9 Flashcards
Which zone of the adrenal cortex releases aldosterone
Zona glomerulosa
What are the functions of aldosterone?
- Recovery of Na+ in the kidney and enhanced K+ and H+ secretion into the urine to balance charge difference (Sodium/potassium homeostasis)
- Water reabsorption / regulation of fluid volume
- Therefore, adjustment of extra-cellular fluid (ECF), including blood volume and pressure
Physical attributes to blood system homestasis of plasma
Volume
Osmolarity
Blood pressure
Control mechanisms of blood system (in addition to fluid intake)
H2O retention
Dilation of arterioles
Na+ retention
Factors that influence Na+ appetite
Brain analyzes various factors resulting in behavioural changes in water and salt intake
Positive factors, resultign in increased intake:
- Aldosterone
- Angiotensin II
Negative:
- Increased Na blood levels
Both positive and negative”
- Arterial/venous baroreceptros
WHich vessels can control their diameter?
Artery
Arterioles
Capillaries
Where is renin secreted and what is its function?
Renin from afferent arterioles in kidney converts angiotensinogen to angiotensin I, activating it
Where is ACE secreted and what is its function?
ACE from endothelial cells of lungs converts angiotensin I to angiotensin II
What is the main control of aldosterone secretion?
adrenal gland is under the influence of trophic hormones from the pituitary (ACTH)
aldosterone, however is not majorly influenced by ACTH
Main controlling factor of aldosterone released is Renin-Angiotensin system
What is ACTH and what is it’s function
Adrenocorticotropic hormone (ACTH) is a hormone produced in the anterior pituitary gland in the brain. The function of ACTH is to regulate levels of the steroid hormone cortisol, which released from the adrenal gland
What are the roles of Angiotensin II?
v increases Na+ absorption and K+ excretion
v vasoconstriction by acting upon blood vessels
v Water retention, higher blood pressure
v Acts upon posterior pituitary – AVP also stimulates water resorption in kidney
Apart from being secreted from afferent arterioles, where else is it produced? What is its role
Renin also found in the brain.
Role is unclear: Local production of angiotensin II ? Induction of thirst?
What stimulates renin release?
- Macula densa cells detect Na+ levels in kidney tubule - > decrease in Na levels stimulates renin release
- Juxtagolomerular cells detect blood pressure via baroreceptors - > decreases pressure= renin release
- Increased renal sympathetic nerve outputs
Other factors: Increased prostaglandins, beta-adrenergic action, decreased arterial pressure
Leads to release of renin form Juxtagolomerular apparatus
How is angiotensin metabolized?
Angiotensin II is converted to less functioning angiotensin III by aminopeptidase
angiotensin III is then converted into degradation products
What leads to rapid./acute pressor response of angiotensin II
CHange in peripheral resistance results in:
1) Vasoconstriction
2) Increased sympathetic discharge
3) increased Adrenal medullary cathecolamine (epinephrin and norepinephrine) release
What leads to slow pressor response of angiotensin II
Change in renal function requires additional factors to be produced
1) Increased sodium reabsorption
2) Renal vasoconstriction
What leads to very slow pressor response of angiotensin II
Structural changes remodelling (vascular and cardiac tissue hypertrophy and remodelling) -> slower, but a longer lasting effect
Where is NA transport regulated by aldosteroen
Mainly distal tubules of kidney
colon
Salivary and Sweat glands
Describe aldosterone receptor
How does it function
Aldosterone is a steroid-> has nuclear receptor -> Mineralocorticoid receptor
aldosterone-> steroid-> nuclear receptor MR??
found in the cytoplasm
when bound to aldosterone and goes into the nucleus
results in the production of structural proteins e.g transport or regulatory proteins (kinases)
regulatory proteins act upon sodium channels in the luminal side of the tubule and Sodium- Potassium ATPase channels on the basal side
thus aldosterone effects are through the control of gene expression
Mechanism of action of aldosterone
In the luminal side (that touched the urine), there are sodium and potassium channles
on the basal side, there’s Na-K ATPase and K channels.
When Na channels on the luminalside are activated by aldosterone, the bring in Na into the cell and transport K out of the cell.
this is balanced by the increased activity of Sodium-potassium ATPase, thus the sodium that was brought into the cells will be transported across the opposite side of the cell into the circulation. leading to sodium reabsorption and potassium excretion
At the same time, as sodium is going in, aquaporins open-> allow for the reabsorption of water
In total, sodium and water are reabsorbed at the same time-> increased blood volume
What structures does aldosterone act upon
Mainly: Distal tubules and collecting ducts of the kidney.
- Also on other secretory systems (sweat glands, salivary glands, colon)
What is the aldosterone’s effect on blood vessels
Sensitizes arterioles to vasoconstrictor agents, vSensitizes arterioles to vasoconstrictor agents
What is the time needed for aldosterone to start acting?
Response has a lag period of 1h, reflecting that aldosterone induced enzymes have to be synthesized de novo
What is Conn’s syndrome
Hypersecretion of aldosterone usually caused by adrenal hyperplasia (60 %) or tumor (40%)
- Results in Excess excretion of K+ and H+=> Serum alkalosis and neuropathy (hypocalcemia)
- Increased water retention
- Increased Na reabsorption
- Increased blood pressure
Natriuretic peptides
Location of secretion
There are 2 types: BNP and ANP
Produced in the heart muscle cells and stored in granules
Natriuretic peptides’ receptors
Receptors are present in the glomeruli, medullary collecting ducts of the kidney, the zona glomerulosa of the adrenal cortex and in peripheral arterioles
Which sex hormones can be produced by adrenal cortex
Zone reticularis cells can produce sex steroids
Mainly androgens, but also some amount of estrogen ->
DHEAS (male sex hormone (androgen)) and androstenedione
Can be converted to testosterone in peripheral tissues.
What is sex steroid production by adrenal cortex regulated by?
regulated by ACTH and hypothalamic CRH
What are the roles of sex hormones produced by adrenal cortex?
Role not entirely clear. Important for body hair growth in females (adrenarche).
Responsible for growth spurt in middle childhood
Congenital adrenal hyperplasia (CAH)- causes and outcomes
there’s a group of mutations that lead to hyperplasia
- > Excessive androgen production
- > Masculinization of genitalia
Normal female vs CAH female
In normal female the gonad does not contain SRY gene
This STY deficient gonad develops Mullerian duct, which then develops into uterus and oviduct in the absence of Anti-Mullerian hormone, AMH
In the absence of testosterone and DHT female external genitalia is developed, instead
In CAH female, the difference is only in the presence of DHT (androgen that stimulates the development of male features), resulting in the Masculinization of external genitalia
WHat is the main enzymatic mutation of CAH
enzyme C21 hydroxylase deficiency
Describe enzyme C21 hydroxylase deficiency
main mutation-. enzyme C21 hydroxylase deficiency
which is the enzyme that lead to aldosterone and cortisol production
c21 is present where cortisol and aldosterone are produced, not in the reticular where sex hormones are produced
c21 deficiency-> less aldosterone and cortisol
Effects:
Less aldosterone-> less water intake and salt intake
Lower cortisol-> lower negative effect on pituitary-> more ACTH is produced)
Less negative effect on hypothalmus-> more CRH is produced)
Overall effect-> more trophic hormones coming to the adrenal glans
Less aldosterone and cortisol, but more trophic hormone-> reticular region is the only region that can respond to trophic hormones-> higher androgen production (DHEA and testosterone)-> Masculinization of external genitalia
Treatment of Congenital adrenal hyperplasia
surgical correction at birth of the adrenal gland
Adrenal medulla and chromaffin cells are part of the__
Adrenal medulla and chromaffin cells are part of the sympathetic nervous system
What is adrenal medulla innervated by ?
adrenal medulla is innervated by sympathetic preganglionic neurons, which release acetylcholine to stimulate medulla cells to release hormones
What is the role of adrenal meduall
releases catecholamines (norepinephrine and epinephrine) to Coordinate fight-flight response to alarm by increasing b.p. and cardiac output, and dilating pupils
What is the precursor of catecholamines
tyrosine
What is the rate limiting step fo Catecholamine synthesis?
tyrosine conversion to dopamine by tyrosine hydroxylase
Steps of norepinephrine and epinephrine production
1) tyrosine conversion to dopamine by tyrosine hydroxylase
2) Dopamine is converted to norepinephrine by Dopamine beta-hydroxylase
3) norepinephrine is converted into epinephrin by PNMT
What is the role of PNMT and what controls PNMT?
- norepinephrine is converted into epinephrin by PNMT
- Cortisol stimulates Phenylethanolamine N-methyltransferase
Which catecholaimes are released in bigger amounts?
80 % of released catecholamines are epinephrine
20 % norepineprine
degradation of catecholamines
Inactivated by monoamine oxidase (MAO) and COMT (catechol-O-methyltransferase) pathways
Other hormones secretion of adrenal medulla
- Granules also contain met-enkephalin (contains methionine) and and leu-enkephalin (contians)
- related to endorphins.
- They are co-excreted with the catecholamines
- Enkephalins may block neurotransmitters (like
morphine) - act as an endogenous analgesics (runners overcoming pain and being euphoric)
__/__ major elements in the “fight or flight” response
Epinephrine/norepinephrine major elements in the “fight or flight” response
What has to be regulated in fight or flight response and why
Blood flow to ensure that energy and nutrients directly go to the brain
Acute Fight-or-flight response
integrated adjustment of many complex processes in organs vital to the response (e.g., brain, muscles, cardiopulmonary system, liver)
effects of Epinephrine in Fight-or-flight response
- rapidly mobilizes fatty acids as the primary fuel for muscle action
- increases muscle glycogenolysis-> more glucose will be available
- mobilizes glucose for the brain by increasing hepatic glycogenolysis and gluconeogenesis
- preserves glucose for CNS by decreasing insulin release leading to reduced glucose uptake by muscle/ adipose
- > brain uptake of glucose is not glucose dependent-> glucose will go to the brain
- Increases cardiac output
effects of norepinephrine in Fight-or-flight response
Norepinephrine elicits responses of the CV system - increased blood flow and decreased insulin secretion.
What is the type of receptors in adrenergic receptor
GPCR
What are the types of adrenergic receptor and what do they bind?
α and β1 receptors bind epinephrine and norepinephrine.
β2 receptors bind primarily epinephrine
Why doe different tissues elicit different responses to catecholamines
Different target tissues have different receptor distributions and hence have different responses
Salbutamol action
Salbutamol activates β2 receptors and dilates bronchioles (relief of asthma); but does not affect beta1 receptors in the heart.
Adrenergic receptor types, potency, action and target
α1: NE≥E; Action: Gq. Target: smooth muscle (skin, GI)
α1: E>NE; Action: Gi (inhibitory); Target: Nerve terminals (synaptic transmission)
β1: NE>E; Gs; Target: Heart, cerebral cortex
β2: E>NE; Action: Gs; Target: lung, smooth muscle, cerebellum
Differences between Epinephrine and Norepinephrine
Epinephrine is faster than norepinephrine – in terms of cardiac stimulation leading to greater cardiac output (b stimulation)
Epinephrin is lower than norepinephrine – in terms of constriction of blood vessels – leading to increased peripheral resistance – increased arterial pressure
Epinephrine is faster that norepinephrine –in terms of increasing metabolism e,g glycogenolysis, changes in insulin secretion
Adrenomedullary disorders
Cuases:
1) Adrenomedullary deficiency: can occur due to surgery, trauma, etc- > reduced secretion of catecholamines
2) Also if cortisol levels are suppressed for any reason (high concentration of cortisol req’d for transcription of PNMT- (PNMT) is an enzyme found primarily in the adrenal medulla that converts norepinephrine (noradrenaline) to epinephrine (adrenaline)), it will lead to epinephrine deficiency
Symptoms: Hypotension, Hypoglycemia (central nervous system and glucocorticoids are more susceptible)
- Adrenal catecholamines not essential for life
Effect of hypoglycaemia on ACTH. aldosterone and cortisol
ACTH is under the influence of hypoglycaemia
since hypoglycaemia stimulates ACTH release, it can affect cortisol
doesn’t affect aldosterone as much because ACTH’s effect on aldosterone is minimal
Pheochromocytoma- what is it and what are the effects?
Pheochromocytoma is a rare tumor of adrenal gland tissue. It results in the release of too much epinephrine and norepinephrine' often not diagnosed until autopsy very general symptoms: • headache • hypertension • sweating • palpitations • chest pain • anxiety • glucose intolerance • increased metabolic rate
what inhibits renin secretion?
ANP, Dopamine
The __ cells, derived from smooth muscle cells, of the afferent arteriole secrete __ when blood pressure in the arteriole falls.
The juxtaglomerular cells, derived from smooth muscle cells, of the afferent arteriole secrete renin when blood pressure in the arteriole falls.
Macula densa cells detect __
Juxtagolomerular cells detect_)
Macula densa cells detect Na+ levels in kidney tubule Juxtagolomerular cells detect blood pressure
Stimuli of Natriuretic peptides secretion
Cardia distention
Sympathetic stimulation
Angiotensin II
results in ANP and BNP secretion
Effect of natriuretic peptides
Peptides that increase the excretion of H2O and Na+
Increases glomerular filtration
Decreased renin release, and consequently ANG II and aldosterone release
Reduces blood volume and pressure
result in decreased blood pressure and volume
Partial loss of 21-hydroxylase
Many mutations result in partial loss of function-> And masculinization is not as extreme
ANG II promotes the release of
catecholamines, aldosterone and AVP
insulin’s effect on ACTH, CRH and cortisol
stimulate corticotropin-releasing hormone (CRH), corticotropin (ACTH), and therefore cortisol secretion
cortisol’s effect on blood glucose levels
increases blood glucose
cortisol and tsh relation
cortisol inhibits TSH secretion
