Lecture 12: Cardiac output, hemodynamics and neuronal influences Flashcards
Key roles of the circulatory system
1) To transport nutrients to tissues (Oxygen, Glucose, lipids, amino acids)
2) To remove metabolic by-products from tissue (Carbon dioxide, Hydrogen ions)
3) To transport hormones so they can exert their effects on target tissues
What are the main components of the circulatory system?
1) A carrier for transport of nutrients/waste/hormones, i.e. blood
2) A system of pipes for the carrier to efficiently move through, i.e. the blood vessels
3) A pump to drive the movement of the carrier through the pipes, i.e. the heart
Key design criteria of the circulatory system
1) Each region of the body must be adequately perfused to meet its specific demands
2) The system must be able to rapidly adapt to changes in demand both globally (i.e. throughout the body) and locally (i.e. in specific tissues)
3) The system must be able to repair itself, or failing that, to adapt to impairments in order to allow the organism to survive
What is the heart’s job?
To impart kinetic energy to the blood, building up a pressure head that drives the flow of blood through the circulatory system
What is the build up of pressure in the cardiac system?
Measure of cardiac work
What does the cardiac cycle refer to
refers to the repetitive, alternating contraction and relaxation phases of the heart,
consists of two stages
What are the two stages of the cardiac cycle?
Systole: Contraction of the heart and ejection of blood. Occurs due to depolarization of the cardiac muscle
Diastole: Relaxation and refilling of the heart. Occurs due to repolarization of the cardiac muscle
Wiggers diagram
See figure
Described the steps of the diagram (1-12)
See figure
1) Atrial pressure increases due to continuous passive movement of blood into atria.
Atrial pressure exceeds ventricular pressure, causing the opening of the left/right atrioventricular (AV) valves (panel A).
2) Ventricular volume increases as blood flows into the ventricles from the atria.
3) Atria become depolarized, represented as the P wave on the EKG.
4) Atria contract and squeeze blood into the ventricles, causing an increase in atrial pressure (panel B)
5) Ventricular pressure increases as ventricular blood volume increases (6), in part due to atrial contraction.
7) The volume at the end of ventricular diastole is known as the end-diastolic volume (EDV ~ 135 ml).
8) Ventricles become depolarized, initiating contraction – represented as the QRS complex on the EKG.
9) Ventricular pressure exceeds atrial pressure causing the closure of the AV valves.
10) At this time point all valves are closed and the ventricle remains a closed chamber. This period is called isovolumetric ventricular contraction (isovolumetric means constant volume) (panel C). Ventricular pressure rises, but volume does not change (11).
12) Ventricular pressure exceeds aortic/ pulmonary pressure causing opening of aortic/pulmonary valves and the ventricles eject blood (panel D).
Describe the steps of the Wiggers diagram (13-24)
13) Aortic/pulmonary pressure increases due to blood forced into the aorta/pulmonary artery.
14) Ventricular volume reduces significantly.
15) The volume of blood at the end of systole is known as end-systolic volume (ESV ~ 65 ml).
Blood volume ejected by each ventricle with each contraction is termed stroke volume (SV).
The proportion of the blood volume ejected by each ventricle with each contraction is termed the ejection fraction (EF).
16) Ventricles become repolarized, represented as the T wave on EKG.
17) As the ventricles relax, ventricular pressure falls below aortic/pulmonary pressure, causing the aortic/pulmonary valves to shut.
18) Aortic/pulmonary valve closure causes a disturbance seen as a notch on the aortic/pulmonary pressure curve.
19) At this time point all valves are closed and the ventricles remain as closed chambers. Ventricular pressure falls. This period is called isovolumetric ventricular relaxation (panel E). Ventricular volume does not change (20).
21) Ventricular pressure falls below atrial pressure and AV valves open.
22) Passive filling of blood into atria results in an increase in atrial pressure.
23) Rapid filling of the ventricles occurs due to increased atrial pressure.
24) Atrial pressure reduces and ventricular filling slows down.
What is end-diastolic volume?
The volume at the end of ventricular diastole
What is isovolumetric ventricular contraction
Occurs during depolarization of ventricles, and all valves are closed and ventricles are a closed chamber
Volume stays the same, but pressure rises
What is end-systolic volume?
ESV
The volume of blood at the end of systole
Around 65 ml
What is stroke volume?
SV
Blood volume ejected by each ventricle with each contraction
SV = EDV-ESV
What is the ejection fraction?
The proportion of the blood volume ejected by each ventricle with each contraction
EF = SV/EDV
What is Isovolumetric ventricular relaxation?
Ventricular volume does not change
Components of the pressure volume loop
See figure
a) closure of mitral valve, start of isovolumetric ventricular contraction
b) opening of aortic valve, start of ventricular empyting
c) closure of aortic valve, start of isovolumetric ventricular relaxation
d) opening of the mitral valve, start of ventricular filling
What does the area under the curve of the pressure volume loop represent
The AUC is a function of cardiac work, or cardiac output
What does the isovolumic pressure-volume curve represent?
(or end-systolic pressure-volume relationship, ESPVR)
Represents the maximal pressure that can be generated at a given ventricular volume, and provides a measure of cardiac contractility.
What is cardiac output? What is it determined by?
Represents the work performed by the heart
Determined by factors extrinsic (factors of the circulatory system) and intrinsic (factors of the heart) to the heart.
It is expressed in liters/min
Formulas for cardiac output
CO = MAP/TPR
CO = HR x SV
CO:cardiac output MAP:mean arterial pressure TPR:total peripheral resistance HR:heart rate SV:stroke volume
What are the extrinsic factors involved in calculation of CO?
MAP, TPR
Characteristics of circulatory system
What are the intrinsic factors involved in calculation of the CO?
HR (beats/min), SV (ml/beat)
Characteristics of the heart
How much blood volume is pumped by each side of the heart?
Same volume by each side
5L/min through pulmonary circulation and 5 L/min through systemic circulation
What is the cardiac reserve?
the difference between the cardiac output at rest and at its peak
the maximum volume of blood that can be pumped by the heart per minute.
How is heart rate modulated?
By the autonomic nervous system
Sympathetic and parasympathetic systems antagonize each other to control HR
In a normal healthy individual, both systems are typically active at any given time.
See figure
What is the effect of the SNS on the heart rate?
via norepinephrine
accelerates heart rate by increasing sinoatrial node firing rate
causes increased cardiac contractility (force of contraction of the heart) by stimulating intracellular calcium uptake and cycling
What is the effect of the PSNS on the heart rate?
via acetylcholine
decelerates heart rate by decreasing sinoatrial node firing rate
has minimal effect on ventricular contractility
Normal action potential in SA node pacemaker cells
Below threshold, SA node pacemaker cells have high [K+] but low [Na+] intracellularly
a slow, constant influx of Na+ leads to progressive depolarization of the cell interior until threshold is hit
meanwhile, there is a low level of K+ leakage via potassium channels
As the resting membrane potential passes threshold, voltage-gated calcium channels open to permit the rapid influx of [Ca2+] and the firing of the action potential
As the cell repolarizes, Ca2+ is both sequestered internally and pumped out
K+ rapidly exits the cell to restore RMP
the Na/K ATPase restores intracellular Na+ and K+ concentrations
See figure
How does SNS stimulation increase HR via the SA node?
Below threshold, there is a constant slow leakage of K+ out of the
cell, resulting in some movement of positive charge out of the cell
Norepinephrine, released from sympathetic nerve endings, inactivates these K+ ion channels
results in build-up of K+ (and thus positive charge) within the cell
also increased inward leak of Na+ and Ca2+, adding to this effect
How are the PSNS and SNS activities synchronized?
By the cardiovascular control centre in the brain stem
What are atropine and propanolol?
Atropine: PSNS blocker
Propanolol: sympathetic blocker
What is epinephrine secreted by? What is the the effect of epinephrine?
aka adrenaline
Secreted into the blood by the adrenal medulla upon sympathetic stimulation
Has similar actions to norepinephrine: an increase in heart rate and contractility.
What are the factors that determine stroke volume?
Venous return - more blood comes back, more pumped out (intrinsic control)
Sympathetic nervous system - constricts veins, which causes blood to return to the heart. Also acts directly on cardiac cells. (extrinsic control)
What is preload?
a measure of the amount of filling that the heart undergoes prior to contraction
What does an increase in preload cause?
An increase in cardiac output/cardiac work by increasing the amount of blood ejected with each contraction
See figure
What is the Frank-Starling law of the heart?
If the amount of blood entering during diastole increases, the heart will stretch
This causes greater tension development and increases the strength of contraction and increases SV
Due to improved actin-myosin cross-bridging (higher sensitivity of myofilaments to calcium)
See figure
Which autonomic nervous system prevails at rest?
In the absence of SNS or PSNS, the heart rate is 100 bpm
This indicate that at normal resting heart rate (70 bpm), the PSNS influence prevails
What causes an upward shift of the Frank-Starling curve?
Activation of the SNS, which causes increased cardiac contractility at any given EDV
Causes increased SV
See figure
What effect does the SNS have on the Frank-Starling curve?
Upward shift
SNS causes increased cardiac contractility at any given EDV
Causes increased SV
See figure
Which hormones mediate the SNS effect on SV? What is the result of this stimulation?
Norepinephrine and epinephrine
Results in enhanced excitation-contraction coupling
Also causes constriction of the veins, which results in greater return to the heart. This increases EDV and CO (intrinsic control)
What is the effect of the SNS on ejection fraction?
Normal SV is 70 ml
Can increase up to 100% with SNS stimulation
See figure
Summary of how CO is controlled
Control of cardiac output is thus achieved by a balance between heart rate and stroke volume control, and is influenced by both intrinsic and extrinsic factors.
See figure
Why does CO decrease with age?
partly because of a reduction in the release of norepinephrine from nerve terminals of the aged heart.
What is blood pressure?
Refers to the force exerted by the blood on the walls of the blood vessels
Usually we are referring to arterial pressure unless otherwise noted.
What is blood pressure?
Refers to the force exerted by the blood on the walls of the blood vessels
Usually we are referring to arterial pressure unless otherwise noted.
Blood flows from areas of high pressure to areas of low pressure.
What is systolic pressure?
Peak arterial pressure during cardiac contraction
Around 120 mm Hg
What is diastolic pressure?
lowest arterial pressure during cardiac relaxation
Around 80 mm Hg
How is blood pressure usually reported?
P systolic / P diastolic
What is pulse pressure?
The pulse that can be felt in an artery lying close to the surface of the skin
The difference between systolic and diastolic pressures; that is, when the blood pressure is 120/80, pp = 40 mm Hg.
What is mean arterial pressure (MAP)?
the average pressure driving the blood forward into the tissues.
BUT, arterial pressure remains closer to diastolic than to systolic pressure for a longer portion of each cardiac cycle
MAP = ((S-D/3) +D or;
MAP = pp/3 +D
What systemic factors influence the circulatory system and the heart?
Local: metabolites, oxygen, tension
Systemic: hormones, nerves system
Act on the heart to affect pumping or act on blood vessels to affect blood flow
How does pressure change in different parts of the circulatory system?
Big changes in the ventricles
Swings in aorta, but not as drastic
Arterioles have loss of pressure.
Capillaries need to have constant pressure, otherwise there would be fluctuations with diffusion
See figure
