22/23: Hemodynamics I/II

8/11/2019 22/23: Hemodynamics I/II

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Transcribed by Anam Khalid Friday, September 19, 2014

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Hemodynamics and Circulatory Disorders General Pathology by Dr. Anthony

Vernillo

[Slide #1] [Hemodynamic and Circulatory Disorders][Dr. Vernillo]Good morning to all of you. Dr. Phelan has given me two lecture slots,

an hour and fifteen minutes each to talk to you about cardiovascular pathology,from the generosity of her heart no pun intended on the use of the word, heart.

And Ive worn my shirt today for this color for this occasion. So, were going to rompour way through cardiovascular disease. Im going to turn this thing off because Ihate facial recognition. Why should it look at my face anyway Okay, and were

going to talk about cardiovascular disease and a few introductory comments then

before we proceed with these slides themselves. If theres ever a disease that kills

and cripples more people in this country, its cardiovascular disease. Theres noother disease that comes close to this one. And it kills and cripples men and women

alike in this country, more than any other. Outstrips cancer, outstrips infectious

disease. And well talk about the reasons for that. It is a leading cause of mortality, or

death. Its a leading cause of morbidity. Does anybody know whatmorbidity is, orwhat the term morbidity means, simply put? Anybody? And thank you for all coming

here, by the way. I appreciate your ambition at this hour in the morning. This is

really against the Geneva Accords that we should have class at 8 oclock inthe

morning. Please right. Morbidity means that youre disabled. Theres a change in

the quality of your lifestyle. You have heart disease and then you wind up with a

stroke and then youre in a wheelchair. Well talk about the pathogenesis of that,

going forward. But thats a prototypical or classic example of morbidity. Thats

exactly right. So lets just talk about a few things going forward. You have a left side,

you got a right side. Left side is the arteriole circulation, also known as the systemic

circulation. Right side is venous. And Dr. Curry just spoke to me recently. She and I

teach the systemic pathology course together. And she told me that she hadmentioned some of these things to you but not in any more significant detail. So Imgoing to pick up a little from that and Im going to set the stage for this topic. What isthe major cause of left failure? Why does the left side fail? Give me a risk factor for

that. Hypertension. Now what does hypertension do to the left heart? Hypertension

is, first of all, an arteriole disease. Its not a venous disease. So if you have increasedhypertension, what does it do to the left side of the heart? You said hypertrophy and

thats right. Why is that? Its got to work harder go ahead. Youre right there.Keep

going with that. It has to work harder because right. Theres more arterial

pressure, its an increased work load. So now you have a heart that gets thick. It getsthicker for reasons related that we dont understand completely but the cells in the

myocardium produce collagen. They produce proteoglycan and they secrete andsynthesize this and the wall thus gets thicker with these macromolecules

synthesized and secreted and become part of the wall. That sounds great, doesnt it?

You go to a gym, you lift weights. I sure as heck dont. And you build up muscle massand the heart muscle does that. Is that good? Why is it not good? Alright so what

youre saying is theres no space for the blood. You have a smaller chamber andwere going to come back to this as we go forward but the other thing is the heart is

less compliant. It cant contract as efficiently. Its thicker, its stiffer, it doesnt work


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well. So now you have an inefficient pump. Thats a problem. So that inefficient

pump cant pump blood forward into the systemic or arterial circulation. Wheredoes it go? If I cant push blood forward through the aorta and into the arterial or

systemic circulation, and hence we call that forward failure, where does the blood

go? Back into the left atrium and then back into what vessel that enters the left

atrium, the pulmonary vein. Remember, that the circulation is reversed. Thepulmonary circulation is reversed from the general systemic circulation. So even

though were on the left side of the heart, which is arteriole, that which end is the

left atrium is the pulmonary vein. Now that blood is backing up into the left atrium.

Where is it going next? Back into the pulmonary vein and then what? All the way

down to the tiniest vessels of a vein which are called venules. And they anastomose

.. this is what you learned in anatomy. It may anastomose or join with smallest of

arteries, capillaries or as the British call them, capillaries. Quite right now. You have

venules that anastomose with capillaries. This heart is failing, it cant pump forward.

Fluid can only go back. What do we call that increased pressure? Increased what?

What type of pressure is it? This is where youre going to have to think through

because pathology is analytical, a lot of it is. Youre gotto use, as they say inBrooklyn, you have to use your kidneys. If that keeps backing up, goes all the way

into those capillaries. Does blood contain water? What is the Greek word for water?

Its a root. What are those things out on the street that the firemen plug their hoses

into? Fire hydrants, hydrants, hydro. Increased hydrostatic pressure. That is one of

the significant categories, one of the significant pathophysiologic categories for

edema. So now all of that blood backs up into the capillaries and those capillaries

form what part of the structure of the air sac? The wall of the air sac. Exactly right.

Now you have all that pressure backing up into the wall. And its an increased

hydrostatic pressure. And it is one, not the only one, but it is one of the major

pathogenetic pathways to edema. This you must remember. Whenever you have

congestion, like night that follows day, you have edema. So once you havecongestion in those capillary walls, the next thing thats going to happen is edema.Where does the edema go? Into what structure, again? The air sacs, right. So now

youre a fish. Because now you have water in your air sacs. And youre going to havedifficulty breathing. This is what we call heart failure, congestive heart failure,

whether its left or whether its right or whether its both left and right because whatboth of those forms the heart failure have in common is edema in the lung, known as

pulmonary edema. And you cant breathe well. What word do we use to describedifficulty in breathing? Anyone? Dyspnea is exactly right. D-Y-S-P-N-E-A. dyspnea.

Difficulty breathing. You cant breathe underwater unless they cut gills and put thembehind your ears. So, now you run into problems breathing. In fact, some heart

failure patients have to sit up on pillows when they sleep because they havedifficulty breathing when they lie flat on their back. And they have difficulty

breathing when they lie flat on their back because all that fluid is just sitting on top

of them. So difficulty breathing lying flat on your back is called orthopnea. O-R-O-T-

H-O-P-N-E-A. P-N-E-A having to do with breathing, ortho- meaning straight or flat

on your back. Difficulty breathing while lying flat on your back. So they have to prop

themselves up with pillows. So that gravity seems to pull some of that fluid down.

And some of the clinicians describe such orthopnea as 1, 2, or 3 pillow orthopnea.


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The more pillows you need, the worse it is. Okay. Now, left heart, pulmonary edema,

we now are into capillaries. Capillaries are going to grow and become larger and

larger structures called arterioles and eventually youre going to enter the right side

of the system. Remember, the pulmonary circulation is reversed. What artery exits

the right ventricle? The pulmonary artery, also known as the pulmonary trunk, also

known as the main trunk. So now all of this pressure is backing up onto that rightside and remember, were going backwards. So as we go backwards to the right side,

all that fluid, all that pressure is building up in that pulmonary artery. What do we

call an increase in blood pressure in an artery? Hypertension. And if we have an

increase in pressure in the pulmonary artery we call it pulmonary hypertension.

Right. Okay, good. I wish my computer was working as well as you guys are right

now. And theres nobody up there to bail me out. Bear with me. Okay, so now we

back up onto the right side. Where is the fluid going to go now? Its backing up intothe pulmonary artery, what chamber gets it next? The right ventricle. Will that right

ventricle hypertrophy over time? What do you think? Remember the left side

hypertrophied because of that increase in pressure, which was an increase in

workload. All that fluid is now backing onto the right side. Now you got fluid backingup onto the right ventricle, does that increase the amount of fluid pose an increased

workload? Whats your best guess? Yes. So whats going to happen to the rightventricle. Its going to undergo hypertrophy too. If you live long enough, some

people drop dead suddenly so they dont have time to hypertrophy anything. So now

that blood backs up into the right atrium. The right atrium is not a muscular wall

anymore than the left atrium is. An atrium just dilates. Thats not so good either.

Because if the atrium stretches, its dysfunctional. Blood cant be moved. And youll

find out that when the atrium cant stretch and it cant function, it can also set the

stage for something called arrhythmia. Well talk about that later. So now blood isbacking up into the right atrium. What two major veins enter the right atrium? The

super and the inferior vena cava is exactly right. Now you got pressure, bloodbacking up into those veins. What is the superior vena cava drain? Your head and

neck. So somebody comes in with the jugular vein which is the branch of the

superior vena cava and that jugular vein is distended. You see this big, thick blue

rope in someones neck, you know something. You know that they actually have

probably have left and right failure. Because everythings backed up. The inferiorvena cava goes down, goes through the liver. Yes, it does. And then it sends out little

hepatic branches and then these little hepatic branches deliver blood to the

sinusoids of the liver. If everything is backing up, then all that blood is backing up

through the inferior vena cava, then its also being dumped into the liver and theliver starts to swell. Thats called hepatomegaly, enlargement of the liver. When

blood backs up in veins, what term do we use to describe it generally, what is theterm? Have you had this in general path? Okay, if you havent yet then tell me so. Itspassive congestion, also known as passive hyperemia, which means excess blood. All

this blood is backing up into veins, this is called passive hyperemia or passive

congestion. Alright. But the fun doesnt end there. The fun doesnt end there.

Because all that blood thats backing up into veins is backing up to veins in your leg.Here we go again. What follows congestion? Edema. So your legs swell. And youve

seen that. Youve seen some of these poor souls in supermarkets. Theyre pushing


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determination, its not mine, its not yours. But you can tell a patient that and guide

them in that direction because, you know, the comment then is and so its probablyshtick on my part, as it were, is if, you know, you dont control your blood pressure,

you dont have to worry about sex because youll be deader than a doornail afterthat. So, you really have to encourage patients to see their physicians and you and I

play a central role in doing that and thats a very important part of what we do.Okay, now Im going to pull this one up now, its finally behaving and I thank you for

your patience, youve been wonderful. Okay, here we go. Wonderful. Look at this.Okay, so what were going to do were going to talk sorry, I dont know why myvoice keeps breaking. I think Im probably going back through puberty again.

[Slide #2] [Components of the Circulatory System]

[Dr. Vernillo]Okay. Were going to be talking about the various components of theheart. Ive given you an overview. Youve been very good listening to all that but this

is what were going to be talking about today, in the next lecture, and in the

conferences. And well be doing some cases. So what I would also encourage you to

do is review this lecture today, review the lecture, I believe I give the next one on the23rd, youll have it. But theyre before the conferences, which you know how the

course is set up. Thats what it does. Review it. So when you come in to the

conferences, youre going to be ready to participate because Im going to call on you

and my students are wonderful. Everybody here is brilliant. They sit in the back of

the room and I call on them and I get this they think theyre in a Harry Pottermovie. They think they sit under the cloak of invisibility. They think somehow if

theyre back there, I dont see them. So I call on them. Why do I call on them? To

torture them? No. To get people to think through because when your patient comes

to see you .. when I was also Im a dentist in my formal life. When you see patients,you have an obligation to see the total. They dont come in with multiple choice

letters stamped on their forehead and they come in with multiple diseases andmultiple drugs and youve really got to have your thinking cap on for them. So, I try

to get you through the process of thinking through because thats what you and I asclinicians are expected to do. Alright, so this is the component of the circulatory

system. The heart, the aorta, the microcirculation what is the microcirculation,

again? Youve had histology, right? Youre looking at me like Im speaking ancientSanskrit over here. What is the microcirculation? Capillaries, venules. Remember we

spoke in the heart failure scenario, the anastomoses between venules and capillaries

and the significance of that structural relationship in disease. Once the left heart

fails and that pressure backs up, it is said that hydrostatic pressure, that increase

hydrostatic pressure makes its way through venules, and capillaries and alveoli, air

sac walls and then pulmonary edema. This is why you learn anatomy. The Britishcall pathology morbid anatomy. And for good reason because when youre studyingpathology, you need to know what the highways are, where the vessels go and so

forth and in cardiovascular disease, thats probably the quintessential place whereyou really need to see that. Aorta, arteries, microcirculation, what is interstitium?

What is the interstitium? Go ahead. Its the area between the air sacs, in this case, ofthe lung. Youre offering good answers, you all are but, you know, this is just for your

own protection, if anyone in here offers a lot of good answers, you realize youre


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going to be vulnerable, dont you? Because your classmates are going to say, dont

answer him! It means you know it and it means we have to understand it! So be

quiet. Im joking. I get that from some of my students. Veins, venules, lymphatics

what do lymphatics do again? Bring fluid back and enter the vascular system. They

dump into the large veins. And in heart failure, they cant do that efficiently.

[Slide #3] [Circulatory Disorders]

[Dr. Vernillo]Okay, now were going to talk about a number of jolly things, here, aswe romp our way merrily through cardiovascular disease. Well talk about disordersof perfusion. Terms are important. Because if you cant speak the lingo, you cant

really articulat the concepts. Thrombosis, embolism, and infarction belong to the

same nightmare. Theyre all related in certain ways and Ill make it clearer how they

are related but theyre all part of the same horror show. Edema well talk about ingreat detail. We spoke about one mechanism of edema and what is that? Increased

hydrostatic pressure seen in the setting of left sided heart failure brought on by

hypertension. Now, why is that? Well, we spoke a few moments ago about an

increased workload. But why else is hypertension such a pernicious or destructivedisease? Because hypertension not only causes the left heart to thicken and become

a less compliant pump less compliant meaning it doesnt pump as well. Its stiff.Its thick and pressure backs up in that left ventricle. So when that left ventricle goes

on to contract in systole and force blood out and relaxes during diastole, some of

that blood is still in there because the pump is less efficient. So, somebody who

comes in and says to you, you know, doc, no offense, youre a nice doctor. But I get

nervous when I see doctors and you take the blood pressure and you should. And

they get 160/100, right? Im nervous. Yea, right. Sure, youre nervous. Yes, I know

youre nervous but when you have a diastolic of 100 or 105, were talking moreabout nerves over here. Or as they in Brooklyn, noives. Were talking heart failure.

If somebodys got a diastolic of 100 or 105, that pump aint a pumpin very well. No,youre not going to say that to your patient. Youre not going to say, oh, hey, you

know, youve got youre probably going into heart failure because theyll probablydie right there if you say that to them. But you know better. So, you know, you would

get on the phone and youd speak to the physician about their blood pressure. Now

you and I dont diagnose hypertension. We dont treat it but we play an extremelyvaluable role in healthcare. Extremely valuable. And one of the roles we play is to

speak to physicians and make them aware of our findings because when you think

about it, you and I both have an ethical obligation here. Were treating the same

patient together, physician and dentist alike. And sometimes that physician may not

know fully whats going on with that patient and if you take care of that patient, that

patient will come back and thank you for this. My goodness, this dentist actuallytakes my blood pressure, talks to my doctor, whats going on here? Ive never had adentist do this. You want to build up your practice? Thats one way to do it. So lets

talk about disorders of perfusion.

[Slide #4] [Perfusion][Dr. Vernillo]And what perfusion is. Its movement of whole blood in the vascular

system, the tissues and body cavities. Thats all it is. Its a general term that refers


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as I nearly fall off my chair to the movement of blood throughout various cavities

and the like.

[Slide #5] [Disorders of Perfusion][Dr. Vernillo]And there are different disorders of perfusion. We mentioned some

of them. Were going to come back to them now. Now that I gave you that overview,youre going to start seeing some of these pieces better connect. Pathology is like a

puzzle. Okay? And the reason I ask you, by the way, to study before you come into a

conference because you get a lot more out of the conferences. Some students dontdo this, so I call on them and they have no idea what Im talking about because they

never went to the lecture. They never listened to the material beforehand oh, its

in the podcast oh, problem there oh, couple days before the exam Ill listen to it.

Do not do that. Because youre not going to get anything out of those conferencesand its going to be a problem. I dont say that to threaten anybody or intimidate

them. Im telling you to be honest and positive that the most you can get out of the

conference is how well you listen in lectures, ask questions beforehand email me.

Email me after these lectures. Ill answer you, alright? So that at least I can help you.When you get into the conference, itll knit even more. Thats the idea. So weregoing to talk about disorders of perfusion. Now, I mentioned hypertension as being

pernicious, destructive, because it causes left ventricular hypertrophy. What does

hypertension do also to the coronary arteries, for example, that feed the heart?

What does it do to them? Its high blood pressure. Would that be a form of injury?Sure in heck would be. Now, one thing youre going learn as we go forward and Im

going to explain this in greater detail in the next lecture and in the conferences is

that when you damage that lining of the artery that faces the bloodstream What

do we call that lining? Endothelium, also known as the initma because it has an

intimate connection with the bloodflow going over it. Right. Thats exactly right. So

when you get injury to that endothelium, we believe that initiates the process ofatherosclerosis or plaques. And those narrow the inside of the artery so the

diameter of the artery, if its like this, its now getting more narrow because youhave these plaques which eventually grow outward into that bloodstream and cause

some degree of obstruction. So theres less blood going through the heart. So

hypertension is destructive for two broad reasons: one, it causes hypertrophy, two,

it damages the coronary arteries, narrows them so less blood gets into the heart. So

this is a real jolly disease to have. Not only is the heart less compliant and stiff and

inefficient as a pump, its even getting less blood on top of that. Thats what

hypertension does. So thats why its very important for patients to understand theneed then to control their hypertension. Okay, disorders of perfusion.

[Slide #6] [Hyperemia]

[Dr. Vernillo]Lets take a look at hyperemia. More blood in the microcirculation,

okay? Active hyperemia. You cut your finger. Its inflamed. More blood gets into thatarea as part of the healing process. Bless you. Thats active hyperemia. Give me

another example of active hyperemia that is not pathological youve given megood answers. Youre outside exercising. Go ahead, say thats a good one too.

Getting red in the face. Somebody shows explicit pictures of you on Youtube. Right.


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That will get you red. I always find it amazing when I hear about people that put the

most explicit information about themselves on their smartphones. Not so smart.

Theyre connected to computers. These dimwits. Dont they realize this? And if they

think anything is safe, let me assure you it isnt anymore. It doesnt exist. We justhave to find more creative ways of making things safe. So heres active hyperemia.

Blushing is a very good answer and youre right. If you cut yourself and you get aninflammation is active hyperemia. Where else? Excuse me? Ah, the man who takes

the high road. Very good. An erection. Lets move on as quickly as we can from that.Thats more blood into arteries, yes. What else? And thats why men as they getolder who have heart problems, and they cant get an erection, thats because they

dont have enough blood getting into their main pole. Okay? What else? Go ahead.

Its not the veins what it is that when you exercise and now youre on the right

path to exercise and this is the other part of active hyperemia. When youreexercising, what are your muscles demanding? More blood, more oxygen to meet

the increased metabolic demand of exercise. It was Mark Twain who could

comment, notably, that whenever he had the urge to exercise, he would lie down

and wait for the feeling to pass. Now then. When you exercise, your muscles demandmore blood, they demand more oxygen. So more blood enters those small arteries,

thats hyperemia. Hyperemia, again, means excess blood, whether its active orpassive. So active hyperemia, blushing, inflammation, physiologic exercise. Where

do we see passive hyperemia? Also known as passive congestion. Just mentioned it

today. Where do we see it? Come on you know the answer. If you give me the wrong

answer, Im not going to electrocute you. I took those buzzers off those chairs a long

time ago. Hmm? Congestion from what? Heart failure. Poifect. So when the left heart

fails, and the right heart fails, then you have total heart failure, also known as

biventricular failure, you have passive hyperemia because all that blood is backing

up from the left side to the right. Its in veins now. Thats passive hyperemia or

passive congestion. Good. Good.

[Slide #7] [Active Hyperemia]

[Dr. Vernillo]So here again, just further active hyperemia increased bloodflow to the microcirculation of an organ due to functional demand. We mentioned

those examples. Microcirculation is flushed with more blood under higher pressure.

Alright. Thats active hyperemia.

[Slide #8] [Active Hyperemia]

[Dr. Vernillo]Examples: blushing we just mentioned that. Inflammation, wementioned that. Functional demand, yea skeletal muscle during exercise, alright?

Now, ischemia. Does anybody know what ischemia is? Youve had general path. Youhave general path now. Did you learn about the term ischemia in this course? Mhm.

Nice. Less blood flow. Yes. Now why would you have less blood flow in the setting of

heart disease? Go back to hypertension, go back to the coronary arteries, what does

hypertension do to the coronary arteries? Damages the intima, promotes

atherosclerosis. Those plaques get big. They narrow the lumen. What is the term we

use to describe narrowing? What is the word that pathologists use to describe

narrowing inside the lumen of an artery? Not vasoconstriction, thats generally


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considered physiologic, yes, thats narrowed but thats not related typically seen

in the setting of disease in the way that heart disease has narrowed arteries. There,

we dont speak of vasoconstriction per se. although you will have vasoconstrictive

compensatory responses in heart disease. Rather in the setting of coronary artery

disease, we speak to stenosis. Narrowing. And that word is used in other diseases as

well. But in the setting of heart disease, were talking coronary artery disease,stenosis. So coronary artery disease is known as atherosclerotic disease. Its known

as ischemic heart disease. Because youve got less blood because those arteries thatnarrowed due to plaques, brought on by continued damage to the intima from

hypertension. And there are other factors that cause coronary artery damage. What

are those? Other than hypertension and theyre leading causes of heart disease. You

know this. What other factors can make somebodys heart very unhappy? High

cholesterols a goodone. What else? Good. Smoking. Smoking is s form of chemicalinjury. Once you injure the endothelium, I dont care what you injure it with,

whether you injure it smoking, whether you injure it with high cholesterol, whether

you injure it with the mechanical elevated high pressure of hypertension injury is

injury is injury is injury. And once you have injury, that initiates the process ofatherosclerosis. And this is why people dont often understand, you know, you seethese commercials on tv about smoking? Tough, tough disease to break. Tough habit

to break. You got a guy and hes standing there talking about his high school football

field I used to sit on those bleachers when I was in high school but now hes

talking to you and hes standing there like this with one leg. Why one leg? Becausehe continued to smoke and he damaged that smoking, that chemical gets all

throughout your system, just doesnt get into your lungs gets into the arteries

feeding his legs. Thats chemical injury to the endothelium, get atherosclerosis in

your leg, in your arteries. And if you get enough atherosclerosis in that artery, what

eventually happens? Yea, you have to amputate the leg. Now, Ill explain why your

leg goes dead in a moment. Thats infarction and Ill explain the pathogeneticsequence of events but most people dont get that concept. You do. But your patient

says, well, I know doctor its bad. I can get mouth cancer. I know its bad, doctor, Icould get lung cancer. Yes, and you can lose your leg too. So well talk about thatgoing forward. Very tough disease, very tough habit. So, ischemia. Why would I have

more blood trying to get into my heart if my coronary arteries are delivering less

blood. Seems a little paradoxical. Why would there be an attempt to get more blood

in there. Why would I have that response if I have a stenotic coronary artery? Is my

myocardium happy? No, its inflamed and damaged. Its got less blood, its got less

nutrients and if the ischemia is really severe, I mean really severe, those heart cells

can start to necrose. So, youve got inflammation because you got injury so the body

responds to this inflammatory setting and the setting of ischemic heart disease,coronary artery stenosis, by trying to pump more blood in there anyway with the

attempt to feed more oxygen and nutrients to that inflamed, damaged heart. Thats

the relationship of active hyperemia, more blood, in the setting of ischemia. Does

that make sense? I like to explain things as much as I can. I also realize that there are

things that I cant explain and this is what youre going to find out about pathologyand certain things in general. Youve got more gaps in our understanding than we do

in our understanding. Its far more gaps. Youve got a lot more ignorance in not


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knowing than knowing. And as clinicians, as you go forward, youve got to start to

think about how you can bridge some of those gaps. The best way you know how

and you can do that only on the basis of the knowledge you already have and I got

one better for you, that knowledge is not perfect. So imagine what its like when yougo into the clinic and you got somebody with a whole bunch of disease and youre

going to remove a tooth to scale teeth, youve really gotta, again, have your thinkingcap on for these people. Okay.

[Slide #9] [Passive Hyperemia][Dr. Vernillo]Passive hyperemia: decreased blood flow to a tissue or organ. We

mentioned that. Its also called congestion and as you right pointed out, a few

moments ago, its seen in this setting of heartfailure. Congestive heart failure. Most

common cause of right failure? Left failure, absolutely.

[Slide #10] [Congestion]

[Dr. Vernillo]Engorgement of an organ with venous blood. So on the right side

when you have right failure from left and all that blood backs up and the liver getsenlarged, we called it hepatomegaly. Thats congestion. Passive hyperemia. Okay.

[Slide #11] [Congested Liver]

[Dr. Vernillo]Heres a picture of an unhappy liver. Now, its all mottled. In other

words, its variegated. It looks kind of red. Let me see if I can dim the light withoutblowing this place up. Lights lets see if this works. Who knows I dont know.

Whatever. No? No. Well at least youre still sitting in your seats. Looks like it even

got brighter. Hmm, yea. Story of my life. Okay. So you see that in the liver then you

have all this mottling. Now, look at the microscopic and look at the gross. Because

these things often correlate. Heres the microscopic picture here. Now, you see all

this red? What is all this red? When you see red, when you see purple, you think ?Blood. So all this red is blood cells packed into what structures of the liver again?

Remember, I mentioned the inferior vena cava, little hepatic veins, blood gets

dumped into the sinusoids. Thats a section of a liver. The liver youre looking atright here, that Im pointing to, that liver cut on my microscopic section. So you have

all of this blood thats packed into sinusoids and the liver gets big and it stretches.And its got a thin capsule on top of it, which also makes it tender and uncomfortable

because the capsule doesnt have much give. So this liver gets very enlarged. Hey, Igot one for ya do you think if this patient lives long enough theyre going to wind

up with problems with liver function? What you think? A priori, without any further

information, that answer is correct and what is an important function that the liver

has? Detoxify drugs, good. What else? Hmm? Okay, glycogen storage. Good point.Thats an anabolic function. What else? I cut myself. I stopped bleeding because? I

make clotting factors. The liver is the organ that makes clotting factors. So if youve

got longstanding liver disease, you can run into impairment with bleeding. You

never think of this, huh? Youve got a patient thats got congestive heart failure,

youre going to scale their teeth, youre worried about a number of things. Maybeyou should ask the physician about whether or not theyre prone to bleed. This is

why we teach you this. And I never stop learning it.


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[Slide #12] [Congested Lower Legs]

[Dr. Vernillo]And then I get off this picture of this individuals not-so-attractivelegs. This is Dr. Phelan trying to illustrate something. But you see these areas here

that Im pointing to? They look bumpy? These are dilated veins. Theyre called what?Varicose veins. Where do you see varicose veins? Except, obviously, on peoples legs

but what are the causes for them? Major cause for varicose veins: pregnancy. Thatsone. Another cause of varicose veins: theres hereditary patterns. They follow

patterns in families. But they represent congestive veins because they get dilated

and blood backs up in them.

[Slide #13] [Passive Hyperemia Causes]

[Dr. Vernillo]Alright. Okay. I was going to say one thing, I forgot what it was. But I

was just trying to tie in a concept. But again, these are the things that, you know, we

need to do going forward. Why you learn this stuff. Because in this curriculum, we

go from one box to another. Oh, yes, I know and you say Im done with this course.

My students give me this. Why you askin me about anatomy again? I passed that.

Well, good. Wonderful. Mazel tov. You passed. Im glad you passed. But you wannaknow somethin? You gotta reapply it and in the pathology, I dont expect people toknow every little nerve, vein, and artery but there are certain things you should

know to understand disease and thats why you learn the anatomy. But Ill give you

one better on this. Its scary in the sense that even though Ive been in this business

for a while when you look at me, I will tell you that I walk into those clinics

sometimes and Im afraid that I dont know enough to help them. And I dont claim

to know it all. Any person who would ever tell you that is on ya-ya land. Nobody can

ever know it all. But the thing thats scary is that we never know it all and surgeons,

and I would be willing to hypothesize this, in fact Id be willing to tell you fromexperience in talking with certain surgeons, is that they sweat or schvitz little drops

of red blood at the 10% they dont know. They may know the 90% but they worryabout the 10% they dont know because, certainly not willfully, some of thosepatients die in that 10%. So when students say to me, just memorize enough

answers to pass an exam, theyre missing the whole story of why theyre studying.Theyre studying not just to pass exams, which is obviously an important objective

here, no one disputes it. Theyre studying for their patients. And some people dontsee that right away. But as you get into the clinic and you treat patients, youre going

to see it right away and theyre going to be diabetics, theyre going to behypertensives, theyre going to come in with all sorts of jolly problems and theyre

going to have multiple medications. And some of them arent even going to knowwhat the devil the pill means. I dont know, I take this blue pill, I have no idea what it

is. You have to know what it is. Because youre treating them. Left ventricularfailure. Look at this slide. See the title in this slide? It says passive hyperemia. Okay.

How is left ventricular failure see the two items under it how are they all

connected? Now the way that they are listed, you dont necessarily know whatcauses what and why. You just see two items under there. I want you to know better

when you can know it, why those two items are there in the first place. As opposed

to just memorizing and hoping that they appear on an exam as (a) and (b). I want

you to better understand it. And they may appear on an exam as (a) and (b) as part


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of a multiple choice question but Im more interest in your understanding why that

is. What is the connection between coronary artery disease and left ventricular

failure again? I heard that sigh. That sigh was an existential sigh that came deep

from someones soul. What is the connection between coronary artery disease andleft ventricular failure? Please well the coronary arteries feed the left ventricle but

if the coronary arteries are damaged by hypertension, is the blood getting or more is the heart getting more or less blood from those coronary arteries? Less. And if the

heart gets less blood, it can undergo failure and then what happens as a result of left

failure? You have passive hyperemia. So you have passive hyperemia, left

ventricular failure, coronary artery disease. The coronary artery disease can lead to

left failure. The left failure can lead to passive hyperemia. Thats the sequence. But

the way that slide is written, you cant tell that. Im explaining it. And this is a

perfectly good slide. Its not a criticism on the slide. I just want you to go beyondwhat youre seeing on the slide. Because if you memorize stuff, youre going to make

yourself slap-silly. Youll be in Bellevue before your time in the psych wards as a

patient. Pulmonary disease. Whats the relationship between left ventricular failure

and pulmonary disease? So coronary artery disease can lead to left ventricularfailure and left ventricular failure can lead to passive hyperemia. Whats theconnection between pulmonary disease and left ventricular failure? Left ventricle

fails, blood goes back through the pulmonary vein and into the lungs and you get

pulmonary edema. Thats the connection between left ventricular failure and

pulmonary disease. So, coronary artery disease can lead to left ventricular failure or

cause it. Whereas, pulmonary disease is an outcome or result of left ventricular

failure. So, when I say on exams to you, which of the following is associated with

something, thats a pretty easy question because it could be a cause or it could be a

result. But if I get more specific with you and I asked you what can cause something,

or what can come out of it, then you have to understand the mechanism better.

Localized obstruction to venous drainage causes passive hyperemia. How doeslocalized obstruction to venous drainage cause passive hyperemia? What is a deep

venous thrombosis? You see this on TV? You have DVT. Right? Everybody gets

excited. Oh my goodness. And it is serious. Its very serious as Ill explain in a fewmoments. What is deep venous thrombosis? You get a thrombus where? What leg

veins? Have they taught you this in anatomy? If they havent tell me they havent. theiliac vein. The popliteal vein. The veins around, above your knee. Femoral vein.

Popliteal. Iliac. In the area above your knee you can get a thrombus. Now weregoing to discuss what a thrombus is in some detail today. What is a thrombus? What

makes it up? What cells principally? What blood cells? Platelets is exactly right. In

fact we used to call platelets thrombocytes. They make up a thrombus. Now, theyre

not the only blood cells that make up a thrombus but they are the major componentof a thrombus. And theyre seen in the setting of injury. When you cut your finger,

you form a hemostatic plug or clot. Thats physiologic. But when those same

mechanisms cause a clot if you will inside a blood vessel in the setting of disease,

thats thrombosis. Thats an intravascular clot. And its really bad news when you

have it there, whether its an artery or a vein and well make that clearer in a fewmoments. So a deep venous thrombosis can happen from stasis of blood flow. What

are the mechanisms that lead to the formation of a thrombus? You had this in


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general path? Famous Viennes Austrian fellow who came up with three postulates

that explain how people get thrombosis. No? Okay. The persons name, Austrianpathologist, by the name of Rudolph Virchow and its called Virchow Postulates. And

what Virchow postulated and I have a slide here tos how you in a few moments on

that is when blood flow undergoes stasis, that is to say when theres congestion it

doesnt move well stasis or theres turbulence of blood flow its not smooth,laminar blood flow, its turbulent or if your blood is kind of sticky. We say that it is

hypercoagulable. Dont worry about writing it down, Ill show you a slide. Any ofthose conditions by themselves and certainly in any combination can be

predisposed to thrombosis. So youre sitting on an airplane and Ive done a lot of

traveling and Im sure some of you have when you live in countries where you go a

great distance and youre sitting there. Why do they tell you to get up? Why do they

tell you to do those dopey-ass exercises where you do this and you do this whatare they trying to do? They want you to get your blood going. When you walk, your

muscles contract on your veins and force blood back up. But when youre sitting,

even if youre healthy, as many of you certainly are, and youre sitting in a chair for a

long period of time, youre going to get stasis of blood in those deep leg veins. Andthat can contribute to a thrombus in a deep leg vein. Thatsa DVT, deep venous

thrombosis. Or you have a patient who goes to the hospital and theyre immobilized,theyre in bed, they cant get out of bed because theyve had major surgery, theyre

not moving theyre predisposed to deep venous thrombosis and in some cases in

those patients, theyll put them on anti-coagulants to prevent that thrombus fromforming. Well talk about that later on next week. Okay, so when that vein, when that

thing forms, its a problem. Its a problem because now you cant get bloodto go

back up because youve got a thrombus in a deep leg vein around your knee. Whats

going to happen to the blood in that vein? A thrombus is now formed. Whats goingto happen to the blood in that vein? Is it moving? What do you think? So, if its not

moving, is there congestion? What follows congestion? Edema, your leg swells. Butthe real kicker in all of this is the patient who gets out of bed, has the swelling in the

leg, in the calf of the leg not a little cow calf down here they got swelling, they

get up and suddenly they clutch their chest and they drop dead. THUMP. What

caused them to die? The clot dislodged and what do we call a dislodged clot? An

embolus. Right. And emboli, almost always come from thrombi. There are other

sources of emboli; amniotic fluid from pregnancy, obstetric complications like that

if you go and you go deep sea diving and you come up too quickly, nitrogen gascan accumulate in your blood vessels, gas can form emboli. Fractured bones, fat can

form emboli. But the vast majority of cases, the very vast majority, emboli come

from pre-existing thrombi. Now if that thrombus, breaking off from that deep

venous thrombosis in that leg vein travels up, where does it go? My iliac vein goesinto my inferior vena cava. Now Im going up through my inferior vena cava. Now

Im going into what chamber in my heart? My right atrium. Then Im going down

into what chamber in my heart? My right ventricle and what major artery comes out

of that right ventricle? The pulmonary artery. Now I got this clot thats done some

traveling and now it gets to my pulmonary artery which has a branch point. Okay?

You have the right and the left pulmonary artery that enter the lung. At that branch

point, thats a bifurcationpoint. Two arteries shoot off the pulmonary artery, the


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right and the left pulmonary artery. That clot is going to lodge right at that branch

point. You think youre going to get any blood into your lung? Hell no. Nuh uh. Nowall that blood suddenly backs up on the right side of your heart. What do you think

happens to you with that sudden damming or backing up of blood on the right side

of your heart? What will happen to your right side function? You go into right failure

and youll die suddenly. Understand. You dont need left failureto die. You dontneed left failure to cause right failure as a cause of death, although its a very

common cause of death. Left causes right failure but let me tell you right failure,independent of left is a very respectable way to drop dead. We call that cor

pulmonale. I mentioned it in the setting of lung disease like emphysema and chronic

bronchitis who call it chronic cor plumonale. But in the example Im giving you right

now where that clot has formed in that bifurcation point, theres a sudden stoppage

of blood and a sudden right sided heart failure from that embolus. A pulmonary

embolus because its now in your lung. And we call that acute cor pulmonale. Often

seen in the setting of pulmonary embolus. A major cause of mortality in this country.

By the way, we mentioned chronic cor pulmonale and we mentioned how the right

ventricle can hypertrophy over time do you think your right ventriclehypertrophies from actue cor pulmonale related to that embolus in that bifurcation

point? Whats your guessand a n umber of you are saying now and youre absolutelyright. And why would that be? Right. Is there enough time for you to make that

muscle thicker? When I was in graduate school and I was doing my doctorate in

pathology, one of my professors said to me, there are four dimensions in pathology.

Four of them. Width, depth, length, and the dimension of time. And time is critical. If

somebody dies suddenly, as in the scenario that we just described with acute cor

pulmonale. They dont have time to hypertrophy their right ventricle. What do you

think happens to their right atrium? Is blood backing up? What do you think

happens to the right atrium? Is it a muscle wall? No, its a measly simple-ass sac,

with a few little dumbass cells in it. So what happens to this sac? It stretches. Andthats not good. Because if it stretches, it cant function. And then you can die

suddenly from arrhythmia and thats usually the cause of death in acute corpulmonale. Well talk more about arrhythmia and how that works. Now, you gotthat. I know you understand that. So thats what Im trying to describe here as we go.

You see all sorts of thrombosis in hepatic veins. Were going to suspend that. Thatstrue. Were going to talk about that more next term in Systemic Pathology and whenwe talk about a syndrome called Budd-Chiari syndrome. Dont worry about thatnow.

[Slide #14] [Chronic Congestion of the Lungs]

[Dr. Vernillo]Okay. Chronic congestion of the lungs. So I got heart failure. Im nothappy. My left ventricle is hypertrophied. My coronary arteries arent doing so well

either. My bloods backing up. Things are getting into my lungs. Increased

hydrostatic pressure, a major pathogenetic mechanism of edema. Were going to betalking about more mechanisms of edema in the conferences next week. So, all that

fluid is getting into my lung. I cant breathe. Im not happy. I belong in New Jersey.Now what? Why would I have interstitial fibrosis? We asked this question earlier.

Where is the interstitium with respect to those air sacs? Sure. Between them. Dont


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be afraid to give me answers. For goodness sakes, youre too shy. For the kind of

money youre paying for an education, dont be shy. So now you got spaces betweenthose air sacs, right? The interstitium. Why the heck would I what does fibrosis

mean? When we say something is fibrotic what does fibrotic or fibrosis? Scar.Collagen is exactly right. Why the heck would I be laying down a collagenous scar

between my air sacs? If I have pulmonary edema, okay. If I have pulmonary edemaand I got water in there, why would I want to put scar around those sacs? To

prevent them from bursting. Because I got fluid in there. And what youre going tounderstand as we go through pathology together and certainly next term,

philosophically and clinically, these kind of responses which are called

compensatory responses can only work for so long before they fail you. This is a

compensatory response; putting collagen down in the interstitium around the

alveolar air sacs to prevent those sacs from rupturing because of all the pulmonary

edema there but what kind of edema is that, by the way? What two flavors does

edema come in? This I know youve had. Well, edema, generally, whether its in the

lung, whether its in your leg ... what are the two general flavors or types of edema?

No? Yes? Transudate and exudate. Transudate is non-inflammatory edema as seenin the setting of heart disease and pulmonary edema which were talking abouttoday. Where do you see exudate, which is pus and schmutz and pus and bacteria?

Where do you see exudate? Pneumonias in the lung, thats a classic example of

pulmonary exudate. Thats the other form of edema. So theres transudate. Theres

exudate. Transudate is non-inflammatory. Exudate is inflammatory. Were talkinghere about transudate. Thats pulmonary edema. It is a non-inflammatory edema. It

is not brought about by infection as in pneumonia. It is brought about by a failing

left heart. Okay.

But the interstitial fibrosis has a problem. Yes, it tries to prevent those air sacs from

rupturing but what problems might that scarring create in the lung? Right. If mylung is turning into a fibrotic knot with all that scar in it, how well is it going to

expand? Not very well at all. So we say that we lose compliance in the lung. We cantexpand our lung as well as we would like to expand it because there is resistant scar

in it. So, compensatory responses again, are meant to save you but only for the short

term because in time, unless the underlying condition is somewhat corrected, these

responses will fail. Theyre a short gap measure but they dont succeed in the long

term. Whats pulmonary hypertension? In left ventricular failure what doespulmonary hypertension refer to? What vessel? The artery, the pulmonary artery.

Why do we have pulmonary hypertension in left ventricular failure? Because left

ventricular failure leads to right ventricular failure. And what happens to the

pulmonary artery? All that blood backs up in the pulmonary artery and we call thatpulmonary artery hypertension. So thats the reason youre seeing pulmonary

hypertension on that screen because left ventricular failure leads to right failure

leads to lung damage leads to pulmonary hypertension and I described that at the

beginning when my computer was having a technological temper tantrum. Now,

macrophages containing hemosiderin. Wheres hemosiderin comin from? You hadthis in physiology. Im sure you had this. Wheres hemosiderin coming from? By the

way, I appreciate the attendance today. I like to see more people but I would also


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like to say this is laudable. Praiseworthy. At this time of the morning. Seriously. I

thought I would be seeing ten people today, maybe five. Now, why? Because I come

from an old school. I thought all the money I was spending for an education I

mean I tell my students with your laptops, if your computers dont work, come inwith a paper and a crayon to take notes if you have to. With the amount of money

youre paying for it. Teasing you. Whats hemosiderin? Wheredoes it come from? Ifeel like Im in the country. I feel like its quiet and all I hear are crickets. Come on.

Wheres the hemosiderin coming from? Say. Hemoglobin. Whats your name? Paul.Brave man, you are. You gave me the right answer. Now, that comes from

hemoglobin. Explain to me whats going on. How is hemosiderin winding up in

macrophages in your lung? Whats the connection there? Go back to whats going on

in the lung in the first place. Go ahead. Dying red blood cells. Whats your name? Kit?

Alright. Youre right. Dying red blood cells. How are the red blood cells getting inthere? How are they winding up in those air spaces for example? Look at the title of

that slide. Chronic congestion of lungs. Increased hydrostatic pressure leads to

pulmonary edema. Quite right. The British put an o in front of the e. Indeed. Now,

that forces many of my graduate professors were Brits brilliant teachers, by theway, but I just love their accent. Now, they would youd have pulmonary edemaand what happens under that increased hydrostatic pressure? What could be

pushed out into those air spaces? In addition to the transudate? Red cells. Now you

got red cells filling up those spaces. What are the macrophages doing there? Theyre

respectable phagocytic cells. Thats exactly right. Theyre cleaning up the red cells.Theyre digesting them. And when they digest those red cells because theyre trying

to get rid of them, theyre saying youre not supposed to be in here, in fact, nothing is

supposed to be in there except air. They start digesting the red cells. They digest the

hemoglobin. And they release hemosiderin. Now, do you want that or thathemosiderin, over time, contributes to a brown discoloration of the lung from the

accumulation of all that hemosiderin pigment due to the breakdown of red bloodcell hemoglobin red blood cells that got into the air spaces under increasedhydrostatic pressure from the failing left heart. Alright. Is the lung over time soft or

is it rather firm? So that when you touch it, it doesnt feel like a nice soft sponge. AndI see this when I did pathology in grad school. I mean, you just the lung are at you

theyre like theyre solid. You cant press on them like a normal lung. Whatsmaking it firm? The fibrosis. So not only is that lung brown, its hard and brown. Orbrown and firm. And we call that brown induration of the lung. Induration means

firm. It means hard from the Latin word durawhich means hard. Alright. Good.

[Slide #15] [N/A]

[Dr. Vernillo]Alright, so heres a picture of an unhappy lung. Take a look at this. Letme just point you at the direction here. All this stuff that youre looking at here

this pink stuff all of this this is a cross-section of lung. This is actually

bronchiole muscle from bronchi so that when they cut this lung, some of the muscle

from the bronchiole walls showed up. So this is not pathology. This is cross-section.

But this is. See this pink stuff? Ill show you. Heres a space. You see where Impointing here, theres a space. And you see this pink stuff all around it? Im pointing

kind of like surrounds it? This is an air space and this pink stuff surrounding it is


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collagen. So this is a lung that has undergone some interstitial fibrosis from chronic

passive congestion of the lung. Chronic because its chronic. Passive congestion orpassive hyperemia because it is a chronic condition from failure from the left. And

theres lung damage. Thats an example of chronic passive congestion of the lung.See that? Makes sense? So when you see these images I want you to now understand

what youre looking at rather than go, huh, Im just going to be a dentist anyway. Idont need to know this.

[Slide #16] [Disorders of Perfusion][Dr. Vernillo]Let me tell you something. I went to another dental school. Im not

saying that because I went to Case Western and about two or three months ago, I

was in Central Park in my favorite restaurant called The Boat House. Charming spot.

Have nice bar, great dinner, and you can look at swans on the lake and everything.

Very Victorian in that sense. And Im seated there having a great time, just thinking

about things. And that same evening we had an alumni convention from Case and it

was about 21stcentury healthcare what we as dentists willdo. They had

physicians there, they had my former dean there, they had people from a placecalled Harvard, which the pilgrims founded. They had a whole bunch of other people

there from all kinds of different professions social workers everything. And the

concept that they were advancing, and youve probably heard this here but Ill

mention it because its appropriate at this juncture is that, as future dentists,

many of us are going to be working in major healthcare centers, the model of that

office above the butcher shop, that routine well, thats still important. I dont

denigrate that at all. Thats still very important and people get help from that and its

an important matter of public service. I dont in any way seem to think against those

models or against other office type of models. Dont misunderstand. The way weregoing in the future is were going towards centers where there are going to be

physicians, dentists, pharmacists, nurses, social workers, and I would like, I dare say,to interject my own little piece of this into it, maybe even ethicists who are all

working together to make sure that that patient receives optimal healthcare, which

means that youre going to have to talk to physicians and understand them. Theyregoing to have to talk to you and understand you. Youre going to be educating each

other. And what we are now seeing is that the healthcare of people who go through

such centers, and we have them, is improved. This is where were going. This isgoing to be your future. Not mine but yours. And assuredly, when I hear some

students saying and I dont say this to be disrespectful with anyone in particular

dont misunderstand well I dont need to know this, Im just going to be a dentist its like please, what are you doing in this profession? Because right now, where

we are as dentists, is we are playing a pivotal role in healthcare. Make no mistakeabout it. And youll come to understand that more and more. But as we move

forward, were going to be seeing health centers. So youve got to have some

understanding of this. You dont have to be a cardiologist, you dont have to be apulmonologist anymore than Im any of those things but you do have to have

enough of an understanding to be able to talk with a physician and ask the questions

because again, youre treating the same patient, both of you.


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[Slide #16] [Disorders of Perfusion]

[Dr. Vernillo]So, we mentioned hyperemia, hemorrhage, another disorder ofperfusion. Thats when youre walking down Nostrand Avenue in downtown

Brooklyn at 3 oclock in the morning and someone tickled your ribs with a knife.And you start bleeding. Thats hemorrhage. Thats blood getting out of you. Thats a

disorder of perfusion, okay? So we mentioned two major disorders of perfusionnow. Hyperemia, active and passive, which we spent some time on. And hemorrhage

which is the next major disorder of perfusion. You bleed.

[Slide #17] [Hemorrhage- causes]

[Dr. Vernillo]And all the causes listed there and were going to be talking about

these next term. Trauma getting your ribs tickled with a knife. Surgery. Whats an

aneurysm? If you dont does anybody know? Go ahead, please In your brain,good. Whats your name? Alright, Shon. Aneurysms can occur in different parts of

the body. They can occur in your brain and they can be congenital when they do. An

aneurysm is a dilatation of an artery. It can also be a dilatation of a left ventricle.

Well explain that conceptfurther. But its a dilatation or a widening of an artery dueto disease. In the brain theyre called congenital aneurysms. Theyre known as berryaneurysms because they look like little berries. What do you think can happen to

those aneurysms? They burst and you bleed and if its in your brain, it can be fatal.

The most common place that we see aneurysms, however, is in the abdominal aorta.

And that is most that is the site, the abdominal aorta, that is the most common sitefor atherosclerosis. Why would atherosclerosis contribute to an aneurysm? How

might it cause it? Whats your best guess? Somebody said it, say it a little louder.

Somebody gave me the right answer. Say it again. Be afraid not. Say it. Thank you. So

the wall gets weaker. Now why would the wall get weaker and stretch and form an

aneurysm with an atherosclerotic plaque sitting there? Does your body like the

plaque? Yes or no? No. And what does your body do to try to get rid of the plaque? Itmobilizes inflammatory cells with enzymes to digest and get rid of it. But those

enzymes that are released from that, those inflammatory cells, in attempting to

digest that plaque and get rid of it, also digest part of the blood vessel wall. So the

wall weakens and it undergoes dilatation. And in the case of an abdominal aneurysm

from atherosclerotic disease, if that ruptures, thats invariably fatal.

Vitamin C deficiency is the cause of hemorrhage. Vitamin C makes collagen so if you

dont have enough collagen you have weaker blood vessel walls. Whats

thrombocytopenia? Thrombocytes are platelets. Okay. What does penia mean? Theterm penia in pathology? Less, right. Fewer thrombocytes or platelets. You have

leukemia. Horrible disease. Leukemic cells start off in bone marrow. Well teach youabout this next term. As those cells multiply, they take over your bone marrow so

you lose red cells, white cells and you lose platelets. Infections can do it. HIV

infection is notorious for causing thrombocytopenia. So is Epstein-Barr. Viral

infections. They can do it. Drugs can cause thrombocytopenia. And there are

autoimmune diseases that can cause thrombocytopenia. So if you dont have enoughplatelets, youre going to hemorrhage. How many platelets do you need to bleed

spontaneously? I look at you you bleed. Thats called spontaneous hemorrhage. No


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trauma, no provocation. I look at the patient the patient is bleeding in front of me.

How many platelets do you need to get to that point? Normal platelets run from

100,000 on the low end to 400,000 on the high end per cubic millimeter of blood,

which is a microliter, not a milliliter. So a cubic milliliter and a microliter are

equivalent. There are one thousand microliters in a milliliter. So you have anywhere

from 100,000 to 400,000 platelets per cubic millimeter or microliter of blood. Ifyour platelet count gets below 20,000, you could bleed without provocation. You

can just ooze and hemorrhage. And in some severe that happens.

Deficiencies of coagulation factors well talk about that next term. What would

cause you to have less coagulation factors? What would make your liver unhappy?

In this country? Jack Daniels, Black Label, Grey Goose. Alcohol; a leading cause of

cirrhosis in this country. Your liver gets turned into a scar. Youre not going to makemuch in the way of coagulation factors. Its called acquired hemophilia. And then

you have the hereditary hemophilias: hemophilia A, hemophilia B, Von Willibrands

disease well talk about these next term but theyre coagulation factor deficiencies

and they bring on hemorrhage.

Gastric ulcers. You can bleed from an ulcer. Duodenal ulcers, peptic ulcers welltalk about those next term.

Esophageal varices. What is a varix? Dilation of a vein. Perfect. In alcoholic liver

disease, people get dilated esophageal varices. Well talk about the mechanism in the

next term in the setting of hepatobiliary disease. But what do you imagine, at this

juncture, would be a major complication associated with esophageal varices? Its a

dilated veins and theyre very, very prominent inside your esophagus. What couldhappen to veins when you eat? They could rupture. You can hemorrhage to death.

And if youre an alcoholic, we could see a lot of esophageal varices in the setting ofliver cirrhosis. If you dont have enough coagulationfactors, youre going to have ahard time stopping the bleeding. And this is why some people die. They

exsanguinate on their own blood.

Viral infections can cause hemorrhage. And invasive tumors can do that because

tumors can sometimes erode arteries and cause bleeding.

[Slide #19] [N/A]

[Dr. Vernillo]So heres petechiae. Petechiae, these little red dots are associatedwith thrombocytopenia. This is an intestinal .. this is GI this is a GI specimen. But

these are all little dots here. Here, here, here, here. Petechiae. Throbmocytopenia.

[Slide #20] [N/A]

[Dr. Vernillo]What is this? Obviously the brain is dead or their brain wouldnt bethere. What is this? What is this goo? What happened to this poor soul? So lets say

this person had heart disease. Lets set up a scenario. Lets bring in somemechanisms. Heart wasnt pumping efficiently. And if a heart doesnt pump

efficiently, blood isnt moving efficiently, is it? Its not pumping efficiently. Theres


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some stasis of blood in that left ventricular chamber. Theres some turbulence of

blood in that left ventricular chamber. And what did good ol Rudolph Virchow sayabout stasis and turbulence? What does that predispose to? Thrombus. Thats

exactly right. And that thrombus can attach to the chamber, the wall of the left

ventricle. That inside chamber. You can actually get a thrombus attaching to that

wall. What kind of a thrombus is that called then if its attaching to a wall? Andtheres a beautiful example of it in Lincoln Center. Actually theres a beautiful

example in the Chicago museum as well. A beautiful example of art. Its called amural because it is on a wall. Mural comes from the Latin word for wall. So you have

a thrombus on the heart wall. We call it a mural thrombus. What do you think can

happen to that mural thrombus sitting inside that left ventricular chamber now? Can

it break off? Can it embolise? Right. And if it embolises, it can go down my aorta,

down my femoral arteries, pick off my popliteal artery, block blood flow under my

leg and give me a gangrenous leg and then I lose a leg. It can go upstream because

emboli are not smart. Theyre stupid little dumbest little particles. They just go with

the flow. They can go down, they can go up. Where would they go up from the left

ventricle? To your brain through what artery in your neck? The carotid. So now theygo up through your carotid. They go through the cerebral arteries that come off that

carotid. And they block off a branch in your brain. What happens to your brain?

What happens to the tissue? It undergoes necrosis. In the case of the brain its

liquifactive necrosis and we call that a cerebral infarction. An infarcted tissue is

dead. What do you think is going to happen to that blood vessel that has that

embolus sitting in it? Is that blood vessel happy? Does your inflammatory system,

you immune system try to get rid of that plug? You bet. And as it tries to get rid of

that plug in that blood vessel in your brain and those cells release enzymes, what

happens to the wall of that blood vessel? It ruptures. Now you have what is called a

hemorrhagic stroke. Thats what youre looking at there. That area in the upper left

as you face it is blood. Thats a hemorrhagic stroke. Its fatal. Stroke is also calledcerebrovascular accident, CVA. And the British call it apoplexy. Apoplexy. Thatsanother word for stroke, cerebrovascular accident. Thromboembolic disease. This is

classically seen in the setting of heart failure. Pretty awful and its hemorrhage inyour brain.

[Slide #21] [Definitions]

[Dr. Vernillo]Okay, this term of definitions youve heard these terms before but

theyre important and Im going to go through them and explain why they are and

the way that I know how to explain them in terms of clinical care. Purpura means

purple. It doesnt mean much of anything. It talks about diffuse hemorrhaging. If you

lets go back to Brooklyn. Its three oclock in the morning. Somebody hits youwith a bat. Up and down. And you turn purple. You have purpura. Thats all it means.

It just means youre turning purple from blood.

These other terms, however, have a little more specificity. Petechiae are small 1 to 2

mm pinpoint hemorrhages I showed you an example a few moments ago, seen in the

setting of what kind of deficiency? Of what type of cell? Thrombocytes. Thats

exactly right. Thrombocytopenia.


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Hematoma. You know, you get some injury, again in Brooklyn at three oclock in themorning. You get hit in the face. You have blood that pools under your tissue like a

blood blister, as some people have called it. Thats a hematoma. Its an accumulationof blood and it causes a swelling.

Ecchymosis is a larger area of hemorrhage. So lets take a look at a few more

examples of this

[Slide #22] [N/A]

[Dr. Vernillo]These little dots are called what kind of hemorrhage? Petechial

hemorrhage. Now, these are associated with thrombocytopenia. This is a patient

who could have a viral infection. In fact, Eppstein-Barr Virus, which causes

infectious mononucleosis in roughly 75% of those cases, they can present with

petechial hemorrhage on the soft palate like that. Now that doesnt mean these

individuals are going to wind up with fatal bleeding. Its a manifestation of a viral

infection that causes thrombocytopenia. But lets say thats a kid who comes in toyou. And that child is, say, eleven years of age. And you see that and you may think

viral infection but suppose the patient has other signs and symptoms. Suppose they

look pale. Suppose they look really pale or theyre very, very fatigued. And they got

that. Then you gotta think, hey, it could be thrombocytopenia but if this child has an

underlying malignancy if this child has leukemia and those leukemic cells aremultiplying in the bone marrow and thats where leukemias start. They originate in

marrow. Once those things start to multiply, they replace platelets, you become

thrombocytopenic. They replace red cells, you become anemic because you lose red

blood cell mass. They replace cells like polymorphs, PMNs, which help you to fight

infection. So this can be an early manifestation or sign in a child of underlying

leukemia. These are the things that you can I see.

[Slide #23] [N/A]

[Dr. Vernillo]This is a hematoma. Larger swelling could be due to any number offorms of injury.

[Slide #24] [N/A]

[Dr. Vernillo]Heres another hematoma here on the lips. See that? Youll see this inyour patients all the time. They probably bite the inside of their lip.

[Slide #25] [N/A]

[Dr. Vernillo]Now, this is grand. Doctor, I bit the inside of my cheek. What wouldyou say about that? That should worry you a little bit because even though you have

an obvious cause even though you have a cuase that the patient bit the inside of

their cheek, they shouldnt be bleeding like this. Thats ecchymotic bleeding. Thatsecchymosis. That, by definition, where petechiae are 1 to 2 mm, this is a good 1 to 2

cm across. Thats major. Ecchymotic bleeds are associated very often withunderlying coagulation factor deficiencies. Just like petechiae are associated with

thrombocytopenia, ecchymotic bleeds, in contrast, are associated with coagulative


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deficiencies. Could you see this in an alcoholic? Sure you could. If this patient had

enough cirrhotic liver disease and they werent making enough coagulation factorsand they bit the inside of their cheek, they could bleed like that. So, the bite as the

cause is not the problem. I mean its a problem in the sense that it precipitated thebleeding. The problem is the pattern of that bleeding. Thats what should disturb

you. Do you think youre going to go taking teeth out in a person like this? Heck no.Id be going back to the physician trying to find out if this patient has an underlying

bleeding disorder before I even touch those teeth. This is why youre learning this.This is what we do.

[Slide #26] [Circulatory Disorders]

[Dr. Vernillo]Okay. So were moving along here. Youre actually being brave souls.

Im fully aware of the fact that the mind can digest only what the seat can endure.But I would encourage you to just stay with me because we will conclude this thing

not too far down the road. Were looking at nine-thirty. So we will, you know, well

conclude it shortly but I do want to get through some of these other points and I do

want to now take a look at these three. And I think what well do is well stop atedema which we can dispense of fairly quickly in the next presentation. In fact,

weve been talking about these concepts all throughout today. So, were basicallynow coming back to the point in our review of these ideas. Thrombosis, embolism,

and infarction represent the triad of hell. They go together. All too often they do in

the setting of heart disease. What does thrombosis do to a coronary artery? If it

completely blocks off that coronary artery and you cant unblock it, what happens to

the heart muscle? It dies. What kind of necrosis is that? Its coagulative. And

whenever you have death of tissue as a result of blockage, either of an artery or a

vein, that is known as an infarction. And a thrombus can also dislodge and that

dislodged thrombus is called an embolism and if that embolism travels far enough

like into your brain thatcan cause an infarction. We saw an example of it when Ishowed you that picture of a cerebral hemorrhage hemorrhagic stroke. So letstake a look at a few of these.

[Slide #27] [Thrombus]

[Dr. Vernillo]This is an aggregation, again, predominately platelets. Again, whenyou injure your finger and cut it. Platelets get into that clot, get into that cut rather,

form a clot and stop you from bleeding. But when those same platelets are inside

your blood vessel and that blood vessels is injured, then having a pathological clot,

which is known as a thrombus, is not such a good deal. Your body, however, doesntdiscriminate. Your bodys saying, hey, I gotta form a clot here. But when it forms

inside a blood vessel, it leads to a whole bunch of problems. That is a pathologicalclot, its a thrombus and you need injury. So if you keep smoking, or if you dontcontrol your high blood pressure, and you keep damaging that endothelium, the

body says bring in the platelets. Bring em in. and when those platelets stick to thatarea, they can form a thrombus and occlude a coronary artery, for example. This is

your bodys response to injury, whether its your finger, whether its the inside of acoronary artery, its the same idea, same mechanism. It doesnt discriminate


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enzymes going to do to that plaque? Digest it. Crack it. Fissure it. Well, for goodness

sakes, if Ive got a plaque now thats sitting there and its cracked and its fissured,whats going to stick in that? Platelets. This is a perfect substrate for a thrombus to

form. But Im going to do you one better than that. If you throw a rock in a stream,those of you who are more country-oriented, if you throw a rock in a stream, what

happens to the water around the rock? Yeah, it ripples, itsturbulent. You see whatare called Eddy currents. Not because Eddy invented them. So youve got this water

around the rock. Eddy currents. Because that water flow is disturbed by the

presence of the rock. Similarly, that atherosclerotic plaque now protruding into the

lumen of that blood vessel, is causing turbulence of blood flow because that blood is

trying to flow over it. And when you have turbulence of blood flow, what does that

predispose to? Virchow again, lets resurrect him one more time. What does

turbulence of blood flow predispose to? Thrombosis. So you got a plaque that for

two very good reasons is very thrombogenic, that is to say attracts platelets. One, it

can be fissured and cracked from inflammation so platelets stick to it. And two, the

turbulence of blood flow around that plaque like that rock in the water, this plaque

in the bloodstream, that turbulence also predisposes to thrombosis. So, plaques arehighly thrombogenic. And if that thrombus gets big enough and occludes the artery,

then the tissue undergoes infarction. Right. It dies. This is what happens. And this is

the problem with this disease. So you could get infarctions all over the place in

arteries, heart, brain, kidney, intestine which is called mesenteric. Once this disease

starts, the only hope you have is controlling it because once its advanced diseasethe patient is constantly, constantly threatened by another attack. When a person

has a heart attack from atherosclerosis and superimposed thrombosis a

myocardial infarction is also known as a heart attack. Once theyve had an

atherosclerotic plaque, once theyve had a thrombus, once part of their heart musclehas died, once theyve had a myocardial infarction or a heart attack or an MI, they

are prone to have another one. And theyre prone to have another one because theirarteries are all damaged anyway. Its only a matter of time before platelets stick insome other artery, feeding that heart somewhere else. So these patients have to be

managed by anticoagulation therapy on an ongoing basis. And you and I as dentists

see these people. And we have to speak to the physician about, you know, were

going to take out a couple of teeth. Were going to scale the teeth, were going to getrid of the plaque or the calculus from those teeth also known as schmutz. Dirt. Weregoing to get rid of this stuff from the teeth. But wait a minute. This patient is a heart

disease patient and is on an anticoagulant like Coumadin or Warfarin to prevent

thrombosis, a philosophical and ethical dilemma. Because while youre trying toprevent this patient form forming a clot, youre also making this patient more prone

to bleed. And where is the balance and you have to speak to the physician beforeyou do that procedure.

[Slide #31] [Atherosclerosis][Dr. Vernillo]Okay. This is a disease of large and medium-sized arteries.

Atherosclerosis does not occur in arterioles. And it doesnt occur in veins. It occursin large and medium-sized arteries. Large artery: your aorta. Medium-sized arteries:

your coronary arteries, your cerebral arteries. It is a disease of arteries and lipids


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accumulate there and it just continues to grow. I will describe to you by the time we

get into those conferences how that happens or how we think that happens.

[Slide #32] [Infarct][Dr. Vernillo]An infarct is dead tissue. Its an ischemic necrosis. Its not ischemia.

Although you can have death of tissue in severe ischemia. Ischemia is reducedperfusion of blood. When that artery becomes occluded by an embolus or a

thrombus, then the tissue dies and then we call it ischemic necrosis and thats aninfarction. Okay and then in the brain, its liquifactive. Elsewhere its coagulative.

[Slide #33] [Pathogenesis of Arterial Thrombosis]

[Dr. Vernillo]Okay, so I think Im going to take another two or three minutes,

then let you go. I want to make sure you get your moneys worth. Dont worry, Dr.Vernillo. We got our moneysworth. I understand. Lets just see. Yea. Were just

going to take it up through here. Lets just do these real quickly. And then this were

going to stop at outcomes after the formation of a thrombus. That were going to go

onto next week. And thats itsown its not complicated. But I just want to take youto this diagram here

[Slide #35] [N/A]

[Dr. Vernillo] which is in honor of Virchow. Yeah okay.


[Dr. Vernillo]So, again, a thrombus is platelets or thrombocytes and it happens in

the setting of injury. So when you smoke or when you dont control your blood

pressure or if youre diabetic and you dont control your disease people who havediabetes have a much greater risk of atherosclerotic heart disease. They start sooner

and its more extensive and well talk about some of the mechanisms that we thinkare operable there. But suffice it to say at this juncture that its injury. And once

theres damage to the endothelium or theres injury, that endothelium is not happyanymore. Ordinarily, that endothelium protects you from thrombosis. It has

anticoagulant properties. But once its injured, it loses those anticoagulant

properties. And platelets can stick to it and you can wind up with a thrombus. Injury

is injury and the more factors you bring into the picture, the worse it gets. So if you

smoke, if you have high lipids, if youre a poorly controlled diabetic, if you havehypertension the more you bring into the mix of each of those diseases. 1 + 1 + 1 +

1 does not equal 4, it equals 104. Risk factors are synergistic. Their outcome, their

effect is not due just to their sum, its greater than their predictive sum. Thats what

synergy means. So when a physician says to somebody, hey, Joe, lose some weightand stop smoking, hes saying to good ol Joe, youve got two risk factors that aregoing to heighten your risk of coronary artery disease. Get rid of them. Stop the

smoking and drop some weight. Very, very hard for lots of people to do. All you need

is one risk factor. All right? You can be as thin as a stick you can be thin but if you

smoke, youre pretty much no better than somebody whos obese in terms of gettingheart disease because youre injuring your coronary arteries just the same. So,

disturbing the anticoagular properties of the blood vessel wall, platelets begin to


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stick fibrin this can contribute to the formation of a thrombus. And of course, if

youve got a plaque under there, so much the better because plaques are, in fact,thrombogenic. And plaques form in the setting of injury. All of this is a culmination

of continued injury to the endothelium from the factors I just mentioned a few

moments ago.


[Dr. Vernillo]You get alterations in blood flow that can predispose to a thrombus.Turbulence, stasis, there they are Virchows postulates. That can happen in the

presence or absence of plaque, as long as theres injury, but the plaque, thats where

you usually see a lot of thrombus formation because that thing is a mess. Platelets

stick to it, its inflamed, turbulence of blood flow, its a real mess.

An increased coagulability of the blood. That can predispose to thrombosis.

Polycythemia is a malignancy of red cells. If you have a lot of red cells in your

bloodstream, more than you should have, blood gets thick. It gets vicid. And itdoesnt move as well and that predisposes to thrombosis and those patients get

polycythemia. Well be talking more about polycythemia next term when we look at

various hemologic malignancies. Oral contraceptives can do that. So any of these

things, whether it be stasis, whether it be turbulence, whether it be increased

coagulability of blood, any of them unto themselves can cause thrombus to form and

all of them together but as we go to this last picture

[Slide #35] [N/A]

[Dr. Vernillo] this is Virchows postulates that weve been talking about today.Its central to the understanding of thrombosis in the setting of heart disease. Heres

a thrombus and notice the difference in the arrows. You have thick arrow here andyou have thinner arrows here. The thicker arrow is thicker because what it is saying

is that thrombosis is rooted, if you will, is central to thrombosis is endothelial injury,

as weve mentioned throughout this particular lecture. And other things will feedinto it. Abnormal blood flow, hypercoagulability of blood, blood that gets thick. Any

one of these factors, be they endothelial injury, abnormal blood flow, and

hypercoagulability can lead to the development of a thrombus. Any one of them. But

th

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