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32 matches in All Departments
The lymphatic system develops and functions in parallel with the
blood circulatory system (termed the "hemovasculature") and
accomplishes transport of interstitial fluids, dietary lipids, and
reverse transport of cholesterol, immune cells, and
antigens-providing a critical homeostatic fluid balance and
transmission of immune cells and mediators back to the
cardiovascular system. Although the daily flow of lymph (normally
1-2 L/day under unstressed conditions) is far lower than that of
daily blood flow (which is 7,500 L/day), without the adequate
functioning of the lymphatics, virtually all organs and tissues
would acutely suffer many different physical and inflammatory
stresses ranging from edema to organ system failure. Although blood
and lymphatic vessels often form in anatomic parallels to one
another, our knowledge of the workings of the lymphatic system, the
fine structure of lymphatic networks, how they function in
different organs, and how they are regulated physiologically and
immunologically are far from parallel; our knowledge of the
lymphatic system still remains at only a tiny fraction of what is
understood about the cardiovascular system. Although both the
cardiovascular and lymphatic systems are important transport
systems, what they transport and how they transport and propel
these very different cargoes could not be more dissimilar. This
book provides an overview of the history of the discovery (and
re-discovery) of the components of the lymphatic system, lymphatic
anatomy, physiological functions of lymphatics, molecular features
of the lymphatic system, and clinical perspectives involving
lymphatics which may be of interest to scientists, clinicians,
patients, and the lay public. We provide a current understanding of
some of the more important structural similarities and differences
between lymphatics and the blood vascular system, their coordinated
control by angiogenic and hemangiogenic growth factors and other
modulators, the fate and lineage determinants which control
lymphatic development, and the roles that lymphatics may play in
several different diseases.
This collaboration of two physiologists and a gastroenterologist
provides medical and graduate students, medical and surgical
residents, and subspecialty fellows a comprehensive summary of
digestive system physiology and addresses the pathophysiological
processes that underlie some GI diseases. The textual approach
proceeds by organ instead of the traditional organization followed
by other GI textbooks. This approach lets the reader track the food
bolus as it courses through the GI tract, learning on the way each
organ's physiologic functions as the bolus directly or indirectly
contacts it. The book is divided into three parts: (1) Chapters 1-3
include coverage of basic concepts that pertain to all (or most)
organs of the digestive system, salivation, chewing, swallowing,
and esophageal function, (2) Chapters 4-6 are focused on the major
secretory organs (stomach, pancreas, liver) that assist in the
assimilation of a meal, and (3) Chapters 7 and 8 address the motor,
transport, and digestive functions of the small and large
intestines. Each chapter includes its own pathophysiology and
clinical correlation section that underscores the importance of the
organ's normal function.
Environmental heat stress is associated with a marked decrease in
orthostatic tolerance (OT), which is defined as the ability to
stand or sit upright without symptoms of dizziness,
lightheadedness, presyncope, or fainting. In most healthy humans,
the autonomic nervous system makes rapid and balanced adjustments
to heart rate and peripheral blood flow, such that most people are
able to stand up "successfully" most of the time, in most
environments. The goal of this book is to discuss various aspects
of the sympathetic neural response to heat stress, how the
sympathetic nervous system coordinates the successful integrative
physiological response to orthostasis, and what happens when it
encounters both challenges simultaneously. We include overviews of
mechanisms of thermoregulation and blood pressure regulation in
humans, with particular focus on control of cardiac output and
neurovascular control mechanisms during heat stress. We discuss the
implications that these changes have for distribution of peripheral
blood flow and, in particular, for blood flow to the cerebral
circulation. The added stressor of dehydration is also discussed,
as it so often goes hand in hand with heat stress. We end with a
brief presentation of countermeasures against the decreases in OT
with heat stress.
The kidney is innervated with efferent sympathetic nerve fibers
reaching the renal vasculature, the tubules, the juxtaglomerular
granular cells, and the renal pelvic wall. The renal sensory nerves
are mainly found in the renal pelvic wall. Increases in efferent
renal sympathetic nerve activity reduce renal blood flow and
urinary sodium excretion by activation of 1-adrenoceptors and
increase renin secretion rate by activation of 1-adrenoceptors. In
response to normal physiological stimulation, changes in efferent
renal sympathetic nerve activity contribute importantly to
homeostatic regulation of sodium and water balance. The renal
mechanosensory nerves are activated by stretch of the renal pelvic
tissue produced by increases in renal pelvic tissue of a magnitude
that may occur during increased urine flow rate. Under normal
conditions, the renal mechanosensory nerves activated by stretch of
the sensory nerves elicits an inhibitory renorenal reflex response
consisting of decreases in efferent renal sympathetic nerve
activity leading to natriuresis. Increasing efferent sympathetic
nerve activity increases afferent renal nerve activity which, in
turn, decreases efferent renal sympathetic nerve activity by
activation of the renorenal reflexes. Thus, activation of the
afferent renal nerves buffers changes in efferent renal sympathetic
nerve activity in the overall goal of maintaining sodium balance.
In pathological conditions of sodium retention, impairment of the
inhibitory renorenal reflexes contributes to an inappropriately
increased efferent renal sympathetic nerve activity in the presence
of sodium retention. In states of renal disease or injury, there is
a shift from inhibitory to excitatory reflexes originating in the
kidney. Studies in essential hypertensive patients have shown that
renal denervation results in long-term reduction in arterial
pressure, suggesting an important role for the efferent and
afferent renal nerves in hypertension.
Pulmonary hypertension is a life-threatening disease with no known
cure. Here we provide a concise yet comprehensive review of the
current knowledge about the pathophysiology of pulmonary
hypertension (PH). The underlying signaling mechanisms involved in
pulmonary vascular remodeling and the exaggerated vascular
contractility, two characteristic features of pulmonary
hypertension, are discussed in depth. The roles of inflammation,
immunity, and right ventricular function in the pathobiology of
pulmonary hypertension are discussed. The epidemiology of the five
groups of pulmonary hypertension (World Health Organization
classification; Nice, 2013) is also briefly described. A clear
understanding of our current knowledge about the pathogenesis of PH
is essential for further exploration of the underlying mechanisms
involved in this disease and for the development of new therapeutic
modalities. This book should be of interest to researchers and
graduate students, both in basic research and in clinical settings,
in the fields of pulmonary vascular biology and pulmonary
hypertension.
Food and water are necessary for survival, but can only be obtained
via ingestive behavior (feeding, drinking, and moving). Survival
thus depends on the ability of the brain to coordinate the need for
water and energy with appropriate behaviors to modify their intake
as necessary for homeostasis. However, the balance of these
behaviors also inherently determines body weight, and imbalances
contribute to the development of weight disorders, such as obesity
and anorexia nervosa. The lateral hypothalamic area (LHA) of the
brain is anatomically positioned to coordinate the sensation of
osmotic and energy status with goal-directed ingestive behaviors
necessary to maintain homeostasis and body weight, and, hence, may
hold insight into the potential treatment for energy balance
disorders. This volume reviews the essential role of the LHA for
the control of body weight, from its historical description as a
""feeding center"" to the current view of this LHA as a cellularly
heterogeneous hub that regulates multiple aspects of physiology to
influence body weight. Furthermore, we evaluate how specific LHA
populations coordinate certain metabolic cues and behaviors, which
may guide the development of pathway-specific interventions to
improve the treatment of energy balance disorders.
This book focuses on the structural, biochemical, and diverse
functional properties of the endothelial luminal membrane
glycocalyx (ELMG), an organelle which constitutes the endothelial
cell "membrane." It is intended to provide the newcomer with a
broad, basic, and brief perspective of the luminal endothelial
vascular membrane, and for the more established investigator, a
basic overview and integrated perspective of the "universe" we
explore. The endothelium is an assortment of heterogeneous
regulatory cells whose cytoplasm and cell membranes are joined,
forming functional units. There is a tremendous amount of
literature on the endothelial cell, constituting seemingly isolated
and distinct fields of encapsulated research. However, the
multifunctional properties of some molecules give rise to an
overlap of findings, frequently ignored between the different
fields. The book is divided into three parts. The first part
concentrates on the structure of the ELMG, with emphasis on
morphological and biochemical composition. The importance of the
chemical composition to the physiological functions of the ELMG,
such as sieving properties, pharmacology, and flow sensing, is the
focus of the second part of the book. Finally, some of the
pathologies associated with ELMG dysfunction are explored in the
last section. The aim is to provide basic and well-established
knowledge in the various individual fields, identify the current
concepts in each area, and discuss their respective strengths and
weaknesses (including hidden problems). Finally, the overall goal
is to integrate areas where overlap is clearly indicated, bringing
them all together to provide the first ever basic, integrative,
panoramic bird's-eye view of the field.
|
Polycystic Kidney Disease (Hardcover)
Christian Riella, Peter G Czarnecki, Theodore I Steinman; Series edited by D. Neil Granger, Ph.D., Joey P. Granger, Ph.D.
|
R1,696
Discovery Miles 16 960
|
Ships in 12 - 17 working days
|
This book reviews important aspects of polycystic kidney diseases,
the latest scientific understanding of the diseases and syndromes,
along with the therapies being developed. Cystic kidney diseases
comprise a spectrum of genetic syndromes defined by renal cyst
formation and expansion with variable extrarenal manifestations.
The most prevalent disorder is the autosomal dominant polycystic
kidney disease (ADPKD). It is the most common monogenetic disorder
in humans and accounts for 4.4% of end-stage renal disease (ESRD)
cases in the U.S. Patients inevitably progress to ESRD and require
renal replacement therapy in the form of dialysis or
transplantation. Through advancements in genomics and proteomics
approaches, novel genes responsible for cystic diseases have been
identified, further expanding our understanding of basic mechanisms
of disease pathogenesis. The hallmark among all cystic genetic
syndromes is the formation and growth of fluid-filled cysts, which
originate from tubular epithelia of nephron segments. Cysts are the
disease, and treatment strategies are being developed to target
prevention or delay of cyst formation and expansion at an early
stage, however no such therapy is currently approved.
The idea of this NATO school was born during philosophical
discussions with Dr Brevard on the present and future of NMR during
a night walk under the palm trees in Biskra during a seminar held
in this oasis. It was clear for us that the recent progress in the
field of NMR, especially inverse spectroscopy and the development
of MAS, was opening new perspectives for chemists. We realised also
that organometallic and inorganic chemists were not clearly
informed about the potentialities of all the new methods. NA TO,
with its summer schools, was offering a good opportunity to propose
to the chemical community a session where those problems would be
largely developped. This School is then the prolongation of the two
previous ones: Palermo in 1976 on "the less receptive nuclei" and
Stirling in 1982 on "the multinuclear approach to NMR spectroscopy"
. It was divided into two sub-sessions: NMR in the liquid state and
NMR in the solid state. This is reflected in the book organization.
As indicated by the title of this School, we were mainly concerned
with the methodological aspects of multinuclear NMR. If many
examples are given, they appear only as a support for the
understanding of the theory or in explanation of some practical
aspects of the different experiments. Each domain is introduced by
a lecture which presents selected examples.
This new edition of a classic text, comprehensively revised
throughout, appraises the emerging challenges to the centrality of
the nation-state international system, such as humanitarianism,
environmentalism, new international legal standards, and concepts
such as "civil society" and "globalism." As inter-governmental and
international non-governmental activities are increasingly being
blended, for example in the area of peace-keeping, this poses a
challenge to the sanctity of the territorial state as the primary
political unit. Similarly, technological and social changes such as
the emergence of the Internet, encourages "borderless" activities
(both legal and illegal) by non-state actors. This book provides
the basis for students to consider a thorough rethinking of our
international system and its prospects for the future in the face
of these fundamental and unprecedented developments. While the book
as a whole is built around the unifying theme of "the management of
cooperation," illustrative cases enhance the individual chapters
and provide the basis for comparative analysis and discussion.
These take the reader through the tangled webs of international
cooperation in such areas as the European Union, NATO, humanitarian
intervention, arms control, transnational criminal organizations,
and global environmental issues. Discussion questions at the end of
each chapter add to the usefulness of this text for students.
Anomalous electron-spin state populations in the Electron
Paramagnetic Re sonance (EPR) spectra of radicals formed during
radio lysis experiments were observed in 1963 by FESSENDEN and
SCHULER [170a]. This phenomenon did not receive much attention at
the time. In 1967, BARGON, FISCHER, and JOHNSEN [5] and
independently WARD and LAWLER [7,8] reported a similar phenomenon
for Nuclear Magnetic Resonance (NMR) spectra taken during radical
reactions: emission or enhanced absorption, or both. The earliest
attempts to explain this new NMR phenomenon treated these effects
in a way similar to that of Dynamic Nuclear Polarization (DNP) or
the Overhauser effect. Although the polarization has a completely
different origin, DNP gave its name to this effect: Chemically
Induced Dynamic Nuclear Polariza tion (CIDNP). [The name Chemically
Induced Dynamic Electron Polarization (CIDEP) was introduced later
by analogy with CIDNP]. After the initial publica tions, all the
new data demonstrated that the first theory could not be correct.
In 1969, a new theory was proposed by CLOSS [18] and independently
by KAPTEIN and OOSTERHOFF [23] and called the radical-pair theory.
This mechanism was proposed to account for the observations of
polarization in both NMR and EPR. The radical-pair theory is based
on weak interactions in a pair of radicals: the strength of
interaction between the electronic states of the radicals depends
in particular on the nuclear-spin states.
The idea of this NATO school was born during philosophical
discussions with Dr Brevard on the present and future of NMR during
a night walk under the palm trees in Biskra during a seminar held
in this oasis. It was clear for us that the recent progress in the
field of NMR, especially inverse spectroscopy and the development
of MAS, was opening new perspectives for chemists. We realised also
that organometallic and inorganic chemists were not clearly
informed about the potentialities of all the new methods. NA TO,
with its summer schools, was offering a good opportunity to propose
to the chemical community a session where those problems would be
largely developped. This School is then the prolongation of the two
previous ones: Palermo in 1976 on "the less receptive nuclei" and
Stirling in 1982 on "the multinuclear approach to NMR spectroscopy"
. It was divided into two sub-sessions: NMR in the liquid state and
NMR in the solid state. This is reflected in the book organization.
As indicated by the title of this School, we were mainly concerned
with the methodological aspects of multinuclear NMR. If many
examples are given, they appear only as a support for the
understanding of the theory or in explanation of some practical
aspects of the different experiments. Each domain is introduced by
a lecture which presents selected examples.
This book focuses on the structural, biochemical, and diverse
functional properties of the endothelial luminal membrane
glycocalyx (ELMG), an organelle which constitutes the endothelial
cell "membrane." It is intended to provide the newcomer with a
broad, basic, and brief perspective of the luminal endothelial
vascular membrane, and for the more established investigator, a
basic overview and integrated perspective of the "universe" we
explore. The endothelium is an assortment of heterogeneous
regulatory cells whose cytoplasm and cell membranes are joined,
forming functional units. There is a tremendous amount of
literature on the endothelial cell, constituting seemingly isolated
and distinct fields of encapsulated research. However, the
multifunctional properties of some molecules give rise to an
overlap of findings, frequently ignored between the different
fields. The book is divided into three parts. The first part
concentrates on the structure of the ELMG, with emphasis on
morphological and biochemical composition. The importance of the
chemical composition to the physiological functions of the ELMG,
such as sieving properties, pharmacology, and flow sensing, is the
focus of the second part of the book. Finally, some of the
pathologies associated with ELMG dysfunction are explored in the
last section. The aim is to provide basic and well-established
knowledge in the various individual fields, identify the current
concepts in each area, and discuss their respective strengths and
weaknesses (including hidden problems). Finally, the overall goal
is to integrate areas where overlap is clearly indicated, bringing
them all together to provide the first ever basic, integrative,
panoramic bird's-eye view of the field.
This collaboration of two physiologists and a gastroenterologist
provides medical and graduate students, medical and surgical
residents, and subspecialty fellows a comprehensive summary of
digestive system physiology and addresses the pathophysiological
processes that underlie some GI diseases. The textual approach
proceeds by organ instead of the traditional organization followed
by other GI textbooks. This approach lets the reader track the food
bolus as it courses through the GI tract, learning on the way each
organ's physiologic functions as the bolus directly or indirectly
contacts it. The book is divided into three parts: (1) Chapters 1-3
include coverage of basic concepts that pertain to all (or most)
organs of the digestive system, salivation, chewing, swallowing,
and esophageal function, (2) Chapters 4-6 are focused on the major
secretory organs (stomach, pancreas, liver) that assist in the
assimilation of a meal, and (3) Chapters 7 and 8 address the motor,
transport, and digestive functions of the small and large
intestines. Each chapter includes its own pathophysiology and
clinical correlation section that underscores the importance of the
organ's normal function.
Pulmonary hypertension is a life-threatening disease with no known
cure. Here we provide a concise yet comprehensive review of the
current knowledge about the pathophysiology of pulmonary
hypertension (PH). The underlying signaling mechanisms involved in
pulmonary vascular remodeling and the exaggerated vascular
contractility, two characteristic features of pulmonary
hypertension, are discussed in depth. The roles of inflammation,
immunity, and right ventricular function in the pathobiology of
pulmonary hypertension are discussed. The epidemiology of the five
groups of pulmonary hypertension (World Health Organization
classification; Nice, 2013) is also briefly described. A clear
understanding of our current knowledge about the pathogenesis of PH
is essential for further exploration of the underlying mechanisms
involved in this disease and for the development of new therapeutic
modalities. This book should be of interest to researchers and
graduate students, both in basic research and in clinical settings,
in the fields of pulmonary vascular biology and pulmonary
hypertension.
Food and water are necessary for survival, but can only be obtained
via ingestive behavior (feeding, drinking, and moving). Survival
thus depends on the ability of the brain to coordinate the need for
water and energy with appropriate behaviors to modify their intake
as necessary for homeostasis. However, the balance of these
behaviors also inherently determines body weight, and imbalances
contribute to the development of weight disorders, such as obesity
and anorexia nervosa. The lateral hypothalamic area (LHA) of the
brain is anatomically positioned to coordinate the sensation of
osmotic and energy status with goal-directed ingestive behaviors
necessary to maintain homeostasis and body weight, and, hence, may
hold insight into the potential treatment for energy balance
disorders. This volume reviews the essential role of the LHA for
the control of body weight, from its historical description as a
""feeding center"" to the current view of this LHA as a cellularly
heterogeneous hub that regulates multiple aspects of physiology to
influence body weight. Furthermore, we evaluate how specific LHA
populations coordinate certain metabolic cues and behaviors, which
may guide the development of pathway-specific interventions to
improve the treatment of energy balance disorders.
The lymphatic system develops and functions in parallel with the
blood circulatory system (termed the "hemovasculature") and
accomplishes transport of interstitial fluids, dietary lipids, and
reverse transport of cholesterol, immune cells, and
antigens-providing a critical homeostatic fluid balance and
transmission of immune cells and mediators back to the
cardiovascular system. Although the daily flow of lymph (normally
1-2 L/day under unstressed conditions) is far lower than that of
daily blood flow (which is 7,500 L/day), without the adequate
functioning of the lymphatics, virtually all organs and tissues
would acutely suffer many different physical and inflammatory
stresses ranging from edema to organ system failure. Although blood
and lymphatic vessels often form in anatomic parallels to one
another, our knowledge of the workings of the lymphatic system, the
fine structure of lymphatic networks, how they function in
different organs, and how they are regulated physiologically and
immunologically are far from parallel; our knowledge of the
lymphatic system still remains at only a tiny fraction of what is
understood about the cardiovascular system. Although both the
cardiovascular and lymphatic systems are important transport
systems, what they transport and how they transport and propel
these very different cargoes could not be more dissimilar. This
book provides an overview of the history of the discovery (and
re-discovery) of the components of the lymphatic system, lymphatic
anatomy, physiological functions of lymphatics, molecular features
of the lymphatic system, and clinical perspectives involving
lymphatics which may be of interest to scientists, clinicians,
patients, and the lay public. We provide a current understanding of
some of the more important structural similarities and differences
between lymphatics and the blood vascular system, their coordinated
control by angiogenic and hemangiogenic growth factors and other
modulators, the fate and lineage determinants which control
lymphatic development, and the roles that lymphatics may play in
several different diseases.
|
Polycystic Kidney Disease (Paperback)
Christian Riella, Peter G Czarnecki, Theodore I Steinman; Series edited by D. Neil Granger, Ph.D., Joey P. Granger, Ph.D.
|
R766
Discovery Miles 7 660
|
Out of stock
|
This book reviews important aspects of polycystic kidney diseases,
the latest scientific understanding of the diseases and syndromes,
along with the therapies being developed. Cystic kidney diseases
comprise a spectrum of genetic syndromes defined by renal cyst
formation and expansion with variable extrarenal manifestations.
The most prevalent disorder is the autosomal dominant polycystic
kidney disease (ADPKD). It is the most common monogenetic disorder
in humans and accounts for 4.4% of end-stage renal disease (ESRD)
cases in the U.S. Patients inevitably progress to ESRD and require
renal replacement therapy in the form of dialysis or
transplantation. Through advancements in genomics and proteomics
approaches, novel genes responsible for cystic diseases have been
identified, further expanding our understanding of basic mechanisms
of disease pathogenesis. The hallmark among all cystic genetic
syndromes is the formation and growth of fluid-filled cysts, which
originate from tubular epithelia of nephron segments. Cysts are the
disease, and treatment strategies are being developed to target
prevention or delay of cyst formation and expansion at an early
stage, however no such therapy is currently approved.
The liver is a vital organ involved in numerous metabolic processes
such as cholesterol and bile acid metabolism, biliary lipid
secretion, and bile formation. Cholesterol balance across the liver
has a crucial effect on influencing plasma total and LDL
cholesterol levels and biliary cholesterol concentrations.
Cholesterol and bile acid biosyntheses are primarily modulated by
negative feedback regulatory mechanisms through the sterol
regulatory element-binding protein isoform 2 (SREBP-2) and the
farnesoid X receptor (FXR) pathways, respectively. The conversion
of cholesterol to bile acids in the liver can balance the fecal
excretion of bile acids, which is an important route for the
removal of cholesterol from the body. Bile formation begins in the
bile canaliculi, and maintenance of the enterohepatic circulation
of bile acids results in a continuous secretion of bile. Hepatic
secretion of biliary lipids is determined mainly by a group of
ATP-binding cassette (ABC) transporters that are located on the
canalicular membrane of hepatocytes, which are regulated by various
nuclear receptors. Bile acids promote bile flow by their osmotic
effects. Also, they are essential for the intestinal absorption of
cholesterol, fatty acids, and fat-soluble vitamins and play an
important role in aiding the digestion of dietary fat. Bile acids
function as signaling molecules and anti-inflammatory agents to
regulate lipid, glucose, and energy metabolism by rapidly
activating nuclear receptors and cell signaling pathways. This
eBook summarizes the progress in the molecular and cellular
mechanisms of cholesterol and bile acid metabolism and the
physical-chemistry of biliary lipids, with emphasis on biliary
lipid metabolism that is regulated by nuclear receptors in the
hepatobiliary system.
The mammalian gastrointestinal mucosa is a rapidly self-renewing
tissue in the body, and its homeostasis is preserved through the
strict regulation of epithelial cell proliferation, growth arrest,
and apoptosis. The control of the growth of gastrointestinal mucosa
is unique and, compared with most other tissue in the body,
complex. Mucosal growth is regulated by the same hormones that
alter metabolism in other tissues, but the gastrointestinal mucosa
also responds to host events triggered by the ingestion and
presence of food within the digestive tract. These gut hormones and
peptides regulate the growth of the exocrine pancreas, gallbladder
epithelium, and the mucosa of the oxyntic gland region of the
stomach and the small and large intestines. Luminal factors,
including nutrients or other dietary factors, secretions, and
microbes that occur within the lumen and distribute over a
proximal-to-distal gradient, are also crucial for maintenance of
normal gut mucosal regeneration and could explain the
villous-height-crypt-depth gradient and variety of adaptation,
since these factors are diluted, absorbed, and destroyed as they
pass down the digestive tract. Recently, intestinal stem cells,
cellular polyamines, and noncoding RNAs are shown to play an
important role in the regulation of gastrointestinal mucosal growth
under physiological and various pathological conditions. In this
book, we highlight key issues and factors that control
gastrointestinal mucosal growth and homeostasis, with special
emphasis on the mechanisms through which epithelial renewal and
apoptosis are regulated at the cellular and molecular levels.
Sepsis is a life-threatening organ dysfunction caused by a
dysregulated host response to infection. Variability in
pathogenesis and complex pathophysiology often delay diagnosis and
create significant challenges for clinical studies in this group of
critically ill patients. Mainly for those reasons, there is no
therapy approved so far to overcome the underlying immune
dysregulation. This book provides an overview about the state of
the art of sepsis diagnostics and potential future therapies.
Chapter 1 focuses on the immunologic staging of sepsis-the key for
successful treatment of the dysregulated hot response. Chapter 2
reveals similarities in the immune response in sepsis and
cancer-opening new avenues for novel therapies. Chapter 3
introduces an important modulator of the immune response-the
endogenous cannabinoid system and elucidates its role in organ
dysfunction in sepsis. Facing the increasing bacterial resistance
to classical antibiotics, Chapter 4 discusses two unique mechanisms
to treat infection and inflammation in sepsis: iron chelation, and
the sphingosine pathway. The authors, all experts in experimental
and clinical sepsis research, seek to provide further understanding
of the complexities of the immune response as the physiological
basis for the development of new therapeutics in sepsis.
Environmental heat stress is associated with a marked decrease in
orthostatic tolerance (OT), which is defined as the ability to
stand or sit upright without symptoms of dizziness,
lightheadedness, presyncope, or fainting. In most healthy humans,
the autonomic nervous system makes rapid and balanced adjustments
to heart rate and peripheral blood flow, such that most people are
able to stand up ""successfully"" most of the time, in most
environments. The goal of this book is to discuss various aspects
of the sympathetic neural response to heat stress, how the
sympathetic nervous system coordinates the successful integrative
physiological response to orthostasis, and what happens when it
encounters both challenges simultaneously. We include overviews of
mechanisms of thermoregulation and blood pressure regulation in
humans, with particular focus on control of cardiac output and
neurovascular control mechanisms during heat stress. We discuss the
implications that these changes have for distribution of peripheral
blood flow and, in particular, for blood flow to the cerebral
circulation. The added stressor of dehydration is also discussed,
as it so often goes hand in hand with heat stress. We end with a
brief presentation of countermeasures against the decreases in OT
with heat stress.
The kidney is innervated with efferent sympathetic nerve fibers
reaching the renal vasculature, the tubules, the juxtaglomerular
granular cells, and the renal pelvic wall. The renal sensory nerves
are mainly found in the renal pelvic wall. Increases in efferent
renal sympathetic nerve activity reduce renal blood flow and
urinary sodium excretion by activation of 1-adrenoceptors and
increase renin secretion rate by activation of 1-adrenoceptors. In
response to normal physiological stimulation, changes in efferent
renal sympathetic nerve activity contribute importantly to
homeostatic regulation of sodium and water balance. The renal
mechanosensory nerves are activated by stretch of the renal pelvic
tissue produced by increases in renal pelvic tissue of a magnitude
that may occur during increased urine flow rate. Under normal
conditions, the renal mechanosensory nerves activated by stretch of
the sensory nerves elicits an inhibitory renorenal reflex response
consisting of decreases in efferent renal sympathetic nerve
activity leading to natriuresis. Increasing efferent sympathetic
nerve activity increases afferent renal nerve activity which, in
turn, decreases efferent renal sympathetic nerve activity by
activation of the renorenal reflexes. Thus, activation of the
afferent renal nerves buffers changes in efferent renal sympathetic
nerve activity in the overall goal of maintaining sodium balance.
In pathological conditions of sodium retention, impairment of the
inhibitory renorenal reflexes contributes to an inappropriately
increased efferent renal sympathetic nerve activity in the presence
of sodium retention. In states of renal disease or injury, there is
a shift from inhibitory to excitatory reflexes originating in the
kidney. Studies in essential hypertensive patients have shown that
renal denervation results in long-term reduction in arterial
pressure, suggesting an important role for the efferent and
afferent renal nerves in hypertension.
The blood-brain barrier (BBB) is a complex and dynamic structure
that protects the brain from cells within the vasculature, from the
immune system and from pathogens. This barrier is present in
arterioles, capillaries and venules and is formed at the level of
adjacent endothelial cells, which are coupled to astrocytes,
microglia, neurons and pericytes. The structure of this endothelial
barrier is unique among endothelia of other organ systems and is
composed of complexes made up of tight, gap and adherens junctions.
In addition, it is the responsibility of the surrounding cellular
elements to maintain the integrity of the junctional complexes and
restrict the entry of substances from the blood into the brain.
Changes in permeability of the BBB during physiologic and
pathophysiologic conditions involve alterations in specific
transporters at the level of the endothelium, activation of
specific cellular second messenger pathways and/or the dissolution
of the junctional complexes composing the BBB. This book focuses on
various aspects that account for the formation and maintenance of
the BBB, and on disease states that compromise this barrier.
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