2.4B. (Pump function of the heart.) Cardiac output and its control. Flashcards
I. Cardiac output
1. What is cardiac output?
Cardiac output (CO) is the volume of blood being pumped by the left ventricle into the aorta per minute
- CO = 5,6 L/min at rest
- CO = HR * SV = 70 beats/min * 80mL = 5600mL/min = 5,6 L/min
I. Cardiac output
2. How to calculate cardiac output (give the values as well)?
- CO = 5,6 L/min at rest
- CO = HR * SV = 70 beats/min * 80mL = 5600mL/min = 5,6 L/min
II. Total peripheral resistance (TPR)
1. Definition of Total peripheral resistance (TPR)
The ratio of arteriovenous pressure difference to the flow through the entire systemic vascular bed (essentially the CO)
II. Total peripheral resistance (TPR)
2. Formula of Total peripheral resistance (TPR)
The ratio of arteriovenous pressure difference to the flow through the entire systemic vascular bed
(essentially the CO)
=> MABP = CO * TPR
III. Stroke volume
1. What is Stroke volume?
SV = amount of blood transported to aorta during systole
III. Stroke volume
2. How to calculate the stroke volume?
The difference between the volume of blood in the ventricle before ejection (end diastolic volume) and the volume remaining in the ventricle after ejection (end systolic volume)
SV = EDV - ESV
- Less than half of the blood volume remains in the ventricles
- Stroke volume (SV) = EDV – ESV = 140mL – 60mL = 80mL
IV. Eject fraction (EF)
1. Definition of Eject fraction (EF)
A measure of how much blood the left ventricle pumps out with each contraction in percentage
- Refers to how well the left ventricle pumps blood with each beat
IV. Eject fraction (EF)
2. How to calculate Eject fraction (EF)
- 0,5 < EF < 0,75 -> more than 1⁄2, but less than 3⁄4 of volume should be ejected
- 0,50 < EF < 0,75 ↔ 1⁄2 < EV <3⁄4
V. 4 factors that determine the CO
1. What are the 4 factors that determine CO?
- Cardiac factors
a) Heart rate
b) Myocardial contractility - Coupling factors (heart + circulation)
a) Preload
b) Afterload
V. 4 factors that determine the CO
2. Definition of cardiac factors
Cardiac factors: strictly cardiac factor, but influenced by hormonal + neural factors
a) Heart rate
b) Myocardial contractility
V. 4 factors that determine the CO
2B. What are characteristics of Myocardial contractility (a cardiac factor)
Myocardial contractility: ability of heart to increase contraction force
- Influenced by SYM activity
- Determines the SV + HR = CO
V. 4 factors that determine the CO
3A. Definition of the coupling factors?
Coupling factors (heart + circulation) – constitute a functional coupling of heart + vessels
a) Preload
b) After load
V. 4 factors that determine the CO - the coupling factors
3B. What is preload?
Preload: force that stretches the relaxed muscle fibers = (blood filling the wall during diastole)
V. 4 factors that determine the CO - the coupling factors
3C. What is afterload?
Afterload: force added to the muscle against which the contracting muscle must act = aortic pressure (left ventricle must generate a greater pressure than the aorta to open the valve)
VI. Regulation of cardiac output
1. What are the 2 types of regulations?
- Heterometric regulation
- Homometric regulation
VI. Regulation of cardiac output - heterometric regulation
2A. What is heterometric regulation?
Refers to how different initial fiber lengths impact the force of contraction
VI. Regulation of cardiac output - heterometric regulation
2B. What are the 2 experiments contributing to the understanding of heterometric regulation?
1) Otto Franck’s experiment
2) Starling’s experiment
VI. Regulation of cardiac output - heterometric regulation
2B. What are the 2 experiments contributing to the understanding of heterometric regulation?
1) Otto Franck’s experiment
2) Starling’s experiment
VI. Regulation of cardiac output - heterometric regulation
2C. Explain Otto Franck’s experiment
- Within physiological limits, the contraction force is directly proportional to the initial fiber length
- Higher diastolic filling (preload) -> stronger contraction (systolic pressure)
- Higher fiber length -> more forceful contraction
- An increase in the initial fiber length of the muscle fiber beyond a certain point will no longer increase the pressure
VI. Regulation of cardiac output - heterometric regulation
2C. Explain Starling’s experiment
Concluded that increased venous return (diastolic filling) to the heart, which increased the filling pressure (EDV) of the left ventricle -> led to a greater SV
- Frank-Starling Law: SV of the heart increases in response to an increase in the blood volume in the ventricles (EDV) when all other factors remain constant
- Heterometric regulation: EDV↑ -> SV↑
VI. Regulation of cardiac output - heterometric regulation
2D. What is Frank-Starling mechanism?
- It states that SV of heart increases in response to an increase in the volume of blood in the ventricles before contraction. The larger vol of blood flows into ventricle, as a consequence, stretches the cardiac muscle fibres, leading to an increase in the force of contraction
- As a muscle fiber is stretched (change in the initial fiber length). Active tension is created by alternating the overlap of thick and thin filaments
-> At this point, interaction between the active binding site on the actin fiber and some myosin heads are inhibited, as there is an overlap of actin fibers - The greatest isometric active tension is developed when a muscle is at its optimal length
-> All of the myosin heads are intact with the binding sites on the actin fiber, and there is no excess in both ways
VI. Regulation of cardiac output - heterometric regulation
2E. Describe Inotropic mechanism
- As a muscle fiber is stretched, sarcomeres must increase in length simultaneously
- The increased sarcomere length increases the sensitivity of troponin C (TnC) to Ca2+
- Increased TnC-sensitivity increases both the rate of cross-bridge attach/detachment and the strength of tension developed by muscle fiber, resulting in a greater SV
VI. Regulation of cardiac output - heterometric regulation
2F. What are the 2 factors that affect the force of contraction?
Increased preload
Increased afterload
VI. Regulation of cardiac output - heterometric regulation
2G1. How can increased preload affect force of contraction?
↑venous return -> ↑ventricular filling (EDV) -> ↑SV
VI. Regulation of cardiac output - heterometric regulation
2G2. How can Increased afterload affect force of contraction?
↑systemic vascular resistance ->↑aortic pressure -> ↓SV
- Increase in afterload leads to arterial pressure rapidly increasing
+) Both systolic and diastolic pressures increase, but the difference between them stays the same, because venous inflow is the same - When afterload is increased, the first heartbeat is unable to pump out the usual amount of blood (due to a greater-than-normal pressure). So, once again, EDV increases
-> More forceful contraction
-> Occurs at a constant venous flow (constant preload)
VI. Regulation of cardiac output - heterometric regulation
2H. What are the Determinants of ventricular filling?
- Venous return: venous pressure, central venous pressure (CVP), right atrial pressure
- Heart rate (duration of diastole): if HR↑ = diastole↓ -> limited time for ventr. filling
- Atrial systole (20%) -> increases ventricular filling
- The border between the atria and ventricles move toward the apex of the heart during (ventricular) systole -> suction of blood from the veins
VI. Regulation of cardiac output - Homometric regulation
3A. What are the characteristics of homometric regulation?
- The force of contraction is changed independently of the fiber length
- The extrinsic regulatory mechanisms (ex: nervous, chemical) may override the intrinsic mechanism to regulate CO
VI. Regulation of cardiac output - Homometric regulation
3A. What are the characteristics of homometric regulation?
- The force of contraction is changed independently of the fiber length
- The extrinsic regulatory mechanisms (ex: nervous, chemical) may override the intrinsic mechanism to regulate CO
VI. Regulation of cardiac output - Homometric regulation
3B. What are the 2 types of nervous control of Homometric regulation?
- Sympathetic: acts through β1-AR (Gs)
- Parasympathetic: acts through M2-R (Gi)
VI. Regulation of cardiac output - Homometric regulation
3C1. What is the molecular mechanism of sympathetic nervous control of homometric regulation?
NE -> β1-AR (Gs) -> AC activity↑ -> [cAMP]↑ -> PKA-activity↑ -> phosphorylation of following proteins:
- L-type VDCC: (same as RyR) becomes activated, allows larger influx of Ca2+
- Ryanodine receptors: responsible for much of the calcium from the lumen of SR
- Troponin I (TnI): inhibits binding of Ca2+ by troponin C (TnC)
-> Tropomyosin returns to its original position (blocking interaction), and facilitates cardiac relaxation
- Phospholamban activated, which regulates the Ca2+-ATPase pump that brings Ca2+ into the SR (SERCA pump)
-> This decreases [Ca2+]IC, but allows for faster relaxation
VI. Regulation of cardiac output - Homometric regulation
3C2. What are the effects of sympathetic nervous control of homometric regulation?
Sympathetic: acts through β1-AR (Gs)
1. Positive chronotropic (HR) effect: ↑If
2. Positive dromotropic (conduction velocity) effect: ↑ICa
3. Positive inotropic (contractility) effect: ↑ICa
4. Positive lusitropic (relaxation) effect: ↑SERCA, ↓troponin Ca2+-affinity
=> Same effects can be achieved by isoproterenol (β-AR agonist)
VI. Regulation of cardiac output - Homometric regulation
3D1. What is the molecular mechanism of parasympathetic nervous control of homometric regulation?
- Parasympathetic: acts through M2-R (Gi)
- ACh -> M2-R (Gi) -> ↓AC activity -> ↓[cAMP] -> ↓PKA
-> Phosphorylation of various structures noted above (ex: Ca2+-ch, TnI) does NOT occur
-> GIRKs are activated through M2-R -> Gβγ-dimer interacts with GIRKs to open them
-> IK-ACh in atria and conduction system are affected
VI. Regulation of cardiac output - Homometric regulation
3D2. What are the effects of Parasympathetic nervous control of homometric regulation?
- Parasympathetic: acts through M2-R (Gi)
- 4 effects
- Negative chronotropic (HR) effect: ↓If, ↑IK-ACh
- Negative dromotropic (conduction velocity) effect: ↓ICa,
- Negative inotropic (contractility) effect: ↓ICa, ↑IK-ACh (ONLY IN ATRIA)
- Positive lusitropic (relaxation) effect: ↓SERCA, ↑troponin Ca2+-affinity
VII. Further factors that influence contractility
1. What are other factors that influence contractility?
- Temperature
- Ionic concentration
- Hypoxia, ischemia:
VII. Further factors that influence contractility
2. How can Temperature influence contractility
- Low temperature exerts negative inotropic (contractility) and chronotropic (HR)
effects on the isolated heart
VII. Further factors that influence contractility
3. How can Ionic concentration influence contractility
- [Ca2+]EC ↑: positive inotropic effect (=↑ICa)
- [K+]EC ↑: negative inotropic effect
VII. Further factors that influence contractility
4. How can Hypoxia, ischemia: influence contractility
- Not enough O2
- Shortening of the ventricular AP, IK,ATP ↑
- Loss of normal ion gradients (especially K+) across the membrane
- Pacemaker channels remain inactivated in depolarized cells
