Understanding Hypertension

• Hypertension is when blood pressure is high enough to pose a risk to overall well-being

Essential Hypertension

• The cause of the elevated blood pressure is unknown
• Affects approximately 90% of hypertension patients
• It has multiple and diverse causes

Secondary Hypertension

• Elevated blood pressure is due to a known cause
• Many of the causes can be permanently cured
• The pathophysiology of high blood pressure leads to the discovery of more secondary hypertension cases

Blood Pressure Stages

• Normal blood pressure is a systolic pressure less than 120mmHg and a diastolic pressure less than or equal to 80mmHg
• Elevated blood pressure is a systolic pressure between 120-129mmHg and a diastolic pressure less than or equal to 80mmHg
• Stage 1 hypertension is a systolic pressure between 130-139mmHg or a diastolic pressure between 80-89mmHg
• Stage 2 hypertension is a systolic pressure greater than or equal to 140mmHg or a diastolic pressure greater than or equal to 90mmHg
• Hypertension is labeled with at least two high readings on at least two separate occasions
• Prehypertension is a systolic pressure between 120-139mmHg and a diastolic pressure between 80-89mmHg
• Blood pressure is equal to cardiac output multiplied by total peripheral resistance (BP = CO * TPR)
• Cardiac output is equal to stroke volume multiplied by heart rate (CO = SV * HR)
• Stroke volume is determined by contractility, preload, and afterload

Blood Pressure Determinants

• Heart supplies pumping pressure
• Blood vessel tone determines systemic resistance
• Kidney regulates intravascular volume
• Renal excretion can completely return blood pressure to normal, regardless of cardiac output or total peripheral resistance
• The maintenance of chronic hypertension requires renal participation
• A normal kidney responds to an increase in blood pressure by augmenting urine volume and sodium excretion, called pressure natriuresis
• A hypertensive kidney requires higher pressure to excrete a given sodium and water load, which may be due to hormonal factors and tubulointerstitial injury
• Hormones modulate the functions of the heart, blood vessels, and kidneys

Baroreceptor Reflex

• Baroreceptors are located in the aortic arch and carotid sinuses
• Baroreceptors sense stretch and deformation of the arteries through mechanically gated channels
• Increased pressure leads to impulse transduction to the central nervous system (medulla oblongata), triggering negative feedback via the autonomic nervous system to decrease blood pressure by inhibiting the sympathetic nervous system and exciting the parasympathetic nervous system
• Peripheral vascular resistance decreases through vasodilation
• Cardiac output decreases through lower heart rate and reduced contractility
• Decreased blood pressure leads to fewer impulses to the medulla oblongata, resulting in increased blood pressure
• Carotid sinus receptors communicate through the glossopharyngeal nerve (CN IX)
• Aortic arch receptors communicate through the vagus nerve (CN X)

Essential Hypertension Specifics

• Indicates a patient has elevated blood pressure without an identifiable cause after examination
• Different underlying defects may be responsible for elevated blood pressure in different populations
• Understanding the pathophysiology of chronic elevated blood pressure is necessary
• Genetics and epidemiology play a role, with strong support for heredity
• First-degree relatives of hypertensive patients and identical twins show concordance
• It is a polygenic disorder involving polymorphisms in genes for angiotensinogen, angiotensin-converting enzyme (ACE), angiotensin type 1 receptor, aldosterone synthase, and alpha-adducin (renal tubular sodium absorption)
• Environmental factors such as low socioeconomic status, exercise patterns, and poor access to healthcare contribute
• Obesity, insulin resistance, and diabetes overlap in inheritance patterns with hypertension
• Systemic abnormalities involved with blood pressure regulation are experimental findings
• The heart may exhibit high cardiac output-based hypertension due to sympathetic overactivity
• Vascular tone may show peripheral vascular resistance-based hypertension due to increased sympathetic activity, abnormal regulation of tone (NO, endothelin, natriuretic factors), and ion channel defects in contractile smooth muscle cells
• The kidney may exhibit volume-based hypertension with excess sodium and water retention, failure to regulate renal blood flow, ion channel defects (reduced basolateral Na+/K+ ATPase), and inappropriate hormone regulation (renin levels should be suppressed by high blood pressure)
• Primary defects may occur elsewhere, including the central nervous system, arterial baroreceptors, and adrenal hormone secretion
• Insulin resistance, obesity, and metabolic syndrome are factors, with increased serum glucose levels leading to increased insulin, resulting in sympathetic activation or smooth muscle cell hypertrophy (mitogenic effect of insulin or platelet-derived growth factor)
• Obesity is directly associated with hypertension due to angiotensinogen from adipocytes, increased blood volume from increased body mass, and increased blood viscosity by adipocyte release of profibrinogen and plasminogen activator inhibitor 1
• Metabolic syndrome includes atherogenic risk factors (hypertension, hypertriglyceridemia, low serum HDL, tendency towards glucose intolerance, truncal obesity), with insulin resistance being central to its pathogenesis
• Essential hypertension typically arises after young adulthood, and its prevalence increases with age; over 60% of Americans older than 60 are hypertensive
• Hemodynamic characteristics of elevated blood pressure in essential hypertension change over time
• Systolic pressure increases throughout adult life, while diastolic pressure increases until about age 50 and declines slightly thereafter
• Diastolic hypertension is more common in young people and displays augmented cardiac output as the principal abnormality
• Isolated systolic hypertension (over age 50) features normal diastolic values and elevated total peripheral resistance as the major hemodynamic finding

Secondary Hypertension Details

• Defined as hypertension with a structural or hormonal cause
• Treatment may differ from essential hypertension and can be curable if identified early
• Age less than 20 or above 50 indicates likely secondary hypertension
• Secondary hypertension often causes dramatic increases in blood pressure, while most essential hypertension is mild to moderate
• Secondary hypertension often presents abruptly in previously normotensive patients, while essential hypertension gradually progresses
• Associated signs and symptoms include renal artery bruit in a hypertensive patient
• Family history reveals that essential hypertension is usually in first-degree relatives, while secondary hypertension more commonly occurs sporadically
• Patient evaluation includes lab tests for general screening such as urinalysis and serum concentration of creatinine and blood urea nitrogen to reveal renal abnormalities
• Serum potassium levels (low in renovascular hypertension or primary aldosteronism), blood glucose levels (increased in diabetes), serum total LDL, HDL, and triglyceride levels, and electrocardiogram (LVH) are measured
• If no abnormalities are found, essential hypertension is assumed
• Common symptoms include repeated UTIs (chronic pyelonephritis with renal damage), excessive weight loss (pheochromocytoma), and weight gain (Cushing syndrome)

Causes of Secondary Hypertension

• Exogenous causes include oral contraceptives (increase RAAS: Estrogen leads to increased angiotensinogen), glucocorticoids, cyclosporine (antirejection drug), erythropoietin (increases blood viscosity), sympathomimetic drugs (common cold medicine), NSAIDs (dose-related augmentation of renal Na+ and H2O retention), alcohol, and cocaine
• Renal causes include renal parenchymal disease (2-4% of hypertensive patients) where damaged nephrons cannot excrete normal Na+ H2O leading to increased intravascular volume and cardiac output, and excessive elaboration of renin is possible even when the filtration rate is not severely reduced
• Renovascular hypertension accounts for approximately 1% of hypertensive patients and involves reduced blood flow past the stenotic region leading to decreased perfusion, causing the kidney to secrete renin; diagnosis is suggested by abdominal bruit (40-60% of affected patients) or unexplained hypokalemia; confirmed by Doppler ultrasonography, CTA, or MRA; therapy is effective with ACE inhibitors or ARBs (avoid with bilateral stenosis) or PCI or CABG for select patients
• Atherosclerosis accounts for ⅔ of renovascular hypertension and occurs mostly in elderly men
• Fibromuscular lesions account for ⅓ of renovascular hypertension and occurs usually in young women
• Mechanical causes include coarctation of the aorta, a congenital narrowing of the aorta where blood pressure is higher in the aortic arch, head, and arms than in the descending aorta and lower extremities; sometimes lower pressure in the left arm compared with the right arm (subclavian artery); midsystolic murmur can be heard between the scapulae; radiography may show coarctation; surgical repair or angioplasty are treatment options, though hypertension may persist due to blunted baroreceptor response; hypertension arises from reduced flow to the kidney leading to increased renin and accelerated atherosclerosis from a stiffened aortic arch, which blunts the normal baroreceptor response to elevated blood pressure

Endocrine Causes

• Condition evaluation includes assessment of characteristic signs and symptoms, hormone level measurement, assessment of hormone secretion in response to stimulation or inhibition, and imaging studies to identify the source of excessive hormone secretion
• Pheochromocytoma accounts for approximately 0.2% of hypertension cases
• Catecholamine-secreting tumors of neuroendocrine cells in the adrenal medulla cause episodic secretion
• Intermittent or chronic vasoconstriction, tachycardia, and other sympathetic-mediated effects
• Paroxysmal rises in blood pressure accompanied by autonomic attacks (severe headache, sweating, palpitations, tachycardia)
• Approximately 10% of cases are malignant
• Plasma/urine catecholamine levels and metabolites (vanillylmandelic acid and metanephrine) are used to identify pheochromocytoma
• Receptor blockers (α and β blockers) and biosynthesis inhibitors are used, with surgical resection being the definitive therapy Adrenocortical hormone excess includes excessive mineralocorticoids (aldosterone, etc.), where hypokalemia is an important marker Primary aldosteronism results from adrenal adenoma or bilateral hyperplasia of adrenal glands and may be as high as 10-15% among hypertensives, with excessive aldosterone and suppressed renin levels
• Glucocorticoid-remediable aldosteronism is an uncommon hereditary form of primary aldosteronism where aldosterone is under the control of ACTH, causing severe hypertension in childhood/young adulthood, and responds to glucocorticoid therapy (ACTH suppression)
• Secondary aldosteronism involves increased angiotensin II production stimulated by renin-secreting tumors and can be caused by oral contraceptives or impaired angiotensin II degradation in liver dysfunction
• Excessive glucocorticoids (cortisol, etc.) increase blood pressure by blood volume expansion and synthesis of components of RAAS, activate mineralocorticoid receptors in renal tubules (sodium retention and K+ excretion); 80% of Cushing syndrome patients have hypertension with Cushingoid features including round face, central obesity, proximal muscle weakness, hirsutism, and can be caused by ACTH secreting adenoma or tumor or adrenal cortisol secreting adenoma
• Thyroid hormone abnormalities affect the cardiovascular system Approximately 1/3 of hyperthyroid and ¼ of hypothyroid patients (primarily diastolic hypertension with an increase in TPR) have hypertension by inducing Na+/K+ ATPases in the heart and vessels, increasing blood volume, and stimulating tissue metabolism and oxygen demand with resulting metabolite accumulation

Consequences of Hypertension

• Clinical signs and symptoms include classic symptoms like headache, epistaxis, and dizziness; flushing, sweating, and blurred vision are more common in hypertensive populations, but most are asymptomatic and diagnosed through blood pressure measurement
• Physical signs include left ventricular hypertrophy (LVH), retinopathy, and arterial bruits
• Organ damage is attributed to increased workload on the heart and arterial damage from elevated blood pressure and atherosclerosis Atherosclerosis of large arteries hinders elasticity, leading to spikes of systolic pressure (can lead to aneurysm rupture)
• Untreated, approximately 50% of patients die of CAD or congestive heart failure, 33% die of stroke, and 10-15% die from renal failure

Impact of Hypertension

• Heart is affected through LVH and diastolic dysfunction, where increased afterload causes concentric hypertrophy (sometimes eccentric hypertrophy with chamber dilation), LV impulse, S4 are physical findings, and the degree of hypertrophy correlates with the development of congestive heart failure, angina, arrhythmias, MI, and sudden cardiac death
• Systolic dysfunction occurs when LV mass is insufficient to balance high wall tension, leading to decreased cardiac output and pulmonary congestion
• CAD presents as accelerated coronary atherosclerosis combined with high systolic workload and a higher chance of post-myocardial infarction complications such as ventricular wall rupture, LV aneurysm, and congestive heart failure
• Cerebrovascular system is affected through hypertension as a major modifiable risk factor for strokes (cerebrovascular accidents), with the magnitude of systolic pressure most closely linked to CVAs
• Hemorrhagic CVA results from the rupture of microaneurysms in cerebral parenchymal vessels, while atherothrombotic CVA results from thrombi formation that break off and embolize to distal vessels
• Occlusion of small arteries can result in multiple tiny infarcts leads to white blood cells leads to lacunae, and reduces collateral flow requires higher perfusion pressure to maintain tissue flow
• Aorta and peripheral vasculature are most commonly affected in the lower extremities, neck, and brain
• Abdominal aortic aneurysm involves dilation of blood vessels below renal levels, with a diameter greater than 6cm having a very high likelihood of rupture
• Aortic dissection involves degenerative changes in the media, high pressure may cause the intima to tear, allowing blood to dissect into the media and propagate further, requiring rigorous blood pressure control or surgical repair
• Kidney damage includes nephrosclerosis, which is the leading cause of kidney failure
• Hyaline arteriolosclerosis involves thickening of vessel walls with hyaline infiltrate
• Fibrinoid necrosis involves smooth muscle hypertrophy and necrosis of capillary walls
• Results in reduced vascular supply and ischemic atrophy of tubules and glomeruli
• Perpetuation of elevated BP in hypertensive renal failure (kidney cannot regulate blood volume)
• Systemic arteries can be visualized by physical examination of the retina
• Hypertensive retinopathy results from damage to vessels caused by high blood pressure
• Acute hypertension causes hemorrhage, exudation of plasma lipids, local infarction, blurred vision if ischemia of the optic nerves, patchy loss of vision from hemorrhagic ischemia
• Papilledema is the swelling of the optic disk from high intracranial pressure when cerebrovascular autoregulation fails (BP at malignant levels), while chronic elevated blood pressure results in the absence of papilledema but arterial narrowing and medial hypertrophy nicks crossing veins
• Arterial sclerosis is evident through ophthalmoscope (copper/silver wiring) in more severe chronic hypertension, which is not life-threatening but evident of long-standing poorly controlled hypertension

Hypertensive Crisis

• Caused by hemodynamic insult superimposed on a chronic hypertensive state
• Rapid pathologic changes such as fibrinoid necrosis cause spiraling increases of blood pressure, volume expansion, and vasoconstriction occur if renal perfusion drops causing an increase of renin and angiotensin
• Hypertensive encephalopathy results from increased intracranial pressure, leading to blurred vision, headache, confusion, somnolence, and potentially coma
• Accelerated malignant hypertension occurs when hypertension results in acute retinal vessel damage
• Angina and/or pulmonary edema may be precipitated from increased load on the left ventricle

Treatment of Hypertension

• Recommended first-line therapy for non-immediate danger patients, effective since the environment plays a role in hypertension (EH and SH to some degree)
• White coat effect: patient anxiety causing increased blood pressure reading; averaging multiple readings taken at ≥2 office visits and/or at home is more reliable; blood pressure measurement outside of a medical setting is recommended to confirm diagnosis and adjust medications; automatic ambulatory blood pressure measurements taken over the daily routine of the patient are more predictive of cardiovascular mortality; on-therapy blood pressure goal is less than 130/80

Nonpharmacologic treatment

• Weight reduction: obesity accounts for 40-60% of hypertension; each 10kg of weight loss results in ~5-20mmHg fall in blood pressure; consistently high correlation between hypertension and obesity, particularly when obesity is more central/abdominal
• Exercise: sedentary normotensive people have a 20-50% higher risk of hypertension; aerobic exercise lowers blood pressure by reducing sympathetic tone
• Diet: high in fruits, vegetables, low-fat dairy, and reduced sodium Moderating or reducing Na+ is helpful since hypertensive patients have a defect in natriuresis; African American and elderly hypertensive patients are more sensitive to salt; low salt diet increases the effectiveness of antihypertensive medication; recommended less than 6g of NaCl (less than 2.3g Na+), which is ½ less than the average person recommends
• Potassium is helpful to replete low serum K+ levels when taking potassium-wasting diuretics.
• Normokalemic hypertensive patients do not need K+ supplements
• Alcohol can cause systolic blood pressure to rise acutely after alcohol consumption
• Low Ca2+ and Mg2+ are associated with elevated blood pressure
• Caffeine ingestion results in transient elevated blood pressure
• Smoking cessation: nicotine stimulates sympathetic tone, increasing blood pressure; the atherogenic effect of smoking may result in renovascular hypertension
• Sleep apnea: treatment of sleep apnea with positive airway pressure shows a small decrease in blood pressure
• Relaxation therapy: reduces stress to lower blood pressure; hypertensive patients often show higher than normal basal sympathetic tone and exaggerated autonomic response to mental stress; biofeedback and meditation depend on the patient's attitude and long-term compliance

Pharmacologic Treatment

• Current guidelines recommend the use of thiazide diuretics (most popular), calcium channel blockers, ACE inhibitors, or ARBs for first-line treatment of EH
  • Diuretics: decreasing circulating blood volume, cardiac output, and mean arterial pressure in mild-to-moderate hypertension patients with normal renal function (mostly effective in African American or elderly persons who are salt-sensitive); reduce the risk of stroke and cardiovascular events; thiazide diuretics and potassium-sparing diuretics promote Na+ excretion in the distal nephron Thiazides may result in undesired side effects such as increased glucose, cholesterol, triglyceride levels, hypokalemia, and hyperuricemia; Mineralocorticoid receptor antagonists inhibit aldosterone and are the preferred therapy for primary aldosteronism
• Loop diuretics are too potent and too short-lived but useful in lowering blood pressure in patients with renal insufficiency (do not respond well to other diuretics)
• Sympatholytics include Beta-blockers and alpha blockers
  • Beta-blockers lower blood pressure through decreased cardiac output through decreased heart rate and mild decreased contractility, and decreased renin leading to decreased Angiotensin II, leading to decreased total peripheral resistance Adverse effects include bronchospasm, fatigue, impotence, hyperglycemia, and altered lipid metabolism
  • Central alpha-adrenergic antagonists lower sympathetic outflow to the heart, blood vessels, and kidneys but have a high frequency of side effects
  • Systemic alpha-adrenergic blocking drugs decrease TPR through SMC relaxation; Diuretic therapy is superior for the prevention of adverse cardiovascular events

Vasodilators

• Calcium channel blockers decrease the influx of Ca2+ which decreases total peripheral resistance, Once-daily-sustained-release is frequently used for hypertension.
• Hydralazine/minoxidil lower blood pressure by relaxing precapillary resistance vessels (can result in reflex increased heart rate)
• RAAS antagonists include ACE inhibitors (Angiotensin Converting Enzyme inhibitors), ARBs (Angiotensin II Receptor Blockers), Direct Renin Inhibitors
  • The ACEI block the conversion from Angiotensin I to angiotensin II, blocking the vasopressor effect of Angiotensin II and the secretion of aldosterone, resulting in decreased TPR; and also increase vasodilator bradykinin; slow the deterioration of renal function in patients with diabetic nephropathy
• Dry cough, hyperkalemia, and azotemia may occur
  • ARB Blocks the binding of Angiotensin II to receptors; Reduces the secretion of aldosterone
  • Direct Renin Inhibitor reduces levels of Angiotensin I and Angiotensin II by binding to the proteolytic site of renin (inhibit the cleavage of angiotensinogen); Antihypertensive effectiveness is no greater compared to other RAAS inhibitors