Hypertension: Types, Complications, and Classification

Hypertension Basics

• Hypertension is blood pressure high enough to pose a risk to overall health.

Essential Hypertension

• Essential hypertension has an unknown cause for blood pressure elevation.
• This type affects ~90% of hypertension patients.
• Essential hypertension is caused by multiple and diverse factors.

Secondary Hypertension

• Secondary hypertension results from a known underlying cause.
• Many of the causes are treatable with a permanent cure.
• Understanding the pathophysiology of high blood pressure leads to discovering more secondary hypertension causes.

Vascular Complications

• The risk of vascular complications from hypertension increases with higher blood pressure values.
• Cutoff points used to define hypertension stages are somewhat arbitrary.

Blood Pressure Classifications:

• Normal blood pressure has a systolic reading 130/80.

Defining Hypertension

• A diagnosis of hypertension necessitates 2 high readings from at least 2 separate occasions.

Blood Pressure Formulas

• Blood pressure = Cardiac Output (CO) x Total Peripheral Resistance (TPR).
• Cardiac Output = Stroke Volume (SV) x Heart Rate (HR).

Stroke Volume Determinants

• Contractility
• Preload
• Afterload

Blood Pressure Determinants

• The heart supplies pumping pressure.
• Blood vessel tone determines systemic resistance.
• The kidney regulates intravascular volume.
• Renal excretion can completely normalize blood pressure, regardless of cardiac output or total peripheral resistance.
• Maintenance of chronic hypertension necessitates renal participation.
• Increased blood pressure leads to augmented urine volume and sodium excretion in normal kidneys (pressure natriuresis).
• Blunted pressure natriuresis is when higher pressure is required to excrete sodium and water in hypertensive kidneys.
• Hormonal factors and tubulointerstitial injury may cause blunted pressure natriuresis.
• Hormones modulate the functions of the heart, blood vessels, and kidneys.

Baroreceptor Reflex

• Baroreceptors are located in the aortic arch and carotid sinuses.
• These receptors sense stretch and deformation of the arteries.
• Increased pressure leads to impulse transduction to the CNS (medulla oblongata), triggering negative feedback via the autonomic nervous system to decrease blood pressure by:
  • Decreasing peripheral vascular resistance (vasodilation)
  • Decreasing CO (lower HR and reduced contractility)
• Decreased blood pressure leads to fewer impulses to medulla oblongata, increasing blood pressure.
• Carotid sinus receptors communicate via the glossopharyngeal nerve (CN IX).
• Aortic arch receptors communicate via the vagus nerve (CN X).

Genetics and Epidemiology of Essential Hypertension

• Heredity plays a strong role in essential hypertension.
• First-degree relatives of hypertensive patients are more likely to have it.
• Identical twins show concordance for hypertension.
• Essential hypertension involves a polygenic disorder.
• Polymorphisms occur in genes for:
  • Angiotensinogen
  • Angiotensin-Converting Enzyme (ACE)
  • Angiotensin Type 1 Receptor
  • Aldosterone Synthase
  • Alpha-Adducin (renal tubular sodium absorption)
• Inheritance patterns of obesity, insulin resistance, and diabetes overlap with hypertension.
• Environmental factors such as socioeconomic status, exercise patterns, and healthcare access play a role.

Systemic Abnormalities in BP Regulation

• Systemic abnormalities include heart defects, in BP regulation, high CO based hypertension and sympathetic overactivity
• Vascular tone: peripheral vascular resistance, based hypertension sympathetic activity
• Abnormal regulation of the vascular tone (NO, endothelin, natriuretic factors)

Experimental Findings with Essential Hypertension

• Defects in BP regulation include systemic abnormalities affecting the heart, vascular tone, and kidneys.
• The heart may exhibit high CO-based hypertension due to sympathetic overactivity.
• Vascular tone may show peripheral vascular resistance-based hypertension with increased sympathetic activity or abnormal tone regulation (NO, endothelin, natriuretic factors).
• Ion channel defects can occur in contractile smooth muscle cells (SMC).
• Volume-based hypertension, excess sodium retention and water, failure to regulate renal blood flow, Ion channel defects, reduced basolateral Na+/K+ ATPase, inappropriate hormone regulation
• Renin levels should be suppressed by high BP

Insulin Resistance, Obesity, and Metabolic Syndrome

• Elevated serum glucose increases insulin, causing sympathetic activation or SMC hypertrophy.
• Obesity is directly associated with hypertension.
• Angiotensinogen is released from adipocytes.
• Blood volume increases with body mass.
• Blood viscosity increases due to adipocyte release of profibrinogen and plasminogen activator inhibitor 1.
• Metabolic syndrome includes atherogenic risk factors, hypertension, hypertriglyceridemia, low serum HDL, glucose intolerance, and truncal obesity.

Natural History of Essential Hypertension

• Essential hypertension typically arises after young adulthood.
• Prevalence increases with age.
• Over 60% of Americans over 60 are hypertensive.
• Hemodynamic characteristics of elevated blood pressure in essential hypertension change over time.
• Systolic pressure increases throughout adult life.
• Diastolic pressure increases until about age 50, then declines slightly.
• Diastolic hypertension is more common in young people, displaying augmented CO as the primary abnormality.
• Isolated systolic hypertension (over age 50) occurs with normal diastolic values, along with elevated TPR.

Defining Secondary Hypertension

• Secondary hypertension is defined by a structural or hormonal cause.
• Treatments differ from those for essential hypertension and are often curable when identified early.

Clues for Secondary Hypertension

• Age: 50 suggests secondary hypertension.
• Severity: secondary hypertension often causes dramatic increases in blood pressure, while essential hypertension is usually mild to moderate.
• Onset: secondary hypertension often presents abruptly in a previously normotensive patient, while essential hypertension progresses gradually.
• Signs/symptoms: Renal artery bruit in a hypertensive patient suggests secondary hypertension.
• Family history: Essential hypertension often occurs in first-degree relatives, while secondary hypertension occurs sporadically.

Patient Evaluation for Secondary Hypertension

• Perform lab tests, including a urinalysis and serum concentration of creatinine and blood urea nitrogen, to reveal renal abnormalities.
• Measure serum potassium levels; low levels may indicate renovascular hypertension or primary aldosteronism.
• Measure blood glucose levels, as elevated levels suggest diabetes.
• Check serum total LDL, HDL, and triglyceride levels.
• Perform an electrocardiogram (LVH).
• If no abnormalities are found, assume essential hypertension.

Common Symptoms of Secondary Hypertension

• Recurring UTIs suggest chronic pyelonephritis with renal damage.
• Excessive weight loss suggests pheochromocytoma.
• Weight gain suggests Cushing syndrome.

Exogenous Causes of Secondary Hypertension

• Oral contraceptives increase RAAS, specifically 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
• Cocaine

Renal Causes of Secondary Hypertension

• Renal parenchymal disease accounts for 2-4% of hypertension cases.
• Damaged nephrons cannot excrete normal Na+ H2O, leading to increased intravascular volume and cardiac output.
• Excessive renin elaboration is possible even when the filtration rate is not severely reduced.
• Renovascular hypertension accounts for ~1% of hypertension cases.
• Reduced blood flow past the stenotic region leads to decreased kidney perfusion, resulting in renin secretion. Abdominal bruit (40-60% affected patients) or unexplained hypokalemia suggests diagnosis.
• Diagnosis confirmed by doppler ultrasonography, CTA, or MRA.
• Therapy effective with ACE inhibitors or ARBs; avoid with bilateral stenosis.
• Atherosclerosis (⅔ of renovascular hypertension) occurs mostly in elderly men.
• Fibromuscular lesions (⅓ of renovascular hypertension) occur usually in young women.

Mechanical Causes of Hypertension

• Coarctation of the aorta is a congenital narrowing of the aorta.
• Blood pressure is higher in the aortic arch, head, and arms than in the descending aorta, branches, and lower extremities.
• Sometimes, pressure in the left arm is lower compared to the right arm (subclavian artery).
• A midsystolic murmur can be heard between the scapulae.
• Radiography may show coarctation.
• Surgical repair or angioplasty treats coarctation, but hypertension may persist due to a blunted baroreceptor response.
• Hypertension from coarctation arises from reduced flow to the kidney, increasing renin, and accelerated atherosclerosis from the stiffened aortic arch, blunting the baroreceptor response.

Endocrine Causes of Hypertension

• Diagnostic evaluation includes characteristic signs/symptoms, hormone level measurement, assessment of hormone secretion, and imaging studies.
• Pheochromocytoma accounts for ~0.2% of hypertension cases; catecholamine-secreting tumors in neuroendocrine cells in the adrenal medulla cause episodic secretion.
• Symptoms include intermittent/chronic vasoconstriction, tachycardia, and sympathetic-mediated effects.
• Paroxysmal rises in blood pressure are accompanied by autonomic attacks (severe headache, sweating, palpitations, tachycardia).
• Approximately 10% are malignant.
• Measure plasma/urine catecholamine levels and metabolites (vanillylmandelic acid and metanephrine) to identify pheochromocytoma.
• Use alpha and beta-receptor blockers and biosynthesis inhibitors.
• Surgical resection is the definitive therapy.

Adrenocortical Hormone Excess

• Excess mineralocorticoids (aldosterone) causes hypokalemia
• Primary aldosteronism results from an adrenal adenoma or bilateral hyperplasia of adrenal glands.
• Primary aldosteronism may be as high as 10-15% among hypertensive patients
• Excessive aldosterone and suppressed renin level
• Glucocorticoid-remediable aldosteronism is a uncommon hereditary form of primary aldosteronism
• Glucocorticoid-remediable Aldosteronism is aldosterone under control of ACTH Severe hypertension in childhood/young adulthood and responds to glucocorticoid therapy (ACTH suppression)
• Secondary aldosteronism
• Increased All production stimulated by renin-secreting tumors and can be caused by oral contraceptives or impaired All degradation in liver dysfunction
• Excess Glucocorticoids (cortisol)
• Excess Glucocorticoids increases blood pressure, causing ↑BP by blood volume expansion and synthesis of components of RAAS
• Excess Glucocorticoids activates mineralocorticoid receptors in renal tubules (sodium retention and K+ excretion)
• Excess Glucocorticoids causes 80% of cushing syndrome patients have hypertension
• Cushingoid features include round face, central obesity, proximal muscle weakness, hirsutism.
• It can be caused by ACTH secreting adenoma or tumor or adrenal cortisol secreting adenoma
• Thyroid hormone abnormalities
• ⅓ of hyperthyroid and ¼ hypothyroid patients have hypertension, affect cardiovascular system

Consequences of Hypertension

• Clinical Signs and Symptoms
• Classic symptoms include headache, epistaxis, dizziness
• Flushing, sweating, and blurred vision are more common in hypertensive populations
• Physical signs include include LVH, retinopathy, arterial bruits
• Organ damage
• Elevated BP and atherosclerosis increase cardiac workload and arterial damage
• Atherosclerosis of large arteries hinders the elasticity, resulting in spikes of systolic pressure
• CAD or congestive heart failure, stroke, renal failure is caused by Untreated hypertension

Cardiovascular Manifestations:

• ↑Afterload causes concentric hypertrophy and diastolic dysfuntion.
• LV impulse, S4 sounds indicate the onset of heart failure.
• Degree of hypertrophy correlates to congestive heart failure, angina, arrhythmias, MI, and sudden cardiac death.
• Systolic dysfunction: LV mass is insufficient to balance high wall tension leading to ↓CO, pulmonary congestion
• CAD: Accelerated coronary atherosclerosis, ventricular wall rupture, LV aneurysm, and congestive heart failure

Cerebrovascular and Vasculature Effects:

• Hypertension is a modifiable stroke risk factor
• Systolic htn is closely linked to CVAs.
• Damage from cerebrovascular accidents include rupture of microaneurysms, thrombi formation, small arteries infarcts, wbc, reduces collateral blood flow.

Aorta and Peripheral Vasculature Damage:

• Hypertension can be most common in lower extremities, neck and brain
• Abdominal aortic aneurysm includes dilation of blood vessels below renal levels
• An aortic aneurysm larger than 6cm has very high likelihood of rupture
• Aortic dissection includes degenerative changes in the media, high pressure may cause intima to tear/propagate further, rigorous BP control or surgical repair needed

Kidney Damage and Renal Artery Stenosis

• Htn causes Nephrosclerosis which is leading cause of kidney failure
• Vessel walls thickening with hyaline infiltrate is caused by Hyaline Arteriolosclerosis
• Smooth muscle hypertrophy and necrosis of capillary walls is caused by Fibrinoid Necrosis
• Result in reduced vascular supply and ischemic atrophy of tubules and glomeruli
• Perpetuation of ↑BP in hypertensive renal failure due to kidney failing to regulate blood volume

Retinal Damage

• Htn allows Systemic arteries be visualized by physical examination
• Hypertensive retinopathy - damage to vessels caused by high BP
• Acute hypertension - Hemorrhage/exudation of plasma lipids, local infarction/ischemia of the optic nerves, loss of vision
• Papilledema - Swelling of optic disk from high intracranial pressure when cerebrovascular autoregulation fails
• Chronic hypertension - Arterial narrowing, sclerosis, medial hypertrophy/crossing veins

Hypertensive Crisis

• Hemodynamic insult (eg: renal acute disease) superimposed on chronic state
• Rapid pathologic changes such as fibrinoid necrosis (spiraling htn), volume expansion and vasoconstriction (↓renal profusion), with ↑renin and ↑angiotensin hormones
• Encephalopathy from ↑intracranial pressure with blurred vision, headache, confusion, somnolence and coma
• Retinal damage with vessel damage
• Angina, pulmonary edema and ventricular load

Treatment of Hypertension

• Non-immediate therapy effective with environmental role
• "White coat effect": patient anxiety causing ↑BP reading
• Reliable results with multiple readings taken at 2+ visits
• Confirm diagnosis/adjust medications with outside measurement
• Daily measurement to predict cardiovascular mortality
• Goal BP <130/80

Nonpharmacologic Treatment

• Obesity accounts for 40-60% of hypertension
• 10kg weight loss causes 5-20mmHg fall in blood pressure
• High correlation between hypertension and obesity
• Sedentary people have 20-50% higher risk of hypertension, Aerobic exercise (jogging/walking/bicycling) shown to ↓BP by reducing sympathetic tone
• Salt reduction is essential
• Decreasing Na+ intake can help since pt's have defects in natriuresis
• African-Americans and elderly are more sensitive to salt intake
• A low salt diet increases the effectiveness of antihypertensive meds
• <6g of NaCl, ½ less than avg person recommended
• Potassium helps repletes low serum K+ levels when taking K+ diuretics
• Normokalemic pt's do not need K+ supplements
• Systolic BP rises acutely following alcohol consumption
• Low Ca2, Mg2 and Caffeine are associated with ↑BP
• Quitting smoking is key
• Nictoine and atherosclerosis increase BP
• Apnea treatment decreases BP
• Relaxation is helpful with ↓stress
• Biofeedback and meditation are useful