Cardiac Physiology

Composition of Blood

• Nearly half its volume is composed of cells.

  • The most numerous cells are erythrocytes (red blood cells)

  • The remainder of the cells are leukocytes (white blood cells)

  • Present are platelets, which are not actually cells but rather cell fragments that play an important role in blood clotting. • The liquid portion of the blood, called plasma, is made up of water containing dissolved proteins, electrolytes, and other solutes.

Parallel arrangement of organs in a systematic circuit

• Each organ is fed by a separate artery, each receives fully oxygenated blood.

• Blood reaches the organs via parallel paths, blood flow to the organs can be independently regulated. Thus, blood flow can be adjusted to match the constantly changing metabolic needs of organs.

Anatomy of the heart

• Atria

• Ventricles

• AV valves

• Semilunar valves

Blood flow through the heart

• Right to lungs

• Left to body

Cardiac Conduction

• Contraction of the heart is systole and blood is ejected from the heart. First atria then ventricles contract.

• Relaxation of the heart is diastole allowing the atrium and ventricles to fill with blood

• Collections of specialised pacemaker cells (nodes) drive the heart beat. (sinoatrial node to AV node to AV bundle to right and left branches (bundle of His.) to purkinje fibres)

  

Specialised Cardiac Muscle Fibre Cells

• Purkinje fibres and the bundle of HIS

• Autorhythmic cells generate little contractile force but coordinate and provide rhythm to the heartbeat (pacemaker cells and conduction fibres)

  

Cardiac Muscle Cells

• Contractile cells

• Branched

• Connected by intercalated discs that have gap junctions that allow muscle AP’s to travel through cardiac muscle.

• Larger diameter to conduct AP’s faster

• Stable resting potential of 90mV and only depolarise when stimulated

• At threshold (-70mV)

  • Na channels open causing depolarisation

  • Slow Ca channels open causing a slow and steady influx at -40mV

  • Near the peak Na channels close and K channels open

  • Small decrease in membrane potential called early repolarization

  • Ca and K balance causing plateau (contracts longer) and muscle contraction halfway through.

  • Ca is transported out and back to SR

  • Sodium potassium pump restores ionic balance with a longer absolute refractory period to prevent summation and tetnus

What triggers the heartbeat?

• Signals originate from the muscle itself - myogenic

• Impulse traveling from the AV node to the bundle of His.

Pacemaker Cells

• Initiate contractions spontaneously generating AP’s

• Usually generate contractions in 2 specific reigions

  • SA node - 80 AP’s per min - 80 beats per min

  • AV node

• The SA and AV node spontanously generate AP’s at different rates - the SA node (pacemaker) is faster driving depolarisation of the AV node

• SA controls heart rate, if damaged other parts may take its role

• No true resting potential

  • Voltage starts at -60mV and spontaneously moves up until the threshold

  • This is due to funny channels that open when the membrane voltage is less than -40mV and allow slow influx of sodium causing pacemaker potential

  • At threshold calcium channels open depoalring further.

  • Spreads to conduction system and contractile myocytes

Cellular Mechanisms

• Resting potential is the potential for K

• NS can make the AP go faster or slower but cannot generate them

• Pacemaker and contractile myocytes have different forms of AP’s

The Cardiac Cycle: Ventricular filling

• Mid to late diastole

• Blood returns to the heart via systemic and pulmonary veins and enters the relaxed atria.

• From there it passes through the AV valves into the ventricles under its own pressure

• The return of blood from the veins to the heart - venous return - occurs because the pressure in the veins is greater than that in the atria.

• During this time, the pulmonary and semilunar valves are closed because ventricular pressure is lower than the aorta and pulmonary artery pressure.

• In late diastole the atria contract driving more blood into the ventricles and the atria relax as systole begins.

The Cardiac Cycle: Isovolumic Contraction

• Ventricles contract raising pressure as the blood stays in

• When the ventricular pressue exceeds the pressure in the atria (early systole) AV valves close and semilunar valves remain closed (ventricular pressure isn’t high enough yet)

• Ends when ventricular pressure is large enough to force open the semilunar valves so blood can leave the ventricles.

The Cardiac Cycle: Ventricular Ejection

• Blood is ejected into the aorta and pulmonary arteries through the semilunar valves

• Ventricular volume decreases falling below aortic pressure.

• This causes the semilunar valves to close (marks being of diastole as blood is no longer being ejected)

The Cardiac Cycle: Isovolumetric Relaxation

• Ventricular myocardium relaxes

• Some blood is present in the ventricles under pressure as it takes a long time for the ventricles to relax.

• Ventricular pressure is too low for the semilunar valves to remain open and too high for the AV valves to open.

• Volume of blood is constant and valves are closed.

Wiggers Diagram

Mean Arterial Pressure (MAP)

• Average pressure in the arteries throughout one cardiac cycle.

• Cardiac Output x Total Peripheral Resistance

• Stroke volume (ml/beat) x HR (beats/min) x Total Peripheral Reistance

• Regulated extrinsically via the nervous, renal and endocrine systems.

• Detected via atrial baroreceptors

Cardiac Output

• Stroke Volume (volume of blood pumped out of each ventricle per min) x Heart Rate

• Rate ventricle pump blood (L/min)

• Determined by stroke volume and HR

Regulation of Contraction of Cardiac Muscle

• Cardiac output

• Controlled by intrinsic and extrinsic factors

  • Intrinsic: Heart, starlings law

  • Extrinsic: Nervous system and hormones

• Starling’s Law

Starling’s Law

• Stroke volume is proportional to preload (volume of blood in ventricles before contractions) (end diastolic pressure stretches the walls of ventricles to largest dimensions)

• Volume ejected = pressure

• Greater amount of blood in ventricles increases contractile strength of ventricles increasing stroke volume.

• Myocardium is stretched more (more volume) increasing sarcomere length, increased sensitivity to Ca²⁺, resulting in stronger contractions.

• Ensures all blood entering the ventricles is expelled and both sides have the same cardiac output.

• Allows the demands of circulation to regulate cardiac output.

Influence of afterload

• Afterload is the atrial pressure load on the myocardium after contraction starts.

• Stroke volume depends on how large a force it works against (atrial pressure)

• When the heart ejects blood ventricular muscle works against atrial pressure

  • Increase in atrial pressure decreases stroke volume

  • Decrease in atrial pressure increases stroke volume

Neural Control of the Heart

• Medulla provides parasympathetic output to the SA & AV nodes via the vagus nerve

• Sympathetic nervous system provides output to SA & AV nodes and ventricular myocardium via the sympathetic cardiac nerve.

  • Increased activity increases stroke volume

• Autonomic nervous system regulates both HR and stroke volume.

Sympathetic Control of Ventricles

• Sympathetic neurons trigger AP’s that release noradrenaline in the SA node triggering contractile cells to contract faster and harder in the ventricles

• AP’s open funny and T-type Ca²⁺ channels causing depolarisation of the SA node

• They project to the AV node and other parts to influence speed of AP’s

• More sympathetic activity increases rate of AP’s decreasing the delay between the atrium and ventricles contracting

• Ventricular contraction starts faster and happens faster decreasing systole duration

  • Critical when HR increases as ventricles are only filled in diastole

  • Diastole decreases more than systole

Noradrenaline in the CNS

• Sympathetic AP’s release noradrenaline causing a cascade that

  • Opens Ca²⁺ channels in the plasma membrane T-type and the sarcoplasmic reticulum

  • Phosphorylates myosin increasing cross bridge cycling

  • Activates SR Ca²⁺ pump, more Ca²⁺ enters sarcoplasmic reticulum and free Ca falls²⁺ faster

• Cases faster contraction of muscle due to increase calcium ions

• Noradrenaline activates G-protein that binds to adenylyl cyclase → ATP → CAMP → Protein kinase →cascade

Parasympathetic Regulation of the Nervous System

• Effects SA node

• Acetylcholine → G-protein → more K⁺ efflux

• Hyperpolarization decreases spontaneous depolarisation.

Regulation of Contraction of Cardiac Muscle

Arterioles

• Vary resistance to regulate distribution of blood flow, control total peripheral resistance and blood pressure.

• BP = Cardiac Output x Total Peripheral Resistance

• Lots of smooth muscle to regulate resistance

• Reduces the mean and pulse pressures for exchange in capillaries to prevent damage.

• Muscular (smooth muscle) for resistance distribution

Endothelium

• Made of epithelial cells that line the cardiovascular system

• Secrete vasoactive substances

• Express enzymes (ACE & Carbonic Anhydrase) on their luminal membranes

• Inner lining.

Smooth Muscle

• Relaxes and contracts blood vessels

Connective Tissue

• Collagen and Elastin

• On the outside for stretch at high pressures

• Prevents overexpansion

Laplace Equation

• T = P X R

• Large diameter needs thick wall due to pressure

Determinants of Cardiac Output

• Spontaneous AP’s via pacemaker cells in the SA node

• Input from autonomic nervous system to SA controls rate AP’s are fired (but heart has its own rhythm)

Intrinsic HR	No input from ANS	100 bmp
Resting HR	Parasympathetic input	55-70 bmp
HR during stress	Sympathetic input	130 - 190 bmp

Regulation of MAP

• Increase in CO₂ same TPR = increased MAP

• Same CO₂ with increased TPR = increased MAP

• At rest extrinsic mechanisms keep MAP consistent via a negative feedback loop

• Controlled neurally and hormonally

• During exercise resistance is controlled by local mechanism including intrinsic factors (metabolites)

Neural Control of MAP

• Medulla controls the collective response and assesses indicators of cardiovascular performance, imput from the hypothalamus for stress response & instructs cardiac system with changes via automatic nervous system.

Sensor	Location
Arterial baroreceptors	Aortic arch & carotid sinus
Low pressure baroreceptors	Right atrium & large systemic veins
Chemoreceptors	Carotid Arteries Proprioceptors Skeletal Muscle & Joints

Atrial Baroreceptors

• Located in aortic arch & carotid sinus

• Sense mean arterial pressure

• Depolarise when stretched - high BP

Autonomic Inputs

• Sympathetic and parasympathic input to SA node to control HR

• Sympathetic nerves go to

  • Ventricular myocardium to control ventricular contractility

  • Veins and arterioles for vascular resistance

Baroreceptor Reflex

Hormonal Control of MAP

• Atrial baroreceptors secrete adrenaline, vasopressin & angiotensin II.

• Adrenaline is released when atrial pressure drops

  • Opens calcium ion channels (for more contractions to increase cardiac output)

  • Increases MAP total peripheral resistance through vasoconstriction in vascular beds and vasodilation in skeletal and cardiac muscle.

Vasopressin & Angiotensin II

Vasopressin	Angiotensin II
Regulated by baroreceptors Released when atrial pressure falls Promotes increase in MAP through vasoconstriction Reduces urine output to maintain plasma volume	Increases when atrial pressure drops Increases MAP through vasoconstriction Reduces urine and stimulates thirst output to maintain/increase plasma volume

Types of capillaries

• Continuous (muscles & CNS): Uninterrupted endothelium lining and only allow diffusion of small molecules.

• Fenestrated (kidneys and endocrine glands): Allow for rapid diffusion of larger molecules through small pores (fenestrations) in their walls.

• Discontinuous (liver spleen and bone marrow): Large gaps and fenestrations and an incomplete basal membrane allowing cells, plasma, and blood to pass through

Types of arteries

Elastic	Muscular
Elastin 40% Largest Store energy	Smooth muscle 50% Arterioles 60% smooth muscle Resistance and distribution

Venules VS Veins

Venules	Veins
Thin smooth muscle Volume reservoir	Thin muscular valves Volume reservoir