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FORMED ELEMENTS OF

BLOOD

BLOOD

Tissue composed of: erythrocytes,


leukocytes, platelets suspended in blood
plasma
Transports oxygen from lungs and
nutrients from GIT to other tissues
Carries carbon dioxide from tissues to
lungs and nitrogenous wastes to kidneys
for elimination
Carries hormones from origins to target
cells

Volume: 5 L (7% of body weight)


45%: RBCs
1%: WBCs, platelets
54%: blood plasma (extracellular matrix)

Cellular elements separated by


centrifugation

Erythrocytes

Corpuscles: red color to blood


Develop in the bone marrow
Extrude nucleus before entering blood
Cytoplasm: hemoglobin
Transport oxygen from lungs to tissues
and CO2 from tissues to lungs
Normal number:
5.4 M/cumm (males)
4.8 M/cumm (females)

Shape: biconcave disc 7.5 u in dm, 1.9 u


thick

Biconcave: increased surface area for


immediate saturation of Hgb with oxygen

Pliable: bell-like or paraboloid when


flowing through narrow capillaries
Due to hydrodynamic forces and viscous drag
Dependent on velocity of flow
Influenced by osmolarity of surrounding
medium

Moderately hypotonic: swell, cup-shaped


More hypotonic: leaky membrane, hemolysis

Shape: also dependent on ATP

Thick smear of fresh blood examined:

Below critical level: become echinocytes


(round up, 10-30 short conical projections):
crenation
Aggregates like stack of coins: rouleaux

Thin blood smears, Wrights stain


Majority stain a deep pink
Few: bluish/greenish tint (basophilic staining of
residual ribosomes): polychromatophilic RBCs
or reticulocytes (0.8% of total RBCs)

Unstained RBCs: pale yellow to tan color


due to Hgb (33% of RBC mass)
4 polypeptide chains: 2 alpha, 2 beta chains
Fe-containing heme group bound to each
chain tetramer
Carbonic anhydrase: catalyzes interaction of
CO2 and water in RBCs to form carbonic acid
that dissociates into hydrogen and
bicarbonate ions

Anemia: reduction in O2-carrying


capacity of blood
Low # of RBCs
Decreased Hgb content

Anisocytosis: abnormal variation in cell


size
Poikilocytosis: diversity in cell shape
Larger than normal: macrocytic
Normal size: normocytic
Smaller than normal: microcytic

Concentration of Hgb

Hyperchromic, normochromic, hypochromic

HgbA (normal adult): 2 alpha, 2 beta


96% of Hgb
2%: 2 alpha, 2 delta
Less than 2%: HgbF: 2 alpha, 2 gamma
Thalassemia: persistence of HgbF

Ultrastructure of RBCs

Plasma membrane: lipid bilayer


No cell organelles
Membrane skeleton: short filaments
Spectrin: form double stranded tetramers
Actin: polymers stabilized by tropomyosin
2 associated proteins (band 4.1 and band 4.9)
Near the middle of spectrin tetramer: ankyrin
(link to cytoplasmic domain of band 3)
Deficiency of spectrin/defective binding of
spectrin:

Hereditary spherocytosis/elliptocytosis

Membrane skeleton:

Provides stability and resilience as RBCs pass


through the vascular system

RBC membrane: antigenic determinants


Basis of ABO blood group system
Antigen A, B, both A and B
Rh antigen

Blood Platelets

Thrombocytes/thromboplastids
Minute, anucleate, colorless corpuscles
Function in clotting of blood at sites of
injury to blood vessels
Protect against excessive blood loss
Thin biconcave discs 2-3 u in diameter
Round or ovoid (flat), fusiform (profile)
150-350 T/cumm of blood

Stained smears: 2 concentric zones


Hyalomere: pale blue peripheral zone made up of
microtubules that maintain discoid shape
Granulomere: thick central region containing
small azurophilic granules

Arise in the bone marrow


Fragmentation of the cytoplasm of
megakaryocytes
Continuously formed and released into the blood
Life span of 9-10 days
Consume oxygen, active metabolism (1-2 small
mitochondria)

Greater concentration of actin and


myosin in hyaloplasm than any other cell
(exc muscle)
Monomeric form in circulation
Clotting: polymerization of actin and myosin
into filamentous form necessary for
contraction

Granulomere: few ribosomes and


scattered particles of glycogen

Membrane-bound small canaliculi: major


pathway for uptake of solutes and discharge
of secretory products upon activation

Membrane-bound granules:
Alpha granules: contain
Platelet factor IV: counteracts heparin
Von Willebrand factor: GP which
facilitates adhesion of platelets to vessel
wall
Platelet derived growth factor: fibroblast
proliferation
Thrombospondin: GP involved in platelet
aggregation in blood clotting

Beta granules: species other than man


Serotonin
ATP
ADP

Function of Platelets

Normally: no tendency to adhere to each


other, to other blood cell or to vessel wall
Disruption of endothelium: become sticky
and rapidly adhere to one another and to
site of injury to initiate blood clotting
Platelet adhesion: sticking of platelets to
solid surfaces
Platelet aggregation: sticking of platelets
to each other

Underlying connective tissue exposed:


Platelets adhere to collagen via a collagenbinding CHON in membrane
Adhesion: activates platelets, causing
breakdown of ATP and release of ADP and
adhesive GPs

ADP:

potent inducer of platelet


aggregation, causing them to adhere in
increasing numbers to those adhering
to collagen

Activated new platelets form a mass called


the platelet thrombus

Concurrent:
Tissue thromboplastin released by injured
endothelial cells: series of reactions that
convert prothrombin to thrombin
Thrombin: catalyzes conversion of fibrinogen
to fibrin that polymerizes to form a meshwork
of fibrils
Fibrils bind to receptors on platelet
membrane: platelets bind together and
entrapping RBCs in fibrin meshwork to form a
blood clot

Activated platelets: morphological


changes
Extend slender processes and release alpha
granules
Thrombospondin: binds to membrane and
promotes further platelet aggregation
Platelet thromboplastin: from phospholipids
(released during degranulation) reacting with
plasma components
Cyclo-oxygenase enzymes: convert PG
endoperoxides to thromboxane
Products of platelet thromboplastin and
thromboxane: accelerate clotting

Within an hour after clot formation


Clot shrinks to half its original size
Due to polymerization of actin and myosin
monomers to form filaments
Hemostasis: occlusion of lumen of vessel by
clot plus vasoconstriction of injured vessel

Growth promoting factors

Contribute to tissue repair by stimulating cell


migration and proliferation

Platelet

derived growth factor (PDGF)


Secreted by platelets, monocytes,
macrophages, endothelial cells
Mitogen for cells of connective tissue
origin
Synthesized in the megakaryocytes in
the bone marrow, reaches blood in the
alpha granules of platelets
Released by platelets when exposed to
thrombin or ADP

PDGF:

Induces chemotactic response in

fibroblasts and smooth muscle cells,


attracting them to sites of injury and
stimulating their proliferation to
initiate repair
Inherited abnormalities of platelets or
deficiencies of plasma factors
Hemophilia: bleeding disorder due to absence
of one plasma factor needed for clotting
Thrombocytopenia: deficient production,
number
Thrombocytopathia: abnormal structure and
function

Leukocytes

Nucleated
Colorless in the fresh state
Spherical in the bloodstream
Pleomorphic ameboid cells in tissues or in
vitro
Granular or nongranular
Granular: eosinophils, basophils,
neutrophils
Nongranular: lymphocytes, monocytes
5-9 T/cumm

Differential count: fairly constant


Neutrophils: 55-60%
Eosinophils: 1-3%
Basophils: 0-0.7%
Lymphocytes: 25-33%
Monocytes: 3-7%

Neutrophil

Most abundant of the granular leukocytes


Blood: 8 hrs before migrating into tissues
7 u in dm in blood; 10-12 u in dried
smears
Nucleus: 2-5 lobes
Young cells: band forms

#: index of entry of new neutrophils in blood

Variability in nuclear form:

Polymorphonuclear leukocyte

Chromatin: deeply staining clumps


Females: X chromosome as a minute
lobule

Cytoplasm: stippled with fine


specific granules and larger
azurophilic granules
Azurophil: (+) for peroxidase,
acid phosphatase, beta
glucoronidase
Specific: (+) for ALP,
collagenase, lysozyme,

First line of defense in bacterial infections


Chemotaxis: migrate up a concentration
gradient
Phagocytic :

Immune phagocytosis
IgG, C3b: coat bacteria, increase efficient

phagocytosis

Nonspecific phagocytosis

Pus: dying and dead neutrophils, other


leukocytes

LCAM-1: adherence of neutrophils to capillary


endothelium at sites of infection
Other activated cells: secrete IL-1 beta, TNF
alpha: stimulate endothelial cells to secrete
ELAM-1

Synthesize

leukotrienes (LTs)
From arachidonic acid
LTB4: promotes adhesion of
neutrophils to endothelium and
emigration into tissues;
chemoattractant for eosinophils,
monocytes
LTC4, LTD4, LTE4: increase
permeability of post- capillary

Eosinophil

Blood: 6-10 hrs before migrating into


connective tissue (8-12 days)
9 u in suspension, 12 u in blood smears
Large specific granules: stain orange-red
Nucleus: bilobed
Chromatin less coarse than that of
neutrophil

Granules

contain:
Aryl sulfatase, betaglucoronidase, acid phosphatase,
histaminase, ribonuclease
3 cationic proteins: major basic
protein (MBP), eosinophil cationic
protein (ECP), eosinophil-derived
neurotoxin: allergic reactions,
parasites
Damage control in allergic
reactions

Basophil

Least numerous of the granular


leukocytes
10 u in stained blood smears
Nucleus: U or J-shaped, may appear
bilobed
Granules: few and larger than those in
eosinophils, metachromatic

Contain histamine and heparin


(metachromasia)

Share some properties with mast cells

Both with granules

Basophils: have receptors for IgE on their


membrane
Reexposure to the same antigen: rapid
degranulation
May

precipitate an asthma attack or


urticaria
Massive systemic release of mediators:
anaphylactic shock

Lymphocyte
2nd most numerous class of leukocytes
7-12 u in dm in blood smears
Nucleus: deeply staining, slightly indented
Thin rim of clear blue cytoplasm
No specific granules, few small azurophil
granules
Large, medium, small: diameter, amount of
cytoplasm
2 types of small lymphocytes: B and T

With distinctive surface molecules that serve as

type specific markers

Principal agents of immune responses


B-lymphocytes

Primary immune response: low level of Ig


Secondary immune response: rapid in onset

Plasma cells
T-lymphocytes
Regulate activity of B-lymphocytes
Helper T cells: provide additional stimulus for

antibody production
Suppressor T cells: depress antibody production

Humoral immune response: antibodies


Cell-mediated immunity
Principal agents: cytotoxic T cells: synthesize
pore-forming protein (porin): lysis of target
cell

Monocyte
Spherical, 9-12 u in diameter in suspension,
17 u in dried blood smears
Larger, more cytoplasm than a large
lymphocyte
Cytoplasm: pale blue-gray tint, few azurophil
granules
Nucleus eccentric and round or reniform
Circulate in blood for 1-2 days before
migrating
Differentiate into tissue macrophages

Ingest senescent cells and cellular debris


Defense against bacterial invasion
Process antigen and present it to lymphocytes

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