Circulation

Fox Chapters 13 and 14 (a figure from chapter 12)

Overview

In multicellular metazoan, need a vascular system (in terestrial plants above mosses, xylem and phloem)
Circulation : Cardiovascular system

Anatomy of the heart

TRANSPARENCY (Review, Introductory Biology)
Fig. 13.10
Chambers of heart
Birds and mammals have 4 chambers
Note that right is drawn on left as if looking into the chest of a supine subject (as I first mentioned when I lectured on Loewi's discovery of vagus stuff, acetylcholine)

Here is the circuit: LA - LV - Arteries (aorta, etc.) (blood pressure taken here) - Arterioles (regulate blood flow to muscles, brain, digestion, kidneys and skin) - Capillaries (near, exchange, WBC's) - venules - veins (no pressure, valves)- RA - RV - Pulmonary arteries - Lung capillaries - Pulmonary veins -

Heart valves and sounds

Fig. 13.11b
pulmonary valve (semilunar) feeds pulmonary arteries
aortic valve (also semilunar) feeds aorta
These valves snap shut from arterial back pressure at the end of systole to make second heart sound- "dub"
Superior and inferior vena cava feed right atrium -> ventricle via tricuspid (atrio-ventricular) valve.
Pulmonary veins feed left atrium -> ventricle via bicuspid (atrioventricular) valve.
Tricuspid & bicuspid snap shut at start of ventricular contraction to make first heart sound- "lub."
If there is backslosh through valves, this is called a heart murmur.

Blood vessels

Fig. 13.26
artery is like hose
blood flow to emptying into vascular bed: regulation by smooth muscle of arteriole
capillary is one layer of endothelial cells (fenestrated or continuous)

TRANSPARENCY (Review, Introductory biology)
Fig. 14.25
- blood spreads out as it goes from arteries -> arterioles -> capillaries and hence moves slower. Pressure goes down during movement arteries -> arterioles -> capillaries (bottom).

Fig. 13.30
Blood moves slowly and with very little pressure in veins. Movement in veins is mostly passive with a series of valves and where contraction of skeletal muscles helps

Fig. 13.37
Lymphatic circulation helps to percolate interstitial fluid back to circulation

Fig. 14.23
Shunts (arteriovenous anastomoses) help to regulate circulation through peripheral vascular beds.

Cardiac cycle and blood pressure

Fig. 13.13
cardiac cycle
Diastole (between heart beats), systole is during ventricular contraction, hence terms systolic and diastolic blood pressure.

Fig. 13.14
Ventricle fills during diastole.
Ventricle empties during systole.
Ventricular pressure builds during systole.

Wiggers diagram.
Relates ventricular pressure to arterial pressure.
Pulmonary pressure is lower than systemic.
Buildup of ventricular pressure opens valve and blood moves to aorta.
As ventricle relaxes, back pressure from artery snaps valve shut.

Ventricular filling

Fig. 14.2
Frank-Starling law.
The greater the ventricular filling, the greater the cardiac output.
This is good! -- recall that the tension length relationship for striated muscle had a peak, but, if the muscle got too long, less force could be generated.
This figure also shows that the sympathetic nervous system moves this curve up.

Measuring blood pressure

It is arterial blood pressure that is usually measured.

Fig. 14.30,
Fig. 14.31
close off artery, when it opens (systolic pressure), blood flow is turbulent and noisy (Korotkoff sounds), when it is always open (diastolic pressure), blood flow is no longer noisy
Blood pressure is measured in arteries
High blood pressure is called the "silent killer."
hypertension 45 million Americans - salt intake is still debated, >140/95 high 140/70 normal
high diastolic is especially bad

Explained by Wiggers diagram, if diastolic b.p. is high, then it takes higher ventricular pressure before valve opens and blood actually moves.

Regulation of blood pressure

Fig. 14.27
Blood pressure is regulated by sensory receptors in aortic arch and carotid sinus.
Goes to medulla oblongata of brain theh out to sympathetic and parasympathetic nervous systems.
There are also brain influences that come down via hypothalamus.

Myocardial cells

Fig. 12.32
Heart muscle cells branch and come together and are joiined at intercalated discs with gap junctions that spread the electrical signal from cell to cell.

cardiac muscle - automatic (explained below)
here is a picture from our histology course of heart muscle cells joined at intercalated discs
(like Figure 12.34)

Electrical activity of heart cells

Fig. 13.20
Electrical - SA (sinoatrial) node (or electrical pacemaker) - spread - automatic.
Sympathetic nervous system speeds it up, parasympathetic nervous system slows it down.
AV (atrioventricular node) is eventually stimulated.
If it were not, it is also automatic but slower and would generate a heart beat in the venticals.
Bundle of His, bundle branches, and Purkinje fibers get ventricular depolarization to happen almost synchronously.

Fig. 13.18
Pacemaker cells have depolarization during diastole because of slow Ca2+ channels.
Pacemake potential-HCN=hyperpolarization cyclic nucleotide (beta-1 adrenergic affects cAMP)
Spike is from Fast Ca2+ channels and Na+ channels
Repolarization uses K+ channels.

Fig. 13.19
Ventricular myocardial cells have long action potentials involving the specific channels shown.

The ECG

Fig. 13.24
Einthoven's triangle to show possible placement of EKG (ECG = electrocardiogram) leads.
Because a lot of cells in heart work together, and because extracellular fluid has high conductivity, electrical activity can be recorded non-invasively.

Fig. 13.22b
P is atrial depolarization.
QRS is ventricular depolarization.
T is ventricular repolarization.

Fig. 13.25
This figure relates EKG to pressure and sounds

Atherosclerosis

Fig. 13.26
(again)
Normally artery has
tunica externa
tunica media
tunica interna (endothelium and elastic layer )

Fig. 13.32
A layer of fat with ccholesterol between media and externa
ulceration lining lumen
atherosclerosis - hardening of the arteries - plaques
atheroma with macrophages
Cholesterol is a problem

Heart attack

General:
Myocardial cells not regenerate (by mitosis in the adult). This is why heart attack is so damaging. The same is true for the nerves in the central nervous system where similar damage is called stroke.
Coronary arteries clog -> myocardial infarction - coronary thrombosis - ischemia (too little blood flow for oxygen delivery)
Angina, chest pain, and referred pain

Platelet aggregation - thrombus (local), embolism (from elsewhere) cause ischemia
tissue plasmogen activator (TPA) dissolve clots
streptokinase thru catheter dissolve clot
aspirin inhibits clotting, coumaden is a strong anticoagulant
catheter with balloon angioplasty insert stent

fibrillation - CPR (keep brain alive, needs O2)
In CPR (cardiopulmonary resuscitation) chest pressure keeps blood flowing a little and rescue breathing keeps blood oxygenated
1 million Americans die/yr reducing since 1971
bypass operations, replace coronary artery with vessel from somewhere else in the body, there are 100,000-200,000/yr operations - 30% may be unnecessary

"heart attack" - myocardial infarction
heart muscle is aerobic
anaerobic metabolism would build up lactic acid and cause pain (angina pectoris)
nitroglycerine relaxes smooth muscle (Viagra and other ED medications would be contraindicated)
heart muscle damage by necrosis (as opposed to apoptosis - programmed cell death)
can be detected in S-T of ECG
uncoordinated contraction of heart muscle - fibrillation
in atria fibrillation is not so important becaus atrial beat only addis a little bit to ventricular filling
in ventricles, it is fatal and hence the importance of defibrillators
re-entry of excitation as electrical signal takes long route around scar tissue after heart attack can contribute to poor ventricular coordination

Risk facrors for heart attack
(1) High blood pressure (the silent killer) -- Wiggers diagram --heart has to work harder to open semilunar valves.
(2) prior heart attack
(3) smoking
(4) diabetes
(5) family history - a dominant allele in hypercholesterolemia (and other genetic factors?)
(6) LDL-low density lipoprotein - made in liver - low LDL receptors help liver take up cholesterol
LDL receptors take out cholesterol which otherwise deposits
HDL may lower deposition - excercise good for this
(7) clotting, especially clumping of platelets) inhibited by aspirin (and coumadin) - hence term "coronary thrombosis" (in coronary artery)

Prevention -
(1) exercise - increase HDL (endothelial cells do not take up)
(2) antioxidants (oxidized LDLs in endothelial cells are bad)
alcohol in moderation (but people who die of cirrhosis rarely have atherosclerosis)
statins (box on p. 412):
(a) block rate limiting step in cholesterol synthesis in liver
(b) secondarily increase LDL receptors

Readings

S. Cohen J Leor Rebuilding broken hearts, Scientific American, November 2004, 44-51

infarct kills cardiomyocytes
noncontractile fibrous cells replace
adjacent healthy myocytes may die
(remodeling)
ventricle wall becomes thinner, distends, might rupture
heart failure
tissue engineering - must have scaffold for cells and blood supply
3-D sponge-like frame made alginate (from algae) frozen
progress so far- can prevent further damage
add controlled release microspheres of growth factors to help angiogenesis

Pacemakers (keep the beat) [working knowledge] M Fischetti, Scientific American, November 2004

wires run in through vein
tips have steroid reservoir to block early inflammation
that keeps contacts healthy
ICD - Implantable cardioverter defibrillator


Exam questions from 2004 - 2008 that relate to this outline:

When, in the heart cycle, do the bicuspid and tricusid valves snap shut?

at the beginning of ventricular contraction

What kind of blood vessels have the highest TOTAL cross sectional area?

capillaries

What does the last Korotkoff sound signify?

the diastolic (arterial) blood pressure

What are the cells that line blood vessels including capillaries called?

endothelial cells

Why is the wall of the ventricle thicker than the wall of the right ventricle?

systemic circulation is higher pressure than pulmonary

What is Einthoven's triangle?

Hook-ups for diagnostic EKG Leads I, II, and III on 2 wrists and left ankle

Long QT Syndrome, diagnosed by a lot of time between the QRS and the T, affects a channel (for what ion?) involved in the repolarization of ventricular myocardial cells?

K+

Cells in what areas depolarize automatically during diastole?

SA node

Although the electrical signal would pass from one myocardial cell to the next, specialized fibers hurry it to much of the ventricular muscle synchronously. What are these fibers?

bundle of His, bundle branches, Purkinje fibers

Why would you die of if there were too much time between heart failure and defibrillation without CPR (cardio-pulmonary resussitation)?

brain would die without O2 (and glucose)

The time between the QRS and the T represents the duration for what specific cell type?

ventricular myocardial cell

For a normal person, slow Ca2+ channels would control heart rate in which specific part of the heart?

SA node

In good health, what part of the body clears LDL (and HDL) from the blood stream?

liver

How does nitroglycerine help to relieve angina pectoris?

relax artery smooth muscle

What is the likely mechanism that antioxidants might prevent heart attacks?

oxidized LDL is bad

Why isn't an atrial beat needed for most of the venous return to go to the ventricles during diatole?

tricuspid and bicuspid valves are open

What does the endothelium line?

blood vessels

If you took statins, what substance would decreased?

cholesterol

How do gap junctions contribute to heart function?

get action potential from one cell to another

Since there is not much blood pressure left, what is needed to help blood flow along in veins?

valves

Taking blood pressure, you inflate the cuff to 180 mm Hg, then lower it. You hear nothing until the systolic pressure is reached. After the diastolic pressure is passed, you hear
nothing. Why do you get sounds only between systolic and diastolic pressures?

turbulent

What causes the second heart sound at the end of systole?

semilunars snap shut

How does aspirin help to prevent heart attacks?

inhibits platelet aggregation

Where does the vena cava (superior and inferior) empty into?

right atrium

At the moment the semilunar valves open, what is the blood pressure in the left ventricle?

same as arterial diastolic

What is the function of an arteriovenous anastomosis?

shunt blood from peripheral vascular bed

What is the endothelium?

cell lining of blood vessels

What is a heart murmur?

a leaky valve

Compare the duration of the isovolumetric portion of the ventricular contraction for someone with high diastolic blood pressure with that for a normal person.

the ventricle would contract further before forcing open the valves to arteries (for high b.p.)

What regulates the precapillary sphincter?

the sympathetic nervous system

"CN" in "HCN channels" stands for "cyclic nucleotide." What do cyclic nucleotides have to do with pacemaker cells?

adrenergic receptor affects cAMP level

Explain the interval between the QRT complex and the T wave in terms of the shape of the myocardial action potential.

that is a long action potential, QRS is depolarization, T is repolarization

How could you get a heart beat if there were no trigger from the SA node?

Eventually the AV node would kick in

At the moment of the last Korotkoff sound, what does the pressure dial show?

diastolic b.p.

What are baroreceptors in the carotid sinus used for?

regulate b.p.

In addition to increasing contractility, what does sympathetic input to the heart do?

regulate heart rate

What is ischemia?

interuption of blood flow and hence oxygen supply

What does a defibrillator do to save your life?

starts heart again, makes it so SA node triggers heart

What does a high HDL/LDL ratio in your blood test results imply?

less risk for coronary artery problems

As opposed to apoptosis, what is the damage to cardiomyocytes in a heart attack?

necrosis

What is it called when you have pain in parts of your body, like your left arm, in a heart attack?

referred pain

What is a thrombus and why is it potentially damaging?

a blood clot that clogs the artery

What event occurs at the end of the isovolumetric contraction of the left ventricle?

Aortic semilunar valve opens

Why do veins need to have valves to ensure forward blood flow while arteries do not?

there is no blood pressure driving the blood

In what way does the Frank-Starling law differ from the striated muscle's length-tension curve?

FS-More stretch (ventricular filling) more contraction, striated weaker when muscle is long

Why is the first part of the ventricular contraction isovolumic?

Bicuspid and tricuspid are closed, semilunars do not open until ventricular pressure > arterial

Heart cells die by cell damage, rather than by programmed cell death (apoptosis). What is the term used for this kind of damage?

necrosis

A blood test shows that a patient has a high HDL to LDL ratio. What does this mean?

these are good numbers re artery health

In an arteriole, what would a precapillary sphincter do under the influence of the autonomic nervous system?

open or close to regulate blood flow to the capillary bed

What valves close right at the start of ventricular contraction?

tricuspid and bicuspid (atrioventricular)

Hyperpolarization cyclic nucleotide (HCN) channels are important in pacemaker cells. Name the relevant and famous cyclic nucleotide, the one controlled by beta-1 adrenergic receptors.

cAMP

In atria, the action potentials are passed from one myocardial cell to the next. Why are there additional fibers (bundle of His, bundle branches, and Purkinje fibers) for ventricles?

to speed the action potentials to the base

Parasympathetic fibers slow the SA and AV nodes below their rate of automaticity. What nerve is this?

vagus, 10th cranial

Above the systolic pressure and below the diastolic pressure, you hear nothing. Why are there Korotkoff sounds between systolic and diastolic pressure?

blood flow is turbulent

What does the Wiggers diagram tell us about the opening of the aortic semilunar valve when the diastolic blood pressure is high?

ventricular pressure would have to be higher to push open the valve

Give an approximate value for the blood pressure in the ventricles during diastole.

zero

What symptom would be noticed if the heart muscle were to attempt anaerobic metabolism?

pain (angina)

What do aspirin, coumaden and the rat poison WARFarin have in common?

they inhibit coagulation

Valves between where and where snap shut at the beginning of ventricular contraction?

atria and ventricles

For part of the heart cycle, ventricular and arterial pressures are equal. How do these two pressures relate the rest of the time?

in diastole, ventricular is lower than arterial

What holds shut the aortic and pulmonary semilunar valves during the beginning of ventricular contraction?

arterial pressure

In addition to the automatic tissues (predominantly SA & AV nodes) to what does the sympathetic nervous system connect and why?

heart muscle to increase contractility

Electrically, what do pacemaker cells during diastole?

depolarize

How come the electrocardiogram can reach as far as the wrists and ankles for recording?

virtually no extracellular resistance

What would happen to the time between Q and T waves with sympathetic activation?

shorten

What is the difference between a thrombus and an embolism?

thrombus clot forms locally, embolism dislodged from elsewhere and arrives at trouble spot

Why would a large area of damage in the heart lead to re-entry of excitation?

the distance from cell to cell to cell would have the spike arriving after the refractory period is over

What type of cell is used for continuous and fenestrated capillaries?

endothelial

What is it that may shunt blood from arteriole to venule to bypass capillary bed in the skin?

arteriovenous anastomoses

In what way is heart muscle different from striated muscle with respect to strength as a function of length?

Frank Starling law has it that fuller (more stretched) ventricle has higher contractility, while striated muscle tension drops off

As cuff pressure is being released, between the systolic blood pressure and the diastolic pressure, your figure indicated that you get "sounds at every systole." Why?

turbulent blood flow

How would nitroglycerine help if you felt a heart attack coming on?

relax smooth muscle in artery

Describe referred pain as it refers to heart attack.

projected to neck, arms

What is it that makes the bicuspid and tricuspid valves close to make the first heart sound ("lub")?

pressure in the ventricles closes these atrio-ventricular valves

Why might a person pass out if (s)he stands without moving for a long time?

muscular contraction contributes to venous return, hence venous pooling

What part of the nervous system would regulate the precapillary sphincter?

sympathetic

During ventricular systole, just when the pressure forces the aortic semilunar valve open, what is the arterial blood pressure?

equal to the diastolic pressure right then

About what fraction of ventricular filling is from the beat of the atria?

a very small amount, the figure shows about 10 out of 80 ml

What happens to the brachial artery when the blood pressure cuff is first fully inflated?

it is completely closed

Suppose your SA node failed to fire. You would probably still have a heartbeat (how?) and it might be reasonably adequate (why?).

AV node would fire, see q 10, most of the ventricular filling does not rely on atria

What happens to the electrical potential of a cell in the sinoatrial (SA) node during diastole?

there is diastolic depolarization in these pacemaker cells until threshold is reached

How do we get recordings from 3 different "leads" in Eindhoven's triangle starting with a positive electrode connected to one wrist, a negative electrode connected to the other, and ground connected to an ankle?

The three so-called "leads" are gotten by swapping (2 at a time) connections to the 3 locations

Before paramedics arrive with the defibrillator, why is cardiopulmonary resuscitation essential?

CPR delivers enough oxygenated blood to the brain to keep it alive

"The bad news is that your cholesterol is high. The good news is that your ratio is good." What would be a good ratio (when the cholesterol level is broken down into its components)?

If HDL/LDL is high

At the peak of systole, how does the pressure in the right ventricle compare with the pressure in the left ventricle?

Way lower pressure in pulmonary circulation

Both branches of the autonomic nervous system (sympathetic and parasympathetic) connect to both nodes of the heart(SA and AV). In addition, the sympathetic nervous system also makes additional connections to the heart (to where? Or for what purpose?).

to muscle to increase strength of contraction

What would happen to the Q-T interval during strenuous exercise?

shorten

What is the function of an arteriovenous anastomosis?

Shunt blood to bypass capillaries in skin to prevent heat loss

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