Regulation Of Tubule Transport Flashcards
How does GFR remain constant with changes in bp?
Autoregulation by
— Bayliss effect
— Tubuloglomerular feedback
What is the primary driving force for fluid movement from lumen into interstitium around PCT cells?
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
What forces determine the fluid and solute uptake into peritubular capillaries?
Starling forces (hydrostatic and oncotic forces)
What fraction of the filtrate does the PT reabsorb?
Always 2/3, even if GFR changes
How does PT keep filtration fraction constant even when GFR changes?
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
Hormonal regulators in PT? Nervous regulation in PT?
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
What % of Na is reabsorbed in the filtered load in the Loop of Henle?
20%
How does the body increase Na+ absorption in the Loop of Henle?
ADH, aldosterone and glucocorticoids stimulate the Na/H exchanger
What relationship do PT and Loop of Henle have between Na reabsorption and GFR?
Load dependent —> always the same fraction reabsorbed
What force predominantly regulates Na absorption in LoH?
Flow rate of ultrafiltrate
How does flow rate regulate Na reabsorption in LoH?
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
What is tubuloglomerular feedback?
How [NaCl] sensed by macula densa cells can:
— change GFR by modulating afferent arteriolar resistance
— regulate renin release from granular cells
What do macula densa cells actually monitor? What happens if this marker increases in concentration?
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
How much Na does DT reabsorb and how?
~7% through NaCl
What upregulates Na reabsorption in DT? What specifically inhibits?
Angiotensin II and aldosterone
Thiazides inhibit
What do the connecting tubules reabsorb? How is this upregulated?
Ca2+ reabsorption, increased by parathyroid hormone
What % of filtered Na do principle cells absorb?
~5%
Through what type of channels do principle cells absorb Na and water?
Amiloride-sensitive ENaC and ADH-sensitive AQP-2 channels
What do type A intercalated cells secrete? How does this compare to type B and why?
Type A secrete H+ and reform HCO3- when blood is acidic
Type B secrete HCO3- and absorb H+ when blood is alkaline
What happens to K+ ions in the principle cells?
Secreted through apical K+ channels down gradient set up by basolateral Na/K
If Na absorption in principal cells from lumen is enhanced by aldosterone, what will be seen regarding K+?
Increased K+ secretion into lumen across apical membrane as Na/K pump stimulated, increasing intracellular [K+]
What can lower Na reabsorption in principal cells?
ANP, acting on ENaC
What causes the conversion of liver-derived angiotensinogen to angiotensin I?
Renin from granular cells in kidney glomeruli
What causes conversion of angiotensin 1 to 2?
ACE predominantly in lungs
What are the two effects of angiotensin 2?
Vasoconstriction
A1 receptor in adrenal cortex to release aldosterone into blood
Effects of aldosterone in kidneys?
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
What does ANP stand for? Think: how can you remember it’s function??
Atrial Natriuretic peptide
Natriuresis = loss of Na in urine
Therefore, encourages the loss of Na in urine
Mechanism of ANP action?
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
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?
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
Osmolarity of plasma?
Osmolarity of urine?
200-800 mOsm
50-1200 mOsm
