THE CARDIOVASCULAR

SYSTEM:
BLOOD

Anthony Sarfo, Pharm. D., MPSGH, MPhil.

Lecturer, Pharmacology & Toxicology.
[email protected]
0506444791
 HUMAN ANATOMY & PHYSIOLOGY
OUTLINE

Semester 2
1. The Cardiovascular System: Blood, heart, blood vessels
2. The lymphatic system
3. Immune system
4. Respiratory system
5. Digestive system
6. Urinary system
7. Fluid, Electrolyte & Acid-Base Balance
8. The Reproductive System
9. Pregnancy & human development

* LABS
04:51 PM 2
 FURTHER READING

• TORTORA, G.J. AND DERRICKSON, B.H. Principles of Anatomy

and Physiology, 13th Edn. New York: Wiley, 2012.

• MARIEB, E. N. AND HOEHN, K. Human Anatomy & Physiology,

9th Edn. Pearson Benjamin Cummings, 2013.

• SALADIN, Anatomy & Physiology: The Unity Of Form And

Function

• GUYTON, A. C. AND HALL, J. E. Textbook of Medical

Physiology. 12th Edn. Philadelphia: Elsevier Science,04:51

2012.PM 3
 OBJECTIVES

• After this lecture, students should be able to;

1. Describe the components of blood
2. Understand and appreciate the functions of blood
3. Describe the processes of haematopoiesis
4. Understand the role of RBCs, WBCs and Platelets in
homeostasis
5. Understand the principles of blood typing and cross-
matching

04:51 PM 4
 OVERVIEW

• The cardiovascular system consists of three interrelated

components:
• Blood
• Heart
• Blood Vessels

• Blood
• contributes to homeostasis by transporting oxygen, carbon dioxide,
nutrients, and hormones to and from body cells.
• helps regulate body pH and temperature, and provides protection against
disease through phagocytosis and the production of antibodies.
• is one of the most useful tissues routinely examined and analysed when
trying to determine the cause of different diseases.

• The branch of science concerned with the study of blood,

04:51 PM 5
blood-forming tissues, and the disorders associated with them
 P H Y S IC AL C H ARAC T E R I S T I C S OF B LOOD

• Thicker (more viscous) than water and flows more

slower than water
• Temperature of 38 °C
• pH 7.4 (7.35-7.45)—slightly alkaline
• 8% of total body weight
• Blood volume
• Male—5 to 6 liters
• Female—4 to 5 liters
• Maintained by Several hormones (aldosterone, antidiuretic
hormone, and atrial natriuretic peptide) which regulate how much
water is excreted in the urine.

04:51 PM 6
 B loo d S am p lin g / W ith d r aw in g Te c h n iq u e s

1. Venipuncture
• Sampling from vein with hypodermic
needle & syringe
• Median cubital vein (antecubital vein)
anterior to the elbow
• Why a tourniquet and closing the
fist???
• Why not stick an artery???

2. Finger or heel stick

• Common technique for blood sugar
monitoring
• Method used for infants
04:51 PM 7
04:51 PM 8
 B L O O D C O M P O S I T I O N

1 Withdraw blood
and place in tube.

04:51 PM 9
 B L O O D C O M P O S I T I O N

1 Withdraw blood 2 Centrifuge the

and place in tube. blood sample.

04:51 PM 10
 B L O O D C O M P O S I T I O N

Formed
elements
Plasma
• 55% of whole blood
• Least dense component
Buffy coat
• Leukocytes and platelets
• <1% of whole blood
Erythrocytes
1 Withdraw blood 2 Centrifuge the • 45% of whole blood
and place in tube. blood sample. (hematocrit)
• Most dense component

04:51 PM 11
 B L O O D C O M P O S I T I O N

• 55% plasma
• 45% FE
• 99% RBCs
• < 1% WBCs and
platelets

04:51 PM 12
 BLOOD PLASMA

• Straw-colored, sticky fluid

• Over 90% water
• 7% plasma proteins
• Albumin, globulins, fibrinogen
• 2% other substances
• Electrolytes – Na+, K+, Ca2+,
Cl-, HCO3-
• Nutrients – glucose, amino
acids, vitamins, etc
• Hormones
• Gases – O2, CO2, etc
Serum
• Waste products – urea, Plasma 13
creatinine, etc
 Plasma proteins
 Most are synthesized in the liver
 Confined to bloodstream
 Albumins
 60% of plasma proteins
 Main contributor to blood osmotic pressure (the
pressure that helps keep water in the bloodstream)

Colloidal osmotic pressure/oncotic pressure
 Contributes to blood viscosity
 Shuttle (lipids, hormones, drugs, calcium & other solutes)
 Buffer.

04:51 PM
04:51 PM
 Plasma proteins - ctd
 Globulins
 ~35% of plasma proteins
 Include immunoglobulins which attack

foreign proteins and pathogens

 Include transport globulins which bind

ions, hormones and other compounds

 Divided into 3 subclasses; from

smallest to largest in molecular weight


Alpha (α), beta (β) and gamma ()
04:51 PMglobulins.
Plasma proteins - globulins
 α-globulins
 mainly transport e.g haptoglobin (Hb),
Ceruloplasmin(Cu); others (lipids, fat-soluble
vitamins, and hormones)
 Prothrombin - promotes blood clotting
 β-globulins
 transport – e.g transferrin (Fe); others(lipids)
 complement proteins - aid in destruction
of toxins and microorganisms
 -globulins

Immunoglobulins - antibodies; combat
04:51 PM
pathogens
Plasma proteins
 Fibrinogen
 Converted to fibrin during clotting
 Removal of fibrinogen leaves serum

04:51 PM
 F O R M E D E LE M E N T S

1. Red blood cells

(erythrocytes)
2. White blood cells
(leukocytes)
• Granular leukocytes
(neutrophils, eosinophils,
basophils)
• Agranular leukocytes
(monocytes, lymphocytes)
3. Platelets (thrombocytes)

04:51 PM 19
Formed Elements
 Only WBCs are complete cells
 RBCs have no nuclei or other organelles
 Platelets are cell fragments
 Most formed elements survive in
bloodstream only few days
 Most blood cells originate in bone
marrow and do not divide

04:51 PM 20
Formed Elements of
Blood

04:51 PM 21
 F O R M AT I O N O F B LO O D C E LLS

• Most formed elements/blood cells last only hours, days,

or weeks
• some lymphocytes—lifetime in years
• Must be replaced continually
• Process of blood cells formation is haematopoiesis or haemopoiesis
• In the embryo
• occurs in the yolk sac, liver, spleen, thymus, and lymph nodes, and
red bone marrow
• In adult
• Occurs only in bone marrow
• Decreases with age—red marrow changes to yellow marrow
• so that haemopoiesis in the adult(by age 20) becomes confined to the central
skeleton(axial skeleton and girdles) and the proximal ends (trabecular
area) of the long bones.
04:51 PM 22
• If the demand for blood cells increases and persists, the areas of red marrow can
 F O R M AT I O N O F B LO O D C E LLS

 In normal marrow:
 75% :WBC & 25% : RBC but more RBCs in circulation??? Lifespan???
04:51 PM 23
 S TA G E S O F B L O O D C E L L F O R M AT I O N

• Pluripotent stem cells (a.k.a. haemocytoblasts)

• 0.05-0.1% of red marrow cells
• replenish themselves as they differentiate into either myeloid
or lymphoid stem cells
• Myeloid stem cell line of development
• progenitor cells (colony-forming units) are specialized to form
specific cell types
• example: CFU-E develops eventually into only red blood cells
• next generation is blast cells
• have recognizable histological characteristics
• develop within several divisions into mature cell types
• Lymphoid stem cell line of development
• pre-B cells & prothymocytes finish their development into B & T
04:51 PM 24
lymphocytes in the lymphatic tissue after leaving the red
H A E M AT OP OI E S I S

CFU—progenitor
cells specialised to
form specific cell
types

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 H AE M OP OIE T IC GR OW T H FAC T OR S

• Regulate differentiation & proliferation of blood cells

1. Erythropoietin (EPO)
• Produced by the kidneys, increase RBC precursors
2. Thrombopoietin (TPO)
• Hormone from the liver, stimulates platelet formation
3. Cytokines
• small glycoproteins produced by red bone marrow cells,
leukocytes, macrophages, fibroblasts, and endothelial cells.
• colony-stimulating factors (CSFs) and interleukins
stimulate white blood cell formation

04:51 PM 26
 Medical Uses of Growth
Factors
 Available through recombinant DNA
technology
 Recombinant erythropoietin (EPO) very
effective in treating decreased RBC
production of end-stage kidney disease
 Other products given to stimulate WBC
formation in cancer patients receiving
chemotherapy which kills bone marrow

granulocyte-macrophage colony-stimulating
factor

granulocyte colony stimulating factor
 Thrombopoietin helps prevent platelet
depletion during chemotherapy
04:51 PM
 B loo d D o p in g

• Boosting the number of RBCs to enhance athletic

performance
• More cells available to deliver O2 to tissues
• Injecting previously stored RBCs before an athletic
events
• Use of EPO
• Dangerous???
• Banned by Olympic committee

04:51 PM 28
RED BLOOD CELLS (RBCs)
Erythrocytes

04:51 PM 29
 H A E M AT OC R IT

• The percentage of total blood volume occupied by RBCs

• Female normal range
• 38–46% (average = 42)
• excessive loss of blood during menstruation
• Male normal range
• 40–54% (average = 47).
• testosterone, stimulates synthesis of erythropoietin (EPO), the hormone
that in turn stimulates production of RBCs.
• Anaemia
• Not enough RBCs or haemoglobin
• Polycythaemia
• Too many RBCs (over 65%)
• This raises the viscosity of blood  high blood pressure and increased risk
of stroke.
04:51 PM 30
• Causes include abnormal increases in RBC production, tissue hypoxia,
Red Blood Cells
(Erythrocytes)
 Contain oxygen-carrying protein
haemoglobin that gives blood its red
color
 1/3 of cell’s weight is haemoglobin
 Males - 13–18g/100ml; Females - 12–16
g/100ml
 Biconcave disk 7-8 microns in diameter
 increased surface area/volume ratio
 shape allows RBCs to stack, bend and flex
for narrow passages (structural protein –
spectrin)
 no nucleus or other organelles
04:51 PM 
no cell division or mitochondrial ATP formation
04:51 PM
Erythrocytes (RBCs)
 Contain the plasma membrane protein
spectrin
 Gives erythrocytes their flexibility
 Allows them to change shape as necessary

 Normal RBC count

 male 4.7-6.1 million/µL; female 4.2-5.4
million/µL
 new RBCs enter circulation at > 2
million/second

04:51 PM
Erythrocyte function
 Erythrocytes are dedicated to
respiratory gas transport
 Haemoglobin reversibly binds with oxygen
and most oxygen in the blood is bound to
haemoglobin
 Major factor contributing to blood
viscosity
 As no. of RBCs ↑ses beyond normal , blood
viscosity rises and blood flows more slowly.
 When no. of RBCs drops below normal, the
blood thins and flows more rapidly.
04:51 PM
Haemoglobin
 Globin chains

Heme
group

 Globin chains
Hemoglobin consists of globin (two alpha and two beta Iron-containing heme pigment.
polypeptide chains) and four heme groups.
 Haemoglobin
 Globin protein consisting of 4 polypeptide chains
 One haeme pigment attached to each polypeptide
chain
 each haeme contains an iron ion (Fe+2) that can combine
reversibly with one oxygen molecule
 Each haemoglobin molecule can carry 4 oxygen
molecules from lungs to tissue cells
 If 1 RBC  250 million haemoglobin molecules,
then each RBC can scoop up about 1 billion
molecules of oxygen!
 Haemoglobin transports 23% of total CO2 waste
from tissue cells to lungs for release (CO2 binds to
04:51 PM
globin’s amino acids rather than the haeme
 Haemoglobin
 Oxyhaemoglobin – haemoglobin bound to
oxygen
 Oxygen loading takes place in the lungs
 Deoxyhaemoglobin – haemoglobin after
oxygen diffuses into tissues (reduced Hb)
 Carbaminohaemoglobin – haemoglobin
bound to carbon dioxide
 Carbon dioxide loading takes place in the tissues
 Methaemoglobin – haemoglobin with Ferrous
ion (Fe2+) converted to ferric iron (Fe3+)
 Carboxyhaemoglobin – haemoglobin bound
to CO
04:51 PM
 Haemoglobin
 Four types of haemoglobin molecules
can be found in human erythrocytes:
 embryonic(Portland, Grower I, Grower 2),
fetal(HbF), and two different types found in
adults (HbA, HbA2 ).
 Each haemoglobin molecule is
designated by its polypeptide
composition.
 HbA(α2β2), HbA 2 (α2δ2), HbF(α22), Grower
1(22), Grower 2(α22)
Normal adult(%): HbA(96-98), HbA2(1.5-
 04:51 PM
 Abnormalities of
Haemoglobin Prd.
 Amino acid sequences in the polypeptide
chains of haemoglobin are determined by
globin genes.
 Two major types of inherited disorders of
haemoglobin in humans:
 Haemoglobinopathies: abnormal
polypeptide chains are produced; mutant
genes
 Thalassaemias and related disorders: chains

are normal in structure but produced in

decreased amounts or absent; defects in the
04:51 PM
regulatory portion of the globin genes
 Abnormalities of
Haemoglobin Prd.
 Widespread mutant genes that cause
the production of abnormal
haemoglobins
 >1000 abnormal Hbs have been
described in humans. They are usually
identified by letter—haemoglobin C, E, I,
J, S, etc.
 E.g Hb S, the α chains are normal but the β
chains are abnormal, because among the
146 amino acid residues in each β
polypeptide chain, one glutamic acid
04:51 PM
residue has been replaced by a valine
“Sickli
ng” in
Red
Blood
Cells Val His Leu Thr Pro Glu Glu …
1 2 3 4 5 6 7 146
Normal erythrocyte has normal
hemoglobin amino acid sequence
in the beta chain.

Val His Leu Thr Pro Val Glu …

1 2 3 4 5 6 7 146
Sickled erythrocyte results from a
single amino acid change in the
beta chain of hemoglobin.
 Erythropoiesis: Red Blood Cell
Production

 Stages
 Myeloid stem cell transformed into
proerythroblast
 In 15 days proerythroblasts develop
into basophilic, then polychromatic,
then orthochromatic erythroblasts,
and then into reticulocytes
 Reticulocytes enter bloodstream; in 2
days mature RBC
04:51 PM
 Erythropoiesis: formation of red
blood cells

Stem cell Committed cell Developmental pathway

Phase 1 Phase 2 Phase 3

Ribosome synthesis Hemoglobin accumulation Ejection of nucleus

Hematopoietic stem Basophilic Polychromatic Orthochromatic

cell (hemocytoblast) Proerythroblast erythroblast erythroblast erythroblast Reticulocyte Erythrocyte

04:51 PM
Erythropoiesis: Production of
RBCs
 Reticulocyte
 orange in colour
 contains a scant reticulum (network)
of clumped ribosomal RNA
 escape from bone marrow into the
blood
 In 1-2 days, they eject the
remaining organelles to become
a mature RBC
04:51 PM
 Normal Reticulocyte Count
 Should be 0.5 to 1.5% of the circulating
RBC’s
 Low count in an anaemic person might
indicate bone marrow problem
 leukaemia, nutritional deficiency or failure of
red bone marrow to respond to erythropoietin
stimulation
 High count might indicate recent blood
loss or successful iron therapy

04:51 PM
 Erythropoiesis
 Circulating erythrocytes – the number
remains constant and reflects a balance
between RBC production and destruction
 Too few red blood cells leads to tissue hypoxia
 Too many red blood cells causes undesirable
blood viscosity
 Erythropoiesis is hormonally controlled
and depends on adequate supplies of
iron, amino acids, and B vitamins

04:51 PM
 Dietary Requirements for
Erythropoiesis
 Nutrients—amino acids, lipids, and
carbohydrates
 Iron
 Available from diet
 65% in Hb; rest in liver, spleen, and bone
marrow
 Free iron ions toxic

Stored in cells as ferritin and hemosiderin

Transported in blood bound to protein transferrin
 Vitamin B12 and folic acid necessary for
DNA
04:51 PM synthesis for rapidly dividing cells
Feedback Control
of RBC Production
 Tissue hypoxia (cells not
getting enough O2)
 high altitude since air has
less O2
 anaemia

RBC production falls below
RBC destruction
 circulatory problems
 Kidney response to
hypoxia
 release erythropoietin
 speeds up development of
04:51 PM
Fate and Destruction of
Erythrocytes
 Life span: 100–120 days
 No protein synthesis, growth, division
 Old RBCs become fragile; Hb
begins to degenerate
 Get trapped in smaller circulatory
channels especially in spleen
 Macrophages engulf dying RBCs in
spleen
04:51 PM
Fate and Destruction of
Erythrocytes
 Haeme and globin are separated
 Iron salvaged for reuse
 Haeme degraded to yellow pigment
bilirubin
 Liver secretes bilirubin (in bile) into
intestines

Degraded to pigment urobilinogen

Pigment leaves body in feces as
stercobilin

04:51 PMGlobin metabolized into amino acids
 Recycling of Haemoglobin
Components

 In macrophages of liver or spleen

 globin portion broken down into amino acids & recycled
 haeme portion split into iron (Fe+3) and biliverdin (green
 Fate of Components of
Haeme
 Iron(Fe+3)
 transported in blood attached to transferrin
protein
 stored in liver, muscle or spleen

attached to ferritin or haemosiderin protein
 in bone marrow being used for haemoglobin
synthesis
 Biliverdin (green) converted to bilirubin
(yellow)
 bilirubin secreted by liver into bile

converted to urobilinogen then stercobilin (brown
pigment in feces) by bacteria of large intestine

04:51 PM
if reabsorbed from intestines into blood is converted
to a yellow pigment, urobilin and excreted in urine
Pathological changes in erythrocyte
morphology

04:51 PM
04:51 PM
 ERYTHROCYTE SEDIMENTATION
RATE (ESR)
 Erythrocytes are only slightly denser than the
suspending plasma hence settle out of whole
blood very slowly.
 Anticoagulated blood is placed in a long, thin,
graduated cylinder(westergren tube) left to
settle. Rate of fall measured.
 Normal ranges(varies with age)
 male: 1 - 13 mm/hr
 female: 1 - 20 mm/hr.
 ESR can be an important diagnostic index
 significantly elevated

infection, cancers, inflammatory diseases, pregnancy,
04:51 PM
etc.

 ESR - ctd
 Cells tend to
sediment faster
when the
concentration of
plasma proteins
increases
(promotes
rouleaux
formation).
04:51 PM
 ERYTHROCYTE
DISORDERS

 Anaemia – blood has abnormally

low oxygen-carrying capacity
 Sign rather than a disease itself
 Blood O2 levels cannot support normal
metabolism
 Accompanied by fatigue, pallor,
shortness of breath, and chills
 lack of O2 for ATP & heat production

04:51 PM
Causes of Anaemia
 Three groups
 Blood loss
 Low RBC production
 High RBC destruction

04:51 PM
Causes of Anaemia: Blood
Loss
 Haemorrhagic anaemia
 Blood loss rapid (e.g., stab wound)
 Treated by blood replacement
 Chronic haemorrhagic anaemia
 Slight but persistent blood loss

Haemorrhoids, bleeding ulcer
 Primary problem treated

04:51 PM
Causes of Anaemia: Low RBC
Production
 Iron-deficiency anaemia
 Caused by haemorrhagic anaemia,
low iron intake, or impaired
absorption
 Microcytic, hypochromic RBCs
 Iron supplements to treat

04:51 PM
Causes of Anaemia: Low RBC
Production
 Pernicious anaemia
 Autoimmune disease - destroys
stomach mucosa
 Lack of intrinsic factor needed to
absorb Vit.B12
 Deficiency of vitamin B12
 RBCs cannot divide  macrocytes
 Treated with B12 injections
 Also caused by low dietary B12
04:51 PM
Causes of Anaemia: Low RBC
Production
 Anaemia due to chronic renal
failure
 Lack of EPO
 Often accompanies renal disease
 Treated with synthetic EPO

04:51 PM
Causes of Anaemia: Low RBC
Production
 Aplastic anemia
 Destruction or inhibition of red
marrow by drugs, chemicals,
radiation, viruses
 Usually cause unknown
 All cell lines affected

Anaemia; clotting and immunity defects
 Treated short-term with transfusions;
long-term with transplanted stem
04:51 PMcells
Causes of Anaemia: High
RBC Destruction
 Haemolytic anaemias
 Premature RBC lysis
 Caused by

Hb abnormalities

Incompatible transfusions

Infections

04:51 PM
 Haemoglobin Abnormalities
 Sickle-cell Anaemia (SCA) – results
from a defective gene coding for an
abnormal haemoglobin: haemoglobin S
(HbS)
 HbS has a single amino acid substitution in
the beta chain

at very low O2 levels, RBC is deformed by
changes in haemoglobin molecule within
the RBC

sickle-shaped cells rupture easily = causing
anaemia & clots

04:51 PM
 Sickle-cell Anaemia (SCA)
 Found among populations in malaria
belt
 Mediterranean Europe, sub-Saharan
Africa & Asia
 Person with only one sickle cell gene
(HbS carrier)
 increased resistance to malaria because

RBC membranes leak K+ & lowered levels
of K+ kill the parasite infecting the red
blood cells

Incomplete plasmodium cycle—infected
RBCs sickle more easily
04:51 PM

Increased ROS (O2-, H2O2) in sickle trait
Sickle-cell Anemia:
Treatments
 Acute crisis treated with transfusions;
inhaled nitric oxide
 Preventing sickling
 Hydroxyurea induces fetal hemoglobin
(which does not sickle) formation
 Blocking RBC ion channels
 Stem cell transplants
 Gene therapy

04:51 PM
Polycythaemia
 Polycythaemia – excess RBCs that
increase blood viscosity
 Main polycythaemias
 Polycythaemia vera

Bone marrow cancer  excess RBCs

Severely increased blood viscosity
 Secondary polycythaemia
 Less O2 available (high altitude) or EPO production
increases  higher RBC count

Blood doping

04:51 PM
WHITE BLOOD CELLS (WBCs)
Leukocytes

04:51 PM 69
WBC Anatomy and Types
 All WBCs (leukocytes) have a nucleus
and no haemoglobin – are the only
complete cells
 Granular or Agranular classification
based on presence of cytoplasmic
granules made visible by staining
 granulocytes

obvious membrane-bound cytoplasmic granules

neutrophils, eosinophils or basophils
 agranulocytes

lack obvious granules
04:51 PM
monoctyes or lymphocytes
Types and relative percentages of leukocytes in
normal blood.
Differential
WBC count
(All total 4800–
Formed 10,800/ µl)
elements
(not drawn
to scale)

Platelets
Granulocytes
Neutrophils (50–70%)
Leukocytes
Eosinophils (2–4%)

Basophils (0.5–1%)
Erythrocytes

Agranulocytes
Lymphocytes (25–45%)
Monocytes (3–8%)
Granulocytes
 Granulocytes
 Larger and shorter-lived than RBCs
 Lobed nuclei
 Cytoplasmic granules stain
specifically with Wright's stain???
 All phagocytic to some degree

04:51 PM
 Neutrophils (Granulocyte)
 Polymorphonuclear Leukocytes (PMNs or
polys)
 Nuclei = 2 to 5 lobes connected by thin
strands
 older cells have more lobes
 young cells called band cells because of
horseshoe shaped nucleus (band)
 Fine, pale lilac practically invisible
granules
 Diameter is 10-12 microns
73
 Neutrophil Function
 Fastest response of all WBC to
bacteria
 Direct actions against bacteria
 release lysozymes which destroy/digest
bacteria
 release defensin proteins that act like
antibiotics & poke holes in bacterial cell
walls destroying them
 release strong oxidants (bleach-like,
strong chemicals) that destroy bacteria 74
Eosinophils
(Granulocyte)
 Nucleus with 2 or 3 lobes
connected by a thin strand
 Large, uniform-sized granules stain
orange-red with acidic dyes
 do not obscure the nucleus
 Diameter is 10 to 12 microns

75
Eosinophil Function
 Leave capillaries to enter tissue
fluid
 Release histaminase
 slows down inflammation caused by
basophils
 Attack parasitic worms
 Phagocytize antibody-antigen
complexes
 Role in allergies and asthma
 76
 Basophils (Granulocyte)
 Large, dark purple, variable-sized
granules stain with basic dyes
 obscure the nucleus
 Irregular, s-shaped, bilobed nuclei
 Diameter is 8 to 10 microns
 Less than 1% of circulating WBCs

77
 Basophil Function
 Involved in inflammatory and
allergy reactions
 Leave capillaries & enter
connective tissue
 Release heparin, histamine &
serotonin
 heighten the inflammatory response
and account for hypersensitivity
(allergic) reaction
 Are functionally similar to mast 78
 Lymphocyte
(Agranulocyte)
 Second most numerous WBC
 Large, dark-purple, circular nuclei with thin rim
of blue cytoplasm
 Small cells 6-9 microns in diameter
 Large cells 10-14 microns in diameter
 increase in number during viral infections
 Mostly in lymphoid tissue (e.g., lymph nodes,
spleen); few circulate in blood
 Crucial to immunity
 T, B, NK

79
 Lymphocyte Functions
 B cells
 destroy bacteria and their toxins
 turn into plasma cells that produces
antibodies
 T cells
 attack viruses, fungi, transplanted organs,
cancer cells & some bacteria
 Natural killer cells
 attack many different microbes & some
tumour cells
 destroy
04:51 PM foreign invaders by direct attack
 Monocyte (Agranulocyte)
 Largest leukocytes, abundant pale-blue
cytoplasm
 Dark purple-staining, U- or kidney-shaped
nuclei
 Leave circulation, enter tissues, and
differentiate into macrophages
 fixed group found in specific tissues

alveolar macrophages in lungs

kupffer cells in liver
 Actively phagocytic cells; crucial against viruses,
intracellular bacterial parasites, and chronic
infections
 wandering group gathers at sites of infection 81
 Monocyte Function
 Take longer to get to site of
infection, but arrive in larger
numbers
 Become wandering macrophages,
once they leave the capillaries
 Destroy microbes and clean up
dead tissue following an infection

82
Emigration & Phagocytosis
in WBCs

 WBCs roll along

endothelium, stick to it &
squeeze between cells.
 adhesion molecules
(selectins) help WBCs stick
to endothelium

displayed near site of injury
 molecules (integrins) found
on neutrophils assist in
movement through wall
 Neutrophils &
macrophages phagocytize
bacteria & debris
 WBC Physiology
 Less numerous than RBCs
 5000 to 10,000 cells/µl of blood
 1 WBC for every 700 RBC
 Leukocytosis is a high white blood cell
count
 infection, strenuous exercise, anesthesia or
surgery
 Leukopenia is low white blood cell count
 radiation, shock, glucocorticoids, anticancer
drugs
 Only 2% of total WBC population is in
04:51 PM
 Differential WBC Count
 Detection of changes in numbers of
circulating WBCs (percentages of each
type)
 indicates infection, poisoning, leukemia,
chemotherapy, parasites or allergy reaction
 Normal WBC counts
 neutrophils 50-70% (up if bacterial infection)
 lymphocyte 25-45% (up if viral infection)

 monocytes 3 -- 8 % (up if fungal/viral

infection)
 eosinophil 2 -- 4 % (up if parasite or allergy
04:51 PM
reaction)
 Production of Leukocytes
 Leukopoiesis is hormonally stimulated by
two families of cytokines (haematopoetic
factors) – interleukins and colony-
stimulating factors (CSFs)
 Interleukins are numbered (e.g., IL-1, IL-2),
whereas CSFs are named for the WBCs they
stimulate (e.g., granulocyte-CSF stimulates
granulocytes)
 Macrophages and T cells are very
important sources of cytokines
 Many haematopoietic hormones are used
04:51 PM
Leukopoi
esis

04:51 PM
 Leukocyte disorders
 Leukopenia
 Leukemias – all fatal if untreated
 Cancer  overproduction of abnormal WBCs
 Named according to abnormal WBC clone
involved

Myeloid leukemia involves myeloblast descendants

Lymphocytic leukemia involves lymphocytes
 Acute leukemia derives from stem cells;
primarily affects children
 Chronic leukemia more prevalent in older

people
04:51 PM
Leukemia
 Cancerous leukocytes fill red bone
marrow
 Other lines crowded out  anaemia;
bleeding
 Immature nonfunctional WBCs in
bloodstream
 Death from internal hemorrhage;

overwhelming infections
 Treatments
04:51 PM
 Bone Marrow Transplant
 Intravenous transfer of healthy bone
marrow
 Treatment for leukaemia, sickle-cell,
breast, ovarian or testicular cancer,
lymphoma or aplastic anaemia

 Procedure
 destroy sick bone marrow with radiation &
chemotherapy
 donor matches surface antigens on WBC

 put sample of donor marrow into patient's vein

04:51 PM
for reseeding of bone marrow
 PLATELETS
(Thrombocytes)

04:51 PM 91
Platelets (Thrombocyte)
Anatomy
 Cytoplasmic fragments of
megakaryocytes
 Blue-staining outer region; purple
granules
 Granules contain serotonin, Ca2+,
enzymes, ADP, and platelet-
derived growth factor (PDGF)
 Act in clotting process
 Normal = 150,000 – 400,000
04:51 PM
 Platelets
 Form temporary platelet plug that helps
seal breaks in blood vessels
 Circulating platelets kept inactive and
mobile by nitric oxide (NO) and
prostacyclin from endothelial cells lining
blood vessels
 Age quickly; degenerate in about 10 days
 Formation regulated by thrombopoietin
 Derive from megakaryoblast
 Mitosis but no cytokinesis  megakaryocyte -
large cell with multilobed nucleus
04:51 PM
Figure 17.12 Formation of platelets.

Stem cell Developmental pathway

Hematopoietic stem Megakaryoblast Megakaryocyte Megakaryocyte Platelets

cell (hemocytoblast) (stage I megakaryocyte) (stage II/III) (stage IV)
Table 17.2 Summary of Formed Elements of the Blood (1 of 2)
Table 17.2 Summary of Formed Elements of the Blood (2 of 2)
COMPLETE BLOOD COUNT
 Screens for anaemia and infection
 Total RBC, WBC & platelet counts;
differential WBC; haematocrit, red
cell indices and haemoglobin
measurements
 Normal haemoglobin range
 infants have 14 to 20 g/100mL of
blood
 adult females have 12 to 16 g/100mL

of blood
04:51 PM
HAEMOSTASIS
 A series of reactions designed for
stoppage of bleeding when blood
vessel is damaged
 During haemostasis, three phases
occur in rapid sequence
 Vascular spasms – immediate
vasoconstriction in response to injury
 Platelet plug formation
 Coagulation (blood clotting)
04:51 PM
 Vascular Spasm (vascular
phase)
 Damage to blood vessel stimulates
pain receptors
 Reflex contraction of smooth muscle of
small blood vessels
 Can reduce blood loss for several
minutes until other mechanisms can
take over
 Only for small blood vessel or arteriole
Platelet Plug Formation
(Platelet phase)
 Platelets store a lot of chemicals in
granules needed for platelet plug
formation
 Clotting factors, Platelet-derived growth
factor (cause proliferation of vascular endothelial
cells, smooth muscle & fibroblasts to repair damaged
vessels), ADP, ATP, Ca2+, serotonin, fibrin-
stabilizing factor, & enzymes that
produce thromboxane A2
 Steps in the process
 (1) platelet adhesion
04:51(2)
PM platelet release reaction

Platelet Adhesion
 Platelets stick to exposed collagen
underlying damaged endothelial cells in
vessel wall
 Platelet Release Reaction
 Release thromboxane A2 & ADP activating
other platelets
 Serotonin & thromboxane A2 are
vasoconstrictors decreasing blood flow through
the injured vessel

102
Platelet Aggregation
 Activated platelets stick together and
activate new platelets to form a mass
called a platelet plug
 Plug reinforced by fibrin threads formed
during clotting process
Blood Clotting
(coagulation phase)
 Blood is transformed from a liquid to a gel
 Clotting is a cascade of reactions in which
each clotting factor activates the next in a
fixed sequence resulting in the formation
of fibrin threads
 Prothrombin activator & Ca2+ convert
prothrombin into thrombin
 thrombin converts fibrinogen into fibrin threads
 Substances required for clotting are Ca+2,
enzymes synthesized by liver cells and
substances released by platelets or
damaged tissues
Clotting factors
Coagulation: Overview

• Three phases of coagulation

– Prothrombin activator formed in both
intrinsic and extrinsic pathways
– Prothrombin converted to enzyme thrombin
– Thrombin catalyzes fibrinogen  fibrin
Coagulation Phase 1: Two Pathways to
Prothrombin Activator
• Initiated by either intrinsic or extrinsic
pathway (usually both)
– Triggered by tissue-damaging events
– Involves a series of procoagulants
– Each pathway cascades toward factor X
• Factor X complexes with Ca2+, PF3, and
factor V to form prothrombin activator
Coagulation Phase 1: Two Pathways to
Prothrombin Activator
• Intrinsic pathway
– Triggered by negatively charged surfaces
(activated platelets, collagen, glass)
– Uses factors present within blood (intrinsic)
• Extrinsic pathway
– Triggered by exposure to tissue factor (TF) or
factor III (an extrinsic factor)
– Bypasses several steps of intrinsic pathway,
so faster
Coagulation Phase 2: Pathway to Thrombin

• Prothrombin activator catalyzes

transformation of prothrombin to active
enzyme thrombin
• Once prothrombin activator formed, clot
forms in 10–15 seconds
Coagulation Phase 3: Common Pathway to
the Fibrin Mesh
• Thrombin converts soluble fibrinogen to
fibrin
• Fibrin strands form structural basis of clot
• Fibrin causes plasma to become a gel-like
trap for formed elements
• Thrombin (with Ca2+) activates factor XIII
which:
– Cross-links fibrin
– Strengthens and stabilizes clot
The intrinsic and extrinsic pathways of blood clotting (coagulation). (1 of 2)

Phase 1
Intrinsic pathway Extrinsic pathway
Vessel endothelium Tissue cell trauma
ruptures, exposing exposes blood to
underlying tissues
(e.g., collagen)

Platelets cling and their

surfaces provide sites for Tissue factor (TF)
mobilization of factors

XII
Ca2+
XIIa
XI VII
XIa
VIIa
IX Ca 2+

IXa
PF3
released by
aggregated VIII
platelets
VIIIa

IXa/VIIIa complex TF/VIIa complex

X
Xa
Ca2+
PF3
Va V
Prothrombin
activator
The intrinsic and extrinsic pathways of blood clotting (coagulation). (2 of 2)

Phase 2
Prothrombin (II)
Thrombin (IIa)

Phase 3
Fibrinogen (I)
(soluble)
Fibrin Ca2+
(insoluble
polymer) XIII

XIIIa

Cross-linked
fibrin mesh
04:51 PM
 Clot Retraction & Blood
Vessel Repair
 Clot plugs ruptured area of blood vessel
 Clot retraction – stabilization of the clot by
squeezing serum from the fibrin strands
 Platelets pull on fibrin threads causing clot
retraction
 trapped platelets release factor XIII stabilizing the
fibrin threads in the presence of calcium ions
 Edges of damaged vessel are pulled together
 Platelet-derived growth factor (PDGF)
stimulates rebuilding of blood vessel wall
 Fibroblasts form a connective tissue patch
 Endothelial cells multiply and restore the
114
 Role of Vitamin K in Clotting
 Normal clotting requires adequate
vitamin K
 fat soluble vitamin absorbed if lipids
are present
 absorption slowed if bile release is
insufficient
 Produced by bacteria in large
intestine
 Required for synthesis of 4 clotting

factors by hepatocytes
04:51 PM
 Haemostatic Control
Mechanisms
 Fibrinolytic system dissolves small,
inappropriate clots & clots at a site of a
completed repair
 fibrinolysis is dissolution of a clot
 Inactive plasminogen is incorporated into the
clot
 activation occurs because of factor XII and thrombin
 plasminogen becomes plasmin (fibrinolysin) which
digests fibrin threads
 Clot formation remains localized
 fibrin absorbs thrombin
 Thrombin not absorbed to fibrin is inactivated by

antithrombin III
 blood
04:51 PM disperses clotting factors
Intravascular Clotting
 Thrombosis
 clot (thrombus) forming in an unbroken blood
vessel

forms on rough inner lining of blood vessel

if blood flows too slowly (stasis) allowing clotting
factors to build up locally & cause coagulation
 may dissolve spontaneously or dislodge &
travel
 Embolus
 clot, air bubble or fat from broken bone in the
blood

pulmonary embolus is found in lungs
 Low dose aspirin blocks synthesis of
04:51 PM
Anticoagulants and
Thrombolytic Agents
 Anticoagulants suppress or prevent
blood clotting
 heparin

administered during haemodialysis and surgery
 warfarin (Coumadin)

antagonist to vitamin K so blocks synthesis of
clotting factors

slower than heparin
 stored blood in blood banks treated with
citrate phosphate dextrose (CPD) that
removes Ca2+
 Thrombolytic agents are injected to
dissolve
04:51 PM clots
Haemostasis Disorders: Bleeding
Disorders
 Inability to synthesize procoagulants by
the liver results in severe bleeding
disorders
 Causes can range from vitamin K

deficiency to hepatitis and cirrhosis

 Inability to absorb fat can lead to

vitamin K deficiencies as it is a fat-

soluble substance and is absorbed along
with fat
 Liver disease can also prevent the liver

from producing bile, which is required

04:51 PM
 Haemophilia
 Inherited deficiency of clotting factors
 bleeding spontaneously or after minor trauma
 subcutaneous & intramuscular hemorrhaging
 nosebleeds, blood in urine, articular bleeding & pain
 Haemophilia A lacks factor VIII(largely males; rare
in females)
 most common
 Haemophilia B lacks factor IX (largely males; rare
in females)
 Haemophilia C (males & females) factor XI
 less severe because alternate clotting activator exists
 Treatment is transfusions of fresh plasma or
concentrates of the missing clotting factor
04:51 PM
 Disseminated Intravascular
Clotting
 Life threatening paradoxical presence of
blood clotting and bleeding at the same
time throughout the whole body
 so many clotting factors are removed by
widespread clotting that too few remain to
permit normal clotting
 Associated with infections, hypoxia, low
blood flow rates, trauma, hypotension &
haemolysis
 Clots cause ischaemia and necrosis leading
to multisystem
04:51 PM organ failure
 Blood Transfusions
 Transfusions are necessary:
 When substantial blood loss occurs
 In certain haemostatic disorders
 Whole blood transfusions are used:
 When blood loss is substantial
 In treating thrombocytopaenia
 Packed red cells (cells with plasma
removed) are used to treat anaemia
 Shelf life of collected blood at 4°C is 35
days
04:51 PM
Human Blood Groups
 RBC membranes have proteins,
glycoprotein & glycolipid antigens on
their external surfaces
 These antigens are:
 Unique to the individual
 Recognized as foreign if transfused into
another individual
 Promoters of agglutination and are referred
to as agglutinogens
 Presence/absence of these antigens are
used to classify blood groups
04:51 PM
 Blood Groups
 Humans have at least 30 blood
groups & over 600 different blood
group antigens occurring on RBCs
 The antigens of the ABO and Rh
blood groups cause vigorous
transfusion reactions when they
are improperly transfused
 Other blood groups (MNS, Duffy,
Lutheran, Kell, Kidd and Lewis) are
mainly used for legalities
04:51 PM
ABO Blood Groups
 The ABO blood groups consists of:
 Two antigens (A and B) on the surface of the
RBCs
 Two antibodies in the plasma (anti-A and
anti-B)
 An individual with ABO blood may have
various types of antigens and
spontaneously preformed antibodies
 Agglutinogens and their corresponding
antibodies (agglutinins) cannot be
mixed without serious haemolytic
04:51 PM
Blood Groups and Blood
Types

04:51 PM
Universal Donors and
Recipients
 People with type AB blood called
“universal recipients” since
have no antibodies in plasma
 only true if cross match the blood
for other antigens
 People with type O blood cell
called “universal donors” since
have no antigens on their cells
 theoretically can be given to
anyone
04:51 PM
 RH blood groups
 Antigen was discovered in blood of Rhesus
monkey
 There are >45(curr. 52) different Rh
agglutinogens, three of which (C, D, and E) are
common
 People with Rh agglutinogens on RBC surface are
Rh+. Normal plasma contains no anti-Rh
antibodies
 Antibodies develop only in Rh- blood type & only
with exposure to the antigen
 transfusion of positive blood
 during a pregnancy with a positive blood type fetus
04:51 PM

 Typing and Cross-
Matching Blood
 Mixing of incompatible blood causes
agglutination (visible clumping)
 formation of antigen-antibody complex that
sticks cells together
 not the same as blood clotting
 Typing involves testing blood with known
antisera that contain antibodies A, B or
Rh+
 Cross-matching is to test by mixing donor
cells with recipient’s serum
 Screening
04:51 PM is to test recipient’s serum
 Transfusion and Transfusion
Reactions
 Transfer of whole blood, cells or plasma
into the bloodstream of recipient
 used to treat anaemia or severe blood loss
 Incompatible blood transfusions
 antigen-antibody complexes form between plasma
antibodies & “foreign proteins” on donated RBC's
(agglutination)
 donated RBCs become leaky (complement proteins) &
burst
 loose haemoglobin causes kidney damage
 Problems caused by incompatibility between
donor’s cells and recipient’s plasma
04:51 PM
 Donor plasma is too diluted to cause problems
Blood Type Testing

?
04:51 PM
 Haemolytic Disease of the
Newborn
 Haemolytic disease of the newborn – Rh+
antibodies of a sensitized Rh– mother cross the
placenta and attack and destroy the RBCs of an
Rh+ baby
 Rh– mother become sensitized when Rh+ blood
(from a previous pregnancy of an Rh+ baby or a
Rh+ transfusion) causes her body to synthesis Rh+
antibodies
 Anti-D (Rh0) immunoglobulin (RhoGAM) can
prevent the Rh– mother from becoming sensitized
 Treatment of haemolytic disease of the newborn
involves
04:51 PM pre-birth transfusions and exchange 132
 R H I N C O M PAT I B I L I T I E S — H a e m o l y t i c D i s e a s e o f t h e N e w
Born

• Rh antibodies are IgG

• Rh− women should receive anti-Rh gamma globulin
(RhoGAM®) before delivery, and soon after every 04:51
delivery,
PM 13
3
miscarriage, or abortion to prevent HDN.
Blood groups & Paternity
Assignment

a. How useful is the ABO/Rh system

in paternity determinations? What
are its limitations?
b. Two men, Agyekum and Attia,
belonging to blood groups A+ and
O+ respectively, claim ownership
to a child with blood type AB- .The
mother is B-. Which of the two
men is the real father of the child?
04:51 PM