Lecture 38: Renal Tubular Function

Question 1

where does tubular reabsorption occur

Answer 1

• across all epi cells lining the nephron

- PCT makes largest contribution

Question 2

why is tubular reabsorption important

Answer 2

• keeps fluid loss through urine at 1-2L/day so prevents dehydration

Question 3

outline the ways that molecules move from the filtrate into the blood and vice versa

Answer 3

• paracellular (between cells); small ions e.g. H2O driven by [Grad]
• transcellular (through cells)
• reabsorption (filtrate to blood)
• secretion (blood to filtrate)
• excretion (eliminated from the body via urine)

Question 4

where are glucose transporters located within the nephron

Answer 4

PCT

Question 5

what glucose transport proteins are located in the early PCT

Answer 5

• SGLT2

- GLUT2

Question 6

what glucose transport proteins are located in the late PCT

Answer 6

• SGLT1

- GLUT1

Question 7

what limits the maximum rate of glucose absorption

Answer 7

the rate at which the transporters can operate

Question 8

when might the glucose transport maximum be exceeded resulting in glucosuria

Answer 8

• diabetes
• dysfunction in reabsorption (Fanconi syndrome)
• induced by drugs e.g SGLT2i

Question 9

why might drugs e.g. SGLT2i be used to induce glucosuria

Answer 9

to remove excess urine from the blood e.g. in diabetes

Question 10

what limits the transport maximum (Tm) of amino acids

Answer 10

speed of the pumps

Question 11

are a majority of amino acids normally reabsorbed or excreted

Answer 11

> 95% aa normally reabsorbed

Question 12

what can result in aminoaciduria

Answer 12

• congenital disorders of aa metabolism

- transport defects (Hartnup disease)

Question 13

where in the nephron does most Na+ reabsorption take place

Answer 13

PCT (70%) by secondary active transport

Question 14

how are most Na+ ions reabsorbed

Answer 14

active transport via transcellular route

Question 15

what drives the reabsorption of Na+ in the PCT and LoH

Answer 15

Na+ gradient between filtrate and cell (maintained by basolateral membrane Na+/K+ pump)

Question 16

what limits Na+ reabsorption

Answer 16

• majority gradient limited

- after most reabsorption occurs, limited by expression of Na+/K+ pump

Question 17

how does aldosterone affect Na+ reabsorption and when might this occur

Answer 17

• ^ Na+ reabsorption
• by ^ expression of Na+/K+ pump
• can occur in conditions where blood osmolarity is low

Question 18

describe the therapeutic potential of Na+ wasting

Answer 18

• reduces reabsorption of Na+ –> allows water to be excreted
• can reduce the blood volume heart has to pump
• help treat conditions e.g. hypertension and HF

Question 19

outline what drugs can be used to achieve Na+ wasting

Answer 19

• spironolactnone
• -> inhibits action of aldosterone on Na+/K+ pump expression
• loop diuretics
• -> inhibit Na+/Cl-/K+ transporter in asc. limb
• thiazides
• -> inhibit Na+/Cl- transporter in DCT

Question 20

how is water reabsorbed

Answer 20

• via paracellular and transcellular routes by osmosis in response to osmotic gradient created by Na+ movement
• follows movement of Na+ ions
• Transcellular passage of water is facilitated by aquaporins

Question 21

how is water predominantly reabsorbed in PCT

Answer 21

paracellularly

Question 22

how is water predominantly reabsorbed in DCT and CDs

Answer 22

transcellularly under control of ADH

Question 23

how does ADH encourage water reabsorption in DCT and CDs

Answer 23

^ permeability by promoting insertion of aquaporins

Question 24

name the mechanism that facilitates H2O reabsorption in LoH

Answer 24

counter current multiplier

Question 25

outline the process of the counter current multiplier

Answer 25

• LoH limbs arr. w/ flow in opposition to that of vasa rect
• Na+ actively pumped out of asc. limb and moves passively into blood
• Conc blood moves along vasa recta towards desc. limb
• promotes H2O reabsorption from desc. limb
• H2O loss from filtrate makes it conc; moves to asc. limb
• Na+ again actively pumped out of asc. limb into vasa recta creating a cycle
• blood and filtrate both became conc. then diluted again

Question 26

what is the net effect of the counter current multiplier

Answer 26

Na+ and H2O are reabsorbed

Question 27

how much urea is reabsorbed in PCT

Answer 27

50%

Question 28

where in the nephron is urea secreted back into tubular lumen and by what process

Answer 28

• facilitated diffusion via urea transport proteins

- asc. loop

Question 29

where does secondary reabsorption of urea take place

Answer 29

CDs

Question 30

how much urea is actually excreted in urine

Answer 30

20%

Question 31

why is the reabsorption of urea very important despite the fact it is a waste product

Answer 31

contributes to hyper-osmolarity of medullary interstitium which makes water reabsorption more effective

Question 32

what is uraemia a clinical indicator of

Answer 32

renal failure
(Px likely to have other conditions due to the lack of kidney function)

Question 33

what is the normal range for urea in plasma

Answer 33

3.3-6.7mmol/L

Question 34

what is tubular secretion

Answer 34

when substances are removed from blood or interstitium to the tubular fluid for excretion in kidneys
(irrespective of glomerular filtration or substance [grad])

Question 35

why is tubular secretion important

Answer 35

• important in elimination of metabolites and toxins e.g. creatinine and uremic toxins via organic cation/anion transporters
• important in clearance of some drugs e.g. antibiotics, NSAIDs and statins

Question 36

how can tubular secretion be measured and for what reason

Answer 36

can be measured from e.g.

• para-aminohippurate clearance (PAH; filtered and secreted
• cinnamoylglycine clearance (CMG; secreted > filtered)
• secretion rates linked to disease progression