Mammalian Cardiovascular Flashcards
at the most basic level, what is circulation responsible for?
delivering vital life substances to body tissues. Including oxygen ,hormones and nutrients and removing waste.
other uses for circulation than delivering and removing substances
immune response, regulation of body temperature and pH, homeostatic functions
which ventricles and atrium of the heart are used for systemic circulation?
left ventricle, right atrium
which ventricles and atrium of the heart are used for pulmonary circulation?
right ventricle - left atrium - left ventricle. (completing double circuit)
features of blood pressures as it passes along systemic circulation
decreases, pulsatile (especially in arteries)
Why is flow continuous despite pulsatile pressure in vessels?
always a forward pressure gradient
what is Poisseullie’s law used for?
how resistance to laminar flow changes along circulation
what is the role of arteries?
Distribution vessels (relatively low resistance)
Why do we use Arterial Blood pressure? (ABP)
little loss of pressure as blood passes through arteries, pressure is essentially the same in all large arteries
Diameter of an artery
30mm
Arteriole diameter
10- 300μm
Why is arteriole total resistance much higher than that of arteries or capillaries?
arteries - much larger diameter, capillaries - much larger number in parallel series.
Uses of arterioles (due to highest resistance)
primary site of control of blood flow in circulation
Capillary diameter
5-10μm
Why does Poisseuille’s law break down for capillaries?
diameter is similar to a red blood cell (-7μm ), allowing for bolus flow.
what is Bolus flow?
erythrocytes travel singularly, separated by segments of plasma. Reduces resistance to flow of blood through capillaries (Fahreus-Linndquist effect)
what is the function of capillaries?
site of exchange between circulation and tissues.
why are all cells close to capillaries?
exchange of substances is primarily by diffusion (X = t2/2D)
why does exchange slow along capillary?
as exchange occurs, between capillaries and interstitial fluid, becomes more similar.
roughly how many capillaries are present per gram of skeletal muscle?
500,000
roughly how many capillaries are pursued at rest ?
20-25% (empty and collapsed)
Capillary anatomy
single layer of endothelial cells connected by inter endothelial junctions, surrounded basement membranes.
where do the structure of capillaries differ
in different organs, gives regional differences in permeabilities to different substances. [e.g. in liver allow passage of newly synthesised plasma proteins, in lungs primarily exhange CO2 and O2]
3 types of capillaries
Continuos, Fenestrated and Sinusoidal (discontinues)
why are water movements across a capillary important?
influence both circulating volume and local interstitial fluid volume
driving forces for water movement across a membrane
convective movements (rather than purely diffusive). Hydrostatic pressure difference and effective osmotic pressure difference.
how does capillary pressure (Pc) change along the length of the capillary?
decreases, due to resistance and outward movement of water, is somewhat pulsatile.
when can Pif be negative?
non-encapsulated organs (WRT atmospheric pressure)
what is interstitial fluid?
complex gel of proteoglycans and water within a network of collagen fibres.
what kind of solutes can exert an osmotic force on capillaries and therefore contribute to colloid osmotic pressure?
only solutes that can not easily cross capillary wall.
what is the most important plasma proteins (colloid) in effective osmotic pressure?
Albumin (globulin and fibrinogen also contribute)
why is it important to regulate blood flow through tissues?
ensures adequate local delivery of O2 and metabolite substrates and remove of products.
why is cardiac output usually proportional to Vo2? (Volume of O2 used per minute)
blood flow is very well matched to metabolic demand
how is flow regulated by the arteries?
by regulating upstream arteriolar resistance (darcys Law)
What are the 3 principle mechanisms for the regulation of arteriolar resistance?
Nerves, hormones/vasoactive substances, local tissue metabolism. (balance of these, often opposing influences)
example of arteriolar resistance being a balance of opposing influences
local demand for local vasodilitation competes with systemic vasoconstrictory signals regulating ABP (arterial blood pressure)
what does local control of arteriole resistance match compared to central autonomic control?
local - local blood flow to local metabolic demand
central - controls total peripheral resistance (TPR) to maintain constant mean ABP
in what forms can local arteriole resistance regulation be?
metabolic, myogenic, vasoactive compounds released from endothelium (NO)
in what forms can central arteriole resistance regulation be?
neurogenic or endocrine (hormonal)
Why is arteriolar smooth muscle arranged circumferentially?
Contraction increases tension in vessels wall and causes vasoconstriction. (relaxation reduces tension, causing vasodilation)
(TENSION)
what allows for tension to arise in vascular smooth muscle?
mostly due to Ca2+ concentration but also modulated by activation of myosin light chain kinase (modulated by phosphorylation)
why is vascular tone not fully understood?
[note: vascular tone is different from arteriole resistance]
multiple regulatory systems with probably some redundancies.
what are the two control pathways for vascular tone?
regulation of myosin binding site of actin by caldesmon and and regulation of myosin light chain by phosphorylation
how can local regulation of blood flow be demonstrated ?
using a cuff that is inflated to above arterial pressure for around 10 minutes. When cuff is removed, large increase in blood flow observed.
what is functional hyperaemia?
significant increased blood flow to area due to change in metabolites (e.g. when observed when removing an inflated cuff from upper arm)
what factors promote vasodilation of systemic arterioles?
reduced P(O2), increased P(CO2), decreased pH, increased adenosine and increased extracellular K+ (and changes accompanying anaerobic metabolism)
why does reduced O2 and increased CO2 cause vasoconsitriction (opposite to in systemic) in pulmonary circulation?
changes reflect poor ventilation, not poor perfusion
why is it important for key organs such as the brain, heart and kidneys to be able to change diameter of arterioles?
To maintain a constant capillary pressure in these organs.
[ note: may be why poor lymphatic drainage of heart and brain}
what time of regulation is present in some organs e.g. brain and heart?
myogenic auto regulation of arteriolar resistance
how does myogenic auto regulation of arteriole resistance affect metabolic auto regulation?
similar effect, increased arterial pressure tends to directly cause vasoconstriction by the myogenic mechanism and indirectly by metabolic mechanism. (increased perfusion washes out local metabolites)
when can acetylcholine dilate arteries?
Only when endothelium is intact (noradrenaline constricts them even when endothelium had been removed)
what is the signal from the endothelium to vascular smooth muscle?
NO (nitric oxide)
what is the role of acetylcholine and bradykinin in the endothelium?
stimulate NO production by the action of NO synthase on L-arginine in the endothelium
what is the effect of NO on vascular smooth muscle?
stimulates guanylyl cyclase, cGMP-dependant protein kinase then phosphorylates MLCK, inhibiting it
how does sildenafil (viagra) work?
reduce cGMP breakdown
other than vasodilator and vasoconstrictor substances, what does the endothelium release?
pro-coagulants, anti-coagulants, fibrinolytics, antibacterials and growth factors. [under physiological conditions, net effect is anti-coagulant and vasodilatory]
what conditions is endothelial damage associated with?
raised vascular resistance, hypertension, atherosclerosis and increased risks cloths.
what is atherosclerosis?
buildup of fats, cholesterol and other substances in and on your artery walls (plaque), which can restrict blood flow. The plaque can burst, triggering a blood clot.
what tissue is relatively unaffected by sympathetic activity? (arteriole resistance)
Brain
what is the effect of sympathetic activity in exercise on. blood vessels?
causes vasoconstriction in some regions and vasodilatation in others. Divert blood from kidneys, gut and skin in favour of heart and skeletal muscles.
what are Eicosanoids used for?
actions on blood vessels, involved in clotting and inflammatory responses.
what are eicosanoids synthesised by?
cyclo-oxygenase (same enzyme inhibited by aspirin)
what is the function of prostaglandins? (type of eicosanoid)
can be vasoconstrictors vasodilators, involved in inflammation and some parturition processes
what is an eicosanoid that is a very potent vasoconstrictor produced by platelets (also cause platelet aggregation)
thromboxane A2 (important part of clotting response)
what eicosanoid blocks actions of thromboxane A2?
prostacyclin produced by endothelium
what is the result of endothelium damage on thromboxane A2 and prostacyclin balance?
favours thromboxane A2, reduced blood flow and clotting.
what is the rationale behind using aspirin to prevent myocardial infarction (in terms of thromboxane A2 and prostacyclin)
irreversibly blocks cox-1 (required for both substances), endothelium has nuclei, can synthesise more prostacyclin, production of thromboxane A2 can’t as produced by platelets.
why is it important to regulate cardiac output?
ensure adequate perfusion of tissues. Critical in determining arterial blood pressure (ABP)
how much control does the heart have on CO?
very little
what experiment was carried out by Guyton et al investigating how the heart effects CO.
replaced right atria of dogs with high-output pumps.
Guyton et al CO experiment observations
cardiac output
reducing pumping capacity of heart below normal reduced cardiac output. BUT - increasing pumping capacity did not increase cardiac output.
Guyton et al CO experiment conclusions
1) heart is required to MAINTAIN CO but 2) heart does not normally limit CO
in veins, what does the pressure have to be (Pv) WRT atmospheric for them to collapse?
1-2 mmHg below atmospheric.
what is the explanation for increasing pumping capacity of the heart not increasing cardiac output?
heart can not increase arteriovenous pressure gradient beyond a point where Pv becomes negative and would cause evens collapse, limiting venous return and cardiac output.
how can directly measure right atrial pressure?
insert catheter via jugular vein
what does a healthy heart do for venous pressure? (measured inserting a catheter via jugular vein)
reduces central venous pressure to almost zero, even at rest
conclusions for increasing heart rate and cardiac output.
changing heart rare by electrical pacing does not greatly change cardiac output as CO is limited by venous return.
what needs to be done in order to allow for the heart to have a greater cardiac output?
creation of arterio-venous fistula to provide pathway for blood to return to heart. (allows sufficient venous return)
what is the main determinant of cardiac output?
Mean systemic filling pressure.
what use happen in order to increase Pa? (CO)
reduce Pv (but be careful not too much to prevent collapse) - solution: raise mean pressure of whole system
why is mean systemic filling pressure the main determinant of CO?
determines maximum FLOW rate (Darcy’s) for a given resistance
what does mean systemic filling pressure represent? (MSFP)
pressure that would eventually exist everywhere in system if the heart stopped (mean pressure in the system)
how can you increase MSFP?
extra filling (e.g blood transfusion or drinking an isotonic solution) or constricting volume e.g. VENOCONSTRICTION
what is the approximate normal blood volume in an adult mammal?
70-80 ml/kg (5l for a 70kg person)
what is meant by ‘unstressed volume’ of circulation?
volume of blood that just fills the circulation without stretching vessels wall (~80% of total in adult mammals)
what is meant by ‘stressed volume’ in circulation?
final 20% of total, Mean pressure will rise. (mean pressure usually around 7-10 mmHg)
which form of vessels are more compliant from veins and arteries?
veins ! when heart pumps a volume of blood from veins to arteries, pressure in arteries will rise more than pressure in veins will fall.
function of arteriovenous pressure gradient
drives blood flow from the arteries to the veins.
what is implied by the maximum arteriovenous pressure gradient being set by the mean filling pressure?
- heart can’t change mean pressure
- mean pressure determines maximum cardiac output.
what is MSFP determined by?
volume of blood and the mean tension in blood vessel walls.
how can you double CO?
increasing blood volume by 20%, doubling stress volume and therefore doubling MSFP and CO
why does arteriolar constriction increase TPR but does not influence MSFP?
less than 1% of blood contained within arterioles (compared to about 60% in small venues and veins)
why does venoconstriction not significantly influence TPR?
primarily determined by resistance of arterioles
where is CO directly measured in the body?
IT’S NOT ! It’s regulated to maintain ABP. (heart responds to changes through intrinsic and extrinsic mechanisms)
Intrinsic mechanism for increasing CO when MSFP increases
Frank-Starling mechanism (starlings “law of the heart”)
what is the principle value controlled by the cardiovascular system?
[mean] arterial blood pressure (ABP)
what are the determinants of ABP?
Cardiac output (CO) and total peripheral resistance (TPR)
how does exercise affect TRP?
greatly reduces it
why is it important for ABP to be kept constant?
blood flow to individual tissues can be regulated just by controlling local arteriolar resistance.
how does blood loss affect circulation
reduces mean systemic filling pressure (MSFP) and therefore CO.
what is systolic blood pressure usual value? [make sure you can annotate pressure diagram)]
120 mmHg (peak)
what is a usual value for diastolic blood pressure?
80mmHg (blood flows away from aorta)
