Transport of Urea, Glucose, Phosphate, Calcium, Magnesium, and Organic Solutes

Question 1

Where is the majority of uptake for nutrients and metabolites?

Answer 1

proximal tubule

via electrogenic Na+-dependent co-transporter

electrochemical gradient driven

facillitative diffusion down chemical gradient into blood stream

Question 2

What happens at the plasma threshold for glucose?

Answer 2

about 15 mM

reabsorption mechanisms saturate or plateau and excretion ensues

Question 3

splay

Answer 3

a shallow transition between no excretion and excretion rather than a shartp cutoff

results from single nephrone differences in glomerular size and proximal tubule length

Question 4

Is the threshold for amino acids higher or lower than that for glucose?

Answer 4

lower, so excretion often limits plasma concentration in conditions of excess

Question 5

Hartnup disease

Answer 5

mutation in transporter for neutral and ring-structured amino acids (ala, ser, phe, trp)

Question 6

collectrin KO

Answer 6

multiple transporters remain in the membrane, but no longer operate due to loss of protein collectrin

uptake of many different aa’s affected

Question 7

location and function of secretion

Answer 7

mechanisms are located in the late proximal tubule

secretion pathways are relatively nonspecific and well-adapted to removing drugs and foreign chemicals

Question 8

reasons why active secretion is needed

Answer 8

chemicals may be unintentionally reabsorbed in the early proximal tubule through carrier non-specificity and bulk paracellular flow

an active extrusion mechanism can achieve the low plasma concentrations necessary to strip hydrophobic compounds from albumin binding sites

Question 9

Why can creatinine be used for measuring GFR?

Answer 9

creatinine is neither reabsorbed nor secreted in significant amounts

Question 10

What are some examples of secreted compounds?

Answer 10

metabolites

neurohormonal agents

drugs

conjugates of clucuronate, glutathione, and sulfate

Question 11

elimination of weak acids and bases via non-ionic diffusion

Answer 11

weak acids are unionized at low pH and thus can diffuse freely across membranes

an alkaline luminal pH causes dissociation and trapping of the charged species

the opposite holds for weak bases which are un-ionized at high pH and trapped at low pH

ex. salicylic acid overdose - elimination promoted by alkalinizing the urine

Question 12

phosphate excretion

Answer 12

80% reabsorbed in proximal tubule

10% reabsorbed in distal convoluted tubule

10% excreted

varies depending on intake

Question 13

regulation of phosphate excretion

Answer 13

concentration usually just exceeds the threshold for excretion, so some is excreted

most important regulator is parathyroid hormone (PHT), which decreases Pi uptake in the proximal tubule

Question 14

PTH

Answer 14

parathyroid hormone

acts to decrease Pi uptake by acting on proximal tubule transporters

releadsed during a decrease in plasma Ca²⁺ and acts on the kidney and intestine to increase Ca²⁺ reabsorption

Pi has to remain low when Ca²⁺ is high to prevent CaPO₄ precipitation

Question 15

mechanism of calcium uptake

Answer 15

65% reabsorbed in the PT, 25% in the TAL, and 8% in the DCT

left over with about 0.5% in urine

flows into the tubule cell through voltage-independent Ca²⁺ channels in the apical membrane

high concentration and negative potential inside causes Ca²⁺ to be pulled in

Ca²⁺ is pumped to the blood through through a Ca²⁺/H⁺ ATPase at low concentrations and a Na⁺/Ca²⁺ exchanger at higher concentrations

paracellular uptake in the PT by concentration and TAL by positive potential

Question 16

regulation of calcium uptake

Answer 16

PTH acts on TAL to increase uptake by increasing time the channels are open

vitramin D increases uptake in distal nephron through protein synthesis

high concentrations of calcium in the plasma acts on a basolateral G-protein linked calcium receptor to reduce apical calcium uptake in the TAL

closing potassium channels depolarizes the cell and reduces the driving voltage for calcium uptake

Question 17

mechanism of magnesium uptake

Answer 17

absorbed predominant ly in the TAL by a paracellular route involving the tight junction channel paracellin-1

families with mutations in this gene have severe renal Mg2+ wasting

driving force is provided by lumen positive voltage