Download Formed Elements of Blood

Formed Elements of Blood
Lecture Objectives
* Overview of Blood Structure &
Function
> Plasma
> Formed Elements
* Formed Elements in Detail
> RBC
> Leukocytes
> Platelets
* Overview of Hematopoiesis
Blood: specilized connective tissue
* Connective tissue = cells +
extracellular components
* Cells = Erythrocytes, Platelets,
Leukocytes
* Extracellular Components
(Plasma) = water, proteins,
dissolved gasses, electrolytes,
nutrients, regulatory
substances, waste materials
* Hematocrit
* Major Functions
Formed Elements of Blood (cells/liter)
* Erythrocytes: female/male =
3.9-5.0/4.3-5.7 x 1012
* Leukocytes
> Lymphocytes (26-27%):
0.9-2.9 x 109
> Monocytes (9%): 0.3-0.9 x
109
> Neutrophils (49-67%):
1.7-7.0 x 109
> Eosinophils (1-5%):
0.05-0.5 x 109
> Basophils (0-0.3%): 0-0.3
x 109
* Platelets
> 150-450 x 109
* CLINICAL CORRELATION:
Anemia
> Usually reflects reduction
in # of erythrocytes: blood
loss, reduced production,
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Formed Elements of Blood
elevated destruction
> Dietary causes: insufficient
dietary iron, vitamin B12,
folic acid
> Pernicious aneia =
autoimmune destruction of
parietal cells that make
intrinsic factor that is
required for vitamin B12
absorption by ilium
RBC's, platelets, neutrophils,
lymphocyte, monocyte (SEM)
* Same cells stained first for
identification in LM - can't tell
by SEM
* Lots of pseudopods on
leukocytes - these cells crawl,
phagocytose
* RBC's - biconcave shape
increases surface area, main
function carry O2 and CO2
* Leukocytes + platelets < 1%
blood volume = buffy coat
* ~ 1000 x more erythrocytes
than leukocytes
Plasma Components
* Water: ~91% of plasma by
weight, = solvent
* Proteins: ~ 7-8% by weight
> Albumin (70 kD)
~ colloid osmotic
pressure: blood &
tissue fluid volume
~ carrier: hormones,
metabolites, drugs
> Globins
~ Ig's (gamma
globulins) =
antibodies (plasma
cells)
~ non-immune
globulins (liver)
- colloid osmotic
pressue
- carriers: copper,
iron, hemoglobin
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Formed Elements of Blood
- fibronectin
- lipoproteins
- coagulation factors
(e.g. fibrinogen)
* Other solutes: ~1% by
weight
> polypeptides,
electrolytes, blood
gasses, hormones, waste
materials...
Erythrocytes in a capillary, thin section
(TEM)
* Biconcave shape
> Increased surface area for
gas exchange
> Very flexible -> keeps
viscosity down despite
high cell number
* Size: 7-8 micron diameter
(ruler)
* Cytoplasm = 33% solution of
hemoglobin
Erythrocyte entering sinusoid in the
spleen
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Formed Elements of Blood
Spectrin-based cell cortex of
erythrocytes
* Contributes to membrane
strength and flexibility
* Helps to maintain biconcave
shape
* Spectrin-based system links
membrane proteins...
* CLINICAL CORRELATION:
Hereditary spherocytosis (HS)
* Mutations in spectrin gene lead
to "egg shaped" RBC's
> Inherited as an autosomal
dominant trait (1 in 4000)
> Usually less than 15% of
the RBC's in elliptical
form
>
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Formed Elements of Blood
Generally benign ~10% of
affected people may
experience hemolytic
crises
> Treatment:
~ Transfusions for
hypoplastic crises and
during the first year or
two of life
~ Splenectomy (post 5
years of age)
CLINICAL CORRELATION: Sickle
cell disease
* Point mutation: surface residue
changes from Glu > Val
* Deoxygenated hemoglobin
(Hb) comea out of solution
* Genetic recessive: but,
heterozygotes may have
problems at high altitude, high
physical stress
* Solid aggregates of Hb:
> Causes abnormal cell
shape - "boats"
> Decreased cell life span
> Increases blood viscosity
-> can block flow in
capillaries causing anoxia
> Most devastating effects:
stroke
> Treatment: hydroxyurea to
reactivate fetal
haemoglobin production
Leukocytes (white blood cells)
* Not permanent blood cells
* Exit circulation and function in
tissues
> Diapedesis (dia = through,
pedesis = to leap)
> Normal cellular
components of connective
tissues
* Live only a few days, die by
apoptosis in connective tissue
* Two classes: granulocytes &
agranulocytes based upon
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Formed Elements of Blood
presence/absence of prominent
"specific granules"
> agranulocytes =
lymphocytes, monocytes
> granulocytes = neutrophils,
eosinophils, basophils
Neutrophil (LM)
* Multi-lobed nucleus
* 10-12 micron diameter
* Specialized phagocyte, first ro
enter area of bacterial infection
or tissue damage
* "Specific" granules: alkaline
phosphatase, collagenase,
lactoferrin (chelates iron,
"starves" bacteria), lysozyme,
and some non-enzymatic
antibacterial proteins
* Azurophilic granules (deep
purple) = lysosomes
> Burst in oxygen
consumption > 02 and
H2O2 (highly reactive
radical, kills ingested
microbe)
> Myeloperoxidase makes
hypochlorite = active
ingredient in bleach
* Few mitochondria
> Glycolysis used instead of
aerobic metabolism
> Why? -- Good for
anaerobic conditions,
inflamed or necrotic tissue
* CLINICAL CORRELATION:
Genetic deficiency in
HNADPH oxidase in
neutrophil azurophilic granules
> deficient 02 burst > children
have persistent infections
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Formed Elements of Blood
Diapedesis and chemotaxis
Neutrophil phagocytosis
Eosinophils
* Bilobed nucleus
* 10-12 micron diameter
* Large eosinophilic (pink-red)
"specific" granules
> Major basic protein (MBP)
(lots of ARG residues) >
forms crystals
> Eosinophilic cationic
protein (ECP) - forms
transmembrane pores: very
potent killing agent
> Eosinophilic peroxidase
(EPO)
> Eosinophil-derived
neurotoxin (EDN)
> Histaminase - neutralizes
histamine
> Arylsufatase - neutralizes
slow-reacting substance of
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Formed Elements of Blood
*
*
*
*
*
*
anaphalaxis (SRS-A)
secreted by basophils
> Collagenase
> Cathepsins - intracellular
acid proteinases
Cytotoxic effects on protzoans
and helminthic parasites ->
MBP, ECP & EPO
Nervous system dysfunction in
parasites -> EDN
Moderation of inflammatory
vasoactive agents ->
histamiase, arylsulfatase
Located in connective tissue
underlying skin, bronchi, GI
tract, uterus, vagina
Respiratory burst > oxidizes
bromide to form hypobromus
acid, more toxic, faster killing
than hypochlorite
Eosinophilia is an indicator of
allergic reactions, helminthic
infections
Basophil (LM)
* 0-1% of leukocytes
* 12-15 micron cell diameter
* Function: release mediators of
inflammation: histamine,
SRS-A (a group of
leukotrienes)
* Display IgE bound to Fc
receptors > reaction with
antigen leads to
activation/degranulation
* 0.5 micron basophilic specific
granules contain histamine,
SRS-A, and heparin sulfate
* Heparin sulfate - role in
inflammation not clear,
negative charge makes specific
granules basophilic
* Note that basophilic granules
almost obscure the multi-lobed
nucleus (different from
eosinophils)
* SRS-A:
> Potent inflammation signal
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Formed Elements of Blood
> Cause smooth muscle
contraction
* Basophils are similar in some
ways to mast cells: may
migrate in to supplement mast
cells in immediate
hypersensitivity reactions
Monocyte (left) and lymphocyte
(right)(LM)
* Monocytes
> 3-8% of leukocytes
> 12-20 micron cell diameter
- can be big cells
> Agranular blue-gray
cytoplasm
> Granules: azurephilic =
lysosomes for
phagocytosis
> Nucleus: oval, horseshoe,
kidney shaped
> Chromatin: "delicate"
distribution, stains less
intensely than in large
> Not terminal: migrate in
blood 14 hours, enters
tissues, -> macrophage
> Macrophage: phagocytic
cells in many places of
body
~ Secondary lymphoid
tissue, liver, lung,
connective tissue
~ Interacts with
lymphocytes to
regulate immune
response (antigen
presentation)
~ Major cell type at
inflammation site after
neutrophils are spent
* Lymphocytes
> 20-30% of leukocytes in
peripheral blood
> Small, most are 6-10
microns in diameter (like
erythrocytes)
>
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Formed Elements of Blood
Undifferentated
lymphocytes leave marrow
and travel to lymphoid
organs and tissues
> Most lymphocytes in blood
= recirculating
immunocompetent cells
~ Types = T, B, NK
> Large lymphocytes (up to
30 micron diameter) =
activated lymphocytes or
natural killer (NK) cells
> Details: lymphoid tissue
lecture, genetics,
immunology course
Lymphocyte (TEM)
Clickers...
Platelets (LM)
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Formed Elements of Blood
Platelet ultrastructure
* No nucleus
* Marginal band of microtubules
* Delta granules
> Very electron dense
> Contain elements picked
up from other cells and
stored temporarily
~ Calcium ions,
pyrophosphate, ADP,
ATP
~ Serotonin absorbed by
platelets from plasma
* Alpha granules
> Coagulation factors =
fibrinogen, factor V, factor
VIII (= von Willebrand
factor)
> Also: fibronectin,
thrombospondin,
platelet-derived growth
factor, other growth factors
(blood vessel repair)
* Lysosomes (aka lambda
granules): Contain hydrolytic
enzymes function late in vessel
repair during clot resorption
* Dense tubular system may be
site of prostaglandin synthesis
Platelet (TEM) showing marginal band
of microtubules
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Formed Elements of Blood
Platelets function in hemostasis
* Adhesion to exposed
connective tissue triggers
platelet aggregation and
formation of primary
hemostatic platelet plug
* Release of alpha and delta
granules:
> More coagulation factors
> Serotonin = potent
vasoconstrictor
> PDGF -> smooth muscle,
fibroblast division
* Primary clot contracts via
platelet actin and myosin ->
resores blood flow
* clot eventually removed by
plasmin (precursor =
plasminogen) + lambda
particles
* CLINICAL CORRELATION:
Glansman's disease: bleeding
disorder - loss of platelet
integrin via recessive mutation
in integrin subunit gene
Generation of platelets
* Megakaryocyte = large
polyploid cell with multilobed
nucleus
* Cell extensions fragment into
platelets
Megakaryocyte processes in sinusoid,
high magnification (SEM)
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Formed Elements of Blood
Megakaryocytes: endomitosis (l),
demarcation channels (r)
Model of major haematopoietic
maturation pathways
* HSC = haematopoietic stem
cell
>
lt = long term
>
st = short term
* CLP = common lymphoid
precursor
* CMP = common myeloid
precursor
* GMP =
granulocyte-macrophage
precursor
* MEP =
megakaryocyte-erythrocyte
precursor
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Formed Elements of Blood
Blood cell precursor morphology
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