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Samenvatting Pathophysiology of Heart and Circulatory System
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Voorbeeld van de inhoud
CARDIAC ENERGETICSArrangement of the cardiovascular system
The arrangement of the cardiovascular system is regulated in series. There are 2 pumps, one on the left
and one on the right side of the heart. The left side of the heart pumps to the systemic circulation and
the right side to the pulmonary circulation. Most major organs lie in parallel. This enables adaptation to
specific needs in blood flow, without affecting the blood flow in other organs. The flow of oxygen can be
described with 4 equations:
The ventilation
o VO2 = BF x Vt (FIO2 – FEO2)
O2 diffusion in the lungs
o VO2 = DLO2 (PO2,alveoli – PO2,lung capillaries)
Cardiac function
o VO2 = p x SV (CaO2 – CvO2)
O2 diffusion in muscle
o VO2 = DMO2 (PO2,capillaries – PO2,mitochondria)
Oxygen is needed to fuel the sarcomeres. This is the smallest contractile unit in muscles and require ATP
to contract. At rest, tropomyosin prevents myosin to interact with actin. Ca2+ is released from the ER
(passive) and binds to tropomyosin. This is removed, so actin and myosin can bind. Ca 2+ is actively
pumped back (lots of ATP needed). The detachment of actin and myosin also requires ATP. The primary
energy source are mitochondria.
Cardiac energetics
Blood flow through the heart: Anatomy of the heart:
Body organs
Inferior or superior vena cava
Right atrium
Tricuspid valve
Right ventricle
Pulmonary arteries
Lungs
Pulmonary veins
Left atrium
Mitral (bicuspid) valve
Left ventricle
Aortic valve
The cardiac cycles consists of 7 phases. Phase 1 is the atrial systole. The AV valves are open and the
aortic and pulmonary valves are closed. This is the atrial kick. Phase 2 is isovolumetric contraction in
which all valves are closed. Isovolumetric contraction is the rapid increase in intraventricular pressure
(myocyte contraction). This abrupt increase in pressure causes the AV valves to close. There is no change
in ventricular volume between the closure of the AV valves and the opening of the aortic and pulmonary
valves. Phase 3 is rapid ejection. The aortic and pulmonary valves are open, while the AV valves are
closed. Phase 4 is reduced ejection. The aortic and pulmonary valves are open and the AV valves are still
closed (ventricular repolarization). Phase 5 is isovolumetric relaxation. Now, all valves are closed, so the
end-systolic volume remains in the ventricle. Phase 6 is rapid filling, when the ventricular pressures fall
below the atrial pressures. Then, the AV valves open, but the aortic and pulmonary valves stay closed.
Phase 7 is reduced filling, where the AV valves are open and the aortic and pulmonary valves are closed.
, Pressure-volume loops (PV-loops) can be used to asses the cardiac function.
In this loop, the LV pressure is plotted against the LV volume at many time
points during the cardiac cycle:
a. Ventricular filling
b. Isovolumetric contraction
c. Ventricular ejection
d. Isovolumetric relaxation
When a muscle operates at a longer length, it can generate more force. This phenomenon is known as
the Frank-starling mechanism. An increased venous return leads to more blood being expelled. So, an
increased venous return increases the EDV (end-diastolic volume), which increases the stroke volume. At
the cellular level, there is an higher affinity of calcium to troponin C. Actin and myosin are brought closer
together when stretched. So, when the venous return is increased, this can generate more force.
The preload is the initial stretching of the cardiac myocytes prior to contraction. When the preload
increases, the end-diastolic volume
increases. The afterload is the load against
which the heart must contract to eject
blood. When the afterload is increased,
there will be an increased pressure. This is
caused by an increase end-systolic volume
and a decrease in stroke volume.
Energy for the pump
1.34 W is the work that the heart generates at rest. The amount of metabolic work (oxygen uptake by
cardiac muscle) that is needed to generate this is 5.3 W, so there is a low efficiency of 25%. The
myocardial efficiency is the internal work divided by the metabolic work. So, there is more energy
needed to get a typical amount of work done. Therefore, in healthy hearts, 75% of the generated
metabolic energy will be converted to heat. In heart failure, there is less than 10% myocardial efficiency,
due to mitochondrial dysfunction.
When the mitochondrial efficiency is at 100%, the ATP/O2 ratio is 6.3. At 80% efficiency, this ratio is
about 5. In severe heart failure, the ATP/O2 ratio can drop to 2. When this happens, there is way less ATP
generated per O2 molecule.
During mitochondrial dysfunction in heart failure, there is less ATP to fuel
the sarcomeres and SERCA pump, leading to cardiac output decrease.
The compensation mechanisms do not work in the long run. O2 is more
often not fully reduced to H2O, which leads to the overproduction of ROS,
such as H2O2 and superoxide in the muscle. These ROS cause
mitochondrial and cellular damage. This damage decreases the myocardial efficiency, which in turn leads
to less ATP (loop). There are multiple ways to explore whether myocardial inefficiencies contribute to
heart failure:
In vivo techniques Within the living
o Metabolic treadmill/bike
Running/cycling performance
VO2 and CO2 measured
Respiratory exchange ratio (CO2/VO2)
RER 0.7 main fuel is fatty acids
RER > 1.0 main fuel is glucose
o PET/MRI
PET = MVO2
MRI = cardiac work
Also in skeletal muscles, assess both muscle types
In vitro techniques In controlled environment (e.g. test tubes)
o Oroboros respirometry
o ATPase activity and tension cost
, Tension cost and ATP usage during force generation
ARRHYTHMIAS
Calcium enters in phase 2 of the action potential (phase 1 is
the sodium influx). This leads to the secondary calcium release
from the SR. This is referred to as CICR, which is the calcium
induced calcium release. So, calcium is important for action
potential and contraction. This calcium binds to myofilaments,
which causes a power stroke (cell shortening/force
development). Afterwards, there is calcium reuptake by the SR
and calcium is release from the myofilaments, which causes
relaxation.
Electrocardiography (ECG)
The heartbeat is generated in the sinus node. From there, it spreads to the atria, the AV-node and via
bundle branches to all cardiomyocytes. The sinus rhythm is the normal healthy rhythm that originates in
the sinus node. When in sinus rhythm, there is a P-wave in the ECG (if not, there is no sinus rhythm).
Every P-wave is followed by a QRS-complex (spread from atria to ventricle). Similarly, every QRS-complex
is preceded by a P-wave. There should be equal distances between heartbeats (PQ-interval same
between each heartbeat). Different parts of an ECG:
P-wave Spread of the depolarization wave through the atria
PR-interval Conduction through AV-node
QRS Spread of the depolarization wave through the ventricles
T-wave Repolarization of the ventricles
Arrhythmias are either caused by disturbances within the cell or by other causes (e.g. cell death and
fibrosis). The assessment of an ECG happens in 7 steps:
1. Rhythm
2. Frequency
3. Conduction times
4. Heart axis
5. P-wave
6. QRS-complex
7. ST-morphology
For rhythm, this can be regular (bradycardia < 60, tachycardia > 110) or irregular (atrium fibrillation).
Atrial fibrillation is a common pathophysiology and gives an increased risk on a stroke. It is a chaotic
depolarising atrium (damaged) and the conduction through the AV-node is not regular, so there will be
an irregular RR-interval (time between 2 QRS-complexes). In this case, there is no P-wave on the ECG
(spread through atria). It gives a risk on stroke, because the atria are not contracting sufficiently and this
causes stasis of the blood in the atria. These people receive blood thinners to decrease the risk of stroke
and they shock the heart to get the heart back into normal rhythm. It is very common, 10% over 65 and
20% over 75 have atrial fibrillation.
The refractory period is the period in which cells cannot be stimulated again. This is essential for the
contraction and relaxation of cardiomyocytes. Because of this, the signal spreads in a specific direction
and not back and forth.
Ventricular fibrillation
When there is ventricular fibrillation, the ventricles are not able to pump blood to the body. This causes
the person to collapse, because the brain doesn’t receive oxygen and nutrients. A specific form of
ventricle fibrillation is commotio cordis. This happens when an object strikes the chest right above the
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