Pathophysiology of the Heart and Circulatory System
Thursday 30 May 2024, 15:30-17:45
LECTURE 1
CIRCULATION AND CARDIAC ENERGETICS
Learning objectives:
- Significance of the arrangement of the cardiovascular system
- Energetics in the healthy heart
- How myocardial inefficiency contributes to heart failure
- How to study myocardial energetics
Functions of the cardiovascular system
- Transport of oxygen (from the lungs to the body tissues, haemoglobin binds oxygen)
- Removal of waste products (to the lungs for exhalation, to the kidneys for excretion)
Cardiovascular system (PO2, mmHg) Systolic and diastolic pressures (mmHg)
Arrangement of the cardiovascular system
- A series of two pumps (left and right side of the heart)
- Cardiac output of both sides of the heart do closely
match
- Parallel arrangement for most major organs
• Major organs are arranges in parallel circuits, which
allows the body to direct blood flow where it is most
needed without compromising flow to other organs
• Example: during exercise, blood flow is increased
to muscles without reducing supply to vital organs
like the brain
,Sarcomeres
The smallest contractile units in muscle fibres. They contain actin and myosin, essential for
muscle contraction. Oxygen is critical because it is used to produce ATP. During aerobic
respiration, oxygen helps convert nutrients into ATP in the mitochondria. ATP is then used
by the sarcomeres to power muscle contractions.
Muscle contraction Muscle relaxation
Muscle contraction and relaxation
- Contraction: ATP binds to myosin heads, causing them to detach from actin. The
hydrolysis of ATP to ADP + Pi provides the energy needed for the myosin heads to
change position and reattach to a new position on the actin filament, pulling it and
causing contraction
- Relaxation: After the nerve impulse ends, Ca2+ is actively transported back into the SR
by Ca2+ pumps. As Ca2+ levels in the cytoplasm drop, Ca2+ dissociates from troponin,
causing tropomyosin to cover the binding sites on actin again. This prevents myosin
from binding to actin, resulting in muscle relaxation
Cardiopulmonary exercise test
The CPET is a diagnostic tool that measures how well the cardiovascular and respiratory
systems work together to deliver oxygen to the muscles and remove carbon dioxide from
the body. Key parameters measured during CPET are VO2 (oxygen uptake/consumption),
VCO2 (carbon dioxide output/production), VE (ventilation), and HR (heart rate)
Symmorphosis
Hypothesis suggesting that biological systems are designed to meet the maximum demand
placed on them without excess capacity. In the context of CPET and the cardiovascular
system, symmorphosis implies that the heart, lungs, and muscles are optimised to function
efficiently under peak exercise conditions.
, CARDIAC ENERGETICS
Where does the heart need energy for?
- Contraction and relaxation (of the myocardium)
- Maintenance of ion gradients (essential for electrical activity and contraction)
- Protein synthesis and repair (to maintain the heart muscle and its function)
PV-loops
Pressure-volume loops represent the changes in
pressure and volume in the left ventricle during a
cardiac cycle. They are useful for understanding
the work done by the heart.
The cardiac cycle
- Sequence of events in one heartbeat
- Systole = contraction
- Diastole = relaxation
Phases of the cardiac cycle:
1. Atrial kick (100ms)
• Contraction of the atria
• Contributes to the final ventricular volume
2. Isovolumetric contraction
• Ventricles contract
• No volume changes; all valves are closed
3. Ejection (270ms)
• Pressure in the ventricles exceeds the pressure in the arteries
• This opens the semilunar valves; blood is ejected into the aorta and a. pulmonaris
4. Isovolumetric relaxation
• Ventricles relax
• No volume changes; all valves are closed
• This causes a rapid decrease in pressure
5. Passive filling
• During the diastole
• Ventricles fill with blood from the atria
• Atrioventricular valves (AV) are open
, Frank-Starling mechanism
The Frank-Starling law of the heart describes how the heart’s stroke volume increases in
response to an increase in the volume of blood filling the heart (end-diastolic volume). This
relationship is crucial for the heart to match its output to the venous return. Key points:
- Length-tension relationship
• Myocardial fibres are stretched by a greater volume of blood = forceful contraction
• Initial length of the cardiac muscle fibres is determined by the EDV
• A higher end-diastolic volume leads to a greater stretch of the fibres
- Stroke volume increase
• A larger force is generated during contraction
• Stroke volume is increased
- Homeostatic mechanism
• Allows the heart to automatically adjust its output to match venous return
• Without relying on external signals
- Clinical implications
• Normal conditions: Ensures efficient pumping of blood
• Pathological conditions: Inadequate cardiac output
In practice
- Increased venous return more blood returns to the heart, increasing EDV
- Fiber stretch increased EDV stretches the myocardial fibres
- Increased contraction force stretches fibres contract more forcefully
- Increased stroke volume stronger contraction results in more ejection
Frank-Starling curves: Show that as EDV increases, stroke volume also increases until a
plateau is reached. Beyond this point, excessive stretching can lead to decreased efficiency.
Thursday 30 May 2024, 15:30-17:45
LECTURE 1
CIRCULATION AND CARDIAC ENERGETICS
Learning objectives:
- Significance of the arrangement of the cardiovascular system
- Energetics in the healthy heart
- How myocardial inefficiency contributes to heart failure
- How to study myocardial energetics
Functions of the cardiovascular system
- Transport of oxygen (from the lungs to the body tissues, haemoglobin binds oxygen)
- Removal of waste products (to the lungs for exhalation, to the kidneys for excretion)
Cardiovascular system (PO2, mmHg) Systolic and diastolic pressures (mmHg)
Arrangement of the cardiovascular system
- A series of two pumps (left and right side of the heart)
- Cardiac output of both sides of the heart do closely
match
- Parallel arrangement for most major organs
• Major organs are arranges in parallel circuits, which
allows the body to direct blood flow where it is most
needed without compromising flow to other organs
• Example: during exercise, blood flow is increased
to muscles without reducing supply to vital organs
like the brain
,Sarcomeres
The smallest contractile units in muscle fibres. They contain actin and myosin, essential for
muscle contraction. Oxygen is critical because it is used to produce ATP. During aerobic
respiration, oxygen helps convert nutrients into ATP in the mitochondria. ATP is then used
by the sarcomeres to power muscle contractions.
Muscle contraction Muscle relaxation
Muscle contraction and relaxation
- Contraction: ATP binds to myosin heads, causing them to detach from actin. The
hydrolysis of ATP to ADP + Pi provides the energy needed for the myosin heads to
change position and reattach to a new position on the actin filament, pulling it and
causing contraction
- Relaxation: After the nerve impulse ends, Ca2+ is actively transported back into the SR
by Ca2+ pumps. As Ca2+ levels in the cytoplasm drop, Ca2+ dissociates from troponin,
causing tropomyosin to cover the binding sites on actin again. This prevents myosin
from binding to actin, resulting in muscle relaxation
Cardiopulmonary exercise test
The CPET is a diagnostic tool that measures how well the cardiovascular and respiratory
systems work together to deliver oxygen to the muscles and remove carbon dioxide from
the body. Key parameters measured during CPET are VO2 (oxygen uptake/consumption),
VCO2 (carbon dioxide output/production), VE (ventilation), and HR (heart rate)
Symmorphosis
Hypothesis suggesting that biological systems are designed to meet the maximum demand
placed on them without excess capacity. In the context of CPET and the cardiovascular
system, symmorphosis implies that the heart, lungs, and muscles are optimised to function
efficiently under peak exercise conditions.
, CARDIAC ENERGETICS
Where does the heart need energy for?
- Contraction and relaxation (of the myocardium)
- Maintenance of ion gradients (essential for electrical activity and contraction)
- Protein synthesis and repair (to maintain the heart muscle and its function)
PV-loops
Pressure-volume loops represent the changes in
pressure and volume in the left ventricle during a
cardiac cycle. They are useful for understanding
the work done by the heart.
The cardiac cycle
- Sequence of events in one heartbeat
- Systole = contraction
- Diastole = relaxation
Phases of the cardiac cycle:
1. Atrial kick (100ms)
• Contraction of the atria
• Contributes to the final ventricular volume
2. Isovolumetric contraction
• Ventricles contract
• No volume changes; all valves are closed
3. Ejection (270ms)
• Pressure in the ventricles exceeds the pressure in the arteries
• This opens the semilunar valves; blood is ejected into the aorta and a. pulmonaris
4. Isovolumetric relaxation
• Ventricles relax
• No volume changes; all valves are closed
• This causes a rapid decrease in pressure
5. Passive filling
• During the diastole
• Ventricles fill with blood from the atria
• Atrioventricular valves (AV) are open
, Frank-Starling mechanism
The Frank-Starling law of the heart describes how the heart’s stroke volume increases in
response to an increase in the volume of blood filling the heart (end-diastolic volume). This
relationship is crucial for the heart to match its output to the venous return. Key points:
- Length-tension relationship
• Myocardial fibres are stretched by a greater volume of blood = forceful contraction
• Initial length of the cardiac muscle fibres is determined by the EDV
• A higher end-diastolic volume leads to a greater stretch of the fibres
- Stroke volume increase
• A larger force is generated during contraction
• Stroke volume is increased
- Homeostatic mechanism
• Allows the heart to automatically adjust its output to match venous return
• Without relying on external signals
- Clinical implications
• Normal conditions: Ensures efficient pumping of blood
• Pathological conditions: Inadequate cardiac output
In practice
- Increased venous return more blood returns to the heart, increasing EDV
- Fiber stretch increased EDV stretches the myocardial fibres
- Increased contraction force stretches fibres contract more forcefully
- Increased stroke volume stronger contraction results in more ejection
Frank-Starling curves: Show that as EDV increases, stroke volume also increases until a
plateau is reached. Beyond this point, excessive stretching can lead to decreased efficiency.
