CVS Mechanics Flashcards
Describe cardiomyocytes:
Rod-shaped and 100um long, with t-tubule invaginations that are 200nm in diameter, carrying action potentials to the sarcoplasmic reticulum, and lining up the Z-lines; many mitochondria located close to the myofibrils to ensure rapid ATP synthesis
What is EC-coupling in cardiomyocytes?
On excitation, depolarisation sensed by L-type Ca2+ channels, opening these to allow extracellular calcium to enter down concentration gradient to sarcoplasm (2mMol to 1nMol) - some calcium will activate myofilaments, but most binds to ryanodine receptors (aka SR Ca2+ release channel), inducing conformational change to open the RyR, causing Ca2+ efflux in calcium induced calcium release
What is the difference between cardiac and skeletal muscle?
DHPR = mechanical link, but does not exist in cardiomyocytes, so L-type calcium channel needed
What is the role of the Ca2+-ATPase pump?
It uses ATP to pump calcium against concentration gradient from cytoplasm to SR for storage
What is the role of the Na+/Ca2+ exchanger?
It uses downhill concentration gradient of Na+ to efflux calcium from cell - so same amount that entered to cause heartbeat is removed again
Summarise the movement of calcium in cardiac muscle contraction
AP opens L-type Ca2+ channels, leading to influx
Influx causes calcium induced calcium release by inducing conformational change in RyR that allows for an efflux from the sarcoplasmic reticulum
Calcium binds to troponin to move tropomyosin
Ca2+-ATPase uses ATP to pump calcium against the concentration gradient back to the SR - so all released by the SR is reabsorbed
Na+/Ca2+ exchanger uses downhill gradient of Na+ to efflux calcium from cell - so all that entered via the L-type Ca2+ channels exits
Result = same [Ca2+] as start
How are the physical properties of cardiac muscle different to skeletal muscle?
More resistant to stretch and less compliant than skeletal muscle, due to properties of the extracellular matrix/cytoskeleton - can’t be overstretched, and only ascending limb of relation important
What are the two types of contraction in cardiac muscle?
Isometric and Isotonic
What is isometric contraction?
There is no change in length but pressure increases in vesicles when valves closed
What is isotonic contraction?
Shortening of fibres leads to ventricular blood ejection when valves open
What is preload?
The weight stretching a muscle before it is stimulated to contract
What is afterload?
The weight not apparent to muscle in its resting state, only encountered after contraction initiates
What is the isometric-preload relationship?
Greater preload leads to greater force because stretches before contraction
What is the Isotonic-afterload relationship?
Greater afterload leads to reduced shortening and velocity
Heavier weight = reduced shortening but same force
What is the preload-afterload relationship?
A greater preload leads to a greater shortening for a given afterload
What are the in vivo correlates of Preload?
Blood filling in diastole stretches resting ventricular walls, and stretch determines the pre-load before ejection - dependent on venous return; measured by end-diastolic volume, end-diastolic pressure and right atrial pressure
What are the in vivo correlates of afterload?
Effectively diastolic blood pressure; afterload is load against which left ventricle ejects blood after opening of aortic valve - any increase decreases isotonic shortening and hence velocity; measured by DBP
How does hypertension affect afterload?
Higher DBP (afterload) means ventricle has to work harder to expel
Considering afterload and preload, what are the factors that affect heart contraction?
Amount of blood filling the ventricle (P)
Pressure in aorta needed to overcome to eject blood (A)
Pressure volume loops:
Name what happens at the four corners (A-D) where A is at the bottom right, going anti-clockwise:
A: Mitral valve closes
B: Aortic valve opens
C: Aortic valve closes
D: Mitral valve opens
Pressure volume loops:
What happens between A and B?
Isovolumic contraction
Pressure volume loops:
What happens between B and C?
Ejection
Pressure volume loops:
What happens between C and D?
Isovolumic relaxation
Pressure volume loops:
What happens between D and A?
Filling
Pressure volume loops:
What are the two axis?
X: (LV) volume (ml)
Y: (LV) Pressure (mmHg)
Pressure volume loops:
What is the effect of increasing the preload?
The total LV will be higher
The pressure at the end of D to A will be slightly higher
Pressure volume loops:
What is the effect of increasing afterload?
The total pressure reached at C will be higher
The volume at C to D will also be higher
What is the optimum preload/afterload to maximise stroke volume?
High preload
Low afterload
What is Starling’s Law of the Heart?
Increased filling/stretching (preload) leads to increased force of contraction, leading to a greater stroke volume so that cardiac output exactly balances venous return (preload)
How is Starling’s Law achieved?
Increased stretching leading to reduced actin-myosin overlap so more crossbridges can be made
Changes in calcium sensitivity: troponin C when stretched has a higher affinity for calcium (ionotropic mechanism)
What is Stroke Work?
Work done to eject blood under pressure
SW = Stroke Volume x Pressure
What is the Law of LaPlace?
When pressure within a cylinder is constant, tension on walls increases with increasing radius
State the equation for law of LaPlace:
Wall tension = Vessel pressure x Vessel radius
What does LaPlace actually mean for the heart?
In order to achieve equal wall tension in each ventricle, pressure in right ventricle must be reduced because it has a larger radius
As left ventricle has a lower radius, it can generate a greater pressure for the same wall tension
Heart failure leads to dilation, producing a larger radius and hence greater wall stress
Which nervous system increases the contractility of the heart?
Sympathetic
How is Myocardial contractility measured?
Ejection fraction
Name the 7 phases of the cardiac cycle:
- Atrial systole
- Isovolumetric contraction
- Rapid ejection
- Reduced ejection
- Isovolumetric Relaxation
- Rapid passive filling
- Reduced passive filling
What happens mechanically in atrial systole?
Atrial contraction to top up ventricular volume
What happens electrically during atrial systole?
Pacemaker potential from SAN
AP flows over atria causing depolarisation and contraction.
Which section of an ECG represents Atrial systole?
P wave
What is the status of the valves during atrial systole?
AV open
SL closed
What are the four heart sounds?
S1 and S2 normal: S1 - AV closure S2 - SL closure S3 and S4 abnormal: S3 - Blood hitting overly compliant LV (can be normal) S4 - Blood hitting non-compliant LV
When are the four heart sounds heard?
S4 - Atrial systole
S1 - Isovolumetric contraction
S2 - Isovolumetric relaxation
S3 - Rapid passive filling
What happens mechanically during Isovolumetric contraction?
Myocardium contracts without fibre shortening to increase pressure but not change volume.
What happens electrically during isovolumetric contraction?
Wave of depolarisation spreads over ventricles causing contraction
What happens mechanically during Rapid ejection?
Pressure gradient outward now exists, so isotonic muscle contraction forces blood into arteries.
What happens electrically during Rapid ejection?
Ventricles depolarised and contraction.
Which phase of the cardiac cycle does the QRS complex represent?
Isovolumetric contraction
What segment of an ECG is represented by rapid ejection?
ST segment
What happens mechanically during Reduced ejection?
Decrease in ventricular pressure reduces pressure gradient so valve begins to close
What happens electrically during reduced ejection?
Ventricles repolarise
How is Reduced ejection represented on an ECG?
T wave
What is happening mechanically during Isovolumetric relaxation?
Ventricles relax and fibre length remains constant
What is happening mechanically during Rapid passive filling?
AV valve opens to allow rapid filling of ventricles down pressure gradient
What is happening mechanically during reduced passive filling?
Most blood already entered ventricle, so slow filling
What is happening electrically during Isovolumetric relaxation, and Passive filling?
Nothing, its diastole
What is end-diastolic volume?
Volume of blood in ventricel just before contraction (110ml)
What is end systolic volume?
Volume of blood in ventricle just before end of blood expulsion (40ml)
What is stroke volume?
End-diastolic - End-systolic
What is normal MAP?
93 mmHg
What is the equation for ejection fraction?
EF = Stroke volume / End-diastolic volume
What is the clinical relevance of the ejection fraction?
Shows how well the heart is working
What are normal and abnormal Ejection fraction?
60-70%, but could be 30-40% in heart failure
What is laminar flow?
Velocity of fluid is constant at any one point, flowing in layers, fastest closest to the centre of the lumen (as some friction with endothelial cell lining)
What is Turbulent flow?
Flow is erratic, forming eddys and prone to pooling - associated with pathophysiological changes to endothelial lining
What is the Parabolic velocity profile?
The further from wall = increased velocity; tangent at any point on the parabolic profile is the shear rate, and that multiplied by the viscosity is the shear stress
What is the impact of shear stress on blood vessels?
Governs how well the endothelial cells work
What is Laminar shear stress?
High level of shear stress, promoting endothelial cell survival and alignment in direction of flow to promote secretions to allow vasodilation and anticoagulation
What is turbulent shear stress?
In turbulent flow, low shear stress promotes endothelial proliferation, apoptosis and shape change - allowing secretions to promote vasoconstriction, coagulation and platelet aggregation - may lead to occlusion; age-related, eddys at branching (e.g. Carotid arteries) worsen with age
What is impact of turbulent flow on BP measurement?
Release of cuff leads to turbulent flow which can be heard with a stethoscope.
What is Poiseuille’s equation?
Resistance = (8 x length x viscosity) / (pi x radius^4)
What is the physiological application of Poiseuille’s equation?
The length and viscosity of blood vessels are effectively constant, so only the radius has an impact on resistance.
What is the importance of Radius and Poiseuille’s equation?
Halving the radius of a vessel decreases flow 16-fold, so capillaries and constricted arterioles have the most resistance to flow
What is Vascular Capacitance/Compliance?
Ability of a vessel to distend and increase its volume with increasing transmural pressure.
What is high compliance?
At a given pressure, the volume increases by a large degree
What is the equation for compliance?
Compliance = Change in Volume / Change in Pressure
What is the compliance of arteries and veins?
Arteries: Low compliance due to large elastic layer recoiling to maintain pressure
Veins: High compliance; distend to store a large volume of blood
What is the Windkessel effect?
Recoil of the arteries ensures continual flow despite pulsatile flow of heart
What is an external modulation of compliance?
Pressure stockings apply external pressure to prevent large increase in volume and prevent pooling
What is an internal modulation of compliance?
Performed by the RAAS (renin)
Endogenous vasodilators/vasoconstrictors and vasoactive drugs
What does the law of LaPlace mean for the vasculature?
Increased radius increases flow but also leads to higher wall stress; a thicker wall is needed to produce the higher tension as the radius increases for a given pressure; increasing radius increases flow, but also requires a thicker wall
What is cardiac output?
CO = Stroke volume x Heart rate
Volume of blood pumped by heart per min
Approx. 5L
What is the average stroke volume?
70ml
What is pulse pressure?
SBP - DBP
Approx. 40mmHg
What is Mean arterial pressure?
DBP + 1/3(Pulse pressure)
Approx 93mmHg
