Volume Regulation and RAS

Question 1

Actions of Angiotensin II:

Answer 1

• Retention of Na+

• Renal arteriolar constriction tends to decreases GFR
• decreases filtered load of Na+
• Direct effect to increase proximal tubular Na+ reabsorption (stimulates Na+/H+ exchange)
• Indirect effect (through aldosterone) to increased Na+ reabsorption by the collecting duct

Net effect: conserve Na+ (and water) to support ECF volume (and cardiac output)

• Vasoconstriction

• Direct effect on vascular smooth muscle
• Indirect effect: Stimulates sympathetic activity via effects on the central nervous system

Net effect: increase total peripheral resistance to support systemic arterial pressure

• Promote acquisition & retention of water

• Stimulates thirst
• acquire water
• Stimulate ADH release
• promotes water retention
• Decreases medullary blood flow

Net effect: conserve and acquire water to increase ECF volume

Question 2

Other Hormones That Act Directly on Tubular Epithelium to Alter Na+ Reabsorption

Answer 2

1. Aldosterone
2. Catecholamines
3. Atrial Natriuretic Peptide (ANP)
4. Endogenous Digitalis-Like Substance

Question 3

Aldosterone

Answer 3

a. Stimuli: Increased circulating AngII levels Decreased plasma Na+ concentration Increased plasma K+ concentration (important regulator of K+ balance)
b. Action: Increase Na+ reabsorption by collecting duct
c. Mechanism: Promotes Na+ entry through the apical ENaC

Question 4

Catecholamines

Answer 4

norepinephrine and epinephrine

a. Stimuli: Activation of Sympathetic Nervous System (i.e. baroreflex response to decreased arterial pressure)
b. Action: Increase Na+ reabsorption by proximal tubule
c. Mechanism: Activates the apical Na+/H+ exchanger

Question 5

Atrial Natriuretic Peptide

Answer 5

a. Stimuli: Atrial stretch (as a result of increased ECF volume)
b. Action: Decrease Na+ reabsorption by collecting duct
c. Mechanism: Inhibits ENaC

Question 6

Endogenous Digitalis-like Substance

Answer 6

a. Stimuli: Increased ECF volume (mechanism unknown)
b. Action: Decrease Na+ reabsorption by all nephron segments
c. Mechanism: Direct effect to inhibit the basolateral Na+-K+-ATPase

Question 7

Challenges to Sodium Balance

Answer 7

1. Spontaneous increase in GFR
2. Abrupt increase in Na+ intake

Question 8

Responses to a Spontaneous Increase in GFR (with stable PNa)

Answer 8

• Glomerulo-tubular Balance

• The proximal tubule reabsorbs a constant fraction of filtered Na+ (67% of filtered load)
• Mechanism: ↑ GFR –> ↑ oncotic pressure of plasma entering the peritubular capillaries –> ↑ reabsorption (Starling forces).
• How much does G-T balance matter?

Net effect: Reduces the impact of an increased filtered load on solute and water delivery to the distal nephron

• Tubuloglomerular Feedback –> ↑ GFR –> ↑ solute and water delivery to the macula densa –> TGF-mediated afferent arteriolar constriction –> ↓ GFR back toward normal.

Net effect: Limits the magnitude of spontaneous increases in filtered load.

Question 9

Responses to an Abrupt Increase in Na+ Intake

Answer 9

• Factors that favor an increase in GFR (filtered load of Na+):

• ↓ plasma oncotic pressure  Starling forces  ↑ GFR ( ↑ ECF volume dilutes plasma proteins)
• ↑ arterial pressure –>↑ capillary hydrostatic pressure in the glomeruli (autoregulation is not perfect)–> ↑ GFR
• ↓ AngII levels –> ↓ renal arteriolar resistance –>↑ RBF & GFR ( ↑ ECF volume  ↓ renin release)
• ↓ sympathetic tone & circulating catecholamines –> ↓ renal arteriolar resistance –> ↑ RBF and GFR ( ↑ arterial pressure sensed by carotid & aortic baroreceptors)

• Factors that decrease tubular Na+ reabsorption (to allow ↑ Na+ excretion):

• ↓ AngII levels –>↓ Na+ reabsorption in proximal tubule
• ↓ aldosterone levels –>↓ Na+ reabsorption in collecting duct ( ↓ AngII levels  ↓ aldosterone release)
• ↓ sympathetic tone & circulating catecholamines –>↓ Na+ reabsorption in proximal tubule
• ↑ ANP levels –> Na+ reabsorption in collecting duct ( ↑ blood volume sensed by atrial stretch receptors)
• ↑ endogenous digitalis-like substance (unknown stimulus) –>generalized ↓ in Na+ reabsorption