adrenal gland final 2
TRANSCRIPT
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SUBJECT: PHYSIOLOGY TOPIC: Adrenal GlandLECTURER: DR. VIC MENDOZADATE: FEBRUARY 2011
Adrenal Gland
Remember: the blood supply of the adrenalgland is designed in such a way that the
blood passing through the cortex will also be
the same blood that will pass through the
medulla
o This means that the medulla is alsoexposed to the hormones produced
by the adrenal cortex!
EmbryologicallyThe cortex is mesodermal, whereas the
medulla is neuroectodermalin origin.
Adrenal Cortex
About 8090% of the weight of the gland Secretes 3 classes of steroid hormones [not
stored but synthesized as needed]
o Because there is no storage, thereare no preformed hormones that
can be secreted right away.
Although it takes longer, steroid
hormones have a longerlasting
effect compared to other hormones
anyway.
Glucocorticoids, mineralocorticoids and sexhormones
Recall Histology: 3 layers of the cortexo Zona Glomerulosa, Fasciculata and
Reticularis
o Glomerulosa: synthesis andsecretion ofmineralocorticoids
o Fasciculata: glucocorticoidso Reticularis: sex hormones
Also, recall that the ratelimiting step in theformation of steroid hormones is the
conversion of cholesterol to pregnenolone.
Mineralocorticoids
For regulation of water and sodium,potassium ion concentrations
Regulation of normal acidbase balance Main mineralocorticoid: ALDOSTERONE
Aldosterone
A steroid hormone responsible forregulating sodium reabsorption in the distal
tubule and the cortical collecting duct
Target cells: Principal [P] Cells Stimulates the synthesis of Na/KATPase
pump
Furthermore, ALDOSTERONE:
Promotes the retention of sodium and water[handinhand]
o Chloride is also retained togetherwith bicarbonate
(This consequently affects acidbase
balance.)
Promotes the loss of potassium through thekidneys and hydrogen ion
(These are also responsible for how Aldosterone
affects acidbase balance)
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Direct stimulators:o Increased extracellular potassiumo Decreased osmolality
Indirect stimulators [RAAS]o Decreased blood pressure
Reduction in kidney perfusion thus
resulting in INCREASED Renin
production, which acts on
Angiotensinogen to eventually yield
Angiotensin II. This can then stimulate
the adrenal cortex to produce more
aldosterone.
o Decreased macula densa blood flow RAAS: Renin AngiotensinAldosterone System
Glucocorticoids
3 classes of glucocorticoids:o Cortisol [major glucocorticoid!]o Corticosteroneo Cortisone
CORTISOLo A steroid hormone that is plasma
bound to corticosteroid binding
globulin [CBG or transcortin]
o Essential for lifeo Net effects of cortisol are catabolic:
prevents hypoglycemia
(very low glucose in the bloodstream)
A person cannot survive for a long time
without glucocorticoids in the body.
If adrenal glands are removed, there will be a
need for exogenous supply
Net effects of cortisol are catabolic
They circulate bound to a globulin but being steroid
hormones, they are capable of crossing cell
membranes. When they detach to CBG, they can
cross the cell membrane because of receptors insidethe cell membrane. Once they enter the nucleus of
the cell, they can promote transcription.
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Physiological actions:
(how it prevents hypoglycemia)
Promotes gluconeogenesis[primarily amino acids coming from catabolism
of skeletal muscle thus providing substrates for
gluconeogenesis]
Promotes breakdown of skeletal muscleprotein
Enhances fat breakdown [lipolysis] Suppresses immune system
[at pharmacological doses: reduces phagocytic
actions of WBCs]
Breakdown of bone matrix[High doses; like when exogenous glucocorticoids
had been administered. Fracture is therefore a
sideeffect of prolonged use of high dose
glucocorticoids.] Reduces fever Suppresses allergic reactions Widespread therapeutic use
[Primarily because it CAN suppress immune
response. Disease entities promoted by
inflammation will be affected, such as bronchial
asthma or lupus, or patients who have
undergone a transplant. Suppression of immune
system is needed so that the body will not reject
the transplanted organ.]
Decreases formation of connective tissue[Thus weakening it. Eg capillaries with CT in its
walls. High doses of glucocort can cause the
supporting CT to disappear leading to easy
bruisability]
Enhance vascular responsiveness tocatecholamines
Inhibit bone formation Increase GFR
[Can promote free water clearance in the
kidneys] Decrease REM sleep
[Modulates wakefulness of a particular person]
Influences brain function: states of cortisolexcess or deficiency cause mood changes
and memory and learning alterations
Cortisol Effects:
Regulation of Cortisol Release
Cortisol release is regulated by the ACTH[secreted by the anterior pituitary; pulsatile
secretion; diurnal rhythm]
Release follows a daily patternCircadianSince ACTH secretion is pulsatile, it follows that
cortisol seems to have a similar pattern.
Negative feedback by cortisol inhibits thesecretion of ACTH and CRH [regulation of
their relationship]
Cortisol also promotes negative feedback tothe hypothalamus
CRH acts on Anterior Pituitary; it stimulatessecretion of ACTH
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**About 10 pulses all throughout the day. Just
before waking up in the morning, there is this big,
big pulse (increase in secretion). This increase in
secretion represents more than half the total
secretion of ACTH in 24 hours.
** Levels of ACTH are actually lower during sleeping
hours, and then the big,big spike, then eventually
goes down. Though its generally really higher during
the day than at night.
ACTH promote secretion of glucocorticoids
Main effects is on the ratelimiting step:transformation of cholesterol to
pregnenolone and from there, it proceeds
Hypothalamus will produce CRH which influences
anterior pituitary Production of ACTH then acts
on adrenal to release further cortisol and this will act
on anterior pituitary decreasing the release of ACTH
Enhanced secretion can be caused by anyform ofstress:
o Physical traumao Infectiono Extreme heat and coldo Exercise to the point of exhaustiono Extreme mental anxiety
Stress and the Adrenal Cortex
Glucocorticoids act for the human organismto adapt to stress
Any form of stress are first perceived by thebrain and other sensory receptors
o The hypothalamus is stimulated torelease CRH
o With high levels of CRH, it willinfluence anterior pituitary to
release more ACTH which will, again,
increase secretion of cortisol from
the adrenal cortex
o Cortisol in bloodstream increasesmetabolism of carbohydrate, fat,
and protein
o Metabolic processing alleviate theeffects of stress therefore reducing
stress
**HypothalamicPituitaryAdrenal Axis
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**Please refer to the Powerpoint if figures are not
clear.
Clinical Correlation:
HyperadrenalismCushings Syndromeo Caused by exogenous
glucocorticoids and by tumours
[adrenal or pituitary] which produce
enhanced levels of glucocorticoids
o Zg tumor increases aldosterone Increase in sodium and
blood pressure
o Zr tumor increases cortisol Excess protein catabolism,
redistribution of fat
omoonfacie [picture]
striae are blood vessels thatare seen because of thinning
out of connective tissue
Addisons Diseaseo Underactivity of the adrenal cortex
[hypoadrenalism] results in
decreased output of glucocrticoids
and aldosterone
o Results from infection, intake ofcertain drugs, etc
o Adrenal cortex is unable to produceenough hormones to supply the
needs of the body
o Plasma sodium decreases and maylead to circulatory collapse
o Symptoms: decreased blood sodium
skin color becomes bronze[crossreaction of ACTH and
MSH; excess ACTH levels]
**MSH is responsible for pigmentation of skin
anemia [RBC deficiency] weakness and fatigue increase in blood potassium
o The only way to survive is to providewith exogenous glucocorticoids [in
the form of drugs]
o
Ex: JFKs suntan might be because ofAddisons disease
Gonadocorticoids
Adrenal sex hormones normally have only avery slight effect on the sex organs
o Because the most important sourceof sex hormones are testis and
ovaries
Consist mainly of androgens and estrogens DHEA in females are main source of
androgens
*note the different layers: remember Endocrine
Histology
*Glucocorticoids have some sodiumretaining
capability [like Mineralocorticoids]
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*Mineralocoritcoids have some glucocorticoid
properties
*PTH is essential to life!
ADRENAL MEDULLA
Embryologically derived frompheochromoblasts [neruoectodermal in
origin]
Differentiate into modified neuronal cellso More of a gland than nerveo Chromaffin cells
Acts like sympathetic ganglion Extension of the sympathetic nervous
system [SNS]
Acts as peripheral amplifier of SNS
Activated by same stimuli as the SNSo Ex: exercise, cold, stress,
hemorrhage
Cells of adrenal medulla synthesize, store,and secrete two types of catecholamines
o Main neurotransmitter in adrenalmedulla is epinephrine
o 80% of secretion of adrenal medullais in the form of epinehphrine
o
Norepinephrine o Small amount ofdopamine can also
be secreted by the medulla [but is
not really counted as one of the
types of cathecolamines]
The hormones produce effects similar tostimulation by the sympathetic nervous
system.
Conversion of norepinephrine toepinephrine requires another
hormone/substance which is cortisol! Cortisol enhances phenylethanolamineN
methyltransferase [PNMT] which is an
enzyme that converts norepinephrine to
epinephrine
Influences blood vessels in the same waythat the peripheral nervous system affects
the vessels
RECEPTORS
o Effectors on which epinephrine andnorepinephrine act and can be grouped
based on their response to each hormone
o Effector organs may contain their cellmembranes
o alpha receptorso beta receptorso or both
o Even though epinephrine or norepinephrinebind to alpha and beta receptors, they do
not evoke same response
o Beta receptor activation linked tostimulating cAMP
oAlpha receptor activation is linked toinhibiting cAMP
Receptor Response
Norepinephrine interacts predominantlywith alpha receptors
Beta receptors have higher affinity forepinephrine
Response of cell haing alpha receptors maybe different completely from the response
of cells with beta receptors for the sametransmitters or hormones
GENRAL RULE:
Tansmitters trigger the receptors, but it isthe receptor that defines the nature of the
response!
EFFECTS OF CATECHOLAMINES
See Figure 1 Last Page
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Catecholamine Synthesis
Elimination of Catecholamines
Stress and Adrenal Medulla [See ppt!]
Fright, fight, or flight response Secretion of epinephrine causes intense
effects that last a very short time
o liver enzymes inactivateepinephrine in about 3 minutes
After epinephrine has been released:
Some blood vessels constrict and othersdilate redistributing blood to the brain andmuscles
Digestion is halted during the emergency bythe diversion of blood from the stomach and
intestines to the skeletal muscle
Other effects:
Blood pressure rises Heart rate increases Blood clotting time reduces RR increase Bronchioles dilate Enzymes in liver Release of epinephrine favors survival of
body
**The figure above shows integrated responses to
stress mediated by the sympathetic nervous system
and the hypothalamopituitaryadrenocortical axis.
**Negative feedback by cortisol can limit an over
response that might be harmful to humans.
CLINICAL:
Pheochromocytoma
A catecholaminesecreting tumour ofchromaffin cells of the adrenal medulla
Adrenal pheochromocytoma (90%) Paraganglioma a catecholamine secreting
tumour of the sympathetic paraganglia
Extraadrenal pheochromocytomaSigns and Symptoms:
Treatment resistant hypertension (95%) Headache Sweating Palpitations Chest pain Anxiety
Classic Triad!
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Glucose intolerance Increased metabolic rate
Diagnosis and Treatment:
Diagnosed by high plasma catecholaminesand increased metabolites in urine
Glucagon stimulation causes a 3foldincrease of plasma catecholamines
No test for adrenal or extraadrenaltreatment is surgical resection
END OF TRANSCRIPTION
Actions of Catecholamine Hormones: