SEMINAR LECTURE

SERIES
<<
John Michaelle Santos, RMT
Hypertension
HYPERTENSION
Epidemiology
● ≥60 years age – SBP of women > men
● Adults: DBP increases progressively with age
● ~55 years DBP decreases due to widening of pulse pressure
● Pulse pressure = SBP – DBP
● United States:
○ 1/3 is non-Hispanic blacks - around 33%
○ Increasing HTN due to obesity
○ African Americans (about 25%) prone to resistant HTN, hence,
more severe and causes higher morbidity and mortality
● Environmental and genetic factors contribute to regional and
racial variation in HTN prevalence
○ Obesity and overweight – strong, independent risk factors
○ Low calcium and potassium intake
○ Alcohol consumption, psychosocial stress, inactivity
Epidemiology
Mechanism
INTRAVASCULAR VOLUME
INTRAVASCULAR VOLUME
● CO = SV x HR
● SV = END DIASTOLIC VOLUME
● END SYSTOLIC VOLUME
● EDV - amount of blood that is being retained in the left ventricle
during the diastole
● ESV - amount of blood retained in the left ventricle during
systole or ejection
INTRAVASCULAR VOLUME
● Sodium
○ Predominant extracellular ion
○ Primary determinant of extracellular fluid volume
○ Increase NaCl intake → increase vascular volume
■ Exceeds capacity of kidney to excrete sodium
■ Increase cardiac output
● Autoregulation
○ To maintain constant blood flow: increased arterial
pressure… increase resistance w/n that bed
INTRAVASCULAR VOLUME
AUTONOMIC NERVOUS SYSTEM
● Adrenergic reflexes modulate blood pressure over the short term
● Adrenergic function contributes to the long-term regulation of
arterial pressure
● Norepinephrine, epinephrine, and dopamine
● Adrenergic neurons synthesize norepinephrine and dopamine which are
stored in the vesicles within the neurons
● Epinephrine is synthesized in the adrenal medulla and released into
the circulation upon adrenal stimulation
● Adrenergic receptors are mediated by guanosine nucleotide-binding
regulatory proteins (G proteins)
AUTONOMIC NERVOUS SYSTEM
● Adrenergic receptors: α and β
● α-receptors are occupied and activated norepinephrine
○ Alpha 1 – post synaptic cell of smooth muscle →
vasoconstriction
○ Alpha 1 – kidney → increases renal tubular reabsorption of
sodium
○ Alpha 2 – presynaptic membranes of postganglionic nerve
terminals that synthesize NE
● β-receptors activated more by epinephrine
○ Beta 1 – heart → stimulates the rate and strength of
cardiac contraction → increase CO
○ Beta 1 – kidney → stimulates renin release →
vasoconstriction
○ Beta 2 → smooth muscles → relaxes vascular smooth muscle →
vasodilation
AUTONOMIC NERVOUS SYSTEM
● Arterial baroreflex is mediated by stretch-sensitive sensory nerve
endings
○ Carotid sinuses and the aortic arch
● Rate of firing of these baroreceptors increases with arterial
pressure → decrease in sympathetic outflow → decrease arterial
pressure and HR
● This is a primary mechanism for rapid buffering of acute
fluctuations of arterial pressure that may occur during postural
changes, behavioral or physiologic stress, and changes in blood
volume.
● Activity of the baroreflex declines or adapts to sustained
increases in arterial pressure → baroreceptors are reset to higher
pressures
RENAL ANGIOTENSIN ALDOSTERONE
● The renin-angiotensin-aldosterone system
○ mediated by hypovolemia
● Three primary stimuli for renin secretion:
○ 1. Decreased NaCl transport
○ 2. Decreased pressure or stretch within the renal afferent
arteriole (baroreceptor mechanism)
○ 3. Sympathetic nervous system stimulation
RENAL ANGIOTENSIN ALDOSTERONE
RENAL ANGIOTENSIN ALDOSTERONE
● Renin increased in the following:
○ 1. Renin-secreting tumors Kidney: benign hemangiopericytomas of
the juxtaglomerular apparatus, renal carcinomas, including
Wilm’s tumors
○ 2. Renin-producing carcinomas: described in lung, liver,
pancreas, colon, and adrenals
○ 3. Renovascular hypertension
○ 4. Obstruction of the renal artery
○ 5. Secondary renal damage: less renindependent
RENAL ANGIOTENSIN ALDOSTERONE
● Angiotensin II is the primary tropic factor regulating the
synthesis and secretion of aldosterone
● Aldosterone synthesis is also dependent on potassium
● Adrenocorticotropic hormone is not an important tropic factor for
the chronic regulation of aldosterone
● Bad effects: fibrosis, endothelial dysfunction, inflammation, and
oxidative stress → increase cardiovascular morbidity and mortality
● Cortisol binds to the mineralocorticoid’s receptor but functions as
a less potent mineralocorticoids than aldosterone
○ Cortisol is converted to cortisone by the enzyme
○ Cortisone has no affinity for the mineralocorticoid receptor
RENAL ANGIOTENSIN ALDOSTERONE
● Primary aldosteronism – mineralocorticoidmediated hypertension
○ Adrenal aldosterone synthesis and release are independent of
renin-angiotensin
○ Renin release is suppressed by the resulting volume expansion
○ High circulating levels of aldosterone → glomerular
hyperfiltration and albuminuria
VASCULAR MECHANISMS
● Vascular radius and compliance of resistance arteries are important
determinants of arterial pressure
○ Hypertension: structural, mechanical, or functional changes
■ Remodeling takes place - geometric alterations in the
vessel wall without a change in vessel volume.
■ Hypertrophic (increased cell size, and increased deposition
of intercellular matrix) or eutrophic vascular remodeling
results in decreased lumen size and, hence, increased
peripheral resistance.
■ Due to apoptosis, low-grade inflammation, and vascular
fibrosis
○ Association between arterial stiffness and hypertension
VASCULAR MECHANISMS
● Vascular endothelium synthesizes and releases several vasoactive
substances
○ Nitric oxide, a potent vasodilator
○ Endothelium-dependent vasodilation is impaired in hypertensive
patients
○ High-resolution ultrasonography before and after the hyperemic
phase of reperfusion that follows 5 minutes of forearm
ischemia.
IMMUNE MECHANISMS, INFLAMMATION,
AND OXIDATIVE STRESS
● Inflammation and alterations of the immune response implicated in
the pathogenesis of vascular injury and hypertension
● Immunity
● Inflammation, vascular stretch, angiotensin II, and salt have all
been shown to result in the generation of reactive oxygen species →
modify T cell function → enhance inflammation
○ ROS (reactive oxygen species)within the renal medulla is a key
determinant of the set point of the renal pressure natriuresis
curve
● Oxidative stress disrupts pressure-natriuresis
PATHOLOGIC CONSEQUENCES OF
HYPERTENSION
● Heart
○ Heart disease: most common cause of death in hypertensive
patients
○ Effect: structural and functional damage
■ LVH, CHF, atherosclerotic CAD and microvascular disease,
and cardiac arrhythmias (AF)
○ CHF: systolic dysfunction due to low ejection fraction,
diastolic dysfunction due to preserved ejection fraction
○ Diastolic dysfunction: early consequence of hypertension-
related heart disease
■ Exacerbated by left ventricular hypertrophy and ischemia
○ Diagnostics
■ Cardiac catheterization provides the most accurate
assessment of diastolic dysfunction
■ Echocardiography
■ Radionuclide angiography
PATHOLOGIC CONSEQUENCES OF
HYPERTENSION
● Brain
○ Stroke is the second most frequent cause of death in the world
○ Elevated blood pressure is the strongest risk factor for stroke
■ Ischemic or hemorrhagic
■ Approximately 85% of strokes are due to infarction, and the
remainder are due to either intracerebral or subarachnoid
hemorrhage.
○ Associated with impaired cognition
■ Beta amyloid deposition in dementia
■ Single infarct dues to occlusion of a “strategic” larger
vessel or multiple lacunar infarcts due to occlusive small
vessel disease resulting in subcortical white matter
ischemia
PATHOLOGIC CONSEQUENCES OF
HYPERTENSION
● Brain
○ Hypertensive encephalopathy
■ Impaired autoregulation of blood flow → vasodilation and
hyperperfusion
■ Severe headache, nausea and vomiting (often of a projectile
nature), focal neurologic signs, and alterations in mental
status
■ Progress to stupor, coma, seizures, and death within hours
PATHOLOGIC CONSEQUENCES OF
HYPERTENSION
● Kidney
○ The kidney is both a target and a cause of hypertension.
○ Primary renal disease is the most common etiology of secondary
HTN
○ MECHANISMS: diminished capacity to excrete sodium, excessive
renin secretion in relation to volume status, and sympathetic
nervous system overactivity
○ Risk factor for renal injury and ESRD
○ Macroalbuminuria (a random urine albumin/creatinine ratio >300
mg/g) or microalbuminuria (a random urine albumin/creatinine
ratio 30-300 mg/g)
■ Early markers of renal injury - take note for proteinuria -
early marker of renal injury
■ Risk factors for renal disease progression and
cardiovascular disease
HYPERTENSION DEFINITION
HYPERTENSION DEFINITION
HYPERTENSION DEFINITION
CLINICAL DISORDERS OF HYPERTENSION
● ~80-95% of hypertensive patients are diagnosed as having primary,
or “essential” hypertension
● 5-20% of hypertensive patients has specific underlying disorder
causing the elevation of blood pressure can be identified
● “Secondary” hypertension, a specific mechanism for the blood
pressure elevation is often more apparent
CLINICAL DISORDERS OF HYPERTENSION
● Obesity and the Metabolic Syndrome
○ Cross-sectional studies indicate a direct linear
correlation between body weight and blood pressure
○ Centrally located body fat is a more important determinant
of blood pressure elevation that is peripheral body fat
○ Dyslipidemia and insulin resistance occurs with HTN- this
clustering of risk factors is often, but not invariably,
associated with obesity, particularly abdominal obesit
○ AE: increase cardiovascular morbidity and mortality
○ Metabolic Syndrome - Constellation of insulin resistance,
abdominal obesity, hypertension, and dyslipidemia
CLINICAL DISORDERS OF HYPERTENSION
● SECONDARY HYPERTENSION
CLINICAL DISORDERS OF HYPERTENSION
● SECONDARY HYPERTENSION
○ Renal Parenchymal Diseases
○ Renovascular Hypertension
○ Primary Aldosteronism
○ Cushing’s Syndrome
○ Pheochromocytoma
○ Miscellaneous Causes
■ Obstructive sleep apnea
■ Coarctation of the aorta
■ Thyroid diseases and acromegaly
■ Hypercalcemia in primary hyperparathyroidism
■ Drugs:
● High-dose estrogens, adrenal steroids,
decongestants, appetite suppressants,
cyclosporine, tricyclic antidepressants, monoamine
oxidase inhibitors, erythropoietin, nonsteroidal
anti-inflammatory agents, cocaine
APPROACH TO THE PATIENT WITH
HYPERTENSION
● History and Physical Examination
APPROACH TO THE PATIENT WITH
HYPERTENSION
● Laboratory Testing
Treatment
● Lifestyle Interventions/modifications
○ Diet, exercise, maintain healthy weight
○ Salt – sodium intake of 2.0 per day (about 5.0 g salt, one
small teaspoon)
○ Alcohol – in moderation to no more than 2030 g of alcohol
per day in men and 10-20 g of alcohol per day in women
Treatment
● Pharmacologic Therapy
○ Diuretics
■ Thiazides
● may be used alone or in combination with other
antihypertensive drugs
● Inhibit the Na+/Cl-pump in the distal convoluted
tubule
● Side effects: hypokalemia, insulin resistance,
increased cholesterol
■ Chlorthalidone
● Structurally similar to hydrochlorothiazide
● It blocks sodium-chloride cotransport in the early
distal tubule
Treatment
● Pharmacologic Therapy
○ Blockers of the Renin-Angiotensin System
■ ACEI or ARB
■ Valsartan has been shown to reduce the risk of
developing diabetes in high-risk hypertensive patients
■ Aliskiren is the first of a class of oral direct
inhibitor of renin activity
■ Adverse Effects:
● Functional renal insufficiency due to efferent
renal arteriolar dilation in a kidney with a
stenotic lesion of the renal artery
● Dry cough and angioedema – ACEI
● Hyperkalemia due to hypoaldosteronism
Treatment
● Pharmacologic Therapy
○ Aldosterone Antagonists
■ Spironolactone
■ Eplerenone
○ Beta blockers
■ β-adrenergic receptor blockers
● Lower blood pressure by decreasing cardiac output
● Reduction of heart rate and contractility
● Central nervous system with effect inhibition of
renin release
○ Alpha-adrenergic Blockers
■ Decreasing peripheral vascular resistance
○ Centrally Acting α2-sympathetic agonists
■ Decrease peripheral resistance by inhibiting
sympathetic outflow
■ Decrease peripheral resistance and venous constriction
■ Clonidine, Methyldopa
Treatment
● Pharmacologic Therapy
○ Calcium Channel Blockers
■ L-channel blockade → reduces intracellular calcium and
blunts vasoconstriction
■ Three classes: Phenylalkylamines (Verapamil),
benzothiazepines (Diltiazem), and dihydropyridines
(Nifedipine-like)
○ Direct Vasodilators
■ Decrease peripheral resistance
■ Hydralazine – induce a lupus-like syndrome
■ Minoxidil – used most frequently in patients with
renal insufficiency
■ Nitroprusside – can be used to treat malignant
hypertension
MALIGNANT HYPERTENSION
● Syndrome associated with an abrupt increase of blood pressure in a
patient with underlying hypertension or related to the sudden onset
of hypertension in a previously normotensive individual.
● the syndrome is recognized by progressive retinopathy (arteriolar
spasm, hemorrhages, exudates, and papilledema), deteriorating renal
function with proteinuria, microangiopathic hemolytic anemia, and
encephalopathy.
RESISTANT HYPERTENSION
● Blood pressures persistently >140/90 mmHg despite taking three or
more antihypertensive agents, including a diuretic
● More common in patients aged >60 years
● Related to “pseudo resistance”
○ High office blood pressures and lower home blood pressures
○ Nonadherence to therapy
○ Identifiable causes of hypertension (obesity and excessive
alcohol intake)
○ The use of any of number of nonprescription and
prescription drugs