Genetic renal problems

Question 1

syndrome of AME?

Answer 1

syndrome of apparent mineralocorticoid excess

• mutation of 11 BSD, which converts cortisol to cortisone.
• important in renal cells since cortisol activates mineralicorticoid receptor (with aldosterone), while cortisone doesn’t
• so, looks like primary aldosteronism

Question 2

how to diagnose syndrome of apparent mineralocorticoid access (AME)?

-inheritance pattern?

Answer 2

-measure blood cortisol/cortisone ratio.

cortisone will be low/undetectable.

-also, gene sequencing, Auto rec.

Question 3

Liddle syndrome

-mech

Answer 3

• “pseudoaldosteronism”
• mutation in ENaC channels, so they are constitutively active. (as if there is lots of aldosterone).
  1. Na enters principal cells, so tubule lumen is negative
  2. negative charge draws K+ from the principal cells. H+ follows the electronegativity as well, from the alpha intercalated cells.

gain of function mutation

Question 4

AME syndrome vs Liddle syndrome:

-how are tx similar and different? why?

Answer 4

AME: can use ENaC blockers or Aldo blockers.

Liddle syndrome: can only use ENaC blockers b/c Aldo blockers don’t affect the constitutive activation of ENaC

Question 5

ENaC blockers vs Aldo blockers:

list them

Answer 5

ENaC: amiloride, triamterene

Aldo: spironolactone, eplerenone

Question 6

Gitelman and Bartter syndromes: what are they?

Answer 6

Bartter: mutation in Na/K/2 Cl transporter in loop of henle. (mimic loop diuretics)

Gitelman: mutation in Na/Cl transporter in DCT (mimic thiazides)

Question 7

mnemonic to remember genetic renal tubular defects

Answer 7

kidneys put out FABulous Glittering Liquid

Fanconi–PCT

Bartter–Loop of henle, loops

Gitelman–DCT, thiazides

Liddle–ENaC

also: syndrome of AME–cortisol to cortisone (11 BHSD loss)

Question 8

Fanconi syndrome

Answer 8

PCT defect. no specific channel–lots of things are not reabsorbed. (aa, glucose, HCO3, PO4, etc)