Cardiovascular physiology

Jana Radosinska

PHYSIOLOGY OF THEVASCULAR SYSTEM

Contents of the lectures

2. part - vascular system

◼ functional morphology of the vessels

◼ general hemodynamics

◼ functions of arteries

◼ functions of capillaries

◼ functions of veins

◼ regulation of the vascular system

◼ specifics of some circulations

◼ lymphatic system

The blood vessels

arteries

capillaries

veins

microcirculation

◼ functional unit - arterioles, capillaries, venules, lymphatic capillaries

http://biology.about.com/od/anatomy/ss/capillary.htm

Arteries

◼ carry blood under the high pressure out to the tissue beds

◼ elastic, muscular

◼ progressively reduce the pulsations in BP

Arterioles

◼ resistant vessels

◼ last part - metarterioles -do not have real tunica media

◼ precapillary sphincter - atthe metarteriole-capillaryjunctions

◼ crucial role in regulating the amount of blood flowing to the tissues

Capillaries

◼ wall - one layer of endothelial cells

◼ exchange vessels

Venules

◼ can constrict to offer resistance (thin muscular layer)

Veins

◼ wall - thinner tunica media compared with arteries

◼ lumen - wider (distensible) compared with arteries (reservoir vessels)

Three-layered structure

1. tunica intima◼ comprises an endothelial cell monolayer +

connective tissue support

◼ tight junctions – seal endothelial cells to each other

◼ crucial role in controlling vascular permeability,vasoconstriction, angiogenesis and coagulation

◼ internal elastic lamina

https://classconnection.s3.amazonaws.com/660/flashcards/2365660/png/untitled1361990992835.png

Endothelium

Definition in 1865 - inner lining of blood vessels and body cavities

modification - definition including only the inner cell stratum of blood and lymphatic vessels

now - monocellular layer that separates all tissues from the circulating blood

Anatomy simple layer of mesenchymal cells

up to 6 x 1013 cells, weights 1 kg, surface area - up to 7 m2

may be continuous or discontinuous (the density of fenestrae varies through vascular beds)

membrane - complex proteins working as receptors or channels

balanced release of autocrine and paracrine substances in response to physical, biological and chemical stimuli

Endothelium - functions

hemostasis, thrombosis and fibrinolysis

◼ luminal surface of endothelial cells is anticoagulant and non-thrombogenic,the platelets and leukocytes do not adhere to it and the coagulation systemremains inactivated

vascular permeability

◼ semipermeable barrier - transcellular and paracellular pathways

leukocyte trafficking

◼ immune response

◼ capture, rolling, adhesion and diapedesis

vasculogenesis (formation of vessels de novo), angiogenesis (formation of

vessels derived from pre-existing vessels)

metabolic functions

◼ endothelial cells can metabolize or activate numerous circulating factors, with or without vasoactive properties - including polypeptide hormones, amines, nucleotides, lipoproteins, metabolites of arachidonic acid and reactive oxygen species

http://content.onlinejacc.org/article.aspx?articleid=1361775

Endothelium - functions

http://www.medscape.org/viewarticle/557238

Endothelial dysfunction:• contribute to several disease processes - hypertension, coronary artery disease,

and other atherosclerotic diseases

2. tunica media◼ smooth muscle cells in extracellular matrix;

connected via gap junctions – form a syncytium (single-unit smooth muscle)◼ Ca-dependent contraction - calmodulin

◼ elastin in large elastic arteries

◼ portions elastin : muscle◼ big arteries - 50% : 20%◼ small arteries - 30% : 40%◼ arterioles - 20% : 50%

◼ external elastic lamina

https://classconnection.s3.amazonaws.com/660/flashcards/2365660/png/untitled1361990992835.png

3. tunica adventitia◼ fibrous connective tissue - net containing collagen

and elastic fibers ◼ function - supporting walls, vasa vasorum and

nerves◼ elastic attachment to the surrounding tissue

collagen – in all three layers

http://yin-informationtechnology.blogspot.sk/2011/01/1024x768-normal-0-false-false-false-en_2973.html

Distribution of the blood

8% - heart cavities

10% - pulmonary circulation

2% - aorta

10% - arteries

1% - arterioles

5% - capillaries

64% - systemic veins

Haemodynamics

blood flow or circulation of the blood

◼ heart activity

◼ dynamic properties of the vessels

◼ blood

➢ regularities of blood flow

➢ velocity of blood flow (cm/s)

➢ units of distance per unit time

➢ blood flow rate (L/s)

➢ units of volume per unit time

➢ type of flow

Average velocity of blood flow

cm/s characteristic

aorta 40 (up to 100)

systolic acceleration diastolic deceleration

continual

changes according muscleactivity, respiration…

arteries 30

arterioles 0.3

capillaries 0.1

venules 1

venas 1-5

vena cava 8-10

Blood flow velocity vs cross-sectional area of the vessels

http://humanphysiology.tuars.com/program/section3/3ch6/s3ch6_3.htm

• in capillaries, the massive cross-sectional area is responsible for the low velocity of blood flow

• the inverse relationship between velocity and cross-sectionalarea

• aorta has a cross-sectional area (2.5 cm2) and an average velocity of 40 cm/s

Blood flow rate vs cross-sectional area

Q = v . A

Q - blood flow rate

v - velocity of blood flow

A - cross-sectional area of

the vessels

velocity of blood flow - inversely proportional to cross-sectional area of the vessel

http://humanphysiology.tuars.com/program/section3/3ch6/s3ch6_3.htm

Haemodynamics - variables

1. blood pressure

2. blood flow

3. resistance of vessels

the similar factors in Ohm's law

current (I) equals the voltage difference (ΔV) divided byresistance (R)

In relating Ohm's Law to fluid flow:

the voltage difference is the pressure difference

the resistance is the resistance to flow offered by theblood vessel and its interactions with the flowing blood

the current is the blood flowhttp://www.themeasureoflife.org/bloodcirculation.htm

Blood pressure

pressure exerted by flowing blood on the vessel wall

in clinics - arterial blood pressure

systolic (BPs) - at the top of systole - the highest

diastolic (BPd) - at the end of diastole - the lowest

dicrotic notch backflow of blood in the arteries when the aortic valve is

closing

indicates the end of systole and the beginning of the diastole

dicrotic notch

Pulse pressure= pressure amplitude

difference between the systolic and diastolic pressure

it represents the force that the heart generates each time it contracts

determined by stroke volume and compliance of thearterial system

calculation: BPs - BPd

low - low stroke volume

high - increase of stroke volume (exercise), stiffness of elastic arteries

Pulse pressure

muscular artery (posterior tibial artery in the ankle) - smaller with a lower compliance →

higher pulse pressure

http://courses.washington.edu/conj/circulation/reflectedPulse.htm

ankle/brachial index◼ noninvasive way to check

your risk of peripheral artery disease

◼ can indicate:

narrowing or blockage of the arteries in your legs

increasing risk of circulatory problems (heart disease or stroke)

http://www.wikiwand.com/en/Ankle-brachial_pressure_index

Pulse pressure- effect of branching in the arterial system

http://courses.washington.edu/conj/circulation/reflectedPulse.htm

Mean arterial pressure

the average level of the blood pressure during cardiac cycle

calculation: MAP = 1/3 BPs + 2/3 BPd

= BPd + 1/3 (BPs - BPd)

is the force that drives blood through the vasculature

Mean arterial pressure

this is pressure that is primarily regulated

tends to remain unchanged in the arterial system, fromascending aorta to peripheral arteries

high heart rate - MAP is closer to the arithmetic average of systolic and diastolic pressure◼ at 200 beats/min –systole and diastole both last for 0.15 s

Blood pressure - determinants

1. cardiac output

2. peripheral resistance

3. elasticity of the arteries

4. blood volume

http://slideplayer.com/slide/8935099/

Cardiac output stroke volume - its increase - ↑BPs

HR - its increase - ↑BPd (shortening of diastole, insufficient time to decrease of BP during diastole)

Peripheral resistance

important for maintenance of BPd

its increase - ↑BPd

Volume of the blood its increase - ↑BP (role for kidneys)

Elasticity of the arteries

Windkessel function

↓elasticity

◼ ↑BPs

◼ ↓BPd

http://www.precisionnutrition.com/doctor-detective-hypertension

https://www.youtube.com/watch?v=2AbPacPQAWM

Factors influencing blood pressure

1. circadian rhythm

2. age

3. sex

4. physical activity

5. breathing

6. intake of meal, emotions, gravitation (posture), pain

Blood pressure - circadian rhythm

in the night - ↓BP by 10-15% → dippers

in non-dippers - the lack of nocturnal BP fall

the prevalence of non-dippers in essential hypertension appears to be about 35%

◼ is associated with more serious end-organ damage

http://www.medicographia.com/2011/01/ambulatory-blood-pressure-monitoring-24-hour-blood-pressure-control-as-a-therapeutic-goal-for-improving-cardiovascular-prognosis/

Blood pressure –age

BPs + BPd gradually increase with age

BPs more (loss of windkessel effect)

Blood pressure - sex

till adolescence - equal BPs the rise in BP with age is greater in males than

in females till menopause

after menopause - equal (or rise more in women)

Blood pressure - physical activity

Isotonic exercise BPs increase usually ranges from 50 to 70 mm Hg

BPd - only minor changes in the normotensives

◼ BPd in the hypertensives tends to increase (lower ability to reduce the peripheral resistance)

◼ several studies indicate that the blood pressure response to isotonic exercise is an early marker for detection of hypertension (resting blood pressure is still normal)

Isometric exercise elevations of both BPs and BPd

Blood pressure - breathing

BP fluctuates with breathing, normally by 5-10 mmHg

maximum - at the beginning of inspiration, then decline during inspiration and increase during expiration

Mechanism - complex

inspiration - increase in negative intrapleural pressure

→ better venous return→ blood pools in pulmonary circulation→ left heart filling reduced and lower stroke volume

Pulsus paradoxus:

http://www.healio.com/cardiology/learn-the-heart/cardiology-review/pulsus-paradoxus

Blood pressure - values

systolic/diastolic

normal range

◼ systolic - up to 140 mmHg

◼ diastolic - up to 90 mmHg

values 140/90 and higher - hypertension!

◼ (sometimes - up to 160/95 - prehypertension)

hypotension - less than 90/60

Blood pressure - measurement

direct method◼ catheterization - by penetrating the arterial wall to

take the measurement, much less common, restricted to a hospital setting

https://www.quora.com/Normal-resting-blood-pressure-for-an-adult-is-approximately-120-80-mm-Hg-Wikipedia-Is-air-pressure-the-reference-point-for-this-measurement

BP measurement - indirect methods

1. Riva-Roci method - palpatory

◼ cuff - compression of brachial artery

◼ palpation of radial pulse - its disappearance → BPs

2. Korotkoff’s auscultationmethod◼ BPs < cuff pressure - no blood flow

◼ cuff pressure just below BPs - origin of the Korotkoff phenomena = caused by turbulent blood flow through the partially occluded artery

◼ cuff pressure just below BPd -disappearance of sounds - laminar blood flow

http://faculty.ksu.edu.sa/15218/Medical%20Books/Medical%20Physiology%202nd%202003%20Rhoades/Medical%20Physiology%202nd%202003

%20Rhoades/smch15.pdf

http://faculty.ksu.edu.sa/15218/Medical%20Books/Medical%20Physiology%202nd%202003%20Rhoades/Medical%20Physiology%202nd%202003 %20Rhoades/smch12.pdf

3. oscillometric method

◼ cuff pressure varies periodically with the cyclic expansion and contraction of the brachial artery

http://elektroarsenal.net/noninvasive-arterial-blood-pressure-and-mechanics.html

Haemodynamics - variables

1. blood pressure

2. blood flow

3. resistance of vessels

Blood flow

the amount the blood passing a given point inthe circulation per unit of time

units: ml/s, L/s, ml/min, L/min

the same volume of blood must flow through each segment of the circulation each minute →

the velocity of blood flow is inversely proportional to vascular cross-sectional area

Blood flow - Hagen–Poiseuille’s law

includes all parameters that influence blood flow

π x r4

Q = ∆P x –––––––––8 x L x η (eta)

Q – blood flow

∆P – blood pressure gradient

r – radius of the vessel

L – length of the vessel

η – viscosity of the blood

Blood flow - Hagen–Poiseuille’s law

π x r4

Q = ∆P x = ∆P x C–––––––––8 x L x η

C - conductance of the vessel - equal to the reciprocal ofresistance◼ increases in proportion to the fourth power of the radius

1––– = RC

∆PQ = –––––– (parallel to Ohm's Law: I = U/R)

R

Determinants of blood flow:

pressure gradient along the vessel

vascular resistance (! r4)

http://slideplayer.com/slide/4253025/

Blood viscosity

characterizes an internal friction of the blood → there will be frictional losses as blood travels through a section of vessel

primarily depends on the attractive forces between particles

Primary determinant for blood viscosity:

hematocrit

http://fblt.cz/en/skripta/v-krev-a-organy-imunitniho-systemu/1-slozeni-krve/

Blood viscosity

shear stress

◼ describes frictional forces (corresponded to the surface) between blood layers

shear rate

◼ difference in velocities between blood layers

Newtonian fluids

◼ viscosity = shear stress/shear rate → shear stress is linear with shear rate

Blood = shear thinning fluid - the viscosity decreases as the shear rate increases

Hagen–Poiseuille’s law - limitations

Newtonian fluids - the viscosity remains a constant independent the speed of flow (only temperature dependent)

pipes - rigid

laminar flow

in vitro in vivo

blood - non-Newtonian fluid (their viscosity is dependent on shear rate= velocity of flow)

vessels - elastic

flow laminar or turbulent

Pattern of flow in vessels - laminar

blood flows in layers

each layer remains the same distance from the vesselwall

parabolic velocity profile

laminar flow - noiseless

https://commons.wikimedia.org/wiki/File:Laminar_and_turbulent_flows.svg

Laminar flow of blood

http://www.physics.usyd.edu.au/teach_res/jp/fluids/viscosity.pdf

Laminar flow of blood

axial flow - the fastest

◼ blood elements (erythrocytes)

next to walls - plasma

plasma skimming

= natural separation of erythrocytes from plasma at bifurcations in the vascular tree

◼ capillary hematocrit - lower by 25%

Pattern of flow in vessels - turbulent

blood flows crosswise

eddy currents are present

blood flows with much greater resistance - eddies increase overall friction - flow rate is reduced → this

causes greater energy loss compared to the laminar flow

turbulent flow - produces vibrational noise

https://commons.wikimedia.org/wiki/File:Laminar_and_turbulent_flows.svg

Turbulent flow

under the physiological conditions

◼ ascending aorta (high flow)

◼ in branching and curvature sites

pathological - stenosis

Reynolds number

its critical value predicts the change of flow to turbulent

◼ starts at about 1000, 2000 and higher - flow is usually turbulent

ρ x v x d Re = ––––––––––

η

http://www.cvphysiology.com/Hemodynamics/H007.htm

Resistance

pressure difference over the volume flow

consequence of friction between blood and walls of blood vessels

is determined by:◼ the length and diameter of individual vessels

◼ the organization of the vessels

◼ physical characteristics of the blood (viscosity, laminar flow vs turbulent flow

◼ extravascular mechanical forces acting upon the vasculature

can be calculated

8 x L x ηR = –––––––––

π x r4

Arrangement of the vessels

1. in series (sequentially)

◼

◼ resistance of the entire system = sum of the resistances offered by each type of vessel

Rtotal=Rarteries+Rcapillaries+Rveins

2. in parallel

◼ vascular beds for various organs

◼ 1/Rtotal=1/R1+1/R2+…+1/Rn

◼ total resistance is less than any of the individual resistances

◼ blood flow to a particular organ can be adjusted without great affection of resistances in the rest of the system

http://humanphysiology.tuars.com/program/section3/3ch6/s3ch6_10.htm

Total peripheral resistance

= the sum of the resistance of all peripheral vasculature in the systemic circulation

arterioles 47%

big arteries

19%

capillaries 27%

veins 7%

Critical closing pressure

stop of the blood flow despite the non-zero blood pressure

arterial pressure threshold below which arterial walls collapse

= 20 mmHg (2,7 kPa)

Certain amount of pressure is required to:

push RBCs through capillaries

counteract the tissue pressure exerted over the vessels

Function of arteries

Elastic arteries - 2 properties:

1. distensibility during systole

◼ part of energy from heart systole is stored as potential energy in the wall of aorta

2. elastic recoil during diastole

◼ potential energy stored in the wall is released to theblood

reduction of the velocity of blood flow during systole

maintenance of blood pressure during diastole

pumping action of the heart is more effective

conversion of pulsatile blood flow to a steady continuous

Muscular arteries ability to vasoconstrict and vasodilate -

can adjust the rate of blood flow

peripheral resistance - maintenance of BPd

Blood flow in arteries:

driving force - heart action + Windkessel function

laminar blood flow (aorta ascendens - turbulent)

oscillations in systole/diastolehttp://slideplayer.com/slide/6881217/

Capillaries

provide the most of exchange between the blood and tissue cells

do not have tunica media, externa - do not have ability to vasoconstrict or vasodilate

pericytes wrapped around the outside of the basementmembrane contain contractile fibers + maintenance ofselective permeability + ability of phagocytosis

http://www.mdpi.com/2073-4409/2/3/621/htm

inner diameter - 4-8 μm - high individual vascularresistance

parallel arrangement - combined resistance is quite low

small diameter + thin wall = short diffusion pathway

are not open under resting conditions in most tissues (skeletal muscle – 10%)

Capillary endothelium

1. fenestrated

◼ glomeruli, intestinalmucosa

2. continuous

◼ lungs, CNS, muscles

3. discontinuous

◼ liver, spleen, bone marrow

structural differences → variationsin capillary permeability

http://www.columbia.edu/~kj3/Chapter6.htm

The passage of molecules

1. diffusion

◼ through the endothelial cells – e.g. O2, CO2, lipid soluble substances (steroid hormones)

◼ through pores, channels, intercellular clefts (glucose, electrolytes)

2. filtration + reabsorption - between the endothelial cells - through endothelial pores - water, ions, small molecules (radius less then 3-6 nm in majority of vessels)

3. pinocytosis – vesicular transport (fatty acids, albumin, somehormones)

Forms of transport: primarily passive

http://physiologyonline.physiology.org/content/27/4/237

Diffusion promoted by:

◼ short distance of travel

thinness of the wall

narrowness of the lumen

proximity to cells

◼ total surface area

◼ velocity of blood flow

the slowest = sufficient exchange time

Amount of diffusion (Fick’s law)

is proportional to diffusion constant (permeability of the membrane for particular molecule) across the barrier, the surface area available for diffusion, and the concentration gradient across the barrier (pressure gradient)

inversely proportional to thickness of the membrane

Filtration + reabsorption

exchange according the changes in pressuredriving forces (either hydrostatic or osmotic)

bulk transport = ultrafiltration – reabsorption

arterial segment of the capillary - ultrafiltration

venous segment of the capillary - reabsorption

Filtration and reabsorption

Opposing forces:

OUT the capillary

1. blood (hydrostatic) pressure

◼ high on arterial end

◼ low on the venous end

2. oncotic interstitial pressure

INTO the capillary

1. oncotic pressure in the capillary

2. interstitial (hydrostatic)pressure

http://www.mhhe.com/biosci/ap/mediaphys2_inprogress/data/circulatory2/027/index.html

Starling forces and factors

blood (hydrostatic) pressure

◼ arterial segment of the capillary - 4.3 kPa

◼ venous segment of the capillary- 2.3 kPa

oncotic interstitial pressure - 0.7 kPa

oncotic pressure in the capillary - 3.7 kPa

interstitial (hydrostatic) pressure - varies from organ to organ (set to 0)

arterial segment

(4.3 + 0.7) - 3.7 = 1.3 kPa

venous segment

(2.3 + 0.7) - 3.7 = - 0.7 kPa

http://www.mhhe.com/biosci/ap/mediaphys2_inprogress/data/circulatory2/028/index.html

http://fblt.cz/en/skripta/x-srdce-a-obeh-krve/2-krevni-obeh/

Edema formation

capillary hypertension = hydrostatic edema (kidney retention, high venous pressure - heart failure, obstruction,…)

hypoproteinemia - malnutrition, liver disease, loos of proteins

lymphedema - impaired lymphatic drainage

alteration of endothelial barrier function (immune - allergic reaction, toxins…)

Veins

lower tone and resistance

venous return - flow of the blood back to the heart

venous return = cardiac output

cardiovascular system = closed loophttp://www.cvphysiology.com/Cardiac%20Function/CF016.htm

Veins

Driving forces to blood flow

1. pressure gradient - vis a tergo

2. muscle pump mechanism

3. respiratory activity

4. cardiac suction - vis a fronte

5. gravitation force

Pressure gradient

residual blood pressure gradient generated bysystole and elastic arteries

venules

12-18 mmHg

blood entering the RA

about 4.6 mmHg (not stable)

https://cnx.org/contents/A4QcTJ6a@3/Blood-Flow-Blood-Pressure-and-

Muscle pump mechanism

contraction of muscles → compression of vein→ increase of blood pressure

requires functional valves → one-way flow

https://cnx.org/contents/A4QcTJ6a@3/Blood-Flow-Blood-Pressure-and-

Muscle pump mechanism

skeletal muscles - leg muscles

pulsation of parallel arteries (arterial pump)

external compression - massage

http://humanphysiology.academy/D.CVS/D.4.%20TheVascularSystem/D.4.4.Veins.html

Intrapleural and abdominal pressure

effect of respiratory activity

blood flow in chest and abdominal cavities

Inspiration

more negative pressure in the chest →

transferred to veins (all the hollow objects) →

veins suck the blood

increase ofintraabdominal pressure

→ blood is pushed into the chest cavity

http://clinicalgate.com/venous-physiology/

Cardiac suction

effect of cardiac cycle

blood flow just before the RA (we do not havevalves between the vena cava and RA)

Ventricular contraction:

apex to base shortening → AV valves move downward → enlargement of atria → atrial pressure drops down → blood is sucked

Gravitation force

drains blood from head and neck

after changing of position (to horizontal)

Regulation of circulation

regulation of the heart

local (intravascular) regulatory mechanisms

extravascular mechanisms

◼ humoral

◼ neural

short-term - maintenance of blood flow in particular part of thebody

◼ vasodilation, vasoconstriction

long-term - maintenance of systemic blood pressure →

pressure gradient

◼ together with control of circulating blood volume by thekidneys

vasoconstriction, vasodilation - commonly usedfor diameter change in arterial system

constriction of vein - venoconstriction

dilation of vein - venodilation

Local regulatory mechanisms

ability of vessel to regulate its own blood flow despite the

changes in perfusion pressure = autoregulation

3 main aims:

1. maintenance of constant perfusion of the tissues

2. maintenance of constant linear blood flow

3. adjustment of the blood flow to the metabolic activity

Local regulatory mechanisms

Mechanisms:

1. myogenic

◼ vascular tone - continuous partially contracted state of vascular smooth muscle in the wall of the vessels

◼ ↑stretch → vasoconstriction → ↑resistance → ↑BP →

stable blood flow (Q=ΔP/R) + prevention of overdistension

◼ well developed in kidneys, brain

http://www.slideshare.net/VNyuntWai/vtone-t-pfsnnw2012

http://www.slideshare.net/VNyuntWai/vtone-t-pfsnnw2012http://ajpheart.physiology.org/content/304/12/H1598

2. metabolic

◼ metabolically active tissue → ↑accumulation of metabolites → vasodilation (relaxation of precapillary sphincter)

lactate → H+

↑ CO2

K+ - ion disturbances

adenosine - synthesis of ATP is reduced

◼ some substances - vasoconstriction (serotonin, thromboxane A2)

Endothelium-derived substances

vasodilating

◼ NO, prostacyclin (PGI2), prostaglandins (PGE2, PGD2),EDHF (Endothelium-Derived Hyperpolarizing Factor)

vasoconstrictive

◼ endothelins, thromboxane A2, prostaglandins (PGH2), angiotensin II

http://jap.physiology.org/content/100/1/318

Hyperemia

increased blood flow to the tissue

1. active (functional)

◼ result of arteriolar dilation

◼ during the increased metabolic activity → release of

vasodilating substances

a. reactive

when the circulation is reestablished after the period of occlusion

2. passive

◼ result of venular dilation

◼ congestion - due to obstruction of blood outflow

Systemic humoral regulation

vasodilating substances

◼ plasmatic kinins

◼ natriuretic peptides

◼ histamine

◼ acetylcholine

◼ VIP (vasoactive intestinal peptide)http://sism5bio.blogspot.sk/

Plasmatic kinins

vasodilator peptides

◼ bradykinin (slow development of gut contraction)

◼ kallidin (lysylbradykinin)

kallikreins - enzymes produced by liver

kininases - peptidases (kininase II = ACE) - kinins are metabolized rapidly (half-time < 15 s)

dilation is mediated by NO and prostacyclin synthesis inendothelial cells

http://www.slideshare.net/tabish0919/bradykinin-by-sid

Natriuretic peptides

„main″ function - increase excretion of Na+ in kidneys

atrial natriuretic peptide - ANP

brain natriuretic peptide - BNP (ventricles of the heart)◼ measured in clinics - an aid in the diagnosis and assessment of

severity of heart failure

CNP (C-type natriuretic peptide), urodilatin (synthetized in tubular cells) - paracrine action

DNP (Dendroaspis natriuretic peptide - isolated from the venom of the green Mamba snake)

stimulus:

◼ atrial, resp. ventricular distension (volumoreceptors)

◼ angiotensin II stimulation

◼ sympathetic stimulation

responses:

◼ renal - increase of glomerular filtration rate and filtration fraction, inhibition of sodium transport in tubules → natriuresis and diuresis

◼ BP and volume decrease - via inhibition of RAAS -inhibition of renal renin release

Histamine

important during inflammation, tissue injury, allergicresponses

H1 receptors - vasodilation + NO release - dominant effect

H2 receptors - vasoconstriction

Vasoactive intestinal peptide

in CNS, PNS - neurotransmitter, neuromodulator

present in the gastrointestinal tract, heart, lungs, thyroid, kidney, urinary bladder, genital organs and the brain

50-100 times more potent vasodilator than acetylcholine

effect mediated by its receptors + NO release

Systemic humoral regulation

vasoconstrictive substances

◼ ADH

◼ angiotensin II

◼ serotonin

http://sism5bio.blogspot.sk/

Antidiuretic hormone

also called - vasopressin ↔ vasoconstriction + BPincrease

synthesis - nucleus supraopticus (paraventricularis) magnocellular neurons

storage - neurohypophysis

stimulus - ↑plasma osmolarity, hypovolemia, ↓BP

http://nootriment.com/vasopressin/

Angiotensin II

AT1 receptors

◼ vasoconstriction

◼ sodium reabsorption, aldosterone release

◼ CNS - norepinephrinerelease

◼ cardiac hypertrophy

https://en.wikipedia.org/wiki/Angiotensin

Serotonin

neurotransmitter in CNS

released from activated platelets

S2 receptors - vasoconstriction (renal vessels)

S1 receptors - vasodilation in skeletal muscles, coronarycirculation

Catecholamines

adrenergic receptors - α, β

α-receptor - vasoconstriction - skin, kidneys, GIT

β-receptor - vasodilation - skeletal muscle

norepinephrine - α

epinephrine - α, β

http://fce-study.netdna-ssl.com/images/upload-flashcards/1018754/2415244_m.jpg

Catecholamines

the affinity of epinephrine is higher for β-receptors

◼ low to medium level → vasodilation

◼ high circulating level → vasoconstriction

◼ SVR - systemic vascular resistance

http://www.cvphysiology.com/Blood%20Pressure/BP018.htm

Systemic neural regulation

Efferent pathways:

sympathetic (noradrenergic) NS

▪ maintains vascular tone

▪ most important = dominant control

▪ variations in vascular tone ↔ variations in

sympathetic tone

Systemic neural regulation

Efferent pathways:

sympathetic cholinergic NS

◼ in skeletal muscles

◼ not important for normal control

◼ vasodilator system

◼ stress - pooling of blood in skeletal muscles of lower limbs (emotional stress - fainting)

parasympathetic NS

◼ not important for systemic control

◼ vasodilation in glands, reproductive (erectile) tissue (mediated by NO release from endothelium)

Vasomotor centre

medulla oblongata, pons

Components according the function:

1. vasoconstrictor part

2. vasodilating

3. sensory

under the influence of higher centres - cortex, hypothalamus

Vasoconstrictor centre → sympathetic NS (vasomotornerves) → smooth muscle in vessels

◼ maintains baseline muscle tone (about halfway between full dilation and full constriction

Vasodilating centre → inhibition of vasoconstrictor centre

Sensory part

receives the inputs from receptors (mainly via N.IX, N.X)

presets the activity of vasoconstrictor and vasodilatingcentres

provides reflex control of many circulatory functions

vasoconstrictor centre (VC)

vasomotor nerves (VM)

vasoconstriction (VCN)

peripheral resistance (PR)

blood pressure (BP)

carotid sinus (CS)

glossopharyngeal nerve (GP)

vasodilator centre (VD)

http://www.physiologymodels.info/cardiovascular/vascular_centers.htm

Afferent pathways = information flow from:

◼ baroreceptors

◼ stimulation - vasodilation

◼ volumoreceptors

◼ chemoreceptors

Interaction of systemic and local regulatory mechanisms

aim: provide blood to vital organs

local mechanisms - ↑ blood flow + central -

vasoconstriction = conflict of interest

hierarchy - different for various organs (tissues)

◼ skin - central dominant

◼ myocardium - local dominant

◼ skeletal muscles

rest - central

activity - local

SPECIFICSOF SELECTED CIRCULATIONS

Heart

blood inside the heart - impossibility for oxygen and nutrients to diffuse from the chambers through all the layers

coronary circulation

◼ origin - just above the aortic valve → pressure inside the aorta- driving force for coronary blood flow (for systemic circulation)

◼ the smallest critical closing pressure → blood flow is present despite the severe hypotension (a.femoralis - blood flow is stopped in 40 mmHg; average vessel - 20 mmHg)

high density of capillaries - 1 capillary = 1 cardiomyocyte

comparison with skeletal muscle

◼ skeletal - fibre diameter 50 μm, capillaries 400/mm2

◼ cardiac - fibre diameter 18 μm, capillaries more than 3000/mm2

better diffusion

◼ short diffusion distances (9 μm)

◼ large diffusion area

myocardium - aerobic metabolism

high extraction of oxygen (70 to 80%) by myocardiumduring rest

high resting blood flow 250 mL/min (200 ml left coronary artery) = 5% of CO

the only possibility in higher demands for oxygen →

increase of blood flow - linear relation between myocardial oxygen consumption and coronary blood flow

blood flow can increase up to 2 L/min = coronary blood flow reserve (= the only practical way to increase oxygen delivery)

Anatomy:

perfusion from the epicardial (outside) surface to theendocardial (inside) surface

http://www.guwsmedical.info/heart-failure/myocardial-blood-flow.html

blood flow - influenced by cardiac cycle

especially left endocardial part of the heart

◼ systole - myocardial extravascular compression - ↓ blood flow

◼ diastole - ↑ blood flow (80%) = pressure-flow paradox

right endocardial part of the heart - higher blood flow in systole

increase of HR – increase demand for oxygen+ marked reduction in the time available forleft coronary perfusion

subendocardial part of LV - more prone to ischemic damage → common site of myocardial

infarction

Regulation of coronary circulation

Autoregulation

1. myogenic - in the range of BP: 70 - 170 mmHg

2. metabolic - ↑ metabolism → ↓pO2, ↑ CO2, ↑ pH, ↑ lactate,

↑ K+, adenosine, prostaglandins, NO = metabolic

(active) hyperemia

Local humoral regulation

vasodilation - after i.v. administration of acetylcholine (via NO release, non-functional endothelium -vasoconstriction), histamine

endothelium - NO, prostaglandin, endothelin-1

Nervous regulation

basal vascular tone - higher → reserve for vasodilation

parasympathetic - weak = mild vasodilation

sympathetic

bigger arteries - α receptors - constriction =prevention of retrograde blood flow during systole

small arteries - β receptors - vasodilation

vasodilation prevails

Systemic humoral regulation

catecholamines

ADH - vasoconstriction (mainly epicardial arteries)

neuropeptide-Y, vasoactive intestinal peptide, substanceP, …

Brain

some similarities with coronary circulation - ↑ metabolicrequirements, ↑ extraction of oxygen, limited anaerobicmetabolism

adults - 700-750 mL/min - about 15% CO

high consumption of oxygen - 50 mL/min ↔ 20% of total

oxygen consumption (brain - 2% of BW)

Regional differences of blood flow

higher blood flow (up to 6-fold) in grey matter (higher density of capillaries) compared to white matter (blood flow -corresponded to metabolism)

concurrent activities

capillaries - less leaky - tight endothelial junctions + surrounding astrocytes and pericytes = BBB = blood brain barrier

BBB exception - circumventricular organs (pineal gland, some areas of the hypothalamus, area postrema,…)

support by glial cells - prevention of overdistension in case of↑BP

Regulation of cerebral circulation

Autoregulation - dominant

1. myogenic - maintenance of stable cerebral blood flow inwide range of BP (55 - 150 mmHg)

2. metabolic - local humoral factors

◼ ↓pO2, ↑CO2, adenosine, ↑K+ – vasodilation

role of endothelium - NO, prostaglandins

autoregulation more precise in brainstem than in cortex (consciousness can be lost long before regulatory functions of brainstem are compromised)

Humoral regulation

catecholamines◼ E - ↑ blood flow (vasodilation - β-receptors)

◼ NE - vasoconstriction - ↓ blood flow (α-receptors)

Nervous regulation - weak

in bigger vessels more important

◼ sympathetic – limited ability to constrict

◼ parasympathetic - limited ability to dilate

Cerebral edema

cranium – rigid

brain, medulla, CSF, vessels, blood - sum of theirvolumes is constant

increase of brain volume (excessive accumulation of fluidin the brain) → intracranial pressure increases → venulesand vein collapse (low intravascular pressure) →

↓outflow → ↑capillary pressure → ↑filtration of fluid →

further ↑ intracranial pressure

compression of arteriols → ↓blood flow

Lungs

2 circulations

◼ pulmonary - between RV and LA

◼ bronchial - from systemic circulation

pulmonary

◼ BP in pulmonary artery - 12-16 mmHg (just sufficient toperfuse the apical areas of the lungs in the erect healthyadult)

◼ in pulmonary vessels - 6-10 mmHg

◼ oncotic pressure - about 28 mmHg → favouring reabsorption of water - prevention of pulmonary oedema (alveoli - available for ventilation)

Pulmonary circulation

blood reservoir - its capacity is changed according thebody needs

volume of the blood - 1L, in capillaries - 100 mL

stroke volume 70 mL - rapid exchange of blood in capillaries

horizontal position - blood volume increase about 400mL

Low vascular resistance - thin and distensible vessel walls

2-3 mmHg/L/min

for blood flow 1 l/min we need 2-3 mmHg

influenced by respiration

Blood flow - same as in systemic circulation

about 5 L/min

2% of blood - via bronchial arteries = nutrition for lungs

acceleration in systole

average velocity about 40 cm/s - occurrence of turbulent flow

Distribution of blood

1. influence of hydrostatic pressure

◼ in vertical position - difference between the highest and the lowest point 30 cm → corresponds to 23 mmHg

◼ apical parts - BP lower about 15 mmHg than in heart level

◼ heart level - BP lower about 8 mmHg than in lung bases

2. alveolar pressure◼ the highest in apical parts - higher than BP → blood flow during

systole only

◼ heart level - lower (+ higher hydrostatic pressure) - higher blood flow

◼ base of lungs - the lowest - lower than BP (systolic and diastolic) -all the capillaries are open

Regulation of pulmonary circulation

Autoregulation

1. myogenic - weak

2. metabolic and local humoral - predominate

partial pressures of respiratory gases

◼ ↓pO2 in alveoli → local vasoconstriction (in surroundingvessels) - transfer of blood to better ventilated parts =hypoxic pulmonary vasoconstriction

◼ (obstruction in blood flow → ↓pCO2 in alveoli →

bronchoconstriction)

◼ ↓pO2 in blood → vasoconstriction

endothelium - NO, prostaglandins, endothelin

Systemic humoral

constriction - norepinephrine, histamine, angiotensin II,thromboxane A2

dilation - bradykinin, acetylcholine, platelet activating factor (PAF)

Nervous regulation

parasympathetic - weak vasodilation

sympathetic innervation – vasoconstriction = decreasethe compliance of the vessels – more blood is availableto the systemic circulation

Kidneys

↑ renal blood flow - 20% of CO (1000 ml/min)

◼ is kept constant in wide range of systemic arterial BPvalues (80-180 mmHg)

2 capillary networks

◼ glomerular - ↑ BP - filtration

◼ peritubular - ↓ BP - reabsorption

capillaries - more leaky

Regulation of renal circulation

myogenic autoregulation -↑ BP → vasoconstriction →

↓ blood flow

http://faculty.ksu.edu.sa/15218/Medical%20Books/Medical%20Physiology%202nd%202003%20Rhoades/Medical%20Physiology%202nd%202003 %20Rhoades/smch23.pdf

BP in glomeruli - via adjusting the resistance of vas afferens and efferens

◼ ↑ BP - due to constriction of vas efferens

◼ ↓ BP - due to constriction of vas afferens

vasoconstriction - ↑ Na+ and Cl- in tubular fluid detected by macula densa, angiotensin II, endothelin, antidiuretic hormone, adenosine, sympathetic nerve stimulation

vasodilation - prostaglandins, bradykinin, ANP, NO

tubuloglomerular feedback

◼ ↑ in glomerular filtration → ↑ fluid (solute) delivery to the macula densa → ↑ reabsorption of NaCl (concentration dependent uptake by Na+-K+-2Cl-cotransporter)→ afferent arteriole constriction

◼ mediated by ATP → generation adenosine → adenosine receptors → ↑Ca2+ in extraglomerular mesangial cells → via gap junctions → afferent arteriole constriction + inhibition of renin secretion

http://faculty.ksu.edu.sa/15218/Medical%20Books/Medical%20Physiology%202nd%202003%20Rhoades/Medical%20Physiology%202nd%202003 %20Rhoades/smch23.pdf

Liver

↑ hepatic blood flow - 30% of CO

2 circulations - 2 inputs, 1 output

◼ nutritive - a. hepatica propria (500 ml/min)

◼ functional - portal - v. portae (1000 ml/min)

◼ both provide oxygen equally

◼ the regulation of both blood flows

hepatic arterial flow increases or decreases reciprocally with the portal venous blood flow (hepatic arterial buffer response) - can compensate about 25% of the decrease or increase in portal blood flow

The liver - high metabolic rate + it is a large organ → the largest oxygen consumption of all organs in a resting person

liver acinus

◼ functional unit of liver tissue - ellipse-shaped

◼ short axis - connection between two adjacent portal triads

◼ long axis - connection between two adjacent central veins

◼ zone II, III - receive less oxygenated blood - moreprone to injury

http://fblt.cz/en/skripta/ix-travici-soustava/5-jatra-a-biotransformace-xenobiotik/

capillaries = sinusoids - more leaky + equipped withKupffer cells (protection from GIT)

splanchnic circulation (including hepatic) - blood reservoir (1/3 of blood)

Regulation of hepatic circulation

autoregulation - myogenic (in a.hepatica propria)

humoral - epinephrine

nervous regulation

◼ sympathetic nerve fibres - vasoconstriction (redistribution of blood)

Skeletal muscle

comprise 50% of BW

◼ at rest - 15-20% of CO

◼ extreme physical activity – 80-90% of CO (active hyperemia)

rhythmic exercise

◼ intermittent blood flow

static exercise – continuous compression – rapid onset offatigue

◼ storage of O2 in myoglobin - for 5-10 s

http://slideplayer.com/slide/5257493/

Regulation of skeletal muscle circulation

local factors dominant - ↑ metabolism → ↓pO2, ↓ATP,↑lactate, ↓pH, ↑K+, higher temperature - vasodilation

nervous regulation – sympathetic NS◼ α receptors - maintenance of basal tone

◼ β receptors - vasodilation

humoral regulation - catecholamines

Skin

small metabolic requirements

main function – protection + thermoregulation

blood flow varies 1-150 mL/100 g/min

presence of AV anastomoses – connect arterioles andveins directly, bypassing the superficial capillaries

◼ acral skin (areas of high surface area/volume) -hands, feet, lips, nose, ears

http://intranet.tdmu.edu.ua/data/kafedra/internal/normal_phiz/classes_stud/en/med/lik/2%20course/4%20Cycle%20Physiology%20of%20breathing/02%20%20Regulation%20of%20breathing.htm

Regulation of cutaneous circulation

nervous

◼ ↓ temperature (peripheral and hypothalamic thermoreceptors) - sympathetic NS – through α receptors – vasoconstriction

humoral

◼ histamine, bradykinin - vasodilation

◼ serotonin, norepinephrine - vasoconstriction

local – less dominant

◼ prolonged ↓ skin temperature - vasodilation (help to

protect the skin from freezing)

The placental and fetal circulation

Placental:

maternal blood – in contact with fetal villi containing fetal vessels –gas and nutrient exchange

blood flow regulated by local production of vasoactive substances

http://faculty.ksu.edu.sa/15218/Medical%20Books/Medical%20Physiology%202nd%202003%20Rhoades/Medical%20Physiology%202nd%202003 %20Rhoades/smch17.pdf

The placental and fetal circulation

Fetal:

presence of 3 structuralshunts:

1. ductus venosus

2. foramen ovale

3. ductus arteriosus

RV and LV pump blood in parallel + blood bypasses the lungs

http://faculty.ksu.edu.sa/15218/Medical%20Books/Medical%20Physiology%202nd%202003%20Rhoades/Medical%20Physiology%202nd%202003 %20Rhoades/smch17.pdf