Basic tidbits on the physiology of the blood.

1. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.
Blood I
PHL 4201: Body fluids & Blood
Dr K.G. Ibrahim (aka Dr Ghandi)
Department of Physiology,
Faculty of Basic Medical Sciences,
College of Health Sciences,
Usmanu Danfodiyo University,
Sokoto.
ghandi.kasimu@udusok.edu.ng

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Red Blood Cells (Erythrocytes)
• Carry hemoglobin, bearing O2 to the tissues
• Contain carbonic anhydrase, which catalyzes
the reaction:
CO2 + H2O H2CO3
- allows large amounts of CO2 to be carried in
solution as HCO3
-
• Hemoglobin is an excellent acid-base buffer

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RBC Size and Shape
• Biconcave discs
• Mean 7.8 x 2.5 microns (thickest) or x 1
micron (center)
• Average volume 90-95 micrometers3
• Redundant membranes allows
deformation to squeeze through
capillaries

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RBC Count and Indices
• Men: 5,200,000 (± 300,000) / mm3
• Women: 4,700,000 (± 300,000) / mm3
- RBC counts can be increased at higher
altitudes

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Hemoglobin and Hematocrit
• Normal hemoglobin concentration is 34 g
per 100 ml of packed cells
• Normal hematocrit (“packed cell volume”)
is 40-45% (slightly lower in women)
• Thus normal hemoglobin is 14-15 g per
100 ml of blood
• O2 carrying capacity is 1.34 ml / g Hgb, or
19-20 ml O2 / 100 ml blood

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Sites of Erythropoiesis
• First few weeks of gestation – yolk sac
• Mid-trimester – Liver (+ spleen, lymph
nodes)
• Last month of gestation through
adulthood – Bone marrow

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Sites of Erythropoiesis by Age

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Hematopoiesis
• Pluripotent hematopoietic stem cells give
rise sequentially to committed stem cells and
mature cells
• Driven by
– Growth inducers (factors; e.g. interleukin-3)
– Differentiation inducers
• Hematopoiesis responds to changing
conditions
– Hypoxia: erythropoiesis
– Infection / inflammation: WBC production

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Blood Cell Lineages

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Erythropoiesis and Anemia

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Regulation of Red Cell Mass
• Red blood cell mass is regulated within a
relatively narrow range to…
– Maintain adequate oxygen carrying capacity
– Avoid excessive blood viscosity
• If the bone marrow is damaged or if
demand for erythropoiesis is extreme,
other parts of the bone marrow may
become hyperplastic, or extramedullary
hematopoiesis may occur.

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Tissue O2 and Erythropoietin

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Formation of Hemoglobin
• Occurs from proerythroblast through
reticulocyte stage
• Reticulocytes retain a small amount of
endoplasmic reticulum and mRNA,
supporting continued hemoglobin
synthesis

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Formation of Hemoglobin

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Types of Globin Chains
• Several types of globin chains resulting from
gene duplication – α, β, γ, δ; MW ~ 16,000
• Predominant form in adults is Hemoglobin A,
with 2 α and 2 β chains; MW 64,458
• Each globin chain is associated with one heme
group containing one atom of iron
• Each of the four iron atoms can bind loosely
with one molecule (2 atoms) of oxygen
• Thus each hemoglobin molecule can transport
8 oxygen atoms

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Variation in Globin Chains
• Modest differences in O2 binding
affinities
• Sickle hemoglobin:
Glutamic acid Valine at AA 6
• Hemoglobin of homozygous individuals
(“SS”) forms elongated crystals when
exposed to low O2
hemolysis, vascular occlusion

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Oxygen Binding to Hemoglobin
• Must be loosely bound – binding in
settings of higher O2 concentration,
releasing in settings of lower
concentration
• Binds loosely with one of the coordination
bonds of iron
• Carried as molecular oxygen (not as ionic
oxygen)

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Degradation of Hemoglobin
• When RBCs rupture, hemoglobin is
phagocytosed by macrophages, particularly
in the liver and spleen
• Iron is released back to transferrin in the
blood to support erythropoiesis or be
stored as ferritin
• Macrophages convert the porphyrin portion,
stepwise, into bilirubin, which is released
into the blood and secreted by the liver into
the bile

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Defense Against Infection
• Our world is teeming with microorganisms,
which can be beneficial or harmful.
• Phagocytes can ingest and destroy invading
organisms, and participate in tissue
reactions that “wall off” infection.
• Other white cells (lymphocytes, next chapter)
mediate responses that destroy or neutralize
specific microorganisms.

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White Blood Cells
• Circulate in blood and may enter the tissues
• Are of six types:
- Polymorphonuclear neutrophils
- “ eosinophils
- “ basophils
- Monocytes
- Lymphocytes (plasma cells)
- Platelets (from megakaryocytes)

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White Blood Cell Counts
• Total WBC ~ 7,000 / mm3
(almost 1,000-fold fewer than RBCs)
• Proportions:
- Neutrophils 62%
- Eosinophils 2.3%
- Basophils 0.4%
- Monocytes 5.3%
- Lymphocytes 30%
• Platelets ~ 300,000 / mm3

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Genesis of White Blood Cells
• Granulocytes and monocytes develop in the
bone marrow, and most remain there until
needed peripherally (number in marrow ~3x
blood; 6-day supply)
• Lymphocytes develop mostly in the
peripheral lymphoid organs (thymus, spleen,
tonsils, lymph nodes, Peyer’s patches)
• Megakaryocytes develop and reside in the
marrow, fragment to release platelets

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Life Span of White Blood Cells
• Granulocytes:
– Circulating, 4 – 8 hours
– In the tissues, 4 – 5 days
(shorter timelines with infection, inflammation)
• Monocytes / Macrophages:
– Circulating, 10 – 20 hours
– As tissue macrophages, months or longer
• Lymphocytes:
– Continuously re-circulate: lymph…nodes…blood
– Long-lived… weeks, months, longer
• Platelets: ~ Replaced every ten days

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Neutrophils and Macrophages
• Neutrophils are mature cells that can respond
immediately to infection
• Monocytes mature in the tissues to become
macrophages
• Both exhibit motility:
– Diapedesis
– Ameboid motion
– Chemotaxis (Chemoattractants: bacterial or tissue
degradation products, complement fragments, other
chemical mediators)

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Neutrophil Margination & Migration

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Phagocytosis
• “Phagocytosis” is the ingestion of particles
• Phagocytes must distinguish foreign particles
from host tissues
• Appropriate phagocytic targets:
– May have rough surfaces
– Lack protective protein coats
– May be immunologically marked for phagocytosis by
antibodies or complement components that are
recognized by receptors on the phagocytes
… this immunologic marking is called
“opsonization”

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Phagocytosis
• Neutrophils: can ingest 3-20 bacteria
• Macrophages: After being activated in the
tissues, are extremely effective phagocytes
(up to ~100 bacteria)
• Macrophages can ingest larger particles…
– Damaged RBCs
– Malarial parasites
• Macrophages can extrude digestion products
and survive and function for many months

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Digestion of Ingested Particles
• In both neutrophils and macrophages,
phagosomes fuse with lysosomes and
other granules to form phagolysosomes
(digestive vesicles)
• These contain proteolytic enzymes, and
in macrophages, lipases (important in
killing tuberculosis bacillus and some
other bacteria)

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Bactericidal Agents
• Bacteria may be killed even if they are not
digested
• Enzymes in the phagosome or in
peroxisomes generate strongly bactericidal
reactive oxygen species…
– Superoxide (O2
-)
– Hydrogen peroxide (H2O2)
– Hydroxyl ions (OH-)
– Myeloperoxidase catalyzes H2O2 + 2 Cl- …
… 2 H+ + 2 ClO-

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Eosinophils
• Eosinophils are weak phagocytes and exhibit
chemotaxis
• Particularly important in defense against
parasites
• Can adhere to parasites and release substances
that kill them (hydrolases, reactive oxygen
species, major basic protein)
• Also accumulate in tissues affected by allergies,
perhaps in response to eosinophil chemotactic
factor from basophils (eosinophils may detoxify
some products of basophils)

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Basophils
• Similar to mast cells adjacent to capillaries
– both cell types release heparin
• Basophils and mast cells both release
histamine, bradykinin, and serotonin
• When IgE bound to receptors on their surfaces
is cross-linked by its specific antigen, mast cells
and basophils degranulate, releasing…
– histamine, bradykinin, serotonin, heparin,
leukotrienes, and several lysosomal enzymes