Circulation Flashcards
Parasympathetic preganglionic fibres
Arise either in brainstem and leave CNS in the cranial nerves or arise in sacral portion of spinal cord and leave through 3rd or 4th sacral spinal roots
Sympathetic preganglionic fibres
Arise in cord between first thoracic segment and second or third lumbar segment and leave through thoracolumbar nerve roots
Preganglionic fibre neurotransmission
Synapse with postganglionic fibres in autonomic ganglia
ACh binds nicotonic ACh receptors on postganglionic fibres
In PSNS ganglia lie close to organs
In SNS ganglia lie close to spinal cord
Postganglionic fibre neurotransmission
PSNS release ACh which bind muscarinic ACh receptors on target organs
SNS release noradrenaline which bind adrenergic receptors on target organs
Cholinergic neurotransmission
ACh synthesised in cytoplasm, stored in vesicles
Vesicles fuse with membrane, release ACh into synaptic cleft
ACh diffuses across and binds cholinergic receptor of postsynaptic membrane (nerve or tissue)
ACh inactivated by AChE
Cholinergic receptors
Nicotinic: found in autonomic ganglia (Nn receptors) and on neuromuscular endplate in skeletal muscle (Nm receptors)
Muscarinic: found on cell membranes of organs innervated by postganglionic parasympathetic fibres
Atropine
Muscarinic receptor antagonist
Increases heart rate and prevents salivation
5 main types of adrenergic receptors
a1: vasoconstriction
a2: neurotransmitter inhibition
b1: increased cardiac rate and force
a2: bronchodilation
b3: lipolysis
Examples of adrenergic agonists
a1: phenylephrine
a2: clonidine
b1: dobutamine
b2: salbutamol
Examples of adrenergic antagonists
a: prazosin
b: beta blockers (atenolol)
Heart rate decrease in response to increased PSNS
ACh release, binds muscarinic cholinergic receptors
Receptors open potassium channels through stimulatory G proteins, close funny channels and T-type calcium channels through inhibitory G proteins
Hyperpolarisation of membrane potential and slower spontaneous depolarisation
AP frequency decreases, HR decreases
Heart rate increase in response to increased SNS
NAdr binds B1 receptors on SA nodal cells activating cAMP which opens funny channels and T-type channels
Slope of spontaneous depolarisation
AP frequency in SA node increases resulting in HR increase
Control of stroke volume
Sympathetic neurons release NE which binds B1 adrenergic receptors
Adenylate cyclase activated, cAMP produced
Increased intracellular calcium, increased contractility, faster calcium removal and faster relaxation
Baroreceptor reflex
Buffers rapid change in arterial pressure and ensures adequate perfusion of vital organs
Afferent input from carotid and aortic receptors increases arterial pressure resulting in increased baroreceptor firing
Increase in activity results in increase in vagal activity and inhibition of sympathetic activity
Chemoreceptor reflexes
Responds to change in oxygen carbon dioxide and pH levels in blood
Sinus and aortic nerves innervate carotid and aortic bodies in response to hypoxia, hypercapnia and low pH
Increase BP, decrease HR
CNS ischaemic response
When blood flow to the brain is very low, very large increase in sympathetic activity occurs causing increased peripheral resistance
Diving reflex
Oxygen conserving response
Stimulation of cranial nerve V and peripheral chemoreceptors
Apnea, bradycardia, peripheral vasoconstriction and increased BP
Blood flow directed to heart and brain
Respiratory sinus arrhythmia
Heart rate increases when we breathe in and decreases when we breathe out
Reflects changes in vagal tone
Heart rate control
Medullary respiratory centre senses change in intrathoracic pressure or sends signal straight to medullary cardiac vagal centre
Change in intrathoracic pressure triggers stretch receptors which sense change in lung volume or cause change in venous return
Change in venous return causes change in arterial pressure or bainbridge reflex
Change in arterial pressure triggers baroreceptor reflex
Change in lung volume due to stretch receptors, baroreceptor reflex and bainbridge reflex send signal to medullary cardiac vagal centre
Medullary cardiac vagal centre causes change in heart rate
Bainbridge reflex
Atrial reflex
Increased heart rate due to increase in central venous pressure
Systolic pressure
Peak pressure
Diastolic pressure
Minimum pressure
Pulse pressure
Systolic pressure - diastolic pressure
Mean arterial pressure calculation
Diastolic pressure + 1/3 pulse pressure
Because ventricles spend 1/3 of their time in systole
ΔMAP = CO x TPR
Arterial compliance
The more compliant the vessel the smaller the pulse
Blood not stored during systole when arteries are rigid causing systolic pressure to increase and diastolic pressure to decrease therefore overall pulse pressure increases
Stroke volume and systolic pressure
Stroke volume = change in arterial volume
As stroke volume increases, systolic pressure increases
Blood pressure techniques
Palpation: allows systolic pressure to be estimated
Auscultatory: allows systolic and diastolic pressure to be estimated
Auscultatory method of blood pressure
High pressure in cuff means artery is completely occluded therefore no flow and no sound - above systolic
No pressure in cuff means artery is completely open therefore laminar flow and no sound - below diastolic
Partially occluded arteries allow blood to spurt through the gap causing turbulence and causing sound (Kortokoff sounds) - between systolic and diastolic
Effects within seconds in response to decreased arterial pressure
Baroreceptors, chemoreceptors and nervous system ischaemic mechanism cause rapid vasoconstriction of veins which pushes blood back into the heart
Increased heart rate and contractility and constriction of most peripheral arteries to impede flow out of arteries
Effects within minutes in response to decreased arterial pressure
Changes in perfusion of the kidney cause Ang II to increase, causing vasoconstriction
Fluid shift through capillaries increases to readjust blood volume
Effects within hours or days in response to decreased arterial pressure
Kidneys via RAAS vital to ensure blood pressure regulation is restored without dependence on salt
Distribution of blood volume
Systemic veins and venules: 60% Capillaries: 5% Systemic arteries and arterioles: 15% Pulmonary blood vessels: 12% Heart: 8%
3 key points about pressure vs cross sectional area of vessels
1) major pressure drop across small arteries and arterioles
2) inverse relationship between blood flow velocity and cross sectional area
3) maximal cross sectional area and minimal flow rate in capillaries
Relationship between pressure, flow and resistance
Q = ΔP / R
Q measured in mL/min
Therefore CO = MAP/TPR
Assumption of CO = MAP/TPR
MAP = P(arterial) - P(venous)
In healthy inviduals, venous pressure is almost 0 therefore we can disregard it and just measure arterial pressure, however in individuals with heart failure, venous pressure is higher and can’t be ignored
Poiseuilles equation
R = (8nL) / (pi x r^4)
Where n = viscosity
L = tube length
r = radius
Poiseuilles assumptions
Steady laminar flow - only in periphery, near the heart flow is pulsatile
Rigid vessels - Larger arteries and veins are compliant and collapsible
Newtonian fluid - viscosity actually not independent of flow rate, blood not always homogeneous
4 determinants of blood viscosity
Temperature - viscosity rises when it’s cold
Haematocrit - viscosity rises when Hct rises (increased resistance)
Shear rate - slow blood flow causes cell aggregation which increases viscosity
Vessel diameter - small vessels have decreased viscosity blood
Autoregulation of blood vessels
Compensate for changes in arterial pressure to maintain flow at constant rate
Therefore blood flow not directly proportional to pressure gradient
2 things that control contractile state of vascular smooth muscle
1) myogenic mechanism
2) vascular endothelial cells (shear stress)
Shear stress
Tangential force of flowing blood on endothelial surface of blood vessels
As flow increases, shear stress increases
Causes NO release and vasodilation
Can cause damage to the endothelium and aggravate atherosclerotic process
Reynolds number
Indicates whether blood flow is laminar or turbulent
When value is more than 2000-3000, flow is turbulent
4 Factors that influence reynolds number
Vessel diameter
Flow rate
Viscosity
Density
Bernoullis principle: 3 factors
Pressure
Gravity
Velocity
Transmural pressure
Pressure difference across wall of vessel
Pressure inside vessel - pressure outside vessel
Laplace equation purpose
Relationship between transmural pressure and circumferential rension in vessel wall
Capacitance
Measure of the volume to rpesure relationship over the entire P/V curve
Change in volume for change in pressure over whole curve
Veins have a large capacitance reflecting their role as storage vessels
Compliance
Stretchability at various points along P/V curve
Change in volume for a given change in pressure at one point
Arteriole function
Control distribution of vascular pressure and flow with a thick continuous layer of smooth muscle in walls allowing changes in vascular resistance
Metarteriole function
Same as arterioles but without the continuous layer of smooth muscle
Often branch at right angles to arterioles
Precapillary sphincter function
Act as gates with a cuff of smooth muscle at the entrance to many capillaries
Open or close to determine number of capillaries open and this determine distribution of capillary blood flow
Precapillary sphincter control
Controlled by local mechanisms, not neural influence
Precapillary resistance vessels
Arterioles, metarterioles and precapillary sphincters
Capillary function
Uniquely suited for rapid exhchange of water and solutes due to high surface area to volume ration and very thin walls
Capillary walls
Made up entirely of endothelium, mostly lipid membrane with an outer coating of mucopolysaccharide basement membrane
Allow lipid soluble molecules to cross through the endothelial cell membrane, whereas lipid insoluble molecules have to pass through holes in the membrane
Shunt vessels
AKA arteriovenous anastamoses
Allow flow to bypass exchange vessels
In skin, blood can be redirected to rediate heat
Venules
Similar to capillaries but some have smooth muscle
Postcapillary resistance vessels
Venules and small veins
Neural regulation of blood flow
Most arterioles receive innervation from sympathetic nerves
Increased sympathetic activity acts via a1-adrenergic receptors to cause vasoconstriction of b2-adrenergic receptors to cause vasodilation
Metabolic regulation of blood flow
In most tissues increasing metabolic rate increases blood flow
Factors that promote dilation of vascular smooth muscle
Decreased tissue oxygen levels Increased CO2 and H+ Lactic acid generation Adenosine, prostaglandins and NO Increased local temperature
Reactive hyperaemia
Increase in blood flow that occurs in tissue when blood flow has been interrupted for a short period, ensuring oxygen is restored
Autoregulation of local blood flow
Return of blood flow towards normal within a few minutes after change in arterial flow, despite change in pressure
Result of changes in circulation metabolites and myogenic mechanism
Myogenic mechanism
When small blood vessels stretch the smooth muscle in the wall contracts
Myogenic mechanism initiation
Initiated by stretch-induced vascular depolarisation which then rapidly increases calcium entry into the cell causing them to contract
Main transcapillary exchange processes
Diffusion
Filtration
Large molecule movement
Flow limited transcapillary transport
Transport of small rapidly diffusing molecules limited by rate of delivery of material to vessel
Diffusion limited transcapillary transport
Transport of large molecules limited by pore size
Diffusion vs filtration
Diffusion is dependent on concentration gradient whereas filtration is dependent on hydrostatic and osmotic pressure differences
5 factors affecting filtration across the capillary membrane
1) filtration coefficient
2) capillary hydrostatic pressure
3) interstitial fluid hydrostatic pressure
4) colloid osmotic pressure of the plasma
5) colloid osmotic pressure of the interstitial fluid
Filtration coefficient
How permeable the capillary wall is to water
Variable between and within tissues
Capillary hydrostatic pressure
Blood pressure in capillary
Variable along capillary
Dependent on pre and post capillary resistance vessels
Interstitial fluid hydrostatic pressure
Normally small but can increase in some cases where oedema is present
Colloid osmotic pressure of the plasma
Due to large plasma proteins (albumin and globulin) in high concentrations in the blood which are not able to freely move across the membrane
Determined by number of molecules in solution
The proteins suck and hold water in their space to maintain intravascular volume
Colloid osmotic pressure of the interstitial fluid
Created by proteins that have leaked out of circulation
Large molecule movement
Can occur by vesicular transport or directly through fenestrations
Functional organisation of lymphatic drainage
Widely distributed network of closed-ended, highly permeable lymph capillaries
Similar in appearance to blood capillaries with large gaps between endothelial cells
One way valves and muscle pumping activity directing flow towards heart
Composition of lymph
Water Proteins Coagulation factors Electrolytes Lipids Cells (especially lymphocytes) Red blood cells when capillary damage has occurred
Lymphatic system function
Lymph allows return of blood components to circulation
Plays a role in absorption from the gut, removal of RBCs form tissues and removing bacteria from tissues and isolating it to nodes
4 factors that determine cardiac output
The cardiac factors: Heart rate Myocardial contractility The coupling factors: Preload Afterload
Venous return is dependent on:
The pressure gradient (venous tone) and vascular resistance (arteriolar)
Venous return vs mean right atrial pressure
VR = CO (input = output)
As MRAP falls, return gradient increases, therefore more flow
At low atrial pressures the curve levels off - large intrathoracic veins collapse, increasing resistance, therefore no further increase in VR
Increased venous tone/blood volume vs MSFP
Increased venous tone/blood volume causes increase in MSFP
Normal conditions: 5 L/min blood volume at 7 mmHg
Small increase volume = large increase MSFP
MSFP
Mean systemic filling pressure
Basically the same as mean circulatory filling pressure because pulmonary circulation only contains 10% blood volume
Effect of transfusion on MSFP
MSFP increases due to increased venous tone
More flow at given MRAP therefore venous return curve shifts up
Effect of haemorrhage on MSFP
MSFP decreased due to decreased venous tonie
Less flow at given MRAP therefore venous return curve shifts down
Effect of increased arteriolar constriction on venous tone
Reduction of venous return at any given RAP
No major effect on MSFP
Effects of increased sympathetic tone
Increased arteriolar resistance and MSFP
Effect of blood transfusion on cardiac function/venous return curves
Doesn’t directly affect cardiac function therefore no change in cardiac function curve
Venous return curve shifted uo as MSFP increases
Effect of sympathetic stimulation on cardiac function/venous return curves
Cardiac function curve shifts up and to the left as a result of increased heart rate and inotropy
Venous return curve shifts up due to increased venous tone and resistance
Effect of supine to erect movement on cardiac function/venous return curves
Upon standing up, increase in venous capacity due to venous pooling, drop in venous pressure at heart causing VR curve to shift down and CO to drop
Effect of exercise on cardiac function/venous return curves
CO curve shifts up due to increased inotropic drive, increased HR and decreased afterload
VR curve shifts up due to increase venous tone, increase rate and depth of respiration and skeletal muscle pumping blood back
Both changes contribute to greatly increased intersection of curves
Effect of heart failure on cardiac function/venous return curves
Heart’s ability to eject blood impaired causing CO drop, increased venous pressure and kidneys retain fluid
Venous return curve shifts up due to hypervolaemia
3 clinical signs of increased venous pressure
Raised JVP
Pulmonary oedema
Peripheral oedema (ankles and feet)
5 ket interventions for heart failure
Diuretics ACE inhibitors Beta blockers Postive inotropes Diet
Diuretics in heart failure
Lower venous pressure
Reduce ventricular size and therefore wall stress
Reduce pulmonary and systemic congestion
ACE inhibitors in heart failure
Vasodilators
Reduce remodelling
Beta blockers in heart failure
Reduce energy demand and improve survival
Positive inotropes in heart failure
Improve contractility
Controls associated atrial fibrillation
Diet in heart failure
Reduce salt to help control blood volume
Symptoms of LHF
Lung crackles Tachycardia Low oxygen levels Paroxysmal nocturnal dyspnoea GI disturbances Weight gain (ascites) Poor blood flow to extremities
Symptoms of RHF
Jugular vein distension
Liver engorgement
Ascites
Peripheral oedema
Heart failure key general symptoms
SOB Lower extremity oedema Decreased exercise tolerance Orthopnoea Unexplained confusion or fatigure Nausea or abdominal pain (due to ascites or hepatic engorgement)
Abnormal findings in heart failure
Tachycardia
Third heart sound (due to floppy ventricles)
Laterally displaced apical pulse
Irregular pulse
Investigations for heart failure
ECG
Brain natriuretic peptide
Chest xray
Echocardiogram
Ejection fraction in heart failure
Either preserved or reduced
Preserved: patients experiencing symptoms with EF higher than 50% (arbitrary value)
Reduced: patients experiencing symptoms with EF lower than 40%
EFs 40 - 50% = borderline
Heart failure with preserved ejection fraction
Diastolic dysfunction
Impaired ability to fill heart, elevated left ventricular diastolic pressures
HFpEF cause
Consequence of concentric remodelling where the muscle cells become wider secondary to increased afterload
Common primary causes include systemic hypertension and aortic stenosis
HFpEF patients
Most often in older hypertensive women
Heart failure with reduced ejection fraction
Systolic dysfunction
Imparied ability of heart to contract with increased EDV
HFrEF cause
Dilated cardiac myopathy
Muscle cells increase in length secondary to remodelling after myocardial infarction
Dilated remodelling
Myocytes get longer resulting in increased stretch but inefficient contraction
Concentric remodelling
Thicker cells causing smaller lumen
Risk factors for HFrEF
Male Obesity Smoking Old age MI
Risk factors for HFpEF
Female Obesity Old age Renal dysfunction Urinary albumin loss Atrial fibrillation
Neurohumoral response to heart failure
Increased in restricted stroke volume due to compensation for impaired cardiac performance
Increased SNS activity increases sodium and water retention, peripheral resistance and inotropy to allow maintenance of CO
Over time, causes additional damage by increasing energy expenditure in energy starved areas causing further remodelling
MI remodelling cycle
MI Decreased ventricular performance Decreased cardiac output Increased sympathetic activity Neurohumoral activation Cardiotoxicity and remodelling Increased demand on heart Increased chance of another MI
Treatment of heart failure
Weigh every day to monitor fluid
Dieretics
Restrict fluid and salt
Exercise (even though exercise intolerance is common)
Digoxin and antiarrhythmics
Nitrates to decrease afterload and prevent excess heart modelling
