Week 1

Acyanotic Congenital Heart Defects

- ASD - VSD - PDA - Congenital Aortic Stenosis - Congenital Pulmonic Stenosis - Coarctation of the Aorta

7 Phases of the Cardiac Cycle

1. atrial contraction 2. isovolumetric contraction 3. rapid ejection 4. slow ejection 5. isovolumetric relaxation 6. rapid ventricular filling 7. slow ventricular filling

Developmental Sequence of the Heart

1.) AV canal Formation 2.) Atrial Septal Formation 3.) Ventricular Septal Formation 4.) Outflow Tract Formation

Functions of Capillary Exchange

1.) Fluid exchange between the blood and interstitium 2.) Delivery of nutrients to tissues 3.) Removal of waste products from tissues 4.) Leukocyte migration between blood and interstitium

The Starling Forces (4)

1.) Hydrostatic pressure in a Capillary (Pc) 2.) Hydrostatic pressure in the interstitial space (Pi) 3.) Oncotic Pressure in the capillary (Pic) 4.) Oncotic Pressure in the interstitial space (Pii)

4 Physiological Causes of Edema

1.) Increased Capillary Hydrostatic Pressure (Pc) 2.) Decreased Capillary Oncotic Pressure (Hypoproteinemia) 3.) Increased Capillary Permeability 4.) Obstruction to Lymphatic flow

5 Parameters that affect Hemodynamics

1.) Individual Vessel Diameter 2.) Total Cross-sectional Areas of Vessels 3.) Velocity of Flow 4.) Blood Pressure 5.) Distribution of Blood Volume

Cyanotic Congenital Heart Defects

1.) Truncus Arteriosus 2.) Transposition of the Great Vessels 3.) Tricuspid Atresia 4.) Tetralogy of Fallot 5.) Total Anomalous Pulmonary Venous Return

Clinical Information and PV Loops

8 Important pieces of clinically useful information about heart function can be obtained from a PV-Loop and they include: · ESV = volume at point D or A on the Loop. · EDV = volume at point B on the loop · SV = EDV - ESV (i.e. B - D or B - A) · EF = (SV/EDV) x 100 · Maximal Afterload (systolic BP): pressure at peak of phase III · Blood pressure (systolic/diastolic): pressure at the peak of phase III/pressure at point C · Pulse Pressure: systolic - diastolic; provides an index on the strength of the pulse. · Stroke Work = energy required to eject blood = Area w/in the PV loop (greater area = greater stroke work).

Stroke Volume

= EDV - ESV; the volume of blood pumped from the LV per beat (mL/beat)

Cardiac Output

= SV x HR; CO is the volume of blood pumped from the LV per minute (L/min)

Dynamic Compliance

A change in vascular tone due to smooth muscle contraction (altered by Sympathetic NS alpha 1 receptors). Affected by constriction of blood vessels (this decreases compliance).

Ejection Fraction

A measure of the heart's efficiency (used to measure the function of the left ventricle). EF = SV/EDV (multiply by 100% to get percentage). Note that a normal EF is between 55-65%.

Static Compliance

A physical property of a vessel determined by the amount of connective tissue present (altered by age and arterial disease both of which can decrease compliance).

Ventricular Septal Formation

A primary septum-muscular fold appears near the apex and grows toward the AV valves. The inlet ventricular septum is another muscular ridge which fuses w/ the primary septum to form the muscular septum. Interventricular foramen is a hole near the top of the septum which closes due to fusion of the right and left bulbar ridges and the posterior endocardial cushion. The top of the ventricular septum is connective tissue while the bottom is muscle.

Ductus Venosus

A shunt which bypasses the liver and carries O2 rich blood from the umbilical vein to the IVC.

Transudate

A type of edema w/o extra proteins (ultrafiltrate). This is what makes up classic pitting edema (from CHF or Liver failure). Unilateral is almost always due to lymphatic disruption.

Slow Ventricular Filling

AKA diastasis continued filling of the ventricle but at a slower rate due to the decreased pressure gradient from atrium to ventricle.

Diastolic Murmurs

Abnormal flow during ventricular diastole. Heard between S2 and S1 (S1 -> S2 -> SSSSSS -> S1 -> S2). These are typically decrescendo murmurs. Two examples are Aortic Valve Regurgitation and Mitral Valve Stenosis.

Systolic Murmurs

Abnormal flow during ventricular systole. Heard between S1 and S2 (S1 -> SSSSSS -> S2). Occurs in Aortic Valve Stenosis and Mitral valve regurgitation.

Edema

Accumulation of fluid due to impaired removal from the interstitium.

Cardiac Muscle Excitation-Contraction Coupling

Action potential travels w/in the Cardiac muscle cells and travels down T-tubules into the muscle cell. When an AP arrives at a diad it encounters and activates L-type Ca2+ channels (DHR receptors). This will create a Ca2+ trigger flux that is responsible for activating Ca2+ induced Ca2+ Release (CICR) from the SR. Note that the size of this trigger regulated by the ANS. Ca2+ binds troponin which then moves tropomyosin away from myosin binding sites on actin allowing binding of myosin to actin and thus a contraction.

Atrial Contraction

Active contraction of the muscle of the left atrium. Result is of this phase is to drive the final 10% of blood into the left ventricle through the mitral valve.

Malformation of the IVC

An abnormality of position of the vein may affect the adjacent organs, such as the ureter, compressing it and causing hydronephrosis.

Isovolumetric Relaxation

Aortic pressure now exceeds ventricular pressure which forces it closed (S2 heart sound). Mitral valve is still closed so there will be no volume change (~50 mL). Ventricle relaxes leading to a huge drop in pressure from 80 mmHg to about 10 mmHg, at which point the mitral valve can open because atrial pressure is above ventricular pressure.

Vitelline Arteries

Arteries to the yolk sac give rise to the arterial supply of the GI tract. By birth these arteries have reorganized to form the three main arteries to the GI tract (Celiac artery (foregut), superior mesenteric (midgut) and inferior mesenteric (hindgut).

Umbilical Arteries

Arteries which are initially paired ventral branches of the dorsal aorta but through remodeling they shift origin to the internal iliac arteries. After birth the proximal portions of the umbilical arteries persist as superior vesicle arteries.

Compliance of Arteries vs. Veins

Arteries: these are high pressure vessels so they operate at the top end of their compliance curves. You can think of them as water balloons. We can pump them full of fluid, but they will have a natural recoil that will bring them back to their OG size. This helps propel the blood through the circulatory system. Arteries have low compliance. Veins: these are low pressure vessels and as such they operate at the lower end of their curve. Easiest to think about these as filling up a plastic bag with water (bag doesn't have a lot of recoil force). Their curve has a much greater slope which means they have a greater compliance.

Individual Vessel Diameter

As blood flows from the aorta to the capillaries the diameter decreases due to vascular branching, but diameter increases from capillaries to veins due to merging of vessels. This parameter is referring to the diameter of an individual blood vessel.

Middle Mediastinum Borders and Contents

Bounded by the anterior margin of the pericardium anteriorly, posterior border of the pericardium posteriorly, the pleura of the lungs laterally, the imaginary line between sternal angle and T4 superiorly, and the diaphragm inferiorly. This cavity contains the heart, pericardial sac, the origin of the great vessels (SVC, ascending aorta, and pulmonary trunk) as well as the cardiac plexus (sympathetic from T1-T4 and parasympathetics (Vagus)) and the phrenic nerves (C3-C5 which innervate the diaphragm).

Anterior Mediastinum Borders and contents

Bounded by the pleura of the lungs laterally, body of the sternum anteriorly, pericardium posteriorly, superior mediastinum superiorly (level of the sternal angle), and finally the diaphragm inferiorly. No major structures are found in the anterior mediastinum. In kids it does contain parts of the thymus (but this goes away by puberty).

Posterior Mediastinum Borders and Contents

Bounded by the pleura of the lungs laterally, pericardial sac anteriorly, T5-T12 vertebrae posteriorly, superior mediastinal (level of T4) superiorly, and the diaphragm inferiorly. Contains the esophagus, Vagus nerve, sympathetic chains, azygos vein, hemiazygos vein, accessory hemiazygos vein, and the thoracic aorta.

Superior Mediastinum Borders and Contents

Bounded by the thoracic outlet up top, the inferior mediastinum on the bottom (which starts at the sternal angle), the manubrium anteriorly, the vertebral bodies of T1-T4 posteriorly, and finally the Pleura of the lungs laterally. This portion of the mediastinum contains the thymus (in kids), great vessels (brachiocephalic artery/veins, SVC, aorta, left common carotid, and left subclavian arteries), trachea, esophagus, thoracic duct, sympathetic chain, phrenic nerves, Vagus nerves, and the recurrent laryngeal nerves.

Vascularization of Cardiac Muscle

Branches of the epicardial arteries (part of the coronary artery system) form anastomoses w/in the myocardium that can provide collateral circulation w/in regions of heart muscle. In the event of gradual arterial occlusion collaterals may increase in size and number to provide alternate routes for blood flow. A good way to look for and recognize blood vessels is by looking for the RBC's w/in them (note that arteries and veins are often in close proximity to each other).

Normal Physiologic Values for Heart Values

CO: ~5 L/min SV: ~90 mL/beat EF: 55-65% EDV: 140 mL ESV: 50 mL HR: 60-100 bpm

Ventricular Defect Causes

Can be detected prenatally. Many close spontaneously. Arise in any part of the IVS, but membranous is the most common. Large VSD's can cause excessive pulmonary blood flow (L -> R shunt) which leads to pulmonary hypertension and cardiac failure in infancy. Muscular VSD's are less common. A common ventricle occurs from failure of the IVS to form altogether.

Atrial Septal Defect (ASD) (Embryology)

Can be due to defects in the ostium secundum (most common), ostium primum (associated w/ Down syndrome), Sinus venosus, and finally a patent foramen ovale (25% of population). Physical exam produces a fixed splitting of the S2 heart sound (aortic/pulmonary closure). This is due to the defect which causes excess flow through the pulmonary valve and thus a later closure of the valve. You hear a systolic ejection murmur in the pulmonary region (turbulent flow). Treatment is based on the Qp (pulmonary flow)/Qs (systemic flow). If the ratio is over 1.5 then you need surgical or catheter based closure.

Obstruction to Lymphatic Flow

Can be due to physical obstruction or due to damage to the lymphatic (i.e. surgery). Reduced flow from interstitial fluid into the lymphatic system. This leads to increased Pi which causes reabsorption, but this exceeds the capillaries' ability to reabsorb which leads to peripheral lymphedema.

Left SVC

Caused by persistence of the left anterior cardinal vein and obliteration of the common cardinal and proximal part of the anterior cardinal veins on the right. Blood from the right is channeled toward the left by way of the brachiocephalic vein. Left SVC drains into the right atrium by way of the coronary sinus.

Afterload vs. Shortening Velocity (Cardiac Muscle)

Cells working against less weight will contract the fastest and have the greatest shortening velocity. (X-axis is afterload in the picture). Small afterload = increased velocity; large afterload = decreased velocity. Note that afterload can pretty much correlate with BP and as such Lower blood pressure = less afterload and thus the heart can pump much faster much easier (vice versa is also true).

Preload vs. Shortening Velocity

Chamber filling (passive stretch) of the heart is also known as preload and this affects the force velocity curve. If the ventricle is fuller and the sarcomere length is increased then the curve shifts up and to the right. If preload is increased, the next contraction will have a faster shortening velocity for a given afterload. Increased Preload = Increased Velocity. (Vice Versa also true).

Paradoxical Embolus

Clot in the deep veins travels to the IVC to the right atrium. From here some may go the normal route to become a PE while others will go through the ASD to the left atrium and then the left ventricle (these can then go anywhere via the aorta).

Turner syndrome congenital heart defect

Coarctation of the Aorta

Continuous Murmurs

Common causes of continuous murmurs are PDA, an AV Fistula, Sinus of Valsalva ruptured aneurysm (Aorta to LA), and a Mammillary souffle. Basically, anything that goes from a high pressure to a low pressure (normally arterial to venous) will produce a continuous murmur that goes through both systole and diastole (normally peaks around S2 and then gets quieter).

Atrial Defect Causes

Common, due to issues in the ostium primum, secundum, or foramen ovale. Can also be due to sinus venosus defects. Common atrium can occur.

Circulatory Changes at Birth

Conversion to postnatal circulation is initiated at the time of birth due to the neonate taking their first breath. Air enters and expands the lungs which causes a drop in pulmonary resistance to blood flow which increases the pulmonary blood flow causing a drop in pressure w/in the RA, RV and pulmonary trunk. The Neonate separating from the placenta is also a trigger. Loss of low vascular resistance placenta leads to increases in the neonate's overall systemic vascular resistance, which leads to increased BP in the Aorta, LV and LA.

Driving Pressure (Delta P)

Delta P = P1 - P2. This pressure tells you the difference between two points along the length of a vessel. This pressure is responsible for blood flow. Delta P of Pulmonary Circuit = P1 (Pulmonary Artery Pressure (PAP)) - P2 (Left Atrial Pressure (LAP)). Delta P of Systemic Circuit = P1 (Aortic Pressure (AP)) - P2 (Right Atrial Pressure (RAP)). Note that Aortic and Pulmonary artery pressure are pulsatile and as such we have to use the Mean Arterial Pressure (MAP) when calculating these (see below).

Portal Vein System Development

Develops from the vitelline veins which arise from the capillary plexus of the yolk sack.

Eccentric Hypertrophy

Dilated cavity in the ventricle. May produce an S3 sound. Due to chronic volume overload (high preload). Commonly seen in Aortic or mitral regurgitation, CHF, pregnancy, and athletes.

Coarctation of the Aorta (Embryology)

Discrete narrowing of the aorta in the region of the ductus arteriosus which leads to left ventricular hypertrophy and collateral vasculature. There is a differential cyanosis in which the upper body is normal but the lower body is cyanotic) as well as claudication. These patients have delayed femoral pulses, elevated BP in the arms over the legs, systolic murmur over the chest/back, and a bicuspid aortic valve. Chest X-ray shows notching on the inferior portion of the rib due to dilation of the intercostal arteries which serve as anastomoses to the coarcted aorta. You can also see a 3 sign on the aorta.

Velocity of Blood Flow

Distance flowed per unit of time (m/s). Large diameter vessels have the highest velocity of flow (arteries and veins). This is due to lower resistance in the vessel walls. Small diameter vessels have the slowest velocity of flow (capillaries). Physiologically it is important for capillaries to be slow to allow for gas and nutrient exchange. Note that vessel diameter and velocity of flow are directly related.

S2

Due to aortic and pulmonic valve closure. Heard the loudest over the aortic and pulmonic areas. Physiological splitting occurs with deep inspiration (increased venous return delays closure of the pulmonic valve). Pathological splitting (fixed splitting) occurs due to conduction anomalies or congenital defects (ASD). These are not accentuated w/ inspiration.

S4

Due to chronic pressure overload; almost always pathologic (atrial contraction phase of diastole). Heard in conditions that cause chronic pressure overload. Low ventricular compliance, thick and stiff ventricular walls due to chronic hypertension, chronic aortic valve stenosis. Produces a gallop rhythm S4-S1-S2. Best heard over the mitral valve area. Ventricular walls thicken because the ventricle is working super hard (concentric hypertrophy). Due to high afterload.

S3

Due to chronic volume overload; may be physiologic or pathologic (in the rapid filling phase of diastole). A physiological S3 may be heard in kids, thin adults, athletes and pregnant women. Seen in aortic or mitral valve regurgitation and CHF. Produces a "gallop" rhythm. It is typically a lower pitch than S1 and S2. Best heard over the mitral valve area. Pathologically it is due to an eccentric heart chamber (dilated). Due to High preload chronically. S1-S2-S3

Afterload and PV Loops

Due to increased afterload there is reduced SV and an increased ESV. This occurs in hypertension and stenotic aortic valves.

S1

Due to mitral and tricuspid valve closure. Heard the loudest over the mitral and tricuspid areas. S1 coincides with carotid pulse or apical impulse. Split S1 can be physiological or pathological. Physiologic splitting is due to normal asynchronous closure of valves (mitral valve closes before tricuspid). Pathologic splitting is due to RBBB.

Dynamic Maneuvers and Cardiac Diagnosis

Dynamic maneuvers are things we can do in the exam to help differentiate some types of murmurs from others. Deep inspiration delays the P2 component of the S2 heart sound. It also increases the intensity of right sided murmurs (Tricuspid regurgitation and pulmonary stenosis). Standing/Valsalva reduce LV filling (preload) which decreases SV and makes murmurs softer. The exception to this is MVP and Hypertrophic obstructive cardiomyopathy. Squatting/Handgrip increases systemic vascular resistance (afterload) which makes murmurs louder. Note that there are 4 early diastolic sounds: S3, Opening snap (mitral/tricuspid stenosis), Pericardial knock (constructive pericarditis), and a tumor plop (atrial myxoma).

Early Blood Flow Through Primitive Heart

Early blood flow is caudal to cranial in the following pathway: Sinus venosus -> Primitive atrium -> through AV valve to primitive ventricle -> Bulbus cordis -> truncus arteriosus into the aortic sac. The primitive heart is an unpartitioned tube through which blood flows in a single stream. The truncus arteriosus connects to the aortic arch arteries.

Exudate

Edema containing extra filtered proteins. This occurs in inflammatory and immunologic responses. Histamine responses can increase capillary permeability and make this possible. Note that this tends to be regionalized.

Slow Ejection

Ejection continues but slows down over time (this is due to reduced pressure). This marks the end of the systolic phase.

Transposition of the Great vessels (Embryology)

Failure of the aorticopulmonary septum to spiral. Lines up the RV w/ the aorta and the LV w/ the pulmonary artery. This gives you two parallel/separate circuits. There is generalized cyanosis at birth which progresses rapidly as the ductus arteriosus closes. Physical exam shows an RV lift and an accentuated S2 (aortic closing). Treated by making a VSD.

Transposition of the Great Vessels (Clinical)

Failure of the helical twist during truncal septation. VSD in 20% of cases. Aorta arises from the right ventricle and the pulmonary trunk from the left. Most kids present w/ cyanosis in the first few days. Incompatible with life unless there is an accompanying VSD or Patent FO, or PDA. Treatment is to give the baby IV prostaglandin to keep the DA open and thus allow mixing of the two circulations.

Persistent Truncus Arteriosus

Failure to partition the truncus arteriosus. Associated w/ VSD. Results in a common outflow channel for both ventricles (body and lungs receive partially deoxy blood). Presents w/ cyanosis. Untreated kids die in 2 years.

Heart Tube Remodeling

First the endocardial cushions develop which divide the atria from the ventricles (this is also where R and L atria/ventricles line up). Remodeling of the heart tube begins w/ venous inflow shifting to the right. As venous flow shifts to the right, the left sinus horn ceases to grow and ultimately becomes the coronary sinus. The right sinus horn is incorporated into the primitive atrium. Septation of the Atria begins in week 4 w/ formation of the Septum primum (ostium primum is gone by week 6). Ostium secundum forms before the ostium primum is closed. Septum secundum forms on the right side of the septum primum. Foramen ovale is left which allows oxygenated blood from the IVC to be shunted to the left atrium (thus bypassing the lungs). Drop in pressure of the RA at birth causes the valve to be stuck to the foramen ovale thus closing it. Remodeling of the AV canals so that the atria and ventricles line up occurs in weeks 5 and 6. Septation of the ventricles starts at the end of the 4th week (muscular and membranous components). The AV valves are formed from mesenchymal tissue proliferations in the ventricular myocardium between the 5th and 8th weeks. The outflow tract will ultimately be partitioned by the endocardial-like cushions into the pulmonary and aortic trunks. The 2 conotruncal ridges grow toward each other at the midline and fuse. As they fuse they will spiral in a right handed twist such that the pulmonary trunk is anterior to the aorta.

Bulk Flow Law (Ohm's Law)

Flow (Q) = Delta P/Resistance (R). Blood flow is affected by several different properties of both blood and blood vessels. First is the radius of the blood vessel (r), second is the length of the blood vessel (L), and third is the viscosity of the blood (eta (h)). The greater the diameter of the blood vessel then the less resistance in that vessel. The shorter the length of the blood vessel then the less resistance in that vessel. Finally, the more viscous the blood then the higher the resistance. The equation listed above can be rewritten to fit the cardiovascular system specifically. Q = CO; DP = MAP and Resistance = Total Peripheral Resistance (or Systemic Vascular Resistance (SVR)) which is TPR for short. We then rewrite the equation for MAP and we get MAP = CO x TPR.

Function of the Foramen Ovale

Foramen ovale is in the middle of the atrial septum (what is left of the ostium secundum). It functions to shunt blood from the R atrium to the L atrium to bypass the lungs (Septum primum remnant acts as the valve).

Septum Secundum

Forms on the right side of the septum primum and leaves a hole called the foramen ovale which has the septum primum acting like a valve to shunt blood from R -> L.

Stroke Volume and PV Loops

Found by subtracting EDV from ESV (B from A or C from D). From this you can see that afterload is inversely proportional to SV while preload and contractility are directly proportional to SV. SV is directly proportional to CO. CO = SV x HR.

Pericardial Layers

From most superficial to the most deep the layers of the pericardium are the mediastinal parietal pleura, the fibrous pericardium, the parietal serous pericardium, and the visceral serous pericardium. The pericardium functions to restrict excessive heart movement and it also functions as a lubricated container for the heart. Note that the pericardial cavity is a potential space.

Placenta

Functions as the fetal lungs, GI tract, liver, and kidneys.

Lymphatics in Fluid Balance

Generally speaking, the forces favoring filtration are greater than those favoring reabsorption. Thus, there is a net loss of fluid from the capillaries. 90% of interstitial fluid is reabsorbed while the remaining 10% becomes the lymph fluid. Filtration occurs at a rate of 20 L/day and reabsorption at a rate of 18 L/day, so this means 2 L is in the lymph vessels. Note that the 18 L/day is pretty much the max that can be reabsorbed, so if there is excess filtration/fluid then the lymphatics pick up the slack. If the lymphatics get overwhelmed, then we get edema.

PV Loop and Heart Failure

Goes through many changes over the years. Decreased contractility which impacts CO. Volume of the heart is very high, but it isn't efficient and there is a small SV. In order to treat this you want to reduce the afterload.

Reabsorption in a Capillary

If NDP equation yields a negative number then this means there is net fluid movement back into a capillary.

Filtration in a Capillary

If NDP equation yields a positive number then this means there is net fluid movement out of a capillary.

Embryologic Equivalent of the LA

In a fully developed heart, the primitive LA is represented by the vestigial left auricle while the smooth walled part originates from the pulmonary veins that grow toward and from the lungs.

Main Measures of Cardiac Function

Includes: pulse pressure, mean arterial pressure, wedge pressure and cardiac output.

Mitral Valve Regurgitation

Increased preload (EDV) which overtime will lead to eccentric hypertrophy and thus an S3 heart sound. There is decreased afterload due to the effective stroke volume being lower (half the SV is going the wrong way through the mitral valve. Note that SV is increased but effective SV is lower. There is also a decrease in ESV. This presents as a holosystolic/pansystolic murmur (no crescendo or decrescendo). Since this is a regurgitation it makes sense that there are no isometric periods on the PV-loop. On the cardiac cycle LA pressure increases acutely and will drop over time as the atrium accommodates to the volume. Note that this often presents w/ Mitral Valve Prolapse (loose chordae tendinae) which produces a mid-systolic click. Murmur Description: This is a pan-systolic murmur best heard in the supine position from the mitral listening area which has the same intensity throughout the entire systolic phase.

Embryologic Equivalent of the RV

Inferior end of the bulbus cordis.

Increased Capillary Permeability

Inflammation causes increased Kf which leads to increased vessel permeability. Increased proteins in the interstitial space (increased Pii), increased filtration (exudate), and finally, this causes peripheral edema (usually localized). This can be due to allergic reactions, inflammation, malignancy, or tissue injury/burns.

Embryonic Blood Vessels

Initial blood vessel formation begins in the mesodermal wall of the yolk sac as well as in the wall of the chorion outside of the embryo proper. Vasculogenesis begins in the splanchnic mesoderm of the embryonic disc. During the 3rd week, blood islands form in the chorion, connecting stalk, and wall of the yolk sac. Blood vessel formation occurs in 3 ways. Vasculogenesis works through FGF-2 induction of hemangioblasts. VEGF then stimulates hemangioblasts to form blood vessels and blood cells. Angiogenesis works via VEGF to cause proliferation of endothelial cells at places where vessels sprout from existing ones. Finally, vascular precursors called angioblasts migrate into organs from other regions.

Internal Features of RV

Interventricular septum; trabeculae carnae (in the wall); Septomarginal trabeculae; conus arteriosus (aka infundibulum; leads to pulmonary trunk through the pulmonary valve); pulmonary semilunar valve; R. AV (tricuspid) valve; papillary muscle (3) and chordae tendinae.

Internal Features of LV

Interventricular septum; trabeculae carnae, aortic vestibule, aortic semilunar valve, L. AV valve (mitral valve), papillary muscle (2) and chordae tendinae.

Eisenmenger Syndrome

L ->R shunting leads to increased pulmonary blood flow and thus irreversible pulmonary vascular damage due to pulmonary hypertension. Eventually the pressure on the R will pass the L and it will shunt the other way (this is where the normally noncyanotic defect becomes cyanotic). Symptoms include dyspnea, clubbing, and polycythemia. Varied treatments including pulmonary vasodilator therapy, avoidance of activities which reduce systemic SVR, avoidance of pregnancy, phlebotomy, and heart-lung transplant.

Formation of the Primitive Heart Tube

Late in the 3rd week or early in the 4th week, paired bilateral endocardial tubes in the splanchnic mesoderm appear on either side of the foregut. Cephalic and lateral folding brings the 2 lateral tubes ventrally into the thoracic region. As the embryo folds in the transverse plane, primordial tubes are formed by the epithelium which approach each other and fuse in the midline. The primary heart tube is initially endothelium which becomes the endocardium. Splanchnopleuric mesoderm invests and differentiates into myocardium and cardiac jelly. Serous epicardium is formed by proepicardial primordium (not from the heart tube). After fusion, a series of constrictions an dilations/bulges appear in the heart tube which forms the Truncus arteriosus, bulbus cordis, primordial ventricle, primordial atrium, and the sinus venosus (divided into right and left horns). By day 22, coordinated contractions of the heart tube are present and they push blood cranially from the sinus venosus.

Oblique Pericardial Sinus

Lies posterior to the heart in the pericardial sac. Bounded laterally by the pericardial reflections on the pulmonary veins and inferior vena cava, and posteriorly by the pericardium overlying the anterior aspect of the heart.

Endocardium

Lines the interior surface of the heart (homologous to the tunica intima of blood vessels). Has 3 sublayers. The inner sublayer includes the endothelium and is attached to connective tissue. The middle sublayer includes more connective tissue and some smooth muscle. Finally, the deepest layer (often called the subendothelial layer) has loose connective tissue that is continuous w/ the myocardium and is the location of the Purkinje fibers as well as blood vessels.

Borders/Surfaces of the Heart

Looking at the heart from an AP view the borders/surfaces are as such: The right side is mostly the right atrium while the left side is the left ventricle. The anterior/sternocostal portion is the right ventricle. The posterior/base (opposite of the apex) is the left atrium. The superior border is mainly the atria, auricles, and great vessels while the inferior border is the right ventricle (and some of the left ventricle).

Rapid Ventricular Filling

Low pressure in the ventricle leads to opening of the mitral valve and thus a fast filling of the ventricle.

Congenital Pulmonic Stenosis (Embryology)

Many people are asymptomatic. Often diagnosed w/ discovery of a heart murmur. Exam produces a harsh crescendo-decrescendo systolic murmur loudest at the left upper and sternal border. Ejection click varies w/ respiration (diminishes w/ deep inspiration). Treated w/ a balloon valvuloplasty (pop open the valve).

Ventricular Septal Defect (VSD) (Embryology)

Membranous is the most common (70%) and it occurs higher in the septum, but it can also be muscular (20%) which occurs lower in the septum. Physical exam shows a pansystolic murmur at the lower left sternal border S2 has normal intensity and splitting. Smaller defects lead to louder murmurs (more turbulent flow). By age 2, 50% of small/medium VSDs undergo spontaneous closure.

Myocardium

Middle layer of the heart wall which represents the greatest mass of the heart wall (homologous with the tunica media of the blood vessels). Contains cardiac muscle cells (thicker in ventricles than atria). Some cardiac muscle cells attach the myocardium to the fibrous skeleton of the heart for a rigid structure against which to contract. Some muscle cells (particularly in the RA) produce endocrine secretions while others become specialized in development for generating/conducting electrical impulses.

Grading Murmurs

Murmurs are described based on their position in the cardiac cycle, site of the murmur (i.e. position of auscultation), intensity, pitch, and conduction. Murmurs are generally graded out of 6. Grade of 1 is very faint, 2 is quiet but heard immediately, 3 is moderately loud, 4 is loud, 5 is heard w/ stethoscope partly off the chest, and finally 6 is no stethoscope needed. Note that systolic murmurs are graded over 6 while diastolic murmurs are graded over 4.

Action Potential Speeds

Nerve Cell is faster than skeletal muscle which is faster than cardiac muscle which is faster than the conductive cells of the heart.

Starling Equation

Net Driving Pressure (NDP) = Kf[Pc - Pi) - (Pic - Pii)] (don't really need to consider Kf so the equation Sheakley wants us to know is NDP = (Pc - Pi) - (Pic - Pii)). Note that Pc - PI gives us the net hydrostatic pressure moving fluid of the capillary (filtration) while Pic - Pii gives us the net osmotic force moving fluid into the capillary (reabsorption). Positive numbers = filtration; negative numbers = reabsorption.

Fick Principle

Note that CO can also be calculated from an Echocardiogram. This principle requires 3 measurements. The first is O2 consumption using a spirometer (VO2). The second is the oxygen content of blood collected from an artery (usually the aorta or pulmonary vein) (Ca). Finally, the third parameter is the oxygen content of blood collected from a mixed vein (i.e. the pulmonary artery) (Cv). Note that mixed veins are places where venous blood from the entire body is accumulated before it is oxygenated (so it can be RA, RV or pulmonary artery). Equation: CO = VO2/(Ca-Cv). Note that we would only use this method today if a patient already had a central line (would not use this method today if only for finding CO).

Embryonic Venous System

Note that there are two venous systems. There is the systemic system which is made up of umbilical and cardinal veins and there is the Portal vein system which is made up of the Vitelline veins. Vitelline returns blood from the yolk sac/gut; umbilical returns blood from the placenta; and cardinal veins return blood from the head and trunk.

Double IVC

Occurs when the caudal portion of the L supracardinal vein fails to regress and forms an abnormal L IVC. Number of variations as to how vessels ultimately empty into the left IVC.

Agenesis of the IVC

Occurs when the right subcardinal vein in the thorax regresses and fails to make connections with the liver. The thorax is drained entirely by the azygos and hemiazygos veins. Hepatic vein enters the RA at the site of the IVC.

Abnormal Origin of the Right Subclavian

Occurs when there is abnormal persistence of the R distal segment and abnormal regression of the R proximal segment. The R subclavian originates directly from the descending Aorta and not the brachiocephalic trunk. Its stem is derived from the right dorsal aorta and must cross the midline behind the esophagus to reach the right arm. Often associated w/ dysphagia and slightly weaker pulse in the right upper extremity.

Right Aortic Arch

Occurs when there is abnormal persistence of the R. distal segment and abnormal regression of the L distal segment. Aorta arches to the right. Usually asymptomatic.

Double Aortic Arch

Occurs when there is abnormal persistence of the distal segment of the R. aortic arch intersegmental artery and its junction with the left dorsal aorta. A vascular ring is formed that surround the trachea and esophagus (this can compress these structures causing issues w/ breathing and swallowing.

Double SVC

Occurs when there is failure of the left brachiocephalic vein to form. No brachiocephalic anastomosis forms. R. SVC forms normally. Result: Left SVC drains venous blood from the left side and drains to the oblique vein which empties into the coronary sinus which dilates to accommodate increased blood flow.

Rapid Ejection

Once the ventricle exceeds the pressure of the aorta then it will open (about 80 mmHg). Due to the high pressure, blood rapidly enters the aorta.

Fibrous Skeleton Image

Outlined in Yellow

Pulse Pressure

PP = Psystolic - Pdiastolic. The magnitude of PP is influenced by conditions that alter arterial compliance and/or stroke volume. Examples of abnormal PP's include Arteriosclerosis (which reduces the compliance of the vascular walls) and Aortic valve stenosis (which reduces SV). Note that PP roughly equals SV/Arterial Compliance, so if compliance decreases then PP will increase (arteriosclerosis) and if SV decreases then PP will decrease (AVS).

Passive vs. Active Tension (Cardiac Muscle)

Passive Tension = tension from stretch of the muscle (preload) Active Tension = Tension from the muscle contracting against a force (afterload)

MAP (Simplified)

Pdiastolic + 1/3(PP). Value can be taken from the aortic pressure curve (along with the PP value).

Internal Features of RA

Pectinate muscle; fossa ovalis; sinus venarum (smooth part); and terminal crest (boundary between pectinate muscle and sinus venarum).

Positive vs. Negative Inotropic Agents

Positive Ionotropic Agents: increase heart rate and force by increases free SR Ca2+. Adrenergic agonists such as NE and Epi bind to B1 adrenergic receptors. Cardiac Glycosides such as digoxin inhibit the Na-K pump which leads to increased intracellular Ca2+. Negative Ionotropic Agents: cause the heart to contract slower and less forcefully. This includes Ca2+ channel blockers or beta blockers such as propranolol. This works by decreasing the Free SR Ca2+.

Tetralogy of Fallot (Embryology)

Presents w/ 4 abnormalities which are VSD, Pulmonic stenosis, an overriding aorta (receiving blood from both ventricles), and RV hypertrophy (trying to pump blood through the stenotic pulmonary valve). Physical exam shows mild cyanosis/clubbing, RV lift, single S2 (aortic component alone due to no pulmonary valve closure; i.e. no splitting), and a systolic ejection murmur. Their symptoms tend to come in "spells" which follow exertion, crying, feeding (presents as cyanosis and hyperventilation). Squatting improves symptoms due to increased SVR and reduced R to L shunting. PROVe.

Embryologic Equivalent of the LV

Primitive Ventricle

Aortic Arches

Primitive arterial pattern is established in the 4th week via the Truncus arteriosus which forms the aortic sac. All aortic arches take their origin from the aortic sac. In humans there are 5 arches (1-4 and 6). 1 and 2 will degenerate while 3-6 will develop. 5 pairs of mesenchymal condensations (arches) develop on either side of the pharynx (correspond to the branchial arches). Each arch is associated w/ a CN. Arch 1: CN V; Arch 2: CN VII, Arch 3: CN IX, Arch 4: Superior Laryngeal n. (CN X), and Arch 6: Recurrent Laryngeal n. (CNX). Arch 1 and 2 largely degenerate w/ the exception of the maxillary artery (arch 1) and the stapedial artery (arch 2). The 3rd arch contributes to formation of the carotid arteries. The 4th arch contributes to small parts of the aortic arch and proximal parts of the right subclavian artery. Finally the 6th arch contributes to the pulmonary arteries.

Slow Response AP (Conductive Cells)

Produced by the conductive cells of the heart. Note that this AP is unique in that it has no true resting potential. Phase 0 is the slow depolarization phase which is produced by the opening of slow L-type Ca2+ channels (produces Ca2+ influx). Note that this differs from normal APs as this uses Ca2+ to depolarize and not Na+. From here the AP skips to phase 3. Phase 3 is the classic repolarization phase . Ca2+ channels inactivate and there is opening of the delayed rectifier K+ channels (Ik) with subsequent K+ efflux. Finally, Phase 4 is the pacemaker potential phase. There is opening of Funny channels (If) which allow for slow Na+ influx into the cell. When the cell reaches threshold it will enter phase 0 and start another AP.

Fast Response AP (Myocardial cells)

Produced by the contractile cells in the atria and ventricles. Divided into 5 phases. Phase 0 is the depolarization phase which is due to opening of the voltage gated Na+ channels and subsequent Na+ influx. Phase 1 is early repolarization through inactivation of Na+ channels and opening of Ito channels (K+ efflux). Phase 2 is the plateau phase through opening of Ca2+ influx via L-type CA2+ channels (this elongates repolarization). Phase 3 is the rapid repolarization phase in which Ca2+ channels are inactivated and there is opening of the delayed rectifier channels (Ik) and subsequent K+ efflux. Finally, phase 4 is the resting membrane potential which is maintained by the opening of inward K+ rectifier channels (K+ efflux; just think of it as rectifying the internal membrane potential). Also the Na/K ATPase helps maintain this.

Transmural Blood Pressure

Pt = Pinside - Poutside. This pressure tells you the pressure difference across a vessel wall. (Inside pressure minus the outside pressure). This influences the vessel diameter. When inside > outside the vessel will dilate; when outside > inside the vessel will constrict. Note that this is the BP we measure with a cuff.

Purkinje Fibers

Purkinje fibers are formed from modified cardiac muscle cells that are specialized for rapid conduction of electrical activity. In typical H&E, Purkinje fibers appear larger and pale compared to cardiac muscle cells (this is because they contain less myofilaments and more glycogen). Purkinje fibers are connected by intercalated disks which provide both mechanical and electrical coupling. Note that there is no discrete border between Purkinje Fibers and the deeper cardiac myocytes.

Resistance Equation

R = (8 x eta x L)/(Pi x r^4). It is important to note that radius is in the denominator so it is indirectly proportional to resistance. Viscosity and length are in the numerator, so they are directly proportional to resistance. Finally, note that radius is raised to the 4th power which makes it the most powerful regulator of resistance. A small change in resistance (i.e. occlusion) can have a large effect on flow. When the radius is doubled you see a 16 fold increase in flow; when it is halved you see a 16 fold decrease in flow.

Decreased Capillary Oncotic Pressure (Hypoproteinemia)

Reduced plasma protein leads to low Pic and thus decreased reabsorption and peripheral edema. This can be due to malnutrition/starvation, liver disease, or kidney disease.

Mitral Valve Stenosis

Results in decreased preload (EDV) and thus a decreased SV which also leads to a decreased afterload. This presents as a diastolic decrescendo murmur with an opening snap. There is no S3 or S4 heart sound because there is no ventricular pathology associated w/ this stenosis. Atrial dilated hypertrophy occurs due to volume back up into the left atrium (can lead to A-fib). W/o a good mitral valve you can't move as much blood through it which leads to less pressure in the LV and thus a spike in pressure in the LA. Murmur Description: this is a diastolic murmur best heard in the supine position from the mitral listening area which is best described as a decrescendo murmur that follows an opening snap. The earlier the opening snap the ore critical the valve condition.

Aortic Valve Stenosis

Results in increased afterload (work of the ventricular muscle) due to the stenosed aortic valve. The stenosed valve raises the pressure needed to push blood through the narrow valve. This results in concentric hypertrophy and thus an S4 heart sound. W/ concentric hypertrophy also comes decreased SV and thus an increased ESV since we cannot eject as much blood. This presents as a systolic crescendo-decrescendo murmur. Note that in AVS the arterial pressure is not a good estimate of afterload because the ventricular pressure increases on the cardiac cycle (see below). Aortic pressure actually decreases due to lowered stroke volume. Murmur Description: this is a systolic murmur best heard in the supine position at the aortic listening area which is best described as a crescendo-decrescendo murmur. It is usually mid to high pitch.

Pacemaker Potentials

SA Node: 60-100 bpm AV Node: 40-60 bpm Purkinje Cells: 20-40 bpm The intrinsic pacemaker activity of these cells is due to the funny channels which allow for spontaneous influx of Na+ during phase 4 of the action potential (this allows the heart to beat w/o NS innervation). The cells in the SA node are the first to reach threshold for activation (phase 4 is faster than the other two areas). Note that all the other conductive cells want to beat at their own pace but are forced to line up with the SA node. AV node and Purkinje cells are slower because they have a slower phase 4 and because they have a more negative repolarization point.

Internal Features of LA

Sac-like smooth walled; opening of the pulmonary veins; interatrial septum; and the auricle which contains the rough pectinate muscle.

Ductus Arteriosus

Shunts blood from the pulmonary arteries to the aorta. Again the goal here is to bypass the lungs. Note that the RV is the workhorse of fetal circulation.

Foramen Ovale

Shunts the majority of the IVC blood across the atrial septum (want to avoid the lungs)

Mean Arterial Pressure (MAP

Since the blood pressure in big arteries is pulsatile, we have to use this value when performing driving pressure calculations. MAP = Pdiastolic + 1/3 (Psystolic - Pdiastolic). Aortic MAP = 91 mmHg. Pulmonary Artery MAP = 14 mmHg. Using these values we can determine that the DP for systemic flow is 93 - 2 = 91 mmHg while the DP for Pulmonary flow is 14 - 5 = 9 mmHg (systemic flow has 10X the pressure of Pulmonary flow).

Cardiac Muscle Mechanics

Skeletal and cardiac muscle show a similar relationship between sarcomere length and force generation. However, skeletal muscle is designed so that thick and thin filament overlap is optimized when the muscle is at rest and further stretching decreases contractility. Cardiac muscle is designed to take advantage of the length-force relationship to match its performance to the volume of blood entering its chambers. In the absence of preload (i.e. an empty heart), sarcomeric length is minimal and the possibility for further shortening and force development is limited. Preloading (filling) the chamber stretches its walls, pulling the actin and myosin further apart. This stretching optimizes the potential for crossbridge formation and thus increases the amount of tension that can be developed during contraction. Strong elastic elements w/in the myocardium (elastin and collagen) resist lengthening beyond an optimum 2.2 um.

Cardiac vs. Skeletal Muscle

Skeletal muscle fibers have the ability to contract independently of each other in response to signals from the primary motor cortex. Cardiac cells function independently of somatic control and the fibers function as a single unit. The impetus for cardiac contraction comes from w/in the musculature itself. Cardiac muscle design also incorporates a different mechanism for regulating contractile force since it is an all or none pump that can't rely on motor unit recruitment (regulated by changes in membrane calcium permeability, which is controlled by the ANS). Cardiac muscle has less extensive T-tubules and they are wider. Skeletal muscle has triads (junctions between T-tubules and SR cisternae) but cardiac muscle has diads. In skeletal muscle activation of the DHR will lead to mechanical opening of the SR and release of Ca2+. In Cardiac muscle the Ca2+ that enters via the DHR is responsible for activating further calcium release from the SR (CICR). Finally, in skeletal muscle it requires 2 Ca2+ to activate troponin but cardiac muscle only requires one.

Borders of the Mediastinum

Superior/inferior it extends from the thoracic outlet and root of the neck to the diaphragm. Anterior/posterior it extends from the sternum to the thoracic vertebrae. Divided into the superior and inferior mediastinum. Inferior is further divided into the anterior, middle, and posterior mediastinum.

Starling's Law of the Heart

Tells you how a change in preload affects cardiac output. If we increase the preload of the heart then the heart will contract more forcefully. This is purely due to a mechanical alignment of actin/myosin into a more favorable length-tension configuration. Note that he Right and left hearts are linked in the amount of blood they pump (they are pretty much equal). Increased venous return would increase preload and thus CO of the RV which would thus increase the preload and thus CO of the left ventricle in turn.

PV Loop Phase IV

Termed the isovolumetric relaxation phase. We have to lower the ventricular pressure down in order to open the mitral valve.

Autonomic Innervation of the Heart

The Cardiac plexus is the combination of sympathetic and parasympathetic innervation of the heart. The sympathetic innervation causes an increase in force and contraction rate. This includes thoracic sympathetic chain, ganglia, and rami communicans as well as cervical chain and ganglia. The parasympathetic innervation slows the heart to its resting rate via the Vagus nerve. Note that pain pathways travel back to the brain through the sympathetic pathways and as such a lot of chest pain is referred pain that appears in other areas.

Aortic Valve Regurgitation

The PV-loop for regurgitation looks very rounded; no isometric periods. In other words, there is never a period of time in which blood is not moving in the heart. There is increased Preload (EDV) due to increased filling due to the backwards flow through the valve. Overtime there is eccentric hypertrophy and thus an S3 heart sound. Since preload is increased there will be increased SV (Starling's law) and thus increased afterload. This presents as a Decrescendo diastolic murmur (no opening snap). Murmur Description: this is a diastolic murmur best heard with the patient leaning forward in Erb's position (left 3rd intercostal space) which is best described as a decrescendo murmur that is high in pitch.

BP and Distribution of Blood volume throughout the Vascular System

The average (mean) blood pressure decreases from arteries -> capillaries -> veins. Blood flows continuously down a pressure gradient from the aorta to the vena cava. Note that pressure is pulsatile in the arteries (peak = systolic pressure; trough = diastolic pressure). Arterioles are the site of the largest pressure drop in blood vessels due to them being the site of greatest resistance. At rest approximately 80% of the blood is in the systemic circulation. 13% is in the arterial system, 5% in capillaries, and 64% is in the venous system (important number as the venous system serves as a reservoir that is utilized during times of low blood volume or pressure).

Parallel Arrangement of Blood Vessels

The blood supply w/in each circulation has a parallel arrangement. This reduces resistance throughout the total system as well as enables independent regulation of blood flow to each organ or region.

AV Canal Formation

The endocardial cushions grow together to form the septum between the Atria and Ventricles. Defects here lead to abnormal connections between atria and ventricles which can be low in the atrium or high in the ventricle.

Fetal Circulation

The fetus is obtaining O2 from mom via placental circulation which is delivered via the umbilical vein. Oxygenated blood reaches the periphery by bypassing the lungs through a series of shunts including the Ductus venosus (bypasses the liver for the IVC), foramen ovale (bypasses pulmonary circulation), and ductus arteriosus (passes from pulmonary trunk to the aorta).

Filtration Coefficient

The filtration coefficient consists of two components; the first is the capillary wall surface area and the second is the capillary hydraulic conductivity. Essentially Kf has to deal with permeability of a capillary wall. Low Kf = low permeability (think BBB) while a high Kf = high permeability (think sinusoids of the liver).

Septum Primum

The first septation of the atria which produces the ostium primum toward the ventricular part of the septum (eventually gets closed)

Persistent AV Canal

The formation and subsequent remodeling of the AV cushions is retinoic acid dependent, so disruption of retinoid signaling often produces AV canal defects. W/ a persistent AV canal the R and L AV canals are not fully divided. Double inlet left ventricle is when the AV canals are separated but they both empty into the left ventricle.

Energy Sources of Cardiac Muscle

The heart beats once per second for the duration of the lifespan (sometimes faster). As such the contractions are always very brief and never sustained. Thus, cardiac muscle has lost the ability to sustain ATP production and contract for more than a few seconds. The heart maintains modest ATP stores that support short contractions and then regenerates these using aerobic pathways when relaxed. The limited anaerobic capability creates a high dependence on O2. If O2 is limited, then the creatine phosphate pool can sustain ATP for 30-40 seconds and then lactate begins to be produced. Prolonged O2 deprivation (minutes) causes irreversible hypoxic muscle damage and MI.

Normal Pressures of the Cardiovascular System

The heart is a dual pump which serves two circulations (systemic and pulmonary). Each circulation receives and ejects the same volume of blood per minute (R CO = L CO). RA pressure is ~ 2 mmHg (equal to the venous system); RV pressure is ~ 25/0 mmHg (remember that ventricles have systolic and diastolic pressures); Pulmonary Artery ~ 25/8 mmHg; LA pressure ~ 5 mmHg; LV ~ 120/0 mmHg; Aorta ~ 120/80.

Windkessel Effect

The heart is an intermittent pump which produces a continuous flow (kind of weird, right?). This effect explains how arterial compliance keeps blood flowing to the systemic circulatory system during ventricular diastole. During systole the arterial system expands to accommodate the full ventricular stroke volume (this is an active pump phase). During diastole the energy stored in the arterial walls during systole will drive blood forward (this is a passive phase). It is important to remember that 2/3 of the active heartbeat is in the diastolic phase, so the this effect is very important in maintaining a constant blood flow to the body.

PV Loop Phase III

The heart is still in systole. This is the ejection phase (rapid and reduced ventricular ejection). Volume at the end of ejection is about 50 mL (ESV; point D). Difference between C and D = Stroke volume. SV = EDV - ESV. The peak of this phase is the Maximum afterload which is an estimate of the Systolic BP. Point D marks the end of systole and beginning of diastole. This is also where the aortic valve closes (S2 heart sound).

Cardiac Looping

The heart tube elongates and simultaneously loops to form an S shape. The result of looping is the 4 presumptive chambers of the future heart which are now in the correct spatial relationship to each other. The bulbus cordis is displaced inferiorly, ventrally, and to the right. Note that the superior end of the bulbus forms the outflow region of the right and left ventricles. The inferior end forms most of the right ventricle. The ventricle gets displaced to the left (becomes mostly the left ventricle). Finally, the primitive atrium is displaced posteriorly and superiorly (gives rise to the rudimentary auricles of the heart).

Calcium Induced Calcium Release (CICR)

The method by which Ca2+ is released in cardiac muscle cells. The size of this trigger is regulated by the ANS. An approximate 1:1 relationship between the number of Ca2+ channels and dependent release channels permits fine adjustments of SR Ca2+ concentration and thus contractility of the heart.

Epicardium

The outer layer of the heart wall, representing the visceral pericardium (homologous to the tunica adventitia of blood vessels). Simple squamous epithelium (mesothelium) and an underlying loose connective tissue where coronary blood vessels, nerves, and ganglia are located. This is also where fat accumulates. Outside of the visceral parietal pericardium is the serous parietal pericardium. Outside the serous layer is the much thicker fibrous pericardium.

Conduction Pathway of the Heart

The pathway begins in the SA Node where the signal originates through spontaneous depolarization. This sends a signal through the atria to depolarize and contract. This electrical wave arrives at the bottom of the atrial chamber and causes the AV node to depolarize. Note that these cells have an intrinsically slower conduction velocity to create a delay between atrial and ventricular contraction. From the AV node the signal will pass down the septum of the heart by the Bundle of His. This will then branch into Left and Right bundles. Once the signal hits the apex it will split and run up the outer walls of the ventricles via the Purkinje Fibers. (This will lead to ventricular contraction).

Electrical conduction in the heart

The process of electrical conduction is carried out by specialized cardiac muscle cells in the walls of the heart that send signals to the heart muscle causing it to contract. Conduction starts in the Right atrium and runs down through the septum and then back up the walls of the ventricles to provide organized contraction of the required elements of the heart so that the heart can serve as an efficient pump.

Coronary Vasculature

The right and left coronary arteries arise directly off the aorta, the branch, and then they supply the myocardium of different regions. The Right coronary artery is the second one to branch off the aorta and is very long. The left coronary artery branches almost immediately. The Right coronary artery gives off the Right marginal artery, the posterior interventricular artery, and the SA nodal artery. The Left coronary artery gives off the Anterior interventricular artery (Left anterior Descending artery (LAD)) and the Circumflex artery. Note that there is variation in how the arteries supply the heart. Dominance depends on origination of the posterior interventricular artery (most common is the right dominant). There is ample collateral circulation. Finally, the majority of veins that drain the blood from the heart will empty into the coronary sinus. The coronary sinus receives blood from the Great cardiac vein, middle cardiac vein and the small cardiac vein.

Significance of the AV node

The slow conduction through the AV node allows time for the blood to fill the ventricles before they contract which helps make the heart a more efficient pump. The AV node is the only normal electrical pathway through the atrial-ventricular border. This is due to the AV ring which is a ring of non-conductive connective tissue separating the atria and ventricles. This allows for specific/coordinated control of conduction through the pathway. Wolff-Parkinson-White Syndrome is where there are multiple electrical pathways between the atria and ventricles which can disrupt normal conduction. These accessory pathways are usually stimulated by certain actions and they are treated through ablation of the accessory pathways.

Embryologic Equivalent of the RA

The trabeculated (pectinate) musculature comes from the original primitive atrium. Smooth portion comes from the right horn of the sinus venosus (aka sinus venarum). Atrial septum is formed by development and the ultimate fusion of septum primum/secundum. Foramen ovale becomes the fossa ovalis after closure.

Microanatomy of Cardiac Valves

The valve has a basic structure, with a core comprising multiple layers of connective tissue of different densities. In AV valves, some of the connective tissue is continuous w/ the chordae tendinae. The connective tissue core of each valve leaflet contains both collagen and elastic fibers and is covered on both sides by endocardium. Note that valves do not contain cardiac muscle (passive structures). At higher magnification you should note that the valve is avascular. The leaflets are normally thin enough to allow nutrients to diffuse from the blood w/in the chambers of the heart. This metabolic support could be compromised if the valve is thickened and/or calcified.

Fibrous Skeleton of the Heart

The wall of the heart contains a fibrous skeleton of dense connective tissue that reinforces the myocardium internally. The skeleton has 4 functions. First it serves as a point of insertion of bundles of cardiac muscle fibers for a rigid structure that muscles can contract against. Second it anchors the cusps/leaflets of the valves. Third it prevents the valves from over dilating. Finally, it electrically isolates the chambers of the heart so that electrical activity has no accessory pathways. The network of collagen and elastin fibers varies in thickness but is most prominent as 4 dense rings surrounding all four of the cardiac valves.

Fetal to Neonatal Circulation Changes

There are two driving factors in causing the transition from fetal to neonatal circulation. The first is removal of the placenta. This causes a loss of the low resistance placenta and an increased arterial resistance. The other big change is the lungs taking in air. This reduces resistance in the lungs and reduces pressure in the RA/RV. Transitional changes from fetal to neonate include Umbilical vein closure and ductus venosus closure days after birth, foramen ovale closure minutes after birth, and constriction/loss of the ductus arteriosus and umbilical artery just hours after birth (due to loss of prostaglandin signaling from the placenta).

Increased Capillary Hydrostatic Pressure (Pc)

There are two physiologic ways to increase Pc which are reducing arteriole resistance (dilate the vessel) and increasing venous resistance (constrict the veins). Pathologic changes that lead to this include Heart failure, kidney disease, and pregnancy (all of these increase blood volume). Other mechanisms are through obstructing veins via liver disease w/ portal vein obstruction or venous thrombosis. Note that right heart failure leads to increased venous Pc while left heart failure leads to increased pulmonary Pc.

Postnatal Circulation

There is closure of the umbilical arteries, umbilical vein, ductus arteriosus, closure of the ductus arteriosus, and closure of the foramen ovale. Foramen ovale closure is due to increased LA pressure and decreased RA pressure (sucks the valve into the foramen which then fuses). Ductus Arteriosus deteriorates due to low prostaglandin levels and high O2 levels.

Preload and PV Loops

There is increased filling (and as such the loop expands further right toward more volume). There is a more forceful contraction due to this increased filling. Note that the afterload increases a little bit, but this is due to increased SV.

Concentric Hypertrophy

Thickened ventricular wall which causes a decreased ventricular chamber area. May produce an S4 heart sound due to decreased ventricular compliance. This is typically due to chronic pressure overload. Two examples of conditions include hypertension and Aortic valve stenosis.

Contractility and PV Loops

This affects CO by moving the active tension curve. Increased Ca2+ leads to increased contractility and thus increased force of contraction (this will increase SV and thus CO). Increased contractility will increase the slope of the active tension line. Note that in conditions such as heart failure there is reduced contractility. Note that when you increase contractility you are ejecting some of the ESV. There are positive (NE and Epi) and negative (propranolol) ionotropic agents which increase and reduce contractility respectively.

PV loop and Exercise

This causes an increase in both preload and contractility which will really increase SV and thus CO.

Patent Ductus Arterioles (PDA) (Embryology)

This communication between the pulmonary artery and the aorta is important in fetal development, but this is no Bueno in adults. Exam produces a continuous machine-like murmur that is left-subclavicular in location. Note that if the patient is Eisenmenger physiology (excessive pulmonary hypertension) then they will have lower extremity cyanosis and clubbing.

Jugular Venous pressure curve

This curve correlates w/ the atrial pressure curve of the cardiac cycle due to their being no valve between the venous system and RA. Both curves show the V-, C-, and A waves. (utilize the image and now what each wave is a result of).

Oncotic Pressure in the Capillary (Pic)

This force pulls fluid into the capillary

Oncotic Pressure in the Interstitial Space (Pii)

This force pulls fluid out of the capillary

Hydrostatic pressure in the interstitial space (Pi)

This force pushes fluid into the capillary

Hydrostatic Pressure in a Capillary (Pc)

This force pushes fluid out of the capillary

Outflow Tract Formation

This forms from the truncus arteriosus and the bulbus cordis. The two truncobulbar ridges fuse and migrate proximal -> distal in a spiral 180-degree twist. This becomes the pulmonary artery and the aorta. The inferior margin forms the membranous septum of the ventricles.

S2 Heart Sound

This heart sound is due to closure of the aortic valve (and pulmonic valve). This causes the dicrotic notch seen on the Aortic Pressure curve of the cardiac cycle (marked in blue in the isovolumetric relaxation phase). Note that the volume at this point is the End Systolic volume of the ventricle.

S1 Heart Sound

This heart sound is due to closure of the mitral (and tricuspid valve). This is responsible for the C-wave on the Left Atrial Pressure curve (marked by pink in the Isovolumetric contraction phase). This also marks the End Diastolic volume of the ventricle (highest volume of the ventricle).

Poiseuille's Law

This is a combo of the bulk flow equation and the resistance equation (just sub in the resistance equation into the Bulk flow equation). Q = (DP x Pi x r^4)/(8 x eta x L). From this we can see that radius is directly proportional to flow (as is DP). We can also see that viscosity and vessel length are indirectly proportional to flow.

Mitral Valve Prolapse

This is a murmur which is due to loose chordae tendinae causing the mitral valve to parachute/balloon into eth atrium due to elevated pressure with systolic contraction. It is best heard from the supine position at the mitral listening area. There is a mid-systolic click which is produced by the sudden prolapse of the leaflet of the mitral valve. The mid-systolic click is often followed by a late systolic murmur. MVP w/ Late Systolic MR = diamond shaped murmur.

Congenital Aortic Stenosis (Embryology)

This is the most common valve lesion by far. Usually occurs when the tricuspid aortic valve becomes a bicuspid valve. Exam produces a harsh crescendo-decrescendo murmur which is loudest at the base of the heart w/ radiation to the neck. Present at birth. There is also an ejection click which differentiates this from a senile aortic stenosis (calcified valve).

Transverse Pericardial Sinus

This lies anterior to the SVC and posterior to the ascending aorta and pulmonary trunk. (open at both ends)

Vessels in Parallel

This organization is due to vessels being branched and stacking on top of one another. Note: the total resistance of this type of system is lower than that of the series system because blood has additional pathways for flow. Total resistance of a circuit containing X number of resistors in this arrangement is equal to the sum of the reciprocals of the individual components.

Vessels in Series

This organization of blood vessels is when all the vessels are one after another w/ no branching. The total resistance of a circuit containing X number of resistors in this arrangement is equal to the sum of the individual components. Rt = R1 + R2 + R3 + R4...

Total Cross Sectional Area of Vessels

This parameter is referring to the total area of all similar vessel types. Total area increases from arteries to capillaries because of vascular branching and decreases from capillaries to veins due to vascular merging. It is important to have a large cross-sectional area in capillaries because this is where nutrient exchange occurs. Note: total cross-sectional area and individual vessel diameter are inversely proportional.

Atrial Septal Formation

Two stages (Septum Primum and Septum Secundum). Septum primum looks like a curtain is pulled from the common atrium (top) toward the floor (where the AV cushion just formed). This will leave a crescent shaped hole in the bottom by the floor termed the ostium primum. A second hole will form in the middle of the septum termed the ostium secundum. The septum secundum is another curtain like structure which runs on the right atrium side of the septum primum. This creates the foramen ovale (previously the ostium secundum) which remains covered w/ a valve like flap via a remnant of the septum primum. (lets blood go from R -> L but not L ->R).

Systemic Venous System Development

Umbilical Veins: During the 5th week the right umbilical vein and proximal part of the left umbilical vein degenerate. At the same time the left umbilical vein forms anastomoses w/ the hepatic sinusoids and newly formed channel termed the ductus venosus. Cardinal Veins: a bilaterally symmetrical cardinal venous system develops in the 3rd to 4th weeks in order to drain the head, neck and body wall. There are Anterior veins (which drain the head and upper limbs) and posterior veins (which drain the trunk and legs). Later in development (5-7 weeks) there are some changes. Posterior cardinal veins are superseded by 2 sets of veins (Subcardinal and Supracardinal). Subcardinal system drains structures of the median dorsal body wall (kidneys and gonads) while the Supracardinal system drain the body wall via the intercostal veins. L thoracic Supracardinal = hemiazygos. R Supracardinal = azygos vein.

Tetralogy of Fallot (Clinical)

Unequal division of the truncus arteriosus caused by anterior displacement of the aorticopulmonary septum. Displacement of the septum leads to Pulmonary valve stenosis, membranous VSD, and overriding aorta, and RV hypertrophy due to higher pressure on the right side. Constellation of abnormalities leads to poor oxygenation of the body and thus cyanosis. Can be corrected surgically.

Wedge Pressure

Used clinically to find an estimate of the pressures of the LA. The Right heart can be measured fairly easily due to the low-pressure venous system but the left heart is harder due to high pressure arteries. This utilizes a Swan-Ganz catheter (balloon tip). Goal is to wedge the balloon in a pulmonary artery and occlude flow so the pressure you get is purely LA. Typical wedge pressure is 8-10 mmHg (note that this is a little high).

Jugular Venous Pressure

Useful for diagnosing cardiac pathologies that alter right heart pressure. Jugular vein distension = increased pressure in the right atrium (may see it pulsing). Example Sheakley used was Pulmonary Hypertension. When pulmonary pressure is increased then the right heart must work harder which leads to increased RV pressure which causes the RA to work harder to get blood into the RV. This will elevate RA pressure and thus venous distension since there is no valve separating the RA from the venous system.

Vascular Compliance

Vascular compliance is a measure of a vessel's ability to passively distend and contract due to changes in pressure (i.e. in order to accommodate blood volume). Compliance (C) = DV/DP. In simple terms it is the stretchiness of a vessel. There are two different types: 1.) Static Compliance 2.) Dynamic Compliance

Remodeling of Embryonic Circulation

Vasculature cannot develop via straightforward tree-like growth. Instead, it undergoes constant remodeling as the embryo grows. Because it is necessary to maintain functional circulation throughout development, larger vessels develop from simple networks which undergo extensive remodeling. Angioblastic plexuses grow and spread throughout the embryo via three processes: · Continued formation of angiocysts (vasculogenesis) · Angiogenesis: budding and sprouting of new vessels from existing Angioblastic cords · Intercalation of new mesodermal cells into walls of existing vessels via vascular remodeling.

Venous Reservoir

Veins are also known as Capacitance vessels because they can act as a reservoir for blood due to their high compliance. Veins are 25X more compliant than arteries. This reservoir is used to increase CO when needed. Important to remember that in a healthy person ~60% of their blood volume is in their veins. Increased sympathetic activity to smooth muscle cells leads to constriction and thus increased vascular tone. This increased tone leads to a decrease in vessel (in this case venous) compliance. When this happens, the venous reservoir will start to be pushed out of the veins and towards the heart, which ultimately results in increased venous return and thus increased CO.

Isovolumetric Contraction

Ventricle is completely filled with blood in this phase (about 120 mL). Once pressure in the ventricle exceeds Atrial pressure then the mitral valve closes (S1 sound). Ventricle begins to contract (aortic is closed still) but no volume changes. The whole point of this phase is to generate pressure (from 10 mmHg to 80 mmHg).

PV Loop Phase I

Ventricular filling phase. Encompasses the rapid/reduced ventricular filling phase as well as the Atrial systole phase of the cardiac cycle. This phase goes from point A to point B. Point A is where the mitral valve is opening (correlates to the V wave on the cardiac cycle diagram). Point B is where the mitral valve closes (S1 heart sound). This marks the beginning of systole and the End Diastolic Volume (EDV; aka Preload) which is normally about 140 mL.

Adult Derivatives of Embryonic Veins

Vitelline: R and L vitelline vines form the portal vein and its tributaries. Proximal part of the R Vitelline vein persists as part of the vena cava. Umbilical: adult remnant of the left umbilical vein persists as the round ligament of the liver and remnants of the ductus venosus persist as the ligamentum venosum. Cardinal: these become the systemic veins. Note: IVC forms from remnants of the four separate systems. R vitelline vein = terminal segment of IVC; R subcardinal vein = segment between liver and kidneys; R Supracardinal vein = abdominal segment inferior to kidneys; R and L posterior cardinal vein = sacral segment of IVC. SVC = supracardinal veins (azygos + hemiazygos).

Dextrocardia

When the heart lies on the right side of the thorax instead of the left due to abnormal heart looping. Can be an isolated defect but this is rarely the case.

PV Loop Phase II

aka the Isovolumetric contraction phase. Both the mitral and aortic valves are closed. From point B to Point C. Point B = start of systole. Remember that the entire purpose of this phase is to generate pressure and push the aortic valve open which is what happens at point C. Note that Point C is equal to diastolic BP.

3 Layers of the Heart

endocardium, myocardium, epicardium

Pulmonary Hypertension Micro

thicker/ fibrotic, more muscular, vasoconstriction, thrombi formation, and finally plexiform lesions all lead to reduced blood flow and higher pulmonary pressure

Clinical Significance of the Pericardium

· Pericarditis: inflammation of the pericardium which causes chest pain and a pericardial friction rub (sounds like rustling silk). · Pericardial effusion: passage of fluid from the pericardial capillaries into the pericardial cavity which may lead to inefficiency of the heart. · Cardiac Tamponade: due to extensive pericardial effusion. Compressed volume does not allow full expansion of the heart. Requires Pericardiocentesis to remove the fluid.