5.1 CV system & adrenal medulla Flashcards
- what are the 3 physical attributes of blood? & their associated control/regulation mechanisms ish?
- what other control mechanism is there?
- all of them are in a ___________
1) volume –> H2O retention
2) blood pressure –> dilation of arterioles
3) osmolarity –> Na+ retention
- in addition to fluid intake!
- continuum!!!! 1 influences another
aorta –> ______ –> ______ –> ______ –> ______ –> ______ –> ______ –> vena cava
- total area of all these vessels = ?
- what is the major determinant of blood pressure in arteries? what does this thing also control? –> all of these things are under control of what?
aorta –> arteries –> arterioles –> capillaries –> venules –> veins –> vena cava
- total cross-sectional area
- diameter of arterioles! –> also controls distribution of blood supply to tissues
- all under control of hormones (ish)
what part ish of capillaries is where pressure of arteries can be regulated + allow for proper speed of blood flow at capillary levels?
- what is super important for exchange at capillaries?
- precapillary sphincters!
- slowness of blood flow at capillaries
- what is sodium appetite?
what are physiological changes that influence sodium appetite? –> which organ? - 3 positive
- 4 negative
- is sodium appetite strongly manifested in normal conditions?
*thirst and sodium appetite graph
- sodium appetite = pushes us to eat salty foods –> makes us increase salt intake
- brain!
POSITIVE: - increase aldosterone
- increase angiotensin II
- changes in brain [Na+] –> decrease [Na+] OR increase osmolarity –> affects Na/K channels = hinders neural propagation and membrane potential
NEGATIVE: - increase [Na+] of blood plasma cerebrospinal fluid
- post-ingestive signals from the gut (increase [Na+], distension) sensed via the vagus nerve
- circulating & CNS peptide hormones/neuromodulators
- arterial/venous baroreceptors (not sure if positive or negative)
- NOT strongly manifested in normal conditions
*thirst: fonction racine carré ish VS sodium appetite: really low and flat at first, halfway, start to increase linearly ish
- aldosterone produced where?
- main functions (2)
- 3 functions as concepts ish
- zona glomerulosa of adrenal cortex
1. recovery/retention of Na+ in the kidney and enhanced K+ secretion into urine to balance charge difference
2. adjustment of extracellular fluid (ECF), including blood volume (bc of osmosis) –> blood pressure!
- regulation of fluid volume
- water absorption
- sodium/potassium homeostasis
how is aldosterone synthesized? pathway!
- cholesterol enters mitochondria using StAR
- cholesterol –> pregnenolone, using CYP11A1
- pregnenolone –> progesterone, using HSD3B2
- progesterone –> 11-deoxycorticosterone, using CYP21A2
- 11-deoxycorticosterone –> corticosterone, using CYP11B1 and CYP11B2
- corticosterone –> 18-OH-corticosterone, using CYP11B2
- 18-OH-corticosterone –> aldosterone, using CYP11B2
- which cells detect Na+ levels in kidney tubule?
- vs which cells detect blood pressure?
- which cells produce renin? in response to what?
- Macula densa cells of distal convoluted tubule (near glomerulus) detect Na+ levels in kidney tubule
- juxtaglomerular cells of afferent arterioles detect blood pressure
- pericytes near afferent arterioles produce renin –> in response to BP or Na+ imbalance
RAAS
- what does renin do?
- what does ACE do?
- what does angiotensin II stimulate? (2)
- aldosterone and angiotensin II increase (3)
- renin from pericytes in kidney converts angiotensinogen (produced in liver) to angiotensin I in liver –> Ang I goes into circulation until lung
- ACE (angiotensin converting enzyme) from endothelial cells of lungs converts angiotensin I to angiotensin II –> ang II goes to kidney and drenal gland
- angiotensin II = main regulator of aldosterone secretion (ACTH has a modest effect) + stimulates AVP, which stimulates water retention in kidney
- increase Na+ absorption, K+ excretion and water retention in kidney
RAAS
- renin found in kidney but also found where?
- how is angiotensin II inactivated?
- also found in brain. local production of angiotensin II? induction of thirst?
- inactivated to angiotensin III by aminopeptidase A
how does aldosterone achieve its functions ish? pathway ish
- aldosterone binds to mineralocorticoid receptor (MR) –> affects gene transcription in nucleus –> increase structural protein + regulatory proteins
- increase/activates sodium potassium pumps on capillary side + increase sodium channels (epithelium sodium channels ENaC) on luminal side
is AVP or aldosterone faster in its action to control volume and BP?
*think about what type of receptor for each!
- AVP –> GPCR –> faster, bc proteins are already there
- aldosterone –> nuclear receptor/TF –> slower, need full transcription/translation before protein is formed
aldosterone acts on sodium/potassium homeostasis:
- sodium transport in which 3 areas of body?
- distal tubules of kidney
- colon
- salivary and sweat glands
- which channels are needed for movement of Na+, K+ and water from where to where? after actions of aldosterone?
- potassium goes out (capillary to distal tubule) –> through Na/K channel + ROMK and BK channels
- sodium goes in (distal tubule to capillary) –> ENaC and Na/K ATPase
- water goes in –> aquaporin 2 and aquaporin 3/4
ALDOSTERONE:
- mainly affects where? but also on other systems (3)
- promotes (2)
- sensitizes arterioles to (3)
- net effect: (2)
- response has a lag period of how long?, reflecting that aldosterone induced enzyme have to be what?
- distal tubules and collecting ducts of kidney –> also on sweat glands, salivary glands and colon
- promotes plasma retention of Na+ and excretion of K+
- sensitizes arterioles to vasoconstrictor agents, AVP and angiotensin II
- net effect = rise in plasma volume and blood pressure
- lag period of 1 hour: reflecting that aldosterone induced enzymes have to be synthesized de novo
- what is conn’s disease?
- usually caused by (2)
- excess excretion of (2) –> leads to (2)
- increased (3)
- hyperaldosteronism (primary alsodetronism)
- hypersecretion of aldosterone usually caused by adrenal hyperplasia (60%) or tumor of adrenal cortex (40%)
- excess excretion of K+ and H+ (bc high aldosterone) –> serum alkalosis and neuropathy (hypokalemia)
- increased water retention, Na reabsorption and blood pressure
*high blood pressure could also be from apparent mineralocorticoid from excess cortisol
- what is addison’s disease?
- caused by (2)
- symptoms (4)
- hypoaldosteronism
- shortage/deficiency of aldosterone production OR impaired function of aldosterone
1. low sodium (hyponatremia)
2. too much potassium (hyperkalemia)
3. low blood pressure
4. metabolic acidosis
*recall Addison’s crisis pathway!
- what do natriuretic peptides do?
- produced where and stored?
- receptors are present in (4)
- functions: increases (3) + reduces/inhibits (4)
- increase excretion of H2O and Na+ (role in BP regulation)
- produced in heart muscle cells and stored in granules
- present in glomeruli, medullary collecting ducts of kidney, zona glomerulosa of adrenal cortex and in peripheral arterioles
INCREASES: - glomerular filtration + water loss (diuresis) + vasodilation
REDUCES: - renin , blood volume and blood pressure
- inhibits aldosterone production
- natriuretic peptides have opposite effects to (2) –> consequence?
- opposite effects to AVP and Ang II –> renin need to make Ang II –> consequence: decrease aldosterone from direct inhibition by natriuretic peptides!
- where is testosterone/androgens synthesized?
- how? pathway? (7 steps)
- zone reticularis in adrenal cortex
1. cholesterol enters mitochondria using StAR
2. cholesterol –> pregnenolone, using CYP11A1
3. pregnenolone –> 17OH-pregnenolone, using CYP17A1
4. 17OH-pregnenolone –> dehydroepi-anderosterone, using CYP17A1
6. dehydroepi-anderosterone –> androstenedione, using HSD3B2
7. androstenedione –> testosterone, using HSD17B
- sex steroids are mainly synthesized where? (which sex steroids?)
- sex steroids synthesis regulated by what?
- what organ (mainly what region) contributes to production of (2) regulated by ACTH?
- these 2 precursors can be converted to what? where? –> role?
- in gonads! female (estrogens and progestogens) male (androgens)
- regulated by gonadotropins
- adrenal cortex (mainly zona reticularis, but also fasciculata) contributes to production of DHEAS and androstenedione –> regulated by ACTH (vs glomerulosa)
- can be converted to testosterone in peripheral tissues (brain, adipose)
- role not entirely clear –> mainly modulate effect of overall [steroid] in circulation –> important for body hair growth (adrenarche) and responsible for growth spurt in middle childhood
CONGENITAL ADRENAL HYPERPLASIA (CAH)
- most common form involves deficiency of what? in which zonas?
- leads to reduced (2)
- exception in ZF? thus…
- low aldosterone leads to (4)
- CAH leads to excessive _________ production in which zona? –> consequence?
- involves deficiency of CYP21A2 (zone glomerulosa and zona fasciculata)
- reduced aldosterone and cortisol
- ZF: produces 21-deoxycortisol –> similar to cortisol but lower glucocorticoid activity (can act though! therefore low aldosterone is the main problem)
- low aldosterone leads to salt wasting, salt and water craving, vomiting and dehydration, low blood pressure (death)
- excessive production of androgen in ZR (hyperactivation of ZR bc not affected by CYP21A2)–> masculinization of genitalia
- total mass of adrenal medulla? about ___% of total adrenal glands weight
- adrenal medulla and _______ cells are part of the what?
- 1g –> 15% of total weight
- chromaffin cells –> part of sympathetic nervous system
- what are chromaffin cells&
- what stimulates chromaffin cells to release what?
- what do these released compounds do?
- modified post-ganglionic cells
- preganglionic neurons release acetylcholine to stimulate chromaffin cells to release catecholamines
- coordinate fight/flight response to alarm by increasing blood pressure and cardiac output + dilating pupils
- catecholamines (which 2) –> synthesized from what?
- pathway? (4 steps)
- rate limiting step?
- which enzyme does cortisol stimulate? (in catecholamine synthesis pathway)
- norepinephrine and epinephrine –> synthesized from tyrosine
1. tyrosine to dopa by tyrosine hydroxylase (rate limiting step! + commits Tyr to cetacholamine synthesis)
2. dopa to dopamine by dopa decarboxylase
3. dopamine to norepinephrine by dopamine b-hydroxylase
4. norepinephrine to epinephrine by PNMT (phenylethanolamine N-methyltransferase)
*cortisol stimulates PNMT!
- hormones in adrenal medulla are released in response to what?
- which % of catecholamines are epinephrine vs norepinephrine?
- in response to appropriate stimuli?
- 80% epinephrine (or adrenaline)
- 20% norepinephrine (or noradrenaline)
explain the fight or flight response –> schéma!
- hypothalamus perceives _______, then activates 2 pathways
- perceives stress!
1. activates SNS:
a) activates adrenal medulla –> releases NE and E into bloodstream
b) impulses activate glands and smooth muscles - both a) and b) lead to neural activity combines with hormones in bloodstream to constitute fight or flight response
2. ALSO activates adrenal-cortical system by releasing CRF –> pituitary gland secretes hormone ACTH –> ACTH arrives at adrenal cortex and release approximately 30 hormones (cortisol, aldosterone, androgens…) –> bloodstream –> leads to neural activity combines with hormones in bloodstream to constitute fight or flight response
FIGHT OR FLIGHT RESPONSE:
- (2) initiate fight or flight response
- __________ adjustments of many complex processes in ________ vital to response (ie: 4)
- occurs at expense of what?
- norepinephrine and epinephrine
- integrated adjustments of many complex processes in organs vital to response (ie brain, muscles, cardiopulmonary system, liver)
- occurs at expense of other organg less immediately involved (ie skin, GIT)
functions of
- epinephrine (5)
- norepinephrine (2)
EPINEPHRINE:
- rapidly mobilizes FA as primary fuel for muscle action
- increases muscle glycogenolysis
- mobilizes glucose for the brain by increase in hepatic glycogenolysis and gluconeogenesis
- preserves glucose for CNS by decreasing insulin release leading to reduced glucose uptake by muscle/adipose (opposes insulin)
- increases cardiac output
NOREPINEPHRINE:
- increase blood flow
- decrease insulin secretion
adrenergic receptors:
- why are there different responses depending on different target tissues?
- drugs specific for ________ of receptors have different effects –> ie salbutamol does what?
- bc different target tissues have different receptor distributions and hence have different responses
- drugs (subtypes) specific for subtypes of receptors have different effects:
Salbutamol activates/ is agonist to b2 receptors and dilates bronchioles (relief of asthma) –> does not affect b1 receptors in the heart
explain pathway of what leads to adrenergic receptors:
- a vs b1 vs b2
- sympathetic preganglionic fiber –> releases acethylcholine –> to sympathetic postganglionic fiber –> releases NE which binds to a and b1 receptors
- sympathetic preganglionic fiber –> releases acethylcholine to adrenal medulla –> secretes E and NE into bloodstream –> E and NE act on a and b1 receptors + E acts on b2 receptors
which receptors (a1/2 vs b1 vs b2) bind which catecholamine?
- potency?
- action?
- target?
- a1/2 and b1 receptors bind NE and E VS b2 receptors bind primarily E
- a1: NE > E –> Gq –> smooth muscle (skin, GI, uterus)
- a2: E > NE –> Gi –> nerve terminals (synaptic transmission)
- b1: NE > E –> Gs –> heart, cerebral cortex
- b2: E > NE –> Gs –> lung, smooth muscle, cerebellum
differences btw NE and E:
- Epinephrine»_space; norepinephrine for 2 things
- norepinephrine > epinephrine for 1 thing –> leads to what?
E»_space; NE:
- cardiac stimulation leading to greater cardiac output (b stimulation)
- in terms of increasing metabolism
E < NE:
- in terms of constriction of blood vessels –> leading to increased peripheral resistance –> increased arterial pressure
