Na and volume homeostasis Flashcards
1
Q
General considerations 1
A
- Na is the primary determinant of ECF
- Plasma volume increases with no change in osmolality when Na levels increase since H20 is reabsorbed accordingly
- Excess dietary salt: increase in ECF, plasma volume, BP, and leads to HTN
- Interstitial loss of NaCl and H20 from ECF leads to decreased plasma volume, BP, and leads to shock
2
Q
General considerations 2
A
-As Na from diet is raised there is a 3 day lag in which Na output t expand b/c it can store Na non osmotically on negatively charged matrix molecules in skin and/or move it into muscle in exchange for K
3
Q
Overview of changes in ECF volume and responses
A
- Decreased ECF volume: decreased CV stretch (in great veins and atria) increases SNS output to kidneys and causes renin release activating RAAS
- Decreased ECF volume also leads to diminished renal perfusion pressure stimulating infrarenal arterial baroreceptoors in the afferent arteriole (myogenic), which stimulates RAAS
- Last thing to stimulate RAAS: macula densa (MD) sensing low NaCl transport
- Increasing ECF volume increases atria stretch and ANP release to vasodilate and cause diuresis
4
Q
RAAS response
A
- Is activates when Na and/or volume is low, and responds by increasing Na reabsorption (all along the nephron) to increase ECF
- RAAS also increases vascular contractility thru ATII to increase BP
5
Q
Juxtaglomerular apparatus (JGA)
A
- Consists of MD (late TAL cells), and juxtaglomerular cells (specialized afferent arteriolar SMCs that make and store renin in granules)
- Renin is released in response to increased cAMP (set off by input from MD or SNS) or decrease in cell Ca (set off by less volume/stretch)
- Ca inhibits release of renin
6
Q
Stimulating renin release 1
A
- Myogenic: decrease mean arterial pressure sensed by baroreceptors in afferent arteriole leads to a decrease in Ca and thus causes renin release
- When there is increased BP/stretch in the afferent arteriole there is an increase in Ca and renin release is inhibited
- Decrease in NaCl transport by NKCC in macula densa: chemical signals are transmitted from MD to afferent arteriole (signals: PGs and NO) to stimulate AC, increase cAMP and release renin
7
Q
Stimulating renin release 2
A
- Neurogenic: decrease in extrarenal baroreceptor firing leads to increase SNS to afferent arteriole to stimulate cAMP production and renin release
- Metabolic: high levels of glc sensed in MD cells leads to increase in renin release
- Hormonal: ATII via AT1 raises Ca levels and inhibits renin release (negative feedback)
- Likewise: ANP activates GC to raise cGMP inhibits renin release
8
Q
Actions of ATII 1
A
- Very rapid effects via AC stimulation or phosphatidylinositol (PI) turnover
- Renal Na and H20 retention: increases Na transporter abundance and activity along the nephron (NHE, NKCC, NCC, ENaC)
- Increases aldosterone production/release
- Aldosterone increases NaCl reabsorption and K/H+ secretion in distal tubule (NCC) and collecting duct (ENaC)
9
Q
Actions of ATII 2
A
- ATII causes systemic vasoconstriction of arterioles
- Regulates GFR by preferentially constricting efferent arterioles and mesangial cells to keep GFR up despite low RBF
- Central role: stimulates thirst, ADH release, NaCl appetite
10
Q
Local RAAS
A
- Can occur to only affect Na reabsorption in one part of the nephron (i.e. proximal tubule)
- Will not effect systemic vasoconstriction
- Activated during renal injury
- Good target to Rx HTN (ACEIs)
11
Q
Aldosterone effects 1
A
- Release stimulated by AGII, high plasma [K], ACTH, and inhibited by ANP
- Released from (and synthesized in) adrenal gland (zona glomerulosa)
- Is a steroid (mineralcorticoid), thus binds to mineralcorticoid receptor (MR), which moves to nucleus to affect gene expression
- It rapidly stimulates synthesis of a S/T kinase Sgk, which increases apical ENaC by decreasing their degradation and increasing their activity, increases Na/K ATPase activity, and increases NCC activity (all rapid)
12
Q
Aldosterone effects 2
A
- Aldosterone also stimulates production of proteins which have delayed effects: increases ENaC and Na/K ATPase
- These effects occur in distal tubule and collecting duct (thus increase Na reabsorption in these location)
- Note: anything that increases Na reabsorption thru ENaC increases the driving force for K and H+ secretion in the collecting duct, thus aldosterone causes K and H+ secretion
13
Q
Regulating availability of MR
A
- The mineralcorticoid receptor, MR, can be bound to by other mineralcorticoids and glucocorticoids (cortisol)
- Since glucocorticoids are 1000X higher levels than mineral corticoids, there must be a mechanism to inactive the glucocorticoids so the MR is not saturated by them
- The nz 11-B hydroxysteroid dehydrogenase (11BOHSD) metabolizes glucocorticoids (cortisol) into inactive forms (cortisone) to prevent saturation and ensure aldosterone can bind
14
Q
Summary of decreased ECF responses
A
- Stimulates thirst (ATII) and Na hunger (same nucleus)
- Renin->ATII also increases NaCl reabsorption in proximal tubule, distal tubule and collecting duct, and stimulates aldosterone release
- Aldosterone increases NaCl reabsorption in distal tubule and collecting duct
- ATII stimulates ADH, which also increase NaCl reabsorption
- Decreased ANP leads to inhibition of ANP effects
- SNS activity increases leading to NaCl reabsorption all along the nephron and increases renin release
- Overal there is decreased NaCl excretion
15
Q
ANP
A
- Released when there is excess ECF, made in atria and stored in granules
- Release in response to increased atrial stretch, which increases Ca and leads to fusion of granules w/ cytoplasm (ANP released into blood)
- When ANP binds to inner medullary collecting duct (IMCD) cells it increases cGMP and inhibits NaCl reabsorption
- It also decreases renin release (which decreases ATII, ADH, and aldo)
- It increases GFR by dilating the afferent arteriole
- Causes systemic vasodilation (increased cGMP leads to decreased cellular Ca) to decrease BP
