Zusammenfassung der Ressource
The adrenal gland
- Learning objectives:
- medulla/cortex - steroid hormone synthesis,
mechanism of action
- Glucocorticoids - physiological effects, therapeutic use, HPA axis
- Mineralocorticoids - effects on Na+ and water metabolism
- Disfunctions of adrenal cortex; adrenal medulla
- Adrenalin and noradrenaline - review of
adrenergic receptors - fight or flight
- Adrenal cortex and
adrenal medulla
- Adrenal cortex:
Anmerkungen:
- Outer part of adrenal gland—produces hormones, such as cortisol (helps regulate metabolism and bodies response to stress) and aldosterone (helps control blood pressure
- corticosteroids
- regulation of metabolic processes
- regulation of K+ and Na+ blood levels
- control of volume of extracellular fluid
- adaptive
changes over
minutes, days,
months
- Adrenal medulla:
Anmerkungen:
- Inner part of an adrenal gland - controls hormones- help you cope with physical and emotional stress.
Main hormones secreted include epinephrine (adrenaline) and norepinephrine (noradrenaline), which have similar functions.
- adrenaline and noradrenaline (epinephrine and norepinephrine)
- responsiveness to stressors - fight or flight
- regulation of metabolic processes
- adaptove changes
over within
seconds to
minutes
- Adrenal gland -
histology
- different zones
produce different
hormones
- CORTEX
- Glomerulosa
- mineralocorticoid
- Fasciculata
- glucocorticoids
- Reticularis
- androgens
- MEDULLA
- Glucocorticoids e.g.
cortisol, corticosterone
- Mineralocorticoids e.g.
aldosterone
- Androgens and Estrogens - small
amount to replace loss of gonadal
steroids - only needed in emergency
situtation
- All generated from CHOLESTEROL
- closely related structures -
different effects
- cholesterol input = diet + formation
from acetate w/in cell
- Adrenal steroid
synthesis
- Cholesterol - absorbed
from the GI tract or synth
from acetate
- Cholesterol is
insoluble in water
and transported with
LDL
- binds to LDL
receptor and
endocytosed
- Steroids are NOT
stored in cortical
cells
- hydrophobic - needs
to bind to a protein to
enter
- so, cholesterol (steroid)
CANNOT be stored but ACETATE
precursor can be
- Steroid action
- Cytoplasmic receptor in
multiple target tissues
- translocates to the
nucleus upon
steroid building
- modulates
transcription of genes
- steroid hormones are
lipophilic - why they must
bind to proteins
- Glucocorticoids
- Cortisol/corticosterone
- secreted from zona
fasciculata - widest
zone of adrenal
cortex
- Diurnal rhythms
- dogs and cats DO NOT
have daily cortisol
rhythms
- Other species - secretion of
CRH synchronised with
sleep-wake-cycle
- animals active during
the day: high cortisol
a.m
- animals active at
night: high cortisol
at onset of
darkness
- stress induced secretion CRH can cause up to 20x
increase in glucocorticoids and override circadian
rhythms
- Glucocorticoids output
and effects
- Control - acute and long term stress
e.g. heat, trauma, cold, pain, fright,
disease + CIRCADIAN rhythm
generator
- Stimulates CRH release from
hypothalamus -> anterior
pituitary
- ACTH stimulates adrenal
cortex - fasciculata cells
(glucocorticoids) -> cortisol
-> peripheral tissue and
target cells
- Corticotrophs, cells
bound to anterior
pituitary, produce
ACTH
- Physiological
effects
- Metabolism
- CHO - stimulation of glucneogenesis
- inhibit effects of insulin - decreased
tissue uptake of glucose
- Protein - stimulation catabolism of proteins -> glucneogenesis
- Fat - during stress/starvation - shift metab from glucose -> fat
- increased LIPOLYSIS (FA
used as fuel - glucose
sparing)
- Hyperglycaemic
- glucneogenesis = synthesis of glucose
from amino acids
- Glucocorticoids - physio
effects
- cardiac, skeletal and vascular
smooth muscle
- Insuffiency - muscle fatigue
- cardiac insufficiency = failure
- Vascular = loss of vasomotor tone
- skeletal = general muscle weakness
- mechanism ill defined
- Nervous system
- affects on mental function,
insufficient = lethargy, apathy,
inability to concentrate
- Excess - hyperactivity,
insomnia, euphoria,
increased sensory
acuity
- mechanism also ill-defined
- Response to stress
- Metabolism
- alertness
- Cardiac, skeletal and vascular smooth muscle
- muscle primed
for escape
- Nervous system
- alertness
- Inflammatory effect of
glucocortisoid
- anti-inflammatory and
immuno-supressive
- inhibit secretion of CYTOKINES
Anmerkungen:
- involved in immune response, produced by T-lymphocytes and mast cells
- inhibit proliferation of immune cells
- inhibit synthesis of antibodies
- increase susceptibility
to infection
- Therapeutic use of
glucocortisoid
- low dose in adrenal
insufficiency
- suppress responses in autoimmune
diseases
- Mineralcorticoids
- e.g. aldosterone
- on release 60% bound to
plasma protein TRANSCORTIN
- released from ZONA GLOMERULOSA
- HALF LIFE -
15-30mins
- release mediated by -
renin/angiotensin system, Na+/K+
concentration
- regulate concentration of
SODIUM and POTASSIUM in
extracellular fluid
- most important stimulation = changes in
ELECTROLYTE levels and WATER BALANCE
- major target = epithelial cells of COLLECTING
TUBULES of KIDNEY - activate Na+ - K+ pumps
- reabsorption of Na+ from fluid in renal tubules =
excretion of K+ in urine. Restoration of blood Na+/K+
balance, blood volume and pressure increased
- Control of mineralcorticoid output
from adrenal cortex
- Adrenal cortex -
Glomerulosa cells
- Aldosterone -> kidney tubules -> increased sodium
reabsorption and K+ secretion = increased blood volume and
pressure
- Liver = Angiotensin - + renin =
angiotensin 1 - + ACE = angiotensin 2 =
stimulates aldosterone release from
glomerulosa cells
- ACE - lungs and kidney. Renin -
JG cells when blood pressure
low, Na+ low and blood volume
low.
- Disfunctions of the adrenal
cortex:
- HYPERADRENOCORTICISM -
Cushing's disease
- overproduction of glucocorticoids
(overproduc of minerglc does not occur in
dom. animals)
- common endocrine disease in dogs,
occasional in cats, rare in horses etc
- Primary hypercorticism (15%) =
adenomas of adrenal cortex =
tumour of pituitary
- Secondary (15%) = ACTH producing
neoplasms of anterior or intermediate
pitu
- Latrogenic hypercorticism = widespread
use of syntheitic glucocorticoids
- Alopecia -
muscle wasting
+ pot belly
- Hirsutism =
failure to shed
seasonal coat
- Disfunctions of the
adrenal cortex
- Hypoadrenocorticism (Addison's
disease)
- undersecretion of glucocorticoids
and mineralcorticoids
- RARE
- Primary hypocorticism -
ATROPHY of adrenal cortex
- Latrogenic hypocorticism
- abrupt withdrawl of
steroid therapy
- Symptoms
- muscle weakness
- poor CV function
- Low BP
- Therapeutic use of
glucocorticoids
- Anti-inflammatory and
anti-allergic effects
- Immunosuppresant in
autoimmune disorders
- NB: careful withdrawl and reduction of dose to
avoid HYPOcorticism - negative feedback on
endogenous cortisol
- Adrenal medulla
- CHROMAFFIN cells - catecholamine storage granules
- Catecholamine - adrenaline + noradrenaline -
secreted by ADRENOMEDULLARY CELLS
- bind to receptors on adipose,
CV, muscular and pancreatic
tissue and CNS
- 'emergency hormone' in response
to adrenergic receptor nature
- Synthesis of
catecholamines
- Tyrosine from diet
(throglobulin and iodine)
- =TH = DOPA -> DDC = Dopamine -> DBH
= Norepinephrine -> PNMT ->
Epinephrine
Anmerkungen:
- TH - thyroid hormone
DOPA-
DDC- DOPA DeCarboxylase
PNMT- Phenylethanolamine N-methyltransferase
- nor/epinephrine from storage granules
- adrenal medulla is primary source of adrenaline
- Secretion of catecholamines
- Classic Ach pathway
- depolarisation, calcium influx, granules fuse
with chromaffin cell membrane - exocytosis
and catecholamine release
- Adrenergic receptors and
physiological effect
- a1, a2, B
- Regulation
- hormonal binding affinity
- receptor concentration
- receptor signalling -G-protein coupled receptors
- ACTIVATION OF 2ND MESSENGERS
- Regulate responsiveness of target cell to catecholamines
- FIGHT OR FLIGHT
- Vasoconstriction in viscera and skin =
increased F/v of heart contraction - little
effect on BF to CNS
- shunt blood and nutrients to heart and muscles
- dilation of coronary arteries + vessels in skeletal m
- Contraction of pilomotor muscles - raise hair
- liberation of nutrient
- HYPERFUNCTION
of
adrenal
medulla
- Pheochromocytomas = tumours
arising from chromaffin cells
- rare and benign = secrete large
quantites of catecholamines =
elevated BP and HR