• The impediment to blood flow

Total peripheral resistance (aka, systemic vascular resistance)

• Describes the resistance to blood flow throughout the entire systemic vasculature (throughout the entire body)

Vascular resistance

• Resistance within a single organ; for example, resistance within in the kidney.

THREE KEY DETERMINANTS OF RESISTANCE:

1. Blood viscosity
2. Vessel length
3. Vessel radius

Blood viscosity

• Is directly proportional to vascular resistance
• Hematocrit (the volume of red blood cells in the blood) is the primary determinant of blood viscosity.
• Clinical correlation: patients with abnormally elevated levels of blood products often manifest strokes from blood clots as a part of a broader hyperviscosity syndrome.

Vessel length

• Directly proportional to resistance
• Blood flow passing through a longer vessel will encounter greater friction, and, therefore, more resistance.

Vessel radius

• Indirectly proportional to resistance. Recall that the radius is the length of a line from the center of a circle to its perimeter; it is half the length of the diameter, which extends from one side to the other.
• The inverse relationship between vessel radius and resistance is NOT linear:
  When the radius decreases, resistance increases exponentially by the fourth power.

Poiseuille equation

• Describes how the determinants of blood resistance interact:
  Resistance = 8 * blood viscosity * vessel length / Pi * radius to the 4th power.

THE ARRANGEMENT OF VESSELS AFFECTS RESISTANCE:

Series resistance:

• Illustrated by the blood vessels of a single organ
• Sum of the individual resistances that blood encounters as it flows through vasculature.
• Pressure decreases as blood moves through the series of vessels because of increasing resistance; it decreases most significantly in the arterioles.

Parallel resistance:

• Illustrated by the branching of the systemic circulation
• Each parallel artery receives a portion of the total blood flow
• Addition of parallel vessels decreases the total resistance
• If resistance within any one of the individual vessels increases, so will total vascular resistance.

Memory aid:

• If this is confusing, think of blowing through multiple straws: the more straws you add, the less resistance there is; but, if one of those straws becomes blocked, overall resistance increases.

• Blood pressure is expressed as the difference, or change in, pressures between two points along a vessel.
• As this statement implies, blood pressure is not constant throughout the cardiovascular system.

Pressure profile graph

Graph Set-Up:

Y-axis =

• Pressure (mm Hg); values 0-120

X-axis =

• Left atrium and left ventricle, which are the chambers of the heart that pump oxygenated blood
• Aorta, which is the largest artery in the body that receives blood directly from the left ventricle
• Large arteries, small arteries, and arterioles
• Capillaries, site of gas exchange
• Veins
• Right atrium and ventricle, which receive deoxygenated blood from the body and send it to the lungs via the pulmonary arteries

Pressure Curve:

Plots two key principles of blood pressure:

• BP changes as blood moves through the body
• BP is pulsatile because of the rhythmic contractions of the heart during the cardiac cycle

Key points of the curve

• In the left atrium, blood pressure is relatively low, at about 5 mm Hg
• It is much higher in the left ventricle and aorta, where it oscillates between 120 and 80 mm Hg
• Arterial pressure rises slightly as it passes through the large arteries, then begins to fall
• Pressure drops significantly as blood moves through the arterioles because they are the site of highest resistance to blood flow
• Within the capillary networks, blood pressure falls to about 4 mmHg by the time it reaches the venous system
• Blood pressure remains low in the right atrium at about 4-6 mm Hg, and rises slightly in the right ventricle
• Within the pulmonary arteries, blood pressure is around 2-4 mm Hg
  — Recall that blood traveling through these vessels travels only a short distance, to the lungs; the low blood pressure is sufficient for lung tissue perfusion, but not so high as to cause damage

Stressed volume:

• Blood within the arterial system is the “stressed” volume; it is under high pressure.

Unstressed volume:

• Blood within the venous system is the “unstressed” volume, as it is under significantly less pressure.
  — Recall that the majority of the blood volume is within the venous, unstressed portion of the circulatory system.

Pulsatility:

• Create a new graph to show the arterial pressure changes of a single cardiac cycle:

Y-axis =

• Pressure (mm Hg); values 80 and 120.

X-axis =

• Time

This curve shows:

• Highest arterial pressure, 120 mmHg, is reached during systole, when the left ventricle contracts and blood is ejected to the aorta
• Lowest pressure, 80 mmHg, is reached during diastole, the period of ventricular relaxation
• Dicrotic notch, (aka, incisura) reflects a temporary drop in pressure after systolic contraction; it is caused by the backflow of blood after the aortic valve closes.

Clinical info:

• Blood pressure is usually reported as systolic pressure over diastolic pressure; 120/80 mm Hg is considered to be a healthy blood pressure.

Pulse Pressure

• Pulse pressure = systolic pressure – diastolic pressure
• Stroke volume is the volume of blood ejected from the left ventricle per beat
• Arterial compliance reflects the ability of the vessel wall to contract or expand to accommodate changes blood flow.

Mean arterial pressure (MAP)

• Mean arterial pressure (MAP) is equal to the diastolic pressure plus 1/3rd of the pulse pressure;
• Is NOT simply the average of the systolic and diastolic pressures; the equation accounts for the fact that the period of diastole is longer than that of systole.
• Mean arterial pressure is determined by cardiac output and peripheral arterial resistance (aka, systemic vascular resistance).

Arterial pressure gradients

Driving pressure gradient

• Refers to the change in pressure between two points along the longitudinal axis of a vessel; P 1 – P 2
• Driving pressure can refer to changes in the overall systemic cardiovascular system or simply within a single organ; for example, knowing the driving pressure at the kidneys is important for understanding renal function and pathology.

Hydrostatic pressure gradient

• Refers to the change in pressure between two points along the axis of a non-horizontal; for example, the femoral arteries, which deliver blood vertically from the heart to the lower extremities; h 1 – h

Transmural pressure gradient

• Refers to change in pressure across the vessel wall; r 1 – r 2
• Transmural pressure is important because it influences vessel diameter, and, therefore, resistance to blood flow.

• 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.