Gene models 2

Question 1

What does the loop of Henle reabsorb?

Answer 1

Na+
Cl-
H2O
Ca2+
Mg2+

Question 2

What is the site of action of loop diuretics?

Answer 2

Reduced sodium chloride reabsorption in the loop of Henle

Question 3

Describe the structure of the loop of Henle

Answer 3

Thin descending limb
Thick ascending limb
Thin ascending limb

Question 4

What is the function of the thin descending limb?

Answer 4

Water absorption
Water permeable

Question 5

What is the function of the thick ascending limb?

Answer 5

Na+ and Cl- absorption

Question 6

What is the function of the thin ascending limb?

Answer 6

Na+ and Cl- absorption
Low water permeability

Question 7

What is the membrane potential in the thick ascending limb?

Answer 7

Negative

Question 8

What is the intracellular sodium conc in thick ascending limb?

Answer 8

Low intracellular sodium conc

Question 9

Where is NKCC2 located?

Answer 9

Apical membrane of thick ascending limb

Question 10

What is the mechanism of NKCC2?

Answer 10

Uses electrochemical driving forces for sodium ->
Brings Na+, Cl- and K+ into the cells after a conformation change in the protein

Question 11

Where is CLCK located?

Answer 11

Basolateral membrane of thick ascending limb

Question 12

Which other membrane protein does CLCK interact with?

Answer 12

Barttin

Question 13

What is CLCK?

Answer 13

A chloride ion channel

Question 14

Where is ROMK located?

Answer 14

On the apical membrane of the thick ascending limb

Question 15

Why is potassium recycled?

Answer 15

There isn’t enough potassium in tubular fluid to support function of NKCC2 so it has to be recycled through ROMK to ensure potassium levels are high enough

Question 16

How do calcium and magnesium interact with the thick ascending limb?

Answer 16

They are reabsorbed paracellularly

Question 17

How is paracellular reabsorption of calcium and magnesium increased?

Answer 17

Greater transcellular transport leads to an increase in paracellular transport

Question 18

Where is Barttin located?

Answer 18

Basolateral membrane in the thick ascending limb

Question 19

What is the function of Barttin?

Answer 19

It interacts with ion channels to aid the function of ion channel

Question 20

How is Bartter’s syndrome inherited?

Answer 20

Genetic inheritance - recessive

Question 21

What is Bartter’s syndrome?

Answer 21

Losing sodium and chloride in urine (salt wasting)

Question 22

Describe the symptoms of Bartter’s syndrome

Answer 22

Polyuria
Hypotension
Alkalosis
Hypercalciuria
Nephrocalcinosis
Hypokalaemia

Question 23

Which proteins have the potential to be mutated in Bartter’s syndrome?

Answer 23

NKCC2
ROMK
CLCK
Barttin

Question 24

Which proteins would be mutated if the cell had high intracellular chloride levels ?

Answer 24

CLCK
Barttin
-> Chloride cannot leave the cell so would accumulate intracellularly

Question 25

What are the effects of mutations in CLCK and Barttin?

Answer 25

Chloride cannot leave the cell -> NKCC2 transport decreases -> Less sodium and chloride absorption -> Not enough potassium recycling so inefficient K+ for ROMK and NKCC2

Question 26

What is the equation for fractional excretion?

Answer 26

Amount in urine / Amount filtered

Question 27

Describe the findings of the ROMK knockout study.

Answer 27

High salt wasting Polyuria Low acidosis No difference in plasma K+

Question 28

What are furosemide and bumetanide?

Answer 28

Class of drugs used to treat high blood pressure

Question 29

What is furosemide and bumetanide side effects?

Answer 29

Polyuria -> Bring ecf volume down to decrease bp

Question 30

Function of the distal tubule

Answer 30

Reabsorption of Na+ , Cl- and Mg2+

Question 31

Where is NCC located?

Answer 31

On the apical membrane of the early distal tubule

Question 32

What is the function of NCC?

Answer 32

Sodium chloride cotransporter

Question 33

How is Gitelman's syndrome inherited?

Answer 33

Genetic inheritance - recessive Due to mutations in the early distal tubule

Question 34

What does a loss of function mutation in NCC result in?

Answer 34

Calcium difference due to calcium channels in apical membrane

Question 35

What is the mechanism of thiazide diuretics?

Answer 35

Target the early distal tubule High bp treatment

Question 36

Name a thiazide diuretic

Answer 36

Chlorothiazide

Question 37

What side effects do thiazide diuretics produce?

Answer 37

Side effects similar to Gittleman's disease

Question 38

Why does having one mutation in ROMK, NCC or NKCC2 protect against hypertension?

Answer 38

Carriers start with a lower bp and end up with a lower bp -> This reduces the risk of cardiovascular disease and therefore, they are less likely to have hypertension