Understanding Hypertension

• Over 70 million Americans, and 1 billion people worldwide, have hypertension
• This represents a major public health concern because hypertension is a major risk factor for coronary artery disease.
• Hypertension is a major risk factor for stroke, heart failure, renal disease, and peripheral vascular disease.
• Elevated BP is usually asymptomatic until an acute cardiovascular event, which makes screening for hypertension a critical aspect of preventive medicine
• With ~90% of affected patients, the etiology of BP elevation is unknown, a condition termed primary or essential hypertension (EH)
• Evidence suggests that the causes of EH are multiple and diverse, however studying the normal physiology of BP control can provide insight into the causation
• High BP attributed to a definable cause is termed secondary hypertension
• Conditions that cause secondary hypertension are important because many are amenable to permanent cure and may carry excess risk beyond elevated BP
• Notably, many of the conditions now understood to cause secondary hypertension were once unknown and considered to be EH
• As more is learned about the pathophysiology of high BP, fewer cases of hypertension will likely be considered of the essential type
• Chapter considers the clinical consequences of elevated BP and approaches to treatment, after giving descriptions of EH and secondary hypertension

Hypertension

• BP values vary widely in the population and tend to rise with age, the risk of a vascular complication increases with higher values

• The cutoff points to delineate stages of hypertension are somewhat arbitrary

• A normal BP is <120 mm Hg systolic and <80 mm Hg diastolic

• A systolic BP ≥ 120 mm Hg is considered "elevated."

• A systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg establishes stage 1 hypertension

• Stage 2 hypertension is present if the systolic BP is ≥140 mm Hg or diastolic BP is ≥90 mm Hg

• A person should not be labeled as hypertensive until obtaining ≥2 high readings on ≥ 2 separate occasions

• Modern analyses confirm that both systolic and diastolic BP elevations contribute significantly to cardiovascular risk

How blood pressure is regulated

• BP is the product of cardiac output (CO) and total peripheral resistance (TPR): BP = CO × TPR

• CO is the product of cardiac stroke volume (SV) and heart rate (HR): CO = SV × HR

• SV is determined by cardiac contractility, the venous return to the heart (preload) and the resistance the left ventricle must overcome to eject blood into the aorta (afterload)

• At least four systems are directly responsible for BP regulation: the heart, the blood vessel tone, the kidney, and hormones

• The renal component of BP regulation deserves special mention

• No matter how high the CO or TPR, renal excretion has the capacity to completely return BP to normal by reducing intravascular volume

• Therefore, the maintenance of chronic hypertension requires renal participation

• Transplantation studies confirm the kidney's role, by transplanting a kidney from a normotensive person into a hypertensive one and vice-versa.

• In the presence of normally functioning kidneys, an increase in BP leads to augmented urine volume and sodium excretion which then returns the BP to normal (pressure natriuresis)

• Pressure natriuresis, is blunted in the kidneys of hypertensive patients

• Higher pressures are required to excrete a given sodium and water load

• This blunted response can be caused by microvascular and tubulointerstitial injury within the kidneys of hypertensive patients impairs sodium excretion, or could be due to hormonal factors

Blood pressure reflexes

• The cardiovascular system has feedback mechanisms that continuously monitor arterial pressure
• Baroreceptor reflex is a mechanism where receptors in the walls of the aortic arch and the carotid sinuses monitor changes in pressure by sensing stretch and deformation of the arteries
• When arterial pressure rises, baroreceptors are stimulated, increasing transmission of impulses to the central nervous system (ie, the medulla)
• Negative feedback signals are then sent back to the circulation via the autonomic nervous system, causing the BP to fall back to its baseline level
• Signals from the carotid sinus receptors are carried by the glossopharyngeal nerve (cranial nerve IX), whereas those from the aortic arch receptors are carried by the vagus nerve (cranial nerve X)
• These nerve fibers converge at the tractus solitarius in the medulla, where the baroreceptor impulses inhibit sympathetic nervous system outflow and excite parasympathetic effects
• The net result is a decline in peripheral vascular resistance (vasodilation) and a reduction in CO because of a lower HR and reduced contractility
• When a fall in systemic pressure is sensed by the baroreceptors, fewer impulses are transmitted to the medulla, leading to a reflexive increase in BP
• The effect of the baroreceptor mechanism is to modulate moment-by-moment variations in systemic BP
• The baroreceptor reflex doesn't prevent the development of chronic hypertension, because the baroreceptors constantly reset themselves
• After a day or two of exposure to higher-than-baseline pressures, the baroreceptor-firing rate slows back to its control value, and a new set point is established

Essential hypertension

• Approximately 90% of hypertensive patients have BPs that are elevated for no readily definable reason and are considered to have EH
• The diagnosis of EH is one of exclusion; the option left to the clinician after considering the causes of secondary hypertension
• EH likely results from multiple defects of BP regulation that interact with environmental stressors
• The regulatory defects may be acquired or genetically determined and may be independent of one another, so EH patients exhibit varied combinations of abnormalities and therefore, have various physiologic bases for their elevated BPs

Genetics and epidemiology

• There is strong support for the role of heredity in EH
• First-degree relatives of hypertensive patients have a higher rate of elevated BP than the general population
• Concordance between identical twins is high and significantly greater than that between dizygotic twins
• No singular, consistent genetic marker for hypertension has been identified, instead, EH is likely a complex polygenic disorder with multiple Loci
• Certain polymorphisms in the genes for angiotensinogen, angiotensin-converting enzyme (ACE), the angiotensin type-1 receptor and aldosterone synthase confer a small increase in the risk of developing hypertension
• Additionally, polymorphisms in the gene for alpha-adducin, a cytoskeletal protein, may be involved in a subgroup of EH patients, possibly by increasing renal tubular sodium absorption
• Significant associations exist among hypertension and obesity, insulin resistance, and diabetes
• As genetics cannot explain the complete basis of hypertension, the environment also plays a role

Experimental findings

• Multiple defects in BP regulation have been found in EH patients and their relatives
• The heart can contribute to a high CO-based hypertension owing to sympathetic overactivity
• When tested under psychologically stressful conditions, hypertensive patients (and their first-degree relatives) often develop excessive HR acceleration compared with control subjects suggesting an excessive sympathetic response
• The blood vessels may contribute to peripheral vascular resistance-based hypertension by constricting in response to increased sympathetic activity
• Abnormal regulation of vascular tone by local substances, including nitric oxide, endothelin, and natriuretic factors, or ion channel defects in the contractile vascular smooth muscle, is another factor towards high vascular resistance
• The kidney can induce volume-based hypertension by retaining excessive sodium and water through failure to appropriately regulate renal blood flow
• The kidney can induce volume-based hypertension by retaining excessive sodium and water due to ion channel defects (reducing basolateral Na+K+-ATPase), which directly causes sodium retention, or due to inappropriate hormonal regulation
• Even normal renin levels are inappropriate in the context of hypertension
• The heart, blood vessels, and kidneys are the organs ultimately responsible for producing the pressure, but primary defects may be located elsewhere as well (eg, the central nervous system, arterial baroreceptors, and adrenal hormone secretion)
• Yet, it's important to remember that without renal complicity, malfunction of other systems would not produce sustained hypertension, since the normal kidney is capable of eliminating sufficient volume to return the BP is normal

Insulin resistance, obesity, and the metabolic syndrome

• Hormone insulin may play a role in the development of EH
• Many people with hypertension, especially those who are obese or have type 2 diabetes, have impaired insulin-dependent transport of glucose into many tissues (insulin resistance)
• As a result, serum glucose levels rise, stimulating the pancreas to release additional insulin
• Elevated insulin levels may contribute to hypertension via increased sympathetic activation or stimulation of vascular smooth muscle cell hypertrophy, which increases vascular resistance
• Obesity itself has been directly associated with hypertension, one explanation for this relationship could be the release of angiotensinogen from adipocytes as substrate for the renin-angiotensin system, augmented blood volume related to increased body mass, and increased blood viscosity caused by adipocyte release of profibrinogen and plasminogen activator inhibitor 1
• Current epidemic of obesity has led to a dramatic increase in the number of people with metabolic syndrome, which represents a clustering of atherogenic risk factors, including hypertension, hypertriglyceridemia, low serum high-density lipoprotein (HDL), a tendency toward glucose intolerance, and truncal obesity

Natural history

• EH characteristically arises after young adulthood

• Its prevalence increases with age, and more than 60% of Americans older than 60 years are hypertensive

• The hemodynamic characteristics of BP elevation in EH tend to change over time

• The systolic pressure increases throughout adult life, while the diastolic pressure rises until about the age of 50 and then declines slightly thereafter, as a result, diastolic hypertension is more common in young people

• A substantial number of hypertensive patients over age 50 have isolated systolic hypertension, with normal diastolic values

• In younger persons with hypertension, elevated BP tends to be driven by high CO in the setting of relatively normal peripheral vascular resistance, termed the hyperkinetic phase of EH

• With advancing age, however, the effect of CO declines, because of development of left ventricular hypertrophy (LVH) and its consequent reduced diastolic filling (which in turn reduces SV and CO)

• Conversely, vascular resistance increases with age due to medial hypertrophy as the vessels adapt to the prolonged pressure stress

• Younger hypertensive patients often display augmented CO as the principal abnormality, and older patients tend to have elevated TPR as the major hemodynamic finding

• EH is a syndrome that may arise from many potential abnormalities, exhibiting a characteristic hemodynamic profile and natural history

• Multiple defects, separately inherited or acquired, act together to chronically raise BP

Secondary hypertension

• Although EH dominates the hypertensive population, a defined structural or hormonal cause for hypertension may be found in a small percentage of patients.

• Identification of such cases is important because the underlying conditions may require specific therapy different from that administered for EH, and these cases are often curable when identified early.

• If secondary hypertension is left uncontrolled, cardiovascular adaptations may develop, analogous to those of long-standing EH, that could cause the elevated pressures to persist even after the underlying cause is corrected

• Secondary forms should be considered in the workup of all patients with hypertension, there are clues that a given patient may have one of the correctable conditions, which is:

  • Age, If hypertension develops before age 20 or after age 50, secondary hypertension is more likely
  • Severity, Secondary hypertension often causes BP to rise dramatically
  • Onset, Secondary forms of hypertension often present abruptly in a patient who was previously normotensive
  • Associated signs and symptoms, The process that induces hypertension may give rise to other characteristic abnormalities, identified by the history and physical examination:
    • A renal artery bruit may be heard on abdominal examination in a patient with renal artery stenosis
    • EH patients often have hypertensive first-degree relatives, whereas secondary hypertension more commonly occurs sporadically

Patient evaluation

• The clinical evaluation of a patient with recently diagnosed hypertension begins with a careful history and physical examination, for clues to secondary forms

• Repeated urinary tract infections may suggest presence of chronic pyelonephritis with renal damage as the cause of hypertension, and excessive weight loss may be an indicator of pheochromocytoma

• Weight gain may point to the presence of Cushing syndrome which is a lifestyle behavior that may contribute to hypertension

• Obstructive sleep apnea is commonly associated with hypertension and should be considered particularly in patients who snore and have medications refractory to hypertension

• Laboratory tests performed include:

  • Urinalysis, measurement of Serum concentration of creatinine and blood urea nitrogen for assessment of renal abnormalities
  • Serum Potassium level (Often low in renovascular hypertension or primary aldosteronism)
  • Blood Glucose Level (Elevated in diabetes)
  • Serum Total and LDL Cholesterol, HDL Cholesterol and Triglyceride Levels to screen for vascular risk.
  • Electrocardiogram (for Evidence of induced LVH)

• If no suggest a secondary form of hypertension is found the patient is presumed to have EH and treated accordingly

• If BP remains elevated despite standard treatments, more detailed diagnostic testing for specific secondary causes may be undertaken.

Exogenous Causes

• Several medications can elevate BP, as an example oral contraceptives may cause secondary hypertension by increasing activity of the renin-angiotensin system
• Estrogens increase the hepatic synthesis of angiotensinogen, leading to greater production of angiotensin II (AII)
• AII raises BP by direct vasoconstriction and by stimulating the adrenal release of aldosterone.
• Aldosterone causes renal sodium retention, and therefore, increased intravascular volume
• Other medications that can raise BP include glucocorticoids, cyclosporine (an antirejection drug in patients with organ transplants), erythropoietin (prescribed to increase bone marrow red blood cell formation, but also elevates BP by increasing blood viscosity and reversing local hypoxic vasodilatation), and sympathomimetic drugs (common in over-the-counter cold remedies)
• Nonsteroidal anti-inflammatory drugs can contribute to hypertension through dose-related augmentation of renal sodium and water retention
• Two other substances that may contribute to hypertension are alcohol and cocaine
• Both are associated with increased sympathetic nervous system activity.

Renal causes

• Given kidney's role in the control of BP, it is not surprising that renal dysfunction can lead to hypertension
• Renal disease contributes to two endogenous causes of secondary hypertension: renal parenchymal disease and renovascular hypertension (renal arterial stenosis)

Renal parenchymal disease

• Renal damage to the kidney can result from diverse pathologic processes

Renal parenchymal disease mechanism of action

• The major mechanism by which injury leads to elevated BP is increased intravascular volume
• Damaged nephrons are unable to excrete normal amounts of sodium and water, leading to a rise in intravascular volume, elevated CO, and hence increased BP
• If renal function is only mildly impaired, BP may stabilize at a level at which the higher systemic pressure (and therefore renal perfusion pressure) enables sodium excretion to balance sodium intake
• Conversely, if a patient has end-stage renal failure, the glomerular filtration rate may be so decreased that the kidneys simply cannot excrete sufficient volume, and malignant-range BP may follow
• Renal parenchymal disease may further contribute to hypertension through the excessive elaboration of renin, even if the glomerular filtration rate is not severely reduced

Renovascular hypertension

• Stenosis of one or both renal arteries leads to hypertension
• Emboli, vasculitis, and external compression of the renal arteries can be responsible, but the two most common causes of RH are atherosclerosis and fibromuscular dysplasia
• Atherosclerotic lesions arise from plaque formation either within the renal artery or in the aorta at the origin of the renal artery
• Fibromuscular lesions consist of discrete regions of fibrous or muscular proliferation, generally within the arterial media

Renovascular Hypertension demographics.

• Atherosclerosis accounts for about two-thirds of cases of RH and occurs most commonly in elderly men.
• Fibromuscular dysplasia accounts for one-third of cases of RH and characteristically occurs in young women

Renovascular Hypertension mechanism of action

• The elevated BP in RH arises from reduced renal blood flow to the affected kidney, which responds to the lower perfusion pressure by secreting renin

• Renin increases the BP through the subsequent actions of All (vasoconstriction) and aldosterone (sodium retention)

• Diagnosis of RH is suggested by abdominal bruit or by unexplained hypokalemia

• The diagnosis can be confirmed by duplex Doppler ultrasonography, computed tomographic angiography (CTA), or magnetic resonance angiography of the renal arteries.

• Therapy of RH with antihypertensive drugs is effective, particularly when an ACE inhibitor or angiotensin receptor blocker is included

• These inhibitors of the renin-angiotensin system negate the hypertensive effects of elevated circulating renin in RH by impeding the formation or action of AII

• These classes of drugs should be avoided, or used cautiously, in patients with bilateral renal artery stenosis, The inhibition of AII may excessively reduce intraglomerular pressure and filtration, thereby worsening renal function

• In select patients with RH, percutaneous catheter interventions or surgical reconstruction of the stenosed vessel may be more effective than continued medical antihypertensive therapy alone.

Mechanical Causes

• Coarctation is an infrequently occurring congenital narrowing of the aorta, typically located just distal to the origin of the left subclavian artery

• The BP in the aortic arch, head, and arms is higher than that in the descending aorta, and can be caused by hypertension

• Hypertension in this condition arises by reduced kidney blood flow stimulating renin-angiotensin system

• High pressures proximal to the coarctation stiffen the aortic arch, blunting the normal baroreceptor response to elevated intravascular pressure

• Clinical clues to the presence of coarctation include symptoms of inadequate blood flow to the legs or left arm, and a midsystolic murmur

• Chest radiograph may show indentation of the aorta at the level of the coarctation

• Treatment options include angioplasty or surgical repair of the coarctation

• Hypertension may not abate completely after mechanical correction, in part because of persistent desensitization of the arterial baroreceptors

Endocrine causes

• Circulating hormones play an important role in the control of normal BP, so endocrine diseases may cause hypertension
• Suspected conditions are evaluated in four ways:
  • Characteristic Signs and Symptoms
  • Measurement of Harmone Levels
  • Assessment of harmone secretion in response to stimulation or inhibition
  • Imaging Studies to identify the source of excessive hormore secretion

Pheochromocytoma

• Pheochromocytomas are catecholamine-secreting tumors of neuroendocrine cells

• Release of epinephrine and norepinephrine by the tumor results in intermittent or chronic vasoconstriction, tachycardia, and other sympathetic-mediated effects

• The Paroxysmal rises in BP are accompanied by autonomic attacks, consisting of severe throbbing headaches, profuse sweating, palpitations, and tachycardia

• Ten percent of pheochromocytomas are malignant.

• Plasma levels of catecholamine are to identify this condition. Or obtain urine catecholamines and their metabolites (eg, vanillylmandelic acid and metanephrine)

• Pharmacologic therapy includes combination of an α-receptor blocker (eg, phenoxybenzamine) combined with a β-blocker

• However, once the tumor is localized by computed tomography, magnetic resonance imaging, surgical resection is required

Adrenocortical harmone excess

• Excess of mineralocorticoids and glucocorticoids, both lead to hypertension

Mineralocorticoids mechanism of action

• Primarily aldosterone, increase blood volume by augmenting reabsorption of sodium into the circulation by the distal portions of the nephron
• Mineralocorticoid activity also causes increased potassium excretion into the urine, and resulting hypokalemia is an important marker of mineralocorticoid activity
• Primary aldosteronism results from adrenal adenoma, or bilateral hyperplasia of the adrenal glands

Assessment of mineralocorticoids

The diagnosis may be suspected by the presence of hypokalemia or severe resistant is confirmed by Plasma aldosterone or a suppressed renin level.

Treatment of mineralocorticoids

• Therapy includes surgical removal of the responsible adenoma (if present)
• Medical management with mineralocorticoid receptor antagonists

Glucocorticoid-remediable aldosteronism

• GRA, is which aldosterone synthesis abnormally comes under the regulatory control of adrenocorticotropic hormone (ACTH)
• Presents as severe hypertension in childhood or young adulthood
• GRA-related BP elevation responds to glucocorticoid therapy, which suppresses ACTH release from the pituitary gland.

Secondary aldosteronism

• Secondary elevation of aldosterone occur in women taking oral contraceptives

Glucocorticoids excess

• Glucocorticoid excess, elevates blood pressure, which expands blood volume and stimulates systhesis for components in renin-angiotensin system.

• Cushing syndrome have some degree of hypertension

• Symptoms include a rounded facial appearance, central obesity, proximal muscle weakness, and hirsutism

• The cause of the excess glucocorticoids may be one of adrenal ACTH (adrenocorticotropic hormone). ACTH-secreting adrenal cortical or a tumour. diagnosis: collect urine over 24 hours for mensuration of cortisol. test: look for where exogenus gluticocorticorids can suppress cortisol secretion.

Thyroid Hormone Abnormalities

• Hyperthyroid and hypothyroid patients have hypertension -thyroid harmones increase blod volume.
• Hyper thyroid patients develop hypertension in cardiac hyperactivity: increase volume, hyper patients demonstrate, diastolic hyper pressure and increase in resistance.
• Activation of the Symp-thetic and adrenal activators mediated by the later affect.

Consequences of hypertension

• Similar effects causes: - high blood pressure is always symptomatic but causes effect of the organs.

Clinical signs and symptoms

• The term classics hypertension includes; Headaches, Dizziness etc.
• However the usefulness had been been called into question studies indicatung its not found regularly: patients in hypertension.
• Other side effects -flushing, blood in vision etc - those appear mmore important than just hypertension.
• Hypertension is not always symptomatic and is diagnosed by just physical exam.
• Several physical signs of hypertension include: LVH (left ventricular hypertrophy) and retinopathy arterial are present especially over the carotid and femoral arteries.

Organ damage caused by hypertension

• (target hypertension) target organ complication reflect degree and duration of BP elevation

• Such as heart - increases stroke risk and other complications that can lead to damage in: heart

• Arerial - damage from walls

• kidney

• retina

• Damage include smooth muscle hypertrophy, cell dysfunction and elastic fiber.

• Hypertension to endothelium, promotes: disrupts, protects, and damages arteries, and also results in plaque ruptures and blood clots.

• Major target: Heart, Cardiovascular system, kidneys, retina and damage in arteries. If untreated: 50% of hypertension

• Heart failure: 33% submit to the troke and 10/15% complication due to renal.

Heart

• Major cardiac - increase effect relate to pressure: accelerates.

Left ventricular Hypertrophy and diastolic dysfunction

• High pressure increases was tension
• Which compensates for hypertrophy, the most common hypertension: however, the high level of increase will dilate ventricle(primary aldostronism).
• LVH increasing stiffness LV and filling may increase diastolic fraction.

Hyper-tension/ physical symptoms

• LvH including -heaving in chest (increased muscles);
• Fourth heart sound L( as left atrium: contracts and stiffened LV. - one strongest for morbillidy and hypertension.
• degree of hypertrophy relates - the damage of Congestive Heat Failure, Angina, Arrthmi.
• Myocardinal infection, - the damage pf suddem damage.

Systolic dysfunction.

Although, LV mass is insufficient, increase pressure, also provoked damage leads to increase (ischema).

coronary Artery disease

• Major contribution and factor is in hypertensive. Reflect: accelerate arterial Sclerosis for blood.

Cardiovascular system

• Hypertension - main risk from Strokes - diastolic, magnitude for both those systems. Hyper-induced strokes: due to Hemorrhagic or- Atherothrombotic (more) which come break off and embolize off to Distel level,
• may from vessels.

Aotra Peripheral vasculature

• Asclerosis increases and leads increase of BP, as well as the arteries and leads to vessels.
• May lead to development of aneurysms in abdomen.

Kidney

Hypertensive-indused nephioscleriosis id the leading - the major cause is kinfey damage from- histology to arteries from.

• Smooth muscles increase -capillary wals damage(termed: ibrin old)
• Mild hypertension in 70% to leas from end stage renal failure.

Retina

• The retina is the only place which hypertension can be noticed by examination. -BP increase and damage. -High BP induced