Adrenal gland

From Iusmphysiology

(Difference between revisions)
(Created page with '*continued here Endocrine control mechanism at 11:11AM on 03/02/11. ==Adrenal glands== *accidentally baleted notes ===Cortex=== ====Glucocorticoids==== *An impt stres…')
Line 4: Line 4:
==Adrenal glands==
==Adrenal glands==
 +
===Objectives===
-
*accidentally baleted notes
+
===Anatomy===
 +
*Next to the kidneys = "ad" "renal"
 +
*Have great blood supply.
 +
**Plumbing is different on the left and right sides.
 +
===Histology===
 +
*Two basic parts: cortex and medulla.
 +
*cortex:
 +
**mesodermal orgin
 +
**Zona glomerulosa
 +
**Zona fasciculata
 +
**Zona reticularis
 +
**GoFaRM = glomerulosa, fasciculata, reticularis, medulla
 +
*Medulla in th emidul
 +
**Ectodermal origin
 +
**Cats: epi, NE
 +
*Cortex on the outside of the whole organ
===Cortex===
===Cortex===
 +
*Part of the HPA axis (hypo, pit, adrenal)
 +
*Hypo makes CRH which is a positive secretory portal hormone
 +
*corticotropes in pit makes acth
 +
*ACTh has several roles on adrenal
 +
**Causes growth in addition to changes in synthesis at adrenal
 +
**Causes overgrowth in disease states
 +
*ACTH can be high when feedback loops are broken
 +
**I.e. cortisol not feedbinb back on hypo or pit, perhaps.
-
====Glucocorticoids====
+
*Separate types of feedback loops
-
*An impt stress response
+
**More when we talk about growth hormone.
-
*Glucocorticoids bind with HSPs then homodimerize to go into the nucleus to be a txn factor.
+
 
 +
====Corticotropin releasing hormone====
 +
*CRF = CRH
 +
*small peptide, hits receptor on pit cells
 +
*Promotes POMC production in corticotropes of pit
 +
*ACTH generated
 +
**39 aa peptide
 +
**AKA corticotropin
 +
**Affects steroidogenic cells of adrenal
 +
***Especially fasciculata and reticularis
 +
***Less role in glomerulosa
 +
 
 +
====ACTH====
 +
*Hits target in cortex of adrenal.
 +
*Binds to an MC2R (receptor)
 +
*Activates cAMP pathways
 +
 
 +
====Cortex regulation by renin-angiotensin and acth====
 +
*Glomerula makes aldosterone
 +
**Responds to reinin-angiotensin
 +
*Fasciculata makes cortisol
 +
**Resonds to ACTH
 +
*Reticularis makes DHEA
 +
**Responds to ACTH
 +
*Reticularis and fasciculata will atrophy if pit is removed.
 +
*All these products of these three zones are steroids.
 +
*Will not be tested on structure of steroids versus sterol.
 +
 
 +
===Zones of the adrenal gland===
 +
*Glomerulosa
 +
**Makes adlosterone and deoxycorticosterone
 +
*Fasciculata
 +
**Makes cortisol and corticosterone
 +
*Reticularis
 +
**Makes Adrostendione and DHEA
 +
*Medulla
 +
**CATS, mostly epi (adrenaline), some NE
 +
 
 +
===Zone histology===
 +
*There is discrete histology
 +
*Think of things as flowing stuff through the area
 +
**If an enzyme is missing, things flow in the other direction.
 +
what?
 +
 
 +
===Stress and the adrenals===
 +
*Short term stress:
 +
**Cats
 +
*Long term stress:
 +
**Corticosteroids via ACTH and the mineralocorticoids (not via ACTH)
 +
 
 +
===Steroidogenesis===
 +
*Structures are for help, not tested.
 +
*He likes this diagram b/c it is layered with the layers: glomerulosa, fasciculata, and reticularis. ("layerd version")
 +
*Estradiol and test are not made at significant amounts in the adrenal.
 +
**Mostly DHEA is made and put in blood
 +
**Test and est made elsewhere.
 +
 
 +
====Glucocorticoids (cortisol)====
 +
*Cortisol is the major glucocorticoid made in humans.
 +
**Released in circadian rhythm
 +
*Go example of thinking about cycles when measuring hormones in pts.
 +
*Stress is a major player in cortosol release
 +
**via CRH-ACTH axis
 +
*A hormone carried in blood by binding proteins.
 +
**Corticoseteroid binding globulin (CBG)
 +
**Albumin
 +
**Transcortin
 +
*Glucocorticoids bind on glucocorticoid receptors, then HSPs then homodimerize to go into the nucleus to be a txn factor.
 +
**Txn factors work with partner prots to affect txn.
 +
**for cortisol, gr does not work direclty with partner proteins.
 +
 
====Cortisol effects on various systems====
====Cortisol effects on various systems====
*Acts on many, many tissues.
*Acts on many, many tissues.
 +
*Read this, know this.
 +
*Most effects are "permissive"
-
====Mineralocorticoids====
+
====Mineralocorticoids (aldosterone)====
*Made by zona glomerulosa
*Made by zona glomerulosa
-
*Aldosterone
+
*Aldosterone is the major one
*Effects:
*Effects:
-
**Increases interstitial levels of ...?
+
**Increases interstitial Na (at the kidney); increases water retention
 +
**Decreases K+ and H+ (at the kidney)
 +
=====Regulation=====
 +
*Read this
-
*skipped some material
+
=====Pathway=====
 +
*Study this, he went really fast.
 +
*Aldosterone binds to cytoplasmic minteralocorticoid recetpors, uses HSPs, homodimersizes, etc.
 +
*Causes Na to be retained.
 +
=====Metabolism of adrenal steroids=====
 +
*You have to make hormone action discrete so we control half-life and such.
 +
*Body has two mechanisms:
 +
**Modifications to inactivate
 +
**Modifications to increase solubility
 +
***Allows loss at urine
 +
**Done by adding sugar groups, etc.
 +
*Metabolites can be key diagnositic tools
 +
**Can help identify tumors
 +
 +
=====A non-receptor mechanism...=====
 +
*Enzymes that convert excessive glucocorticoids into non-responsive, non-MR binders gives us a way to control signaling if there's too much aldosterone.
 +
 +
====Adnrogens====
 +
*Major = adrostendione and DHEA
 +
*These are not present much in the adrenals b/c they are produced where blood flow in the adrenal exits.
 +
 +
=====Adrenarch=====
 +
*Important for driving adrenarch.
 +
*This helps develop: pubic hair, auxillary hair, acne, and adult body odor.
 +
*one disease term is virulization; means that there is an excess of androgens and this axis is elevated
===Adrenal diseases===
===Adrenal diseases===
 +
*Can be of excess or of insufficiency.
====Addison's disease====
====Addison's disease====
*JFK had Addison's disease.
*JFK had Addison's disease.
-
*ADrenocortico insufficiency:
+
*Adrenocortico insufficiency:
-
**Too little cortisol
+
**Too little cortisol being produced
*Primary Cause:
*Primary Cause:
**Autoimmune
**Autoimmune
**Infectious
**Infectious
*Secondary cause
*Secondary cause
-
**PIt doesn't make enough ACTH (1 in 100K)
+
**Pit doesn't make enough ACTH
 +
**1 in 100K so rare
*Presentation:
*Presentation:
-
**Low cortisol,
+
**Low cortisol
-
**hypoglycemia,
+
**hypoglycemia
**high ACTH
**high ACTH
-
***b/c no feedback, could lead to adrenal hypertrophy,  
+
***b/c no feedback:
-
***could lead to odd coloring  
+
****could lead to adrenal hypertrophy,  
 +
****could lead to odd coloring b/c it increases ACTH which has the sequence of the MSH hormone so it can activate the MSHr
**high sex hormone precursors like ADHEA.
**high sex hormone precursors like ADHEA.
 +
**Loss of the aldosterone axis
 +
 +
====Adrenal insufficiency====
 +
*This diagram explains how to differentially diagnose adrenal issues.
 +
*It's a function of the ACTH and Cortisol levels
 +
**When ACTH is low...
 +
**If cortisol is low...
*Adrenal insufficiency occurs in pit in the 2nd and 3rd from the left.
*Adrenal insufficiency occurs in pit in the 2nd and 3rd from the left.
Line 54: Line 187:
*An umbrella term for overproduction of ACTH
*An umbrella term for overproduction of ACTH
**If it is a pit ACTH-producing tumor, then it is the disease.
**If it is a pit ACTH-producing tumor, then it is the disease.
 +
*Primary is adrenocorticol carcinoma or adenoma
 +
*Can also be caused by excessive exogenous glucocorticoids
 +
**And when stopped suddenly can cause an acute form of Addison's disease
-
====Cushing's disease====
+
====Cushing's '''disease'''====
 +
*A ''specific form of Cushing's syndrome''.
 +
**'''Secondary cushing's syndrome'''
*Tumor of the pit htat makes ACTH
*Tumor of the pit htat makes ACTH
*Similar outcome to syndrome (too much cortisol)
*Similar outcome to syndrome (too much cortisol)
Line 61: Line 199:
*Presentation:
*Presentation:
**Key are high bp and high blood sugar.
**Key are high bp and high blood sugar.
 +
Read it yourself
 +
**Recall that these are all caused by high levels of cortisols
====Other====
====Other====
-
*Other tumors that make ACTH or something that mimics ACTH.
+
*Other tumors (in other parts of the body) that make ACTH or something that mimics ACTH.
 +
**"Ectopic ACTH secretion"
 +
**A certain rare type of lung cancer does this.
====Hypoaldosteronism====
====Hypoaldosteronism====
 +
*These pts usually present with hyperkalemia and hyponatremia.
 +
**Also have orthostatic hypotension.
*He won't test us on enzyme names in the flow chart of steroid production.
*He won't test us on enzyme names in the flow chart of steroid production.
-
*spaced out a bit
+
====Primary aldosteronism====
-
 
+
*Conn syndrome
 +
**Production of aldosterone-producing adenoma.
 +
See slide
====Congenital adrenal hyperplasia====
====Congenital adrenal hyperplasia====
 +
*Babies tested at birth.
 +
*Deficiency of certain steroid synthesis enzymes
 +
*Low cortisol
 +
*High ACTH b/c of low feedback
 +
*Can be high androgens (not always)
 +
*1:16k, thus tested
 +
*Enzymes:
 +
**The enzyme missing affects the outcome
 +
**He named four major classes
 +
*Outcomes by outcome of deficiency:
 +
**Low mineralocorticoids
 +
***Vomiting due to salt wasting, dehydration, death
 +
**Excess mineralocoriticoids
 +
***Hypertension
 +
**Get the others.
 +
 +
=====21-hydroxylase deficiency=====
 +
*90% of CAH cases are this.
 +
*Prevalent in Askanazi jews.
 +
*Salt wasting
 +
*Low cortisols
 +
*High levels of androgen precursors
 +
**Leads to virulization
 +
 +
=====11-beta hydroxylase deficiency=====
 +
*Stops cortisol
 +
*build up of DHEA
 +
*You can make DOC, though, which can have corticosteroid affects.
 +
**Causes low-renin hypertension.
 +
*more rare
 +
 +
=====17-hydroxylase defciency=====
 +
*Got confused, read about it, see email.
 +
*The most rare.
 +
 +
=====3-hydroxysteroid dehydrogenase II=====
 +
*Low androgen, cortisol, and mineralocorticoids
 +
*Causes....
 +
 +
 +
====Catecholamine deficiencies====
 +
*Adrenal medulla can be seen as modified part of autonomic nervous system.
 +
**Fight or flight.
 +
*Cells are anlogous to autonomic postganglionic symp fibers.
 +
*main homrons are adrenaline and nor-adrenaline
 +
**From tyrosine
 +
**Main ring is a catechol
 +
*Which is made is determined by which enzymes are present.
 +
**Cells usually make one or the other, not both.
 +
**The enzyemes are methyl-transferases.
 +
***Use folate?
 +
*Made by chromaffin cells
 +
**Granules are produced that hold the cats
 +
**Can be released rapidly.
 +
*80% adrenaline, 20% noradrenaline.
 +
 +
=====Signaliing====
 +
*Adrennergic receptors
 +
**Alpha
 +
***Interact with epi and norepi
 +
**Beta
 +
***More specific for epi
 +
***Beta blockers
 +
 +
 +
*Pathways:
 +
**Alpha 1 is main positive signal
 +
**alpha 2 is a feedback and has some negative actions
 +
**Major actions; read them.
 +
 +
 +
*Metabolism:
 +
**We look for vanillic acid
 +
***A biproduct is vanillymandelic acid
 +
***found in urine for "certain diseases"
-
*stopped taking notes....
+
*medullary dysfunction
 +
**Hypofunction: orthostatic hypotnesion, low blood pressure, etc.
 +
***Often due to surgery to remove entire adrenal
 +
**Hyperfucntion:
 +
***Could be due to tumors or ectomic tumors (phaeochromocytomas)
 +
****Produces too much catecolamines
 +
****Often given blockers of adrenergic receptors
 +
****Elevated HR, bp, palpitations, sweating, headaches, psychiatric symptoms (religious delusions), et cetera.
 +
****Manic symptoms
*stopped here on 03/02/11 at 12PM.
*stopped here on 03/02/11 at 12PM.

Revision as of 17:46, 4 March 2011


Contents

Adrenal glands

Objectives

Anatomy

  • Next to the kidneys = "ad" "renal"
  • Have great blood supply.
    • Plumbing is different on the left and right sides.

Histology

  • Two basic parts: cortex and medulla.
  • cortex:
    • mesodermal orgin
    • Zona glomerulosa
    • Zona fasciculata
    • Zona reticularis
    • GoFaRM = glomerulosa, fasciculata, reticularis, medulla
  • Medulla in th emidul
    • Ectodermal origin
    • Cats: epi, NE
  • Cortex on the outside of the whole organ

Cortex

  • Part of the HPA axis (hypo, pit, adrenal)
  • Hypo makes CRH which is a positive secretory portal hormone
  • corticotropes in pit makes acth
  • ACTh has several roles on adrenal
    • Causes growth in addition to changes in synthesis at adrenal
    • Causes overgrowth in disease states
  • ACTH can be high when feedback loops are broken
    • I.e. cortisol not feedbinb back on hypo or pit, perhaps.


  • Separate types of feedback loops
    • More when we talk about growth hormone.

Corticotropin releasing hormone

  • CRF = CRH
  • small peptide, hits receptor on pit cells
  • Promotes POMC production in corticotropes of pit
  • ACTH generated
    • 39 aa peptide
    • AKA corticotropin
    • Affects steroidogenic cells of adrenal
      • Especially fasciculata and reticularis
      • Less role in glomerulosa

ACTH

  • Hits target in cortex of adrenal.
  • Binds to an MC2R (receptor)
  • Activates cAMP pathways

Cortex regulation by renin-angiotensin and acth

  • Glomerula makes aldosterone
    • Responds to reinin-angiotensin
  • Fasciculata makes cortisol
    • Resonds to ACTH
  • Reticularis makes DHEA
    • Responds to ACTH
  • Reticularis and fasciculata will atrophy if pit is removed.
  • All these products of these three zones are steroids.
  • Will not be tested on structure of steroids versus sterol.

Zones of the adrenal gland

  • Glomerulosa
    • Makes adlosterone and deoxycorticosterone
  • Fasciculata
    • Makes cortisol and corticosterone
  • Reticularis
    • Makes Adrostendione and DHEA
  • Medulla
    • CATS, mostly epi (adrenaline), some NE

Zone histology

  • There is discrete histology
  • Think of things as flowing stuff through the area
    • If an enzyme is missing, things flow in the other direction. 
what?

Stress and the adrenals

  • Short term stress:
    • Cats
  • Long term stress:
    • Corticosteroids via ACTH and the mineralocorticoids (not via ACTH)

Steroidogenesis

  • Structures are for help, not tested.
  • He likes this diagram b/c it is layered with the layers: glomerulosa, fasciculata, and reticularis. ("layerd version")
  • Estradiol and test are not made at significant amounts in the adrenal.
    • Mostly DHEA is made and put in blood
    • Test and est made elsewhere.

Glucocorticoids (cortisol)

  • Cortisol is the major glucocorticoid made in humans.
    • Released in circadian rhythm
  • Go example of thinking about cycles when measuring hormones in pts.
  • Stress is a major player in cortosol release
    • via CRH-ACTH axis
  • A hormone carried in blood by binding proteins.
    • Corticoseteroid binding globulin (CBG)
    • Albumin
    • Transcortin
  • Glucocorticoids bind on glucocorticoid receptors, then HSPs then homodimerize to go into the nucleus to be a txn factor.
    • Txn factors work with partner prots to affect txn.
    • for cortisol, gr does not work direclty with partner proteins.


Cortisol effects on various systems

  • Acts on many, many tissues.
  • Read this, know this.
  • Most effects are "permissive"

Mineralocorticoids (aldosterone)

  • Made by zona glomerulosa
  • Aldosterone is the major one
  • Effects:
    • Increases interstitial Na (at the kidney); increases water retention
    • Decreases K+ and H+ (at the kidney)
Regulation
  • Read this
Pathway
  • Study this, he went really fast.
  • Aldosterone binds to cytoplasmic minteralocorticoid recetpors, uses HSPs, homodimersizes, etc.
  • Causes Na to be retained.
Metabolism of adrenal steroids
  • You have to make hormone action discrete so we control half-life and such.
  • Body has two mechanisms:
    • Modifications to inactivate
    • Modifications to increase solubility
      • Allows loss at urine
    • Done by adding sugar groups, etc.
  • Metabolites can be key diagnositic tools
    • Can help identify tumors
A non-receptor mechanism...
  • Enzymes that convert excessive glucocorticoids into non-responsive, non-MR binders gives us a way to control signaling if there's too much aldosterone.

Adnrogens

  • Major = adrostendione and DHEA
  • These are not present much in the adrenals b/c they are produced where blood flow in the adrenal exits.
Adrenarch
  • Important for driving adrenarch.
  • This helps develop: pubic hair, auxillary hair, acne, and adult body odor.
  • one disease term is virulization; means that there is an excess of androgens and this axis is elevated

Adrenal diseases

  • Can be of excess or of insufficiency.

Addison's disease

  • JFK had Addison's disease.
  • Adrenocortico insufficiency:
    • Too little cortisol being produced
  • Primary Cause:
    • Autoimmune
    • Infectious
  • Secondary cause
    • Pit doesn't make enough ACTH
    • 1 in 100K so rare
  • Presentation:
    • Low cortisol
    • hypoglycemia
    • high ACTH
      • b/c no feedback:
        • could lead to adrenal hypertrophy,
        • could lead to odd coloring b/c it increases ACTH which has the sequence of the MSH hormone so it can activate the MSHr
    • high sex hormone precursors like ADHEA.
    • Loss of the aldosterone axis

Adrenal insufficiency

  • This diagram explains how to differentially diagnose adrenal issues.
  • It's a function of the ACTH and Cortisol levels
    • When ACTH is low...
    • If cortisol is low...
  • Adrenal insufficiency occurs in pit in the 2nd and 3rd from the left.

Cushing's syndrome

  • Diseases of excess of cortisol
  • Could be an adrenal tumor making too much cortisol.
  • Causes really low ACTH b/c lots of feedback on the Pit
  • An umbrella term for overproduction of ACTH
    • If it is a pit ACTH-producing tumor, then it is the disease.
  • Primary is adrenocorticol carcinoma or adenoma
  • Can also be caused by excessive exogenous glucocorticoids
    • And when stopped suddenly can cause an acute form of Addison's disease

Cushing's disease

  • A specific form of Cushing's syndrome.
    • Secondary cushing's syndrome
  • Tumor of the pit htat makes ACTH
  • Similar outcome to syndrome (too much cortisol)
  • Can tell the diff b/c ACTH is high.
  • Presentation:
    • Key are high bp and high blood sugar. 
Read it yourself
    • Recall that these are all caused by high levels of cortisols

Other

  • Other tumors (in other parts of the body) that make ACTH or something that mimics ACTH.
    • "Ectopic ACTH secretion"
    • A certain rare type of lung cancer does this.

Hypoaldosteronism

  • These pts usually present with hyperkalemia and hyponatremia.
    • Also have orthostatic hypotension.
  • He won't test us on enzyme names in the flow chart of steroid production.


Primary aldosteronism

  • Conn syndrome
    • Production of aldosterone-producing adenoma. 
See slide

Congenital adrenal hyperplasia

  • Babies tested at birth.
  • Deficiency of certain steroid synthesis enzymes
  • Low cortisol
  • High ACTH b/c of low feedback
  • Can be high androgens (not always)
  • 1:16k, thus tested
  • Enzymes:
    • The enzyme missing affects the outcome
    • He named four major classes
  • Outcomes by outcome of deficiency:
    • Low mineralocorticoids
      • Vomiting due to salt wasting, dehydration, death
    • Excess mineralocoriticoids
      • Hypertension
    • Get the others.
21-hydroxylase deficiency
  • 90% of CAH cases are this.
  • Prevalent in Askanazi jews.
  • Salt wasting
  • Low cortisols
  • High levels of androgen precursors
    • Leads to virulization
11-beta hydroxylase deficiency
  • Stops cortisol
  • build up of DHEA
  • You can make DOC, though, which can have corticosteroid affects.
    • Causes low-renin hypertension.
  • more rare
17-hydroxylase defciency
  • Got confused, read about it, see email.
  • The most rare.
3-hydroxysteroid dehydrogenase II
  • Low androgen, cortisol, and mineralocorticoids
  • Causes....


Catecholamine deficiencies

  • Adrenal medulla can be seen as modified part of autonomic nervous system.
    • Fight or flight.
  • Cells are anlogous to autonomic postganglionic symp fibers.
  • main homrons are adrenaline and nor-adrenaline
    • From tyrosine
    • Main ring is a catechol
  • Which is made is determined by which enzymes are present.
    • Cells usually make one or the other, not both.
    • The enzyemes are methyl-transferases.
      • Use folate?
  • Made by chromaffin cells
    • Granules are produced that hold the cats
    • Can be released rapidly.
  • 80% adrenaline, 20% noradrenaline.

=Signaliing

  • Adrennergic receptors
    • Alpha
      • Interact with epi and norepi
    • Beta
      • More specific for epi
      • Beta blockers


  • Pathways:
    • Alpha 1 is main positive signal
    • alpha 2 is a feedback and has some negative actions
    • Major actions; read them.


  • Metabolism:
    • We look for vanillic acid
      • A biproduct is vanillymandelic acid
      • found in urine for "certain diseases"


  • medullary dysfunction
    • Hypofunction: orthostatic hypotnesion, low blood pressure, etc.
      • Often due to surgery to remove entire adrenal
    • Hyperfucntion:
      • Could be due to tumors or ectomic tumors (phaeochromocytomas)
        • Produces too much catecolamines
        • Often given blockers of adrenergic receptors
        • Elevated HR, bp, palpitations, sweating, headaches, psychiatric symptoms (religious delusions), et cetera.
        • Manic symptoms


  • stopped here on 03/02/11 at 12PM.
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