Genetics of Hypertension Flashcards
What does short, intermediate, and long-term regulation of BP?
Short: sympathetic system, CNS, baroreceptors: affect CO and TPR
INtermediate: humoral factors regulate TPR
Long term regulation: kidney regulates TPR
What’s the hemodynamic profile in hypertension? Change from prehypertension to hypertension?
Prehypertension: more salt, more volume, more CO, normal systemic vascular resistance, high blood pressure
Some change in autoregulation of blood flow
- we still don’t know what causes this shift
Hypertension: normal CO, increase in SVR, still high blood pressure
Glucocorticoid remediable aldosteronism: what causes it?
Aldosterone synthase is close to 11-OHase, a glucocorticoid synthesis protein
These merge together to form a chimeric gene that makes aldosterone but has the regulatory portion of the glucocorticoid synthesis
So you keep making aldosterone independently of volume/BP status!!!
Inherited disorder
Findings: HBP, familial pattern, suppressed renin, high aldosterone
Glucocorticoid remediable aldosteronism: treatment?
Give patient cortisol –> suppresses the aldosterone production
Apparent mineralocorticoid excess: what causes it? presentation? treatment?
Both aldosterone and cortisol bind the mineralocorticoid receptor (MR) in the kidney
Defect in 11-B hydroxysteroid dehydrogenase 2 mutation –> can’t convert cortisol to cortisone –> build up of cortisol & activation of MR receptor –> increased aldosterone production –> increased Na reabsoroption in collecting duct –> high blood pressure
Maintain appropriate suppression of aldo but pt gets htn bc so much cortisol
Give antagonist to MR
Recessive dz
Low renin, low aldosterone, high bp, high urinary cortisol levels
Licorice ingestion: how can it cause htn?
Licorice –> glycyrrhizic acid which inhibits the same enzyme as in AME (apparent mineralocorticoid excess) so you can’t convert cortisol to cortisone
Primary aldosteronism: presentation?
htn, low renin, high aldo: suggests some mechanism of aldo production
Imaging shows either:
(1) adrenal adenoma: tumor
Cushing’s: more cortisol productio
Conn’s: more aldo production
(2) adrenal hyperplasia: inverted Y or V shaped area of adreal gland with fat limbs/legs; too big to be normal
Primary aldosteronism - treatment?
If unilateral, surgical removal of the adrenal
If bilateral, give them mineralocorticoid antagonists
Most are benign and unilateral
What mutation is implicated in aldoserone producing adenomas?
K-channel mutation that’s usually responsive to K levels
Means it’s always open to K+
Leads to uncontrolled aldosterone production, bc aldosterone is responsive to ang II and K+ levels
Renal artery stenosis: presentation?
high blood pressure
Bruit in upper abdomen, subcostal area- unilateral usually
Normal serum potassium
Normal renin & aldo levels
Sonogram shows one kidney is smaller than the other
What can cause narrowing of the renal arteries?
Fibromuscular dysplasia: “string of pearls” appearance to renal artery; due to overgrowth of the cells of the artery
Bilateral renal artery stenosis: due to atherosclerosis of the renal arteries; lots of narrowing can reduce flow to the kidneys; ultrasound and doppler ultrasound can help you diagnose it
What’s the pathogenesis of renal artery stenosis to hypertension?
Stenosed kidney: decreased renal perfusion & increased local renin/ang II production
+
Normal kidney: Increaesd blood flow & decreased local renin & ang II, impaired Na excretion
–>
increased circulating renin & ang II, increased symp activation, increased aldo production, increased Na retention
–>
Vasoconstriciton, Extracellular volume expansion
–>
Hypertension
What are the 3 phases of renovascular hypertension?
Phase 1: weeks-months
- high renin
- htn due to vasoconstriction
- reversible
Phase 2: months-years
- normal renin due to vol expansion and htn
- volume dependent htn
- reversible, if you remove the stenosis
Phase 3: years
- normal renin
- RAS independent htn
- changes in vasculature leading to increased TPR
- poorly reversible
**Don’t get tricked by normal renin!!!
How can you diagnoe renovascular htn?
Renin can be high but normal levels do not rule out renal artery stenosis!
Imaging studies: MR angiography, CT angiography, angiography
Can be due to fibromuscular dysplasia in young individuals - treat wtih angioplasty
Due to atherosclerotic dz in older individuals w CV risk factors
- suspect pre-existing periph vasc dz or long history of smoking, recurrent flash pulm edema
- treatment with angioplasty+ stent placement
Pheochromocytoma: what is it?
Neuroendocrine tumors arising in adrenal medulla producing excess catecholamines
