1. Definitions
1.1. Preload
1.1.1. Can be defined as the initial stretching of the cardiac myocytes prior to contraction. Preload, therefore, is related to muscle sarcomere length.
1.2. Afterload
1.2.1. Can be defined as the pressure the heart must work against to eject blood during systole.
1.3. Chronotropy
1.3.1. Can be defined as heart rate
1.4. Inotropy
1.4.1. Can be defined as the heart's contractility
1.5. Cardiac Output
1.5.1. Can be defined as the volume of blood pumped into the aorta and venous return is the volume of blood that comes back to the right atrium which should be equal to cardiac output.
1.6. Contractility
1.6.1. Can be defined as the strength of contraction at any given end-diastolic volume.
1.7. EDV
1.7.1. End diastolic volume is the volume of blood in the right and/or left ventricle at end load or filling in (diastole) or the amount of blood in the ventricles just before systole.
1.8. SV
1.8.1. Stroke volume is the volume of blood pumped from the left ventricle per beat.
1.9. ESV
1.9.1. End systolic volume is the volume of blood in a ventricle at the end of contraction, or systole, and the beginning of filling, or diastole. ESV is the lowest volume of blood in the ventricle at any point in the cardiac cycle.
1.10. EF
1.10.1. Ejection fraction refers to the amount, or percentage, of blood that is pumped (or ejected) out of the ventricles with each contraction. It is calculated by doing SV/EDV and it should be about 50%
2. Heart Failure
2.1. What is it?
2.1.1. When the heart is unable to maintain a normal cardiac output at normal filling pressures.
2.1.2. Reduced cardiac output leads to under filling of the arterial circulation.
2.1.3. A permanent state of insufficient cardiac output owing to the failure of the heart to properly contract or relax as a result of stretching/thinning or hypertrophy/stiffening, respectively, of the ventricular walls.
2.2. What causes it?
2.2.1. Valvular insufficiencies
2.2.2. Patent ductus arteriosus (PDA)
2.2.3. Septal defects
2.3. Steps leading to heart failure
2.3.1. 1. Disease
2.3.2. 2. Decreased cardiac output
2.3.2.1. a. Compensatory increase in blood volume
2.3.2.2. b. Increases preload
2.3.2.3. c. Enhances SV through the Frank Starling mechanism
2.3.3. 3. Compensation (adaption)
2.3.4. 4. Maladaptation
2.3.5. 5. Heart failure
2.4. When compensations become deleterious
2.4.1. Venous Pressure
2.4.1.1. a. Preload is increased
2.4.1.2. b. EDV and SV are increased
2.4.1.3. c. This can lead to increased capillary pressure and oedema
2.4.2. Heart Rate
2.4.2.1. a. Increase HR
2.4.2.2. b. Increased contractility
2.4.2.3. c. Increased relaxation
2.4.2.4. d. Increased oxygen consumption causing hypertrophy and arrhythmias
2.5. Natriuretic Peptides
2.5.1. Types
2.5.1.1. ANP
2.5.1.1.1. Atrial Natriuretic Peptide
2.5.1.2. BNP
2.5.1.2.1. Brain Natriuretic Peptide
2.5.2. What are their use?
2.5.2.1. They do the opposite of aldosterone
2.5.2.2. Can be used as a diagnostic marker in heart failure
2.5.3. Mechanism
2.5.3.1. Reduce blood volume by stimulating excretion of salt and water by the kidney (glomerular arteriole dilation)
2.5.3.2. Relax vascular smooth muscle (stimulates cGMP formation) so vasodilation reducing TPR
2.5.3.3. Inhibits the RAAS
3. Stroke Volume Regulation
3.1. Mechanical Method
3.1.1. Ventricular end-diastolic volume (VEDV) can be increased
3.2. Neuronal Method
3.2.1. Sympathetic nerve activity can be increased to the heart
3.3. Hormonal Method
3.3.1. Plasma epinephrine can be increased.
4. Frank-Starling Mechanism
4.1. Starlings Law of the Heart
4.1.1. Starling Curve
4.1.2. The energy of contraction of a cardiac muscle fibre is proportional to the initial fibre length at rest. This can be shown by the Starling Curve
4.2. How muscle stretch relates to contraction strength
4.2.1. When the raised VEDV or VEDP occurs, it causes the stretching of the cardiac muscle there is increased exposure of the myosin heads on the thick filament to the actin. This means there are more cross-bridges being formed and the force of contraction is therefore higher.
4.3. Starlings Forces
4.3.1. The movement of fluid across capillaries depends on four variables known as the starling forces.
4.3.1.1. Hydrostatic pressure in the capillary (Pc)
4.3.1.2. Hydrostatic pressure in the interstitium (Pi)
4.3.1.3. Oncotic pressure in the capillary (pc )
4.3.1.4. Oncotic pressure in the interstitium (pi )
5. Venous Return Regulation
5.1. Volume of blood in the circulation
5.1.1. This is reduced in haemorrhage
5.2. Distribution of blood between the central and peripheral veins
5.2.1. Sympathetic nerve activity regulates peripheral venous tone
5.2.2. Gravity and movement
5.2.2.1. Standing pools venous blood in legs, reducing CVP and stroke volume
5.2.2.2. Movement operates the calf muscle pump, so raises CVP and stroke volume
5.2.2.3. Thoracic pump on inspiration, inthrathoracic pressure is negative and abdominal pressure is positive
6. Reflexes
6.1. Arterial Baroreceptor Reflex
6.1.1. Detects changes in blood volume
6.1.2. Integrating centre is the medullary cardiovascular centre
6.1.3. Receptors are high pressure receptors
6.2. Atrial Receptor Reflex
6.2.1. Receptors lie within the walls of the atria
6.2.2. Detects changes in blood volume
6.2.3. Receptors are low pressure stretch receptors
7. Action Potentials
7.1. Pacemaker Potentials
7.1.1. Graph
7.1.1.1. Pacemaker Potential Graph
7.1.2. Seen in the SAN
7.1.3. Conductive properties
7.1.4. Steps in the action potential propagation
7.1.4.1. 1. Sodium ions are slowly moving into the cell through leaky channels however the wall is practically impermeable to potassium ions so they are not moving out.
7.1.4.2. 2. There is a switch from sodium ions moving in to calcium ions through T type channels and then once the threshold is met L type calcium channels are opened and calcium ions rapidly diffuse into the cell causing depolarisation and creating an action potential.
7.1.4.3. 3. Then the cell becomes permeable to potassium ions which rapidly diffuse out of the cell causing repolarisation.
7.2. Ventricular Potentials
7.2.1. Graph
7.2.1.1. Ventricular Myocytes Graph
7.2.2. Steps in the action potential propagation
7.2.2.1. 0. Rapid depolarisation with fast sodium ion channels open
7.2.2.2. 1. 'Notch' is where the fast sodium ion channels close
7.2.2.3. 2. Plateau is where there is a slow inward current of calcium ions entering the cells and an outward current of potassium ions exiting
7.2.2.4. 3. Repolarisation is where the inward calcium ion current inactivates and the outward potassium current dominates
7.2.2.5. Resting membrane potential
7.2.3. Contractile properties
8. Stroke Work Regulation
8.1. Intrinsic Regulation
8.1.1. Movement along a starling curve
8.1.2. Change in filling pressure and muscle resting length
8.2. Extrinsic Regulation
8.2.1. Movement from one starling curve to another due to sympathetic stimulation
8.2.2. Increased contractility at constant filling pressure
8.2.3. Positive inotropism
8.3. What does it increase in?
8.3.1. 1. Rate of force development
8.3.2. 2. Rate of relaxation
8.3.3. 3. Maximal force developed
9. Arterial Pressure
9.1. Systolic arterial pressure
9.1.1. Peak pressure in the arteries when the left ventricle is ejecting blood during ventricle systole
9.2. Diastolic arterial pressure
9.2.1. The residual pressure in the arteries when the left ventricle is filling during ventricular diastole.
10. Important Equations
10.1. Flow = Driving force / Resistance
10.2. Cardiac output = Arterial pressure / Total peripheral resistance
10.3. Mean arterial pressure = Cardiac output x Total peripheral resistance
11. Lymphatic Regulation
11.1. What causes oedema?
11.1.1. Excess filtration
11.1.2. Defective reabsorption
11.1.3. Defective lymphatic drainage
11.2. What are the consequences of oedema?
11.2.1. Increased capillary permeability
11.2.2. Increased capillary pressure
11.2.3. Decreased plasma protein and so decreased oncotic pressure
11.2.4. Decreased lymphatic drainage
11.2.5. Volume and pressure overload
12. CO Determinants
12.1. Cardiac Factors
12.1.1. Heart Rate
12.1.2. Myocardial Contractility
12.2. Coupling Factors
12.2.1. Preload
12.2.2. Afterload
13. Preload
13.1. How to measure?
13.1.1. The central venous pressure is an indicator of the right ventricular preload
13.1.2. The left atrial pressure is an indicator of the left ventricular preload.
13.2. What are it's deteminants?
13.2.1. Circulating fluid volume/venous return
13.2.2. Venous tone
13.2.3. Myocardial compliance
13.3. What happens when it is excessive?
13.3.1. Increased atrial pressure
13.3.2. Increases venous pressure
13.3.3. Signs of congestion
14. Heart Rate
14.1. What are it's determinants?
14.1.1. Parasympathetic System
14.1.1.1. Vagus nerve
14.1.1.2. Innervates SA and AV nodes
14.1.1.3. Innervates small amount to atria
14.1.1.4. Negative chronotropic effects
14.1.1.5. Release acetylcholine which open fewer channels for sodium ions
14.1.1.5.1. Reduction in the levels of cAMP which causes potassium Ach channels to hyperpolarise and oppose the inward pacemaker current.
14.1.2. Sympathetic System
14.1.2.1. Adrenergic fibres
14.1.2.2. Innervates SA and AV nodes
14.1.2.3. Innervates atria and ventricles
14.1.2.4. Positive chronotropic effects
14.1.2.5. Release noradrenaline which opens more channels for sodium ions
14.1.2.5.1. It does this firstly by allowing the conversion of ATP into cAMP with the addition of adenyl cyclase.
14.1.2.5.2. This cAMP can then go on to protein kinase A which can do 3 main things;
14.2. How are cardiac receptors affected?
14.2.1. Beta 1 adrenergic receptors
14.2.1.1. Sympathetic stimulation
14.2.1.1.1. i. Altered voltage gating of the inward current during phase 4 by it being switched on earlier
14.2.1.1.2. ii. Phosphorylation of the slow calcium channels so they conduct more calcium
14.2.1.1.3. iii. Faster repolarisation by earlier activation of potassium currents
14.2.2. Muscarinic M2 receptors
14.2.2.1. Parasympathetic stimulation
14.2.2.1.1. Acetylcholine acts on muscarinic M2 receptors on the SA node and the AV node.
14.2.2.1.2. They are linked via a G protein to potassium ion channels
14.2.2.1.3. It is also linked via an inhibitory G protein to adenylate cyclase which inhibits cAMP formation and can therefore also be a weak negative inotrope in the atria only.
14.2.2.1.4. Presynaptic muscarinic receptors can inhibit norepinephrine release from the sympathetic nerve terminals and can therefore change the sympathetic tone and the vagal tone.
15. Myocardial Contractility
15.1. What diseases impair it?
15.1.1. Dilated cardiomyopathy (DCM)
15.1.2. Coronary vascular disease
15.1.3. Hypertrophic cardiomyopathy (HCM)
15.1.4. Pericardial effusion
15.2. How is it regulated?
15.2.1. Intracellular calcium levels
15.2.1.1. It is this calcium which makes the cardiac muscle contract as when the ions come into contact with troponin C on the actin, contraction can commence.
15.2.1.2. In order to relax, calcium must be returned to the sarcoplasmic reticulum using CaATPase and ATP. There is also some facilitated transport using a sodium/calcium exchanger also using ATP.
15.2.1.3. Cardiac muscle has graded responses in terms of the force of contraction and these depend on intracellular calcium ion concentration.
15.2.2. Positive Inotropism
15.2.2.1. Calcium
15.2.2.1.1. As calcium ion concentration increases, the force increases and this is known as positive inotropism.
15.2.2.1.2. This works by a method called excitation-contraction coupling, at high calcium ion concentration, troponin binds 4 calcium ions per molecule to produce cross-bridges. Usually troponin is not saturated and therefore, more cross-bridges can be formed if more calcium ions are made available.
15.2.2.2. Neuronal/Hormonal
15.2.2.2.1. The actions of norepinephrine and epinephrine on the heart
15.2.3. Negative Inotropism
15.2.3.1. Neuronal/Hormonal
15.2.3.1.1. Acetylcholine is a weak negative inotrope (in the atria only) as the Ach potassium channel is hyperpolarised when present and this opposes the inward pacemaker current.
15.3. Contraction force
15.3.1. How can contraction force be altered?
15.3.1.1. Alter the length-tension relationship of the heart (preload)
15.3.1.2. Change the cytosolic free calcium ion concentration
15.3.1.3. Change the sensitivity of the myocardial contractile proteins to calcium ions
15.3.2. An increase in the contractile force caused by sympathetic stimulation allows the ventricle to:
15.3.2.1. Handle a greater preload
15.3.2.2. Empty more completely
15.3.2.3. Do all this against an increased afterload
15.3.2.4. Deliver an increased stroke volume (even when increased heart rate reduces the time available for filling)
15.3.3. Other determinants
15.3.3.1. Oxygen supply
15.3.3.1.1. Contraction weakens if supply is decreased by;
15.3.3.2. Excess potassium ions
15.3.3.2.1. Hyperpolarises excitable cells
15.3.3.2.2. Weakens contraction
15.3.3.2.3. Blocks conduction system
15.3.3.2.4. Slows heart rate (heart is flaccid and dilated)
15.3.3.3. Calcium
15.3.3.3.1. Too much causes spastic contraction
15.3.3.3.2. Too little causes cardiac flaccidity
15.3.3.4. Cardiac Structure
15.3.3.4.1. There is structural adaptation to long-term alterations in volume or pressure loading of the ventricles. This is mediated by many factors:
16. Afterload
16.1. What diseases cause pressure overload?
16.1.1. Hypertension
16.1.1.1. Systemic
16.1.1.2. Pulmonary
16.1.2. Narrowing of blood outflow tract
16.1.2.1. Aortic stenosis
16.1.2.2. Pulmonic stenosis
16.2. Consequences of an increased afterload
16.2.1. Increased afterload reduces the stroke volume and increases the end diastolic pressure.
16.2.2. This graph shows how SV is affected by afterload
16.3. How is afterload rectified?
16.3.1. When there is increased resistance to flow from the left ventricle there is direct opposition to ejection.
16.3.2. To maintain stroke volume at an increased afterload the heart must contract more forcefully (increased contractility).
16.3.3. The sympathetic nervous system's influence is required to maintain the cardiac output during this time. (Inotropic effect)
17. Arteriolar Radius Regulation
17.1. Metabolic
17.1.1. In most vascular beds the rate of blood flow closely related to the metabolic activity of the tissue.
17.1.2. Oxygen is the main controlling factor as a fall in supply weakens basal tone and allows passive vasodilation.
17.1.3. The constant demand for a sustain elevated oxygen supply leads to vascular growth (angiogenesis).
17.1.4. Other requirements of tissues that must be matched include;
17.1.4.1. Adenosine
17.1.4.2. Phosphate ions
17.1.4.3. Carbon dioxide
17.1.4.4. Lactate
17.1.4.5. Osmality
17.2. Neural
17.2.1. Arteries, arterioles, veins, muscular venules and arteriovenous anastomoses are all innervated by sympathetic vasomotor fibres.
17.2.2. The dominant effect of sympathetic nerve stimulation is vasoconstriction acting through alpha-adrenoreceptors on the vascular smooth muscle cells (VSMC).
17.2.3. The heart and brain however have a weak vasoconstrictor system.
17.2.4. Beta adrenoreceptors are restricted to skeletal muscle and heart VSMC and cause vasodilation.
17.2.5. Continuous sympathetic vasoconstrictor stimulus to VSMC creates a resting sympathetic tone.
17.3. Hormonal
17.3.1. Both epinephrine and norepinephrine are released into the blood stream from the adrenal medulla when its sympathetic nerves are stimulated.
17.3.2. The overall effect is vasoconstriction.
17.3.3. The renin-angiotensin system releases the substance angiotensin II which is a powerful vasoconstrictor and causes cardiac hypertrophy.
17.3.4. Vasopressin, also know as ADH, is a vasoconstrictor too.
17.3.5. The vasodilators are:
17.3.5.1. Bradykinin
17.3.5.2. Histamine
17.3.5.3. Prostaglandins
18. Vasculature Regulation
18.1. Central Control
18.1.1. Responsible for the vascular requirements of the whole animal
18.1.2. It is dependent on the cardiovascular centre
18.1.3. It acts indirectly on the VSMC of muscular arteries and arterioles through baroreceptors and chemoreceptor reflex arcs
18.2. Peripheral Control
18.2.1. Fine tuning of local vascular beds in particular organs to meet their individual requirements
18.2.2. It works directly on the VSMC through metabolic and mechanical stimuli
18.2.3. Works indirectly on VSMC via the endothelial cells and again through the metabolic and mechanical stimuli.