• The amount of blood that passes by a given point in a given amount of time.
• Calculated using a variant of Ohm’s Law of electricity:
  Q = Change in driving pressure/resistance of vessel wall.
• Average total blood flow, at rest, is approximately 5 L/min, and is equal to cardiac output; cardiac output is the volume of blood pumped to the aorta per minute.

Change in blood flow

• Blood flow to target organs is constantly readjusted to accommodate their metabolic needs.
• The most efficient way to achieve this is to change the radius of blood vessels, and, therefore, the resistance to blood flow.
  — Vasoconstriction shrinks vessel radius, so resistance increases, which causes blood flow to decrease.
  — Vasodilation widens vessel radius, so resistance decreases, and blood flow increases.

Clinical correlation:

• Atherosclerosis, which is the build up of fats, cholesterols, and other materials on the vessel wall in the form of plaque, which reduces the vessel, increases resistance, and restricts blood flow to tissues, starving them of necessary nutrients.
• If atherosclerotic plaque detaches from the vessel wall, it can become lodged within smaller vessels and completely obstruct blood flow (such as in stroke).

VELOCITY OF BLOOD FLOW:

Refers to the linear distance blood travels in a given amount of time.

• Velocity = Q/A; Q refers to blood flow, A refers to the cross-sectional area of the vessel (area = pi multiplied by the radius squared).

LAMINAR VS. TURBULENT FLOW

Laminar flow

Aka, streamlined, flow refers to normal, linearly flowing layers of blood.

• The layers of laminar-flowing blood create a parabolic profile because the velocity of blood flow is highest in the central layers, and lowest at the vessel wall.

Turbulent flow

• Blood layers mix and run radially and axially.
• Turbulent flow results from irregularities within the vessels, such as valves or clots that alter blood velocity, or from changes in blood viscosity.
• Such blood flow can result in reduced tissue perfusion; the body may try to compensate by increasing blood pressure.

Clinical correlation:

• Turbulence produces sounds that can be auscultated (with a stethoscope).
  Bruits refer to arterial murmurs, and can be indicative of vessel shunts or stenoses (narrowing).
• Cardiac murmurs often refer to structural valvular disease.

CARDIAC WORK:

A measurement of ventricular power.

Commonly used cardiac physiologic measurements:

• Left ventricular stroke work
• Cardiac minute work, which is a measurement of volume work and pressure work.

Cardiac work is stroke work

• The work the heart performs in each beat to eject blood.
  — Work = distance x force.

Left ventricular stroke work:

• Stroke Volume x Aortic Pressure
• Stroke volume is the distance; aortic pressure is the force

Cardiac Minute Work:

Cardiac work per unit time.

• Cardiac minute work = Heart Rate x Left Ventricular Stroke Work.
  – Heart rate introduces the element of time.
• Left ventricular stroke = Stroke Volume x Aortic Pressure (as we’ve previously shown).
• Thus:
  Cardiac minute work = Heart Rate x Stroke Volume x Aortic Pressure.
  – Recall that Heart Rate x Stroke Volume = Cardiac Output
  – Cardiac output is key to evaluating heart performance.

• So, we can re-write the equation again to show that:
  Cardiac Minute Work = Cardiac Output x Aortic Pressure.
  — With this re-arrangement, we can see that cardiac minute work is the product of both volume work and pressure work.
  Thus, increased cardiac output and/or aortic pressure causes increased cardiac work.

MYOCARDIAL OXYGEN CONSUMPTION:

Myocardial oxygen consumption correlates directly with cardiac minute work.
— Of the two components (volume work and pressure work), pressure work is the primary driver of myocardial oxygen consumption.
– This is because pressure work is more metabolically costly than volume work.

Cardiac Hypertrophy:

• Characterized by thickened myocardium:
  Increased pressure work raises myocardial oxygen consumption, and, in response to increased demand, the myocardium hypertrophies.
• In both aortic valve stenosis and systemic hypertension, increased left ventricular pressure work causes left ventricle hypertrophy.
• In pulmonary hypertension, increased right ventricular pressure work causes
  right ventricular hypertrophy.

FICK PRINCIPLE

Used to calculate cardiac output by measuring myocardial oxygen consumption; the calculation is based on the principle of the conservation of mass.

Cardiac output = (Total oxygen consumption) / (Oxygen content of the pulmonary vein – Oxygen content of the pulmonary artery)

Example problem:

• A patient’s total body oxygen consumption is 200 ml of oxygen per minute;
• The oxygen content of the pulmonary vein is 0.15 ml oxygen per ml blood.
• The oxygen content of the pulmonary artery is 0.10 oxygen per ml blood.
  — This gives us a cardiac output of 4000 ml per minute.

• The cardiac cycle describes the electrical and mechanical events that occur with each heart beat.
  • Its duration is reciprocal to heart rate, i.e., an increase in heart rate decreases the duration of the cardiac cycle (in other words, the faster the heart beats, the faster each cardiac cycle completes).
  • Lasts approximately 800 milliseconds.

Diastole and Systole:

• Diastole
  • The period of time when the atria or ventricles relax to passively fill with blood.

• Systole
  • The period of time when the atria or ventricles actively contract to pump blood.

• Valves
  • The atrioventricular and semilunar valves regulate blood flow through the heart.
  • They do so by opening or closing in response to pressure changes within the heart and great vessels.

7-STEP DIAGRAM

Because the cardiac cycle is continuous, we could begin our diagram at any point; we begin with atrial systole.

1. Atrial Systole

• Initiated by the P wave, which triggers atrial depolarization.
  • The atria contract, which increases inter-chamber pressure and forces a small amount of blood into the ventricles (about 10% of total ventricular volume).

Be aware that atrial contraction is NOT the primary mechanism by which blood flows from the atria to the ventricles; by the time atrial systole occurs, passive ventricular filling has already occurred.

• Atrial contraction is followed by a period of diastole, which overlaps with ventricular systole.

2. Early Ventricular Systole

• Initiated by the QRS complex, which triggers ventricular depolarization.
• The early phase of ventricular systole comprises isovolumetric contraction, during which the ventricles contract only enough to raise inter-chamber pressure and close the atrioventricular valves; NOT enough to force open the semilunar valves of the great vessels.

It helps to know that “iso” means equal, or same – ventricular pressure changes, but volume remains the same.

• The closing of the AV valves can be heard as the first heart sound (S1) during auscultation.
• As a result of AV valve closure, blood is temporarily held within the high-pressure ventricles, as it cannot move “backwards” into the atria, nor can it enter the aorta and pulmonary trunk.

3. Mid Ventricular Systole

• During mid ventricular systole, the ventricular myocytes (muscle cells) forcefully contract, and increase ventricular pressure above the vascular pressure of the great vessels.
• Thus, the semilunar valves are pushed open, and blood is rapidly ejected from the ventricles.

4. Late Ventricular Systole

• Repolarization of the ventricles begins (reflected by the T wave on the ECG).
• Ventricular pressure falls, and, as a result, blood ejection slows.
  • Meanwhile, venous return raises atrial pressures.

5. Early Ventricular Diastole

• Reduced ventricular pressure closes the semilunar valves.
  • Thus, this is a period of ventricular isovolumetric relaxation.
  • Although ventricular pressure is reduced, the volume of blood remains the same.
• Left arterial pressure (LAP) continues to rise as venous return moves blood into the atria.

6. Mid Ventricular Diastole

• Muscular relaxation reduces ventricular pressure enough to open the atrioventricular valves.
  • This allows passive ventricular filling.

7. Late Ventricular Diastole

• Continued ventricular filling results in increased ventricular pressure.
  • This reduces the rate of passive filling.

CARDIAC MUSCLE CELLS
Contractile (99%) cells contract and relax.
Autorhythmic (1%) initiate and transmit action potential.

CONDUCTION PATHWAY OF A SINGLE CARDIAC CONTRACTION

1. SINOATRIAL NODE

• The sinoatrial (SA) node is located in the upper wall of the right atrium, near the opening of the superior vena cava.
• Pacemaker: fastest rate of autorhythmicity, therefore, sets heart rate.
  — Action potential originates here.

2. ATRIOVENTRICULAR NODE

• The AV node is located at the base of right atrium, adjacent to septum.
• It is the only electrical communication between the atria and the ventricles, and that it delays impulses to facilitate peak cardiac output.
  — AV nodal delay: delays impulses, maximizes stroke volume, increases cardiac output.

3. BUNDLE OF HIS

• Originates at AV node, splits at interventricular septum into left and right bundle branches.

4. PURKINJE FIBERS

• Spread upward through ventricular walls.
  — Ventricles contract.

CARDIAC MUSCLE CELL ACTION POTENTIAL

PHASE 0: DEPOLARIZATION

The initial rise of the curve.

Sodium moves rapidly into cell; calcium moves slowly into the cell.

PHASE 1

Peak of curve.

Voltage-gated sodium channels close.

PHASE 2: PLATEAU PHASE

Curve plateaus.

Potassium moves rapidly out of cell, while calcium moves slowly into the cell.
— Calcium enters from both the extracellular space and sarcoplasmic reticulum, and is the cause of the plateau.

PHASE 3: RAPID REPOLARIZATION

Curve declines.

Calcium channels close and potassium moves rapidly out of cell.
Potassium and sodium ion positions in regards to the sarcolemma are reversed.

PHASE 4: RESTING POTENTIAL

Low curve.

The resting potential is maintained by leaky potassium channels.
The sarcolemma is impermeable to sodium during this period.

• Long absolute refractory period in cardiac muscle cells: phase 0 to phase 3
  Second action potential cannot be initiated; thus, it is a protective mechanism against tetanus (state of maximal contraction).

BLOOD VESSELS

transport blood throughout the body.

The vascular system comprises the following components:

• The arterial system, which includes arteries and arterioles that carry blood away from the heart.
• The capillary system, which comprises complex networks of capillaries termed ‘beds’ that facilitate molecular exchange between the tissues and circulation.
• The venous system, which includes postcapillary venules, venules and veins that return blood to the heart.
  • These vessels join to form a closed system through which the heart pumps blood.

Capillary Details:

• Capillary beds merging into precapillary venules; the precapillary venules facilitate exchange like the capillaries do, but also function as a major transit point for white blood cells (a key component of the immune response) as they move into and out of the circulation.
• Precapillary venules merge into a venule; venules continue to permit molecular change and white blood cell movement.
• The venules connect to veins; veins are the largest of the vessels returning blood to the heart.

Vessel Cross-Sections & Physiologic Functions

• Blood vessel walls are generally organized into three layers:
  • Tunica intima, the innermost layer, which contains a layer of epithelium surrounded by connective tissue
  • Tunica media, the middle layer, which contains variable amounts of smooth muscle and elastic connective tissue
  • Tunica adventitia, the outermost layer, which comprises mainly collagen; elastic lamina supports the tunica adventitia, anchoring blood vessels to nearby organs and providing stability.
• The thickness and relative compositions of these layers vary between vessels.

Three types of arteries:

• Elastic arteries, which are the largest.
• Muscular arteries, which branch from elastic arteries.
• Arterioles, which are the smallest and branch from muscular arteries.

Cross section of an elastic artery:

• From deep to superficial, draw:
  • A thin tunica intima, a thick tunica media, and a thin tunica adventitia.
  • The tunica media in elastic arteries contains a notably large amount of elastic connective tissue, which enables them to expand and recoil as the heart contracts and ejects blood into circulation.
  • The aorta is an example of an elastic artery.

Cross section of a muscular artery as follows

• From deep to superficial
  • A thin tunica intima, a thick tunica media and a thin tunica adventitia.
  • Show that the tunica media in muscular arteries contains abundant smooth muscle, which allows them to regulate blood flow by vasoconstriction (a contraction of smooth muscle that narrows the lumen) and vasodilation (a relaxation of smooth muscle that widens the lumen).

Cross section of an arteriole as follows:

• A thin tunica intima, a thick tunica media, and a thin tunica adventitia.
  • Tunica media includes a varying amount of smooth muscle.
  • Smooth muscle in the tunica media of arterioles also functions in vasoconstriction and vasodilation, allowing arterioles to regulate the flow of blood into capillary beds.

Components of a capillary bed:

• 4 types of vessels broadly referred to as capillaries:
  • Metarterioles, or precapillaries, which are not true capillaries but pass through capillary beds
  • Continuous capillaries, which are the most abundant
  • Fenestrated capillaries, which are found in the kidneys, small intestine and endocrine glands
  • Sinusoidal capillaries, which are found in the spleen, liver and bone marrow

Features of true capillaries

• Comprise endothelial cells.
• Continuous capillary have continuous walls of endothelial cells connected by tight junctions.
• Lacks smooth muscle, and a basement membrane surrounds it.
• This thin endothelial wall facilitates molecular exchange between the lumen of the continuous capillary and the surrounding tissue.

Features of fenestrated capillaries

• Continuous wall of endothelial cells with a number of pores called fenestrations.
• Continuous basement membrane surrounds the wall of endothelial cells.
• Fenestrations produce greater permeability than that of continuous capillaries.
• Fenestrated capillaries can be found in specialized tissues that require more rapid and extensive molecular exchange.

Features of sinusoidal capillaries

• Large gaps between endothelial cells.
• Discontinuous basement membrane surrounds these endothelial cells.
• The large gaps between endothelial cells and incomplete basement membrane permit even greater permeability than that of fenestrated capillaries.
• Sinusoidal capillaries facilitate the passage of red and white blood cells and are found in specialized organs within which such movement regularly occurs.

Vessels of the venous system

• Postcapillary venules, which form when capillaries merge
• Venules, which form when postcapillary venules merge
• Veins, such as the venae cava, which are the largest of these vessels and form when venules merge

• The venous system returns blood to the heart.
• In general, the vessels of the venous system have thinner walls and larger lumens than the arterial system, with less defined elastic and muscular features.

Cross section of a postcapillary venule

• Walls are porous and that the tunica media is very thin.
  • The porous walls of postcapillary venules facilitate the movement of white blood cells into and out of circulation. – White blood cells function in the immune response, which will be discussed elsewhere.

Cross section of a venule

• Walls are thin, but thicker than postcapillary venule.
  • Porous walls for passage of white blood cells.

Cross section of a vein

• Deep to superfiical: thin tunica media and a thick tunica adventitia.
  • Tunica adventitia is the largest layer in veins and contains a small amount of smooth muscle, unlike arterial walls where smooth muscle is limited to the tunica media.
  • Tunica intima and the tunica media are thinner than in the elastic and muscular arterial walls.
  • The venae cava are the largest veins in the body and return blood to the right atrium of the heart.
  • Many veins, particularly in the limbs and extremities, contain valves formed by the tunica intima, which prevent backflow of blood.

Clinical Correlations:

• Faulty valves cause a back-flow of blood, which manifests as varicose veins and can result in stasis dermatitis.

Overview of Heart Anatomy:

• Inferior chambers are the right and left ventricles, which are separated by the interventricular septum.
• Superior chambers are the right and left atria, which are separated by the interatrial septum.

• Great vessels that enter and exit the heart:
  • The paired pulmonary veins enter the left atrium.
  • The aorta arises from the left ventricle.
  • The pulmonary trunk arises from the right ventricle and splits to form the pulmonary arteries.
  • The superior vena cava and inferior vena cava both drain into the right atrium.

• Four valves ensure unidirectional blood flow through the chambers of the heart:
  • Right and left atrioventricular (AV) valves are between the atria and ventricles.
  • Semi-lunar valves are at the bases of the pulmonary trunk and aorta.

Path of blood flow through lungs, heart, and body:

1. Within the lungs, blood picks up oxygen.
2. Travels through pulmonary veins to left atrium.
3. From the left atrium, oxygen-rich blood passes through the left atrioventricular valve, then enters the left ventricle.
4. The left ventricle pumps this blood through the aortic semilunar valve and into the aorta, which is the major systemic artery.
5. From the aorta, oxygen-rich blood is distributed via systemic arteries to the body tissues.
6. Oxygen moves out of the bloodstream and into the body tissues, and,
   Metabolic waste, including carbon dioxide, move into the blood.
7. Systemic veins carry the oxygen-poor blood away from body tissues,
   and drain into the superior and inferior vena cavae.
8. The superior and inferior vena cavae drain directly into the right atrium of the heart.
9. From the right atrium, blood passes through the right atrioventricular valve, and into the right ventricle.
10. The right ventricle contracts and pumps the blood past the pulmonary semi-lunar valve, and into the pulmonary trunk, which splits to form the left and right pulmonary arteries.
11. The pulmonary arteries carry the oxygen-poor blood to the lungs, where carbon dioxide is released and the blood is re-oxygenated; from here, the re-oxygenated blood enters the pulmonary veins, and the cycle continues.

The cardiac veins carry deoxygenated blood from the myocardium to the right atrium.

• Cardiac veins are classified by their blood-flow return to the heart:
  • The coronary sinus (and its four major tributaries) drains into the right atrium.
  • The anterior cardiac veins drain directly into the right atrium.
  • The small cardiac veins drain directly into the nearest chamber.

Pathway of venous return to the coronary sinus:

The coronary sinus is a wide, short vessel that drains directly into the right atrium. It runs in the posterior coronary sulcus.

• Four major tributaries:
  • Great cardiac vein
  • Left posterior ventricular vein
  • Middle cardiac vein
  • Small cardiac vein

Anterior interventricular vein

• Arises near the apex of the heart and travels superiorly (within the anterior interventricular sulcus).
• Once it reaches the coronary sulcus, the anterior interventricular vein becomes the great cardiac vein.
  • Travels posteriorly to drain directly into the left end of the coronary sinus (be aware that some texts do not name the anterior interventricular vein separately; instead, they refer to this entire vessel as the great cardiac vein).

Right marginal vein

• Travels superiorly along the right side of the heart.
• At the coronary sulcus, the right marginal vein becomes the small cardiac vein.
  • Wraps posteriorly to drain directly into the right end of the coronary sulcus (in some individuals, the right marginal vein drains directly into the right atrium).

Middle cardiac vein

• Arises near the apex and runs in the posterior interventricular sulcus (hence, it is also called the posterior interventricular vein).

Left posterior ventricular vein

• Arises between the great and middle cardiac veins.

Anterior cardiac veins

• Arise on the superior surface of the right ventricle, and drain directly into the right atrium.

Smallest cardiac veins

aka, venae cordis minimae, aka, thebesian veins

• Valveless vessels that drain directly into the cardiac chambers, particularly the right atrium.

Vein – Artery Associations:

• The anterior interventricular vein travels with the anterior interventricular artery.
• The middle cardiac vein travels with the posterior interventricular artery.
• The small cardiac vein travels with the right coronary artery.
• The right marginal vein travels with the right marginal artery.

In Summary:

The great cardiac and left posterior ventricular veins drain regions of the myocardium supplied by the left coronary artery;
The middle and small cardiac veins drain regions of the myocardium supplied by the right coronary artery.

Coronary arteries supply the myocardium with oxygenated blood.

Right coronary artery:

• Arises directly from the right side of the aorta (specifically, from the right aortic sinus) and travels posteriorly within the coronary sulcus.
• Branches:
  • Sinoatrial nodal branch (aka, sinoatrial nodal branch).
  • Right marginal branch.
  • Posterior interventricular branch (aka, the PDA, posterior descending artery), which travels within the posterior interventricular groove (aka, sulcus).

Left coronary artery:

• Arises directly from the left side of the aorta and travels posteriorly within the coronary sulcus (the left coronary artery is sometimes referred to as the left main stem vessel).
• Branches:
  • Circumflex artery, which gives off the left marginal artery.
  • Anterior interventricular branch (aka, the LAD, left anterior descending artery), which travels within the anterior interventricular groove (aka, sulcus).

Areas served by the right coronary artery:

• The right atrium
• Most of the right ventricle
• The sinoatrial node (in 60% of individuals)
• The atrioventricular node (in 80% of individuals)

Areas served by the left coronary artery:

• Left atrium
• Most of the left ventricle
• Most of the interventricular septum
• The sinoatrial node (in 40% of individuals)

Three common patterns of arterial supply:

• Right-dominant pattern, in which the posterior interventricular artery branches from the right coronary artery; this is the most common pattern.
• Left-dominant pattern, in which the posterior interventricular artery branches from the left coronary artery; this is less common.
• Codominance, in which both the right and left coronary arteries contribute to the posterior interventricular artery.
• Occasionally, individuals will have only one coronary artery, or will have accessory coronary arteries.

Additional Information:

• In general, the coronary arteries are functional end vessels, which means that there is little to no redundancy in the blood supply of the myocardium.

• Two common exceptions to this rule:
  • Anastomoses between the anterior and posterior interventricular arteries
  • Anastomoses between the right and left coronary arteries

• Anastomoses provide alternative pathways, called collateral channels, through which oxygenated blood can reach the myocardium.

Clinical correlations:

• Occlusion (aka, blockage) of a coronary artery can cause ischemia and myocardial infarction (heart attack).
  • Treatments for coronary artery occlusion include:
    Coronary angioplasty, in which the clogged artery is widened at the site of the obstruction.
    Coronary artery bypass graft surgery, in which vascular segments from elsewhere in the body (eg, the great saphenous vein, internal thoracic arteries, or radial arteries) are grafted to the heart to circumvent the obstructed coronary arteries.