physiology of blood
TRANSCRIPT
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Presentation Out line
1. Objectives
2. Introduction
3. Blood volume and constituent
4. Plasma constituents
5. Erythrocytes and blood grouping
6. Leukocytes and immune responses
7. Platelets and Hemostasis
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1.Objectives
At the end of this session, students will able to:
List the functions of blood
Appreciate blood composition
Understand the structure and functions of RBCs,
WBCsand platelets.
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2. Introduction
The Only Fluid tissue in the body.
Specialized type of connective tissue in which formed
elements are suspended in non living fluid matrix called
plasma.
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3. Blood volume and constituent
Physical Characteristics of Blood
viscosity: sticky opaque fluid, due to the presence of
RBCs(sticky and thick), Viscosity (thickness) = 4 – 5.
color :
o Scarlet red-high oxygen
o Dark red-poor oxygen
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PH: 7.35-7.45
Temperature: Blood temperature is slightly higher than
body temperature.
Blood volume: 5–6 L for males; 4–5 L for
females. Blood accounts for approximately 8% of body
weight.
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The amount of blood varies with body size, changes in
fluid concentration, changes in electrolyte concentration,
and amount of adipose tissue.
Density ( specific gravity): Refers to the weight of blood
compared to water.
Specific gravity of H20 is taken as 1(i.e.,1 ml of H2O
weighing 1 gm at 4 oc).
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Male:1.052-1.063
female:1.050-1.058 ( i.e.,1 ml of whole blood
weighing 1.060gm).
Osmolarity = 300 mOsm or 0.3 Osm, reflects the
concentration of solutes in the plasma.
Salinity = 0.85%, Reflects the concentration of NaCl in the
blood.
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Functions of blood
Blood performs a number of functions dealing with:
1. Substance distribution (Transportation )
2. Regulation of blood levels of particular
substances
3. Body protection
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Cont’d……
1.Distribution (Transports )
o Oxygen from the lungs and nutrients from the
digestive tract to the tissues .
o Metabolic wastes from cells to the lungs and kidneys
for elimination
o Hormones from endocrine glands to target organs
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Cont’d….
2.Regulations
o Appropriate body temperature by absorbing and distributing
heat to other parts of the body
o Maintaining body PH in the body tissues using buffer system.
o Maintaing adequate fluid volume in the circulatory volume.
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3. protection
o Hemostasis
Activating plasma proteins and platelets.
Initiating clot formation when a vessel is broken.
o infection : Synthesizing and utilizing antibodies.
Activating complement proteins. Activating WBCs to
defend the body against foreign invaders.
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Composition of Blood
2 major components
Liquid = plasma (55%)
Formed elements (45%)
Erythrocytes / red blood cells (RBCs)
Leukocytes / white blood cells (WBCs)
Platelets, fragments of megakaryocytes in marrow
( thrombocytes ).
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Components of Whole Blood
Withdraw blood and place in tube
1 2 Centrifuge
Plasma (55% of whole blood)
Formed elements
Buffy coat:leukocyctes and platelets(<1% of whole blood)
Erythrocytes(45% of whole blood)
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Cont’d……
Plasma -55%
Buffy coat
RBCs =45%
Plug
Capillary tube
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4. Plasma constituents
Blood plasma : straw colored sticky fluid, includes:
Water = 90-92%.
Proteins = 6-8%. Albumin,globilin and clotting proteins
Organic nutrients – glucose, carbohydrates, amino acids
Electrolytes – sodium, potassium, calcium, chloride,
bicarbonate.
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Non protein nitrogenous substances – lactic acid, urea,
creatinine.
Respiratory gases – oxygen and carbon dioxide.
Plasma proteins
Albumins:
accounts 60% of Wt,Most abundant plasma protein.
Carrier to shuttle molecules through the circulation
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Important blood buffer.
maintain osmotic pressure of the blood.
Globulins : Accounts 36% of the plasma protein.
α and β globulins have role in transport.
γ globulins are in immuno globulins( IgG, IgA).
Clotting proteins : account for 4%
‾ Fibrinogen and Prothrombin.
Serum
Plasma with clotting factors removed, yellowish color. 18
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Serum: Plasma with clotting
factors removed, yellowish color.
Determined by means of
electrophoresis
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Cont’d……..
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.
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Cont’d…….
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.
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Blood
(4.8%) (95.1%) (0.1%)
Plasma
Hormones
MonocytesBasophilsEosinophilsNeutrophils
(54–62%) (1–3%) (<1%) (3–9%) (25–33%)
GlobulinsAlbumins
(92%) (7%)
N2 O2 CO2
Platelets Red blood cells Proteins Nutrients Gases
45% 55%
WastesWaterWhite blood cells Electrolytes
Vitamins
Lymphocytes Fibrinogen
Formed elements
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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5. Red Blood Cells ( RBCs)
Shape: flexible biconcave cell that is thinner at the center
and thicker at the edges
Diameter: ~ 7.5 um
- Mature, No nucleus and organelles.
Has greater surface area/volume ratio, Therefore, can bend
and twist to pass through the narrow capillaries very easily.
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The major forms of cell in the blood.
The average number of RBCs are 5 million/ mm3
blood or 5 x106 / μl of blood.
Lack of mitochondria.
Each RBC contains 280 million haemoglobin.
Half-life app.120 days.
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Hematocrit (Hct) / Packed cell volume (PCV)
Hematocrit (Ht): is the percentage by volume of packed RBC.
Procedure :
1. Centrifuge of un –coagulated blood at a high speed (10-15 min).
2. RBC precipitate down to the bottom.
3. The plasma portion remains floating.
The cells that settle down to the bottom (mainly RBCs) form the
hematocrit or packed cell volume (PCV).
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Normal value:
Males: 47% ± 5%
Females: 42% ± 5%
HCT increase in
polycythemia and
dehydration states.
Decrease in anemia
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Function of RBCs :
1. Carries hemoglobin that in turn transports respiratory
gases (O2 and CO2).
2. Carbonic anhydrase (CA): An enzyme located in RBC
membrane.
CO2 + H2O CA H2CO3 = HCO-3 + H+
CA increases the rate of this reaction 5000 fold.
Good to transport CO2 from the tissues to the lung very fast.
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Haemoglobin : Consists of globulin and heme.
Globulin
Two alpha(α) chain polypeptide
Two beta(β) chain polypeptides
Heme: Each heme is present in one peptide chain and
contains an iron {Fe++} that combines reversibly with one
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Each polypeptide has one heme group, each heme with
Fe2+ carries one O2 molecule, total = 4- O2 molecules
Are carried with in Hb molecule.
1g Hb binds with 1.34 ml O2
15g Hb/dl x 1.34 ml O2 = 20.1 ml O2/100 ml blood.
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The polypeptide chain (the Globin unit) determines the
physical characteristics of the Hb-molecule. Thus, there exists:
a. Adult Hb (Hb A): 2α + 2β
b. Fetal Hb (Hb-F): 2α + 2γ
c. Sickle cell (Hb-S): glutamic acid is replaced by valine
at Beta- chain so on.
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Saturation of Hb: refers to the number of O2 molecules
combined with Hb.
The Hb molecule combine maximally with 4 molecules of O2
in a cascade manner(100%saturated),by Oxygenation reaction,
each binding facilitates further binding of O2.
50 % saturation: means that Hb binds with 2 molecules of O2.35
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Hematopoiesis/ hemopoieisis
RBC and other blood cells are produced in the Bone
marrow.
All cells emerge from undifferentiated (uncommitted ) stem
cells in the Bone marrow.
Stem cells: All formed elements derived from
single population36
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Stem cells: All formed elements derived from single population
Proerythroblasts : Develop into red blood cells
Myeloblasts: Develop into basophils, neutrophils,
eosinophils
Lymphoblasts: Develop into lymphocytes
Monoblasts: Develop into monocytes
Megakaryoblasts: Develop into platelets
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Hematopoiesis
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Erythropoiesis.
A. Embryonic life: RBC are produced in the liver, spleen
and lymph nodes.
B. Infants (5 years old): Red bone marrow of all cells.
C. Adults (after age 20): Membranous bones like
ribs, sternum, vertebrae and pelvic bones.
- But not in long bones like femur or tibia (fat).
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Stem cells differentiate to produce committed stem cells
called hematocytoblasts that in turn produce :
1. Proerythroblast: where Hb synthesis begins, big nucleus.
2. Basophile erythroblast: cell divide, continues
3. Polychromatophil erythroblast: Hb synthesis increases
and fills the cytoplasm, nucleus size decreases.
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4. Ortochromatic erythroblast: Nucleus decreases.
5. Reticulocytes: Contains Hb, no nucleus and the cell is
expelled from the bone to circulation.
6. Erythrocytes: Mature form of RBC without nucleus,
filled with Hb.
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Physiological Mechanism
1. Low oxygen(Hypoxia ) that occurs in the kidney cells.
2. Kidney then produce a hormone called erythropoietin.
3. Erythropoietin is transported by the blood to bone marrow.
4. Bone marrow produces and releases a increased RBC .
Increased or adequate O2 then blocks the formation of more RBC.
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Organs involved in erythropoiesis
Kidney : Erythropiotein
Liver : Store protein, vit.B12& folic acid ,Synthesize globin ,
Produce Erythropiotein 10%.
Bone Marrow: Site of RBCs formation
Stomach: intrinsic factor.
Small Intestine: absorption of Iron, vitamins, and amino acids.
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Substances necessary for RBC maturation
A. Vitamin B12: requires intrinsic factor for absorption
- Important for DNA synthesis and thus for cell division.
Deficiency of Vit B12 : Megaloblastic anemia.
Characterized : macrocytic cells (big Hb in
cytoplasm) Because of their big size, the cells rupture
when passing through the capillary wall.
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Insufficient of intrinsic factor causes , Maturation failure
for Vit. B12 is call pernicious anemia.
B. Folic acid: important in DNA synthesis.
c. Iron: Necessary for RBC formation.
D.Trace elements : (Co, Vit. Copper etc).
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Destruction of RBCs The absence of nucleus in erythrocytes prevents them
from synthesizing proteins and other important
substances necessary for survival.
The cells become weak and fragile and die after about
120 days.
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The older red cells are phagotizised by macrophage cells of
the reticuloendothelial system that are located in the liver,
spleen, and bone marrow cells.
The macrophages release the Hb-molecule that is broken down
into:
a. its protein part (Globin) and
b. Heme part
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Steps in the destruction of RBC:
1. RBC = Globin + Heme
2. Globin = Broken to AA’s > used for protein synthesis
3. Heme = Fe2+ + poryphrine rings.
4. Fe 2+ = stored in the liver > used for new Hb synthesis.
5. Pyrol rings > oxidation to green pigment called Biliverdin and
later reduced to bilirubin.
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a. Bilirubin + serum albumin > reach liver.
b. Bilirubin conjugates with glucuronic acid in liver.
C. Liver releases bilirubin as bile to Small intestine.
D. Bacteria's change bilirubin into:
Strrcobilinogen > stercobilin , feces (brown color).
Uribilinogen > Urobilin > Urine (yellow).
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Life Cycle of a Red Blood Cell
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Clinical correlations: Anemia
A decrease in;
1- RBC number or/and
2- Hb content Below the normal for that sex and age.
1.Decreased RBC Number.
- Blood loss : e.g, hemorrhage
- A plastic anemia: bone marrow destruction (X-ray)
- Maturation failure anemia: pernicious anemia.
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Microcytic Hypochromic Anemia: Low levels of
hemoglobin in RBCs due to chronic blood loss
resulting in low Fe2+ levels in newly produced
RBCs.
2. Hemolytic Anemia: Different abnormalities of
RBCs that make RBCs fragile and rupture easily.
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Hereditary Spherocytosis: RBC develop as small
spherical cells . These spherical cells easily rupture by
slight compression.
Sickle-cell Anemia:
Genetic mutation causing abnormal beta chains.
HgS exposed to low O2 concentrations, it precipitates into
long crystals that cause the cells to become sickle-shaped.
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Effects of Anemia
• Due to decrease O2 supply to tissues.
1- Fatigue, muscle weakness
2- Mental effects: lack of concentration and dizziness , even Faintining
3- CVS effects: tachycardia, palpitation, heart failure if not treated
4- nausea & anorexia
5- Retarded growth in children
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Polycethemia
is abnormal increase of RBC in the circulation.
Two types
1. Polycethemia Vera (8-9 million)
Tumerous or cancerous production causes highly engorged blood.
genetic mutation in the hemocytoblastic cell line that increases
RBC production. Hematocrit values can reach 70%
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2. Secondary Polycethemia;
Mostly Physiologic
Increase in RBC production due to hypoxic tissues.
e.g. high altitudes.
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Effect of polycethemia on the circulatory system
1. Increased viscosity causes sluggish blood movement.
2.thrombosis and obstruction of different blood vessels.
3.decreased blood flow to tissues and Decreased delivery of O2 to
tissues.
4.Hct increases and so blood volume, blood pressure and work of
the heart increases.
RX: aim to remove RBC by; phlebotomy, blood donation61
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6.Blood Groups
Erythrocytes contain genetically determined surface
antigens( agglutinogens).
Blood plasma contains antibodies(agglutinins )that react
with specific antigens.
Blood is named according to surface antigens that are
present.
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Types of blood group
In humans, there are two known blood groups that
are clinically important:
a. The ABO-Blood groups
b. The Rh- Blood group factors
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ABO Blood Group In the ABO system, blood is classified primarily on the
Basis of the A and B antigens present on the surface of
red blood cell membranes (erythrocytes).
Secondly, blood is classified on the basis of the naturally
occurring antibodies (agglutinins) in the serum .
A person whose red cells possess the A -antigen has anti-B
antibody in his serum and is classified as Blood group A.
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If B antigen is present in the Red cell membranes, Anti-A
antibody is present in his serum and the person is designated
as Blood group B.
If Both AB antigens are present on Red cells, then he has
no antibody, so is AB blood group.
If No antigens are present on red cells, he is O Type and
has both anti A and B antibody in his serum. 65
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ABO Blood Group
4 blood types – A, B, AB, O
Types are identified by antigens located on the RBC surface. 66
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ABO-blood group
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Typing and cross-matching – process by which blood
type is identified and donor blood is tested for possible
transfusion.
Transfusion:
Type O is a Universal Donor.
Type AB is the Universal Recipient.
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Blood group O
Universal Donor.
No antigens on their cell-membrane surfaces and therefore can
not agglutinate if transfused to any blood types.
Receive only from persons with blood group “O” only
because , they have anti- A & anti-B antibodies in the plasma.
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Blood group AB
Universal recipient
they have no antibodies in their blood to cause
agglutination reactions.
Have antigen A and B, AB can donate blood only to a
person with blood AB, not to other.
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Method of blood typing
Procedures:
1. On a slide at opposite ends , drops of anti- A antibody and
Anti-B antibody are added at opposite sides.
2. 2-3 drops of Blood (RBC’s) are added on the prepared
antibodies and changes for agglutination are observed after
a few minutes.
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A. If agglutination occurs on anti-A antibody (sera), then the
blood is Blood Group A.
B. If agglutination occurs on anti-B antibody , the blood is
Blood Group B.
C. If there is agglutination in both A and B-antibodies, then it
is Blood Group AB.
D. If no agglutination occurs, then it is Blood Group O.73
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Agglutination Reaction
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Donators and Recipients
Donators 1. O can donate blood to group A, B, AB, and O2. A “ A & AB only3. B “ B & AB only 4. AB “ AB only
Recipients 1. O can receive blood from group O only2. A “ A & O only3. B “ B & O only4. AB “ A, B, O, & AB
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RH Blood Group
Named after Rhesus monkey.
Consists of over 50 related antigens, the most clinically
significant is D,C,E,c ,d and e.
The type D antigen is more antigenic and widely prevalent in
the population.
Rh+, having type D antigen, 85% of the population
Rh-,lack of type D antigen , 15% of the population 77
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• A person with Rh negative(-)blood does not have Rh
antibodies naturally in the blood plasma.
• If they receive blood that is Rh positive (+) , antibodies
form but not a problem.
• The second exposure can produce a transfusion reaction
(Hemolysis and possible kidney damage).
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Rh incompatibility
Father Rh + = Rh + means he has D antigen on his RBC
membrane.
Mother Rh- = No Rh factor(no D antigen).
Marriage:
1. Rh+ father X Rh- mother = Rh + fetus.
2. During birth through placenta , Rh+ blood (antigens) of the
fetus leak (enter) to mothers blood and sensitizes her.79
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3. Mother ‘s blood produces anti-Rh antibodies (anti-D
antibodies ) against the Rh+ blood.
4. During the 2nd pregnancy and there after, the Anti-Rh+
antibodies (agglutinins) enter into the fetus and agglutinate or
hemolyze the RBC’s the fetus.
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This type of hemolytic disease is called
Erythroblastosis fetalis.
If the baby is born alive from the incidence, then there is a
higher risk of being Anemic and jaundiced.
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Prevention
• Shortly after each birth of an Rh+ baby, the mother is given
an injection of anti-Rh antibodies (or Rhogam).
These passively acquired antibodies destroy any foetal
cells that got into her circulation before they can elicit an
active immune response in her.
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Bio 130 Human Biology
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19-84
Erythroblastosis Fetalis
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7. White Blood Cells( Leukocytes ) and immune response
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Properties The only formed element that are complete cells.
Normal number: 4000-10,000 / mm3 of blood
Mobility: Are highly mobile and reach tissue fluids.
When infection occurs, WBC increase in number e.g.,
Neutrophils.
Life span : Many (not all) live only a few days, may be b/s of
their engagement with pathogens.
Grouped into two main categories.
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Granulocytes : contain specialized membrane-bound
cytoplasmic granules.
Contain cytoplasmic granules that stain specifically
(acidic, basic, or both) with Wright’s stain
Are larger and usually shorter-lived than RBCs.
Have lobed nuclei, Are all phagocytic cells.
include neutrophils, eosinophils and basophiles. 87
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Agranulocyte : Lack obvious granules; Lymphocytes and Monocytes.
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Granulocytes
1.Neutrophils: Make up 60 to 70% of WBC’s.
Diameter of 10-15 μm, Phagocytic
First to arrive at infections.
Nucleus 2-5 lobes (increase with cell age)
Increase: stress, burns and bacterial infections.
Decrease: Radiation exposure, B12 deficiency.89
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2.Eosinophils : Account for 1-4% of WBCs
10 –12 um in diameter, Nucleus 2–3 lobed
Increase: allergic reactions, parasitic infections and
autoimmune disease.
1. Kill parasitic worms
2. Destroy antigen-antibody complexes.
3. Inactivate some inflammatory chemical of allergy (histamine). 90
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3. Basophils: Account for 0.5% -1% of WBCs.
Liberate heparin and histamines during allergic reactions.
Intensify inflammatory response
Increase: Allergic reactions, leukemia, cancers,
hypothyroidism.
Decrease: Pregnancy, ovulation, stress, hyperthyroidism
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Agranulocyte
1. Lymphocytes: Make up 20 to 25% WBC’s
Small: 6-9 um in diameter, Large: 10-14 um, Nucleus is round
or slightly indented.
B cells produce antibodies.
T cells attack viruses, cancer cells, and transplanted tissues
Natural killer cells attack infectious microbes and tumor cells.92
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2. Monocytes
Account for 4-8% of WBCs and the largest WBCs.
They leave the circulation enter tissue and differentiate
into macrophages.
Activate lymphocytes to mount an immune response.
Phagocytize bacteria, dead cells, and other debris.
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mobility through the tissues
1. Diapedesis: WBC Squeeze out through the capillary pore (e.g.
Neutrophils, Monocytes ).
2. Amoeboid motion: Produce pseudopodia and reach the microbes in
the tissues
3. Chemotaxis: WBC are attracted by chemicals or toxins produced by
the microbe or inflamed tissues
4.Phagocytosis: engulfing and destroying e.g., Neutrophils,
macrophages .
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Clinical correlation
Leukemia (increased WBC No):
cancerous production of WBC.
These occurs:
a. in the bone marrow
b. in the lymph.
Their increased production takes the space of platelets &
RBC causing anemia + impaired blood clotting 97
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Leucopenia: Decreased production of WBC
- Bone marrow stops producing them
- Drug poison, X-rays
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Practical hematology/leukocyte differential
Lists the different percentages of leukocytes
↑Neutrophils : Bacterial Infection
↑ Lymphocytes: Viral Infection
↑ Monocytes: Chronic Infection
↑ Basophils: Allergic Rxns
↑Eosinophils: parasitic infections
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8. Platelets and Hemostasis
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Platelets/Thrombocytes
Small, non nucleated (anucleated), round/oval cells/cell
fragments.
Their size ranges 1-4-m in diameter.
The cytoplasm stain pale blue and contain many pink
granules.
They are produced in the bone marrow by fragmentation of
megakaryocytes, which are large and multinucleated cells.101
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• Their primary function is preventing blood loss from
hemorrhage by forming a platelet plug
• Normal value – 150,000 to 300,000/mm3.
Platelets have a life span of approximately 10 days.
Senescent platelets are removed by the spleen.
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Attracted to hemorrhage.
Plugs leaks.
Promotes constriction of blood vessel.
Triggers inflammation.
Initiates clotting.
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• Hemostasis refers to the stoppage/arresting of bleeding.
• Actions that limit or prevent blood loss include:
• Blood vessel spasm
• Platelet plug formation
• Blood coagulation
Hemostasis
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Blood coagulation
Triggered by cellular damage and blood contact with
foreign surfaces.
• A blood clot forms
• Causes the formation of clot via a series of reactions
which activates the next in a cascade
• Occurs extrinsically or intrinsically. 107
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Extrinsic clotting mechanism
• Triggered when blood contacts damaged blood vessel
walls or tissues.
• Chemical outside of blood vessel triggers blood
coagulation.
• Triggered by tissue thromboplastin (factor III) (not
found in blood).
•
•
• .
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• A number of events occur that includes factor VII, factor X, factor V,
factor IV, and factor II (prothrombin).
Intrinsic clotting mechanism
Triggered when blood contacts a foreign surface
• Chemical inside blood triggers blood coagulation
• Triggered by Hageman factor XII (found inside blood)
• Factor XII activates factor XI which activates IX which joins with
factor VIII to activate factor X.
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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Tissue damage
Releases
Factor Vll
Factor X
(Ca+2)
(Ca+2)
Activates (Ca+2)
Converts
Converts
(Ca+2)
(Ca+2)
Activates
Activates
Factor V
Fibrin
Factor lX
Factor Xl
Factor X
Activates
Activates
Activates
Activates
Activates
Hageman Factor Xll
Factor V
StabilizesFactor Xlll
Extrinsic ClottingMechanism
Tissue thromboplastin(Factor lll)
Blood contactsforeign surface
Intrinsic ClottingMechanism
Prothrombinactivator
Prothrombin(Factor ll)
Thrombin(Factor lla)
Fibrinogen(Factor l)
Fibrinclot
Factor Vlllplatelet phospholipids
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Fate of Blood Clots
• After a blood clot forms it retracts and pulls the edges of a
broken blood vessel together while squeezing the fluid
serum from the clot.
Platelet-derived growth factor stimulates smooth muscle
cells and fibroblasts to repair damaged blood vessel walls.
Plasmin digests the blood clots.
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Clinical correlations
1. Hemophilia A: Deficiency of Factor VIII accounts for
85% cases. Almost exclusively in males.
Females are usually carriers, caused by a gene mutation
on the “X” chromosome. Occurs in about 1/10,000 male
births
Other Hemophilias account for another 15% ,Hemophilia B (Factor
IX),Hemophilia C (Factor XI) and Hemophilia D (Factor XII)
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2.Thrombocytopenia: Abnormally low levels of platelets.
Usually below 50,000/ μl of blood.
3.Thrombus: Abnormal clot that develops in a blood
vessel.
4.Embolus: Free thrombic clots carried in the blood that
usually get caught in arterioles in the brain, kidney, and
lungs.
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Practical hematology/Tests for Bleeding
1. Bleeding time : The time interval that takes between start of
bleeding (oozing) until arrest of blood. Normal duration : 3-6 min
2. Clotting time: The duration of time it takes for the blood to clot
(normal duration is 3-8 min).
3.Prothrombin time: Deals with the duration of formation of
Prothrombin after addition of oxalate and Ca2+ ions to the blood.
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Reading assignment on immunity