Physiology of Body Fluids

Bruce Grand. Koeppen Dr., PhD , Bruce A. Stanton PhD , in Renal Physiology (Fifth Edition), 2013

Osmolarity and Osmolality

Osmolarity and osmolality are oftentimes confused and incorrectly interchanged. Osmolarity refers to the number of solute particles per 1 Fifty of solvent, whereas osmolality is the number of solute particles in one kg of solvent. For dilute solutions, the departure betwixt osmolarity and osmolality is insignificant. Measurements of osmolarity are temperature dependent because the volume of solvent varies with temperature (i.e., the volume is larger at higher temperatures). In dissimilarity, osmolality, which is based on the mass of the solvent, is temperature independent. For this reason, osmolality is the preferred term for biologic systems and is used throughout this and subsequent capacity. Osmolality has the units of Osm/kg H iiO. Because of the dilute nature of physiologic solutions and because h2o is the solvent, osmolalities are expressed every bit milliosmoles per kilogram of water (mOsm/kg HtwoO).

Table 1-ane shows the relationships among molecular weight, equivalence, and osmoles for a number of physiologically meaning solutes.

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Miscellaneous Physical, Chemical, and Microbiological Test Methods

Vitthal S. Kulkarni Ph.D. , Charles Shaw Ph.D. , in Essential Chemistry for Formulators of Semisolid and Liquid Dosages, 2016

11.1.four Osmolality (USP<785>)

Osmolarity and osmolality are units of solute concentration that are frequently used in reference to biochemistry and body fluids, and are related to the tonicity of the formulation. If the tonicity is too far from isotonic, certain products (e.g., ophthalmic solutions and suspensions) will cause stinging on awarding. Sodium chloride is frequently used to adjust the osmolality of a formulation. Osmolality is measured using an osmometer by, for example, freezing point depression of the solution. As with pH, osmolality tin exist measured and adjusted on the majority material, and measured and monitored on the finished product at the time of release and on storage.

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Disturbances of Free Water, Electrolytes, Acid-Base of operations Balance, and Oncotic Force per unit area

In Veterinary Medicine (Eleventh Edition), 2017

Isotonic, Hypertonic, and Hypotonic Crystalloid Solutions

The tonicity of the solution is an of import clinical effect. Complete understanding of the tonicity concept requires differentiation of two terms, osmolality and osmolarity. Osmolality is the number of dissolved particles per kilogram of solution and is expressed every bit mOsm/kg of solution. The normal plasma osmolality in large animals is approximately 285 mOsm/kg, and plasma osmolality is aggressively dedicated past increasing water intake (osmolality >285 mOsm/kg) or promoting free water excretion (osmolality <285 mOsm/kg). The correct term in plasma and extracellular fluid is osmolality, because this gene is measured in the laboratory; however, often the term osmolarity is used because one L of lactated Ringer's solution closely approximates 1 kg of lactated Ringer's solution and because osmolarity can be easily calculated from the concentration of electrolytes in the fluid solution. Osmolarity is the number of particles per liter of solution and is expressed as mOsm/L of solution.

One kilogram (1 50) of plasma from an adult large beast has two components, seventy g of poly peptide and 930 g of plasma water. Accordingly, the osmolality of normal plasma (285 mOsm/kg) is equivalent to a plasma water osmolarity of 306 mOsm/Fifty ({285 mOsm/kg}/{0.93 L/kg}). Ringer's solution, 0.9% NaCl, and 1.3% NaHCO3 are therefore considered isotonic solutions because they distribute in plasma water and have calculated osmolarities of 309, 308, and 310 mOsm/50, respectively.

The normal plasma osmolarity for solutions to exist administered to large animals is approximately 306 mOsm/L; solutions tin therefore be defined equally isotonic (300–312 mOsm/50), hypertonic (>312 mOsm/L), or hypotonic (<300 mOsm/L). Using this categorization, it is readily apparent that some routinely used crystalloid solutions are hypotonic; in particular, lactated Ringer'due south solution (275 mOsm/L) is mildly hypotonic and 5% dextrose (250 mOsm/L) is moderately hypotonic, although, as glucose is metabolized, five% dextrose becomes an increasingly hypotonic solution. Erythrocytes are resistant to increases in plasma osmolarity, whereas they are susceptible to mild decreases in osmolarity; this is the basis of the red blood cell fragility test in which red claret cell suspensions are placed in solutions of decreasing osmolarity. Because of hypotonic-induced hemolysis, parenterally administered fluids should ideally be isotonic or hypertonic.

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Sodium Disorders

Jamie M. Burkitt Creedon DVM, DACVECC , in Modest Animal Critical Intendance Medicine (2nd Edition), 2015

Osmolality and Osmotic Pressure level

An osmole is ane mole of any fully dissociated substance dissolved in h2o. Osmolality is the concentration of osmoles in a mass of solvent. In biologic systems, osmolality is expressed equally mOsm/kg of water and can be measured using an osmometer. Osmolarity is the concentration of osmoles in a volume of solvent and in biologic systems is expressed equally mOsm/L of water. In physiologic systems there is no appreciable difference between osmolality and osmolarity, so the term osmolality will be used for the rest of this discussion for simplicity. Every molecule dissolved in the full trunk water contributes to osmolality, regardless of size, weight, accuse, or composition. 3 The most arable osmoles in the extracellular fluid are sodium (and the accompanying anions chloride and bicarbonate), glucose, and urea. Because they are the virtually plentiful, these molecules are the main determinants of plasma osmolality in good for you dogs and cats.

Plasma osmolality (mOsm/kg) in healthy animals can be calculated by the equation shown in Box 50-1. 4,5 As this equation shows, plasma sodium concentration is the major determinant of plasma osmolality.

Osmoles that practise non cross the jail cell membrane freely are considered effective osmoles, whereas those that practice cross freely are termed ineffective osmoles. The water-permeable cell membrane is functionally impermeable to sodium and potassium. As a result, sodium and potassium molecules are effective osmoles and they exert osmotic force per unit area across the cell membrane. The internet movement of h2o into or out of cells is dictated past the osmotic force per unit area gradient. Osmotic pressure causes water molecules from an surface area of lower osmolality (college water concentration) to motion to an surface area of higher osmolality (lower water concentration) until the osmolalities of the compartments are equal.

When sodium is added to the extracellular space at a concentration greater than that in the extracellular fluid, intracellular volume decreases (the cell shrinks) as water leaves the prison cell along its osmotic force per unit area gradient. Conversely, cells swell when gratis h2o is added to the interstitial space and water moves intracellularly along its osmotic force per unit area slope.

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Disorders of Sodium and Water

Stephen P. DiBartola , in Fluid, Electrolyte, and Acid-Base Disorders in Minor Animal Practice (Fourth Edition), 2012

Osmolality

The osmolality of a solution refers to the concentration of osmotically active particles in that solution. Osmolality is a function just of the number of particles and is not related to their molecular weight, size, shape, or charge. One mole of a nondissociating substance (e.g., glucose or urea) dissolved in 1   kg of water decreases the freezing point of the resultant solution by 1.86° C. Such a solution has an osmolality of 1 Osm/kg or 1000 mOsm/kg.

The term osmolarity refers to the number of particles of solute per liter of solution, whereas the term osmolality refers to the number of particles of solute per kilogram of solvent. When considering the physiology of body fluids, the deviation between osmolality and osmolarity is negligible considering body fluids typically are dilute aqueous solutions. In clinical medicine, the term osmolality is used, and the osmolality of trunk fluids usually is measured past freezing-bespeak low osmometry. A solution is said to be hyperosmotic if its osmolality is greater than that of the reference solution (often plasma) and hypoosmotic if its osmolality is less than that of the reference solution. An isosmotic solution has an osmolality identical to that of the reference solution.

The normal plasma osmolality of dogs and cats is slightly college than that of humans and ranges from 290 to 310 mOsm/kg in dogs and from 290 to 330 mOsm/kg in cats. In ane study, twenty dogs under resting conditions had plasma osmolality values of 292 to 308 mOsm/kg with a mean value of 301 mOsm/kg. 67 In a study of the effects of sodium bicarbonate infusion in cats, baseline serum osmolality ranged from 290 to 330 mOsm/kg. 22 Plasma osmolality tin can be estimated from the equation:

Calculated Plasma Osmolality = two Na + BUN 2.viii + glucose xviii

where BUN is claret urea nitrogen. In this equation, the concentrations of urea and glucose in milligrams per deciliter are converted to millimoles per liter by the conversion factors two.eight and xviii. The measured osmolality should not exceed the calculated osmolality past more than than ten mOsm/kg. 42, 149 If it does, an aberrant osmolal gap is said to exist present. This occurs when an unmeasured solute (i.e., 1 not accounted for in the equation) is present in big quantity in plasma (east.g., mannitol or metabolites of ethylene glycol) or when hyperlipemia or hyperproteinemia results in pseudohyponatremia (run into section on Hyponatremia with Normal Plasma Osmolality). 42, 50, 56

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Man Immunoglobulin Preparations

Matthew S. Karafin MD , Beth H. Shaz MD , in Transfusion Medicine and Hemostasis (Second Edition), 2013

Preparation and Administration

Production

IVIG production is strictly regulated by IUIS/WHO (International Union of Immunological Societies/World Health Organization) and multiple requirements are necessary for advisable IVIG production. Specifically, IVIG requires the following:

•

the source material must be plasma obtained from a minimum puddle of 10,000 donors;

•

the product must be costless of prekallikrein activator, kinins, plasmin, preservatives, or other potentially harmful contaminants;

•

IgA content and IgG amass levels need to be as depression as possible;

•

the product must contain at least 90% intact IgG;

•

the IgG should maintain opsonin activity, complement binding, and other biological activities;

•

the IgG subclasses should be present in similar proportions to those in normal pooled plasma;

•

antibody levels against at least ii species of bacteria (or toxins) and two viruses should be determined;

•

the product must demonstrate at least 0.1 IU of hepatitis B antibody per ml and a hepatitis A radioimmunoassay titer of at to the lowest degree 1:1000;

•

the manufacturer should specify the contents of the final production, including the diluent and other additives, and whatever chemic modification of the IgG.

Plasma Collection

IVIG is derived from pools of plasma collected either by whole blood donations as recovered plasma (twenty%) or by apheresis equally source plasma (80%).

Processing

Manufacturers differ in the steps used to fractionate, purify, and stabilize Ig; methods used to inactivate and/or remove viruses; and formulation of the final product. Cold ethanol is commonly used for fractionation; and so the product is purified by filtration, chromatography, and/or precipitation. Viral inactivation is accomplished by rut and chemical/enzymatic methods. To limit IgG aggregates, ion substitution chromatography, treatment with pepsin at a pH of 4, polyethylene glycol, and/or stabilizers such every bit sucrose, glucose, glycine, maltose, sorbitol, and/or albumin are used.

Selecting a Product

Products are available in liquid or lyophilized forms. The lyophilized forms tin be reconstituted to a variety of different concentrations and osmolarities depending on the corporeality of liquid used and the selection of liquid (sterile h2o, five% dextrose, or 0.nine% saline), depending on the manufacturers' instructions. No other medications or fluids should be mixed with IVIG. Unlike IVIG products have differences in concentration of additives, IgA content, osmolarity, osmolality, and pH. These factors should be considered based on the patient's clinical history (Tabular array 37.two). For example, IVIG with glucose should exist used with intendance in diabetics. Additionally, the antibody titers and biologic function of dissimilar products are non typically tested, even though there may be potentially clinically meaning differences betwixt products. Most hospital pharmacies only stock a limited number of IVIG products.

Table 37.2. Variables to Consider When Choosing an IVIG Product

Variable Clinical Significance
Sucrose The FDA issued a warning letter of the alphabet stating that the administration of sucrose- containing products may increase the risk of development of astute renal failure. Patients at increased chance include those with whatever degree of pre-existing renal insufficiency, diabetes mellitus, age &gt;65 years, book deletion, sepsis, paraproteinemia, and concomitant nephrotoxic drugs.
Sorbitol Patients with hereditary fructose intolerance who receive sorbitol- or fructose-containing products may develop irreversible multi-organ failure.
Glucose Glucose-containing products should exist used with caution in patients with diabetes or renal dysfunction and the elderly.
Glycine Glycine-containing products are associated with increased frequency of vasomotor events.
Maltose Some glucose monitors may interpret maltose as glucose and give falsely elevated results, which may result in iatrogenic insulin overdose.
Sodium High sodium products should be charily given to patients with centre failure or renal dysfunction, neonates, young children, the elderly, and those at risk for thromboembolism.
pH Depression pH products should be administered cautiously to those with compromised acrid-base compensatory mechanisms, such as neonates or those with renal dysfunction.
Osmolality and osmolarity The osmolality and osmolarity should exist considered in patients with heart disease or renal dysfunction, young children, the elderly, and those at risk for thromboembolism.
Volume The volume should be considered when administering IVIG to volume-sensitive patients, including patients with renal dysfunction, eye disease, the elderly, neonates, and small-scale children.

Modified from Hillyer CD, Silberstein LE, Ness et al. (eds). (2007). Blood Banking and Transfusion Medicine: Bones Principles &amp; Practice, 2nd edition. San Diego, CA: Elsevier.

Administration

The FDA has approved IM and IV Ig products; subcutaneous assistants is an off-label utilize that may be helpful when venous access is difficult or for habitation cocky-administration. The IVIG infusion line used should exist separate from other infusion lines. The charge per unit of infusion for those not previously exposed to IVIG should be low and can be increased gradually equally defined by the specific IVIG product used (see manufacturers' instructions). Infusion rates in the elderly, patients at risk for renal dysfunction, or patients at run a risk for thrombosis, should also be slow. Vital signs should be monitored every 15 minutes for the first 60 minutes and then every 30–hr.

Adverse Events

Adverse furnishings occur in approximately three–15% of infusions. Nigh of the common agin reactions, such as headache, nausea, vomiting, chills, fever, and malaise, seem to be related to the rate and/or dose of infusion. Other common adverse reactions include erythema, phlebitis, eczema, myalgias, flushing, rash, diaphoresis, puritus, bronchospasm, chest hurting, dorsum pain, dizziness, and blood pressure level changes.

Adverse reactions that are dose related (see below) may be ameliorated by decreasing the rate of infusion or administration of the total dose over 2–5 days. In addition, agin reactions differ among different preparations, such that patients may tolerate one product better than another product. Lastly, improved manufacturing processes currently in place return IVIG free of enveloped and not-enveloped viruses and should not be considered as a run a risk of IVIG use.

While rare, known severe complications can occur with IVIG assistants. The master complications are reviewed below.

Anaphylactic Reactions

Individuals who are IgA deficient and have anti-IgA may accept anaphylactic reactions to IVIG products. These patients develop severe symptoms including hypotension, wheezing, and shortness of breath. These reactions crave halting the infusion and providing epinephrine, antihistamines, corticosteroids, fluids, and oxygen every bit the clinical situation requires. There are products with low IgA levels (≤2.2 μg/ml) for use in IgA deficient individuals.

Aseptic Meningitis

This is characterized by astringent headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea, and vomiting beginning half-dozen–48 hours afterwards infusion. The etiology of this complication is unknown simply may be due in part to the osmotic changes within the brain due to the IVIG infusion. Patients with a history of migraine and who accept received high-dose Ig handling appear more susceptible. Certain IVIG brands are more prone to this complexity. The cerebrospinal fluid demonstrates pleocytosis and elevated protein. The symptoms resolve in hours to days, and may be prevented prophylactically with a premedication of steroids and anti-migraine medications, slowing charge per unit, and/or dividing dose over more than days.

Hemolytic Transfusion Reactions

A recent review demonstrated a 1.half dozen% incidence of decreased hemoglobin later on IVIG administration, particularly in non-group O women in an inflammatory land receiving big doses of IVIG. The proposed machinery is from passively transfused anti-A and/or anti-B antibodies within the product.

Infectious Disease Transmission

The take a chance of infectious disease transmission is almost nil due to donor interview and testing, fractionation, and boosted pathogen inactivating and removal steps (such as ultrafiltration).

Passively Caused Antibodies

Patients who receive IVIG may passively acquire a diversity of antibodies, including anti-HBc and anti-CMV, and therefore this may result in false positive serologic testing. The testing tin can either be repeated at a later time interval or nonserologic methods can be used to determine the presence of the infectious amanuensis. Blood group antibodies may also be passively acquired, particularly anti-A and/or anti-B, resulting in a positive direct antiglobulin test or rarely meaning hemolysis.

Renal Failure

The FDA issued a warning letter in 1998 regarding the association of administration of sucrose-containing IVIG products and astute renal failure (Table 37.2).

Thromboembolic Events

IVIG has been associated with deep venous thrombosis, myocardial infarction, cerebrovascular accidents, transverse sinus thrombosis, and pulmonary embolism, possibly related to increase in claret viscosity after IVIG administration. Patients who received large doses chop-chop every bit well as elderly, overweight or immobilized patients and patients with cardiovascular disease are thought to be at highest risk for this complication.

Transfusion-Related Acute Lung Injury (TRALI)

A single case report of possible TRALI occurred after IVIG administration.

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Enteral Feeding

D.L. Waitzberg , R.Southward. Torrinhas , in Encyclopedia of Food and Health, 2016

Formulation

The EN can be administered intermittently or continuously. Pick of pathway for EN administration and the type of infusion to be adopted will influence its conception design. This too involves determining the total period for nutrition administration, the volume to be infused, infusion rate, if gravity drip volition be used, and in which course it will exist provided (infusion pump or past bolus). Table two outlines the programming of EN co-ordinate to feeding tube positioning in pre- or postpyloric location.

Table 2. Programming of EN according to feeding tube positioning

Tube feeding position Volume Osmolality Fractionation Administration time
Tum Allows high-book supply Hyperosmolar solutions are tolerated, but the college solution osmolality the slower stomach elimination Depends on the total volume/twenty-four hour period and patient tolerance. Lower fractionation (four to six times per twenty-four hours) and higher volume in each supply may be used Nearly 120 drops per min (or fourth dimension (min)   =   full volume (ml)/6) from the outset of therapy
Postpyloric During intermittent supply, the volume should not exceed 300   ml   h−   1 in adapted patients Better tolerance for formulations with less than 550   mOsm   l−   ane; dripping of hyperosmolar solutions should be strictly controlled by using infusion pump Continuous or intermittent fractionation, generally between six and eight supplies per twenty-four hour period in each 3   h Initial phase: 60 drops/min (or time (min)   =   full volume (ml)/3); 'adjusted' phase: 120 drops per min (or time (min)   =   total book (ml)/6)

Enteral formulations should be nutritionally consummate when used as sectional nutrition or as a supplement to patients with normal oral ingestion; or nutritionally incomplete when used merely as a supplement diet. The evaluation of the digestive and absorptive capacity of the patient should be performed for better enteral formula selection ( Scheme 2 ).

Scheme 2. Planning for selection of enteral diets.

Several enteral formulations are based on fresh nutrient, processed food, or both fresh and processed nutrient. Therefore, nutrients comprising EN are more often than not the aforementioned constituents of a normal diet, consumed by the oral route, including carbohydrate (twoscore–60% total energy needs), protein (fourteen–20% full energy needs), fat (15–xxx% energy needs), and fiber (twoscore–20   g   fifty−   1 ). Different factors should exist considered to facilitate the choice of the well-nigh appropriate enteral conception for patients with EN indication, such as caloric density, osmolarity and osmolality, administration pathway, source and complexity of nutrients, and disease.

The EN caloric density (kcal   ml−   i) should be based on the patient's full calorie needs versus the book of enteral diets to be administered per solar day. Enteral diets with higher energy density have a lower corporeality of h2o, which can range from 690 to 860   ml   fifty−   i diet. The categorization of enteral formulas, co-ordinate to its energy density, is shown in Tabular array 3 .

Table iii. Categorization of enteral formulas according to its free energy density

Energy density Value (kcal   ml−   1) Formula
Very low &lt;   0.half-dozen Sharply hypocaloric
Low 0.vi–0.viii Hypocaloric
Standard 0.9–1.two Normocaloric
High i.3–1.5 Hypercaloric
Very high &gt;   one.v Sharply hypercaloric

Vitamin and mineral supply varies according to the specific needs of the patients and their illness. In the specific nutritional needs, you should evaluate the indication of additional micronutrient supplementation, even when the formulation, per se, achieves those values recommended by the Recommended Dietary Allowance (RDA). Clinical nutritional patient evaluation should include objective and/or subjective indicators to identify, as early equally possible, any risk of specific micronutrient deficiency for information technology to be immediately corrected and/or prevented.

Some specialized and very specific formulations to particular clinical situation (east.g., renal failure) are bereft in some vitamin and mineral supply. Therefore, EN dietary planning attends to the demand for supplementation or not of these micronutrients. For the long-term use of incomplete enteral feeding, the supplemental vitamins and minerals should be indicated.

In patients with malabsorption syndromes, investigate the possible fat soluble vitamins (A, D, E, and One thousand) deficiency to correct it shortly. In that location is a lack of specific vitamin and mineral recommendations for critically ill patients. Nevertheless, in such a status, the needs of antioxidant nutrients are increased due the oxidative stress, and it is recommended to supplement vitamins A, C, and E, zinc, and selenium.

EN osmolality (mmol   l−   1 solution) and osmolality (mOsm   kg−   i water) are associated with its digestive tolerance. Although the stomach tolerates diets with higher osmolality, more distal portions of the gastrointestinal tract respond better to isosmolares formulations. Therefore, hyperosmolar diets infused by gastrostomy or nasogastric feeding tube have better digestive tolerance when compared with assistants by postpyloric or jejunal probes.

The nutrients that about touch the osmolality of a solution are simple carbohydrates (mono- and disaccharides), which take greater osmotic outcome than the higher molecular weight carbohydrates (starch); minerals and electrolytes, due the property of its dissociation into smaller particles (due east.g., sodium, potassium, and chloride); hydrolyzed proteins; crystalline amino acids; as well as medium-chain triglycerides, because they are more soluble than long-chain triglycerides. The more hydrolysates components contains the formulation, the higher its osmolality.

Enteral diets should not exceed the value of the renal solute load tolerated past the kidneys (800–1200   mOsm, in normal situation). Renal solute load can exist calculated by adding 1   mOsm for each mEq of sodium/potassium/chloride, and 5.vii   mOsm (adults) or 4   mOsm (children) for each gram of protein from its formula. Special attention should be given to critical clinical situations, such as sepsis, postoperative, polytrauma, and severe burn, where the urine becomes very dense, with high osmolality (around 500–yard   mOsm   kg−   1), even under appropriate hydration.

Chiefly, the influence of the medication osmolality is usually neglected. The mean osmolality of liquid medications administered orally or past feeding tube ranges from 450 to x   950   mOsm   kg−   ane water. Certain manifestations of gastrointestinal intolerance may exist related to the medication, although it is often attributed to enteral formulation.

In specific clinical situations, there may be demands for change in the types of nutrients used; the quantity and/or grade these should be presented. In such cases, nutritional therapy becomes more specialized. These adaptations involve changes from unproblematic source of nutrients used until its physicochemical and structural modifications. Thus, specialized formulations for enteral use may provide different sources of vitamins, minerals, carbohydrates, lipids, and proteins, and these nutrients may exist presented in their entirety or hydrolyzed (wholly or partly) structure.

Some specialized EN formulations are part of immunonutrition. The immunonutrition is a nutritional intervention that explores the particular activity of various nutrients in alleviating inflammation and modulating the allowed system, in which are included the omega-three fatty acids, arginine, glutamine, nucleotides, and antioxidants. There is a current consensus that perioperative immunonutrition can beneficiate elective surgical patients, especially those malnourished patients submitted to major gastrointestinal surgery. In these patients, administration of enteral diets containing n-three PUFA, nucleotides and arginine contributes to decrease postoperative infectious and noninfectious complications and must be initiated 5–7 days preop (500–1000   ml day−   1) and maintained in the postoperative menses.

Although the benefit of using this enteral formula combining different nutrients with immunomodulatory functions is well established in surgical patients, information are lacking to confirm or guide the effective and safe use of enteral diets containing isolated immunonutrients in dissimilar clinical populations, including arginine and glutamine. In hemodynamically stable condition, arginine may offer immunologic and metabolic benefits, but its participation in the synthesis of nitric oxide may constitute a potential risk for septic patients. Enteral glutamine should be considered to treat burn patients and trauma victims, but there is not sufficient evidence for its use in critically ill patients with failure of multiple systems.

Other nutrients that may compose specialized EN formulations include the branched concatenation amino acids (BCAAs). BCAAs provide primary fuel for skeletal muscle during stress and sepsis. Therefore, leucine, isoleucine, and valine may exist added to specialized EN formulas equally supplemental metabolic sources to attend the metabolic needs of skeletal muscle during hypermetabolic weather.

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