Module 4 Section 4 (Tubular Reabsorption)

Question 1

Describe the process of transepithelial transport using sodium as an example.

Answer 1

There are 5 steps involved in transepithelial transport:

1) The substance must cross the luminal membrane.
2) The substance must pass through the cytosol.
3) The substance must cross the basolateral membrane.
4) It must diffuse through the interstitial fluid.
5) It must cross the capillary wall to enter the plasma.

This transport can be both passive and active. Rather than specifically describe the absorptive process for each of the filtered substances returned to the plasma, we will discuss the general mechanisms involved in the important case of Na+ reabsorption.

The reabsorption of Na is both active and passive.

• It moves passively across the luminal membrane, but the movement of it across the basolateral membrane is by active transport involving the Na K ATPase pump.
• Due to the large volume of Na that is reabsorbed, its transport accounts for 80% of the energy needs of the kidney. By actively transporting Na into the interstitial fluid, it helps to keep the cytosol Na conc low to allow for the passive diffusion across the luminal membrane.
• The mechanism of passive transport of Na across the luminal membrane varies throughout the various segments of the tubule.
  • In the proximal tubule, Na crosses by a cotransport carrier that simultaneously moves organic nutrients, such as glucose and amino acids. These nutrients are transferred by secondary active transport, as they use the conc gradient of Na established by the Na K ATPase pump to be transported against their concentration gradient, along with the passive transport of Na.
• In contrast, in the collecting duct, Na passively enters the epithelial cells through a Na channel.

Question 2

Describe how the reabsorption of sodium is regulated.

Answer 2

In the proximal tubule and the loop of Henle, a constant percentage of the filtered Na is reabsorbed regardless of the total amount of Na within the body fluids.
- In the distal tubule, however, the reabsorption of a small percentage of the filtered Na is subject to hormonal control

RAAS:

• The most important, and most well-known, hormonal system involved in the regulation of Na is the renin-angiotensin-aldosterone system (RAAS).
• Within the juxtaglomerular apparatus, there are granular cells that secrete renin into the blood.

Atrial Natriuretic Peptide (ANP):

• ANP is another hormone involved in the regulation of Na and water.
• Its actions are opposite to those of aldosterone in that ANP release reduces Na load and BP.
• When blood volume incr (or there’s an incr in venous return) stretch receptors in the left atrium, aortic arch, and carotid sinus stimulate the release of ANP.
• It has three main actions.
  1) It directly inhibits Na reabsorption in the distal tubules so there is more Na excreted in the urine.
  2) It inhibits both renin and aldosterone secretion.
  3) It dilates the afferent arterioles and incr GFR. As more salt and water are filtered, more salt and water are excreted.
• *Check chart on slide 13**

Question 3

Define Tm and explain why it is important in the reabsorption of necessary substances.

Answer 3

Any substance that is actively reabsorbed will bind to a specific carrier protein in the plasma membrane. B/c there are a limited # of carrier proteins in a membrane, there is a limit to how much of a substance can be reabsorbed. This is designated as the tubular, or transport, maximum (Tm).

For any given substance, if its conc in the tubular fluid exceed its Tm, then the excess will be excreted in the urine.

The plasma conc at which the Tm is exceeded is the renal threshold. T

• The plasma conc of many substances are essentially regulated by the kidneys and this carrier-mediated limitation.
• Ex: phosphate.
• In contrast, some substances, like glucose, have a Tm but their plasma conc are not regulated by the kidneys.
• *Check chart on slide 14**

Question 4

Describe the reabsorption of water along the entire tubule.

Answer 4

Water is passively reabsorbed all along the tubule as it follows sodium.

The following indicates how much water is reabsorbed at various locations within the kidney:

1) Proximal tubule = 65% (117 litres a day!)
2) Loop of Henle = 15%
3) Distal and collecting tubules = 20%

The fraction of water reabsorbed in the proximal tubule and loop of Henle is constant, despite the Na and H2O load in the body.

The proportion of water reabsorbed in the distal tubule and collecting tubule can vary depending on hormonal influences and the hydration state of the body.

Water flows through water channels called aquaporins.

• Those in the proximal tubule are always open allowing the flow of water by osmosis.
• Those in the distal tubule are under control by vasopressin, so they are not always open.

Na alone doesn’t produce the osmotic driving forces to bring H2O from the tubules into the peritubular capillaries. The plasma-colloid oncotic pressure of the peritubular capillaries also produces a strong osmotic drive for water reabsorption.

Question 5

The glomerular filtrate that enters the tubules is identical to plasma with the exception of plasma proteins. That is, there is no selectivity to glomerular filtration.

Tubular reabsorption includes the processes by which water and other necessary solutes are returned to the plasma, while allowing waste products to remain in the filtrate. What are the 2 steps of reabsorption?

Answer 5

1) Reabsorption begins w/ either active or passive movement of substances from the tubule -> the interstitial space.
2) Reabsorption then continues w/ passive movement of substances from the interstitial space back -> the bloodstream.

Question 6

True or false: tubular reabsorption is highly selective and variable.

Answer 6

True

In general, the tubules have a high reabsorptive capacity for substances needed by the body, and a low reabsorptive capacity for substances not needed by the body. Since water and solutes are critical for maintaining homeostasis, their tubular reabsorption is high

Check chart on slide 3 for the comparison of percentages of reabsorbed and excreted substances // Focus on the trend, not the #s

Question 7

Define transepithelial transport (sometimes called transcellular transport).

Answer 7

It’s the movement of solutes across an epithelial cell layer through the cell.

Question 8

Discuss the structure of the tubule.

Answer 8

The tubule is composed of a single layer of epithelial cells.

• The area of the epithelial cells that are in contact with the tubule lumen = the luminal membrane
• The area of the epithelial cells that are in contact with the interstitial fluid is the basolateral membrane.

Question 9

The membranes from neighbouring epithelial cells are not in contact (other than where there are tight junctions connecting them). What may occur as a result of this?

Answer 9

B/c of this, any substance that enters an epithelial cell cannot transport it to a neighbouring cell, the substance must move through the cell -> the interstitial space.

Question 10

Since 99.5% of all filtered Na+ is reabsorbed, this process is highly controlled. Na+ can be reabsorbed to various extents along the entire tubule. What is the reason for this?

Answer 10

The reason why Na+ is reabsorbed in so many places is that it is critical to the reabsorption of many other substances.

Question 11

What are the different locations of Na+ reabsorption within the kidney?

Answer 11

The proximal tubule:

• 76% of Na+ is reabsorbed
• Reabsorption of Na+ in this segment of the nephron is neededf or the reabsorption of glucose, amino acids, water, Cl, and urea

The ascending limb of the loop of Henle:

• It absorbs 25% of the total reabsorbed Na+
• In the ascending limb of the loop of Henle, Na+ along with Cl are essential to either concentrate, or dilute, the urine depending upon the body’s needs

The distal and collecting tubules:

• They collectively reabsorb 8% Na+.
• It is here that Na+ reabsorption is under hormonal control and plays a key role in regulating ECF volume and secretion of both K and H+.

Question 12

For a substance moving from the tubular membrane to the peritubular capillary, order the steps of transepithelial transport in the sequence in which they occur.

• The substance must cross the basolateral membrane
• The substance must cross the luminal membrane
• It must diffuse through the interstitial fluid
• It must cross the capillary wall to enter the plasma
• The substance must pass through the cytosol

1)
2)
3)
4)
5)

Answer 12

1) The substance must cross the luminal membrane
2) The substance must pass through the cytosol
3) The substance must cross the basolateral membrane
4) It must diffuse through the interstitial fluid
5) It must cross the capillary wall to enter the plasma

Question 13

What are the 3 primary triggers of renin secretion related to Na hormonal regulation?

Answer 13

1) When the granular cells detect a drop in BP, they secrete renin.
2) The granular cells are innervated by the SNS and will release renin when sympathetic activity incr.
3) The macula densa cells in the tubular portion of the juxtaglomerular apparatus are sensitive to the Na and when there is a decr in luminal Na, the macula densa cells trigger the granular cells to secrete renin.

Question 14

Once renin has been secreted into the blood, a series of events occur to regulate Na within the blood. What are the sequence of events involved in the RAAS system?

Answer 14

Renin:
- Once secreted, renin acts like an enzyme to convert angiotensinogen -> angiotensin I.

Angiotensin-converting enzyme:
- When circulating angiotensin I passes through the lungs, it is converted -> angiotensin II by the enzyme angiotensin converting enzyme (ACE).

Angiotensin II:
- Angiotensin II, in turn, stimulates the adrenal cortex to release aldosterone.

Aldosterone:
- Aldosterone then causes an incr in Na reabsorption in the distal and collecting tubules.

Question 15

Define angiotensinogen.

Answer 15

A protein made in the liver that is present at high concentrations in the plasma

Question 16

Under the influence of aldosterone, tubular epithelial cells incr the insertion of Na channels in the luminal membrane and Na K ATPase carriers in the basolateral membrane. What is the combined result?

Answer 16

Combined, this results in a greater passive flow of Na out of the tubular fluid.

This enhanced Na retention also causes incr water retention (remember that water follows Na) and will therefore increase arterial BP.

Watch vid on slide 12

Question 17

True or false: for many electrolytes, such as P and Ca, the kidneys help to regulate their plasma concentration.

Answer 17

True

Question 18

How do the kidneys regulate phosphate?

Answer 18

Regulation of the plasma conc of P within the kidney is achieved b/c the renal threshold for P is the same as the normal plasma conc of P.

Since our diets are very rich in P, after eating, there is a rise in the plasma conc. This incr the filtered load of P but since the max for reabsorption is the same as the plasma P conc, all P above the normal plasma concentration is excreted in the urine.
- This restores the plasma P conc to normal.

Question 19

True or false: unlike the reabsorption of organic nutrients like glucose and amino acids, the reabsorption of P and Ca are under hormonal control.

Answer 19

True

Hormones can alter their renal thresholds to modulate their reabsorption to match the body’s needs.

Question 20

Discuss the hormonal control of phosphate.

Answer 20

Parathyroid hormone (PTH) can alter the renal thresholds for P and Ca and can adjust the quantity of conserved electrolytes, depending on the body’s needs.

A fall in plasma concentration results in 2 effects which help raise the circulating level back to normal.

1) B/c of the inverse relationship b/w the P and Ca conc in the plasma, a fall in plasma P incr plasma Ca, which directly suppresses PTH secretion.
- In the presence of reduced PTH, P reabsorption by the kidneys incr, returning plasma P conc toward normal.
2) A fall in plasma also incr activation of vitamin D within the kidney, which then promotes absorption in the intestine.

Check graphs on subpage of Slide 15

Question 21

True or false: glucose plasma concentrations are not regulated by the kidneys.

Answer 21

True

Question 22

What is the regular plasma concentration of glucose?

Answer 22

The plasma conc of glucose is normally 100mg per 100mL of plasma.

Question 23

Glucose is small enough that it is freely filterable and the concentration in Bowman’s capsule filtrate is the same as it is in the plasma. Given that the normal GFR is 125 ml/min, we can calculate that 125 mg/min glucose is filtered. This is what is called the filtered load of a substance. How is it calculated?

Answer 23

Filtered load = plasma concentration x GFR

Filtered load of glucose = 100 mg/100 mL x 125 ml/min = 125 mg/min

As seen in the graph (SLIDE 16), any increase in GFR results in a proportional increase in its filtered load.

Question 24

From what you have now learned about glucose and plasma concentrations in the kidney, at what plasma concentration will glucose start appearing in the urine? (Refer to the graph for reference on slide 17)

Answer 24

In the case of glucose, its normal Tm is 375 mg/min. This means that for all filtered loads of glucose below 375 mg/min, 100% of the glucose will be reabsorbed.

Only when the filtered load of glucose exceeds 375 mg/min will glucose appear in the urine.

Question 25

Using what you have learned thus far about the kidneys’ ability to filter glucose, explain why this increase in glucose in the urine exists.

Answer 25

Ordinarily, urine contains no glucose because the kidneys are able to reabsorb it all.

Bowman’s capsule collects the filtrate that the glomerulus forms which includes urea, electrolytes, and glucose.
- The filtrate then passes into the proximal tubule to be reabsorbed.
- Proximal tubule, however, can only reabsorb a limited amount of glucose.
• When blood glucose levels exceed about 160-180 mg/100 mL, the proximal tubule is overwhelmed and begins to excrete glucose into the urine.

Question 26

The secondary active reabsorption of glucose and amino acids is linked to the Na+ K+ ATPase pump. What else depends on it?

Answer 26

The passive reabsorption of Cl, H2O, and urea also depends on this active Na+ reabsorption mechanism.

Question 27

Discuss the reabsorption of chloride.

Answer 27

Despite the high conc of Cl in the plasma, the kidneys do not directly regulate it.

The majority of Cl does not undergo transepithelial transport, rather it leaves the tubular fluid by moving b/w the epithelial cells.

• It goes down its electrochemical gradient, essentially following the amount of Na+ reabsorption.
• Therefore, the amount of Cl reabsorbed is determined by the amount of Na reabsorbed.

Question 28

Discuss the reabsorption of urea.

Answer 28

Though urea is a waste product from the breakdown of protein, a large amount of urea is reabsorbed.

The conc of urea at the beginning of the proximal tubule is the same as the plasma concentration of urea so there is no net diffusion.

• However, as fluid moves through the proximal tubule, its volume is reduced by 2/3 as H2O is reabsorbed so the tubular conc of urea increases three-fold.
• B/c of this, it’s passively reabsorbed.
• With each pass through the nephron, only 40-50% of plasma urea is filtered and excreted from the body.

Question 29

Blood urea, measured as blood urea nitrogen (BUN), has historically been used as a measure of renal failure. What would occur during renal failure?

Answer 29

During renal failure, less urea is excreted so it accumulates in the plasma and can be clinically measured.

Question 30

Now that you have an idea of how renin and Na+ are regulated, match the correct responses to complete the chart:

• Aldosterone
• Angiotensin
• Angiotensin converting enzyme (ACE)
• Angiotensin I

From left to right CHECK SLIDE 22

1) Liver -> ___
2) Kidney -> Renin -> ___
3) Lungs -> ___ -> Angiotensin II
4) Adrenal cortex -> ___ -> 5) Kidney

Answer 30

1) Liver -> Angiotensinogen
2) Kidney -> Renin -> Angiotensin I
3) Lungs -> Angiotensin Converting enzyme (ACE) -> Angiotensin II
4) Adrenal cortex -> Aldosterone -> 5) Kidney