Sept 10: start: 24.07
Foam cells can appear anywhere.
1. Coronary Artery Disease
Narrowing of the lumen of one or more of one or more of the conronary arteries.
Usually due to Atherosclerosis’s. Atherosclerosis is the irregular distribution of
blood lipid deposits in the intima of large and medium arteries.
Narrowing of lumen means reducing the area where blood flows through. The
artery has three layers: intima-the most internal layer that we have that is in
contact with the blood. Right at the intima, there are tiny cells that form, this cell is
called Endothelium. Cells that make up the structure is called endothelium. Purpose
acts as a barrier, a layer of cell that covers the entire circumference of the lumen. It
is a selective barrier, allows certain things to pass, MOST IMPORTANT: Reacts to
things that happen in our blood. If we have anything to happen to our blood,
the endothelium releases chemicals that artery dilate or constrict. Therfore
vasoacivity. Ability of artery to dilate or constrict depends on many things. You
have also innervations that goes here, but you also have the ability of the
endothelium, allows the artery to respond to whatever is present in our blood.
There are some molecules that are released within the tissue depending on what we
are doing first of all, so if we are exercising, that allows it to respond in a dilation or
constrictive way. If we have alterations in blood pressure, it constricts or dilates
depending on what is necessary to equilibrate or maintain the blood pressure.
(30 min) Second layer is called Media: Made up of main component: smooth
muscle cells. Function of smooth muscle cells is to control the narrowing or
dilation (ability to control it). This is what allows it. When they relax, dilate, when
they contract, constricts lumen. Its exactly between the three layers= MEDIA layer
(30:30) The most outer layer is called: Adventitia. Made up of mainly connective
tissue, and elastin (provides elasticity to the structure) , collagen (provides
rigidity). So an artery must be able to expand to accommodate alterations to blood
volume, but has to be able to constrict and alter its diameter.
(31. 44) So what happens to CAD is that in the narrow disk of lumen here, there is
an accumulation of lipids in other cells that makes it narrowing. It is also known
as hardening or calcify of the arteries.
Artherosceleresis is hardening of the arteries, as a result of plaque that builds up
the side of the artery walls. It can happen everywhere. We typically talk heart, but
can happen in the femoral (leg), or the brain (carotid, stroke). Can happen in
different part of the body. We typically stress just heart. It does not just at one area.
(33:42) When it happens at the heart, known as coronary artery disease, can cause
ischemia (lack of 02 blood flow to the heart), congestive heart failure (heart is not working properly as there is no nutrition and 02, tissue lose its ability to
contract and dies). Instead of blood flow in one direction, blood stays in the heart,
and gives the congestive feeling. When the heart does not pump properly. This is
(34:49) Angina pectis (pain in the chest). Chest pain is the product of ischemia .
In other words when lack of oxygen and nutrients in heart muscle cells occur, pain
Myocardial infarction (heart attack), cardiac arrest when the heart fails (just
When atherosclerosis to the brain (cerebral vascular disease, or carotid artery)
causes stroke. -.-
In peripheral area, limits exercise ability. In leg muscles, very difficult to tolerate to
exercise as lack of O2 to leg. Muscle cell needs to be perfused with 02 and nutrients.
Blood flow is important as it also carries away byproducts of metabolism.
Telling someone who is sedentary to start exercise could challenge its system, it
could also collapse.
At resting conditions, myocardium 250ml blood to the heart. The hear uses 30ml.
The heart not only sends 02, it needs 02 for itself. Approximately 5 percent of
cardiac output (SV TIMES HR). SV- How much it pumps out by one beat. How much
work our heart does. 5 percent of whatever our pumps out, goes to whatever
needs the heart needs itself. Heart is only 0.5 percent of the total body weight.
If we exercise, it is more important as there is increase demand of O2.
Picture of how:
healthy normal artery. Direct contact with blood.
When the situation in a bad shape. When we have a severe occlusion. X-ray of chest,
using contrast, see occlusions. When point is far down, only small portion of heart,
but if its high up, the entire section that is irrigated by that artery is compromised.
Most plaque occur most at branching of the arteries. One thing that is interesting
is that when we have a branching point, because the blood flows in one direction,
when it branches, it causes turbulent in blood flow it causes little damage to
structure of the artery. If we have the right toxic environment, it triggers the
process of start to accumulate plaque. No problem if its normal function
This takes us to the physiopathology of the problem. 1. The main cause of atherosclerosis is an inflammatory disease. In which
immune mechanisms interact with metabolic risks factors to initiate,
propagate and activate lesions in the arterial wall.
2. Dyslipidemia → _Biochemical disorder characterized by one or more
abnormal levels of blood lipids (Table 1).
Toxic environment= metabolic risks factor (favours formation of plaque).
Hypertension, arterial damage.
When do we have inflammation normally? (Trip, bruise, when there is an
mechanical impact, when cells are broken, damage the tissue, body tries to repair,
needs to have inflammation, migration, distribution of specific components of blood
that goes to that area to solve the problem). In order to solve problem, need to
increase blood flow, increase macrophages to that area. Macrophages engulph
damage tissue (clean up damage) so that can form new cells and repair. In
order for this to happen need to irrigate the tissue. Therefore swelling, warm, occurs.
Painful because cell release chemicals that promotes pain.
(52:20) antinflammatory drugs: To contain the inflammatory process and pain
associated. It makes it more tolerable. Slow down the inflammatory response only.
Two types of antinflamatory drugs: 1. Steroidal, 2. Non steroidal.
What is the difference? Non steroidal, contain the process but don't block it
completely. They just manage it (reduce the pain). Drugs that complexly block it
(corticoids) don't feel the pain at all (which is dangerous) They block fiberblasts
TG are lipids, cholesterol is a lipid.
HDL, LDL, CHYOLOMICRONS, ARE THE CARRIERS, LIPOPROTEINS. Need carriers as
they are not soluble in water.
How much carriers may prevent arthersclerosis.
(59:54) How does the process typically take place. This diagram in a bottom
crosses section of an artery. We have intima layer (the endothelial cells is the
rectangular shape). Directly in contact with blood. Media, made up of smooth
muscle cells, the adventitia.
(1:01) What happens when we have a small injury, on the structure because of
changing flow, or turbulence in that area, it causes an inflammatory, small lesion,
macrophages they migrate in the blood to there, they try to fix the problem. The
problem is that if there are too much lipid in the circulatory (Scavenger receptors on
macrophages, it identifies things that nobody wants to have in the body, it loves
when there are lots of fat, high cholesterol, when HDL is low, when LDL is high,
macrophages take them in. The problem is that when they take them in, they become foam cells. They now change their function. Now they accumulate in that
area. Underneath endothelial cells. Now they form something called fatty streaks.
Often found in young people (Starts when young). This is stage 2. The process of
atherosclerosis starts. If early stage, we can still get rid of fatty streaks but if
environment doesn't change, build more and more. Later on, foam cells release
“chemo attractants” a chemical that attracts something else. These chemicals
tell smooth muscle cells to migrate from the media layer into the intima. (stage
3). It lifts the endothelial cells and now causes more damage. Causes more injury,
stimulate more microphages to come, eat fat cells, become foam cells and now the
process is amplified (positive feedback). Proliferation and migration of smooth
endothelial cells alters endothelial damage
(1:07) Stage 4: Fibrous plaque cells secrete fibrous material that forms a cap.
Cells are trapped and begin to die. Endothelial cells now dies, not enough oxygen,
nutrients, now a fibrous caps is created. Now we have an encapsulated structure,
the bump keeps growing, over years progress to the point it blocks the structure. No
flow of exchange, necrotic tissue (tissue dies)
(1:08) Stage 5. When it becomes very serious. When the cap calcifies it looses
flexibility. Hemorrphaging can occur now as when structure becomes rigid and
(1:14) Exercise improves all structures. Makes it more elastic, and improves lipid
Lipids are not soluble in water, therefore cannot ciculate in blood. Therefore 4
lipoproteins that vary in contact, where they come from, and what they chew.
Chylomicrons: COME FROM GUT (intestine) MAINLY TG (85 percent)!!!!!! Very
little proteins, very little cholesterol. A droplet of reprocessed lipid synthesized in
epithelial cells of the small intestine which enters the blood via the lymph. Comes from
liver, diet. LEAST DENSE of plasma protein!. Diet - intenstine, breaks down with
acids, 3 fatty acid + glycerol erythrocyte (cell lining of intestine takes) up fatty acid
+glycerol, puts back together to form triglyceride, packed backed into chylomicron, sent
through the lympth system. Most tryglycerides will be present in chylomicrons.
SEPT 12 2013:
(5:21) VLDL- Very low density lipoprotein (55 percent TG less than chylomicrons).
COME FROM LIVER!
Rich carbohydrate diet, stores as glycogen, too much carbohydrate, transformed into fat
by liver, it sends it out into circulation as VLDL. Sends it out to circulatory.
Pasted from the notes: Generated by the liver by packaging TG, cholesterol,
phospholipids and apoB-100. VLDL is secreted into the blood where it receives apoCII
and apoE, as well as cholesterol esters from HDL. It is converted to IDL (intermediary
density lipoprotein) in the blood stream by digestion of its TG by lipoprotein lipase (LPL). The TG of IDL may be degraded to produce LDL or may return to the liver where it
binds to cell surface receptors, is taken up by endocytosis, and is degraded by lysosomal
(7:29) LDL: Low density lipoprotein (~10% TG, 20% proteins, 10% Cholesterol, 35%
cholesterol esters, 20% phospholipids). Much richer in cholesterol level. Conversion
of VLDL. When VLDL interacts with other tissues and cells, they eventually become
LDL molecules. Bad thing to have in high amounts from blood test. Bad because?
(causes: 1. Free radical attack LDL and create something called modified LDL, the
scavenger receptor on macrophage recognizes the LDL particle with more affinity,
so it will take in even more! Creates more foam cells 2. Whatever it has in it, it is used
to deliver the fats from LDL). The role of LDL is to deliver lipids to the cells!
Delivering lipids to tissue as its richer in cholesterol (most important molecules for
tissues). It reaches an artery, it donates fat to macrophage there, and form foam cells.
(12:00) HDL: (Produced mainly by the liver, and a little bit of gut) Poor in triglycerides.
Has substantial amount of cholesterol esters. Chemically speaking both are the same
between HDL and LDL. Positive. What differentiates the two is where HDL is found.
HDL is synthesized in the liver and gut. It accepts cholesterol from peripheral tissues
such as cells in the walls of blood vessels. In other words, while LDL gives away
cholesterol (negative, accumulate foam cells), HDL does the opposite. HDL now takes
these cholesterol to the liver and now degrades the HDL. HDL is reverse cholesterol
transport away from the circulation. Protects the cells and tissues. Liver internalizes it
and breaks it apart.
What does the liver do with cholesterol: Creates bile, which is important for fat
metabolism. Helps emulsifies lipids.
As pasted from notes: cholesterol is converted to cholesterol ester, part of which is
transferred to VLDL by CETP and returned to the liver by IDL and LDL. The liver
reutilizes the cholesterol, converting it bile acids, or excretes it directly into the bile
(Fig 4). HDL, therefore, tends to lower blood cholesterol levels, which is associated with
When HDL is high, LDL is low= GOOD THING!
It is where it is located that determines if it is a good thing or not.
When we eat: Intestinal cells take up the lipids. They make chylomicrons from intestine.
They come through what pathway? Through the lymph system.
What is the difference between lympth system and circulatory system? Lymphatic
system is open system. Circulatory system is where blood circulates. Lympathetic
system runs with Lympth. Lympth is found in insertitutial fluid (no RBC, other cells of
immune system). Lumphatic Enter different parts of the cell (prevents infections). (Is the
check of breast cancer- any nodes in breasts that are altered). Lymphanoids are like filters where if one cell becomes modified, immune system will then attack it, swells, and then
it becomes painful.
Chylomicrons. They first enter the lymphatic system (carries most of the lipid) as they
are so afraid of water. Eventually they get into the circulatory system. As they circulate
they pass through many kinds of tissues. They pass through for example: muscle, and
fatty tissue. Main function other particle is to distribute its content (From diet, the lipids)
need to get to the cells, by the blood, then for it to donate its content to the cells and
tissues. It first needs to interact the capillary level of the structure of the cells. It needs the
Presence of lipoprotein lipase. As the name suggests, it breaks down lipids and
lipoproteins. So chylomicrons, when they made in the gut, they also come with one
particular protein that is hanging out on the surface of the particle—its called APOC2. It
has to have it there, as this protein is what anchors with LPL (recognizes APOC2)
and activates the enzymes and now can break down triglycerides (fatty acid+
glycerol). The lumen of the capillary has the LPL. When chylomicrons come, it allows
time for the chylomicrons to interact with the LPL because of the APOC2 (which is on
the chylomicrons). When the particles anchor with LPL it cleaves the bonds of glycerol
and fatty acid. Fatty acids go into the cells and get used.
When we eat lipids, not only eating fat, there is also some carbohydrates presence. And if
it’s after a meal, at the same time that this process is occurring. There is another thing
that takes place. The glucose level in circulation goes up. If glucose level goes up, if
glucose level goes up what happens? Insulin level goes up as it is released, and promotes
storage. So after a meal, as we finish and these processes are taking place. Our blood
glucose level goes up, insulin goes up so now we have lipoprotein lipase breaking down
lipids into fatty acids. What doe the insulin tell the muscle to do? Store and use some of
the lipids. The same it does to adipose tissue to store. The main hormone to tell body
to store is insulin. So when the environment favors the body to store the energy, we
will have increase level of stored lipids.
(29:45) Fat cells and muscle cells do not use glycerol’s. Where does it go? Covert the
glycerol to glucose would be (gluconeogenesis- Make new glucose from sources not
carbohydrates). Glycerol is an alcohol, another thing that can be used is amino acids
(proteins). But obviously after a meal, do we need to make more gluclose? So then what
will the liver to do?
(32:05) What it will do most likely is take that glycerol and make fatty acids again to
store in the liver. But what the liver does is that it takes all these stuff (cholesterol, amino
acids, glycerol) forms with another important step here. As the chylomicrons travels
through the blood and donate triglycerides to its cells and tissues its starts shrinking
because the load is being taken up.
(32:25) As it shrinks shrinks shrinks..it becomes chylomicron remnants, which is a
much smaller particle. This small particle also has receptors on the liver that internalize
these chylomicrons remnant’s here. They form a vesicle and goes into the liver by
endocytic vesicle. Along with the glycerol, fatty acids, amino acids they can fuse with
the vesicle and form VLDL and send it to the circulation again! Glycerol carbon + fatty acid= esterification bond.
Cholesterol, obtained by the liver from the remnants, inhibits cholesterol synthesis
As pasted from the notes as previous:
Generated by the liver by packaging TG, cholesterol, phospholipids and apoB-100
Fate of VLDL: VLDL TG is degraded by LPL (also has APOC2), forming IDL (as
they shrink). IDL can either be endyctosed by the liver via receptor mediated process or
futher digested, mainly by hepatic triacyglycerol lipase (HTGL) to form LDL. LDL
may be oxidized and taken up by “scavenger” receptors in macrophages. The
scavenger pathways plays a role in atherosclerosis. Pheripheral cells have LDL cells that
can bind LDL and take its content (in normal individual). However in times where too
much lipids, macrophages will be very active. If there are lots of HDL present, they
would take these cholesterol away.
HDL does not have APOC2 so that is why it is not able to give cells cholesterol while
LDL has it.
Every cell in the body has potential to make cholesterol. Even if we go on a diet that
is 100 percent clear of cholesterol, our body will be able to make cholesterol. Why:
we need it to make hormones.
A. Cholesterol biosynthesis:
You take acetate (2 carbons) from the body from different sources (fat,vinegar), Acetate
gets converted to HMG-CoA. Once it gets into HMG-CoA it needs to get converted to
Mevalonic Acid. In order to do so, it needs HMG-CoA Reductase----- (few more steps)
and it becomes cholesterol. Cholesterol acts a feedback mechanism (negative). As the
cell produces cholesterol, it suppresses HMG-Co- reductase. Most people with high
cholesterol, is not because they eat too much cholesterol, they are producing too much
cholesterol. It is the negative feedback that does not working properly. Scientist then
develop a drug that suppress the conversion. (Lipitor) inhibiting HMG-Co-A reductase.
B. Enterohepatic Circulation
Another thing important about cholesterol. Liver coverts cholesterol to bile. Bile is then
released into the GI tract (intestine!) and along with bile, you have a little bit of free
cholesterol for digestive purposes. Very little of this bile is excreted. Of the free
cholesterol, 50 percent comes out in feces, the other 50 is reasorbed. Bile, only 3 percent
is eliminated 97 percent is reabsorbed. Elimination of cholesterol is very little. What if
we now use drugs that increase the rate of excretion of cholesterol excretion. Some drugs
inhibit the reabsorption of bile. This is indirect way, because increase the excretion of
bile, now we have to take more cholesterol from the circulation to make more bile.
SEPT 17 LECTURE:
Effects of exercise: Decrease total cholesterol. Decrease LDL (dramatic), increase HDL. Greater improvements in blood lipid profile are achieved with increased exercise
loads of 1200 to 2200 kcal/week. 2200kcal/week is almost exercise everyday!
Exercise has no effect on drugs.
Pharmacological treatment for dyslipidemia and potential implications for exercise
testing and prescription.
1. Bile acid sequestratrants- Drugs that lower tryglyceride level by decreasing
reabsorption of the bile and more excretion from liver. This increase bile production
and thus decrease triglyceride levels in blood.
2. Fibric acid derivatives: Increasing blood HDL cholesterol levels.
3. HMG-CoA reductase inhibitors. Inhibits the coversion of HMG-CoA to Mevalonic
acid- cholesterol. Therefore inhibits the production of cholesterol
4. Cholesterol absorption inhibitor. Bile and cholesterol cannot go back into the
circulation through the GI tract (intestine). It blocks absorption. It binds to
cholesterol and makes cell not able to use it.
Most popular: HMG-CoA very efficient for reducing body ability to produce
The chronic physical activity of cardiovasculatory function and aerobic fitness
in healthy adults and cardiac patients.
VO2= Q x (a-v)o2
Q= cenral component, (A-V)= pheripheral component, extraction of O2. Most dependent
component as can have high Q but low extraction.
Rate pressure product: HR X SBP (systolic blood pressure)
Systolic blood pressure is the force of contraction of heart (Indicator of how strong the
heart is, higher means more powerful heart)
Positive chronotrophic effect: Increase HR
Positive inotrophic effect: Increase blood pressure
For a cardiac patient: A heart transplant, not all nerves are connected, therefore not as
@ Maximal values: Oxygen uptake increases both for healthy individual and cardiac patients.
Logic: Increase mitochondria content, increased capillary, enzymes for oxidative capacity.
Leads to also increase for Cardiac output as better arterial venous O2 blood return for
healthy individual but no change to cardiac patients.
Systolic blood pressure: no change as it also has a maximal value (it cant really go up)
Increase to (A-V)o2 values to both cardiac and normal person.
HR=> No change to decrease in normal individual (most dependent on age, you cant
really change it that much max heart rate= 220-age). For cardiac patient, no change at
all(heart is just as weak, cant do maximal exercise).
No change to systolic BP or Rate pressure product.
Endurance level: Increase to both!!
Ejection fraction (Increase in healthy, no change to decrease in cardiac patients= heart is
@ Submaximal values (things decrease except stroke volume)
Oxygen uptake: Stays the same to decrease. Since have more mitochondrias, and
capillaries. O2 uptake stays the same or decrease (as it needs less oxygen to do the same
Heart rate decrease (system does not have to work as hard), sv increase, systolic blood
pressure decrease, rate pressure product decrease.
@Resting Values (Entire system is more efficient)
O2 uptake: No change for both
HR: Decrease for both. System is more efficient
Rate pressure product: Decrease
HR decreases @normal, submaximal for both but at maximal
HR @maximal, no change to decrease (as system is more efficient, but also there is a
maximal value it could be: 220-age) Cant really change it that much.
Rate pressure product decreased for both @normal, submaximal Systolic blood pressure decreased for @submaximal because heart does not have to
work as hard (not much change to @maximal as it cant go up any higher, not much
change to decrease to normal, not much opportunity to show efficiency),
Cardiac Output for @maximal: Has increasing effect whiles @submaximal does not is
because machine has more ability to reach higher thresholds while at submaximal, the
machine does not have to work as hard.
For a cardiac patient at maximal: Cardiac output
Target zone training: 70-85 percent of peak heart rate reserve (reserve= something we
have extra). HRR therefore is at maximal heart rate- normal heart rate (how much we
have left to use)
SEPT 19 2013
Type of training chosen should be best suited to the individual.
Research of 1984:
Gain in VO2max is most gained via 70-85 percent of HRmax
Figure says: If we increase the intensity of exercise intensity, we see an increase an
increase in how much we gain in VO2 max, but once we gain above 85 percent of
VO2max there is little benefit.
Percent of VO2max is lower than percent of HRmax values typically by 20 percent
=if you go beyond 85 percent of HR max, not good.
Atherosclerosis: typically recommend aerobic exercise training.
Elevated values of systolic and diastolic blood pressure after TWO OR MORE
PROPERLY measured, seated BP readings (not disturbed, and easily disturbed for
Blood pressure: The force of blood against the walls of arteries. If peripheral
resistance is high, blood pressure will be high too.
Present in 20 percent of the general population. Most part, there are no symptoms
The events of a cardiac cycle in the arterial circuit have been described as PRESSURE
The pressure pulse has to limbs: The ascending (anacrotic), descending (dicrotic). It
has Zenith (systolic) and a nadir(diastolic). Systolic pressure is largely determined by the force and volume of blood ejected by
the left ventricle into the aorta.
Diastolic pressure by the resistance to VOLUME Displacement presented by the
Greatest pressure drop in arterial circuitry occurs at the level of peripheral arteriole,
which therefore is the prime regulator of DIASTOLIC pressure.
Blood pressure is recorded as two numbers—the systolic pressure (as the heart beats)
over the diastolic pressure (as the heart relaxes between beats). The measurement is
written one above or before the other, with systolic number on top and diastolic number
on the bottom. For example, a blood pressure measurement of 120/80 mmHg (millimeters
of mercury) is expressed verbally as “120 over 80”.
(22:45) The Riva Rocci/Korotkov Method
Indirect measurement of blood pressure.
It has to be assumed that there is no beat-to-beat or second-to-second variation in
blood pressure, which is known not to be true.
Handcuff cuts blood flow, and then when we gradually release pressure, first sound we
hear is the result of the pressure of the cuff and the blood inside the artery will be equal.
So any reduction in pressure, will allo