HTN background info Flashcards
CO x PR = ?
- Arterial Pressure - CO determined by: HR, contractility, blood volume, venous return - Peripheral resistance determined by arteriolar constriction (remodeling)
Why is the Poiseuille formula important when considering blood pressure?
- A decrease in the radius of the blood vessel can lead to a significant increase to resistance of the vessel (by a factor of 4) - Remodeling –> decreased radius - Also, w/ remodeling, we also get proliferation of parallel vessels (vs vessels in series) and see another significant increase in resistance * 1/total R = 1/R1 + 1/R2 + 1/R3…
What is the prevalence w/ HTN?
- ↑ w/ agem but lower in women before menopause (estrogen is protective) - > for AA - ~1/3 are asymptomatic and unaware that they have HTN
Predominant HTN form in elderly?
Isolated systolic HTN; often untrx * ~1/2 are receiving trx and only ~1/2 of those are being treated adequately
Modifiable RFs in pts w/ HTN?
smoking, 2nd hand smoke, DM, dyslipidemia/hypercholesterolemia, overwt/obese, physical inactivity/low fitness, unhealthy diet
Relatively fixed RFs for HTN?
CKD, FHx, ↑ age, low socioeconomic/educational status, M > F, obstructive sleep apnea, psychosocial stress
Normal BP in adults?
SBP < 120 mmHG & DBP < 80 mmHG
Elevated BP in adults?
120-129 mmHg/ <80 mmHg
Define Stage I HTN
SBP: 130-139 mmHg or DBP 80-89 mmHg
Define Stage 2 HTN
SBP > or = 140 or DBP > or + 90
What is the ultimate regulator of BP and why?
Renal blood volume pressure control bc of its “infinite gain” - Noting that blood volume changes lead to changes in renal secretions/excretions
BP set point changes
In HTN, the BP set-point is reset to a higher level, but can be either salt-resistant or salt sensitive - All pts are told to limit sodium intake bc increases sodium-retaining hormones that we can block
What is Primary HTN?
- Most common form (~92%)
- Can be subdivided:
- Low renin (~25% more common in AA & elderly)
- Normal renin (~60%)
- High renin
- no identifiable cause
- chronic progressive d/o
- drugs ↓ BP but do not trx underlying cause
What is secondary HTN?
- HTN w/ identified primary cause
- some people can be cured by treating the underlying cause
Conditions suggestive of secondary HTN?
- Renal Parenchymal Dz (UTI, obstruction, PCKD)
- REnovascular dz
- Primary aldosteronism
- Obstructive sleep apnea
- Drug or alcohol induced
- Pheochromocytoma
- Cushing’s syndrome, hypothyroidism, hyperthyroidism, aortic coarctation, etc.
Frequently used meds that ↑ BP
EtOH, immunosuppressants, amphetamines, OCs, antidepressants, NSAIDs, atypical antipsychotics, recreational drugs, caffeine, systemic corticosteroids, decongestants, angiogenesis inhibitors, herbal supplements, tyrosine kinase inhibitors
Srug targets for lowering BP
What is the sympathetic baroreceptor reflex?
- A reflex circuit that keeps arterial pressure at preset level on a second by second basis
- Stretch receptors located in carotid sinus and aortic arch
- Opposes attempts to reduce arterial pressure with drugs
- Sympathetic nerves innervate the heart and travel along the BVs, forming multiple synapses such that the nerves resemble a sting of beads
What are the Baroreceptor effector mechanisms?
- alpha-1 adrenergic receptors located on the BVs to cause vasoconstriction; helps maintain venous return w/ postural changes
- alpah-2 adrenergic receptors act in brain and in periphery in a presynaptic feedback inhibitory manner to ↓ sympathetic tone
- beta-1 adrenergic receptors ↑ HR and contractility, and stimulate renin secretion by the kidneys
- Beta-2 receptors dilate sk m vasculature
Response of BP, PR, CO, & HR w/ different receptor stimulation
What is phentolamine?
- alpha-receptor antagonist
- Short 1/2 life of ~ 19 minutes, w/ 97% gone in ~95 min
- Adverse effx: acute prolonged hypotensive episodes, orthostatic hypotension, tachycardia, and cardiac arrhythmias; weakness dizziness, flushing, nasal stuffiness, NVD
What is Phenoxybenzamine?
- alpah-R antagonist; non-competitive
- Adverse effx similar to phentolamine, plus miosis and occasional severe allergic rxns (angioedema)
What happens if a daily a2-agonist or beta-blocker is stopped abruptly?
REBOUND HTN
- unmasked beta-Rs –> excessive cardiac stimulation in response to nml CNS tone –> tachy, HTN, angina pectoris, MI, arrhythmias
- Stopping alpha2-agonists releases CNS brake on SNS tone –> excessive SNS tone
Why the decreased use in beta-blockers?
- Beta-blocker use does not prevent MI, HF, or death as well as other therapies
- is assoc w/ significantly higher incidence of stroke
Describe the RAS
- Angiotensin I cleaved from Angiotensinogen by renin is cleaved by ACE –> angiotensin II
- Acitve Ang II can ↑ aldosteron secretion –> ↑ Na-K echange in the nephron–> retention of sodium and water (K loss) –> ↑ Blood vol –> ↑ BP
- Active Ang II can cause direct systemic vasonconstriction (arterioles and veins) –> ↑BP
- Ang II –> renal vasoconstriction –> ↓ renal BF –> ↓ GFR –> rentention of H2O and Na+ –> ↑ BV –> ↑ BP
What are the effx of Angiotensin II?
- vasoconstriction –> ↑ TPR
- ↑ EC fluid volume by stimulating thirst, stimulating aldosterone secretion (retains Na+), & stimualtes ADH secretion (retain H2O)
- Contributes to CV remodeling & causes more permanent changes in the BVs so less vasoconstriction is required to maintain a small bore
What classes of drugs effect angiotenisn II formation of axn?
- Aliskirin: blocks the conversion of angiotensinogen to angiotensin I by renin
- ARBS: block the AT1 receptor
- ACEI: blocks ACE, which is needed to convert AT1 –> AT2
Why is there in an increase in TPR seen in chronic HTN pts?
- It seems to follow an initial ↑ in CO, suggesting that colume overload was at fault, and TPR ↑ to compensate
- In some instances, ↑ TPR is the initiating event
RAS Inhibition Effects in the Kidney
- GFR falls d/t ACE inhibition –> ↑ serum creatinine in all pts
- Preserves kidney function in hyperfiltrating diabetics
- can also harm physicials…<30% ↑ likely ok if no hyperkalemia
