MEDIUM TO LONG-TERM REGULATION OF BLOOD PRESSURE

Prof Lam Sau Kuen

Department of Physiology

1 2014.11.19 Wed MBBS Stage II UMMP Class of 2013

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Blood Pressure

Pull out, Betty! Pull out! . . . You’ve hit an artery!

Learning Objectives

• Normal arterial blood pressure (BP)

• Regulation of BP – Short-term regulation of BP

• Baroreceptor reflex • Chemoreceptor reflex • Central nervous system (CNS) ischaemic response

– Medium to long-term regulation of BP

• Renin-angiotensin-aldosterone system (RAAS) • Role of the kidney in long-term regulation

• High BP (hypertension)

– Guidelines

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NORMAL ARTERIAL BP

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Pressure on Vessel Walls

• BP is the lateral pressure exerted by a volume of blood on the walls of the blood vessels as it flows through the vessels

• Arterial BP → BP in aorta and arteries

• Venous BP → BP in veins

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Arterial Blood Pressure

• Systolic and diastolic BP

• Systolic BP (SBP): – 120 mmHg (90 – 130 mmHg) – Highest pressure recorded when

left ventricle is contracting (systole)

– Exerting maximal force on blood

• Diastolic BP (DBP): – 80 mmHg (60 – 90 mmHg) – Lowest pressure recorded when

left ventricle is relaxing (diastole) – Due to elastic recoil and arteriolar

resistance

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Arterial BP

• Normal BP: 120/80 mmHg

• Pulse pressure (PP) • PP = SBP – DBP • PP = 120 – 80 = 40 mmHg

• Mean arterial pressure (MAP)

• MAP = DBP + 1/3 PP • MAP = 80 + 13.3 = 93.3

mmHg (~100 mmHg) • Mean pressure in arteries

during a cardiac cycle • Mean driving force to push

blood through capillaries

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Importance of normal MAP

• To ensure adequate driving force to perfuse tissue

• To prevent extra heavy load on heart (afterload)

• To prevent damage to blood vessels

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Arterial (Systemic) and Pulmonary BP

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• BP is dependent upon:

Cardiac output (CO)

Total peripheral resistance (TPR)

Blood volume

• BP is given by:

BP = CO x TPR

CO = SV X HR

BP = SV X HR X TPR

Changes in SV or HR or TPR or blood volume will alter BP

Each of these factors can be manipulated by drug therapy

Determinants of BP

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Factors Affecting Cardiac Output

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TPR or systemic vascular resistance (SVR):

• Amount of friction against blood flow

• Determined by

– Sympathetic activity

– Diameter of arterioles (resistance vessels)

↓ TPR ↑ TPR

(vasodilation) (vasoconstriction)

TPR

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Summary of Factors affecting BP

REGULATION OF BP

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Regulation of BP

• Short-term regulation – Fast – Sec-to-sec – “Spurts” – Neural (autonomic reflexes) – Baroreceptor mechanism – Acts by changing CO or TPR – For survival

• Medium to long-term regulation

– Slow – Min-to-min, hour-to-hour, day-to-day, month-to-month, year-to-year – Basal level – Hormonal – Renin-angiotensin-aldosterone system (RAAS) – Involves the kidneys – Acts by regulating blood volume through kidneys

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Short-term Regulation of BP

• Responds within seconds to daily ambulatory changes in BP

• Involves autonomic reflexes • Baroreceptor mechanism

(reflex) (main) • Chemoreceptor reflex • CNS ischaemic response

• Regulates BP by altering CO or TPR

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Baroreceptor Mechanism

Sensory organs: Baroreceptors in carotid sinus + aortic arch

Integrating centre: Cardiovascular centre (CVC) in

medulla

Effector organs: • Heart - SA node - Ventricle • Arterioles

Afferent nerves: • Vagus • Glossopharyngeal

Efferent nerves: • Sympathetic • Parasympathetic

Negative feedback

Stimulus: ↑ or ↓ in BP Response: ↓ or ↑ in BP

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Sensory Organs: Baroreceptors

• Stretch receptors • Respond to blood pressure changes • Located in carotid sinus and aortic arch • Also in large arteries of neck and thorax

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Integrating Centre: Cardiovascular Centre (CVC) in Medulla

CVC

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Effector Organs: Heart and Arterioles

• Sympathetic stimulation:

↑ rate of SA node and conduction

velocity in the AV node

↑ force of contraction of

myocardium

Vaso- and venoconstriction

• Parasympathetic stimulation:

↓ excitability of both SA and AV

node by hyperpolarizing the

membrane during diastole

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Baroreceptor Reflex

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Baroreceptor Reflex: When BP increases

↑ BP: ↑ stretch of baroreceptors → ↑ impulses generated → ↑ impulses to CVC → CVC inhibited → ↓ sympathetic outflow → ↑ parasympathetic outflow → to heart: → ↓ HR, ↓ force of contraction, ↓ SV → ↓ CO → to arterioles: → vasodilation → ↓ TPR BP = SV X HR X TPR → ↓ BP

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Baroreceptor Reflex: Increase in BP

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Baroreceptor Reflex: When BP decreases

↓ BP: ↓ stretch of baroreceptors → ↓ impulses generated → ↓ impulses to CVC → CVC not inhibited → ↑ sympathetic outflow → ↓ parasympathetic outflow → to heart: → ↑ HR, ↑ force of contraction, ↑ SV → ↑ CO → to arterioles: → vasoconstriction → ↑ TPR BP = SV X HR X TPR → ↑ BP

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Baroreceptor Reflex: Decrease in BP

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Chemoreceptor Reflex

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• Chemoreceptors – Carotid bodies – Aortic bodies

• Respond to: – Increase in plasma CO2 (decrease in

pH) • More sensitive

– Decrease in O2

• Less sensitive • Impulse sent to CVC • Increase sympathetic outflow • Increase HR and force of contraction • Increase in CO and hence BP • More blood flows to lungs for removal

of CO2 and intake of O2

CNS Ischaemic Response

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• Last ditch response to increase BP • Stimulus: MAP < 60 mmHg

Long-term Regulation of BP

• Medium to long-term regulation – Slow – Min-to-min, hour-to-hour, day-to-

day, month-to-month, year-to-year

– Involves hormonal regulation of blood volume by kidneys

• By controlling water balance – Water intake = water

output – Antidiuretic hormone

(ADH) or arginine vasopressin (AVP)

• By controlling Na+ balance – Na+ intake = Na+ output – RAAS – Natriuretic peptides (NP)

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Water Balance

• AVP • Hormone that regulates ECF fluid

volume • Synthesised in hypothalamus • Stored and released from posterior

pituitary gland • Triggers for secretion

• Hypovolaemia • Hypotension • Extracellular hyperosmolarity • Angiotensin II • Sympathetic stimulation

• Acts on renal collecting ducts via V2 receptors to increase reabsorption of water

• Increases blood volume, CO and hence BP

• Also causes vasoconstriction 30

Water Balance

• Water intake = water output

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Na+ Balance

• Na+ intake = Na+ output

• Na+ – Most important ECF ion – Most abundant ion – Major determinant of ECF vol – Thus determines BP

• Controlled by RAAS

– Reabsorption of Na+

• Counter-regulated by natriuretice peptides (NP)

– Atrial NP (ANP) from atrial walls – Brain BP (BNP) from ventricular walls – Excretion of Na+

• Handled by kidneys

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Renal Regulation of Blood Pressure

• In the kidney – Juxtaglomerular apparatus (JGA)

• Located in cortex

• Unique segment:

– Thick ascending limb of the loop of Henle passes between the afferent and efferent arterioles of its own glomerulus

• Three special tissues:

– Macula densa – point of contact between ascending limb and arterioles (modified thick aLoH cells)

– JG cells – modified smooth muscle cells of afferent arterioles (granular cells) that synthesise and secrete renin

– Lacis cells (extraglomerular mesangial cells), not granular but also secrete renin

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JGA

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Sensory Receptors in JGA

• Two sensors are present in the JGA

• In macula densa

– Sensory receptors that detect changes in Na+ concentration in tubular fluid of PCT

• In afferent arteriole

– Baroreceptors (stretch receptors) that detect changes in perfusion pressure of arterial blood

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Renal Regulation of Blood Pressure

• Decrease in BP perfusion pressure

• Or Na+ filtered concentration in tubular

fluid

• Results in stimulation of renin secretion from

JG cells

• Renin angiotensin II formation

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Renal Regulation of Blood Pressure

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Renal Regulation of Blood Pressure

• Role of kidneys

– Aldosterone increased Na+ (and water) reabsorption from CD

– Action of ADH on vasopressin receptors (V2) increased water reabsorption from CD

• Result in ECF volume expansion and an increase in BP

Renal Regulation of Blood Pressure

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Figure 26.9

Maintenance of Blood Pressure Homeostasis

HYPERTENSION

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Hypertension

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• Guidelines

– WHO-ISH: 140/90 mmHg (MAP 106.7, normal – 93.3, set-point resets)

– JNC-VII: 140/90

• Optimum <120/<80 (115/75 “new” normal)

• >120/>80 now considered to be pre-hypertension – higher risk of developing hypertension

– BHS: 140/90

– Malaysia: 140/90

• Risk is important and in diabetes: 130/80 mmHg

• Two types:

– Primary – cause largely unknown – etiology poorly understood

– Secondary – cause known – due to disease process

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High Blood Pressure: Risk Factors

• Age

• Race

• Heredity (“Bad” genes)

• Diet – high fat and salt

• Stress

• Inactivity

• Obesity

• Smoking

• Alcohol consumption

• Diabetes

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High Blood Pressure: Symptoms

• Silent killer

• Patients are usually asymptomatic until substantial vascular damage occurs

• In more severe cases

– Persistent throbbing headaches

– Blurred vision

– Nausea and vomiting

– Ringing in ears - tinnitus

– Chest pain

– Swollen feet

– Mini-strokes

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Treating Hypertension

Lifestyle

Changes

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Treating Hypertension

CLASSES OF DRUGS MECHANISM OF ACTION

Diuretics Increase urine volume

Beta-blockers Decrease HR

Decrease ventricular contractility

Calcium antagonists/blockers Block Ca2+ channels

Vasodilation

ACE inhibitors Inhibit conversion of angiotensin I to angiotensin II

Vasodilation

Angiotension II-receptor antagonists

Block receptors

Vasodilation

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