Regulation of NaCl Balance Flashcards
What is the relationship between the amount of Na+ that we ingest and the amount we excrete?
The amount of NaCl excreted by the kidneys can vary widely. Under conditions of salt restriction (i.e., a low NaCl diet), virtually no Na+ appears in the urine. Conversely, in persons who ingest large quantities of NaCl, renal Na+ excretion can exceed 1000 mEq/day. The kidneys require several days to respond maximally to variations in dietary NaCl intake. During the transition period, excretion does not match intake, and the person is in either positive (intake > excretion) or negative (intake < excretion) Na+balance. When Na+ balance is altered during these transition periods, the ECF volume changes in parallel. Water excretion, regulated by AVP, also is adjusted to keep plasma osmolality constant, effectively resulting in isosmotic changes in ECF volume. Thus with positive Na+ balance, the ECF volume expands, whereas with negative Na+ balance, the ECF volume contracts. In both cases no change in plasma [Na+] occurs. These changes in ECF volume can be detected by monitoring changes in body weight. Ultimately, renal excretion reaches a new steady state and NaCl excretion once again is matched to intake. The time course for the adjustment of renal NaCl excretion varies (from hours to days) and depends on the magnitude of the change in NaCl intake. Adaptation to large changes in NaCl intake requires a longer time than adaptation to small changes in intake.
NOTE: The figure is true for a euvolemic person, perhaps not true in other situations
In addition to the slide, answer these questions at the end.
- What does that tell us how Na+ is handled by the kidney?
- If the filtered load of the solute is greater than the excretion rate then the solute is […]
- If the excretion rate is greater than the filtered load then the solute is […]
- See slide for calculations.
- Na+ is freely filtered by the kidney and is reabsorbed, not secreted. In addition, the amount of Na+ excreted in equivalent to the amount ingested/day
- reabsorbed
- secreted
Describe the locations and relative amounts of Na+ that are reabsorbed in the different parts of the nephron.
During euvolemia, Na+ handling by the nephron can be explained by two general processes:
- Na+ reabsorption by the proximal tubule and loop of Henle is regulated so that a relatively constant portion of the filtered amount of Na+ is delivered to the distal tubule. The combined action of the proximal tubule and loop of Henle reabsorbs approximately 92% of the filtered amount of Na+, and thus 8% of the filtered amount is delivered to the distal tubule.
- Reabsorption of this remaining portion of the filtered amount of Na+ by the distal tubule and collecting duct is regulated so that the amount of Na+ excreted in the urine closely matches the amount ingested in the diet at steady state. Thus these later nephron segments make final adjustments in Na+ excretion to maintain the euvolemic state.
What is the role of aldosterone in regulating Na+ levels in the blood and urine.
Aldosterone is the primary regulator of Na+ reabsorption by the distal tubule and collecting duct and thus of Na+ excretion. When aldosterone levels are elevated, Na+ reabsorption by these segments is increased (excretion is decreased). When aldosterone levels are decreased, Na+ reabsorption is decreased (excretion is increased).
What is transcellular and paracellular movement of solutes?
In the nephron, a substance can be reabsorbed or secreted through cells, the so-called transcellular pathway, or between cells, the so-called paracellular pathway
Na+ reabsorption in the PCT varies depending on whether the Na+ is being reabsorbed by the first or second half of the PCT. Describe the reabsorption of Na+ in the first part of the PCT.
Na+-K+-ATPase pump in the basolateral membrane moves Na+ out of the cell into the blood and K+ into the cell –> lowers intracellular [Na+] and increases intracellular [K+] –> low intracellular [Na+] and high [Na+] in tubular fluid generates electrochemical gradient that favors Na+ movement into the cell and makes interior of the cell electrically negative with respect to the tubular lumen. Na+ can then be reabsorbed either by transcellular or paracellular mechanisms.
Transcellular
- Na+-H+ antiporter: Na+ entry with H+ extrusion from the cell
- Symporter mechanisms, including Na+-glucose, Na+–amino acid, Na+-Pi, and Na+-lactate.
- The glucose and other organic solutes that enter the cell with Na+ leave the cell across the basolateral membrane by passive transport mechanisms.
- Any Na+ that enters the cell across the apical membrane is sensed by Na+-K+-ATPase pump and pump is stimulated to increase its rate of Na+ extrusion into the blood, thereby returning intracellular Na+ to normal levels.
Na+ reabsorption in the PCT varies depending on whether the Na+ is being reabsorbed by the first or second half of the PCT. Describe the reabsorption of Na+ in the second part of the PCT.
Na+ is mainly reabsorbed with Cl− across the transcellular pathway. Na+/K+ ATPase establishes low [Na+] inside cell so that Na+ can enter across the luminal membrane through the parallel operation of a Na+-H+ antiporter and one or more Cl−-base antiporters. Secreted H+ and base combine in the tubular fluid and reenter the cell, so the operation of the Na+-H+ and Cl−-base antiporters is equivalent to NaCl uptake from tubular fluid into the cell. Na+ leaves the cell through the Na+-K+-ATPase mechanism, and Cl− leaves the cell and enters the blood through a K+-Cl− symporter and a Cl− channel in the basolateral membrane.
Some NaCl also is reabsorbed across the second half of the proximal tubule by a paracellular route. Paracellular NaCl reabsorption occurs because the rise in the Cl− concentration in the tubule fluid in the first half of the proximal tubule creates a Cl− concentration gradient. This concentration gradient favors the diffusion of Cl− from the tubular lumen across the tight junctions into the lateral intercellular space. Movement of the negatively charged Cl− causes the tubular fluid to become positively charged relative to the blood. This positive transepithelial voltage causes the diffusion of positively charged Na+ out of the tubular fluid across the tight junction into the blood. Thus in the second half of the proximal tubule, some Na+ and Cl− are reabsorbed across the tight junctions (the paracellular pathway) by passive diffusion. The reabsorption of NaCl establishes a transtubular osmotic gradient that provides the driving force for the passive reabsorption of water by osmosis.
Both the thin ascending and thick ascending limbs of Henle can reabsorb NaCl, but do so by different mechanisms. Describe the reabsorption that occurs in the thin ascending limb.
The thin ascending limb reabsorbs NaCl by a passive mechanism. The reabsorption of water but not NaCl in the descending thin limb increases the [NaCl] in tubule fluid entering the ascending thin limb. As the NaCl-rich fluid moves toward the cortex, NaCl diffuses out of tubule fluid across the ascending thin limb into the medullary interstitial fluid, down a concentration gradient directed from tubule fluid to interstitium.
Both the thin ascending and thick ascending limbs of Henle can reabsorb NaCl, but do so by different mechanisms. Describe the reabsorption that occurs in the thick ascending limb.
Na+-K+-ATPase maintains a low intracellular [Na+], which provides a favorable chemical gradient for the movement of Na+ from the tubular fluid into the cell. The movement of Na+ across the apical membrane into the cell is mediated by the Na+-K+-2Cl− symporter (NKCC2), which couples the movement of Na+ with K+ and 2Cl−. Using the potential energy released by the downhill movement of Na+ and Cl−, this symporter drives the uphill movement of K+ into the cell against its concentration gradient (see image). The K+ channel in the apical plasma membrane allows the K+ transported into the cell by NKCC2 to recycle back into tubule fluid for the continued operation of NKCC2.
A Na+-H+ antiporter in the apical cell membrane also mediates Na+ reabsorption as well as H+ secretion (HCO−3 reabsorption) in the thick ascending limb. Na+ leaves the cell across the basolateral membrane through the Na+-K+-ATPase pump, whereas K+, Cl−, and HCO−3 leave the cell across the basolateral membrane by separate pathways.
Increased NaCl transport by the thick ascending limb increases the magnitude of the positive voltage in the lumen, and this voltage is an important driving force for the reabsorption of several cations, including Na+, K+, Mg++, and Ca++ across the paracellular pathway.
- How is Na+ reabsorbed in the early part of the DCT?
- What effect do thiazide diuretics have on this process?
- The early DCT represents the end of […] of filtrate.
- The initial segment of the distal tubule reabsorbs NaCl into the cell across the apical membrane via a Na+-Cl− symporter. Na+leaves the cell through the action of Na+-K+-ATPase, and Cl− leaves the cell by diffusion through Cl−channels.
- NaCl reabsorption is reduced by thiazide diuretics, which inhibit NCC.
- Thus dilution of the tubular fluid begins in the thick ascending limb and continues in the early segment of the distal tubule
Describe the reabsorption of Na+ in the late DCT and collecting duct through principal cells.
Both Na+ reabsorption and K+ secretion by principal cells depend on the activity of Na+-K+-ATPase in the basolateral membrane. By maintaining a low intracellular [Na+], this transporter provides a favorable chemical gradient for the movement of Na+ from the tubular fluid into the cell. Because Na+ enters the cell across the apical membrane by diffusion through Na+-selective channels in the apical membrane, the negative voltage inside the cell facilitates Na+ entry. Na+ leaves the cell across the basolateral membrane and enters the blood through the action of Na+-K+-ATPase. Na+ reabsorption generates a lumen-negative voltage across the late distal tubule and collecting duct, which provides the driving force for Cl− reabsorption across the paracellular pathway
Angiotensin 2
- Net effect on kidney
- Locations it exerts effects
- Triggers for its production
- Potent stimulatory effect on NaCl and water reabsorption
- PCT, TAL, DCT
- Decrease in the extracellular fluid (ECF) volume activates the renin-angiotensin-aldosterone system, thereby increasing the plasma concentration of angiotensin II
Atrial Natriuretic Peptide
- Effect on kidney
- Where / when is it produced
- Inhibit NaCl and water reabsorption
- Atria, stimulated by a rise in blood pressure and an increase in the ECF volume
- Reduce the blood pressure
- Decreasing TPR
- Vasodilate afferent and efferent arterioles on glomerulus –> increase RBF and GFR –> increase filtration NaCl –> increase NaCl and water excretion
- What is Effective Circulating Volume (ECV)?
- What is its relationship to ECF?
- How are alterations in ECV restored?
- ECV is not a measurable and distinct body fluid compartment. The ECV refers to the portion of the ECF that is contained within the vascular system and is “effectively” perfusing the tissues. More specifically, the ECV reflects the perfusion of those portions of the vascular system that contain the volume sensors
- In a healthy person, ECV varies directly with ECF
- Change Na+ excretion to restore normal ECV (euvolemia)
