Download 1 Physiology week 9 – Cardiovascular (flow/BP)

Physiology week 9 – Cardiovascular (flow/BP)
Biophysics of blood flow
Flow=pressure/resistance
Laminar flow
Parabolic distribution of velocity – infinitely thin layer next to vessel wall doesn’t move, greatest velocity in
centre of stream.
This applies up to a critical velocity, above which flow is turbulent.
Turbulence
Probability of turbulence (and resistance to blood flow) related to diameter of the vessel and viscosity of blood.
Reynolds number=probability of turbulence
p=density D=diameter V=velocity n=viscosity
Plasma is 1.8 times more viscous than water, whole blood is 3-4 times more viscous.
Viscosity depends on the haematocrit (percentage of blood volume occupied by red cells).
The clinical effect of viscosity differs from that derived from Poiseuille- Hagen formula below.
In large vessels, haematocrit increases viscosity.
In arterioles, capillaries and venules the effect is less due to the nature of flow in these vessels.
Incr turbulence is due to
“critical velocity”
Smaller diameter
Decreased viscosity
Velocity
Important to differentiate between velocity (displacement per unit time) and flow (volume per unit time)
Velocity V=Flow (Q) / cross sectional area (A)
Therefore slow in capillaries because much higher cross-sectional area
Poiseuille-Hagen Formula
Describes basic factors which determine rate of flow of blood through a blood vessel
Pressure drop in a fluid flowing through a long cylindrical pipe
(assumes flow is laminar, viscous and incompressible)
‘flow varies directly and resistance inversely with the fourth power of the radius’
Critical closing pressure – the pressure within a vessel lumen at which blood flow ceases.
Law of Laplace
P=T/r (for spherical structure this is 2T/r)
W can be ignored in thin walled structures.
(transmural P = P inside - P outside – since tissue pressure inside body is negligible, p = pressure inside viscus.)
The smaller the diameter of vessel, smaller the tension on wall necessary to balance distending pressure.
In heart, dilated ventricle must generate greater tension to produce given pressure therefore work is greater.
Arterial and arteriolar circulation
Aorta flow is phasic, ranging from 120m/s in systole to negative value in diastole. (average is 40m/s)
Arterial flow becomes progressively continuous due to elastic recoil of the vessel walls (Windkessel Effect) though
pulsatile flow is necessary for optimal organ function.
Pulse pressure – difference between systolic and diastolic pressure
Mean pressure – approximation – diastolic pressure plus one third of the pulse pressure.
Effect of gravity=0.77mmHg/cm from heart. (if heart=100, head=60, feet=180)
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Resistance vessels
‘small arteries and arterioles are the principal site of peripheral resistance’.
Measurement of Blood Pressure
Auscultation
Inflatable (Riva-Rocci) cuff attached to mercury manometer, wrapped around arm, stethoscope over
brachial artery (at heart level so no effect of gravity)
Cuff inflated over expected systolic BP
Slowly lower pressure – when SBP just exceeds cuff pressure, spurt of blood passes with each heart
beat – tapping sound heart below cuff
Lower more – sounds louder then dull and muffled
Disappear at diastolic pressure
(but diastolic where sound muffled after exercise, in children, hyperthyroidism, aortic insuff)
Korotkoff sounds – due to turbulent flow in narrowed, where flow though constriction exceeds critical velocity
1. 1st, snapping heard at systolic pressure
2. 2nd, murmurs heard between systolic and diastolic pressure (unknown significance)
3. 3rd, loud, crisp tapping sound (unknown significance)
4. 4th, within 10mmHg above diastolic, thumping and muting
5. 5th, silence as pressure drops below diastolic
If use small cuff – BP incorrectly high
Can have auscultatory gap between systolic and diastolic
Palpate radial artery for when pulse returns (=systolic), ~2-5mmHg lower than auscultatory method
Also can directly measure through arterial line
Capillary circulation
5% of blood in capillaries at any one time.
Starling Forces
Rate of filtration any point along capillary depends on hydrostatic P gradient and osmotic P gradient.
Net flow varies between capillary beds.
Capillary hydrostatic pressure 30mmHg at arterial end, 10mmHg at venous end
Plasma colloid osmotic pressure 28mmHg
Interstitial fluid pressure –3mmHg
Interstitial fluid colloid osmotic pressure 8mmHg
Net outward force at arterial end = (30+3+8)-28=13
Net inward force at venous end = 28-(10+3+8)=7
Pulse pressure 5mmHg arterial end, zero at venous end.
Transit time 1-2 seconds.
Venous circulation
Capacitance vessels
A large amount of blood can be added to veins before there is a significant rise in venous pressure
Aided by contraction of muscles, negative intrathoracic pressure during inspiration.
Venular pressure 12-18mmHg, 5mmHg in great veins of thorax.
Normal right atrial pressure is 0mmHg but can vary between –5 and 30mmHg
Flow velocity – 10m/s
CVP
= Rt atrial pressure
= 0 (range -5 to +5)
Factors that determine CVP
1. balance between venous return and ability of heart to pump out of RA
2. factors affecting venous return: gravity, intraabdominal pressure (pregnancy), hypo/hypervolaemia, venodilation
(drugs/fainting), sympathetic tone (vasoconstriction), arteriolar dilation (sepsis, drugs, anaphylaxis), resistance
to venous return (tamponade, tumour)
3. factors affecting ability of heart to pump: contractility, hypertrophy (athlete), failure, MI (RV), arrhythmias, AF
(volume, filling time and contractility), resistance to RV (Pulm valve stenosis), PE, LVF, hypoxia, tension PTX
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Venous return
Normal value 5-5.5l/min
Major factors influencing venous return to the heart:
Circulating blood volume
Sympathetic and parasympathetic tone
Muscle pump
Rt atrial pressure (intrathoracic and intracardiac pressure and factors that influence them like phases of
respiration, tamponade, PEEP)
VR = venous return
Psf = mean systemic filling pressure
PRA = right atrial pressure
RVR = resistance to venous return
Relationship between Rt atrial pressure and venous return:
1. Downslope – reduced driving pressure
2. plateau – collapse of vein walls
3. normal value for MSPF = 7mmHg
4. normal value for mean RAP = 0mmHg
Halving the resistance allows twice the blood flow – curve up
Changes in pressure and velocity as blood flows through the systemic circulation
Rapid fall in pressure in arterioles (main site of peripheral resistance)
Pressure falls very slightly in large and medium arteries because resistance to flow is small
TA (total cross-sectional area) is maximal in capillaries and venules (4.5cm2 in aorta cf 4500cm2 in capillaries)
RR (relative resistance)
Autoregulation and control of blood pressure
‘autoregulation describes the capacity of the tissues to regulate their own blood supply’
Most vascular beds have intrinsic capacity to compensate for moderate changes in perfusion pressure by changes in
vascular resistance so that blood flow remains relatively constant.
Myogenic theory of autoregulation – distension of vessel → incr pressure stretches vascular smooth muscle →
contraction of muscle
Metabolic theory of autoregulation – vasodilator substances accumulate in active tissues → relaxation of smooth muscle
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Local control
Myogenic and metabolic factors
Chemical factors
Adenosine - released in response to hypoxia. Carbon dioxide, Potassium, Lactate, Histamine
Substances released by endothelium
Nitric oxide
From arginine, activate guanylyl cyclase - produce cGMP - mediate smooth muscle relaxation
Release stimulation by Arterial wall sheer stress; Bradykinin; ATP; Parasympathetic nerves
Causes dilation of upstream vessels in response to local vasodilation
Half life 6 seconds
Local vasodilators - Prostacyclin, kinins
Local vasoconstrictors - Endothelin, thromboxane, serotonin
Hormonal control
Vasoconstrictors
Circulating adrenaline and noradrenaline
Produced by adrenal medulla
Both increase force and rate of cardiac contraction
Noradrenaline produces vasoconstriction in most if not all organs via alpha1 receptors
Adrenaline dilates blood vessels in skeletal muscle and liver via beta2 receptors.
Angiotensin II
Formed from angiotensin I by the action of renin. Vasoconstrictor, increased aldosterone so
incr Na and water retention
Renin secretion at any given time is determined by the summed activity of several factors.
Angiotensin II feedback
Afferent arteriolar pressure decrease results in increased renin secretion.
Sodium reabsorption across macula densa decreased absorption causes incr renin
Stimulation of beta 1 adrenoceptors by circulating catecholamines - incr renin
Increased sympathetic activity via renal nerves.
Prostaglandins (especially prostacyclin) stimulate renin secretion.
Increases aldosterone secretion and therefore increases reabsorption of sodium and water.
Vasopressin/ADH
More powerful than angiotensin, from posterior pituitary
Actions mostly related to acute haemorrhage/volume loss and control of water reabsorption
Vasoconstrictor
Endothelins
Act in a paracrine fashion and bind to specific receptors.
Released in response to endothelial injury
Haemodynamic actions
Contracts vascular smooth muscle – initial depressor response then pressor response.
Cardiac effects
Positive inotropic and chronotropic effects.
Vasoconstriction of coronary arteries.
Neuroendocrine effects
Increase levels of ANP, renin, aldosterone, catecholamines.
Modulates synaptic transmission.
Renal effects
Increase renal vascular resistance
Decreases glomerular blood flow and GFR
Increase sodium reabsorption through haemodynamic actions, decrease sodium
absorption by inhibiting sodium potassium ATPase.
Respiratory effects
Produces bronchoconstriction
GIT effects
Enhances gluconeogenesis
Regulates gastrointestinal blood flow
Vasodilators
Kinins
Bradykinin and lysylbradykinin.
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Derived from HMW kininogen and LMW kininogen respectively by the action of plasma
kallikrein and tissue kallikrein.
Tissue kallekrein found in many tissues incl glandular tissue, pancreas, prostate, gut, kidney
Kallikrein is activated by factor XII and catalysed by plasmin.
Bradykinin and lysylbradykinin are metabolized to active fragments by kininase I.
Inactivated by kininase II (ACE).
Primarily limited to tissues although also found in circulating blood.
Act via bradykinin receptors.
Actions
Contraction of visceral smooth muscle.
Relaxation of vascular smooth muscle
Increased capillary permeability
Attract leucocytes
Serotonin
Histamine (from basophils and mast cells)
Prostaglandins
Prostacyclin (and thromboxane A2)
Balance aggregation/vasoconstriction effects of thromboxane and antiaggregation
/vasodilation effects of prostacyclin
Nervous system control
Receptors
Baroreceptors
Stretch receptors in walls of heart and blood vessels.
Carotid sinus (just above bifurcation of common carotid) – pick up rise or fall
Aortic arch – pick up rise
Stimulated by distension of the structure causing increased rate of discharge.
inhibits tonic discharge of vasoconstrictor nerves
excites vagal innervation of heart
producing vasodilation, venodilation, drop in BP, bradycardia, decree cardiac output
Afferents pass via glossopharyngeal and vagus nerves to the medulla.
Afferents end on the nucleus of the tractus solitarius resulting in glutamate transmission.
Project to the RVLM and stimulates GABA inhibitory neurons.
When baroreceptors detect decreased arterial pressure:
1. decr firing rate of Herings nerve
2. CN IX transmits to vasomotor centre
3. decr parasymp outflow to heart
4. incr symp outflow to heart
5. incr symp outflow to vessels
6. incr HR and contractility
7. arteriolar and venous constriction
Low pressure receptors in atria and pulmonary arteries
Effective in control of sudden volume change - volumer (atrial stretch) reflex
Stretch causes
Reflex dilatation of afferent arterioles in the kidney
Decreased vasopressin/ADH secretion by the hypothalamus
Release ANP
Tachycardia (direct effect or Bainbridge reflex)
Chemoreceptors
Play a secondary role in BP control – more active in respiratory control
Vasomotor control
Vasomotor center in the medulla oblongata.
Both vasoconstrictor and vasodilatory areas
Neurons project directly to sympathetic preganglionic neurons in intermediolateral gray
column of cord.
Set point = neutral MAP for vasomotor centre ~100mmHg
Inputs
Factors affecting the vasomotor center
Influenced by peripheral baroreceptors, peripheral chemoreceptors and higher neural centres
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- NA vasoconstrictor fibres descend from medullary vasomotor centre via spinal cord
to smooth muscle in walls of arterioles
- Peripheral baroreceptors in carotid sinus and aortic arch respond largely t ochanging
BP and act to inhibit vasoconstrictor centre
- Peripheral chemoreceptors in carotid bodies and aortic bodies respond to hypoxia
and act to excite the vasoconstrictor centre
Outputs
Vascular innervation
Noradrenergic vasoconstrictor fibres
Vasoconstrictor fibres some tonic activity – sympathectomy causes vasodilation
Sympathetic vasodilator fibres to skeletal muscle
Cardiac innervation
Noradrenergic sympathetic nerves inotropic and chronotropic action.
Cholinergic vagal nerve negative inotropic and chronotropic action
Cholinergic fibres have tonic activity (vagal tone) – division of vagus causes tachy
Timeline of factors in regulation of arterial pressure
Seconds-minutes: baroreceptors, chemoreceptors, CNS ischaemic receptors
Minutes-hours: stress (stretch) relaxation, RAS vasoconstriction, blood volume changes and fluid shift through capillaries
Longer term: renal compensation via aldosterone, blood volume changes, salt intake
Control of HR
Factors that incr HR also incr BP, except raised ICP and hypotension/tachy by stimulation of atrial stretch receptors
Incr HR:
Decr activity baroreceptors in arteries, LV and pulm circulation
Incr activity atrial stretch receptors
Inspiration, Excitement, Anger, Painful stimuli, Hypoxia, Exercise, Adrenaline, Thyroid hormones , Fever
Bainbridge reflex
Decr HR:
NA
Incr activity baroreceptors in arteries, LV and pulm circulation
Expiration, Fear, Grief, Stimulation pain fibres in trigeminal nerve, Incr ICP
Valsalva response
Blood pressure rises at onset of strain due to increase intrathoracic pressure adding to the aortic pressure.
Increased intrathoracic pressure causes reduced venous return and cardiac output.
This causes tachycardia and increased peripheral vascular resistance.
At cessation, intrathoracic pressure returns to normal but peripheral vessels are constricted, causing hypertension,
This stimulates baroreceptors and blood pressure is returned to normal by vasodilation and bradycardia.
Bainbridge reflex
- aka atrial reflex
- increase HR due to increase central venous pressure
- increased blood volume detected by stretch receptors in atria at venoatrial junctions
- Bainbridge reflex and baroreceptor reflex act antagonistically to control HR
o baroreceptor reflex incr HR when BP drops/blood volume drops
o Bainbridge reflex inc HR when blood volume incr
Bezold-Jarisch reflex
- causes shallow/slow breathing and bradycardia
- prolonged upright posture – pooling in legs – decr intracardiac volume
- resultant hypotension – sensed by carotid sinus baroreceptors – triggers autonomic signals increasing HR and
contractility
- however, pressure receptors in wall and trabeculae of underfilled LV may then sense stimuli and send signals
that trigger paradoxical bradycardia and decrease contractility, causing hypotension
- usually occurs with nitrates and serotonin agonists
Cushing reflex
- nervous system response to increased intracranial pressure
- results in Cushing's triad - widening pulse pressure, irregular breathing, bradycardia
- usually seen in terminal stages of acute head injury, may indicate imminent brain herniation
- also be seen after intravenous administration of NA and similar drugs
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incr ICP – incr hydrostatic P of CSF until gradually exceeds MAP - cerebral arterioles become compressed, decr
cerebral blood supply
o chemoreceptors in hypothalamus sense cerebral ischemia (decr pH and incr pCO2) - activation
sympathetic nervous system
alpha-1 adrenergic receptors in arteries cause vasoconstriction – incr TPR, incr BP to try to
maintain perfusion of brain
incr contractility and cardiac output
o baroreceptors in carotids detect incr BP
trigger parasympthetic response via vagal stimulation
• bradycardia
o also caused by incr ICP impinging on vagal nerve - parasymp response
Usually chemoreceptors of brain and baroreceptors of carotid sinuses work together to incr or decr BP
In Cushing reflex, two sensors receiving mixed signals - even with sympathetic stimulation, which would
normally produce tachycardia, there is bradycardia
Pressure-Volume Loop left ventricle
Factors determining myocardial O2 demand
1. HR
2. Intramyocardial tension
3. Contractile state of myocardium
(OR SV and MAP)
Effect of increase in preload or afterload on myocardial demand:
Both increase myocardial O2 demand
Changes in afterload have greater affect than changes in preload
Ventricular work per beat correlates to O2 consumption
Work = SV x MAP
Stroke work LV is 7x that of RV
Theoretically volume changes and pressure changes should affect myocardial O2 consumption equally
Pressure work produces greater incr in O2 consumption that volume work (reason not understood)
Tension in wall of hollow viscus proportional to radius
Myocardial fibres stretched with incr SV in dilated heart
Incr radius increases wall tension – incr O2 consumption
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