Blood

and Hematopoiesis

TA: Breann Yanagisawa

Johns Hopkins Pathobiology Program
September 8, 2014

 Lecture Overview
Blood Physiology
FuncIons, components, cell types, hematopoiesis,
homeostasis, hemostasis
Blood Pathology
Techniques, Red blood cell disorders, white blood
cell disorders
 Blood Physiology FuncIons
Blood is important in many funcIons including:
TransportaIon of:
Oxygen and nutrients
Metabolic waste for eliminaIon
Hormones
RegulaIon of:
Body temperature
Body Issue pH
Fluid volume
PrevenIon of:
Blood loss through cloPng mechanisms
InfecIon through immune mechanisms
 Blood Physiology Components
Blood is made up of two
main parts:
Plasma liquid
Mostly water and dissolved
solutes
Proteins
Albumin
CloPng factors
Non-protein substances
Nutrients, metabolic
byproducts,
hormones, etc.
Formed elements cells
Buy coat
Erythrocytes Adapted from Human Anatomy and Physiology 2nd Edi8on, Marieb
 Blood Physiology Cell Types
Erythrocytes (Red Blood Cells)
Most abundant (45% of
blood volume hematocrit)
Males: 47% 5%, Females
42% 5%
Biconcave disc
Anucleate

Main funcIon: oxygen

transport
Adapted from Human Anatomy and Physiology 2nd Edi8on, Marieb
 ASH Teaching Slides: Blood Cells

The appearance of normal circulating blood is

relatively uniform with little variation in size and
shape. Red blood cells will have an area of paleness
in the center, which is approximately one-third the
diameter of the cell.

Maslak, P. ASH Image Bank 2008;2008:8-00044. Copyright 2008 American Society of Hematology.
 Blood Physiology Red Blood Cells
High surface area to volume
raIo
Hemoglobin
Globin: two , two chains
Heme: four heme groups
containing iron (Fe)
Bind easily to oxygen
Carbon dioxide transport
back to lungs

Adapted from Human Anatomy and Physiology 2nd Edi8on, Marieb

 Blood Physiology White Blood Cells
Leukocytes White blood cells
Less abundant (<1% of blood volume)
4,800-10,800/uL of blood

Main funcIon: immune response

Two categories:
Granulocytes
Agranulocytes
 Blood Physiology White Blood Cells
Granulocytes

Adapted from Human Anatomy and Physiology 2nd Edi8on, Marieb

 Blood Physiology - Granulocytes
Neutrophil
Acute bacterial infecIons
Chemically adracted to
sites of inammaIon
PhagocyIc
Life span: hours - days
Peter Maslak, ASH Image Bank 2011; 2011-3776

Appearance
MulIlobed nucleus
Small cytoplasmic
granules; pink and purple
Pinkish cytoplasm
Peter Maslak, ASH Image Bank 2011; 2011-3608
Copyright 2011 American Society of Hematology. Copyright restrictions may apply.
 Blood Physiology - Granulocytes
Eosinophil
ParasiIc worm
infecIons
Lysosome lled granules
Life span: days
Peter Maslak, ASH Image Bank 2011; 2011-3776

Appearance:
Bilobed nucleus
Large cytoplasmic
granules; red
Reddish cytoplasm
Peter Maslak, ASH Image Bank 2011; 2011-2677
Copyright 2011 American Society of Hematology. Copyright restrictions may apply.
 Blood Physiology Granulocytes
Basophil
Inammatory response
and vasodilaIon
Histamine containing
granules
Life span: hours to days Peter Maslak, ASH Image Bank 2011; 2011-1590

Appearance:
Bilobed nucleus
Large cytoplasmic
granules; purple and black
Purplish cytoplasm

Peter Maslak, ASH Image Bank 2011; 2011-2582

Copyright 2011 American Society of Hematology. Copyright restrictions may apply.
 Blood Physiology White Blood Cells
Agranulocytes

Adapted from Human Anatomy and Physiology 2nd Edi8on, Marieb

 Blood Physiology - Agranulocytes
Lymphocyte
Immune response
T cells: act directly against
enemies
B cells: anIbody
producIon Peter Maslak, ASH Image Bank 2011; 2011-2046

Life span: hours to years

Appearance
Small; low cytoplasm to
nucleus raIo
Spherical nucleus
Pale blue cytoplasm
John Lazarchick, ASH Image Bank 2011; 2011-1049

Copyright 2011 American Society of Hematology. Copyright restrictions may apply.

 Blood Physiology - Agranulocytes
Monocyte
CirculaIng macrophages
PhagocyIc
Life span: months

Peter Maslak, ASH Image Bank 2011; 2011-1591

Appearance
Kidney bean shaped
nucleus
Gray-blue cytoplasm

Peter Maslak, ASH Image Bank 2011; 2011-1662

Copyright 2011 American Society of Hematology. Copyright restrictions may apply.
 Blood Physiology - Hematopoiesis
FormaIon of blood cells
Approx 100 billion new cells
turned out each day!
Occurs in bone marrow
Red bone marrow
All blood cells arise from
the hematopoieIc stem cell
(HSC)
RelaIvely rare
1-4 HSCs per 100,000
nucleated marrow cells
Erythropoiesis = red blood
cells
Leukopoiesis = white blood
cells

"603 Anatomy of Long Bone" by OpenStax College - Anatomy & Physiology, Connexions Web site. hdp://cnx.org/content/col11496/1.6/, Jun 19, 2013.. Licensed under CreaIve Commons AdribuIon 3.0 via Wikimedia
Commons - hdp://commons.wikimedia.org/wiki/File:603_Anatomy_of_Long_Bone.jpg#mediaviewer/File:603_Anatomy_of_Long_Bone.jpg
 Blood Physiology - Erythropoiesis
ErythropoieIn (EPO)
Glycoprotein hormone
Mainly synthesized in the kidneys; some in liver
Hypoxia-inducible factor (HIF)
Increases EPO producIon
Degraded by oxygen-sensiIve enyzmes
Accumulates in low oxygen concentraIons
 Blood Physiology Leukopoiesis
Appearance of surface receptors that respond
to specic hormones and growth factors
Released by supporIng cells in red bone
marrow or mature leukocytes:
Interleukins
IL-2, IL-3, etc.
Colony-sImulaIng factors (CSFs)
G-CSF = granulocyte colony-sImulaIng factor
Adapted from Human Anatomy and Physiology 2nd Edi8on, Marieb
 Blood Physiology - Platelets
Megakaryocytes
Myeloid stem cell
Undergo repeated mitoses with no cytokinesis
Regulatory hormone = thrombopoieIn

Adapted from Human Anatomy and Physiology 2nd Edi8on, Marieb

 Blood Physiology Homeostasis
Red blood cell destrucIon
100-120 day lifespan
DegeneraIng red cells get caught in spleen
(smaller circulatory channels)
Engulfed and degraded by macrophages
Globin chains broken down to amino acids reused
Iron porIon is stored for reuse
Remaining heme degraded to bilirubin
Binds to albumin for transport and eventual excreIon
Adapted from Human Anatomy and Physiology 2nd Edi8on, Marieb
 Blood Physiology - Hemostasis
Stoppage of bleeding
Requires cloPng factors and released
substances
3 major steps:
Vascular spasm
Primary CloPng
Platelet plug formaIon
CoagulaIon Secondary CloPng
 Blood Physiology Hemostasis
Vascular Spasm
VasoconstricIon induced by:
Direct injury to vascular smooth muscle
Chemicals released by surrounding endothelial cells
and platelets
Reexes iniIated by local pain receptors
Main outcome: reduced blood ow
 Blood Physiology - Hemostasis
Platelet Plug FormaIon
Nitric oxide and prostacyclin
Normally released from endothelial cells; prevents
platelet aggregaIon
Damaged endothelium
Exposed collagen bers; platelets sIck
von Willebrand factor (VWF) forms stable bridge
between collagen and platelets
Platelets release chemical messengers that recruit
more platelets and increase the vascular spasm
 Blood Physiology - Hemostasis
CoagulaIon
FormaIon of a clot via brin threads
Carried out by cloPng factors
Exist in blood in inacIve form
Protein cleavage acIvates them
3 Phases of coagulaIon:
1. FormaIon of prothrombin acIvator
Extrinsic vs. Intrinsic pathways
2. Conversion of prothrombin to thrombin
3. Fibrinogen molecules joined into brin mesh
Adapted from Human Anatomy and Physiology 2nd Edi8on, Marieb
 Blood Physiology - Hemostasis
Liver
Most cloPng factors synthesized here
Vitamin K (green leafy vegetables)
Factor II (Prothrombin)
Factor VII
Factor IX
Factor X
Calcium
Plays a major role in many of the cloPng cascade
reacIons
Adapted from Human Anatomy and Physiology 2nd Edi8on, Marieb
 Blood Physiology - Hemostasis
Fibrinolysis
Plasminogen (inacIve) integrated into clot
Fibrin digesIng
Endothelial cells secrete Issue plasminogen acIvator
(tPA)
AcIvated Factor XII, thrombin
Plasmin (acIvated Plasminogen)
AnIcoagulants
AnIthrombin III present in plasma
Protein C
 Lecture Overview
Blood Physiology
FuncIons, components, cell types, hematopoiesis,
homeostasis, hemostasis
Blood Pathology
Techniques, Red blood cell disorders, white blood
cell disorders
 Blood Pathology - Techniques
Blood Smears (Wrights Giemsa)
hdps://www.youtube.com/watch?v=R1DU_N6eazg

Complete Blood Count (CBC)

Cell counts
Hemoglobin
Hematocrit
Red cell specic tests
Bone Marrow ExaminaIon
Trephine biopsy
Bone marrow aspiraIon
Flow Cytometry
 ASH Teaching Slides: Blood Cells

Normal blood smear. The four larger cells shown are called
granulocytes, a type of white blood cell.

Maslak, P. ASH Image Bank 2008;2008:8-00067. Copyright 2008 American Society of Hematology.
 Bone Marrow ExaminaIon
Bone marrow biopsy (gross specimen) - 1.

Peter Maslak, ASH Image Bank 2011; 2011-1715

Copyright 2011 American Society of Hematology. Copyright restrictions may apply.

 Bone Marrow ExaminaIon
Normal Bone Marrow Aspirate - 1.

Peter Maslak, ASH Image Bank 2011; 2011-3158

Copyright 2011 American Society of Hematology. Copyright restrictions may apply.
 Flow Cytometry

Copyright 2000 by Eric Martz; BD Biosciences

Blood Pathology Erythroid Disorders
Anemias lacking blood
Too few red blood cells
HemolyIc anemia
Mismatched blood transfusion
Too lidle hemoglobin
Iron-deciency anemia microcytes
Abnormal hemoglobin
Sickle-cell anemia
Single base mutaIon in normal hemoglobin chain
 HemolyIc Anemia
Microangiopathic hemolytic anemia - 1.

Peter Maslak; Lisa Southern;, ASH Image Bank 2013; 2013-4048

Copyright 2013 American Society of Hematology. Copyright restrictions may apply.
 Sickle Cell Anemia
Sickle cell disease &ndash; RBC morphology - 1.

John Lazarchick, ASH Image Bank 2011; 2011-3958

Copyright 2011 American Society of Hematology. Copyright restrictions may apply.
Blood Pathology Erythroid Disorders
Polycythemia many blood cells
Polycythemia vera
Bone marrow cancer; increased blood viscosity
Blood Pathology Leukocyte Disorders
Leukopenia low white blood cell count
Leukemia high white blood cell count
Acute: quickly advancing; blast-type cells
Chronic: slowly advancing; more mature cells
 Class QuesIons
Why is Wrights Giemsa stain used instead of
H&E?
I couldnt nd a deniIve answer, but it appears
that the stain oers beder dierenIaIon
potenIal between dierent blood cell types:
hdp://en.wikipedia.org/wiki/Wright's_stain