Clinical Approach to Assessing Acid-Base Status: Physiological vs Stewart.

Evaluation of acid-base status depends on accurate measurement of acid-base variables and their appropriate assessment. Currently, 3 approaches are utilized for assessing acid-base variables. The physiological or traditional approach, pioneered by Henderson and Van Slyke in the early 1900s, considers acids as H+ donors and bases as H+ acceptors. The acid-base status is conceived as resulting from the interaction of net H+ balance with body buffers and relies on the H2CO3/HCO3- buffer pair for its assessment. A second approach, developed by Astrup and Siggaard-Andersen in the late 1950s, is known as the base excess approach. Base excess was introduced as a measure of the metabolic component replacing plasma [HCO3-]. In the late 1970s, Stewart proposed a third approach that bears his name and is also referred to as the physicochemical approach. It postulates that the [H+] of body fluids reflects changes in the dissociation of water induced by the interplay of 3 independent variables-strong ion difference, total concentration of weak acids, and PCO2. Here we focus on the physiological approach and Stewart's approach examining their conceptual framework, practical application, as well as attributes and drawbacks. We conclude with our view about the optimal approach to assessing acid-base status.

Diagnosis and Management of Hyponatremia: A Review.

Importance: Hyponatremia is the most common electrolyte disorder and it affects approximately 5% of adults and 35% of hospitalized patients. Hyponatremia is defined by a serum sodium level of less than 135 mEq/L and most commonly results from water retention. Even mild hyponatremia is associated with increased hospital stay and mortality. Observations: Symptoms and signs of hyponatremia range from mild and nonspecific (such as weakness or nausea) to severe and life-threatening (such as seizures or coma). Symptom severity depends on the rapidity of development, duration, and severity of hyponatremia. Mild chronic hyponatremia is associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures. In a prospective study, patients with hyponatremia more frequently reported a history of falling compared with people with normal serum sodium levels (23.8% vs 16.4%, respectively; P < .01) and had a higher rate of new fractures over a mean follow-up of 7.4 years (23.3% vs 17.3%; P < .004). Hyponatremia is a secondary cause of osteoporosis. When evaluating patients, clinicians should categorize them according to their fluid volume status (hypovolemic hyponatremia, euvolemic hyponatremia, or hypervolemic hyponatremia). For most patients, the approach to managing hyponatremia should consist of treating the underlying cause. Urea and vaptans can be effective treatments for the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure, but have adverse effects (eg, poor palatability and gastric intolerance with urea; and overly rapid correction of hyponatremia and increased thirst with vaptans). Severely symptomatic hyponatremia (with signs of somnolence, obtundation, coma, seizures, or cardiorespiratory distress) is a medical emergency. US and European guidelines recommend treating severely symptomatic hyponatremia with bolus hypertonic saline to reverse hyponatremic encephalopathy by increasing the serum sodium level by 4 mEq/L to 6 mEq/L within 1 to 2 hours but by no more than 10 mEq/L (correction limit) within the first 24 hours. This treatment approach exceeds the correction limit in about 4.5% to 28% of people. Overly rapid correction of chronic hyponatremia may cause osmotic demyelination, a rare but severe neurological condition, which can result in parkinsonism, quadriparesis, or even death. Conclusions and Relevance: Hyponatremia affects approximately 5% of adults and 35% of patients who are hospitalized. Most patients should be managed by treating their underlying disease and according to whether they have hypovolemic, euvolemic, or hypervolemic hyponatremia. Urea and vaptans can be effective in managing the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure; hypertonic saline is reserved for patients with severely symptomatic hyponatremia.

Iso-osmolar hyponatremia from polyethylene glycol.

Understanding and applying pathophysiological concepts to patient care is an important skill for physicians in the clinical setting. Here, we present a case that demonstrates how the application of common physiological concepts relating to the widely accepted hyponatremia algorithm led to an accurate diagnosis of hyponatremia. This case documents iso-osmolar hyponatremia caused by orally administered polyethylene glycol absorption in the gastrointestinal tract. Herein, we discuss the workup and differential diagnosis for iso-osmolar hyponatremia in juxtaposition with the pathophysiological mechanisms unique to this case. We discuss these pathophysiological mechanisms based on the patients' laboratory data and responses to therapeutic interventions.

Ecosystem stability and Native American oyster harvesting along the Atlantic Coast of the United States.

The eastern oyster (Crassostrea virginica) is an important proxy for examining historical trajectories of coastal ecosystems. Measurement of ~40,000 oyster shells from archaeological sites along the Atlantic Coast of the United States provides a long-term record of oyster abundance and size. The data demonstrate increases in oyster size across time and a nonrandom pattern in their distributions across sites. We attribute this variation to processes related to Native American fishing rights and environmental variability. Mean oyster length is correlated with total oyster bed length within foraging radii (5 and 10 km) as mapped in 1889 and 1890. These data demonstrate the stability of oyster reefs despite different population densities and environmental shifts and have implications for oyster reef restoration in an age of global climate change.

Narrative Review of Hypercoagulability in Small-Vessel Vasculitis.

Pauci-immune necrotizing and crescentic glomerulonephritis (GN) is the most common etiology of rapidly progressive GN. Clinical presentation in those afflicted is usually related to rapid loss of kidney function. We report the case of a 70-year-old woman who came to medical attention for signs and symptoms related to lower-extremity deep vein thrombosis (DVT). At presentation, the patient had biochemical abnormalities consistent with active GN, which quickly progressed to rapid loss in kidney function requiring renal replacement therapy. Kidney biopsy revealed small-vessel vasculitis with glomerular crescents. Serologic studies were negative for antineutrophil cytoplasmic antibody antibodies and other causes of acute GN. Plasmapheresis, immunosuppressive, and anticoagulant therapies were prescribed. Absence of other apparent end-organ involvement with vasculitis pointed toward renal-limited small-vessel vasculitis, yet presence of unprovoked DVT argues for systemic vascular inflammation. This case illustrates that venous thrombosis can be the presenting manifestation in patients with vasculitis and silent, severe end-organ involvement. The epidemiology and pathophysiology of venous thromboembolism in small-vessel vasculitis are discussed in this report.

Pink Urine Syndrome: A Combination of Insulin Resistance and Propofol.

Pink urine syndrome is mostly seen in patients treated with propofol anesthesia. The pink color is attributed to the presence of large concentrations of uric acid (and pigment), which is excreted in large amounts when propofol is given. We describe a case of propofol-induced pink urine syndrome and perform a comprehensive, evidence-based review. We discuss prior case studies already published in the literature as we speculate on the pathophysiology and how it translates to a clinically relevant entity.

The physiology of uric acid and the impact of end-stage kidney disease and dialysis.

Uric acid-mediated biological effects are milieu dependent. In a physiological milieu, serum uric acid serves as an antioxidant; when homeostasis is perturbed, divergent effects are observed depending on the clinical context. Several epidemiologic studies indicated the presence of a direct relationship between higher concentrations of serum uric acid and cardiovascular mortality; yet not all studies support this conclusion. Although high serum levels of uric acid are associated with higher mortality in patients with nondialysis-dependent chronic kidney disease and perhaps in those with end-stage kidney disease receiving peritoneal dialysis, the opposite relationship is seen in patients with end-stage kidney disease on hemodialysis. This review discusses the pathologic mechanisms associated with elevated serum uric acid levels by clinical context; examines the interplay between uric acid metabolism and modality of renal replacement therapy; and presents hypotheses to rationalize the disparate associations between incremental levels of serum uric acid and survival across the continuum of kidney disease and by type of renal replacement therapy.

Poly(N-(2-Hydroxypropyl) Methacrylamide)-Valproic Acid Conjugates as Block Copolymer Nanocarriers.

We report nanoassemblies based on block copolymers of N-(2-hydroxypropyl) methacrylamide (HPMA) in which drug cleavage enhances the biological compatibility of the original polymer carrier by regeneration of HPMA units. Drug release via ester hydrolysis suggests this approach offers potential for stimuli-responsive drug delivery under acidic conditions.

Metabolic Acidosis or Respiratory Alkalosis? Evaluation of a Low Plasma Bicarbonate Using the Urine Anion Gap.

Hypobicarbonatemia, or a reduced bicarbonate concentration in plasma, is a finding seen in 3 acid-base disorders: metabolic acidosis, chronic respiratory alkalosis and mixed metabolic acidosis and chronic respiratory alkalosis. Hypobicarbonatemia due to chronic respiratory alkalosis is often misdiagnosed as a metabolic acidosis and mistreated with the administration of alkali therapy. Proper diagnosis of the cause of hypobicarbonatemia requires integration of the laboratory values, arterial blood gas, and clinical history. The information derived from the urinary response to the prevailing acid-base disorder is useful to arrive at the correct diagnosis. We discuss the use of urine anion gap, as a surrogate marker of urine ammonium excretion, in the evaluation of a patient with low plasma bicarbonate concentration to differentiate between metabolic acidosis and chronic respiratory alkalosis. The interpretation and limitations of urine acid-base indexes at bedside (urine pH, urine bicarbonate, and urine anion gap) to evaluate urine acidification are discussed.

Personal Attitudes Toward Weight in Overweight and Obese US Hemodialysis Patients.

OBJECTIVE: Overweight and obesity have become increasingly common among end-stage renal disease patients on hemodialysis. Yet, little attention has been given to what hemodialysis patients themselves think of their weight, how they perceive it affects their health, and their attitudes about or desire for weight reduction. We explored these issues using a survey that we designed specifically for the dialysis population. DESIGN AND METHODS: Sixty-six chronic hemodialysis patients from a US urban center with a body mass index ≥25 kg/m2 and stable weight were recruited to participate in a cross-sectional study. The 12-question weight-related survey was validated by retesting a random portion of the study population. RESULTS: Based on test-retest results, the survey had good to excellent validity. Seventy-nine percent of patients were black, 49% were male, 29% were overweight, and 71% were obese. In general, the patients underestimated their weight excess though 73% were interested in weight loss, of whom nearly half reported attempting to do so mostly through diet and exercise. The majority of participants interested in losing weight felt that doing so would improve their physical and emotional health. The most common barrier to weight reduction was a belief that it was too difficult (55%), followed by a lack of motivation, money, time, resources, and knowledge. Diet was the most common weight loss strategy (85%) considered, whereas bariatric surgery was the least common (6.1%). CONCLUSIONS: A majority of overweight and obese hemodialysis patients believe their excess weight is adversely impacting their health and quality of life and therefore wish to lose weight.

Grafting-From Proteins Using Metal-Free PET-RAFT Polymerizations under Mild Visible-Light Irradiation.

We report a new strategy toward polymer-protein conjugates using a grafting-from method that employs photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization. Initial screening of reaction conditions showed rapid polymerization of acrylamides under high dilution in water using eosin Y as a photocatalyst in the presence of a tertiary amine. A lysozyme-modified chain transfer agent allowed the same conditions to be utilized for grafting-from polymerizations, and we further demonstrated the broad scope of this technique by polymerizing acrylic and styrenic monomers. Finally, retention of the RAFT end group was suggested by successful chain extension with N-isopropylacrylamide from the polymer-protein conjugates to form block copolymer-protein conjugates. This strategy should expand the capabilities of grafting-from proteins with RAFT polymerization under mild conditions to afford diverse functional materials.

We Use Dialysate Potassium Levels That Are Too Low in Hemodialysis.

Sudden cardiac death accounts for a quarter of all deaths in hemodialysis patients. While this group is at high risk for cardiovascular events, there are certain modifiable factors that have been associated with higher risk of sudden cardiac death. These include short dialysis time, high ultrafiltration rate, and dialysate with a low potassium or calcium concentration. While it is impossible to discern the relative contribution of each of these factors, our review focuses on the role of dialysate potassium concentration in sudden cardiac death. Retrospective studies have identified low potassium dialysate (<2-3 mEq/l) as a risk factor for sudden cardiac death, particularly in patients with predialysis serum potassium concentrations <5 mEq/l. However, patients with predialysis hyperkalemia (≥5.5 mEq/l) may be an exception since a significant association of low potassium dialysate with sudden cardiac death was not observed in this subgroup. Dialysis prescribers must employ alternatives to low dialysate potassium concentrations to achieve potassium control such as increasing dialysis time and frequency, dietary restriction of potassium, prevention and treatment of constipation, discontinuation of medications contributing to hyperkalemia and traditional (or newer, better tolerated) potassium binding resins. Finally, one must also address other factors associated with sudden cardiac death such as short dialysis time, high ultrafiltration rate, and low calcium concentration dialysate.

Role of Polymer Architecture on the Activity of Polymer-Protein Conjugates for the Treatment of Accelerated Bone Loss Disorders.

Polymers of similar molecular weights and chemical constitution but varying in their macromolecular architectures were conjugated to osteoprotegerin (OPG) to determine the effect of polymer topology on protein activity in vitro and in vivo. OPG is a protein that inhibits bone resorption by preventing the formation of mature osteoclasts from the osteoclast precursor cell. Accelerated bone loss disorders, such as osteoporosis, rheumatoid arthritis, and metastatic bone disease, occur as a result of increased osteoclastogenesis, leading to the severe weakening of the bone. OPG has shown promise as a treatment in bone disorders; however, it is rapidly cleared from circulation through rapid liver uptake, and frequent, high doses of the protein are necessary to achieve a therapeutic benefit. We aimed to improve the effectiveness of OPG by creating OPG-polymer bioconjugates, employing reversible addition-fragmentation chain transfer polymerization to create well-defined polymers with branching densities varying from linear, loosely branched to densely branched. Polymers with each of these architectures were conjugated to OPG using a "grafting-to" approach, and the bioconjugates were characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The OPG-polymer bioconjugates showed retention of activity in vitro against osteoclasts, and each bioconjugate was shown to be nontoxic. Preliminary in vivo studies further supported the nontoxic characteristics of the bioconjugates, and measurement of the bone mineral density in rats 7 days post-treatment via peripheral quantitative computed tomography suggested a slight increase in bone mineral density after administration of the loosely branched OPG-polymer bioconjugate.

Polymerization-induced thermal self-assembly (PITSA).

Polymerization-induced self-assembly (PISA) is a versatile technique to achieve a wide range of polymeric nanoparticle morphologies. Most previous examples of self-assembled soft nanoparticle synthesis by PISA rely on a growing solvophobic polymer block that leads to changes in nanoparticle architecture during polymerization in a selective solvent. However, synthesis of block copolymers with a growing stimuli-responsive block to form various nanoparticle shapes has yet to be reported. This new concept using thermoresponsive polymers is termed polymerization-induced thermal self-assembly (PITSA). A reversible addition-fragmentation chain transfer (RAFT) polymerization of N-isopropylacrylamide from a hydrophilic chain transfer agent composed of N,N-dimethylacrylamide and acrylic acid was carried out in water above the known lower critical solution temperature (LCST) of poly(N-isopropylacrylamide) (PNIPAm). After reaching a certain chain length, the growing PNIPAm self-assembled, as induced by the LCST, into block copolymer aggregates within which dispersion polymerization continued. To characterize the nanoparticles at ambient temperatures without their dissolution, the particles were crosslinked immediately following polymerization at elevated temperatures via the reaction of the acid groups with a diamine in the presence of a carbodiimide. Size exclusion chromatography was used to evaluate the unimer molecular weight distributions and reaction kinetics. Dynamic light scattering and transmission electron microscopy provided insight into the size and morphologies of the nanoparticles. The resulting block copolymers formed polymeric nanoparticles with a range of morphologies (e.g., micelles, worms, and vesicles), which were a function of the PNIPAm block length.

Is routine multivitamin supplementation necessary in US chronic adult hemodialysis patients? A systematic review.

Because of concern that United States (US) chronic hemodialysis patients are at high risk for the development of vitamin deficiencies, the great majority of such patients are routinely supplemented with a multivitamin. This policy is supported by major US dialysis providers and nonprofit organizations. Yet routine multivitamin supplementation expands hemodialysis patients' already large pill burden, probably accounts for many millions of dollars in annual costs, and in light of previous reports may even carry with it the possibility of increased risk of adverse outcomes. An analysis of the benefits of routine multivitamin supplementation in US patients is therefore in order. We performed a systematic review of the medical literature between 1970 and 2014 using the Ovid MEDLINE database to address this question. We conclude that there is insufficient evidence to support routine multivitamin use and recommend that the decision to supplement be made on an individual basis.

Gauging differential health among the sexes at Windover (8Br246) using the Western Hemisphere Health Index

Assessment of intrapopulation human health provides information concerning social structure, division of labor, and lifestyle. Differential health among the sexes can provide clues to social roles, resource acquisition and status within prehistoric populations. Windover (8Br246) is an Archaic mortuary pond located in eastern central Florida. Its occupation spans over 500 years and dates to 7000 years BP. Over 168 well-preserved individuals were excavated, providing a glimpse into life during Florida's Archaic. Through the application of the Western Hemisphere Health Index, we find that males within the group experienced better overall health than females. Males outscore females in quality of life, percent of maximum scores, stature, anemia, dental disease, and infection. Females out-score males in enamel hypoplasia and degenerative joint disease. Causative factors for observed differential health are examined and include activity levels, sexual division of labor, access to resources, and the physiological demands of childbearing.

Gauging differential health among the sexes at Windover (8Br246) using the Western Hemisphere Health Index.

Assessment of intrapopulation human health provides information concerning social structure, division of labor, and lifestyle. Differential health among the sexes can provide clues to social roles, resource acquisition and status within prehistoric populations. Windover (8Br246) is an Archaic mortuary pond located in eastern central Florida. Its occupation spans over 500 years and dates to 7000 years BP. Over 168 well-preserved individuals were excavated, providing a glimpse into life during Florida's Archaic. Through the application of the Western Hemisphere Health Index, we find that males within the group experienced better overall health than females. Males outscore females in quality of life, percent of maximum scores, stature, anemia, dental disease, and infection. Females out-score males in enamel hypoplasia and degenerative joint disease. Causative factors for observed differential health are examined and include activity levels, sexual division of labor, access to resources, and the physiological demands of childbearing.