Blood

 Blood – a fluid connective tissue

Functions of blood:
 1. Distribution
a. deliver O2 and nutrients to cells
b. remove metabolic waste
c. transport hormones to targets
 2. Regulation
a. maintain body temp →distribute heat from
muscles
b. maintain pH
c. maintain fluid volume
 3. Protection
a. restrict loss at injury (clotting)
b. prevent infection (leukocytes)
Characteristics of blood
-pH 7.4
-temperature 38°C / 100.4°F
-total volume 4-6 L (9-11 pints)
to estimate your own blood
volume:
7% body weight in kg =
blood in L
(1 kg = 2.2 lb)
(weight lb / 2.2) X 0.07
Composition of blood:
 plasma: ~55% water + soluble
proteins
Blood cells = formed elements:

-Erythrocytes: ~45%
transport O2
-Leukocytes: < 1%
defense
-Platelets: < 1%
cell fragments,for clotting
Plasma:

-90% water + dissolved solutes

(nutrients, gasses, hormones,
wastes, ions, proteins)
Plasma Proteins (~8% of total
plasma) -7.6g/100ml (5X more
proteins than interstitial fluid)
-These proteins remain in
plasma, not absorbed by cells for
nutrients
Albumins
(60% of plasma proteins)
Produced by the liver
Functions:
◦ -act as pH buffer for blood
◦ -contribute to osmotic pressure of
◦ blood (keep water in blood)
◦ -transport fatty acids and hormones
Globulins
(35% of plasma proteins)
A. Gamma globulins / Antibodies /
Immunoglobulins:
◦ -produced by plasma cells in the
◦ lymphatic system
◦ -function to attack foreign substances
B. Alpha and Beta globulins /
Transport globulins:
◦ -produced by the liver
◦ -function to transport small or insoluble
compounds to prevent filtration loss by
kidney
Clotting Factors
(4% of plasma proteins)
◦ -produced by the liver
◦ -11 total, fibrinogen most abundant
◦ -all function to promote or form a clot
◦ (serum = plasma – fibrinogen)
Other (1% of plasma proteins)
◦ -From liver:
 -metabolic enzymes and antibacterial
proteins
◦ -From endocrine organs:
 -hormones
Hematopoiesis

blood cell production

-all formed elements arise from
the same progenitor cell: the
hemocytoblast, located in the red
bone marrow
Occurs in the red bone marrow. In
adults ,haemopoiesis is confined in
flat bones, irregular bones, ends of
long bones, i. e the sternum, ribs,
pelvis & skull.
Erythrocytes (RBCs)
-99.9% of the formed elements of
blood
-1/3 of total body cells
(average human = ~75 trillion cells)
-Average RBC count = 4.2-6.3
million/μl
◦ Hematocrit = % of whole blood occupied
by formed elements (mostly
erythrocytes: 99.9% )
 male = 46%
 female = 42%
structure
-biconcave
disc
-7.8μm
diameter
-large
surface area
for gas
exchange
-can fold
and stack to
pass narrow
vessels
Erythrocytes (RBCs)
mature erythrocytes lack all
organelles
◦ -no division, no repair
◦ -low metabolic demands
-lifespan < 120 days
-cell is 97% hemoglobin protein
(red color)
◦ -hemoglobin transports O2 and some
CO2
Hemoglobin Molecule (Hb)
-2 α chains
-2 β chains
 -each chain has one heme group with
iron in center:
 iron binds O2
◦ Oxyhemoglobin = O2 bound, bright red
◦ Deoxyhemoglobin = no O2, burgundy
 -fetalHb binds O2 more strongly than
adult: insures transfer of O2 from mom
 -most O2 is carried in blood bound to
Hb (some in plasma)
 -only 20% CO2 carried by Hb:
◦ Carbaminohemoglobin - CO2 bound to
amino acids on α /β chains, not on heme
 Oxygen transportation

280million Hb/ RBC X 4 hemes/Hb, each heme binds 1 O2 = >1 billion

O2 per RBC (25 trillion RBC per person)

when plasma O2 is low, Hb
releases O2 and binds CO2
-at lungs CO2 exchanged for O2
by diffusion
ERYTHROPOIESIS
red blood cell formation
-2 million/ sec (1 oz new blood per day)
-occurs in reticular CT in red bone marrow,
in spongy bone
Erythropoiesis
1. Hemocytoblast differentiates into myeloid
stem cell
2. followed by many stages of differentiation,
all involve ↑ protein synthesis
3. cell fills with Hb, loses organelles (nucleus
too)
4. 3-5 days reticulocytes are formed (Hb +
some ribosomes), released into blood, 1-2%
of total blood RBCs
5. 2 days in circulation lose ribosomes (no
more protein synthesis) = mature
erythrocyte

 -Vitamin B12 necessary for erythropoiesis for

stem cell division
 Lack B12 = pernicious anemia
Erythropoietin (EPO)
-hormone, released by kidney during
hypoxia
(low O2)
-stimulate RBC production:
-↑ cell division rates (up to 30million/sec)
-↑ Hb synthesis = ↓ maturation time
“blood doping” = injecting EPO or RBCs to
enhance athletic performance: ↑ O2 to
tissues, but also ↑ hematocrit/viscosity =
clots, stroke, heart strain
Kidney failure often = low RBCs due to lack
of EPO
Erythrocyte Recycling /
Destruction
 -old/damaged RBCs removed by
phagocytes
in spleen, bone marrow and liver by
reticuloendothelial cells.
 -replaced by new, ~1% turnover per day
phagocytosed cells broken down:
-protein → amino acids, released for use
-heme →
◦ 1. iron removed, bound to transferrin in blood
for recycling back to bone marrow (new RBCs)
◦ 2. pigment → biliverdin (green)
◦ biliverdin → bilirubin (yellow-green),
◦ released into blood, filtered by liver, excreted
in bile
◦ 3. in gut, bilirubin → urobilins (yellow) &
stercobilins (brown) via bacteria
◦ urobilins absorbed, excreted in urine
◦ stercobilins remain in feces
Blood Types
-allcell membranes have surface
antigens: indicate “self” (antigen
= substance that triggers
immune response)
-RBCs have 50+, 3 important for
transfusion:
agglutinogens: A, B, D
The ABO & Rhesus
System
Type A blood = surface antigen A
(40%)
Type B blood = surface antigen B
(10%)
Type AB blood = both A + B
antigens (4%)
Type O blood =neither A nor B
antigen (46%)
Rh+ = surface antigen D (85%)
Rh- = no D antigen (15%)
The ABO & Rhesus
System
Type A blood = antibodies
against B antigen
Type B blood = antibodies
against A antigen
Type AB blood = neither antibody
Type O blood = antibodies
against both A & B
Rh (Rhesus) Factor
Up to 8 genes determine if a
person is Rh positive.
The most common of these are
the C, D & E genes which
determine if a person has C, D
and/or E antigens on the walls
of the cells.
People who do not have Rh
antigens on their cell
membranes are Rh negative
Antibody/Antigen
Reactions
When antibodies in plasma react
with antigens on cell membranes,
they bind to the cells causing the
cells to clump.
The clumping of cells due to
antigen/antibody reactions is
called agglutination
Agglutinated cells block the flow
of blood disrupting circulation and
the distribution of O2, gases and
nutrients
-antibodies against D antigen only form
upon
exposure and are small enough to cross

placenta
blood typing always done before
transfusion to prevent body wide
agglutination
-if blood type unknown: type O- =
universal donor: it lacks all 3
agglutinogens (A, B, D) so no risk of
agglutination by antibodies in anyone
Leukocytes (WBCs)
-< 1% total blood volume
-5 types
-functions:
◦ -defend against pathogens
◦ -remove toxins and wastes
◦ -remove abnormal/damaged cells
-all have nuclei & organelles, no
hemoglobin
-6000-9000 leukocytes/μl blood
-use blood to travel to tissues, not
permanent residents of blood
characteristics:
1. ameoboid movement
2. diapedesis (move out of
blood):
◦ a. margination = adhere to vessel
◦ b. emigration = pass between
endothelial cells
3. exhibit positive chemotaxis
4. phagocytosis (3 of 5) engulf
pathogens and debris
Types of Leukocytes
Granulocytes
Neutrophil (a.k.a PMNs)
(polymorphonuclear leukocytes)
 -Non-specific defense
 -Phagocytic
 -50-70% of WBCs
 -3-5 lobed nucleus
 -12μm diameter
 -Granules contain enzymes and
defensins
 -Very mobile: first at injury
 -Life span less than10h
Functions:

-Respiratory burst: H2O2 & O2

-, kill phagocytosed things
-Degranulation: release
defensins, lyse bacteria
-Prostaglandins: induce
inflammation to stop spread of
injury
-Leukotrienes: attract phagocytes
Eosinophil
-Non-specific Functions:
-Phagocytosis of
defense
-Phagocytic antibody covered
objects
-2-4% of WBCs -Defense against
-Bilobed nucleus parasites:
-12μm diameter exocytose toxins
-Granules on large pathogens
-Reduce
contain
toxins
inflammation:
anti-inflammatory
Life span 9 d
chemicals/
enzymes
Basophil
 In tissues = Mast Functions:
cell  Inflammation
 -Non-specific Allergic response
defense (via histamine)
 -Not phagocytic
 -Less than 1% of
WBCs
 -“U” shaped
nucleus
 -8-10μm diameter
 -Granules contain
Histamine: dilate
blood vessels
 Heparin: prevents
clotting
 -Life span 9 d
Monocyte Functions:
In tissues =Macrophage  -Phagocytosis: virus &
 -Non-specific defense
bacteria
 -Phagocytic= multiply  Synthesize and release
and ‘wall off’ a site of chemicals; cytokines
infetion e.g interlukin 1
 -2-8% of WBCs  -Attract phagocytes
 -Kidney shaped  -Attract fibroblasts for
nucleus scar formation
 -15μm + diameter  -Activate lymphocytes:
 -Circulate 24 h, exit to mount immune
to tissues = response
 Links non specific with
macrophage
 -Life span several specific immunity
defense systems
months  ↑in microbial infections,
collagen & infective bowel
conditions.
monocytes
 Macrophage: important in inflammation
and immunity.
 Monocyte –macrophage system.
(reticuloendothelial system)-includes both
mobile and fixed monocytes and
macrophages within the body.
 Fixed macrophages:
◦ Histiocytes in CT
◦ Synovial cells in joints
◦ Langerhans cells in skin
◦ Microglia in brain
◦ Kupffer ells in the liver
◦ Alveolar macrophages in the lungs
◦ Sinus lining macrophages (reticular cells in the
spleen, thymus & lymph nodes)
◦ Mesangial cells in the glomerulus
◦ Osteoclasts in bone
Lymphocyte Function depends
-Immune response on type, 3 types:
-20-30% of WBCs B cells: humoral
-Large round immunity (secrete
nucleus antibodies)
-5-17μm diameter T cells:
-Migratory cellmediated
between blood and immunity (attack
tissues foreign cells)
-Most in lymphatic NK cells: immune
system surveillance
-Life span days to (destroy abnormal
lifetime tissue)
Leukopoiesis(WBC
production)
Myeloid stem cells → Basophils,
Eosinophils, Neutrophils,
Macrophages as directed by
specific colony stimulating factors
(CSF) produced by Macrophages
and T cells (different CSF
(hormone) results in different
cell)
Platelets (Thrombocytes)
-flattened discs, 2-4μm diameter, 1μm
thick
-cell fragments, no nucleus
-constantly replaced, 9-12 d in circulation,
then phagocytosed by cells in spleen
-350,000 / μl blood
-Thrombopoietin from the kidneys
stimulates production
-1/3 of total platelets held in reserve in
spleen, mobilized for crisis
 Functions:
◦ -transport clotting chemicals, release when
activated
◦ -form patch (platelet plug) over damaged
vessel
◦ -contract wound after clotting (contain actin
and myosin)
 THROMBOCYTOPOIESIS
-Megakaryocyte in bone marrow breaks of membrane enclosed cytoplasm to
blood
-Each megakaryocyte can produce ~4000 platelets
-Induced by thrombopoietin from kidney and CSF from leukocytes
Thrombocytopenia = too few platelets < 80,000/μl, results in bleeding
and petechia
Thrombocytosis = too many plateletsv> 1 million/μl, due to cancer or
infection, clotting risk
Hemostasis
steps
1. vasoconstriction
Platelet in contact with damaged
vessels becomes sticky and adhere to
the damaged wall. They then release
platelet factors (serotonin) which
constricts the vessel, reducing blood
flow. Other chemicals for
vasoconstriction include, thromboxane
released by the damaged vessel itself.
2. platelet plug formation; Platelets -
Form temporary plug by clumping
together and release other factors e.g
ADP which attracts more palatelets to
the site forming a temporary seal/
plug.
3. coagulation: complex series of
steps, involves +feedback mechanism.
Involves xiii factors of coagulation.
Results in formation of insoluble thread
like mesh of fibrin which traps blood
cells and stronger than the palatelet
plug.
Platelet factors - React with Calcium
(Ca2+) & other clotting factors in the
plasma to initiate clot formation.
Thromboplastin - a
lipid (Tissue Factor)
released from
injured cell
membranes which
accelerates the
clotting process.
•A plasma protein
(Prothrombin) is
converted by
prothrombin
activator into an
enzyme Thrombin
•Thrombin converts
the plasma protein
Fibrinogen into the
insoluble protein
Fibrin
Fibrin forms a mesh
which glues the
platelets & RBCs
together to form the
clot.
Prothrombin activator can be formed
in two ways
Extrinsic pathway; occurs rapidly, with
tissue damage outside circulation.
Damaged tissues releases
thromboplastin (TF) which initiates
coagulation.
Intrinsic pathway; slower, confined in
circulation, triggered by damage to
blood vessel endothelium and platelet
adherence.
After sometime the clot shrinks and
paltelet contracts squeezing out
serum,shrinkage pulls the edges of
vessels together and reduces blood
loss closing the hole in the vessel,
4. Fibrinolysis
Involves the removal of the clot
and initiation of the healing
process
Plasminogen present in the clot is
converted to plasmin
Plasmin mediates breakdown of
fibrin to waste products removed
by phagocytosis.
Healing process then restores the
integrity of the vessel.
Control of coagulation
Heparin - A natural anticoagulant
which prevents clot formation by
inhibiting thrombin formation
The binding of thrombin to a special
thrombin receptor on the cells lining
the blood vessels: once bound
thrombin is iinactivated.
Perfect smooothness oof blood
vessels lining restricts paltelet
adherence.
Factors Affecting Clot
Formation
Vitamin K - Required by liver
to produce prothrombin &
several other clotting factors.
Calcium - Necessary for
prothrombin conversion into
thrombin & fibrinogen
conversion into fibrin.
Thromboplastin - Speeds up
clot formation from 3 - 6
minutes to 15 seconds.
Factors Affecting Clot
Formation
Heparin - A natural anticoagulant
which prevents clot formation by
inhibiting thrombin formation.
Sodium Citrate - An agent used on
glassware & instruments to
prevent coagulation by tying up
Calcium.
Plasmin (Fibrinolysin) - Breaks
down clots by dissolving the fibrin
after the clot is no longer needed