Transcript BLOOD - Doctor Jade Main

BLOOD
Blood
• fluid connective tissue
• contains specialized cells-formed
elements
• suspended in matrix-plasma
• containing-collagen & elastic fibers
–protein fibers are in solution-visible
during clotting process
Functions
• transports & distributes nutrients,
gases, hormones & waste products
• regulates pH & ion composition of
interstitial fluids
• restricts fluid loss at injury sites
• defends against toxins & pathogens
• helps to maintain body temperature
Composition
• 8% of total body weight
–5-6 liters in males
–4-5L in females
• Temperature-38oC
–just above body temperature
• Viscosity 5X more viscous than
water
• pH between 7.35-7.45
Composition
• Whole blood = plasma +
formed elements
• red blood cells (RBCs)
• white blood cells (WBCs)
• platelets
• Centrifuged-separates into
three parts
• Bottom-erythrocytes
(RBCs)
• top-plasma
• junction of RBC & plasmabuffy coat
– contains WBCs &
platelets
Plasma Composition
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46-63% of blood volume
92% water
plasma proteins-made by liver
Albumin-60%
– major contributor to osmotic pressure
– transports fatty acids, steroid & thyroid hormones
• Globulins-35%
– from smallest to largest in molecular weights-alpha, beta &
gamma globulins
– used to transport hormones, metal ions, triglycerides and
lipids
– includes antibodies or immunoglobins
• defend against infections and foreign materials
• Fibrinogen-4%
– blood clotting
– fibrinogen is cleaved into fibrin-basic framework of clot
Erythrocytes
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most numerous of formed elements
number varies with health & altitude
– Peruvians who live 18,000 feet above sea
level may have as many as 8.3 x 106
RBCs/µl
contain hemoblobin (Hb)
– red pigment which transports O2 & CO2
– gives blood its color
Ratio of RBC/plasma is hematocrit
– % of whole blood occupied by cellular
elements: 40-45%-women; 37-48%-men
– almost entirely due to volume of RBCs
– provides estimate of packed cell volume
(PCV)
– PCV increases with dehydration & with
erythropoietin-protein which stimulates RBC
production
RBCs are a major contributor to blood viscosity
– as numbers increaseviscosity
increasesblood flow slowsblood
thinsflows more rapidly
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RBC Structure
simple-small, biconcave disc
plasma membrane-no nucleus & no organelles
bag of Hb
no nucleuscannot divide or make proteins
– can’t repair its self and has a short life span-120
days
shape is directly related to function-most important
transport of O2
– large surface area, relative to volume
– 30% more surface area than spherical cells
– larger surface area makes for faster gas
exchange
shape allows them to stack like dinner plates
– allows for smoother flow of blood through
vessels
Flexible
– able to pass through small capillaries
Modify shape in response to osmotic changes
– Hypotonic solutionswellsforms sphere
without disrupting integrity of membrane
– Hypertonic solutionshrinksforms spikey
surface
No mitochondria
– generate ATP anaerobically via glycolysis
– do not need O2- makes them very efficient O2
transporters
Hemoglobin (HB) Structure
• red pigment
• formed by 4 globular polypeptide
chains
• 2 & 2
• each chain has a molecule of heme
• each heme has iron (Fe) molecule
• each Fe can carry one molecule of
oxygentherefore each HB
molecule can carry 4 molecules of
oxygen
• Fe binds with O2
oxyhemoglobin bright red
• Fe-O2 bond is weak
• can separate easily without
damage to Fe or O2
• Hb from which O2 has separated is
deoxyhemoglobindark red
Hemoglobin Functions
• Transport gases-O2 &
CO2
– there are 280X106
Hb molecules in
each RBC
– each contain 4
heme groups
– gives blood
capacity to carry a
billion O2 molecules
• amount of O2 bound
depends on O2
content of plasma
Leukocytes-White Blood Cells
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less numerous than RBCS
1% of total blood volume
provide protection against
infections
complete cells
– typically have lobed nuclei,
organelles & no Hb
two groups based on appearance
after staining
Granulocytes
– contain cytoplasmic inclusions
– Basophils
– Eosinophils
– Neutrophils
Agranulocytes
– contain only a very few stained
granules
– Lymphocytes
– Monocytes
Neutrophils
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60-70% of circulating WBC population
live only about 10 hours
twice size of RBC
Nucleus-polymorphonuclear
– varied nuclear shapes
– mature have 3-5 lobes connected by slender nuclear
strands
cytoplasmic granules in cytoplasm are packed with
lysosomal enzymes & bacteria killing compounds
produced in response to acute body stress
– infection, infarction, trauma, emotional distress
can double in a few hours
highly mobile
– first WBC to arrive at injury site
specialize in attacking & digesting bacteria
when binds to bacteriummetabolic rate increases
H2O2 -hydrogen peroxide & O2- superoxide anions are
produced which kill bacteria
neutrophil + bacterium will fuse with a lysosome which
contains digestive enzymes & defensins
defensins kill bacteria & lysozymes digest them
makes prostaglandins & leukotrienes during this process
– restricts spread of infection & attracts other
phagocytotic cells
cell kills its self in the process
Neutrophils + other waste = pus
Eosinophils
• 2-4% of WBCs
• bilobed nuclei
• contain deep red
granules
• population increases
sharply during
parasitic infections &
allergic responses
• release histaminases
which combat the
effects of histamine
Basophils
• smallest part of WBC population0.5-1%
• large, deep purple granules in
cytoplasm
– hides nucleus
• increase in number during
infections
• leave blood & develop into mast
cells
• granules contain histamine,
serotonin & heparin
• histamine increases blood flow to
area which dilates blood vessels
• heparin prevents blood clotting
Monocytes
• largest agranulocytes
• 3-8% of WBC population
• nucleus is large
– clearly visible
– ovoid or kidney shaped
• cytoplasm contains sparse,
fine granules
• arrive in large numbers at
the site of an infection
• enlarge & differentiate into
wandering macrophages
Lymphocytes
• second most numerous circulating leukocyte25-33%
• Nucleus-large, round or slightly dimpled on one
side
• continually migrates from blood stream through
peripheral tissues & back to blood stream
• life span varies from several days to years
• B cells or B lymphocytes
– bone marrow derived
– make antibodies which attack foreign
antigens
• T lymphocytes or T cells
– thymus dependent cells
– provide cell mediated immunity
– attack foreign cells
• Natural Killer Cells
– immune surveillance cells
– detect &destroy abnormal tissue cells
– may help prevent cancer
Differential Cell Count
• determines number of each type of WBC in a
sample
• gives valuable information
• pathogens, infections, inflammation & allergic
reactions change WBC numbers
• count of different types can help to diagnose
disease and illness
• Leukopenia
– inadequate number
• Leuocytosis
– Excessive number
Blood Cell Formation
• all formed elements arise from
a single cell type: pluripotent
stem cell
• Hemocytoblast
• hematopoietic stem cell or
hemocytoblast
• rare-one in 10,000 bone
marrow cells
• cell differentiates along
maturation path which leads to
different kinds of blood cells
• each type produced in
different numbers in response
to needs & regulatory
factors-cytokines or
hormones
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Hemopoietic Tissues
Tissues producing blood cells
first-yolk sac
– makes stem cells that migrate
into embryo populate bone
marrow, liver, spleen &
thymus stem cells multiply &
give rise to blood cells
throughout fetal development
Liver
– primary site of RBC production
during 2-5th month neonatally
is liver & spleen
– stops making blood cells at
time of birth
Spleen
– stops soon after but continues
to make white blood cells
throughout life
red bone marrow produces all
formed elements from infancy
onward
Erythropoiesis
• inadequate oxygen (hypoxia)kidney EPO (erythopoietin)
stimulates production of RBCs
• Hemoblasts myeloid stem cellsproethryoblastearly erythroblasts
• early erhtyhroblasts multiply & make hemoglobinlate erythroblast
normoblast
• once normoblast accoulates 34% Hborganelles are ejected, nucleus
degeneratescell collapses inwardreticulocyte
• still has ribosomes & rough ER; leaves bone marrow
• matures in two daysmature erythrocyte
RBC LifeCycle
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RBC is terminally differentiated
cannot synthesize proteins, enzymes or
renew membranes
life span-about 120 days
engulfed & destroyed by phagocytotic cells in
liver, spleen and bone marrow
process is hemolysis
once hemolyzed-parts are broken down
globular proteins are disassembled into
amino acids
Heme splits from globin of HB molecule
Iron is stripped from hemebiliverdin
(green, organic compound)bilirubin
(orange/yellow pigment)released into
blood binds albumin transported to liver
for excretion in bile
– If circulating levels cannot be handled by
liverhyperbilirubinemia-condition
which turns peripheral tissues
yellowjaundice
Fe salvaged for reuse
toxic to body-must be stored &
transported bound to a protein
Tranferrin used for iron transport
hemosiderin for iron storage
in bone marrow Fe is taken into the
mitochondria of developing RBCs and is used
to make heme
WBC Production-Leukopoiesis
• begins with same pluripotent stem used in erythropoiesishemocytoblast
• differentiate into distinct types of CFUs-colony forming units
• CFUs go on to produce 3 cell lines committed to a certain outcome
• Myleoblasts
• Monoblasts
• Lymphoblasts
Leukopoiesis
Platelets-Thrombocytes
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not cells in strictest sense
– Fragments
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continuously replaced
always present-not active unless damage
has occurred
Thrombocytosis
– too many
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Throbocytopenia
– Too few
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if numbers drop below 50 X 103/ul there
is danger of uncontrolled bleeding
Functions
– contain chemicals for clotting
– form temporary platelet plug needed in
clotting
– secrete growth factors
– secrete chemical to attract neutrophils
and monocytes to site of inflammation
Thrombocytopoiesis
• occurs in bone marrow
• thrombopoieten-secreted by liverstimulate growth & maturation of
hemocytoblastsrepeated mitosis (up to 7X) without nuclear or
cytoplasmic divisionvery large polypoloid cell-megakaryocyte
• presses against sinusoid wallruptureplatelet fragments
• life span-about 5 – 9 days
Hemostasis
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cut or damaged blood vessels bleed
outflow must be stopped before shock & death occur
accomplished by solidification of blood or coagulation
also called clotting or hemostasis
clotting is
fast
localized
carefully controlled
three phases
– vascular spasm
– platelet plug formation
– coagulation phase
Vascular Spasm Phase
• blood vessels vasoconstrict
–diameter decreases at injury
site
• immediate & most effective in
small vessels
• contraction exposes underlying
basement membrane to
bloodstream
Platelet Plug Formation
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endothelial cell membranes become sticky
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sticky membranes allow platelets to adhere to injury
site
forms temporary plug within 1 minute of injury
as platelets keep arriving continue sticking to each
otherplatelet aggregationplatelet plug
plug seals break in vessel
as arrive become activatedchange shape
become more spherical & develop cytoplasmic
processes that extend toward other platelets
Release
– ADP-adenosine diphosphate
• aggregating agent
– Serotonin
• enhances vascular spasms
– Enzymes that help make Thromboxane A2
• recruits & activates more platelets &
stimulates vascular spasms
– PDGF
• platelet derived growth factor
• promotes vessel repair
– Calcium
• required for platelet aggregation
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Coagulation Phase
• occurs in asequence of steps
• requires 13 clotting factors
called procoagulants
• designated by Roman numerals
– many circulate as
proenzymes- inactive
precursors
• converted to active forms
during clotting process
• activated by proteolytic
cleavage & active proteases
• all but 3 are made & released
by the liver (III, IV, VIII)
• all but 2 (III & VIII) are always
present in blood
• activated platelets release 5
during platelet phase (III, IV, V,
VIII & XIII)
Coagulation Cascade
• activation of one
proenzymeactivates
another proenzyme
• chain reaction or reaction
cascade
• 2 reaction pathways to
coagulation:
• extrinsic
• Intrinsic
• Both lead to the formation of
prothrombinase
• at this point the two unitecommon pathway
Extrinsic Pathway
• shorter & faster-fewer
steps
• TF-tissue factor or
thromboplastin or clotting
factor III is released by
damaged blood vessels
• leaks into blood (extrinsic
to it)
• TF binds Ca++ & Factor VII
forming an enzyme
complex
• complex cleaves Factor X
(prothrombinase) active
factor X
• first step in common
pathway of coagulation
Intrinsic Pathway
• more complex & slower
• activators are in blood or
in direct contact with it
(intrinsic to it)
• contact with collagen
fibers or even glass of a
collecting vialactivates
Factor XII
• Begins a series of
reactions
• activated factors VIII & IX
combine to form enzyme
complex which activates
Factor X
Common Coagulation Pathway
• the two paths unite at a
common
pathwaythrombin
synthesis
• begins when activated
Factor X or
prothombinase converts
prothombin or Factor
IIthrombin
• Thrombin cleaves
fibrinogen or Factor I
(soluble)insoluble fibrin
The Clot
• fibrin glues platelets
together forming intertwined
web
– structural basis of a clot
• thrombin & Ca++ activate
Factor XIII-fibrin stabilizing
factor
• cross linking enzyme
• forms covalent bonds
between fibrin molecules
converting them into
insoluble meshwork
• stabilizes clot
Clot Retraction
• further stabilizes clot
• occurs minutes after
initial clot formation
• platelets contain
contractile proteins-actin
& myosin
• these contract pull
fibrin strands together
• squeezing out serum
compacts clot
• functions to:
• pull torn edges of broken
vessel together
• reduce size of damaged
area
Rebuilding
• begins with clot formation
• PDGFstimulates smooth muscle cells &
fibroblast division to rebuild vessel wall
– angiogenesis
• Thrombin, factors VII & X promote healing
by stimulating growth of new blood vessels
at site of damage
Fibrinolysis
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hemostasis is not complete until clot has been dissolved
plasminogen is incorporated into clot as it forms
nearby cells release TPA-tissue pasminogen activator
binds to fibren and activates plasimnogen converting it
to plasmin
• plasmin digests fibrindissolving clot
Control of Clotting
• clotting must be carefully
regulated
• inappropriate formationlife-threatening
– too much-thrombus
• clotting-restricted by
several mechanisms
• 1. Platelets do not adhere
to normal endothelium
– intact endothelial cells
convert membrane lipids into
prostacyclin
• blocks platelet adhesion &
aggregation
• limits platelet plug to area of
damage
Control of Clotting
• Plasma contains
anticoagulants
– Antithrombin III
inactivates thrombin
– Heparin accelerates
activation of
antithrombin III
enhances inhibition
of thrombin synthesis
Control of Clotting
• 3. Endothelial cells
release
thrombomodulin-binds
to thrombin converts
it into enzyme that
activates protein c
• Protein Cinactivates
clotting factors &
stimulates plasmin
formation
Thromboembolytic Disorders
• Undesirable
clottingthrombus
– blood clots in unbroken
vessels
• gets into coronary
circulationheart attack
• thrombus that breaks away
& floats freeembolus
• Cerebral embolusstroke
• Pulmonary emboluslung
• Conditions that roughen
endothelium encourage clot
formation– Arteriosclerosis
Bleeding Disorders
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Thrombocytopenia
– deficient platelet number
– can result in spontaneous bleeding from small vessels
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– liver makes procoagulants & when unable to do so result is severe bleeding
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Deficiency of Vitamin K
– may be a cause of liver dysfunction
– cofactor needed for synthesis of factors II, VII, IX, X & proteins C & S
– blocking action of vitamin K helps prevent inappropriate clotting
• Warfarin-vitamin K antagonist
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not enough produced or mutant version fails to perform properly
von Willebrand disease-most common
Hemophilia A-classic-factor VIII deficiency
antihemophilic factor-hemophilia B
factor XI deficiency-hemophilia Cactor XI deficiency-in both sexes
Lowered Calcium
– affects nearly all clotting pathways
– any lowering of Ca impairs blood clotting
Hemophilia Inheritance
ABO Blood Types
• blood type-determined by
presence or absence of
antigens-A and B
• Presence of A-blood type
A
• Presence of B-blood type
B
• Presense of both-blood
type AB
• Absence of both-blood
type O
ABO Blood Types
• antibodies begin to appear in
plasma 2 to 8 months after
birth
• person produces antibodies
against antigens that are not
present on his or her RBCs
• Blood type A-makes antibody
B
• Blood type B-makes antibody
A
• Blood type O-makes
antibodies A & B
• Blood type AB-does not make
antibodies
Blood Type
• Antigens are often referred to as agglutinogens
• Antibodies-immunoglobulins are made by immune
system in response to foreign material-agglutinins
• antibody adheres to foreign material & eliminates it
• presence of antigens on cells is a way for immune
system to decide whether substance is foreign or not
• immune system ignores surface antigens on your RBCs
• when blood-type antigen senses foreign antigen has
entered system alerts immune system to create
antibodies to that antigen
– antibodies attach themselves to foreign antigens
destroy them
• when attack foreign cellsclump together-agglutinatetermed agglutination
Agglutination
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Antibodies react against A or B antigen except those of one’s own RBCs
person with antigen A produces anti-B antibodiesattack type B antigens
person with antigen B produces anti-A antibodiesattack type A antigens
person with neither A or B antigens produces both anti-A & anti-B antibodies
person with both antigens A & B will produce no antibodies
When antibody meets specific surface antigenRBCs agglutinate & may
hemolyze
– Cross reaction or transfusion reaction
– can be dangerous to receive wrong blood type during a transfusion
Compatibility can be verified with blood typing
– mix small sample of blood with anti-A or anti-B antibodies-called
antiserum
– presence or absence of clumping is determined for each type of
antiserum
– clumping only with anti-A serum blood type A
– clumping only with anti-B serumblood type B
– clumping with both antigensblood type AB
– Absence of clumping with either antigenblood type O
Universal Donor & Recipient
• Type O-universal donor
–no surface antigensrecipient’s
blood can have antibodies but there
will be no clumping
• Type AB-universal receiver
–holds no antibodies to react with
antigens
Antigen D-Rh Factor
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rhesus antigen
in Rh negative individuals D antigen is missing
84% of humans are Rh positive
Blood Type A+ carries A & Rh antigens
shouldn't mix A+ with A- blood
blood must also be typed for Rh factor
Anti-D antibodies are not normally found in blood as anti a and b
antibodies are
form only in Rh negative individuals who are exposed to Rh positive
blood
Rh negative person receives Rh positive transfusionrecipient
produces anti-d antibodies
Anti-d does not appear instantaneously
presents little danger
if person gets another Rh positive transfusion, his or her anti-D could
agglutinate donor’s RBCs