Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Physiology and Pharmacology of Cells > L4 - Renal Diseases > Flashcards

L4 - Renal Diseases Flashcards

1
Q

What kind of inheritance is Liddle’s syndrome?

A

Autosomal dominant
Gain of function mutation in ENaC
Na channel function enhanced

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the symptoms of Liddle’s syndrome?

A 
Na+ and fluid retention
Hypertension
Hypokalaemia
Metabolic alkalosis
Low renin and aldosterone levels
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How does the body try and compensate for the hypertension?

A

Low renin and aldosterone levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the subunits of ENaC?

A

Alpha, beta, gamma subunits 1:1:1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Where is the Liddle’s mutation found in ENaC?

A

Found in COOH tail of beta or gamma subunits

Deletion of proline rich motifs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the importance of proline rich motifs?

A

Important endocytosis
Allows ENaC to interact with a ubiquitinate ligase so it can be removed from membrane
If motif deleted endocytosis rate slowed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What causes hypertension and hypokalaemia in ENaC mutant?

A

In mutant more channels open in principal cell as they cannot be removed by endocytosis

  • Excessive Na and water uptake – hypertension
  • More Na uptake means more K secretion – hypokalaemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What causes metabolic alkalosis in ENaC mutant?

A

In the alpha intercalated cell high Na reabsorption from tubular fluid leaves a negative membrane potential
Leads to an excess of H+ secretion
Creates a transepithelial potential

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

In a normal individual what sequence of events happens after a rise in BP?

A

Decrease in renin and aldosterone release
Low aldosterone in principal cells
Loss of ENaC from apical membrane of principal cells
Reduction in Na reabsorption
Fall in BP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

In a Liddle’s individual what sequence of events happens after a rise in BP?

A

Hypertension – high BP
Low renin and aldosterone – compensation mechanism
Cannot remove ENaC from apical membrane principal cells
No reduction in Na reabsorption so hypertension persists
High Na reabsorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the main treatment for Liddle’s syndrome?

A

Amiloride

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the effect of Amiloride when used as treatment in an infant?

A

Reverses high BP
Concentration of Na stays constant but total Na content of plasma changes with an expansion of ECF volume
Reverses loss of K
pH decreases due to a reduced loss of H+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What effect does spironolactone have on treatment of Liddles syndrome?

A

No effect

MR receptor antagonist (target for aldosterone)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is diabetes insipidus?

A

Polyuria with compensatory polydipsia - thirst

Dehydration can be a serious issue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the inherited conditions of diabetes insipidus?

A

1 : 25,000-30,000

Problems with AVP – AQP2 system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the sequence of events that happens in the principal cells of the collecting duct resulting in water absorption?

A

Vasopressin receptor 2 binds AVP
Stimulates receptor leading to activation of PKA
Leads to phosphorylation of AQP2 in vesicles underneath apical membrane
Vesicles fuse with membrane and insert new AQP2
Osmotic driving force for water to enter through AQP2 and out through AQP3+4
- AQP3+4 are constitutively active
Rate limiting factor for water reabsorption is AQP2 in apical membrane

17
Q

What are the 4 types of diabetes insipidus?

A

Central
Gestational
Nephrogenic
Primary polydipsia

18
Q

What is central diabetes insipidus?

A

Impaired AVP production

Acquired or congenital

19
Q

What is gestational diabetes insipidus?

A

Decreased AVP levels
Metabolism by placental enzymes
Only seen in pregnant women

20
Q

What is nephrogenic diabetes insipidus?

A

Impaired effect of AVP

Acquired or congenital

21
Q

What is central primary polydipsia diabetes insipidus?

A

Suppressed AVP production

Excessive H2O intake

22
Q

What are the causes of central acquired diabetes insipidus?

A

Infection
- In hypothalamus or posterior pituitary gland
- Inability to respond to changes in osmolarity of plasms or release vasopressin
Head trauma
Surgery

23
Q

What are the causes of central congenital diabetes insipidus?

A

67 mutations in AVP gene
Many mutations important for transport of AVP from hypothalamus to posterior pituitary
- Not transported to pituitary glans
- Not released
- Released but not active
As though they are not releasing AVP at all

24
Q

What are the causes of nephrogenic acquired diabetes insipidus?

A

More common
Lithium – bipolar affective disorder treatment
- Impacts on ability to reabsorb water
Some antibiotics, antifungals, antineoplastic agents
Hypokalemia and hypercalciuria
- Reduction in AQP2 levels in the kidney
Acute and chronic renal failure

25
Q

What are the causes of nephrogenic congenital diabetes insipidus?

A

Mutations in

  • AVPR2 gene – x linked
  • AQP2 gene – impact trafficking (dominant) or function (recessive) of protein
26
Q

When do the symptoms of nephrogenic diabetes insipidus occur?

A

In infants

27
Q

What are the symptoms of nephrogenic diabetes insipidus?

A

Hypernatrimic dehydration – low volume and enhanced Na concentration in plasma
Poor feeding
Skin dryness
Depressed anterior fontanel – some components of skull haven’t fused (depression at front)

28
Q

What are the treatments for central diabetes insipidus?

A

Desmopressin
Given through a nasal spray
It activates vasopressin receptors

29
Q

What are the 4 different treatments for nephrogenic diabetes insipidus?

A

Cell permeable antagonists
Cell permeable agonists
Compounds that bypass vasopressin 2 receptor signalling
Compounds that can target different parts of pathways downstream of vasopressin receptor

30
Q

How can cell permeable antagonists be used to treat diabetes insipidus?

A

1st type
- Target misfolded vasopressin 2 receptor to the membrane
- Then replaced with AVP
2nd type
- Cross the membrane and enter the cell
- Activates misfolded vasopressin 2 receptor signalling – PKA activation

31
Q

How can cell permeable agonists be used to treat diabetes insipidus?

A

Aid correct folding and trafficking

Then activates vasopressin 2 receptor signalling

32
Q

How can compounds that bypass vasopressin 2 receptor signalling be used to treat diabetes insipidus?

A

Target directly downstream – bypass the mutation
Target prostaglandin receptor
- Activation of cAMP
- Insertion of AQP2 into membrane

33
Q

What are the 5 compounds that target different parts of the pathway downstream of vasopressin receptors?

A 
Prostaglandin receptor agonists 
Stimulating cGMP levels
Stimulating cAMP levels
Statins  
Heat shock protein 90 inhibitors
34
Q

How can prostaglandin receptor agonists be used to treat diabetes insipidus?

A

Induce AQP2 expression and membrane abundance

35
Q

How can cGMP level be used to treat diabetes insipidus?

A

PDE5 inhibitors – prevent breakdown cGMP

Stimulates insertion of AQP2

36
Q

How can cAMP levels be used to treat diabetes insipidus?

A

PDE4 inhibitors – prevent breakdown cAMP

Stimulates insertion of AQP2

37
Q

How can statins be used to treat diabetes insipidus?

A

Prevent internalisation AQP2

38
Q

How can heat shock protein 90 inhibitors be used to treat diabetes insipidus?

A

Allows misfolded AQP2 to reach the membrane

Physiology and Pharmacology of Cells (13 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions