physiology of the cvs i - uniba.sk · cardiovascular physiology jana radosinska. physiology of the...
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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