Hypertension Lecture 8 PDF

Calli Cook, DNP, APRN, FNP-C, FAANP Clinical Associate Professor NHWSON Objectives: Part 1 Describe the general organization and function of the systemic circulation Briefly describe the characteristics of each segment of the vascular system from arteries to veins The primary roles of blood:...

Calli Cook, DNP, APRN, FNP-C, FAANP Clinical Associate Professor NHWSON Objectives: Part 1 Describe the general organization and function of the systemic circulation Briefly describe the characteristics of each segment of the vascular system from arteries to veins The primary roles of blood: Homeostatic Function of the Circulator System • Carry oxygen from the lungs to the tissues and carbon dioxide from the tissues for elimination from the lungs • Nutrients from the digestive tract to the tissues • Metabolic waste products from the tissues to their point of elimination • Hormones from their point of production to the site of action • Immune system components Blood Flow Pulmonary Circulation • The pulmonary circulation originates from the right ventricle with the pulmonary artery. • The primary goal of the pulmonary circulation is to oxygenate blood and remove carbon dioxide • Oxygenated blood is returned to the left atrium by means of the pulmonary veins. • Despite the same amount of total blood flow, pressure and vascular resistance are about five- to ten-fold lower in the pulmonary circulation compared with that in the systemic circuit. Systemic Circulation • Systemic circulation starts with the aorta, which receives output from the left ventricle, and branches into numerous parallel vascular circuits, each receiving a fraction of the cardiac output. • Each circuit dynamically adapts to the tissues’ metabolic needs • During exercise and rest cardiac output varies. • Redistribution of blood flow is an adaptive mechanism that ensures that blood is being directed to areas with greater metabolic need during times of increased activity. • Vital organs such as the brain are always active and receive similar blood flow under both conditions. Question 1 Which of the following best describes blood flow during exercise? • Redistribution of blood flow is an adaptive mechanism that ensures that blood is being directed to areas with greater metabolic need during times of increased activity • Redistribution of blood flow ensures that blood is directed to areas with decreased metabolic need during times of increased activity • Blood flow does not change with activity • Blood flow only changes in relationship to wall tension Structure and Properties of Blood Vessels General Structure • Most vessels have three layers (from inner to outer): 1. Tunica intima: • single layer of endothelial cells forming the vessel lining, basement membrane • and a layer of elastic fibers (internal elastic lamina) 2. Tunica media: • Concentric layers of smooth muscle cells 3. Tunica externa: • Strong connective tissue • Capillaries: • Have uniquely thin walls composed of only endothelial cells and basement membrane (no elastic fibers or VSM). Comparative Structure of Blood Vessels • The size and ratio of wall components in blood vessels vary greatly • Blood flow in the systemic circulation is driven by the pumping action of the left ventricle • The pressure is highest in the aorta and falls throughout the circuit because of vascular resistance • Arteries have much thicker walls compared with veins and thus can withstand higher pressures • Arteries branch into arterioles • Representing the primary site (70% to 80%) of systemic vascular resistance • Consider diameter Endothelial Cells • The endothelial cells form a barrier that contains blood within the lumen of the vessel and controls the passage of solutes and cells from the circulation into the subendothelial space. • Endothelial cells secrete substances that modulate contraction of SMCs in the underlying medial layer. • These substances include vasodilators (e.g., NO and prostacyclin) and vasoconstrictors (e.g., endothelin) • Endothelial cells can also modulate the immune response. • In the absence of pathologic stimulation, healthy arterial endothelial cells resist leukocyte adhesion and thereby oppose local inflammation. • However, endothelial cells respond to local injury or infection by expressing cell surface adhesion molecules, which attach monocytes to the endothelium and chemokines • The normal endothelium provides a protective, nonthrombogenic surface with homeostatic vasodilatory and anti-inflammatory properties Vascular Smooth Muscle Cells • SMCs within the medial layer of normal muscular arteries have both contractile and synthetic capabilities. • SMCs produce vasoactive and inflammatory mediators, including interleukin (IL)-1 and IL6, and tumor necrosis factor (TNF). • In normal arteries, most SMCs reside in the medial layer • During atherogenesis, medial SMCs can migrate into the intima, proliferate, and augment synthesis of extracellular matrix macromolecules while they dampen contractile protein content. (makes SMC pathologic) Properties and Disorders of Large Arteries Objectives: Part 2 • Describe the relationship between vascular pressure and the development of tension in the blood vessel wall. • Apply the law of Laplace to the development of vascular wall hypertrophy or an aneurysm in a patient with poorly controlled hypertension. • Identify the role of large artery elastic recoil in maintaining diastolic pressure • Describe the steps, processes, cells, and mediators involved in atherosclerotic plaque development and progression • Distinguish between the long-term processes of plaque formation and the rapid process of vessel occlusion upon erosion or rupture of the atherosclerotic plaque. Biophysics of Wall Tension • Blood pumped into the aorta by the left ventricle generates a push on the vessel wall (hydrostatic pressure) • This pressure is highest in the aorta and large arteries • Large arteries must withstand high pressure at a relatively large radius • To reduce wall tension and avoid rupture, large arteries have much thicker walls compared with walls of veins of similar size. • Wall tension (T) is increased by both pressure (P) and radius (r), but decreased by wall thickness (h). Clinical Examples of Vascular Wall Tension • Vascular Hypertrophy: • Increase in wall thickness helps to offset the effect of increased pressure and decrease wall tension. • However, if elevated blood pressure is sustained over time, the thicker vascular walls become fibrotic and can lead to secondary problems • Vascular Aneurysm: • Sustained high arterial pressure can cause a progressive increase in vascular radius • This sets up a vicious cycle in which the vessel begins to dilate, further increasing its radius, and therefore wall tension. • This forms a vascular aneurysm Case courtesy of The Radswiki, Radiopaedia.org, rID: 11534 Question 2 • High arterial pressure has consequences for blood vessels, according to the Law of Laplace. Which of the following occurs when the arterial wall weakens in response to the increased pressure, causing a viscous cycle of dilation, increased radius, increased tension, and ultimately a weakened wall? • • • • Hypertrophy Atherosclerosis Aneurysm Heart failure Biophysics of Vascular Compliance • All blood vessels stretch under pressure • Arteries are less compliant than veins but are subjected to greater pressure changes as they receive the stroke volume of the heart during systole. • The aorta and large arteries contain an abundance of elastic fibers that stretch during systole and return to their original shape and size during diastole. • This elastic recoil of the large arteries helps to maintain diastolic blood pressure and thus tissue perfusion between heart beats. • When arterial walls become less compliant, patients may present with an increase in systolic blood pressure and a decrease in diastolic pressure and blood flow • Veins are much more compliant than arteries • 60% to 68% of the circulating blood volume is typically stored at relatively low pressures in the systemic veins and venules Elastic Recoil Biophysics of Flow Velocity • Blood flow velocity and cross-sectional area are inversely related • Blood velocity is highest in the aorta and large arteries and lowest in the capillaries. • Flow velocity is directly related to shear stress (friction of the blood sliding past and pulling on the endothelial cell surface parallel to the direction of flow) • Slow blood velocity is also the foundation for capillary function • Allows for exchange of water and blood-borne substances between blood and interstitial fluid Biophysics of Shear Stress • Laminar flow and high velocity in large arteries cause shear stress • Hydrostatic pressure further acts on the vessel wall by maintaining a perpendicular distending force that contributes to wall tension • Endothelial cell and smooth muscle layers generate and respond to a variety of biochemical mediators • Most important is the production of nitric oxide • NO promotes vasodilation, maintaining vessel patency and vascular wall health and lowering blood pressure Pathology of Flow • In turbulent flow, such as downstream from an atherosclerotic plaque and in areas of vascular branching, endothelial shear stress is reduced, leading to decreased nitric oxide production. • Decreased endothelial nitric oxide production is a hallmark of endothelial dysfunction that contributes to and accompanies atherosclerosis. • Elevated sheer stress cannot increase nitric oxide production, but rather contributes to endothelial damage and exacerbates atherosclerosis (HTN). Properties of Arterioles Objectives: Part 3 • List the factors controlling vascular resistance • Provide an overview of factors regulating blood pressure • Identify the major role played by vascular smooth muscle cells and the sympathetic nervous system in blood pressure regulation • Describe the cellular mechanisms that cause contraction of vascular smooth muscle (VSM) and give examples of mediators that stimulate VSM contraction • Describe the cellular mechanisms that cause VSM relaxation and give examples of mediators that stimulate VSM relaxation • Review the steps of baroreflex responses to states of acute hypotension and acute hypertension • Recognize the hypotheses regarding the pathogenesis of primary hypertension • Identify the consequences of poorly managed hypertension and the strategies used to improve blood pressure management. • Compare and contrast the pathophysiology of the different forms of shock. Structure and Function • Help maintain the systemic vascular resistance (SVR) • Abundance of sympathetic NS activity • Stimulation of α-adrenergic receptors results in vasoconstriction, whereas stimulation of β2-receptors promotes vasodilatation. • Major pathophysiological changes: • Hypertension • Shock Biophysical Determinants of Blood Pressure • Mean arterial pressure (MAP) is the average driving pressure in the circulatory system. • MAP = DBP + ((SBP-DBP) ÷ 3) Biophysical Determinants of Blood Pressure • Vascular resistance refers to the tendency of the branching and narrowing blood vessels to hinder blood flow, MAP drives this gradient • MAP is influenced by cardiac output and systemic vascular resistance, each of which is influenced by several variables. Determinates of Vascular Resistance • Length of the blood vessel • Viscosity of blood: An increase in hematocrit will increase blood viscosity and increase systemic vascular resistance • Radius of the vessel: This is the main factor controlling vascular resistance on a minute-tominute basis. Decreasing the radius of the vessels increases vascular resistance. Increasing the radius of the vessels would have the opposite effect • Radius affects the vascular resistance the most Distribution of Vascular Resistance • Pressure is highest in the left ventricle during systole and drops throughout the cardiovascular circuit as vascular resistance opposes the flow of blood. • Flow will only occur from an area of higher pressure to an area of lower pressure. • The greatest drop in MAP occurs at the arterioles, as the arterioles represent the greatest amount (~70%) of resistance in the systemic circulation. Dual Role of Arterioles • Increasing arteriolar resistance by arteriolar constriction will increase pressure in the arteries; however, decrease pressure in the capillaries following those arterioles • In contrast, vasodilation reduces the arteriolar resistance. Decreased total peripheral resistance reduces arterial pressure while increasing pressure reaching the capillaries • In hypertension, arteriolar resistance may be too high, causing an elevation in blood pressure and the potential for reduced tissue perfusion due to decreased capillary pressure and flow. • In contrast, in shock, there is dangerous decrease in arterial blood pressure and the potential for loss of fluid into the tissues due to increased capillary pressure and flow Regulation of Blood Pressure Four Sites of BP Regulation Resistance arterioles • Arterioles represent the primary site of vascular resistance maintaining normal blood pressure Capacitance venules • Veins and venules can alter cardiac output and blood pressure by regulating venous return (preload) Cardiac Output • Cardiac output = heart rate × stroke volume • An increase in HR or SV will increase CO and thus blood pressure Kidneys • Site of blood volume regulation BP Regulation Regulation of Blood Pressure Short Term • Neural • Baroreceptor reflex • Hormonal • Angiotensin II • Vasopressin • Local • Nitric Oxide • Bradykinin • Endothelin • Prostaglandins • Goal: Alter vascular resistance Long Term • Hormonal • Aldosterone • Vasopressin • Natriuretic peptides • Goal: alter blood volume by modulating fluid output Smooth Muscle Contractile Cells • Action potentials open voltage-gated calcium channels, initiating smooth muscle cell contraction. • Once contracted, the actin–myosin crossbridges do not completely relax; rather, they stay in a state of moderate contraction. • This state is supported by low levels of tonic firing of sympathetic vasoconstrictor fibers. • These mechanisms are important for overall blood pressure maintenance. Endothelial Factors • Nitric oxide is essential for maintaining normal blood flow during physiological conditions. Nitric oxide diffuses out of the endothelial cells to the underlying smooth muscle and causes relaxation by increasing cGMP production. • Endothelial dysfunction is common in diabetes, hypertension, and atherosclerosis, causing decreased nitric oxide production and contributing to vascular pathology. • Prostacyclin (PGI2) is an endothelium-derived vasodilator. In endothelial cells, PGI2 is produced from arachidonic acid by cyclooxygenase-2 (COX-2) and other enzymes. • ET1 is an endothelium-derived vasoconstrictor peptide. ET1 activates ETA receptors on VSM to cause vasoconstriction. Under healthy physiological conditions, ET1 production is minimal. • Increased ET1 production has been implicated in the pathogenesis of primary pulmonary arterial hypertension Endothelial Factors Cellular vs. Extrinsic VSM regulation • Cellular: As electrically excitable cells, smooth muscle cells can have action potentials that open voltagegated calcium channels and cause contraction. • Vascular calcium channels are the target of one class of antihypertensive medications: calcium channel blockers. • Extrinsic: Vasoconstriction is linked to Gq and phospholipase C activation. This leads to IP3 generation and release of calcium from intracellular stores. • Extrinsic: Vasodilation occurs through inhibition of MLCK and activation of myosin light-chain phosphatase (MLCP). Gs-coupled receptors increase intracellular cAMP, which inhibits MLCK. Cellular Extrinsic EC and VSMC Vascular Autoregulation • Maintain constant local blood flow despite changes in MAP • Very important to the brain and kidneys • Two hypotheses: 1. Myogenic hypothesis suggest that acute pressureinduced stretch of the arterial and arteriolar walls stimulates immediate constriction, while a rapid pressure drop elicits vasodilation 2. Metabolic hypothesis of autoregulation suggests that decreased pressure and flow result in buildup of vasodilator metabolites that produce vasodilation, while increased pressure and flow wash out vasodilator metabolites, producing vasoconstriction RAAS • Low blood pressure is detected by the juxtaglomerular apparatus of the nephrons of the kidney, and renin is secreted. • Renin is an enzyme that catalyzes the conversion angiotensinogen to angiotensin I. • Angiotensin I circulates through vasculature and is converted to angiotensin II by angiotensin-converting enzyme (ACE) • Angiotensin II is a potent vasoconstrictor and is also the key regulator of adrenal aldosterone secretion. • Aldosterone, the final mediator of the RAAS, stimulates sodium conservation through its actions on the distal nephron. • Angiotensin II acts within the hypothalamus to stimulate thirst, further promoting fluid acquisition and retention to support blood volume. (can further worsen HF since they are already fluid overload) Mediators that Regulate Resistance Vascular Effect Mediator Receptor Constriction/ increased resistance NE α1 Dilation/ decreased resistance G Protein Epinephrine Angiotensin II (ATII) AT1 Vasopressin (AVP) V1 Endothelin-1 (ET1) ETA Thromboxane A2 (TXA2) TP Epinephrine β2 Adenosine A2 Prostacyclin (PGI2) IP Second Messenger Type of Regulation IP3—calcium release Neural Endocrine Gq Paracrine cAMP ↑ Paracrine Gs Nitric oxide (NO) sGC None Atrial natriuretic NPR (pGC) peptide (ANP) None Endocrine cGMP ↑ Paracrine Endocrine Summary of Vascular Resistance • Arteriolar resistance is determined by the balance of local and systemic vasodilator and vasoconstrictor influences in health and disease. • Changes in arteriolar resistance elicit opposite changes in arterial pressure (MAP) and capillary pressure. • Vasoconstrictor dominance can cause tissue ischemia and hypertension, whereas vasodilation can cause potentially lifethreatening hypotension and tissue edema. Mediator Source Major Function in Resistance, Regulation in Health or Disease NE Sympathetic vasoconstrictor fibers Blood levels show circadian rhythm, highest when awake at upright posture Tonic activity at a1 receptors is the primary factor in normal blood pressure maintenance Prevents orthostatic hypotension Mediators and Mechanisms of VSM Contraction Epinephrine Adrenal medulla Blood levels lower than NE, highest when awake at upright posture Some activity at a1 receptors Levels increase with exercise contributing to β2-mediated vasodilation supplying skeletal muscles Angiotensin II (ATII) Renin, ACE generated Blood levels low at rest Primary effects are on sodium and blood volume regulation Vasoconstricting activity at AT1 receptors Major target of antihypertensive drugs Mediator Source Major Function in Resistance, Regulation in Health or Disease Vasopressin (AVP) Posterior pituitary hormone Major role in water conservation by the kidneys Increased secretion stimulated by hypotension and hypovolemia augments sympathetic vasoconstriction Mediators and Mechanisms of VSM Contraction AVP and its analogues can be used pharmacologically to support blood pressure during hypotensive/shock states Atrial natriuretic peptide/BNP Released from cardiac atria/ventricles in response to stretch Normally low circulating levels; BNP increases in heart failure Primary action is on the kidneys, reducing circulating volume by stimulating natriuresis and diuresis Secondary action is vascular smooth muscle relaxation Breakdown by the enzyme neprilysin is targeted by the heart failure drug sacubitril Mediators and Mechanisms of VSM Contraction Mediator Source Major Function in Resistance, Regulation in Health or Disease Prostacyclin (PGI2) Normal endothelial cells Tonically produced; inhibits platelet aggregation and promotes vasodilation Nitric oxide (NO) Normal endothelial cells Tonically produced; diffuses to smooth muscle layer and promotes vasodilation Mechanism of vasodilation produced by acetylcholine and bradykinin Target of nitrate vasodilator drugs Endothelin (ET) Damaged endothelial cells Potent vasoconstrictor Mediates trauma-induced vasoconstriction, limiting blood loss Endothelin antagonism is effective at reducing pulmonary arterial hypertension Mediators and Mechanisms of VSM Contraction Mediator Source Major Function in Resistance, Regulation in Health or Disease CO2, H+, K+, adenosine Local tissues with high metabolic activity Mediators of local flow increase in response to high metabolic demand, producing vasodilation This is proposed as the mechanism of metabolic autoregulation Bradykinin Produced locally in areas of tissue inflammation Contributes to cardinal signs of inflammation: redness, swelling, heat, and pain, through vasodilation Histamine Released by mast cells in areas of trauma or allergic responses Contributes to inflammatory and allergic vasodilation and increased vascular permeability Can cause severe tissue swelling and contribute to anaphylactic shock Mediators and Mechanisms of VSM Contraction Mediator Source Major Function in Resistance, Regulation in Health or Disease PGD2 and PGE2 Released by white blood cells in the process of inflammatory responses Contribute to inflammatory and allergic vasodilation Released by platelets in conditions of vascular and tissue trauma Contributes to vasoconstriction that reduces blood loss after vascular trauma TXA2 PGE2 and PGI2 increase vasodilation and blood flow in the renal medulla VSM Signaling: Putting it all together • Rapid adaption for short term changes Baroreflexes • Stretch-sensitive sensors in the carotid sinus and the aortic arch respond to increases or decreases in vessel distention. • Increased stretch increases the action potential firing rates. • Decreased pressure relaxes the stretch on the sensory endings, thus decreasing their action potential firing rates. • Increases in arterial pressure (stretch) increase baroreceptor sensory fiber activity to the medulla (parasympathetic). • NTS (medulla) neurons also project to cardioinhibitory center, resulting in decreased heart rate (which decreases cardiac output) and decreased sympathetic vasoconstriction (which decreases peripheral resistance) returning the blood pressure to normal. Baroreflex Pathway • Decreased arterial pressures reduce action potential firing rate of baroreceptors. • Medullary responses include decreased vagal flow and increased sympathetic stimulation. • Sympathetic stimulation of the sinoatrial node increases heart rate, and stimulation of the cardiac ventricles stimulates contractility, increasing cardiac output. • At the same time, sympathetic vasoconstrictor activity increases, resulting in VSM contraction and increased peripheral resistance. The effect of these alterations is to restore normal arterial pressure. Response to Hypotension Clinical Vignette 2 • 32-year-old female admitted to an acute psychiatric unit is found sitting down in the floor of her room. She reports fainting. • PMHx: Depression and HTN (recently started on amlodipine 5mg) • Physical Exam: Blood pressure: 130/75 (sitting) 105/64 (standing), Pulse: 79bpm (no change), Respiratory rate: 18 breaths per minute. Lungs: CTAB. CV RRR, no MGR • What is the most likely cause of her spell? Vasovagal Syncope • The afferent limb of the reflex arc begins with a trigger. It is thought that this trigger, usually in combination with central hypovolemia results in increased cardiac contractility in the setting of a relatively underfilled left ventricle. This may trigger mechanoreceptors in the ventricle that signal via vagal afferents to the central nervous system. (poorly understood). • The efferent limb of the reflex arc is better understood. Increased vagal firing (increased parasympathetic activity) at the sinus node and the atrioventricular node causes a decrease in heart rate. • At the same time, decreased sympathetic activity results in decreased vascular tone in both arterioles and venules. The results in decreased preload, venous return, and ventricular volume. • This results in a drop in the patient's mean arterial pressure. • Cerebral autoregulation results in constant cerebral blood flow over a wide range of mean arterial pressures, but when the mean arterial pressure falls below the body's ability to autoregulate, the patient loses consciousness. Question 6 • An acute drop in blood pressure will not cause which of these baroreflex compensatory responses? • Increased firing of parasympathetic fibers to the heart • Increased firing of sympathetic nerves to the kidney stimulating renin release • Increased firing of sympathetic fibers to vascular smooth muscle • Increased firing of sympathetic fibers to the heart to increase cardiac output Hypertension Pathophysiology of HTN • Hypertension: >130 mm Hg systolic or >80 mm Hg diastolic pressure (per book) • Two hypotheses of origin: • Initial defect in sodium and water retention that increases vascular volume and cardiac output. This is predicted to result in vasoconstriction by generalized autoregulation. • Chronically increased sympathetic tone that leads to vasoconstriction and RAAS activity. • These hypotheses are not mutually exclusive, and data also support a role for increased sodium intake, obesity, and a state of chronic inflammation as contributing factors to the hypertension seen as a component of the metabolic syndrome Other Possible Theories of HTN Causes of HTN • Primary HTN: • 95% of cases • Uncommon before the age of 20 (but growing!) • Secondary HTN: • Underlying cause present: Renal disease, Primary hyperaldosteronism, Cushing’s syndrome, Pheochromocytoma, Coarctation of the aorta, Pregnancy, OSA, thyroid disease • 10-15% of cases HTN and End Organ Damage Complications Contributing Factors Atherosclerosis Shear stress, endothelial injury, and inflammation Coronary heart disease Atherosclerosis, left ventricular hypertrophy, increased oxygen demand Heart failure Increased afterload, myocardial remodeling Stroke Atherosclerosis, inflammation/hypercoagulability, aneurysm rupture Kidney disease Vascular wall hypertrophy and hyaline arteriosclerosis Retinopathy Endothelial damage, leakiness and rupture, vessel narrowing Aneurysm formation and rupture Turbulent flow, high pressure, vascular wall thickening and ischemia Peripheral arterial disease Atherosclerosis, endothelial injury, inflammation HTN and End Organ Damage • 45% of adults in the United States have a blood pressure greater than 140/90 mm Hg or are being treated for hypertension • About 80% of people with hypertension are aware of the diagnosis and 75% are receiving treatment Epidemiology • Hypertension is controlled in only 52% of those affected • Adequate blood pressure control reduces the incidence of: • acute coronary syndrome by 20–25% • stroke by 30–35% • heart failure by 50%. HTN Diagnosis • A single elevated blood pressure reading is not sufficient to establish the diagnosis of hypertension. • The major exceptions to this rule are hypertension presenting with unequivocal evidence of life-threatening end-organ damage or blood pressure is greater than 220/125 mm Hg but life-threatening end-organ damage is absent. • 3-month delay in treatment of hypertension in high-risk patients is associated with a twofold increase in cardiovascular morbidity and mortality • The 2017 guidelines from the American College of Cardiology and American Heart Association (ACC/AHA) define normal blood pressure as less than 120/80 mm Hg, elevated blood pressure as 120–129/less than 80 mm Hg, stage 1 hypertension as 130–139/80–89 mm Hg, and stage 2 hypertension as greater than or equal to 140/90 mm Hg. Guideline Differences in Management Guidelines1 Cardiovascular Risk Threshold for Pharmacotherapy (mm Hg) ACC/AHA Not increased > 140/90 < 130/80 (reasonable) Hypertension Canada Not increased > 160/100 < 140/90 (< 130/80 for diabetes) ESH/ESC Not increased > 140/90 All < 140/90, most < 130/80, not < 120 ACC/AHA Increased < 130/80 < 130/80 (recommended) Hypertension Canada Increased > 140 systolic ESH/ESC Increased > 130/80 120–130/< 80 ACC/AHA > 65 yr Risk due to advanced age > 130/80 < 130 systolic Hypertension 4 Canada Increased Not specified ESH/ESC > 65 yr Not increased > 140/90 2 3 3 4 5 Target (mm Hg) < 120 systolic 4 Not specified 130–140/> 80 6 Nonpharmacologic Therapy Modification Intervention Resulting Decrease in Blood Pressure Weight loss Target BMI 18.5–24.9 5–20 mm Hg/10-kg loss DASH diet Fruit, vegetables, low fat dairy 8–14 mm Hg Sodium intake < 100 mmol/day (< 6 g salt) 2–8 mm Hg Alcohol intake Male ≤ 2 drinks/day Female ≤ 1 drink/day 4 mm Hg Exercise Aerobic 30 min/day Dynamic 90-150 min/week Isometric (hand grip 4 repetitions 3 times/week) 5–10 mm Hg Mindfulness Meditation and breathing control 5 mm Hg BP thresholds and recommendations for treatment and follow-up Normal BP (BP<120/80 mm Hg) Promote optimal lifestyle habits Elevated BP (BP 120-129/<80 mm Hg) Stage 1 hypertension (BP 130-139/80-89 mm Hg) Nonpharmacologic therapy (Class I) Clinical ASCVD or estimated 10-y CVD risk ≥10% No Management of HTN Reassess in 1 year (Class IIa) Reassess in 3-6 mo. (Class I) Nonpharmacologic therapy (Class I) Reassess in 3-6 mo. (Class I) Optimal lifestyle habits Nonpharmacologic therapy • Healthy diet • Weight loss for patients who are overweight or obese • Weight loss, if needed • Physical activity • Tobacco cessation, if needed • Moderation of alcohol consumption REASSESSMENT CHECKLIST Measure BP Yes Nonpharmacologic therapy and BP-lowering medication (Class I) Nonpharmacologic therapy and BP-lowering medication (Class I) Reassess in 1 mo. (Class I) BP Goal Met • Heart-healthy diet (such as DASH) No • Sodium restriction • Potassium supplementation (preferably in dietary modification)a Assess and optimize adherence to therapy • Increased physical activity with structured exercise program Consider intensification of therapy • Limitation of alcohol to 1 (women) or 2 (men) standard drinks per dayb Stage 2 hypertension (BP ≥140/90 mm Hg) a b Yes Reassess in 3-6 mo. (Class I) Unless contraindicated by the presence of chronic kidney disease or use of drugs that reduce potassium excretion. In the United States, one standard drink is equivalent to 12 oz of regular beer (usually about 5% alcohol), 5 oz of wine (usually about 12% alcohol), or 1.5 oz of distilled spirits (usually about 40% alcohol). Identify white-coat hypertension or a white-coat effect Document adherence to treatment Reinforce importance of treatment Assist with treatment to achieve BP target Evaluate for orthostatic hypotension in select patients (eg, older or with postural symptoms) Talk to your patients about substances that should be avoided, limited or stopped to help maintain a healthy BP. Recommended Treatment Based on Coexisting Condition Antihypertensive Medication Indication Heart failure Diuretic Beta-blocker ACE Inhibitor ARB √ √ √ √ √ √ Following MI √ √ √ Diabetes √ √ √ √ √ √ Recurrent stroke prevention √ √ Aldosterone antagonist √ √ High coronary disease risk Chronic kidney disease Calcium channel blocker √ √ Clinical Vignette 3 • A 49-year-old female with a history of type 2 diabetes, obesity, hypertension, and migraine headaches presents for follow-up. • DM is treated with an oral sulfonylurea and metformin. Her diabetes has been under fair control with a most recent hemoglobin A1c of 7.4%. • Hypertension was diagnosed 5 years ago when blood pressure (BP) measured in the office was noted to be consistently elevated in the range of 160/90 mmHg on three occasions. L.N. was initially treated with lisinopril, starting at 10 mg daily and increasing to 20 mg daily, yet her BP control has fluctuated. • Microalbuminuria was detected on an annual urine screen • Physical examination reveals an obese woman with a BP of 154/86 mmHg and a pulse of 78 bpm. Clinical Vignette 3 • What are the effects of controlling BP in people with diabetes? • What is the target BP for patients with diabetes and hypertension? Less than 130/80 • Which antihypertensive agents are recommended for patients with diabetes? Add a beta blocker or calcium blocker, consider weight loss The Initiation and Titration of Anti-hypertensive Medications Step 1 ACE inhibitor/ARB or Calcium channel blocker or Thiazide diuretic Step 2 ACE inhibitor/ARB plus Calcium channel blocker or thiazide diuretic5 Step 3 ACE inhibitor/ARB plus calcium channel blocker plus thiazide diuretic Step 4 ACE inhibitor/ARB plus calcium channel blocker plus thiazide diuretic plus spironolactone Physiologic effects of antihypertensive medications Question 3 • Which organ system shows the largest impact of chronically, poorly managed hypertension? A. Gastrointestinal B. Renal C. Respiratory D. Dermatologic Shock Shock • Shock is a clinical state of severely decreased blood pressure and blood flow that greatly reduces tissue perfusion and oxygenation. If this state is not quickly corrected, irreversible tissue damage occurs and can lead to death • Three stages of shock: • Compensated (fixable) • Decompensated (reduced fixable) • Irreversible (impending doom) Stages of Shock Compensated Shock Decompensated Shock Irreversible shock Arterial pressures may not reflect the full magnitude of the insult. A transitional phase of shock that reduces the likelihood for recovery. Vascular damage is extreme, and death is imminent. Baroreceptors and RAAS are activated Tissue damage becomes widespread, and severely ischemic tissues release inflammatory markers CO2 accumulates and lactic acid levels rise, along with other products of tissue hypoxia Severe hypoxia promotes anaerobic metabolism, resulting in widespread lactic acidosis, leading to loss of sympathetic tone and rapid circulatory collapse. Shock Types Type of Shock Examples Primary Problem Initial Hemodynamic Change Hypovolemic Blood loss Low circulating volume ↓ Preload, ↓ CO, ↑ TPR (trying to compensate) Generalized decrease of peripheral resistance ↓ TPR, blood pooling in periphery, ↓ venous return, ↓ preload, ↓ CO Neurogenic shock (spinal cord injury, drug overdose) Loss of sympathetic tone ↓ TPR, blood pooling in periphery, lack of cardiac compensation, ↓ CO Myocardial infarction Impaired cardiac contractility ↓ CO, ↑ TPR Papillary muscle rupture Acute mitral regurgitation Cardiac tamponade, pulmonary embolism, tension pneumothorax Physical block of vasculature or of cardiac filling Dehydration Distributive Anaphylactic reaction (type 1 hypersensitivity) Systemic infection (septic shock) Cardiogenic Obstructive ↓ CO, ↑ TPR Shock Treatment • All forms of shock are managed with urgent, invasive support measures with close monitoring, fluid replacement, and administration of pressor agents. • Ventilate • Infuse (fluid resuscitation) • Pump (admin. Vasoactive agents) Question 8 • A patient with a tree-nut allergy presents to the Emergency Department after accidently ingesting peanuts. The patient has shortness of breath, decreased blood pressure, and swelling. Which clinical diagnosis and type of shock are you most concerned about? A.Anaphylaxis; Distributive B.Myocardial infraction; Cardiogenic C.Septic; Distributive D.Pulmonary embolism; Obstruction Properties and Disorders of Capillaries Objectives: Part 4 • Identify the four pressures (Starling forces) that influence capillary filtration and reabsorption, and predict the effect on these capillary fluid movements as each factor increases or decrease, while all other factors are held constant • Describe the factors that promote edema formation and relate those factors to the mechanisms and mediators of local acute inflammation Capillaries • Capillaries are a collection of narrow branching blood vessels that are located between the arterioles and venules. • Capillary walls are a single endothelial cell thick with a small amount of basement membrane, perfect for nutrient exchange • Three types: 1. Continuous • Most abundant • Allow for some nutrient exchange; however, the do NOT permit movement of plasma proteins. This allow the capillary to exert a force called colloid osmotic pressure retaining fluid within the capillary lumen 2. Fenestrated • Found in the intestines, kidneys, and endocrine organs • Have higher rates of fluid exchange, including small proteins 3. Sinusoids • Found in spleen, liver, and bone marrow • Have large gaps between endothelial cells, and discontinuous basement membranes Capillaries Continuous (most common) Fenestrated Sinusoids Capillary Fluid Exchange • Net fluid exchange across capillary walls is influenced by a summation of capillary and interstitial pressures. • Hydrostatic pressures that push water and small dissolved molecules away from the source across the capillary walls. • Hydrostatic net pressure gradient favors filtration- fluid movement outward across the wall • Colloid osmotic pressure pulls water and small dissolved molecules toward the source across the capillary walls • Net colloid osmotic pressure favors reabsorption- inward fluid movement across the wall Capillary Fluid Exchange • As the capillary hydrostatic pressure gradually drops from the arteriole end to the venous end, the rate of fluid movement across the wall changes accordingly. • Consequently, capillary filtration is relatively high in the arteriolar end of the capillary, but a substantial portion is reabsorbed in the venous end of the capillary. • This aids in nutrient delivery and waste removal Lymphatics • Interstitial fluid arising from capillary filtration forms lymph. • Lymph vessels become lined with smooth muscle that slowly contracts when filled with lymph. • Lymph vessels eventually converge at lymph nodes that filter fluid proteins and are active in immune responses. • The lymph then proceeds back into the circulation, primarily through the subclavian vein. Conditions Associated with Edema Formation: Vasodilation • Arteriolar vasodilation allows higher hydrostatic pressure to be sustained to the level of the capillaries, in turn, increase the rate of lymph formation • Vasodilatory edema is a hallmark of local inflammation. When tissue trauma triggers an innate immune response, histamine is released into the region. • Histamine promotes vasodilation and increased capillary permeability, both of which favor filtration over reabsorption and produce the cardinal inflammatory sign of swelling. Conditions Associated with Edema Formation: Increased Venous Pressure • Deep venous thromboses increases venous pressures in the affected region. This pressure greatly increases capillary hydrostatic pressure (venule) and promotes filtration along the capillary length. • This is manifested by edema and pain in the affected limb. • Right-sided heart failure is also known to cause fluid retention and increase systemic venous pressures, promoting peripheral edema. • Main signs include peripheral edema. • Venous hypertension can occur in the legs, particularly in older adults, due to incompetence of venous valves and decreased effectiveness of leg muscle activity to compress the leg veins. • Main signs of this syndrome of venous insufficiency is ankle edema. Conditions Associated with Edema Formation: Hemodilution • Liver disease, malnutrition, and some kidney diseases can lead to reductions of circulating albumin reducing the colloid osmotic pressure. • This reduction in osmotic pressure promotes widespread edema • Hemodilution that reduces colloid osmotic pressure is also a prevalent scenario in EDs, where patients are volume expanded with intravenous fluids containing glucose and electrolytes, but no proteins, after major hemorrhagic losses. Conditions Associated with Altered Lymph Clearance: Vasoconstriction • Baroreflexes promote intense sympathetic vasoconstriction that maintains arterial pressure but greatly reduces capillary hydrostatic pressure. This promotes reabsorption of fluid along the length of the capillaries, a phenomenon sometimes termed autotransfusion. • Loss of skin turgor is a physical manifestation of this fluid shift, particularly in children and youth. • Capillary refill is also slowed due to the generalized vasoconstriction. Question 9 • A patient presents with a venous thrombosis. How would you interpret the illustration describing the clinical situation? A.Increased capillary filtration due to increased capillary hydrostatic pressure B.Decreased reabsorption due to reduced colloid osmotic pressure C.Obstruction of lymph flow causing edema due to changes in tissue pressures Lifespan considerations Objectives: Part 6 • Explain how the vascular changes associated with aging impact the systolic and diastolic blood pressure • Describe the effect of age-related vascular changes on the heart Pediatric HTN • At age of 13, the current ranges for adults apply. • In 2017, normative tables were revised and adjust for age, sex, and height. • Elevated blood pressure should be confirmed with three separate measurements and should be measured by auscultation Ashraf, M., Irshad, M., & Parry, N. A. (2020). Pediatric hypertension: an updated review. Clinical hypertension, 26(1), 22. https://doi.org/10.1186/s40885-020-00156w BP/HTN Age 1–< 13 Years Age > 13 Years Normal BP <90th percentile < 120/< 80 mmHg Elevated BP ≥90th percentile to <95th percentile or 120/80 mmHg to <95th percentile (whichever is lower) 120/< 80– 129/< 80 mmHg Stage 1HTN ≥95th percentile to <95th percentile+ 12 mmHg or 130/80–139/89 mmHg (whichever is lower) 130/80– 139/89 mmHg ≥95th percentile + 12 mmHg Stage 2 HTN or ≥ 140/90 mmHg (whichever is lower) ≥140/90 mmHg Age (Years) Pediatric HTN: BP requiring further investigation Ashraf, M., Irshad, M., & Parry, N. A. (2020). Pediatric hypertension: an updated review. Clinical hypertension, 26(1), 22. https://doi.org/10.1186/s40885-020-00156w Boys Girls SBP (mmHg) DBP (mmHg) SBP (mmHg) DBP (mmHg 1 98 52 98 54 2 100 55 101 58 3 101 58 102 60 4 102 60 103 62 5 103 63 104 64 6 105 66 105 67 7 106 68 106 68 8 107 69 107 69 9 107 70 108 71 10 108 72 109 72 11 110 74 111 74 12 113 75 114 75 ≥13 120 80 120 80 Endothelial Changes with Aging • Endothelial dysfunction as we age is signaled by changes in balance of the vasodilators nitric oxide and PGI2 and the vasoconstrictors ET1, TXA2, and angiotensin II. • ROS increase with aging and further deplete NO • This creates a net reduced ability of the vessel to dilate and a reduction of antithrombotic properties. Arterial Stiffness