Regulation of Renal Blood Flow

Int. J. Med. Sci. 2010, 7 http://www.medsci.org 260IInntteerrnnaattiioonnaall JJoouurrnnaall ooff MMeeddiiccaall SScciieenncceess 2010; 7(5):260-266 © Ivyspring International Publisher. All rights reserved Research Paper Changes of uterine blood flow after vaginal radical trachelectomy (VRT) in patients with early-stage uterine invasive cervical cancer Kota Umemura1, Shin-ichi Ishioka1 , Toshiaki Endo1, Tsuyoshi Baba1, Yoshiaki Ezaka1, Kunihiko Naga-sawa1, Madoka Takahashi1, Masahito Mizuuchi1, Nanako Iwami1, Hidefumi Adachi1, Noriko Takeda1, Mit-suharu Tamagawa2, Tsuyoshi Saito1 1. Department of Obstetrics and Gynecology, Sapporo Medical University, Sapporo Hokkaido, Japan 2. Department of Radiology, Sapporo Medical University, Sapporo Hokkaido, Japan  Corresponding author: Shin-ichi Ishioka, Department of Obstetrics and Gynecology, Sapporo Medical University. Mi-nami 1-jo, Nishi 16-chome, Chuo-ku, Sapporo Hokkaido, Japan 064-8543. Tel. +81-11-611-2111 (ext. 3373); Fax +81-11-563-0860; e-mail: ishioka@sapmed.ac.jp Received: 2010.06.02; Accepted: 2010.08.04; Published: 2010.08.05 Abstract Background. Vaginal radical trachectomy (RT) ligates and cuts several arteries supplying the uterus. Changes of blood supply to the uterus in two patients who experienced pregnancy and delivery were studied by using 3-D CT scanning. Effects of changes of blood supply to the uterus on the pregnancy courses were also examined. Methods. Vascular distribution in the uterus was studied in two patients who received vaginal RT after delivery. Effects of changes of vascular distribution after vaginal RT were studied with respect to pregnancy courses and cervical functions. Results. New arterial vascularization from the ascending branches of uterine arteries or other arteries occurred, and these new vessels seemed to supply blood to the remaining cervix. Differences of fetal growth and histopathological changes in the placenta between the two patients could not be detected. Conclusion. Ligation and cutting of several supplying arteries by RT induces new areterial vascularization and it does not seem to affect fetal growth and placental function. Key words: Radical trachelectomy, uterine cervical cancer, 3-D CT scanning Introduction Uterine cervical cancer is one of the most com-mon cancers diagnosed in women of reproductive age. Thanks to the progress of the cervical cancer screening system, the mortality rate of patients with cervical cancer has decreased in Japan over the past twenty years1. However, the number of patients with early invasive cervical cancer during reproductive age is increasing. Not a few of them hope to preserve their fertility. Recently, radical trachelectomy (RT) with pelvic lymphadenctomy has become a valuable fertil-ity-preserving treatment option for these patients in Japan2-4. We have already performed 20 vaginal RTs with laparoscopic lymphadenectomy, and have expe-rienced five pregnancies and four deliveries so far. As we reported before, in pregnant patients who under-go this operation, premature labor and the following occurrence of preterm premature rupture of the membrane (pPROM) are thought to be the most troublesome pregnancy-related complications3. Var-ious factors such as lack of a protective effect against vaginal infection or the lack of mechanical support of the residual cervix due to the dissection of the uterine cervix Regulation of Renal Blood Flow Regulation of Renal Blood Flow Bởi: OpenStaxCollege It is vital that the flow of blood through the kidney be at a suitable rate to allow for filtration This rate determines how much solute is retained or discarded, how much water is retained or discarded, and ultimately, the osmolarity of blood and the blood pressure of the body Sympathetic Nerves The kidneys are innervated by the sympathetic neurons of the autonomic nervous system via the celiac plexus and splanchnic nerves Reduction of sympathetic stimulation results in vasodilation and increased blood flow through the kidneys during resting conditions When the frequency of action potentials increases, the arteriolar smooth muscle constricts (vasoconstriction), resulting in diminished glomerular flow, so less filtration occurs Under conditions of stress, sympathetic nervous activity increases, resulting in the direct vasoconstriction of afferent arterioles (norepinephrine effect) as well as stimulation of the adrenal medulla The adrenal medulla, in turn, produces a generalized vasoconstriction through the release of epinephrine This includes vasoconstriction of the afferent arterioles, further reducing the volume of blood flowing through the kidneys This process redirects blood to other organs with more immediate needs If blood pressure falls, the sympathetic nerves will also stimulate the release of renin Additional renin increases production of the powerful vasoconstrictor angiotensin II Angiotensin II, as discussed above, will also stimulate aldosterone production to augment blood volume through retention of more Na+ and water Only a 10 mm Hg pressure differential across the glomerulus is required for normal GFR, so very small changes in afferent arterial pressure significantly increase or decrease GFR Autoregulation The kidneys are very effective at regulating the rate of blood flow over a wide range of blood pressures Your blood pressure will decrease when you are relaxed or sleeping It will increase when exercising Yet, despite these changes, the filtration rate through the 1/4 Regulation of Renal Blood Flow kidney will change very little This is due to two internal autoregulatory mechanisms that operate without outside influence: the myogenic mechanism and the tubuloglomerular feedback mechanism Arteriole Myogenic Mechanism The myogenic mechanism regulating blood flow within the kidney depends upon a characteristic shared by most smooth muscle cells of the body When you stretch a smooth muscle cell, it contracts; when you stop, it relaxes, restoring its resting length This mechanism works in the afferent arteriole that supplies the glomerulus When blood pressure increases, smooth muscle cells in the wall of the arteriole are stretched and respond by contracting to resist the pressure, resulting in little change in flow When blood pressure drops, the same smooth muscle cells relax to lower resistance, allowing a continued even flow of blood Tubuloglomerular Feedback The tubuloglomerular feedback mechanism involves the JGA and a paracrine signaling mechanism utilizing ATP, adenosine, and nitric oxide (NO) This mechanism stimulates either contraction or relaxation of afferent arteriolar smooth muscle cells ([link]) Recall that the DCT is in intimate contact with the afferent and efferent arterioles of the glomerulus Specialized macula densa cells in this segment of the tubule respond to changes in the fluid flow rate and Na+ concentration As GFR increases, there is less time for NaCl to be reabsorbed in the PCT, resulting in higher osmolarity in the filtrate The increased fluid movement more strongly deflects single nonmotile cilia on macula densa cells This increased osmolarity of the forming urine, and the greater flow rate within the DCT, activates macula densa cells to respond by releasing ATP and adenosine (a metabolite of ATP) ATP and adenosine act locally as paracrine factors to stimulate the myogenic juxtaglomerular cells of the afferent arteriole to constrict, slowing blood flow and reducing GFR Conversely, when GFR decreases, less Na+ is in the forming urine, and most will be reabsorbed before reaching the macula densa, which will result in decreased ATP and adenosine, allowing the afferent arteriole to dilate and increase GFR NO has the opposite effect, relaxing the afferent arteriole at the same time ATP and adenosine are stimulating it to contract Thus, NO fine-tunes the effects of adenosine and ATP on GFR 2/4 Regulation of Renal Blood Flow Paracrine Mechanisms Controlling Glomerular Filtration Rate Change in GFR NaCl Role of ATP and Absorption adenosine/Role of NO Effect on GFR Increased GFR Tubular NaCl increases ATP and adenosine increase, causing vasoconstriction Vasoconstriction slows GFR Decreased GFR Tubular NaCl decreases ATP and adenosine decrease, causing vasodilation Vasodilation increases GFR Increased GFR Tubular NaCl increases NO increases, causing vasodilation Vasodilation increases GFR ...BioMed Central Page 1 of 11 (page number not for citation purposes) Journal of Circadian Rhythms Open Access Research Daily rhythm of cerebral blood flow velocity Deirdre A Conroy* 1 , Arthur J Spielman 1,2 and Rebecca Q Scott 3 Address: 1 Department of Psychology, The Graduate School and University Center of the City University of New York, New York, USA, 2 Department of Neurology and Neuroscience, New York Presbyterian Hospital, New York, USA and 3 Department of Health Psychology, Albert Einstein Medical College at Yeshiva University, Bronx, USA Email: Deirdre A Conroy* - deirdre.conroy@att.net; Arthur J Spielman - thrilla834@aol.com; Rebecca Q Scott - beckyqscott@yahoo.com * Corresponding author Abstract Background: CBFV (cerebral blood flow velocity) is lower in the morning than in the afternoon and evening. Two hypotheses have been proposed to explain the time of day changes in CBFV: 1) CBFV changes are due to sleep-associated processes or 2) time of day changes in CBFV are due to an endogenous circadian rhythm independent of sleep. The aim of this study was to examine CBFV over 30 hours of sustained wakefulness to determine whether CBFV exhibits fluctuations associated with time of day. Methods: Eleven subjects underwent a modified constant routine protocol. CBFV from the middle cerebral artery was monitored by chronic recording of Transcranial Doppler (TCD) ultrasonography. Other variables included core body temperature (CBT), end-tidal carbon dioxide (EtCO2), blood pressure, and heart rate. Salivary dim light melatonin onset (DLMO) served as a measure of endogenous circadian phase position. Results: A non-linear multiple regression, cosine fit analysis revealed that both the CBT and CBFV rhythm fit a 24 hour rhythm (R 2 = 0.62 and R 2 = 0.68, respectively). Circadian phase position of CBT occurred at 6:05 am while CBFV occurred at 12:02 pm, revealing a six hour, or 90 degree difference between these two rhythms (t = 4.9, df = 10, p < 0.01). Once aligned, the rhythm of CBFV closely tracked the rhythm of CBT as demonstrated by the substantial correlation between these two measures (r = 0.77, p < 0.01). Conclusion: In conclusion, time of day variations in CBFV have an approximately 24 hour rhythm under constant conditions, suggesting regulation by a circadian oscillator. The 90 degree-phase angle difference between the CBT and CBFV rhythms may help explain previous findings of lower CBFV values in the morning. The phase difference occurs at a time period during which cognitive performance decrements have been observed and when both cardiovascular and cerebrovascular events occur more frequently. The mechanisms underlying this phase angle difference require further exploration. Background It has been well documented that cerebral blood flow velocity (CBFV) is lower in sleep [1-7] and in the morning shortly after awakening [8-10] than in the afternoon or evening. Generally accepted theories about the time of day changes in CBFV attribute the fall in CBFV to the Published: 10 March 2005 Journal of Circadian Rhythms 2005, 3:3 doi:10.1186/1740-3391-3-3 Received: 21 December 2004 Accepted: 10 March 2005 This article is available from: http://www.jcircadianrhythms.com/content/3/1/3 © 2005 Conroy et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Journal of Circadian Rhythms 2005, 3:3 http://www.jcircadianrhythms.com/content/3/1/3 Page 2 of 11 (page number not for citation purposes) physiological processes of the sleep period and the increase during the day to waking processes. The low CBFV in the morning is thought to be a consequence of the fall in the overall reduced metabolic level [8,10,11] and reduced cognitive processing [12]. Additionally, the reduced BioMed Central Page 1 of 7 (page number not for citation purposes) Journal of Circadian Rhythms Open Access Research Clock mutation affects circadian regulation of circulating blood cells Katsutaka Oishi †1 , Naoki Ohkura †2 , Koji Kadota 3 , Manami Kasamatsu 1 , Kentaro Shibusawa 4 , Juzo Matsuda 2 , Kazuhiko Machida 4 , Shuichi Horie 2 and Norio Ishida* 1,5 Address: 1 Clock Cell Biology Research Group, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305–8566, Japan, 2 Clinical Molecular Biology, Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Suarashi, Sagamiko, Tsukui, Kanagawa 199–0195, Japan, 3 Agricultural Bioinformatics Research Unit, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113–8657, Japan, 4 Department of Hygiene and Public Health, School of Human Sciences, Waseda University, 2-579-15 Mikajima, Tokorozawa, Saitama 359–1192, Japan and 5 Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305–8502, Japan Email: Katsutaka Oishi - k-ooishi@aist.go.jp; Naoki Ohkura - n-ohkura@pharm.teikyo-u.ac.jp; Koji Kadota - kadota@iu.a.u-tokyo.ac.jp; Manami Kasamatsu - manaminama@hotmail.com; Kentaro Shibusawa - ksh@med.juntendo.ac.jp; Juzo Matsuda - jmatsuda@med.teikyo- u.ac.jp; Kazuhiko Machida - mk167235@waseda.jp; Shuichi Horie - shorie@eiyo.ac.jp; Norio Ishida* - n.ishida@aist.go.jp * Corresponding author †Equal contributors Abstract Background: Although the number of circulating immune cells is subject to high-amplitude circadian rhythms, the underlying mechanisms are not fully understood. Methods: To determine whether intact CLOCK protein is required for the circadian changes in peripheral blood cells, we examined circulating white (WBC) and red (RBC) blood cells in homozygous Clock mutant mice. Results: Daytime increases in total WBC and lymphocytes were suppressed and slightly phase- delayed along with plasma corticosterone levels in Clock mutant mice. The peak RBC rhythm was significantly reduced and phase-advanced in the Clock mutants. Anatomical examination revealed hemoglobin-rich, swollen red spleens in Clock mutant mice, suggesting RBC accumulation. Conclusion: Our results suggest that endogenous clock-regulated circadian corticosterone secretion from the adrenal gland is involved in the effect of a Clock mutation on daily profiles of circulating WBC. However, intact CLOCK seems unnecessary for generating the rhythm of corticosterone secretion in mice. Our results also suggest that CLOCK is involved in discharge of RBC from the spleen. Background The number of circulating white blood cells (WBC) involved in immune defense is subject to high-amplitude circadian rhythms [1,2]. Periodic changes in the number of leukocytes circulating in the peripheral blood might result from several factors. These include the distribution of circulating and marginal cell components of tissues and organs, influx from storage sites, cell proliferation, release of de novo cells into the circulation, and cell destruction and removal [2]. The underlying mechanisms of circadian changes in circulating blood cells have not been fully elu- cidated, although the numbers of monocytes, natural Published: 02 October 2006 Journal of Circadian Rhythms 2006, 4:13 doi:10.1186/1740-3391-4-13 Received: 31 August 2006 Accepted: 02 October 2006 This article is available from: http://www.jcircadianrhythms.com/content/4/1/13 © 2006 Oishi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Journal of Circadian Rhythms 2006, 4:13 http://www.jcircadianrhythms.com/co Open Access Available online http://ccforum.com/content/9/4/R363 R363 Vol 9 No 4 Research Renal blood flow in sepsis Christoph Langenberg 1 , Rinaldo Bellomo 2 , Clive May 3 , Li Wan 1 , Moritoki Egi 1 and Stanislao Morgera 4 1 Research fellow, Department of Intensive Care and Department of Medicine, Austin Hospital, and University of Melbourne, Heidelberg, Melbourne, Australia 2 Director of Intensive Care Research, Department of Intensive Care and Department of Medicine, Austin Hospital, and University of Melbourne, Heidelberg, Melbourne, Australia 3 Senior Researcher, Howard Florey Institute, University of Melbourne, Parkville, Melbourne, Australia 4 Consultant Nephrologist, Department of Nephrology, Charité Campus Mitte, Berlin, Germany Corresponding author: Rinaldo Bellomo, rinaldo.bellomo@austin.org.au Received: 20 Jan 2005 Revisions requested: 14 Mar 2005 Revisions received: 1 Apr 2005 Accepted: 14 Apr 2005 Published: 24 May 2005 Critical Care 2005, 9:R363-R374 (DOI 10.1186/cc3540) This article is online at: http://ccforum.com/content/9/4/R363 © 2005 Langenberg et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/ 2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Introduction To assess changes in renal blood flow (RBF) in human and experimental sepsis, and to identify determinants of RBF. Method Using specific search terms we systematically interrogated two electronic reference libraries to identify experimental and human studies of sepsis and septic acute renal failure in which RBF was measured. In the retrieved studies, we assessed the influence of various factors on RBF during sepsis using statistical methods. Results We found no human studies in which RBF was measured with suitably accurate direct methods. Where it was measured in humans with sepsis, however, RBF was increased compared with normal. Of the 159 animal studies identified, 99 reported decreased RBF and 60 reported unchanged or increased RBF. The size of animal, technique of measurement, duration of measurement, method of induction of sepsis, and fluid administration had no effect on RBF. In contrast, on univariate analysis, state of consciousness of animals (P = 0.005), recovery after surgery (P < 0.001), haemodynamic pattern (hypodynamic or hyperdynamic state; P < 0.001) and cardiac output (P < 0.001) influenced RBF. However, multivariate analysis showed that only cardiac output remained an independent determinant of RBF (P < 0.001). Conclusion The impact of sepsis on RBF in humans is unknown. In experimental sepsis, RBF was reported to be decreased in two-thirds of studies (62 %) and unchanged or increased in one-third (38%). On univariate analysis, several factors not directly related to sepsis appear to influence RBF. However, multivariate analysis suggests that cardiac output has a dominant effect on RBF during sepsis, such that, in the presence of a decreased cardiac output, RBF is typically decreased, whereas in the presence of a preserved or increased cardiac output RBF is typically maintained or increased. Introduction Acute renal failure (ARF) affects 5–7% of all hospitalized patients [1-3]. Sepsis and, in particular, septic shock are important risk factors for ARF in wards and remain the most important triggers for ARF in the intensive care unit (ICU) [4- 8]. Among septic patients, the incidence of ARF is up to 51% [9] and that of severe ARF (i.e. ARF leading to the application of acute renal replacement therapy) is 5% [7,10]. The mortality rate associated with severe ARF in the ICU setting remains high [2-5,11]. A possible explanation for the high incidence and poor out- come of septic ARF relates to the lack of specific therapies. This, in turn, relates to our poor understanding of its pathogen- esis. 327 ARF = acute renal failure; CLP = cecal ligation and puncture; LPS = lipopolysaccharide; RBF = renal blood flow. Available online http://ccforum.com/content/9/4/327 Abstract The clinical complexity of sepsis and the regional variability in renal blood flow present a difficult challenge for the clinician or investigator in understanding the role and clinical importance of reduced blood flow in the pathophysiology of sepsis-induced acute renal failure. Understanding the role of regional microvasculature flow and interactions between endothelium and white blood cells in the local delivery of oxygen and substrates is of critical importance. Therefore, measuring total renal blood flow may not permit an adequate understanding of the role of altered hemodynamics in septic patients who develop acute renal failure. Langenberg and colleagues [1] have completed an exhaustive literature review documenting the effect of sepsis on total renal blood flow (RBF) in humans and in animal models of human sepsis. This is an extremely important area of study because sepsis is the major cause of acute renal failure (ARF) in hospitalized patients, the incidence of sepsis is increasing at a rate of 1.5% per year [2], and the 28-day mortality rate in cases of severe sepsis is as high as 50% [2,3]. In a prospective study [4] the incidence of ARF in sepsis was 19%, in severe sepsis it was 23% and in septic shock it was 51%. Understanding the role, and the determinants, of RBF alterations in the pathophysiology of sepsis-induced ARF is therefore of critical clinical importance. The finding of heterogeneity in RBF during sepsis should be of little surprise. First, sepsis is a heterogeneous disease process for several reasons, including the bacteria (Gram- negative or Gram-positive) or toxin (lipopolysaccharide; LPS) involved, the route of delivery (intraperitoneal, intravenous, or cecal ligation and puncture (CLP)), the rate of delivery, the genetic make-up of the patient or animal (high versus low cytokine responders), clinical stage of sepsis (early versus late), and the associated co-morbid conditions (congestive heart failure), to name just a few. For example, many previous studies have used the administration of LPS in high dose to initiate a ‘sepsis-like syndrome’ [5]. Although the LPS model can have a role in helping to understand the sepsis phenotype, many investigators now favor the use of the CLP model for several reasons. First, sepsis is a complex phenomenon and although it is in part due to the generation, release and biologic reactions of LPS, additional factors are present in clinical sepsis that are more completely modeled by bacterial-generated models such as CLP [6]. Second, although both LPS and CLP models had similar mortality rates, there were significant differences in the kinetics and magnitude of cytokine production. The very rapid production and extremely high levels of tumor necrosis factor- α and cytokines in response to LPS resulted in a vasoconstrictive phenotype with reduced cardiac output. However, the CLP model resulted in an early hyperdynamic phase characterized by low vascular resistance, low blood pressure and increased cardiac output. These differences were borne out in the review of the literature by Langenberg and colleagues [1]. Perhaps the therapeutic approaches for sepsis based on cytokine production after an LPS challenge might therefore be misdirected because the LPS model does not accurately reproduce the cytokine profile in sepsis. The above-mentioned variables, plus additional variables including the volume status of the animal, will then influence the effect of sepsis on RBF in any clinical or experimental setting. That cardiac output was the one determinant variable of RBF, in a multi-variant analysis, is an important observation on the essential role of cardiac output in patients with sepsis and ARF. However, as pointed out by Langenberg and colleagues [1], glomerular filtration rate can decrease even ... effects of adenosine and ATP on GFR 2/4 Regulation of Renal Blood Flow Paracrine Mechanisms Controlling Glomerular Filtration Rate Change in GFR NaCl Role of ATP and Absorption adenosine/Role of NO... rate of blood flow Review Questions Vasodilation of blood vessels to the kidneys is due to more frequent action potentials less frequent action potentials B When blood pressure increases, blood. .. vessels supplying the kidney will to mount a steady rate of filtration 3/4 Regulation of Renal Blood Flow contract relax A Which of these three paracrine chemicals cause vasodilation? ATP adenosine