Mechanisms of whole body, respiratory, acid-base buffering: a first computer-model test of three physicochemical, acid-base theories.

Acid-base disorders are currently analyzed and treated using a bicarbonate-centered approach derived from blood studies prior to the advent of digital computers, which could solve computer models capable of quantifying the complex physicochemical nature governing distribution of water and ions between fluid compartments. An alternative is the Stewart approach, which can predict the pH of a simple mixture of ions and electrically charged proteins; hence, the role of extravascular fluids has been largely ignored. The present study uses a new, comprehensive computer model of four major fluid compartments, based on a recent blood model, which included ion binding to proteins, electroneutrality constraints, and other essential physicochemical laws.

Physicochemical properties of abnormal blood acid-base buffering.

This paper describes two new features ) development of physicochemically based, two-compartment models describing acid-base-state changes in normal and abnormal blood and ) use of model results to view and describe physicochemical properties of blood, in terms of Pco as the causative independent variable and effected [H] changes as the dependent variable. Models were derived from an in vitro experimental study, where normal blood was made both hypoproteinemic and hyperalbuminemic and then equilibrated with CO. Strong-ion gap (SIG) values were selected to match model and experimental pH.

Mechanisms of Blood pH Changes in Venovenous Extracorporeal Membrane Systems: Roles of Hemoglobin-Ion Binding and Donnan Equilibrium.

An equilibrium model was developed to understand interrelated, physicochemical mechanisms leading to blood pH and electrolyte distribution changes in patients because of venovenous extracorporeal membrane oxygenation (ECMO) and carbon dioxide removal. The model consists of plasma and red cell compartments between which water and small ions can move to establish an equilibrium state. Governing forces are as follows: 1) ionic electroneutrality in each compartment; 2) osmotic equilibrium between compartments; 3) mass balance of small ions other than bicarbonate; 4) oxygen (O 2 )-dependent hemoglobin (Hb)-Cl binding in red cells; 5) albumin binding to Cl - , Ca 2+ , and Mg 2+ in plasma; and 6) chemical equilibria of carbonates and phosphates in each compartment.

Peritoneal physicochemical transport mechanisms: Hypotheses, models and controversies.

This study answers criticisms by Waniewski et al. of the recent paper by Wolf on peritoneal transport kinetic models. Their criticisms centre on the accuracy of the data used for model fits, the hypothesis presented, which involves changes in glucose membrane parameters at high peritoneal glucose concentration and on the necessary techniques required to achieve accurate model parameter estimation.

Mechanisms of Acid-Base Kinetics During Hemodialysis: a Mathematical-Model Study.

This study contrasts the abilities and mechanisms of two physicochemical, mathematical models to predict experimental bicarbonate kinetics, hence, buffer transport, during a hemodialysis (HD) treatment in chronic renal failure patients. The existing Sargent model assumes that the body fluids can be described as a single, homogeneous extracellular fluid (EC) compartment whose volume decreases because of a constant ultrafiltration rate during HD. Bicarbonate and acetate transport between HD fluid and the EC compartment are by convection and diffusion with acetate metabolized in that compartment.

Mechanisms of Peritoneal Acid-Base Kinetics During Peritoneal Dialysis: A Mathematical Model Study.

To investigate mechanisms of acid-base changes during peritoneal dialysis (PD), a mathematical model was developed that describes kinetics of peritoneal bicarbonate, CO2, and pH during the dwell with both high and low lactate-containing dialysis fluids. The model was based on a previous modification of the Rippe 3-Pore model of water and solute kinetic transport across the peritoneal membrane during the PD dwell. A central feature of the present modification is an electroneutrality constraint on peritoneal-fluid ion concentrations, which results in the conclusion that peritoneal bicarbonate-concentration kinetics are entirely dependent on the kinetics of the other ions.

Are transient changes in capillary surface area required to explain peritoneal transport in renal failure patients?

Background: Waniewski postulated a transient increase in peritoneal capillary surface area to fit their model predictions to experimental data of Heimburger measured in renal failure (RF) patients undergoing peritoneal dialysis (PD) but with only a 3.86% glucose dialysis fluid. The present aim is to propose a new mathematical model of the patient PD procedure that could closely fit the complete Heimburger measurement set without this postulate.

Physicochemical Models of Acid-Base.

Physicochemical models have played an important role in understanding, diagnosing, and treating acid-base disorders for more than 100 years. This review focuses on recent complex models, solved using computers, and shows how these models provide new understanding and diagnostic approaches in acid-base disorders. These advanced models use the following physicochemical principles: (1) chemical equilibrium, (2) conservation of mass, (3) electroneutrality, and (4) osmotic equilibrium to describe the steady-state distribution of HO and ions in the four major body-fluid spaces, cells, interstitium, plasma, and erythrocytes, and show how this distribution is changed by fluid infusions and losses through renal and gastrointestinal physiological processes.

Hemoglobin-Dilution Method: Effect of Measurement Errors on Vascular Volume Estimation.

The hemoglobin-dilution method (HDM) has been used to estimate changes in vascular volumes in patients because direct measurements with radioisotopes are time-consuming and not practical in many facilities. The HDM requires an assumption of initial blood volume, repeated measurements of plasma hemoglobin concentration, and the calculation of the ratio of hemoglobin measurements. The statistics of these ratio distributions resulting from measurement error are ill-defined even when the errors are normally distributed.

Hyperglycemia-induced hyponatremia: Reevaluation of the Na correction factor.

This study addresses the clinically important relationship between the decreases in plasma Na and the increases in plasma glucose concentrations seen in diabetes and other hyperglycemic syndromes. This plasma 'Na correction factor', is generally accepted as 1.6mM Na per 100mg% glucose (0.

A head to head evaluation of 8 biochemical scanning tools for unmeasured ions.

We aimed to evaluate the sensitivity and specificity of 8 biochemical scanning tools in signalling the presence of unmeasured anions. We used blood gas and biochemical data from 15 patients during and after cardio-pulmonary bypass. Sampling time-points were pre-bypass (T1), 2 min post equilibration with priming fluid containing acetate and gluconate anions (T2), late bypass (T3) and 4 h after surgery (T4).

Comprehensive diagnosis of whole-body acid-base and fluid-electrolyte disorders using a mathematical model and whole-body base excess.

A mathematical model of whole-body acid-base and fluid-electrolyte balance was used to provide information leading to the diagnosis and fluid-therapy treatment in patients with complex acid-base disorders. Given a set of measured laboratory-chemistry values for a patient, a model of their unique, whole-body chemistry was created. This model predicted deficits or excesses in the masses of Na(+), K(+), Cl(-) and H2O as well as the plasma concentration of unknown or unmeasured species, such as ketoacids, in diabetes mellitus.

Whole body acid-base and fluid-electrolyte balance: a mathematical model.

A cellular compartment was added to our previous mathematical model of steady-state acid-base and fluid-electrolyte chemistry to gain further understanding and aid diagnosis of complex disorders involving cellular involvement in critically ill patients. An important hypothesis to be validated was that the thermodynamic, standard free-energy of cellular H(+) and Na(+) pumps remained constant under all conditions. In addition, a hydrostatic-osmotic pressure balance was assumed to describe fluid exchange between plasma and interstitial fluid, including incorporation of compliance curves of vascular and interstitial spaces.

A comprehensive, computer-model-based approach for diagnosis and treatment of complex acid-base disorders in critically-ill patients.

We have developed a computer-model-based approach to quantitatively diagnose the causes of metabolic acid-base disorders in critically-ill patients. We use an interstitial-plasma-erythrocyte (IPE) model that is sufficiently detailed to accurately calculate steady-state changes from normal in fluid volumes and electrolyte concentrations in a given patient due to a number of causes of acid-base disorders. Normal fluid volumes for each patient are determined from their sex, height and weight using regression equations derived from measured data in humans.

A mathematical model of blood-interstitial acid-base balance: application to dilution acidosis and acid-base status.

We developed mathematical models that predict equilibrium distribution of water and electrolytes (proteins and simple ions), metabolites, and other species between plasma and erythrocyte fluids (blood) and interstitial fluid. The models use physicochemical principles of electroneutrality in a fluid compartment and osmotic equilibrium between compartments and transmembrane Donnan relationships for mobile species. Across the erythrocyte membrane, the significant mobile species Cl⁻ is assumed to reach electrochemical equilibrium, whereas Na(+) and K(+) distributions are away from equilibrium because of the Na(+)/K(+) pump, but movement from this steady state is restricted because of their effective short-term impermeability.

Disequilibrium between alveolar and end-pulmonary-capillary O2 tension in altitude hypoxia and respiratory disease: an update of a mathematical model of human respiration at altitude.

We have previously formulated and validated a mathematical model specifically designed to describe human respiratory behavior at altitude. In that model, we assumed equality of alveolar and end-pulmonary-capillary oxygen tensions. However, this equality may not hold true during rapid and prolonged changes to high altitudes producing severe hypoxia as can occur in aircraft cabin decompressions and in some respiratory diseases.

A mathematical model of human respiration at altitude.

We developed a mathematical model of human respiration in the awake state that can be used to predict changes in ventilation, blood gases, and other critical variables during conditions of hypocapnia, hypercapnia and these conditions combined with hypoxia. Hence, the model is capable of describing ventilation changes due to the hypocapnic-hypoxia of high altitude. The basic model is that of Grodins et al.

Cadmium and mercury cause an oxidative stress-induced endothelial dysfunction.

We investigated the ability of cadmium and mercury ions to cause endothelial dysfunction in bovine pulmonary artery endothelial cell monolayers. Exposure of monolayers for 48 h to metal concentrations greater than 3-5 microM produced profound cytotoxicity (increased lactate dehydrogenase leakage), a permeability barrier failure, depletion of glutathione and ATP and almost complete inhibition of the activity of key thiol enzymes, glucose-6-phosphate dehydrogenase (G6PDH) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In contrast, metal concentrations less than 1-2 microM induced increases in glutathione and thiol-enzyme activities with minimal changes in LDH leakage, barrier function and ATP content.

The anti-cancer drug, doxorubicin, causes oxidant stress-induced endothelial dysfunction.

The anticancer drug doxorubicin (DOX) is toxic to target cells, but also causes endothelial dysfunction and edema, secondary to oxidative stress in the vascular wall. Thus, the mechanism of action of this drug may involve chemotoxicity to both cancer cells and to the endothelium. Indeed, we found that the permeability of monolayers of bovine pulmonary artery endothelial cells (BPAEC) to albumin was increased by approximately 10-fold above control, following 24-h exposure to clinically relevant concentrations of DOX (up to 1 microM).

Menadione causes endothelial barrier failure by a direct effect on intracellular thiols, independent of reactive oxidant production.

Menadione (MQ), a quinone used with cancer chemotherapeutic agents, causes cytotoxicity to endothelial cells (EC). Previous studies have suggested that MQ induces an oxidative stress and dysfunction in EC by either increasing hydrogen peroxide (H(2)O(2)) production or depleting intracellular glutathione (GSH), the main intracellular antioxidant. Since a primary function of EC is to form a barrier to fluid movement into tissues, protecting organs from edema formation and dysfunction, our aim was to see if MQ would cause a barrier dysfunction and to ascertain the mechanism.