Urology Review

Question 1

Define osmolarity.

Answer 1

Osmolarity is a measure of the solute (particle) concentration in a solution (osmoles / liter).

Question 2

What is the normal range of plasma osmolarity?

Answer 2

275-295 mosmoles/L

Question 3

Why does a high salt diet lead to an increase in blood pressure?

Answer 3

Increased salt in the diet leads to increased total body sodium so water is taken in to maintain osmolarity and this increases ECF fluid volume. This increases the pressure in the system i.e. increased blood pressure.

Question 4

Salt is often added to food to improve the flavour. Why does salt improve the flavour, but too much salt make food taste bad, and how do we sense this?

Answer 4

Salt is one of the 5 basic taste sensations, it is sensed by a specific sense of cells located on the tongue. At low salt concentrations the sensation is positive but as the concentration increases the sensation becomes aversive.

Question 5

Which part of the brain is central to alter appetite for salt?

Answer 5

Lateral Parabrachial nucleus. This region takes information from other areas as well as from neurotransmitters including serotonin and glutamate and in euvolemia the main outcome is inhibition of sodium intake.

Question 6

What proportion of filtered sodium load is taken up by
1. Distal convoluted tubule
1. Thick ascending limb of the loop of Henle
1. Proximal convoluted tubule

Answer 6

1. Distal convoluted tubule
   About 5%
2. Thick ascending limb of the loop of Henle
   About 25%
3. Proximal convoluted tubule
   About 65%

Question 7

What proportion of renal blood flow is filtered into the nephrons?

Answer 7

20%

Question 8

What is the effect of increased tubular sodium concentration on the juxtaglomerular cells of the macular densa?

Answer 8

Increased sodium uptake through the Na/K/Cl triple transporter, leading to release of adenosine and ATP.

Question 9

Which cells respond to the adenosine by reducing renin production?

Answer 9

Extraglomerular mesangial cells.

Question 10

Why does the release of adenosine lead to a reduction in GFR in the short term?

Answer 10

It causes the afferent SMCs to contract reducing renal plasma flow and therefore GFR.

Question 11

What is the effect of low tubular sodium at the macular densa on the production of Angiotensin II?

Answer 11

It increases it because it stimulates the production of renin leading to angiotensinogen conversion to AI and finally to AII.

Question 12

Where in the tubular system does aldosterone work?

Answer 12

DCT (distal end of the DCT) and CT.

Question 13

Where is aldosterone released from?

Answer 13

Adrenal cortex.

Question 14

What is the effect of AII on aldosterone release?

Answer 14

It increases it.

Question 15

How does aldosterone affect potassium balance?

Answer 15

It increases potassium secretion by stimulating sodium uptake: increased Na⁺/K⁺ ATPase expression will increase the rate of K⁺ uptake and combined with the increase in Na⁺ reabsorption from the lumen (and excretion in to the blood) this will lead to increased K⁺ excretion.

Question 16

What is the effect of hypoaldosteronism on plasma renin?

Answer 16

It causes and increase in plasma renin because of the reduction in sodium reabsorption and the consequent loss of water reducing ECF and therefore BP. This leads to low sodium in the nephron and therefore the release of renin.

Question 17

What are the 6 major locations of baroreceptors?

Answer 17

• Atria
• Right ventricle
• Pulmonary vasculature
• Carotid sinus
• Aortic arch
• JGA

Question 18

What are the effects of ANP on sodium reabsorption in the PCT?

Answer 18

Reduced Na⁺ reabsorption.

Question 19

What proportion of filtered potassium load is reabsorbed by
1. Distal convoluted tubule
1. Thick ascending limb of the loop of Henle
1. Proximal convoluted tubule

Answer 19

1. Distal convoluted tubule
   Variable depending on potassium status ranges from 3% reabsorbed to secretion of 50%
2. Thick ascending limb of the loop of Henle
   About 20%
3. Proximal convoluted tubule
   About 65%

Question 20

What happens to plasma K⁺ after a meal?

Answer 20

It initially increases then it is taken up into cells by the activity of the Na⁺/K⁺ ATPase.

Question 21

Calculate the osmolarity of a solution containing 120mM NaCl, 5mM KCl, 10mM Na2HPO4, 5mM glucose at physiological pH.

Answer 21

285 mosmoles/L

Na = (120 + 20) mM =140 mM
Cl = (120 +5) mM = 125 mM
K = 5 mM
HPO4 = 10mM
Glucose = 5mM

Question 22

A salmon swims from the sea into its home river. It is covered in small parasitic lice, why do the lice die?

Answer 22

The fish moves from a high salt to a low salt region. The sea lice are adapted to a high salt environment but are suddenly exposed to the low salt environment. Their cell membranes are semi-permeable and their extracellular and intracellular osmolarity is normally set to that of sea water. In the low salt environment, they take up water and their extracellular osmolarity drops. Now because their intracellular osmolarity is higher than the external osmolarity their cells take up water and swell. As they cannot regulate their osmolarity well, cell swelling leads to cell death and eventually to death of the parasite. Indeed, infected fish are known to swim back into fresh water to reduce their parasitic load. It isn’t perfect, the parasites have developed some mechanisms of resisting these changes and survive longer if they are “attached to a fish” than if they are not.

Question 23

Two groups of genetically identical (salt-sensitive) mice of the same age and weight were analysed to determine the effect of salt on blood pressure. One group were fed a high salt diet for 4 weeks and one group were fed a low salt diet for 4 weeks. At the end of the experiment, their blood pressure, and ECF fluid volume were compared. Normal mouse values and potential data from the experiment are shown in the table.

Which data were likely to have been produced by the mice fed the high salt diet and which mouse line the low salt diet?

Answer 23

1= Low salt, 6 = High salt
The low salt diet with decrease ECF volume and therefore blood pressure (compare group 1 with control)
The high salt diet will increase ECF volume and therefore blood pressure (compare group 6 with control)

Question 24

You are developing a new diuretic drug that targets a specific transporter protein
The effects of the drug in whole animals are as follows
* Reduced renin production
* Increased sodium excretion to 8% of filtered load
* An early reduction in GFR that is prevented by co-treatment with furosemide

Which part of the nephron does this drug work in?
1. PCT
1. DCT
1. Thick Ascending limb of the Loop of Henle
1. Juxtaglomerular apparatus
1. Collecting duct

Answer 24

The drug acts in the PCT. Theoretically diuretics that act in the PCT could increase loss of sodium by up to 65% of the filtered load as that the amount of Na reabsorbed in the PCT. Typically, they work in the 5-10% range (they would have to block all sodium uptake mechanisms to reach the 65% mark). By increasing flow and/or reducing Na reabsorption they will stimulate tubular glomerular feedback (TGF) by increasing Na uptake through the NKCCT2 in the JGA. Furosemide inhibits this because it blocks the NKCCT2. Other sites of action do not lead to effects on TGF with the exception of the TAL but these are NKCCt2 inhibitors so increase GFR as they inhibit TGF.

Question 25

Diuretics work by increasing the osmolarity of the tubular fluid. Carbonic anhydrase inhibitors, mannitol, furosemide, are all diuretics that act in nephron segments prior to the juxtaglomerular apparatus. Which of these diuretics would lead to an early reduction in GFR by activating tubulo-glomerular feedback? Carbonic anhydrase inhibitors reduce PCT sodium reabsorption, mannitol is an osmotic diuretic as it is not reabsorbed and furosemide is a loop diuretic.
1. Mannitol and carbonic anhydrase inhibitors
1. Furosemide only
1. Carbonic anhydrase inhibitors and furosemide
1. Carbonic anhydrase inhibitors only
1. All three of them

Answer 25

The answer here is (1). For this you need to know that the mechanism of tubuloglomerular feedback requires increased Na load in the distal nephron and a functional NKCCT2. All three give increased Na load (mannitol because it increases flow a bit like an increase in GFR) in the distal nephron. BUT furosemide does this by inhibiting NKCCT2 so this increase can’t be detected by the JGA.

Question 26

You are part of a team developing a series of diuretic drugs and examining their effects in animals.

Each drug acts on a specific segment of the nephron. What is the order (from PCT to CCT) of sites of action of these drugs
1. D1 then D2 then D3 then D4
1. D2 then D1 then D4 then D3
1. D3 then D1 then D2 then D4
1. D3 then D4 then D1 then D2
1. D2 then D3 then D1 then D4

Answer 26

D1 works in the DCT and is acting in a manner similar to a thiazide the hint here is the increase plasma calcium and this occurs when sodium uptake is inhibited in the DCT.
D2 blocks the same channel as furosemide as the effects aren’t additive so it works in the TAL, it causes the biggest increase in loss of sodium and it increases GFR. D3 works in the PCT as it reduces GFR so activates tubule-glomerular feedback. An additional, hint to tubule-glomerular feedback is the effect of adenosine receptor blocker. D4 works in the CCT, it only produces a small increase in sodium excretion and doesn’t affect GFR or plasma Ca. So the order is D3, then D1 then D2 then D4 (answer 3)

Question 27

Why do diabetics have polyuria?

Answer 27

There is normally no glucose in the tubular fluid in the distal part of the nephron. If glucose is present it will increase the osmolarity of the tubular fluid. This will reduce the osmotic gradient between the tubule and plasma and lead to a reduction in water reabsorption. More water in the urine means more frequent urination. i.e. the glucose acts as an osmotic diuretic.