The Pericardium

First, we imagine the heart and great vessels in context with the diaphragm and lungs.

• The fibrous pericardium forms a loose “bag” around the heart; it is attached to the central tendon of the diaphragm.
• The serous pericardium comprises two layers and a space:
  – The parietal layer lines the fibrous pericardium.
  – The visceral layer, which is the outer covering of the heart; thus, the visceral layer of the pericardium is the epicardium of the heart.
• The pericardial cavity is between the parietal and visceral layers; this small space typically contains less than 50 mL of fluid,which allows for free movement of the heart.
• The pericardium has a limited ability to respond to injury,which is often key to its pathology:
  – In response to injury, the pericardium increases fluid production; this fluid can contain fibrin and inflammatory cells.
  – The pericardium can distend to hold this fluid, but only up to a point.

Pericarditis – Inflammation

• The most common pericardial disease, and, it can lead to others.
• Pericarditis is inflammation (‘itis’) of the pericardium.
  Signs & Symptoms:
• Sharp chest pain, which may radiate to the shoulder.
  – Pain is often relieved upon sitting up or leaning forward.
• Pericardial friction rub, which is often characterized as a squeaking or scratching sound.
• Elevated biomarkers: white blood cells, erythrocyte sedimentation rate (ESR), C-reactive protein, and, in some cases, cardiac troponin.
• ECG changes in 4 stages
  – Can help distinguish pericarditis from myocardial infarction.
  – Stage I: Diffuse concave ST-segment elevation and PR-segment depression, which can be seen in most leads (all except for aVR).

Note that, in myocardial infarction, the ST segments are typically convex and not diffuse.

– Stage II: Normalization of the ST and PR segments, and flattened T-waves.
– Stage III: Inverted T-waves.
Stage IV: T-waves either normalize or persist as inverted waves.

Treatment: Aspirin, NSAIDs, and NSAIDs; corticosteroids may be considered if these drugs fail.

Causes of Pericarditis

Many cases are idiopathic.

Causes of pericarditis vary by population. For example, in richer countries, viral and post-surgical causes prevail; in poorer countries, tuberculosis is a significant cause of pericarditis.

Some causes are associated specific types of pericarditis; for example, some bacteria can cause purulent pericarditis.

• Pathogens, especially HIV, Coxsackie virus, Streptococcus, Staphylococcus, and Tuberculosis, can cause pericarditis. It is thought that many idiopathic cases are caused by viruses.
• Metabolic disorders, such as occurs in kidney failure (uremic pericarditis)
• Autoimmune disorders, particularly Rheumatoid Arthritis and Systemic Lupus Erythematosus
• Cancers, especially of the breast or lung, and Hodgkin lymphoma
• Drugs, including penicillin and some anticoagulants
• Myocardial infarction
• Cardiac surgery or trauma
• Radiation therapy

• Constrictive pericarditis can occur when chronic inflammation leads to fibrosis or calcification of the pericardium.
  – This produces a tough, inelastic shell around the heart that impairs diastolic filling.
  – Impaired diastolic filling can lead to peripheral venous congestion and Kussmaul’s sign
  Kussmaul’s sign is characterized by increased jugular venous pressure during inspiration.

Pericardial Effusion – Fluid accumulation

• Fluid accumulation (in some cases, 100s of mL) in the pericardial cavity.
• Causes of pericardial effusion are similar to, and include, pericarditis.
  – Recall that increased fluid production is one way that the pericardium responds to injury.
• Hemorrhagic effusions can also occur, and tend to result from trauma, myocardial infarctions, and vessel rupture.
• Diagnosis often entails echocardiogram, CT, or MRI, which allows us to see the quantity and location of excess pericardial fluid.
• If pericardial effusion occurs in the absence of pericarditis, the patient may not experience any symptoms.
• Pericardial friction rub may be heard (but not necessarily).
• ECG changes include  tachycardia, electrical alternans, and low QRS voltage.

Cardiac Tamponade – Fluid from effusion impedes filling.

Also called pericardial tamponade

• Occurs when the pressure from the pericardial effusion impedes filling.
  – Recall that the pericardium can distend to hold excess fluid only up to a point; cardiac tamponade occurs when the elastic limit of the pericardium is surpassed, and the accumulating pericardial fluid exerts pressure on the heart.
  – Most likely to occur when fluid accumulates rapidly, but can also occur when a large volume of fluid accumulates over time.
• When the pressures on the heart that impede filling are too high, cardiac tamponade can lead to shock.
• Key clinical indications: tachycardia, high jugular venous pressure, and pulsus paradoxus
  – Pulsus paradoxus is characterized by a 10 mmHg or more drop in arterial blood pressure upon inspiration.
• Treatment: Drainage of the excess fluid from the pericardial cavity.

• Intrinsic, aka, local, regulation ensures that blood flow and nutrient supply matches the needs of target tissues.
• Intrinsic mechanisms respond to local changes in metabolic products and/or transmural pressure via changes in vascular resistance.

Intrinsic control:

• Autoregulation
• Active hyperemia
• Re-active hyperemia

Autoregulation

– Maintains constant local blood flow despite fluctuations in systemic mean arterial pressure.
– Is particularly important for the brain, which requires a constant supply of oxygen and other nutrients.
– As long as mean arterial pressure remains between 60-160mmHg, autoregulation of vessel diameter maintains a nearly constant cerebral blood flow of 50 ml/100 g/min.
– However, there are limits to what autoregulation alone can achieve: outside of the ideal pressure range, cerebral blood flow will increase and decrease depending on mean arterial pressure.
In stroke or brain hemorrhage, there is often dysfunction of cerebral autoregulation.

Active Hyperemia

Reflects the positive correlation between blood flow and tissue metabolic requirements:

• Skeletal muscle oxygen consumption drives blood local blood flow.
  – As skeletal muscle activity increases, so does its oxygen consumption.
  – In response, vasodilation increases local blood flow and oxygen supply to meet increased demand.
  – During periods of vigorous exercise, there will be vasodilation to increase blood flow to the skeletal muscles.

Re-active Hyperemia

Occurs in response to a period of decreased blood flow.

• Typically, baseline blood flow is constant over time.
• When blood flow is obstructed, oxygen debt accumulates in the tissues of the hand.
• Removal of the obstruction enables blood flow to resume, even above baseline levels to make up for oxygen debt.
• As an unintended consequence, hyperemia can occur when clinicians mechanically unclog a clotted vessel and this phenomenon can have deleterious effects.

Proposed Explanations

Myogenic Hypothesis

• Assumes that the goal is to maintain vascular wall tone despite changes in blood flow.
• Increased blood flow raises the transmural pressure, which stretches the vascular smooth muscle cells of the smooth muscle layer.
• In response, the vascular smooth muscle cells initiate vasoconstriction:
  – Contraction of the smooth muscle maintains the vascular wall tone and reduces blood flow.
  – Myogenic hypothesis can explain autoregulation, in which the vasculature responds to changes in mean arterial pressures, and, therefore, transmural pressure. But it does not explain active nor re-active hyperemia, which are responses to changes in local oxygen needs.

Metabolic Hypothesis

• Assumes that the goal is to match oxygen supply and demand.
• Increased skeletal muscle tissue activity results in the production of vasodilator metabolites
• The vasodilator metabolites (as their name suggests) induce vasodilation of nearby vessels
• Thus, blood flow and oxygen supply increases
• Eventually, increased blood flow washes away the vasodilator metabolites and blood flow returns to baseline.
• The metabolic hypothesis explains autoregulation and active and re-active hyperemia.

• 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).