Gene models 2 Flashcards
What does the loop of Henle reabsorb?
Na+
Cl-
H2O
Ca2+
Mg2+
What is the site of action of loop diuretics?
Reduced sodium chloride reabsorption in the loop of Henle
Describe the structure of the loop of Henle
Thin descending limb
Thick ascending limb
Thin ascending limb
What is the function of the thin descending limb?
Water absorption
Water permeable
What is the function of the thick ascending limb?
Na+ and Cl- absorption
What is the function of the thin ascending limb?
Na+ and Cl- absorption
Low water permeability
What is the membrane potential in the thick ascending limb?
Negative
What is the intracellular sodium conc in thick ascending limb?
Low intracellular sodium conc
Where is NKCC2 located?
Apical membrane of thick ascending limb
What is the mechanism of NKCC2?
Uses electrochemical driving forces for sodium ->
Brings Na+, Cl- and K+ into the cells after a conformation change in the protein
Where is CLCK located?
Basolateral membrane of thick ascending limb
Which other membrane protein does CLCK interact with?
Barttin
What is CLCK?
A chloride ion channel
Where is ROMK located?
On the apical membrane of the thick ascending limb
Why is potassium recycled?
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
How do calcium and magnesium interact with the thick ascending limb?
They are reabsorbed paracellularly
How is paracellular reabsorption of calcium and magnesium increased?
Greater transcellular transport leads to an increase in paracellular transport
Where is Barttin located?
Basolateral membrane in the thick ascending limb
What is the function of Barttin?
It interacts with ion channels to aid the function of ion channel
How is Bartter’s syndrome inherited?
Genetic inheritance - recessive
What is Bartter’s syndrome?
Losing sodium and chloride in urine (salt wasting)
Describe the symptoms of Bartter’s syndrome
Polyuria
Hypotension
Alkalosis
Hypercalciuria
Nephrocalcinosis
Hypokalaemia
Which proteins have the potential to be mutated in Bartter’s syndrome?
NKCC2
ROMK
CLCK
Barttin
Which proteins would be mutated if the cell had high intracellular chloride levels ?
CLCK
Barttin
-> Chloride cannot leave the cell so would accumulate intracellularly
What are the effects of mutations in CLCK and Barttin?
Chloride cannot leave the cell ->
NKCC2 transport decreases ->
Less sodium and chloride absorption ->
Not enough potassium recycling so inefficient K+ for ROMK and NKCC2
What is the equation for fractional excretion?
Amount in urine / Amount filtered
Describe the findings of the ROMK knockout study.
High salt wasting
Polyuria
Low acidosis
No difference in plasma K+
What are furosemide and bumetanide?
Class of drugs used to treat high blood pressure
What is furosemide and bumetanide side effects?
Polyuria ->
Bring ecf volume down to decrease bp
Function of the distal tubule
Reabsorption of Na+ , Cl- and Mg2+
Where is NCC located?
On the apical membrane of the early distal tubule
What is the function of NCC?
Sodium chloride cotransporter
How is Gitelman’s syndrome inherited?
Genetic inheritance - recessive
Due to mutations in the early distal tubule
What does a loss of function mutation in NCC result in?
Calcium difference due to calcium channels in apical membrane
What is the mechanism of thiazide diuretics?
Target the early distal tubule
High bp treatment
Name a thiazide diuretic
Chlorothiazide
What side effects do thiazide diuretics produce?
Side effects similar to Gittleman’s disease
Why does having one mutation in ROMK, NCC or NKCC2 protect against hypertension?
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
