HYPERTENSION Regulation of Blood pressure

Mohammad Ilyas, M.D.

Assistant Clinical Professor

University of Florida / Health Sciences Center

Jacksonville, Florida USA 1

Outline

1. Definition, Regulation and Pathophysiology

2. Measurement of Blood Pressure, Staging of Hypertension and Ambulatory Blood Pressure Monitoring

3. Evaluation of Primary Versus Secondary

4. Sequel of Hypertension and Hypertension Emergencies

5. Management of Hypertension (Non-Pharmacology versus Drug Therapy)

6. The Relation Between Hypertension: Obesity, Drugs, Stress and Sleep Disorders.

7. Hypertension in Renal diseases and Pregnancies

8. Pediatric, Neonatal and Genetic Hypertension

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Regulation of Blood Pressure

• There are two basic mechanisms for regulating blood pressure:

(1) Short-term mechanisms, which regulate blood vessel diameter, heart

rate and contractility

(2) Long-term mechanisms, which regulate blood volume

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Regulation of Blood Pressure

• The body responds to variations in the effective circulating

volume in two steps:

(1) The change is sensed by the pressure receptors; (Sensors)

(2) These receptors then activate a series of effectors that restore

volume by varying vascular resistance, cardiac output, and

renal Na+ and water excretion.

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Short-Term Regulation

• Rising blood pressure Stretching of arterial

walls Stimulation of baroreceptors in carotid,

sinus, aortic arch, and other large arteries of the

neck and thorax Increased impulses to the brain

from baroreceptors Increased parasympathetic

activity and decreased sympathetic activity

Reduction of heart rate and increase in arterial

diameter Lower blood pressure

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Baroreceptors

• These are the stretch receptors present in the wall of blood vessel

(Carotid Sinus and Aortic Arch) and Heart (Atria at the junction

of SVC and Pulmonary vein).

• These receptors are located in the adventitia, consist of extensively

branched, knobby, coiled, intertwined ends of myelinated nerve fiber.

• In chronic Hypertension these receptors reset to maintain an elevated

blood pressure.

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Baroreceptors

• Baroreceptors sense stretch and rate of stretch by generating

action potentials (voltage spikes)

• Located in highly distensible regions of the circulation to

maximise sensitivity

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Response of single baroreceptor fiber to change in pressure

From “An Introduction to Cardiovascular Physiology” J.R. Levick

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These receptors works more effectively in MAP between 80 – 160 mm of Hg.

Carotid sinus receptors are physiologically more important than Aortic arch receptors.

Atrial Baroreceptors are of 2 types:

Type-A- Active during systole.

Type-B- Active during diastole.

Atrial stretch receptors also respond to hypovolemia by increasing the secretion of AVP, Renin and Aldosterone.

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Increased Parasympathetic Activity

Effect of Increased Parasympathetic and Decreased Sympathetic Activity on Heart and Blood Pressure:

1. Increased activity of vagus (parasympathetic) nerve

2. Decreased activity of sympathetic cardiac nerves

3. Reduction of heart rate

4. Lower cardiac output

5. Lower blood pressure

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Decreased Sympathetic Activity

Effect of Decreased Sympathetic Activity on Arteries and Blood Pressure:

1. Decreased activity of vasomotor fibers (sympathetic nerve fibers)

2. Relaxation of vascular smooth muscle

3. Increased arterial diameter

4. Lower blood pressure

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Short-term Regulation of

Rising Blood Pressure

1. Rising blood pressure

2. Stretching of baroreceptors

3. Increased impulses to the brain

4. Increased parasympathetic activity

5. Decreased sympathetic activity

6. Slowing of heart rate

7. Increased arterial pressure

8. Reduction of blood pressure

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Short-term Regulation of

Falling Blood Pressure

Falling blood pressure Baroreceptors inhibited Decreased impulses to the brain Decreased parasympathetic activity and increased sympathetic activity

Three effects:

1. Heart: increased heart rate and increased contractility

2. Vessels: increased vasoconstriction

3. Adrenal gland: release of epinephrine and norepinephrine which enhance heart rate, contractility, and vasoconstriction

• Increased blood pressure

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Sympathetic Activity on

Heart and Blood Pressure

Effect of Increased Sympathetic Activity on Heart and Blood Pressure:

1. Increased activity of sympathetic cardiac nerves

2. Decreased activity of vagus (parasympathetic) nerve

3. Increased heart rate and contractility

4. Higher cardiac output

5. Increased blood pressure

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Vasomotor Fibers

Effect of Increased Sympathetic Activity on Arteries and Blood Pressure:

1. Increased activity of vasomotor fibers (sympathetic nerve fibers)

2. Constriction of vascular smooth muscle

3. Decreased arterial diameter

4. Increased blood pressure

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Sympathetic Activity on

Adrenal Gland and Blood Pressure

Effect of Increased Sympathetic Activity on Adrenal Glands and Blood Pressure:

1. Increased sympathetic impulses to adrenal glands

2. Release of epinephrine and norepinephrine to bloodstream

3. Hormones increase heart rate, contractility and vasoconstriction.

Effect is slower-acting and more prolonged than nervous system control.

• Increased blood pressure

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Chemoreceptors

• Very similar to baroreceptors, except that they respond to chemical changes.

• At low O2 or high CO2 or H+ (as occurs during low pressure because of

decreased blood flow), chemoreceptors are stimulated.

• Chemoreceptors excite the vasomotor center, which elevates the arterial

pressure.

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CNS Ischemic Response

• If blood flow is decreased to the vasomotor center in the lower brainstem

and CO2 accumulates, the CNS ischemic response is initiated.

• Very strong sympathetic stimulator causing major vasoconstriction and

cardiac acceleration.

• Sometimes called the “last ditch stand”.

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Auto-regulation of Blood Pressure

• It occur both at tissue level (local Regulation) and at systemic level (systemic Regulation)

LOCAL REGULATION:

• Capacity of tissue to regulate its own blood flow is called as Autoregulation.

• It is well developed in kidney and also seen in brain, liver, heart, intestine and skeletal muscle.

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Auto-regulation of arterioles (in the absence of external stimuli)

Myogenic mechanism

( response to mechanical stimulus):

• Vessels Smooth Muscle (VSM) fiber contract

when it stretched and relaxes when pressure

in the vessel increases.

• Net effect: maintenance of near constant

blood flow for a particular metabolic level.

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Metabolic mechanism

Accumulation of metabolites like Lactate, Phosphate, histamine, CO2, H+,

NO, K+ and adenosine (Specially in skeletal muscle)

Decrease in O2, and pH, causes vasodilatation in arteriole and increases

the blood flow to the tissue

Whereas increased O2, TXA2, Endothelin, substance-P, serotonin causes

vasoconstriction

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Chemical Physiologic role Source Type

Nitric oxide (NO) Paracrine mediator Endothelium Local

Atrial natriuretic peptide

ANP

Reduce blood pressure Atrial myocardium, brain

Hormonal

Vasoactive intestinal peptide (VIP)

Digestive secretion, relax smooth muscle

Neurons Neural, hormonal

Histamine Increase blood flow Mast cells Local, systemic

Epinephrine (b2) Enhance local blood flow to skeletal muscle, heart, liver

Adrenal medulla Hormonal

Acetylcholine (muscarinic)

Erection of clitoris, penis Parasympathetic neurons

neural

Bradykinin Increase blood flow via nitric oxide

Multiple tissues Local

Adenosine Enhance blood flow to match metabolism

Hypoxic cells local

Vascular Smooth Muscle (VMS) relaxants

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Vascular Smooth Muscle (VMS) Contraction

Chemical Physiologic role Source Type

Nor Epi (a ) Baroreceptor reflex Sympathetic neurons Neural

Endothelin Paracrine Vascular endothelium Local

Serotonin Platelet aggregation, smooth muscle contraction

Neurons, digestive tract, platelets

Local, neural

Substance P Pain, increased capillary permeability Neurons, digestive tract Local, neural

Vasopressin Increase blood pressure during hemorrhage

Posterior pituitary Hormonal

Angiotensin II Increase blood pressure Plasma hormone Hormonal

Prostacyclin Minimize blood loss from damaged vessels before coagulation

endothelium local

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Neural Control

Systemic Regulation

Other than venules and capillaries all vascular system are innervated.

Both cholinergic and adrenergic nerve plexuses lies on adventia and extend branches to the surface of VSM, only the neurotransmitters reach the inner part of VSM by diffusion and exert there effect.

There is no tone in cholinergic system, but the vasoconstrictor fibers are tonically active so sympathectomy causes vasodilatation in most of vessels.

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Vasomotor Control

• In CNS the control of Blood Pressure is

exerted by groups of neurons in Medulla,

collectively called as Vasomotor area.

• Impulse from this area both by sympathetic

system and vagal discharge regulate the HR,

stroke volume and vessel diameter.

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Long-Term Regulation of BP

Long-term regulation of blood pressure is primarily accomplished by altering blood volume.

The loss of blood through hemorrhage, accident, or donating a pint of blood will lower blood pressure and trigger processes to restore blood volume and therefore blood pressure back to normal.

• Renin-Angiotensin System

• Anti-Diuretic Hormone

• Atrial Naturetic Peptide

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Renin-Angiotensin System

• Renin – hormone that acts as an enzyme; released when arterial

pressure drops – i.e., when renal perfusion is inadequate

• Helps raise arterial pressure

• Can be life-saving system in circulatory shock

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Factors affecting Renin secretion:

Stimulatory:

o Increased sympathetic activity via renal nerve.

o Increased circulating catecholamine.

o Prostaglandins.

Inhibitory:

o Increased Na+ and Cl- delivery to macula densa.

o Increased afferent arteriolar pressure.

o Angiotensin-II.

o Vasopressin

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Vasoconstriction

NE

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Arteries

Veins

Reduced renal

blood flow

Juxtaglomerular

apparatus

Renin

Angiotensinogen

Angiotensin I

Angiotensin II

Increased

pre-load

Increased

after-load

vasoconstriction

Increased aldosterone

secretion

Sodium retention

Fluid re-absorption

Increased

blood volume

Renin/angiotensin/aldosterone system (RAAS)

LV filling pressure)

(LV pressure

beginning of systole)

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Aldosterone Mechanism

• Aldosterone promotes increased reabsorption

of sodium from the kidney tubules.

• Each distal convoluted tubule winds through the

kidney and eventually empties its contents into a

urine-collecting duct.

• The peritubular capillaries absorb solutes and

water from the tubule cells as these substances

are reclaimed from the filtrate.

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Sodium Reabsorption

• Aldosterone stimulates the cells

of the distal convoluted tubule

to increase the active transport

of sodium ions out of the

tubule into the interstitial fluid,

accelerating sodium

reabsorption.

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Water Reabsorption

• As sodium moves into the bloodstream, water follows. The reabsorbed water

increases the blood volume and therefore the blood pressure.

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Vasopressin (ADH)

• Arginine vasopressin (AVP), antidiuretic hormone (ADH), Neuro-hypophysial hormone

• Its two primary functions are to retain water in the body and to constrict blood vessels.

• Vasopressin is a peptide hormone that increases water permeability of the kidney's collecting

duct and distal convoluted tubule by inducing translocation of aquaporin-CD water channels in

the kidney nephron collecting duct plasma membrane.

• It is derived from a pre-pro-hormone precursor that is synthesized in the hypothalamus and

stored in vesicles at the posterior pituitary. Most of it is stored in the posterior pituitary to be

released into the bloodstream.

• It has a very short half-life between 16-24 minutes.

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ADH in Distal Convoluted Tubule

• ADH promotes the reabsorption of water from the kidney by stimulating an

increase in the number of water channels in the distal convoluted tubules

and collecting tubules (ducts).

• These channels aid in the movement of water back into the capillaries,

decreasing the osmolarity of the blood volume and therefore blood pressure.

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ADH in Distal Convoluted Tubule

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A short-term effect of increased osmolarity

• A short-term effect of increased osmolarity is the excitation of

the thirst center in the hypothalamus.

• The thirst center stimulates the individual to drink more water and

thus rehydrate the blood and extracellular fluid, restoring blood

volume and therefore blood pressure.

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Atrial Natriuretic Peptide (ANP)

• ANP is a 28-amino acid peptide that is synthesized, stored, and released by

atrial myocytes in response to atrial distension, angiotensin II stimulation,

endothelin, and sympathetic stimulation (beta-adrenoceptor mediated).

• Elevated levels of ANP are found during hyper-volemic states, which occurs

in congestive heart failure.

• ANP is first synthesized and stored in cardiac myocytes as pre-pro-ANP,

which is then cleaved to pro-ANP and finally to ANP.

• ANP is the biologically active peptide 41

Atrial Natriuretic Peptide (ANP)

This hormone is stored and secreted by muscle of Atrium and to some extent ventricle and its secretion is stimulated by ECF volume and ingestion of Na+

Dilating afferent arteriole and relaxing mesangial cells

Inhibiting Na+ reabsorption in renal tubule

Relaxing the VSM of arteriole and venule

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Regulation of Cardiovascular System

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Summary

1. In the short-term, rising blood pressure stimulates increased parasympathetic activity, which leads to reduced heart rate, vasodilation and lower blood pressure.

2. Falling blood pressure stimulates increased sympathetic activity, which leads to increased heart rate, contractility, vasoconstriction, and blood pressure.

3. Long-term blood pressure regulation involves renal regulation of blood volume via the renin-angiotensin mechanism and aldosterone mechanism.

4. Increased blood osmolarity stimulates release of antidiuretic hormone (ADH), which promotes reabsorption of water, and excites the thirst center, resulting in increased blood volume and blood pressure.

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Summary

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