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

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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

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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

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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

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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

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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

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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 ,

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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

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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

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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

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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

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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

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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

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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

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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.