Renal Tubular Function 2

Question 1

What are the two functionally distinct components of the loop of Hence?

Answer 1

1. Descending limb -
2. Thick ascending limb
   The key function is to create a hyperosmolar interstitial space in the medulla to drive water loss from the defending limb and cortical collecting duct

Question 2

Describe the function of the descending limb

Answer 2

Permeable to water, which leaves the filtrate because of osmotic force.
Mostly paracellulary

Question 3

Describe the function of the thick ascending limb

Answer 3

Can sustain an osmotic gradient of about 200mOSm/kg
Uses the Na+/K+/2Cl- cotransporter to move ions out of the filtrate. Common abbreviation NKCC2
K+ recycling through the apical membrane is necessary in order to ensure that the transporter can maintain its role of transporting large quantities of Na+ and Cl-

Question 4

Where does furosemide act?
What does it do?
What are its uses?
What are its side effects?

Answer 4

Acts in the ascending limb (a loop diuretic)
Blocks Na+/K+/2Cl- co-transporter
Allows up to 20% of filter Na+ to be excreted, causing enormous natriuresis and diuresis.
Uses: cardiac failure, renal failure
Side effects: K+ loss, leading to cardiac dysrhythmias
Other SE’s: hypovolaemia, milk metabolic alkalosis, loss of Mg2+ and Ca2+ (loss of filtrate +ve charge)

Question 5

Describe the effect of a counter-current mechanism in the loop of Henle

Answer 5

see khan academy

Question 6

How is Na+ absorbed in the distal tubule?

Answer 6

Via Na+/Cl- tranporters

Then Na+ leaves basolateral membrane via K+/Cl- symporter

Question 7

What are thiazides?
Where do they act?
What do they do?
What are their uses?
What are their side effects?

Answer 7

Thiazides (bendroflumethiazide, hydrochlorothiazide) and thiazide-like drugs (indapamide)
- act in the distal tubule
- block Na+/Cl- cotransporters
- moderately effective diurectics
- used as a diuretic, in conjunction with furosemide
Side effects - increased uric acid, hyperglycaemia, hyponatraemia

Question 8

Describe Na+, K+ and water transports in the collecting ducts

Answer 8

H2O - via aquaporins
Na+ - ENaC channels
K+ = enters filtrate via K+ channels

Question 9

What does amiloride do?

Answer 9

Inhibits ENaC channels.

Potassium sparing diuretic

Question 10

Describe the role of aldosterone and ADH in water tranport in the collecting ducts

Answer 10

Aldosterone stimulates the synthesis of the Na+/K+ATPase on the basolateral membrane.
ADH increases number of AQP2 on the apical membrane

Question 11

What does spironolactone do?
What is its mechanism of action?
When is it used?
What are its side effects?

Answer 11

Potassium sparing diuretic
Blocks effects of aldosterone in the collecting ducts
Used in heart failure (K+ sparing)
Side effects: gynacomastia, menstrual disorders, testicular atrophy, hyperkalaemia

Question 12

Describe urea countercurrent multiplication

Answer 12

In the late distal tubule and cortical collecting duct (urea impermeable), as water is removed, the urea conc rises. In the medullary collecting duct the urea diffuse out of the urea-permeable tubule. Urea permeability is increased by ADH, by increasing expression of UT-A1
The urea, now in the medullary interstitial space, contributes significantly to the high osmotic pressure in the medulla.
Hence there is a urea countercurrent, out of the collecting duct and into the Loop of Henle, which further aids water reabsorption in the medulla.