Blood, Vessels and Pressure Phys Lect

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0Physiology Lecture Notes: Blood, Blood Flow, Resistance and Pressure

What is Blood and what does it do?


Blood is a fluid connective tissue that is pumped by the heart and flows through all the blood vessels of
the body. It delivers oxygen (O 2), nutrients and warmth to the tissues, and removes carbon dioxide (CO 2)
and metabolic wastes from cells. Healthy easy flowing blood is key to good health. Blood also has a vital
role in circuiting cells, hormones and other signal molecules that aid in the protection, repair, defense,
and maintenance of homeostasis in the body.

What are the Components of Blood?


As a connective tissue blood must have cells, fibers and ground substance. It has all of these and the best
way to consider blood is to view it as two main elements. Cellular and Fluid. If we take a test tube of
blood and spin it in a centrifuge at high speeds it will separate out into two parts: The Cellular (or
Formed) elements, and the fluid component of blood is called Plasma.

The Cellular elements are the cells of blood which include erythrocytes or red blood cells (RBCs),
leukocytes or white blood cells (WBCs), and platelets which are fragments of cell cells. The plasma is the
straw colored fluid that sits on top (the supernatant) of the spun sample. It contains many important
substances that are critical to the body. About 92% of plasma water that suspends all of the other
elements of the blood. See the figure below of the spun sample of blood in the test tube for the list of
amazing substances found in plasma.

 Glucose, Amino acids, Pro-s, Hormones


 Fatty acids, Triglycerides, Cholesterol, Vitamins
 Ions/Electrolytes (Na+, K+, Cl-, Ca2+, H+, HPO42-Mg2+
…SO42-, Zn2+, HCO3-…)
 Urea, Uric acid, Creatinine, Bilirubin, Ammonia…
 O2 and CO2 (dissolved in plasma)

Blood has 2 parts: Plasma (fluid) and Formed Elements (cells).


Blood pH ranges from 7.35 to 7.45. Typically, arterial blood has
a higher pH (average of 7.41, so it is more basic), whereas
venous blood has a lower pH (average 7.35 so it is more acidic).
The blood is more acidic (lower pH) in venous blood because
there is more dissolved CO2, which forms carbonic acid.

What is an ABG? Arterial Blood Gases (ABG) is the most accurate representation of a patient’s clinical
status with regard to a blood test that measures the pH, levels of oxygen (O2) and carbon dioxide (CO2)
from an artery. The test is used to check the function of the patient’s cardiopulmonary system and their
ability to deliver O2 and remove CO2.

Blood brings warmth to wherever it flow. Blood is slightly warmer than normal body temperature (Tb), it’s
about 38°C (or 100.4 °F), compared to 37.1°C (or 98.6 °F) for an average internal Tb reading. As blood
flows along blood vessels friction and resistance are experienced, producing heat.
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Composition of Blood
Blood is a specialized fluid connective tissue in the body that transports nutrients, O 2, CO2 and waste
products around the body inside blood vessels. Your body constantly circulates blood to ensure growth,
repair, protection, and to maintain homeostasis across the entire body.

Below shows blood sample: a) mixed; and b) spun in a centrifuge, which shows the 2 major components.
a) b)
Blood consists of two major portions:
1) The liquid portion called plasma (~55% of blood volume).
This fluid portion contains glucose, amino acids, protein, hormones,
Buffy Coat ions (electrolytes), etc., as well as dissolved O2 and CO2.
(WBCs)
2) The formed elements or blood cells (~45% of blood
volume). The
vast majority of cells are erythrocytes (red blood cells or
RBCs), also
leukocytes (white blood cells or WBCs) and platelet cells.

Blood constitutes about 8% of adult body weight, with males having between 5 to 6 L and females having
between 4–5 liters of blood.

General Characteristics of Blood


In its natural flowing state, blood is homogenized, meaning its diverse elements are mixed, uniformly and
evenly distributed. The color of blood is not always the same and ultimately it indicates its level of
oxygenation. Blood is bright red in its highly oxygenated state, this is due to the binding of oxygen (O 2) to
the heme containing portion of the pigmented molecule hemoglobin (Hb)! When there is less O2 bound
to these sites, the color of blood becomes dusky red/purple and with even less the color becomes blue.
This is why images depicting the systemic circuit show arteries containing red blood and veins containing
blue blood, it is indicative of the O2 content of the blood.

Blood Viscosity
Blood is viscous fluid, meaning it is ‘thick’ and dense. The viscosity of blood is about five (5) to six (6) times
greater than that of water. This is primarily due to the presence of plasma proteins and various cells
within the blood. Since viscosity is a measure of resistance to flow, the high viscosity of blood has a
significant impact on blood flow and pressure. Imagine if you were trying to drink water through a straw
and compare that to drinking honey through the same sized straw. Which would be easier and why? The
water, because it is less viscus, thus less resistant to flow.

The Blood Plasma


Like other fluids in the body, plasma is composed primarily of water: In fact, it is about 92% water.
Dissolved or suspended within this water is a mixture of substances, most of which are proteins. There are
literally hundreds of substances dissolved or suspended in the plasma, though many of them are found
only in very small quantities. Note: Serum is a fluid that remains after the clotting factors have been
removed from plasma.
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Plasma Proteins
Plasma is about 92% water, and essentially the rest of plasma volume is made of proteins, about 7%.
There are three (3) major groups of plasma proteins, plus regulatory proteins, as follows:

 Albumin - most abundant plasma protein accounts for about 60% of all plasma proteins. It is made
by the liver and delivered to blood by way of the sinusoidal capillaries in the liver. Albumin is what
egg whites are made of, a slippery and thick fluid, and helps explain how plasma proteins
contribute to blood viscosity. These molecules serve as transport binding proteins for insoluble
lipids (fatty acids and cholesterol), to facilitate transport of hydrophobic lipids in the watery
plasma. Albumin is the most significant contributor to the osmotic pressure of blood (COP), the
force generated in solution by proteins that can draw water across blood vessel walls from tissues
into the bloodstream. This in turn helps to maintain both blood volume and blood pressure.

 Globulins – make up about 35% of plasma proteins in three subgroups: alpha, beta, and gamma
globulins. The alpha and beta are made in the liver and transport iron, lipids, and fat-soluble
vitamins A, D, E, and K to cells. Gamma globulin are antibodies (immunoglobulins) involved in
immunity and the only plasma proteins not made by the liver, but by leukocytes (plasma cells).

 Fibrinogen – only accounting for about 5% of the plasma proteins, it is essential for blood clotting.
Fibrinogen is an inert (inactive) enzyme made by the liver. It is cleaved into the active fibrin during
the coagulation phase of hemostasis.

o Regulatory - Less than 1% of the total plasma proteins. These are enzymes, proenzymes and
hormones that are circulated by various tissues in the body at any one time. Levels of these
change constantly and often described separately to the 3 plasma proteins categories listed above.

Note regarding the differences between the various Plasma Proteins.


There are two types of alpha globulins are made in the liver, alpha 1 and 2. Essentially they carry out
the same function: acting as enzymes and transporters for hormones, cholesterol, and copper (Cu)
through the bloodstream. They also work to help or facilitate or inhibit the actions of other enzymes.

There are two types of beta globulins (beta 1, and 2). Like alpha, they transport hormones, lipids and
minerals. However, they do not participate in enzymatic activities, but instead assist in immune
responses against bacteria and parasites.

The gamma globulins, unlike alpha and beta, are made by the immune cells, lymphocytes and plasma
cells, to act as antibodies or immunoglobulins. Lymphocytes and plasma cells produce these
antibodies or immunoglobulins, to interact with antigens that arise externally. Thus, gamma globulins
(immunoglobulins) are involved in the immune response.

Other Solutes Dissolved in Plasma


In addition to proteins, plasma contains a wide variety of other substances that are essential to a healthy
functioning body. These include: glucose, amino acids, vitamins, fatty acids, triglycerides, cholesterol,
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+ + - 2+ + 2- 2+ 2- 2+ -
ions/electrolytes (Na , K , Cl , Ca , H , HPO4 Mg …SO , Zn , HCO …) urea, uric acid, creatinine, bilirubin,
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ammonia and dissolved gases O2 and CO2.

Blood Cell Formation Overview


All red and white blood cells are produced in the
red bone marrow by a process of hematopoiesis.

All cells, red, white, or platelets start with the exact same hematopoietic stem cells. As shown in the flow
chart on previous page the multipotent hematopoietic stem cell (hemocytoblast) generates all blood cells.

The Red Blood Cells (Erythrocytes)


As seen in the figure above, the myeloid stem cell generates 4 cells, one of which is the pro-erythroblast,
the stem cells for RBCs. As these cells mature they begin to extrude the nucleus and fill with hemoglobin
and they become reticulocytes - which are immature red blood cells. These cells become bright red
erythrocytes ready to squeeze from the red bone marrow and enter into the circulation via capillaries to
begin their journey around the body.

The RBC’s are Special for many Reasons


Firstly, RBCs are the most abundant type of blood cell, in fact, more than 99% of cells in blood are RBCs.

The RBC is highly specialized for its purpose, which is to transport gases, Oxygen (O 2) and some Carbon
Dioxide (CO2). These cells lack many of the organelles found in most cells – they have no nucleus, no
ribosomes, and no mitochondria. With so few organelles, these leaves a lot more room for more
hemoglobin (Hb) molecules. Each RBC contains about 250 million hemoglobin molecules, which helps
transport O2 and CO2 in the body.
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RBCs are very small cells, in fact they are the smallest blood cell in terms of
diameter, ranging from 7 to 8 µm. They are also are very flexible cells
because they contain the membrane protein spectrin, which gives elasticity
to the cell, enabling it to squeeze through the smallest blood vessels. This
cell can almost fold in half when traversing very narrow vessels.

An important reason RBC do not have any mitochondria is because they do


not want to use the O 2 they are carrying, and the mitochondria are for making ATP – in the presence of
O2. RBCs still need ATP, but they generate it anaerobically (without using O 2). In order to do this they need
to contain enzymes in their cytosol for glycolysis, so they can to make limited ATP w/out using the O 2 they
are transporting. The cell markers (antigens) on the external surface of the RBC are made from
glycoproteins and glycolipids and determines your blood type (discussed later).

The red bone marrow makes all blood cells, including RBCs. There are about 2.5 million RBCs per sec
produced and released into the circulation.

One RBC contains 250 million Hb molecules. This works out


to be that 1 RBC can carry as many as 1 billion molecules of
oxygen (O2). The Hb binds and transports Oxygen (O2) and
some Carbon Dioxide (CO2) in the body. The Hb molecule
contains 4 globin portions (2 α and 2 β chains). At the center
of each globin is an iron (Fe) containing Heme molecule.
There are about 2.5 million RBCs per sec produced and
released into the circulation. Count to two: 1 one thousand,
2 one thousand – you’ve made about 5 million RBCs in that
time span.

As a consequence of their specializations, RBCs have a


limited life span and can circulate around the body for up to 120 days, until they become worn out. With
no real organelles inside the cell, they have limited repair capability. The older or damaged RBCs are culled
(removed) from circulation by specialized cells (macrophages) in the spleen and liver. If 2.5 million RBCs
are being made per second to maintain homeostasis, this means approximately 2.5 million RBCs are being
removed from circulation each second. If there is a need for more RBCs, the kidneys release the hormone
erythropoietin (means ‘red cell maker’) to stimulate RBC production in the red bone marrow.

In a lab it is measured by spinning a sample of blood in a hematocrit tube with a high speed centrifuge. In
the process the heavier elements (cells) separate from the lighter (fluid) plasma, with the formed
elements settling at the bottom of the hematocrit tube. Suspended on the top of the sample is the straw
colored liquid that is plasma, which can also be called the supernatant - this comes from a Latin word
meaning ‘to swim above’ or to ‘float on the surface’. In between these two separated portions of spun
blood is a layer called the buffy coat. This is due to its opaque color. It normally constitutes less than 1%
of a blood sample and is composed of the white blood cells (WBCs) also called leukocytes, and the
platelets, (also called thrombocytes) which are actually cell fragments. A thrombus means blood clot, and
platelets are involved in clotting of the blood, so this name is a great indicator of function.
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Blood hematocrit can be measured from the spun blood sample, and it referred to as is the packed red
blood cell volume or packed cell volume (PCV) of blood. Basically it measures the % of RBCs in the total
volume of blood. Normally, about 45% of a blood sample is erythrocytes.
Hematocrit can vary because like all other physiological parameters, it exists in a range. In general, it can
range from about 36 to 50%, but there are important factors that influence that range, including gender,
age, geographical location and other conditional factors.
 Normal hematocrit for females: Range 37 to 47% (average 41%).
 Normal hematocrit for males: Ranges 42 to 52% (average 47%).

The values for the other cells present in blood (WBCs and platelets), is so small that it’s not normally
considered with the hematocrit value.

General Life Spans of the various Blood Cells


With limited repair capability, RBCs have a limited life span (120 days). Worn, older and damaged RBCs
are removed from the circulation in the sinusoidal capillaries by macrophages in the spleen and liver.
Red blood cells (RBCs) have a life span of about 120 days and white
blood cells (WBCs) have a life span that ranges from 13 to 20 days.
Platelet cells have a very short lifespan, normally just 5-9 days,
predominantly because they are expended in clotting and do not carry
on extensive metabolic activity. The normal number of leukocytes
(WBCs) in blood is 5,000 to 10,000 per cubic millimeter (mm 3) or micro
liter (µL).

If more RBCs are needed, the kidneys release the hormone


erythropoietin to stimulate RBC production in the red bone marrow.
Anemia is a condition in which there is a
deficiency in the O2 carrying capacity of blood that is due to a decrease in
RBCs or hemoglobin. There are many forms of anemia, and regardless of the
form it commonly results in pallor (paleness), weakness and weariness.

There are 3 basic categories of Anemia


Inadequate Erythropoiesis = Low hematocrit. e.g., Inadequate nutrition (iron
deficiency), e.g., Low RBC production hormone levels (erythropoietin), e.g.,
pernicious anemia (B12 deficiency).
Hemolytic Anemia = Abnormal breakdown of RBCs, e.g., Sickle cell anemia.
Hemorrhagic Anemia = Loss of blood volume, e.g., trauma, hemophilia, ruptured aneurysm.

Some useful Terms and Definitions for this Section:


Hypoxia - state in which the O2 is insufficient for normal life functions.
Hypoxemia - occurs when arterial O2 supply is below normal, typically below 95% O2 saturation.
Oxyhemoglobin - compound formed when O2 is bound to hemoglobin, becomes HbO2.
Carbaminohemoglobin - compound when CO2 binds Hb. About 10% of CO2 in blood carried this way.
Carboxyhemoglobin - complex of carbon monoxide (CO) and Hb that forms in red blood cells.
Polycythemia - elevated hematocrit (too many RBCs in blood); can be adaptive or pathological.
Sickle Cell Anemia - genetic blood disorder in which the β subunit of the globin of Hb has a mutation,
causing malformed RBCs, leading to deformed RBCs that take on a characteristic sickle shape.
Thalassemia – caused by an inadequate amount or an abnormal form of Hb in blood. Genetic disorder
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leading to the destruction of RBC and anemia. The etymology of ‘thala’ comes from the Greek word for
‘sea’ as it was first known around the Mediterranean, and of course ‘emia’ means blood.
The White Blood Cells or Leukocytes

Granular Leukocytes - Have cytoplasmic granules containing powerful enzymes & substances for defense.
Neutrophils make up 60-70% of total leukocyte count in human blood. These are very active in
phagocytosing bacteria, their activity and death in large numbers forms the pus of wounds. They defend
against bacterial and fungal infection.

Eosinophils primarily deal with parasitic infections and are also the predominant inflammatory cells in
allergic reaction (e.g. asthma, hay fever and hives). They engulf and destroy foreign cells.

Basophils are responsible for allergic and antigen responses by releasing histamine at the site of tissue
injury causing vasodilation, and for release heparin to limit the size of a forming blood clot.

Agranular Leukocytes - do not contains granules in cytoplasm.


Lymphocytes are in blood and also more common in the lymphatic system. In general they engulf and
destroy viruses and release antibodies. The blood has three types of lymphocytes: Natural Killer (NK)
cells, T cells and B cells. The NK Cells recognize foreign cells with abnormal cell markers or proteins on cell
membrane, and detect cancerous and viral infected cells. The T cells undergo maturation in the thymus
(where they get their name), and provide cellular-level immunity by physically attacking foreign or
diseased cells directly. The B cells undergo a maturation process in the bone marrow and can form plasma
cells which produces antibodies (immunoglobulins) that bind to specific foreign or abnormal components
of plasma membranes. This is also referred to as humoral (body fluid) immunity.

Monocytes in the blood phagocytose (engulf and destroy) microorganisms, cancerous cells, dead
leukocytes and cellular debris. They also present pathogens to T cells for recognition so that an antibody
response may be mounted. Unlike neutrophils, monocytes are able to replace their lysosomal contents
and have a longer active life. Eventually monocytes leave the bloodstream to become tissue
macrophages which remove dead cell debris as well as attacking microorganisms.

Leukocytosis is used to describe a high WBC count, whereas leukemia is caner of the WBCs. Leukopenia is
low WBC count, which is almost always related to a decrease in neutrophils

Platelet cells are very small and they are not actually cells, but fragments of a larger type of cell called a
megakaryocyte. Platelet cells are also called thrombocytes. Because they play a significant role in
thrombosis (formation of a blood clot). The function of platelet cells is to prevent blood loss by starting a
chain reaction that leads to initiation of blood clotting. Platelet are very small, being 2–3 µm in diameter.
Compare that to a RBC that is from 7-8 µm. Most platelets are biconvex discoid (lens) shaped cell
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fragments that have many granules but no nuclei. These cells play a major role in blood clotting
(hemostasis). Between 150,000 and 400,000 are found in each micro liter (µL) of blood.
Also see information, exercises and questions about blood cells in the Human Physiology Lab manual.
Overview of ABO Blood Groups (Types)
A blood type (also called a blood group) is a classification of blood based on the presence or absence of
genetically determined ‘flags’ or cell markers on the surfaces of RBCs called antigens (also referred to as
agglutinogens). It is the plasma of blood that contains antibodies (also called agglutinins). The Antigens -
these determine blood type. The ABO blood group is based on two antigens called A and B (see below).
Individuals whose RBCs display only antigen A, have blood type A. Individuals who display only antigen B
have blood type B. If both A and B antigens are displayed, the result is type AB blood. The absence of both
A and B antigens results in type O blood. Fill in the blood types for the RBCs below:

Blood Type = ______ Blood Type = ______

Blood Type = ______ Blood Type = ______

The Natural Antibodies


There are natural antibodies in blood plasma. The anti-A antibody reacts with and attacks antigen A, and
the anti-B antibody reacts with and attacks antigen B. Therefore, a person cannot have antibodies in their
plasma that match their blood type because the antibodies would attack the antigens of their own red
blood cells and may clump. Hence, if you have an A on your RBC, then your plasma has only B antibodies,
no A antibodies. This is because if a RBC carrying an antigen were to mix with plasma that contains the
corresponding antibodies - agglutination or ‘clumping’ of blood would occur. This is bad if you want blood
to flow and help keep you alive. As you can imagine, antigens and antibodies are of critical importance in
blood transfusions. If certain bloods are mixed, agglutinated cells become lodged in small capillaries
throughout the body and, over a period of hours, the cells can swell, rupture, and release hemoglobin into
the blood, this is called hemolysis. Therefore, certain blood types cannot be mixed!

Rh Blood Group
The Rh system is the second most significant blood-group system that is commonly
used. It is much more involved than this, but simply put the Rh factor is another
RBC marker and you either have the Rh antigen (Rh positive or Rh +), or you do not
(Rh negative or Rh-). Together with the ABO blood typing, the absence or presence
of the Rh factor is also included in the comprehensive blood grouping. For instance,
if a person has type A antigen on their red blood cell and no Rh factor, then their
blood type is A- (A negative).
How would you name the Blood Type on the RBC shown to the upper right? = ____________

A compelling analogy for the 8 blood types is the picture


to the left of the 8 donuts. The icings represents the A B
antigens and the sprinkles represent the having the
additional Rh factor. Note how the plain donut, without
any sprinkles even, represents type O- blood!
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Hemolytic Disease of the Newborn (HDN)


The Rh factor can be important during a second pregnancy and childbirth. Under normal circumstances,
human plasma does not contain anti-Rh antibodies. If, however, a woman who is Rh - becomes pregnant
with an Rh+ child, then her blood may produce antibodies that will react with the blood of a subsequent
child. The first child is unaffected, as the mother's body has not yet produced antibodies. This can lead to
a reaction and hemolysis may occur in the fetal blood, produced by fetal maternal incompatibility called
hemolytic disease of the newborn (or fetus), and could be fatal for the newborn infant.

Hemostasis - Stopping Blood Loss.


The word hemostasis indicates the function (hemo = blood, stasis= stationary) = stopping blood. This is the
process in the body that prevents hemorrhage, which is excessive bleeding leading to loss of blood
volume. This is a protective measure, to prevent excessive blood loss and tissue damage.

There are 3 Steps for Hemostasis to Occur


1. Vascular spasm
2. Platelet plug formation
3. Coagulation (blood clotting)

1) Vascular Spasm
Vascular smooth muscle (VSM) in walls of ruptured/damaged blood vessel contract – pain receptors are
the signal and endothelial cells release endothelin, a vasoconstrictor! This reduces blood flow/loss.
Interestingly, all endothelial cells of vessels have an outer coating of prostacyclin, a platelet cell repellant!
Only when endothelial cells are damaged and this layer is gone, can platelets cells become activated.
 
2) Platelet Plug - this occurs as platelet cells are activated accumulate and adhere at the site of vessel
injury. A damaged (ruptured) vessel exposes collagen – this triggers platelet cells (via pseudopods) to stick
to damaged vessel. Then platelets degranulate releasing: Serotonin (yes, the NT!) here it acts as a
vasoconstrictor; Prostaglandins, vasoconstrictors; ADP, this attracts and degranulates more platelets.
 
All of this causes platelet cell aggregation (a positive feedback loop) and the cycle continues until it is
broken when the small vessel is sealed.
 
3) Coagulation (blood clotting) - this part is complex and it the final crescendo in reducing bleeding. It
involves the conversion of the plasma protein fibrinogen into insoluble fibrin threads which create a net-
like framework necessary for blood clotting to occur. Pro-coagulants (clotting factors) activate the steps to
form a series of reaction cascades.

 Extrinsic Pathway: Factors released by damaged tissues begin the cascade.


 Intrinsic Pathway: Factors found in blood begin cascade (platelet degranulation).
 Common Pathway: Both the intrinsic and extrinsic pathways lead to the common pathway, in
which fibrin is produced to seal off the vessel.

Common Pathway
Once factor X has been activated by either the intrinsic or extrinsic pathway, the enzyme prothrombinase
converts factor II, the inactive enzyme prothrombin, into the active enzyme thrombin. Then, thrombin
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converts factor I, the insoluble fibrinogen, into the soluble fibrin protein strands. Factor XIII then stabilizes
the fibrin clot. There’s a whole other series of enzymes to dissolve the clot when no it’s longer required.
Blood Vessels of the Body
The blood that is pumped by the heart is transported to and from the body by blood vessels. There are
five basic types of blood vessels in the body.
1. Arteries:
Both large elastic and muscular arteries have 3 layers. Role is for transporting High Pressure Blood
and maintaining Blood Pressure.
2. Arterioles:
Have 2 layers, including vascular smooth muscle (VSM), can exhibit large changes in diameter =
‘Resistance’ vessels.
3. Capillaries:
Have only 1 layer, 1 cell thick, called endothelium, for exchange (3 types of beds).
4. Venules:
Have 2 layers, for collection of blood from capillary beds.
5. Veins:
Have 3 layers and venous valves. For return of Low Pressure blood to heart.

The different types of blood vessels vary in their structures, but they share some similar general features.
Each blood vessel has the same innermost layer called the endothelium, made of simple squamous
epithelium. All vessels have a lumen, the central area through which blood flows. In general blood vessels
transport blood in this vessel order: Arteries, arterioles, capillaries, venules and veins. This leads back to
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the heart. There are some important exceptions (e.g., portal systems) but most commonly it is in this
sequence of vessels that blood is circulating.
Arteries and arterioles have thicker walls than veins and venules because by virtue of their close proximity
to the heart, they are handling blood at a far greater pressures than the thinner walled venules and veins.
By the time blood has traveled to the capillaries and entered venules, the pressure initially imparted on it
by the ventricles of the heart contracting has significantly diminished. In comparison to arteries, veins
encounter much lower pressure from the blood that flows through them. Their walls are considerably
thinner and their lumens are correspondingly much larger in diameter, this allows more blood to flow
with less vessel resistance. In addition, veins also contain venous valves that assist the unidirectional flow
of blood back toward the heart. This is very important as the lower pressure of veins in the extremities
makes it necessary to have additional strategies to promote adequate venous return.

The Blood Vessels in more Detail


An artery is a blood vessel that conducts blood away from the heart. All arteries have thick walls in order
to withstand the high pressure of blood ejected from the heart, it is the arteries closest to the heart that
have the thickest walls, with 2 layers elastic fibers on either side of the tunica media (smooth muscle).
These are called elastic arteries.

An elastic artery is also known as a conducting or transport artery, because the large diameter (over 10
mm) enables it to accept a large volume of blood from the heart and conduct it to smaller branches. The
elastic fibers allow the vessels to expand in response to the infusion of blood pumped from the ventricles.
Once the blood passes, the vessels then recoil due to elasticity. This is important for 2 reasons: 1) flexible
vessels expansion reduces resistance to blood flow, thus the heart does not have to work harder as it
would if vessels were stiff and inflexible (as in atherosclerosis); 2) the recoiling of the vessel after the
heart pumps acts to maintain blood the pressure gradient that drives the blood in the arterial system.

Arteries have very thick walls, but smaller lumens than veins, a characteristic
that helps to maintain the pressure of blood moving through the system. vein

Together, their thicker walls and smaller diameters give arterial lumens a more artery
rounded appearance in cross section than the lumens of veins (see drawing).

Arterioles
After arteries, blood flows into arterioles, like the name implies, they are ‘tiny’
arteries that then deliver blood to a capillaries. These vessels essentially have 2 layers, the inner
endothelium and a layer of vascular smooth muscle (VSM). These vessels have diameters (or lumens) that
can dramatically change by either contraction of the VSM, which causes vasoconstriction, or relaxation of
the VSM, which causes vasodilation. Vasoconstriction causes a decrease in blood flow and an increase
blood pressure. Vasodilation causes an increase in blood flow and a decrease blood pressure. Because of
this, arterioles are referred to as the Resistance vessels. All blood vessels exhibit vascular tone due to the
partial contraction of smooth muscle. The importance of the arterioles is that they are the primary site of
both resistance and regulation of blood pressure. The diameter of arterioles can be controlled by neural
and chemical controls. Vasoconstriction and vasodilation in the arterioles are the primary mechanisms for
distribution of blood flow and are a big influencer on peripheral resistance.

Capillaries
A capillary is the smallest, thinnest blood vessel – it is the exchange vessel for the body. It exchanges
gases, nutrients and waste between the blood and the surrounding cells and interstitial fluid, a process
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called perfusion. The diameter of a capillary ranges from 5–10 µm. This is snuggly for the passage of RBCs
that range from 7-9 µm. The term microcirculation describes blood flow through capillaries.
Capillaries are composed of a single layer of endothelial cells surrounded by a basement membrane. For
capillaries to function, their walls must be ‘leaky’, meaning they need to allow substances to pass through
them. There are 3 major types of capillary beds, which differ in their degree of “leakiness”.
The 3 types of capillaries are: 1) continuous, 2) fenestrated, and 3) sinusoidal capillaries.

1) Continuous Capillaries – These are the most common type of capillary in the body, found in
almost all vascularized tissues. They are characterized by tight junctions between endothelial cells.
Metabolic substance, such as water, glucose, and small lipophilic molecules like gases and
hormones, as well as leukocytes can pass between cells. Both capillaries and venules are the
primary sites of diapedesis, this refers to the passage of white blood cells through intact
endothelial cell linings of vessel walls into the interstitial spaces and tissues. Capillaries associated
with the brain are part of the blood-brain barrier and have a thicker basement membrane (from
astrocyte extensions) to restrict the movement of many substances.

2) Fenestrated Capillaries – These are capillaries that are characterized by having pores (or
fenestrations, a Latin word meaning ‘window’) in their walls. These pores make this capillary bed
more permeable or ‘leakier’ to larger molecules. The location of fenestrated capillaries is found
where this additional leakiness is needed and include the kidneys, which filter the blood, synovial
joints, some regions of the small intestine, as well as the hypophyseal portal system (connection
between hypothalamus and anterior pituitary gland).

3) Sinusoidal Capillaries – These are the least common type of capillary bed and the most leaky!
They are characterized by an incomplete basement membrane and large, extensive intercellular
gaps between adjacent endothelial cells. This, combined with intercellular clefts and fenestrations
makes these vessels leakiest of all capillaries and allow large molecules, including plasma proteins
and even cells to pass in and out. These vessels are also very convoluted, meaning they twist and
turn. This promotes even slower blood flow through sinusoidal vessels, allowing for greater time
for exchange of gases, nutrients and wastes. Sinusoids are found most predominately in the liver
and the spleen, in addition to red bone marrow. This capillary bed allows for the passage of blood
cells that can only move through the large openings. The liver also requires extensive specialized
sinusoid capillaries in order to process the materials brought to it by the hepatic portal vein from
both the digestive tract and spleen, and to release large plasma proteins into circulation.

Shown below here is a summary of 3 types of capillary beds.


13

Continuous Fenestrated Sinusoidal


Metarterioles and Capillary Beds
The term ‘meta’ means beyond, so this vessel is beyond an arteriole but not quite a capillary. A
metarteriole is a short micro-vessel that links arterioles and capillaries by way of a precapillary sphincter
that forms a ring around and encircles the entrance to capillary beds. Each metarteriole arises from a
terminal arteriole and branches to supply blood to a capillary bed that may consist of 10–100 capillaries.

The precapillary sphincters (which is circular smooth muscle cells where the metarteriole connects with
the capillary) act to closely regulate blood flow from a metarteriole to the capillaries it supplies. The
capillaries are widespread and abundant, this is why precapillary sphincters are very important, because if
all of the capillary beds were open at the same time, they would soon hold all of the blood in the body! If
that were the case, then would be no blood in arteries, arterioles, venules, veins, or the heart itself. The
default is that precapillary sphincters are closed. When local tissues need O2 or nutrients, or have excess
waste products, the precapillary sphincters open, allowing blood to flow and exchange to occur before
closing again. If all of the precapillary sphincters in a capillary bed are closed, blood will flow from the
metarteriole directly into a thoroughfare channel and then into the venous circulation, bypassing the
capillary bed entirely. This creates what is known as a vascular shunt (like an anastomoses). In addition,
an arteriovenous anastomosis may bypass the capillary bed and lead directly to the venous system.

The flow of blood in capillaries is not smooth and continuous, but rather more irregular and pulsating.
This is called vasomotion and is regulated by signals molecules that are triggered in response to changes
in internal conditions, such as O 2, CO2, H+, and lactic acid levels. If metabolic demand (e.g., during exercise
or digestion) is increased, the capillary beds open. This is compared to periods of rest or sleep, where
vessels are largely more closed.

Venules
A venule is basically a small vein (from 8–100 µm) that collects blood from multiple capillaries exiting a
capillary bed. As they continue to travel back to the heart, venules join to form veins. The walls of venules
consist of endothelium, plus an outer layer of connective tissue. Recall that venules and capillaries are the
primary sites of diapedesis, such that there is still some degree of exchange that occurs in venules with
the local tissues.

Veins
The largest blood vessels in the body, in terms
of diameter, are veins. A vein by definition is a
blood vessel that carries blood back toward the
heart. Veins, like arteries, are composed of 3
layers, however veins have much thinner walls
compared to arteries but have larger lumens.
Often the lumen of veins are described as
‘irregular’, but this is typically because when
sectioned vessels are viewed it is when the
vessels are empty, and the thinner walled veins
tend to collapse when they are empty.
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Veins are low-pressure vessels, and for this reason they typically have venous valves that assist in
returning blood to the heart, preventing backflow inherent in low blood pressure vessels. The regular
arrangement of valves along a vein also act to segment the vessel. This ensures that even when there is a
drop in pressures and the blood falls back (see diagram below), it can only drop back as far as the last
valve, closing the valve in the process. When the pulsatile pressure of the blood increases again it pushes
the valve open once more allowing flow in one direction only. In addition, the blood cannot fall back from
that segment once it has advanced.

Varicose Veins are enlarged, swollen, and convoluted


(twisting) veins, often appearing blue or dark purple. Most
often caused by insufficient venous valves that cannot
completely close and therefore allow back flow. This causes
blood to pool and exert more strain on the subsequent
valve, which can then become insufficient, causing the
contorted formation of the vein. Varicose veins are
generally benign, but cause aching pain and discomfort or
may signal an underlying circulatory problem. Treatment
involves compression stockings, exercise, or procedures to
close or remove the veins.

Veins act as a Large Blood Reservoir


In terms of where the blood in the cardiovascular system resides while a person is at rest, the answer is,
at rest the vast majority of blood is in the venous system. In this way, veins are considered to the ‘blood
reservoir' of the body. In the systemic circuit, the veins have about 65% of the total blood volume at any
given time. Large veins have the capacity to expand (distend) and store large volumes of blood, even at a
low pressure. The large diameters and relatively thin walls of veins make them much more distensible
than arteries. This is why veins are said to be capacitance vessels, as they have the ability to hold high
volumes of blood. When veins constrict, they have the potential to deliver a great volume back to the
heart. That is important.

Constriction of Large Veins


Vasoconstriction of large veins can produce a large amount of blood returning to the heart, which is called
venous return. As we have already seen in discussions of cardiac output, increases in venous return cause
an increase in end diastolic volume (EDV), which increases in preload. These increases cause the cardiac
muscle to stretch and the ventricles to contract more forcefully, increasing stroke volume. This enables
the mobilization of blood from the low pressure venous system, back into the central pump and quickly
into the high pressure arterial system for subsequent redistribution to other parts of the circulation.

Again, since veins hold this ‘venous reserve’, vasoconstriction of veins can very quickly redistribute the
great volume of blood from the low pressure venous system to the high pressure arterial system. This
change in the distribution of blood makes it ready to deliver to tissues in need. The integration center for
this redistributed is the vasomotor center located in the medulla oblongata (MO). Recall this center is
one of the three ‘vital centers’ in the MO and is for the control of blood vessel diameter. The vasomotor
center sends out sympathetic stimulation to the vascular smooth muscle (VSM) of veins, causing venous
constriction which sets the redistribution of blood in motion.

The Circulatory System – Brief Comments on Lymphatic Vessels


15
The movement of water and solutes back and forth across a capillary wall is constantly occurring. Recall
there is a small residual amount of this ‘tissue fluid’ which remains in the interstitium, and this is
ultimately returned to the cardiovascular system by lymphatic vessels of the lymphatic system. In terms
of tissues fluid regulation, it is the extensive lymphatic vessels of the body that provide the one way
drainage of tissue fluid back to the heart. In this way, the cardiovascular and lymphatic are linked
together as the circulatory system. Normally of the fluid that is pushed out of a capillary at the arterial
end, about 90% of it is reabsorbed at the venous (lower pressure) end. Therefore, about 10% of that fluid
remains in the interstitium (tissues spaces) and is called interstitial fluid (or tissue fluid). It is continuously
drained by the one way lymphatic vessel in the tissues. These are called initial lymphatics vessels (or
lymphatics capillaries). Once the interstitial fluid enters the initial lymphatics, the fluid becomes lymph.
The word lymph is Latin for ‘clear water’ or ‘colorless fluid’, because it is clear and colorless, although it
can also appear as opaque. Generally it has very no proteins in it and very few cells, except when
circulating leukocytes (namely T cells and B cells) are present.

With relation to blood pressure within the cardiovascular system, an increased blood volume in a vein can
increase the pressure within it, which has a domino effect and reflects back to smaller veins, venules, and
even the capillaries. This elevated pressure not only promotes greater flow of fluids out of the capillaries
and into the interstitial fluid, but also hampers the reabsorption of fluid back into the capillaries. This can
cause an excessive increase in tissue fluid around cells, a condition called edema. Edema is deleterious
because it expands the distance for exchange to cells, and this hampers vital gas and nutrient exchange in
the tissues. Significant edema has many potential causes, including hypertension and heart failure, severe
protein deficiency, renal failure, and many others. Later we will examine the changes in transcapillary
fluid dynamics that cause edema.

Blood Flow through the Cardiovascular System


Pressure, Volume, Flow and Resistance
Liquids and gases flow from areas of higher pressure to areas of lower pressure - that is to say, they flow
down their pressure gradients. The high pressure generated when the ventricles contract forces blood to
flow into vessels that exist at lower pressure. The pressure of the fluid (blood pressure) continues to fall
as blood moves away from the heart. The vessels with the highest pressure are the aorta and other large
systemic arteries. Veins are the vessels with lowest pressures, with the inferior vena cava being the
lowest. Blood flow in the body is expressed in volume of blood per unit of time. The matter of resistance
to flow will be expanded upon in the section below outlining the issue ‘Resistance Opposes Flow’.

Compressing a Fluid Raises its Pressure


Blood pressure is the Hydrostatic Pressure (HP) of blood, and it falls off over distance as energy is lost to
friction. Ventricular contraction compresses the volume of the ventricle and increases the pressure. This is
the driving pressure created within the ventricles to drive blood through the vessels. As the heart
chambers relax, pressure falls and allows blood to flow in (thus volume increases). Just like chambers,
blood vessel volume can also change. In the body, when vessel vasodilation occurs (an increase in blood
vessel diameter) this results in increased blood volume in that vessel and decreased pressure. When
vasoconstriction occurs (a decrease in blood vessel diameter), this results in decreased blood volume in
that vessel and increased pressure.

Blood Pressure
As a reminder, the term systole means contraction and also implies ejection of blood. The term diastole
means relaxation and indicates filling. Systemic arterial blood pressure is measured in mmHg and
16
recorded as systolic pressure (the high #) over diastolic pressure (the low #). For example, normal blood
pressure is presented as 120/80 mmHg. This measure is giving information about how hard the heart is
working when it’s contracting (in systole) and when relaxing (in diastole).
Mean Arterial Blood Pressure
The average blood pressure is reported as mean arterial pressure (MAP) in arteries. This is a calculated
mean, which is not a strict average but the formula takes into account that the heart at rest spends more
time in diastole than in systole. The MAP formula is:
MAP = Diastolic Pressure + 1/3 (Systolic-Diastolic Pressure)
Sample calculation: If we use standard values of systolic pressure = 120 mmHg and diastolic pressure 80
mmHg. The MAP would be = 80 + 1/3 x (120 − 80) = 93 mmHg.

Typically, normal MAP falls in the range of 70–110 mmHg. If MAP falls under 60 mmHg for an extended
time, blood pressure will not be high enough to ensure circulation to and throughout the tissues, which
results in ischemia, a restriction in blood supply to tissues. A condition called hypoxia (inadequate
oxygenation of tissues) is associated with ischemia. Hypoxemia is low O 2 levels in systemic arterial blood,
which can of course lead to hypoxia. Note: Neurons are very sensitive to hypoxia.

Blood Flows Down its Pressure Gradient


Blood moves down its pressure gradient, the highest pressure being generated from the ventricles of the
heart, going to the various tissues and then back to the heart. Blood flows from an area of higher pressure
to one of lower pressure. The difference in pressure between 2 ends of a tube creates a pressure gradient
(P). For example, from below P = P1 – P2
Flow  P P2
P1
(blood flow is directly proportional
to the pressure gradient)

Fluid flow depends on the change in pressure from one region to the next. The greater the pressure
gradient, the greater the driving force for fluid flow. We can derive from this that the Pressure Gradient is
the driving force for blood flow.

Resistance Opposes Flow


Blood flowing through blood vessels encounters friction from the vessel walls and the components of
blood colliding with each other. The term Resistance (R) refers to the tendency of the cardiovascular
system to oppose blood flow. Increased resistance leads to decreased flow. Thus, Flow 1/R ( =
proportional to). In other words, this equation can read as: Flow is indirectly proportional to Resistance,
the flow is less when the resistance is greater (if the pressure gradient is kept constant).

There are three parameters that contribute to resistance to flow of fluid through tube:
1. Tube Length (L) - as the tube lengthens, resistance increases. In the body, length is determined by
the anatomy of the vascular system and this remains fairly constant.

2. Fluid Viscosity () - describes the 'thickness' of a fluid. The viscosity of blood is about 5-6 times
greater than water (due to blood cells and plasma proteins). The more viscous the fluid the greater
the resistance to flow. The viscosity of blood in the body is normally maintained to remain constant.

3. Tube Radius (r) - the radius can be simplified to mean the diameter of the tube. As the radius of the
tube decreases, the resistance to flow increases; conversely, as the radius of the tube increases, the
17
resistance to flow decreases. This parameter does not remain constant in the body - the diameter of
blood vessels change continuously - thus, the radius of blood vessels is the main determinant of
resistance to blood flow in the body.
The relationship between these parameters and flow of a fluid through a tube can be expresses by:
Poiseuille's Equation: R = 8 L/ r4

Where the numbers 8 and π (pi) are constants. The number pi represents the ratio of a circle’s
circumference to its diameter. The variables for vessel length (L), viscosity (η) and radius (r) are also
shown. This formula however, can be simplified in humans to this: R  1/r4. This is because the other
factors are fairly constant in the human body, such that blood vessel radius becomes the main
determinant of peripheral resistance (R). Vasoconstriction leads to increased resistance and decreased
flow. Vasodilation leads to decreased resistance and increased flow. Therefore, blood flow is described by
this formula:

Flow  P OR P
R 1/r4
If the driving force remains constant, flow varies inversely with resistance (determined by radius, r).

Vessel Diameter, Cross Sectional Area, Velocity Flow of and Blood Pressure
It is critical to understand blood flow and pressure in relation to the specific type of blood vessel. It is
particularly important to know what is occurring at the capillaries. If we examine the graphs below, it
focuses on what is occurring at the capillaries. The anatomy of the capillary beds is such that they have
the smallest diameters (a) but because there are so many of them, they have the greatest cross-sectional
area (b). The actual area they cover is the greatest of any vessel in the body. This makes sense since their
function is exchange at the tissues, so the greater the area the better the coverage. As the vessels move
closer to the heart, the pressure continues to drop, this ensures that blood is always flowing back to the
heart (c). The speed (velocity) of blood is seen in (d) shows that it decreases dramatically as the blood
moves from arteries to capillaries. This is perfect for the role of capillaries, the very low flow rate allows
greater time for exchange to occur, and picks up again as blood exits the capillaries to return to the heart.
18

a)

c)

b)
d)

Note: The arterioles are the resistance vessels, because they can change the size of their lumen greatly,
and this can dramatically change the flow of blood from arteries, which also impacts pressure, as the
greater the resistance to flow, the greater the driving force of the pressure must be to overcome it! This
explains why vasodilation and vasoconstriction of arterioles play more significant roles in regulating blood
pressure than do the vasodilation and vasoconstriction of other vessels.

The 4 main Factors that Affect Mean Arterial Pressure (MAP)


1. Cardiac Output (HR and SV, which relates to EDV and preload)
2. Peripheral Resistance (blood vessel length, blood viscosity, and diameter of blood vessels)
3. Total Blood Volume
4. Distribution of Blood in the Body

1. Cardiac Output
As we have already seen, CO is the measure of blood pumped from one ventricle of the heart and is
measured in liters per minute (L/min). It is directly controlled by Heart Rate and Stroke Volume. If either
(or both) of these parameters go up, CO is increased and this will increase MAP! Any factor that decreases
HR or SV (or both), will decrease CO and therefore decrease MAP.

Factors that will increase Cardiac Output are:


a) Sympathetic Innervation.
b) Hormones (epinephrine and norepinephrine, thyroid hormones).
c) Increased venous return (increase preload) increases Ca2+ levels, and increase force (SV).
19
Factors that will decreases Cardiac Output are:
a) Parasympathetic innervation.
b) Hormones (ANP, BNP).
c) Decreased Ca2+ levels (decreased SV).

Therefore, factors that causes CO to increase, will usually elevate MAP (if blood vessel diameter and
peripheral resistance are constant), and factors that cause CO to decrease will usually depress MAP
(again, if blood vessel diameter and peripheral resistance are constant). A significant role in the ANS and
the antagonistic effects of the Sympathetic and Parasympathetic divisions of the ANS.

2. Peripheral Resistance
As we have already discussed, peripheral resistance encompasses the various ways that resistance to flow
can arise. It includes blood vessel length, blood viscosity, and diameter of blood vessels. All of these
contribute to afterload.

Vessel Length and Diameter


The length of a blood vessel is directly proportional to its
resistance: The shorter the vessel, the lower the resistance
and the greater the flow (if all else held constant).
Conversely, the longer the vessel, the greater the resistance,
and the lower the flow (if all else held constant).

As blood flows along a vessel surface, the greater the surface


area of the vessel (the longer it is), the more it will impede
the flow of blood. And the shorter the vessel, the lower the
resistance and the greater the flow. As adults the length of our blood vessels is relatively constant under
normal physiological conditions. A person of 150 lbs. has about 60,000 miles of vessels in their body!
Taller and larger people ultimately have longer vessels, which tends to increase peripheral resistance.
Again, these blood vessel lengths are fairly constant in most adults.

Blood Viscosity
This relates to the ‘thickness’ of blood, the more viscous, the greater its resistance and the more resistant
it is to flow. Centipoise is the unit of dynamic viscosity, described as the amount of force necessary to
move a layer of liquid in relation to another liquid. Water has a viscosity of 1 centipoise (cps) at 20°C.
20

The viscosity of blood is directly proportional to resistance and


inversely proportional to flow – this means that any factor that
increases blood viscosity will increase its resistance to flow (thus
flow will decrease if all else is constant). And, any factor
decreasing viscosity of blood will decrease its resistance to flow
(thus flow will increase if all else is constant). As the chart to the
left shows, blood is thicker than water, and honey is about 200 to
300 times thicker than blood!

Normally the viscosity of blood is fairly constant. The more


hydrated (watery) the blood is, the less viscous it is. Normally the
two primary factors determining blood viscosity are the cells and
the plasma proteins in blood. Since 99% of the cells in blood are
RBC (erythrocytes), conditions that affect erythropoiesis (RBC
production) can alter blood viscosity, e.g., polycythemia or
anemia. Since most plasma proteins are made by the liver,
conditions that affect liver function can also change the blood
viscosity and alter blood flow. Liver abnormalities like hepatitis,
cirrhosis, and drug toxicities can alter blood content and viscosity.
While leukocytes and platelets are normally a small component of
the formed elements, some conditions with severe overproduction can impact viscosity as well.

Blood Vessel Diameter (radius)


Of the three (3) factors that affect resistance to fluid flow through a tube (length, viscosity and diameter
of the tube), it is blood vessel diameter that is the most significant in its impact on resistance.

All vessels with vascular smooth muscle (VSM) exhibit vascular tone, which is the baseline contractile
state of a vessel and determines diameter (thus resistance to flow). The diameter of many vessels may
change quite frequently in the course of a day. It may occur in response to a number of signals (neural,
hormonal, and local) that will trigger vasodilation or vasoconstriction.

The effect of vessel diameter (often equated with radius for convenience) on resistance is very significant
and is indirectly proportional (or inverse): When blood vessel diameter is increased, less blood is flowing
across and contacting the vessel wall, this lower friction and results in lower resistance, subsequently
increasing blood flow. When blood vessel is decreased, there is more blood contact with the vessel wall,
this increases friction, which increases resistance, therefore decreasing blood flow.

Even slight changes in vessel diameter (radius) will causes huge changes in resistance to flow. This is
because if we go back to our simplified version of Poiseuille's Law (with little r being the most influential
factor), R = 1/r4. This means if an arteriole dilates to two times its size, the resistance (R) to flow is now
1/16th its original value and this means flow is now increased 16 times. Do the math! If we just double the
vessel’s radius (diameter) this is then raised to the power of four in the formula, so small changes in
diameter can have an enormous impact on resistance and thus flow. If a vessel constricts to ½ of its
original radius, the resistance to flow will increase 16 times!

This is why vasodilators and vasoconstrictors are so important in the body.


21

Table 1. Important Endogenous Vasoconstrictors and Vasodilators in the Human Body.

Note: Activation of β adrenergic receptors leads to relaxation of smooth muscle in the lung, and dilation
and opening of the airways. The β adrenergic receptors are coupled to a stimulatory G protein of adenylyl
cyclase. This enzyme produces the second messenger cyclic adenosine monophosphate (cAMP).
3. Total Blood Volume
Hopefully the relationship between total blood volume and Mean Arterial Pressure (MAP) will be self-
evident. If we take a very simple analogy of a water balloon it can become very clear. If the water in the
water balloon represents the total blood volume in a body, then the more water we add to the closed
water balloon, the greater the pressure will become inside it. The balloon, like the circulatory system, is
closed so any additional volume will increase the pressure within it. In the body, as the total blood volume
increases, this will result in an increase in MAP.

If we take a pin and prick the full water balloon and water starts to leak out, this decrease in the total
volume of water in the balloon will result in a decrease in the pressure of the balloon. Thus, decreases in
total blood volume in the body will result in a decrease in MAP.

Typically the total blood volume for a 150 lbs man is about 5.0 L. Out blood
volume is very closely regulated homeostatically and for this reason typically
does not exhibit large changes, although depending on our state of hydration
we can small variations in total blood volume.

Hypovolemia means lower than normal blood volume. This can be caused by
dehydration, by hemorrhage (bleeding, internally or externally), vomiting,
from having severe third degree burns, or as a consequence of various
medications to treat hypertension. For whatever reason hypovolemia occurs,
it will have the effect of lowering MAP (if all other factors are held constant).
22
An individual may be down 10–20 % of their blood volume and still be asymptomatic since the body is
very effective at regulating and maintaining blood pressure. The treatment for hypovolemia is the
replacement of the fluid that has been lost, including doing so with intravenous solutions.

Hypervolemia, is higher than normal (or excessive) fluid volume. This may be caused by retention of
water and Na+, which may occur in some forms of renal (kidney) disease. It can also occur in those with
congestive heart failure, liver cirrhosis, hyperaldosteronism (too much of the hormone aldosterone), or
glucocorticoid steroid treatments. Reestablishing volumetric homeostasis in these instances will depend
on addressing the primary condition that triggered the hypervolemia. For whatever reason hypervolemia
occurs, it will have the effect of inreasing MAP, (if all other factors are held constant).

Note: It is important to recognize that fluid intake (or lack of it) can have an impact on total blood volume
and therefore on MAP.
 If there is an increase in fluid intake, this can lead to an increase in MAP.
 If there is a decrease in fluid intake, this can lead to a decrease in MAP.

The kidneys can conserve water to reduce the loss of vascular volume, but it cannot make more water!
Thus, when the body needs to prevent a decrease in MAP, it conserves water by reducing the filtration (or
work) done by the kidney until vascular volume is in the normal range.

4. Distribution of Blood in the Body


The pumping action of the heart propels the blood into the arteries, from an area of higher pressure
toward an area of lower pressure. If blood is to flow from the veins back into the heart, the pressure in
the veins must be greater than the pressure in the atria of the heart. Two factors help maintain this
pressure gradient between the veins and the heart. First, the pressure in the atria during diastole is very
low, often approaching zero when the atria are relaxed (atrial diastole). Second, two physiologic “ pumps”
increase pressure in the venous system. The skeletal muscle pump and the respiratory pump that have
already been mentioned in the first section of cardiac physiology notes.

The Blood in the Systemic Venous System


At rest, approximately 65 to 67% of the total blood volume resides in systemic veins. Therefore, any
action that increases the flow of blood through the veins will increase venous return to the heart. As
mentioned previously, all vessels have some tone so that they do not completely distend with the
addition of blood to them. Even large veins maintain vascular tone to prevent them from merely
distending and absorbing that force, which would dampen the flow of blood. Keeping that in mind, we will
see that vasoconstriction in the systemic venous system actually enhances blood flow retuning to the
heart.
23
As seen in the figure to the left, the vast majority of
blood at rest is residing in the systemic veins, this
particular image shows 60 to 70%, this can vary but
stating that the average is about 65% is reasonable.

Venous Vasoconstriction: As previously discussed,


vasoconstriction of an artery or arteriole decreases
the radius, increasing resistance and pressure, but
decreasing flow. This is different for venous
vasoconstriction. Vasoconstriction increases
pressure within a vein as it does in an artery, but in
veins, the increased pressure increases flow! One
reason is that the one way valves do not allow that
increase in pressure to move the blood in any
direction but back to the heart. Also, the thin and
irregular walls of veins create a more rounded lumen
when constricted, providing less surface area for
friction, thus less resistance to flow.

Remember that the pressure in the atria (where this


venous blood is flowing), is very low, approaching
zero for part of the relaxation phase of the cardiac cycle. Thus, venous vasoconstriction increases the
return of blood to the heart. It follows that venous vasoconstriction increases the preload (or EDV) and
this stretches cardiac muscle. Not only does the sarcomere become optimal length, but more Ca 2+ comes
into the cells. This increases the force contraction, leading to a great stroke volume (SV). In summary, at
rest, most blood is in venous system = Venous Reservoir. If there is a decrease in MAP, the mobilization of
blood from the venous to the arterial system will increase MAP. The fastest most effective way to
redistribute blood is by vasoconstriction of the systemic veins by the Sympathetic division of the ANS.

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