case 7 - renal physiology

Question 1

what is the difference between the cortical and juxtamedullary nephrons

Answer 1

the cortical nephrons are located much further up into the cortex than the juxtamedullary nephrons

Question 2

what do the juxtamedullary nephrons have

Answer 2

particularly long loops of Henle, that dip way down into the medulla close to the renal papilla and it is these long nephrons that are responsible for your ability to produce concentred urine

Question 3

what is the counter-current multiplier

Answer 3

loop of henle

Question 4

what is the counter current exchanger

Answer 4

vasa recta

Question 5

what is the descending limb impermeable to

Answer 5

the descending limb is impermeable to NaCl - cannot exit

Question 6

what is the ascending limb impermeable to

Answer 6

The ascending limb is impermeable to water - cannot exit

Question 7

what is the max gradient difference between the tubular fluid concentration and the interstitial fluid concentration

Answer 7

200mOsm/Kg

Question 8

what happens in the loop of henle

Answer 8

Water moves out of the tubule in the descending limb, and this means the fluid is more concentrated.

Then it goes into the ascending limb, and this is where NaCl leaves which decreased the concentration.

Question 9

what does this process do

Answer 9

dilutes the urine. and means we have reabsorbed water and sodium and chloride

Question 10

how is urine concentrated

Answer 10

in the actions of ADH (vasopressin)

Question 11

what produces ADH and where is it stored

Answer 11

this hormone is produced in the hypothalamus and is stored in the posterior pituitary.

Question 12

when is ADH released

Answer 12

It is released into the general circulation in response to a number of factors, primarily an increase in plasma osmolality. So therefore if you become dehydrated, osmoreceptors in the hypothalamus detect that, and this causes the release of ADH into the circulation

Question 13

what does ADH do to the collecting duct

Answer 13

ADH makes the collecting duct permeable to water and therefore water is reabsorbed and you end up with a concentrated urine - maximum conc. urine = 1200mOsm/g

Question 14

what does ADH bind to when it is released into the circulation

Answer 14

when ADH is released into the circulation, it binds to V2 receptors on the collecting duct cells and activation of V2 receptors by ADH, leads to the insertion of water channels, specifically, AQP2 into the membrane on the apical side

Question 15

what happens in the absence of AQP2

Answer 15

this membrane is not permeable to wayer

Question 16

what does water leave through

Answer 16

The water leaves through AQP3/4 on the basolateral side of the membrane - these are permanently inserted

Question 17

how much potassium is lost in urine

Answer 17

92%

Question 18

what happens to potassium in the proximal tubule

Answer 18

65% K+ reabsorbed

Question 19

what happens to K+ in the loop of henle

Answer 19

25% K+ reabsorbed

Question 20

what happens to K+ in the distal and collecting duct

Answer 20

Variable K+ reabsorption and secretion

Question 21

what happens in the proximal tubule to urine

Answer 21

The net charge of the urine at the start of the proximal tubule is negatively charged but through selective reabsorption and K+ ions being introduced, it becomes positively charged. As a result of this, potassium ions that are now in the tubule fluid will move through passive diffusion through a parallel cellular pathway back into the blood. So potassium is reabsorbed down the electrochemical gradient in the proximal tubule.

Question 22

what happens in the collecting duct

Answer 22

Further down in the collecting duct, we also see reabsorption of potassium. The transporter NKCC2 is taking up sodium and chloride as part of the concentration process as tubular fluid is going up the ascending limb. At the same time, to maintain electrical neutrality between sodium and chloride, potassium is also taken into the cell. So potassium can be reabsorbed through this mechanism and leave through potassium channel on the basolateral membrane.

Question 23

what is on the apical side of the membrane in the collecting duct

Answer 23

On the apical side, there is another potassium channel called ROMK2. This channel allows recycling of potassium, so when ROMK2 opens, potassium floods out and can be picked up again by NKCC2 and recycled.

Question 24

what are the two different cell types in the collecting duct

Answer 24

There are two types of cells in the collecting duct, the principal cell and the intercalating cell.

Question 25

what are the two different potassium channels on the apical side of the mmrabne

Answer 25

There are two different potassium channels, ROMK1 and 3 on the apical side of the membrane which allows potassium to enter the tubular fluid.

Question 26

what happens in situations where we need to retain sodium and reabsorb it

Answer 26

In situations where we need to retain sodium and reabsorb it, there is a channel on the basolateral side which allows potassium to flow out of the intracellular fluid and back into the blood. This will be a situation where we need to conserve potassium.

Question 27

what is another mechanism of aldosterone via potassium

Answer 27

Another mechanism of aldosterone is it reverses the direction of the potassium channel on the basolateral membrane. So now potassium instead of going from the intra cellular space to the extracellular space is doing the opposite. - it is flowing into the cell because there is a movement of potassium ions out through ROMK1 and 3.

Question 28

what is this stimulated by

Answer 28

high K+ plasma loss

Question 29

what happens in a situation when we have acidosis

Answer 29

In a situation where we have acidosis, we have a situation in the intercalated cells. What happens in these cells, is if we need to retain potassium or we need to get rid of hydrogen ions, we can pump hydrogen ions out in exchange for potassium ions being pumped in. This requires energy. In this situation, if we are seeing acidosis, or low plasma potassium, and we need to retain potassium ions, these two pumps are activated.

Question 30

what happens if we have hypo/hypercalcaemia:

Answer 30

lower/raise depolarisation threshold

Question 31

what happens if we have hypo/hypermagnesaemia:

Answer 31

raise/lower heart rate

Question 32

what happens in the proximal and loop of Henle in Ca2+ and Mg2+ reabsorption

Answer 32

91% of Ca2+ reabsorbed - paracellular route
89% Mg2+ reabsorbed - paracellular route

Question 33

what happens in the distal in Ca2+ and Mg2+ reabsorption

Answer 33

3-7% Ca2+ reabsorption
5-6 Mg2+ reabsorption

Question 34

what is the calcium channel on the apical side of the membrane

Answer 34

the calcium channel on the apical side of the membrane is the TRPV5 channel

Question 35

what is calcium transporter through the cell bound to

Answer 35

Calcium is transported through the cell bound to calbindin-D28k

Question 36

what are the two routes via which calcium leaves the cell

Answer 36

Calcium can exit the cell through one of two routes; there is a calcium ATPase pump which pumps calcium out against a concentration gradient and specifically in the distal tubule, we have PMCA1b and NCX1

Question 37

what is this process regulated via

Answer 37

Klotho - endocrine regulator on the apical side
PTH, vitamine D and sex hormones on the basolateral side

Question 38

what is the magnesium channel and what do we know about it

Answer 38

We know there is a magnesium channel called the TRPM6 channel. Electrical gradient. This stimulated epidermal growth factor.