Circulation
Types of circulatory systems
• diffusion is slow – circulation (bulk flow) for the distribution of oxygen and nutritients
• other solutions also exist – trachea in insects, intense enteric system in parasites, etc.
• open circulation– low pressure, slow flow– slow way of living– exception – insects, because of the tracheal
system
• closed circulation– high pressure, fast flow, fast regulation– active life– e.g. difference between snails and cephalopods;
vertebrates and invertebrates in general
• further development: separated circuits in vertebrates for the body and lungs – high pressure would cause filtration in lungs
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Circulatory system of mammals
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 12-3.
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Human heart
Berne and Levy, Mosby Year Book Inc, 1993, Fig. 24-10
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Valves in the heart
Berne and Levy, Mosby Year Book Inc, 1993, Fig. 24-11
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Electrical activity of the heart
• vertebrate heart is miogenic – see Aztec rituals
• principal pacemaker: sinoatrial node • 2x8 mm, built up by modified muscle cells• AP is followed by slow hypopolarization –
hyperpolarization induced mixed channels (Na+, Ca++) and K+ inactivation
• NA and ACh changes the pacemaker potential in different directions through cAMP effecting the hyperpolarization induced channel
• in the atrium – rudimentary conduction system
• AV-node, 22x10x3 mm, in the interatrial septum
• bundle of His, bundle branches (Tawara), Purkinje fibers
• SA, AV nodes 0.02-0.1 m/s, muscle cell 0.3-1 m/s, specialized fibers 1-4 m/s (70-80 vs. 10-15 )
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Electrocardiogram
• fibers in the atria and in the ventricles are activated in synchrony
• high-amplitude signal• vector and scalar ECG• Einthoven triangle• diagnostic importance -
infarction, angina• mean electrical axis• arrhythmias
– premature depolarization extrasystole, compensatory pause
– fibrillation - atrial, ventricular (soap operas)
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 12-8.
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Cardiac cycle
Berne and Levy, Mosby Year Book Inc, 1993, Fig. 24-13
8/27
Regulation of cardiac output I.
• cardiac output = heart rate x stroke volume• frequency is regulated mainly by the
autonomic nervous system• stroke volume depends on the myocardial
performance that in turns depends on intrinsic and extrinsic factors
• heart rate at rest is about 70/minute• during sleep it is less by 10-20, in children
and small animals it can be much higher (hummingbird)
• emotional excitation, exercise: 120-150• parasympathetic inhibition dominates in rest
from the vagal nerves – ganglion on the surface or in the wall of the heart
• asymmetric: right - SA, left - AV• acting through muscarinic receptors• beat-to-beat regulation – fast elimination
9/27
Regulation of cardiac output II.
• sympathetic innervation: lower 1-2 cervical, upper 5-6 dorsal segments
• relay in stellate ganglion• beta adrenergic effect through cAMP -
positive chronotropic, inotropic, dromotropic, batmotropic effects
• slow effect, slow elimination• asymmetric innervation: right -
frequency, left – strength of contraction• other effects:
– baroceptor reflex– respiratory sinus arrhythmia: rate increases
during inspiration, decreases during expiration
– explanation: vagal activity increases during expiration (asthma), filling of the heart (preload) increases frequency
10/27
Myocardial performance• intrinsic factors: Starling´s law of the heart,
or the Frank-Starling mechanism - 1914• myocardial performance increases with
preload to a certain extent• length of skeletal muscles is optimal at rest,
length of heart muscles is optimal when stretched
• increased preload:– first the heart cannot pump out the increased
venous volume – end systolic volume increases– larger end-diastolic volume – stronger contraction –
new equilibrium, increased volume is pumped out
• increased peripheral resistance:– first the heart cannot pump out the same volume
against the increased resistance – end systolic volume increases
– larger end-diastolic volume – stronger contraction – new equilibrium, increased volume is pumped out
• extrinsic factors: most important: sympathetic effect – strength of contraction increases
11/27
Hemodynamics• circulation cannot be described by simple
physical rules: those apply for homogenous fluids flowing by laminar flow in rigid tubes
• it is worth to examine those rules as we don’t have any other choice
• basic principles:– v - linear velocity (cm/s)– Q - flow (cm3/s)– v = Q / A – linear velocity depends on the cross
sectional area – Q = P / R – analogous to Ohm’s law
P * * r4 8 * * lQ = ---------- R = --------- 8 * * l * r4
• arterioles have high resistance because of the small „r”
• relations between viscosity and hematocrit• turbulent and laminar flow – measurement
of blood pressure
12/27
The arterial system
• large volume, distensible wall, terminated by a large resistance - “Windkessel”
• punctured tire, Scotch pipe, etc.• small variation in pressure, continuous flow• decreases the workload of the heart – heart
should pump stroke volume in 1/6 time• terms: systolic/diastolic pressure, pulse
pressure, mean arterial pressure• mean arterial pressure depends on the
blood volume in the arterial system and on the distensibility of the walls of the arteries
• pulse pressure depends on stroke volume and compliance
• heart copes with increased venous return and peripheral pressure through the arterial system
13/27
Microcirculation I.
• in most tissues cells are less than 3-4-cells distance from the nearest capillary
• length 1 mm, diameter 3-10 • arteriole - metarteriole - precapillary
sphincter - capillary - pericytes• arteriovenous anastomosis (shunt) • nutritional and non-nutritional circulation
(thermoregulation) – rat’s tail, rabbit’s ear, etc.
• growth of capillaries depends on demand – babies born before term are put into incubators – upon removal, lens are invaded by capillaries - blindness
• capillary permeability depends on location (function)
• easy penetration for lipid soluble substances
• for hydrophilic ones it depends on capillary type
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Microcirculation II.• continuous capillary
– continuous basal membrane, gaps of 4 nm, 7 nm pinocytotic vesicles
– muscle, nervous tissue, lung, connective tissue, exocrine glands
• fenestrated capillary– continuous basal membrane, pores– everything can penetrate, except proteins and
blood cells– kidney, gut, endocrine glands
• sinusoidal capillary– large paracellular gaps crossing through the
basal membrane– liver, bone marrow, lymph nodes, adrenal cortex
• hydrostatic pressure difference - filtration
(2% out, 85% back) – exchange of materials• filtration - reabsorption – Starling’s
hypothesis • edema: gravidity, tight socks, heart failure,
starving, inflammation, elephantiasis ,
15/27
Regulation of peripheral circulation
• central and local regulation – location-, and time-dependent
• target: arteriole, metarteriole, sphincter muscles
• sympathetic innervation in most cases• strong, long-term contraction without Na-
channels – single-unit smooth muscle• local regulation
– basal miogenic tone– metabolic regulation - adenosine
• external regulation: sympathetic vasoconstriction
• parasympathetic effect e.g. on saliva glands, possibly artifact (bradykinin)
• humoral effect: NA in low concentration dilates ( -adrenergic), in high concentration contracts (-adrenergic) vessels
16/27
Venous system• veins have thin-walls and large volume –
capacity vessels• maximal pressure is about 11 mmHg, but
contains half of the blood volume• effect of gravitation: U-shaped tube,
pressure difference is the same standing and laying – hydrostatic pressure is huge at the turn
• role of the muscle pump and the valves• effect of inspiration – Valsalva's maneuver;
in trumpet players - pressure can be around 100-400 mmHg
• thrombus and embolus• venomotor tone – standing in attention,
fighter pilots, circulatory shock, returning of astronauts
• jumping out of bed - 3-800 ml displaced into legs – cardiac output decreases by 2 l
17/27
Coupling of heart and vessels I.
• balance of blood flow: pumped volume = volume flowing through the periphery
• pumped volume is influenced by: heart beat, contractility of heart, preload, afterload
• the last two are coupling factors – influenced by both the heart and the vessels
• two important relationships should be considered
• cardiac function curve – Starling’s law – vessels can be replaced by tubes
• vascular function curves – increase of cardiac output decreases central venous pressure – heart can be replaced by a pump
• blood is moved by the difference of mean arterial pressure and central venous pressure
• these pressure values depend on blood volume and compliance in the respective systems
18/27
Coupling of heart and vessels II.
• circulation stops: mean circulatory pressure, when heart restarts it pumps blood from the venous into the arterial system
• the two function curves act against each other – moving water in a circular channel
• equilibrium is reached – many phenomena, such as heart failure can be explained by this
• in case of physical exercise, bleeding, veins contract – internal infusion
• sympathetic effect – cardiac function curve is shifted upward
• increase in peripheral resistance shifts both curves downward – balance depends on several factors
19/27
Coronary circulation I.
• heart cannot accumulate oxygen dept, as it never stops – it is always aerobic
• at rest consumption is 8-10 ml/100g/min O2, that is 25-30 ml/min for a 300 g male heart
• total consumption is 250 ml/min, this is 12% of that
• the stopped heart (dog) has a consumption of 2 ml/100g/min O2
• O2 extraction is very high: venous blood has a saturation of about 25% (20 mmHg)
• during physical exercise blood flow can only increase from 180-240 ml/min to 900-1200 ml/min
• many mitochondria, scarce mioglobin and glycogen
• utilizes everything: glucose, lactate, fatty acids, ketone bodies, amino acids
20/27
Coronary circulation II.• coronary arteries – surround the heart• very good blood supply, 8-10 times as many
open capillaries than in the functioning skeletal muscle – almost one capillary/muscle cell
• hypertrophy can deteriorate nutrition• end-artery system: almost no overlap – fast
occlusion, <10% blood, slow – anastomosis • myocardial infarct - necrosis• blood supply of left ventricle stops during
systole• heart rate – systole/diastole ratio!• autoregulation is crucial (between 60-180
mmHg), basal miogenic tone, metabolic regulation (adenosine, NO)
• NA – indirect vasodilatation, direct (weak) vasoconstriction – coronary constriction, emotional excitation, increased O2 need – death can occur
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Cerebral circulation• high O2 (3-4 ml/100g/min) and glucose need• irreversible damage after 3-6 minutes• mass is 2% of bodyweight, circulation 15%, O2
consumption 25%• circle of Willis – right and left a. carotis and a.
vertebralis – moderate contralateral circulation• specialty: closed space – constant blood flow • local differences, measurement: 85Kr, 133Xe, PET• tumor, bleeding, edema – severe consequences• autoregulation very strong between 60-160
mmHg - mechanism unknown• metabolic regulation: adenosine, NO, CO2, K+
• no sympathetic tone at rest• 3 compartments: intracellular, interstitial, liquor• interstitial fluid and liquor: low protein content,
compared to plasma lower K+ , higher NaCl• blood-brain, blood-liquor barrier,
circumventricular windows
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Splanchnic circulation• gastrointestinal tract, liver, spleen, pancreas• blood flow 25 % of total, strongly variable• 18 % of total blood volume (1 l) – blood
store, half can be released into circulation
• the liver (1.5 kg) uses 20% of total O2 consumption
• a. hepatica, hepatic portal vein - portal circulation – effectiveness of pills and suppositories
• some local regulation (functional hyperemia after meals), increase is only 50 %
• strong central regulation by the sympathetic nervous system– splanchnic vasoconstriction compensates for
vasodilatation in muscles during exercise, peripheral resistance and blood pressure stable
– constriction of veins provides internal transfusion
• in some animals the spleen is a blood store
23/27
Skeletal muscle circulation• 40-50% of body mass (young man), 20 % of
circulation• strong exercise: circulation 20 l, muscles get
80%• at rest: central regulation, during exercise:
metabolic - K+, adenosine (?), H+
• on blood vessels not only 1 adrenoreceptors, but 2 as well – more sensitive for adrenalin - dilatation
• main effect still constriction• stimulation of the limbic system,
hypothalamus, cortex – in some species dilatation - cholinergic sympathetic fibers
• role: preparation for exercise, simulated death
• redistribution of blood flow during exercise – overall vasoconstriction (resistance), venous contraction (volume) – percentages change, but increase of cardiac output more important
24/27
Skin circulation• typical non-nutritional blood flow• 100 ml/min would be sufficient, but 3-500
ml/min flows• serving thermoregulation: thermal exchange
and evaporation• at apical parts (fingers, nose, ears, etc.):
surface-to-volume ratio large - arteriovenous anastomosis toward the venous plexus – if open, intense flow, more heat loss
• strong central regulation: sympathetic innervation, 1 receptor - constriction
• dilatation is achieved by a decrease in this tone
• sweat glands receive sympathetic cholinergic innervation - bradykinin - dilatation
• psychical reactions on the head, neck, upper part of the chest: embarrassment, anger - flushing; fear, anxiety, sorrow - paling; military test
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Central regulation I.
• regulator neurons are in the medulla (formerly: pressor and depressor centers) – that is why any increase in brain volume can be fatal
• input: reflex zones, direct CO2, H+ effect
• output: vagal nerve and the sympathetic nervous system – tonic activity at rest: slow heart beat, vasoconstriction in muscle, skin, intestines
• chemo-, and mechanoreceptors – information for the control of breathing and for the long-term regulation
• part of the receptors found in compact zones, they induce circumscribed reflexes
• receptors in the high-pressure system (baroceptors): carotid and aortic sinuses – „buffer nerves” carry the information to the n. tractus solitarius (belongs to the caudal cell group)
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Central regulation II.• receptors of the low-pressure system (atrial
volume receptors): at the orifice of the v. cavae and the v. pulmonalis, as well as at the tip of the ventricles
• activated by volume increase, effect similar to baroceptor effect, but long-term responses more important – production of ADH and aldosterone decreases
• special receptor group in the atrium: Bainbridge - reflex – filling increase, frequency increase – one factor in sinus arrhythmia
• chemoreceptors: glomus caroticum and aorticum activated by CO2 increase and O2
decrease (below 60 mmHg) – latter is more important as CO2 acts also directly in the medulla – heart frequency decreases, vasoconstriction
• „sleeping pill” for native people (and biology students): pressing the sinus caroticum
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End of text
Conduction system of the heart
Berne and Levy, Mosby Year Book Inc, 1993, Fig. 23-25
Heart-lung preparation
Berne and Levy, Mosby Year Book Inc, 1993, Fig. 25-16
Cross sectional area and velocity
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 12-24.
Pressure changes
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 12-26.
Windkessel function
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 12-28.
Effect of increased venous return
Berne and Levy, Mosby Year Book Inc, 1993, Fig. 27-10
Effect of increased resistance
Berne and Levy, Mosby Year Book Inc, 1993, Fig. 27-13
Microcirculation
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 12-36.
Types of capillaries
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 12-36.
Starling’s hypothesis
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 12-39.
Effect of blood volume changes
Berne and Levy, Mosby Year Book Inc, 1993, Fig. 30-6
Effect of resistance changes
Berne and Levy, Mosby Year Book Inc, 1993, Fig. 30-7
Model of the circulatory system
Berne and Levy, Mosby Year Book Inc, 1993, Fig. 30-2
Coupling between the heart and the vasculature
Berne and Levy, Mosby Year Book Inc, 1993, Fig. 30-12
Effect of sympathetic tone
Berne and Levy, Mosby Year Book Inc, 1993, Fig. 30-9
Autonomic nervous system
Eckert: Animal Physiology, W.H.Freeman and Co., N.Y.,2000, Fig. 11-15.
Spinal nerves
Kiss-Szentagothai, Medicina, 1964, Fig. III-90
Regulation of circulation
Fonyo, Medicina, 1997, Fig. 23-2
caudal neurons
preganglionic vagal neurons
reflexogenic zones
primary afferents
rostro-ventro-lateral neurons
sympathetic preganglionic neurons
sympathetic postganglionic
neurons
heart vessels adrenal medulla
Carotid sinus
Berne and Levy, Mosby Year Book Inc, 1993, Fig. 29-8
Autonomic nervous system I.
• peripheral and central nervous system - PNS-CNS
• CNS: brain + spinal chord• PNS: nerves + ganglia (sensory and
vegetative) + (enteric nervous system)• afferent and efferent, somatic and vegetative• afferent: similar organization – primary
afferent neuron outside of the CNS• efferent: location of motoneurons, outflow,
peripheral relaying, transmitter, target• there are two divisions of the autonomic
nervous system: sympathetic and parasympathetic
• vegetative fibers in spinal nerves • not every organ is innervated by both
divisions, effect is not everywhere antagonistic
• sympathetic: general effects• parasympathetic: localized effects
Autonomic nervous system II.• preganglionic fibers (B-fibers)
– sympathetic and parasympathetic: ACh binding to neuronal nicotinic ACh receptors - ionotropic, opening of Na+-K+ mixed channel - antagonist: e.g. hexamethonium
• postganglionic fibers (C-fibers)– parasympathetic: ACh binding to muscarinic ACh
receptors - IP3 increase, and opening (direct effect) or closing (indirect effect) of K+-channels - antagonist: atropine, agonist: carbachol
– sympathetic: 90% NE, 10% ACh (salivary gland, sweat gland, vasodilatation in skeletal muscles) 1 - IP3 increase - Ca++ release from internal stores –
contraction in smooth muscles, e.g. vessels, sphincters in the intestines, iris radial muscle - NE > Adr
2 - cAMP decrease – mostly autoreceptor 1 - cAMP increase - Ca++ - in the heart - chrono-, and
inotropic effect - NE = Adr 2 - cAMP increase - Ca++ pump - relaxation in smooth
muscles, e.g. bronchioles, skeletal muscle vessels - Adr >> NE
- agonist: phenylephrine, antagonist: phenoxybenzamine
- agonist: isoprotenerol, antagonist: propanolol
Elephantiasis I.
Elephantiasis II.