Term
| Why is it critical for the amount of sodium ingested in a given day to be equal to the amount that is excreted? |
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Definition
| Extracellular Na is the major determinant of EC fluid volume, so if their is a change in sodium balance, you will be hyper or hypovolemic |
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Term
| What hormones regulate ECFV by altering Na excretion by the kidney? |
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Definition
1) Angiotensin 2
2) Aldosterone
3) Arginine Vasopressin (ADH)
4) BNP |
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Term
| What happens physiologically when you inject a lot of salt in a short period of time? |
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Definition
1) There is an initial delay until the rate of Na excretion increases to match Na intake
2) Increase in excretion is accompanied by increase in ECFV and body weight
** The opposite is true as well** |
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Term
| Where is Na+ reabsorbed in the kidney? |
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Definition
1 lb a day!
1) 65% is proximal tubule
2) 25-30% in LOH
3) 3-5% in Distal tubule
4) 1-3% in collecting duct
1-2 is bulk of reabsorption
3-4 is fine tuning |
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Term
| How can the kidney regulate sodium excretion? |
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Definition
1) Changes in filtered load of Na
2) Changes in fraction of filtered Na that is reabsorbed |
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Term
| How can changes to Glomerular capillary filtration rate alter GFR? |
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Definition
| Faster capillary filtration rates are associated with slower rises in oncotic pressure, and vice versa. |
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Term
| How does Na reabsorption occur in the proximal tubule? |
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Definition
65% of filtered Na is reabsorbed here in an ISOOSMOTIC manner
1) Na/K-ATPase in basolateral PM provides driving force by decreasing Na+ concentration in the intermembrane space.
2) Sodium is then brought in across the apical PM via co-transporters and exchanges that utilize this gradient (It is finally brought into the interstitium via the basolateral Na/K ATPase and the Na/HCO3- transporter)
**Some Na transport also occurs with chloride via the paracellular pathway in the late proximal tubule** |
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Term
| How does the Na/HCO3- transporter act to bring sodium across the basolateral PM into the interstitial space? |
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Definition
1) There is a negative intraluminal potential created by the Na/K+ ATPase.
2) HCO3- takes advantage of this potential and 3HCO3- anions are transported across the membrane along with 1Na+ cation. |
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Term
| What happens to sodium once it reaches the interstitial space after reabsorption in the proximal tubule? |
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Definition
Either
1) Eners peritubular capillaries via 'drag forces,' where INCREASING oncotic pressure or DECREASING hydrostatic pressure in the peritubular capillary will increase Na and water reabsorption (RATE-LIMITING STEP of Na reabsorption across the proximal tubule)
2) Leaks back across tight junctions into the tubular lumen. |
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Term
| What will happen to sodium reabsorption in the proximal tubule if peritublar capillary hydrostatic pressure is decreased and capillary oncotic pressure in increased? |
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Definition
| Less hydrostatic and more oncotic means INCREASED Na and water reabsorption. |
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Term
| How does Na reabsorption occur in the Loop of Henle? |
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Definition
25-35% of filtered sodium is reabsorbed here (50% paracellularly and 50% transcellularly)
- No active transport takes place in thin limbs, and only takes place in the TAL.
1) Transcellular- Na crosses apical membrane via Na,K,2CL co-transporter (inhibited by loop diuretics), and then crosses the basolateral membrane via the Na/K ATPase
2) Paracellular- K+ is recycled across apical plasma membrane via K+ channels called ROMK channels, creating a POSITIVE LUMEN potential.
- Na+, Ca2+ and Mg2+ is driven across the paracellular pathway by this positive potential (energy-free) |
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Term
| How can sodium reabsorption occur in the TAL of henle without expending energy? |
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Definition
50% of the sodium reabsorbed here goes by the energy-free "Paracellular route."
1) K+ recycling across apical membrane of endothelial cells via ROMK channels creates a lumen positive potential.
2) This potential drives paracellular movement of Na+, Ca2+ and Mg2+ from the lumen to the interstitium |
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Term
| How does Na reabsorption occur in the Distal nephron? |
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Definition
4-8% of filtered Na+ goes here. High resistance epithelium means little back leak across paracellular path.
1) Early distal convoluted tubule uses Na+,Cl- co-transporter (activated by aldosterone and inhibited by thiazide diuretics)
2) Late convoluted tubule and collecting tubule uses ENaC (activated by aldosterone and inhibited by K sparing diuretics (amiloride and triamterene), trimethoprim and spironolactone.)
3) Transcellular transport of Ca2+ and Mg2+ also occurs (vs. Paracellular in LOH)
4) Na+ enters interstitium via Na/K ATPase |
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Term
| What agents act on the early distal convoluted tubule and the late distal convoluted tubule/collecting duct to alter sodium reabsorption (and thus water reabsorption). |
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Definition
1) Early distal convoluted uses Na/Cl co-transporter (electron-neutral symport)
- Activated by Aldosterone
- Inhibited by Thiazide diuretics
2) Late/Collecting duct= ENaC channel
- Activated by aldosterone and ADH
- Inhibited by K sparing diuretics (amiloride and triamterene)
- Inhibited by Trimethoprim (bactrim)
- Inhibited by Spironolactone (aldosterone antagonist) |
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Term
| Which important hormones increase/decrease Na reabsorption, and thus modulation extracellular fluid volume? |
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Definition
Increase (Na reabsorption and ECFV)
1) Angiotensin 2
2) Alodosterone
3) Arginine vasopressin (ADH)
Decrease (increase sodium excretion)
1) ANP
2) Dopamine
3) Endothelin
4) Ouabain |
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Term
What is the net effect of Angiotensin II on GFR?
What about in terms of sodium reabsorption in the proximal and distal nephron? |
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Definition
MAINTAINANCE (at low concentrations)
1a) Initially causes selective efferent arteriole constriction, which decreased RBF and increases hydrostatic pressure in the glomeruli, INCREASING the filtration fraction while MAINTAINING GFR (FF= GFR/RPF)
1b) Increase in glomerular capillary pressure is countered by increase in rate of rise of glomerular oncotic pressure, which opposes effects on ang-2 on GFR
2a) Increased peritubular oncotic pressure with decreased peritubular hydrostatic pressure leads to an increase in Na (and H20) reabsorption in the proximal nephron.
- AngII also stimulates Na/H exchange in proximal tubule
2b) Increased Aldosterone release leads to increased Na reabsorption in the distal nephron via ENaC stimulation |
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Term
| How does Angiotensin II increase systemic blood pressure? |
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Definition
Remember, Ang2 is released by JG cells in response to decreased "effective" arterial volume (CHF or cirrhosis)
1) Arterial vasoconstriciton
2) Increasing proximal tubular Na reabsorption
3) Release of aldosterone, increasing distal tubular Na reabsorption |
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Term
| How is renin release regulated? |
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Definition
1) Amount of solute delivered to macular densa in terms of Cl- (function of solute reabsorption)
2) Stretch of afferent arteriole (plasma volume)
3) SNS
4) PGE stimulates renin release |
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Term
| What is the difference in terms of functional activation between low and high concentrations of Ang 2 in the circulation? |
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Definition
1) Low concentrations only contract efferent arterioles
- Increase GFR initially by increasing hydrostatic pressure while, but tempered by decreasing RPF, which increases the rate of rise in the oncotic pressure in the glomerular capillary (increased Filtration Fraction)
- As fluid crosses constricted efferent arteriole, fall in hydrostatic pressure is greater than would be in dilated state, leading to a lower hydrostatic pressure in the peritubular capillary (coupled with an Increased oncotic pressure), which alters tubular sodium reabsorption.
2) High concentrations contracts both efferent and afferent arterioles, |
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Term
| How does increased AngII influence sodium reabsorption in the proximal tubule? |
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Definition
1) Increased peritubular oncotic pressure with decreased peritubular hydrostatic pressure leads to an increase in Na (and H20) reabsorption in the proximal nephron.
2) AngII also stimulates Na/H exchange in proximal tubule |
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Term
| What is the effect of increasing Arginine Vasopressin levels on sodium reabsorption in different segments of the nephron? |
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Definition
Can be activated by AngII signaling
1) Activates Na/K/2Cl co-transporter in TAL, and increases Na transport across cells lining the TAL and into the interstitium (transcellular)
2) Activates NCC and ENaC in distal nephron. |
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Term
| What is the effect of increasing Aldosterone levels on sodium reabsorption in different segments of the nephron? |
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Definition
Secreted from adrenal cortex in response to Ang II and increased plasma K+ (why ACE-i lead to hyperkalemia), to increase sodium reabsorption.
Acts on distal nephron
1) Activates Na-Cl co-transporter, ENaC in distal convoluted tubule (via mRNA and post-translational modifications)
2) Increasing basolateral Na/K ATPase activity in collecting duct |
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Term
| How do ANP and "Third factors" influence sodium reabsorption? |
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Definition
- ANP released by atrial myocytes in response to stretch
- Third factors are Ouabain analogues secreted by hypothalamus.
1) Increases GFR
2) Inhibits reabsorption in inner medullary collecting tubule by inhibiting the Na/K ATPase (increasing urinary excretion). |
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Term
| How do Dopamine, Endothelin and PGE increase urinary sodium excretion (decreasing reabsorption)? |
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Definition
1) Dopamine
- Inhibits Na/H exchanger and Na/K-ATPase in proximal tubule
- Also inhibits distal segments
2) Endothelin
- Inhibits ENaC in distal nephron
3) PGE
- Prostacyclin and PGE2 enhance renin secretion by JG cells
- PGE2 dilates efferent and afferent arterioles and promotes excretion by inhibiting reabsopriton in TAL and cortical collecting duct. |
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Term
| How does the SNS modulate sodium handling in the nephron? |
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Definition
1) Stimulation of renin secretion leading to increase in AngII and Aldosterone
2) Directly enhances renal Na reabsorption in proximal tubule |
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