Adrenal gland sympathoadrenal system
Download
1 / 33

ADRENAL GLAND; SYMPATHOADRENAL SYSTEM - PowerPoint PPT Presentation


  • 111 Views
  • Uploaded on

ADRENAL GLAND; SYMPATHOADRENAL SYSTEM. Adrenal Gland. 3 arterial supply sources Perfuse gland Periph  center Sinusoids Medulla receives blood w/ cortex prod’s Medulla has own arterial supply. Medulla, cortex diff embryo origins Cortex from posterior abdominal wall lining

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' ADRENAL GLAND; SYMPATHOADRENAL SYSTEM ' - gertrude-lehmann


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

Adrenal gland
Adrenal Gland

  • 3 arterial supply sources

    • Perfuse gland

      • Periph  center

      • Sinusoids

      • Medulla receives blood w/ cortex prod’s

    • Medulla has own arterial supply


  • Medulla, cortex diff embryo origins

    • Cortex from posterior abdominal wall lining

    • Medullary pheochromocytes from sympathogonia

      • Neural crest cells

      • Also give rise to neuroblasts;  sympathetic ganglia

  • SF-1 req’d for adrenal gland dev’t

    • Also gonads, ventromedial nucleus of hypothal

    • Also DAX-1 req’d

  • During dev’t, pheochromoblasts migrate to other areas (aorta, organ of Zuckerkandl)


Adrenal cortex
Adrenal Cortex

  • Produces steroid hormones

  • Cholesterol-processing enz’s in sER, inner mitoch membr

    • Tubulovesicular mitoch

      • Much inner membr surface area

      • Much P450scc

  • Parenchymal cells can produce cholesterol de novo

    • Mainly endocytosis of LDL

    • Cholesterol-rich lipid droplets in cytoplasm

  • Capsule + 3 cell layers


Adrenal medulla
Adrenal Medulla

  • Mod’d sympathetic ganglion

    • BUT no axons at targets

    • Release catecholamines to ECF  bloodstream

  • Cells = pheochromocytes

    • Axonless secr cells

    • Two cell subpopulations

      • Same cell pop’n under diff physiologic states

        • Concent cortisol exposure

      • Noradrenaline (norepinephrine) producing cells

      • Adrenaline (epinephrine) producing cells

    • Secrete prod’s from granules  ECF by exocytosis


Catecholamines
Catecholamines

  • Synth’d from L-tyrosine

  • Dopamine, noradrenaline, adrenaline

  • L-tyr in plasma (1-1.5 mg/dL)

  • Active transport into cells

  • Conversion L-tyr by 4 enz’s

    • Compartmentalized

  • Adrenal medulla catecholamine output approx 80% adrenaline

    • BUT plasma ratio 9:1 noradrenaline: adrenaline


1 tyrosine hydroxylase
1) Tyrosine Hydroxylase

  •  Ring hydroxylation to L-DOPA (L-Dihydroxy-PhenylAlanine)

  • Contains Fe+2; tetrahydrobiopterin cofactor

  • Activity reg’d by preganglionic nerves

    • Get phosph’n PKA, PKC and calmodulin-dependent kinases

  • Long-term stim’n  upreg’n transcription, translation

  • Incr’d L-DOPA  prod inhib’n


2 dopa decarboxylase aromatic l amino acid decarboxylase
2) DOPA Decarboxylase (aromatic L-amino acid decarboxylase)

  • Pyridoxal phosphate cofactor

  • End product in CNS

  • Stored in secretory vesicles

    • Enter by active transport

    • MVATs (Vesicular MonoAmine Transporters)


3 dopamine b hydroxylase dbh
3) Dopamine b-Hydroxylase (DBH)

  •  side chain hydroxylation to noradrenaline

  • Contains Cu; Vit C cofactor

  • Rxn w/in secretory vesicle

  • End prod in symp nerves, most central catecholaminergic neural tracts


4 phenylethanolamine n methyltransferase pnmt
4) Phenylethanolamine N-MethylTransferase (PNMT)

  •  N-methylation to adrenaline

  • Methyl donor = S-AdenosylMethionine

  • Cytoplasmic

    • Noradrenaline leaves vesicle

      • Passive transport

      • Concent gradient

    • Adrenaline must reenter secretory vesicle

      • Active transport


PNMT

  • Expression depends on high local cortisol

    • From adrenal cortex

    • Through sinusoid system

  • Transcr’l activation of PNMT gene through ligand-act’d glucocort receptor

    • Also other transcription factors

  • Also activity stim’d by glucocort

  • Adrenaline  prod feedback inhib’n

  • Also found in kidney, lung, pancreas

  • Also nonspecific NMT

    • Contributes to periph conversion norepi to epi


Secretory vesicles
Secretory Vesicles

  • Catecholamine storage

  • Active transport via VMATs

    • ATP-driven proton pump

    • In vesicle membranes

    • pH, electrical gradient

    • Antiporter

  • 12 transmembr helical segments

    • Related to plasma membr monoamine transporters


Catecholamine release from storage vesicles
Catecholamine Release from Storage Vesicles

  • ACh rel’d from preganglionic fibers

    •  Nicotinic receptors

    • Get depol’n pheochromocytes

    •  act’n voltage-gated Ca channels

    •  influx Ca

    •  exocytosis of secretory vesicles

      • Chromogranins, DBH, ATP, other peptides released


Actions of catecholamines
Actions of Catecholamines

  • Circ’ng catecholamines reach most tissues

    • BUT cannot penetrate

      • BBB

      • Fetus

    • Fetal prod’n (mostly norepi) through fetal zone

      • Impt in intrauterine life (cardiovascular responses)

      • Large

      • Placenta expresses catecholamine degrading enzymes

  • Placental norepi transporter

    • Delivers circ’ng fetal chatechol’s for degrad’n


Adrenergic receptors
Adrenergic Receptors

  • Heptahelical, G-prot-linked transmembr receptors

  • 2 categories: a and b, subcategories

  • a – affinity for adrenaline > noradrenaline

    • a1 (A, B, D) mostly use Gaq G prot’s

      • Usually activate PLC ( PKC and DAG and intracell Ca through IP3)

      • And/or activate PLA2

    • a2 (A, B, C) varied

      • Gai and G0 couple to decr’d activity adenylyl cyclase

      • Can  act’n K+ channels, inhib’n Ca channels, act’n PLC and/or PLA2

  • b – affinity for adrenaline > noradrenaline

    • All (1, 2, 3) use Gas G prot  act’n ad cyclase


Tissue

Receptor Subtype

Heart

beta1

Adipose tissue

beta1beta3?

Vascular Smooth Muscle

beta2

Airway Smooth Muscle

beta2


Physiological implications of sympathoadrenal catecholamines
Physiological Implications of Sympathoadrenal Catecholamines

  • Gen’l: activates fight/flight mech’s

    • Mobilizes energy, redist’s blood

  • Opposes parasymp

    • Promotes digestion, storage of energy

    • BUT distinct target cell pop’ns w/in organs

  • Many targets; overall

    • Incr’s cardiac output, blood pressure

    • Bronchodilation  matched perfusion w/ incr’d ventilation

    • Blood diverted from viscera and skin to muscle

      • Retain blood to brain

    • Mobilize fuel from energy stores


  • Stress  sympathoadrenergic, adrenocortical systems activated simultaneously

    • Catecholamines instantaneous action

      • From adrenal medulla and symp neurons

      • Rapid elimin’n w/ end release

    • Cortisol delayed 20-30 mins, action prolonged

  • Involved in body weight regulation

    • Leptin secr’d by adipocytes

      • Acts on hypothal  decr’d appetite, incr’d energy expenditure

    • Adipocytes have b3 receptors

      • More responsive to norepi

    • Stim’n receptors  enhanced lipolysis  red’n fat stores  decr’d leptin

  • BUT apparently not mediated through adrenal medulla


Dopamine
Dopamine

  • Five receptor types

    • All G-prot coupled heptahelical

    • D1 stim’s adenylyl cyclase

      •  vasodilation in splachnic region

    • D2 inhibits adenylyl cyclase

  • Impt: antihypertensive, natriuretic through autocrine/paracrine mech’s

    • Opposes aldosterone


Catecholamine elimination
Catecholamine Elimination

  • Short-lived mol’s

    • 10 sec to 1.7 min

  • 50-60% assoc’d w/ albumin

  • Elimin’n

    • At synapse, ISF near symp neurons

      • Reuptake into nerve terminals

      • Reenter vesicles via VMAT OR

      • Become degraded by MAO

    • In target cells

      • Degraded by Catechol-O-MethylTransferase (COMT)

    • 5% directly filtered into urine


  • MAO

    • In outer mitoch membr

    • Substr’s also serotonin, histamine

    • Oxidizes amino grp  aldehydes

    • Further ox’d by nonspecific aldehyde deHase

    • Ultimate prod dihydroxymandelic acid (DOMA)

  • COMT – extraneuronal degradation

    • Uses SAM as methyl donor

    • Impt to circ’g catecholamines

  • Get final conjugation

    • Sulfate, glucuronate in liver, gut

    • Excr’n through urine


ad