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1

Describe reabsorption in the loop of hence?

Water reabsorption is very important in the loop of henle. Allows us to produce a urine with different osmolality (50-1200 mOsm/kg water). Urine volume can vary (0.5-20L per day).

2

What are the type of nephrons?

1. Short loop nephrons - uses sodium chloride.
2. Long loop nephrons - uses sodium chloride and urea. This allows us to subdivide the medulla into an outer and inner medulla.

3

Describe how reabsorption works in short loop nephrons?

Salt will flow down the proximal tube, where it will flow down the loop and it will hit the thick ascending limb where sodium is transported into the interstitium. A transporter NKCC2 will bring sodium, 2 chlorides and 1 potassium (recycling) into the cell. And sodium will be pumped out into the ECF. There are tight water junctions so water can't travel paracellularly.

4

Why does furosemide target?

It targets NKCC2.

5

Describe the counter-current multiplication effect?

Because there is increased salt in the interstitium (from sodium being excreted in the TAL) water will leave the thin descending limb into the interstitial to chase the salt. So osmolality will increase, and then when the fluid meets the TAL there is a continuous process as salt is being pumped out. Osmolality at the loop will be 600mOsm/kg water.

6

Where does the water go?

The water is taken away buy the straight vasa recta blood vessels. They flow counter-current to the flow in the nephron. The water extracted out from the nephron in the thin ascending limb won't dilute the salt in the interstitium as it is being taken away by the blood.

7

What happens if you speed up blood flow in the vasa recta?

Wash-out will occur, patient can't concentrate their urine.

8

Describe how reabsorption works in the early distal convoluted tubule?

Tubular fluid leaving the TAL is dilute (not much alt but still has water). Further dilution of the tubular fluid by removal of NaCl but not water. Sodium/chloride transporter will reabsorb sodium into the cell but not water (still tight junctions).

9

How do thiazide diuretics work?

They block the Na/Cl transporter in the early distal convoluted tubule. This will stop sodium from being reabsorbed into the cells, less ECF volume, lower BP. These are used to treat hypertension and heart failure. This will stimulate more sodium to be reabsorbed by the ENaC channel, thus more potassium will have to be secreted by the ROMK channel. Thiazide diuretics can cause hypokalemia, which can cause ventricular arrhythmias.

10

What are the cells in the late distal convoluted tubule, connecting tubule and collecting duct?

1. Intercalated cell.
2. Principal cell.

11

How do principal cells work?

Their primary role is to reabsorb sodium and to secrete potassium. Sodium is reabsorbed through a channel called ENaC. By sodium being reabsorbed into the principal cells it makes the lumen more negative (electronegative as you are taking away the positive charge). This will drive the secretion of potassium into the lumen through the ROMK channel.

12

What does amiloride do?

It is a potassium-sparing diuretic. It acts on ENaC.

13

How does aldosterone affect principal cells?

It will stimulate sodium reabsorption and potassium secretion. They bind to receptors, which activate gene expression which turns on a activators which supercharge the ENaC channel and they make more ENaC.

14

What is the early effect of aldosterone?

Activate ENaC channels.

15

What is the late effect of aldosterone?

Making more ENaC channels and more Na+/K+/ATPase channels.

16

How do intercalated cells work?

they are important for acid-base balance and potassium absorption. they secrete hydrogen ions through hydrogen ATPase and H+/K+/ATPase. Filtered bicarbonate will react with hydrogen to create carbonic acid which will be transported into the cell into carbon dioxide and water where it is then turned into bicarbonate and hydrogen ions. The bicarbonate is then secreted into the ECF.

17

Why is it important that intercalated cells secrete H+ and bicarbonate?

Normal body fluid pH is 7.4. pH is related to the hydrogen concentration. Body fluid pH is determined by the carbon dioxide and bicarbonate buffer system.

18

What is diffusion trapping?

It is where excess hydrogen ions (after all bicarbonate has been reabsorbed) combines with NH3 - this is because a pH of 4.5 is the max urine attainable, and it is not enough to exert all dietary hydrogen ions. Ammonia (NH3) freely diffuses but NH4+ (charged) is trapped in the urine and excreted (voiding the H+).

19

What happens to the water in the late distal convoluted tubule, connecting tubule and the cortical collecting duct?

It depends on whether you are producing ADH. ADH causes aquaporin water channels to be inserted into the apical membrane. Water will be reabsorbed rather than excreted in the urine. Response to ADH is rapid (vesicles rapidly inserted or re-internalised).

20

What happens to water reabsorption in the outer medulla collecting duct?

The amount of water you will move depends on ADH. When ADH is high urine is concentrated, and when ADH is low urine is dilute.

21

Describe passive hypothesis?

When ADH is present water gets taken out of the collecting duct this makes urea high in concentration in the collecting duct. ADH will also increase the permeability of the collecting duct to both water and urea. High urea concentration and high permeability so water will be deposited out in the interstitum. Water also flows into this region and dilutes the interstitial osmolality. As a result of this sodium chloride will move out of the tip of the ascending limb into the interstitial by osmosis.