Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

FHB Exam 4 > Endocrine 6: adrenal glands continued > Flashcards

Endocrine 6: adrenal glands continued Flashcards

1
Q

Define mineralocorticoids.

A
  • steroid hormones that affect water and sodium balance
  • primarily aldosterone
  • other steroids can have the same effect (ex: 11-deoxycorticosterone (DOC), which is an aldosterone precursor)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Where are the aldosterone sites of action?

A
  • kidney DT
  • colon
  • salivary duct
  • sweat ducts
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Describe aldosterone’s mechanism of action at its main target site, the kidney.

A

Overall: increased K excretion, increased Na and water reabsorption

  • increased extracellular K stimulates aldosterone
  • aldosterone stimulates Na/K ATPase to kick K out and bring Na back in
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How does the Renin-Angiotensin system regulate Aldosterone (RATA)?

A
  • decreased blood volume and blood pressure signals renin release from JGA of the kidney
  • angiotensinogen is released from the liver
  • renin cleaves angiotensinogen to angiotensin I
  • ACE converts that to angiotensin II
  • angiotensin II acts as a vasoconstrictor AND stimulates aldosterone release from the adrenal cortex ZG
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Compare and contrast the mechanisms of action of Aldosterone and AVP on osmoregulation.

A

ALDOSTERONE

  • regulates extracellular volume
  • stimulates Na and water reabsorption at the kidney
  • stimulates K excretion
  • increases blood volume and pressure

AVP

  • regulates free water balance
  • increases water permeability of distal tubule to stimulate water retention
  • decreases osmolarity, which affects sodium balance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe aldosterone action inside the cell.

A
  • target cell = mineralocorticoid target cell
  • binds to MR-chaperone
  • chaperone protein dissociates
  • MR-aldosterone translocated to nucleus
  • acts as TF
  • –> signals inactivation of cortisol by converting it to cortisone via 11B-HSD2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe inactivation and reactivation of cortisol.

A
  • in MR cells, cortisol => cortisone via 11B-HSD2 (dehydrogenase)
  • in GR cells, cortisone => cortisol via 11B-HSD1 (reductase)
  • process is dependent on NADPH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is carbenoxolone?

A

drug that inhibits 11B-HSD2
=> unable to inactivate cortisol
=> excess binding to MR
=> excess aldosterone functions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What drugs block 11B-HSD2?

A
  • carbenoxolone

- licorice

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe the relationship between cortisol, 11B-HSD1, and T2DM.

A
  • local production of 11B-HSD1 leads to increased cortisol
  • increased cortisol => excess MR binding
  • leads to increased local water retention
  • can lead to obesity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the main function of the zona reticularis?

A

makes weak androgens (DHEA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Characterize the weak androgens/DHEA.

A
  • low affinity for androgen receptors
  • serve as precursors for higher affinity androgens (testosterone and estrogen)
  • metabolite = androstenedione
  • decline with age (after 30)
  • increases libido in women (primary source of androgen and estrogen in postmenopausal women)
  • responsible for adrenarche (axillary and pubic hair)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Overview the cholesterol precursor biosynthetic pathway.

A
  1. cholesterol is synthesized in the cytosol or taken in by HDL/LDL
  2. cholesterol enters the mitochondria via StAR protein and enzyme P450scc/desmolase/gene CYP11A1 (activated by ACTH)
  3. inside the mitochondria, it becomes pregnenolone, which is needed for all subsequent pathways
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the significance of the enzyme 3B-HSD?

A
  • in the ZG and ZF, this enzyme is required to change pregnenolone to progesterone
  • converts delta 5 to delta 4 double bonds
  • hence, these zones are called delta 4 pathways, while ZR is a delta 5 pathway
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the mechanism of hormone production in the Zona Fasciculata?

A
  1. cholesterol => pregnenolone (P450scc/desmolase/CYP11A1)
  2. pregnenolone => progesterone (3B-HSD
  3. progesterone => 17-OH-progesterone (17-hydroxylase/CYP17)
  4. 17-OH-progesterone => 11-deoxycortisol (21-hydroxylase/CYP21A2)
  5. 11-deoxycortisol => cortisol (11-hydroxylase/CYP11B1)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

List the important enzymes of cortisol production.

A

ZF

  1. P450scc/desmolase/CYP11A1
  2. 3B-HSD
  3. 17-hydroxylase/CYP17
  4. 21-hydroxylase/CYP21A2
  5. 11-hydroxylase/CYP11B1
17
Q

Where is 17-hydroxylase made?

A

only in ZF and ZR

18
Q

Where is CYP11B2 made?

A

only in ZG

19
Q

Describe what a 21-hydroxylase deficiency can lead to.

A
  • most common cause of Congenital Adrenal Hyperplasia
  • cannot make cortisol => no negative feedback => excess ACTH => constant stimulation of adrenals => proliferation and hyperplasia => excess DHEA, no glucocorticoids, no mineralocorticoids
  • Sx: masculinization (virilization), ambiguous genitalia, sodium loss/hypotension, hyperkalemia, high plasma renin (no aldosterone), high ACTH
20
Q

Explain the symptoms of 21-hydroxylase deficiency.

A
  • excess ACTH b/c loss of negative feedback mediated by cortisol
  • excess DHEA b/c constant stimulation of HPA
  • no aldosterone/MR activity => can’t control osmolarity => excess renin => loss of sodium and water => hypotension
  • masculinization and ambiguous genitalia due to excess DHEA/androgens
21
Q

What is the mechanism of hormone production in the Zona Glomerulosa?

A
  1. cholesterol => pregnenolone (P450scc/desmolase/CYP11A1)
  2. prenenolone => progesterone (3B-HSD)
  3. progesterone => 11-deoxycorticosterone (11-DOC) (21-hydroxylase/CYP21A2)
  4. 11-DOC => corticosterone (11-hydroxylase/CYP11B2)
  5. corticosterone => 18-OH-corticosterone (18-hydroxylase/CYP11B2)
  6. 18-OH-corticosterone => aldosterone (18-oxidase/CYP11B2)
22
Q

List the important enzymes in the zona glomerulosa.

A
  1. P450scc/desmolase/CYP11A1
  2. 3B-HSD
  3. 21-hydroxylase/CYP21A2
  4. CYP11B2 - 11-hydroxylase
  5. CYP11B2 - 18-hydroxylase
  6. CYP11B2 - 18-oxidase
23
Q

Contrast CYP11B1 to CYP11B2.

A

CYP11B1 - found in ZF

  • 11-hydroxylase
  • converts 11-deoxycortisol to cortisol in the ZF
  • stimulated by ACTH

CYP11B2 - found in ZG

  • 11-hydroxylase (11-DOC => corticosterone)
  • 18-hydroxylase (corticosterone => 18-OH-corticosterone)
  • 18-oxidase (18-OH-corticosterone => aldosterone)
  • stimulated by RATA
24
Q

What is the CYP11B2 complex called?

A

aldosterone synthase

25
Q

Describe what an 11-hydroxylase/CYP11B1 deficiency can lead to.

A
  • 2nd main cause of CAH
  • cannot produce cortisol in ZF => excess ACTH due to loss of negative feedback
  • increased DHEA/androgens due to constant stimulation of adrenals
  • low aldosterone
  • high MR activity
  • Sx: hypertension, hypokalemia, masculinization
26
Q

Explain the symptoms of CYP11B1/11-hydroxylase activity.

A
  • excess ACTH due to loss of negative feedback mediated by cortisol
  • excess ACTH stimulation of adrenals leads to excess DHEA/androgens => masculinization, CAH
  • buildup of progesterone in ZF will cause 21-hydroxylase/CYP21A2 to push it into a parallel pathway that produces 11-DOC => acts as MR => stimulates sodium and water retention => hypertension and hypokalemia
  • b/c the excess MR activity by 11-DOC is keeping blood pressure high, renin will not stimulate aldosterone production => low levels of aldosterone
27
Q

Describe the mechanism of hormone production in the Zona Reticularis.

A

ZR (delta 5 pathway)

  1. cholesterol => pregnenolone (P450scc/desmolase/CYP11A1)
  2. pregnenolone => 17-OH-pregnenolone (17-hydroxylase/CYP17)
  3. 17-OH-pregnenolone => DHEA (CYP17)
  4. DHEA => DHEAS
  5. DHEA => androstenedione (minor product)
28
Q

List the important enzymes of the Zona Reticularis.

A
  1. P450scc/desmolase/CYP11A1
  2. 17-hydroxylase/CYP17
  3. CYP17
29
Q

Describe what a 17-hydroxylase/CYP17 deficiency can lead to.

A
  • rare cause of CAH
  • no cortisol, no DHEA => high ACTH
  • excess 11-DOC => low aldosterone, high MR activity
  • Sx: hypertension, hypokalemia, feminization, pseudohermaphaditism,
30
Q

Compare the symptoms of 21-hydroxylase/CYP21A2, 11-hydroxylase/CYP11B1, and 17-hydroxylase/CYP17.

A

21-hydroxylase = cannot make cortisol or aldosterone
- excess ACTH => excess DHEA => CAH, masculinization, ambiguous genitalia
- no aldosterone/MR (can’t make 11-DOC) => renin is stimulating the ZG but no aldosterone released in response to low BP => continued loss of sodium and water => hypotension, hyperkalemia => high plasma renin
OVERALL: no cortisol, no aldosterone, excess DHEA (masculinization, hypotension)

11-Hydroxylase/CYP11B1 = cannot make cortisol
- excess ACTH => excess DHEA => CAH, masculinization, ambiguous genitalia
- excess 11-DOC => excess MR activity => sodium and water reabsorption => hypertension, hypokalemia
- high blood volume and blood pressure => no renin stimulation => low aldosterone
OVERALL: no cortisol, excess 11-DOC/MR, excess DHEA (maculinization, hypertension)

17-hydroxylase/CYP17 = cannot make cortisol or DHEA
- excess ACTH
- feminization (pseudohermaphaditism) due to low DHEA
- excess 11-DOC => hypertension, hypokalemia
- low aldosterone
OVERALL: no cortisol, no DHEA (feminization, hypertension)

31
Q

List the ACTH targets and their effects in the adrenal.

A
  1. activates StAR => steroid biosynthesis
  2. stimulates cellular hypertrophy, cortisol synthesis, DHEA (CYP17), 11-hydroxylase (CYP11B1)
  3. dopamine to norepinephrine in the medulla
32
Q

Define chromaffin cells.

A
  • adrenal medulla cells
  • mostly release epinephrine
  • under sympathetic control
  • require cortisol to convert norepi to epi in the medulla
33
Q

What are the physiological effects of epinephrine?

A
  • arousal: pupil dilation, sweating, bronchial relaxation
  • metabolic: gluconeogenesis in the liver, breakdown of fat and glycogen to release glucose
  • cardiovascular: vasoconstriction of blood, increased HR
34
Q

What stimulates epinephrine release?

A
  • acute stress
  • cortisol
  • sympathetic stimulation
    => characterized by rapid release and rapid return
35
Q

Compare the acute and long-term stress responses.

A

Acute = catecholamines

  • stimulated by sympathetics
  • norepinephrine stimulates CRH
  • norepinephrine has short term responses (arousal)

Long-Term = cortisol

  • stimulated by CRH and HPA axis
  • negative feedback loop
  • inhibits rest and digest, immune, inflammation
  • creates epinephrine
36
Q

Recall the metabolism and excretion of catecholamines.

A
  • facilitated by MAO and COMT
  • creates metanephrine/noremetanephrine metabolites
  • MAO+AD and COMT lead to VMA
  • VMA in urine used diagnostically to test for catecholamine releasing tumors
37
Q

Define pheochromocytomas.

A
  • chromaffin cell tumor leads to catecholamine overproduction
  • Sx: unresponsive HTN, migraines, tachycardia
  • DDx: urinary VMA
  • Tx: surgery, alpha/beta-blockers
38
Q

Why are pheochromocytomas the 10% tumor?

A
  • 10% malignant
  • 10% lead to stroke
  • 10% recurrence after surgery
  • 10% bilateral
  • 10% children
  • 10% familial
  • 10% extra-adrenal
  • 10% present with MEN

FHB Exam 4 (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions