Heart Flashcards
Potential energy = ?
mass x gravity x height
Why must blood flow change with O2 not glucose usage?
O2 runs out before glucose does
Why must skeletal muscle perfusion be controlled?
Maximal perfusion is impossible
What is the epicardium?
Thin connective tissue covering heart
What is the SA node innervated by?
Vagus nerve
What cells are platelets fragments of?
Megakaryocytes (bone marrow cell which produces platelets)
What are the three plasma proteins?
Fibrinogen, albumin, globin
What electrically divides the atria and ventricles?
Collagen proteins within the rings
Equation relating power and flow?
Power = flow x gravity x height
What is the critical closing pressure?
As pressure increases flow increases, but some elastic arteries snap shut and need minimum pressure
What is the P wave?
atrial depolarisation
What is the PQ delay from?
AV delay
What is the QRS phase?
Ventricular depolarisation
What is the QR interval?
Spreading down septum
What is the RS interval?
Spreading up sides of ventricules
What is the ST phase?
Plateau phase (ventricular contraction)
What is the T wave?
Repolarisation of ventricles
Which valve closes between ventricular filling and isovolumetric contraction?
Mitral valve closes
Which valve closes between ventricular ejection and isovolumetric relaxation?
Aortic valve closes
Does aortic or ventricular pressure get higher?
Aortic
What are the aortic and ventricular pressures like when flow into aorta is at maximum?
Equal
What kind of blood flow does aortic stenosis cause?
Turbulent blood flow
How does heart rate affect the ratio of systole:diastole?
Lowers the ratio
Why is right ventricular pressure lower than left?
Lung resistance to blood flow is less
When does most coronary blood flow occur?
Diastole - usually squeezed shut by pressure
What is angina?
Temporary insufficiency of blood flow to heart causing acidosis and pain
What is the value of central venous pressure?
Very close to zero
What is the usual value of total peripheral resistance?
1
What is Fick’s principle in the heart?
Blood flow is proportional to the difference between O2 concentration as blood goes in compared to when it comes out
How do you measure cardiac output using O2?
rate of O2 from air / (arterial conc O2 - venous conc O2)
What is the dicrotic notch?
Sudden drop in pressure after systolic contraction - caused by backflow of arterial blood while valve is still closing, coincides with aortic valve closure
Velocity = ?
Flow / cross-sectional area
How does stenosis of the aortic valve affect velocity and pressure?
Increases velocity, decreases pressure
Blood pressure in foot is higher so how does blood flow up pressure gradient?
Trade gravitational energy for pressure
What is Darcy’s law?
Q is proportional to (P1 - P2) so Q = (P1-P2)/R so CO = (Pa - CVP)/TRP
Two types of fluid flow?
Turbulent or laminar
How does laminar flow affect blood cells and endothelial lining?
Blood cells not colliding, little damage to endothelial lining
What is a cell deficient marginal layer?
Red blood cells in centre during laminar flow
Where does turbulent flow occur?
Ventricle and aorta (large diameter, high velocity)
What is Reynolds number?
Ratio of inertial forces (disordering) and viscous forces (ordering)
Equation of Reynolds number?
(velocity x diameter x density)/viscosity
Above what value of Reynolds number is turbulent flow?
2000
Definition of viscosity?
Force required to move fluid at a certain rate
Force and velocity are shear ?
Force = shear stress, velocity = shear rate
Viscosity = ?
shear stress / shear rate
Why are high and low viscosity bad?
High is bad because heart must work harder, low is bad because need more blood pumped for the same pressure
What determines resistance during laminar flow?
Internal friction within fluid
Resistance is proportional to?
Tube length, viscosity and 1/radius^4
Flow = ?
[(P1-P2) x pir^4] / 8nL
Wall tension = ?
Transmural pressure x radius
Why does smooth muscle have wall tension? What about larger blood vessels and capillaries?
To resist transmural pressure - larger blood vessels need more, endothelial wall is enough in capillaries
What is preload?
End diastolic pressure OR volume of left ventricle OR stretch on myocytes of left ventricle
How does VR affect preload?
Raised VR = raised preload because higher venous pressure = more blood back to heart
Stretch = wall tension SO what is preload proportional to?
End diastolic pressure x cubedroot of volume
What is Starling’s preparation?
Aorta ligated (brain not functioning, blood still goes through coronary circulation), external circuit to change and measure venous pressure, arterial pressure, resistance and compliance, aorta connected to pressure gauge, rubber tubes can be squeezed
What represents the elastic aorta in Starling’s preparation?
Air chamber
Which ventricle is Starling’s law for?
Both
What is the ANREP effect?
10 minutes after stretch a rise in force ocurs
Why does Starling’s law require extrinsic controls?
Could cause arterial pressure to rise too high
Ratio of pre:postganglionic fibres in sympathetic neurones?
1:10
Ratio of pre:postganglionic fibres in parasympathetic neurones?
1:3
Which neurotransmitter can be released further away and diffuse?
NA
Which neurotransmitters do parasympathetic neurones use?
ACh - nicotinic then muscarinic
Which neurotransmitters do parasympathetic neurones use?
ACh (nicotinic) then NA
Where are Beta1 receptors found?
Heart and interstitial smooth muscle
Where are Beta2 receptors found?
Bronchi and vascular smooth muscle (relax)
What are alpha 2 receptors?
Presynaptic receptors
What are alpha 1 receptors?
Traditional receptors (vasoconstriction)
Are pre and postganglionic myelinated or unmyelinated?
Pre is myelinated, post is unmyelinated
How do catecholaines affect metabolic rate?
Stimulate it (maintains effects of neuronal sympathetic activity)
Which cells need catecholamines?
Ones with no sympathetic innervation
What proportion of their maximum diameter does tone keep arterioles at?
1/2
Is there more or less tone in the parasympathetic nervous system? What’s the exception and why?
Less tone apart from vagus (to keep heart rate depressed)
What takes up noradrenaline which has leaked?
Sympathetic neurones and smooth muscle
Where do preganglionic fibres in adrenal medulla terminate? What is released?
Modified nerve cells, release 80% adrenaline and 20% noradrenaline
What kind of incompetence does heart transplant cause? Why?
Chronotropic incompetence - higher resting heart rate and slower rise due to no vagus nerve
What does dromotrophy mean?
Conduction
Why is length-tension curve a straight line that carries on increasing in cardiac muscle?
Better overlap and more sensitive to Ca2+
What is mean systemic pressure “zero point” value?
7mmHg
What happens to venous pressure with every heartbeat?
Goes down a little bit
In arteries CO=?
ABP-MSP / TPR
In veins VR = ?
MSP-RAP / RVR
What happens in transmural pressure gets too low?
Vessels will collapse
What value is central venous pressure normally at?
Close to zero
What happens to stroke volume if heart rate goes up?
Decreases
What happens to pressure and CO if circulation is constricted?
Both increase`
What happens to MSFP, CO and RAP is stressed volume is doubled?
MSFP and CO double, RAP still zero
WHat connects myosin to Z line?
Titin
WHy does heart have increased Ca2+ sensitivity?
Decreased lattice spacing
Three causes of shock?
Hypovolaemic, cardiogenic, distributive
Two effects of sympathetic stimulation?
Venoconstriction causing increased MSFP and heart rate
Cause of heart failure?
Heart doesn’t know body is unable to increase cardiac output
Effects of heart failure?
MSFP and RAP still increase, but if RAP increases so must capillary pressure so get oedema
How do Guyton’s curves work?
A graph for CO and VR, when they are equal you know the actual values since CO and VR must be equal
Components of septicaemic shock?
Distributive and cardiogenic components
Pulse pressure = ?
P systolic - P diastolic
What increases pulse pressure?
Excercise, age, aortic valve leakage
Where are the stretch receptors?
Carotid sinus and aortic arch
Which nerves do stretch receptors connect to?
Carotis sinus nerve to nerve IX and vagus
Which valve closes at the start of systole?
Mitral
Which valve closes at the start of diastole?
Aortic
What happens to mean ABP if baroreceptors are denervated?
MEAN ABP stays the same but has less of a tight range
WHat in brain area that baroreceptors and chemoreceptors feed into?
NTS in medulla (nucelus tractus solitarius)
What does NTS stimulate?
Cardioinhibitory area, vasomotor area
What does cardioinhibitory area increase?
Vagal tone
What does vasomotor area increase?
Sympathetic tone
WHich pathway do cardioinhibitory and vaso-motor areas use?
Bulbospinal pathway to preganglionic sympathetics
Why can CO be measured using O2 consumption?
Oxygen consumption is proportional to CO
Which adrenoceptors are for NA and which for adrenaline?
NA = alpha1 and beta1, A = beta2
Where is alpha1 adrenoceptor and what does it do?
Vascular smooth muscle esp skin, for vasoconstriction
Where is beta1 adrenoceptor and what does it do?
Cardiac, increased HR and contractility
Where is beta2 adrenoceptor and what does it do?
Vascular smooth muscle esp skeletal, vasodilation
Why are arterioles a good place to regulate flow?
Big drop in pressure here and muscular walls
What regulates arteriole diameter?
Availability of actin to myosin, activity of myosin head
What happens to arterioles in low O2?
Dilate
What’s involve in local control of arteriole diameter?
Metabolites, myogenic (stretch), paracrine (from endothelium/inflammatory)
What does caldesmon do to muscle?
Actin and myosin can’t bind
What removes caldesmon from actin?
Calmodulin or phosphorylation
What is the myogenic effect?
Tension in walls is proportional to radius, if you try and stretch it tension will go up so it shrinks
What do NA and ACh cause endothelium to do in normal blood vessels?
NA causes constriction, ACh causes relaxation
What does damage done by obesity, smoking and diabetes to endothelial lining cause?
Less vasodilatory signalling pathways, so vasoconstriction
What is shear-stress induced release of NO?
Signalling upstream, metabolites all washed downstream and make endothelium produce NO, turbulence where the is big diameter change, NO diffuses upstream - so waste products determine blood flow
What does NO synthase inhibitor do?
Acts as paracrine regulator, diffuses into smooth muscle, hyperpolarises it, reduces Ca2+, inhibits MLCK, turned off by phosphodiesterases
How does NA cause SR Ca2+ release?
NA > alpha1 receptor > G-protein (Galphaq) > PLC > IP3 > SR Ca2+ release
How does adrenaline cause decreased MLCK activity?
adrenaline > beta2 receptor > G-protein (Galphas) > adenyl cyclase > cAMP > PKA > decreased MLCK activity
Which metabolite reduces Ca2+?
NO
What increases Ca2+?
NA, depolarisation, stretch
What inhibits MLCK?
adrenaline (via beta2) and NO
What activated MLCK?
Ca2+ - CaM
How does aspirin work?
Inhibits cyclo-oxygenase 1 irreversibly, inhibits thromboxane which causes platelet aggregation (also inhibits PGI2 which does the opposite but inhibits this less)
What is the carotid sinus composed of?
Modified smooth muscle
What are the carotid bodies?
Chemoreceptors
How does positive ionotropic effect work?
NA > beta1 > AC > cAMP > PKA. Then, the PKA sensitizes troponin to Ca2+, phosphorylates DHP to increase Ca2+ conc, inhibits phospholamban so inhibition of SERCA removed so Ca2+ stored inside SR for next time
Flow of X equals?
capillary area x permeability of X x change in conc
Volume flow =
hydraulic permeability x (change in hydrostatic pressure - change in colloid osmotic pressure)
How is autotransfusion caused?
Low venous pressure and sympathetic arteriolar constriction causes fluid to move back to blood
What does lymphoedema cause in skin?
Moves it away from capillaries
What is congestive heart failure?
Raised atrial pressure with lower arterial pressure than the body wants
What changes are there during the fast phase of exercise hyperaemia?
Increased extracellular K+ from act pots, decreased O2, decreased pH, increased lactic acid, increased extracellular ATP and ADP, increased CO2 and temperature
How can you measure blood flow during exercise hyperaemia?
Venous occlusion plethysmography, invasive flow monitoring, or IR spectroscopy
Is circulation or breathing at fault for muscle limit?
Circulation (muscles could do more if given more blood)
What is the secondary chemoreceptor response?
Response to response to hypoxia
What are the two causes of hypoxia?
Inability to breathe, reduced O2 concentration
What are the two ideal responses to hypoxia?
Conservation of O2, increased blood to tissues
How do inwardly rectifying channels work?
Increased in extracellular K+ should cause depolarisation but does opposite in smooth muscle (hyperpolarises, closes Ca2+ channels, muscle relaxes) because ions coming in makes it easier for ions to get back out
What do inwardly rectifying channels cause?
K+-induced vasodilation from local vasodilatory stimuli
What is central venous pressure in a healthy heart?
0
What do low pressure baroreceptors detect?
RAP (if elevated it suggest circulation is overfilled so can’t maintain venous pressures like in heart failure
What happens if low presure baroreceptors are denervated?
Rise in mean ABP
What do low pressure baroreceptors detect?
SHort term changes in ABP
What do low pressure baroreceptors do with increased pressure?
Firing rate increases, goes to NTS via vagus, then to hypothalamus, decreases fluid and sodium retention
What is functional hyperaemia?
Increased local blood flow e.g. following inflated cuff experiment
What changes are there in arterioles following increased metabolism or reduced blood flow?
Reduced PO2, increased PCO2, decreased pH, increased adenosine, increased extracellular K+
What local changes stimulate vasodilation?
Decreased pH and increased lactic acid
When can acetylcholine not dilate arteries?
When endothelium is not intact
Which tissues have more beta2 than alpha1 receptors?
Coronary blood vessels and skeletal muscle
What do beta2 receptors trigger?
Vasodilation
What does NA from sympathetic nerves do?
Acts on alpha1 receptors allowing skeletal muscle blood flow to be restricted if necessary
What do ACh and NA do to arteries?
ACh dilates them, NA constricts them
How does endothelium removal affect NA action on capillary artery constriction?
It doesn’t
What is the signal from the endothelium to vascular smooth muscle?
NO
How is NO production stimulated?
ACh and bradykinin stimulate production by the action of NO synthase on L-arginine in the endothelium
What is bradykinin?
A vasodilator peptide
How does NO inhibit MLCK?
Lipophilic, diffuses quickly, stimulates soluble guanylyl cyclase in vascular smooth muscle, a cGMP dependent protein kinase then phosphorylates MLCK
How does viagra work as a vasodilator?
Reduces cGMP breakdown and inhibits cGMP-specific phophodiesterase type 5
What things does the endothelium release?
Pro-coagulants, anti-coagulants, fibrinolytics, antibacterials, growth factors
What are eicosanoids?
Arachidonic acid derivatives involved in clotting and inflammatory responses
What synthesizes eicosanoids?
Cyclo-oxygenase
WHat is the vasoconstrictory prostaglandin?
PG-F
What is the vasodilatory prostaglandins?
PGs I, D E
What produces thromboxane A2?
Platelets
What does thromboxane A2 do?
Vasoconstrictor, also causes platelet aggregation
WHat opposes thromboxane A2 action?
Prostacyclin
What produces prostacyclin?
Produced by endothelium
Why can endothelium damage lead to reduced blood flow and clotting?
Alters balance between prostacyclin and thromboxane A2 in favour of thromboxane A2
What is interstitial oedema?
If rate of fluid movement out of capillaries is greater than removal by lymphatics
What can localised oedema result from?
Lymphatic blockage, increased capillary leakiness to proteins in inflammation, ischaemia reperfusion injury and in the brain following head injury
How much must interstitial fluid volume increase before general oedema is noticable?
30%
What is ischaemia?
Restriction in blood supply to tissues, causing a shortage of oxygen and glucose needed for cellular metabolism
Why can you get heart failure and hypertension at the same time?
Get heart failure when ABP is lower than the set point and can’t be raised, body responds to this as it does to haemorrhage (venoconstriction, arteriolar vasoconstriction, and fluid retention) which raises TPR and MSFP
Why can TPR influence CO in a failing heart?
Maintianing CO with increased TPR needs increased cardiac work
What do the symptoms of heart failure result from?
Inability to increase CO, increased atrial pressure
WHich drugs can inhibit response to low blood pressure?
ACE inhibitors, diuretics, beta adrenergic blockers, by lowering MSFP and TPR
What does rise in interstitial K+ do during exercise hyperaemia?
Hyperpolarises arteriolar smooth muscle which closes VG Ca2+ channels and therefore relaxes the muscle - should cause depolarisation however may do opposite because of enhanced NaKATPase and enhanced inward rectifying channels
What blocks inwardly rectifying K+ channels?
Barium
How does muscle pump cause functional hyperaemia?
Contraction accelerate VR which enhances CO but may also reduce venous pressures to enhance pressure gradient through capillaries
In cats, what do sympathetic cholinergic nerves do to blood flow at the start of exercise?
Increase it
What do increased oxygen offloading cause in RBCs?
ATP and NO release
What do ectonucleotideases do?
Produce vasodilatory adenosine by ATP
WHat enhances ectonucleotidease activity?
Low O2
How is some ATP released by active muscle?
Partly by GFTR channels in response to reduced intracellular pH linking pH changes to vasodilation
How does adenosine cause vasodilation?
Acts on A2A receptors to increase cAMP levels in smooth muscle which activates PKA which in turn opens K ATP channels, hyperpolarises cell
Why is venoconstriction and increased sympathetic stimulation needed is exercise?
Because exercise causes TPR drop which needs CO increase to maintain ABP
What happens during blood loss?
Lowered MSFP, low VR and CO, lowered blood pressure, baroreceptors detect changes, reduce inhibition of medullary vasomotor areas, symp nerves increase arteriolar and venous tone and HR, vagal tone to heart decreases, catecholamines, ATII and ADH released
What happens if blood is still being oxygenated during hypoxia?
Ideal response is to increase CO to compensate
What is reflex response to reduced amount of O2 as in diving?
Detected by carotid and aortic bodies, chemorecptors and then integrated in the medulla, causes slowed heart rate and systemic vasoconstriction mediated by vagal reflex and sympathetic nervous system - DIVE REFLEX
What does the dive reflex cause?
Keeps cardiac work to a minimum and the sympathetic drive overwhelms the metabolic vasodilation to divert available blood to tissues with little sympathetic vasoconstrictor innervation (brain and heart)
What is response to reduced PO2 from altitude?
Secondary chemoreceptor response - reduced PO2 causes increased rate and depth of breathing but then pulmonary stretch receptors send afferent impulses via vagus nerve to medulla and stimulate vasomotor centre, causes venoconstriction, inhibits cardio-inhibitory centre and causes pattern of vasodilation/constriction favouring vital tissues causing net CO rise
