Renal Transport Mechanisms

Question 1

• What five barriers must a substance cross to be reabsorbed?

Answer 1

• Luminal cell membrane
• Cytosol
• Basolateral cell membrane
• Interstitial fluid
• Capillary wall

Question 2

• Why do we filter so much only to reabsorb 99%?

Answer 2

• Foreign substances are filtered into the tubule
  
  • Certain substances are secreted into the filtrate (toxic in high concentration)
• FIltering ions and water into the tubule makes regulation simple

Question 3

• What things are reabsorbed (and at what percentages) in the proximal convuluted tubule?

Answer 3

• Glucose-100%
• Amino Acids-100%
• Urea-50%
• Sodium-65-70%
• Water-65-70%
• Potassium-70%
• Phosphate-70%
• Calcium-70%
• Magnesium-30%

Question 4

• What things are reabsorbed (and at what percentages) in the proximal straight tubule?

Answer 4

• Phosphate-15%

Question 5

• What is reabsorbed (and at what percentages) in the thick ascending LOH?

Answer 5

• Sodium-25%
• Potassium-20%
• Calcium-25%
• Magnesium-60%

Question 6

• What things are reabsorbed (and at what percentages) in the Distal Convuluted Tubule?

Answer 6

• Sodium-5%
• Calcium-8%
• Magnesium-5%
• H20 and urea-variable

Question 7

• What things are reabsorbed (and at what percentages) in the collecting duct?

Answer 7

• Sodium-3%
• Water and urea-variable

Question 8

• What is the “workhorse” of the PCT? Where is it located?

Answer 8

• Na+/K+ ATPase
• Basolateral membrane

Question 9

• What are the two ways by which a substance can be transported across the tubule lumen and into the interstitial space?

Answer 9

Transcellular (thru the cell)

Paracellular (between the cell)

Question 10

• What types of channels are found on the apical surface of the proximal convuluted tubule?

Answer 10

• Sodium leak channels (majority of Na+ reabsorption)
• Na+/H+ exchanger (antiporter)
• Aquaporin Is
• SGLT I and 2

Question 11

• How does the Na+/H+ exchanger (NHE3) work?

Answer 11

• Pumps a Na+ in and a H+ ion out
• H+ combines with HCO3- in the tubular lumen via CA- H2CO3 then dissociates into H2O and CO2
• H2O can get into the cell via AQP1s
• CO2 diffuses into the cell
• CO2 and H2O combine again to form H2CO3 which spontaneously dissociates into H+ and HCO3-
• HCO3- is transported into the interstitial fluid via transporter
• H+ goes back into tubular lumen via Na+/H+ exchanger

Question 12

What are the two important consequences of the Na+/H+ exchanger?

Answer 12

• Sodium reabsorption
• Bicarbonate reabsorption

Question 13

• How does chloride reabsorption in the proximal tubule work?

Answer 13

• Early in the proximal tubule, a lot of water (compared to Cl-) is reabsorbed
  
  • Leads to an increase in Cl- conc in the lumen
• Later segement of the proximal tubule-Na+ and H2O have been reabsorbed, Cl- concentration has increased by 20%
• Provides a chemical gradient that drives chloride movement passively along paracellular pathway down its concentration gradient

Question 14

• Where in the proximal tubule are the SGLT 2 and SGLT 1 located? What side of the membrane are they on? What type of transporter are they?
• Which is most responsible for reabsorption of glucose

Answer 14

• SGLT 2 is located on the apical side of the first and second segments of the proximal tubule
• SGLT 1 is located on the apical side of the third segement of the proximal tubule
• Both are symporters (transporting Na+ and glucose in the same direction-into the cell)
• SGLT 2 responsible for 90% glucose reabsorption

Question 15

• Which of the SGLT transporters has high affinity and low capacity?
• Which of the SGLT transporters has low affinity and high capacity?

Answer 15

SGLT 1 and GLUT 1

SGLT 2 and GLUT2

*High affinity rewuires only a lower concentration to fill binding sites*

Question 16

• What is the transport maximum for glucose?
• What happens beyond this point?

Answer 16

• When all SGLT1 and SGLT2 receptor sites are occupied
• 375 mg/min (Plasma glucose level of 200)
• No more glucose can be reabsorbed and is excreted into the urine

Question 17

• What transporters are found on the descending loop of henle?
• What is a key feature about the descending LOH?

Answer 17

• Aquaporin I (ON BASOLATERAL SIDE)
• Permeable to water but impermeable to solutes
• (as you go down the descending LOH, the filtrate becomes hyperosmolar as water is leaving and solutes become more concentrated (can get as high as 1400 mOsm)

Question 18

• What is the key feature about the ascending (thick and thin) LOH?

Answer 18

• Permeable to solutes (NaCl)
• Impermeable to water (lots of tight junctions and no aquaporins)

Question 19

• What are key transporters found on the thick ascending LOH? On which side of the cell are they found?

Answer 19

• APICAL SIDE
  
  • NaK2CL Transporter
  • K+ Leak channels (K+ leave cell)
• BASOLATERAL SIDE
  
  • Na+/K+ ATPase
  • Cl- leak channels (Cl- leave cell)

Question 20

• How does the NaK2Cl transporter work?

Answer 20

• Located on apical surface of thick ascending LOH
• Gradient provided by Na+/K+ ATPase on basolateral side pumping Na+ out of the cell (creates a gradient for sodium to move), the K+ leak channel on the apical surface enabling K+ to leave (and permitting influx of K+ via concentration gradient) and Cl- leak channels on the basolateral side enabling Cl- to leave and giving Cl- a gradient to move down
• NET EFFECT: One positive charge and two negatively charge particles have been reabsorbed from the lumen (leads to a transepithelial positive voltage)
  
  • Drives the movement of Na+, Ca2+, and Mg2+

Question 21

• How do loop diuretics (furosemide) work?

Answer 21

• Inhibit Na+/Cl- reabsorption by competing for the Cl- binding site on the NaK2Cl transporter

Question 22

• What transporters are present in the distal tubule? On which side of the membrane are they located?

Answer 22

• Na+-Cl- (NCC) cotransporter on apical surface
• Cl- leak channel on basolateral surface
• Na+/K+ ATPase on basolateral surface
• Relatively impermeable to water

Question 23

• How do thiazide diuretics work?
• What are they used for?

Answer 23

• Inhibit NCC and enhance Ca2+ reabsorption in the distal tubule by increasing Na/Ca2+ exchange
• Reduce excretion and increase absorption of Ca2+
• Used to treat kidney stones and osteoporosis
• Decreases blood volume and pressure
• Inhibits reabsorption of NaCl

Question 24

• What is special about the collecting duct?
• What types of transporters are found in the collecting duct? On which side of the membrane?

Answer 24

• The collecting duct reabsorbs based on what the body needs and is regulated by hormones (primarily aldosterone and PTH)
• Na+/K+ ATPase on basolateral side
• AQP II on apical side (influenced by ADH/AVP/Vasopressin, ANP, BNP)
• ENAC on apical side (influenced by aldosterone)

Question 25

* What are the goals of aldosterone * What does it respond to directly? * What does it respond to indirectly?

Answer 25

* Increase NaCl and water reabsorption * Increase K+ secretion * Directly responds to an increase in plasma K+ concentration * Indirectly responds to decreases in Na+, ECF volume and arterial pressure

Question 26

* An increase in plasma K+ will lead to an increase in aldosterone secretion and an increase in _ and \_

Answer 26

* K+ secretion in the tubules * Urinary excretion of K+

Question 27

* Which hormone activates aldosterone? * What happens as a result?

Answer 27

* Angiotensin II * Increase in aldosterone * Increase in Tubular Na+ reabsorption (**ENACs on apical surface)**

Question 28

* What is the MOA of loop diuretics such as **furosemide?**

Answer 28

* Inhibits the NaK2Cl transporter on the apical surface of the thick ascending LOH * Decreased reabsorption of Na,K,Cl * Diuresis * Increased urine output

Question 29

* How does K+ sparing spirinolactone work?\*\*

Answer 29

* **Aldosterone dependent** * **Inhibits Na+/K+ exchange in distal tubule and collecting duct and promotes K+ retention and Na+ and water loss** * **Hypotensive effect**

Question 30

* Describe the steps that occur when you have a water deficit

Answer 30

1. ADH secretion increases 2. More H2O reabsorption in the collecting duct 3. Small volume of concentrated urine excreted (can be concentrated up to 1200 mOsm)

Question 31

* Decribe the key steps that occur with water excess

Answer 31

* No ADH secreted * Distal and collecting tubules remain impermeable to water * Tubular fluid entering the distal tubule is hypotonic (100 mOsm/L) having lose salt without an accompanying loss in H2O in ascending LOH) * As the hypotonic fluid passes through the distal and collecting tubules, the medullary osmotic gradient cannot exert any influence b/c the late tubule is impermeable to H2O * In absence of ADH, 20% of filtered fluid that enters that distal tubule is not reabsorbed * Excretion of wastes and other solutes remains constant * Net result=large volume of dilute urine

Question 32

Answer 32

* Proximal tubule 67% * Descending LOH 15% * Distal Tubule (Early part) 0% * Late Distal tubule and collecting duct (8-15%)

Question 33

***_What hormones influence Na+ reabsorption and where do they act in the nephron?_***

Answer 33

* Proximal tubule * 65-70% Na+ reabsorption * Angiotensin II, NE, Epi, Dopamine * LOH * 25% Na+ reabsorption * Aldosterone, Angiotensin II * Distal Tubule * 5% Na+ reabsorption * Aldosterone, Angiotensin II * Late Distal Tubule and Collecting Duct * ~3% Na+ reabsorption * Aldosterone, ANP, BNP, urodilatin, uroguanylin, guanylin, angiotensin II