CHAPTER 19 CARDIOVASCULAR SYSTEM--THE BLOOD
The cardiovascular system includes the
blood, the heart and the blood vessels (3 chapters).
Hematology--study of blood and
blood-forming tissues
Blood is a liquid CT. Its functions:
1. Transportation
Oxygen/carbon dioxide
Nutrients/waste
Heat
Hormones
2. Regulation
pH by buffers
Body temp
Water content of cells
3. Protection
Clotting protects against blood loss
Phagocytic white blood cells
Specialized plasma proteins which protect against disease
Blood is heavier, thicker and more
viscous than water
The temp of blood is about 100.4o
F
pH is 7.4 (7.35-7.45)
Blood makes up 8% of body weight
Blood volume averages 5-6 liters (1.5
gal) in males and 4-5 liters (1.2 gal) in females
Salt content is equal to 0.9% NaCl (normal saline)
Blood has 2 major components:
55% plasma--watery liquid
containing dissolved substances
45% formed elements--cells and
cell fragments
FIGURE 19.1 P. 668
As they would be found in the body, red
blood cells are red; white blood cells and platelets are colorless. When we
look at them on slides, they are stained with various dyes to give them color.
The most commonly used stain is Wright’s stain. This makes red blood
cells pink and white blood cells and platelets purple. If blood is removed, put
in a tube, and spun in a centrifuge before it clots, the result is:
91.5% water and 8.5% solutes, most of
which are proteins. Solutes:
1. Proteins—these make up
most of the solutes and are almost all synthesized by the liver
a.
Albumins--54%--synthesized by the liver---contribute to blood osmotic pressure
and act as transport proteins for several hormones
b.
Globulins--38%--some of these are synthesized by the liver and act as transport
proteins; another group is made up by the antibodies (immunoglobulins),
produced by plasma cells
c. Fibrinogen--7%--produced by the
liver and functions in blood clotting
2. Wastes--urea, uric acid,
creatinine, bilirubin--these are mostly breakdown
products of protein metabolism
3. Nutrients--absorbed from the
digestive system and transported to body cells
4. Regulatory
substances—enzymes, hormones, vitamins and cofactors
5. Gases--oxygen, carbon dioxide,
nitrogen
6. Electrolytes—Na+,
K+, Ca2+, Cl` , HCO3`
, HPO42` and
others—help maintain osmotic pressure and serve as essential minerals
1. Erythrocytes--red blood cells
(RBC)
2. Leukocytes--white blood cells
(WBC)
a. Granular
leukocytes (granulocytes)
1) Neutrophils
2) Eosinophils
3) Basophils
b. Agranular
leukocytes (agranulocytes)
a) B cells
b) T cells
c) Natural killer cells
2) Monocytes
3. Thrombocytes (platelets)
Blood cells are formed by the process
of hemopoiesis or hematopoiesis. During various periods of embryonic and fetal
life blood cells are formed in the yolk sac, liver, spleen, thymus gland, lymph
nodes and bone marrow. After birth hematopoiesis takes place mainly in the red
bone marrow of the sternum, ribs, cranial bones, vertebrae, pelvis, and
proximal epiphyses of humerus and femur. Special cells called pluripotent
hematopoietic stem cells (hemocytoblasts) differentiate from mesenchyme during
embryonic development and travel to marrow cavities as bones form. There they
remain, constantly dividing and giving rise to all blood cells and platelets as
follows:
Pluripotent stem cells
Myeloid stem cells
Lymphoid stem cells
Several
types of progenitor cells
Pre B cells
Prothymocytes
Can't reproduce
6 different precursor cells:
B lymphoblast
T lymphoblast
1. ProerythroblastsàRBC
2. MegakaryoblastàPlatelets
B lymphocyte
T lymphocyte
3. Monoblastà Monocytes
4. Myeloblastà Neutrophils
5. Eosinophilic myeloblastà Eosinophils
6. Basophilic myeloblastà Basophils
There are a few
additional types of stem cells found in red bone marrow. Some of these produce
reticular cells, adipocytes, dendritic cells, etc.—several types of cells
other than blood cells.
Except for some
lymphocytes, blood cells live for short periods of time and are constantly
replaced. The number of RBC and platelets should always remain about the same.
The number of WBC constantly changes in response to invaders, allergies, etc.
New RBC and all new WBC other than lymphocytes are produced only in bone
marrow. The lymphocytes do originate in bone marrow, but these WBC are able to
divide outside bone marrow and produce large number of cells just like the
original.
Growth factors which may stimulate production
of blood cells include:
1. Erythropoietin--stimulates
erythrocyte precursors
2. Colony stimulating factors
(CSFs)--various ones stimulate all WBC or just a
certain kind
3. Interleukins--certain
white blood cells
4. Thrombopoietin—platelets
Some of these now are produced by
recombinant DNA technology and used to treat patients such as those undergoing
chemotherapy for cancer.
RBC--make up 99% of formed elements and
contain hemoglobin, which carries oxygen and is responsible for the color of
blood.
Mature RBC are
biconcave discs. This shape gives the RBC a large surface area and great
flexibility. However, RBC lack a nucleus, so they
cannot reproduce, carry on extensive metabolic activity, or synthesize new
membranes and organelles as they wear out. The plasma membrane encloses
cytoplasm with hemoglobin dissolved in it. The hemoglobin was synthesized while
the developing RBC still had a nucleus to direct it. They have no mitochondria
and produce all of their energy anaerobically, which means they do not use up
the oxygen they carry.
Hemoglobin makes up 33% of a RBC's
weight--normal values:
12-16gm/100ml blood in females
13.5-18 in males
The % of blood volume occupied by RBC
is called the hematocrit. Normal values:
38 - 46 (42) in females
40 - 54 (47) in males
Special proteins on the surface of RBC
give us our blood groups.
Physiology--function of RBC is
transportation of oxygen. One hemoglobin molecule consists of a protein called
globin combined with 4 iron-containing heme molecules. The iron combines with
oxygen in the lungs to form a weak chemical combination called oxyhemoglobin,
which breaks down in tissues and releases the oxygen. Each RBC contains about
280 million hemoglobin molecules (X4=1,120,000,000 oxygen molecules per RBC).
Hemoglobin also helps transport carbon dioxide (about 13% of the total) in the
form of carbaminohemoglobin.
Life span is about 120 days (4 months).
Fixed macrophages in the spleen and liver recognize and remove wornout RBC.
Normal values:
Males 5.4
million/cubic microliter
of blood
Females 4.8
million
To maintain this number, 2 million new
RBC per second must enter circulation.
After phagocytosis, the hemoglobin is
recycled. The globin is broken down to amino acids, which can be reused to
build more hemoglobin or other proteins. The heme portion is broken down to:
1. Iron, which attaches to a
plasma protein called transferrin. In this combined form the iron is carried to
muscle cells, the liver, and the spleen. There it is released from the
transferrin and attached to one of two storage proteins, either ferritin or
hemosiderin. When needed, the iron is picked up again by transferrin and
delivered to the bone marrow. We are never supposed to have free iron either in
the blood or the tissues. It is always attached to an organic molecule.
2. Bilirubin---this is the
non-iron portion of heme. It travels in the blood to the liver for excretion in
bile.
Biliverdin (released directly from the RBC’s heme)
Bilirubin (transported in blood to liver)
Secreted
into bile, which enters intestines where
bilirubin is converted by bacteria to:
Urobilinogen
Some
absorbed back into
Most
changed to:
blood and converted to:
Urobilin (eliminated in urine)
Stercobilin (eliminated in feces)
Erythropoiesis is the process of RBC
formation. It occurs in red bone marrow with a myeloid stem cell as the first
step from the pluripotent hematopoietic stem cell (this is the one which could
become any type of blood cell). The myeloid stem cell gives rise to a
proerythroblast, which is committed to becoming a RBC. Developing RBC go
through a series of steps. At first a nucleus is present and cell components
including hemoglobin are synthesized. The nucleus is then cast out and the
center of the cell indents. The stage that leaves the bone marrow is called a
reticulocyte.
If RBC or hemoglobin production
lag, anemia may result. If the blood is unable to deliver enough oxygen
to tissues this is hypoxia. Hypoxia causes the kidneys to release a hormone,
erythropoietin, to speed up RBC production. Anemia can involve:
Lack of iron to make hemoglobin
Lack of amino acids to
make globin
Lack of vitamin B12
Sickle cell disease--genetic defect
causes 2 "wrong" amino acids in hemoglobin. This abnormal hemoglobin
forms crystals inside the RBC and distorts them into a rigid sickle shape which
may block small capillaries. The abnormal RBC also do
not live a full life span, which leads to anemia.
These have a nucleus and do not contain
hemoglobin.
A. Granular leukocytes have lobed
nuclei and visible granules in the cytoplasm when stained with Wright's stain.
All develop from a myeloid stem cell and include 3 types:
1. Neutrophils--nuclei with 2-6
lobes. Also called polymorphonuclear leukocytes. Pale lilac granules in cytoplasm.
2. Eosinophils--nucleus usually
has 2 lobes and large prominent reddish-orange granules in cytoplasm.
3. Basophils--nucleus bilobed or
irregular, often an S shape. Large blue-black granules obscure the nucleus.
B. Agranular leukocytes--no visible
cytoplasmic granules, 2 kinds:
1. Lymphocytes--dark rounded
nuclei with a small amount of sky-blue cytoplasm visible as a rim around the
nucleus.
2. Monocytes--larger and have an
indented kidney-bean or horseshoe-shaped nucleus. More blue
cytoplasm is visible and has a foamy appearance. Monocytes leave the
bloodstream and differentiate into macrophages.
WBC have
surface proteins called major histocompatibility antigens, which are unique to
each person. These are not usually matched for blood transfusions but determine
compatibility for transplants.
The function of WBC is defense of the
body, in several ways.
1. Phagocytosis--neutrophils and
monocytes ingest invading microbes and dead tissue cells. Injured tissue
releases chemicals which attract these cells (chemotaxis). WBC are drawn to the area and leave the capillaries by the
process of emigration (diapedesis).
Neutrophils
arrive first, beginning within minutes. They mainly engulf invading bacteria
and then attack them with lysozyme and other chemicals to inactivate them. In
action neutrophils have a short life span (hours).
Monocytes arrive
more gradually but finally in great numbers. After leaving the blood they
differentiate into macrophages. Each macrophage can attack large numbers of
bacteria but these also do most of the cleanup of dead tissue.
2. Immune response--the cells
involved are various types of lymphocytes. A foreign substance (most often
foreign protein) that enters the body and triggers this type of response is called
an antigen. In a complicated series of steps, B lymphocytes differentiate into
plasma cells and produce antibodies, which can bind to the antigens that caused
their production and inactivate them. T lymphocytes are required at certain
points in this process. T lymphocytes can also be produced to directly attack
certain types of invaders and inappropriate cells.
3. Miscellaneous
a.
Eosinophils--enter tissues, release certain enzymes and phagocytize
antigen-antibody complexes. They tend to limit the inflammatory response. Most active in allergies and parasitism.
b.
Basophils--release chemicals such as histamine that intensify allergies and the
inflammatory reaction. No phagocytosis. Mast cells of connective tissue are
similar to basophils.
1. Granulocytes and monocytes are
formed in red bone marrow ONLY and do not divide outside this tissue.
2. Lymphocytes are originally
formed in red bone marrow (myeloid tissue) and leave to go into various body
tissues. If more of a certain type is needed, the original cell may divide
(proliferate) in lymphoid tissue (lymph nodes, spleen, tonsils, thymus) or in the bloodstream.
WBC have
indeterminate life spans, depending on type and conditions in the body
(anywhere from hours to years). Normal white count is 5,000-10,000 per
microliter. Leukocytosis is an increase in the white count; leukopenia is a
decrease. In addition to the total number of all white cells, the percentage of
each type present is important. To determine this, a differential white count
is performed. Normal values:
Neutrophils 60-70%
Lymphocytes 20-25
Monocytes 3-8
Eosinophils 2-4
Basophils .5-1
TABLE 19.2 P. 678 SIGNIFICANCE OF HIGH/LOW WHITE CELL COUNTS
THROMBOCYTES (PLATELETS)
Develop from megakaryoblasts, which
become megakaryocytes in bone marrow. These large cells break apart and the
fragments, which are bits of cytoplasm wrapped in plasma membrane
enter the circulation. They function in clotting and repair of damaged vessels.
Life span 5-9 days and normal count is 150,000-400,000 per microliter.
SUMMARY OF FORMED ELEMENTS
COMPLETE BLOOD COUNT (CBC)
This test is very commonly used to get
the following information:
·
Total
count for RBC, WBC, and platelets
·
Differential
white count
·
Hematocrit
·
Hemoglobin
HEMOSTASIS--stoppage of bleeding
Hemorrhage is the term for excessive
blood loss.
3 basic mechanisms of hemostasis:
1. Vascular spasm
3. Blood coagulation (clotting)
These usually work very well in tiny
vessels and less successfully in larger ones.
1. Vascular spasm--immediately
following injury to a blood vessel, the smooth muscle of the wall contracts to
reduce blood loss.
2. Platelet plug formation---also
occurs very quickly
a. Platelet adhesion--inactive
circulating platelets are tiny and disc-shaped. In response to the presence of
damaged endothelial cells, platelets stick to the damaged area of the blood
vessel
b. Platelet release
reaction--activated platelets become larger and change from disc to a sphere,
form spines and begin to release a number of chemicals from granules in their
cytoplasm:
1) Activate
nearby platelets by releasing ADP and a prostaglandin, thromboxane A2
2) Cause
vasoconstriction by releasing serotonin and thromboxane A2
3) Make all
platelets in the area sticky (ADP)
c. Platelet plug--platelets stick
together and form a mass. The gathering of platelets is platelet aggregation
and the platelet plug is the result. The platelet plug can completely stop
blood loss in a small vessel. In larger injuries, the fibrin threads of the
clot stick to the platelet plug.
Platelets also contain fibrin
stabilizing factor, which helps strengthen a blood clot, and plate-derived
growth factor, which promotes repair o damaged blood vessels.
3. Coagulation (clotting)--this occurs
when blood forms a gel consisting of protein fibers called fibrin in which the
formed elements are trapped. Clotting involves a number of enzymes and other
chemicals called clotting factors (coagulation factors). Most are in the
plasma, some are released from platelets, and one is released from damaged
tissue cells.
TABLE 19.4
P. 684 CLOTTING
FACTORS
There are 12 clotting factors in all,
numbered I-V, no VI, VII-XIII. Most of these factors are present at all times
but in an inactive form. They can be quickly activated when needed. Clotting is
a series or cascade of reactions in which one coagulation factor activates the
next which in turn activates the next and so on. If one step cannot take place
the whole reaction stops. Clots normally form in 3 - 6 minutes.
Coagulation (clotting) occurs to stop
blood loss from a damaged vessel. It also occurs when blood is drawn from the
body in a syringe, tube, etc. In a test tube, a gel (the clot) forms and
settles to the bottom. A yellowish liquid remains at the top. This is called
serum. It is different from plasma because serum does not contain the clotting
factors---plasma does. (As the clot forms, the clotting factors wind up at the
bottom of the tube in the clot.)
Stages of coagulation:
1. Formation of prothrombin
activator (prothrombinase)
2. Conversion of prothrombin into
thrombin
3. Conversion of fibrinogen to
fibrin
Stage 1--The formation of prothrombin
activator (prothrombinase) occurs by a combination of 2 mechanisms:
a. Extrinsic pathway--occurs
rapidly within seconds. A protein called tissue factor enters blood from
damaged cells OUTSIDE the blood vessels and initiates the formation of
prothrombin activator, an active enzyme.
1)This
process begins when tissue factor (thromboplastin) leaks into the blood from
damaged cells outside the blood vessel. There must be a hole or tear in
the blood vessel for the tissue factor to enter, as well as damaged tissue
outside the vessel.
2)Tissue
factor begins a series of reactions that activate Factor X.
3) Activated Factor X
combines with Factor V to form prothrombin activator
4) Ca2+
ions are needed in these steps
b. Intrinsic pathway--requires
several minutes and is initiated INSIDE the damaged blood vessels. This pathway
can act even if only cells of the blood vessel are damaged with there is no
hole in the vessel wall. Through a different series of steps the result is the
same, the formation of prothrombin activator. Platelet phospholipids are
involved in this pathway. The instrisic pathway can also be activated by
contact with glass or plastic (tube or syringe).
Stage 2--Prothrombin activator and Ca
ions catalyze the conversion of prothrombin to thrombin. Prothrombin is an
inactive form of an enzyme, synthesized in the liver and found in blood plasma.
Thrombin is the active enzyme.
Stage 3--Thrombin, in the presence of
Ca ions, converts soluble fibrinogen to insoluble fibrin threads. As the formed
elements are pushed through these threads by blood circulation, they become
trapped and form the clot. Fibrin threads stick to the platelet plug and the
walls of the vessel. Other effects of thrombin:
a. Accelerates the formation of
prothrombin activator
b. Activates platelets, which
reinforces their aggregation & the release of more platelet phospholipids
c. Activates factor XIII, which
strengthens and stabilizes the clot
After the initial formation of the clot
plugs the vessel, clot retraction (tightening of the clot) follows. The fibrin
threads contract and pull the edges of the damaged vessel together.
The next step is repair of the damaged
vessel wall. Fibroblasts migrate to the area and begin to form new connective
tissue for the outsideof the vessel wall. After this is well
along, nearby endothelial cells divide to form a new lining for the damaged area.
Time required for these steps varies, depending on the size of the vessel,
severity of the injury, etc.
Vitamin K is not one of the clotting
factors but is necessary for normal clotting because without it the liver
cannot synthesize factors II, VII, IX and X. The vitamin is produced by
bacteria in the large intestine and requires fat for absorption.
Hemophilia--hereditary deficiency of a
clotting factor. Severe bleeding follows even minor injuries. Most cases (80%)
are classic hemophilia (hemophilia A) and the missing factor is VIII. This type
occurs mostly in males (sex-linked). Other missing factors lead to other types
of the disease. Treatment is daily injections of the missing factor or fresh
plasma transfusions during bleeding episodes.
Fibrinolysis is the dissolution of a
clot. This occurs due to an enzyme, plasmin, which dissolves the fibrin
threads. This enzyme in an inactive form, plasminogen, is incorporated into all
clots. At the appropriate time, it becomes activated by factors in the healing
vascular endothelium and dissolves the clot.
Thrombolytic agents are new drugs which
can be injected into the body to dissolve harmful clots such as those that
cause a large percentage of heart attacks. These include streptokinase and t-PA
(tissue plasminogen activator).
Blood clots can be good news or bad
news. They must be limited to damaged areas and appropriate size. They should
occur only immediately after an injury, reach only the size necessary to stop
blood loss, and never occur in unbroken vessels. Natural factors which usually
see to this:
1. Smoothness of normal
endothelium
2. Absorption of thrombin into the
clot by fibrin
3. Coagulation factors diluted in
circulating blood
4. A prostaglandin that inhibits
platelet adhesion and release (prostacyclin)
5. Natural anticoagulants in the
blood
a. Antithrombin III (AT-III)—blocks factors XII, XI,
IX, X, II
b. Protein C—blocks V and VIII
c. Heparin-increases the activity of AT-III
Heparin is extracted from animal
tissues and used in IV lines, open heart surgery and hemodialysis to prevent
clotting. Heparin or some other agents that tie up Ca ions are used to prevent
clotting in lab samples and donated blood.
Patients who need a decrease in
clotting ability are given anticoagulants. Aspirin is a mild anticoagulant.
Warfarin (coumadin) is a much stronger one. It inactivates Vitamin K and slows
synthesis of the 4 clotting factors for which the vitamin is required.
Donated blood and often blood for lab
tests must not be allowed to clot. Various anticoagulants are used for this
purpose. Most of them act by tying up calcium ions, which are required at many
points in the coagulation process.
In spite of natural safeguards,
coagulation may occur in unbroken vessels (thrombosis). A clot of this type is
called a thrombus and will tend to become overly large and brittle. Some
factors which favor the formation of thrombi are:
Irregular or rough vessel walls
Vascular damage that does not
actually break the wall
Chemicals such as nicotine
Infections
Prolonged inactivity that leads to
sluggish flow or pooling of blood in veins such as leg veins
Although the thrombi themselves can
cause problems, a big concern is the fact that thrombi have a tendency to let
pieces break off to be carried in the blood to other parts of the body. This
can result in the blockage of important arteries at some distance from the
clot. Pulmonary (lung) emboli are especially common, and a large one can be
fatal.
RBCs have on their surface antigens
called agglutinogens or isoantigens. The 2 most important groups of these are
ABO and Rh. Many other less significant antigens are also found, for a total of
24 known groups, but it is rare for any besides ABO and Rh to cause major
problems in matching blood.
Inherited from both
parents—everyone has 2 genes for this. Possibilities:
A—put A
antigens on all RBC
B—put B antigens on all RBC
O—no antigens on RBC
Results:
AA Type A
AO
BB Type
B
Table 19.5 % of
various populations
BO
having each type
P. 685
AB
OO Type O
All persons have in their plasma
antibodies against any ABO antigen they don’t synthesize.
|
BLOOD TYPE |
ANTIGENS ON RBC |
ANTIBODIES IN PLASMA |
|
TYPE A |
A |
B |
|
TYPE B
|
B |
A |
|
TYPE AB |
BOTH A & B ON ALL RBC |
NONE |
|
TYPE O |
NONE |
BOTH A & B |
Blood type must be matched for
transfusions because recipients’ antibodies will attack the corresponding
antigen and cause donated RBC to rupture (hemolysis). This destroys the RBC and
the release of the chemicals they contain into the bloodstream can severely
damage the kidneys and other organs.
Procedures for matching:
1. Typing—matches ABO and Rh groups---done when blood
is donated or patient first enters hospital
2. Cross-matching—small amounts of donor RBCs and
recipient’s plasma are mixed immediately before a transfusion. If no
agglutination (clumping) occurs, the match is suitable.
Blood is mixed with drops of solutions
containing known antibodies.
|
|
Anti-A
Anti-B
(A antibodies) (B antibodies)
Agglutination (clumping) occurs when
antibody/antigen react.
Clumps in A only—Type A
Clumps in B only—Type B
Clumps in both A &
B—Type AB
No clumps—Type O
Type
O—universal donor—no antigens on RBC
These would
only be used in emergencies—best to match correctly. Rh group must
also be
considered. The universal recipient would have to be Rh positive; universal
donor Rh
negative.
ABO antigens
are secreted into saliva and other body fluids by 80%
of the
population (secretors). Can be used to match semen samples,
gum,
cigarettes, etc.
This system
is also based on the presence of antigens on the surface of the
RBCs. People
who have Rh antigens on their RBC are Rh+; those who do
not are Rh-.
Unlike the
ABO group, plasma of Rh- persons does not contain Rh
antibodies
unless exposure to the antigen occurs, as in a transfusion
of Rh+ blood.
One of the
most serious situations involving the Rh factor is
hemolytic
disease of the newborn. For this to occur, the mother is
always Rh-.
The father and the fetus (baby) are Rh+. If the RBC of
baby get into
the blood of the Rh- mother, she will react by
producing
antibodies that will destroy the Rh+ cells. Unfortunately,
the
antibodies can cross the placenta and affect all of the baby’s
RBC. Normally
there is little exchange of blood cells between the
mother and
the fetus, but late in pregnancy and during delivery (or
abortion or
miscarriage) enough Rh+ RBC may enter the mother’s
circulation
to cause her to form large numbers of Rh antibodies. In
subsequent
pregnancies, these antibodies will be produced rapidly in large numbers
as soon as
any Rh+ RBC slip into her blood. They will then begin to
cross the
placenta in large numbers early in the pregnancy and attack the blood cells
of another
Rh+ fetus. (If the fetus is Rh- it would not be affected.)
Now all Rh-
mothers are given injections of anti-Rh gamma
globulin
(RhoGAM) during pregnancy and at the time of delivery if the
fetus is Rh+.
This prevents the mother from making her own anti-Rh
antibodies
and protects future babies.
ABO
antibodies do not cross the placenta (too big).