L12. Renal phys: proximal tubule-> loop of henle

Question 1

How is the GFR in the renal corpuscle kept at a constant rate despite changes in systemic blood pressure that should cause stronger hydrostatic pressure

Answer 1

Renal autoregulation by feedback mechanisms that constrict the afferent to decrease blood flow and GFR back to normal or moderately constrict efferent arteriole to increase the GFR back to normal/ dilate the afferent arteriole.
Both Extrinsic and intrinsic mechanisms,

Question 2

What are the mechanisms that go into place when GFR is too high - extrinsic and intrinsic

Answer 2

Intrinsic: When GFR is too high, there is higher NaCl levels in the distal tube-> macula densa cells release paracrine signals-> afferent arteriole constricts

• myogenic mechanism is increased arterial pressure stretches the afferent arteriole inducing it to constrict which offsets the pressure increase.

Ext: Symp activation in BV constricts afferent arteriole at a high level of excitation eg during shock.

Question 3

What are the mechanisms that go into place when GFR is too low - extrinsic and intrinsic

Answer 3

Intrinsic:
Low GFR= less Cl- passing macular densa cells->paracrine signals-> JG cells release Renin
Low GFR= less hydrostatic pressure->decreased stretch of afferent arteriole (myogenic)

Extrinsic

• Renin produces angiotensin 2 which constricts the efferent arteriole
• angiotensin 2 ->aldosterone release: increased uptake of Na+ at the distal nephron to increase blood volume.

-Symp activation at lower levels increases renin release by JG cells, and increases proximal tubule Na+ and water absorption acting to retain water and Na+

Question 4

What is the renorenal reflex

Answer 4

Sympathetic afferents from the kidney simultaneously inhibit the efferent sympathetic input from the brain. So when it receives feedback that it has enough Na+ and water it will inhibit the sympathetic activation to increase retention of those things

Question 5

What happens at the proximal tubule

Answer 5

• Reabsorption of all glucose and amino acids, 2/3 of Na+, K+, H2O. 2/3 of Cl- at the late proximal tubule
• Proximal tubule is also the site of SECRETING organic cations/anions/ drugs through transporters which exchange oppositely charged ions.

Question 6

How are glucose, amino acids, Na+, water and K+ reabsorbed in the early proximal tubule

Answer 6

These cells have basolateral Na/K/ATPase to make low Na+ inside the cell, where there is high Na+ in the lumen.
This drives active Synporters for Na+/glucose. Water moves by paracellular osmosis and this helps K+ reabsorption by solvent drag.

Question 7

What are the ways that the body gets the HCO3- they use tor regulate pH and what effect does this have on the proximal tubules pH

Answer 7

1. Na+ uptake through exchanger synporters drives H+ extrusion into the lumen of the tubule, decreasing the pH.
2. This drives the HCO3- to go back into H2O and CO2 which allows them to enter the cell (requiring brush border and cytoplasm carbonic anhydrase).
3. Inside it makes HCO3- again and transported across the basolateral membrane back into the blood. 90% reabsorbed.
4. New bicarbonate is also generated from glutamine, with the ammonia secreted by the Na+/NH3 transporter into the lumen.

Question 8

How is Cl- reabsorbed

Answer 8

In the late proximal tubule Chloride becomes concentrated > ECF due to early reabsorption of water and other solutes so it moves down conc gradient paracellularly which induces Na+ paracellular reabsorption.

Question 9

What is the osmotic drive to extract the water from the collecting duct and thin limb and the part played by the vasa recta

Answer 9

Within the medulla there is a concentration gradient in the interstitium due to the deposition of NaCl at the outer medulla. Vasa recta carries the water reabsorbed back into the cortex, losing it as it descends into the conc gradient but then regaining it as it leaves.
This requires slow blood flow for optimal exchange therefore increased bp can lead to urine washout - loss of concentrating urine

Question 10

What are the steps to setting up the concentration gradient in the outer medulla

Answer 10

1. Na in the lumen of the Thick Ascending limb is transferred to the ECF through NKCC2 and NaKATPase (with some Cl-).
2. Water is not able to follow due to water tight junctions in TAL
3. ECF between the TAL and ThinDL becomes hypertonic so water passing down TDL can move into the ECF where it it goes into the Vasa recta in a counter current direction to tubular fluid flow.
4. This increases the osmolality of fluid in the TDL but TAL osm is decreased due to NKCC2.
5. This creates a gradient with 300 at the top and 600 mosmol at the bottom of the outer medulla.