Renal handling of Na, Cl, and H2O week 2 Flashcards
T or F: Na+, Cl-, and H2O are freely filtered and are also secreted.
True and false. Na+, Cl-, and H2O are all freely filtered but are not secreted. They are all reabsorbed.
Is Na+ reabsorption mainly active or passive? Is it reabsorbed via the transcellular route, paracellular route, or both?
Is Cl- reabsorption mainly active or passive? Is it reabsorbed via the transcellular route, paracellular route, or both? What is Cl- reabsorption linked to?
How is H2O absorbed? What is water reabsorption linked to?
Na+ reabsorption is active, via the transcellular route and is powered by the basolateral Na-K-ATPase.
Cl- reabsorption is passive (paracellular) and active (transcellular). Regardless of route, it is always coupled somehow to Na+ reabsorption. Indeed, parallel Cl- reabsorption is implied when describing Na+ reabsorption.
H20 reabsorption is by osmosis and secondary to reabsorption of solute, particularly Na+ and those dependent on Na+ reabsorption.
What are the main pathways for Na+ output? What is the major pathway?
Most Na+ output is in the urine. In Figure 4.1 (attached), about 80% of the ingested Na+ ends up in the urine. This large proportion in the urine should not be confused with the fact that nearly all filtered Na+ (>99%) is reabsorbed. The kidneys manage urine Na+ output to balance daily Na+ intake.
List the sites of Na+ reabsorption of the nephron and the percentage of filtered Na+ each part reabsorbs.
What percentage of filtred Na+ is excreted in urine?
What is an essential part of Na+ reabsorption in all nephron segments? Why is it so important?
In all nephron segments an essential part of Na+ reabsorption is the primary active transport of Na+ by the Na-K-ATPase (i.e. Na+ pumps) in the basolateral membrane. These pumps keep intracellular Na+ levels low. This is significant because low intracellular Na+ levels means that Na+ in the tubular lumen (present at a higher concentration) can move into the cell down its electrochemical gradient (across the apical membrane).
Explain the mechanism of Na+ reabsorption in the proximal tubule. Discuss how Na+ is moved across the apical and basolateral membranes.
Na+ Reabsorption Stepwise:
- Na-K-ATPase keeps intracellular Na level low. This means there is a gradient across apical membrane.
- Filtered Na+ is transported across apical membrane several ways (coupled to reabsorption of other molecules, see attached figure)
- Na+ entering the cell is then moved across basolateral membrane.
Important Points: Reabsorption of other solutes are linked to Na+ reabsorption.
Without the Na-K-ATPase, the Na+ gradient that powers reabsorption of Na & other solutes would not exist.
State what percentage of filtered Cl- is reabsorbed in each portion of the nephron. Explain your answer.
Cl- reabsorption is dependent on Na+ reabsorption. The tubular locations that reabsorb Cl- (as well as percentages of Cl- reabsorption) parallel those for Na+ described previously (see attached). To understand this, it is helpful to keep in mind the “electronuetrality rule”. For any volume of fluid (no membranes separating things here), the fluid will contain equal numbers of anions and cations. In our case, if the filtrate contains ~140 mEq of Na+ then it will also contain ~140 mEq of anions. Most of these anions will be Cl- (~110 mEq) and some will be bicarbonate (~24 mEq). There are obviously numerous other cations (K+ , Ca2+ etc.) and anions (SO4 2-, PO4 3- etc.) present. However, our focus here is on Na+ and Cl- which out number the others (and rather dramatically so).
What are the routes of Cl- reabsorption in the proximal tubule? Which is dominant?
Explain the mechanism of Cl- reabsorption in the proximal tubule. Discuss how Cl- is moved across the apical and basolateral membranes.
There are 2 routes of Cl- transport. One is paracellular through the tight junctions (that are not so “tight” in the proximal tubule). The Cl- moves along the paracellular route down its electrochemical gradient. Most Cl- transport in the proximal tubule occurs via the paracellular route.
The other Cl- transport route is transcellular through the epithelial cells. The transcellular route uses (in a relatively complicated way) the energy stored in the Na+ gradient to move Cl- into the cell across the apical membrane. The Cl- that enters the cell can then move across the basolateral membrane down its electrochemical gradient (this is facilitated by transport proteins).
The things to remember here about Cl- reabsorption are, 1) it depends on Na+ reabsorption and, 2) it occurs via two routes (para- and transcellular).
The kidneys must be able to separate water from salt. What is evidence that the kidneys are able to do this?
Kidney’s must be able to “separate salt from H20”. Obvious but important. If you drink excess H20 (no salt), then your kidneys must excrete the excess H20. If you eat excess salt (no H20), then your kidneys must excrete the excess salt. Evidence that the kidney is doing this is the body’s capacity to generate dilute (hypoosomtic compared to plasma) or concentrated (hyperosmotic compared to plasma) urine.
What are the sources of water loss? Where is the most lost in the body?
he two sources of body water are food/drink and metabolically produced water. Water is lost from the body via the GI track, skin, lungs and kidneys. Water loss from skin and lungs is sometimes called insensible water loss because you are usually unaware of it. Fecal or GI water loss is usually small. In a normally hydrated person, the kidneys account for about 60% of daily water loss and this water loss usually offsets exactly the water gained per day.
State the percentage of H2O reabsorbed by each portion of the nephron.
Explain how H2O reabsorption in different parts of the nephron compares to Na+ reabsorption.
Generally, how are H2O and Na+ reabsorption from collecting ducts controlled?
About 65% of filtered water is reabsorbed from the proximal tubule. About 10% is reabsorbed from the loop of Henle. The collecting duct reabsorbs between 5% and >24% of the filtered water. Water and Na+ reabsorption are compared in Figure 4.5 (attached) to make four significant points (listed below).
1) H2O and Na+ are reabsorbed from the proximal tubule in equal amounts.
2) H2O and Na+ are both reabsorbed from the loop of Henle but the part of the loop where each is reabsorbed is different. H2O is reabsorbed from the thin descending limb while Na+ is reabsorbed from the thick ascending limb. Overall, more Na+ than H2O is reabsorbed from the loop of Henle.
3) Na+ is reabsorbed from the distal tubule. H2O is not.
4) H2O and Na+ are reabsorbed from the collecting duct but the amounts of each are variable and controlled by a number of factors (to be discussed later).
Water moves down an ____ gradient.
osmotic
What are the 2 things that H2O movement depends on?
What are the 3 pathways by which water may move down an osmotic gradient across kidney epithelial cells?
- How much H2O moves will depend on, A) the size of the osmotic gradient present and, B) the relative H2O permeability of the different possible diffusion pathways.
- Water may simply diffuse through the lipid bilayer. It may diffuse through aquaporins (H2O channels) in the membrane. It may also diffuse through the tight junctions between cells.
What is the maximum urine concentration? What is the minimum urine concentration?
What is obligatory water loss? How may circumstances change obligatory water loss?
The kidney can produce urine with a maximal concentration of ~1400 mmoles/L during a period of extreme dehydration. This is close to 5 times the plasma osmolarity. Minimum urine osmolarity is usually reported to be ~50 mmole/L. The body normally needs to excrete about 600 mmoles/day of solute (e.g. urea). Thus, the minimal amount of H2O needed for this much solute to be excreted is 600/1400 or ~0.43 L/day. This is the minimum amount of urine the body must produce to rid itself of this solute. This is the obligatory water loss. This number may vary depending on circumstances. For example, fasting may result in some tissue catabolism releasing excess solute that must be excreted and thus this would increase the obligatory water loss.
What is the H2O permeability like of basolateral membranes of epithelial cells in different parts of nephrons?
Explain the H2O permeability of tight junctions and apical membranes in different parts of nephrons.
The basolateral membranes of epithelial cells all along the nephron are all highly H2O permeable due to the presence of aquaporins. However, the H2O permeability of the apical membranes and the tight junctions vary along the nephron. The apical membranes (& tight junctions) of the proximal tubule and descending limb of the loop of Henle are highly H2O permeable. The apical membrane (& tight junctions) of the ascending limb of the loop of Henle and the distal tubule are not H2O permeable (i.e. they are H2O impermeable). The tight junctions of the collecting duct are also not H2O permeable. The apical membrane of the collecting duct has an intrinsically low H2O permeability but this is regulated and under certain circumstances the H2O permeable of this membrane can increase substantially.
Explain why HCO3-, glucose, and amino acid concentration decreases with distance along the proximal tubule.
HCO3-, glucose and aa’s are reabsorbed by Na-dependent mechanisms (see figure). The concentration of all of these substances decreases to almost zero.
In the attached figure, note that although Cl- is reabsorbed in the proximal tubule, its concentration rises as you go farther along the proximal tubule. Explain the reason for this.
At the start of the proximal tubule, the Cl- concentration in the tubular fluid is the same as that in plasma. As the tubular fluid moves along the proximal tubule H2O is reabsorbed and the Cl- concentration in the tubular fluid increases. Remember, it is HCO3 - (not Cl- ) that follows Na+ reabsorption early in the proximal tubule and so Cl- is initially left behind. This is why the Cl- concentration initially rises. Note that it levels off even though H2O is continually being reabsorbed. This means that Cl- is being reabsorbed in the later regions of the proximal tubule in about equal proportion to H2O reabsorption. In these later regions of the proximal tubule, it is the Cl- anion that is following Na+ reabsorption (not HCO3 - because HCO3 - levels have dropped). The increase in tubular Cl- concentration also provides a Cl- gradient that drives passive paracellular Cl reabsorbed (later along the proximal tubule). As previously mentioned, most Cl- is reabsorbed in the proximal tubule occurs via the paracellular route.
Explain the concept of iso-osmotic volume reabsorption and why it occurs.
What portion of the nephron is iso-osmotic volume reabsorption characteristic of?
The proximal tubule is highly H2O permeable. Thus, even a tiny trans-tubular osmotic gradient is sufficient to drive H2O out of the proximal tubule. Indeed, 65% of filtered water is reabsorbed from the proximal tubule in exactly this situation. The osmolarity of the tubular fluid at the start of the proximal tubule is, of course, similar to that of plasma. As this fluid moves along, solute is reabsorbed and this 1) locally lowers the osmolarity of the tubular fluid and 2) locally elevates the osomolarity of the interstitium. This small very local osmolarity difference is what drives H2O through the cells and tight junctions. The reabsorbed H2O and solute is then carried away by the peritubular capillaries. Then, a little more solute is reabsorbed and the same thing happens again. The point here is that every little bit of solute reabsorbed drives a little bit of H2O to be reabsorbed. The result is that, at each point along the proximal tubule, nearly equal proportions of solute and H2O are reabsorbed. In this way, the volume of the tubular fluid decreases but its overall osmolarity remains relatively constant. This is often called iso-osmotic volume reabsorption. This is a fundamental characteristic of the proximal tubule which arises as a consequence of its very high H2O permeability. This iso-osmotic volume reabsorption is evident in Figure 4.6 as the straight line across the graph (labeled Na+ and osmolarity). Since Na+ is by far the most abundant solute, its concentration closely mirrors the tubular fluid’s osmolarity.
How does the Loop of Henle separate Na+ and H2O reabsorption? What does this result in as it pertains to the osmolarity of the tubular fluid in this region of the nephron?
Unlike the proximal tubule, the loop of Henle (over its entire length) always reabsorbs proportionally more Na+ (~25% of its filtered load) than H2O (~10% of its filtered load). Thus, the fluid leaving the loop is always more dilute (hypo-osmotic) compared to the fluid entering it. As shown in Figure 4.5 earlier (attached), there is a physical separation of H2O and Na+ reabsorption. The descending limb of the loop only reabsorbs H2O, not Na+ . The ascending limb of the loop (thick & thin) only reabsorbs Na+ , not H2O.
Explain the mechanism of Na+ reabsorption in the thick ascending limb of loop of Henle. State what transporters are present and what is required for function.
Why is the ascending limb often called a “diluting segment”?
At the basolateral membrane, Na+ is transported by the Na-K-ATPase as previously described. However, the Na+ transport mechanism at the apical membrane is unique to this region of the nephron. Apical Na+ transport is mediated by the Na-K-2Cl symporter. Using the energy stored in the Na+ gradient, this symporter simultaneously moves 1 Na+ , 1 K+ and 2 Cl- from the tubular fluid into the cell.
The Na-K-2Cl symporter requires all 3 ions be present in order to work. It would then seem that Na+ reabsorption would cease once tubular K+ was depleted (i.e. K+ being the least abundant of the 3 ions). However, the apical membrane of the ascending thick limb has K+ channels that allow K+ to leak back into the tubular lumen. Thus, K+ moves back and forth across the apical membrane keeping the Na-K-2Cl symporter going (i.e. moving Na+ into the cell). As stated above, the ascending limb of the loop of Henle reabsorbs Na+ (not H2O). Consequently, this segment of the nephron acts to dilute (reduce osmolarity of) the tubular fluid and thus the ascending limb is often called a “diluting segment”. The result is that the tubular fluid that enters the distal convoluted tubule is hypo-osmotic (more dilute) compared to plasma.
Explain the mechanism of Na+ reabsorption in the distal tubule.
Why is the distal tubule also known as a diluting segment?
Like the ascending limb of the loop of Henle, the distal tubule is essentially impermeable to H2O (i.e. tight junctions & apical membrane have very low H2O permeability). Also like the ascending limb, Na+ is reabsorbed from the distal tubule (~5% of the filtered Na+ load). However, the apical transport mechanism is different as shown in Figure 4.8. The apical membrane in the distal tubule contains the Na-Cl symporter. Powered by the energy stored in the Na+ gradient, this symporter simultaneously moves Na+ and Cl- from the tubular fluid into the cell.
The H2O permeability of distal tubule (like the ascending limb of the loop) is always very low and unchanging. Thus, essentially no H2O is reabsorbed from the tubular fluid as it flows through the distal tubule. However, Na+ is reabsorbed and thus the already hypo-osmotic tubular fluid becomes even more hypo-osmotic as it moves through the distal tubule. In other words, the distal tubule also acts as a so called “diluting segment”. The important point here is that the distal tubule delivers hypo-osmotic tubular fluid (compared to plasma) to the collecting duct.
Explain Na+ reabsorption in principal cells of the collecting duct.
What hormone regulates Na+ reabsorption in these cells?
The apical Na+ transport mechanism in principal cells is a Na+ channel. These are not the same type involved in the action potential in nerves and muscles. These are blocked by amiloride, not TTX (i.e. tetrodotoxin). These Na+ channels are also regulated by aldosterone (a steroid hormone) and this regulation is key to maintaining whole body Na+ homeostasis.
