Clinical Hypertension + Physiology of HTN Flashcards
What is blood pressure? Determined by? Factors that affect this?
Arterial blood pressure is the force the blood exerts against the arterial wall. Arterial blood pressure is, therefore, mainly determined by the amount of blood within the arterial system. More blood equals more pressure. The amount of blood entering the arterial system is determined by cardiac output and the amount of blood leaving the system is determined by peripheral resistance.
An increase cardiac output ejects more blood into the arterial system and arterial blood pressure increases.
An increased peripheral resistance limits the amount of blood leaving the arterial system and arterial blood pressure increases. The kidneys influence the total blood volume which directly influences cardiac output.
Define Systolic Blood pressure? Diastolic blood pressure? Pulse Pressure? Mean arterial blood pressure?
Systolic blood pressure (SBP): peak pressure during contraction of the heart (systole). It is the force exerted by the volume of blood against the arterial wall when the heart contracts.
Diastolic blood pressure (DBP): minimum arterial pressure during relaxation of the heart (diastole). It is the force exerted by the volume of blood against the arterial wall when the heart is relaxed.
Pulse pressure = SBP – DBP
Mean arterial blood pressure = DBP + 1/3 (SBP – DBP) Since atmospheric pressure is 760 mmHg, mean arterial blood pressure is actually 863 mmHg (i.e., 760 + 93). Zero reference point!
Factors influencing blood pressure?
Rise in aortic pressure from its diastolic to systolic value is determined by?
The rise in aortic pressure from its diastolic to systolic value is determined by the compliance of the aorta as well as the ventricular stroke volume, along with the diastolic arterial blood pressure (it serves as the baseline for systolic arterial blood pressure).
Explain compliance in the Aorta?
In the arterial system, the aorta has the highest compliance, due in part to a relatively greater proportion of elastin fibers versus smooth muscle and collagen. This serves the important function of dampening the pulsatile output of the left ventricle, thereby reducing systolic and pulse pressures (systolic minus diastolic arterial pressure). If the aorta were a rigid tube, the pulse pressure would be very high. Because the aorta is compliant, as blood is ejected into the aorta, the walls of the aorta expand to accommodate the increase in blood volume. As the aorta expands, the increase in pressure is determined by the compliance of the aorta at that particular range of volumes. The more compliant the aorta, the smaller the pressure change during ventricular ejection. Therefore, aortic compliance is a major determinant, along with stroke volume, of the systolic arterial pressure.
Systolic arterial pressure with age?
Systolic arterial pressure increases with age because aortic compliance decreases with age. When stroke volume is injected into the aorta, the compliant aorta expands and absorbs the force. The more compliant, the greater the expansion and the lower the systolic pressure.
Explain wave reflection?
Explain the effect of increased or decreased arterial compliance on Pulse Pressure?
increased arterial compliance. Pulse pressure is the difference between systolic and diastolic blood pressure. Increasing the compliance of an artery will decrease pulse pressure.
Decreased arterial compliance. Decreasing the compliance of an artery will increase pulse pressure. To understand these concepts, visualize a garden hose that has a minimal ability to stretch compared with that of a balloon. Opening the faucet introduces a bolus of water into the hose, and the wall of the hose will stretch minimally compared with that of a balloon with the same bolus of water. Therefore, the pressure that the water will impose on the wall of the hose will be much greater than that imposed on the wall of the balloon. If a vessel has a decreased compliance, then the vessel is unable to expand and absorb the energy imparted by the blood during systole. Consequently, systolic blood pressure increases. Likewise, the less compliant vessel has a reduced rebound effect, and diastolic blood pressure is reduced. Together, the increase in systolic pressure and decrease in diastolic pressure result in an increased pulse pressure
What is stroke volume determined by?
Stroke volume is determined by the force of ventricular contraction and the volume of venous return. The sympathetic nervous system increases the force of contraction. The sympathetic nervous system also increases venous return by causing venoconstriction. The kidneys, via a variety of hormones and hemodynamic factors, influences total blood volume.
Explain the Autonomic nervous effects on the heart?
The autonomic nervous system exerts a profound influence on the heart due to its ability to modulate cardiac rate (chronotropy), conduction velocity (dromotropy), contraction (inotropy), and relaxation (lusitropy). Given the ability to modulate both cardiac rate and stroke volume, the autonomic nerves provide an important mechanism to rapidly adjust cardiac output
Increasing Venous return to the heart?
Veins contain less smooth muscle and receive a sparser sympathetic innervation than arterioles. They are also more distensible and able to accommodate large volumes of blood and therefore serve primarily as capacitance vessels. Because volume varies directly with the square of the vessel radius, changes in the caliber of the veins is an effective means to change tissue volume. Sympathetic constriction of capacitance vessels is therefore an important mechanism to decrease tissue blood volume. Blood that is forced out of the veins returns to the heart, increasing end-diastolic volume and, via the Frank-Starling mechanism, increasing stroke volume and cardiac output.
What is the diastolic arterial pressure? How does HR affect it? Peripheral resistance increase?
Diastolic arterial blood pressure is the pressure that is exerted on the walls of the arteries between heart beats when the heart is relaxed. It is the minimum pressure in the entire cardiac cycle. So, it basically represents amount of blood in arterial system during diastole. The amount of blood in the arteriole system when the heart is filling in diastole is determined by heart rate and peripheral vascular resistance at the level of the arterioles! They maintain your diastolic blood pressure. For example, if there is an increase in heart rate, there is more blood being ejected into the arteries (increased inflow) and less time for the blood to run out of the arteries during diastole. Arterial volume, therefore, rises to a higher value than before and diastolic pressure increases as a result. The opposite occurs if heart rate decreases. If there is an increase in peripheral vascular resistance, blood gets “trapped” on the arterial side of the circulation (meaning less blood leaves the arteries). Consequently, diastolic blood pressure increases.
Peripheral resistance is affected by? Blood flow affected by this how?
The diameter of the arteriole is THE MOST important factor in determining the rate of flow through a vessel.
Even small changes in vessel caliber can have relatively large effects on vascular resistance and blood flow.
If resistance increases, blood flow out of the arterial system decreases and pressure within the vessel increases.
If resistance decreases, blood flow out of the arterial system increases and pressure within the vessel decreases.
Arterial baroreceptor responses to an increase or decrease in arterial pressure?
Match the following to the graph:
- Right vagal stimulation. The right vagus nerve innervates the sinoatrial (SA) node of the heart. Stimulation of the right vagus nerve inhibits the sinoatrial node.
- Phenylephrine administration. Phenylephrine is an alpha1-adrenergic receptor agonist.
A = Right vagal stimulation: A decrease in heart rate in response to right vagal stimulation will have an effect on arterial pressure. Recall that arterial pressure is a product of cardiac output and total peripheral resistance. Furthermore, cardiac output is a product of heart rate and stroke volume. Thus, a decrease in heart rate will result in a decrease in cardiac output. Consequently, the reduction in both heart rate and cardiac output decreases arterial pressure. Alternatively, a perturbation that increases heart rate will increase arterial pressure. Strong vagal stimulation may completely abolish the discharge rate of the SA node. If vagal stimulation is continued, the heart may beat spontaneously via the spontaneous activation of the AV node. However, the AV node discharges at a lower rate than the SA node, and thus the heart rate paced by the AV node will be slower than that previously paced by the SA node.
B = Phenylephrine Administration: Phenylephrine acts on the alpha-adrenergic receptors of the vasculature to elicit vasoconstriction. The vasoconstrictor response will elicit an increase in total peripheral resistance. Because mean arterial pressure is a product of cardiac output and total peripheral resistance, an increase in total peripheral resistance results in an increase in arterial pressure. The increase in arterial pressure activates arterial baroreceptors located in both the carotid sinus and the aortic arch, which results in a baroreflex-mediated decrease in heart rate caused by vagal activation and sympathetic withdrawal.
Match the following to the graph:
- Epinephrine administration. Epinephrine is a nonspecific beta-adrenergic receptor agonist.
- Bilateral carotid occlusion. Bilateral carotid occlusion below the carotid sinus reduces arterial pressure in the carotid sinus.
- Nitroglycerine administration. Nitroglycerine is a nitric oxide donor.
- Ouabain administration. Ouabain is a Na+/K+- ATPase inhibitor.
- Atropine administration. Atropine is a nonspecific muscarinic receptor antagonist.
- Right stellate stimulation. Sympathetic fibers from the right stellate ganglion innervate the SA node of the heart. Stimulating the right stellate ganglion will increase sympathetic stimulation to the heart.
C = Epinephrine Administration: In the virtual experiment, epinephrine was administered at a physiological concentration. This is an important point because either a vasodilatory or vasoconstrictor response will prevail depending on the dose or concentration of epinephrine. This is because there are two major types of adrenergic receptors that epinephrine could bind to, alpha- and/or beta-adrenergic receptors. alphaAdrenergic receptors can be further subdivided into alpha1- and alpha2-adrenergic receptors. Activation of vascular alpha-adrenergic receptors elicits vasoconstriction. The beta-adrenergic receptors can also be further subdivided into beta1- and beta2- adrenergic receptors located on the heart and vasculature, respectively. Activation of beta-adrenergic receptors increases heart rate and contractility (beta1) and vasodilation (beta2). Epinephrine has a greater affinity for beta-adrenergic receptors; however, it can also bind to alpha-adrenergic receptors. Thus, epinephrine can induce vasoconstriction or vasodilation. In addition, epinephrine always causes an increase in heart rate and contractility. At physiological concentrations, epinephrine preferentially binds to betaadrenergic receptors because the affinity of epinephrine to beta-adrenergic receptors is greater than that to alpha-adrenergic receptors. Thus, the vasodilator response will prevail. However, at pharmacological concentrations, epinephrine will first bind to beta2adrenergic receptors and then, once the beta-adrenergic receptors are saturated, epinephrine will bind to alpha-adrenergic receptors. Because there are a greater number of alpha-adrenergic receptors than beta2-adrenergic receptors, the vasoconstrictor response will predominate.
D = Bilateral Carotid Occlusion: The carotid sinus is a small dilation of the internal carotid artery located just above the bifurcation of the common carotid artery. Arterial baroreceptors, which are stretch receptors that monitor the pressure in the arterial circulation, are located in the carotid sinus as well as in the aortic arch. The arterial baroreceptors are stimulated by distension of the vessels in which they are located, and they fire at an increased rate when the pressure in these vessels rises. Bilateral carotid occlusion below the carotid sinus will lower the pressure in the carotid sinus and cause the baroreceptors (located in the carotid sinus) to decrease their firing rate. This will cause an arterial baroreflex-mediated vagal withdrawal as well as an increase in sympathetic nerve activity to the heart and vasculature. Consequently, heart rate and total peripheral resistance will increase. The increase in heart rate and total peripheral resistance increases arterial pressure. Note, however, that the pressor response during this perturbation activates the aortic baroreceptors. The increased firing rate of the aortic baroreceptors in response to this perturbation sends signals to the vasomotor centers in the medulla of the brain to cause vagal activation as well as sympathoinhibition to the heart and vasculature. Therefore, the pressor and tachycardic response to bilateral carotid occlusion will be buffered by the opposing responses of the aortic baroreceptors.
E = Nitroglycerine Administration: Nitroglycerine is a nitric oxide donor that acts directly on vascular smooth muscle to elicit vasodilation. The vasodilation will cause a decrease in total peripheral resistance, which lowers arterial pressure. This decrease in arterial pressure will unload the arterial baroreceptors in the carotid sinus and in the aortic arch, resulting in an arterial baroreflex-mediated increase in heart rate caused by vagal withdrawal and sympathetic activation.
F = Ouabain Administration: The increase in arterial blood pressure in response to ouabain can be explained by discussing the effect of ouabain on intracellular calcium. An exchanger mechanism, which removes intracellular Ca+ by exchanging 3 Na+ for 1 Ca++, exists on the sarcolemma. The energy for this exchange is primarily supplied by the Na+ gradient. Under normal conditions, Na1 concentration is high outside the cell relative to that inside of the cell. The Na+-K+-ATPase pump maintains this gradient by pumping 3 Na+ out of the cell in exchange for 2 K+. Any intervention that increases the Na+ gradient will augment the exchanger, thereby increasing the extrusion of Ca++ from the cell. Conversely, any intervention that decreases the Na+ gradient will attenuate the exchanger and increase intracellular Ca++. Ouabain inhibits the Na+-K+-ATPase. As intracellular Na+ increases in the presence of ouabain, the gradient is decreased and the Na+/Ca++ exchanger mechanism slows. This slowing causes intracellular Ca++ to increase, which enhances cardiac inotropy. The increased contractility will increase stroke volume and lead to an increase in cardiac output. Because peripheral resistance is unchanged, an increase in cardiac output will lead to an increase in arterial pressure.
G = Atropine Administration: Cardiac muscarinic receptors are activated by acetylcholine, which is the neurotransmitter of the PNS. Administration of the muscariniccholinergic receptor antagonist atropine will block the effect of the vagus nerve (parasympathetic innervation) on the heart. This is analogous to removing your foot from the brake of your car. Subsequently, heart rate will increase. In resting humans, the increase in heart rate is dramatic because heart rate is predominantly controlled by the PNS. The increase in heart rate will also cause an increase in cardiac output, which in turn will increase arterial pressure.
H = Right Stellate Stimulation: Stimulation of the right stellate ganglion increases sympathetic stimulation to the SA node, which in turn increases heart rate. This is analogous to stepping on the gas of your car. However, compared with the increase in heart rate after the administration of atropine, the increase in heart rate is much less dramatic. The reason for this difference is the presence of the PNS. Recall that heart rate is under simultaneous control of the PNS and SNS. Thus, the heart rate response to activation of one component will be opposed by the antagonistic action of the other component.
Match the following to the graphs:
- Increased arterial compliance. Compliance is defined as the change in volume per unit change in volume. Compliance is an index of how easily thevessel can be stretched. A vessel with an increased compliance has a greater volume for each unit change in pressure.
- Decreased arterial compliance. A vessel with a decreased compliance has a smaller volume for each unit change in pressure.
I = Increased Arterial Compliance: Arterial blood pressure is defined as the pressure exerted by the blood against the arterial walls. The volume of blood in the vessel determines the pressure exerted by the blood. Therefore, an increase in the volume of blood results in an increase in arterial pressure. It is important to note, however, that the volume of blood being ejected by the heart remains the same during this perturbation; only the compliance of the vessel has changed. The net result of an increase or decrease in compliance does not change mean arterial pressure even though changes in pulse pressure occur. Pulse pressure is the difference between systolic and diastolic blood pressure. Increasing the compliance of an artery will decrease pulse pressure. To better understand the concept of compliance, compare an artery to a rubber band. A rubber band has an elastic property that allows it to stretch if a force is applied to it. If the rubber band has a high compliance, it can be easily stretched. If the rubber band is let go, it rebounds quickly and forcefully to its original state. Conversely, if the rubber band has a low compliance, it cannot be easily stretched and the rebound effect is reduced. During systole, a vessel with high compliance expands, and consequently, systolic blood pressure decreases. During diastole, the vessel rebounds and delivers energy into the vascular system, and consequently, diastolic blood pressure increases. The decrease in systolic pressure and increase in diastolic pressure lead to the decreased pulse pressure that is associated with an increase in arterial compliance.
J = Decreased Arterial Compliance: Decreasing the compliance of an artery will increase pulse pressure. To understand these concepts, visualize a garden hose that has a minimal ability to stretch compared with that of a balloon. Opening the faucet introduces a bolus of water into the hose, and the wall of the hose will stretch minimally compared with that of a balloon with the same bolus of water. Therefore, the pressure that the water will impose on the wall of the hose will be much greater than that imposed on the wall of the balloon. If a vessel has a decreased compliance, then the vessel is unable to expand and absorb the energy imparted by the blood during systole. Consequently, systolic blood pressure increases. Likewise, the less compliant vessel has a reduced rebound effect, and diastolic blood pressure is reduced. Together, the increase in systolic pressure and decrease in diastolic pressure result in an increased pulse pressure.
Untreated HTN risks?
50% die from coronary artery disease
33% die from stroke
10-15% die from renal failure
For every 10mm rise in arterial pressure, there is a 30% increase in cardiovascular risk
What are the five H’s of HTN?
Hypertension
Hyperglycemia
Hyperlipidemia
Hypercoaguability
Hyperinflammation
Initial therapies for HTN?
Thiazide diuretics recommended as initial therapy for most patients without a compelling indication for another class of drug
Beta blockers are not recommended for initial therapy
Black patients: Thiazides and calcium channel blockers recommended for initial therapy
Under 80 HTN guidelines? Age above 80?
Age < 80 < 140/90
Age > 80 < 150/90
What do we do for non-black patients under and over the age of 60?
ACEI or ARBS for Non-Blacks under the age of 60
CCB or Thiazides for Non-Blacks over the age of 60
HTN guidelines?
Blood pressure lowered to < 140 mmHg systolic For most patients with a systolic BP > 160 mmHg
THRESHOLD > 160 mmHg systolic Including those with DM-CKD-CHD Stroke or TIA
A key exception are patients over the age of 80 in whom a target of 140-150 mmHg is recommended
important implication of the JNC 8 versus 7?
JNC VIII versus JNC VII
Almost 6 million American adults will no longer be classified as needing hypertensive medication
Almost 14 million American adults who were previously considered as not meeting treatment guidelines will now be considered as having their blood pressure under reasonable control
Explain the sprint study?
Patients treated to achieve a systolic pressure of 120 mmHg Three medications were utilized: Chlorothaladone Amlodipine Lisinopril Controls treated to a target of <140 mmHg Intensive treatment < 120 mmHg Average of two medications Results Intensively treated patients 30% Reduction in CV events 25% Reduction in All Cause Mortality
For each 20mmHg increase in systolic BP or a 10mmHg increase in diastolic there is a?
For each 20mm of Hg increase in systolic BP or a 10mm Hg increase in diastolic blood pressure >115/75 “The Real Normal Blood Pressure” There is a 2 fold increase in morbidity associated with stroke and coronary artery disease
optimal profile to not get cardiovascular disease?
Blood pressure < 120/80
Total cholesterol < 180 mg/dL
Non smoker
Non diabetic
Major cardiovascular risk factors?
Age
Hypertension
Obesity
Dyslipidemia
Diabetes Mellitus
Cigarette smoking
Physical inactivity
Microalbuminuria (30-300 mg/24 hours)
Family history of premature CVD: Men < 55, Women < 65
Chronic renal failure (GFR < 60cc per minute/1.73m2)
What is CHAOS syndrome?
Coronary heart disease – Congestive Heart Failure
Hypertension - Hyperlipidemia
Adult onset diabetes mellitus
Obesity Stroke
Physiological effects of insulin resistance?
Amplifies the adrenergic response
Increases peripheral vascular resistance
Increases renal Na and H2O reabsorption
Adversely effects the vascular endothelium
All obese people are HYPERINSULINEMIC
Diagnostic workup of HTN?
Assess risk factors and comorbidities
Review Medications Prescription – Non Prescription
Ascertain identifiable causes of hypertension
Assess presence of target organ damage Heart Brain Kidney Retina
What are the Physiologic alterations in hypertensive vascular disease?
Physiologic Alterations in Hypertensive Vascular Disease
Increased Extra Cellular Fluid Volume
Wet hypertensives have low renin levels:
35% of the hypertensive cohort have low renin levels
50% of the hypertensive cohort have normal renin levels
15% of the hypertensive cohort have high renin levels
Abnormal Renal Function Abnormal renal perfusion activates the renin angiotensin system
Vasoactive Factors - Diminished Capacity Increased peripheral resistance Amplification of the sympathomimetic response
Increased Cardiac Output – Increased Volume
Once the hypertension becomes fixed and the disease runs its course, diminished cardiac output usually results
Explain some of the target end organ damage in HTN?
Heart – Cardiac dysfunction – LVH – CAD - AF
Carotid Artery – Increased Intima – media thickness
Brain – Impaired cognitive function
Kidneys – Reduced GFR – microalbuminurea
Eyes - Retinal arteriolar narrowing
Endothelium - Dysfunctional
How to take blood pressure?
Seated, arm at heart level
Five minutes of quiet rest
No caffeine or nicotine within 30 minutes
Disappearance of sound (Phase V) should be used for the diastolic measurement
Sphygmomanometer bladder should encircle at least 80% of the arm’s circumference and the width should be 2/3 of the length between the patient’s shoulder and elbow BP normally the highest between 6am and 10am Nocturnal dip should be at least 10% 24 hour ambulatory blood pressure monitoring becoming the standard of care (NICE)
Pseudohypertension?
A cuff pressure that exceeds the true interarterial pressure because of stiff vessels
CLUES:
Treatment resistance Absence of end organ damage LVH PVD Nephropathy Retinopathy
Risk factors of HTN?
Genetic mechanisms
Sensitivity to a high salt diet
Increased vascular responsiveness
Over activity of the renin angiotensin system
Elevated sympathetic tone
Deficient diet Magnesium-Potassium
Visceral fat – Omental and/or mesenteric fat
What is secondary HTN?
Onset before age 30 or after age 50
Sudden onset
Previously well-controlled with medications but now escalating
Systolic > 180mmHg and/or diastolic > 110mmHg
Causes of secondary HTN?
Medications NSAIDS - Oral contraceptives
Renal Vascular Parenchymal
Pheochromocytoma
Primary Hyperaldosteronism
Coarctation of the aorta
Rib notching – absence of lower extremity pulses
Hyperthyroidism
Cushing’s Syndrome Truncal obesity – purple striae
What do we see with coarctation of the aorta? associated findings?
Coarctation of the Aorta Narrowing - Constriction Infolding of the aorta opposite to the closed ductus arteriosus Maybe associated with congenital aortic stenosis, ASD or VSD
Associated Findings: Rib notching Absence or delayed pulses in the lower extremities Midsystolic ejection murmur heard over the anterior part of the chest and the back Bicuspid aortic valve ≈ 50%
Some exam findings with secondary HTN? and what do they mean?
Flank mass – polycystic kidney
Abdominal bruits – renovascular disease
Absent femoral pulses – coarctation of the aorta
Truncal obesity – Cushing’s syndrome
Orthostatic hypotension – sweating – pheochromocytoma
Medications that may raise BP?
Oral contraceptives Age > 35 smoking alcohol Activate the RAS with Na and H2O retention
Steroids
Nonsteroidal anti-inflammatory agents
Less vasodilitory prostaglandins
Nasal decongestants
Tricyclic antidepressant
Erythropoietin, cyclosporine
Cocaine: Stimulates catacholamines
Prevalence of the etiologies of secondary HTN?
Renal vascular hypertension 5-10%
Estrogen induced hypertension 3-5%
Primary aldosteronism 3-5%
Pheochromocytoma < 1%
Drug related < 1%
Cushing’s Syndrome < 0.5%
Hyperthyroidism < 0.5%
Vasculitis <0.5%
What is a Pheochromocytoma? Arise where? Metastasize to where?
An adrenal medullary tumor composed of chromaffin cells derived from the neural crest
Majority arise in the adrenal medulla, mostly on the right
10% extra-adrenal (paragangliomas)
3-4% are malignant
Metastasizes to regional lymph nodes, liver, lung and bones
Clinical features of the Pheochromocytoma?
Clinical triad of Pheochromocytoma
Headache, Perspiration, Palpitations
Other signs and symptoms: Tremulousness Sudden severe headache Pallor, perspiration, palpitations Unusual lability of blood pressure Severe or accelerated hypertension Hypermetabolic state – weight loss Severe retinopathy Orthostatic hypotension
Diagnosis of Pheochromocytoma?
Excessive excretion of catecholamines and metabolites or excessive plasma concentrations or both
24-hour urinary metanephrines, epinephrine, norepinephrine, dopamine
Interference: Caffeine, nicotine, theophylline, calcium channel blockers, beta and alpha blockers, tricyclic antidepressants
How do we localize Pheochromocytoma? How do we treat?
Computed tomography MRI – best modality Scintigraphy
Preoperative treatment with adrenergic blocking drugs (Phenoxybenzamine) Beta blockers Alpha1 blockers Alpha-beta blockers Surgical excision
Aldosteronism is what percent of HTN? common etiologies of it?
0.5% to 2% of hypertensive population
Unilateral aldosterone producing adenoma (70%)
Bilateral adrenal hyperphasia (30%)
Clinical features of Aldosteronism?
Hypertension – moderate to severe
Hypokalemia
Mild Metabolic Alkalosis Exchange of K ions and H ions for Na ions
Hypernatremia
May be resistant to pharmacologic intervention
Screening tests for aldosteronism?
Urinary Potassium With a serum potassium < 3 meq 24 hour urinary potassium > 30 meq
Plasma aldosterone concentration (P.A.C.)
Peripheral renin levels (P.R.A.)
How can we confirm primary aldosteronism?
Hypokalemia with inappropriate kaliuresis
Low plasma renin activity, P.R.A.
Nonsuppressible aldosterone level By the IV administration of Na Cl and measurement of urinary aldosterone
Normal glucocorticoid level
Treatment of Primary aldosteronism?
Aldosterone producing adenoma – surgery
Pharmacologic treatment – Spironolactone, Eplerenone
Second step agents – Calcium channel blockers
A.C.E. inhibitors – Thiazide diuretics
What are renal parenchymal diseases that can increase BP?
Glomerulonephritis
Chronic pyelonephritis
Polycystic kidney
Connective tissue disease
Renal Vascular HTN?
Atherosclerotic narrowing of one or both renal arteries Fibromuscular dysplasia of the renal artery
Non-pharmocoligic treatments for HTN?
Weight reduction
Restriction of alcohol
Sodium restriction [1.5 gm Na] Average American intake 4 grams: 1500 mg Daily or Less
Persons over 50 Persons with hypertension, diabetes or chronic renal disease, Congestive heart failure Chronic renal disease is defined as an estimated GFR < 60ml/min/1.73 m3
African Americans 98.6% of the above exceed the stated limit 2300 mg Daily or Less (1 teaspoonful)
Role of other medications
Tobacco avoidance
Biofeedback and relaxation
Exercise: 30 minutes a day most days of the week (5) Average reduction in BP 4-9 mmHg Improves endothelial function Peripheral vasodilitation Reduces plasma levels of catecholamines Improves heart rate variability
Modification of dietary fats
D.A.S.H. diet: DASH Diet 8-10 servings of fruits and vegetables per day Low-fat dairy products Low total fat Low saturated fat A DASH diet has been shown to reduce the systolic BP in hypertensive patients by 8-14 mmHg
Goals of HTN treatment?
Goals of Therapy
Maintain blood pressure within an acceptable range without compromising cerebral, cardiac, sexual or renal function or adversely effecting the quality of life
Less than 75% of patients prescribed antihypertensive medications are still under treatment after 6 months
Characteristics of the ideal anti-hypertensive?
Reduces vascular smooth muscle tone to reduce peripheral vascular resistance
Maintains cardiac output and heart, kidney and brain perfusion
Does not have a Negative or positive chronotropic or inotropic effect
Does not expand intravascular volume
Does not have metabolic side effects
Thiazides and related sulfonamide diuretics for BP control? Dosing of the thiazides?
Effective in older and African-American patients who tend to have a low renin type of hypertension
Not effective with a serum creatine of more than 2mg/dL or with a creatinine clearance of less than 30cc/min
Concern about metabolic consequences
DRUG OF CHOICE JNC VIII without other compelling indications
Hydrochlorothiazide 12.5-25 mg 50 mg=max Half-life 6 -12 hours
Metolazone 1.25 mg 10 mg
Chlorthalidone 12.5 mg 50 mg Half-life 24-72 hours 1.5 – 2 times as potent as HCTZ
NICE Thiazides of choice: Chlorthalidone or Indapamide
Thiazides side effects?
Increase total and LDL cholesterol
Hypokalemia – hypomagnesia
Elevated uric acid
Glucose intolerance
Activate the renin angiotensin system and the sympathomimetic system by reducing extra cellular fluid volume
Increased blood viscosity
The serum K+ is reduced by approximately 0.5 mEq
On the usual dose of a thiazide diuretic fluid and electrolyte complications usually occur during the first 2 weeks of therapy before a new steady state is established
Loop diuretics dosing? Advantages? Disadvantages?
Bumetanide 0.5 mg 5mg
Furosemide 20-40 mg 320 mg
Advantage - effective in chronic renal failure and severe heart failure
Disadvantage - short duration of action Inhibit Na-K-2 CL Symporter thereby increasing The urinary excretion of Na, K, and CL
Explain the potassium sparing agents? Dosing and actions?
Amiloride 5 mg 10 mg
Triamterene 50 mg 300 mg
Amiloride and Triamterene inhibit the renal epithelial sodium channels at the distal tubule causing naturesis and reduced potassium excretion They are not effective blood pressure reducing agents
Aldosterone Receptor Blockers
Eplerenone 50mg 100m
Spironolactone 25 mg 100mg
Explain sodium reabsorption in the kidneys (location)?
Proximal tubule 60 - 70%
Ascending loop of Henle (thick portion) 20 – 30%
Distal convoluted tubule 10 – 15%
Beta blocker drugs effectiveness?
Effective in the younger white hypertensive
Effective in patients with a high renin level
Secondary preventive agent, in patients who have had a myocardial infarction
Response poorer in blacks and the elderly
Problems with Beta Blockers?
May impair exercise performance
Decrease HDL cholesterol
May decrease cardiac output and increase peripheral resistance
Beta-blockers do not work well with ARBs or ACEI since they already have an anti-renin effect
Beta blockers are not very effective in reducing left ventricular mass in hypertension
Beta blockers are not a first line antihypertensive agent in JNC VIII
Beta blocker indications?
Beta-blockers should be restricted to these specific indications: Patients with a history of an MI Patients in CHF Tachyarrhythmias LV dysfunction
Explain Carvedilol
Beta 1 – Beta 2 – Alpha 1 antagonist
Alpha to Beta ratio 1-10
Antioxidant antiproliferative effect
At high concentrations has a calcium blocker effect
Explain Bisoprolol and Nebivolol?
Bisoprolol Highly selective Beta 1 receptor antagonist
Nebivolol Selective Beta 1 antagonist Increases Nitric Oxide production
Alpha adrenergic blockers effects for HTN? Side effects?
Improve lipid profile,
increase HDL Decrease triglycerides
Diminish total peripheral resistance (Vasodilatation)
Increased risk of development of congestive heart failure in the ALLHAT trial (Fluid retention)
Side Effects Orthostatic hypotension Syncope Drowsiness Dizziness
ACE inhibitor effective populations?
Effective in younger and white patients who often have normal or increased renin levels
May help to retard the progression of diabetic renal disease by reducing intraglomerular pressure
Angiotensin I to Angiotensin II conversion can also be achieved by the Chymase or Cathepsin pathways
Effects of ACE inhibitors?
Reduce preload and after load
Effective in 80-90% of hypertensive patients
No adverse CNS effects
No adverse effect on lipid levels Heart rate and cardiac conduction unaffected
Renal function is usually preserved or improved
Prevents the degradation of bradykinin
Stimulates the synthesis of vasodilator prostaglandins
No adverse effect on exercise tolerance
Reduce Aldosterone effect
Reduce Angiotensin II effect
Compelling indications to use an ACE inhibitor?
Diabetes mellitus
Left ventricular dysfunction
Side effects of ACE inhibitors?
Cough
Hyperkalemia
Hypotension
Dysgeusia
Neutropenia
Angioedema
Rash
Elevated serum creatinine
Renal failure
Actions of Angiotensin 2?
Increases Na and H2O reabsorption at the distal tubule Increases intravascular volume
Vasoconstriction and the release of aldosterone
Stimulates the release of catecholamines from adrenergic neurons and the adrenal medulla
Acts in the central nervous system to stimulate thirst, release antidiuretic hormone, and increase sympathomimetic activity
Angiotensin 2 blockers action? drugs? Side effects?
Losartin - Valsartin – Candesartin Telmisartin - Irbesartin
Selectively blocks the binding of angiotensin II to the AT1 receptors found in heart, lung, kidney and the adrenal cortex
No clinically important metabolic side effects
Explain the Calcium channel blockers? Drugs and the various things they block?
Nondihydropyridine Calcium Channel Blockers
Benzothiazopine Calcium Channel Blocker: Diltiazem CD 180-360 mg
Phenylalkyamine Calcium Channel Blocker: Verapamil Sustained Release 120-480 mg
Dihydropyridine Calcium Channel Blockers No Chronotropic or Ionotropic affect
Amlodipine 2.5-10 mg
Felodipine 5-20 mg
Nicardipine 60-120 mg
Nifedipine (GITS) 30-90 mg
Women and Calcium channel blockers?
Observational study: 1763 women age 55-74 More than 2 fold risk for invasive ductal and invasive lobular breast carcinoma in women taking CCB’s for 10 years or longer
Possibly due to inhibition of apoptosis
Current recommendations for HTN?
Current Recommendations Diagnosis of hypertension should be made with 24 hour ambulatory monitoring
Approximately 30% of diagnoses made on office blood pressure determinations are false positives
Initial Treatment < 55 ACEI than CCB
> 55 CCB than ACEI
Third drug if needed probably a thiazide Chlorthalidone or Indapamide Beta Blockers have been downgraded T
Hypertension in the Very Elderly Trial?
Mean Duration of Follow up 2.1 years Trial terminated for ethical reasons 21% reduction in overall mortality in the treated group Significant Decrease in Deaths from: Heart Failure Stroke Cardiovascular causes Cardiac causes
HOPE trial?
9,297 patients 55 or older
Vascular disease or diabetes plus one other risk factor
No heart failure or EF < 40%
10 mgm Ramipril or placebo for a mean of 10 years
Antihypertensive Lipid lowering agent Antiplatelet agent Plus Ramipril 10 mg daily Reduced Myocardial infarction 20% CV death 26% Stroke 32%
ACCOMPLISH trial?
50% had a previous coronary event 11,500 patients average age 68 Benazepril + Amlodipine 131/78 Benazepril + Hydrochlorthiazide 132/74 Beta blockers continued where indicated
Trial terminated after 36 months Primary endpoints Death from CV causes Non-fatal MI or stroke Coronary revascularization Hospitalization for angina
Relative risk reduction of 19.6% in the Benazepril + Amlodipine group
What is resistant HTN?
Failure to achieve goal blood pressure (< 140/90 mm Hg) (< 150/90 mm Hg) using 3 different drugs with pharmacologically complementary mechanisms, one of which is an appropriately dosed diuretic
All 3 drugs given in maximally tolerated doses
Taking 4 drugs and at treatment goal Patients adhering to an adequate and appropriate drug regimen Encompasses 7-9% of all treated hypertensives
Etiology of Resistant HTN?
Pseudoresistant Hypertension
Suboptimal treatment regimen
Non adherence to treatment program
Alcohol/illicit drugs
Medications prescribed over-the-counter
Obstructive sleep apnea
Insulin resistance
Secondary hypertension
Resistant HTN patient profile?
Patients with resistant hypertension are more likely to be
African-American
Have High body mass index
Have impaired kidney function
Have a history of coronary heart disease, heart failure, stroke or diabetes
44% of U.S. adults over the age of 70 have chronic Kidney disease
What do we do with Resistent HTN?
Aggressive monitoring of therapy
Ensure tolerability of medication
Educated patient
Collaborative therapy
What is a Hypertensive urgency?
Elevated blood pressure without acute progressive target organ damage
24 hours to reduce blood pressure
Hypertensive emergency?
Blood pressure > 180 mmHg systolic and/or > 120 diastolic
Acute progressive vascular damage to end organ structures
Ischemic symptoms due to increased vascular resistance
Must reduce blood pressure within one hour
Severe HTN seen in which clinical settings?
Severe Hypertension in the Following Clinical Settings
Aortic dissection
Acute left ventricular failure (pulmonary edema)
Acute renal failure
Unstable angina or myocardial infarction
Focal neurological damage (thrombotic or hemorrhagic stroke)
Hypertensive encephalopathy
Symptoms of HTN emergency?
Headache, visual disturbances, sensory changes
Localized neurological signs – seizures
Dyspnea – pulmonary edema
Chest pain – acute ischemic episode
Grade III or IV hypertensive retinopathy
Drugs to treat a HTN emergency?
Nicardipine HCl (Cardene) Dose 5-15mgm/hr IV infusion
Sodium Nitroprusside (Nitropress) Dose 0.25-10ug/kg/min by IV infusion
Nitroglycerin (NitroBid)
Dose 5-150ug/min by IV infusion
Enalaprilat (Vasotec IV)
Dose 0.625-1.25mgm bolus injection over 5 min followed by 1.25mgm IV every 6 hours
