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Phys, pharm > Gene models 2 > Flashcards

Gene models 2 Flashcards

1
Q

What does the loop of Henle reabsorb?

A

Na+
Cl-
H2O
Ca2+
Mg2+

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2
Q

What is the site of action of loop diuretics?

A

Reduced sodium chloride reabsorption in the loop of Henle

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3
Q

Describe the structure of the loop of Henle

A

Thin descending limb
Thick ascending limb
Thin ascending limb

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4
Q

What is the function of the thin descending limb?

A

Water absorption
Water permeable

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5
Q

What is the function of the thick ascending limb?

A

Na+ and Cl- absorption

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6
Q

What is the function of the thin ascending limb?

A

Na+ and Cl- absorption
Low water permeability

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7
Q

What is the membrane potential in the thick ascending limb?

A

Negative

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8
Q

What is the intracellular sodium conc in thick ascending limb?

A

Low intracellular sodium conc

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9
Q

Where is NKCC2 located?

A

Apical membrane of thick ascending limb

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10
Q

What is the mechanism of NKCC2?

A

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

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11
Q

Where is CLCK located?

A

Basolateral membrane of thick ascending limb

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12
Q

Which other membrane protein does CLCK interact with?

A

Barttin

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13
Q

What is CLCK?

A

A chloride ion channel

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14
Q

Where is ROMK located?

A

On the apical membrane of the thick ascending limb

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15
Q

Why is potassium recycled?

A

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

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16
Q

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

A

They are reabsorbed paracellularly

17
Q

How is paracellular reabsorption of calcium and magnesium increased?

A

Greater transcellular transport leads to an increase in paracellular transport

18
Q

Where is Barttin located?

A

Basolateral membrane in the thick ascending limb

19
Q

What is the function of Barttin?

A

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

20
Q

How is Bartter’s syndrome inherited?

A

Genetic inheritance - recessive

21
Q

What is Bartter’s syndrome?

A

Losing sodium and chloride in urine (salt wasting)

22
Q

Describe the symptoms of Bartter’s syndrome

A

Polyuria
Hypotension
Alkalosis
Hypercalciuria
Nephrocalcinosis
Hypokalaemia

23
Q

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

A

NKCC2
ROMK
CLCK
Barttin

24
Q

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

A

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

25
Q

What are the effects of mutations in CLCK and Barttin?

A

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

26
Q

What is the equation for fractional excretion?

A

Amount in urine / Amount filtered

27
Q

Describe the findings of the ROMK knockout study.

A

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

28
Q

What are furosemide and bumetanide?

A

Class of drugs used to treat high blood pressure

29
Q

What is furosemide and bumetanide side effects?

A

Polyuria ->
Bring ecf volume down to decrease bp

30
Q

Function of the distal tubule

A

Reabsorption of Na+ , Cl- and Mg2+

31
Q

Where is NCC located?

A

On the apical membrane of the early distal tubule

32
Q

What is the function of NCC?

A

Sodium chloride cotransporter

33
Q

How is Gitelman’s syndrome inherited?

A

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

34
Q

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

A

Calcium difference due to calcium channels in apical membrane

35
Q

What is the mechanism of thiazide diuretics?

A

Target the early distal tubule
High bp treatment

36
Q

Name a thiazide diuretic

A

Chlorothiazide

37
Q

What side effects do thiazide diuretics produce?

A

Side effects similar to Gittleman’s disease

38
Q

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

A

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

Phys, pharm (31 decks)

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