Adrenal gland

From Iusmphysiology

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*80% adrenaline, 20% noradrenaline.
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*Adrennergic receptors
*Adrennergic receptors
**Alpha
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Revision as of 17:51, 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.
    • "I mislabeled the diagram – 17 hydroxylase is enzyme 3a not 3b – therefore low androgens and cortisol result. You can get high levels of DOC and therefore hypertension and hypokalemia. Due to the renin control system, aldosterone levels are not high."
  • 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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