Unit 3:
Hematology: Blood
Dr. Moattar Raza Rizvi
Physiology
Basic functions of Blood
Trasports
• Oxygen and nutrients (removes waste products)
• Hormones delivered to target organs
Regulates
• Body temperature, pH
Protects
• Against blood/fluid loss via hemostasis
(coagulation)
• Against infection via contribution to inflammatory
and immune responses.
Blood: Properties
•
•
•
•
•
•
•
•
Sticky
Opaque
Salty-metallic taste
Color varies according to oxygen content
More dense than water and 5x more viscous
pH: 7.35-7.45 (reservoir for bicarbonate ions)
Temperature: 38°C
Volume (4-6 litres; adult).
The Composition of Whole Blood
• Blood is the body’s only fluid tissue (a
connective tissue)
• 2 major components
– Liquid = plasma (55%)
– Formed elements (45%)
• Erythrocytes, or red blood cells (RBCs)
• Leukocytes, or white blood cells (WBCs)
• Platelets or Thrombocytes
The Composition of Whole Blood: Plasma
Plasma
(55% of whole blood)
Buffy coat:
leukocyctes and
platelets
(<1% of whole blood)
1 Withdraw blood
and place in tube
2 Centrifuge
Formed
elements
Erythrocytes
(45% of whole blood)
• Hematocrit
• Males: 47% ± 5%
• Females: 42% ± 5%
The Composition of Whole Blood: Plasma
• Hematocrit
• Males: 47% ± 5%
• Females: 42% ± 5%
The Composition of Whole Blood: Plasma
• Blood plasma components:
– Water = 90-92%
– Proteins = 6-8%
• Albumins; maintain osmotic pressure and viscosity of
the blood
• Globulins
– Alpha and beta globulins are used for transport purposes
– Gamma globulins are the immunoglobulins (IgG, IgA, etc)
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–
–
–
• Fibrinogen; a clotting protein
Organic nutrients – glucose, carbohydrates, amino acids
Electrolytes – sodium, potassium, calcium, chloride,
bicarbonate
Nonprotein nitrogenous substances – lactic acid, urea,
creatinine
Respiratory gases – oxygen and carbon dioxide
The Composition of Whole Blood: Formed Elements
Formed Elements
• Formed elements comprise 45% of blood
• Erythrocytes, leukocytes, and platelets make up the
formed elements
– Only WBCs are complete cells
– RBCs have no nuclei or organelles, and platelets are just
cell fragments
• Most formed elements survive in the bloodstream for
only a few days
• Most blood cells do not divide but are renewed by
cells in bone marrow
Erythrocytes (RBCs)
• Biconcave disc
– Folding increases surface area (30% more surface area)
– Plasma membrane contains spectrin
• Give erythrocytes their flexibility
• Anucleate, no centrioles, no organelles
– End result - no cell division
– No mitochondria means they generate ATP anaerobically
• Filled with hemoglobin (Hb) - 97% of cell contents
– Hb functions in gas transport
• Hb + O2
HbO2 (oxyhemoglobin)
• Most numerous of the formed elements
– Females: 4.3–5.2 million cells/cubic millimeter
– Males: 5.2–5.8 million cells/cubic millimeter
Erythrocytes (RBCs)
Erythrocytes (RBCs) Function
• Erythrocytes are dedicated to respiratory gas transport
• Hemoglobin reversibly binds with oxygen and most
oxygen in the blood is bound to hemoglobin
– Hb functions in gas transport
• Hb + O2
HbO2 (oxyhemoglobin)
• Composition of hemoglobin
– A protein called globin
• made up of two alpha and two beta chains
– A heme molecule
• Each heme group bears an atom of iron, which can bind to one
oxygen molecule
• Each hemoglobin molecule thus can transport four molecules of
oxygen
Structure of Hemoglobin
Hemoglobin
• Oxyhemoglobin – hemoglobin bound to oxygen
– Oxygen loading takes place in the lungs
• Deoxyhemoglobin – hemoglobin after oxygen diffuses
into tissues (reduced Hb)
• Carbaminohemoglobin – hemoglobin bound to carbon
dioxide
– Carbon dioxide loading takes place in the tissues
Life Cycle of Red Blood Cells
The life span of an erythrocyte
is 100–120 days
Travels about 750 miles in
that time
Iron is transported from liver in
blood plasma by beta-globulins
as transferrin
Erythropoietin Mechanism
Start
Normal blood oxygen levels
Increases
O2-carrying
ability of blood
Stimulus: Hypoxia due to
decreased RBC count,
decreased availability of O2
to blood, or increased
tissue demands for O2
Reduces O2
levels in blood
Enhanced
erythropoiesis
increases RBC
count
Erythropoietin
stimulates red
bone marrow
Kidney (and liver to a
smaller extent) releases
erythropoietin
Production of Erythrocytes
• Hematopoiesis – blood cell formation
• Production of Erythrocytes: Erythropoiesis
– Occurs in the red bone marrow (myeloid tissue)
• Axial skeleton and girdles
• Epiphyses of the humerus and femur
• Marrow contains immature erythrocytes
Blood Hematocrit
• The % volume occupied by red blood cells is known as the
hematocrit.
• Volume occupied by white blood cells is relatively small.
Hematocrit under various circumstances
Leukocytes (WBCs)
• Leukocytes, the only blood components that are complete cells:
– 4,800 - 10,000/cubic millimeter
– Protect the body from infectious microorganisms
– Can leave capillaries via diapedesis
– Move through tissue spaces (amoeboid motion)
– Many are phagocytic (possess numerous lysosomes)
• Two major types of leukocytes
– Granulocytes: Neutrophils, Eosinophils, Basophils
– Agranulocytes: Monocytes, Lymphyocytes
• Leukocytosis – WBC count over 11,000/mm3
– Normal response to bacterial or viral invasion
• Leukopenia - a decrease in WBC count below 4,800/mm3
• Leukemia - a cancer of WBC
Granulocytes
Are all phagocytic cells
Cell Type
Neutrophils
Characteristic features
Account for 65-75% of total
WBC’s
Multilobed nucleus
AKA “polys” or PMN’s
Major Functions
Ingest and destroy invading
microorganisms
Participate in acute
inflammation
(polymorphonuclear)
Eosinophils
Eosinophils account for 1–4%
of WBCs
Bilobed nucleus
Phagocytic especially against
parasitic infection
Basophils
Account for 0.5-1% of all
WBCs
Have U- or S-shaped nuclei
Migrate to tissues to become
mast cells; release of histamine
contributes to inflammation
Helps in allergic reactions
Agranulocytes
Cell Type
Characteristic features
Major Functions
Monocyte
Monocytes account for 3–7% They leave the circulation, enter
of leukocytes
tissue, and differentiate into
They are the largest
macrophages
leukocytes
They have purple-staining, Uor kidney-shaped nuclei
Lymphocyte
Account for 20-25% or more
of WBCs and:
Have large, dark-purple,
circular nuclei with a thin rim
of blue cytoplasm
Most important cells of the
immune system
There are two types of
lymphocytes: T cells and B cells
T cells - attack foreign cells
directly
B cells give rise to plasma cells,
which produce antibodies
Platelets
• Their granules contain serotonin, Ca2+, enzymes, ADP,
and platelet-derived growth factor (PDGF)
• Platelets function in the clotting mechanism by forming
a temporary plug that helps seal breaks in blood vessels
• Platelets not involved in clotting are kept inactive by
Nitric Oxide (NO) and prostaglandins
• Survive 5-9 days
Normal blood cellular elements & typical human blood cell count
Human Blood Groups
• RBC membranes have glycoprotein 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 or absence of these antigens is used to
classify blood groups
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
cannot be mixed without serious hemolytic reactions
Blood Groups
• There are 4 blood types
–
–
–
–
–
A, B, AB, O
Type A has “A” antigen, and B antibodies
Type B has “B” antigen, and A antibodies
Type AB has “A” and “B” antigen, and NO antibodies
Type O has NO antigen and “A” and “B” antibodies
Rh Blood Groups
• Presence of the Rh agglutinogens on RBCs is
indicated as Rh+; 85% of population is +
• Lack of antigen indicated as Rh -; 15% of popn.
• Anti-Rh antibodies are not spontaneously formed
only in Rh– individuals
Transfusion Reactions
Hemostasis Blood Clotting
Hemostasis is the complex process by which platelets, plasma, and coagulation factors
interact to control bleeding.
When a blood vessel ruptures, local
vasoconstriction (decrease in the
caliber of blood vessels) occurs to
decrease blood flow to the area.
Platelets and clotting factors
become activated when exposed
to the collagen layer of the
damaged blood vessel.
Platelets clump together
(aggregate) by binding to the
collagen, forming a loose
platelet plug.
Hemostasis
Hemostasis = Opposite of hemorrhage stops bleeding
Too little hemostasis too much bleeding
Too much hemostasis thrombi / emboli
Three major steps:
1.Vasoconstriction
2.Platelet plug Temporarily blocks the hole
1.Platelet-derived cytokines further the process
3.Coagulation cascade (= clot formation seals hole until
tissues repaired)
1.Two pathways: Extrinsic and Intrinsic
4.After vessel repair, plasmin dissolves the clot
StepsofHemostasis
How Blood clots
Two coagulation pathways converge onto common pathway
1.Intrinsic Pathway. Collagen exposure. All factors needed are
present in blood. Slower.
2.Extrinsic Pathway. Uses Tissue Factors released by injured cells
and a shortcut.
How Blood clots
Coagulation Factors
Made up of plasma proteins—except for factor IV (calcium), which is a mineral,
and factor III (thromboplastin), which is a lipoprotein released from tissue
Produced in the liver
Activated in a chain reaction, with each one in turn activating the next factor in
the chain.
Factor I Fibrinogen
Factor II Prothrombin
Factor III Tissue thromboplastin
• Converts prothrombin to
thrombin as blood starts to
clot
• Converts to fibrin
when blood clots
• Inactive precursor to
thrombin
Factor IV Consists of
calcium ions
Factor V Labile factor
(proaccelerin)
Factor VII proconvertin
• Functions during the
combined pathway phase of
the coagulation system
• Activated by Factor III in
the extrinsic system
• Required throughout
the entire clotting
sequence
Coagulation Factors
Factor VIII
Factor IX
• Antihemophilic
factor
• Required during the
intrinsic phase of the
coagulation system.
• Plasma thromboplastin
component
• Required in the intrinsic
phase of the
coagulation system
Factor XI
Factor XII
• Plasma
thromboplastin
antecedent
• Required in the
intrinsic system
• Hageman
factor
• Required in the
intrinsic system
Factor X
• Stuart factor (StuartPrower factor)
• Required in the combined
pathway of the
coagulation system
Factor XIII
• Fibrin-stabilizing factor
• Required to stabilize
fibrin strands in the
combined pathway phase
of the coagulation system
Roles of thrombin in hemostasis
Anticoagulants
• Clotting ‫ تخثر‬can be prevented by Ca+2 chelators
(e.g. sodium citrate or EDTA)
• or heparin which activates antithrombin III (blocks
thrombin)
• Coumarin blocks clotting by inhibiting activation of
Vit K
• Vit K works indirectly by reducing Ca+2 availability
Complete the following questions:
1. Diapedesis is the process by which the WBC’s comes out of blood
capillaries.
2. Erythropoiesis is the formation of red blood cells.
3. Erythrocytopenia is the decrease in the number of RBC.
4. Hematocrit is the percentage of blood cells in the blood.
5. Instrument used to determine RBC count Hematocytometer
6. Hemolysis is breaking of RBC.
7. Hemometer instrument used to know percentage of hemoglobin in
blood.
8. Leukocytosis is increase in number of WBC’s
9. Erythrocytosis is increase in number of RBC’s.
10. Leukopenia is decrease in number of WBC’s.
11. Red blood cells in human does not contain nucleus and
mitochondria
12. Give the terms used for decrease in RBC and WBC count.
13. Blood is fluid connective tissue
1.
2.
3.
4.
5.
6.
7.
8.
Write the functions of blood?
Write the composition of blood?
Write the different types of White blood cells?
What is hemoglobin and its function?
What is the life span of RBC?
Write the functions of platelets?
Name the different types of blood groups in our body.
Name the antigens and antibodies present in blood group A, B,
AB and O?
9. Name any 3 blood anticoagulants?
10. Name the plasma proteins found in blood with function?
11. Define blood coagulation? The property of blood to change
from fluid to get state within a few minutes after it comes in
contact with air is blood coagulation.
12. What is the role of vitamin K? Vitamin K is essential for the
formation of blood clot.