol activates MR
ENaC
What electrolyte abnormality results from increased ENaC activity
Hypernatremia
What blood pressure effect results from excess MR activation
Hypertension
What potassium abnormality results from increased ROMK activity
Hypokalemia
What acid base disorder results from MR activation in intercalated cells
Metabolic alkalosis
Which disease can overwhelm 11β HSD2 due to high cortisol
Cushing syndrome
What substance in black licorice inhibits 11β HSD2
Glycyrrhetinic acid
What condition mimics hyperaldosteronism when 11β HSD2 is inhibited
Pseudo hyperaldosteronism
Which collecting duct cell type secretes hydrogen ions
Alpha intercalated cells
Which receptor do alpha intercalated cells express
Mineralocorticoid receptor
Do alpha intercalated cells express 11β HSD2
Yes
Which apical pump secretes hydrogen ions in alpha intercalated cells
H+ ATPase
Which apical exchanger secretes both hydrogen and potassium
H+ K+ ATPase
Which basolateral exchanger moves bicarbonate into blood
AE1
What ion is exchanged for bicarbonate by AE1
Chloride
How does excess aldosterone affect hydrogen secretion
Increases secretion
What enzyme generates new hydrogen and bicarbonate inside the cell
Carbonic anhydrase
What happens to intracellular bicarbonate during excess hydrogen secretion
Accumulates
How does bicarbonate exit alpha intercalated cells
Via AE1
What plasma change results from bicarbonate accumulation
Increased plasma bicarbonate
What acid base disorder results from this process
Metabolic alkalosis
Which enzyme converts cortisone to cortisol in the liver
11β HSD1
Where is 11β HSD1 primarily expressed
Hepatocytes
During what metabolic state is 11β HSD1 activity increased
Prolonged fasting
What metabolic pathway is enhanced by hepatic cortisol
Gluconeogenesis
Which hormones act with cortisol to maintain glucose during fasting
Glucagon and epinephrine
What is the renal role of 11β HSD2
Protect kidney from cortisol MR effects
What is the hepatic role of 11β HSD1
Amplify cortisol metabolic effects
What are the adrenal cortex layers from outer to inner
Glomerulosa fasciculata reticularis
Which adrenal layer produces aldosterone
Zona glomerulosa
Which adrenal layer produces cortisol
Zona fasciculata
Which adrenal layer produces DHEA
Zona reticularis
Which adrenal structure produces catecholamines
Medulla
What is the primary stimulus for aldosterone release
Angiotensin II
What electrolyte directly stimulates aldosterone secretion
Potassium
What pituitary hormone weakly stimulates aldosterone
ACTH
What hormone stimulates zona fasciculata
ACTH
What hormone stimulates zona reticularis
ACTH
Where is CRH produced
Paraventricular nucleus
Which neurons secrete CRH
Parvocellular neurons
How does CRH reach the anterior pituitary
Hypophyseal portal system
Which pituitary cells respond to CRH
Corticotrophs
What prohormone is secreted by corticotrophs
POMC
Which enzyme cleaves POMC into ACTH
PC1
Which adrenal zones respond to ACTH
Fasciculata and reticularis
What brain structure links stress to CRH release
Amygdala
Does stress directly release cortisol
No
What is the hormonal sequence from stress to cortisol
CRH then ACTH then cortisol
What two sites receive negative feedback from cortisol
Hypothalamus and pituitary
Do cortisol receptors mediating feedback have high or medium affinity
Medium
When is cortisol feedback strongest
When cortisol is elevated
Where is DHEA produced
Zona reticularis
What percentage of DHEA leaves the adrenal unchanged
About ninety percent
What fraction of DHEA is converted to testosterone in the adrenal
About ten percent
Which enzyme converts DHEA to androstenedione
3β HSD
Which enzyme converts androstenedione to testosterone
17β HSD
Which enzyme converts androgens to estrogens
Aromatase
Is aromatase present in the adrenal cortex
No
What tissues contain aromatase
Ovaries adipose skin
What is the main estrogen source before menopause
Ovaries
What percent of estrogen comes from adipose before menopause
About ten percent
What is the main estrogen source after menopause
Adipose tissue
What percent of estrogen comes from adipose after menopause
Up to seventy percent
What condition causes excess DHEA from high ACTH
ACTH dependent Cushing syndrome
What androgen related symptom may occur in females
Hirsutism
What reproductive effect can excess androgens cause
Amenorrhea
What does Cushing syndrome describe
Hypercortisolism from any cause
What does Cushing disease describe
Pituitary ACTH secreting adenoma
Which is more common endogenous cause
Cushing disease
What defines ACTH dependent Cushing syndrome
Excess ACTH driving cortisol
What defines ACTH independent Cushing syndrome
Autonomous adrenal cortisol secretion
What happens to ACTH in ACTH independent disease
Suppressed
What tumor causes Cushing disease
Corticotroph adenoma
Why does cortisol fail to suppress ACTH in Cushing disease
Tumor lacks cortisol receptors
What happens to CRH levels in Cushing disease
Suppressed
What happens to adrenal glands in chronic ACTH excess
Bilateral hyperplasia
What is a common source of ectopic ACTH
Small cell lung carcinoma
Can cortisol suppress ectopic ACTH secretion
No
What happens to adrenal size in ectopic ACTH syndrome
Hyperplasia
What causes metabolic alkalosis in hypercortisolism
Excess MR activation
What electrolyte abnormalities accompany alkalosis in Cushing syndrome
Hypokalemia
What blood pressure change occurs in chronic cortisol excess
Hypertension
What glucose abnormality occurs in Cushing syndrome
Hyperglycemia
What happens to muscle protein in chronic cortisol excess
Catabolism
What immune effect does cortisol have
Immunosuppression
What is the untreated five year survival of Cushing syndrome
About fifty percent