Gas Bubble Dynamics in the Human Body

Gas Bubble Dynamics in the Human Body

First Edition

Saul Goldman

University of Guelph, Department of Chemistry, the Guelph-Waterloo Centre for Graduate Work in Chemistry and the Guelph-Waterloo Physics Institute, Guelph, ON, Canada

J. Manuel Solano-Altamirano

Benemérita Universidad Autónoma de Puebla, Facultad de Ciencias Químicas, Puebla, Pue., México

Kenneth M. Ledez

Memorial University, Faculty of Medicine, Health Sciences Centre, St. Johns NL, Canada

Table of Contents

Cover image

Title page

Copyright

Dedication

List of figures

About the authors

Preface

Acknowledgments

1: Bubbles in the body: The not so good, the bad, and the ugly

Abstract

1.1 Introduction

1.2 Causes and origins of bubbles in the body

1.3 Circulation fundamentals

1.4 Cell membranes and microparticles

1.5 Transport and exchange of gases

1.6 Bubble physics, anatomy, and biology

1.7 Forces promoting and inhibiting bubble movement

1.8 How do bubbles cause symptoms, signs, and damage?

1.9 Protections against bubbles

1.10 The formation and growth of bubbles

1.11 Patent foramen ovale and mechanisms for bypassing the pulmonary bubble filter

1.12 Tissue gas content and fast or slow tissues

1.13 MBs, MPs, BBs, SBs, NBs, and NPs in gas-bubble disease

1.14 Genomic responses to gas bubbles

1.15 Composition of gas within bubbles

1.16 A gas-fluid and gas-tissue interface is not harmful to all tissues

1.17 Prevention of bubbles in the body

Appendix A Appendix on pressures and tensions

2: Driving force of gas-bubble growth and dissolution

Abstract

2.1 Introduction

2.2 Background

2.3 The driving force of gas-bubble growth

2.4 A general measure of dissolved solute volatility from solution

2.6 Surface tension

2.7 Mechanical, chemical, and thermodynamic equilibrium

2.8 Supersaturation and undersaturation functions for gas mixtures

2.9 Empirical confirmation

Problems

3: Rates of gas-bubble growth and dissolution in simple liquids

Abstract

3.1 Introduction

3.2 The Diffusion equation

3.3 Solutions of the Diffusion and Laplace equations

3.4 Reduction to a finite system

3.5 Expressions for (∂c/∂r)R,t for two three-region models

3.6 Empirical confirmation

Problems

4: Estimating the radii and lifetimes of small gas bubbles suspended in simple liquids

Abstract

4.1 Introduction

4.2 Diffusion models for solute transport around a gas bubble in a simple liquid

4.3 Expressions for (∂c/∂r)R,t

4.4 Analytic working equations for the LHF2, LHF3, and LHV3 models for a fixed ambient pressure

4.5 Variable ambient pressure

4.6 Numerical working equations for the four models based on Dirichlet boundary conditions, Henry’s law at the bubble surface, and a fixed or variable ambient pressure

4.7 Application of Neumann versus Dirichlet boundary conditions

4.8 Numerical results

4.9 Summary

Problems

5: AGEs in scuba diving and in DCS-like problems in breath-hold diving

Abstract

5.1 Introduction

5.2 Bubble filtering by the lungs and right-to-left shunting

5.3 Conditions for AGE contraction or expansion

5.4 System selection

5.5 Estimation of AGE transit times

5.6 Arterial inert gas equations for scuba and breath-hold diving

5.7 A simple compartmental model for the brain and the inner ear

5.8 Growth and dissolution of an AGE lodged in a capillary

5.9 Examples of AGE growth and dissolution

Problems

6: Gas bubbles in soft tissue-like solids

Abstract

6.1 Introduction

6.2 Theory

6.3 Results

6.4 Relation to previous work on viscoelastic materials

6.5 Summary

Problems

7: The evils that bubbles do…

Abstract

7.1 Introduction

7.2 The importance of gas load

7.3 Clinical syndromes

7.4 DCS is (mostly) about excess dissolved inert gas in tissues and venous blood

7.5 Other gas-bubble disease locations and mechanisms

7.6 Mixed and combined effects

7.7 Systemic, vascular, and inflammatory effects

7.8 Vasoactive agents

7.9 Comparisons between decompression illnesses and CPB

7.10 Doppler and ultrasound bubble detection

7.11 Real-life case examples

8: Compartmental decompression models and DCS risk estimation

Abstract

8.1 Introduction

8.2 Deterministic Decompression Theory

8.3 Graphical distinction between deterministic and probabilistic approaches

8.4 The probabilistic approach

8.5 Fitting probabilistic models to dive data

8.6 Interconnected Compartmental Models

8.7 Applications of a Mammillary model for P(DCS) predictions

8.8 Some practical issues

Problems

9: Treating the evils that bubbles do

Abstract

9.1 Introduction

9.2 First of all, do not make things worse

9.3 Diagnosis and decisions

9.4 Bubble shrinkage

9.5 Potential novel therapeutic and procedural interventions

9.6 Are there any bubbles left?

9.7 Outcomes of case examples

10: Gas-bubble dynamics in the treatment of gas-bubble disease: Merging medicine and math

Abstract

10.1 First of all, turn off the tap…

10.2 Applying bubble dynamics principles to clinical decisions

10.3 Physical basis of the bubble model

10.4 Applications of Eqs. (10.20) and (10.21) to predict the effects of time, ambient pressure, bubble size, and breathing gas on the dynamics of gas-bubble dissolution

10.5 Treating bubbles with pressure

10.6 Summary and conclusions

10.7 The future of bubbles in the body…

Appendix: Solutions to problems

Chapter 2

Chapter 3

Chapter 5

Chapter 8

Index

Copyright

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Notices

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Dedication

I would like to dedicate my contribution to this book to the memory of the late David N. Zweig, my math teacher at (the former) Baron Byng High School in Montreal.

Mr. Zweig taught math superbly well and was both a mensch and the best teacher I have ever had. His geometry classes were particularly memorable, probably because he taught them in a way that showed his students what the human mind can achieve. More importantly, he did this in a way that showed these achievements were made by real people like the Pythagoreans, who were students—much like us. They were dedicated and worked hard at their intellectual pursuits, but they also liked to party, and would celebrate the discovery of new theorems with a major feast. I will always remember him standing near a window, chalk on his hands and jacket, with the sun shining down on him after writing out a proof on the blackboard.

He instilled in me a lifelong passion for the world of ideas, which profoundly influenced the direction of my life.

S. Goldman

I would like to dedicate my contribution to this book to Juan Carlos Ramírez García, who is currently a member of the Faculty of Chemical Sciences of the Meritorious Autonomous University of Puebla.

Ever since I met Juan Carlos, back when I was in high school, I was always impressed by his enthusiasm for science and his selfless work and actions in encouraging young people to follow scientific careers. During his training lectures for the Chemistry Olympiad, I remember his encouraging all of us to choose a scientific career, and his enthusiasm for science as a real and rewarding career option in Mexico. My academic career would not have been what it is today without his counsel.

J.M. Solano-Altamirano

I would like to dedicate my contribution to the writing of this book to Lucas Butler, his dad John Butler, and his mom Paula Butler. At the time of writing, May 2017, Lucas is 13 years old. Lucas has been a major inspiration for my interest in cerebral gas embolism (CAGE). I am making this dedication with the permission and approval of Lucas, John, and Paula. Lucas was born with complex congenital heart disease and even after cardiac surgeries has a significant right-to-left shunt. As a newborn, Lucas suffered from a major episode of CAGE due to bubbles in an intravenous infusion. He was profoundly unstable and it was a major challenge to treat him in the hyperbaric chamber. Along with my colleague, Dr. Geoff Zbitnew, this case was published (see the citation following). A CT scan demonstrated three bubbles in arteries in his brain. Although such scans should not be considered necessary when the clinical situation is clear, the presence of bubbles eventually led to Lucas being referred to me and his subsequent treatment in the hyperbaric chamber. A repeat CT scan demonstrated that the bubbles were gone after the first hyperbaric oxygen treatment. Lucas is a remarkable boy who has faced many challenges in his life as a consequence of his heart disease and the air bubbles to his brain. With help and hard work he has regained use of his arms and hands and legs. Considering how desperate the situation was and the long delay to treatment, things could have turned out much worse. The courage and strength of Lucas, and the love and help of his parents, has been remarkable. They have kept in touch with me for the past 13 years. Recently, when I met with them all, I was astonished to see Lucas walking on his own without any aid or device! And Lucas is smart and doing well in school. Not only that, Lucas is a great person and a source of tremendous pride to his parents and to me. Lucas has been one of the greatest inspirations in my medical career and I hope will similarly inspire readers of this book to understand the real-life importance of gas-bubble disease to individual people. Thank you, Lucas, all the best for the future and please continue to keep in touch!

Dr. Kenneth M. LeDez

K.M. LeDez, G. Zbitnew, Hyperbaric treatment of cerebral air embolism in an infant with cyanotic congenital heart disease, Can. J. Anaesth. 52 (4) (2005) 403–408.

List of figures

Fig. 1.1 Overview of the circulatory system 3

Fig. 1.2 The movement of gas and blood into and out of the lungs 4

Fig. 1.3 Schematic representation of the branching structure of arterial and venous vessels 5

Fig. 1.4 Simplified anatomical structure of blood vessels, demonstrating a lumen lined by endothelium and the wall structure 6

Fig. 1.5 Schematic illustration of watershed and luxury perfusion. 6

Fig. 1.6 Basic cellular membrane structure 7

Fig. 1.7 Possible mechanisms for microparticle formation 9

Fig. 1.8 Different shapes of intravascular and autochthonous bubbles 15

Fig. 1.9 Putative structure of the stabilizing skin or coating around a gas microbubble 16

Fig. 1.10 Forces promoting and inhibiting intravascular bubble movement 18

Fig. 1.11 The effect of arterial and venous structures on bubble-bubble encounters and bubble shapes and movement 18

Fig. 1.12 Schematic overview of the pulmonary bubble filter in its role of eliminating gas bubbles from circulating venous blood 20

Fig. 1.13 Bubble dynamics in the pulmonary filter 20

Fig. 1.14 Gas exchange in pulmonary alveoli 21

Fig. 1.15 Δμ/kT vs. R 27

Fig. 1.16 Schematic representation of a PFO within a simplified sketch of the heart 30

Fig. 1.17 Schematic illustration of the main factors that influence the rate at which tissues take up dissolved inert gas 32

Fig. 1.18 Schematic representation of the washout of inert gases from tissue compartments after depressurization from exposure to increased depth (pressure), with different half-times, from fast to slow. 33

Fig. 1.19 Illustration of washin and washout patterns for a fast (t1/2 = 3 min) and a slow (t1/2 = 60 min) tissue 33

Fig. 1.20 Microparticles form by budding off from cell membranes 36

Fig. 1.21 Schematic illustration of genomic responses to gas bubbles 39

Fig. 1.22 Illustration of some factors determining the composition of gas within bubbles in arterial blood 40

Fig. 2.1 Solute flow between phases 51

Fig. 2.2 Solute flow in a mixture of solutes 60

Fig. 3.1 Solute concentration gradient 67

Fig. 3.2 Three-region model geometry 69

Fig. 3.3 Solute concentration profile 71

Fig. 3.4 Geometry of mass flowing through a volume 76

Fig. 4.1 Three-region model geometry 85

Fig. 4.2 Dissolution times (Laplace vs. Diffusion equations) 99

Fig. 4.3 Solute concentration obtained through Dirichlet and Neumann boundary conditions 100

Fig. 4.4 Dissolution time (Dirichlet vs. Neumann boundary conditions) 101

Fig. 5.1 AGEs in the arterial system 109

Fig. 5.2 Brain and inner ear parallel compartmental model 120

Fig. 5.3 AGE dissolving times (fixed depth vs. variable depth) 122

Fig. 5.4 N2 partial pressures (low-risk dive) 123

Fig. 5.5 Bubble radius evolution (low-risk dive) 124

Fig. 5.6 N2 partial pressures (lung collapse vs. no lung collapse) 126

Fig. 5.7 Bubble radius evolution (breath-hold dive) 127

Fig. 5.8 N2 partial pressures evolution (breath-hold dive) 128

Fig. 5.9 N2 arterial and tissue partial pressures evolution (repetitive breath-hold dive) 129

Fig. 5.10 Bubbles evolution (repetitive breath-hold dive) 129

Fig. 5.11 Bubble radius evolution: brain vs. inner ear (repetitive breath-hold dive) 130

Fig. 6.1 Pressure gradients in a simple liquid vs. an elastic medium 137

Fig. 6.2 Gas bubble embedded in an elastic shell 141

Fig. 6.3 Reduced radius vs. reduced time (Diffusion vs. Laplace equations) 154

Fig. 6.4 Bubble growth and dissolution conditions 155

Fig. 6.5 Bubble evolution (the effect of shear modulus) 155

Fig. 7.1 Basic anatomy of the arch of the aorta 164

Fig. 7.2 Incomplete obstruction of an artery by a gas bubble 165

Fig. 7.3 Arterial supply of the spinal cord 167

Fig. 7.4 Schematic showing hypothetical links between microparticles and decompression stress 178

Fig. 8.1 Haldane’s decompression model of the body 188

Fig. 8.2 Allowable pressure ratios for the original and modified Haldane tissues 190

Fig. 8.3 Probabilistic vs. deterministic (or barrier-based) models 191

Fig. 8.4 General three-compartmental system 209

Fig. 8.5 Three-compartment Catenary and Mammillary models 215

Fig. 8.6 The effect of gas bubbles on a Ruffini Type II Corpuscle 218

Fig. 8.7 The three-compartment Mammillary model (3CM), with the risk restricted to the central compartment only 220

Fig. 8.8 P(DCS) predictions of five models for a direct-ascent from saturation 221

Fig. 8.9 Effect of ascent rate on P(DCS) for a no-stop dive to 100 fsw for 25 min 223

Fig. 8.10 Effect of a stop on a very low-risk dive (60 fsw for 40 min) 223

Fig. 8.11 The effect of stop time on P(DCS) reduction, for one low-risk and two high-risk dives on air, as predicted by the 3CM model 229

Fig. 8.12 Two equal-area plots for p1(t) vs. t 231

Fig. 9.1 Therapeutic effects of movement and reduction of length or diameter of bubbles 241

Fig. 10.1 Reduced diffusion of gas out of a bubble stuck at an arterial bifurcation, for two slightly different conditions 256

Fig. 10.2 Three-region model geometry 257

Fig. 10.3 Illustration of the mechanism of gas-bubble dissolution based on solute diffusion in the medium 263

Fig. 10.4 Breathing O2 vs. air effect on dissolution time 266

Fig. 10.5 Diameter vs. time for three N2 bubbles with the patient breathing pure O2 at 1 ATA 267

Fig. 10.6 Diameter of two N2 bubbles with the patient breathing pure O2 in a chamber pressurized with pure O2 at 2.8 ATA 268

Fig. 10.7 Dissolution time for N2 and He bubbles 270

Fig. 10.8 Bubble diameter evolution for He and N2 bubbles 270

Fig. 10.9 Length (L) of a sausage-shaped bubble vs. ambient pressure (P) 272

Fig. 10.10 Pfree vs. L 273

Fig. 10.11 N2 fraction in breathing mixture that maintains a constant nitrogen concentration in arterial blood 275

Fig. 10.12 Diagrammatic representation of the effects of bubbles and hyperbaric oxygen in gas-bubble disease 281

Fig. 10.13 A central challenge of gas-bubble dynamics in the human body: extending the model on the left to those on the right 281

Fig. A.1 Bubble contraction rate (Laplace vs. Diffusion) 286

Fig. A.2 Bubble contraction rate (Laplace 2-region vs. LHV3 3-region) 286

Fig. A.3 Effect of ascent/descent rate on bubble contraction rate 287

Fig. A.4 Rate of bubble expansion for bubble in capillary of supersaturated tissue 287

Fig. A.5 Arterial pressure, Part, vs. depth for scuba and breath-hold diving 288

About the authors

Saul Goldman is a Professor Emeritus in the Chemistry Department at the University of Guelph, Guelph, Ontario, Canada. He got his BSc in 1964 and PhD in 1969, both in Chemistry from McGill University in Montreal. Upon receiving his PhD, he was awarded the D.W. Ambridge Prize, given to the top-ranked PhD graduate in the Physical and Applied Sciences at McGill. After his doctoral work, he took up a postdoctoral position in the Chemistry Department at the University of Florida in Gainesville, Florida, supported in part by a National Research Council (Canada) fellowship. Following this, he assumed a faculty position in the Chemistry Department at the University of Guelph in 1972, where he has been ever since. His research interests lie in the areas of Physical Chemistry, Chemical Physics, and Molecular Physics. More specifically, he has worked on the application of Thermodynamics, Kinetics, Statistical Mechanics, Monte Carlo and Molecular Dynamics simulations, both to fundamental problems and to applied problems that are of particular interest in engineering and molecular biology. The fundamental work included the application of statistical-mechanical perturbation theory for the development of molecular-level theories of liquids and solutions. The engineering applications included the application of virial expansions for predicting the gas-phase solubility of volatile organic solids and essential oils in supercritical CO2, which is relevant to developing separation techniques using supercritical fluid extraction. The applications to molecular biology focused on identifying the physical basis of ion selectivity, and K+-selective ion channels (KcsA, IRK1) were selected for this purpose. One goal was to predict the unitary (single-ion) current in such a channel. This required the development and use of specialized forms of molecular dynamics, applied to a structural model of the channel’s selectivity filter. His more recent research involves trying to understand the physical basis for various forms of decompression sickness, the arterialization of venous gas emboli, and the physical factors that affect the stability and longevity of autochthonous inert gas bubbles in extravascular tissue. A particular focus here is the role of tissue elasticity on gas-bubble stability and pressure. His work was done mostly in collaboration with undergraduate and graduate students, postdoctoral fellows, research associates, and faculty colleagues. The funding for his work came from research grants awarded by the Natural Sciences and Engineering Research Council of Canada. His competitive, peer-reviewed core funding (in the form of Operating and Discovery Grants) has continued uninterrupted over the course of the past 44 years. He is the author or coauthor of about 90 peer-reviewed articles, many published in high-impact journals including: Journal of Physical Chemistry, Journal of Chemical Physics, Molecular Physics, Physical Review, and Journal of General Physiology. He is also an avid recreational scuba diver with about 1200 logged dives, a former low-level equestrian (hunter/jumper), and a current high-level amateur winemaker. His wines have been awarded many medals, including a coveted Best of Show for his 2001 California Chardonnay.

Juan Manuel Solano Altamirano is an Assistant Professor in the Faculty of Chemical Sciences at the Meritorious Autonomous University of Puebla, Puebla, Mexico (Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, México). He got his BSc in Chemistry in 2003 and PhD in Physics in 2009, both from the Meritorious Autonomous University of Puebla. The subject of his PhD thesis was in the field of Mathematical Physics. After this, he took a postdoctoral position at the CINVESTAV campus in Monterrey. This was supported by a National Council of Science and Technology (Conacyt, Mexico) fellowship, and was for the period 2010 to part of 2011. Afterwards, he took a Research Associate position in the Chemistry Department of the University of Guelph from 2011 to 2014. Following this in 2015, he worked as a C++ Programmer in the Extreme Light Infrastructure Beamlines project, which is coordinated by the National Academy of Sciences of the Czech Republic. Subsequently, starting in December 2015, he was appointed Assistant Professor in the Faculty of Chemistry of the Meritorious Autonomous University of Puebla, where he currently works. His research interests are strongly focused on interdisciplinary problems, with a bias toward their theoretical and computational aspects. His current research is in the following four main areas: (1) Chemical physics applied to the study of bubble dynamics in the human body, using classical methods such as classical thermodynamics, diffusion of gases in liquids and soft solids, and thermodynamics of elastic media. (2) Theoretical and quantum chemistry, including thermochemical and fundamental problems, such as the nature of the chemical bond, as well as practical methods for determining intramolecular bond energies. Within this area he develops open-source code (DensToolKit) for studying scalar and vector fields derived from electron density and the topological features of electron density. (3) Molecular dynamics simulations of granular matter, which includes development of models, algorithms, and software for two-dimensional systems. (4) In the field of lasers, he is interested in developing algorithms for spot recognition and wave-front reconstruction. Due to the highly interdisciplinary nature of his research interests, his work has been and continues to be carried out collaboratively with other researchers, particularly Saul Goldman, and other colleagues in Mexico and Europe. He is coauthor of 12 peer-reviewed articles all published since 2007, several of which are in high-impact journals, such as Physical Review Letters, Physical Review E, Soft Matter, Computer Physics Communications, and Sensors. In his leisure time, he enjoys drawing, playing the guitar, and open-source-related pursuits.

Kenneth M. LeDez is Associate Professor in the Faculty of Medicine, Memorial University, Health Sciences Center, St. John’s, Newfoundland and Labrador, Canada. He is an anesthesiologist and former Research Director and academic Chair of the Discipline of Anesthesia at Memorial University. After graduating from medical school at the University of Dundee, Scotland and undertaking training in anesthesia in London; he returned to his native Canada in 1985 for a research fellowship at the Hospital for Sick Children in Toronto and later additional residency training in anesthesia at the University of Toronto. It was there that Dr. LeDez revitalized the hyperbaric medicine service during a fellowship in hyperbaric medicine. He played a key role in founding the Canadian Chapter of the Undersea and Hyperbaric Medical Society (now the Canadian Undersea and Hyperbaric Medical Association [CUHMA]) and was the first President. As Chair of the CUHMA Standards of Practice and Patient Safety Committee he was the editor and lead author of the Guidelines to the Practice of Hyperbaric Medicine and Provision of Hyperbaric Oxygen Treatment in Canada. He is a past Vice-President of the Undersea and Hyperbaric Medical Society (UHMS) and on the Editorial Board of the Canadian Journal of Anesthesia for 9 years. Dr. LeDez led the effort to establish national physician certification in hyperbaric medicine in Canada and this culminated in the approval of the Diploma in Hyperbaric Medicine by the Royal College of Physicians and Surgeons of Canada. Now as Chair of the Specialty Committee for Hyperbaric Medicine he is leading the effort to implement the Diploma. Dr. LeDez has more than 30 years’ experience in hyperbaric medicine. He has been providing medical coverage for saturation diving in the offshore oil industry in Newfoundland and Labrador for 25 years by providing diving medicine services to Atlantic Offshore Medical Services. Dr. LeDez is recognized as a Specialist in Diving and Hyperbaric Medicine by the Canada-Newfoundland and Labrador Offshore Petroleum Board and the Canada-Nova Scotia Offshore Petroleum Board. He is Medical Director of the Hyperbaric Medicine Service at Eastern Health in St. John’s, Newfoundland and Labrador. For over two decades he has represented Canada on the International Standards Organization committee (TC121) on Anesthesia and Respiratory Equipment. During his career, Dr. LeDez has published multiple articles and abstracts related to anesthesiology and hyperbaric medicine. He is married and has five young boys. Although now too busy to continue as a pilot, Dr. LeDez is an enthusiastic sailor, scuba diver, and underwater videographer.

Preface

This is perhaps a unique book, written by a combination of chemistry-physics-maths experts on the one hand, and a hyperbaric medicine physician on the other. Despite the plethora of equations and calculations, physicians and others interested in diving and hyperbaric medicine, and those involved in any of the numerous fields of medicine and health care where accidental gas embolism may occur, should not feel intimidated. There is ample detailed consideration of how bubbles affect the human body, and implications for treatment. Where the math gets more intense, material is separated into shaded sections headed In Greater Detail and For the Math Mavens. This makes it easy for readers with a lesser focus on calculations to skip past these sections, or to later go back and peruse them to see how complex this material can be and to get a better idea of where some of the predictions and conclusions come from. Other sections deal more with Medical Matters. Chapters 1, 7, 9, and the final chapter, Chapter 10, have a strong clinical focus, whereas in Chapters 2–6 and 8, the focus is on the physics and chemistry of gas bubbles. These chapters develop the equations and describe the calculations needed to understand and predict the dynamical behavior of gas bubbles in the body from a physical and mathematical basis. These chapters also contain problem sections intended to give hands-on experience with the application of the equations, and a Solutions to Problems appendix is provided at the end of the book.

Readers who come from a physical or mathematical science background should similarly not feel intimidated by the chapters with a clinical medical focus. The important physiological and medical issues relating to circulation and to the cardiovascular and pulmonary systems are explained in Chapter 1, in a manner that does not assume detailed medical knowledge. Throughout the book, figures illustrate key concepts that will enable readers from all backgrounds to quickly grasp the detailed principles involved.

This book is about how bubbles interact with the human body; however, they form or wherever they come from, and is not a manual on how to calculate safe decompression profiles. As explained in the book, bubbles can no longer be thought of as just pockets of gas. To understand the current state of knowledge of the dynamic effects of bubbles it is essential to also explore microparticles, microbubbles, and what happens when both these small coated particles, and larger bubbles, interact with physiological systems, and the resulting profoundly complex biological reactions. This publication is also not intended to be a detailed book on the molecular biology and molecular pathology of bubbles. Although these topics are considered, the goal is to provide a big picture view of the formation, growth, biological effects, dissolution, and elimination of gas bubbles. The numerous references will provide ample opportunities for the reader to explore in greater detail the biology and physics of bubble dynamics. The top of each chapter provides a brief summary and guidance on the nature of the topics covered. Where it is helpful, there are cross-references between the chapters to aid understanding and to point out the connections between the clinical and physical material. The goal of the authors is to enable the reader to have an up to date, state-of-the-art-and-science understanding of the dynamics of gas bubbles in the human body.

Saul Goldman, University of Guelph, Guelph, ON, Canada

Juan Manuel Solano Altamirano, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico

Kenneth M. LeDez, Memorial University, St. Johns, NL, Canada

Acknowledgments

It is a pleasure to acknowledge the help that was provided to me by my wife Ethel R. Goldman. Her level-headed, sound advice for dealing with operational issues that arose during the writing of this book is much appreciated.

Saul Goldman

May 2017

I profoundly thank my parents Humberto and Agustina, and my brothers Mauricio, Daniel, and Diego, as well as my friend Julio Manuel, for all their support and patience during the writing of this book.

Juan Manuel Solano Altamirano

May 2017

I would like to acknowledge the patience and support of my wife, Lori Gordon, and my five young boys, Kendall (14), Kaden (13), Colton (10), Carson (8), and Quinton (6), during the writing of this book.

Kenneth M. LeDez

May 2017

1

Bubbles in the body: The not so good, the bad, and the ugly

Abstract

Understanding the anatomy and physiology of the cardiovascular and pulmonary systems is essential to appreciate the dynamics of bubbles in the body, including the structure of arterial and venous vessels, cell membranes and the transport of gases. Bubbles may be spherical, but if larger than the diameter of an enclosing vessel will become sausage-shaped (cylindrical with hemispherical end-caps). Microbubbles and microparticles play important roles in decompression sickness (DCS) and arterial gas embolism (AGE). Bubbles may be stabilized by a surrounding skin of molecules and thereby persist much longer than would be expected otherwise. The pulmonary bubble filter is a crucial defense against venous bubbles entering the arterial circulation, but may be bypassed by a patent foramen ovale and other mechanisms. The uptake and elimination of inert gases may be described by washin and washout exponentials. The appendix describes fundamental concepts of gas pressures in the body.

Keywords

Microbubble; Microparticle; Patent foramen ovale; Pulmonary bubble filter; Bubble; Alveolus; Circulation; Cell membrane; Inert gas; Diffusion; Oxygen; Oxygen 93; Carbon dioxide; Nitrogen; Argon

We hate to be the ones to burst your bubble, but…

The authors

Main Topics

• Causes and origins of bubbles in the body

• Anatomy and function of the circulatory system

• Branching structure of the circulation

• Pulmonary bubble filter

• Pressures and gas tensions

Medical Matters

• Formation and role of microparticles

• Vascular vulnerabilities

• Inflammatory responses to bubbles

• Ischemia/reperfusion injury due to bubbles

1.1 Introduction

Bubbles in the human body are not just from diving but also arise from medical procedures, trauma, and other situations. There is no definitely known physiologic role for bubbles in the body. Evolution has provided defenses against many biologic threats although for bubbles these may be somewhat limited. Many sections of this book contain calculations and equations of varying complexity. One rule or equation that holds generally true in the human body is:

Bubbles = Bad.

How bad depends on many factors that are discussed in this book.

1.2 Causes and origins of bubbles in the body

Gas bubbles can form in or enter the tissues or blood from a number of sources [1, 2]:

• Depressurization/decompression.

• Disruption or trauma to gas cavities within the body.

• Injection into the bloodstream by various mechanisms, many due to medical interventions.

• Rupture of alveoli (lung sacs) and the vessels that surround them due to over-pressurization or other injury.

• Being injected or forced into the body from other exogenous sources, such as industrial compressed gas tool accidents.

• Counterdiffusion, where an inert gas is breathed that is different than the one that is supersaturating tissues.

The source of the gas may result directly in bubbles, or the bubbles may form as a consequence of a reduction in ambient pressure or other physical influences. When breathing compressed gases, such as in SCUBA or other diving, the gas is inhaled through the lungs. The term gas-bubble disease will be used when necessary to encompass all circumstances when medical disorders are related to the presence of gas bubbles in the body. In most cases of decompression sickness (DCS) the location of bubbles is not known. This chapter deals primarily with circulation and the pulmonary system, with particular emphasis on their relation to the formation, dissolution, and transport of gas bubbles in the body. Blood circulation is driven by pressure differences, while the formation, growth, and dissolution of gas bubbles can be driven by pressure and/or gas tension differences. The main concepts are first explained and illustrated descriptively, with the more quantitative physical underpinnings described subsequently. But because of the complexity of the body and the variety of conditions encountered, we will have to distinguish between: absolute and relative (or gauge) pressure, ambient pressure, hydrostatic pressure, gas partial pressure, and gas tension (in addition to arterial, venous, and tissue gas tensions). All this can be a confusing distraction. So to maintain continuity of the conceptual material, we separate the discussion of the measures of pressure and tension from the main text, and describe them separately in Appendix of this chapter. A more detailed discussion of gas tension and its relation to the chemical potential and bubble growth and dissolution is reserved for Chapter 2.

1.3 Circulation fundamentals

The human body is an immensely complex structure. It is important to be familiar with the overall anatomy and function of the circulation (Fig. 1.1) and the general configuration of gas and blood flow in the lungs (Fig. 1.2) (see also [3–6]). Blood flows from the left atrium into the left ventricle from which it is pumped into the main artery (aorta), then the arteries, arterioles, and then to tiny capillaries from where oxygen and nutrients pass to the cells and tissues. A small percentage of fluid is collected into lymphatic vessels but most of the circulating blood passes from the capillaries into venules, veins, and then to the right atrium. From there, blood flows to the right ventricle and is then pumped to the pulmonary arteries and arterioles and then to the capillaries that surround the alveoli (lung sacs) in the lung, where all gas exchange occurs. From the pulmonary capillaries blood then flows to the pulmonary veins and then to the left atrium.

Fig. 1.1 Overview of the circulatory system . (A) Main arteries and veins of the human circulatory system. The human body exchanges oxygen, carbon dioxide, nutrients, hormones, and many other substances, and eliminates excess inert gas, by means of circulating blood. (B) Functional representation of the circulatory system. The heart (central section) supplies blood rich in O 2 to the head and the rest of the body (upper and lower sections). CO 2 is eliminated and O 2 is taken on by exchange in the lungs ( left and right sections; see also Fig. 1.2). (Figure (A) is a modification of a Wikipedia scheme,