Hoorcollege 1:
The cardiovascular system is made up of the heart and the blood vessels. Together, they
ensure that all organs and tissues of the body receive the oxygen and nutrients they need,
while also removing waste products like carbon dioxide.
The heart has two essential pumping functions:
1. It pumps deoxygenated blood (zuurstofarm bloed) to the lungs. In the lungs, carbon
dioxide is exchanged for oxygen.
2. It pumps oxygenated blood (zuurstofrijk bloed) to the rest of the body through the
arteries, providing oxygen and nutrients to all organs and tissues.
Together with the blood vessels, the heart ensures adequate perfusion (voldoende
doorbloeding). If this perfusion is too low, organs cannot function properly and this can be
life-threatening.
The amount of blood the heart pumps per minute is called the cardiac output
(hartminuutvolume). This depends on two things:
1. Contraction of the muscle (samentrekken).
2. Relaxation of the muscle (ontspannen).
For the heart to work effectively, 2-3 billions of cardiomyocytes (CMs) (heart muscle cells)
must contract and relax in a perfectly coordinated way. If there is a discordance (wanorde,
niet gecoördineerd) between contractions, blood flow becomes chaotic and the person may
develop dangerous arrhythmias (hartritmestoornissen).
Excitation–contraction coupling
This means: how an electrical signal (excitation) in cardiomyocytes (heart muscle cells)
leads to a mechanical contraction (samentrekking) of the heart.
→ In short: electrical signal → action potential → calcium entry → contraction.
Automation of the heart: The heart can beat independent of hormonal of neuronal input
Spontaneous activity
- Spontaneous active: means that certain heart cells automatically depolarise (they
gradually let ions leak until they reach the threshold).
→ This makes them “self-firing” – they don’t need an external trigger like nerve
stimulation.
- Pacemaker cells: These special cells are called pacemaker cells (pacemakercellen).
→ The most important pacemaker is located in the sinoatrial node (SA node /
sinusknoop) in the right atrium.
→ These cells set the rhythm for the whole heart. Once they fire, the signal spreads
through the atria and ventricles, making the entire heart contract in a coordinated
way.
,The conduction system ensures the heart beats in the correct sequence:
1. SA node starts the impulse → atria contract.
2. AV node delays the signal → ventricles can fill.
3. AV bundle, bundle branches, and Purkinje fibers rapidly spread the
signal → ventricles contract from bottom up.
Pacemaker cells: special heart cells in the sinoatrial (SA) node that can
spontaneously generate action potentials. They set the rhythm of the
heartbeat.
The graph shows the membrane potential (membraanpotentiaal) of SA node cells over time.
Unlike normal heart muscle cells, pacemaker cells do not have a stable resting potential.
→ Instead, their voltage slowly drifts upward until it reaches a threshold (drempelwaarde).
→ Once the threshold is reached, an action potential is triggered automatically.
→ Normal ventricular heart muscle cells They have a stable resting potential (stabiel
rustpotentiaal) around –90 mV.
→ They have an unstable resting potential (instabiel rustpotentiaal).
→ Instead of staying at –90 mV, their voltage slowly creeps upward during Phase 4
→ Why? Because of special ion channels:
● Sodium (Na⁺) leaks in continuously (via funny channels, If).
● This makes the inside of the cell more positive over time.
Phase 4: Prepotential (spontaneous depolarisation):
→ Sodium (Na⁺) ions slowly leak into the cell through special “funny channels” (If).
→ This makes the inside of the cell gradually more positive.
→ This slow rise in voltage is why the SA node spontaneously reaches threshold.
Phase 0 – Depolarisation
→ When threshold is reached (around –40 mV), calcium channels open.
→ Calcium (Ca²⁺) rushes into the cell → this creates the steep rise of the action potential.
→ In pacemaker cells, calcium (not sodium) is the main driver of depolarisation.
Phase 3 – Repolarisation
→ Potassium (K⁺) channels open, allowing K⁺ to flow out.
→ This makes the inside of the cell more negative again, returning the potential to around
–60 mV.
→ Then the cycle restarts with Phase 4.
,this is the action potential of a ventricular muscle cell. It looks similar to the slide on
pacemaker cells, but here you see why ventricular cells have a stable resting potential
and how their action potential is different
→ Ventricular cells start at –90 mV, which is very stable.
→ They stay at this resting potential until they are stimulated by an impulse coming from
pacemaker cells.
→ This is different from pacemaker cells, which don’t stay flat but slowly drift upward.
3 Phases of the action potential:
1.Rapid depolarisation (snelle depolarisatie)
→ Trigger: a signal arrives.
→ Sodium (Na⁺) channels open → Na⁺ rushes inside the cell.
→ Voltage shoots up to about +30 mV.
2.Plateau phase (plateaufase)
→ Unique to cardiac muscle!
→ Calcium (Ca²⁺) channels open slowly and calcium enters.
→ At the same time, potassium (K⁺) leaves, balancing the charge.
→ Result: the voltage stays relatively flat (the “plateau”).
→ This is crucial because calcium entry triggers contraction of the muscle.
3. Repolarisation (repolarisatie)
→ Calcium channels close.
→ Potassium (K⁺) leaves the cell.
→ Voltage drops back down to –90 mV.
→ The cell is ready for the next impulse..
Refractory periods (rechts aangegeven)
● Absolute refractory period (ARP, absolute refractaire periode):
→ The cell cannot be stimulated again (no new action potential possible).
→ This protects the heart from tetanus (constant contraction).
● Relative refractory period (RRP, relatieve refractaire periode):
→ The cell can respond, but only to a very strong stimulus.
● Supranormal period (SP, supranormale periode):
→ The cell is extra sensitive, even a weaker stimulus could trigger an action potential.
Formula: CO = SV × F
→ CO (Cardiac Output, hartminuutvolume) = the total amount of blood pumped by the heart
per minute.
→ SV (Stroke Volume, slagvolume) = how much blood the heart pumps per beat.
→ F (Frequency / HR, hartslagfrequentie) = how many times the heart beats per minute.
, → So: Cardiac Output = Stroke Volume × Heart Rate
Example: at rest
Stroke volume (SV) ≈ 80 ml/beat.
Heart rate ≈ 63 beats/min.
Cardiac output (CO) ≈ 5 L/min.
→ That’s enough to supply oxygen and nutrients to the body when sitting calmly.
Example: during heavy exercise (untrained person)
→ Stroke volume increases to about 100 ml/beat (the heart pumps more strongly).
→ Heart rate increases to about 180 beats/min.
→ Cardiac output = 18 L/min (more than 3× the resting value).
→ So during exercise, the heart massively increases its output to meet the muscles’ oxygen
demand.
1. Parasympathetic system (left side)
→ Controlled by the vagus nerves (nervus vagus).
→ Neurotransmitter: Acetylcholine (ACh).
→ Binds to muscarinic (M) receptors in the atria (mainly the SA
node and AV node).
Effect:
→ Slows the heart rate (negative chronotropy).
→ Has little to no direct effect on ventricular contraction strength.
2. Sympathetic system (right side)
→ Controlled by thoracic spinal nerves.
→ Neurotransmitter: Norepinephrine (noradrenaline) released directly from nerve endings.
→ Hormone: Epinephrine (adrenaline) can also be released into the bloodstream by the
adrenal glands.
→ These chemicals bind to beta (β) receptors in both atria and ventricles.
Effect:
→ Increases heart rate (positive chronotropy).
→ Increases contraction strength (positive inotropy).
Graph (left side: membrane potential over time)
→ The wavy line shows the pacemaker potential of SA node cells.
→ Under sympathetic stimulation, the slope of the rising phase (depolarisation) becomes
steeper.
→ This means the cells reach threshold (drempelwaarde) faster.
→ Result: more frequent action potentials → higher heart rate.
→ So: sympathetic stimulation makes the pacemaker “tick faster.”
The cardiovascular system is made up of the heart and the blood vessels. Together, they
ensure that all organs and tissues of the body receive the oxygen and nutrients they need,
while also removing waste products like carbon dioxide.
The heart has two essential pumping functions:
1. It pumps deoxygenated blood (zuurstofarm bloed) to the lungs. In the lungs, carbon
dioxide is exchanged for oxygen.
2. It pumps oxygenated blood (zuurstofrijk bloed) to the rest of the body through the
arteries, providing oxygen and nutrients to all organs and tissues.
Together with the blood vessels, the heart ensures adequate perfusion (voldoende
doorbloeding). If this perfusion is too low, organs cannot function properly and this can be
life-threatening.
The amount of blood the heart pumps per minute is called the cardiac output
(hartminuutvolume). This depends on two things:
1. Contraction of the muscle (samentrekken).
2. Relaxation of the muscle (ontspannen).
For the heart to work effectively, 2-3 billions of cardiomyocytes (CMs) (heart muscle cells)
must contract and relax in a perfectly coordinated way. If there is a discordance (wanorde,
niet gecoördineerd) between contractions, blood flow becomes chaotic and the person may
develop dangerous arrhythmias (hartritmestoornissen).
Excitation–contraction coupling
This means: how an electrical signal (excitation) in cardiomyocytes (heart muscle cells)
leads to a mechanical contraction (samentrekking) of the heart.
→ In short: electrical signal → action potential → calcium entry → contraction.
Automation of the heart: The heart can beat independent of hormonal of neuronal input
Spontaneous activity
- Spontaneous active: means that certain heart cells automatically depolarise (they
gradually let ions leak until they reach the threshold).
→ This makes them “self-firing” – they don’t need an external trigger like nerve
stimulation.
- Pacemaker cells: These special cells are called pacemaker cells (pacemakercellen).
→ The most important pacemaker is located in the sinoatrial node (SA node /
sinusknoop) in the right atrium.
→ These cells set the rhythm for the whole heart. Once they fire, the signal spreads
through the atria and ventricles, making the entire heart contract in a coordinated
way.
,The conduction system ensures the heart beats in the correct sequence:
1. SA node starts the impulse → atria contract.
2. AV node delays the signal → ventricles can fill.
3. AV bundle, bundle branches, and Purkinje fibers rapidly spread the
signal → ventricles contract from bottom up.
Pacemaker cells: special heart cells in the sinoatrial (SA) node that can
spontaneously generate action potentials. They set the rhythm of the
heartbeat.
The graph shows the membrane potential (membraanpotentiaal) of SA node cells over time.
Unlike normal heart muscle cells, pacemaker cells do not have a stable resting potential.
→ Instead, their voltage slowly drifts upward until it reaches a threshold (drempelwaarde).
→ Once the threshold is reached, an action potential is triggered automatically.
→ Normal ventricular heart muscle cells They have a stable resting potential (stabiel
rustpotentiaal) around –90 mV.
→ They have an unstable resting potential (instabiel rustpotentiaal).
→ Instead of staying at –90 mV, their voltage slowly creeps upward during Phase 4
→ Why? Because of special ion channels:
● Sodium (Na⁺) leaks in continuously (via funny channels, If).
● This makes the inside of the cell more positive over time.
Phase 4: Prepotential (spontaneous depolarisation):
→ Sodium (Na⁺) ions slowly leak into the cell through special “funny channels” (If).
→ This makes the inside of the cell gradually more positive.
→ This slow rise in voltage is why the SA node spontaneously reaches threshold.
Phase 0 – Depolarisation
→ When threshold is reached (around –40 mV), calcium channels open.
→ Calcium (Ca²⁺) rushes into the cell → this creates the steep rise of the action potential.
→ In pacemaker cells, calcium (not sodium) is the main driver of depolarisation.
Phase 3 – Repolarisation
→ Potassium (K⁺) channels open, allowing K⁺ to flow out.
→ This makes the inside of the cell more negative again, returning the potential to around
–60 mV.
→ Then the cycle restarts with Phase 4.
,this is the action potential of a ventricular muscle cell. It looks similar to the slide on
pacemaker cells, but here you see why ventricular cells have a stable resting potential
and how their action potential is different
→ Ventricular cells start at –90 mV, which is very stable.
→ They stay at this resting potential until they are stimulated by an impulse coming from
pacemaker cells.
→ This is different from pacemaker cells, which don’t stay flat but slowly drift upward.
3 Phases of the action potential:
1.Rapid depolarisation (snelle depolarisatie)
→ Trigger: a signal arrives.
→ Sodium (Na⁺) channels open → Na⁺ rushes inside the cell.
→ Voltage shoots up to about +30 mV.
2.Plateau phase (plateaufase)
→ Unique to cardiac muscle!
→ Calcium (Ca²⁺) channels open slowly and calcium enters.
→ At the same time, potassium (K⁺) leaves, balancing the charge.
→ Result: the voltage stays relatively flat (the “plateau”).
→ This is crucial because calcium entry triggers contraction of the muscle.
3. Repolarisation (repolarisatie)
→ Calcium channels close.
→ Potassium (K⁺) leaves the cell.
→ Voltage drops back down to –90 mV.
→ The cell is ready for the next impulse..
Refractory periods (rechts aangegeven)
● Absolute refractory period (ARP, absolute refractaire periode):
→ The cell cannot be stimulated again (no new action potential possible).
→ This protects the heart from tetanus (constant contraction).
● Relative refractory period (RRP, relatieve refractaire periode):
→ The cell can respond, but only to a very strong stimulus.
● Supranormal period (SP, supranormale periode):
→ The cell is extra sensitive, even a weaker stimulus could trigger an action potential.
Formula: CO = SV × F
→ CO (Cardiac Output, hartminuutvolume) = the total amount of blood pumped by the heart
per minute.
→ SV (Stroke Volume, slagvolume) = how much blood the heart pumps per beat.
→ F (Frequency / HR, hartslagfrequentie) = how many times the heart beats per minute.
, → So: Cardiac Output = Stroke Volume × Heart Rate
Example: at rest
Stroke volume (SV) ≈ 80 ml/beat.
Heart rate ≈ 63 beats/min.
Cardiac output (CO) ≈ 5 L/min.
→ That’s enough to supply oxygen and nutrients to the body when sitting calmly.
Example: during heavy exercise (untrained person)
→ Stroke volume increases to about 100 ml/beat (the heart pumps more strongly).
→ Heart rate increases to about 180 beats/min.
→ Cardiac output = 18 L/min (more than 3× the resting value).
→ So during exercise, the heart massively increases its output to meet the muscles’ oxygen
demand.
1. Parasympathetic system (left side)
→ Controlled by the vagus nerves (nervus vagus).
→ Neurotransmitter: Acetylcholine (ACh).
→ Binds to muscarinic (M) receptors in the atria (mainly the SA
node and AV node).
Effect:
→ Slows the heart rate (negative chronotropy).
→ Has little to no direct effect on ventricular contraction strength.
2. Sympathetic system (right side)
→ Controlled by thoracic spinal nerves.
→ Neurotransmitter: Norepinephrine (noradrenaline) released directly from nerve endings.
→ Hormone: Epinephrine (adrenaline) can also be released into the bloodstream by the
adrenal glands.
→ These chemicals bind to beta (β) receptors in both atria and ventricles.
Effect:
→ Increases heart rate (positive chronotropy).
→ Increases contraction strength (positive inotropy).
Graph (left side: membrane potential over time)
→ The wavy line shows the pacemaker potential of SA node cells.
→ Under sympathetic stimulation, the slope of the rising phase (depolarisation) becomes
steeper.
→ This means the cells reach threshold (drempelwaarde) faster.
→ Result: more frequent action potentials → higher heart rate.
→ So: sympathetic stimulation makes the pacemaker “tick faster.”
