Cardiovascular system Flashcards
How much blood is there in the circulatory system of typical adult?
~5L
How much interstitial fluid is there in a typical adult?
~10L
What is the structure of the heart?
- The heart is a double pump. The left side generates enough pressure to drive the flow of blood through the systemic circulation while the right side generates enough pressure to drive the flow of blood through the pulmonary circulation.
- Although they contract in synchrony with each other, they are somewhat functionally independent.
What is the arrangement of vessels in the circulatory system?
Heart → Artery → Arteriole → Capillary → Venule → Vein → Heart
What are the exceptions the the general arrangement of vessels in the circulatory system?
- Portal venous system: First capillary bed leads into portal vein which then leads into second capillary bed, before returning to the heart via the systemic venous system.
- Shunt vessel: Blood vessels that connect arterioles straight to venules, allowing capillary beds to be bypassed?
What is the advantage of the arrangement of the circulatory system?
- Capillary beds are arranged in parallel to each other.
- This reduces their resistance relative to if they had been connected in series.
What is the essential function of the heart?
- To perfuse the tissue of the brain (in upright position).
- The heart generates more pressure than the theoretical minimum to perfuse the brain. This energy allows blood to be pumped to the brain against the resistance of peripheral vessels. It also acts as fail-safe for any events that might cause sudden decrease in pressure (e.g. standing up from supine).
What is the conversion between mmH2O and mmHg?
mmHg = mmH2O/13.5
What are the risks of high blood pressure?
- Increased metabolic demand.
- Short term: Aneurysms.
- Long term: Atherosclerosis (vascular damage) → Heart attack/stroke, kidney damage.
Clinically, what is considered as high blood pressure?
- Systolic: >140mmHg
- Diastolic: >90mmHg
What is the function of the cardiovascular system?
Short term:
- To supply O2 to the tissues.
- Removal of metabolic waste (e.g. CO2)
Long term:
- To supply nutrients to the tissues.
- To maintain body temperature.
- To drive the ultrafiltration in the kidneys (excretion).
- To act as transport system for hormones (communication).
- Reproduction (structure formation due to pressure)
- Defence (immunity)
What is the minimum flow rate of the blood determined by?
- O2 demand of tissues.
- This is because there are few other systems involved in regulating O2 supply to tissues.
What is the purpose of storing blood?
It allows us to increase cardiac output by increasing venous return.
What are the main control points for the cardiovascular system?
- Mean arterial pressure (MAP)
- Tissue perfusion
- Distribution of blood volume
- Blood volume
- Venous return
What are extrasystoles (ectopic beats)?
Extra beats not triggered by the normal pacemaker regions.
Which vessels store the most blood?
Small veins and venules (~60% TBV)
What are the layers of the heart?
- Epicardium: Layer of connective tissue lining heart.
- Myocardium: Bulk of heart, containing cardiac myocytes.
- Endocardium: Innermost layer formed by epithelial cells.
Which vessels experience the largest pressure drop across them?
Arterioles, indicating that they have the highest resistance.
What is the composition of blood?
- 45% cells (mostly red blood cells, some white blood cells, platlets)
- 55% plasma
What is the composition of plasma?
- Water
- Plasma proteins
- Nutrients
- Antibodies
- Electrolytes
- Lipids
- Hormones
What is serum?
Plasma with clotting factors removed.
Why is blood pressure needed?
- To pump blood up to the brain.
- To provide pressure for ultrafiltration in the kidneys.
- To keep pressure above critical losing pressure of small arteries and prevent their collapse.
What are the stages of the cardiac cycle?
- Ventricular filling (500ms): Blood flows from the great veins passively into the ventricles through the atria. This accounts for 100ml (~80%) of end-diastolic volume.
- Atrial systole: Atrial contraction forces ~20ml of blood (~20%) into the ventricles.
- Isometric contraction (50ms): Ventricles begin to contract. Intraventricular pressure aortic pressure and the semi-lunar valves open, allowing blood to flow from the ventricles into the aorta. Maximum flow occurs when aortic pressure = ventricular pressure. When aortic pressure far exceeds ventricular pressure, there is a small backflow of blood into the left ventricle from the aorta which immediately closes the semi-lunar valves. This is responsible for the dichrotic notch seen in the ventricular pressure curve.
- Isometric relaxation (80ms): Walls of the ventricles begin to relax. However, because ventricular pressure > atrial pressure, the atrioventricular valves remain closed and the pressure inside the ventricles decrease but the volume remains constant.
What is responsible for the passive flow of blood into the ventricles during ventricular filling?
- Kinetic energy of venous blood.
- Suction from expanding ventricles.
What are the volumes associated with the cardiac cycle?
- End-diastolic volume = 120ml (100ml [~80%] passive, 20ml [~20%] atrial systole).
- End systolic volume = 40ml (~30% EDV).
- Stroke volume = 80ml (~70% EDV).
- The SV:ESV ratio is the ejection ratio.
What is responsible for the heart sounds?
- The “lubb” sound is caused by closing of the atrioventricular valves.
- The “dubb” sound is caused by the closing of the semilunar valves.
What is responsible for the continued flow of blood against pressure gradient in the last 1/3 of ventricular systole?
Despite the aortic pressure being greater than the ventricular pressure, ventricular blood still possesses more overall mechanical energy than aortic blood (especially kinetic energy). This means that blood flows down mechanical energy gradient from ventricles into the aorta against pressure gradient.
What are the stages of the atrial cycle?
- Atrial systole occurs before ventricular systole and causes the a wave.
- The c wave occurs immediately after the beginning of ventricular systole during isometric contraction of the ventricles, which compresses the atria and causes a transient increase in pressure.
- The v wave begins to rise immediately after the isometric contraction phase, as the atria begin filling up with blood and the pressure increases as the AV valves are closed.
What is the relationship between heart rate and phase lengths?
- As heart rate increases, ventricular systole shortens by small amounts.
- Ventricular diastole shortens significantly, giving less time for the heart to fill, decreasing EDV and SV.
- If heart rate > 180 bpm, cardiac output begins to decrease (although this is rarely physiological and main limit to CO is still VR).
What does the area bound by a pressure-volume curve indicate?
Work done by the heart during each heart beat.
What are the methods of measuring cardiac output?
- Fick’s principle: Gold standard
- Doppler effect: Use ultrasound to measure velocity of blood.
- Bio-impedance: Blood vessel put in strong magnetic field. Flow of blood produces voltage proportional to rate of flow.
- Thermodilution
What are the advantages and disadvantages of each method?
- Fick’s principle and thermodilution are more accurarte methods, but are also slow to respond to changes. They are also invasive so are usually only used to measure steady-state CO.
- Doppler and bio-impedance are more responsive, but are less accurate, so are used to measure immediate CO.
What is a peripheral resistance unit?
- PRU = mmHg∙ml^-1∙s
- 1 PRU is a vessel with resistance that results in a flow of 1 ml∙s^-1 (in ml∙s^-1) generated between 2 points with pressure difference of 1 mmHg.
What is the TPR for an average adult ?
1 PRU
What are 3 situations in the circulation when flow does not follow Darcy’s law?
- Flow from the aorta to the foot: Aortic pressure ~90 mmHg while pressure in foot ~180 mmHg.
- Flow out of the left ventricle into the aorta in the last 1/3 of ventricular systole is against pressure gradient.
- Pressure is low at the stenosed vessel despite being high in the left ventricles.
What does Bernoulli’s law state?
Flow between point A and point B in the steady state is proportional to the difference in the fluid’s mechanical energy.
What happens to pressure when blood enters narrower vessels?
- Pressure decreases as blood enters narrower vessels.
- This is because flow needs to increase in narrower vessels to compensate for narrower diameter.
- Velocity increases, so pressure energy converted to kinetic energy in order to increase velocity (GPE stays constant).
Why is aortic stenosis not energy efficient?
- As velocity of blood is increased, more turbulent flow occurs and more energy is lost as heat.
- When the vessel widens again, the pressure energy is lost and cannot be recovered, resulting in a permanent drop in blood pressure.
What causes blood to flow from left atrium into aorta against pressure gradient?
- The blood in the aorta has more potential and pressure energy compared to blood in the aorta.
- However, contraction of the heart gives ventricular blood more momentum, so it has more kinetic energy compared to aortic blood and more mechanical energy in total.
What causes blood to flow from aorta to feet against pressure gradient?
- Blood in the feet are lower down compared to aortic blood. A lot of its pressure energy comes from GPE being converted into pressure energy, so blood in the feet have much less GPE compared to aortic blood.
- Aortic blood in total, has more mechanical energy than blood in feet, so blood flows from aorta to feet, even against pressure gradient.
What is significant about laminar flow of blood?
- Shearing effect means that red blood cells are concentrated to the centre of the vessel.
- This minimises the interactions between red blood cells and the vascular endothelium.
What are the advantages of the shear effect in blood vessels?
- Minimises friction between red blood cells and vascular endothelium, reducing amount of energy needed to drive blood flow through narrow vessels.
- Minimises possibility of red blood cells sustaining damage while flowing through vessels, and decreasing the chance of thromboses forming.
What is the critical Reynold’s number where turbulent flow occurs?
2000
What is the relationship between turbulent flow and pressure?
Turbulent flow is proportional to square root of pressure gradient.
How does blood flow through capillaries?
Single-file flow
What is haematocrit?
% RBC content in blood
What is the problem with turbulent flow?
- Turbulent flow damages the vascular endothelium.
- This can lead to formation of plaque, which increases the chance of clots forming via positive feedback mechanism.
What is responsible for high blood viscosity?
- Plasma proteins.
2. Red blood cells (haematocrit) - Main determinant.
What is the consequence of having too high blood viscosity?
- Higher pressure needed in order to drive same flow rate.
- More work needs to be done by the heart, which increases the chance of having heart attack.
What is the consequence of having too low blood viscosity?
- Fall in total peripheral resistance, which decreases the mean arterial pressure.
- This could result in shock.
- More work needs to be done by the heart in order to maintain adequate MAP to perfuse tissues and prevent shock by producing higher CO.
What is the Fåhraeus-Lindqvist effect?
- Blood in blood vessels with diameters
What is the significance of single-file flow?
- Single file flow requires that red blood cells become slightly deformed.
- Conditions that prevent this from happening, e.g. sickle-cell anaemia, disrupt blood flow in capillaries.
Why do capillaries offer so little resistance?
- Lots of them in parallel.
2. Fåhraeus-Lindqvist effect reduces viscosity of blood flowing though capillaries.
What is the significance of La Place’s law in terms of blood vessels?
- It shows that for a given pressure, the tension that needs to be withstood by arterial walls increase as the radius increases. This means that larger vessels (e.g. aorta) needs to have thicker walls compared to smaller vessels in order to withstand same pressure.
- Under La Place’s law, even a slight contraction of the arteriole smooth muscles would lead to positive feedback mechanism causing total collapse of the vessel. This is only avoided by the fact that the vessels are resistant to collapse.
What are the mechanisms that drive blood flow back to the heart?
- Inertia left from blood being ejected from the heart during ventricular systole.
- Muscle pump: Blood being ‘squeezed’ back to the heart from the lower parts of the body. Valves in the veins prevent backflow of blood.
- Respiratory pump: Contraction of the diaphragm during respiration decreases intra-thoracic pressure and increases intra-abdominal pressure.
What is the problem with venous pooling?
- The veins have very high compliance.
- High blood pressure in the lower parts of the body means that the walls of the veins expand and blood pools in the lower parts of the body, which effectively removes it from the circulation and decreases VR.
- This is countered by venoconstriction and the muscle pumps.
- Absence of muscle pumping when standing still for extended periods of time causes a drop in CO, leading to drop in MAP and loss of consciousness.
How were different variables altered in the heart-lung preparation?
- Preload: Blood reservoir was raised/lowered physically in order to in increase/decrease preload.
- Afterload: Windkessel was used. This was an air chamber surrounding a rubber tubing. Pressure could be changed in the chamber in order to change the diameter of the rubber tubing and thus vary the resistance to blood flow out of the heart.
What is the Frank-Starling mechanism?
The Frank-Starling mechanism states that the greater the preload on the heart, the greater the stroke volume and thus the greater the cardiac output.
What is preload?
The stretching force (wall tension) experienced by cardiac myocytes in the walls of the heart (mainly left ventricle) prior to contraction. This is proportional to the end diastolic pressure via La Place’s law.
What is the sequence of events during the FSM?
↑ Venous return → ↑ End-diastolic pressure → ↑ End-diastolic volume → ↑ Preload → ↑Contractility → ↑ Stroke volume → ↑ CO
What is the underlying mechanism behind the FSM?
- Key mechanism is still the sliding filament model used to describe the length-tension relationship in skeletal muscles. That is, when cardiac muscle is not stretched, the actin filaments overlap with each other and disrupt cross-bridge cycling. When the muscle is stretched, there is a better overlap between actin and myosin, resulting in more cross-bridges formed and thus more tension generated.
What are the limitations of the AV Hill model in describing the FSM?
- The length-tension relationship in cardiac muscle is much steeper than skeletal muscles.
- Additional mechanisms are responsible for this steepness, including the lattice spacing and Ca2+ sensitivity increase.
What are the purposes of the FSM?
- Intrinsic mechanism to ensure that VR is matched with CO, preventing a build-up of blood in the venous system which may otherwise result in oedema.
- It is also responsible for maintaining constant CO despite variations in TPR.
How does the FSM maintain CO despite variations in TPR?
- When TPR increases, afterload increases, which increases the force the heart needs to pump blood against.
- Initially, this decreases the stroke volume, which increases end-systolic volume and thus increases end-diastolic volume in the next stroke (assuming VR is constant).
- By the FSM, this increases the stroke volume and thus increases the contractility of the heart, allowing more blood to be pumped out of the heart despite increased resistance, thus maintaining a constant CO.
What is the difference in divergence between the sympathetic and parasympathetic nervous systems?
- Sympathetic: 1:10
- Parasympathetic: 1:3
What are the adrenergic receptors?
- α1 (NAd): Vasoconstriction
- α2 (non-selective): Pre-synaptic receptors
- β1 (non-selective): Heart and intestinal smooth muscle
- β2 (adrenaline): Bronchi and vascular smooth muscle (dilation)
What are the differences between pre-ganglionic and post-ganglionic fibres?
- Pre-ganglionic fibres are usually myelinated type-B fibres.
- Post-ganglionic fibres are usually unmyelinated type-C fibres.
What are the differences between sympathetic and parasympathetic nerve terminals?
- Parasympathetic nerve terminals are similar to NMJs.
- Sympathetic nerve terminals are varicosities.
What is tone?
Continual basal firing rate in the nervous system.
What is normal sympathetic tone?
~1 Hz
What is the difference between sympathetic and parasympathetic tone?
There is usually less parasympathetic tone compared to sympathetic tone, except in the heart where it is required to depress heart rate.
How is sympathetic adrenergic transmission terminated?
- Re-uptake into pre-synaptic terminal and storage into vesicles until ready to be re-released.
- Uptake into effector cells (e.g. smooth muscle) at post-synaptic terminal and breakdown by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT).
What is the significance of the difference in sympathetic and parasympathetic innervation of the heart?
- Sympathetic fibres innervate the whole of the heart while parasympathetic fibres mainly innervate the SAN and AVN.
- Sympathetic stimulation has large effects on heart rate and stroke volume while parasympathetic stimulation mainly affects heart rate and not so much stroke volume.
What is the role of the ANS in the control of the cardiovascular system?
- Intrinsic control mechanisms, like the FSM, are much slower to respond compared to ANS-mediated extrinsic control.
- ANS coordinates feed-forwards control.
- ANS coordinates whole body response, ensuring that intrinsic mechanisms (which are isolated) don’t cause any adverse effects on the body as a whole.
What is the equation for cardiac output?
CO = HR x SV
What is the role of the heart in the maintenance of CO?
- The heart is not the limiting factor of CO, but is essential in maintaining it.
- At rest, if the pumping capacity of the heart is increased, the CO remains fairly constant.
- If the pumping capacity of heart is decreased, the CO drops substantially.
What is mean systemic filling pressure (MSFP)?
The pressure that would be present in the circulation if the pumping capacity of the heart were to be removed.
How does MSFP limit the cardiac output?
- The heart is unable to change the overall pressure in the system, so it does not affect MSFP.
- Instead, it is able to ‘shift’ pressure from one area to another, creating high pressure in the arteries while maintaining low pressure in the veins.
- The pressure in the veins cannot drop below 0 mmHg as that is lower than atmospheric pressure and would cause venous collapse.
- When CO increases too much and causes venous pressure to drop below 0, the veins collapse and limits VR, thus limiting CO.
What is significant about the pumping capacity of the heart at rest?
At rest, the pumping capacity of the heart is capable of producing much higher CO than it does. It is only being limited by the amount of VR capable.
How can MSFP be increased?
- Increasing TBV
2. Decreasing volume of circulation (i.e. venoconstriction)
How is MSFP generated?
By filling the circulation beyond unstressed volume into the stressed volume.
What is the significance of compliance in the activity of the heart?
Because the arteries are much less compliant than the veins, shifting a volume of blood from the veins into the arteries increases arterial pressure much more than it decreases venous pressure. Consequently, a much greater pressure gradient can be created between arterial and venous side before venous pressure drops below 0 mmHg.
Why are small veins/venules considered capacitance vessels?
They contain ~60% TBV.
How does increasing TBV increase MSFP?
Increasing TBV increases the amount of blood in the stressed volume, thus increasing MSFP.
How does venoconstriction increase MSFP?
Venoconstriction maintains constant TBV, but increases the proportion of stressed volume in comparison to the unstressed volume.
What is resistance to venous return (RvR)?
- Collective term reflecting all of the difficulties faced by venous blood in returning to the heart.
- It can be decreased by the action of the muscle and respiratory pump.
What are the consequences of cardiac failure?
- In cardiac failure, the pumping capacity of the heart decreases, which causes a decrease in MAP.
- The body responds by venoconstriction, in an attempt to increase MSFP and thus CO. However, the heart is unable to accommodate for this increase in VR so RAP increases.
- This increases capillary hydrostatic pressure, leading to oedema.
What is shock?
MAP is too low in order to maintain adequate perfusion of tissues in the body.
What are the different types of shock?
- Hypovolaemic shock (↓MSFP → ↓CO)
- Cardiogenic shock (↓SV → ↓CO)
- Distributive shock (↓TPR → ↓CO)
- Obstructive shock (inadequate local perfusion, e.g. emboli)
What are the types of distributive shock?
- Septic shock: Systematic vasodilation as a result of secretion of vasodilatory agents by pathogens in the blood.
- Neurogenic shock: Systematic vasodilation as a result of loss of sympathetic innervation.
- Anaphylactic shock: Systematic vasodilation as a result of secretion of vasodilatory agent in response to allergic reaction.
What is normal MSFP in adults?
7 mmHg
What type of system is used by the body in order to control blood flow through the organs?
- Constant pressure/variable flow system.
- This system ensures that despite not being able to directly measure flow, the body is able to vary local resistance in order to control flow.
What are the receptors involved in maintenance of MAP?
- High pressure baroreceptors
- Low pressure baroreceptors
- Chemoreceptors
What are the locations of the HPBs and their innervations?
- Aortic sinus (vagus nerve)
- Carotid sinus (glossopharyngeal nerve)
What is the mechanism of action of HPBs?
- When MAP too high, there is increased stretch on the HPBs.
- This causes an increase in firing rate of the HPBs, which stimulate afferent sensory fibres innervating them..
- Sensory fibres transmit signal into NTS (Nucleus Tractus Solitarius) in the medulla and stimulate inhibitory interneurones.
- Inhibitory interneurones inhibit sympathetic neurones via vasomotor centre and decrease sympathetic tone.
- Excitatory interneurones excite parasympathetic neurones via the cardioinhibitory centre and increases parasympathetic tone to the heart via the vagus nerve.
What are the differences between carotid sinus HPBs compared to aortic sinus HPBs?
- Carotid sinus HPBs are more sensitive compared to aortic HPBs.
- Aortic HPBs are sensitive over a wider range of blood pressures.
What are the locations of the LPBs (cardiopulmonary baroreceptors) and their innervation?
- Atria
- Junction between atria and great veins
- Ventricles
- All LPBs are innervated by the vagus nerve
What is the mechanism of action of LPBs?
- Increased RAP as a result of increased MSFP causes increased stretch and firing rates of LPBs, generating signals in afferent sensory fibres.
- Signals carried to various centres of the medulla via the vagus nerve.
- Causes a range of responses that all aim to decrease ECF volume by excreting more NaCl and water.
- This decreases TBV, which decreases MSFP.
What are the responses of LPB reflex arcs?
- Increased heart rate.
- Decreased renal sympathetic tone causing vasodilation of renal vessels and increased rate of NaCl excretion.
- Inhibits release of ADH from posterior pituitary.
- Possibly inhibition of thirst and sodium appetite.
What reasons are there to believe that HPBs are not responsible for maintaining long-term MAP?
- Denervation of HPBs has no effect on mean MAP but does increase the variations in MAP values, which emphasises its short-term control over MAP.
- The reference value of HPBs reset when exposed to 2+ days of chronic hypertension. This is evident as the firing rate steadily decreases over time until it reaches normal levels despite increased MAP.
What physiological states may trigger feedforward cardiovascular responses?
- Exercise
- Emotions
- Pain
How does the medulla oblongata communicate with the sympathetic nervous system?
Via glutamateric bulbospinal neurones
What are the effects of increased sympathetic stimulation on the cardiovascular system?
- Vasoconstriction → ↑TPR → ↑MAP (α1)
- Venoconstriction → ↑MSFP → ↑VR → ↑CO → ↑MAP (α1)
- ↑HR → ↑CO (β1)
- ↑SV → ↑CO (β1)
- Adrenaline release (N2 ACh)
What is significant about cardiac and skeletal muscle
They contain higher proportion of β2 compared to α1, which are more responsive to adrenaline and are vasodilators. The balance of adrenaline and sympathetic NAd dictates the state of their vessels.
What are the effects of increased parasympathetic stimulation on the heart?
↑HR and ↑SV (Muscarinic ACh)
What is the relationship between local blood flow and O2 demand?
There is a positive correlation between blood flow and O2 demand, suggesting that local blood flow is matched to demand.
What is the principle behind control of local blood flow?
- The circulation is a constant pressure-variable flow system.
- MAP is maintained by feedback systems, allowing local flow to be varied simply by changing the local resistance.
What are the normal functions of local and systemic control?
- Local control is usually used to cause vasodilation.
- Systemic control is usually used to cause vasoconstriction.
What are the 2 ways by which smooth muscle tone can be controlled?
- Regulating number of available myosin binding sites on actin.
- Regulating rate of cross-bridge cycling.
What is functional hyperaemia?
The increase in blood flow to a respiring tissue in response to an increased rate of metabolism.
What factors are involved in local metabolic control of vascular smooth muscle tone?
- PO2
- PCO2
- pH
- [K+]e
What is the effect of decreased PO2?
NO and PGI2 (prostacyclin) released, which are both vasodilators.
What is the myogenic control of VSM tone?
Increased stretch on smooth muscles due to increased blood pressure (and thus local flow) increased VSM tone and thus causes vasoconstriction, reducing local flow. This is caused by activation of stretch-activated ion channels.
What is autoregulation?
- Local feedback system involving myogenic and metabolic control.
- Keeps local flow constant despite changes is MAP.
What are the functions of autoregulation?
- Allows local flow to remain constant despite changes in MAP, matching supply to demand. This is especially important in the kidneys as flow determines GFR.
- Counteracts increase in wall tension as a result of increases in MAP, which prevents damage to the arteriolar walls.
What are the effects of NO on VSM?
- NO stimulates guanylyl cyclase, which converts GTP into cGMP.
- cGMP stimulates PKA and PKG.
- PKA phosphorylates MLCK, which inhibits it.
- PKG has number of effects:
- Promotes SERCA
- Promotes K+ channels
- Inhibits PM Ca2+ channels
- Inhibits Ca2+-release channels
What stimulates NO release?
- ACh
- Bradykinins
- Shear-stress
- Majority work by promoting NO synthase
What are the forms of local vascular control?
- Metabolic
- Myogenic
- Paracrine (e.g. NO)
What are the forms of systemic vascular control?
- Sympathetic
- Endocrine
What is the mechanism of action of α1 adrenoreceptors?
IP3 pathway induces Ca2+ release from SR
What is the mechanism of action of β2 adrenoreceptors?
cAMP pathway causes phosphorylation and inhibition of MLCK
How does aspirin work?
- Thromboxane A2 is vasoconstrictor produced by platlets.
- PGI2 is vasodilator produced by endothelial cells.
- Aspirin inhibits COX-1 which is needed to synthesise both substances.
- Endothelial cells have nuclei and synthesise more COX-1 and produce PGI2.
- Platlets don’t have nuclei and cannot synthesis more COX-1, so doesn’t produce thromboxane A2.
- Increase in [PGI2] and decrease in [thromboxane A2] causes anti-inflammatory effect of aspirin.
What is the effect of shear-stress induced NO release?
Causes vasodilation upstream from point of shear stress.
What are the substances that capillaries are permeable to?
- O2, CO2 (transcellularly)
- Water (trans-/paracellularly)
- Solutes (paracellularly)
What are the types of capillaries?
- Continuous: Does not allow movement of plasma proteins.
- Fenestrated: Has holes, or fenestrations, through which plasma proteins can be exchanged.
- Sinusoidal: Extra wide interendothelial junctions as well as fenestrations allow unobstructed movement of plasma proteins.
What is the width of typical interendothelial junctions in capillaries?
10-15 nm
What is the purpose of capillaries being tortuous?
- Substantially increases surface area, maximising efficiency of diffusion.
- Allows for movement of surrounding tissue without damaging capillaries.
What is Fick’s law of diffusion?
Rate of diffusion = ([X]c-[X]if) x Area/Diffusion distance x diffusion coefficient
What are the terms of Fick’s law related to?
- [X]c depends on flow of blood and rate of diffusion.
- [X]if depends on rate of diffusion and rate of uptake of X by the tissues.
- Area and diffusion distance depends on number of capillaries perfused.
- Diffusion coefficient depends on the permeability of the capillaries to X, which can be modified by substances such as cytokines and histamine.
What are the principles behind Starling filtration-reabsorption?
- At the arteriolar end of the capillary, outwards hydrostatic pressure gradient is greater than inwards osmotic pressure gradient, resulting in net filtration of fluid out of capillaries into IF.
- At the venous end of capillary, hydrostatic pressure decreases as a result of resistance. Inwards osmotic pressure gradient is greater than outwards hydrostatic pressure gradient, resulting in net reabsorption of fluid from IF into capillaries.
What factors influence Starling filtration-reabsorption?
- Pc can be increases as a result of increasing CVP and RAP (e.g. in heart failure), increasing net filtration.
- Pc can be decreased as a result of arteriolar vasoconstriction due to sympathetic stimulation.
What causes transcapillary autotransfusion?
Haemorrhage → ↓TBV → ↓MSFP → ↓RAP → ↓Pc → ↓Filtration → Net reabsorption of fluid from IF into bloodstream.
What is the consequence of the revised filtration model involving the subglycocalyx space?
- As water is reabsorbed, colloid osmotic pressure in the subglycocalyx space increases and opposes reabsorption.
- This results in far less reabsorption than predicted by the Starling equation.
- Consequently, there is net filtration across capillaries in most tissues.
What are the circulatory functions of the lymphatics system?
- Drains excess fluid filtered out of capillaries in tissues and prevents its accumulation.
- Carries proteins lost from capillaries into tissues back into into circulation.
How much fluid is lost from the circulation per day?
2-4L
What is the structure of lymph vessels?
- Lymph vessels contain valves to prevent back flow of lymph.
- This also allows lymph to drain back into the circulation via the muscle pump.
- Larger lymph vessels have smooth muscles that contract to aid in lymphatic return.
What is lymphodema?
Oedema caused by blockage of lymph vessel.
What are the causes of oedema?
- ↑Pc (↑RAP, vasoconstriction…)
- ↓πc (↓[albumin] due to starvation)
- ↑σ (histamine, cytokines)
- Disrupted lymphatics drainage
What are the consequences of oedema?
- Systemic oedema: Increases diffusion distance between cells and capillaries, decreasing nutrient/O2 exchange and may lead to ischaemia.
- Pulmonary oedema: Causes alveoli to be flooded with IF, which prevents gas exchange and decreases efficiency of gas exchange.
What are the paradoxical responses of the body to ↓MAP during heart failure?
- ↑TPR
- Venoconstriction (↑MSFP)
- ↑ Heart rate
What are the principles behind treating heart failure?
- Pumping capacity of the heart cannot be increased.
- Treatment is based on counteracting paradoxical responses of body to heart failure.
What are the treatments for heart failure?
- β-blockers
- Diuretics
- ACE inhinbitors
What is the main cardiovascular stress during exercise?
- Blood flow increases as muscle arteriolar resistance decreases in response to increased metabolic activity by vasodilation (functional hyperaemia).
- TPR decreases and so there is a significant drop in MAP.
What are the variations in muscular blood flow during exercise?
- Phase 1: Sudden increase in blood flow following the beginning of exercise.
- Phase 2: Gradual increase in blood flow levelling off at a constant value.
What are the mechanisms by which blood flow increases through muscles during exercise?
- Feedforward
- Functional hyperaemia
- Endocrine (adrenaline)
What are the factors responsible for phase 1 of muscle blood flow during exercise?
- ↑[K+]e
2. Muscle pump (↓RvR)
What are the effects of ↑[K+]e on blood flow in muscles during exercise?
- ↑[K+]e causes hyperpolarisation of smooth muscle PM.
- This is due to 2 effects:
1. Less current flow through inward rectifying K+ channels.
2. Increased activity of electrogenic Na+/K+-ATPase. - Hyperpolarisation closes voltage-gated Ca2+ channels, decreasing [Ca2+]i and causing smooth muscle relaxation.
What are the factors responsible for phase 2 of muscle blood flow during exercise?
- ↑[K+]e
- ↓PO2
- ↑NO
- ↓pH
- Adrenaline
What are the feedforward responses in exercise coordinated by?
- Cortex and other higher processing centres of the brain.
- Coordinates feedforward responses reflecting a decision to exercise.
- This may involve the medial pre-frontal cortex.
What are the feedforward responses to exercise?
- Increased sympathetic tone to heart causes ↑HR and ↑SV. Leads to ↑CO.
- Increased sympathetic tone to vascular smooth muscle causes vasoconstriction and reduced blood flow to renal and splanchnic circulation. Leads to ↑TPR.
- Increased sympathetic tone causes venoconstriction, leading to ↑MSFP.
- Stimulation of adrenaline release.
What are the feedback responses to exercise?
- Muscle pump leads to ↓RvR and thus ↑VR and ↑CO.
What are the roles of baroreceptors during exercise?
Moderate exercise:
- During moderate exercise, feedforward mechanisms are so good that there is often no change in MAP, or even an increase in MAP at the onset of exercise.
- This would normally cause baroreceptor response to decrease MAP. Central mechanisms ensure this does not occur by resetting the set-point of these baroreceptors.
Intense exercise:
- Vasodilation in muscles overwhelm the feedforward response and a drop in MAP is experienced.
- Baroreceptors mediate the feedback mechanism to restore MAP.
What evidence is there to suggest that circulation id the limiting factor of maximum muscle power output?
Maximum power output when 2 legs are used is less than double the maximum power output compared to when only 1 leg is used.
What are the events that take place as a consequence of haemorrhage?
- ↓TBV
- ↓MSFP
- ↓VR
- ↓CO
- ↓MAP
What are the short-term responses to haemorrhage ?
- ↑HR and ↑SV → ↑CO
- ↑ Sympathetic tone → Vasoconstriction in splanchnic/renal/skin → ↑TPR
- Venoconstriction → ↑MSFP
- Vasoconstriction of renal arterioles → ↓GFR → ↓Urine production
- Transcapillary autotransfusion
What are the principles behind long-term responses to haemorrhage?
- Restore fluid
- Restore colloid
- Restore red blood cells
How is fluid restored post-haemorrhage?
- Stimulation of thirst
- Stimulation of Na+ appetite
How is colloid restored post-haemorrhage?
Synthesis by the liver
How are red blood cells restored post-haemorrhage?
- Decreased O2 carrying capacity of blood causes release of hypoxia-induced factors.
- Kidneys stimulated to secrete erythropoetin.
- Bone marrow stimulated to produce more RBCs.
