PATHOPHYSIOLOGY OF HYPERTENSION

Blood pressure (P)

measured in mm HG

Force per unit area exerted on vessel wall by blood

Usually measured as arterial BP

= CO x TPR

Resistance (R)

opposition to flow

Amount of friction blood encounters through the vessel

Mostly encountered in the peripheral (systemic) circulation = peripheral resistance

Increased (R) = increased vessel length, decreased vessel diameter, increased blood viscosity

entire periphery = total peripheral resistance (TPR)

Blood flow (F)

measured in mL/minute

Volume of blood flowing through an area → entire vascular system = cardiac output (CO)

= Δ P/R

Inc. Δ P = Inc. F, Dec. Δ P = Dec. F, directly proportional to BP

Inc. R = Dec. F, inversely proportional to resistance

Systolic blood pressure (SBP)

Peak pressure during cardiac contraction (systole)

First Korotkoff sound

CO is the primary determinant

Diastolic blood pressure (DBP)

Nadir pressure when ventricles are filling (diastole)

Fifth Korotkoff sound (silence)

TPR is the primary determinant

Pulse pressure (PP)

Measure of arterial wall tension

SBP – DBP

Mean arterial pressure (MAP)

Average pressure throughout the cardiac contraction cycle

(SBP x 1/3) + (DBP x 2/3)

Expected that ~1/3rd of time is spent in systole and ~2/3rds in diastole

Regulation of Arterial Blood Pressure

Directly increase fluid volume: - Inc. intake of sodium/water, dec. sodium/water excretion via reduced renal function

Increased volume → increases CO

Fluid/humoral regulation

Excessive amounts of volume in blood

Stimulation of renin-angiotensin-aldosterone system (RAAS)

Vasopressin or anti-diuretic hormone (ADH)

Reduced Amount of Volume in Blood

Increased Levels of atrial natriuretic peptide (ANP)

Renin-Angiotensin-Aldosterone System (RAAS) Stages

Dehydration, sodium deficient, or hemorrhage: → Reduced volume → Reduced blood pressure

Juxtaglomerular cells in renal afferent arterioles sense change: → Release Renin

Renin: converts angiotensinogen (released from the liver) to angiotensin I

Angiotensin converting enzyme (ACE) converts angiotensin I → angiotensin II (and has a dual function degrading bradykinin)

Angiotensin II stimulates: Aldosterone release which then directly increases Na/water reabsorption; Sympathetic activation and vasoconstriction directly through neuronal/local pathways

Neuronal regulation of Arterial Blood Pressure - CNS

Stimulation of presynaptic α2 → inhibits norepinephrine release

Stimulation of presynaptic β → causes norepinephrine release

Neuronal regulation of Arterial Blood Pressure - ANS

Stimulation of α1 → vasoconstriction

Stimulation of α2 → vasoconstriction

Stimulation of β1 → increases HR and contractility → increases CO

Stimulation of β2 → vasodilation

Both α1 and α2 cause narrowing of vessel which increases TPR

Baroreceptors in Mechanical Regulation of Arterial BP

Mechanoreceptors in the walls of large arteries

Recognizes changes in the stretch of the walls

Sensing acute changes for short-term regulation

Normal Response to acute BP increase: decreased sympathetic outflow causing vasodilation

Normal Response to acute BP decreased: Increased sympathetic outflow causing vasoconstriction

Consequence of Baroreceptor Dysfunction

BP stays elevated in acute BP increases

Syncope or near-syncope occurs in acute BP decrease; organ perfusions may be reduced

Local regulation of Arterial Blood Pressure

Vascular endothelium (inner lining of blood pressure)

Vasoactive substances synthesized within endothelial cells affect tone

Local changes in pH and/or O2 affect endothelium function

Ex: increases in O2 demand local vasodilation to increase blood flow/O2 supply

Vasoconstricting Substances in the Vascular Endothelium

Angiotensin II

Endothelin I

Vasodilating Substances in the Vascular Endothelium

Prostacyclin

Bradykinin

Nitric oxide

Normal BP

Systolic BP < 120 mm Hg AND Diastolic BP < 80 mm Hg

Elevated BP

Systolic BP 120–129 mm Hg AND Diastolic BP < 80 mm Hg

Hypertension Stage 1 BP

Systolic BP 130–139 mm Hg OR Diastolic BP 80-89 mm Hg

Hypertension Stage 2 BP

Systolic BP ≥ 140 mm Hg OR ≥ Diastolic BP ≥90 mm Hg

Primary Hypertension

Also known as essential hypertension, typically classified as Stage 1 or Stage 2

Between 90-95% of hypertension is primary

No one cause identified (not “secondary” to one factor), but rather multifactorial

Multiple dysfunctions in regulation processes: Inherited or intrinsic defects in renal adaptive mechanisms, Excess RAAS activation, Over-activity of sympathetic nervous system, Endothelial dysfunction

Many associated risk factors

Modifiable Risk Factors

Cigarette smoking

Overweight/obesity

Physical inactivity

Unhealthy diet

Diabetes mellitus

Dyslipidemia

Gestational diabetes, pre-eclampsia

Relatively Fixed Risk Factors

Increased age

Male sex

Family history

Psychosocial stress

Low socioeconomic/education status

Obstructive sleep apnea

Chronic kidney disease

Auto-immune inflammatory disorders

Clinical presentation of Primary Hypertension

May appear healthy and/or may already have identified risk factors

May have lifestyle that favors higher BP and/or a family history of HTN

Often asymptomatic or have non-specific symptoms (e.g., headaches, flushing)

Diagnosis: Primary Hypertension

BP persistently above threshold – generally, requiring an average of TWO or more readings on TWO or more separate occasions

Can be measured with either: Sphygmomanometer in-office, Automated devices out-of-office (HBPM, ABPM)

Secondary Hypertension

About 5% of hypertension is secondary – often not considered unless drug-resistant or presenting with other clinical features

Has a discrete and identifiable cause

Most common causes of Secondary Hypertension

Chronic kidney disease

Obstructive sleep apnea

Primary aldosteronism

Medications

Less common causes of Secondary Hypertension

Thyroid disorders

Pheochromocytoma

Cushing’s syndrome

Aortic coarctation

Primary hyperparathyroidism

Potential Medication Causes of Secondary Hypertension

Sympathomimetics - Amphetamines, cocaine, anorexiants (e.g., phentermine), decongestants (e.g., pseudoephedrine, phenylephrine)

Estrogen-containing agents - > 30 mcg of estrogen

Antidepressants - Monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), selective norepinephrine receptor inhibitors (SNRIs)

Atypical antipsychotics - Olanzapine and clozapine

Certain migraine medications - triptans, ergotamines

Other Causes of Secondary Hypertension

Glucocorticoids

NSAIDs

Immunosuppressants (e.g., cyclosporine or tacrolimus)

Tyrosine kinase inhibitors (e.g, sunitinib, sorafenib)

Angiogenesis inhibitor (e.g, bevacizumab)

Erythropoiesis-stimulating agents

Sodium containing antiacids

Herbal Supplements - Ma Huang (ephedra), St. John’s Wort, Yohimbine

Alcohol, Caffeine, Nicotine, and Licorice

Orthostatic hypertension Diagnosis

Confirm by screening blood pressure lying down/sitting (for 5+ mins) and then standing

Blood pressure is normal when lying/sitting, then increases upon standing

Criteria = SBP increase of > 20 and/or DBP increase of > 10

Pseudo-hypertension

Falsely elevated BP measurement

More likely in elderly with atherosclerosis due to brachial artery being stiff and difficult to compress with BP cuff

Resistant Hypertension Diagnosis

BP not controlled with 3 antihypertensive medications that have complementary mechanisms of actions (1 drug should be a diuretic) and are at optimal doses

OR, BP controlled with ≥ 4 antihypertensive medications

Associated risk factors - Older age, black patients, chronic kidney disease, diabetes, obesity

Hypertensive Crises Diagnosis - Hypertensive Urgency

SBP > 180 and/or DBP > 120 without signs/symptoms of acute target organ damage

May be asymptomatic or with mild symptoms (e.g., mild headache, epistaxis, anxiety)

Usually due to withdrawal or non-adherence to antihypertensives

Hypertensive Crises Diagnosis - Hypertensive Emergency

SBP > 180 and/or DBP > 120 WITH signs/symptoms of acute target organ damage (TOD)

Signs/symptoms of acute TOD: Chest pain, increased SOB, vision changes/blind spots, stroke symptoms (i.e., FAST) or other concerns for neurologic deficits, fluid retention/decreased urine output

Acute effects of target organ damage (TOD): Heart

Acute coronary syndrome (ACS)

Decompensated heart failure (HF)

Acute effects of target organ damage (TOD): Brain

Stroke

Transient ischemia attack (TIA)

Hypertensive encephalopathy

Acute effects of target organ damage (TOD): Peripheral vasculature

Aortic dissection

Acute effects of target organ damage (TOD): Kidneys

Acute kidney injury (AKI)

Acute effects of target organ damage (TOD): Eyes

Retinal hemorrhage