Control of Absorption and Secretion in the Nephron

Question 1

What is the main difference between glomerular filtration and tubular reabsorption ?

Answer 1

Unlike glomerular filtration, tubular reabsorption is highly selective

Question 2

Give examples of molecules which are completely reabsorbed. What is the effect of this on their excretion ?

Answer 2

Glucose and amino acid reabsorption is almost complete so excretion is zero.

Question 3

Give examples of molecules whose excretion is variable. Why is that the case ?

Answer 3

Many ions such as sodium, chloride and bicarbonate are also highly reabsorbed but their rates of reabsorption and so excretion are highly variable and controlled.

Question 4

Give examples of molecules which are poorly absorbed. What is the effect of this on their excretion ?

Answer 4

Waste products such as urea and creatinine are poorly absorbed and excreted in large amounts.

Question 5

How does the body control the composition of body fluids ?

Answer 5

Controlling the rate at which the tubules reabsorb different substances independently of one another permits the control of body fluid composition.

Question 6

What transport processes are required for reabsorption processes ?

Answer 6

ACTIVE TRANSPORT

SECONDARY ACTIVE TRANSPORT

Question 7

Define active transport. Give an example of active transport used in reabsorption in the nephron.

Answer 7

Active transport can move a solute against an electrochemical gradient and requires energy derived from metabolism. It needs a pump that uses ATP.

• In the kidney tubular cells an example of this is the transport of sodium through the tubular epithelia.
• The sodium-potassium pump transports sodium from the interior of the cell across the basolateral membrane creating a low intracellular sodium concentration and negative intracellular electrical potential.
• This causes sodium to diffuse from the tubular lumen into the epithelial cells through the brush border.

Question 8

Define secondary active transport.

Answer 8

Two or more substances interact with a specific membrane protein (a carrier molecule) and are transported together across the membrane.
As one of the substances diffuses down its electrochemical gradient (eg sodium) through facilitated diffusion, the energy released is used to drive another substance (eg. glucose) against its (electro)chemical gradient. Does not require ATP directly as a pump.

Question 9

Give an example of secondary active transport used in reabsorption in the nephron.

Answer 9

• SGLT – sodium glucose co-transporter (uses sodium facilitated diffusion down its concentration gradient, to drive reabsorption of glucose, so in the same direction as Sodium)
• NHE-Na/H Exchanger (uses sodium facilitated diffusion to drive H+ secretion into tubular lumen)

Question 10

What proportion of filtered load of sodium and water is reabsorbed in the PT ?

Answer 10

• 65% of filtered load of sodium and water reabsorbed here.

Question 11

Describe the cellular ultrastructure and transport characteristics of the loop of Henle.

Answer 11

• 20 % of filtered water and 25% of filtered sodium, chloride and potassium reabsorbed.
• Thin descending segment permeable to water-diffusion.
• Ascending limb impermeable to water.
• Thick ascending limb has active transporters and absorbs sodium chloride and potassium.
• Other ions absorbed too.
• Co-transporters important there.

Question 12

Describe the mechanisms of sodium, chloride and potassium transport in the thick ascending limb.

Answer 12

1) Na-K-Cl cotransporter (NKCC)
• Takes one molecule of sodium, one potassium ion, and two chloride ions (so electroneutral) from tubular lumen to cell.
• Uses Na+ gradient to drive uptake of K+ and Cl-.
• Once inside:
-Na+ gets pumped out through Na+ K+ ATPase
-K+ goes out through potassium channels
-Cl- goes out through chloride channels

2) Na+ H+ exchanger (Na+ in, H+ into tubular lumen)

3) Paracellular diffusion
In the loop of Henle, tubular lumen becomes positive compared to interstitium, which is where you get uptake of divalent cations through paracellular diffusion (i.e. Mg++, Ca++, also some Na+ and K+)

Question 13

Where do loop diuretics work, in the kidney ? How ? Give examples of loop diuretics.

Answer 13

Loop diuretics act in thick ascending limb. Inhibit Na+ K+ Cl- cotransporter, which leads to less reasborption of Na+ and Cl- into interstitium, which means interstitium in medulla does not have such a high concentration of solutes, so cannot absorb as much water, so end up peeing more water. BV drops, so BP drops (antihypertensive)

Examples: furosemide

Question 14

Describe the cellular ultrastructure and transport characteristics or the early and late distal tubule.

Answer 14

• 5% of filtered load of sodium absorbed here.
• Impermeable to water.
• Pumps/absorbs sodium,
chloride and potassium just like the thick ascending limb loop of Henle.
• Urine becomes more dilute.
• Late section has 2 cell types.
• Principal cells absorb H2O and sodium ions.
• Intercalated cells absorb K+ and secrete H+ ions.

Question 15

Describe the mechanism of sodium chloride transport in the early distal tubule.

Answer 15

Similar to thick ascending limb:

• Na+ pump still basolateral
• Na+ Cl- cotransport (rather than Na+ K+ Cl- cotransporter), bringing Na+ and Cl- into cell.
• Na+ gets pumped out through Na+ K+ ATPase
• Cl- goes out through chloride channels

Question 16

Which drugs acts in early distal tubule ? How ?

Answer 16

Thiazide like diuretics.

Inhibit Na+ Cl- cotransporter. If block this transporter, less reasborption of Na+ and Cl- into interstitium, which means interstitium in medulla does not have such a high concentration of solutes, so cannot absorb as much water, so end up peeing more water. BV drops, so BP drops (antihypertensive).

Question 17

Describe the mechanism of sodium, potassium and chloride (and water) transport in the Principal cells of late distal and cortical collecting ducts.

Answer 17

PRINCIPAL CELLS (absorb H2O and sodium ions)

-Na+ K+ ATPase basolaterally creates sodium
gradient (pumps 3 Na+ out of cell into interstitium and 2 K+ inside cell)
-ENAC channels (Na+ channels) on apical surface enable transport of Na+ into cell down concentration gradient
-K+ can either be reabsorbed into interstitiual fluid via basolateral membrane K+ channels, or effluxed into lumen via K+ Cl- cotransporter on apical surface (or transported into lumen via K+ channels on apical surface)
-Cl- that is secreted (into lumen, via K+ Cl- co-transporter) usually comes back, either through Cl-
channels, or through paracellular pathway (since at late distal collecting tubules, lumen negative so chloride driven back in towards intersititium).

OVERALL, Principal cells tend to reabsorb Na+ (and Cl-) and excrete K+.

-Water also taken up across these cells (reabsorbed) especially in presence of ADH which makes them more permeable

Question 18

Describe the mechanism of sodium, potassium and chloride (and water) transport in the alpha-intercalated cells of the late distal and cortical collecting ducts.

Answer 18

ALPHA INTERCALATED CELLS

Important for excretion of excess protons when blood pH
is falling in acidosis.

-CO2 and H2O come together to make carbonic acid, catalysed by intracellular carbonic anhydrase.
Carbonic acid will then dissociates into bicarbonate and protons.
-In these cells, protons expelled in apical surface into lumen through H+ ATPase, and by K+ H+ ATPase (both using active transport) which pump protons out.
-Bicarbonate formed is reabsorbed via chloride bicarbonate exchangers.
-K+ (from K+H+ ATPase) can be reabsorbed via K+ channels
-Cl- (from HCO3- Cl- exchanger) can be reabsorbed via Cl- channels

Question 19

Describe the mechanism of sodium, potassium and chloride (and water) transport in the beta-intercalated cells of the late distal and cortical collecting ducts.

Answer 19

BETA INTERCALATED CELLS

Important for excretion of excess bicarbonate when blood pH is increasing in alkalosis.

-CO2 and H2O come together to make carbonic acid, catalysed by intracellular carbonic anhydrase.
Carbonic acid will then dissociates into bicarbonate and protons.
-Protons pumped out (reabsorbed) across basolateral surface via H+ ATPase.
-Bicarbonate excreted via Pendrin transporter AKA Cl- HCO3- exchanger).
-In some cases, can recycle bicarbonate back in again and get rid of chloride via chloride bicarbonate sodium exchanger (use Na gradient to reabsorb bicarbonate and secrete Cl-)
-Cl- brought inside the cell by Pendrin transporter can be transported into interstitial fluid via Cl- channels on basolateral membrane.

Question 20

Describe the cellular ultrastructure and transport characteristics of the medullary collecting ducts.

Answer 20

• Absorbs less than 10% of filtered water and sodium ions.
• Final site for processing urine and so determine urine output and composition.
• Vital to producing dilute or concentrated urine.
• Impermeable to water unless ADH is present.
• Permeable to urea and has urea transporters (ADH).
• Can secrete H+ ions so plays a role in acid/base balance.

Question 21

What are the main factors which may allow precise regulation of body fluid volumes and solute concentrations through excretion of different solutes and water at variable rates and sometimes independently of each other ?

Answer 21

HORMONES (allow regulation of tubular reabsorption)
NERVOUS SYSTEM (both directly and indirectly through increased hormone formation)

Question 22

Identify the main hormones responsible for specificity of tubular reabsorption, naming their site of action and effects.

Answer 22

1) Aldosterone
- Collecting tubule and duct
- Increased NaCl and H2O reabsorption, Increased K+ secretion

2) Angiotensin II
- PT, Thick Ascending loop of Henle, DT, CT
- Increased NaCl and H2O reabsorption, Increased H+ secretion

3) ADH
- DT/Collecting Tubule and Duct
- Increased H2O reabsorption

4) Atrial Natriuretic Peptide
- CDs
- Decreased NaCl reabsorption

5) Parathyroid Hormone
- DCT
- Decreased PO4 (3-) reabsorption, increased Ca++ reabsorption

Question 23

Where is aldosterone released ? What is its site of action ?

Answer 23

• Released from the adrenal cortex.

* A major renal tubular site of action of aldosterone in on the principal cells of the cortical collecting duct.

Question 24

What are the actions of aldosterone in the kidney ?

Answer 24

• Important regulator of sodium reabsorption (increases it) and potassium excretion.

1) Stimulates the sodium-potassium ATPase pump on the basolateral side of the cortical collecting tubule membrane.
2) Increases the sodium permeability of the luminal side
of the principal cell membrane (increases ENaC permeability)
3) Stimulates apically located H+-ATPase in intercalated cells resulting in proton secretion

Question 25

Which kinds of drugs act on the principal cells ? How do they act ?

Answer 25

• Aldosterone antagonists (spironolactone), “competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule”
• Na+ channel blockers (Amiloride), block ENaC channel to prevent intake of Na+ from tubular lumen

Overall, antihypertensive by reducing Na+ reabsorption into interstitium, which means interstitium in medulla does not have such a high concentration of solutes, so cannot absorb as much water, so end up peeing more water. BV drops, so BP drops (antihypertensive).

Question 26

How is Angiotensin II release triggered ?

Answer 26

Acts during haemorrhage and loss of salt and water.

Question 27

Identify the main effects of Angiotensin II.

Answer 27

1) Stimulates aldosterone release from the adrenal cortex
2) Constricts afferent and/or efferent arterioles in the kidney
3) Directly stimulates sodium reabsorption in the proximal
convoluted tubule, the Loops of Henle, the distal convoluted tubules and the collecting ducts.
4) Stimulates the sodium potassium ATPase on the basolateral side of the tubular epithelia, as well as the Na+ HCO3- cotransporter in that membrane which both result in Na+ brought to interstitial fluid. Also stimulates the sodium-hydrogen exchange on the luminal/apical membrane especially in the proximal tubule (AT1 receptors for it on both basolateral, and apical membranes), which results in sodium transported from tubular lumen to the cell.

OVERALL, increases body fluid and solute levels.

Question 28

What is the main effect of ADH ? How does it do this ?

Answer 28

Helps body to conserve water, by increasing the water permeability of the distal convoluted tubule, collecting tubule and collecting duct (+urea in IMCD). In order to do this:

• ADH binds to specific V2 receptors (on basolateral membrane) and through signal transduction mechanisms stimulate the movement of a vesicular associated intracellular water channel called aquaporin 2 to the apical (luminal) surface of the epithelial cells (this makes apical surface permeable to water so water can diffuse into cell via osmosis)
• Constitutively active aquaporin 3 channels (active regardless of ADH) on basolateral membrane then allow water to be transported into interstitial fluid, and blood.

Question 29

Describe the permeability of distal tubules and collecting ducts in the absence of ADH.

Answer 29

In the absence of ADH the permeability of the distal tubules and collecting ducts to water is low.

Question 30

How permanent is the movement of a vesicular associated intracellular water channel called aquaporin 2 to the apical (luminal) surface of the epithelial cells, as a result of ADH ?

Answer 30

This is reversible to allow control of water permeability of these distal sections of the tubule.

Question 31

What is the trigger for Atrial Natriuretic Peptide release ?

Answer 31

Atrial natriuretic peptides are secreted by the cardiac atria when they are distended by increased blood volume.

Question 32

How can the NS affect absorption/secretion in the kidney ?

Answer 32

Sympathetic nervous system activity can decrease sodium and water excretion mainly by constricting renal arterioles and so decreasing glomerular filtration rate (decrease blood flow to vasa recta, so increasing medullary interstitial osmolality). Can also increase angiotensin II formation (renin release) to increase tubular reabsorption and so decrease excretion of sodium and water.