Regulation Of Tubule Transport

Question 1

How does GFR remain constant with changes in bp?

Answer 1

Autoregulation by
— Bayliss effect
— Tubuloglomerular feedback

Question 2

What is the primary driving force for fluid movement from lumen into interstitium around PCT cells?

Answer 2

Active transport of Na+ from filtrate into interstitium (Na/K pump sets up gradient in basolateral surface, ENaC moves across apical surface) creating osmotic gradient

Question 3

What forces determine the fluid and solute uptake into peritubular capillaries?

Answer 3

Starling forces (hydrostatic and oncotic forces)

Question 4

What fraction of the filtrate does the PT reabsorb?

Answer 4

Always 2/3, even if GFR changes

Question 5

How does PT keep filtration fraction constant even when GFR changes?

Answer 5

Increase transport through carriers with increased solute

Starling forces:
—If GFR goes up, hydrostatic pressure into capillary increases, and backflux through tight junctions is small
—If GFR goes down, hydrostatic pressure WITHIN peritubular capillaries is bigger, such that there is more backflow through tight junction opposing movement of fluid from interstitium into peritubular capillaries

Question 6

Hormonal regulators in PT? Nervous regulation in PT?

Answer 6

Acidosis, sympathetic nerves releasing noradrenaline, angiotensin II stimulate Na/H exchanger: PLC —> IP3 —> Ca2+ —> stimulates kinase —> phosphorylates Na/H exchanger

Parathyroid hormone inhibits Na/H exchanger: Adenylate Cyclase —> cAMP —> phosphorylates and inhibits kinase —> inhibits Na/H exchanger

Question 7

What % of Na is reabsorbed in the filtered load in the Loop of Henle?

Answer 7

20%

Question 8

How does the body increase Na+ absorption in the Loop of Henle?

Answer 8

ADH, aldosterone and glucocorticoids stimulate the Na/H exchanger

Question 9

What relationship do PT and Loop of Henle have between Na reabsorption and GFR?

Answer 9

Load dependent —> always the same fraction reabsorbed

Question 10

What force predominantly regulates Na absorption in LoH?

Answer 10

Flow rate of ultrafiltrate

Question 11

How does flow rate regulate Na reabsorption in LoH?

Answer 11

Increased flow rate gives tALH less time to absorb Na

This means higher [NaCl] in TALH increase reabsorption through NKCC

Also increases NaCl delivery to Macula Densa cells, which will feedback to glomerulus and stimulate adjustment of afferent arteriolar resistance

Question 12

What is tubuloglomerular feedback?

Answer 12

How [NaCl] sensed by macula densa cells can:

— change GFR by modulating afferent arteriolar resistance
— regulate renin release from granular cells

Question 13

What do macula densa cells actually monitor? What happens if this marker increases in concentration?

Answer 13

Cl absorption through NKCC

Increased Cl absorption causes release of ATP from basolateral membrane, which is converted to adenosine

Adenosine diffuses to nearby SMCs in afferent arteriole causing constriction

Question 14

How much Na does DT reabsorb and how?

Answer 14

~7% through NaCl

Question 15

What upregulates Na reabsorption in DT? What specifically inhibits?

Answer 15

Angiotensin II and aldosterone

Thiazides inhibit

Question 16

What do the connecting tubules reabsorb? How is this upregulated?

Answer 16

Ca2+ reabsorption, increased by parathyroid hormone

Question 17

What % of filtered Na do principle cells absorb?

Answer 17

~5%

Question 18

Through what type of channels do principle cells absorb Na and water?

Answer 18

Amiloride-sensitive ENaC and ADH-sensitive AQP-2 channels

Question 19

What do type A intercalated cells secrete? How does this compare to type B and why?

Answer 19

Type A secrete H+ and reform HCO3- when blood is acidic

Type B secrete HCO3- and absorb H+ when blood is alkaline

Question 20

What happens to K+ ions in the principle cells?

Answer 20

Secreted through apical K+ channels down gradient set up by basolateral Na/K

Question 21

If Na absorption in principal cells from lumen is enhanced by aldosterone, what will be seen regarding K+?

Answer 21

Increased K+ secretion into lumen across apical membrane as Na/K pump stimulated, increasing intracellular [K+]

Question 22

What can lower Na reabsorption in principal cells?

Answer 22

ANP, acting on ENaC

Question 23

What causes the conversion of liver-derived angiotensinogen to angiotensin I?

Answer 23

Renin from granular cells in kidney glomeruli

Question 24

What causes conversion of angiotensin 1 to 2?

Answer 24

ACE predominantly in lungs

Question 25

What are the two effects of angiotensin 2?

Answer 25

Vasoconstriction

A1 receptor in adrenal cortex to release aldosterone into blood

Question 26

Effects of aldosterone in kidneys?

Answer 26

Binds to cytoplasmic receptor to form a complex that acts as a transcription factor up regulating transcription of:

• apical ENaC
• basolateral Na/K
• proteins involved in metabolic production of ATP

Question 27

What does ANP stand for? Think: how can you remember it’s function??

Answer 27

Atrial Natriuretic peptide

Natriuresis = loss of Na in urine

Therefore, encourages the loss of Na in urine

Question 28

Mechanism of ANP action?

Answer 28

Antagonises RAAS by raising intracellular cGMP levels (activating PKG):

— afferent dilation, efferent constriction increasing GFR
— reduces renin, aldosterone and ADH release
— inhibits Angiotensin II, ADH and aldosterone actions

Question 29

How does ADH increase expression of AQP2 channels on apical membrane of principal cells? What is the trigger? Where does water leave in the basolateral membrane?

Answer 29

Binds to V2 receptors, Gs-coupled

PKA phosphorylates cytoskeletal elements to cause fusion of vesicles containing AQP-2 channels

Triggered by increased osmolarity of blood

Water leaves basolateral surface from AQP-3

Question 30

Osmolarity of plasma?

Osmolarity of urine?

Answer 30

200-800 mOsm

50-1200 mOsm