Pathophysiology of Hypertension PDF

Pathophysiology of Hypertension Michael Levin DO FACOI FASN Clinical Professor of Medicine: PCOM Chair: Division of Nephrology  Pathophysiology of Hypertension Objectives 1. Define the hemodynamic determinants of systemic hypertension. 2. Recognize primary and secondary f...

Pathophysiology of Hypertension Michael Levin DO FACOI FASN Clinical Professor of Medicine: PCOM Chair: Division of Nephrology  Pathophysiology of Hypertension Objectives 1. Define the hemodynamic determinants of systemic hypertension. 2. Recognize primary and secondary forms of hypertension. 3. Illustrate the role of the kidney in systemic hypertension 4. Recognize the role of renin, angiotensin II, aldosterone, and the sympathetic nervous system in the pathogenesis of hypertension. 5. Discuss the risk factors and complications for hypertension 6. Be able to implement the above objectives when evaluating various cases of hypertension  Definition of terms Blood pressure (BP) – Force per unit area exerted on the wall of a blood vessel by the blood Expressed in mm Hg Measured as systemic arterial BP in large arteries near the heart – The pressure gradient provides the driving force that keeps blood moving from higher to lower pressure areas Resistance (peripheral resistance) – Opposition to flow – Measure of the amount of friction blood encounters – Generally encountered in the peripheral systemic circulation Three important sources of resistance – Blood viscosity – Total blood vessel length – Blood vessel diameter  Major determinants for the Cardiac Output Contractility Heart rate Preload (EDV) Afterload (resistance) Causes for hypertension through an increase of cardiac output are: ↑ of contractility and heart rate (β-adrenergic stimulation) ↑ of preload through an increase in venous return: – ↑ circulating blood volume (Na and water retention) – Vasoconstriction of the venous system (α- adrenergic stimulation)  Factors influencing the peripheral resistance – Blood viscosity The “stickiness” of the blood due to formed elements and plasma proteins – Blood vessel length The longer the vessel, the greater the resistance encountered - Diameter of blood vessel Frequent changes alter peripheral resistance resistance varies inversely with the fourth power of vessel radius – E.g., if the radius is doubled, the resistance is 1/16 as much  Relationship between blood flow, blood pressure and resistance  Determined by: Cardiac output – Venous return - determines the stroke volume (SV) (CO) – Neural/Hormonal controls Exercis BP activates cardiac centers in e medulla Activity of respiratory pump Sympathetic Parasympathetic (ventral body cavity activity activity pressure) Activity of muscular pump Epinephrine in (skeletal muscles) Sympathetic blood venoconstriction Venous return Contractility of cardiac muscle EDV ESV Stroke volume (SV) Heart rate (HR) Initial stimulus Physiological response Resul Cardiac output (CO = SV x HR) t  Control of the Vascular Resistance Autoregulation in two concomitant forms: Neural control ( quick) – autonomic nervous system Hormonal/humoral factors: (slow) Vasoconstrictors Endothelin catecholamines thromboxane, prostaglandins F, angiotensin I & II Vasodilators Nitric Oxide prostacyclins, prostaglandins E, kinins  Autoregulation ↓ tissue perfusion → local hypoxia → release of vasodilating agents (H+, K+ , adenosine, prostaglandins) → release of NO from endothelial cells →↓ resistance → ↑ tissue perfusion ↑ tissue perfusion → ↓ local concentration of vasodilating agents → release of endothelin (very potent vasoconstrictor) by endothelial cells → ↓ tissue perfusion This is a factor that can stabilize the blood pressure at a higher than normal value since ↑ BP → ↑ tissue perfusion → ↑ resistance → ↑ BP  Blood pressure regulation mechanisms Short term regulation Neural mechanisms: Baroreceptor/Chemoreceptor Baroreceptor initiated reflexes ( receptors in the aortic arch and carotid sinuses) (result - decreasing pressure) ↑ BP → stimulation of baroreceptors Vasomotor center inhibition Vasodilation Stimulation of the ↓HR ↓ BP cardioinhibitory center Mechanism is inefficient in controlling HTN because the receptors will adapt to a constant higher value of BP (higher value becoming the new “normal”)  Blood pressure regulation mechanisms Baroreceptor reflexes initiated by the left atrium and pulmonary circulation (result - decreasing pressure) ↓ sympathetic stimulation ↓ HR ↓BP ↑ blood volume ↓ renin release ↑Na+excretion ↓ blood ↓ ADH release ↑water excretion volume  Blood pressure regulation mechanisms Chemoreceptor regulated reflexes (result – increase in blood pressure) Stimulation of ↓ O2 Generalized chemoreceptors in ↑CO2 vasoconstriction carotid sinuses and ↑ H+ aortic arch Mainly involved in controlling ventilation. Can exacerbate preexisting systemic HTN in patients with sleep apnea or pulmonary HTN in patients with COPD  Blood pressure regulation mechanisms Long term mechanisms: Hormonal/humoral mechanisms Renin angiotensin aldosterone (RAA) mechanism Main system responsible for Na+ retention and increase in BP Release of renin at the level of the juxtaglomerular apparatus (JGA) is controlled by 4 mechanisms. - Baroreceptor mechanisms (↓MAP → ↑ renin release) - Chemoreceptor mechanism (↓ Na+ conc. In the macula densa of JGA → ↑ renin release) - Neural mechanism(↑ sympathetic activity → ↑ renin) - Humoral mechanism(↑ angiotensin II → ↓ renin) (-) feedback Natriuretic peptides (produced by the atrium, ventricles and brain) ANP/BNP - They are involved in the long-term regulation of sodium and water balance, blood volume and arterial pressure. There are two major pathways of natriuretic peptide actions: 1) vasodilator effects 2) renal effects that leads to natriuresis and diuresis. - They serve as a counter-regulatory system for the renin-angiotensin-aldosterone system.  Cardiovascular and Renal Actions of Natriuretic Peptides Natriuresis Diuresis Improve glomerular filtration rate & filtration fraction Inhibit renin release – ↓ circulating angiotensin II – ↓ circulating aldosterone Systemic vasodilation Arterial hypotension Reduced venous pressure Reduced pulmonary capillary wedge pressure  Risk factors Obesity correlated with insulin resistance High intake of sodium Alcohol consumption Lack of physical exercise Diabetes mellitus Dyslipidemia (hypercholesterolemia) Stress Smoking Decrease in the intake of calcium, magnesium and potassium Hy pe Glo rte ba ns l S ion yst on em th ic E e Hu ffec m to an f Bo dy  Hypertension Hypertension is defined as 130/80 mmHg or higher Classification: Essential hypertension (primary) Secondary hypertension