Physiology Correlations for Mendelian Forms of Hypertension Flashcards
Describe the presentation of AME (Syndrome of Apparent Mineralocorticoid excess)
- Low birth weight
- Failure to thrive
- Severe hypertension in early childhood
- Extensive organ damage
- Renal failure
In AME, what happens with plasma renin and aldosterone levels?
Low plasma renin activity
Low plasma aldosterone levels
What gene defect is seen in AME?
11-ß-HSD2 gene
What is the function of 11-ß HSD2?
How does its function aid in diagnosis of AME?
Converts cortisol to cortisone
Meausre urine cortisol to cortisone ratio - in most patients with a defective enzyme, the urinary free cortisone levels are very low or undetectable
What type of inheritance is associated with AME?
Autosomal recessive
Liddle syndrome is also known as ____________
Pseudoaldosteronism
What characteristics are associated with pseudoaldosteronism?
- Hypertension - young onset, severe
- Hypokalemia
- Metabolic Alkalosis
What RAA system components have low levels and activity in pseudoaldosteronism (Liddle syndrome)
Low plasma renin activity
Low plasma aldosterone AND urinary aldosterone
What genes can be sequenced to confirm the diagnosis of Pseudoaldosteronism
SCNN1G
SCNN1B
Liddle syndrome is associated with a _____ __ ______mutation in the renal _____ channel
gain of function; ENaC
Mutations in LIddle Syndrome lead to increased absorption of _______ leading to hypertension
sodium
Where does aldosterone act and what function does it serve?
- Acts in principal cells of late distal tubule and collecting duct
- Increases Na+ reabsorption , increases K+ secretion
Cortisol and aldosterone can bind to the mineralcorticoid receptor with equal affinity but aldosterone is the primary effector. Why is this?
Cortisol is quickly converted to cortisone upon entering into the cell
What medication is used to reduce endogenous cortisol production (decrease sodium channel activity) in AME?
Amiloride
Triamterene
What medications block the mineral corticoid receptor in AME?
Spironolactone
Eplerenone
Other therapies for AME treatment?
Potassium repletion
Dexamethasone for ACTH suppression
How does Bartter syndrome present?
- Early childhood
- Growth and mental retardation
- Polyuria and Polydipsia
- Hypercalciuria
How does Gitelman syndrome present?
- Adolescence/Adulthood
- Cramping of arms and legs
- Fatigue
- Hypomagnesemia
- Polyuria and nocturia
What are the clinical findings in Bartter syndrome?
Hypokalemia
Hyperreninemia
Hyperaldosteronism
Metabolic Alkalosis
What pattern of inheritance is associated with Gitelman syndrome?
Autosomal recessive
Which portion of the renal tubule has the following characteristics…
Reabsorbs 25% of filtered Na+
Impermeable to water
Drives reabsorption of sodium, potassium, magnesium, and calcium
Thick ascending loop of Henle
What part of the renal tubule is succeptible to thiazide diuretics?
Early distal tubule
What genes are mutated in Bartter syndrome?
Genes that encode proteins in the ascending part of Henle’s loop:
BSND, CLCNKA, CLCNKB, KCHJ1, SLC12A1
What genes are mutated in Gitelman Syndrome?
Mutations in SLC12A3 or less commonly CLCNKB
In Bartter syndrome, tubular defect mimics chronic _____ _______ injestion
loop diuretic
In Gitelman syndrome, tubular defect mimics ______ _______ ingestion
thiazide diuretic
Which disease (Bartter syndrome or Gitelman syndrome) has a worse prognosis?
Bartter syndrome (life expectancy is reduced in severe cases)
