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Chapter 19: The Cardiovascular
System: The Blood
Blood
Liquid connective tissue
3 general functions
Transportation
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1.
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Gases, nutrients, hormones, waste products
Regulation
2.
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pH, body temperature, osmotic pressure
Protection
3.
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Clotting, white blood cells, proteins
Copyright 2009, John Wiley & Sons, Inc.
Components of Blood
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Blood plasma – water liquid extracellular matrix
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91.5% water, 8.5% solutes (primarily proteins)
Hepatocytes synthesize most plasma proteins
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Albumins, fibrinogen, antibodies
Other solutes include electrolytes, nutrients, enzymes,
hormones, gases and waste products
Formed elements – cells and cell fragments
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Red blood cells (RBCs)
White blood cells (WBCs)
Platelets
Copyright 2009, John Wiley & Sons, Inc.
Copyright 2009, John Wiley & Sons, Inc.
Formed Elements of Blood
Copyright 2009, John Wiley & Sons, Inc.
Formation of Blood Cells
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Negative feedback systems regulate the total
number of RBCs and platelets in circulation
Abundance of WBC types based of response
to invading pathogens or foreign antigens
Hemopoiesis or (See Video)
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Red bone marrow primary site
Pluripotent stem cells have the ability to
develop into many different types of cells
Copyright 2009, John Wiley & Sons, Inc.
Copyright 2009, John Wiley & Sons, Inc.
Formation of Blood Cells
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Stem cells in bone marrow
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Reproduce themselves
Proliferate and differentiate
Cells enter blood stream through sinusoids
Formed elements do not divide once they
leave red bone marrow
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Exception is lymphocytes
Copyright 2009, John Wiley & Sons, Inc.
Formation of Blood Cells
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Pluripotent stem cells produce
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Myeloid stem cells
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Lymphoid stem cells give rise to
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Give rise to red blood cells, platelets, monocytes, neutrophils,
eosinophils and basophils
Lymphocytes
Hemopoietic growth factors regulate differentiation
and proliferation
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Erythropoietin – RBCs
Thrombopoietin – platelets
Colony-stimulating factors (CSFs) and interleukins – WBCs
Copyright 2009, John Wiley & Sons, Inc.
Red Blood Cells / Erythrocytes
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Contain oxygen-carrying protein hemoglobin
Production = Destruction w/ at least 2
million new RBCs/second
Biconcave disc – increases surface area
Strong, flexible plasma membrane
Glycolipids in plasma membrane responsible
for ABO and Rh blood groups
Lack nucleus and other organelles

No mitochondria – doesn’t use oxygen???
Copyright 2009, John Wiley & Sons, Inc.
Hemoglobin (280 million mol. per RBC)
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Globin – 4 polypeptide chains
Heme in each of 4 chains
Iron ion can combine reversibly with one oxygen
molecule
Also transports 23% of total carbon dioxide
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Combines with amino acids of globin
Nitric oxide (NO) binds to hemoglobin
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Releases NO causing vasodilation to improve blood flow
and oxygen delivery
Copyright 2009, John Wiley & Sons, Inc.
Shapes of RBC and Hemoglobin
Copyright 2009, John Wiley & Sons, Inc.
Red Blood Cells
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RBC life cycle
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Live only about 120 days
Cannot synthesize new components – no nucleus
Ruptured red blood cells removed from circulation
and destroyed by fixed phagocytic macrophages
in spleen and liver
Breakdown products recycled (See Video)
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Globin’s amino acids reused
Iron reused
Non-iron heme ends as yellow pigment urobilin in urine
or brown pigment stercobilin in feces
Copyright 2009, John Wiley & Sons, Inc.
Formation and Destruction of RBC’s
Copyright 2009, John Wiley & Sons, Inc.
Circulation for about
120 days
7
3
Reused for
protein synthesis
Amino
acids
Globin
4
6
5
Fe3+
Fe3+ Transferrin
2 Heme
Fe3+
Ferritin
Transferrin
Bilirubin
9
1 Red blood cell
Biliverdin
Bilirubin
11
10
death and
phagocytosis
Small
intestine
Kidney
13
12
Urobilin
Macrophage in
spleen, liver, or
red bone marrow
Bilirubin
Urobilinogen
Stercobilin
Urine
Liver
Feces
+
Globin
+
Vitamin B12
+
Erythopoietin
8 Erythropoiesis in
red bone marrow
Bacteria
Key:
in blood
Large 14
intestine
in bile
Erythropoiesis
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Starts in red bone marrow
with proerythroblast
Cell near the end of
development ejects nucleus
and becomes a reticulocyte
Develop into mature RBC
within 1-2 days
Negative feedback
balances production with
destruction
Controlled condition is
amount of oxygen delivery
to tissues
Hypoxia stimulates release
of erythropoietin
White Blood Cells/ Leukocytes
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Have nuclei
Do not contain hemoglobin
Granular or agranular based on staining
highlighting large conspicuous granules
Granular leukocytes
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Neutrophils, eosinophils, basophils
Agranular leukocytes
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Lymphocytes and monocytes
Copyright 2009, John Wiley & Sons, Inc.
Functions of WBCs
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Usually live a few days
Except for lymphocytes – live for months or years
Far less numerous than RBCs
Leukocytosis is a normal protective response to
invaders, strenuous exercise, anesthesia and
surgery
Leukopenia is never beneficial
General function to combat invaders by
phagocytosis or immune responses
Copyright 2009, John Wiley & Sons, Inc.
Emigration of
WBCs
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Many WBCs leave the
bloodstream
Emigration (formerly
diapedesis)
Roll along endothelium
Stick to and then
squeeze between
endothelial cells
Precise signals vary for
different types of WBCs
Copyright 2009, John Wiley & Sons, Inc.
WBCs (Table 19.2 and 19.3)
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Neutrophils and macrophages are active
phagocytes
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Neutrophils respond most quickly to tissue
damage by bacteria
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Attracted by chemotaxis
Uses lysozymes, strong oxidants, defensins
Monocytes take longer to arrive but arrive in
larger numbers and destroy more microbes
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Enlarge and differentiate into macrophages
Copyright 2009, John Wiley & Sons, Inc.
Copyright 2009, John Wiley & Sons, Inc.
WBCs
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Basophila leave capillaries and release
granules containing heparin, histamine and
serotonin, at sites of inflammation
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Intensify inflammatory reaction
Involved in hypersensitivity reactions (allergies)
Eosinophils leave capillaries and enter tissue
fluid
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Release histaminase, phagocytize antigenantibody complexes and effective against certain
parasitic worms
Copyright 2009, John Wiley & Sons, Inc.
Copyright 2009, John Wiley & Sons, Inc.
Lymphocytes
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Lymphocytes are the major soldiers of the
immune system
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B cells – destroying bacteria and inactivating their
toxins
T cells – attack viruses, fungi, transplanted cells,
cancer cells and some bacteria
Natural Killer (NK) cells – attack a wide variety of
infectious microbes and certain tumor cells
Copyright 2009, John Wiley & Sons, Inc.
Copyright 2009, John Wiley & Sons, Inc.
Platelets/ Thrombocytes
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Myeloid stem cells develop eventually into a
megakaryocyte
Splinters into 2000-3000 fragments
Each fragment enclosed in a piece of plasma
membrane
Disc-shaped with many vesicles but no nucleus
Help stop blood loss by forming platelet plug
Granules contain blood clot promoting chemicals
Short life span – 5-9 days
Copyright 2009, John Wiley & Sons, Inc.
Stem cell transplants
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Bone marrow transplant
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Recipient's red bone marrow replaced entirely by healthy,
noncancerous cells to establish normal blood cell counts
Takes 2-3 weeks to begin producing enough WBCs to fight
off infections
Graft-versus-host-disease – transplanted red bone marrow
may produce T cells that attack host tissues
Cord-blood transplant
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Stem cells obtained from umbilical cord shortly before birth
Easily collected and can be stored indefinitely
Less likely to cause graft-versus-host-disease
Copyright 2009, John Wiley & Sons, Inc.
Hemostasis
Sequence of responses that stops bleeding
3 mechanisms reduce blood loss
Vascular spasm
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1.
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Platelet plug formation
2.
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3.
Smooth muscle in artery or arteriole walls
contracts
Platelets stick to parts of damaged blood vessel,
become activated and accumulate large
numbers
Blood clotting (coagulation)
Copyright 2009, John Wiley & Sons, Inc.
Platelet Plug Formation
Copyright 2009, John Wiley & Sons, Inc.
Red blood cell
Platelet
Collagen fibers
and damaged
endothelium
11 Platelet adhesion
Liberated ADP,
serotonin, and
thromboxane A2
22
Platelet release reaction
Platelet plug
33
Platelet aggregation
Blood Clotting
3.
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Blood clotting
Serum is blood plasma
minus clotting proteins
Clotting – series of
chemical reactions
culminating in formation of
fibrin threads
Clotting (coagulation)
factors – Ca2+, several
inactive enzymes, various
molecules associated with
platelets or released by
damaged tissues
Copyright 2009, John Wiley & Sons, Inc.
3 Stages of Clotting
1.
2.
3.
Extrinsic or intrinsic pathways lead to formation
of prothrombinase
Prothrombinase converts prothrombin into
thrombin
Thrombin converts fibrinogen (soluble) into fibrin
(insoluble) forming the threads of the clot
Copyright 2009, John Wiley & Sons, Inc.
(a) Extrinsic pathway
Tissue trauma
(b) Intrinsic pathway
Blood trauma
Damaged
endothelial cells
expose collagen
fibers
Tissue
factor
(TF)
Damaged
platelets
Activated XII
Activated
platelets
Ca2+
Ca2+
+
Platelet
phospholipids
Activated X Activated X
V
1
Ca2+
Ca2+
V +
PROTHROMBINASE
(c) Common
pathway
Ca2+
Prothrombin
(II)
THROMBIN
Ca2+
2
XIII
Fibrinogen
(I)
Activated XIII
Loose fibrin
threads
STRENGTHENED
FIBRIN THREADS
3
Blood Clotting
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Extrinsic pathway
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Fewer steps then intrinsic and occurs rapidly
Tissue factor (TF) or thromboplastin leaks into the blood
from cells outside (extrinsic to) blood vessels and initiates
formation of prothrombinase
Intrinsic pathway
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More complex and slower than extrinsic
Activators are either in direct contact with blood or
contained within (intrinsic to) the blood
Outside tissue damage not needed
Also forms prothrombinase
Copyright 2009, John Wiley & Sons, Inc.
Blood Clotting: Common pathway
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Marked by formation of prothrombinase
Prothrombinase with Ca2+ catalyzes conversion of
prothrombin to thrombin
Thrombin with Ca2+ converts soluble fibrinogen
into insoluble fibrin
Thrombin has 2 positive feedback effects
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Accelerates formation of prothrombinase
Thrombin activates platelets
Clot formation remains localized because fibrin absorbs
thrombin and clotting factor concentrations are low
Copyright 2009, John Wiley & Sons, Inc.
Blood Groups and Blood Types
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Agglutinogens – surface of RBCs contain
genetically determined assortment of
antigens
Blood group – based on presence or absence
of various antigens
At least 24 blood groups and more than 100
antigens
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ABO and Rh
Copyright 2009, John Wiley & Sons, Inc.
ABO Blood Group
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Based on A and B antigens
Type A blood has only antigen A
Type B blood has only antigen B
Type AB blood has antigens A and B
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Type O blood has neither antigen
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Universal recipients – neither anti-A or anti-B antibodies
Universal donor
Reason for antibodies presence not clear
Copyright 2009, John Wiley & Sons, Inc.
Antigens and Antibodies of ABO Blood
Types
Copyright 2009, John Wiley & Sons, Inc.
Hemolytic Disease
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Rh blood group
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People whose RBCs have
the Rh antigen are Rh+
People who lack the Rh
antigen are RhNormally, blood plasma
does not contain anti-RH
antibodies
Hemolytic disease of the
newborn (HDN) – if blood
from Rh+ fetus contacts Rhmother during birth, anti-Rh
antibodies made
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Affect is on second Rh+
baby
Copyright 2009, John Wiley & Sons, Inc.
Typing Blood
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Single drops of blood are
mixed with different
antisera
Agglutination with an
antisera indicates the
presence of that antigen
on the RBC