Download Review of Normal Vascular Concepts

It is expected that students will have reviewed this
content PRIOR to coming to class. There may be 1-2 items
from the review of Lipids and Fats on the exam.
Anatomy and Physiology Review: Lipids and Fats
Lipids are chemical compounds that are found in foods and in our bodies. Major lipids include:
 Neutral fats (triglycerides),
 phospholipids, and
 cholesterol.
Triglycerides provide energy for metabolic processes. They share this function equally with
carbohydrates. The basic units of phospholipids and cholesterol are fatty acids. Their major function is to
form cell membranes for all of the body's cells and they also provide other intracellular functions.
How are Lipids Transported?
Dietary fats are absorbed via intestinal lymphs to form "chylomicrons". The chylomicrons are
transported to the venous blood from the lymph system. Chylomicrons are removed from blood
plasma within one hour of entry into the system. They exit the blood as the blood passes by the liver
and fat tissue. Fat tissue contains an enzyme, "lipoprotein lipase". This enzyme hydrolyzes the
triglycerides into fatty acids and glycerol. The fatty acids then rapidly diffuse into the fat cells. Once
in the fat cells, the fatty acids rapidly reform into triglycerides.
Responding to Energy Needs
When fat is needed for energy, it must be transported to the tissues where it is needed. It is
transported in the form of Free Fatty Acids (FFA). Fat does this by again hydrolyzing the stored
triglycerides, which then breakdown into fatty acids and glycerol. Upon leaving the fat cell, the fatty
acids bind reversibly with albumin (the major plasma protein) and become "free fatty acids". The
normal FFA level in the body is about 15 mg/100 ml of plasma. Although this level is very small, it
still accounts for almost all of the lipids being transported. FFA has an extremely rapid turnover rate,
being replaced about every 2 to 3 minutes. This makes it a very rich and highly available (renewable)
energy source!
Any condition that increases the need for use of FFA for energy will have an increased amount of
FFA in the blood. Two examples are starvation and diabetes. In both cases, the person cannot use
carbohydrates for energy. Once chylomicrons have been properly stored in the body (as previously
described), the remainder stays in the blood as lipoproteins. Lipoproteins contain both lipids and
proteins. They are smaller units than chylomicrons but with similar composition.
Review of Normal Vascular Concepts
Normal Blood Concentrations
Plasma Value (mg/100 ml)
Triglycerides
160
Lipoprotein Protein
200
Cholesterol
180
Phospholipids
160
Total Lipoproteins
700
5 Major Types of Lipoproteins Classified by density
Chylomicrons
Chylomicrons have the least density and are the largest of the lipoproteins. They are composed
of dietary triglycerides. They are formed in the small intestine.
VLDL - "Very Low-Density Lipoproteins"
VLDL have high concentrations of triglycerides and moderate concentration cholesterol.
Synthesized and released by the liver.
IDL - "Intermediate-Density Lipoproteins"
IDLs are composed of endogenous triglycerides and cholesteryl esters. IDLs provide the primary
source of LDL.
LDL - "Low-Density Lipoproteins"
Are the primary carriers for cholesterol -- The "bad" guys!!
HDL - "High-Density Lipoproteins"
About 50% of HDL is composed of protein with a small concentration of lipids. Synthesized and
released by the liver. The "Good Guys"!
Where are lipoproteins formed & what do they do?
Lipoproteins are formed in the liver. Their chief function is to transport special lipids throughout the
body. Triglycerides are synthesized from CHO in liver. They are transported to fat tissue and other
peripheral tissues primarily in VLDLs. LDLs are the residual of VLDL after they have undergone
delivery to the fat tissue, where they have dropped off large quantities of triglycerides,
phospholipids and protein. Think of LDLs as being the "garbage" or left-overs! HDLs transport
cholesterol away from the peripheral tissues to the liver. They play an important part in preventing
atherosclerosis.
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Where does cholesterol come from?
The exogenous (outside of the body) source is primarily from the diet. It is absorbed by the GI tract
into the intestinal lymph with triglycerides. It can form esters with fatty acids (about 70%) in the
plasma. The endogenous (within the body) source of cholesterol is synthesized by liver. It is formed
within the cells of the body and circulates in the lipoproteins in the plasma. Cholesterol is
considered a major factor in atherosclerosis development.
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Components of Blood Pressure
Students: Please familiarize yourselves with the following terms and their meanings. Why review
these concepts? Because they comprise the hemodynamics of blood pressure! They are also the basis
for the drugs used to manipulate blood pressure AND vessel size in treatment of angina. Do not need
to know in great detail at this point, but a general understanding is needed.
Cardiac Output (CO)
The primary function of the heart is to impart energy to blood in order to generate and sustain an
arterial blood pressure necessary to provide adequate perfusion of organs. The heart achieves
this by contracting its muscular walls around a closed chamber to generate sufficient pressure to
propel blood from the cardiac chamber (e.g., left ventricle), through the aortic valve and into the
aorta.
Each time the heart beats, a volume of blood is ejected. This stroke volume (SV), times the
number of beats per minute (heart rate, HR), equals the cardiac output (CO).
CO = SV x HR
Stroke volume is expressed in ml/beat and heart rate in beats/minute. Therefore, cardiac output is
in ml/minute. Cardiac output may also be expressed in liters/minute.
Stroke Volume (SV)
Ventricular stroke volume (SV) is the difference between the ventricular end-diastolic volume
(EDV) and the end-systolic volume (ESV). The EDV is the filled volume of the ventricle prior to
contraction and the ESV is the residual volume of blood remaining in the ventricle after ejection.
In a typical heart, the EDV is about 120 ml of blood and the ESV about 50 ml of blood. The
difference in these two volumes, 70 ml, represents the SV. Therefore, any factor that alters either
the EDV or the ESV will change SV.
SV = EDV - ESV
Central Venous Pressure (CVP)
Venous pressure is a term that represents the average blood pressure within the venous
compartment. The term "central venous pressure" (CVP) describes the pressure in the thoracic
vena cava near the right atrium (therefore CVP and right atrial pressure are essentially the
same). CVP is an important concept in clinical cardiology because it is a major determinant of
the filling pressure and therefore the preload of the right ventricle, which regulates stroke volume
through the Frank-Starling mechanism.
A change in CVP (DCVP) is determined by the change in volume (DV) of blood within the
thoracic veins divided by the compliance (Cv) of the these veins according to the following
equation:
DCVP = DV / Cv
Therefore, CVP is increased by either an increase in venous blood volume or by a decrease in
venous compliance. The latter change can be caused by contraction of the smooth muscle within the
veins, which increases the venous vascular tone and decreases compliance.
Preload
Preload can be defined as the initial stretching of the cardiac myocytes prior to
contraction. Preload, therefore, is related to the sarcomere length. Because sarcomere length
cannot be determined in the intact heart, other indices of preload are used such as ventricular
end-diastolic volume or pressure. For example, when venous return is increased, the enddiastolic pressure and volume of the ventricle are increased, which stretches the sarcomeres
(increases their preload). As another example, hypovolemia resulting from a loss of blood due to
hemorrhage leads to less ventricular filling and therefore shorter sarcomere lengths (reduced
preload).
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Changes in ventricular preload dramatically affect
ventricular stroke volume by what is called the FrankStarling mechanism. Increased preload increases
stroke volume, whereas decreased preload decreases
stroke volume by altering the force of contraction of the
cardiac muscle.
The concept of preload can be applied to either the
ventricles or atria. Regardless of the chamber, the
preload is related to the chamber volume just prior to
contraction.
Afterload
Afterload can be thought of as the "load" that the heart must eject blood against. In simple terms,
the afterload is closely related to the aortic pressure.
This relationship is similar to the Law of LaPlace, which states that wall tension (T) is
proportionate to the pressure (P) times radius (r) for thin-walled spheres or cylinders. Therefore,
wall stress is wall tension divided by wall thickness. The exact equation depends on the geometry
because of different constants for different shapes, and for this reason, the above relationship is
expressed as a proportionalityThe pressure that the ventricle generates during systolic ejection is
very close to aortic pressure, unless aortic stenosis is present. At a given pressure, wall stress
and therefore afterload are increased by an increase in ventricular inside radius (ventricular
dilation). A hypertrophied ventricle (thickened wall) reduces wall stress and afterload. Hypertrophy
can be thought of as a mechanism that permits more muscle fibers (actually, sarcomere units) to
share in the wall tension that is determined at a give pressure and radius. The thicker the wall, the
less tension experienced by each sarcomere unit.
the CO and SVR, but rather by direct or indirect measurements of arterial pressure. From the
aortic pressure trace over time, the shape of the pressure trace yields a mean pressure value
(geometric mean) that is less than the arithmetic average of the systolic and diastolic pressures
as shown to the right.
Frank-Starling Mechanism (Law)
In the late19th century, Otto Frank found using isolated frog hearts that the strength of ventricular
contraction was increased when the ventricle was stretched prior to contraction. This observation
was extended by the elegant studies of Ernest Starling and colleagues in the early 20th century
who found that increasing venous return, and therefore the filling pressure of the ventricle, led to
increased stroke volume in dogs. These cardiac responses, which occur in isolated hearts as well
as in intact animals and humans, are independent of neural and humoral influences on the heart.
In honor of these two early pioneers, the ability of the heart to change its force of contraction and
therefore stroke volume in response to changes in venous return is called the Frank-Starling
mechanism (or Starling's Law of the heart).
Adapted from: Cardiovascular Physiology Concepts by Richard E Klabunde, Ph.D. Published by
Lippincott Williams & Wilkins, 2005. (ISBN: 078175030X)
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