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MS&A – Modeling, Simulation and Applications 18

Antonio Fasano · Adélia Sequeira

Hemomath
The Mathematics of Blood
MS&A

Volume 18

Editor-in-Chief

Alfio Quarteroni

Series Editors
Tom Hou
Claude Le Bris
Anthony T. Patera
Enrique Zuazua
More information about this series at http://www.springer.com/series/8377
Antonio Fasano • Adélia Sequeira

Hemomath
The Mathematics of Blood

123
Antonio Fasano Adélia Sequeira
Fabbrica Italiana Apparecchi Biomedicali Instituto Superior Técnico
(FIAB) Universidade de Lisboa
UniversitJa degli Studi di Firenze Lisboa, Portugal
Firenze, Italy

ISSN 2037-5255 ISSN 2037-5263 (electronic)

MS&A - Modeling, Simulation & Applications
ISBN 978-3-319-60512-8 ISBN 978-3-319-60513-5 (eBook)
DOI 10.1007/978-3-319-60513-5

Library of Congress Control Number: 2017951447

© Springer International Publishing AG 2017

This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of
the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,
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Will all great Neptune’s ocean wash this
blood clean from my hand? (Macbeth,
William Shakespeare, Act 2, Scene 2,
1605-6).
Preface

Medicine is a fascinating field whose progress has been exponentially accelerated

from the moment it met technology. Mathematics, along with physics and chemistry,
participates in such an exciting experience, which actually started long ago.1
In the present book we focused our attention on one of the most intriguing
branches of medicine: hematology. Blood has an extremely complex behavior at all
scales. It is complicated as a fluid (to the point that many different, often mutually
contrasting, rheological models have been proposed), it contains very smart cells,
able to perform a huge number of operations, and it carries a great number of
large and small molecules, each with one or more tasks. Moreover, it constantly
interacts with all organs providing oxygen and nutrients, exchanging gases in the
lungs, carrying throughout the body hormones synthesized by endocrine glands,
and cells defending the organism from the attack of foreign agents. Blood also takes
metabolites to their final destination (the kidneys).
Such a monumental physiology goes in parallel with an even more intricate
pathology, since there are so many different ways of perturbing a system which
works perfectly in a rather narrow range. In this framework mathematics can play
an important role. In which way? It is not so simple to describe some general rule
for the construction of a mathematical model. It is not just a matter of choosing the
appropriate equations. Putting together a number of appropriate equations could
lead to a system which is simply not manageable. Moreover equations contain
coefficients and if the model has to give practical answers, then such coefficients
must be known from experiments. Therefore quite often completeness is in conflict
with practice. The more difficult are the phenomena to be studied, the more
necessary is to simplify equations, and simplifications always need to be justified
and kept within a tolerance degree guaranteeing that the reduced model is still
meaningful, at least for some specific target.

1
See the recent book: F.A. Duck. Physicists and Physicians: A History of Medical Physics from
the Renaissance to Röntgen. Institute of Physics and Engineering in Medicine, 2013.

vii
viii Preface

Blood-related topics are so numerous and each subject has been so widely
studied that it would be unthinkable to write an encyclopedic book. We will just
deal with some aspects of particular importance, showing old and new approaches
of mathematicians. We found extremely interesting, and also quite amusing, to
examine the historical development of the branches of medicine we dealt with. Of
course in a very synthetic way. Sometimes old ideas may look ridiculous, and we
confess that here and there we have played around the striking contrast between old
and new, emphasizing the naivety of our ancestors. Nevertheless, we want to stress
that the old civilizations and their masters were facing a task which was extremely
arduous and that even mistakes of great minds may have contributed in a way to
the progress of science. If on the contrary they have been an obstacle to the path
towards truth those who have to be blamed are not Hippocrates, Aristotle, Galen,
and the other fathers of medicine, but the strenuous vacuity of their followers.
On the other hand, when we “ultrafiltrate” history (to anticipate a term we will
extensively use in the chapters on kidneys and dialysis) the view emerging from
such a compressed perspective is so distorted that we should abstain from hastily
judging those who have mistakenly opposed the genial ideas mining their obsolete
world. Obstinate blindness is nothing but the natural and often justifiable instinct
of preserving the cultural environment we are born in, which pushes us to react
negatively to what may look the arrogant extravagance of self-appointed innovators.
Indeed, in sciences as in the arts, among the crowd of those proposing new ideas,
very few are really able to change the course of history, because this requires an
exceptional mind and the exceptional bravery of taking on seemingly impossible
challenges. We will encounter some of these towering characters on our path and
we will try to communicate our personal admiration, so that the reader does not get
the impression of being just looking at tombstones, but can somehow imagine the
excitement of the great people who made medicine what is today.
Due to its interdisciplinary character, the book is addressed to a large audience.
To clinicians, with the hope of elucidating the practical importance of mathematics
in medicine, to mathematicians with a taste for applications, but also to all scientists
(engineers, biologists, technicians, etc.) working in or close to medical areas. In
addition, even people with no scientific background can enjoy at least the pages
dedicated to the history of the relevant branches of medicine and the biological
introductions to the various subjects. A last remark is about footnotes. There are
many. In a sense they make a parallel book, containing a lot of lateral thoughts
and pieces of information, frequently of historical character, which in our opinion
provide answers to questions that may arise naturally.
The book deals with several specific aspects: blood rheology, blood coagulation,
blood ultrafiltration (natural and artificial), gas exchanges, the role of blood in heat
transfer, blood generation, and leukemia. All chapters follow the scheme: historical
background, physiological basis (including pathologies), mathematical modeling.
The subject of ultrafiltration is divided in two chapters: one small (kidneys) and, one
large (hemodialysis) for the reason that the two processes are significantly different.
The literature on kidney modeling is not large and we illustrated our own approach
to the problem, resulting from the applications of concepts on microcirculation
Preface ix

illustrated in the first chapter. This explains why it is much shorter than all other
chapters. Nevertheless we kept it separate because of its absolute peculiarity.
The authors are indebted to various eminent physicians for their advice. Among
them we quote in particular Dr. Jeremy Mizerski (cardiosurgeon in Warsaw)
and Prof. Rosanna Abbate (Head of the Consult and Laboratory Service for
Atherothrombotic Disorders for the Hospital and Medical School of the Uni-
versity of Florence, Italy). We also thank several colleagues for their interest
and encouragement. A precious support came from the personnel of the Library
of the Department of Mathematics & Informatics U. Dini of the University
of Florence, who efficiently provided hundreds of papers. The company FIAB
(Firenze, Italy) has also to be thanked for the help in retrieving research mate-
rial on electrophysiology. We acknowledge the partial financial support of the
Portuguese FCT—Fundação para a Ciência e a Tecnologia through the PHYS-
IOMATH project “Mathematical and Computational Modeling of Human Physiol-
ogy” (EXCL/MAT-NAN/0114/2012) http://www.physiomath.com, and the project
UID/Multi/04621/2013 of the CEMAT—Center for Computational and Stochastic
Mathematics, Instituto Superior Técnico, University of Lisbon.
We want also to deeply acknowledge Prof. Willi Jäger and Prof. Alfio Quarteroni
for their useful suggestions and their favorable comments.
Finally, we thank two persons at Springer, Annika Elting and Elena Griniari, who
have been particularly helpful in solving some important practical problems during
the final stage of publication.

Firenze, Italy Antonio Fasano

Lisboa, Portugal Adélia Sequeira
Contents

1 Hemorheology and Hemodynamics .. . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 1

1.1 Historical Remarks .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 1
1.2 The Human Circulatory System . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 14
1.2.1 Systemic Circulation . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 14
1.2.2 Mathematical Models for Blood Flow Dynamics .. . . . . . . . . . . . 17
1.3 Blood Rheology .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 38
1.3.1 Blood Components . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 38
1.3.2 Non-Newtonian Properties of Blood .. . . . . .. . . . . . . . . . . . . . . . . . . . 40
1.3.3 Constitutive Models for Blood . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 44
1.4 Hemodynamics and Microcirculation .. . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 50
1.4.1 A New Approach to Modeling Microcirculation .. . . . . . . . . . . . . 50
1.4.2 The Microcirculation Model . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 52
1.5 Vasomotion .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 55
1.5.1 The Elusive Phenomenon of Vessel Oscillations .. . . . . . . . . . . . . 55
1.5.2 Arterioles .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 58
1.5.3 Venules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 60
1.6 Atherosclerosis .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 62
1.6.1 The Pathogenesis of Atherosclerosis . . . . . .. . . . . . . . . . . . . . . . . . . . 63
1.6.2 Mathematical Modeling . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 64
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 67
2 Blood Coagulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 79
2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 79
2.2 Historical Remarks .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 81
2.3 Cells and Proteins Intervening in the Formation
and Dissolution of Clots . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 88
2.3.1 Blood Cells and Coagulation .. . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 89
2.3.2 Platelets Regulators .. . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 94
2.3.3 The Coagulation Factors . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 95
2.3.4 Fibrinolysis Factors .. . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 100
2.3.5 Factors Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 101

xi
xii Contents

2.4 The Cell-Based Model for Secondary Hemostasis . . . . . . . . . . . . . . . . . . . . 102

2.4.1 Secondary Hemostasis . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 103
2.4.2 Fibrinolysis.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 108
2.5 Bleeding Disorders .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 109
2.6 The 3-Pathway Cascade Model . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 117
2.7 Anticoagulant Drugs, Thrombolytic Drugs,
Hemophilia Therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 120
2.7.1 Anticoagulant Drugs .. . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 120
2.7.2 Thrombolytic Drugs . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 124
2.7.3 Hemophilia Therapies . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 124
2.8 Mathematical Models for Blood Coagulation . . . . .. . . . . . . . . . . . . . . . . . . . 125
2.8.1 ODE’s Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 126
2.8.2 PDE’s Models .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 131
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 146
3 Blood Filtration in Kidneys .. . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 159
3.1 Historical Remarks .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 159
3.2 General Structure of Kidneys .. . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 161
3.3 Calculating Glomerular Filtration Rate . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 165
3.4 The Steady Flow and the Glomerular Filtration Rate . . . . . . . . . . . . . . . . . 168
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 170
4 Extracorporeal Blood Ultrafiltration . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 171
4.1 Historical Remarks .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 171
4.2 The Hollow Fibers Dialyzer . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 174
4.2.1 General Description of the Apparatus . . . . .. . . . . . . . . . . . . . . . . . . . 174
4.2.2 A Mathematical Model Based on the Upscaling
Technique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 177
4.2.3 Modeling the Device . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 179
4.2.4 Modeling the Body Reaction .. . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 190
4.2.5 Modeling the Evolution of Masses and Volumes.. . . . . . . . . . . . . 192
4.3 Numerical Simulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 196
4.4 Going Further . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 199
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 201
5 Extracorporeal Blood Oxygenation .. . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 205
5.1 About Extracorporeal Blood Treatments.. . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 205
5.2 Gases in Blood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 206
5.3 Historical Remarks .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 206
5.4 Mathematical Models .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 212
5.4.1 Heart-Lung Machine.. . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 212
5.4.2 ECMO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 215
5.4.3 IMO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 220
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 222
6 Blood and Heat Transfer .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 227
6.1 Historical Remarks .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 227
Contents xiii

6.2 The Bioheat Equation .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 231

6.3 Hyperthermia: General Characteristics and Historical
Information .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 234
6.4 Mathematical Models .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 237
6.4.1 Hyperthermia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 237
6.4.2 Assessing the Thermal Damage .. . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 241
6.4.3 Therapeutic Hypothermia . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 243
6.4.4 Laser Induced Thermal Therapy (LITT).. .. . . . . . . . . . . . . . . . . . . . 245
6.5 Treatments by High Intensity Focused Ultrasound (HIFU) .. . . . . . . . . . 250
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 255
7 Thermal Ablative Procedures in the Treatment of Heart
Arrhythmia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 265
7.1 Physiological and Historical Notes. . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 265
7.2 Importance of Mathematical Models.. . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 275
7.3 RF Ablation Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 278
7.4 Cryoablation Models .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 283
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 287
8 Blood and Cancer .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 295
8.1 Historical Remarks .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 295
8.2 Hematopoiesis and Types of Blood Cancer .. . . . . . .. . . . . . . . . . . . . . . . . . . . 298
8.3 Mathematical Models .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 307
8.3.1 Hematopoiesis: Onset of Leukemic Disorders . . . . . . . . . . . . . . . . 307
8.3.2 Cyclic Leukemic Disorders . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 309
8.3.3 Treatment of Leukemic Disorders . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 313
8.3.4 Leukemia and the Immune Response . . . . . .. . . . . . . . . . . . . . . . . . . . 319
8.3.5 Bone Marrow/HSCs Transplantations . . . . .. . . . . . . . . . . . . . . . . . . . 322
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 324

Index . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 331
Acronyms

ABM Agent Based Model

ADP Adenosine-Di-Phosphate
AF Atrial Fibrillation
AIDS Acquired Immune Deficiency Syndrome
ALE Arbitrary Lagrangian Eulerian
ALK Anaplastic Lymphoma Kinase
ALL Acute Lymphoblastic Leukemia
AML Acute Myeloid Leukemia
AMP Adenosine-Mono-Phosphate
APC Activated Protein C
APL Acute Promyelocytic Leukemia
APTT Activated Partial Thromboplastin Time
ASA Acetylsalicilic Acid
AT Antithrombin
ATP Adenosine-Tri-Phosphate
AVNRT Atrio-Ventricular Nodal Reentrant Tachycardia
BMI Body Mass Index
BSA Body Surface Area
BW Body Weight
CD Cluster of Differentiation
CEM Cumulative Equivalent Minutes
CLL Chronic Lymphocytic Leukemia
CLP Common Lymphoid Progenitor
CML Chronic Myelogenous Leukemia
CMP Common Myeloid Progenitor
CSC Cancer Stem Cell
CSF Colony Stimulating Factor
CT Computed Tomography
DAE Differential Algebraic Equation
DIC Disseminated Intravascular Coagulation
DLBCL Diffuse Large B-Cell Lymphoma

xv
xvi Acronyms

DPD Dissipative Particles Dynamics

DTI Direct Thrombin Inhibitors
DVT Deep Venous Thrombosis
EBV Epstein-Barr Virus
ECBF Extracorporeal Blood Flow
ECG Electrocardiogram
ECM Extracellular Matrix
ECMO Extracorporeal Membrane Oxygenator
ELPT Euler-Lagrange Particle Tracking
ETL Esophageal Thermal Lesion
FAB French-American-British (leukemia classification system)
FPM Fluid Particle Model
FSI Fluid-Structure Interaction
FU Forming Unit
GFR Glomerular Filtration Rate
GVHD Graft-vs-Host-Disease
HDL High-Density-Lipoprotein (good cholesterol)
HHV Human Herpes Virus
HIFU High Intensity Focused Ultrasound
HIT Heparin Induced Thrombocytopenia
HIV Human Immunodeficiency Virus
HL Hodgkin Lymphoma
HMWK High Molecular Weight Kininogen
HSC Hematopoietic Stem Cells
HSP Heat Shock Protein
IB Immersed Boundary
IFE Immersed Finite Elements
IMO Intravenous Membrane Oxygenator
ITP Idiopathic (or Immune) Thrombocytopenic Purpura
IVOX Intravenous Oxygenator
LBM Lattice Boltzmann Method
LDL Low-Density-Lipoprotein (bad cholesterol)
LET Luminal Esophageal Temperature
LITT Laser Induced Thermal Therapy
LMWH Low Molecular Weight Heparin
MMP Matrix Metalloproteinase
MPN Myeloproliferative Neoplasms
MRT Magnetic Resonance Tomography
NHL Non-Hodgkin Lymphoma
NKC Natural Killer Cell
NOACS Novel Oral Anticoagulants
NS Navier-Stokes
NSCHL Nodular Sclerosis Classical Hodgkin Lymphoma
ODE Ordinary Differential Equation
PAI Plasminogen Activator Inhibitor
Acronyms xvii

PC Protein C
PDE Partial Differential Equation
PLA Plasmin
PLS Plasminogen
PRCP Prolyl-Carboxypeptidase
PS Protein S
PT Prothrombin Time
PTLD Posttransplantation Lymphoproliferative Disorders
PTT Partial Thromboplastin Time
PVI Pulmonary Vein Isolation
PZ Protein Z
RBC Red Blood Cell
RFA Radiofrequency Ablation
RSC Reed-Sternberg Cell
SCA Sickle-Cell Anemia
SMC Smooth Muscle Cell
SVT Supraventricular Tachycardia
TAFI Thrombin Activatable Fibrinolysis Inhibitor
TAR Thrombocytopenia with Absent Radius
TD Thermal Damage
TF Tissue Factor
TFPI Tissue Factor Pathway Inhibitor
TIMP Tissue Inhibitor of Metalloproteinase
tPA tissue Plasminogen Activator
TTP Thrombotic Thrombocytopenic Purpura
TXA Thromboxane
VA Venous-Arterial (ECMO)
VT Ventricular Tachycardia
VV Veno-Venous (ECMO)
vWF von Willebrand Factor
WBC White Blood Cell
WHO World Health Organization (leukemia classification system)
WPWS Wolff-Parkinson-White syndrome
WSS Wall Shear Stress
Chapter 1
Hemorheology and Hemodynamics

Abstract In this first approach to the subject we start describing a few basic facts
about blood composition and about the circulatory system. Such notions will be
enriched in the rest of the book, when needed. Concerning modeling, this chapter
is devoted to the debatable question of the rheological properties of blood and to
the various ways the circulatory system has been described in a mathematical way,
both at the scale of main vessels and at the level of microcirculation. The peculiar
phenomenon of vessels oscillation (vasomotion) will be considered briefly, and the
literature on the mathematical modeling of diseases like atherosclerosis, affecting
blood flow through arteries, will be illustrated.

1.1 Historical Remarks

The importance of blood for life must have been clear to human kind from the most
remote antiquity, with a lot of implications at the religious level. In the Leviticus
(the third book of the Torah) it is stated that “life is in blood” as a strong motivation
not to eat meat containing fresh blood. In the ancient world health and diseases
have been expressions of supernatural powers, depending on the will of gods and
demons. These views have dominated for millennia before medicine could acquire
a scientific basis. In this mix of logic and magic blood always had a fundamental
role. Think of the rites of blood offering and of blood drinking, common to many
ancient civilization. While these cruel rites have (almost) completely disappeared,
the belief in blood related miracles has survived to our days. Indeed, still today
astonishing miracles involving blood are the subject of great debates, in a number
and a variety of forms which is simply amazing, as everybody can realize by a quick
search on the web.1

1
Perhaps the most emblematic case is the miracle of the “liquefaction” of Saint Januarius’ blood.
It is less known that the blood of many other saints periodically exhibits the same phenomenon.
Saint Januarius (San Gennaro), the patron of Naples, died as a martyr around 305 AD , beheaded
at the Solfatara Crater. According to the legend, his blood was collected by a pious woman
(Eusebia) and preserved till our days (after many vicissitudes) in a sealed transparent container.
A thousand of years later the saint’s relics ended in Naples and in 1389 chronicles started reporting
the miracle. In our days the blood is exposed three times a year and upon mild agitation (most
of the times) the reddish dust turns into liquid. Many explanations have been attempted for this

© Springer International Publishing AG 2017 1

A. Fasano, A. Sequeira, Hemomath, MS&A 18,
DOI 10.1007/978-3-319-60513-5_1
2 1 Hemorheology and Hemodynamics

In this section we will deal very briefly with the way blood has been treated in
medicine from the antiquity to the nineteenth century. The aim is just to provide
a sketchy framework of how hematology, one of the most sophisticated branch of
medicine for its strong connection with biochemistry, emerged from obscurity.
Egyptians had great familiarity with the inside of the human body through
the practice of mummification, but it would be wrong to look for an anticipation
of modern anatomy in the thirteen surviving papyri treating medical subjects.2
Nonetheless Egyptians knew the main blood vessels (in number of 46, reaching
every part of the body) and the leading role of heart.3 The most important medical
papyri are: the Edwin Smith Papyrus (written around 1700 BC, but based upon much
earlier material),4 the Ebers Papyrus (existing in a copy of the sixteenth century BC,
but probably having its roots back to 3000 BC),5 and the Kahun Gynecological
Papyrus (nineteenth century BC). The Edwin Smith Papyrus is attributed to a
legendary, semi-divine character, the physician Imhotep who lived during the
twenty seventh century BC. The papyrus (mainly dealing with wounds healing),
though less naive than medical doctrines developed much later, can hardly be
considered a really scientific document and the suggested remedies could easily
be fatal to the patients because they could produce infections. However, Egyptians
expertise in medicine was deeply revered even among the Greeks, to the point that
it was praised by Homer in the Odyssey (c. 800 BC) (Figs. 1.1 and 1.2).
In comparison the clay tablets from the fabulous Ashurbanipal’s library in
Nineveh (seventh century BC) reveal a much more mystic approach to medicine.
Heart was the center of intellectual activity and blood was the essence of life. The
organ presiding over circulation was the liver. For the Assyrians illness was a divine
punishment (the same word, shêrtu, denoted illness and sin), so the main effort for
physicians was to identify which one of the thousands of gods they believed in had
been offended by the sick person.
Egyptians and Mesopotamians certainly practiced bloodletting as a therapy for
numerous illnesses.
Biblical medicine shared with contemporary civilizations the divine influence on
health, but it was characterized by the great importance attributed to hygiene as an
essential tool to prevent infections, an attitude that was achieved in modern times
only with the birth of microbiology.

intriguing phenomenon (including some thixotropic mixture prepared in the middle ages [93]).
A professor of molecular biology of the University Federico II of Naples (prof. G. Geraci) has
performed experiments with a sample of old blood saved in a sealed vial and with his own blood,
suitably aged, reproducing the same “miracle”, thus concluding that “liquefaction” may well be
just a blood property [94].
2
For a history of ancient Egyptian medicine see e.g. [59].
3
Though all kinds of body fluids were thought to flow through the heart. For instance semen was
believed to be provided to testicles by two dedicated vessels (Ebers Papyrus).
4
The translation [21] with splendid reproductions of the Smith Papyrus is available on line.
5
The English translation [22] (parallel to [21]) is available on line.
1.1 Historical Remarks 3

Fig. 1.1 Plates vi and vii of

the Edwin Smith papyrus
[Rare Book Room, New York
Academy of Medicine]

Fig. 1.2 The Ebers Papyrus

[University of Leipzig
Library]

The most influential character in western civilization under the point of view of
medicine was certainly Hippocrates (ca. 460 BC–ca. 370 BC),6 whose theory that
health depends on the equilibrium of the four humours (blood, phlegm, black bile
and yellow bile) was to become an unquestioned paradigm for centuries (Figs. 1.3
and 1.4).
The idea of the four humours parallels the one of the four basic elements
(earth, water, air, fire) by the famous Greek philosopher Empedocles (fifth century
BC). Hippocrates’ theory was somehow anticipated by Alcmaeon of Croton (fifth
century BC), who was one of the first to distinguish arteries and veins on the basis
of direct observations practicing animals dissection.

6
Dates largely uncertain.
4 1 Hemorheology and Hemodynamics

Fig. 1.3 Bust of Hippocrates

[National Archaeological
Museum, Athens]

Fig. 1.4 Portrait of Galen

[unknown copyright holder]

It is worth mentioning that interpreting health as the equilibrium of “entities” was

also a distinctive characteristic of oriental doctrines, at least as old. The Ayurveda,
the traditional Indian medicine, has mythological origins and is probably 5000 years
old.7
One of its basic principles is that health requires the equilibrium of three internal
vital forces, the doshas (Vata, Pitta and Kapha), whose combination determines the
spiritual and physical constitution (Prakriti) of each individual. The Ayurveda is

7
One of the oldest surviving text is Charaka Samhita (Fig. 1.5), written in Sanskrit (fifth to third
century BC ).
1.1 Historical Remarks 5

Fig. 1.5 A page from the Charaka Samhita

still largely practiced. It also contemplates bloodletting (Rakta Mokshana) as one of

the “five actions” (Panchakarma).8
As old, and as actual, as Ayurveda is the traditional Chinese medicine, also
inspired to the concept of equilibrium of two “principles”: yin and yang, opposite
and complementary.9 More forces take part in the game: Qi and the Five Elements
(Wu Xing). Curiously for us, the five elements have a significant intersection with
Empedocles’ elements (namely: water, earth, fire, the other two being wood and
metal).10 The reference text of traditional Chinese medicine is the Inner Canon
of Huangdi (Huangdi Neijing). Probably written between the sixth and the third
century BC, the book makes reference to the legendary Yellow Emperor (Huangdi),
supposed to have reigned between 2698 BC and 2599 BC.11
Qi has a strict relationship with blood (Xue), to which it is intrinsically connected.
Actually blood was considered the physical form in which Qi flows in the body,
being at the same time its driving force. In turn blood nourishes the organs

8
Two classes of medical approaches can be adopted to recuperate the broken equilibrium: Samana
(for light alterations), and Shodana aimed at expelling the corrupted doshas. Panchakarma belongs
to the second class.
9
Physical manifestations of yin and yang are natural opposites like dark and light, male and female,
life and death, moist and dry, sun and moon, etc.
10
One more proof of how humans have tried to interpret life and the physical world on the basic
of recurrent principles. Striking similarities can be found also among the many myths explaining
creation.
11
A legendary, semi-divine figure between myth and history, he was credited with the invention of
almost anything which started Chinese civilization.
6 1 Hemorheology and Hemodynamics

generating Qi in the typical duality permeating this old discipline. Bloodletting has
an important role in Chinese medicine and it is meticulously described [145].
Galen of Pergamon (131–201), who acquired great fame in Rome where he
became known as Aelius (Claudius) Galenus, adopted Hippocrates’ theory in
his writings, refining it with the combination of the four temperaments (choleric,
melancholic, sanguine, phlegmatic) and the four qualities (cold, warm, moisty, dry).
The main merit of Hippocrates was to separate medicine from religion (that in
Greece was then dominated by the cult of Asklepios). To our eyes this may look
a simple statement, but it was actually a giant leap towards the evolution of a
scientific basis, though, to put it bluntly, much of ancient medicine was basically
harmful to patients.
Bloodletting was raised to the state of an art by Galen (for whom it had the scope
of reinstating the lost humors equilibrium) and considered an effective treatment
almost to our days, until it was demonstrated to be normally useless or, in most
cases, even dangerous. The practice peaked during the first half of the nineteenth
century, when it was believed to cure an enormous variety of illnesses, to the point
that leeches (Hirudo medicinalis) (Fig. 1.6) were raised in farms and sold in huge
numbers (estimated order of magnitude: one hundred million a year in Europe). We
will return to leeches in the chapter about coagulation since they secrete one of the
most powerful anticoagulants. Today bloodletting by phlebotomy is used only for
few very specific conditions.
For a history of bloodletting see e.g. [168, 241] and [100].12
Blood circulation has intrigued people from the early times of medicine, but most
of the claims put forward before the sixteenth century were wrong. A concise but
illuminating review is [2] (Fig. 1.7).
Aristotle (384–322 BC) stated that the heart (for him a three-chambered organ)
was the seat of the soul and how deeply that concept penetrated our civilization
is very clear since even today the two words are sometimes used as synonyms.
A positive influence of Aristotle on the study of human body came from his opinion
that no one is going to make any use of his body after death. This encouraged the
practice of corpse dissection, through which many discoveries were made at the
time. Vivisection was performed by Erasistratus (304–250 BC) and Herophilus
(335–280 BC)13 not only on animals, but also on criminals who had received a life

12
In this paper it is reported how extremely heavy bloodletting accompanied the last days of Charles
II and of George Washington.
13
Erasistratus (304–250 BC ), a renowned Greek physician active in Syria, came to the conclusion
that heart is a pump. Though he made some remarkable progress in understanding the role of brain
and nerves, he believed (as many others) that arteries carried the “spiritual substance” (pneuma).
In other words, arteries were full of air and if by chance they were contaminated by blood it
would have caused illness. It is amazing that at that time there was a controversy about the path of
drunk liquids: somebody claimed that they went to the trachea (a name probably due to Erisistratus
himself) eventually reaching the lungs. He stated instead that anything which is ingested goes
through the esophagus to the stomach. He opposed the practice of bloodletting. Herophilus (335–
280 BC ) established that the brain, and not the heart, was in control of motion.
1.1 Historical Remarks 7

Fig. 1.6 Bloodletting by leeches [Historia Medica (Bruxellae, 1639), Wellcome Library, London]

Fig. 1.7 Bust of Aristotle [National Museum of Rome]

sentence,14 even publicly: a fact later reported with praise by the famous Roman
physician Cornelius Celsus Aulus (ca. 25 BC–ca. 50 AD).
Many wrong views of revered characters like Hippocrates, Aristotle and Galen
have long dominated western medicine and there were times in which contrasting
them could lead to ecclesiastic tribunals. It is interesting to note that the humors
theory found its way through Islamic medicine: the Persian Avicenna (Ib Sīnā,
980–1037) (Fig. 1.8) based his Canon of Medicine (1025) on Hippocrates’ and
Galen’s thought. Another Persian, Razi (Muhammad ibn Zakariyā Rāzī, 865–
925) (Fig. 1.9) an eclectic scientist very famous in his times, was instead a strenuous
antagonist. He explicitly questioned several of Galen’s claims on the basis of his
own experimental observations.

14
The practice was legal in Alexandria.
8 1 Hemorheology and Hemodynamics

Fig. 1.8 Portrait of Avicenna

[Wellcome Images, photo no:
M0000768]

Fig. 1.9 Portrait of al-Razi

[Wellcome Images, Photo
number: L0005053]

A great merit towards the foundation of medicine as a modern science goes to

Andreas Vesalius (Fig. 1.10) (Latinized from Andries van Wesel) (1514–1564),
whose revolutionary work opened a new era in physiology. It is interesting to
note that Vesalius studied Razi’s books and that he based his famous massive
treatise De humani corporis fabrica libri septem (1543) on direct observation of
dissected human bodies. He pointed out several of Galen’s mistakes (particularly in
the description of circulatory system), indifferent to the harsh criticism of Galen’s
followers.15 According to allegations that recent biographers tend to dismiss (though
based on written documents), he could have received a death sentence in Spain

15
He was particularly adversed by his former teacher, Franciscus de la Boe (1478–1555), better
known as Jacobus Sylvius or Jacques Duboi, who was an irreducible worshiper of Galen’s works,
to the point that if he had to admit that something in the human body was different from what Galen
1.1 Historical Remarks 9

Fig. 1.10 Portrait of Andreas

Vesalius [De humani corporis
fabrica (1543)]

because it was reported that during an autopsy the heart of the would-be dead was
seen to pulsate. The sentence might have been commuted to the obligation of a
pilgrimage to Jerusalem. What is sure is that he died in a ship wreckage during
the return trip. We recall that, precisely the year Vesalius was born, Leonardo da
Vinci (1452–1519) went to Rome, were he was accused of sorcery for his activity on
cadavers dissection, which he had to stop because of the immense risk of opposing
the Vatican.16 Had Galen or Aristotle leaved on to those days they would have been
horrified by the stupidity of their false disciples.
The famous treatise Exercitatio anatomica de motu cordis et sanguinis in
animalibus (1628) by William Harvey (Fig. 1.11) (1578–1657) is considered to be
the first correct systematic description of blood circulation (limited to great vessels:
microcirculation was a later discovery).17 Another celebrated English physician
from the seventeenth century was Thomas Willis (1621–1675), remembered for
his discovery of the loop supplying blood to the brain (circle of Willis).

had described, then the mistake was in the body, in the sense that it had modified since Galen’s time.
Sylvius was nevertheless the author of important discoveries in brain anatomy.
16
The list of scientists condemned by the Catholic Church for heresy is impressive. The case of
Galileo Galilei is emblematic (1632). Despite their reputation, non-catholic Christian churches
were not more tolerant about heresy, which most of the times consisted just in interpretations of the
Scriptures (or of real world) different from the ones officially adopted by this or that Confession.
An emblematic case was the one of the Spanish born Michael Servetus (1509–1553), Vesalius
contemporary, and also a physiologist, who dared oppose Galen’s authority, providing his own
description of pulmonary circulation [218]. Serveto was burnt at the stake (alive and with sulfur on
his head) in Geneva, victim of the fanatic hate of John Calvin because of his refusal of the concept
of Trinity.
17
We must recall that about three centuries earlier Ala-al-Din Abu al-Hasan Ali Ibn Abi al-Hazm
al-Qarshi al-Dimashqi (known as Ibn Al-Nafis, 1213–1288), among his many other discoveries,
described pulmonary circulation [238].
10 1 Hemorheology and Hemodynamics

Fig. 1.11 Portrait of William

Harvey [National Portrait
Gallery, London]

Let us also mention Andrea Cesalpino, Italian anatomist and botanist, (1519–
1603) who proved that the heart is the only engine responsible for blood motion,
and that the liver has nothing to do with it, as somebody was still claiming (clearly
Erasistratus’ work had been forgotten), and that blood moves from and to the heart.
Shortly afterwards came the important contributions by the English eclectic scientist
Stephen Hales (1677–1761), who determined the blood volume in the body, the
heart output18 and who first measured arterial blood pressure.
For all these people blood was just a fluid. The composition of blood could
become known only after the progress of microscopy, mainly in the Netherlands,
where the invention of the microscope is attributed to Hans and Zacharias Jannsen
(resp. father and son), at the end of the sixteenth century, who were spectacle makers
in Middelburg (the Netherlands). It seems that Zacharias made the first telescope
shortly before Galileo Galilei. Other Dutch scientists are mentioned in connection
with the birth of microscope, including Christiaan Huygens (1629–1695) and
Cornelius Jacobszoon Drebbel (1572–1633), who became famous for having built
the first submarine (1624). The studies of Anthony (or Antonie) Leeuwenhoek
(1632–1723), in the wake of Jan Swammerdam (1637–1680), opened the way to
microbiology (Fig. 1.12).

18
This is a good place to mention a remarkable scientist, the German physiologist Adolf Eugen
Fick (1829–1901), mainly known for two things: (1) the Fick’s principle for the determination of
the cardiac output on the basis of the ratio between oxygen consumption and the arterio-venous
oxygen difference; (2) the formulation of Fick’s law for diffusion, paralleling Fourier’s law for heat
conduction.
1.1 Historical Remarks 11

Fig. 1.12 Portrait of

Anthonie Leeuwenhoek
[Rijksmuseum, Amsterdam]

With the help of his instruments he studied Red Blood Cells19 (1674), previously
identified in frogs blood by Jan Swammerdam (1658) and independently observed
by Marcello Malpighi (Fig. 1.13) (1628–1694).20
Intact RBCs have been identified in old bodies: in 2012 the oldest RBCs have
been found in the frozen mummy known with the nickname Ötzi (the iceman, Homo
tyrolensis, who lived around 3300 BC).
The discovery of platelets (1842), which are much smaller, had to wait for the
construction of more powerful microscopes (it will be illustrated in the chapter on

19
Cells were first observed at the microscope by the physicist Robert Hooke (1635–1703) in a thin
sample of cork (1665). He did not know what “cells” were, but he called them that way because
of their particular and regular arrangement in the sample, resembling the one of monks cells.
Hooke was an extremely versatile man in many disciplines. He can be considered the founder of
elasticity theory, but he was also an engineer, astronomer, a paleontologist, an architect (a friend of
Christopher Wren), Unfortunately he was in contrast with the president of the Royal Society, Isaac
Newton, and that obscured his reputation in life. Only two centuries later cells were identified as the
basic constituents of all living beings (by Theodor Schwann (1810–1882), a German physiologist,
and Matias Jakob Schleiden (1804–1881), a German botanist).
20
Malpighi first described RBC’s as fat corpuscles (1663). Malpighi was also the discoverer of
capillaries (1661) and of the filtrating units in kidneys, bearing his name. It is worth mentioning
here an extraordinary character, Athanasius Kircher (1602–1680), a German Jesuit scholar, who
wrote a great number of books in different areas. Kircher is mostly remembered for having built
a machine for automatic music composition (the Arca Musurgia, 1650). An expert microbiologist,
he was rightly convinced that the plague was caused by a microorganism (today known as the
Yersinia pestis bacterium) that he thought to have found in blood with the help of the microscope
in 1658. Most probably he had instead observed RBCs, the same year as Swammerdam.
12 1 Hemorheology and Hemodynamics

Fig. 1.13 Portrait of

Marcello Malpighi [Carlo
Cignani, Getty Images]

coagulation).21 It is instead rather surprising that White Blood Cells (WBCs) or

leukocytes were discovered in blood a year later (1843), despite the fact that they
are much larger. Actually they had been previously observed in pus, but it took
time to understand they were blood components. In that year the discovery was
reported independently by the French medicine professor Gabriel Andral (1797–
1876) and by William Addison (1802–1881),22 an English physician who was the
first to claim they can cross blood vessels wall to reach infection spots.
The nineteenth century was very rich of discoveries concerning blood. Lionel
Beale (1828–1906) wrote a treatise [16] which became very famous, where he
illustrated in great detail the blood constituents known at his time. A very concise
report on the discovery of blood cells is the paper [105].
We will return to this and other subjects in medicine history in other chapters
of this book. In particular we postpone a detailed description of blood cells in the
chapters devoted to blood rheology and blood coagulation and the one about blood
and cancer.
Coming to our times, we just recall that the ABO blood group system was discov-
ered by the Austrian born biologist and physician Karl Landsteiner (1868–1943),23

21
There is some controversy about the discovery of platelets, generally attributed to the French
physician Alfred Donné (1801–1878) in 1842.
22
It seems however that even Anthony Leeuwenhoek had observed them as early as 1678.
Many others described cells of that kind in pus and other physiological fluids (see [220]). The
French anatomist Joseph Lieutaud (1703–1780) called them “globuli albicans” (1749) [135]. The
lymphatic system was then described by William Hewson (1739–1774) [109].
23
He formerly identified groups A, B, C, but “C” was later changed to “0” (zero). He was also
the discoverer of the polio virus. The story of the ABO groups is actually more complicated. It is
today recognized that the Czech serologist Jan Janský (1873–1921) had provided the complete
4-group classification (including group AB) before Landsteiner, who had nevertheless worked
independently.
1.1 Historical Remarks 13

Fig. 1.14 Photograph of Karl

Landsteiner [Vienna 1901]

Fig. 1.15 Photograph of

Alexander Solomon Wiener.
Lillian & Clarence de la
Chapelle Medical Archives.
NYU Health Sciences Library

who, together with the American Alexander Solomon Wiener (1907–1976), an

eclectic scientist who even authored mathematical papers, discovered the Rhesus
Factor (1937),24 which may be present (Rh+) or not (Rh) on the surface of RBCs.
Landsteiner can be considered the father of blood transfusion and received a Nobel
prize in 1930 (Figs. 1.14 and 1.15).
Blood complexity is accompanied by an extremely rich history of discoveries
which after all is not the scope of this book. Occasionally we are going to see more,
as we said.

24
From the name of the monkey species (Rhesus) used in their tests.
14 1 Hemorheology and Hemodynamics

1.2 The Human Circulatory System

Mathematical modeling and simulations of the human circulatory system is a

challenging wide-range research field that has seen a tremendous growth in the
last few years and is rapidly progressing, motivated by the fact that cardiovascular
diseases are a major cause of death in developed countries. The continuous
development of surgical techniques such as angioplasty, stents placements, etc.
has given a great impulse to the investigation of blood flow in vessels. The
acquisition of medical data and the understanding of the local hemodynamics and
its relation with global phenomena, in both healthy and pathological patient-specific
cases, using appropriate and accurate numerical methods, play an important role in
the medical research. This helps, for instance, in predicting the consequences of
surgical interventions, or in identifying regions of the vascular systems prone to the
formation and growth of atherosclerotic plaques or aneurysms.
This section contains a brief description of the cardiovascular physiology relevant
to the investigation of the mathematical and numerical modeling of blood flow in
the human circulatory system [190]. A quick overview of the so-called geometrical
multiscale approach of the cardiovascular system is also given. For a detailed study
of related Physiology, see e.g. [102, 217].

1.2.1 Systemic Circulation

The cardiovascular system consists of two major parts, the systemic (or large)
circulation and the pulmonary (or small) circulation, connected by the heart, the
only source of energy for propelling blood throughout the vessels network.
The heart is a muscular organ with four pumping chambers, the left and right
atria and ventricles. The two pairs are separated by a septum and communicate
through the mitral and tricuspid valves, respectively. The aortic and pulmonic (or
pulmonary) valves open during systole when the ventricles are contracting, and
close during diastole, when the ventricles are filled by contracting atria through the
open mitral and tricuspid valves. During isovolumic contraction and relaxation,25
all four valves are closed. The heart is a complex organ with a pumping function
due to the contraction of its muscle fibers activated by electro-biochemical stimuli.
We will return to the physiology of heart stimulation in Chap. 7.
The systemic and pulmonary circuits are formed of three main types of vessels:
arteries, capillaries and veins, subdivided according to their diameters that range
over several orders of magnitude, and the wall thickness that decreases considerably

25
The isovolumic contraction is a short transient phase preceding actual ventricles contraction, just
before the sudden aortic pressure raise, during which the mitral valve closes (first heart sound). The
isovolumetric relaxation is an equally short phase, accompanying the rapid aortic pressure drop,
during which the mitral valve closes (second heart sound).
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sagen uit West-Indië
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Title: Mythen en sagen uit West-Indië

Author: Jr. Herman van Cappelle

Illustrator: Willem Backer

Release date: November 14, 2023 [eBook #72126]

Language: Dutch

Original publication: Zutphen: W. J. Thieme & Cie, 1926

Credits: Jeroen Hellingman and the Online Distributed

Proofreading Team at https://www.pgdp.net/ for Project
Gutenberg. With special thanks to Jude Eylander and
others for the music transcription.

*** START OF THE PROJECT GUTENBERG EBOOK MYTHEN EN

SAGEN UIT WEST-INDIË ***
[Inhoud]

[Inhoud]

MYTHEN EN SAGEN UIT WEST-INDIË

[Inhoud]
… aan den rand van den afgrond strekte zij hare armen
uit, Zie blz. 137.

[Inhoud]
MYTHEN EN SAGEN
UIT WEST-INDIË

DOOR
Dr. H. VAN CAPPELLE.
GEÏLLUSTREERD DOOR
WILLEM BACKER
 ZUTPHEN—W. J. THIEME & CIE—
MCMXXVI

[V]

[Inhoud]

Aan mijne vrienden

C. VAN DRIMMELEN,

Oud-Agent-Generaal voor de Immigratie, Oud-Lid van den Raad van

Bestuur in Suriname, den sympathieken strijder voor de belangen der
Amerikaansche Negerbevolking en mijn onvermoeiden tochtgenoot
door de Binnenlanden van het District Nickerie, die met zijn helderen
blik in de Negerpsyche onzen zwarten arbeiders een vaderlijke
leidsman was

en

Dr. HERMAN F. C. TEN KATE,

den Nederlandschen Anthropoloog en wereldreiziger—den
eminenten kenner en vriend der Indianen,

draag ik dezen bundel op.

H. VAN CAPPELLE. [VII]

[Inhoud]
 VOORWOORD.

Wanneer wij onder West-Indië niet alleen de eilandenreeks verstaan,

die, tusschen den 10en en 28en graad N.B. gelegen, zich in een boog
van de Zuidspits van Florida tot de Noordkust van Zuid-Amerika
uitstrekt, en de noordelijke omranding van de Caraïbische Zee vormt,
doch ook het gedeelte van het vasteland van Zuid-Amerika, dat onder
den naam Guyana bekend is en dat ten N. door den Atlantischen
Oceaan en den Orinoco, ten O. door den Atlantischen Oceaan, ten Z.
door de Amazonen-rivier en de Rio Negro en ten W. door de Orinoco
en de Cassiquiare begrensd wordt, mag de titel van dezen bundel der
Mythen- en Legenden-serie gerechtvaardigd zijn, daar het overgroote
deel der hierin opgenomen mondelinge overleveringen niet op de
West-Indische eilanden, doch in Guyana is bijeengebracht.

Dat ik uit den rijken schat van Mythen, Sagen, Legenden enz. die nog
bij de zoo sympathieke, helaas! voortdurend afnemende
oorspronkelijke bevolking van Guyana, de Indianen—op de eilanden
bijna geheel verdwenen—een belangrijk deel van het materiaal voor
dezen bundel heb gekozen, en dat ik deze verzameling in de tweede
plaats aan den onuitputtelijken rijkdom, die de mondelinge litteratuur
van het nu in West-Indië zoozeer overheerschende element, de
Negerbevolking, aan den folklore-onderzoeker verschaft, ontleend
heb—lag voor de hand.

In dezen bundel, waarin de voortbrengselen van den geest van twee

der meest uit elkander loopende volken der aarde met elkander
vergeleken kunnen worden, kan het den lezer zeker niet duidelijker
worden gemaakt, dat Mythen, Sagen en Legenden, die als overoude
herinneringen uit lang vervlogen tijden zijn blijven voortleven, een
getrouwe afspiegeling zijn van het leven en denken van een volk, en
dat, hoe groot, ook in geestelijk opzicht, de volken onderling mogen
verschillen, telkens een eenheid, ook in denken, naar voren treedt,
die onmiskenbaar op een gemeenschappelijken oorsprong heenwijst.

Hoewel in dezen bundel niet alleen vertellingen voorkomen, die hetzij

Mythen, hetzij Sagen of Legenden moeten genoemd worden, doch
ook dierenfabels rijkelijk vertegenwoordigd zijn, [VIII]is de titel, die het
eerst voor dezen bundel in de gedachte kwam, behouden.

Over de bezwaren, welke er voor een kunstenaar, die in het land van
herkomst geen studies maakte, aan verbonden zijn, om, in
overeenstemming met de andere bundels van Thieme’s mythen- en
legenden-serie, treffende plaatsen uit den tekst te illustreeren, ben ik,
den lezerskring in aanmerking genomen, voor welken deze bundel in
de eerste plaats bestemd is, ten slotte heengestapt. Dankbaar mag ik
erkennen, dat de veelbelovende kunstenaar Willem Backer, voor
wien niets te veel was, om in de gedachtenwereld en het zieleleven
van twee hem geheel vreemde menschenrassen door te dringen, met
zijn rijke phantasie en zijn illustratief-decoratief talent belangrijk tot de
poging heeft bijgedragen, om door middel van hunne geestelijke
voortbrengselen het leven van twee zoo belangwekkende
vertegenwoordigers van het menschdom uit te beelden. Het in beeld
brengen van de voorstelling der Indianen en der Negers, die, evenals
andere natuurvolken, in hunne vertellingen de dieren als menschen
laten optreden en willekeurig in elkander laten overgaan, heeft nog
geen ander illustrator aangedurfd. Onze zoölogen zullen dus aan een
spin met twintig, in plaats van met acht pooten, geen aanstoot mogen
nemen.

Ten gerieve van hen, die dieper in het aantrekkelijke onderwerp

wenschen door te dringen, heb ik een, uit den aard der zaak,
onvolledig litteratuur-overzicht laten voorafgaan, waarnaar de
Nederlandsche lezer door de in den tekst tusschen haakjes
geplaatste letters verwezen wordt.
Een woord van bijzonderen dank ben ik hier verschuldigd aan mijn
vriend, den Heer C. van Drimmelen, en niet minder aan diens
echtgenoote, Mevrouw B. E. C. van Drimmelen, geb. Wolff, die
steeds bereid waren, op mijne vragen betreffende gewoonten en de
taal der Surinaamsche Negers te antwoorden, terwijl hier ook een
woord van dank op zijn plaats is aan de Uitgeefster, de Firma W. J.
Thieme & Cie, voor hare medewerking, om dit deel harer Mythen- en
Legenden-serie boven het volume harer reeds verschenen bundels te
laten uitdijen.

Moge deze verzameling er toe bijdragen, de Indianen en de Negers

in een ander licht te doen schijnen, dan waarin de oningewijde van
het blanke ras hen, met andere gekleurde [IX]rassen, gewoon is te
beschouwen en tevens bij den lezer de overtuiging te vestigen, dat
de eertijds onderstelde psychische kloof tusschen Blanken en de
gekleurde rassen niet bestaat, en dat zoowel het Indiaansche als het
Negerras, bij verstandige en goede leiding, voor hoogere
ontwikkeling alleszins vatbaar zijn en beiden hunne plaatsen zullen
kunnen innemen op den naar hooger strevenden weg, dien het
menschdom met zijn vele stamverwante elementen heeft ingeslagen.
[XI]

[Inhoud]
 GEBEZIGDE LITTERATUUR.
B.a. W. H. Barker, and C. Sinclair. West-African folk-tales 📘. London, George
G. Harrap and Company, 1917.
B. H. W. Brett. Legends and myths of the aboriginal Indians of British Guyana.
Londen, (omstreeks 1880).
C.a. Dr. H. v. Cappelle. Bij de Indianen en Boschnegers van Suriname. Elseviers
Maandschrift 1902, No, 4, 5 en 6.
C.b. —— De Binnenlanden van het District Nickerie. Met talrijke platen en
afbeeldingen en een overzichtskaart. Hollandia-drukkerij, Baarn, 1901.
—— Zelfde werk in Fransche uitgave, getiteld: Au travers des forêts vierges
de la Guyane hollandaise. Baarn, Imprimerie Hollandia, Paris, Ch. Béranger,
Editeur, 1905.
C.c. —— Essai sur la Constitution Geólogique de la Guyane hollandaise. Zelfde
uitgevers, 1907.
C.d. —— Surinaamsche negervertellingen. Elsevier’s Maandschrift, 1904, blz.
314–327.
C.e. —— Surinaamsche negervertellingen. Bijdrage tot de kennis van West-
Indische neger-folklore. (Bijdragen tot de Taal-, Land- en Volkenkunde van
Ned.-Indië, Deel 72, Afl. 1 en 2, 1916).
C.f. —— De Kankantrie. De Boschgouverneur van den Surinaamschen neger.
Elseviers Maandschrift, Maart 1905.
Co.a. C. van Coll. Gegevens over Land en Volk van Suriname. (Bijdragen tot de
Taal-, Land- en Volkenkunde van Ned. Indië, 1903).
Co.b. —— Contes et légendes des Indiens de Surinam. (Anthropos II, III. 1907 en
1908).
Cr. Florence Cronise and Henry W. Ward. Cunnie Rabbit, Mr. Spider and the
other beef. 📘 West-African folk-tales. London. Swan Sonnenschein and Co.
1903.
D. Chas Daniel Dance. Chapters from a Guianese log-book. Demerara 1881.
Di. C. van Drimmelen. De Neger en zijn cultuurgeschiedenis (West-Indische
Gids. December 1925).
E. Paul Ehrenreich. Die Mythen und Legenden des Südamerikanischen
Urvölker. Berlin 1905.
El. A. B. Ellis. The Tsji-speaking peoples of the Gold-coast of West-Africa.
London, Chapman and Hall, 1887.
El.a. —— The Ewe-speaking peoples of the Slave-coast of West-Africa. London,
Chapman and Hall, 1890.
El.b. —— The Yoruba-speaking peoples of the Slave-coast of West-Africa.
London, Chapman and Hall, 1894.
Ga. Albert S. Gatschet. A Migration-legend of the Creek-Indians. Philadelphia.
D. S. Brinton, 1884.
Go. C. H. de Goele. Beiträge zur Völkerkunde von Surinam (Arch. für
Ethnographie. Band XIX. Leiden 1908).
H. J. H. J. Hamelberg. Cuenta di nansi (Derde Jaarverslag van het Geschied.,
Taal-, Land- en Volkenkundig Genootschap te Willemstad, 1899).
Ha. J. Chandler Harris. Uncle Remus and his sayings. The folklore of the Old
Plantation. 📘 Londen—New-York.
Hu. Alex. von Humboldt. Ansichten der Natur. Stuttgart, 1849.[XII]
Hu. Alex. von Humboldt. Zelfde werk in Nederl. Vertaling door Dr. E. M. Beima.
Leiden, 1850.
Je. Walter Jekyll. Jamaican song and story. Londen, David Nutt, 1907.
Jo. Dr. J. P. Josselin de Jong. Blackfoot Texts from the Southern Peigans.
(Verh. Kon. Akad. v. Wetensch., Afd. Letterkunde. Nieuwe Reeks. Deel XIV,
1914.)
Joh. Harry H. Johnston. The Negro in the New World. London, Methuen and Co.
1910.
K. Dr. Herman F. C. ten Kate. Reizen en onderzoekingen in Noord-Amerika.
Leiden, E. J. Brill, 1885.
K.a. —— Over Land en Zee. Zutphen, W. J. Thieme & Cie., 1925.
K.b. —— De Benedenlandsche Indianen, in Encyclopedie van Ned. West-Indië.
1914.
K.c. —— De Indiaan in de Letterkunde. (De Gids. Jaargang, 1919).
Ko. H. van Kol. Naar de Antillen en Venezuela. Leiden, A. W. Sijthoff, 1904.
N. Robert H. Nassau. Where animals talk. West-African Folk-lore Tales. 📘
Londen, Duckworth and Co.
P.a. F. P. en A. P. Penard. De menschenetende aanbidders der Zonneslang.
Paramaribo, 1907.
P.b. —— Surinaamsch bijgeloof. (Bijdr. tot de Taal-, Land- en Volkenk. van Ned.-
Indië, Deel 67, Jaargang 1912).
P.c. A. P. Penard. Surinaamsche Volksvertellingen. (Bijdragen tot de Taal-, Land-
en Volkenkunde van Ned. Indië. Deel 80. Jaarg. 1924).
P.d. A. P. en E. E. Penard. Surinam Folk-tales. (The Journal of American
Folklore. Vol. XXX No. CXVI. 1917).
Ph. Jhr. L. C. van Panhuys. Artikel: Boschnegers in de Encyclopedie van West-
Indië. 1914.
R. Walter E. Roth. An inquiry to the animism and folklore of the Guiana
Indians. (Thirtieth annual report of the Bureau of American Ethnology to the
Secretary of the Smithsonian Institution. Washington 1915).
R.a. —— An introductory study of the arts, crafts and customs of the Guiana
Indians. (Thirty-eighth annual report of the Bureau of American Ethnology
enz. Washington 1916–1917).
S. F. Stähelin. Buschneger-Erzählungen von Surinam. (Hessische Blätter für
Volkskunde. Jaarg. 1908 en 1909).
T. E. F. Im Thurn. Among the Indians of Guiana. London 1883.

[XIII]

[Inhoud]
 INHOUD.
Blz.
Voorwoord.
Overzicht der geraadpleegde litteratuur.
I. Mythen, Sagen en Legenden der Indianenbevolking van
West-Indië 1
Inleidende beschouwingen 1
Lijst en inhoud der verhalen 7
Indianen-vertellingen 65
II. West-Indische Neger-folk-lore 197
Inleidende beschouwingen 197
De Surinaamsche anansi-tori en hare oorsprong 203
Lijst en inhoud der Surinaamsche Neger-vertellingen 235
De anansi-tori en het bijgeloof, door M. H. Nahar 246
Vertellingen der Surinaamsche Stadsnegers 258
De anansi-tori der Surinaamsche Boschnegers 342
Neger-vertellingen uit het West-Indische Eilanden-gebied 350
Curaçaosche Neger-vertellingen. Cuenta di Nansi 350
Creoolsche folk-lore van St.-Eustatius 360
Neger-vertellingen van Jamaica 365
III. Bijvoegsels.
Neger-spreekwoorden 380
Avond op het water in Sierra Leone. Naar Florence M.
Cronise en Henry Ward 385
Dierenfabel, verteld door een Bantoe-neger van den
Mpongwe-stam uit West-Afrika, naar Robert H. Nassau 393
IV. Verklarend register 396

[XV]
[Inhoud]
 LIJST VAN ILLUSTRATIES.
Tegenover bldz.
Aan den rand van den afgrond strekte zij hare armen
uit Titel
.… en niettegenstaande Haboeri met zijn parel hare
vingers bijna stuk sloeg, wilde zij niet los laten 64
.… toen hij, in zijn tijdelijk verblijf komend, een vrouw
in de hangmat zag liggen en geen baboen op den
barbakot 88
Daarna stortte het bootje met het slachtoffer en al zijn
zandvlooien omlaag 100
.… een hut waarvoor een stokoude vrouw zat, die in
werkelijkheid een kikvorsch was 108
.… want haar man zat zoowaar in levenden lijve in de
hut 116
.… want plotseling legde de gier het veerenkleed af,
en veranderde in een vrouw 128
.… durfden zij niet naderbij komen 160
In twee groote kanoa’s verlieten de strijders de plaats
waar de moord op Majapawari geschied was 192
Daar deze negerzangen, ter begeleiding der
eentoonige roeibewegingen, in Suriname aan een
tocht op het water even onafscheidelijk verbonden
zijn geworden 224
Heer Spin rolde in zijn uniformjas over den grond 256
.… ging tusschen zijn kinderen staan en vroeg .… 272
„Goeden dag, waarde vriendin” 276
Wanneer zij haar maal gereed had, riep zij haar
vriend met luide stem 280