Cardiovascular Physiology Lecture w/ Dr.

Kerrick 4 April 2011

The Topic of This Lecture Is: Overview of Cardiovascular Physiology

The cardiovascular (CV) system maintains homeostasis via pumps, vessels, and
organs.
o This refers to temperatures, O2 levels, H+ concentration, osmolarity, etc.
o Circulating plasma has only 3L of fluid. The interstitial & intracellular compartments
have 12L & 30L.
Major arteries are pressure reservoirs, such that normal systemic BP is around 80-120
mmHg.
o Resistance to blood flow is in arterioles, while exchange of solutes, fluids, and
gases is in capillaries.
Venules and veins are more compliant, with lower BP. Blood flow is
accomplished by valves.
o In pulmonary circulation, BP is only 8-24 mmHg. All the vessels are very
compliant (low resistance).
The composition of the interstitial fluid is related to the chemical composition of arterial
blood.
o In order to accomplish this, there must be adequate flood flow through incoming
vessels.
In terms of CV circuitry, all of the organs are considered to be in parallel, though the lungs
are in series.
o The blood distributed to each organ varies and is more tightly regulated in certain
areas.
o Skeletal muscle, the skin, and the kidneys receive more blood in response to
exercise.
Conversely, blood flow to the brain and cardiac muscle stays pretty much
constant.
The rate of laminar flow is equal to the change in pressure over resistance (Q = P/R).
o Resistance is measured as 8L/r4, with radius being by far the most important
physiological factor.
Stroke volume (SV) is the volume of blood pumped out of the left ventricle with each
contraction (L/beat).
o SV is a product of ventricular distensibility during diastole, ventricular contractility
during systole, aortic/pulmonary artery pressure, and the volume of venous return
(Frank-Starling Law).
Strength of contraction is mediated by the sympathetic nervous system
(ionotropic).
o Heart rate (HR) is measured as beats/minute. Cardiac output (CO) = SV*HR
(L/min, usually around 5).
HR is controlled by the parasympathetic and sympathetic systems
(chronotropic).
In ventricular diastole, blood flows from atria to distensible ventricles, yielding enddiastolic volume (EDV).
o In systole, ventricular muscles are actively contracting, the AV valves are closed,
and blood flows out.
So, ventricles fill with blood at low pressure and empty due to contractioninduced pressure.
o The contraction of cardiac muscle cells must be synchronized to occur at regular
intervals.
The valves must open and close fully to avoid stenosis or regurgitation,
respectively.
Ventricles must fill adequately during diastole and contract forcefully in
systole.

 Electrical conduction of the heart begins at the sinoatrial (SA) node in the right
atrium.
o APs spread over the atria & reach the AV node, causing a slight delay before
ventricular contraction.
o Electricity then flows through the bundle of His to the apex of the heart, then via
Purkinje fibers.
This allows the ventricles to contract from bottom to top, ejecting blood
appropriately.
Adrenergic sympathetic fibers act on receptors in the SA and AV nodes and atrial and
ventricular myocytes.
o NE acts to increase HR, AP conduction velocity, contractile force, & rate of
relaxation (CO increases).
o Cholinergic parasympathetic fibers act on M2 receptors at the same sites, except
the ventricles.
This results in decreased heart rate with little effect on stroke volume (CO
decreases).
The Frank-Starling Law refers to the fact that increased ventricular EDV yields increased
SV.
o This is related to the elasticity of the heart. The more its stretched, the more it is
able to contract.
The radius of vessels decreases from the 2.5 cm aorta to 30 m arterioles to 5 m
capillaries.
o Resistance is primarily a product of smooth muscles that surround arterioles.
These muscles are controlled by adrenergic receptors and local
vasoactive chemicals.
o Cross-sectional area increases (4.5 cm2 to 4500 cm2) due to the vast numbers of
smaller vessels.
o Radius increases and cross-sectional area decreases in the venous system (venules
vena cavae).
Veins are richly innervated by sympathetic fibers, with the goal of increasing
venous return.
Blood contains cells (erythrocytes, leukocytes, and platelets) and plasma, a solution of
salts and proteins.
o Electrolytes include Na+, K+, Cl-, CO32-, etc. Proteins are albumins, globulins, and
fibrinogens.
Nutrients and waste products are transported in the blood as well.
o Serum refers to the contents of blood plasma except for the proteins.

Cardiovascular Physiology Lecture w/ Dr. Landowne 4 April 2011

The Topic of This Lecture Is: Electrical Activity of Cardiac Cells

Electricity passes from the SA node to the AV node through the bundle of His to Purkinje
fibers.
o The ventricular septum has a membranous portion near the bundle of His. The
rest is muscular.
o Purkinje cells are modified cardiac myocytes that have a larger diameter and better
conductivity.
The right ventricle contracts slightly before the left ventricle.
The SA node has an AP with a pacemaker potential and a slow rising phase.
o The atrial action potentials are almost instantaneous and repolarize rapidly. It
looks like a tilted A.
o The AV node AP appears similarly, but its depolarization is slightly slower & in
response to the atria.
If theres diminished atrial conductivity (or SA node failure), the AV node fires
spontaneously.
o Purkinje fibers have an instantaneous depolarization followed by a plateau phase
(Ca2+ influx).
Endocardial ventricular fibers appear similarly, though the plateau is less
pronounced.
There is a slight delay as electricity passes into the epicardial ventricular
fibers.
Repolarization occurs in the epicardium before the endocardium.
o Atrial depolarization is seen on an EKG as a P wave. The QRS complex is
ventricular depolarization with simultaneous atrial repolarization. The T wave is
ventricular repolarization.
In a cardiac myocyte, there are a number of channels. The first of which are Na+v
channels.
o There are also the L-type Ca2+v channels, which are also known as DHP receptors.
o There are three K+ channels: K+IR (inward rectifier), K+Vs (slow), and K+Ve (transient).
The resting potential of cardiac cells is determined by the inward rectifier
K+ channels.
These channels are unusual. They close in response to depolarization;
others open.
o With regard to pumps, there is the Na+/K+ ATPase and the Ca2+-ATPase, and a
Na+/Ca2+ symport.
o The resting potential of cardiac cells is the product of the Nernst equation
(60*log[K+o]/[K+i], etc).
Internal: [Na+] = 15 mM; [K+] = 150 mM; [Cl-] = 5 mM; [Ca2+] = 10-7 M
External: [Na+] = 145 mM; [K+] = 5 mM; [Cl-] = 120 mM; [Ca2+] = 2 mM
Memorize these again

In fast cardiac muscle depolarization, there is a foot of depolarization before Na+v

channels rapidly open.
o Simultaneously, the K+IR channels close, ensuring that the depolarization reaches
+20 mV (phase 0).
The K+Ve channels open transiently, dropping the potential to about 0 mV
(phase I).
o Following this, Ca2+v channels and K+Vs channels open, yielding a plateau phase
(phase II).
At a certain point of repolarization, Ca2+v channels close, causing more rapid
repolarization.
o At around -90 mV, the K+Vs channels close and the K+IR channels open (phase III).
o The resting phase of these cells, in which the heart is in diastole, is termed phase
IV.

 Slow action potentials are seen at the SA and AV nodes, which have a minimal potential
of roughly -60 mV.
o Funny Na+v channels (If) open due to hyperpolarization, causing spontaneous
depolarization.
o There are both T-type and L-type Ca2+v channels. T-type Ca2+v channels open early in
depolarization.
The L-type Ca2+v channels are primarily responsible for the strong
depolarization.
o The L-type Ca2+v channels close in response to the opening of K+v channels.
Many of these channels are regulated by the autonomic nervous system through GPCRs.
o NE acts on receptors to increase Gs activity, increasing cAMP and If activity and
thus, faster HR.
ACh acts on M2 receptors, increasing Gi activity. Less cAMP yields less If
activity & lower HR.
o On ventricular cells, which have fast depolarization, receptors have a different
effect.
Here, cAMP increases PKA, phosphorylating proteins like the Ca2+v and K+Vs
channels.
This increases the amplitude of the plateau while shortening the duration of
the AP.
The net result is a stronger contraction with a longer period of
ventricular filling.

Cardiovascular Physiology Lecture w/ Dr. Champney 4 April 2011

The Topic of This Lecture Is: Review of CV Anatomy and Histology

The heart lies in the left side of the thorax, with the bare area of the pericardium near
the 5th intercostal.
o The pericardium provides a sac for the heart, diminishing the resistance to its
expansion.
o Because of the tilt of the heart, the right ventricle is actually anterior, near the
midline.
Laterally, the only visible chamber is the left ventricle, with the apex placed
anteriorly.
The phrenic nerve runs laterally near the heart, with the vagus nerve
being slightly posterior.
o Posteriorly, the right atrium is visible, along with the posterior interventricular
septum.
o Aside: the left recurrent laryngeal nerve arches around the aortic arch near the
ligamentum arteriosum, which was the ductus arteriosis during embryological
development.
The right atrium receives deoxygenated blood from the superior and inferior vena
cavae.
o The right auricle is an appendage seen dorsally near the aorta.
The musculi pectinati form the anterior wall of this chamber.
o The foramen ovale is visible within the chamber, along with the coronary sinus.
o The right atrioventricular valve (tricuspid valve) is seen as well, permitting flow to
the right ventricle.
The cusps of the tricuspid valve are supported by papillary muscles and the chordae
tendinae.
o The moderator band stretches from the muscili pectinati to the walls of the
ventricle.
o Blood from the right ventricle flows through the pulmonary semilunar valve to
the pulmonic trunk.
The left atrium receives oxygenated blood from the pulmonary veins. It is smoother than
the right atrium.
o The posterior wall of the atrium contains the trebeculae carnae, identical to the
musculi pectinati.
o The left auricle is also visible dorsally, and the foramen ovale can also be seen here.
o Both the left atrium and left ventricle have thicker walls than the right side due to
higher BP.
Blood passes into the left ventricle via the left atrioventricular valve (bicuspid/mitral
valve).
o This valve is also supported by papillary muscles and chordae tendinae.
o Blood leaves the left ventricle via the aortic semilunar valve, flowing into the
aortic arch.
o The ventricles are divided by the interventricular septum, which may have
defects.
During systole, the semilunar valves are open, and the AV valves are closed. The opposite
occurs in diastole.
o The pulmonic valve is anterior to the aortic valve, which supplies the adjacent
coronary arteries.
The coronary arteries are supplied during diastole by blood flowing back from the aorta.
o This blood has slightly lower pressure. It remains there due to the closure of the
aortic valve.
o The right coronary artery runs into the coronary sulcus, which separates the
atrium and ventricle.
In 60% of patients, the SA node is supplied by the right coronary artery.

The acute marginal artery runs with the small cardiac vein toward the
hearts apex (S&M).
The right coronary terminates as the posterior interventricular artery
(right descending).
It runs with the middle cardiac vein (PM) on the posterior side of the
heart.
o The left coronary artery is shorter. It divides into the circumflex & anterior
interventricular arteries.
The anterior IV artery (left descending) runs with the great cardiac vein
(AG).
The circumflex artery also runs in the coronary sulcus, though it courses
posteriorly.
In 15-30% of patients, the circumflex artery forms the posterior IV
artery.
These patients are left heart dominant, instead of the normal right
heart dominance.
The cardiac veins all drain in the coronary sinus, which leads into the right
atrium.
There are also Thebesian veins that drain right into the hearts atria and
ventricles.
Sympathetic innervation of the heart is from the T1-T5 level after synapsing on the
cervical ganglia.
o The cardiac plexus includes fibers from the superior, middle, and inferior cervical
ganglia.
It is possible for patients with neck problems to display cardiac symptoms.
This can be explained embryologically, for the heart descended during
development.
o The dorsal motor nucleus of CN X (medulla) sends preganglionic PSNS fibers
to the heart.
The heart has an endogenous rhythm that is often set by the SA node at the base of the
superior vena cava.
o The atria contract and provide electrical innervation to the AV node, then the
bundle of His.
o The right bundle branch carries electricity to the apex, then contraction occurs
from bottom to top.
The right ventricle contracts, so the anterior papillary muscles contract,
closing the AV valve.
For auscultation, sounds are heard where the blood is flowing to, not at the valve itself.
o The mitral valve is heard at the apex, and so on. Remember APT M 2245.
On an AP radiograph of the heart, the SVC, right atrium, and IVC are seen on the right
side.
o On the left side, the aortic arch, pulmonary artery, and right ventricle (apex) are
visible.
o The right ventricle cannot be seen, as it lies directly on the midline.
The cross-sectional anatomy of the heart is important for understanding CT scans.
o The apex lies laterally toward the left side, though its still quite anterior. The aorta
is posterior.
The coronary arteries can be well-visualized on angiography, so review the anterior and
oblique views.

Here Begins the Histology Portion of the Lecture

The heart has three layers, the most exterior of which is the epicardium, made of
mesothelium.

The epicardium has a subepicardial layer of loose connective tissue, with nerves,
vessels, and fat.
There is also a pericardial cavity containing serous fluid.
o The myocardium contains cardiac myocytes, which is the thickest layer.
These fibers are striated with a central nucleus. They contain intercalated
disks, etc.
Purkinje fibers stain more clearly than other myocytes, as they exist to
propagate APs.
There are also hormone-containing cells that secrete atrial natriuretic
peptide (ANP).
o Most Purkinje fibers are seen in the subendocardial layer, which is part of the
endocardium.
The endocardium is the fibroelastic layer, containing simple squamous
epithelial cells.
All blood vessels have three layers (tunics) the intima, media, and adventitia, separated
by elastic lamina.
The tunica intima is made of simple squamous endothelial cells that form the basal
lamina.
o These endothelial cells allow for transcytosis, diapedesis, secretion of clotting
factors, maintenance of vascular tone, and movement of blood cells.
o Beneath these cells lies the subendothelial layer that creates loose connective
tissue.
o The internal elastic lamina separates the tunica intima from the tunica media.
The thickness of the tunica media varies. It contains helically-arranged smooth muscle
cells.
o These cells maintain muscle tone and allow for contraction of vessels when
required.
There are also some elastic fibers, collagen, and proteoglycans.
o In large arteries, the external elastic lamina separates the tunica media from the
tunica adventitia.
The tunica adventitia consists only of loose connective tissue, made of fibroblasts and
collagen.
o The vasa vasorum are seen in large vessels. Nervi vascularis mediate vascular
contraction.
Small vessels do not require vasa vasorum, as diffusion is sufficient for
nutrient transport.
Very large vessels (the aorta and its branches, common iliacs, and pulmonary trunk) are
elastic arteries.
o These vessels have thin elastic laminae (internal & external) and more than 40
smooth muscle layers.
o There are numerous elastic fibers. The tunica adventitia is also thin with many vasa
vasorum.
o Marfans syndrome refers to defective elastic fibers, increasing the likelihood of
aortic aneurysms.
Any named artery is probably a muscular artery (conducting artery), with 3-40 layers of
smooth muscle.
o They have thick elastic fibers (both internal and external) and few elastic fibers.
Arterioles only have 1-2 layers of smooth muscle, but they determine TPR and regulate
blood pressure.
o The internal elastic lamina is thin or absent, and there is never an external elastic
lamina.
o In some locations, there are metarterioles that form anastomoses (shunts) with
venules.
o

These are seen in skin (thermoregulation), erectile tissue, and the tips of
fingers and toes.
The carotid sinus is a baroreceptor on the internal carotid artery innervated by CN IX.
o The carotid body is at the carotid bifurcation. It measures CO32- and is innervated
by CN IX & CN X.
The aortic bodies are also chemoreceptors, though theyre innervated solely
by CN X.
Capillaries are the functional end of the CV system. Theyre a single layer of simple
squamous endothelium.
o The cells are fused by tight junctions. Their basal lamina associate with pericytes
(stem cells).
There are a large number of pinocytotic vesicles that facilitate diffusion of
nutrients.
o Continuous capillaries (type I) have no pores. Transport must be across the
endothelial cells.
These are found in muscle, lung, nervous, and connective tissues.
o The pores of fenestrated capillaries (type II) have diaphragms, except in the
renal glomerulus.
Rapid diffusion is simpler, but there is still an endothelial lining.
These are seen in the intestines, pancreas, kidneys, and endocrine glands.
o Type III capillaries are discontinuous. The basal lamina is incomplete with large,
open pores.
Found in the liver, bone marrow, spleen, and lymphoid organs, transport is
very easy.
Around 70% of blood volume lies in venules, as these have lower pressure and allow for
pooling.
o Postcapillary venules have a very thin endothelium with reticular fibers and
pericytes.
Larger venules will have smooth muscle cells, but these are uncommon.
o High endothelial venules are specialized to encourage diapedesis of leukocytes
from lymph nodes.
Small veins appear similarly to venules, though they have a smooth muscle layer.
o Medium veins have valves and thick adventitia. Theyre numerous & often parallel
muscular arteries.
The valves are simply folds of the endothelial cells of the tunica intima.
o Large veins also have valves and thick tunica adventitia. They have a large lumen
as well.
The largest veins (vena cavae) may have longitudinal smooth muscle in the
adventitia.
o In general, arteries have substantially thicker walls and smaller lumens than veins.
The largest change in pressure/speed of flow occurs at the level of arterioles due to
smooth muscles.
o Cross-sectional area is maximized at the capillary level, simply because of their
vast numbers.
The lymphatic system exists to carry away excessive extracellular fluid and bring it to
the venous system.
o They appear similar to veins. They have valves, are thin-walled, and have almost no
tunica media.
Even the largest lymphatic vessel, the thoracic duct, has virtually no
smooth muscle.

Cardiovascular Physiology Lecture w/ Dr. Myerburg 5 April 2011

The Topic of This Lecture Is: Electrical Activity of the Heart

 The fibrous skeleton of the heart is electrically silent. It just provides a scaffold for the
other structures.
o The specialized conduction system refers to the nodes, bundle of His, and
related fibers.
o Working muscles comprise the rest of the heart, powering compression of the
atria and ventricles.
Propagation of an electrical potential is contingent upon the stimulus reaching the
threshold potential.
o During an action potential, there is a brief moment where the cellular potential is >
0 mV.
Theres an imbalance of time in which Na+v and Cl-v channels are open. This is
quickly rectified.
The inside is positive with respect to the outside. This overshoot is the
reversal potential.
o This favors the stimulation of tissue in front of the impulse, so there is
regenerative propagation.
Thus, once a tissue is depolarized, tissues downstream are spontaneously
depolarized.
o The first part of a tissue to be depolarized is also the first part to be repolarized
(normally).
The heart consists of a low-resistance syncytium of cells linked longitudinally by gap
junctions.
o There are also lateral/transverse junctions, but these have slightly higher
resistances.
The plateau phase exists for electrical stability & mechanical opportunity (normal heart
rate is maintained).
o Conduction velocity of the upstroke is correlated with the stability & duration of the
plateau phase.
o This can be demonstrated by increasing the resting potential from -90 mV and
stimulating it.
Ion channels are typically tetrameric and attached to a modulator peptide and the
cellular cytoskeleton.
o The ion pore is specific for a particular ion and opens/closes in response to the
environment.
In an action potential, Na+v channels are open for a very short time, but allow a massive
influx of Na+.
o L-type Ca2+v channels are activated later (around -30 mV). They stay open much
longer.
o Again, the transiently-open K+Ve channels are responsible for reducing the reversal
potential.
Slow-opening K+Vs channels repolarize the cell, and eventually the L-type
Ca2+v channels close.
At about -90 mV, the K+Vs channels close and the K+IR channels open,
stabilizing the potential.
o There are also K+ATP channels that are closed when ATP is present. When ATP
dissociates, they open.
Recovery of excitability is voltage-dependent, based on the relative refractory period of
the cell.
o In order to get a second impulse to conduct, the cell must be at around -65 mV.
o The refractory period is NOT time-dependent, as the rate of repolarization can be
readily altered.
Physiologically, this is related to heart rate. The refractory period decreases
as HR increases.

Refractory periods vary in tissues. Purkinje fibers are ~250 msec; ventricular
muscles are ~170 msec.
Atrial tissue has a shorter time course of repolarization. Its APs appear similar
to a nerves.
o The epicardium has a shorter plateau than the endocardium due to a greater influx
of K+.
Because of this, repolarization paradoxically goes from the epicardium to the
endocardium.
For this reason, the T wave deflects in the same direction as the P wave &
QRS complex.
In the AV node, Na+ does not play a role in the upstroke. Instead, its slowly-activating Ltype Ca2+v channels.
o Here, recovery of excitability is dependent upon time, not voltage.
o Decremental conduction from the atria AV node; incremental from the AV node
Bundle of His.
Cardiovascular Physiology Lecture w/ Dr. Kerrick 5+6 April 2011
o

The Topic of This Lecture Is: The Cardiac Cycle

The lead II EKG reads from the right arm to the left leg. Its the one with the pretty P,
QRS, and T waves.
The P-R interval is the time of transmission from the AV node to the bundle of His.
o The Q-T interval is the period in which all ventricular cells are depolarized.
o Diastole is the period from the end of the T wave to the beginning of the R wave.
Between the T and P waves, the pacemaker cells are slowly depolarizing.
The P wave is the depolarization of the atria. A rise in atrial pressure (the a wave) is seen
immediately after.
o Ventricular pressure rises slowly in diastole as the chambers passive fill with blood.
A huge spike in ventricular pressure is seen after the R wave (ventricular
depolarization).
This rapid rise occurs in isovolumetric contraction, as all four valves
are closed.
o The incisura (dichrotic notch) is a small, transient rise in aortic pressure after
aortic valve closure.
This occurs shortly after the T wave, as the ventricles relax, decreasing their
pressure.
After the semilunar valve closes, there is a period of isovolumetric
relaxation.
o The c wave is caused by the AV valves bulging into the atria after ventricular
contraction.
The v wave rises slowly as the atria passively fill, until the AV valves open
after the T wave.
o Following opening of the AV valves, there is a period of rapid blood influx into the
ventricles.
There is then a period of diastasis (minimal filling) until the next P wave.
End-diastolic volume (EDV) is the amount of blood in ventricles just before
the R wave.
o During systole, blood is rapidly ejected from the ventricles until the aortic valve
closes.
The minimal amount of blood is end-systolic volume (ESV). EDV - ESV =
SV.
o S1 (lub) is heard during the QRS complex when the AV valves close and the
semilunar valves open.
After the T wave, when the semilunar valves close, S2 (dub) can be heard.
Pathologic sound: S3 is related to ventricular filling (normal in kids; heart
failure in adults).

Pathologic sound: S4 is associated with atrial contraction (P wave) and a stiff

ventricle.
EDV is the primary factor of CO. Its related to the difference between filling pressure &
ventricular pressure.
o Filling pressure is also termed preload, so blood flow in = (Preload
VP)/Resistance.
Cardiac function curves plot preload against CO. The curves shift up with
the addition of NE.
o Ventricular filling time is equal to the period of diastole (tdiastole), which is 1/(Heart
Rate tsystole).
A compliant heart allows more flow into the ventricles. C = V/P. It
decreases with age.
During diastolic filling, there is passive stretching of ventricular muscle until the AV valve
closes.
o After isovolumetric contraction, the ventricles are stimulated to contract; the
muscles shorten.
o Pressure rapidly increases as blood is ejected, then falls, and the aortic valve closes
again.
There is then isovolumetric relaxation. The AV valves open, and diastole
resumes.
o Ventricular volume (radius) is related to pressure and tension (length) via P = T/r.
Increasing tension or decreasing ventricular volume yields increased
pressure.
The biggest factor contributing to SV is Starlings Law, which is that increased EDV
begets a higher SV.
o This is based on a length-tension curve that incorporates resting and postcontraction tensions.
o A larger preload increases the resting tension of the heart by increasing muscle
length.
This allows the heart to pump more blood out with each beat.
o At a given afterload, cardiac muscle has the same post-contractile length
regardless of the preload.
So, the longer the muscle was before, the more contraction there is, and the
greater the SV.
o Afterload is the pressure that cardiac muscle must pump against, the systolic BP.
A higher afterload (hypertension) causes the muscle to have a longer postcontractile length.
o Sympathetic innervation (NE) causes more shortening at a given muscle length
(more contractility).
The functional result of this is a lower ESV at any particular EDV, and thus,
greater SV.
o SV is increased by higher filling pressure and by NE. Its decreased by higher
afterload (MAP).
Heart rate is decreased by the chronotropic effects of ACh and increased by
NE.
Again, NE increases heart rate (chronotropic) and cardiac contractility (stroke volume,
inotropic).
o It also decreases cardiac AP duration, minimizing the detrimental effect of high HR
on filling time.
It increases the rate of cardiac relaxation (lusitropic), for a similar reason.
o Again, filling time (tdiastole) is 1/(HR tsystole). As HR increases, tsystole decreases &
tdiastole increases.

Cardiovascular Physiology Lecture w/ Dr. Kerrick 6 April 2011

The Topic of This Lecture Is: The Heart as a Pump

ATP production of cardiac muscle is almost entirely aerobic, thanks to a high number of
mitochondria.
o Theres a high concentration of myoglobin to bind O2, so the heart is very sensitive
to O2 levels.
There is little glycogen and creatine phosphate. The anaerobic reserve is
quite low.
As such, any ischemia related to heart perfusion can cause rapid, irreversible
damage.
o About 25% of myocardial O2 consumption is basal metabolism; the rest is for muscle
contraction.
Isovolumetric contraction is half of that 75%, though the O2 use is dependent
on afterload.
o Stroke work is defined by the area of the pressure-volume curve seen earlier.
ATP usage is much higher when increasing pressure than when increasing
volume.
o Energy cost is the energy per beat, multiplied by heart rate (J/beat * beat/min).
The index of energy demand is the peak systolic pressure * HR.
Cardiac output can be measured by the Fick principle: Xtc = CO * ([X]in-[X]out), measured
via blood O2 levels.
o CO = Xtc / ([X]in-[X]out) = 250 mL O2/min / (200-150 mL O2/L of blood) 5 L blood/min
Cardiac contractility is normally estimated by echocardiography (ultrasound), looking
at cardiac geometry.
o Cardiac angiography can estimate it via injection of a radiopaque dye, then using
radiographs.
o Radionuclide ventriculography measures changes in radioactivity during
ventricular contraction.
o All of these methods provide info regarding ejection fraction (EF) via SV and EDV,
as EF = SV/EDV.
Increasing contractility will shift the pressure-volume curve to the left at any
afterload.
The curve will also get steeper, such that higher afterloads have diminished
effects.
Cardiovascular Physiology Lecture w/ Dr. Landowne 6 April 2011
The Topic of This Lecture Is: Mechanical Activity of Cardiac Cells

After Ca2+ enters the cells via DHP receptors (L-type channels), the ions bind to
ryanodine receptors.
o These receptors release Ca2+ from the sarcoplasmic reticulum. About 80% of the
Ca2+ is from this.
This is different than in skeletal muscle, in that the strength of contraction
can be varied.
Ca2+ binds to cardiac troponin-C, causing contraction. The ions then
dissociate.
o SERCA is an ATPase pump that pumps Ca2+ back into the sarcoplasmic reticulum
(again ~ 80%).
There is also a surface Ca2+-ATPase pump (5%) and a Na+/Ca2+
exchanger (15%; 3 Na+ per Ca2+).
o Binding of NE to -receptors phosphorylates and activates both DHP and ryanodine
receptors.
This increases the contractility of the heart (positive inotropic effects).
NE cAMP PKA also phosphorylates phospholamban, increasing SERCA
activity.

This is the lusitropic effect mentioned earlier; the rate of relaxation is

increased.
In isometric contraction, tension increases while length is unchanged.
o The strength of this contraction is based on the amount of overlap between actin
and myosin.
Passive tension (resting tension) increases as the length of the muscle
increases.
But, maximal overlap occurs at an intermediate length. The active tension
curve rises & falls.
o In a healthy heart, passive stretch is sufficient to reach the tension required for
contraction.
In an isotonic contraction, muscle length shortens in order to maintain tension.
o Physiologically, the heart deals with afterload and utilizes both isometric and
isotonic contractions.
o Isometric contraction is first. A 1g weight is lifted against gravity; the 2g weight is
on the ground.
To lift the 2g weight, tension must be increased without changing the muscle
length.
When the 3g of tension is reached, the muscle is able to shorten and lift both
weights.
However, it is not able to contract as much as it could when there was
only 1g.
o The 1g weight in this is preload (EDV). The 2g weight is the afterload (aortic
pressure; MAP).
The isometric phase is during isovolumetric contraction.
Increasing contractility via NE affects both isometric and afterloaded contractions.
o There is a greater peak isometric tension at any given EDV (preload).
o The muscle is also able to shorten more at any particular afterload, so SV increases.
Wall tension is equal to pressure * radius (T = P*r). This is Laplaces law, using the
ventricles as cylinders.
o This explains why tension increases as they fill with blood (higher radius), for
pressure is constant.
o Afterload is really the tension in the ventricular wall as it compresses against aortic
pressure.

Cardiovascular Physiology Lecture w/ Dr. Landowne 7 April 2011

The Topic of This Lecture Is: Normal Electrocardiograms

ECGs utilize three primary leads that allow for visualization of the electrical events of the
heart.
o These events are: atrial depolarization quiet period passage through the AV
node
septal depolarization ventricular depolarization synchronized
ventricular repolarization
o The standard leads are typically the right arm, left arm, and left leg (foot). The right
leg is a ground.
These form six limb leads. Three of these are unipolar, and three are bipolar.
Bipolar leads: RA(-) LA(+) is lead I. RA(-) LF(+) is lead II. LA(-)
LF(+) is lead III.
These vectors form Einthovens triangle & respond differently to
electric potentials.
In the unipolar leads (aVR, aVL, & aVF), the center of the heart is the
negative end.
aVR bisects leads I & II. aVL bisects leads I & III. aVF bisects leads II
and III.
o Six other leads are placed on the chest. V1 & V2 are at the sternal borders of the 4th
intercostal space.
V4 is in the 5th space at the midclavicular line; V6 is in the 5th intercostal at
the midaxillary line.
V3 and V5 are placed between those, also within the 5th intercostal
space.
The chest leads use the limb leads as the negative ends. They measure
activity in the horizontal plane, while the limb leads measure activity in the
vertical plane.
In any lead, depolarization parallel to the leads orientation, from (-) to (+) causes an
upward deflection.
o If the depolarization is perpendicular to the leads orientation, there is no response.
o If its at an angle between those, there is a deflection with lower amplitude.
The standard EKG has an x-axis of 25 mm/sec, with each small box being 1 mm and 40
msec.
o On the y-axis, every mm responds to 0.1 mV. Like the x-axis, theyre grouped into
sets of five.
o The EKG trace also includes intervals (times) and segments (levels).
The intervals we care about are the PR and QT intervals, which include the P
and T waves.
The PR and ST segments are the flat parts between waves. They should be at
the same level.
The QRS complex has a naming system, based on which deflections are seen on the
paper.
o The first download deflection is always Q. The upward deflection is R; the second
downward one is S.
Different leads will appear differently, so missing waves do not signify a
disease.
If theres a second upward deflection (R), thats a sign of an AV bundle block.
o The first part of the QRS complex is septal depolarization, which moves roughly
from right to left.
Lead I shows a strong downward deflection. Leads II moves slightly down. This
is the Q wave.
However, leads III shows a slight upward deflection, so it does not have a Q
wave.

Next, the whole right ventricle depolarizes, moving down and to the left, parallel to
lead II.
All three leads show upward deflections (R wave). Lead II is equivalent to
lead I plus lead III.
o When the depolarization is nearly complete, it moves slightly up and to the left.
This makes a positive deflection in lead I and a slight negative deflection in
lead II (S wave).
The depolarization goes from (+) to (-) on lead III, so that has a strong
downward deflection.
o There is then a period of quiescence before repolarization, so everything is at
baseline.
Lead I does not have a T wave. Lead III does not have a Q wave. Lead II has
all three.
The angle of the heart is measured with 0 on the right side and +90 being on the
bottom.
o The electrical axis of the heart uses aVL as -30, lead I as 0, lead Ii as +60,
and lead aVF as +90.
Whichever lead has the strongest upward deflection for the R wave
determines the axis.
o The normal axis in an adult is between 0 and +90, although 0 -30 isnt
necessarily a problem.
An infarct of the left ventricle can lead to right axis deviation, and vice
versa.
Similarly, left ventricular hypertrophy cause a left axis deviation, and
vice versa.
Bundle blocks can also lead to deviation of the hearts axis, as can
mechanical deviation.
o Determining the angle involves looking at the net deflection of the QRS complex.
So, if aVF has no net deflection, the heart could be presumed to be at 0.
o

Cardiovascular Physiology Lecture w/ Dr. Landowne 11 April 2011

The Topic of This Lecture Is: Peripheral Vascular System

Cardiac output can be measured with ultrasound, via the velocity time integral, crosssectional area, and HR.
o The velocity and area refer to blood passing through the aortic valve.
Flow (Q, mL/sec) = mean velocity (cm/sec) * area (cm 2).
o Laminar flow treats fluids as concentric rings that expand to fill the radius of the
vessel.
Blood flows more rapidly at the center than it does near the wall due to
friction.
The velocity is proportional to distance (r2), as is area (r2), so resistance is
proportional to r4.
o Turbulent flow occurs if blood is too viscous, or if valves are insufficient or
regurgitant.
It is also seen if the radius of a vessel rapidly increases (like blood entering a
ventricle).
Again, Q is equal to pressure change over resistance (P/R), so P = Q * R, where R is
(/8L)*r4.
o In vessels, the pressures being referred to are inlet and outlet pressure.
o I have no idea if this is important, but 1 mmHg = 1.37 cm H2O. Mercury is heavier
than blood.
Circulation does not consist of a single tube, obviously. Vascular resistance functions in
series and in parallel.
o Pipes in series have the same flow, but different resistances, so the pressure drop
across each varies.
Rs is equal to Rn, so adding more vessels invariably increases resistance.
o However, when in parallel, the total resistance is less than any vessels individual
resistance.
1/Rp = (1/Rn) This equation for TPR relates to flow through all of the
systemic organs.
The pipe with the lowest resistance gets the most flow, and P doesnt
change.
Another equation for CO is MAP/TPR, which is thus equal to HR*SV.
In the arterial system, flow velocity drops from 500 mm/s in the aorta to 0.5 mm/s in the
capillaries.
o This is primarily a product of the branching of the arterial system (same flow, but
larger area).
Most of the bodys blood (60%) is held in the veins, and about 12% is in the
arteries.
o Blood pressure is pulsatile in the aorta and larger arteries. It is not evident in the
arterioles.
The pulsatile pressure is due to the wave-like nature of the blood flow from
the heart.
The pulse pressure is larger in arteries as the waves crash into the
arterioles.
o There is a huge pressure drop (100 mmHg 25 mmHg) in the arterioles due to
decreased radius.
In capillaries, the pressure drop from 25 mmHg to 0 mmHg drives blood flow toward
venules.
o There are also transmural pressures (hydrostatic and osmotic) that well talk
about later.
o Arteriolar constriction increases the pressure drop and raises arterial pressure.
It also decreases the pressure change for capillaries.

 All blood vessels have compliance, measured as the volume change for a given change in
pressure (V/P).
o Veins have a substantially higher compliance than arteries, so a small P greatly
alters volume.
o Physiologically, V is SV and P is the pulse pressure (Ppulse = Psystolic Pdiastolic).
Blood pressure is measured by inflating cuff pressure beyond arterial pressure, which halts
arterial flow.
o When cuff pressure is decreased, blood is allowed to flow again. The turbulent flow
can be heard.
o This turbulent flow can be heard until cuff pressure drops low enough to allow for
laminar flow.
The point at which turbulent flow is heard is systolic BP. When it stops,
thats diastolic BP.
o MAP is measured as Pdias + Ppulse/3. Pulse pressure provides information regarding
SV; MAP = CO*TPR.
The reason for this equation is that we spend thrice as much time in diastole
than systole.
Ppulse increases with age because elderly people have decreased compliance.

Cardiovascular Physiology Lecture w/ Dr. Mr. Barrett 12 April 2011

The Topic of This Lecture Is: Capillaries and Lymphatics

In a capillary bed, blood passes through many parallel capillaries, connected by

metarterioles.
o Pericytes contain smooth muscle and act as precapillary sphincters that can
redirect flow.
o When pericytes contract, they effectively shut off blood flow to the associated
capillary.
Thromboxane can stimulate contraction. Irreversible contraction occurs
after ischemia.
Conversely, NE and low pH stimulate the relaxation of pericytes.
o Capillaries can be bypassed via arteriovenous anastomoses (in the skin, this
confers warmth).
Substances cross capillary walls via four major pathways.
o O2, CO2, and permeable solutes are able to freely diffuse across the membranes.
o Ultrafiltration holes permit passage of H2O and small solutes (ions, amino acids,
sugar, urea, etc).
These can move in the spaces between endothelial cells that form tight
junctions..
The inner side of endothelial cell contains many glycans, like heparin, that
form a glycocalyx.
These block the passage of large proteins and prevent RBCs from
sticking to the wall.
o Receptor mediated transporters (transferrin, etc.) and active transporters (e.g.
glucose) also exist.
The control of fluid exchange through ultrafiltration holes is extremely important.
o Hydrostatic pressure favors movement of fluid into the interstitium. Oncotic
pressure () opposes it.
The filtration rate is equal to K * [(Pc Pi) - (c i)], which is Starlings
equation.
o Capillary pressure is measured by a micropipette that sucks up RBCs. Its between
25-45 mmHg.
Hydrostatic pressure steadily decreases from the arteriolar to the venular end
of a capillary.
o Oncotic pressure is due to the fact that there are very few proteins in the
interstitium.
This pressure is relatively stable throughout the distance of the capillary.
It does, however, rise slightly when water is filtered out of the capillary.
o Arteriolar end: P 37 mmHg & 28 mmHg (+11). Venular end: P 17 mmHg
& 25 mmHg (-8).
Excessive filtration increases interstitial volume, which increases Pi. That acts to prevent
edema.
o There is a safe range of hydrostatic pressure in which these feedback mechanisms
work.
o The interstitium has tissues that act as a gel, resisting collapse due to dehydration.
The mechanical strength of collagen fibrils resists expansion in an attempt to
avoid edema.
o In right heart failure, venous pressure rises, and hydrostatic P always exceeds .
There is net filtration (edema). This is also seen at low blood protein levels
(decreases c).
It is not seen in arterial hypertension because of the pressure drop across
arterioles.
o Increased capillary permeability to proteins can be due to excessive bradykinin
or histamine levels.

CIQ inhibitors lead to tissue proteases that convert kininogen to bradykinin.

Bacterial sepsis increases histamine. Both mechanisms reduce c, leading to
net filtration.
This type of inflammatory-mediated edema is termed angioedema.
o Inadequate lymphatic drainage can also lead to edema, perhaps after surgical
lymph node removal.
Understanding the causes of edema is extremely important.
Lymph capillaries are blind-ended pouches permeable to both fluids and proteins
(including erythrocytes).
o They are made of endothelial cells similar to normal capillaries. They are held open
by fibrils.
These fibrils are stretched when interstitial volume is increased, opening the
lymph vessels.
Valves act to push fluid away from the lymph capillaries and toward the
subclavian vein.
o Lymphedema can be identified by injecting radiolabeled albumin and seeing where
it accumulates.
Angiogenesis is due to proliferation of endothelial cells and pericytes from the tips of
capillaries.
o As tumors become hypoxic, they release VEGF, other growth factors, angiopoitin-I,
H+, and NO.
o Matrix metaloproteases digest a pathway into tissues, allowing for migration of
cells.
These tubes form and come together as capillary loops, eventually making
tight junctions.
As these loops mature, their permeability to proteins is reduced.
o Intrinsic factors that oppose angiogenesis include endostatin, angiostatin, IFN-,
and more.
Drugs that inhibit it include anti-VEGF antibodies and thalidomide.
o Macular degeneration involves angiogenesis, as immature blood vessels are
excessively permeable.
The retina is then lifted away from the choroid due to proteins and H 2O.
o Angiogenesis also contributes to inflammation-induced bone loss in arthritis.

Cardiovascular Physiology Lecture w/ Dr. Kerrick 13 April 2011

The Topic of This Lecture Is: Venous Return

As a rule of thumb, central venous pressure is equivalent to cardiac filling pressure,

a product of EDV.
o As cardiac filling pressure increase, as does stroke volume (on a parabolic curve).
o The peripheral venous compartment is a low pressure reservoir (7 mmHg) with
high compliance.
Most of the bodys blood is stored there before going to the vena cavae and
right atrium.
o The central venous compartment (vena cavae & atrium) stores little blood and
isnt very compliant.
Venous return is related to the difference in pressure in the peripheral and central
venous compartments.
o Since the peripheral pressure is a normally at 7 mmHg, Pcv determines the filling
pressure.
Pcv affects the left heart, since both sides of the heart have equal output.
Filling pressure of the right heart is thus proportional to filling pressure of the
left heart.
Most importantly, increases in Pcv decrease venous return. If Pcv Ppv, theres
no return.

Peripheral pressure can be increased by blood volume or sympathetic venous

tone.
This will increase venous return for any given Pcv, and more pressure is
needed to stop flow.
In this way, the venous function curve is shifted upward (and to the
right).
The venous function curve is shifted to the left by hemorrhage, severe
sweating, & diarrhea.
It is shifted to the right by transfusion, fluid retention, or transcapillary
reabsorption.
Increasing central venous pressure increases cardiac output (Starling Law), but decreases
venous return.
o As such, the body reaches a balance, with P cv being around 2 mmHg and CO being
around 5 L/min.
Central venous pressure must be at a value where CO is equal to venous
return.
o Sympathetic activity shifts the cardiac function curve to the left and the venous
return curve right.
o All changes in cardiac output are caused by a shift in one of these curves, or both.
CO and venous return always stabilize at the level where the curves intersect.
For example, after hemorrhage, Pcv decreases to about 1 mmHg, so there is a decrease in
filling pressure.
o This is evidenced by a decrease in venous return and stroke volume (CO) by
Starings Law.
o Sympathetic activity raises heart rate, and CO rises to 4 L/min. Pcv must decrease to
0 mmHg.
o The SNS then causes venous constriction, raising Pcv to 1 mmHg and CO & venous
return to 5 L/min.
A depressed cardiac function curve and/or a right-shifted venous function curve leads to
higher Pcv.
o The converse is true for low Pcv, but its almost always a left-shifted venous function
curve (LSVFC).
Pcv can be estimated on a person non-invasively by changing their posture and looking at
jugular veins.
o The veins should cease pulsating as the head is tilted forward.
If they continue to protrude while the person is a more upright position, Pcv
must be high.
o A flow-directed venous catheter can be inserted into a pulmonary arteriole and
deflated.
The wedge pressure measured there is a good measure of left ventricular
filling pressure.
o

Cardiovascular Physiology Lecture w/ Dr. Dahl 13 April 2011

The Topic of This Lecture Is: Control of the Vascular System

Blood flow is important for delivery of O2 and nutrients, removal of CO2 and H+, and
balancing ions.
o Perfusion of organs, including the heart, can be vastly increased when needed by
vasodilation.
The exceptions to this are the CNS & kidneys, which are normally nearly
maximally perfused.
Interestingly, the largest increase in activity is seen when the salivary glands
are stimulated.
o The extremely high perfusion rate of the kidney is matched by the adrenal and
thyroid glands.
Most regulation of blood perfusion occurs at the level of arterioles, with 1 layer of smooth
muscle.
o Metarterioles have similar sizes, but they are incompletely enveloped by smooth
muscle.
At rest, blood flows through a preferential channel that is slightly larger than true
capillaries.
o When demand is increased, precapillary sphincters open, giving access to more
capillaries.
o Some tissues, like the dermis, have arteriovenous anastomoses.
Gap junctions connect smooth muscle and endothelial cells, assisting control of the
contractile state.
o While not important for the passage of NO, they are required for movement of
EDHF.
o Nervous innervation goes to smooth muscle (NE), and also to endothelial cells
(ACh).
Yes, in skeletal muscle arterioles, there are sympathetic cholinergic fibers.
2+
The Ca required for smooth muscle contraction enters by voltage (VOC), storage (SOC),
or receptors (ROC).
o Ca2+ influx due to voltage or ligands stimulates Ca2+ release from the sarcoplasmic
reticulum.
o For vascular smooth muscle, chemomechanical coupling with NE on 1
receptors, leading to intracellular IP3 release, is more common than
electromechanical coupling.
Maximal vasodilation is achieved by CGPR and epinephrine binding to 2 receptors
(Gs).
o This hyperpolarizes the cell by activating K+ channels and increases cAMP and PKA.
The latter causes depletion of Ca2+ via the Ca2+-ATPase and the Na+/Ca2+
exchanger.
The IP3 receptor and MLK may also be inhibited.
o NO released from endothelial cells stimulates cGMP, and that activates PKG.
That activates MLC phosphatase, inhibits IP3 receptors, and hyperpolarizes
the cell via K+.
Venous tone is maintained by passive distension and external compression, rather than
basal tone.
o While both arteries and veins have sympathetic innervation, arteries use more local
vasodilators.
Vasodilators include CO2, lactic acid, H+, K+, NO, CGRP, NO, ATP, adenosine, histamine,
and bradykinin.
o CO2, lactic acid, H+, and K+ are produced at higher levels when cells are very active.
o Adenosine is either made directly or produced when ATP is broken down
extracellularly.

Histamine is produced by mast cells and increases capillary permeability along

with dilation.
Vasoconstriction agents include NE, angiotensin-II, ADH, and endothelins (made in
response to injury).
o Epinephrine causes vasodilation at low, circulating doses, but constriction at high
concentrations.
This is because Epi normally stimulates 2 receptors, but can activate 1 at
high doses.
Parasympathetic fibers innervate the nodes of the heart, but not the myocardium.
o They are also required for the constriction of blood vessels on external genitalia for
erection.
Sympathetic cholinergic fibers are seen on skeletal muscle arterioles and in the adrenal
medulla (NE & Epi).
o Epi increases cardiac output (1) & decreases TPR (2), raising systolic BP and
lowering diastolic BP.
o NE has little cardiac effect, but raises TPR (1). This raises MAP, unlike Epi.
Angiotensin-II (A-II) is formed from angiotensinogen after processing by renin and ACE.
o It acts on the adrenal cortex to increase aldosterone. Along with direct actions on
the proximal tubules of the kidney, this decreases Na+ and H2O excretion, increasing
blood volume.
A-II acts on the hypothalamus to increase thirst, and drinking raises blood
volume as well.
o A-II also acts on peripheral arterioles as a vasoconstrictor, increasing TPR and
raising MAP.
o The actions of A-II can be blocked by ACE-inhibitors and by A-II receptor
blockers (ARBs).
The vasodilator hypothesis explains that local vascular control exists to ensure removal
of metabolites.
o Since increased activity yields higher metabolite concentration, vasodilation is
necessary.
o The O2 demand hypothesis is that hypoxia prevents the contraction of
precapillary sphincters.
Regardless of the explanation, activity results in active hyperemia (increased blood
flow).
o Also, transient ischemia or occlusion causes a short period of reactive hyperemia.
o Active hyperemia is best explained by the O2 demand hypothesis.
Reactive hyperemia is best explained by the vasodilator hypothesis.
Whatever.
Purinergic receptors for ATP on endothelial cells raise Ca2+ levels, stimulating eNOS to
produce NO.
o ATP is released by erythrocytes (and endothelia cells) in response to shear stress
and hypoxia.
o The ATP binds to P2Y receptors, and NO acts to relax precapillary sphincters and
increase perfusion.
o Human RBCs & myocardial endothelial express pannexin-1, a large channel that
permits ATP release.
Within a range of MAP, the kidneys can maintain a fixed flow rate for its perfusion. The
CNS does this too.
o If there is a sustained increase in arterial pressure, blood flow increases, then drops
to a steady state.
The two hypotheses for autoregulation of blood flow are the metabolic theory and the
myogenic theory.
o The metabolic theory is based on the fact that flow washes out the vasodilatory
substances.
o

Smooth muscles rapidly adapt to stretch. Contraction is mediated by

mechanosensitive channels.
They will only fire at a slightly increased rate. This is the myogenic theory.
Arterioles in skeletal muscle have much more basal tone than those in skin and the gut.
o During moderate exercise, large perfusion increases are seen in the heart, skeletal
muscles, and skin.
o Low concentration infusions of Epi cause vasodilation in skeletal muscles and
constriction in the skin.
This is due to the higher volume of 2 receptors in muscle arterioles.
An infusion of a high concentration of Epi causes significant vasoconstriction
(1) in both.
An infusion of any concentration of NE has the same effect.
o Metabolic dilation occurs prominently in skeletal muscle arterioles, but not
elsewhere.
The heart, skeletal muscle, and brain are mainly under metabolic vascular control.
o Vascular control of the kidneys, skin, and gut is mediated primarily by the nervous
system.
Control of coronary blood flow is mainly by adenosine released from myocardial cells,
along with ATP.
o The neural influences on the coronary arterioles are at 2 receptors, not 1.
o Coronary arterioles are embedded in ventricular muscle, so they are subject to
pressure.
The right heart is able to receive perfusion during systole, as it has lower
pressure.
The left side, however, can only be perfused during diastole. Flow is reversed
during systole.
o Also, the endocardial cells deal with much higher pressure than the epicardial ones.
The most likely place for a myocardial infarction is the endocardium of the
left ventricle.
Contraction of skeletal muscle also compresses blood vessels, but the contraction is not in
sync.
o Because of that, any interruption of perfusion is very transient.
Excessive metabolic demands of skeletal muscle can result in cramping.
o Collateral vasoconstriction shunts blood toward active muscles and maintains
peripheral resistance.
o Cholinergic sympathetic fibers result in vasodilation in anticipation of exercise.
Cerebral blood flow is essentially constant, regardless of physical activity.
o There is pronounced autoregulation of perfusion by metabolic factors with minimal
neural influence.
Blood pressure must drop below 60 mmHg before the brain cannot
compensate.
Cerebral blood flow is mediated primarily by changes in PCO2, not PO2.
o To note, particular parts of the brain receive more blood flow at different times.
At rest, the guts receive about a quarter of cardiac output, but after eating, this can
double.
o Inhibition of the sympathetic nervous system increases perfusion, primarily to
remove metabolites.
o Activating the SNS causes blood to shift to the central venous pool, increasing CO.
A significant amount of blood volume is stored in the splanchnic system, so
this is important.
Perfusion of the kidneys decreases slightly with moderate exercise and drastically at
maximal exertion.
o The autoregulation of the kidney is the Bayliss effect, which is almost exclusively
myogenic.
o

Maximal exertion & pronounced vasoconstrictor activity can limit filtration and
damage the kidneys.
Blood flow to the skin increases sharply in moderate exercise, but maximal exertion
decreases its perfusion.
o Changes in flow are mainly for temperature regulation. Reduction conserves heat,
and vice versa.
Flow can be decreased to 5% or increased by up to 10 times, so theres a
huge range.
o Perfusion is required for production of sweat, as H2o is pulled out by the glands.
The arteriovenous anastomoses allow for greatly increased perfusion at low
resistance.
The blood enters into superficial vessels that allow heat to dissipate by
convection.
I dunno where else to put this. Hydralazine is a drug that increases cGMP, like NO. Its an
anti-hypertensive.
o

Cardiovascular Physiology Lecture w/ Dr. Kerrick 15 April 2011

The Topic of This Lecture Is: Regulation of Arterial Pressure

Arterial pressure is equal to CO * TPR, mediated primarily by sympathetic input to the

heart and arterioles.
o There are baroreceptors in the carotid sinus and aortic arch. They send info to the
medulla (NST).
o When MAP is elevated, the rostral ventrolateral medulla is inhibited & the
raphe nucleus is excited.
The RVLM normally activates preganglionic sympathetic nerves; the RN
inhibits them.
The result of both pathways is release of tonic sympathetic innervation
of the CVS.
The preganglionic parasympathetic fibers from the nucleus ambiguous are
also activated.
The baroreceptors are stretched by pressure. They have steady and pulsatile (rate of
change) components.
o The steady component is most sensitive around 120 mmHg; the pulsatile one is
closer to 100 mmHg.
o Increased baroreceptor activity decreases sympathetic nerve activity from the
medullary centers.
At low MAP, neural activity is high, and there is a strong effector response.
Baroreceptors adapt very quickly, so they are not able to effect long term
changes.
Figure 9-3 in the Lange book actually summarizes everything wed ever need to know
about this lecture.
o Everything that follows this describes what happens after hemorrhage.
Sympathetic activity increases, yielding increased arteriolar and venous tones, cardiac
contractility, and HR.
o Vasoconstriction increases TPR and capillary pressure, which decreases fluid
reabsorption.
Increased blood volume, along with the venous tone, increases peripheral
venous pressure.
o Increased Ppv will increase Pcv. Higher filling pressure and the greater contractility
raise the SV.
HR is raised by the SNS and the lack of PSNS innervation, so that increases
CO as well.
o With both cardiac output and total peripheral resistance increased, MAP rises in
response.
The MAP set point of the medullary center can be affected in a number of manners.
o Exercise and alarm raise the set point. The former is likely due to transient ischemia
in static exercise.
Raised intracranial pressure, low PO2, or high CO2 (ischemia) do too. This the
Cushing reflex.
The Cushing reflex is characterized by paradoxically raised MAP
despite bradycardia.
A drop in Pcv raises it due to a baroreflex. Cutaneous pain (mild) also raises it.
o Vasovagal syncope, severe pain, and increased P cv will lower the set point.
o If MAP and sympathetic activity (like HR) change in the same direction, its due to
set point changes.
Conversely, if the changes oppose each other, the cause is peripheral, not
central.
The neural operating curve (MAP vs. sympathetic activity) and the effector curve
(sympathetic activity vs. MAP) can be plotted with each other by switching the axes of the
neural operating curve.

The effector curve is rises almost linearly. The neural curve falls sharply, but
plateaus at 100 mmHg.
o If something causes a drop of MAP, the effector curve is shifted down and to the
right.
Theres a transient loss, but the effector curve intersects with the neural near
100 mmHg.
o An influence that raises the set-point shifts the neural operative curve up and to the
right.
Sympathetic activity rises slightly to meet the new curve, and MAP rises a bit.
o If both influences occur simultaneously, MAP is still increased due to the neural
curves plateau.
Long-term blood pressure is regulated not through the baroreceptor reflex, but through
blood volume.
o Recall that a drop in blood volume lowers Ppv, shifting the venous function curve
to the left.
Pcv decreases, lowering filling pressure (and SV), so CO and MAP drop as well.
Similarly, increasing MAP increases urinary output, causing a drop in blood volume.
o This is done by decreasing renal sympathetic activity and increasing glomerular
capillary pressure.
The lack of sympathetic activity lowers arteriolar constriction (more
hydrostatic pressure).
That increases the glomerular filtration rate, which lowers the release of
renin.
o Less renin leads to less A-II and less aldosterone. Less Na+ and H2O are reabsorbed
in the tubules.
Greater glomerular filtration and less reabsorption increase the urinary
output.
o Very small increases in MAP cause HUGE increases in urinary output if fluid intake
remains the same.
The curve is basically a straight line rising asymptotically if MAP exceeds 120
mmHg.
The body tries to keep at MAP at a level that ensures that fluid intake equals
urinary output.
Other hormones, like ANF and ADH, play a role in fluid levels as well.
o

Cardiovascular Physiology Lecture w/ Dr. Kerrick 19 April 2011

The Topic of This Lecture Is: Cardiovascular Response to Physiological Stress

Changes in respiration affect the cardiovascular system, such that inspiration increase
cardiac output.
o A drop in intrathoracic pressure decreases Pcv, leading to increases in venous
return and filling pressure. More cardiac filling increases SV, CO, and MAP, so
arterial baroreceptors fire faster.
SV is also increased by reduced pulmonary vascular resistance (less
afterload).
The cardiopulmonary baroreceptors fire quickly as well, affecting the
medullary CV centers.
Stretch receptors on airways inhibit vagal activity to the SA node, decreasing
HR.
o The baroreceptor reflex acts to increase PSNS activity and decrease sympathetic
activity.
HR and contractility decrease, along with venous constriction and TPR.
o Fun fact: yawning greatly decreases intrathoracic pressure; coughing fits increase it.
The Valsalva maneuver increases intrathoracic pressure, with
compensatory changes after.
Ones posture also affects the CV system, since pressure is greater at the feet than it is at
the heart.
o In recumbency, pressure at the heart is 100 mmHg and pre-arteriolar pressure is 95
mmHg.
In the capillaries, it drops to 25 mmHg. Venous pressure is 5 mmHg (and 0
mmHg at the IVC).
o When standing, arterial pressure at ones feet can be as high as 185 mmHg, just
due to gravity.
Pressure in the capillaries is around 115 mmHg, increasing filtration and
causing edema.
The decreased blood volume lowers Pcv, which decreases SV and so on.
Venous pressure is substantially increased (95 mmHg), and its compliance
leads to pooling.
o Postural differences are dealt with by sympathetic vasoconstriction and the
skeletal muscle pump.
The vasoconstriction has a very mild effect. The skeletal muscle pump is
where its at.
Vasoconstriction is mediated by a raised set point in the medullary CV
centers.
o The sympathetic nervous system also raises HR and SV.
Long-term, increased sympathetic activity causes fluid retention.
The pump decreases capillary pressure, & venous blood is literally pumped
back to the heart.
Shortly after contraction, arterial pressure is still high, but P pv is pretty
low.
o Despite reflexive responses, SV and CO remain slightly decreased while standing.
However, they are successful in raising HR and TPR, as those are unaffected
by standing.
In strenuous exercise, CO increases up to 18 L/min, HR goes as high as 160 bpm, ejection
fraction goes from 60% to 80%, systolic BP rises to 150 mmHg, but diastolic BP and Pcv do
not change.
o Pcv doesnt change, as the cardiac function and venous function curves both shift up
and left.
o Blood flow increases greatly to the heart, skin, and (most importantly) to skeletal
muscle.

Cerebral blood flow remains constant, while the kidneys and guts get to
of normal.
Exercise increases skeletal muscle metabolism, and local metabolites cause vasodilation.
o That leads to a decrease of TPR, so arterial baroreceptors slow their firing rate.
o The cortex, skeletal muscle chemoreceptors, and those baroreceptors act on the
medullary centers.
The set point for MAP is increased, so theres an increase in CO and venous
and arterial tone.
o Heat production from skeletal muscle affects the hypothalamic temperature
centers.
Cholinergic sympathetic nerves are activated, increasing sweat gland activity
(dissipates heat).
Local metabolites and decreased sympathetic activity decrease sympathetic
tone to the skin.
o Through these mechanisms, blood flow decreases to systemic organs but increases
to the skin.
o The sympathetic response is needed to raise MAP despite a drop in TPR from
muscular vasodilation.

Cardiovascular Physiology Lecture w/ Dr. Webster 22 April 2011

The Topic of This Lecture Is: Metabolism of the Heart

The heart has a very small ATP reserve, so synthesis of ATP is efficiently correlated with
utilization.
o Cardiac cells produce ATP from glucose & FFAs, maintaining high levels to increase
available energy.
o FFAs are the preferred source, but oxidation obviously requires O2. Thus, ischemia is
a bad thing.
Without O2, FFAs accumulate in the cytosol and damage cell membranes as
detergents.
The production of pyruvate from glucose is inhibited by this cellular damage.
A human heart can survive for around 4 hours during an ischemic episode.
o Under normal resting conditions, 95% of energy produced for the heart is from FFAs.
More carbohydrates are utilized as energy demands are increased, as in
exercise.
For immediate energy supply, ATP & creatine are converted to phosphocreatine & ADP
by creatine kinase.
o Phosphocreatine can then be converted back to ATP in different parts of the cell.
Two molecules of ADP can be acted upon by adenylate cyclase to form ATP
and AMP.
o By these processes, ATP formed in the mitochondria can be carried to myofilaments
for contraction.
Activity of the enzymes used for conversion and transport is correlated with
cardiac demand.
o Fatty acids are transported to the heart as soluble triglycerides, mostly LDLs and
VLDLs.
FFAs must be extracted for use. If that is not efficient, there are
cardiomyopathies.
FFAs are not water soluble. Molecules must go from the blood to cells, then into the
mitochondria.
o Cells require 100 nmol/min/gram at rest. The mitochondria suck FFAs in through
glycoproteins.
o To go through capillaries, FFAs are bound to albumin before diffusing across the
endothelium.
FFAs within triglycerides (VLDLs) must first be acted upon by lipoprotein
lipase.
o FFAs bind to FABP to enter the sarcoplasm, where they generate acyl-CoA.
A fatty acid translocase (FAT/CD36) and a fatty acid transporter also
assist in movement.
o Carnitine is needed for transport of long-chain FAs across the inner mitochondrial
membrane.
It forms a complex with acyl-CoA and is moved by CAT translocase.
Carnitine crosses the outer membrane by CPT1 and back across the inner
membrane by CPT2.
Once in the mitochondrial matrix, the FFA is still saturated with acyl-CoA.
o Three enzymatic reactions convert saturated acyl-CoA to acetyl-CoA, FADH2, H2O,
and NADH.
o Acetyl-CoA then enters the citric acid cycle, forming reducing equivalents for the
ETC.
NADH and FADH2 act at different complexes to allow for -oxidation of the
FFAs. Yay! ATP!!
Low-carb diets are based on the idea that the heart prefers fats to glucose, but thats
hogwash.

In the presence of O2, pyruvate can be converted to acetyl-CoA by pyruvate

dehydrogenase (PDH).
During ischemia, lactate is formed instead, which eventually leads to
acidosis.
o So, both pyruvate dehydrogenase and -oxidation generate the same intermediate,
acetyl-CoA.
If theres too much acetyl-CoA, citrate is formed, and that goes back to the
cytoplasm.
o Citrate activates malonyl-CoA, which blocks the transport of fatty acyl-CoA to the
mitochondria.
Citrate also inhibits PFK, stopping glycolysis (there will be less pyruvate).
o Conversely, -oxidation activates PPAR, which inhibits PDH (via PDH-kinase) and
malonyl-CoA.
These processes allow for glucose sparing, but theyre inhibited by
adrenaline and insulin.
o AMP protein kinase is activated at low levels of ATP. It sensitizes activity of
insulin.
AMP-PK activates the fatty acid transporter, stimulates PFK, and inhibits
malonyl-CoA.
o These explain how the fatty acid and glucose metabolism pathways are able to
communicate.
Availability dictates utilization. Just after eating, glycolysis is dominant over oxidation.
Glycolysis is stimulated by adrenergic stimulation and ischemia, but lessened
during fasting.
The PPAR enzymes are activated by increased levels of dietary fatty acids, which are the
ligands.
o They mediate the activity of all of the transport enzymes involved in movement of
FFAs.
They heterodimerize with retinoid X receptors (RXRs) and bind to
promoters in cell nuclei.
o There is co-activator, PGC-1, that affects mitochondrial biogenesis & activity of
oxidation enzymes.
The estrogen-related receptors (ERRs) have similar activities.
o These molecules lead to activation of entire families of genes, allowing for chronic
regulation.
o PPARs and their co-activators are activated in diabetes, but they are less effective.
o

Cardiovascular Physiology Lecture w/ Dr. Mrs. Barrett 14 April 2011

The Topic of This Lecture Is: Transport of O2 and CO2

Ficks law of diffusion is Vgas = (Area/Thickness) * Dgas * (PA PB). The pressures those in
alveoli and blood.
o Area, thickness, and the diffusion coefficient are pretty much constant, so P is all
we care about.
Hemoglobin (Hb) transports O2 and CO2 in the blood. It also buffers pH and maintains
pressure gradients.
o Each molecule of Hb can bind 4 O2 molecules, since there are four heme-subunits.
o Theres a non-linear Hb saturation curve that well see a million times of PO2 vs.
% saturation of Hb.
In mixed venous blood, PO2 is about 40 mmHg. In arterial blood, its around
100 mmHg.
The curve is basically flat from 60-100 mmHg, so Hb saturation is
unchanged.
Below 60 mmHg, the saturation of Hb drops in a linear fashion.
o There is positive cooperativity of heme-subunits. Binding 1 O2 encourages
binding of more.
At 40 mmHg, Hb is still about 75% saturated with O2. Its 50% saturated at a
PO2 of 27 mmHg.
o We normally breathe air that is 21% O2, so PO2 100 mmHg. With 100% O2, it rises
to like 700 mmHg.
o Although most O2 in the blood is carried by Hb, a small amount is dissolved. Thats
what diffuses.
As such, O2 must first dissociate from Hb before it can enter cells.
O2 carried by Hb = % saturation * [Hb] * O2 binding capacity. The latter two are the O2
capacity.
o Normal Hb O2 binding capacity = 1.34 mL O2/g Hb. Normal [Hb] = 15 g/dL. O2
capacity = 20.1 mL O2/dL.
The % Hb saturation is via the PO2 curve. Dissolved O2 = 0.003 mL/dL/mm Hg
* PO2.
o In arterial blood with PO2 = 100 mmHg and % saturation = 97.5%, the O2 in Hb is
19.6 mL O2/dL.
The dissolved amount is 0.003 * 100 mmHg = 0.3 mL O 2/dL. The total is
about 20 mL O2/dL.
o In venous blood with PO2 = 40 mmHg and % saturation = 75%, the O2 in Hb is 15.1
mL O2/dL.
The dissolved amount is 0.003 * 40 mmHg = 0.12 mL O 2/dL. The total is
about 15.2 mL O2/dL.
o When breathing 100% O2, PO2 is 673 mmHg. The O2 on Hb doesnt change much
(20.1 mL O2/dL.)
There is much more dissolved O2 (0.003 * 673 mmHg = 2.0 mL O2/dL). The
total is 22.1 mL/dL.
Breathing air with more O2 increases arterial PO2 with no effect on tissues.
Giving pure O2 to athletes is the stupidest fucking thing ever.
The Hb saturation curve is right-shifted by increased temperature, higher PCO2, and
lower pH.
o This makes sense, because tissues require more O2 to be off-loaded as energy is
consumed.
2,3-BPG also favors O2 off-loading. It is seen in higher levels in people living
at high altitudes.
The T form (taut) of Hb has less O2 affinity than the R form (relaxed).
These conditions stabilize the T form, so O2 dissociates and diffuses.

Since fetuses operate at lower pressures, fetal Hb has a left-shifted saturation

curve (less 2,3-BPG).
o Carbon monoxide (CO) also greatly shifts the curve to the left. Additionally, it
displaces O2 on Hb.
Carboxy-Hb has CO bound to it. It reduces arterial O2 content and O2 delivery
to tissues.
Methemoglobin, which has an oxidized Fe group, is also bad. It cant carry
O2 at all.
Carbon dioxide is also carried by Hb, forming carbamino-Hb. It then carries CO2 back to
the lungs.
o CO2 is also buffered to HCO3- and H+. Protons also bind to Hb. The HCO3- stays in the
plasma.
All of these processes occur within red blood cells.
o Some CO2 dissolves in blood, about 20 times more than the amount of O2 that does.
o The PCO2 of blood varies from 46 mmHg in venous to blood to 40 mmHg in arterial
blood.
Donated blood has a 6 week lifespan because the cells lose 2,3-DPG and become less
flexible.
o People who get newer blood have better outcomes than those that get blood closer
to 42 days old.
New methods for delivering O2 are needed due to scarcity and possibility of infections.
o One method involves liquids (perfluorocarbons) that better dissolve O2. This
requires higher PO2.
o Another method considered adding Hb on its own, but it causes massive
vasoconstriction.
It normally enters into capillary walls and binds NO (a potent vasodilator).
Thousands of methods have been tried to make Hb more bulky, but nothing
works.
o

Cardiovascular Physiology Lecture w/ Dr. Salathe 11 April 2011

The Topic of This Lecture Is: Pulmonary and Bronchial Circulation

Bronchial circulation refers to the systemic supply of oxygen to the bronchial tree and
the pleura.
o This is contrasted with the pulmonary circulation, which is how venous blood is
oxygenated.
o With regards to lung anatomy, the trachea diverges into primary, secondary, and
tertiary bronchi.
The tertiary bronchi are the bronchopulmonary segments, separated by
connective tissue.
Each of these independent areas is supplied by one branch of the
pulmonary artery.
The segments are shaped like cones with the tip pointing toward the
hilum.
o These continue to diverge and become smaller and smaller, until become terminal
bronchioles.
These then yield respiratory bronchioles and finally, alveoli.
o The divisions of bronchi are important to understand, as pulmonary arteries
accompany them.
This is not true for the veins, because gas exchange is no longer wanted at
that point.
Pulmonary arteries arise from the pulmonary trunk and travel parallel with bronchi and
bronchioles.
o They stay outside the walls of these airways, and they are roughly the same size.
Bronchial vessels are much, much smaller, as they actually perfuse the
airways.
Pulmonary vessels carry close to 100% (something like 95%) of blood to the
lungs.
o In a histological slide, it is evident that bronchi and pulmonary arteries are about
the same size.
Pulmonary arteries have less muscle, less elastin, and less contractility than
systemic ones.
They are normally dilated, and in general, appear similar to systemic veins.
o Bronchi and the pulmonary arteries are surrounded by alveoli.
Capillaries lie in the interalveolar septum, separated from alveolar air space by the
thin alveolar wall.
o They are most readily identified by the presence of erythrocytes.
o Gases pass through a complete basal lamina with few pinocytotic vesicles and many
tight junctions.
External to these are type I squamous alveolar cells that comprise the
epithelium.
The blood-air barrier is somewhere between 0.1 to 1.5 m in thickness.
Pulmonary veins follow the intersegmental planes between bronchopulmonary
segments.
o The larger ones may parallel the main bronchi. These veins lack valves and drain to
the left atrium.
Bronchial arteries are very small. They arise from the thoracic aorta to give
oxygenated blood to the lungs.
o There is a lot of anatomical variation of these arteries. They can arise from many
places on the aorta.
o They perfuse the bronchi, bronchioles, and most importantly, the visceral pleura.
There is typically one right bronchial artery and two left bronchial arteries.
o Bronchial veins are in the walls of bronchi/bronchioles, draining to the azygos &
hemiazygos veins.

Some of this deoxygenated blood goes inadvertently to the pulmonary veins.

This occurs via anastomoses, yielding a physiological right-to-left heart
shunt.
o Bronchial capillaries are in the mucosa of the bronchi/bronchiole walls, providing
nutrients.
This circulation should be considered as part of the systemic circulation.
o After lung transplants, the bronchial arteries are not reconnected. They transmit
little blood (5%).
In pulmonary physiology, TPR is referred to as pulmonary vascular resistance (PVR).
o For systemic blood flow, P is 98 mmHg, and Q is about 5 L/min, so PVR is about 20
mmHg/L/min.
In pulmonary circulation, P is 10 mmHg; Q is the same. PVR there is only 2
mmHg/L/min.
o Capillaries are closed if alveolar pressure (PA) exceeds the pressure within the
capillary lumen (Pa).
At the end of inspiration and exhalation, PA roughly equals atmospheric
pressure.
Everything regarding blood pressure is calibrated to that, so 1 atm 0
mmHg.
The apex of the lung (zone 1) is not well-perfused, as PA normally exceeds Pa, so the
capillaries collapse.
Zone 1 does not exist when one is supine, since its dependent on gravity.
o In zone 3, at the base of the lung, theres constant blood flow, as Pa and Pv exceed
PA.
o Zone 2 is the magic area where Pa > PA > Pv. Theres a gradient of flow based on
capillary constriction.
The closer the capillary is to zone 3, there more flow there is.
o If a patient is on a ventilator, alveolar pressure is constant. It is increased from
say, 0 to 15 mmHg.
This requires the person to create greater arterial pressures to sustain blood
flow.
However, the ventilator prevents the collapse of alveoli and diminishes
hypoxia.

 Resistance is mediated by lung volume, hypoxia, and exercise.

o The optimal volume for blood flow (least resistance) is at the end of expiration
(residual volume).
When inhaling to total lung capacity, the capillaries are squeezed by alveolar
expansion.
At maximal exhalation, resistance is increased, as extra-alveolar vessels do
not open fully.
o Hypoxia increases the arterial pressure required to achieve a given amount of
blood flow.
Low O2 in the alveoli increases resistance due to arterial constriction.
o Exercise increases perfusion by increasing arterial pressure and decreasing
pulmonary vascular resistance, as there is recruitment of more areas of the lung
(resistance is in parallel).
The vessels also dilate, which decreases resistance too. Theres recruitment
and distension.
It is thus possible to greatly increase cardiac output, just by decreasing PVR.
The lungs have metabolic functions as well. It is there that ACE converts angiotensin-I to
angiotensin-II.
o It also inactivates bradykinin, 5-HT, PGE, PGF2, NE, and histamine (dont memorize
that).
If the bronchial arteries rupture, they can result in hemoptysis (coughing up blood).
o This is often secondary to bronchiectasis, which is the excessive dilation of
airways.
o As these vessels can run near the anterior spinal arteries, embolisms can have
major consequences.