Chapter 17 - Blood

J.F. Thompson, Ph.D. & J.R. Schiller, Ph.D. & G. Pitts, Ph.D.
 Chapter 17 - Blood
 Use the video clips to review blood cell morphology

 CH 17 RBC Morphology
 CH 17 WBC Morphology
Overview: Composition of Blood
 A liquid connective tissue
 A mixture
 the formed elements - living blood cells & platelets
 the plasma – the fluid matrix
 Denser and more viscous than water
 due to dissolved ions & organic molecules, especially plasma
proteins, and to the blood cells
 composition and volume regulated by CNS & hormones
 Temp - 38° C
 pH - 7.4 (critical to be between 7.35 and 7.45)
 Volumes differ between sexes, conditional on many factors
 Females - average 4-5 L
 Males - average 5-6 L
Functions of Blood
 Transport and Distribution
 delivery of O2, nutrients, and hormones
 removal of CO2 and metabolic wastes
 Regulation of Internal Homeostasis
 body temperature
 pH
 fluid volume
 composition of the interstitial fluid/lymph
 Protection
 necessary for inflammation and repair
 prevents blood loss by hemostasis
(coagulation)
 prevents infection
Overview: Composition of Blood

 Blood sample
 spin it
 separates into 2 parts
 plasma
• ~55% of the volume
• straw colored liquid on top
 formed elements - ~45% of the volume
• red blood cells
• buffy coat - white blood cells and platelets
 Hematocrit = “packed cell volume”
 percentage of formed element measured in a blood sample
 about 45%
Blood Components

Refer to Tables
17-1 and 17-2
In your text.
Components of Blood - Plasma
 Plasma
 92% water
 7% proteins
 1% other solutes
Components of Blood - Plasma
 Proteins important
for osmotic balance
 albumin (60%)
 transports lipids
 steroid
hormones
 fibrinogen (4%) -
blood clotting
 globulins (35%) –
many different
proteins with a
wide variety of
functions
 globulin classes α,
β, and γ
 1% other
regulatory proteins
Components of Blood - Plasma
 Other solutes
 Waste products -
carried to various
organs for removal
 Nutrients – glucose
and other sugars,
amino acids, lipids,
vitamins and
minerals
 Electrolytes (ions)
 Regulatory
substances
 enzymes
 hormones
 Gases - O2, CO2, N2
Components of Blood - Formed
Elements

 Formed elements
 >99% red blood cells
 <1% white blood cells
and thrombocytes
(platelets)
Components of Blood - Formed
Elements
 Erythrocytes, or
Red Blood Cells
(RBC’s), for O2 and
CO2 transport

 RBCs’ hemoglobin
also helps buffer
the blood

IMPORTANT!
Note the
differences in
relative size and
appearance!
Components of Blood - Formed
Elements  Leukocytes (White
Blood Cells)
 Granular leukocytes
(granulocytes)
 neutrophils
 eosinophils
 basophils
 Agranular leukocytes
(agranulocytes)
 lymphocytes - T
cells, B cells
 monocytes 
tissue
macrophages
 Thrombocytes
(platelets)
Hematopoiesis
 Blood cell formation
 All blood cells come from
pluripotent hematopoietic
stem cells
(hemocytoblasts)
 reside in red bone
marrow
 give rise to 5 types of
precursor cells
 precursors develop
into RBCs, WBCs and
“giant”
megakaryocytes
which produce
platelets by
cytoplasmic
fragmentation
 Production of Erythrocytes

 Erythropoiesis
 RBC production
 controlled by hormones, especially erythropoietin (EPO) from
the kidney
 three phases of RBC maturation
 production of ribosomes
 synthesis of hemoglobin
 ejection of the nucleus and reduction in organelles
 leave bone marrow as reticulocytes  mature in the blood
stream to become erythrocytes
RBC Production - Erythropoiesis (cont.)
 Reticulocyte count
 Reticulocyte
 final stage before mature RBC
 released into blood where final maturation occurs

 Count reticulocytes to evaluate the health of the

marrow stem cells or the response of red bone marrow
to erythropoietin (EPO)
 low count - bone marrow not responding
 high count - replacement production or abnormal
circumstances
 Production of Erythrocytes

 Regulation of RBC production

 regulated by negative feedback
 O2 levels monitored in kidneys
 hypoxia increases RBC production
 production stimulated by erythropoietin (EPO) from kidneys
 Numbers
 ♂ - 5.4 million RBC’s/ml (testosterone stimulates EPO synthesis)
 ♀ - 4.8 million RBC's/ml
 2 million cells released into blood/second
 RBC Production - Anemia
 Anemia – symptoms of reduced O2 carrying capacity of the blood
 Causes
 Insufficient number of RBC’s
 hemorrhage - loss of RBC’s
 hemolytic anemia - premature RBC destruction due to transfusion
reaction, various diseases, or genetic problems
 aplastic anemia
• destruction or inhibition of hematopoietic components in bone marrow
• tumors, toxins, drugs, or irradiation
 Decreased hemoglobin content in the RBCs
 iron (heme) deficiency - insufficient iron due to diet or poor absorption
 pernicious anemia - lack of Vitamin B12
• Vitamin B12
– common in the diet
– needed for developing RBC cell division
• intrinsic factor needed for proper B12 absorption, often deficient and the
actual cause of the B12 deficiency
RBC Production - Anemia
 Abnormal Hgb - hereditary
 Thalassemias
sickled cells  Greeks, Italians (Mediterraneans)
 reduced or absent globin
synthesis
 RBC’s delicate - may rupture
 low RBC count
 Sickle Cell Anemia
 Africans, African-Americans
 Substitution mutation of 1 AA in
the hemoglobin molecule
changes the shape, flexibility &
lifespan of the RBCs
• prevents adequate O2 transport
• sickled cells lodge in and block
capillaries
 Need two copies of the abnormal
recessive gene for Sickle Cell
Disease
 One normal, one abnormal copy:
increased resistance to malaria =
Sickle Cell Trait
RBC Production - Erythropoiesis (cont.)
 Hematocrit (Hct)
 % of blood that is RBC’s
 ♂ : 40-54% (47%), ♀: 38-46% (42%), Why?
 Indicates RBC production and state of hydration
 Abnormal Hct
 high altitude – hypoxia 
 athletes - blood doping 
 polycythemia 
 anemias 
 hemorrhage 
 malaria 
 cancer 
 chemotherapy 
 radiation 
 drugs 
RBC Structure

 ~280 million Hgb molecules/cell

 Hgb for O2 transport

 Bi-Concave shape
 greater surface area/volume
ratio increases gas diffusion
 flexibility allows passage
through narrow capillaries
 RBC Physiology

 O2 combines with Hgb in lungs

 O2 gas not very soluble in H2O
 Hemoglobin transports O2 Hemoglobin
 2 α globin chains & 2 β globin chains
 4 heme groups (lipid)
 each heme binds an iron ion (Fe²+) that carries 1 O2
RBC Life Span
 Differential WBC Count

Eosinophil
Lymphocyte 2-4%
20-25%

Neutrophil
Monocyte 60-70%
3-8%

Basophil
0.5-1%
 Lymphocytes - Physiology
 Immune response through lymphocytes responding to
antigen (AG)

 An antigen is:
 any chemical substance recognized as foreign when
introduced into the body
 substance (usually proteins) that stimulate immune
responses
 Lymphocytes - Physiology
 Two main types of lymphocytes
 B-cells
 particularly active in attacking bacteria
 develop into plasma cells to produce antibodies (Ab)
• bind to antigen to form antibody-antigen (Ag-Ab) complexes
• complexes prevents Ag from interacting with other body cells
or molecules
• memory B cells – dormant until future exposure to Ag
 T-cells
 attack viruses, fungi, transplants, cancer, some bacteria
 4 types of cells
• cytotoxic (killer) T cells - destroy foreign invaders
• helper T cells - assist B cells and cytotoxic T cells
• suppressor T cells – help bring immune response to an end
• memory T cells - dormant until future exposure to Ag
 Leukocyte Life Span and Number
 Life span determined by activity

 Ingesting foreign organisms, toxins, shortens life

 Healthy WBC's – majority last days, but some last

months to years

 During infection, WBCs may only live hours

 engorge with ingested organisms, necrotic cells, toxins,
Ab-Ag complexes
 often die and lyse (burst)
 Leukocyte Life Span and Number
 5,000 - 10,000 WBC’s/mm3 blood
 RBC/WBC ratio 700/1

 Differential WBC count (a standard clinical lab report)

 Neutrophils 60-70%
 Lymphocytes 20-25%
 Monocytes 3-8%
 Eosinophils 2-4%
 Basophils 0.5-1%

 Abnormal proportions are correlated with different

types of disease processes
 Leukocyte Number Abnormalities
 Leukopenia = decreased numbers
 malnutrition, chronic disease states
 drug induced - glucocorticoids, anti-cancer drugs, etc.

 Leukocytosis = increased numbers

 Normal component of inflammatory response to injuries and
infections

 Leukemia, Lymphomas = grossly increased numbers, abnormal

forms; many subcategories
 bone marrow and blood stream (leukemia) or tissue spaces
(lymphoma) fill with cancerous (nonfunctional) leukocytes
 crowds out other cells types
 anemia
 bleeding
 immunodeficiency
 Leukocyte Disorders
 Generally a descendent
of a single cell

 different types of cells

 myelocytic leukemia
 lymphocytic leukemia

 under different
cancerous conditions
 acute - if derived
from -blast type cells
 chronic - if derived
from later stages
Thrombocytes - Platelets

 Development
 Megakaryocytes shed small cytoplasmic fragments
 Each fragment surrounded by plasma membrane
 Anatomy
 250,000-400,000/mm3
 No nucleus, disc shaped
 2-4 µm diameter with many granules
Thrombocytes - Platelets (cont.)
Physiology
• Short life span (5-9
days)

• Help plug small holes

in blood vessels

• Granules contain
regulatory factors
which serve several
important functions
in:
• coagulation
• inflammation
• immune defenses
Thrombocytes - Platelets (Granules)

 alpha granules
 clotting factors
 platelet derived growth
factor (PDGF)
 dense granules
 Ca++, ADP, ATP
 Thromboxane A2,
 vasoconstrictors
 clot promoting enzymes
Hemostasis
 3 mechanisms exist to stop bleeding

 First - Vascular Spasm

 Blood vessel constricts when damaged
 vessel wall smooth muscle contracts immediately
 blood flow slows through vessel
 local trigger or autonomic reflex?
 Hemostasis (cont.)
 Second - Platelet Plug Formation
1) Platelet adhesion
 platelets stick to exposed collagen
 tissue factors activate platelets

2) Platelet release reaction

 platelets attach to other platelets
 release granule contents (thromboxane A2)
 promote vasoconstriction, platelet activation
and aggregation

3) Platelet aggregation  platelet plug

 blocks blood loss in small vessels
 less effective in larger vessels
Hemostasis (cont.)
 Third - Coagulation
 Gel formation
(clotting) in blood
plasma traps the
formed elements

 Thrombosis -
clotting in a
normal vessel

 Hemorrhage -
slowed clotting
may lead to
bleeding
 Hemostasis - Coagulation
 A complicated process that
functions as a positive
feedback cascade
 Fibrinogen  Fibrin traps
blood cells
 2 pathways – extrinsic &
intrinsic unite in a
common final process
 Pathways involve 12
numbered factors and
additional helpers (esp.
Ca++) in clot formation
 Hemostasis - Coagulation (cont.)
 Stage 1: Prothrombinase Extrinsic Pathway Intrinsic Pathway
formation
 Prothrombinase
catalyzes Prothrombin
conversion to Thrombin
 Stage 1 has 2 parts
 Part 1: Extrinsic
Pathway
• Rapid (seconds)
• Tissue factor (TF)
enters blood from
tissue
• Ultimately activates
prothrombinase

Prothrombinase
 Hemostasis - Coagulation (cont.)
 Stage 1: Prothrombinase Extrinsic Pathway Intrinsic Pathway
formation (cont.)
 Part 2: Intrinsic
Pathway
 Slower (minutes)
 Activators in blood –
from damaged red blood
or endothelial cells
activate clotting
 Extrinsic pathway also
activates Intrinsic
pathway
 Ultimately activates
prothrombinase
 Ca2+ is required for
activation of both paths!
Prothrombinase
 Hemostasis - Coagulation (cont.)
 Stage 2 - Common
Pathway
 Thrombin Formation
 requires enzyme
Prothrombinase &
Ca++ ions
 catalyzes
prothrombin 
thrombin +

 Thrombin accelerates
formation of
prothrombinase
(positive feedback) +
Prothrombinase
 Thrombin accelerates Common
platelet activation 2. Pathway

(positive feedback)
Hemostasis -
Coagulation (cont.)
 Stage 3 - Common Pathway
 Fibrin formation
 activated enzyme thrombin
with Ca++ ions catalyzes
fibrinogen  fibrin
• fibrinogen (soluble)
• fibrin (insoluble)
 Fibrin
 Protein threads attach to
vessel and tissue surfaces
 Absorbs & inactivates 90% of
thrombin, limits clot formation
3.
Hemostasis - Coagulation (cont.)
 Clot retraction and repair
 clot retraction is also known as syneresis
 platelets continue to pull on fibrin threads closing
wound
 formed elements are trapped in fibrin threads,
some serum may leak out
 Hemostatic control mechanisms
 important that clot formation remains local, not
systemic
 several mechanisms work together:
 fibrin absorbs remaining local thrombin
 removal of local clotting factors - washed away
 endothelial cells inhibit platelet aggregation
 Hemostasis - Coagulation (cont.)
 Fibrinolysis - dissolution of a clot,
begins within 2 days
 plasminogen trapped in clot
 many factors convert plasminogen
into plasmin (fibrinolysin)
 thrombin
 activated factor XII
 tissue plasminogen activator
(t-PA)
 Plasmin
 enzymatically digests fibrin
threads
 digests fibrinogen, prothrombin,
and several clotting factors
 Hemostasis - Coagulation (cont.)
 Thrombolytic (clot-dissolving) agents can be used
clinically
 chemical substances which activate plasminogen
 streptokinase, tissue plasminogen activator (t-PA), etc.

 Anticoagulant naturally present in blood - heparin

 produced by mast cells, basophils
 used clinically to prevent blood clotting in lab blood
samples
 inhibits thrombin and the intrinsic pathway
 Hemostasis - Coagulation (cont.)
 Other anticoagulants
 Warfarin (coumadin) - Vitamin K antagonist
 slow acting, takes days to start and stop its action
 common ingredient in many rat poisons
 Vitamin K
• produced by intestinal normal flora bacteria
• required for synthesis of factors II (prothrombin), VII, IX, X
 Aspirin & related NSAIDs
 blocks platelet aggregation
 prevents formation of thromboxane A2

 CPD (citrate phosphate dextrose)

 removes Ca2+ by chelation
 used for blood collected in blood banks for transfusion
 Hemostasis - Coagulation (cont.)
 Intravascular Clotting
 Roughened endothelium (atherosclerosis, trauma,
infection) or slow blood flow may result in
spontaneous clot (thrombus) formation, thrombosis

 Thrombus released into blood becomes

thromboembolus
 pulmonary embolus – may be immediately fatal
 other materials include air, amniotic fluid, tumor cells,
or trauma debris

 Angioplasty - may trigger thrombus formation or

fragmentation and release
 Blood Types
• RBC surface has genetically determined antigens, agglutinogens

• ABO blood typing

– 2 glycolipid
agglutinogens, A & B
– one gene from each
parent, A, B or O
– 6 combinations - AA,
AB, AO, BB, BO, OO (no
agglutinogens)
 Agglutinins
 Naturally occurring antibodies produced in response to the
agglutinogens not present in your blood
 React in antigen-antibody response to blood not of your type
 blood type AB = universal recipients
 blood type O = universal donors
Blood Types (cont.)

DONOR RECIPIENT
Blood Types (cont.)
 Rh typing – named for the Rhesus monkey Ag
 those expressing Rh antigens are Rh+
 Those without Rh agglutinogens are Rh-
 normally, blood does not contain Rh agglutinins
 immune system only makes agglutinins in
response to specific exposure to Rh antigens
 Rh sensitivity does not occur until second
transfusion
 hemolytic disease of the newborn =
erythroblastosis fetalis (many “blue babies” prior to
WWII)
 Blood Types (cont.)
 Hemolytic disease
of the newborn

Since the 1960s, it

has been possible
to prevent
hemolytic disease
of the newborn by
administering a
therapeutic
injection of Rh
antibodies into the
Rh- maternal
circulation within
72 hours after
delivery of an Rh+
infant.
End Chapter 17