Physiology of the Heart

Haematopoiesis

• A totipotent stem cell is one that can divide to produce all cell types of an organism.
• The correct order of haematopoiesis is: self-renewal, developmental pathway, committed cells, differentiated functional cell.
• Red blood cells:
  • Have a biconcave shape
  • Are approximately 7 μm in diameter
  • Do not have a nucleus
  • Respire anaerobically
  • Are removed by the liver and spleen
• Site of haematopoiesis:
  • In a fetus, it occurs in the liver throughout intrauterine life
  • In an adult, it occurs in the bone marrow

Erythrocytes

• Normoblasts have a diameter of 6-8 μm
• Eosinophils:
  • Have a lifespan of several days
  • Leave circulation within 2-6 hours of release from bone marrow
• Platelets have a diameter of 1-2 μm

Anaemia

• Causes of anaemia:
  • Impaired production
  • Increased destruction (haemolytic)
  • Blood loss
• Folic acid treats megaloblastic anaemia
• Vitamin B12 deficiency causes anaemia, but folic acid does not treat it

Blood Groups and Transfusions

• Blood groups:
  • A and B antigens on cells, corresponding antibodies in plasma
  • AB blood type can receive A, B, AB, and O blood types
• Complications of blood transfusions:
  • Blood type incompatibility
  • Transmission of infection
  • Fever
  • Impaired clotting
• Rh sensitisation:
  • Occurs when an Rh- individual is exposed to Rh+ blood
  • Can lead to haemolytic disease in subsequent pregnancies

Cardiac Cycle

• Heart rate decrease with increasing heart size due to ventricular conduction taking longer to propagate
• Cardiac output is essentially proportional to body size
• Stroke volume decreases at very high heart rates due to less time for ventricular filling
• High heart rate is associated with poor prognosis in patients with cardiovascular disease

Initiation of the Heartbeat

• Hermann Stannius used frog hearts to demonstrate that the primary pacemaker in the frog heart was the sinus venosus, but when that is isolated, the atria contains a secondary slower pacemaker.
• The sinoatrial node is located in the right atrium and has the fastest intrinsic rate
• Features of a P cell include:
  • Poorly differentiated
  • Few mitochondria
  • Numerous membrane invaginations called caveolae
  • Large cell size

Control of Cardiac Output

• The funny current (a key player of the membrane clock theory) is considered unusual because it is an inward current activated when the membrane potential repolarises

• cAMP increases the effect of the funny current, and sympathetic stimulation increases heart rate

• Ivabradine is the only specific bradycardiac agent licensed for clinical use### Cardiac Conduction and ECG

• Bundle Branch Block: a delayed wave of excitation in the ventricle, suggesting an issue with conduction down the His Bundle.

• Ischaemia: the ventricle is not firing off potentials as it should, causing a change in the PR interval.

• Genetic mutation: a change in the action potential duration and hence the PR interval, due to a mutation in ion channels.

• Myocardial infarction: a reduced action potential in the ventricles, affecting contraction.

Pacemakers and Heart Rate

• Hierarchy of pacemakers: sinus node, atrioventricular node, His bundle, Purkinje fibres.
• Digoxin: a drug that slows down heart rate.

ECG and Cardiac Cycle

• Q wave: represents depolarisation of the ventricular walls.
• Atrial depolarisation: represented by the P wave on an ECG.
• Ejection fraction: the percentage of blood pumped out of the ventricle with each contraction.

Cardiac Cycle

• Sequence of events for stage 1 of systole: left atrial pressure > left ventricular pressure, pulmonary valve opens, and blood flows into the left ventricle.
• Pressure-Volume loop: shows the pressure and volume changes that occur in a single cardiac cycle.

Venous Pulse and Pressure

• Components of the venous pulse: A wave, C wave, V wave, X wave, Y wave.
• C wave: caused by the transmitted carotid pulse.
• X wave: related to atrial relaxation.
• A wave: right atrial contraction.
• V wave: corresponds to venous filling when the tricuspid valve is open.
• Hydrostatic pressure: relative to heart level, and higher in the foot when standing.

Heart Sounds and Murmurs

• "Lub" heart sound: associated with the closure of the atrioventricular valves.
• "Dup" heart sound: due to the closure of the semilunar valves.
• Gallop rhythm: when systolic pressure is raised and S2 and S3 can be heard as a gallop.
• Heart murmurs: due to turbulence in the blood and caused by valve stenosis or regurgitation.

Control of Cardiac Output

• Factors that affect cardiac output: preload, afterload, contractility, and heart rate.
• Preload: the degree of stretch of a ventricle immediately before it contracts at the end of diastole.
• Afterload: the force against which a ventricle pumps to eject blood.
• Frank-Starling Law: the total energy liberated at each heartbeat is determined by the diastolic volume of the heart and therefore by the muscle fibre length at the beginning of contraction.

Troponin and Calcium Sensitivity

• Components of troponin: TnC, TnT, and TnI.
• Length-dependent activation: occurs in cardiac muscle only, and is contributed to by separation of myofilaments.
• Calcium sensitivity: an increase in calcium binding sites leads to increased contractility.Here are the study notes for the provided text:
• Muscle Physiology*

Titin's Role in Muscle Function

• Titin interacts with both myosin and actin
• Thought to be responsible for increased sensitivity of TnC to calcium
• Increased sarcomere length pulls on titin, drawing the actin and myosin closer together, increasing force by increasing access of actin headgroups to myosin, which favors the formation of cross bridges
• Titin acts on myosin binding protein C

Heart Function

Blood Pressure and Cardiac Output

• It takes less pressure to fill the right ventricle than the left ventricle because the right ventricular wall is thinner and more compliant
• An increase in end-diastolic pressure (EDP) increases the stroke volume by increasing the force of contraction by the cardiac muscle, but this is not considered an increase in contractility
• In the normal ranges of right atrial pressure (RAP) and mean arterial blood pressure (mABP), CO is controlled by both RAP and mABP/afterload
• An increase in afterload causes a decrease in cardiac output (CO) at very high levels of mABP
• Preload for the right side of the heart is equivalent to central venous pressure (CVP)

Compensatory Mechanisms in Heart Failure

• During heart failure, cardiac output may decrease to a level which is insufficient to provide enough blood for the body's metabolic needs
• Compensatory mechanisms that may be activated include:
  • Activation of the sympathetic nervous system (SNS) to increase heart rate and cardiac contractility
  • Activation of the renin-angiotensin-aldosterone system (RAAS) to increase fluid retention
  • Venoconstriction to increase central venous pressure (CVP)
  • Increased contractility of the heart

Control of Blood Pressure

Baroreceptor Reflexes

• Baroreceptor reflexes are found in the carotid sinuses and aortic arch
• These reflexes help to regulate blood pressure

Equations Relating to Blood Pressure

• Mean blood pressure (MBP) is calculated as the time-weighted average of the systolic and diastolic blood pressures or 2/3 x diastolic blood pressure (DBP) plus 1/3 x systolic blood pressure (SBP)
• Cardiac output (CO) is related to blood pressure by the equation: CO x total peripheral resistance (TPR) = MBP

Neurogenic Model of Blood Pressure Control

• The sympathetic nervous system (SNS) can contribute to the long-term control of blood pressure, along with the kidneys

Guyton's Hypothesis

• The stabilisation of blood pressure over the long term is due to there being a constant extracellular fluid volume, which requires there to be a constant sodium content in the body

Measurement of Blood Pressure

• Blood pressure is typically measured in the radial artery
• The pressure wave becomes larger as it moves down the arterial tree due to arterial stiffness

Contributors to Total Peripheral Resistance

• Arterioles are the major contributors to total peripheral resistance (TPR)

Long-term Regulation of Blood Pressure

• The kidneys are responsible for the long-term regulation of blood pressure

Pressure Natriuresis

• Pressure natriuresis is the phenomenon by which an increase in blood pressure leads to an increase in sodium excretion

Factors Affecting Blood Pressure

• Sodium intake can affect blood pressure
• Increased sodium levels can lead to an increase in blood pressure
• Decreased sodium levels can lead to a decrease in blood pressure

This quiz assesses your understanding of the heart's physiology, including preload, afterload, and the Frank-Starling Law. It also covers troponin and calcium sensitivity.