Term
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Definition
Blood pressure: Over time, if the force of the blood flow
is high, the tissue that makes up the walls of arteries
gets stretched beyond its healthy limit.
Blood pressure measures the force pushing outwards on arterial walls. |
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Term
| Problems from too much force |
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Definition
Vascular weaknesses
Rupture
Strokes and aneurysms
Vascular scarring
scar arteries and veins.
catch debris such as cholesterol, plaque or blood cells traveling in the bloodstream.
Increased risk of blood clots
Trapped blood can form clots
Increased plaque build-up
If pieces of plaque break off and travel to other parts of the body, or if the build-up completely blocks the vessel, then heart attacks and strokes occur.
Tissue and organ damage from narrowed and blocked arteries
Ultimately, the arteries and veins on the other side of the blockage do not receive enough freshly oxygenated blood, which results in tissue damage.
Example: Increased workload on the circulatory system
When pipes get clogged and therefore narrow, the pressure is much greater. |
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Term
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Definition
To reduce the measured blood pressure levels
less than 140 mm Hg systolic
less than 90 mm Hg diastolic (140/90)
In diabetics or with kidney diseases: 130/80 mm Hg
Primary or essential hypertension
(90-95%): reason unknown: genetic, environment, obesity, diet
Secondary hypertension
Definite cause: hyperaldosteronism, oral contraception,
renovascular disease, renal disease |
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Term
| Determinants of Systemic Blood Pressure |
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Definition
| Blood pressure (BP) is the product of cardiac output (CO) and systemic vascular resistance (SVR), and CO is the product of heart rate (HR) and stroke volume (SV). These determinants are altered by a number of homeostatic mechanisms. Heart rate is increased by the sympathetic nervous system (SNS) and catecholamines and decreased by the parasympathetic nervous system (PSNS). Stroke volume is increased by contractility and preload and decreased by afterload (not shown); all of these determinants are important parameters for cardiac function. Preload is altered by changes in venous tone and intravascular volume. The SNS and hormones, including aldosterone, antidiuretic hormone (ADH), and natriuretic peptides, are the major factors affecting intravascular volume. Systemic vascular resistance is a function of direct innervation, circulating regulators, and local regulators. Direct innervation comprises α1-adrenergic receptors (α1-AR), which increase SVR. Circulating regulators include catecholamines and angiotensin II (AT II), both of which increase SVR. A number of local regulators alter SVR. These include endothelial-derived signaling molecules such as nitric oxide (NO), prostacyclin, endothelin, and AT II; and local metabolic regulators such as O2, H+, and adenosine. SVR is the major component of afterload, which is inversely related to stroke volume. The combination of a direct effect of SVR on blood pressure and an inverse effect of afterload on stroke volume illustrates the complexity of the system. ↑ indicates a stimulatory effect; ↓ indicates an inhibitory effect on the boxed variable. |
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Term
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Definition
| Excessive Na+ and water retention->Volume based hypertension |
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Term
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Definition
Dysfunction in endocrine system: regulation of basal sympathetic tone
Atypical stress response, baroreceptors,
Examples: Excessive secretion/production
Catecholamine (pheochromocytoma)
Aldosterone by adrenal cortex (primary aldosteronism)
Thyroid hormones (Hyperthyroidism) |
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Term
| Physiologic control of blood pressure and sites of drug action |
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Definition
| Figure 10-1 Physiologic control of blood pressure and sites of drug action. Blood pressure is the product of cardiac output and PVR. These parameters are regulated on a systemic level by the sympathetic nervous system and the kidneys. Antihypertensive drugs act to suppress excessive sympathetic activity and modify renal function to counteract the mechanisms responsible for hypertension. Sites of action of the following drugs are shown: (1) vasodilators, (2) beta-adrenoceptor antagonists (beta;-blockers), (3) alpha-adrenoceptor antagonists (beta;-blockers), (4) angiotensin receptor antagonists, (5) centrally acting sympatholytics, (6) ACE inhibitors, and (7) diuretics. The vasodilators, sympatholytic drugs, and angiotensin inhibitors reduce PVR; beta;-adrenoceptor blockers reduce cardiac output; and diuretics promote sodium excretion and reduce blood volume. ACE = angiotensin-converting enzyme; PVR = peripheral vascular resistance. |
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Term
| Blood pressure is directly related to peripheral vascular resistance. |
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Definition
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Term
| Actions of antihypertensive drugs on the renin-angiotensin-aldosterone axis. |
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Definition
| Figure 10-3 Actions of antihypertensive drugs on the renin-angiotensin-aldosterone axis. β-Adrenoceptor antagonists inhibit sympathetic stimulation of renin secretion. ACE inhibitors block the formation of angiotensin II and inhibit the breakdown of bradykinin, a vasodilator. Angiotensin receptor antagonists (e.g., losartan) block AT1 receptors in smooth muscle and adrenal cortex. ACE = angiotensin-converting enzyme. |
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Term
| Effects of ACE inhibitors in patients with bilateral renal artery stenosis. |
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Definition
| Figure 10-4 Effects of ACE inhibitors in patients with bilateral renal artery stenosis. Renal blood flow is reduced in the presence of bilateral renal artery stenosis. In affected patients, glomerular filtration is maintained by elevating efferent arteriolar pressure via vasoconstriction produced by angiotensin II. By blocking the formation of angiotensin II, ACE inhibitors can severely impair glomerular filtration and lead to renal failure. ACE = angiotensin-converting enzyme; GFR = glomerular filtration rate. |
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Term
| Pharmacologic Effects of Commonly Used Antihypertensive Agents |
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Definition
| Antihypertensive agents modulate blood pressure by interfering with the determinants of blood pressure. Many of these antihypertensive drugs have multiple actions. For example, renin–angiotensin system blockers, such as ACE inhibitors and AT1 antagonists, alter the levels of local regulators and circulating regulators, and affect renal Na+ retention and venous tone. BP, blood pressure; CO, cardiac output; SVR, systemic vascular resistance; HR, heart rate; SV, stroke volume; CCB, Ca2+ channel blockers; ACE, angiotensin converting enzyme. |
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Term
| Compensatory Homeostatic Responses to Antihypertensive Treatment |
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Definition
| When blood pressure is lowered by pharmacologic interventions, homeostatic responses are activated to increase blood pressure. These homeostatic responses can be divided broadly into baroreceptor reflexes and renal perfusion reflexes. Baroreceptor reflexes originating in the aortic arch and carotid sinus increase sympathetic outflow, leading to tachycardia, increased contractility, and vasoconstriction; these effects all increase blood pressure. Sympatholytics, such as β-antagonists, blunt the tachycardia and contractility responses by interrupting the sympathetic nervous system. α1-Antagonists inhibit vasoconstriction but have minimal effects on tachycardia or contractility. Decreased renal perfusion causes increased release of renin from juxtaglomerular cells of the kidney. Renin then cleaves angiotensinogen to angiotensin I, which, in turn, is activated to the potent vasoconstrictor angiotensin II (not shown). Angiotensin II increases adrenal secretion of aldosterone, which acts on principal cells of the collecting duct to increase Na+ (and, therefore, water) reabsorption. The increased Na+ reabsorption increases intravascular volume, and thereby results in increased blood pressure. Diuretics interrupt this homeostatic response by decreasing Na+ reabsorption from the nephron; renin inhibitors prevent the generation of angiotensin I; angiotensin converting enzyme (ACE) inhibitors interrupt the formation of angiotensin II; and AT1 antagonists prevent the target-organ signaling of angiotensin II. |
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Term
| What is your opinion? AT1 receptor antagonist affects both SVR and Cardiac output |
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Definition
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Term
| What is ischemia: Heart (Myocardial Ischemia or MI) |
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Definition
Coronary: Left anterior descending (LAD)
Occlusion
Heart gets oxygenated blood
during diastole
Ischemia: block in supply of blood |
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Term
| Classification of Ischemic Heart Disease |
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Definition
| Ischemic heart disease is divided into two broad categories: chronic coronary artery disease and acute coronary syndromes. Stable angina is the prototypical manifestation of chronic coronary artery disease. Acute coronary syndromes constitute a series (not necessarily a linear progression) of clinical presentations, including unstable angina, non-ST elevation myocardial infarction, and ST elevation myocardial infarction. |
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Term
| Ischemic heart disease is categorized in to two major types: Chronic artery disease and acute coronary syndromes. |
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Definition
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Term
| Chronic Coronary Artery Disease |
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Definition
Characterized by impaired coronary vasodilator reserve
Under stress the heart requires increased blood (coronary blood flow)
Resulting in imbalance between myocardial supply and demand
->Cardiac abnormalities: poor contraction of the ischemic regions of heart
Imbalances in myocardial oxygen supply and demand occur mainly because of
Coronary flow reduction and endothelial dysfunction |
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Term
| Coronary Flow reduction (CFR) |
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Definition
Coronary vasculature->Large vessels Proximal epicardial and Small vessels Distal endocardial
Epicardial vessels are sites for atheroma formation
Angina pectoris is the main clinical manifestation of chronic CAD
Ability to modulate blood flow is referred as the coronary flow reserve
CFR = maximal CBF/ resting CBF |
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Term
| Pathophysiology of Anginal Syndromes |
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Definition
| A. Normal coronary arteries are widely patent, the endothelium functions normally, and platelet aggregation is inhibited. B. In stable angina, atherosclerotic plaque and inappropriate vasoconstriction (caused by endothelial damage) reduce the vessel-lumen diameter, and hence decrease coronary blood flow. C. In unstable angina, rupture of the plaque triggers platelet aggregation, thrombus formation, and vasoconstriction. Depending on the anatomic site of plaque rupture, this process can progress to non-Q wave (non-ST elevation) or Q wave (ST elevation) myocardial infarction. D. In variant angina, atherosclerotic plaques are absent, and ischemia is caused by intense vasospasm. |
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Term
| Effect of Coronary Artery Occlusion on Resting and Maximal Coronary Blood Flow |
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Definition
| The dotted line depicts resting coronary blood flow, and the solid line represents maximal blood flow when there is full dilation of distal coronary arteries. Comparison of these two lines shows that maximal coronary blood flow is compromised when the lesion occludes more than about 50% of the arterial lumen, whereas resting coronary blood flow is relatively unaffected until the lesion exceeds about 80% of the arterial diameter. The y-axis represents coronary artery blood flow relative to the flow in a resting coronary artery with 0% occlusion. |
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Term
| Pathogenesis of Acute Coronary Syndromes |
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Definition
| A. A normal coronary artery has an intact endothelium surrounded by smooth muscle cells. B. Endothelial cell activation or injury recruits monocytes and T lymphocytes to the site of injury, leading to development of a fatty streak. C. Continued oxidative stress within a fatty streak leads to development of an atherosclerotic plaque. D. Macrophage apoptosis and continued cholesterol deposition cause further plaque organization, and may induce the expression of additional inflammatory proteins and matrix metalloproteinases. At this stage, the cap of the fibroatheroma remains intact. E. Continued inflammation within an atherosclerotic plaque leads to thinning of the fibrous cap and, eventually, to plaque erosion or rupture. Exposure of plaque constituents to the bloodstream activates platelets and the coagulation cascade, with resulting coronary artery occlusion. |
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Term
| Pharmacologic Management of Acute Coronary Syndromes |
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Definition
| All patients with chronic coronary artery disease are given aspirin unless a life-threatening contraindication is present. β-Antagonists, nitrates, calcium channel blockers, ACE inhibitors, and ranolazine are primarily used to reduce myocardial oxygen demand. All patients with symptoms that raise concerns about a possible acute coronary syndrome are given aspirin and, if tolerated, a β-antagonist. Sublingual or intravenous nitrates can also be given to relieve chest discomfort and minimize ischemia. Electrocardiographic (ECG) findings of ST elevation should prompt emergency measures to open the occluded artery, either with a thrombolytic agent (thrombolysis) or mechanical revascularization (angioplasty). Additional adjunctive pharmacologic therapies for ST elevation myocardial infarction may include aspirin, β-antagonists, nitrates, heparin, ADP receptor antagonists, and GPIIb–IIIa antagonists or bivalirudin. For patients with acute coronary syndrome but no ST elevation on the electrocardiogram, laboratory assays of myocyte damage (e.g., troponin I or troponin T) determine whether the patient is classified as experiencing unstable angina or non-ST elevation myocardial infarction. In either case, management generally includes administration of aspirin, β-antagonists, nitrates, ADP receptor antagonists, and bivalirudin or heparin with GPIIb–IIIa antagonists. For all patients with acute coronary syndrome, postmyocardial infarction management should include modification of risk factors; possible addition of lipid-lowering agents (statins), ACE inhibitors, and aldosterone receptor antagonists; and continuation of aspirin and ADP receptor antagonists. |
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Term
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Definition
A chronic illness with incurrent episodes of acute decomposition
Multifactorial in etiology
The primary cause of heart failure is left ventricular contractile
dysfunction
Multiple disease state can result in contractile dysfunction
Majority of Left HF attributed to CAD |
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Term
How does furosemide improve the symptoms
What does candesartan do to his regimen
What options would be available if Mr. N goes in to decomposition acutely? |
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Definition
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Term
| Common clinical Problem/ Pathophysiology: |
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Definition
5 million patients in US presently with 500,000 new diagnosis each year
5 year mortality rate 50% |
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Term
| Heart failure is a major cardiovascular disease of multifactorial origin. The main cause of HF is left ventricular contractile dysfunction. |
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Definition
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Term
| Normal Left Ventricular Pressure-Volume Loop |
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Definition
| Mitral valve (MV) opening allows the left ventricular (LV) volume to increase as the chamber fills with blood during diastole. When ventricular pressure exceeds left atrial pressure, the mitral valve closes. During the isovolumetric phase of systolic contraction, the left ventricle generates a high pressure, which eventually forces open the aortic valve (AV). Ejection of the stroke volume ensues, and the aortic valve closes when aortic pressure exceeds LV pressure. Isovolumetric relaxation returns the ventricle to its lowest pressure state, and the cycle is repeated. Stroke volume (i.e., the volume of blood ejected with each contraction cycle) is the difference between end-diastolic volume (EDV) and end-systolic volume (ESV). EDP, end-diastolic pressure; ESP, end-systolic pressure. |
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Term
| Determinants of Cardiac Output |
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Definition
| Changes in preload, afterload, and myocardial contractility alter the pressure-volume relationship of the cardiac cycle. A. Increases in preload (lines 1, 2, 3) result in greater stretch of ventricular myocytes, development of greater ventricular end-diastolic pressure, and ejection of greater stroke volume (the Frank–Starling mechanism). Note that the end-systolic volume (ESV) is the same in each case, because the contractility of the heart has not changed. B. Increases in afterload (points 1, 2, 3) create greater impedance to left ventricular output and result in proportionately decreased stroke volume (the difference between end-diastolic volume [EDV] and ESV). The end-systolic pressure is linearly related to ESV; this linear relationship is called the end-systolic pressure-volume relationship (ESPVR). C. Increases in myocardial contractility (lines 1, 2), as occurs after administration of a positive inotrope, shift the ESPVR up and to the left, resulting in increased stroke volume. |
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Term
| The Frank–Starling Relationship in Heart Failure (HF) |
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Definition
| Left panel: The normal Frank–Starling relationship shows a steep increase in cardiac output with increasing ventricular end-diastolic pressure (preload). Point A describes the end-diastolic pressure and cardiac output of a normal heart under resting conditions. With contractile dysfunction (untreated HF), cardiac output falls (B) and the Frank–Starling curve flattens, so that increasing preload translates to only a modest increase in cardiac output (C). This increase in cardiac output is accompanied by symptoms of high end-diastolic pressure, such as dyspnea. Treatment with a positive inotrope, such as digitalis, shifts the Frank–Starling curve upward, and cardiac output increases (D). The improvement in myocardial contractility supports a sufficient reduction in preload that the venous congestion is relieved (E). Right panel: Two of the principal pharmacologic treatments of HF are afterload reduction (e.g., ACE inhibitors) and preload reduction (e.g., diuretics). Afterload reduction (F) increases cardiac output at any given preload, and thereby elevates the Frank–Starling relationship. Preload reduction (G) alleviates congestive symptoms by decreasing ventricular end-diastolic pressure along the same Frank–Starling curve. |
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Term
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Definition
| Increase in cardiac output with increasing end-diastolic pressure (preload) |
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Term
| HF (contractile dysfunction) |
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Definition
Curve is flat, cardiac output falls
Strategy: to decrease preload (diuretics), decrease afterload (ACE inhibitors)
Positive inotropes
The goal is to elevate the curve upwards |
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Term
| Positive inotropes can be used to increase cardiac output in HF patients |
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Definition
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Term
| Neurohumoral Effects of Heart Failure |
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Definition
| Compromised cardiac function leads to decreased arterial blood pressure, which activates baroreceptors that increase sympathetic outflow. α-Adrenergic sympathetic outflow (α) causes vasoconstriction, an effect that increases afterload. The increased afterload creates a greater pressure against which the heart must contract, and thereby increases myocardial O2 demand. β-Adrenergic sympathetic outflow (β) increases juxtaglomerular cell release of renin. Renin cleaves angiotensinogen to angiotensin I, and angiotensin I is then converted to the active hormone angiotensin II (AT II). AT II has a direct vasoconstrictor action; it also increases aldosterone synthesis and secretion. Aldosterone increases collecting duct Na+ reabsorption, leading to intravascular volume expansion and increased preload. Together, the increased afterload and preload increase myocardial O2 demand. In the already compromised heart, these increased stresses can lead to worsening heart failure. |
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Term
| Pharmacologic Modulation of the Neurohumoral Effects of Heart Failure |
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Definition
| Many therapeutic agents used in the management of heart failure modulate the neurohumoral systems that are activated by compromised cardiac function. The renin-angiotensin–aldosterone system can be inhibited by (1) β-adrenergic antagonists, which inhibit renin release by the juxtaglomerular cells of the kidney; (2) ACE inhibitors, which prevent the conversion of angiotensin I to the active hormone angiotensin II; and (3) spironolactone, which competitively antagonizes aldosterone binding to the mineralocorticoid receptor. Diuretics promote Na+ excretion, and thereby counteract the Na+ retention stimulated by activation of the renin-angiotensin–aldosterone system. Venodilators counteract the effect of intravascular volume expansion by increasing peripheral venous capacitance and thereby decreasing preload. Direct arterial vasodilators alleviate the α-adrenergic receptor-mediated and angiotensin II receptor-mediated vasoconstriction induced by increased sympathetic outflow. Cardiac glycosides, β-adrenergic agonists, and cardiac phosphodiesterase inhibitors are also used in HF to increase myocardial contractility (not shown). |
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Term
| Mechanisms by which digoxin exerts its positive inotropic effect on the heart. |
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Definition
Figure 12-2 Mechanisms by which digoxin exerts its positive inotropic effect on the heart. Digoxin inhibits the sodium pump (ATPase) in the sarcolemma and increases the concentration of intracellular sodium. The high sodium concentration increases the activity of the sodium-calcium exchanger (Ex), thereby causing more calcium to enter the cardiac myocyte. Calcium activates muscle fiber shortening and increases cardiac contractility, which, in turn, increases stroke volume at any given fiber length (preload).
Digoxin inhibits the sodium pump (ATPase)In Sarcoplasmic Reticulum->[Na+]i->Increased activity Na-Ca exchanger->[Ca2+]i->Increased cardiac contractility->Increases stroke volume (preload) |
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Term
| Effect of drug treatment on ventricular performance. |
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Definition
| Figure 12-3 Effect of drug treatment on ventricular performance. Effects of the following drugs or drug combinations are shown: (1) a diuretic or a nitrate; (2) nitroprusside or an ACE inhibitor; (3) a positively inotropic drug plus a vasodilator; (4) dobutamine; and (5) digoxin. The positively inotropic drugs increase stroke volume at any given fiber length and thereby decrease venous pressure and preload. Some vasodilators (e.g., ACE inhibitors) decrease afterload and thereby increase stroke volume. Vasodilators can also decrease preload. |
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Term
| Drug treatment and ventricular performance |
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Definition
The positively inotropic drugs increase stroke volume at any given fiber length and thereby decrease venous pressure and preload
Some vasodilators (e.g., ACE inhibitors) decrease afterload and thereby increase stroke volume
Vasodilators can also decrease preload |
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Term
| Digoxin increases intracellular calcium by inhibiting sodium pump |
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Definition
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Term
| Comparison of normal (A) and atherosclerotic (B) arterial walls. |
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Definition
| Figure 15-1 Comparison of normal (A) and atherosclerotic (B) arterial walls. Steps in the pathogenesis of atherosclerosis are as follows: (1) Damage to the endothelium is followed by invasion of macrophages. (2) Endothelial and macrophage growth factors stimulate smooth muscle cells to migrate into the tunica intima and to proliferate. (3) Oxidized cholesterol accumulates in and around macrophages (foam cells) and muscle cells. (4) Collagen and elastic fibers form a connective tissue matrix that results in a fibrous plaque. |
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Term
| Sites and mechanisms of drugs for hyperlipidemia. |
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Definition
| Figure 15-2 Sites and mechanisms of drugs for hyperlipidemia. Ezetimibe inhibits the absorption of dietary and biliary cholesterol from the intestines. The HMG-CoA reductase inhibitors block the rate-limiting step in cholesterol biosynthesis. The bile acid-binding resins inhibit the reabsorption of bile acids from the gut. Niacin inhibits the secretion of VLDLs from the liver, while fibrates such as gemfibrozil stimulate lipoprotein lipase to increase the hydrolysis of VLDL triglycerides and the delivery of fatty acids to adipose and other tissues. IDL = intermediate-density lipoprotein. |
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Term
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Definition
| inhibits the absorption of dietary and biliary cholesterol from the intestines |
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Term
| HMG-CoA reductase inhibitors |
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Definition
| block the rate-limiting step in cholesterol biosynthesis. |
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Term
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Definition
| inhibit the reabsorption of bile acids from the gut. |
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Term
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Definition
| inhibits the secretion of VLDLs from the liver |
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Term
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Definition
| Fibrates such as gemfibrozil stimulate lipoprotein lipase to increase the hydrolysis of VLDL triglycerides and the delivery of fatty acids to adipose and other tissues. |
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Term
Home work assignments:
What are the mechanisms of action of β-blockers?
What is the mechanism of action of glycosides at cellular level?
What agents or interventions are used in secondary prevention of MI?
What is the initial therapy for acute myocardial infraction?
Describe the current options for medical therapy of congestive heart failure?
What are the current strategies in hypertensive treatment? |
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Definition
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