Clinical Hypertension + Physiology of HTN

Question 1

What is blood pressure? Determined by? Factors that affect this?

Answer 1

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.

Question 2

Define Systolic Blood pressure? Diastolic blood pressure? Pulse Pressure? Mean arterial blood pressure?

Answer 2

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!

Question 3

Factors influencing blood pressure?

Answer 3

Question 4

Rise in aortic pressure from its diastolic to systolic value is determined by?

Answer 4

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).

Question 5

Explain compliance in the Aorta?

Answer 5

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.

Question 6

Systolic arterial pressure with age?

Answer 6

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.

Question 7

Explain wave reflection?

Answer 7

Question 8

Explain the effect of increased or decreased arterial compliance on Pulse Pressure?

Answer 8

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

Question 9

What is stroke volume determined by?

Answer 9

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.

Question 10

Explain the Autonomic nervous effects on the heart?

Answer 10

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

Question 11

Increasing Venous return to the heart?

Answer 11

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.

Question 12

What is the diastolic arterial pressure? How does HR affect it? Peripheral resistance increase?

Answer 12

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.

Question 13

Peripheral resistance is affected by? Blood flow affected by this how?

Answer 13

 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.

Question 14

Arterial baroreceptor responses to an increase or decrease in arterial pressure?

Answer 14

Question 15

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.

Answer 15

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.

Question 16

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.

Answer 16

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.

Question 17

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.

Answer 17

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.

Question 18

Untreated HTN risks?

Answer 18

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

Question 19

What are the five H’s of HTN?

Answer 19

Hypertension

Hyperglycemia

Hyperlipidemia

Hypercoaguability

Hyperinflammation

Question 20

Initial therapies for HTN?

Answer 20

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

Question 21

Under 80 HTN guidelines? Age above 80?

Answer 21

Age < 80 < 140/90

Age > 80 < 150/90

Question 22

What do we do for non-black patients under and over the age of 60?

Answer 22

ACEI or ARBS for Non-Blacks under the age of 60

CCB or Thiazides for Non-Blacks over the age of 60

Question 23

HTN guidelines?

Answer 23

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

Question 24

important implication of the JNC 8 versus 7?

Answer 24

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

Question 25

Explain the sprint study?

Answer 25

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

Question 26

For each 20mmHg increase in systolic BP or a 10mmHg increase in diastolic there is a?

Answer 26

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

Question 27

optimal profile to not get cardiovascular disease?

Answer 27

Blood pressure \< 120/80 Total cholesterol \< 180 mg/dL Non smoker Non diabetic

Question 28

Major cardiovascular risk factors?

Answer 28

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)

Question 29

What is CHAOS syndrome?

Answer 29

Coronary heart disease – Congestive Heart Failure Hypertension - Hyperlipidemia Adult onset diabetes mellitus Obesity Stroke

Question 30

Physiological effects of insulin resistance?

Answer 30

Amplifies the adrenergic response Increases peripheral vascular resistance Increases renal Na and H2O reabsorption Adversely effects the vascular endothelium All obese people are HYPERINSULINEMIC

Question 31

Diagnostic workup of HTN?

Answer 31

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

Question 32

What are the Physiologic alterations in hypertensive vascular disease?

Answer 32

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

Question 33

Explain some of the target end organ damage in HTN?

Answer 33

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

Question 34

How to take blood pressure?

Answer 34

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)

Question 35

Pseudohypertension?

Answer 35

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

Question 36

Risk factors of HTN?

Answer 36

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

Question 37

What is secondary HTN?

Answer 37

Onset before age 30 or after age 50 Sudden onset Previously well-controlled with medications but now escalating Systolic \> 180mmHg and/or diastolic \> 110mmHg

Question 38

Causes of secondary HTN?

Answer 38

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

Question 39

What do we see with coarctation of the aorta? associated findings?

Answer 39

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%

Question 40

Some exam findings with secondary HTN? and what do they mean?

Answer 40

Flank mass – polycystic kidney Abdominal bruits – renovascular disease Absent femoral pulses – coarctation of the aorta Truncal obesity – Cushing’s syndrome Orthostatic hypotension – sweating – pheochromocytoma

Question 41

Medications that may raise BP?

Answer 41

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

Question 42

Prevalence of the etiologies of secondary HTN?

Answer 42

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%

Question 43

What is a Pheochromocytoma? Arise where? Metastasize to where?

Answer 43

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

Question 44

Clinical features of the Pheochromocytoma?

Answer 44

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

Question 45

Diagnosis of Pheochromocytoma?

Answer 45

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

Question 46

How do we localize Pheochromocytoma? How do we treat?

Answer 46

Computed tomography MRI – best modality Scintigraphy Preoperative treatment with adrenergic blocking drugs (Phenoxybenzamine) Beta blockers Alpha1 blockers Alpha-beta blockers Surgical excision

Question 47

Aldosteronism is what percent of HTN? common etiologies of it?

Answer 47

0.5% to 2% of hypertensive population Unilateral aldosterone producing adenoma (70%) Bilateral adrenal hyperphasia (30%)

Question 48

Clinical features of Aldosteronism?

Answer 48

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

Question 49

Screening tests for aldosteronism?

Answer 49

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.)

Question 50

How can we confirm primary aldosteronism?

Answer 50

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

Question 51

Treatment of Primary aldosteronism?

Answer 51

Aldosterone producing adenoma – surgery Pharmacologic treatment – Spironolactone, Eplerenone Second step agents – Calcium channel blockers A.C.E. inhibitors – Thiazide diuretics

Question 52

What are renal parenchymal diseases that can increase BP?

Answer 52

Glomerulonephritis Chronic pyelonephritis Polycystic kidney Connective tissue disease

Question 53

Renal Vascular HTN?

Answer 53

Atherosclerotic narrowing of one or both renal arteries Fibromuscular dysplasia of the renal artery

Question 54

Non-pharmocoligic treatments for HTN?

Answer 54

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

Question 55

Goals of HTN treatment?

Answer 55

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

Question 56

Characteristics of the ideal anti-hypertensive?

Answer 56

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

Question 57

Thiazides and related sulfonamide diuretics for BP control? Dosing of the thiazides?

Answer 57

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

Question 58

Thiazides side effects?

Answer 58

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

Question 59

Loop diuretics dosing? Advantages? Disadvantages?

Answer 59

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

Question 60

Explain the potassium sparing agents? Dosing and actions?

Answer 60

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

Question 61

Explain sodium reabsorption in the kidneys (location)?

Answer 61

Proximal tubule 60 - 70% Ascending loop of Henle (thick portion) 20 – 30% Distal convoluted tubule 10 – 15%

Question 62

Beta blocker drugs effectiveness?

Answer 62

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

Question 63

Problems with Beta Blockers?

Answer 63

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

Question 64

Beta blocker indications?

Answer 64

Beta-blockers should be restricted to these specific indications: Patients with a history of an MI Patients in CHF Tachyarrhythmias LV dysfunction

Question 65

Explain Carvedilol

Answer 65

Beta 1 – Beta 2 – Alpha 1 antagonist Alpha to Beta ratio 1-10 Antioxidant antiproliferative effect At high concentrations has a calcium blocker effect

Question 66

Explain Bisoprolol and Nebivolol?

Answer 66

Bisoprolol Highly selective Beta 1 receptor antagonist Nebivolol Selective Beta 1 antagonist Increases Nitric Oxide production

Question 67

Alpha adrenergic blockers effects for HTN? Side effects?

Answer 67

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

Question 68

ACE inhibitor effective populations?

Answer 68

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

Question 69

Effects of ACE inhibitors?

Answer 69

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

Question 70

Compelling indications to use an ACE inhibitor?

Answer 70

Diabetes mellitus Left ventricular dysfunction

Question 71

Side effects of ACE inhibitors?

Answer 71

Cough Hyperkalemia Hypotension Dysgeusia Neutropenia Angioedema Rash Elevated serum creatinine Renal failure

Question 72

Actions of Angiotensin 2?

Answer 72

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

Question 73

Angiotensin 2 blockers action? drugs? Side effects?

Answer 73

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

Question 74

Explain the Calcium channel blockers? Drugs and the various things they block?

Answer 74

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

Question 75

Women and Calcium channel blockers?

Answer 75

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

Question 76

Current recommendations for HTN?

Answer 76

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

Question 77

Hypertension in the Very Elderly Trial?

Answer 77

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

Question 78

HOPE trial?

Answer 78

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%

Question 79

ACCOMPLISH trial?

Answer 79

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

Question 80

What is resistant HTN?

Answer 80

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

Question 81

Etiology of Resistant HTN?

Answer 81

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

Question 82

Resistant HTN patient profile?

Answer 82

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

Question 83

What do we do with Resistent HTN?

Answer 83

Aggressive monitoring of therapy Ensure tolerability of medication Educated patient Collaborative therapy

Question 84

What is a Hypertensive urgency?

Answer 84

Elevated blood pressure without acute progressive target organ damage 24 hours to reduce blood pressure

Question 85

Hypertensive emergency?

Answer 85

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

Question 86

Severe HTN seen in which clinical settings?

Answer 86

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

Question 87

Symptoms of HTN emergency?

Answer 87

Headache, visual disturbances, sensory changes Localized neurological signs – seizures Dyspnea – pulmonary edema Chest pain – acute ischemic episode Grade III or IV hypertensive retinopathy

Question 88

Drugs to treat a HTN emergency?

Answer 88

``` 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