Pathophysiology of HTN Flashcards
key steps for proper BP measurements
- properly prepare the pt
-rest quietly for ~5 min
-pt should be relaxed, sitting, both feet on floor, remove clothing under the cuff, no recent caffeine or smoking - use proper technique for BP measurements
-BP cuff size should be appropriate
-use an upper arm measurement, around the level of the heart/right atrium - take the proper measurements needed for dx and tx of elevated BP/HTN
- properly document BP readings & average multiple readings
normal blood pressure
SBP < 120 AND DBP < 80
elevated blood pressure
SBP 120-129 AND DBP < 80
stage 1 HTN
SBP 130-139 OR DBP 80-89
stage 2 HTN
SBP 140+ OR DBP 90+
primary (essential) HTN - defined
*unknown cause
*likely genetic & environmental influences
secondary HTN - defined & when to suspect it
*due to an identifiable cause
*consider secondary HTN if…
-refractory or resistant HTN
-young age of onset (<30 in adults)
-associated hypokalemia
-abrupt onset or significant increase in HTN in a short period of time
-very severe HTN
refractory/resistant hypertension - defined
*blood pressure that is still not at goal despite treatment with 3 medications at max tolerated dose, all from different classes, including a diuretic
hypertensive urgency vs. emergency
*both have severe HTN: BP 180/120 or higher
*HTN urgency: no end organ damage
*HTN EMERGENCY: SIGNS OF END ORGAN DAMAGE:
-pulmonary edema
-papilledema, ICH
-MI/elevated troponins
-AKI
-aortic dissection
white coat hypertension - defined
*HTN only seen in doctor’s office
*normal BP at home, however, pt is more nervous in medical setting, so blood pressures are higher
*this can be confirmed with 24h ambulatory BP monitoring
masked hypertension - defined
*opposite of white coat HTN
*blood pressure is NORMAL in the doctor’s office but runs HIGH AT HOME
*detected through 24h ambulatory BP monitoring
lifestyle interventions to treat HTN
*WEIGHT LOSS
*heart healthy diet (ex. DASH diet)
*low salt diet
*exercise/increased physical activity
*decrease alcohol consumption
*treatment of OSA with CPAP
suspected pathogenic mechanisms in HTN
- abnormal kidney handling of sodium & plasma volume
- activation of sympathetic nervous system
- activated RAAS
- likely other environmental & genetic factors
effects of abnormal kidney handling of sodium & plasma volume → HTN
*excess Na+ (and thus excess water) content in blood → higher blood pressure
pressure natriuresis
*mean arterial pressure increases as sodium intake increases
*2 clinical categories:
1. salt sensitive:
-more likely to respond to diuretic and dietary salt restriction
-have lower renin levels
2. salt insensitive:
-more likely to respond to RAAS blockade
-have higher renin levels
effects of RAAS → HTN
angiotensinogen → angiotensin I → angiotensin II → aldosterone
*end result = INCREASED BLOOD PRESSURE / VOLUME
*rate limiting step = RENIN RELEASE (recall: renin converts angiotensinogen to angiotensin I)
angiotensin II - effects leading to increased blood pressure
*sodium reabsorption
*water reabsorption (increased ADH)
*vasoconstriction
*increased sympathetic tone
*increased salt appetite
*increased thirst drive
end result: increased BP/blood volume
aldosterone - effects leading to increased blood pressure
*salt reabsorption → increased blood volume
*potassium excretion
*acid excretion
end result: increased BP/blood volume
factors that cause renin release
*decreased renal perfusion (systemic hypotension or low afferent arteriole pressure)
*increased sympathetic activity/tone
*decreased flow through tubules or decreased distal Na+ delivery (detected by macula densa)
*beta1 adrenergic stimulation
*low sodium diet
effects of aldosterone in the principal cell in the collecting duct
aldosterone (made by adrenal cortex) binds mineralocorticoid receptor (MR) inside principal cells → increased activity of Na+/K+ ATPase AND increased activity of ENaC → increased reabsorption of sodium into blood & wasting of potassium in urine
medications that turn off steps of RAAS cascade
- ACE inhibitors (-prils) - block conversion of Ang I to Ang II
- ARBs (-sartans) - block binding of Ang II to its receptor
- aldosterone antagonists (spironolactone, epleronone) - block effects of aldosterone
effects of increased salt intake on RAAS activity
*as salt intake increases, the RAAS system should be turned OFF
risk factors for HTN
*obesity
*decreased nephron number
*family hx of HTN
*race (more common in Black pts)
*increasing age
*smoking
*male sex
*substantial alcohol use
*sedentary lifestyle
*low SES
*insulin resistance
*high dietary sodium intake
genetic disorders associated with HTN
- Liddle Syndrome
- Syndrome of Apparent Mineralocorticoid Excess (SAME)
- Pseudohypoaldosteronism type 2 / Gordon Syndrome
- Glucocorticoid Remediable Hyperaldosteronism (GRA)
Liddle Syndrome - inheritance pattern & genetics
*autosomal dominant
*gain of function mutation of the ENaC channel located in the apical membrane on the principal cell in the collecting duct
*results in excessive Na+ reabsorption and excessive K+ wasting
Liddle Syndrome - electrolyte impacts
- excessive Na+ reabsorption
- hypokalemia (excessive K+ wasting)
- metabolic alkalosis
- hypertension
- low-to-normal serum aldosterone
Liddle Syndrome - clinical presentation
*young person with high blood pressure
*family hx of HTN (particularly at a young age)
*hypokalemia
*metabolic alkalosis (due to K+/H+ exchange in the alpha-intercalated cells)
METABOLIC ALKALOSIS + HYPOKALEMIA + HTN (low serum aldosterone)
Liddle Syndrome - effects on RAAS
*gain of function of ENaC channels → excessive Na+ reabsorption → volume expansion → DECREASED RENIN
*decreased renin → decreased Ang II → decreased aldosterone
Liddle Syndrome - treatment
*block ENaC: potassium sparing diuretics: amiloride, triamterene
primary hyperaldosteronism vs. Liddle Syndrome
*both: HTN, hypokalemia, metabolic alkalosis
*Liddle Syndrome: LOW ALDOSTERONE
*primary hyperaldosteronism: HIGH ALDOSTERONE
Syndrome of Apparent Mineralocorticoid Excess (SAME) - inheritance pattern & genetics
*autosomal recessive
*mutation of 11 beta-hydroxysteroid dehydrogenase, causing it to be inactivated
*this enzyme normally converts cortisol to cortisone; inactivation of enzyme → activation of mineralocorticoid receptors by excess cortisol
*notably - a LOT of black licorice ingestion can cause a similar phenotype (glycyrrhizic or glycyrrhetinic acids in licorice inhibits the same enzyme)
Syndrome of Apparent Mineralocorticoid Excess (SAME) - clinical features
*infants with low birth weight, failure to thrive
*severe HTN
*hypokalemia
*metabolic alkalosis
*low serum aldosterone (cortiol tries to be the SAME as aldosterone)
Syndrome of Apparent Mineralocorticoid Excess (SAME) - effects on RAAS
*cortisol is stimulating the mineralocorticoid receptor (same receptor that aldosterone stimulates)
*increased Na+ reabsorption → volume expansion → decreased renin
*decreased renin → decreased Ang II → decreased aldosterone
pseudohypoaldosteronism type 2 / Gordon Syndrome - inheritance pattern & genetics
*autosomal dominant
*gain of function mutation of the Na+/Cl- cotransporter in DCT (opposite of thiazide diuretics; opposite of Gitelman syndrome)
pseudohypoaldosteronism type 2 / Gordon Syndrome - electrolyte impacts
*excessive Na+ reabsorption → increased blood volume
*less delivery of Na+ to the cortical collecting duct, so K+ cannot be excreted
pseudohypoaldosteronism type 2 / Gordon Syndrome - clinical presentation
*HTN
*HYPERKALEMIA
*metabolic acidosis
*normal kidney function
pseudohypoaldosteronism type 2 / Gordon Syndrome - treatment
*thiazide diuretics
glucocorticoid remediable hyperaldosteronism (GRA) - inheritance pattern & genetics
*autosomal dominant
*genetic crossover between 2 genes causes the creation of a chimeric aldosterone synthase gene which is controlled by ACTH release instead of Ang II
glucocorticoid remediable hyperaldosteronism (GRA) - clinical presentation
*HTN (resistant, often at a young age)
*metabolic alkalosis
*family hx of HTN and/or premature hemorrhagic stroke
glucocorticoid remediable hyperaldosteronism (GRA) - treatment
*glucocorticoids to suppress ACTH release
Bartter Syndrome - inheritance pattern & genetics
*autosomal recessive
*inactivating mutation in the NKCC channel in thick ascending loop of Henle (loop diuretic channel)
note - this is a cause of HYPOtension
Bartter Syndrome - clinical presentation
*presents in infancy/childhood
*growth delay
*volume depletion
*hypokalemia, hypomagnesemia, hypochloremia, metabolic alkalosis
*HYPERCALCIURIA
*usually HYPOTENSION or normotension
remember - pts with Bartter Syndrome act like they have been on LOOP diuretics
metabolic alkalosis + hypokalemia + hypercalciuria + hypotension
Gitelman Syndrome - inheritance pattern & genetics
*autosomal recessive
*inactivating mutation in the Na+/Cl- cotransporter in the DCT
*acsts like a thiazide diuretic (causes hypercalcemia)
*opposite of Gordon syndrome
note - this is a cause of HYPOtension
Gitelman Syndrome - clinical presentation
*usually presents in childhood, teen, or early adult years
*volume depletion
*hypokalemia, hypomagnesemia, hypochloremia, metabolic alkalosis
*HYPOCALCIURIA
*usually HYPOTENSION or normotension
remember - pts with Gitelman Syndrome act like they are on THIAZIDE diuretics
metabolic alkalosis + hypokalemia + hypocalciuria + hypomagnesemia + hypotension
Bartter Syndrome vs. Gitelman Syndrome
*HIGH URINE CALCIUM (hypocalcemia) = Bartter (acts like a loop diuretic)
*LOW URINE CALCIUM (hypercalcemia) = Gitelman (acts like a thiazide diuretic)
pseudohypoaldosteronism type 1 - inheritance pattern & genetics
*autosomal dominant or sporadic
*loss of function defect in ENaC or mineralocorticoid receptor
*essentially, unresponsive to the effects of aldosterone
pseudohypoaldosteronism type 1 - clinical presentation
*presents in neonatal period or early infancy
*salt wasting, failure to thrive
*HYPOTENSION
*hyperkalemia
pseudohypoaldosteronism type 1 - treatment
high salt diet/NaCl supplements
monogenic disorders of BP regulation: ENaC channel in principal cells of collecting duct
*Liddle’s Syndrome = gain of ENaC function → hypertension
*Pseudohypoaldosteronism type I = loss of ENaC function → hypotension
monogenic disorders of BP regulation: NKCC channel in loop of Henle
*Bartter’s Syndrome = loss of NKCC function → hypotension
monogenic disorders of BP regulation: Na+/Cl- cotransporter in DCT
*pseudohypoaldosteronism type 2 (Gordon) = gain of NCC function → hypertension
*Gitelman’s syndrome = loss of NCC function → hypotension
