2 mendelian HTN Flashcards
What are the actions of aldosterone on tubular reabsorption?
- acts in principle cells of late distal tubule and collecting duct
- increases Na and water reabsorption, increases K secretion
What are the actions of Ang II on tubular reabsorption?
- acts on proximal tubule, thick ascending limb, distal tubule
- increases Na and water reabsorption, increases H secretion
What are the actions of ADH on tubular reabsorption?
- acts on distal tubule/collecting duct
- increases water reabsorption
What are the actions of ANP on tubular reabsorption?
- acts on the distal tubule/collecting duct
- decreases Na reabsorption
What are the actions of PTH on tubular reabsorption?
- acts on the proximal tubule, thick ascending limb, and distal tubule
- decreases phosphate reabsorption, increases Ca reabsorption
What is AME?
- syndrome of Apparent Mineralocorticoid Excess
- autosomal recessive
- presents with:
- low birth weight/FTT
- severe childhood HTN
- extensive organ damage (renal failure)
- prognosis usually poor due to progression of disease at time of diagnosis
- findings similar to primary aldosteronism
- HTN
- hypokalemia, metabolic alkalosis
- low plasma renin and plasma/urine aldosterone
What is the pathophysiology of AME?
- mutation/loss of function of the 11beta-HSD2 enzyme (responsible for conversion of cortisol to inactive cortisone)
- rare, often from consanguineous relationship
- activation of mineralocorticoid receptor by cortisol is usually limited by its inactivation to cortisone
- with the mutation, cortisol saturates the MR
- over-activates ENaC in the late distal tubule
- induces HTN and hypokalemia
- with the mutation, cortisol saturates the MR
Describe the clinical symptoms of Liddle syndrome
- also known as pseudoaldosteronism
- autosomal dominant
- findings similar to other mineralocorticoid excess syndromes:
- HTN (young onset, severe)
- hypokalemia, metabolic alkalosis
- low plasma renin
- low plasma/urine aldosterone
What is the pathogenesis of Liddle syndrome?
-
gain of function mutation in the renal ENaC (alpha, beta, or gamma subunit mut leads to constitutive expression)
- increases absorption of sodium, leading to HTN
- confirmation possible by sequencing of SCNN1A, SCNN1B, and SCNN1G genes
What are some treatments for AME?
- block mineral corticoid receptor (Aldosterone Ant)
- spironolactone, eplerenone
- sodium channel blockers
- amiloride, triamterene
- potassium supplementation
- ACTH suppression (reduces endogenous cortisol production)
- dexamethasone
What are some treatments for Liddle syndrome?
- decrease sodium channel activity
- amiloride, traimterene
- aldosterone ant is NOT helpful (recall, the problem is with ENaC not aldosterone/receptor)
**with treatment, prognosis is good (without, CV/renal complications from uncontrolled HTN often occur)
Compare AME and Liddle syndrome
What is Bartter syndrome?
- autosomal recessive (loss of function)
- multiple types, all affecting different channels/genes
- Na-K-2Cl cotransporter
- apical K channel
- Cl channel
- defects in ascending limb of the loop of henle (thick and thin; sites of loop diuretic action)
- urine concentrating capacity severely impaired
What are the presenting symptoms of Bartter syndrome?
- severe HTN
- growth and developmental delays
- polyuria and polydipsia (increased urine output and thirst)
**usually presents early (prenatal, infancy, or childhood)
What is Gitelman syndrome?
- autosomal recessive
- mutation of the Na-Cl cotransporter (SLC12A3) in the distal tubule
- site of thiazide diuretic action
- urine concentrating capacity normal or mildly impaired
Compare Bartter and Gitelman syndrome
