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Blood
Chapter 16

Chapter 16: The Circulatory System: Blood

Introduction
Dr. Tate gives a brief historical overview of blood at the beginning of the chapter. I'd like to add more
recent 'history:' what did you learn in A&P I that relates to what you will be learning in this chapter? Don't
hesitate to go back to earlier chapters as you come across references to them, throughout the semester –
it's a good habit and a great way to reinforce what you learned.

To prepare yourself to really understand this chapter, you should start by scanning the chemistry chapter
to refamiliarize yourself with ions, proteins, and the properties of water. You should definitely review
osmosis and membrane transport. And, read about blood tissue in the tissues chapter. Finally, for future
reference, make a list of tissues you know are avascular.

Functions

You might assume that the functions are easy to learn and remember, but I have a study tip for you: relate
each function to the elements or properties of the blood

For example: Transporting heat depends on the ability of water to carry heat, and the circulation of the
blood from the body's core to the surface, where heat radiates and warm water evaporates from sweat.
Start with the list of functions given in the text; write them in the form of a list, then for each, write the part
(s) of the blood responsible for that function. After making this list, if I asked you what part of the blood is
responsible for thermoregulation, you should be able, without hesitation, to answer that this is a function of
the water in the plasma.

Composition

Examine Figure 16.1. Can you translate this image into an outline? See if you can do this by yourself,
then look at mine:

1) Other fluids and tissues make up 92% of the body's weight

2) Blood 8% of body weight

a) Plasma 55% by volume

i) Proteins 7% by weight

(1) Albumins 58%

(2) Globulins 38%

(3) Fibrinogen 4%

ii) Water 91% by weight

iii) Other solutes 2% by weight

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(1) Ions

(2) Nutrients

(3) Waste products

(4) Gases

(5) Regulatory substances

b) Formed elements 45% by volume

i) Platelets 250,000 – 400,000 per cubic mm

ii) White blood cells 5,000 – 9,000 per cubic mm

(1) Neutrophils 60% - 70%

(2) Lymphocytes 20% - 25%

(3) Monocytes 3% - 8%

(4) Eosinophils 2% - 4%

(5) Basophils 0.5% - 1%

iii) Red blood cells 4,200,000 – 6,200,000 per cubic mm

This is the beginning of an outline….incorporate additional information you get from reading the text, as
you go through. Compare it to the outline at the end of the chapter, and to the information I give you in
Apache Online. If you can use an outline form in writing your own notes, you not only make sure you have
all the information; you also have the interrelationships between concepts. As a next step, add in the
functions listed in Table 16.1. Then answer the first 2 questions on page 465. Always take the time
to stop and answer these questions as you are reading each chapter.

Take the short quiz on blood's functions and properties; then continue with the section on plasma.

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Plasma
Plasma is 91% water – what blood functions are related to the properties, quantity, and movement of
water?

Plasma Proteins

Plasma proteins make up about 7% of plasma. Review protein structure in chapter 2, especially
concerning active sites for ligands. Active sites are important not only for enzymes, but also for the many
transport proteins in the plasma.

As all plasma proteins are colloidal, they are all negatively charged on their surfaces. Positively-charged
ions in the plasma can reversibly bind to plasma proteins. Collectively, the plasma proteins create the
colloid osmotic pressure (COP) of the blood and are the major contributors to plasma viscosity.

Plasma proteins are classified into two major categories, along with some minor ones.

The biggest category at 58% is the albumins. Albumin is a protein that gives a slippery, viscous quality –
it's the main protein in egg white, so you can get some idea of what it's like. If you've ever cooked with
eggs, you know that beating them makes egg whites foamy (the basis of meringue), and the same thing
can happen with albumins in the body fluids. In cases of drowning, there is often a rather stiff pile of foam
exuding from the mouth of the victim.

Various, slightly different forms of albumin (thus, the plural 'albumins') are manufactured by the liver cells
(the hepatocytes). In addition to being an important component in maintaining the blood's osmotic
pressure, albumin is able to hold onto positive ions such as calcium and hydrogen (thus contributing to pH
balance), and also has an active site that binds bilirubin, one of the major waste products of red blood cell
destruction.

The second biggest category, at 38%, is a hodge-podge of different proteins, all of which are about the
same size, called globulins. These colloidal proteins are further subdivided, based on size, into three

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categories: alpha globulins, beta globulins, and gamma globulins. Alpha and beta globulins,
manufactured by hepatocytes, are typically involved in one of three functions: transport, clotting, or
defense against infection. Transport globulins carry various substances that don't dissolve well in the
water of plasma: substances such as lipid-soluble hormones (the steroids and thyroid hormones) and
heavy metals such as iron and copper. While you don't need to memorize a long list of these, it's
important to recognize them when they come up, and remember that they belong in this category. If you
flip back to the endocrine chapter, you'll see a reference to these 'binding proteins' in the blood, that carry
the bound form of lipid hormones. Some other alpha or beta globulins are the proenzymes involved in the
clotting mechanism and its regulation; we'll look at these separately. We'll look at clotting proteins later in
this chapter, and those involved in defense when we study immunity, in the next chapter we take up.

Gamma globulins are an entirely different class of plasma proteins; these are antibodies, made by cells of
the immune system. We'll study them with immunity.

Next in our list of plasma proteins is fibrinogen, a single protein that makes up about 4% of the plasma
protein total. You might wonder why a single protein is so abundant; the answer lies in the function of this
protein: it is used to make blood clots. Because it is used up in clot formation, there is a large amount of it
available.

All that's left is transient proteins – those that are just 'passing through' as they move from where they are
produced to where they are used…the hormones and enzymes (or proenzymes) that are involved in
various regulatory mechanisms, for example. All together, these make up only about 1% of the total
plasma proteins, and so really aren't part of this story. Many proenzymes, and at least one prohormone,
are made by the liver, although some of the enzymes found in blood have escaped from dying cells.
These can often be useful diagnostically, as some are characteristic of a particular organ. So, a simple
blood test can often reveal liver damage, or heart attack.

Except for most of the hormones, some of the enzymes, and the gamma globulins, plasma proteins are
made by the liver. There is an amazingly high turnover rate, as these proteins only last about 2 hours
before being recycled; the liver produces about 4 g of new plasma proteins per hour. Remember this
when we study blood pressure and circulation: this will relate to malnutrition and liver disease. Start now
keeping a list of liver functions, as this organ is pivotal to many systems, rather than being solely devoted
to any one system. For example, the liver is not a major endocrine organ, but that doesn't make its
secretions unimportant. Review somatomedins (insulin-like growth factor, or IGF) produced by the liver,
and remember the role of somatomedins as mediators of growth hormone function.

Plasma Solutes

Aside from water and proteins, everything else in the plasma is a solute – it dissolves in the water of the
plasma. These are listed in Table 16.1, but only in a very basic way. We'll be adding to the detail of these
throughout the semester, so it helps to have an organizational framework for now. Functional categories
that are useful are: organic versus inorganic, gases versus solids, or nutrients versus wastes.

While most students are familiar with the ions, gases, and nutrients, but not usually the wastes, it helps to
have a brief introduction to these. Because of the abundance of nitrogen in proteins, and the ability to
detect nitrogen easily in chemical tests, an entire category of wastes, the nonprotein nitrogenous wastes
(NPN), is used to diagnose disease, usually kidney disease (if NPNs are high). Chief among these is
urea, a waste compound made by the liver from ammonia and carbon dioxide. Its value, blood urea
nitrogen (BUN) can detect liver disease as well.

Electrolytes have a major impact on two vital areas: fluid balance and pH balance. While these will be
studied in more detail in a later chapter, we'll be working on them with each system. Remember the
normal pH range in human blood, and review the hormones that regulate ions (particularly aldosterone,
and the calcium-regulating hormones).

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Review the nature of cations and anions, and the definitions of pH, acid, base, and salt (ch. 2). Then,
review the sodium-potassium pumps of cells (ch. 3) – which ion is pumped which way, and how much?

Carbon dioxide, being carried from cells (where it is generated) to the lungs (where it is excreted) has a
major impact on blood pH, because it interacts with water (most significantly in the presence of the
enzyme carbonic anhydrase, found in RBCs) to form carbonic acid. So, fluids with high CO2 concentration
have a lower pH.

CO2 + H2O → H2CO3

Carbonic acid can spontaneously dissociate to form ions; it is the free hydrogen ion that directly affects the
pH:

H2CO3 → HCO3-(bicarbonate) + H+

There is a short video of this process in Apache Online; look for it in the Blood Learning Module.

Both of these reactions are freely reversible, depending chiefly on the concentration of carbon dioxide and
hydrogen ions (or pH).
So, which has a higher pH: blood coming into the lungs, or blood leaving the lungs? Hover HERE for the
answer.

Take the short quiz on plasma; then continue with the section on blood cell production.

Formed Elements
A simple blood test involves separating the elements of the blood by centrifugation. The separated blood
shows the straw-yellow plasma distinct from the cellular elements, which are separated into a thin 'buffy
coat' on top of a thick red layer. The buffy coat contains both WBCs and platelets.

The 'formed elements' of the blood include all the cellular elements. Why don't we just refer to them as
cells? Well, not all of them are cells. There are, of course, the red blood cells (erythrocytes) and the white
blood cells (leukocytes), but the last major category consists of platelets, which are cell fragments. We
use the term thrombocyte to refer to platelets even though they are not whole cells.

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Analysis of formed elements is a basic component of most blood tests (explained at the end of the
chapter). Two common word roots are used to refer to too many or too few cells: 'cytosis' and 'penia.' So,
thrombocytopenia means a deficiency of platelets, and leukocytosis means an overabundance of WBCs.

Blood Cell Production

Hemopoiesis is also called hematopoiesis. The rate of production of new cells in the red marrow is
staggering; more than 2 million new RBCs are formed every second. If the RBC count remains stable,
how many RBCs are destroyed every second?

As with any rapidly dividing cell, blood stem cells are vulnerable to mutation. Many drugs, as well as
radiation and toxins, can suppress these cells, causing aplastic anemia. This is a common side effect of
some cancer treatments. We worry about radiation's affect on stem cells, so we always cover the body
with a lead apron when someone needs radiography.

As an embryo begins development, the yolk sac produces the first blood cells, and forms the first blood
vessels; otherwise, how would the cells move into the embryo proper? After the fetus' liver and spleen are
formed, hematopoietic stem cells migrate to these organs and produce blood cells at least until birth. After
ossification begins, the red marrow forms as blood stem cells move into spongy bone. The amount of red
marrow increases with growth, but the extent of red marrow shrinks as the bones enlarge. In a small child,
red marrow extends into the limbs, but in an adult, red marrow ends at the hip and shoulder joints – unless
production must increase for some reason; then red marrow can expand back into the limb bones. What
are the chances of radiating red marrow when taking 'X-rays' of an adult's broken wrist?

Marrow for biopsies is easily removed with a sternal puncture. A greater volume of marrow, needed for a
transplant, can be taken from a hip bone. Marrow cells can be given through a vein; they find their way
from the circulating blood to the marrow. Why would marrow be removed prior to chemotherapy, and
returned to the same patient after chemotherapy is over?

Hemopoiesis is shown in Fig. 16.2. One step is left out: the original hemocytoblast first differentiates into
either a myeloid stem cell or a lymphoid stem cell. Lymphoid stem cells form the various lymphocytes;
myeloid stem cells form everything else. To simplify the diagram, the amount of cell division is also not
shown. Many of the stem cells, including the hemocytoblasts, have a very high rate of division. Cell
division requires certain vitamins, including B12 and folic acid; a deficiency of these will impact particularly
RBC production, since these are most abundant. (One proerytrhoblast forms 16 RBCs, due to cell division
at several stages.)

The fate of any one stem cell is determined, at least in part, by the stimulation of various growth factors:
hormones or paracrine secretions that stimulate the cell to differentiate into a specific type. Known growth
factors include erythropoietin, thrombopoietin, and colony-stimulating factors for specific types of WBCs.

Pernicious anemia is a deadly disorder caused by a deficiency of vitamin B12. This vitamin is large and
complex, and is digested by stomach acid unless protected by a substance secreted by the stomach – this
substance is called intrinsic factor (the vitamin is the extrinsic factor). As we age, production of intrinsic
factor can decline, leading to a B12 deficiency. Can you figure out why B12 has to be supplemented by
injection, not ingestion?

Take the short quiz on blood cell production; then continue with the section on erythrocytes.

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Erythrocytes
RBCs (red blood cells, or erythrocytes) are basically flexible bags of hemoglobin (Hb), with at least one
extra function thrown in. Hemoglobin's primary function is to carry oxygen, but it also has an essential role
in carbon dioxide transport. The structure of Hb is a complex protein with four subunits, each with a
protein unit called a globin and a cofactor called heme, made of a porphyrin ring with a central iron. In
Figure 16.4b, the porphyrin surrounds the central Fe. There are several variants of globin molecules; the
two most common are called alpha and beta, but there is also a fetal type. Be sure not to confuse
globins with globulins!

Genetic mutations to the globin genes affecting Hb structure result in Hb that tends to clump rather than
stay suspended in the RBC cytoplasm. Individuals with mutations on both chromosomes carrying the
globin gene are afflicted with anemias, including sickle cell anemia and various thalassemias. In all of
these, the RBC structure is more fragile, and hemolysis (rupture of red blood cells) is common. Hemolytic
anemia results as the RBC numbers drop faster than they can be replaced. On the other hand, carrying a
single mutation makes the RBCs somehow more resistant to malaria; both sickle cell anemia and
thalassemia originated in areas of the world where malaria is a major problem and used to cause many
deaths. Can you see the advantage of having the mutation in such an area?

Porphyria is a group of disorders stemming from inability to form proper porphyrin rings. Some symptoms
include craving to taste blood, and blistering of the skin in sunlight – thus the legend of vampires….other
symptoms include strange behavior, and a peculiar blue color in the urine; King George III of England was
said to suffer from porphyria, which may have contributed to the dissatisfaction of American colonists with
English rule.

Because so many RBCs are produced – and needed – the process must be tightly regulated. There are at
least three different regulatory loops involved: RBC production, RBC destruction, and iron absorption and
storage.

RBC production is regulated by hypoxemia, an abnormally low level of oxygen in the blood. The oxygen
content of the blood is monitored by at least 3 organs – the 2 kidneys, plus the liver – and if it falls too low,
they secrete a hormone/growth factor, erythropoietin (EPO). EPO stimulates both cell division and
differentiation in hemopoiesis, to increase the rate of erythropoiesis.

Anything that diminishes blood flow to the kidneys, which produce most of the EPO, can cause an
excessive secretion of EPO, making the RBC production go too high – a condition called polycythemia.
Polycythemia increases blood viscosity, putting a strain on the heart. On the other hand, kidney disease
often reduces EPO output, resulting in anemia. This is a common problem with dialysis patients and has
been corrected with the availability of exogenous EPO. It's not uncommon that the first sign of kidney
failure is the fatigue that signals anemia.

RBC production can only be maintained if required nutrients are available in sufficient amounts. This

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includes basics such as calories and protein, and the vitamins needed for rapid cell division (mostly B12
and folic acid), but also iron. Iron is modified in the stomach, bound to a stomach factor, then absorbed
into the blood through the small intestine – but only if the beta globulin that carries iron, transferrin, isn't
already saturated. If it is, the iron absorbed by the gut epithelium is simply sloughed off when the cells
die. Iron that is picked up by transferrin can be carried to the liver for storage as ferritin or delivered to the
red marrow for erythropoiesis. Iron stored as ferritin can also be delivered by transferrin to the red marrow
if insufficient iron is delivered from the diet. In evaluating an anemic patient's problem, the amount of iron
bound to transferrin can be determined by a blood test. There's a really tragic disorder in which iron is
stored in the body to the point of toxicity and death. There can be so much iron in the body that it would
set off a metal detector. Would you predict an iron deficiency in someone whose stomach is removed?

The immature RBCs reach the circulating blood while still in the reticulocyte stage. The small amount of
remaining endoplasmic reticulum in these cells will disappear in a few days, but the cells can be
distinguished with light microscopy. The reticulocyte count, normally 0.5 - 1.5% of circulating RBCs, is
diagnostically useful: too high, and the RBC production must be high; too low indicates a depression in
RBC production.

RBC destruction is also carefully regulated. Since RBCs have a fairly short life span (about 120 days),
and there are so many of them (about 25 trillion total), there has to be a high capacity to remove them.
Macrophages in the liver and spleen catch, phagocytose, and digest RBCs (the old, inflexible cells are
most easily caught). Hemoglobin, along with other cellular proteins, is broken down - the globin simply
digested down to amino acids, which are easily reused. The iron from the heme is stored and recycled,
using transferrin and ferritin. The rest of the heme molecule is converted to bilirubin, one of the NPN
wastes. If its concentration gets too high, jaundice results. The liver is responsible for removing bilirubin,
by secreting it into the bile, which gets its green color from bilirubin.

Bilirubin on its way to the liver binds to albumin (bilirubin is a lipid, and won't dissolve well in plasma). The
liver conjugates the bilirubin to make it more water soluble; the conjugated bilirubin mostly goes into the
bile, but some escapes into the blood. Too much conjugated bilirubin in the blood might indicate blocked
bile ducts in the liver or between the liver, gall bladder, and duodenum. A blood test can be used to
distinguish conjugated bilirubin from unconjugated bilirubin, to help determine a cause for jaundice.

RBC Functions: transport of respiratory gases

The respiratory gases include oxygen and carbon dioxide. Review the chemistry of O2 and CO2. Are they
polar or nonpolar? Neither of these is particularly hydrophilic; both are much more soluble in lipids (such
as the plasma membrane of a cell) than in water. Because of this, the concentration of these gases in
plasma is very low. Carbon dioxide is slightly more soluble than oxygen, and some of it can be converted
to carbonic acid as well, slowly, in the plasma, just spontaneously.

Still, the amount of oxygen and carbon dioxide that has to be carried by the blood is huge – thus the need
for 25 trillions RBCs (about 5 million in every microliter of blood). These cells are anucleate biconcave
disks. This shape gives them a high surface area and a lot of flexibility – at least while they're young. As
they age, they become more brittle, likely to get caught in the tight turns of capillaries of the liver and
spleen. RBCs don't have mitochondria - no risk, then, that they will consume the oxygen they are
carrying.

Each iron in a Hb molecule can reversibly bind one molecule of oxygen, so each Hb can carry up to four
oxygen molecules. In oxygenated blood in systemic arteries, almost every Hb carries 4 O2s, and we refer
to it as 100% saturated and use the term oxyhemoglobin. With a normal Hb level of 15 g in 100 ml of
blood, that much blood can hold 20 ml of oxygen. When a person is resting, blood returning to the lungs is
about 75% saturated, meaning that on average each Hb is carrying about 3 O2s. With increasing activity
levels, the amount of oxygen delivered to tissues increases, so blood returning to the lungs can have an
O2 saturation as low as 25% (one O2 per Hb), but never 0%. Even so, blood returning to the lungs is

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called deoxygenated, although it can carry a lot of oxygen.

Review skin color in chapter 5, especially jaundice, cyanosis, pallor, and erythema. What is the color of
deoxygenated blood?

The carbon dioxide is carried by loosely attaching to an amino acid on the globin part of the Hb molecule,
and the combination is called carbaminohemoglobin. In the tissues, gas exchange occurs – for every
oxygen given up to a cell, a carbon dioxide is picked up. The reverse happens in the lungs.

After Hb, the most abundant protein in RBCs (a very distant second) is the enzyme carbonic anhydrase,
which speeds the conversion of carbon dioxide to carbonic acid, increasing the amount of carbon dioxide
that can be carried in the blood.

Hemoglobin is a colloidal protein – as such, it can attract the hydrogen ions freed when carbonic acid
dissociates (making Hb a fine buffer). The bicarbonate, although formed inside the RBCs, is carried in the
plasma.

We'll go over this again, and add more detail, when we study the respiratory system.

Take the short quiz on erythrocytes; then continue with the section on leukocytes.

Leukocytes
There are two basic ways to categorize WBCs: by how they look in a differential stain, and how they are
formed.

By appearance, WBCs are divided into 2 groups: granulocytes and agranulocytes.

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By derivation, lymphocytes differentiate at a much earlier stage than all other cells. (Refer back to the
earlier study of hemopoiesis.) Lymphoid stem cells are scattered throughout the body, in small clusters of
lymphoid tissue found in mucous membranes, tonsils, thymus, and spleen.

Myeloid stem cells stay in the red marrow, differentiating into RBCs, platelets, and all other kinds of
WBCs. The myeloid stem cell, under the influence of growth factors, can differentiate into a granulocyte-
macrophage colony forming unit, meaning monocytes and granulocytes are derived from the same stem
cell. Other growth factors (sometimes referred to as colony stimulating factors, or CSFs) can stimulate an
increase in granulocytes or monocytes, which differentiate into macrophages in the peripheral tissues.
Further differentiation of the 3 kinds of granulocytes probably depends on other CSFs.

Many WBCs apparently stay in the marrow; others move into the peripheral tissues, so that the circulating
numbers in the blood can rise very quickly in just a few hours, causing leukocytosis (abnormally high
WBC count). Too few WBCs is called leukopenia. WBCs can slide out of capillaries and crawl through
tissue spaces.

In this video, you can see a neutrophil chasing bacteria through a layer of erythrocytes.

WBCs are involved in defense against infection and reaction to cell damage; their functions will be studied
in a later chapter.

You learn to identify the basic types of WBCs in lab.

Take the short quiz on leukocytes; then continue with the section on platelets and hemostasis.

Platelets and Hemostasis

Platelets are associated with hemostasis, which is the process of preventing blood loss. Hemostasis is
typically divided into 3 parts: vascular spasm, platelet plug formation, and coagulation. Platelets can be
involved in all 3 of these processes.

Platelets come from giant cells in the red marrow, called megakaryocytes. Refer back to Figure 16.2.
These cells differentiate from the myeloid stem cells, just as RBCs, granulocytes, and monocytes. The
megakaryocytes accumulate cytoplasmic granules and specialized membrane along their margins; these
pinch off in little pieces about half the diameter of RBCs, forming the platelets. Because these are not
whole cells, they are not officially included in whole cell counts; to include platelets, use the term 'formed
elements' instead of 'blood cells.' Still, they are often referred to as thrombocytes and conditions of
platelets often are derived from this term, such as thrombocytopenia and thrombopoietin.

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Platelets look like they can't do much – but they are like little chemical bombs waiting for the signal to
explode. They can crawl around on vessel surfaces, and swallow small particles, too. The surface of a
platelet bristles with receptors and signaling molecules, and new tests can determine from a simple blood
sample if platelets have been activated anywhere in the body, a sign of blood clotting (although, they can't
pinpoint where!). At least one potential cancer drug was dropped, because it caused a reaction by the
platelets. Platelets' main functions are to plug small leaks in vessel walls, and to start the coagulation
process of stopping big leaks as well, but there is still much about these cell fragments that is simply not
known.

A positive feedback loop occurs when platelets are activated, as you can see in Figure 16.9.

The usual cause of activation is exposure of the collagen deep to the lining of blood vessels (the
endothelial cells). This occurs when a vessel is torn or cut, but also when an endothelial cell is infected or
damaged, as can happen with the plaque formation associated with atherosclerosis. In this situation, a
clot can form in a vessel already partially blocked by the plaque, cutting off blood flow entirely.

Platelets, once activated, become sticky – and other platelets stick, and become activated, and stick; the
growing platelet plug can block a small vessel, and initiate clotting in a large vessel. Any platelet that is
activated but doesn't stick initiates a second mechanism that prevents it from starting a plug elsewhere.
Healthy endothelium is coated with prostacyclin, which repels platelets.

One of the functions augmented by platelets is vascular spasm. The spasm is initiated by smooth muscle
in a vessel wall; smooth muscle automatically contracts when it's irritated, as when it is cut or more so
when it's torn. Infection or other chemical stimuli can also trigger a spasm in a vessel that's not bleeding;
such a spasm can trigger a transient ischemic attack, or TIA. Activated platelets secrete chemicals that
excite contraction of the smooth muscle.

Coagulation

Coagulation involves the activation of clotting factors from the plasma. See Figure 16.10. As with platelet
plug formation and vascular spasm, a clot forming where it isn't needed can do more harm than good, so
clotting is carefully regulated. Most of the clotting factors are proenzymes; they form a cascade, in which
each enzyme activates multiple copies of the next, until the amount of activated clotting factors is highly
amplified. This system allows a large reaction in a short period of time, but any shortage or defect in any
one of the clotting factors can bring the entire process to a halt. A common example of this is classic
hemophilia, in which clotting factor VIII is deficient due to a sex-linked genetic mutation. Because the
gene for factor VIII is carried on the X chromosome, and females carry two copies of this chromosome,
they are less likely than males to fail to produce any normal factor VIII. (There are other forms of
hemophilia that are not sex-linked.) Many of the clotting factors are formed by the liver, and several
require vitamin K for their synthesis. While some vitamin K is formed by bacteria normally found in the
colon, some comes in the diet as well. Vitamin K deficiency can occur if the colon must be removed, but
liver disease is a more common cause of deficiency of these procoagulants.

When a vessel breaks and bleeds, a clot forms not only within the broken vessel, but also in the tissue
surrounding the vessel. This external clotting is triggered by tissue clotting factors and follows an extrinsic
pathway. The clot within the vessel is triggered by platelets activated by exposure to collagen and follows
an intrinsic pathway. The cascade for the intrinsic pathway has more steps, so is more amplified, than the
extrinsic pathway. Both extrinsic and intrinsic pathways end in the same series of steps, so this part is
called the common pathway. Calcium is required for all three pathways, so removing calcium from blood
is one way to prevent coagulation in donated blood. The final steps involve activation of fibrin, which is
found in the plasma as the inactive precursor fibrinogen. A deficiency of fibrinogen can cause excessive
bleeding; during pregnancy, fibrinogen level climbs higher than usual.

Once a clot has stopped the bleeding, it needs to stop growing. Clotting factors are carried off
downstream beyond the affected branch, and diluted and deactivated. At the clot itself, some

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anticoagulants will retard growth beyond what's needed. The clot will retract, expelling serum, stabilizing
the clot, and bringing the broken vessel walls closer together.

After the vessel heals, the clot needs to dissolve, a process called fibrinolysis shown in Figure 16.11. A
major clot dissolver is the enzyme plasmin, which was activated from its precursor plasminogen (a normal
plasma protein made by the liver) as the clot was being formed; it is slow to act, and doesn't usually
dissolve the clot until healing as occurred. The activation of plasmin is also aided by a chemical secreted
by the endothelial cells, called tissue plasminogen activator (tPA). This substance can also be given by
injection to bust clots in coronary or cerebral arteries, ending the heart attack or stroke.

Clots forming where they're not needed can cause major problems, but so can bleeding. The regulation
of clotting allows for rapid activation to reduce blood loss, coupled with multiple triggers to make sure clots
don't form unnecessarily. Diseased endothelium, such as is seen in atherosclerosis, is a common trigger
of abnormal clotting, but in some cases clots will form simply because blood flow is stagnant. Two
common occurrences of this are deep venous thrombosis (DVT) and atrial fibrillation. In DVT, venous
stasis (slow blood flow) in the legs (such as in bedridden patients) or inflammation of the veins (phlebitis)
can trigger clot formation. A thrombus is a clot forming attached to a vessel wall. The thrombus can break
loose, forming an embolus (a flowing clot), which can lodge in a small vessel elsewhere. Because of the
circulatory pattern, the next small vessel is usually in the lungs, and a pulmonary embolism forms, which
can be fatal. In atrial fibrillation, the flow of blood stagnates, and clots form in the slowly moving blood.
One strong heart beat can move the clots into circulation; if in the left side of the heart, the next small
vessel is likely in the cerebral arteries, resulting in stroke.

Functions and properties of the blood affect every organ system, which is why we study it first. We will
return, again and again, to reinforce and add to what you know and understand about the blood.

Take the quiz on platelets and hemostasis, then study the section on blood types.

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Assigned Reading: Blood Grouping

Read the section on blood types; you should be able to answer the following questions after reading the
text.

What happens in a transfusion reaction?

What is an antigen? What is an antibody?

What happens with agglutination?

What is hemolysis, and why does it happen?

What are the types and characteristics of each type in the ABO blood group?

What ABO types have antigens that would cause a transfusion reaction?

What ABO type does not have naturally-occuring antibodies in the plasma?

Why does the Rh blood group have only 2 types, positive and negative, and what does that mean?

In what situation is HDN a risk?

Take the short quiz on blood types. Then, take the blood self test in Apache Online.

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