Week 1 - Haemodynamics and Vascular Control Flashcards
Define cardiac output + what regulates it
CO = The flow of blood from the heart into the circulation (vol. of blood pumped from ventricle per beat)
Regulated By:
- heart size
- ventricular contractility*
- duration of ventricular contraction*
- preload
- afterload*
- Modulated by the autonomic nervous system
Sympathetic nerves increase force and rate of contraction
Parasympathetic nerves reduce rate only
What is the relationship between heart rate (HR), stroke volume (SV) and cardiac output (CO)
SV = vol. of blood pumped form left ventricle during each systolic contraction
CO = HR x SV
- SV ↑ in response to ↑ in vol. of blood in ventricles
- As preload + cardiac myocyte stretch more the CO increases
- Sympathetic stimulation ↑ contractility (↑ myocyte stretch / right atrial pressure) = greater ↑ in CO due to ↑ HR
- Stimulating parasympathetic nervous system causes ↓ in CO due to reduced HR
List the heart valves and their roles
ROLE: keep blood flowing in one direction / prevent back flow of blood
LEFT SIDE:
Bicuspid valve (AV) - controls blood flow from atrium into ventricles
- diastolic filling = blood entering ventricles + ventricular pressure ↑
- end- diastolic volume = when ventricles are full / ↑ pressure = valves shut
Aortic valve (SL) - controls blood flow from ventricle into aorta
- 80 mmHg is when the aortic valve opens, allowing blood to be pumped out into aorta
- vol. of blood in ventricle ↓ BUT pressure ↑ due to contraction
- ↓ in vol. eventually leads to ↓ in pressure = SL valve shuts
RIGHT SIDE:
Tricuspid valve (AV) -
Pulmonary Valve (SL)
isovolumetric contraction - when both valves are shut = no change in vol. as blood isn’t escaping aorta or atrium
What is preload + afterload, what factors affect them and how do they affect cardiac function
Preload - how stretched ventricles are before contracting
- more stretched the ventricle, the more energy (+ O2) the myocytes consume per contraction
- during diastole, atrial pressure reaches its highest point
- this drives blood into ventricles, which stretch to accommodate blood
= the degree of stretch is the preload
Afterload - pressure the heart has too work against to pump blood
(force heart pumps against tot eject blood)
- the greater the pressure is the more energy (+O2) myocytes will consume
- during systole pressure in left ventricle exceeds that in aorta
- this drives blood from ventricle into systemic circulation
- the greater the difference in pressure between ventricle + aorta = the greater the flow.
The higher the aortic pressure, the more it resists flow (cardiac output) from the ventricle
Describe the anatomy of the circulation
- Blood flows away from heart through arteries then arterioles (smaller) to capillaries
- Blood returns through venules then veins (bigger)
Systemic Circulation - arteries carry oxygenated blood
Pulmonary Circulation - arteries carry de-oxygenated blood
Cerebral Circulation - brain circulation
Describe the structure of blood vessels (+ compare different vessels)
Arteries:
- thick muscular walls (helps withstand high pressure blood is pushed through them at)
- elastic recoil (allows them to accommodate stress of pulsatile flow)
- low compliance = hard to stretch
- smaller, more round lumen
Veins:
- thinner, less muscular walls
- less elastic recoil
(by time blood reaches veins pressure has ↓ and blood flow is smooth)
- high compliance = easy to stretch = can accommodate large vol. of blood
- majority of blood is in veins (act as reservoir for blood as veins are more complaint)
Capillaries:
(receive blood from arteries)
- narrow (RBC cells move in single file)
- walls are a monolayer of endothelial cells (= quick diffusion across)
- NO smooth muscle layer
- found at site where O2, CO2, metabolites + nutrient exchange occurs
- one-way valves (in lumen) which prevent back flow of blood (blood is usually moving against gravity
Muscular walls - made of smooth muscle cells (which wrap around vessel)
- contraction of these cells = vessels constrict
- relaxation of cells = vessels dilate
Endothelium - are endothelial cells that line interior surface of all vessels
- they form a barrier between circulating blood + the rest of artery / vein wall (forms endothelium)
Define blood vessel compliance and resistance
Compliance = how easily vessel stretches in response to internal pressure
- compliance = changing in vol. / change in pressure
- arteries have low compliance (hard to stretch)
- veins have high compliance
Resistance = the driving force to push blood through vessel is provided by pressure drop
- resistance = pressure ÷ flow (R = P ÷ F)
At a constant flow:
- ↓ in resistance causes pressure gradient to ↓
- ↑ in resistance causes pressure gradient to ↑
What is the significance of Poiseuille’s Law
Law describes the flow resistance of an individual vessel in terms of radius (r), length (L) of vessel and viscosity (n) of blood flowing through vessel
Resistance is directly proportional to blood viscosity + vessel length
- as viscosity ↑ = resistance also ↑
- shorter vessels have ↓ resistance
Resistance is inversely proportional to vessel radius
- as radius ↑ = resistance ↓ (to 4th power)
Flow is proportional to 4th power of radius
- ↓ diameter will ↓ blood flow
- ↓ diameter will ↑ pressure
What is the structure of the vascular system
Vascular smooth muscle:
- shorter than other muscle cells
- non-excitable
- stimulated to contract by agonist binding to receptor on cell surface
- contract in gradual + graded manner (depending on how much agonist present)
Vascular smooth muscle contractile proteins (actin / myosin) aren’t arranged in a regular pattern instead have dense bodies which anchor contractile proteins at various points in the plasma membrane
- fibres are pulled towards centre when cell stimulated causing cell to shorten + bulge in middle
What is the role of vascular smooth muscle tone (vasoconstriction) in controlling blood flow + pressure
Diameter of vessel depends on balance of internal pressure + wall tension
As pressure ↑ diameter will also ↑
- if pressure is too low (a.k.a critical closing pressure) = wall collapses = blood flow is prevented
- if pressure is too high = wall will start to break apart
As muscle cells contract generates tension = muscle constricts = diameter ↓
↑ muscle tone (vasoconstriction) causes ↑ in internal pressure = diameter increase is much smaller
- smaller change in diameter gives larger change in pressure
Arteries (flow autoregulation)
- surge in pressure causes muscle to contract = ↑ tone = more tension + constricted vessel
- ↑ resistance to flow tp balance ↑ pressure + maintain flow
- myogenic tone
What are the consequences of changing vascular muscle tone in arteries + veins
Smooth muscle contraction increases tone of a blood vessel + reduces its diameter
Arteries:
- will provide resistance to blood flow
- most significant in the smallest arteries (i.e. arterioles)
- if arterial muscle tone is altered it would change flow resistance + blood pressure
Veins:
- reduces blood vessel volume
- particularly important in the large veins where it increases venous pressure + cardiac filling
- if venous muscle tone is alter it would change cardiac function
How is vascular smooth muscle tone regulated
- Capillaries, veins, arterioles and venules are innervated by sympathetic nerves, very rarely have parasympathetic nerves
- Stimulation of sympathetic system causes relate of adrenaline or noradrenaline
- both work together + modulate tone
- act at adrenoreceptors BUT each has diff. effects + affinities
- response of each depends on ratio of a1 to b1 receptors in wall + binding affinities of each
α1-adrenergic receptors
- on all vascular smooth muscle
- receptors can be found in GI tract
- evokes vasoconstriction when activated by agonist = ↓ blood flow
- noradrenaline more potent than adrenaline
β1-adrenergic receptors
- evokes ↑ in heart rate + myocardial contraction = ↑ blood flow
β2-adrenergic receptors
- on smooth muscle cells of arterioles in cardiac and skeletal muscle
- evokes vasodilation when activated by agonist = ↑ blood flow
- adrenaline much more potent than noradrenaline
Resistance in Blood Flow Network / Regulation
- Total resistance and pressure drop is lower in blood vessels arranged in parallel (compared to in series)
- Changing resistance of a few vessels in large parallel network has little effect on total resistance to blood flow
- Resistance decreases by increasing the number of parallel vessels (= more paths for blood to flow)
- Total resistance falls when blood moves from large artery (aorta) to small one (capillaries) because vessels small vessels are present in large numbers
- total resistance to flow in parallel < resistance of smallest vessel
How does the body regulate blood flow and blood pressure in different areas of circulation
Arterioles ~ have a small diameter = small amount of constriction / dilation has a big effect on blood flow
Capillaries ~ DON’T have smooth muscle = can’t constrict / dilate to change flow
not always open have precapillary sphincters which can:
1. constrict = blood entry is prevented (closed)
2. open = ↓ flow resistance + ↑ blood flow
Reduced internal pressure + radius decreases blood flow
Dilating vessel by 2 fold will ↑ blood flow by 4 fold
- Pressure is ↑ in arterial system and during systole
- Pressure is ↓in venous system and diastole
- Largest drop in pressure occur across arterioles
- As vessels gets smaller, pressures is more constant because elasticity in arteries damp down pressure changes before reaches capillaries
- Oscillations in trace (from large arteries) are due to pulsatile nature of heartbeat
Define peripheral resistance + its role in regulating blood pressure
TPR (total peripheral resistance) - total resistance is systemic vasculature
TPR = (MAP - RAP) ÷ CO
- R = P ÷ F (P is total systemic pressure | F is CO)
- MAP = mean arterial pressure
- RAP = right arterial pressure
- units = PRU
MAP:
- needs to be kept in narrow range to avoid hypertension / hypotension
- modulated by changing CO, TPR or both
- MAP =CO x TPR
CO:
- depends on O2 need of the body
- e.g. CO ↑ during exercise due to sympathetic nerve activity (↑ cardiac contractility + rate)
Peripheral (a.k.a. systemic) circulation has high resistance + high pressure
Total pulmonary resistance
- Total pulmonary resistance is a measure of total resistance to flow across the circulation of the lungs.
- Calculated in same way as TPR
- except the total pressure is mean pulmonary artery pressure - left atrial pressure
Pulmonary circulation has low resistance + low pressure
What are the consequences of constricting / dilating arteries or veins
- Constricting a vessel ↑ resistance to flow and will reduce blood flow
- Dilating vessel will ↓ resistance and ↑ increase flow
- Small change in vessel diameter has large effect on flow
- Constricting veins esp. large ones (venoconstriction) ↓ total vascular volume + ↑ blood squeezed into heart
- ↑ blood in heart = ↑ venous return + ↑ preload
- venoconstriction results in ↑ SV and ↑ end0diastolic volume
Resistance is inversely proportional to vessel diameter / radius
Outline the processes mediating homeostatic control of blood flow
- Heart function - heart rate + contractility controls CO
- Flow resistance - modulated by arteriolar vasoconstriction or vasodilation, changes pressure in vessels = afterload affected
- Blood volume - affects preload + SV (depends on venous constriction / dilation, interstitial fluid + fluid balance)
Maximal flow = arterioles become maximally stretched + unable to dilate more
Blood flow is controlled at systemic and local level
Systemic Systems:
- maintains stable flow conditions i.e. MAP
- Controls CO (total flow rate), changing CO can ↑ or ↓ flow
- not all organs metabolise at same rate = change distribution to organ without changing CO (↑ flow to certain organs which require it without ↑ flow elsewhere, instead ↓ flow to other organs)
- Change flow to vessels without changing flow to each organ (i.e. vessels in specific area dilate to ↑ flow + vessels in other area constrict to ↓ flow to redirect it to where its needed)
Local Systems:
- ensures stable flow in all tissues
- delivers O2 + nutrients to meet local tissue demand
- tissue adjust flow to meet demand e.g dilation / constriction2
- removes products of metabolism
How is blood pressure sensed by the body (homeostasis)
ARTERIAL BP:
- If pressure too ↑ = vessels + organ damage
- causes high hydrostatic pressure in capillaries = fluid is forced out into interstitial fluid = oedema + dehydration
- If pressure is too ↓ = vessel collapses because elasticity of artery requires opening pressure
Homeostasis:
- Pressure sensitive receptors in areas of circulation (e.g. baroreceptors) - sense changes in MAP
- Afferent neuronal pathways signal this change to CNS + efferent pathways send instructions to arteries to correct change
- Cardiovascular centre (between efferent + arteriole pathway) generates response when there is a change from ideal MAP
How baroreceptors and chemoreceptors control blood flow (neural control)
- Baroreceptors
- in ascending aorta, aortic arch and carotid sinus
- respond to stretching of wall when BP ↑ = more AP produced + fired
- respond to rapid changes in pressure = will bring firing rate of AP back to normal - Chemoreceptors
- located in carotid and aortic bodies
- detect changes in blood pH, O2 and CO2 levels
Signals from both receptors are relayed to Cardiovascular Centre in medulla oblongata (brain)
- centre communicates info received to vessels by changing rate of AP firing in sympathetic nerves
How does autonomic nervous system contribute to regulation of blood pressure
Cardiovascular centre is part of the autonomic nervous system
- it receives signals leading to changes in heart and blood vessel activity
Centre has 3 components:
1. Cardioaccelerator center (symapthetic)
- stimulates heart by ↑ heart rate + stroke volume
2. Vasomotor center (sympathetic)
- controls vessel diameter by modulating smooth muslce contraction
3. Cardioinhibitor center (parasympathetic)
- slows heart rate by signalling via the vagus nerve
Afferent Signals:
(afferent = neurones which carry info. from body to CNS)
- Includes baroreceptors, chemoreceptors, dehydration, stress etc.
- receptors send signals to centre when detect a change which results in adjustments
Efferent pathways include:
(efferent = from CNS to body organs)
- sympathetic nerves
- parasympathetic nerves
Sympathetic activate alpa1 and beta1 receptor on smooth muscle
Parasympathetic doesn’t supply nerves to cardiac muscle or vascular smooth muscle (very rare)
How does humoral system contribute to regulation of blood pressure
- Adrenaline from the adrenal gland (epinephrine)
- adrenaline is related during sympathetic nerve simulation (acts as hormone)
- Chromaffin cells are a modified postganglionic neurone (have capillaries for exchange of substances)
- also contain synthetic pathway for noradrenaline (stored in granules)
- cells also have enzyme (phenylethanolamine-N-methyl transferase) which methylates most of noradrenaline to create adrenaline
1. when symapthetic system is stimulated preganglionic neurones release acetylcholine, which crosses synapses + binds to nicotinic receptors
2. stimulates release of granules from chromaffin cells, contents enter blood stream via capillaries
3. adrenaline (+ small amounts of noradrenaline) circulates around body to its target receptors
4. vasoconstrictor effect - The renin-angiotensin-aldosterone system
- Angiogtensinogen circulates body, when comes in contact with renin cleaves it into angiotensin I
- As angiotensin I circulates through lungs ACE (enzyme) cleaves it into angiotensin II (potent) which interact with angiotensin receptor 1 (AT1)
- Causes vasoconstriction in vascular smooth muscle via contraction (= narrowed vessels = ↑ resistance)
- Angiotensin II acts on AT1 receptors on sympathetic nerve endings (noradrenaline release)
- Angiotensin II acts on AT1 receptors on adrenal gland = aldosterone released
- aldosterone promote retention of Na+ and H2O = ↑ blood volume + ↑ CO = ↑ BP - Vasopressin (anti-diuretic) from the hypothalamus
- Main action is to inhibit diuresis but also constrict blood vessels + ↑ BP
- Synthesised in the hypothalamus in the brain (in neurosecretory cells)
1. secreted in response to ↑ in blood osmolarity or a ↓ in blood volume
2. secreted hormone enters blood in capillaries+ binds to vasopressin 1 receptor (V1)
- V1 receptors mediate reabsorption of Na = Na is retained + H2O = ↑ arterial BP
- V1 receptors on smooth muscle cell constrict when stimulated = ↑ arterial BP
What is the difference between functional + reactive hyperaemia
Hyperaemia = body adjusts blood flow to meet the metabolic needs of the different tissues
Functional hyperaemia:
A physiological response in:
- skeletal muscle (during exercise)
- brain
- heart (due to ↑ rate / work)
- GI tract (after meal)
Reactive hyperaemia:
- response after artery occlusion or tissue ischaemia + metabolites build up
Understand the time scales over which systems controlling blood pressure respond to a change in pressure??
- BP can change slowly or quickly
- Slow changes may be caused by dehydration, changes in environment, chronic disease, altered emotional state
What systems regulate BP:
1. Baroreceptor and chemoreceptor = short term / immediate
2. Fluid shift (water exchange between blood + interstitial fluid) and renin-angiotensin-aldosterone system
3. Kidney response (mediates changes in blood volume) e.g. vasopressin = long term
