Effective Arterial Blood Volume Research Articles

A Review of Terlipressin in Hepatorenal Syndrome: Targeting Endothelial Dysfunction and Subsequent Cardiovascular Adverse Events.

Hepatorenal syndrome (HRS) is a serious complication of decompensated liver cirrhosis that results in acute kidney injury (AKI). The mortality rate is high. Endothelial dysfunction secondary to liver cirrhosis is a key driver of the development of portal hypertension, which is eventually complicated by ascites and HRS. Ultimately, splanchnic vasodilation and excess gut lymph production result in ascites, low effective arterial blood volume, and maladaptive compensatory mechanisms that contribute to renal hypoperfusion and injury. While the only curative treatment is liver transplantation, vasoconstrictors and albumin have been the mainstay of treatment for candidates who are ineligible or waiting for transplantation. On September 14, 2022, terlipressin, a V1 vasopressin receptor agonist, was approved by the Food and Drug Administration for the treatment of HRS-AKI. In clinical trials, terlipressin plus albumin have been superior to albumin alone and equivocal to noradrenaline plus albumin in renal function improvement. Terlipressin, however, does not improve survival, is costly, and is associated with severe adverse events-including severe cardiac and vascular complications. The aim of this review is to provide an overview of terlipressin pharmacology, adverse events-with a focus on cardiovascular complications-and comparative randomized controlled trials that resulted in the Food and Drug Administration's approval of terlipressin. New literature since its approval and ongoing clinical trials will also be highlighted.

Hyponatremia in the Context of Liver Disease.

Hyponatremia is common in patients with liver disease and is associated with increased mortality, morbidity, and a reduced quality of life. In liver transplantation, the inclusion of hyponatremia in organ allocation scores has reduced waitlist mortality. Portal hypertension and the resulting lowering of the effective arterial blood volume are important pathogenetic factors, but in most patients with liver disease, hyponatremia is multifactorial. Treatment requires a multifaceted approach that tries to reduce electrolyte-free water intake, restore urinary dilution, and increase nonelectrolyte solute excretion. Albumin therapy for hyponatremia is a peculiarity of advanced liver disease. Its use appears to be increasing, while the vaptans are currently only given in selected cases. Osmotic demyelination is a special concern in patients with liver disease. Serial checks of serum sodium concentrations and urine volume monitoring are mandatory.

Recent Advances in the Management of Hepatorenal Syndrome: A US Perspective

Acute kidney injury (AKI) is a common complication among decompensated patients with cirrhosis and is associated with significant mortality. 1 Garcia-Tsao G. Parikh C.R. Viola A. Acute kidney injury in cirrhosis. Hepatology. 2008; 48: 2064-2077 Crossref PubMed Scopus (441) Google Scholar In this setting, the most common phenotypes of AKI are hypovolemic/prerenal, acute tubular injury/necrosis, and hepatorenal syndrome (HRS). In this article, the most recent terminology put forth by the International Club of Ascites is used, HRS-AKI, which replaces the prior term HRS type 1. 2 Angeli P. Gines P. Wong F. et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. Gut. 2015; 64: 531-537 Crossref PubMed Google Scholar HRS-AKI is a devastating complication of advanced cirrhosis occurring in approximately 17% of AKI cases 1 Garcia-Tsao G. Parikh C.R. Viola A. Acute kidney injury in cirrhosis. Hepatology. 2008; 48: 2064-2077 Crossref PubMed Scopus (441) Google Scholar and is associated with a high 90-day mortality rate of 45% to 51%. 3 Wong F. Pappas S.C. Curry M.P. et al. Terlipressin plus albumin for the treatment of type 1 hepatorenal syndrome. N Engl J Med. 2021; 384: 818-828 Crossref PubMed Scopus (86) Google Scholar ,4 Sanyal A.J. Boyer T.D. Frederick R.T. et al. Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT-0401 and REVERSE randomised clinical studies. Aliment Pharmacol Ther. 2017; 45: 1390-1402 Crossref PubMed Scopus (54) Google Scholar The pathophysiology of HRS-AKI is complex. 5 Biggins S.W. Angeli P. Garcia-Tsao G. et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome: 2021 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021; 74: 1014-1048 Crossref PubMed Scopus (110) Google Scholar Because of portal hypertension, blood pools in the splanchnic circulation, leading to decreased effective arterial blood volume. As a result, endogenous vasoconstricting systems are activated, leading to sodium and water retention and decreased kidney perfusion. Overlapping with this process there also is increased gut permeability, bacterial translocation, and up-regulation of systemic inflammatory mediators, a secondary cascade that contributes further to impaired kidney perfusion and concomitantly leads to the functional kidney injury seen in HRS-AKI. These dynamic pathophysiologic changes could be potentiated further by infections, acute-on-chronic liver failure (ACLF), or variceal bleeding.

S1396 Response-Guided Ascites Mobilization in Patients of Acute on Chronic Liver Failure (ACLF) With Acute Kidney Injury Treated With Slow Albumin, Furosemide and Vasoconstrictor Therapy (SAFI+T) versus Standard Treatment

Introduction: Acute-on-chronic liver failure (ACLF) with increasing organ failure is associated with poor outcome. Severely deranged systemic hemodynamic and decreased effective arterial blood volume contributes to tissue damage and organ failure. Response guided therapy with albumin, vasoconstrictors and furosemide may help overcome effective hypovolemia improve diuresis and impact survival. Methods: In observation cohort, 56 patients with ACLF (CANONIC criteria) complicated with AKI ( S.Cr ³ 1.5, >50% increased S.cr from baseline), ascites (≥ Grade II) were enrolled. 30 patients (GROUP I) received response guided(Urine sodium >80mmol/day) slow albumin-furosemide infusion ± terlipressin (SAFI±T), while 26 patients (GROUP II) received standard medical therapy. 28-day survival, ascites mobilization (nil or grade 1), reversal of AKI and adverse events were noted. Laboratory evidences for improvement in various pathophysiological alterations; endotoxemia, cytokine storm, neutrophil dysfunction and secondary infections, following SAFI±T were evaluated. Results: Alcohol and sepsis were the commonest etiologies for chronic and acute insult respectively. Ascites was completely mobilized in 18/30 (60%) patients in Group I (SAFI±T) and 7/26 (26.9%) in Group II (p< 0.05). At 28 days the survival analysis showed, Group I 23/30 (76.4%) and Group II 14/26 (53.8%) (P=< 0.05). There was a lower incidence of hospital acquired infection in Group I of 6.7% vs 38.4% in Group II (p=0.05) and the same was reflected in serum endotoxin and pro-inflammatory cytokine levels; IL-6 and IL-1b showed significant reduction in Group I. Serum endotoxin and TNF-a level increased in Group II despite SMT while it showed significant fall in SAFI+T arm post treatment. Renal artery resistive index was significantly lower after SAFI(T) therapy (0.84 to 0.72) (p< 0.05) as similar trend emulated in UNa level. Conclusion: Patients with ACLF treated with SAFI+T protocol had higher natriuresis, enhanced urine output, complete ascites removal, and improved renal function with a faster mean duration of treatment and better 28-day survival. An in-hospital infection rate was lower. Ascites mobilization was associated with improvement in gut permeability, endotoxemia, pro-inflammatory cytokines, and NETosis in the SAFI+T cohort, showing an association between ascites mobilization and improved pathophysiologic dysfunctions.

Response Guided Slow Infusion of Albumin, Vasoconstrictors and Furosemide Improves Ascites Mobilization and Survival in Acute on Chronic Liver Failure: A Proof-of-Concept Study.

Background and AimsAcute-on-chronic liver failure (ACLF) with increasing organ failure is associated with poor outcomes. Severely deranged systemic hemodynamics and decreased effective arterial blood volume contribute to tissue damage and organ failure. Response-guided therapy with albumin, vasoconstrictors, and furosemide may help overcome effective hypovolemia, improve diuresis and impact survival.MethodsIn the observation cohort, 230 patients with ACLF (CANONIC criteria) with ascites (≥Grade II) and ACLF ≥Grade I were enrolled. A total of 136 patients (GROUP I) received response-guided (urine sodium >80mmol/day) slow albumin-furosemide infusion ± terlipressin (SAFI ± T), while 94 patients (GROUP II) received standard medical therapy. Twenty-eight-day survival, ascites mobilization (nil or grade 1), and adverse events were noted. In another mechanistic cohort (n = 40), laboratory evidences for improvement in various pathophysiological alterations; gut permeability, endotoxemia, cytokine storm, neutrophil dysfunction, and hemodynamic alterations following SAFI ± T/Noradrenaline (NAdr) were evaluated.ResultsAge, gender, CLIF-C-ACLF, SOFA and MELD scores, ACLF grades and urine sodium were not different between the two groups in the observation cohort. Ascites was mobilized in 102/136 in GROUP I (SAFI ± T) and 23/94 in GROUP II (p < 0.05). Twenty-eight-day survival was significantly higher in GROUP I = 103/136 (75.7%) vs GROUP II = 50/94 (53.2%), (P = <0.001). All those who were unable to reach urine sodium >80 mmol/day died. Four patients in GROUP I developed scrotal gangrene. In the mechanistic cohort, 72% of patients survived with significant improvement in gut permeability, endotoxemia, serum cytokines, neutrophil dysfunction, and hemodynamic alterations.ConclusionAscitic fluid mobilization by response-guided SAFI ± T/NAdr therapy improves survival by improving splanchnic and systemic hemodynamics, decreasing gut congestion, gut permeability, and endotoxemia, improving neutrophil functions, and reducing pro-inflammatory cytokines in circulation.

Differentiating Electrolyte and Fluid Disorders

Abstract Vasopressin or anti-diuretic hormone (ADH) is a nonapeptide that is synthesized in the hypothalamus and plays an important role in the control of the body’s osmotic balance, blood pressure regulation and kidney function. ADH induces expression of water transport proteins in the late distal tubule and collecting duct to increase water re-absorption. ADH is produced by neurons within the supraoptic nuclei of the hypothalamus, stored in secretary vesicles and transported through the hypothalamic-hypophyseal tract and released in the posterior pituitary. The secreted hormones then enter nearby fenestrated capillaries where they enter the body’s systemic circulation. These neurons express osmo receptors that are responsive to blood osmolarity and respond to changes as little as 2 mOsm/L. Therefore slight elevations in osmolarity result in secretion of ADH. ADH acts in the kidneys to increase water re-absorption, thus returning the osmolarity to baseline. ADH is also secreted in times of hypovolaemia. Decreased arterial blood volume is sensed by bar receptors in the left atrium, carotid artery and aortic arch and the signal transported to the vagus nerve which directly stimulates the release of ADH. ADH then promotes water re-absorption in the kidneys to increase effective arterial blood volume and increase blood pressure to maintain tissue perfusion. Osmolarity and volume status are the two greatest factors that affect ADH secretion. There are three pathologic states related to ADH.

Pathogenesis and Treatment of Refractory Oedema in Nephrotic Syndrome

Oedema is a hallmark feature of nephrotic syndrome (NS) and can cause significant patient morbidity. The pathogenesis of oedema formation is complex and results from abnormalities in sodium retention, inter-play of neurohormonal factors, and changes in capillary filtration barrier. Salt retention is often primary (‘overfill’ theory) because of increased sodium-potassium adenosine triphosphatase activity in the collecting duct cells, increased direct epithelial sodium channel activation (ENaC) by urinary proteases (independent of aldosterone), and an overall increased effective arterial blood volume. However, a subset of patients with NS, especially children, demonstrate decreased effective arterial blood volume (‘underfill’ theory) and secondary sodium retention as the primary mechanism of oedema formation. Increased capillary permeability and vascular inflammation contributes as well. Loop diuretics with or without salt-poor albumin are the mainstay of therapy in adults, although no large clinical trials exist to guide diuretic choice or dosage. Combination diuretic therapy is recommended to achieve multi-site nephron blockade and overcome diuretic resistance, which is a frequent challenge. Use of direct ENaC inhibitors (amiloride) in combination with loop diuretics may be especially beneficial given the primary role of ENaC in sodium retention. Aquaretics such as vasopressin receptor antagonists may have a role in treatment as well. Well-designed clinical trials are essential to guide therapy of refractory oedema in NS. In this review, the authors discuss the pathogenesis of oedema formation in patients with NS and propose a treatment algorithm for management of resistant oedema based on the limited available evidence.

Management of Cirrhotic Ascites under the Add-on Administration of Tolvaptan.

Tolvaptan is a recently available diuretic that blocks arginine vasopressin receptor 2 in the renal collecting duct. Its diuretic mechanism involves selective water reabsorption by affecting the water reabsorption receptor aquaporin 2. Given that liver cirrhosis patients exhibit hyponatremia due to their pseudo-aldosteronism and usage of natriuretic agents, a sodium maintaining agent, such as tolvaptan, is physiologically preferable. However, large scale studies indicating the patients for whom this would be effective and describing management under its use have been insufficient. The appropriate management of cirrhosis patients treated with tolvaptan should be investigated. In the present review, we collected articles investigating the effectiveness of tolvaptan and factors associated with survival and summarized their management reports. Earlier administration of tolvaptan before increasing the doses of natriuretic agents is recommended because this may preserve effective arterial blood volume.

English

BACKGROUND The increased propensity for acute kidney injury (AKI) in patients with cirrhosis stems from haemodynamic abnormalities typical for patients with cirrhosis and ascites. 15 which is due to development of portal hypertension and portosystemic collaterals with splanchnic and systemic vasodilatation, resulting in decrease in effective arterial blood volume with increase in renin angiotensin-aldosterone system (RAAS), sympathetic nervous system and non-osmotic release of antidiuretic hormone causing sodium retention, increased intravascular volume, and a hyperdynamic circulatory state, 16 complemented with increased production of nitric oxide which is considered the main cause of vasodilatation in cirrhosis. Mechanism of renal dysfunction in cirrhosis includes portal hypertension &amp; its accompanying haemodynamic abnormalities15 leading to increased synthesis of endogenous vasodilatory compounds such as nitric oxide leading to vasodilatation in splanchnic &amp; systemic arterial systems ultimately leading to activation of reninangiotensinogen–aldosterone system causing compensatory renal vasoconstriction &amp; hypo-perfusion resulting into renal failure. We wanted to study the clinical profile of patients with AKI who presented to a tertiary care hospital in Bangalore. METHODS Ninety-four patients of either gender admitted in the department of gastroenterology at a tertiary care hospital with age &gt; 18 years with either diagnosed or newly diagnosed case of cirrhosis of liver (including both compensated &amp; decompensated cases) admitted with acute kidney injury diagnosed according to International Club of Ascites Classification were enrolled in this study. The sample size was based on number of eligible patients admitted to tertiary care hospital during the study period. Details of the study were explained to them and consent was taken either from the patient or their attender. RESULTS Most patients were in the age group &gt; 60 yrs. with 32 male patients (45.07 %) in the age group of 40 - 60 years &amp; 13 female patients (56.52 %) in the age group of &gt; 60 yrs. 78.7 % of patients developed AKI before hospital admission i.e., at community level; whereas 21.3 % of patients developed AKI after hospital admission i.e., they had normal creatinine level on admission. CONCLUSIONS Pre renal AKI was the most common cause of AKI followed by hepatorenal syndrome &amp; acute tubular necrosis (ATN) comprising 52.1 %, 28.7 % &amp; 19.1 % respectively. KEYWORDS AKI, Cirrhosis, ATN

High expression of a vascular stricture-related marker is predictive of an early response to tolvaptan, and a low fractional excretion of sodium is predictive of a poor long-term survival after tolvaptan administration for liver cirrhosis.

Tolvaptan is a newly available diuretic that has a specific function in water reabsorption inhibition. Given that spironolactone or furosemide induces the aggravation of cirrhotic hyponatremia and dehydration, tolvaptan affects the management strategy of liver cirrhosis. Representative predictive markers of its response include renal function-related markers such as urea nitrogen or creatinine. However, vascular function-related markers have not been well investigated. We investigated the effect of the vascular function-related marker asymmetric dimethylarginine (ADMA) and the effective arterial blood volume (EABV) marker, fractional excretion of sodium (FENa), on the early tolvaptan response and survival in liver cirrhosis. We prospectively recruited 49 patients who required add-on tolvaptan for refractory ascites or edema. Laboratory data were obtained immediately before and 1day after tolvaptan administration. Patients exhibiting >1.5kg weight loss after 1week were categorized as early responders to tolvaptan. Patients were followed for a median of 200days and were assessed for survival. Early responders showed lower creatinine levels (<1.0mg/dL), and higher ADMA levels (≥0.61nmol/mL) than others in a multivariate analysis. Patients with a shorter survival were positive for hepatocellular carcinoma and had a low FENa (<0.35%). Early responders showed higher ADMA levels reflecting vascular stricture, suggesting that higher vascular tonus is required for a tolvaptan early response. Patients with a shorter survival showed a lower FENa, reflecting a lower EABV and suggesting that adequate EABV is required for the prolonged survival after tolvaptan administration.

Pathophysiology and Pathology of Acute Kidney Injury in Patients With COVID-19.

Acute kidney injury (AKI) is common among hospitalized patients with Coronavirus Infectious Disease 2019 (COVID-19), with the occurrence of AKI ranging from 0.5% to 80%. The variability in the occurrence of AKI has been attributed to the difference in geographic locations, race/ethnicity, and severity of illness. AKI among hospitalized patients is associated with increased length of stay and in-hospital deaths. Even patients with AKI who survive to hospital discharge are at risk of developing chronic kidney disease or end-stage kidney disease. An improved knowledge of the pathophysiology of AKI in COVID-19 is crucial to mitigate and manage AKI and to improve the survival of patients who developed AKI during COVID-19. The goal of this article is to provide our current understanding of the etiology and the pathophysiology of AKI in the setting of COVID-19.

Recent insights into sodium and potassium handling by the aldosterone-sensitive distal nephron: a review of the relevant physiology.

In recent years, our understanding of the physiology of the aldosterone-sensitive distal nephron (ASDN) has greatly advanced thanks to the discovery of the complex with-no-lysine kinase (WNK) signaling and the molecular characterization of the epithelial sodium channel (ENaC). A series of studies, initially focused on rare tubulopathies such as Gordon and Liddle syndromes, eventually led to a partial elucidation of the so-called "aldosterone paradox", the traditional explanation of the physiology of such disparate conditions such as hyperkalemia and low effective arterial blood volume. The physiology of the ASDN is herein illustrated in light of the novel acquisitions in an easy-to-understand fashion, with the aim of giving the practicing nephrologist a solid "first glance" into this exciting but challenging field. Focus is on ion channels and transporters, their regulation by key hormones such as aldosterone and angiotensin II, and dietary implications.

Hypotension in Cirrhosis.

Circulatory and cardiac compromise in cirrhosis has been well studied. The primary pathophysiology stems from portal hypertension, which is induced from an increased resistance to flow secondary to distorted sinusoidal architecture and is further sustained from an increase in portal venous flow.1 Portal hypertension induces both progressive splanchnic and systemic vasodilation mediated via nitric oxide and other vasoactive molecules secondary to endothelial stretching and sheer stress.2 A hyperdynamic state then ensues with an increase in cardiac output, increase in heart rate, and a low systemic vascular resistance secondary to systemic vasodilatation. The decreased effective arterial blood volume activates neurohormonal systems such as the renin‐angiotensin‐aldosterone system (RAAS), leading to further volume expansion via sodium and water retention. However, because of portosystemic shunting and splanchnic vasodilatation, effective central blood volume remains low and the hyperdynamic state continues, eventually leading to high‐output heart failure (Fig. ​(Fig.1).1). A lower mean arterial pressure (MAP) of 60 to 65 mm Hg is often tolerated in compensated and stable patients through these compensatory mechanisms, which allow end‐organ perfusion to be maintained.1, 2 Any degree of insult to this system can result in significant hypotension and decompensation. Open in a separate window Figure 1 Pathophysiology of hypotension in cirrhosis.

Albumin in Cirrhosis: More Than a Colloid.

Albumin has repeatedly been shown to be beneficial in treating patients with decompensated cirrhosis. We reviewed the medical literature regarding indications for the use of intravenous albumin in cirrhosis, with particular focus on the ways in which albumin can help mitigate hepatorenal physiology. Albumin has long been used as the preferred agent for volume expansion in patients with decompensated cirrhosis. It is used in conjunction with vasoconstrictors for the treatment of type 1 hepatorenal syndrome, and in combination with antibiotics for the treatment of spontaneous bacterial peritonitis. When given at the time of large volume paracentesis, albumin is known to help reduce the incidence of post-paracentesis circulatory dysfunction. Recently, albumin has been shown to improve outcomes in hospitalized patients with cirrhosis and hyponatremia, and has also shown promise in reducing mortality and hospitalizations in outpatients with both diuretic resistant and uncomplicated ascites. It is increasingly clear that these benefits derive from a combination of the oncotic and non-oncotic properties of albumin, and from the effects of albumin administration on effective arterial blood volume. Albumin is an effective treatment for multiple complications encountered in patients with decompensated cirrhosis.

Approach to Hyponatremia in Cirrhosis.

The patient in the case presented with hypervolemic hyponatremia associated with ascites and edema. The sNa concentration of 120 mmol/L is bordering severe hyponatremia and is associated with renal insufficiency. The management of this patient includes free water restriction, holding diuretics, and consideration of albumin infusion (Fig. ​(Fig.1).1). Tolvaptan is not recommended in patients with liver disease. Furthermore, hyponatremia and renal dysfunction are associated with poor prognosis. If the hyponatremia is persistent, liver transplant evaluation should be considered. Open in a separate window Figure 1 Algorithm depicting suggested management of hyponatremia in the patient with cirrhosis.

Severe Persistent Hyponatremia: A Rare Presentation of Biliary Fluid Loss

Hypotonic hyponatremia is caused by a serum sodium level of <135 mEq/L in the setting of excess solute loss accompanied by free water retention because of antidiuretic hormone release, subsequent to decreased effective arterial blood volume. Acute hyponatremia can have various neurological manifestations, including drowsiness, lethargy, coma, seizures, respiratory depression, and even death. In this article, we present a case of a 41-year-old man who presented with hyponatremia as a result of sodium containing biliary fluid loss and resultant renal free water retention in response to increased antidiuretic hormone secretion. He underwent placement of a cholecystostomy tube for acalculous cholecystitis and was found to be persistently hyponatremic despite repletion with sodium-containing fluids. Once the cholecystostomy tube was removed, the patient’s sodium levels improved, and his symptoms resolved. Our case highlights choleuresis as an unusual but significant cause of hyponatremia in patients who have external biliary drainage.

Fluid balance concepts in medicine: Principles and practice.

The regulation of body fluid balance is a key concern in health and disease and comprises three concepts. The first concept pertains to the relationship between total body water (TBW) and total effective solute and is expressed in terms of the tonicity of the body fluids. Disturbances in tonicity are the main factor responsible for changes in cell volume, which can critically affect brain cell function and survival. Solutes distributed almost exclusively in the extracellular compartment (mainly sodium salts) and in the intracellular compartment (mainly potassium salts) contribute to tonicity, while solutes distributed in TBW have no effect on tonicity. The second body fluid balance concept relates to the regulation and measurement of abnormalities of sodium salt balance and extracellular volume. Estimation of extracellular volume is more complex and error prone than measurement of TBW. A key function of extracellular volume, which is defined as the effective arterial blood volume (EABV), is to ensure adequate perfusion of cells and organs. Other factors, including cardiac output, total and regional capacity of both arteries and veins, Starling forces in the capillaries, and gravity also affect the EABV. Collectively, these factors interact closely with extracellular volume and some of them undergo substantial changes in certain acute and chronic severe illnesses. Their changes result not only in extracellular volume expansion, but in the need for a larger extracellular volume compared with that of healthy individuals. Assessing extracellular volume in severe illness is challenging because the estimates of this volume by commonly used methods are prone to large errors in many illnesses. In addition, the optimal extracellular volume may vary from illness to illness, is only partially based on volume measurements by traditional methods, and has not been determined for each illness. Further research is needed to determine optimal extracellular volume levels in several illnesses. For these reasons, extracellular volume in severe illness merits a separate third concept of body fluid balance.

Polyuria: A Pathophysiologic Approach

Polyuria: A Pathophysiologic Approach

Abstract P144: Association Between Hypertension and Thyroid Abnormalities Among Hospitalized United States Patients: Data From National Inpatient Sample

Introduction: Disorders of thyroid, hyperthyroidism and hypothyroidism, are established risk factors for hypertension. Comparison of these risk factors in terms of association has not been done. Methods: National Inpatient Sample database from 2009 - 2011 was utilized to explore relationship between hypertension and three categories of thyroid hormone levels (hyperthyroidism, hypothyroidism and euthyroidism). Multivariate logistic regressions were used to establish the association among all thyroid hormone level groups. We utilized STATA version 13.0 (College Station, TX) to perform the analyses. Results: Hypertension was more common in patients with hypothyroidism and hyperthyroidism in comparison to euthyroidism (Table 1). Multivariate analysis with logistic regression (controlled for age, sex, race, smoking, obesity, dyslipidemia, diabetes, Charlson comorbidity index) demonstrated that hypertension had a greater association with hyperthyroidism (OR 1.20; CI: 1.17 - 1.23) than hypothyroidism (OR 1.09; CI: 1.08 - 1.10). Discussion: T3 dilates peripheral arterioles and decreases systemic vascular resistance which stimulates renin secretion and increases effective arterial blood volume. Also, it increases heart rate and cardiac contractility. These mechanisms lead to increase in blood pressure. On the other hand, the mechanism with hypothyroidism is not fully recognized. It is thought to be secondary to increase in systemic vascular resistance. Through our study, we can conclude that the risk of hypertension is greater in patients with hyperthyroidism than with hypothyroidism.

Osmolality and blood pressure stability during hemodialysis.

Homeostatic regulation of plasma osmolality (POsm) is critical for normal cellular function in humans. Arginine vasopressin (AVP) is the major hormone responsible for the maintenance of POsm and acts to promote renal water retention in conditions of increased POsm. However, AVP also exerts pressor effects, and its release can be stimulated by the development of effective arterial blood volume depletion. Patients with end-stage renal disease on hemodialysis, particularly those with minimal or no residual renal function, have impaired ability to regulate water retention in response to AVP. While hemodialysis can assist with this task, patients are subject to relatively rapid shifts in volume and electrolytes during the procedure. This can result in the development of transient osmotic gradients that lead to the movement of water from the extracellular to the intracellular space. Hypotension may result-both as a consequence of water movement out of the intravascular compartment, but also from impaired AVP release and inadequate vascular tone. In this review, we explore the evidence for POsm changes during hemodialysis, associations with adverse outcomes, and methods to minimize the rapidity of changes in POsm in an effort to reduce patient symptoms and minimize intra-dialytic hypotension.