Hypertension

PES Institute of Medical Sciences & Research
Topic :
Presenter : Dr. Shodhan Patel
Designation : 1st yr PG
Department : GENERAL MEDICINE
Moderator : Dr. Harshavardhan

Epidemiology
• obesity ad weight gain are strong, independent risk factors for
hypeertension
• age related increase in blood pressure may be augmented by
a high NaCl intake.
• low dietary intake of calcium and potassium also may
contribute to risk of hypertension
• the urine sodium-to-potassium ratio (an index of both sodium
and potassium intake) is a stronger correlate of blood
pressure than is either sodium or potassium alone
• alcohol consumption, psychosocial stress and low levels of
physical activity also may contribute to hypertension

Mechanisms of Hypertension
1. Intravascular Volume:
• Primary renal disease is the most common etiology of secondary hypertension.
• Mechanisms of kidney-related hypertension include a diminished capacity to
excrete sodium, excessive renin secretion in relation to volume status, and
sympathetic nervous system overactivity.
• Determinants of arterial
pressure:

Contd..
• Pressure-natriuresis:
• As arterial pressure increases in response to a high NaCl intake, urinary sodium
excretion increases and sodium balance is maintained at the expense of an
increase in arterial pressure.
• This phenomenon may involve a subtle increase in the glomerular filtration rate,
decreased absorbing capacity of the renal tubules, and possibly hormonal factors
such as atrial natriuretic factor.

Contd...
• NaCl-dependent hypertension may be a consequence of a decreased
capacity of the kidney to excrete sodium, due either to intrinsic renal
disease or to increased production of a salt-retaining hormone (mineralo-
corticoid) resulting in increased renal tubular reabsorption of sodium.
• End stage renal disease (ESRD) is an extreme example of volume
dependent hypertension.

2. AUTONOMIC NERVOUS SYSTEM
• Adrenergic reflexes modulate blood pressure over the short term
• Norepinephrine, epinephrine, and dopamine all play important roles in
tonic and phasic cardiovascular regulation
• The activities of the adrenergic receptors are mediated by guanosine
nucleotide-binding regulatory proteins (G proteins) and by intracellular
concentrations of downstream second messengers.

Contd...
• Adrenergic receptors have been divided into two principal types: α and β.
These types have been differentiated further into α1, α2, β1, and β2
receptors.
• α Receptors are occupied and activated more avidly by norepinephrine
than by epinephrine, and β receptors by Epinephrine > Norepinephrine
• α1 Receptors are located on postsynaptic cells in smooth muscle and
elicit vasoconstriction

Contd...
• α2 Receptors are localized on presynaptic membranes of postganglionic
nerve terminals that synthesize norepinephrine and when activated by
catecholamines, α2 receptors act as negative feedback controllers,
inhibiting firther norepinephrine release
• In the kidney, activation of α1-adrenergic receptors increases renal
tubular reabsorption of sodium
• Different classes of antihypertensive agents either inhibit α1 receptors or act as
agonists of α2 receptors and reduce systemic sympathetic outflow

Contd...
• Myocardial β1 receptors stimulates the rate and strength of cardiac
contraction and consequently increases cardiac output
• β1 Receptor activation also stimulates renin release from the kidney
• Another class of antihypertensive agents acts by inhibiting β1 receptors.
Activation of β2 receptors by epinephrine relaxes vascular smooth muscle and
results in vasodilation.

Contd...
• Baroreceptors increases with arterial pressure, and the net effect is a
decrease in sympathetic outflow, resulting in decreases in arterial
pressure and heart rate.
• Baroreflex control of blood pressure deteriorates with advancing age,
hypertension, and atherosclerosis.
• Pheochromocytoma is the most blatant example of hypertension related
to increased catecholamine production

3. VASCULAR MECHANISMS
• Vascular radius and compliance of resistance arteries are important
determinants of arterial pressure.
• Hypertrophic (increased cell size and increased deposition of
intercellular matrix) or eutrophic vascular remodeling results in
decreased lumen size and, hence, increased peripheral resistance.
• Increased arterial stiffness results in increased pulse wave velocity of
both incident and reflected waves. The consequence is augmentation of
aortic systolic pressure and a reduction of aortic diastolic pressure, i.e.,
an increase in pulse pressure

Contd...
• Activity of the Na+-H+ exchanger is increased in hypertension, and this
may result in increased vascular tone.
• Endothelin is a vasoconstrictor peptide produced by the endothelium,
and orally active endothelin antagonists may lower blood pressure in
patients with resistant hypertension.

4. IMMUNE MECHANISMS, INFLAMMATION, AND
OXIDATIVE STRESS
• T cells and B cells of immune system causes vascular injury
• Reactive Oxygen Species (ROS) within the renal medulla
may disrupt pressure-natriuresis and thereby potentiate the
development of hypertension

PATHOLOGIC CONSEQUENCES OF
HYPERTENSION
 HEART:
• Hypertensive heart disease is the result of structural and functional adaptations
leading to left ventricular hypertrophy, increased atrial size, CHF, atherosclerotic
coronary artery disease, microvascular disease, and cardiac arrhythmias,
including atrial fibrillation
 BRAIN
• Stroke
• Cognitive decline (by deposition of beta amyloid)
• Multiple lacunar infarcts (due to occlusion of small vessels)
• Hypertensive encephalopathy

Contd...
 KIDNEY
• Focal necrsis of the glomerular tuft
• Renal injury
• ESRD
 PERIPHERAL ARTERIES
• Periperal Arterial Disease ( Ankle- Brachial index <0.90)
• Arterial stiffness
• Vascular remodelling

Defining Hypertension
• Clinically hypertension may
be defined as that level of
blood pressure at which the
institution of therapy reduces
blood pressure–related
morbidity and mortality
• Hypertension be defined as
systolic blood pressure ≥130
mmHg or diastolic blood
pressure ≥80 mmHg

Note:
• Cardiovascular disease risk doubles for every 20-mmHg increase in
systolic and 10-mmHg increase in diastolic pressure
• Night time blood pressures are generally 10–20% lower than daytime
blood pressures, and an attenuated night time blood pressure “dip” is
associated with increased cardiovascular disease risk
• The rate of rise of blood pressure in the early morning (blood pressure
“surge”) may also predict a higher risk of cardiovascular event

Contd...
 White coat hypertension:
Elevated office blood pressures with normal ambulatory readings
 Masked hypertension:
normal office blood pressure and elevated out-of-office blood pressure

PRIMARY HYPERTENSION
• Primary hypertension tends to be familial and is likely to be the
consequence of an interaction between environmental and
genetic factors.
• In younger patients with mild or labile hypertension, cardiac
output may be increased and peripheral resistance may be
normal

Secondary causes for Hypertension

Rare Mendelian forms of Hypertension

OBESITY AND THE METABOLIC SYNDROME
• Centrally located body fat is a more important determinant of blood
pressure elevation than is peripheral body fat
• Hypertension and dyslipidemia frequently occur together and in
association with resistance to insulin-stimulated glucose uptake
• The constellation of insulin resistance, abdominal obesity, hypertension,
and dyslipidemia has been designated as the metabolic syndrome
• An antinatriuretic effect of insulin may contribute to the development of
hypertension

RENAL PARENCHYMAL DISEASES
• Renal disease is the most common cause of secondary hypertension
• Hypertension is present in >80% of patients with chronic renal failure
• Hypertension is more severe in glomerular diseases than in interstitial
diseases such as chronic pyelonephritis
• Proteinuria >1000 mg/d and an active urine sediment are indicative of
primary renal disease.

RENOVASCULAR HYPERTENSION
• Hypertension due to an occlusive lesion of a renal artery, renovascular
hypertension, is a potentially curable form of hypertension
• Renovascular hypertension should be considered in patients with other
evidence of atherosclerotic vascular disease
• Severe or refractory hypertension, recent loss of hypertension control or
recent onset of moderately severe hypertension, carotid or femoral artery
bruits, flash pulmonary edema, and unexplained deterioration of renal
function or deterioration of renal function associated with an angiotensin-
converting enzyme inhibitor (ACEI) should raise the possibility of
renovascular hypertension

Contd...
• Contrast arteriography remains the “gold standard” for evaluation and
identification of renal artery lesions.
• If renal artery stenosis is suspected and if the clinical condition warrants
an intervention such as percutaneous transluminal renal angioplasty
(PTRA), placement of a vascular endoprosthesis (stent), or surgical renal
revascularization, imaging studies should be the next step in the
evaluation

PRIMARY ALDOSTERONISM
• Excess aldosterone production due to primary aldosteronism is a
potentially curable form of hypertension
• The consequences are sodium retention, hypertension, hypokalemia, low
PRA, cardiovascular disease, and kidney damage
• Primary aldosteronism should be considered in all patients with refractory
hypertension
• The ratio of plasma aldosterone (PA) to PRA (PA/PRA) is a useful
screening test

Contd...
• A ratio >30:1 in conjunction with a PA concentration >555 pmol/L (>20
ng/dL) reportedly has a sensitivity of 90% and a specificity of 91% for an
aldosterone-producing adenoma
• The two most common causes of sporadic primary aldosteronism are an
aldosterone-producing adenoma and bilateral adrenal hyperplasia
• Hypertension generally is responsive to surgery in patients with adenoma
but not in patients with bilateral adrenal hyperplasia

CUSHING’S SYNDROME
• Cushing’s syndrome is related to excess cortisol production due either to
excess ACTH secretion (from a pituitary tumor or an ectopic tumor) or to
ACTH-independent adrenal production of cortisol
• Hypertension occurs in 75–80% of patients with Cushing’s syndrome
• The mechanism of hypertension may be related to stimulation of
mineralocorticoid receptors by cortisol and increased secretion of other
adrenal steroids

PHEOCHROMOCYTOMA
• Catecholamine-secreting tumors are located in the adrenal medulla
(pheochromocytoma) or in extra-adrenal paraganglion tissue
(paraganglioma) and account for hypertension in ~0.05% of patients
• In a small percentage of patients, epinephrine is the predominant
catecholamine secreted by the tumor, and these patients may present
with hypotension rather than hypertension
• Inherited pheochromocytomas may be associated with multiple
endocrine neoplasia (MEN) type 2A and type 2B, von Hippel-Lindau
disease, and neurofibromatosis

Contd...
• Laboratory testing consists of measuring catecholamines in either urine
or plasma, e.g., 24-h urine fractionated metanephrine excretion or
plasma-free metanephrines under standardized conditions
• The urine measurement is less sensitive but more specific
• The next step would involve imaging of the abdomen and pelvis (CT or
magnetic resonance imaging)
• Peripheral α-adrenergic antagonists may be used to control blood
pressure
• Surgical excision is the definitive treatment of pheochromocytoma and
results in cure in ~90% of patients

MISCELLANEOUS CAUSES OF HYPERTENSION
• Hypertension occurs in >50% of individuals with obstructive sleep apnea
• Hypertension appears to be due to sympathetic activation caused by
intermittent hypoxia and fragmented sleep
• Continuous positive airway pressure (CPAP) and bilevel positive airway
pressure (BiPAP) administered during sleep are effective therapies for
obstructive sleep apnea
• Coarctation of the aorta is the most common congenital cardiovascular
cause of hypertension
• A blowing systolic murmur may be heard in the posterior left interscapular areas

Contd...
• Thyroid diseases and acromegaly, cause hypertension
• Mild diastolic hypertension may be a consequence of hypothyroidism,
whereas hyperthyroidism may result in systolic hypertension
• Primary hyperparathyroidism, may result in hypertension
• Hypertension also may be related to a number of prescribed or over-the-
counter medications and other substances

Basic laboratory tests for initial evaluation

Treatment

Pharmacological therapy

Oral Drugs used in Treatment of Hypertension

Contd...

BLOOD PRESSURE GOALS OF ANTIHYPERTENSIVE
THERAPY
• The maximum protection against combined cardiovascular endpoints is
achieved with pressures <135–140 mmHg for systolic blood pressure
and <80–85 mmHg for diastolic blood pressure
• According to 2017 guidelines developed by the ACC/AHA, the
recommended goal of blood pressure control for the primary and
secondary prevention of cardiovascular disease is a blood pressure
<130/80 mmHg, including patients with diabetes mellitus and chronic
kidney diseases

Contd...
• In hypertensive patients without elevated ASCVD risk, the clinical trial
evidence is strongest for a target blood pressure of 140/90 mmHg
• Resistant hypertension refers to patients with blood pressures
persistently >140/90 mmHg despite taking three or more
antihypertensive agents, including a diuretic
• In the absence of a specific identifiable cause, mineralocorticoid receptor
antagonists, especially spironolactone, have been demonstrated to be
the most effective add-on drugs for the treatment of resistant
hypertension

HYPERTENSIVE EMERGENCIES
• Severe asymptomatic hypertension (systolic blood pressure ≥180 mmHg
or diastolic blood pressure ≥120 mmHg) is considered a hypertensive
“urgency”
• but when accompanied by acute target damage, it is considered a
hypertensive “emergency”

Contd...
• In hypertensive individuals, the upper and lower limits of autoregulation
of cerebral blood flow are shifted to higher levels of arterial pressure, and
rapid lowering of blood pressure to below the lower limit of autoregulation
may precipitate cerebral ischemia or infarction as a consequence of
decreased cerebral blood flow
• Renal and coronary blood flows also may decrease with overly
aggressive acute therapy
• In patients with a hyper_x0002_tensive urgency, except for those with
acute aortic dissections or hemorrhagic strokes, blood pressure is
generally gradually lowered over 24 h to ~25% of the initial value

Malignant Hypertension
• The syndrome of malignant hypertension is an example of a
hypertensive emergency that is 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
• Pathologically, the syndrome is associated with diffuse necrotizing
vasculitis, arteriolar thrombi, and fibrin deposition in arteriolar walls
• Fibrinoid necrosis has been observed in arterioles of kidney, brain,
retina, and other organs

Contd...
• Clinically, the syndrome is recognized by progressive retinopathy
(arteriolar spasm, hemorrhages, exudates, and papilledema),
deteriorating renal function with proteinuria, microangiopathic hemolytic
anemia, and encephalopathy
• Historic inquiry should include questions about the use of monoamine
oxidase inhibitors and recreational drugs (e.g., cocaine, amphetamines)
• In patients with encephalopathy, the initial goal of therapy is to reduce
mean arterial blood pressure by no more than 25% within minutes to 2 h
or to a blood pressure in the range of 160/100–110 mmHg
• Aggressive reductions of blood pressure should be avoided

Contd...
• If thrombolytic therapy or endovascular treatment is to be used, the
recommended goal is to reduce blood pressure to <185 mmHg systolic
pressure and <110 mmHg diastolic pressure before thrombolytic therapy
is initiated
• In addition to pheochromocytoma, an adrenergic crisis due to
catecholamine excess may be related to cocaine or amphetamine
overdose, clonidine withdrawal, acute spinal cord injuries, and an
interaction of tyramine-containing compounds with monoamine oxidase
inhibitors. These patients may be treated with phentolamine or
nitroprusside

Reference
• HARRISON’S Principles of Internal Medicine - 21st Edition
• Davidson’s Principles and Practice of Medicine - 23rd Edition

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