http://www.missouri.edu/~huxleyv/bloodpressure2000.html

[Guest guest]

This is a wonderful find. I'm finally beginning

to understand how my symptoms are interconnected. I'm having a

dreadful day, can't pee enough, my waist is swelling and I have an awful

headache. Maybe there is a reason we should monitor our BP.

Why has no doctor bothered to explain this to me??? I realize it is

a bit of reading and raises questions as well as answering them.

Has anyone on the list been seen by and endocrinologist? Seems they

might help with regulating all the regulators. Have a look at the

webpage, the diagrams are very useful.

REGULATION OF ARTERIAL BLOOD PRESSURE

Learning Objectives:

A. Understand the principles of negative feed back

and

homeostasis; possess the ability to describe how

blood

pressure control is a negative feedback system.

B. Identify the sequence of events in the short

term

control of arterial blood pressure.

C. Be able to identify the cardiac pressure

control

mechanisms and the sensor mechanisms; their

characteristics with respect to response timing

and

sensitivity.

Companion Reading:

Reading: Ch. 18. Nervous Regulation of the

Circulation,

and Rapid Control of Arterial Pressure.

In:Textbook of

Medical Physiology, 10th ed., A.C. Guyton & J.E.

Hall,

eds., W.B. Saunders:St. Louis, 2000

I. Introduction: Arterial blood pressure is maintained within

a

narrow range over a wide variety of conditions. Normally, only

massive changes in activity result in substantial changes in

pressure. Arterial blood pressure control is necessitated by

the

need to maintain a constant internal environment for optimal

cellular performance.

A. Homeostasis: From the Greek, homeo, for

" similar " or

" like " and stasis, meaning " state

of standing " : thus a

constant and optimal environment.

B. Negative feedback: Homeostatic mechanisms act

to

minimize differences between actual and optimal

responses

of a system and are biological examples of

negative

feedback control (e.g. body temperature).

C. Blood Pressure: The pressure to which we are

referring

is arterial blood pressure, Pa. As you will

recall from

the Biophysics lecture, Figure 5, the pressures

you

measure are systolic (Ps) and diastolic (Pd)

pressures,

respectively.

1. Ps: The systolic

pressure is the highest

pressure achieved in the

blood vessels and is

dependent main on the

rate of blood input into

the the aorta per unit

time. In practical terms

this is given by CARDIAC

OUTPUT; thus anything

that alters CO

automatically alters Ps (e.g.

exercise, emotion,

fever, aortic regurgitation,

digitalis, b blockers,

etc.). A persistent

increase in Ps is

accepted widely as a major

risk factor of ischemic

heart disease.

2. Pd: The diastolic

pressure is the lowest

pressure achieved in

systemic arteries and is

depends chiefly on the

rate of blood flow

leaving the systemic

arteries per unit time.

This in turn is indexed

by the TOTAL PERIPHERAL

RESISTANCE, thus

anything that alters TPR has a

profound influence

on Pd. An increase in TPR

as occurs with arterial

vasoconstriction of

hypervolemia will

increase Pd; a fall in TPR, as

occurs with

vasodilatation and hypovolemia (as

occurs with hemorrhage)

will decease Pd. Unlike

Ps, Pd is less

likely to be affected by

psychological or

emotional factors, thus a

persistent elevation

in Pd should be take

seriously.

3. Hypertension: A

patient is defined as

hypertensive when their

blood pressure is

greater than expected

for their age, sex and

race on at least 3

separate occasions under

resting conditions

whether symptoms are present

or not.

In practice the

diagnosis of hypertension is

made if BP is at or

above 160/95 on casual

examination in patients

less than 50 years of

age, or if it is

persistently above this level

in older patients.

It is noteworthy that this

number is considered too

high a cut off during

pregnancy or in those of

African descent.

II. CONTROL SYSTEMS:

[image]

A. Sensor/Effector/Monitor: The controlled

variable

(temperature) level is sensed (what is the

value?),

compared against a reference (is it more or less than

the

setting of the dial), and action is taken to bring it

back

to the desired level. The action in

response to the

error signal is taken via an effector mechanism (turn

the

furnace/air conditioner on or off). If the

response

increases, a signal is fed back to an effector

mechanism

in a negative or inhibitory manner so the

subsequent

response is reduced. Conversely, a decrease in

response

elicits an increase.

B. Control of Blood Pressure: For arterial blood

pressure

regulation there must be a monitoring system and

a

compensatory system where a change in pressure

induces

alterations to adjust automatically the balance

between

inflow and outflow so that the total blood flow

through

the circulation does not exceed the capacity of the

pump.

On sympathetic stimulation, the neurotransmitter

norepinephrine (NE) is released. NE stimulates

cardiac

activity and constricts the blood vessels (+).

When

cholinergic nerves (vagi, for example) are stimulated,

the

neurotransmitter acetylcholine (ACh) is

released. ACh

depresses cardiac activity (-).

C. Effector Mechanisms, or how a change is brought

about.

The cardiovascular system has a dual effector

mechanism:

1. Cardiac Output

and

2. Total Peripheral

Resistance. A single

effector system in a

house to control

temperature would use a

furnace: on or off. In

a dual effector system,

both an air conditioner

and a furnace would be

used.

It should be obvious

that both CO and TPR would

be used to control DP:

DP = CO * TPR.

D. Sensors: Blood pressure is sensed via

specialized

organs, the baroreceptors (also called

pressoreceptors),

located in the carotid sinuses and the aortic

arch. Other

receptors, chemoreceptors sense chemical changes, and

are

discussed in IV.4.c. below.

E. Control:

1. Afferent signals

transmitted from the

pressoreceptors by

sensory nerves to the

medullary cardiovascular

centers in the brain

stem.

2. Efferent signals

divide into two pathways:

a. Parasympathetic via the vagus nerve

and

b. Sympathetic nerves to the heart and

peripheral vasculature.

[image]

F. Integration:

The Arterial Pressoreceptor Reflex:

1. Increased Pa

stretches pressoreceptors in

carotid sinus and aortic

arch walls.

2. This stimulates

firing of Hering's nerve and

increased discharge

along afferent nerves via

glossopharyngeal nerve

to tractus solitarius in

medullary area of brain

stem.

3. Increased

parasympathetic (vagal) stimulation

of the heart leading

to

4. Decreased cardiac

activity.

5. Simultaneously with

(3) sympathetic nerve

activity is inhibited

thus withdrawing

sympathetic input to

heart and periphery.

6. Because of (3) and

(5) cardiac contractility

decreases and

7. Heart rate

decreases

8. Because of (5)

vasoconstrictor tone is

decreased thereby

9. Increased capacitance

and

10. Increased

arterial vessel radius.

11. C.O. decreases with

(6) and (7);

12. TPR decreases

with (9) and (10) thus

13. Pa decreases

..

G. Summary of Reflex Mechanism: Following an INCREASE

in

Pa, 4 events occur leading to a decrease in Pa and

return

to control levels:

1. Bradycardia

2. Reduced cardiac

vigor

3. Vasodilatation

4. Venodilation

H. Heart Rate: is determined by the balance

between

inhibitory effects, on the pacemaker, of

acetylcholine

released by the parasympathetic system (vagus) and

the

excitatory effects of norepinephrine released from

the

sympathetic nerve endings.

I. Aliases: Other names for the reflex

include:

1. Carotid sinus

reflex

2. Baroreceptor

reflex

3. Depressor

reflex

J. Following a decrease in Pa the same reflex arc is

used

to re-establish balance.

With a decrease in Pa, fewer impulses are carried

along

the afferents resulting in an increase in

sympathetic

response by releasing inhibition and a decrease

in vagal

tone thus an increase in cardiac action; vaso-

and

venoconstriction increase thereby increasing

blood

pressure. The proportional contribution of the 4

events

leading to altered TPR and CO (e.g. veno- and

vasoconstriction, heart rate and contractility) will

vary

according to conditions.

K. Summary: Reflex responses require a

" Closed-loop " .

Opening the loop provides one method for determining

what

mechanisms come into play in the feed-back

system. Open

loops tend to lead to positive feed back

situations.

III. Cardiovascular Control Centers: The neural centers for

cardiovascular system control are not well defined. Four basic

areas:

A. Medullary Control: Neurons responsible for

integration

of afferent impulses and origin of efferent impulses

for

homeostatic control of blood pressure.

B. Hypothalamic Control: Hypothalamus, a

generalized

center of control of the autonomic nervous

system,

modifies activity of bulbar region. The pons

does not

appear to be involved in baroreceptor reflex.

The

suprebulbar centers of great importance (e.g. rage

&

exercise). Hypothalamus involved in blood flow

changes in

response to temperature; activity via

sympathetics.

C. Cerebral-Spinal Control: Impulses originating

in

forebrain may have bearing on psychogenic

disorders.

D. Spinal Control: Local ischemia and consequent

hypoxia

of the brain stem can stimulate the medullary

vasomotor

and cardioinhibitory centers directly resulting

in

vasoconstriction and bradycardia. If the

vasoconstriction

raises the BP above normal then the bradycardia

is

reinforced reflexively by stimulation of the

systemic

arterial baroreceptors. If the fall in CO (from

the

decrease in heart rate) dominates then peripheral

vasoconstriction will be enhanced by unloading of

the

baroreceptors.

Clinically this response, the Cushing response, is

only

seen during severe generalized hypotensive episodes

(BP<50

mmHg) or when intracranial pressure raises

sufficiently to

induce ischemia of the hind brain. In patients

with

suspected elevation in intracranial pressure, both

pulse

rate and blood pressure are monitored (as occurs in

head

injury or brain tumor). Slowing of the pulse

with a

simultaneous raise in BP is an ominous sign.

IV. Cardiovascular Sensors: Effective cardiovascular control depends

on the data provided by sense organs to the control centers of the

brain. Stimulation of cardiovascular and pulmonary

mechanoreceptors

(stretch, tension, pressure) leads to reflex inhibition of

circulatory and respiratory activity.

A. Local Control: Refer to Microvascular

Transport

lecture.

B. Arterial Pressure Receptors:

1. Location and

Structure: nerve endings are

located in carotid sinus

and the aortic arch.

The carotid sinus

endings run along Hering's

nerve; those from the

aortic arch run along the

trunk that also carries

the vagus nerve. Thus

clamping the carotid

arteries will isolate the

action of the receptors

in the carotid sinuses

from those in the aortic

arch; severing the

vagus nerves will open

the reflex loop

completely.

2. Sensitivity and

Response: Pressoreceptors

respond to artery wall

stretch with an increase

in transmural

pressure. Firing rate increases

as a function of

pressures above 60 mmHg. The

reflex system is most

responsive to changes in

Pa between 60 and 160

mmHg.

3. Frequency of

Response: is also determined by

the rate of change in

stretch of the receptors.

Thus there are bursts of

activity with each

pressure pulse.

[image]

C. Chemoreceptors:

1. Location: near

carotid sinus, in the walls of

the common carotid

artery and aortic arch.

Chemoreceptor endings

from the sinus run along

the IXth nerve; those

from the common carotid

and aortic arch run in a

nerve trunk that also

carries the

vagi.

2. Sensitivity of the

nerve endings to:

a. decreased PO2

b. increased PCO2

c. increased [H+].

3. Response:

Primary function of the

chemoreceptors is in the

regulation of

respiration and

stimulation results in marked

hyperpnea along with

mild tachycardia and

vasoconstriction.

Thus chemoreceptor

stimulation results in

increased pulmonary

ventilation (stimulation

of respiratory centers

in medulla oblongata)

and increased blood

pressure via peripheral

vasoconstriction

(increased TPR and via

stimulation of medulla

oblongata cardiovascular

centers), thus:

a. Decreased Q due to low Pa leads to

chemoreceptor activation.

b. Arterial hypoxia and hypotension

synergistic and produce a vigorous

response.

c. Chemoreceptor normally quiet but

sensitive to changes.

d. If PO2 in respired air low,

vasoconstriction elicited reflexly is

nullified by local vasodilatation

resulting from hypoxia and the HR (and

CO) is increased.

D. Cardiac Receptors:

1. Atrial receptors: are

primarily " stretch "

receptors giving rise to

two responses: neural

and hormonal.

a. Neural responses: Afferent

impulses are conducted along the

sensory fibers of the vagus to the

medullary circulatory control center.

i. " A " receptors, discharge

a little during atrial

systole. When stimulated

they exert a strong

vaso-constrictor influence

on the kidney to influencing

renal blood flow and fluid

excretion.

ii. " B " receptors, are the

predominant stretch

receptors and are stimulated

by passive stretch of the

atria, usually during later

diastole. If stimulated the

reflex response is like the

baroreceptor, e.g.

inhibition of sympathetic

and excitation of

parasympathetic.

iii. Bainbridge Reflex:

reflex tachycardia caused by

rapid atrial distention. It

can only be elicited when

the initial heart rate is

slow. While this reflex is

referred to in almost every

text book you will be

pleased to know that it has

only been documented in dog

hearts and not in the hearts

of humans or primates. Hey,

I'm supposed to make sure

that you get all the data!

b. Left Atrial Volume Receptors:

respond to increases transmural

pressure: e.g. from increased left

atrial volume. Impulses transmitted

to the osmoregulatory centers of the

hypothalamus result in reduced ADH

(antidiuretic hormone, vasopressin)

secretion thereby increasing body

water loss. Reflex hypotension and

bradycardia sometimes follow left

atrial distention. With hemorrhage

and decreases in left atrial pressure,

ADH secretion is increased to induce

water retention.

c. Hormone secretion: Atrial

natriuretic peptide (ANP). Mammalian

atria have secretory granules

containing a small peptide, ANP. ANP

is secreted on stretch of the atria.

This potent, short lived peptide:

induces renal secretion of sodium and

increase diuresis thus serving to

decrease volume. ANP appears to acts

to decrease CO by decreasing systemic

resistance and by increase capillary

filtration.

2. Ventricular (mostly

left ventricle)

Responses: Bezold-Jarish

Reflex: results from

ventricular wall

distention stimulating the

ventricular

mechanoreceptors. Receptors appear

to be active only with

extreme conditions to

protect the ventricle

from volume overload

(elicit hypotension and

bradycardia). The

response is a reflex

vagal slowing of the heart

and simultaneous

inhibition of sympathoadrenal

activity. The

reflex protects against cardiac

overstrain, pulmonary

edema, and hypovolemia

whenever cardiac

distention is excessive (think

of the CHF cases).

The reflex, transmitted by

afferent vagal fibers,

is thought to exert its

sympathetic block via

release of endogenous

opiods likely acting on

the delta-type opiod

receptors in the

brain.

E. Response Times: Overall, blood pressure

control

invokes an integrated system of several elements

with

varied times of response and potency. The

systems are

classified according to rate of response between

fast

acting and long term. Today's lecture dealt with

the

" very fast " category; long term

compensatory systems are

covered in greater detail in the Renal (next) portion

of

the course.

1. Fast Acting

Mechanisms: those mechanisms that

exert their control over

the pressure regulatory

systems in seconds or

minutes following a change

in pressure.

a. Seconds: All the nervous pressure

control mechanisms are the first to

respond in a matter of seconds and are

fully active within a minute:

i. Baroreceptors

ii. Chemoreceptors

iii. Central nervous system

Ischemic Response: Cessation

of blood flow to the brain

invokes excitation of the

medullary centers such that

systemic vasoconstriction

brings about a * in

pressure. Response

initiated by inadequate

blood flow to brain.

iv. Relative potency: CNS >

Baro > Chemo

b. Minutes: 3 systems are activated

within minutes and fully active within

30 min.

i. Stress-relaxation:

changes in vasculature.

When Pa decreases it also

decreases in blood storage

areas (veins, spleen, liver

and lungs). The vessel size

decreases adapting to the

change in pressure and

restore normal

hemodynamics. Limited to

acute changes in blood

volume between +30% and

-15%.

ii. Capillary-fluid shift:

With a shift in Pa there is

a corresponding change in

Pc. This causes fluid to

move across the capillary

membrane. This shift in

fluid will alter blood

volume thereby altering TPR

and CO thus altering

pressure.

a. Increased Pc

results in

increased

filtration of

fluid out of the

vessels; this

decreases

intravascular

volume; venous

return decreases,

mean filling

pressure

decreases, thus

stroke volume

decreases, CO

decreases, blood

pressure

decreases.

b. A decrease in

Pc induces the

opposite set of

responses.

iii. Renin-Angiotensin

Vasoconstriction: decreased

Pa decreases Q stimulating

juxto-glomerular secretion

of renin into the blood.

Renin, an enzyme, converts

angiotensinogen to

angiotensin I in the plasma

which is then converted to

angiotensin II in the small

vessels of the lung.

Angiotensin II will remain

active in the blood for

about one minute and

increases blood pressure by

stimulating arteriolar and

venular constriction.

2. Slow or Long term

Mechanism: effects exerted

over hours and days

(These topics will be

covered more extensively

by Dr. Freeman)..

a. Renal blood volume pressure control

mechanism: acts via the kidney to

alter blood volume.

b. Aldosterone: hormone secreted by

the adrenal cortex.

[image]

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vancouver, bc Canada

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