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Circulation
2/27
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
5/27
Valves in the heart
Berne and Levy, Mosby Year Book Inc, 1993, Fig. 24-11
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Electrical activity of the heart
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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.
Cardiac cycle
8/27
Berne and Levy, Mosby Year Book Inc, 1993, Fig. 24-13
9/27
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
10/27
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
Myocardial performance
11/27
• 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
Hemodynamics
12/27
• 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
Q = ---------8 *  * l
8 *  * l
R = -------- * r4
• arterioles have high resistance because of the
small „r” 
• relations between viscosity and hematocrit
• turbulent and laminar flow – measurement of
blood pressure
The arterial system
13/27
• 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 
Microcirculation I.
14/27
• 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
Microcirculation II.
15/27
• 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 , 
Regulation of peripheral
circulation
16/27
• central and local regulation – location-, and
time-dependent
• target: arteriole, metarteriole, sphincter
muscles
• sympathetic innervation in most cases
• strong, long-term contraction without Nachannels – 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
Venous system
17/27
• 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 100400 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
Coupling of heart and vessels I.
18/27
• 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 
19/27
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
Coronary circulation I.
20/27
• 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
Coronary circulation II.
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• 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
Cerebral circulation
22/27
• 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
Splanchnic circulation
23/27
• 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
Skeletal muscle circulation
24/27
• 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
Skin circulation
25/27
• 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
Central regulation I.
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• 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)
Central regulation II.
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• 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
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
rostro-ventrolateral neurons
caudal
neurons
preganglionic
vagal neurons
primary
afferents
sympathetic
preganglionic
neurons
reflexogenic
zones
sympathetic
postganglionic
neurons
heart
Fonyo, Medicina, 1997, Fig. 23-2
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 - PNSCNS
• 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.