Cardiopulmonary Physiology
Millersville University
Dr. Larry Reinking
Chapter 2 - Composition, Properties and Functions of Blood
The central focus of this course is blood. In the first part of the course we will examine
how blood is propelled to the tissues and in the second, how gases are transported by this vital
fluid of life. Although blood is a collection of individual cells in fluid a medium, many
physiologists refer to the blood as an organ. It is possible to devote an entire course
(hematology) or even a career to the study of blood. However, this chapter will deal with only
basic aspects of the blood needed for our understanding of the cardiopulmonary system. Chapter
3 will deal with the physics of blood.
Functions of Blood
In this course we will focus on the transport of gaseous O2 and CO2 by the blood. The
blood is also involved in many other functions like the transport of nutrients (glucose or free fatty
acids), transport of waste materials (ions, urea, ketones, bilirubin, H2O, etc.), regulation (ions,
body temperature and pH), transport of endocrine signals (epinephrine, thyroid hormone,
steroids, etc.) as well as immunologic activities. A final function of blood is hemostasis, the
prevention of blood loss, which will be examined at the end of this chapter.
Composition of Blood
Although it is tempting to equate blood with a simple fluid like water, it is really a very
complex liquid. Unlike water, blood is a colloid, has three times the viscosity of water, a higher
density (1.056 vs. 1.0 for water) and, in a most perplexing fashion, changes properties under
different circumstances.
In humans the amount of blood in an individual is equal to 8.5-9% of the body mass.
Thus, a 70 kg individual has about 6 liters of blood. Blood volumes, however, can be quite
variable and are influenced by physical activity, bed rest, pregnancy, obesity, degree of hydration
and season. Males usually have a larger blood volume than females.
Blood is mostly water and is comprised of a fluid component, the plasma, and the
formed elements or cellular portion.
Plasma - Plasma is the straw colored fluid component of the blood. This coloration is caused by
bilirubin which is a by-product of hemoglobin break down. By volume, plasma is about 60% of
the blood and, in turn, plasma is about 90% water. The major solutes, by weight, in plasma are
proteins (7-9%) of which albumin is the most abundant. Other solutes such as ions, urea and
sugar make up less than 1% of the plasma. The protein composition of the plasma is listed
below:
Protein
Albumin
Globulins
Fibrinogen
% of Plasma
≈4
≈3
≈0.3
Function
Osmotic balance of
blood
Transport and Immunity
Blood clotting
Table 2.1
Plasma Proteins
Serum is plasma after it has clotted, that is, plasma minus fibrinogen.
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Formed Elements - The cellular elements of the blood account for about 40% of the volume and
include erythrocytes, leukocytes and platelets.
Leukocytes (or white blood cells) - There are several types of leukocytes which play a role in
responses to infectious agents, tissue repair and immune reactions. These motile cells retain their
nuclei and have a size of 6-20 m in diameter. A normal count for total leukocytes ranges from
6,000 to 10,000 per cubic mm of blood (mm3 = l = 10-6 l). Depending on the cell type, they are
formed in the bone marrow or in one of the lymph organs.
Platelets - These formed elements are fragments of the megakarocytes which are located in the
bone marrow. They are small (2-5 m) and have normal counts of 250,000-300,000/mm3 of
blood. Platelets are involved in hemostasis.
Erythrocytes (or red blood cells) - These cells, which are produced in the bone marrow, are by
far the most numerous type of cell in the blood. Red blood cell quantities are determined by
direct microscopic counts in a small volume or via the hematocrit (packed cell volume after
centrifugation). Typical adult values for erythrocytes are:
Gender
female
male
Hematocrit
42%
47%
RBC/mm3
4,700,000 (±300,000)
5,200,000 (±300,000)
Table 2.2
Erythrocyte Values
Erythrocytes are rather unusual in that they do not have a nucleus or most of the
cytoplasmic organelles that we associate with a eucaryotic cells. They do contain glycolytic
enzymes (for anaerobic metabolism) and high levels of carbonic anhydrase (for CO2 transport).
Consistent with their function of O2 transport, red blood cells have lots of hemoglobin (one third
of the weight of the cell). In men, on average, blood contains 16 grams of hemoglobin/100 ml
while for women have a slightly lower value (14 g/100 ml).
Size and Shape of the Red Blood Cell
The erythrocyte is often described as a ‘biconcave’ disk that is about 8 m in diameter
and 2 m thick at the outer edge. At the center of the disk is a depression (formerly occupied by
the nucleus) that is 1 m thick. The unique shape of this cell is maintained by a series of
cytoskeletal proteins that include spectrin, actin, ankryin and band 4.1. Many capillaries are
smaller than the erythrocyte diameter. Hence these cells are flexible and squeeze through the
smaller capillaries. Tank-tread type movement of the erythrocyte membrane has been observed
as they pass through capillaries and may have significance in enhancing gas exchange.
Life Span of Red Blood Cells
Erythrocytes have an average life of about 120 days. This short life span is probably due
to the fact that the cell membrane is being constantly distorted as the cells are squeezed through
capillaries and that there is no nucleus to direct cellular repairs.
Consider the following - The total number of red blood cells in a typical person is
about 30 x 1012 (5 x 106 RBC/mm3 x 6 liters x 106 mm3/liter). If the life span of
these cells is 120 days, each day, the marrow is producing 250 billion cells. In one
second, 2.9 million red blood cells are produced!
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Control of Erythrocyte Production
The number of red blood cells in the circulation is controlled within narrow limits. There
must be enough cells to deliver oxygen to the tissues but not too many. An excess number of
erythrocytes increases viscosity and impedes blood flow.
In adults, red blood cell production takes place in the bone marrow. Stem cells in the
marrow give rise to nucleated proerythroblasts which become erythroblasts. These cells then
begin to produce hemoglobin and lose their cytoplasmic organelles and nuclei. At the end of this
process a small cell which has minimal remnants of organelles (a reticulocyte) enters the
circulation and within a few days becomes a mature erythrocyte. Vitamin B12 and folic acid,
which are involved in the replication of DNA, are essential components in the production of new
red blood cells.
Red blood cell production (also called erythropoiesis) is controlled by a feedback loop
which involves the hormone erythropoietin. Erythropoietin, a circulating glycoprotein (34,000
molecular weight, 166 amino acids) is released from the kidneys (85%) and the liver (15%).
Tissue hypoxia (as would be associated with too few red blood cells) is the specific trigger that
stimulates renal erythropoietin release; the role and mechanism of release for liver erythropoietin
is not known. Erythropoietin, in turn, stimulates the bone marrow to increase production of
certain stem cells (called erythropoietin-sensitive stem cells) and after 2-3 days the number of
circulating erythrocytes increases, thus eliminating the original hypoxic stimulus. The following
diagram summarizes this control system:
Figure 2.1
Control of Erythrocyte Production
Genetically engineered erythropoietin (rEPO, Procrit) has been available for human use
for several years. It has been used to treat anemias resulting from kidney failure. This drug is a
much needed addition for kidney patients, because erythropoietin is not provided by dialysis
therapy. Erythropoietin is also widely used to treat individuals undergoing cancer chemotherapy.
It is also interesting that rEPO has also become 'a drug of abuse' in some sports such as
competitive bicycling.
Anemia
Anemia refers to a deficiency in the number of red blood cells (Hct < 35%). There are
several types of anemias:
Blood Loss Anemia - Following a severe hemorrhage plasma volume is replaced in 1-3 days;
total replacement of red blood cells may take 3-4 weeks.
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Aplastic Anemia - In this type of anemia the bone marrow stops production of red blood cells.
Aplastic anemia may be caused by exposure to high radiation levels or certain chemicals.
Maturation Failure Anemia - In this case improper stem cell development produces large,
poorly functioning megaloblasts. This may be the result of a vitamin B12 deficiency, poor
intestinal absorbtion of B vitamins (pernicious anemia) or folic acid deficiency.
Hemolytic Anemia - This type of anemia is the result of fragile erythrocytes which have a
very short life span. Hemolytic anemias can be caused by immunological responses
(transfusion reactions, Rh incompatibilities in newborns, auto immune responses, etc. ),
malaria, hereditary abnormalities in the red blood cells (e.g. sickle cell anemia) and certain
drugs.
Polycythemia
This term refers to the presence of an elevated number of red blood cells (Hct > 55%).
Polycythemia is a standard response to the hypoxia encountered at high altitudes. Polycythemia
vera is a situation of greatly elevated red blood cell count (hematocrits of 60-70%) and volume
caused by a marrow tumor. The main problem with polycythemia is that an increased viscosity
of the blood creates excess work for the heart.
Reference Values for Blood
The following table lists selected clinical laboratory values for human blood - (S) =
serum, (P) = plasma, (B) = whole blood:
Test
Chloride (S)
Cholesterol (S)
Glucose, fasting (P)
Iron, total (S)
Osmolality (S)
P CO2, arterial (B)
pH (B)
P O2, arterial (B)
Potassium (S)
Protein, total (S)
Sodium (S)
Urea nitrogen (S)
Normal Adult Range
96-106 mEq/L
120-220 mg/dL
75-105 mg/dL
50-150 g/dL
280-295 mOsm/kg H2O
35-45 mm Hg
7.35-7.45
75-100 mm Hg
3.5-5.0 mEq/L
6.0-8.0 gm/dL
135-145 mEq/L
8-23 mg/dL
Table 2.3
Normal Values for
Human Blood
Hemostasis
Hemostasis refers to the prevention of blood loss and blood clotting. Obviously this topic
is important since the cardiovascular system will not work if the blood is lost. Perhaps more
important is the realization that a heart attack or stroke is the direct result of a blood clot. Clot
‘busters’, which will be discussed in this section, have become a standard treatment following
heart attacks. Hemostasis has four sequential phases which are discussed below:
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1. Vascular Spasm - Immediately following trauma to a small artery or arteriole, the vessel
wall may contract and, perhaps, even close the lumen. The degree of contraction is related to the
degree of trauma. A crushing injury may cause several centimeters of vascular spasm while a
razor slash will cause almost none. The vascular spasm appears to be mediated by a local reflex
and by the release of serotonin from platelets in the area of injury.
2. Platelet Plug - When a vessel is damaged, the blood is exposed to collagen (collagen is one of
the most abundant animal proteins). The presence of collagen on the vessel wall and in the blood
causes platelets to change shape, form burr-like processes on their surface and become ‘sticky’.
These platelets then attract other platelets to the site of injury by releasing ADP and serotonin. A
temporary patch, the platelet plug, rapidly forms. This step in hemostasis is especially important
for dealing with the many small injuries that we encounter each day. A simple act like clapping
the hands, for example, will rupture many small blood vessels.
Prostaglandin-like Substances (eicosanoids) - Eicosanoids are the product of arachidonic acid
metabolism and are involved in a wide range of activities including the clotting mechanism and
blood vessel tone. This class of molecules includes the prostaglandins, prostacyclins,
thromboxanes and the leukotrienes.
Also consult Figures in your lecture packet
In terms of platelet aggregation, the prostacyclins and the thromboxanes have an
important regulatory function. Prostacyclin is produced in blood vessel walls. When
prostacyclin binds to the surface of platelets the production of cyclic adenosine monophosphate
(cAMP) is stimulated. Elevated intracellular levels of cAMP inhibits platelet aggregation.
Thromboxane A2 is produced within platelets. When stimulated by conditions that promote
clotting (e.g. collagen) thromboxane A2 levels rise and the production of cAMP is inhibited. As
a result, platelet aggregation is enhanced. In addition, prostacyclin causes vasodilation while
thromboxane promotes vasoconstriction. The following diagram, Figure 2.2, summarizes this
process:
Figure 2.2
Actions of
Prostacyclin and
Thromboxane
Also consult Figure in your lecture packet.
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A variety of analgesic and anti-inflammatory agents inhibit arachidonic acid metabolism
at one point or another in the synthetic pathways. As you are aware, aspirin has platelet
inhibiting actions and is recommended, in small doses, as a stroke preventative.
3. Blood Clotting (blood coagulation) - The coagulation of blood is initiated with 15-20
seconds of a hemorrhage. (This term should not be confused with blood agglutination, which is
the clumping of blood cells due to antibodies.) Blood clotting is a complicated process that
involves a cascade of reactions in which one blood factor (an enzyme) is activated. This
activated factor then converts the next factor to its active form and so on. The end result is the
conversion of plasma fibrinogen to soluble fibrin. Soluble fibrin is sticky and forms a
scaffolding for a blood clot. The following simple diagram illustrates the key features of clot
formation:
Figure 2.3
Overview of
Blood Coagulation
A more detailed depiction of blood clotting appears in Figuresof the lecture packet.
Note the following points in Figure of the lecture packet.
The numbering sequence of factors makes little sense. This is because the factors were
assigned numbers in the chronological order of their discovery.
Many steps require Ca2+.
Platelet Factor 4 is an anti-heparin
The products of some steps promote the precursor steps to their own formation (i.e., positive
feedback or a vicious cycle).
Factor VIII is absent in hemophiliacs.
Many of these factors such as prothrombin are produced in the liver. Vitamin K is needed for
this production.
Following the formation of soluble fibrin, these protein filaments intermesh and trap
blood cells. After a period of time, the fibrin molecules cross-link and contract, pulling the clot
and vessel wall inward.
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Prevention of Clotting - The prevention of clotting is necessary in lab glassware and in certain
clinical situations. The following methods prolong clotting time:
Smooth Surface - The intrinsic pathway will not be initiated if the blood does not bind to the
surface of vessel such as a catheter or test tube. This is accomplished by using hydrophobic
linings such as Teflon or silicon.
Heparin - Heparin is a naturally occurring anticoagulant that inhibits factors IX, X, XI and XII.
Protamine reverses the effects of heparin.
Calcium Chelation - Since so many of the steps in Figure require Ca2+, blood clotting can be
effectively prevented by chelating (i.e., binding) this ion. Oxalates, citrate and EDTA are
frequently used calcium chelators.
Coumarins - Coumarins (warfarins) prevent blood clotting by inhibiting the action of vitamin
K. Recall that vitamin K is needed for production of factors such as prothrombin. The
effects of coumarins can be reversed with high doses of vitamin K.
4. Fibroblast Invasion or Clot Lysis - Clots are only temporary and are either followed by
invasion of fibroblasts and the formation of fibrous scar tissue or by clot lysis. Clot lysis
involves the activation of plasminogen which is trapped in the clot. The active form, plasmin, is
an enzyme that lyses fibrin, fibrinogen and other clotting factors. The degradation products from
these reactions also inhibit further action of thrombin.
Figure 2.4
Clot Lysis
Injured cells slowly release tissue plasminogen activator (TPA) which promotes the
formation of plasmin and eventual clot lysis. A variety of compounds also promote the
conversion of plasminogen to plasmin. These include streptokinase (derived from strep.
bacteria), staphalokinase (from staph. bacteria) and urokinase (purified from urine).
Streptokinase and genetically engineered TPA are used as early treatments of myocardial
infarction (heart attacks). Blood also contains a low level of a protein, anti-plasmin, which
inactivates the fibrinolytic action of plasmin. The level of plasmin must rise above a certain level
before it becomes effective and, thus, this serves as an effective system for preventing plasmin
from interfering with normal blood clotting.
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