Blood
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Plasma and Cellular Elements of Blood
Hematopoiesis
RBC Physiology
Coagulation
Blood = connective tis sue
extracellular
matrix:
Plas m a
color ??
volume ??
specialized cells:
(Form e d e le m e nts )
RBCs
WBCs
Plate le ts
Plasma
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Water
Plasma proteins
• Albumin (60%)
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Osmotic Gradient
• Globulins (Ab)
• Fibrinogen
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Molecules
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Electrolytes
Nutrients
Trace Elements
Dissolved gases
Serum = Plasma – Clotting factors
Hem(at)opoiesis =
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Blood Cell Formation
Few uncommitted, pluripotent stem
cells in red bone marrow throughout
life time (Fig 16-2)
Controlled by cytokines, e.g.
• Erythropoietin (hormone or cytokine?)
• CSFs (Colony-stimulating factor)and
ILs (interleukins): e.g. M-CSF, IL-3 (=
multi CSF)
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Neulasta (pegfilgrastim) is a CSF
• Thrombopoietin (TPO)
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Some Terminology:
• Anemia vs. Leukemia vs. leukocytosis vs.
leukopenia
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Any of various acute or chronic neoplastic diseases of the
bone marrow in which unrestrained proliferation of white
blood cells occurs, usually accompanied by anemia,
impaired blood clotting, and enlargement of the lymph
nodes, liver, and spleen.
Leukemias (“white blood”) group of cancerous conditions of
WBCs. Named according to the abnormal WBC type
primarily involved (e.g. lymphocytic leukemia, myelocytic
leukemia). Leukemia is acute (quickly advancing - mostly in
children) if it derives from blast-type cells like
lymphoblasts, and chronic (slowly advancing - mostly in
adults) if it involves proliferation of later cell stages like
myelocytes.
Leukemia, lymphoma and myeloma are cancers that
originate in the bone marrow (in the case of leukemia and
myeloma) or in lymphatic tissues (in the case of
lymphoma).
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Leukemia, lymphoma and myeloma are considered to be
related cancers because they involve the uncontrolled
growth of cells with similar functions and origins. The
diseases result from an acquired (not inherited) genetic
injury to the DNA of a single cell, which becomes abnormal
(malignant) and multiplies continuously. The accumulation
of malignant cells interferes with the body's production of
healthy blood cells and makes the body unable to protect
itself against infections.
Leukemia - Leukemia is a malignant disease (cancer) that
originates in a cell in the marrow Non-Hodgkin Lymphoma
- Lymphoma is a general term for a group of cancers that
originate in the lymphatic system
Hodgkin Lymphoma - Hodgkin lymphoma (also known as
Hodgkin's disease) is a specialized form of lymphoma and
represents about 8 percent of all lymphomas diagnosed
each year
Myeloma - Myeloma is a cancer of plasma cells, a type of
white blood cell found in many tissues of the body, but
mainly in the marrow
Myelodysplastic Syndromes - Myelodysplastic syndromes
are a group of diseases that originate in an early bloodforming cell in the marrow
Leukopenia at
http://www.merck.com/pubs/mmanual/section11/chapte
r135/135a.htm
EPO Regulates RBC Production
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“Hormone” synthesized by kidneys
in response to hypoxemia
EPO gene cloned in 1985 
Recombinant EPO now available
(Epogen, Procrit)
Use in therapy, abuse in sport
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Bone marrow damage from
chemotherapy
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Chronic renal failure
Your book calls it a cytokine
because it is made on demand, not
stored. (p540).
Trivia Dept.: Neulasta®
(pegfilgrastim) stimulates
production of WBC
Running Problem:
Blood Doping
The Erythrocyte (RBC)
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Biconcave Disk, 7 μ
diameter, Carry O2
120 day lifespan
No mitochondria, no
nucleus
• ATP from glycolysis
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Bag of Hb
HCT = hematocrit = PCV
MCV-Mean Cell Volume
• ↓ in Fe-deficiency anemia
Hemoglobin (Hb)
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[Hb] often reported in CBC
• Four globulin proteins (Fig 18-8)
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Two αTwo βEach has the heme group
Heme is a porphyrin that binds Fe
Fe is considered a trace mineral
• Meat, beans, spinach
• Stored in liver, “recycled”
• Fe deficiency
Hemoglobin (Hb) Synthesis and
Breakdown
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Requires iron (Fe) + Vit. B12 (cobalamin)
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Reversible binding between Fe & O2
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Hb Breakdown:
• Hb → Bilirubin → bile.
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Hyperbilirubinemia
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Too fast causes icterus (jaundice)
• HbA vs. HbF
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Fetal Hb has two  chains instead of two  chains
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HbF is designed to steal oxygen from maternal blood in placenta.
Replaced shortly after birth.
CO is a product of incomplete combustion (complete combustion
producesCO2 and H2O.) This obviously includes exposures to fires by
victims and fire fighters but also includes smokers (cigars produce more
CO than cigarettes - up to 20% CO Hb possible). Exhaust fumes are a
common source of CO exposure. A recent report detailed high levels of CO
exposure in enclosed pickup truck beds from a backdraft of exhaust fumes
into the back of the truck.
Carbon monoxide also binds coordinately to heme iron atoms in a manner
similar to that of oxygen, but the binding of carbon monoxide to heme is
much stronger than that of oxygen. The preferential binding of carbon
monoxide to heme iron is largely responsible for the asphyxiation that
results from carbon monoxide poisoning.
RBC Disorders
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Too high PCV:
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Polycythemia vera
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Dehydration
(PCV ~ 60-70%)
Anemias (O2 carrying capacity of blood too low)
• Hemorrhagic anemia  Fe deficiency anemia
• Hemolytic anemia, due to genetic diseases (e.g.
Hereditary spherocytosis) or infections
• Pernicious anemia
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Vit. B12 Deficiency
• Aplastic anemia
• Renal anemia
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↓ EPO
• Sickle Cell Anemia
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Polycythemia vera most commonly due to bone marrow
cancer. Hematocrit can become as high as 80%. Secondary
poycytemia when less oxygen is available (high altitudes)
or EPO production increased. Polycythemia vera is a clonal
stem cell disorder characterized by excessive erythrocyte
production. Its etiology is not fully established, but
hypersensitivity to interleukin-3 may play a role in the
sustained erythrocytosis observed in this disease.
Polycythemia vera usually occurs within the age range of
20-80, with 60 being the mean age of onset. The disease is
slightly more common in males than in females. Clinical
features include headaches, weakness, weight loss, and
pruritus (itching without visible eruption on the skin).
Major Criteria
total RBC vol men > 36 mg/kg; women >32 mg/kg
arterial 02 saturation > 92%
Splenomegaly
Fe deficiency anemia USUALLY A SECONDARY RESULT OF
HEMORRHAGIC ANEMIAS. But also due to inadequate
intake of iron containing foods or impaired absorption.
Results in microcytes (pale small RBCs)
Pernicious anemia (p.621) leads to large pale cells due to
developing RBCs not dividing.
Aplastic anemia due to some toxic chemicals and drugs and
ionizing radiation. E.g.: arsenic, chloramphenicol. Fallout
from nuclear bomb, excessive exposure to X-rays. Cancer
and cancer chemotherapy. Marrow destruction of course
affects all formed elements, anemia is just one symptom.
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Sickle cell anemia HbS instead of
normal HbA. One in 100 black
newborns in US. Malaria connection:
RBCs loose potassium which is
essential for survival of parasite
(plasmodium)
Platelets = Thrombocytes
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Megakaryocyte (MK) is
polypoid. Mechanism?
MK produces ~ 4,000 platelets
• Lifespan 10 days.
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Platelets contain granules filled with clotting
proteins & cytokines
Activated when blood vessel
wall damaged
Hemostasis
= Opposite of hemorrhage  stops bleeding
 too much bleeding
Too much hemostasis  thrombi / emboli
Too little hemostasis
Three major steps:
1. Vasoconstriction
2. Platelet plug Temporarily blocks the hole
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Coagulation cascade (= clot formation seals hole
until tissues repaired)
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4.
Platelet-derived cytokines further the process
Two pathways: Extrinsic and Intrinsic
After vessel repair, plasmin dissolves the clot
Steps of Hemostasis
Vessel damage exposes collagen
fibers
Platelets adhere to collagen
& release factors
+ feedback loop
local vasoconstriction
decreased blood flow
&
platelet aggregation
platelet plug formation
Steps of Hemostasis cont.
1.
Two coagulation pathways converge
onto common pathway
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Intrinsic Pathway. Collagen exposure. All
factors needed are present in blood. Slower.
Extrinsic Pathway. Uses Tissue Factors
released by injured cells and a shortcut.
Usually both pathways are triggered
by same tissue damaging events.
The different factors can be subject
to a variety of problems
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2.
Hemophilia
Hypercoagulable states
Vit K needed for
synthesis of
several clotting
factors
Structure of Blood Clot
Plasmin,
trapped in clot,
will dissolve
clot by
fibrinolysis
SEM x 4625
Clot formation limited to
area of injury: Intact
endothelial cells release
anticoagulants (heparin,
antithrombin III, protein C).
Clot Busters & Anticoagulants
Dissolve obsolete or
unwanted clots
Prevent coagulation by
blocking 1 or more steps in
fibrin forming cascade
Enhance fibrinolysis
Inhibit platelet adhesion
plug prevention
Urokinase,
Streptokinase & t-PA
Examples:
Examples:
Coumadin (warfarin) blocks Vit K
EDTA chelates Ca2+
Aspirin prevents platelet plug
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Coumarin and warfarin block Vit K action
(Vitamin K is cofactor in synthesis of
several coagulation factors.
Ca chelators (EDTA and citrate) only in
vitro
Heparin inhibits activity of thrombin
(produced by basophils)
Aspirin prevents platelet plug fomation
Hemophilia
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It is sometimes called Christmas disease after
Stephen Christmas, the first patient described
with this disease. In addition, the first report of
its identification was published in the Christmas
edition of the British Medical Journal.
In more recent history, royal watchers know that
Queen Victoria of Britain's son Leopold had
hemophilia, and that two of her daughters, Alice
and Beatrice, were carriers of the gene. Through
them, hemophilia was passed to the royal
families in Spain and Russia, leading to one of
the most famous young men with the disease,
Tsar Nicholas II's only son Alekei.