Hypotonicity

Ophthalmic Dosage Forms. Ophthalmic preparations can be solutions, eg, eye drops, eyewashes, ointments, or aqueous suspensions (30). They must be sterile and any suspended dmg particles must be of a very fine particle size. Solutions must be particle free and isotonic with tears. Thus, the osmotic pressure must equal that of normal saline (0.9% sodium chloride) solution. Hypotonic solutions are adjusted to be isotonic by addition of calculated amounts of tonicity adjusters, eg, sodium chloride, boric acid, or sodium nitrate. 

Aperture impedance measurements of cell volume must take into account the osmolaUty and pH of the medium. A hypotonic medium causes cells to swell a hypertonic medium causes them to shrink. Some manufacturers of aperture impedance counters deHberately provide hypertonic electrolytic media for red blood cell measurements. The shmnken red cells not only become more nearly spherical and thus less affected by orientation, but also less deformable than cells in isotonic media and thus less affected by differences in hemoglobin content. 

Cell wall Peptidoglycan a rigid framework of polysaccharide cross-linked by short peptide chains. Some bacteria possess a lipopolysaccharide- and protein-rich outer membrane. Mechanical support, shape, and protection against swelling in hypotonic media. The cell wall is a porous nonselective barrier that allows most small molecules to pass. 

Blood and lymph are approximately isotonic to a cell so that cells do not gain or lose liquid when bathed in these fluids. Pure water is hypotonic and may cause cells to swell and burst. During intravenous feeding, injections, and storage of cell tissue, a salt (saline) solution is used with a concentration of solutes that is essentially isotonic with blood (and hence, with the cell) to prevent cell damage. 

The congenital diseases are also inherited, but they are characteristically expressed at birth or in very early infancy. Victims of congenital muscle disease are often hypotonic and weak at birth. The severity of the congenital diseases of muscle is also highly variable the diseases ranging from the slowly progressive, compatible with an essentially normal lifestyle, to the rapidly progressive and fatal in very early life. 

Some types of injections must be made iso-osmotic with blood serum. This applies particularly to large-volume intravenous infusions if at all possible hypotonic solutions cause lysis of red blood corpuscles and thus must not be used for this purpose. Conversely, hypertonic solutions can be employed these induce shrinkage, but not lysis, of red cells which recover their shape later. Intraspinal injections must also be isotonic, and to reduce pain at the site of injection so should intramuscular and subcutaneous injections. Adjustment to isotonicity can be determined by the following methods. 

It has been known for some time that the Cl -conductance of epithelial cells can, in addition to its regulation via cAMP, be enhanced by increases in cytosolic Ca " (cf. Fig. 3). This has been shown with Ca -ionophores [120,121] or with hormones increasing cytosolic Ca such as carbachol, neurotensin, ATP, etc. [50,103,104]. Usually these agonists have dual effects. They increase the Cl - as well as the K" -conductance [104]. Stubs et al. [122] have shown that CF cells still increase their Cl -conductance in response to ATP. Another mechanism of Cl -channel activation has been described in whole-cell patches of colonic carcinoma and RE cells [123,124] when the cells are exposed to hypotonic media they swell and increase their Cl -conductance. This is a rather general phenomenon which is present in a lot of cells [11]. In their effort to reduce cell volume in hypotonic media (regulatory... 

The immunoglobulin fraction from each bleed was purified by use of a recirculating isoelectric focusing (RIEF) technique (Bier et al. 1979). The whole serum was diluted 1 3 with urea, to yield a final urea concentration of 3 M, and then desalted by electrodialysis. The urea was added to prevent precipitation under hypotonic conditions. Ampholine (1 percent w/v, pH 3.5 to 10, LKB... 

If serum sodium rises more than 150 mEq/L or when euv-olemic, switch to hypotonic fluid replacement. Lactated Ringer s solution may prolong ketoacid production by promoting alkalinization... 

Change to hypotonic saline or dextrose 5% in water to correct free water deficit once intravascular replete ° Primarily water depletion... 

TBW depletion (often referred to as dehydration ) is typically a more gradual, chronic problem compared to ECF depletion. Because TBW depletion represents a loss of hypotonic fluid (proportionally more water is lost than sodium) from all body compartments, a primary disturbance of osmolality is usually seen. The signs and symptoms of TBW depletion include CNS disturbances (mental status changes, seizures, and coma), excessive thirst, dry mucous membranes, decreased skin turgor, elevated serum sodium, increased plasma osmolality, concentrated urine, and acute weight loss. Common causes of TBW depletion include insufficient oral intake, excessive insensible losses, diabetes insipidus, excessive osmotic diuresis, and impaired renal concentrating mechanisms. Long-term care residents are frequently admitted to the acute care hospital with TBW depletion secondary to lack of adequate oral intake, often with concurrent excessive insensible losses. 

Fluids can be classified further according to their tonicity. Isotonic solutions (i.e., normal saline or 0.9% sodium chloride [NaCl]) have a tonicity equal to that of the ICF (approximately 310 mEq/L or 310 mmol/L) and do not shift the distribution of water between the ECF and the ICF. Because hypertonic solutions (i.e., hypertonic saline or 3% NaCl) have greater tonicity than the ICF (greater than 376 mEq/L or 376 mmol/L), they draw water from the ICF into the ECF. In contrast, hypotonic solutions (i.e., 0.45% NaCl) have less tonicity than the ICF (less than 250 mEq/L or 250 mmol/L) leading to an osmotic pressure gradient that pulls water from the ECF into the ICF. The tonicity, electrolyte content, and glucose content of selected fluids are shown in Table 24—3. 

Half-normal saline is a hypotonic fluid that provides free water in relative excess when compared to the sodium concentration. This crystalloid is typically used to treat patients... 

D5W is a solution of free water and dextrose that provides a modest amount of calories but no electrolytes. Although it is technically isotonic, it acts as a hypotonic solution in the body. 

Hyponatremia is very common in hospitalized patients and is defined as a serum sodium concentration below 136 mEq/L (136 mmol/L). Clinical signs and symptoms appear at concentrations below 120 mEq/L (120 mmol/L) and typically consist of agitation, fatigue, headache, muscle cramps, and nausea. With profound hyponatremia (less than 110 mEq/L [110 mmol/L]), confusion, seizures, and coma maybe seen. Because therapy is also influenced by volume status, hyponatremia is further defined as (1) hypertonic hyponatremia (2) hypotonic hyponatremia with an increased ECF volume (3) hypotonic hyponatremia with a normal ECF volume and (4) hypotonic hyponatremia with a decreased ECF volume.16... 

Hypotonic hyponatremia with an increase in ECF is also known as dilutional hyponatremia. In this scenario, patients have an excess of total body sodium and TBW however, the excess in TBW is greater than the excess in total body sodium. Common causes include CHF, hepatic cirrhosis, and nephrotic syndrome. Treatment includes sodium and fluid restriction in conjunction with treatment of the underlying disorder—for example, salt and water restrictions are used in the setting of CHF along with loop diuretics, angiotensin-converting enzyme inhibitors, and spironolactone.15... 

In hypotonic hyponatremia with a decreased ECF volume, patients usually have a deficit of both total body sodium and TBW, but the sodium deficit exceeds the TBW deficit. Common causes include diuretic use, profuse sweating,... 

Hypernatremia is a serum sodium concentration greater than 145 mEq/L (145 mmol/L) and can occur in the absence of a sodium deficit (pure water loss) or in its presence (hypotonic fluid loss).19 The signs and symptoms of hypernatremia are the same as those found in TBW depletion. Symptoms of hypernatremia are evident with a serum concentration greater than 160 mEq/L (160 mmol/L) and usually consist of thirst, mental slowing, and dry mucous membranes. Signs and symptoms become more profound as hypernatremia worsens, with the patient demonstrating confusion, hallucinations, acute weight... 

Hypotonic solution such as dextrose 5% and 1/2 normal saline or similar fluid... 

Lithium can cause hypotonicity and cyanosis in the neonate, usually termed the floppy baby syndrome. Most data indicate normal neurobehavioral development once these symptoms resolve. Lithium is readily transferred via breast milk. Breast-feeding is not advised for patients who are taking lithium.30... 

Decreased peak and mean urinary flow rate (less than 10 to 15 mL/s) on uroflowmetry decreased urinary flow rate is not specific for BPH it can also be due to other urological disorders (e.g., urethral stricture, meatal stenosis, or bladder hypotonicity)... 

Possible intestinal leak/perforation, diffuse peritonitis, sepsis, mild dehydration, and hypovolemic hypotonic hyponatremia... 

Commonly administered LVPs include such products as Lactated Ringers Injection USP, Sodium Chloride Injection USP (0.9%), which replenish fluids and electrolytes, and Dextrose Injection USP (5%), which provides fluid plus nutrition (calories), or various combinations of dextrose and saline. In addition, numerous other nutrient and ionic solutions are available for clinical use, the most popular of which are solutions of essential amino acids or lipid emulsions. These solutions are modified to be hypertonic, isotonic, or hypotonic to aid in maintaining both fluid, nutritional, and electrolyte balance in a particular patient according to need. Indwelling needles or catheters are required in LVP administration. Care must be taken to avoid local or systemic infections or thrombophlebitis owing to faulty injection or administration technique. 

It is important that injectable solutions that are to be given intravenously are isotonic, or nearly so. Because of osmotic pressure changes and the resultant exchange of ionic species across red blood cell membranes, nonisotonic solutions, particularly if given in quantities larger than 100 mL, can cause hemolysis or cre-nation of red blood cells (owing to hypotonic or hypertonic solutions, respectively). Dextrose, sodium chloride, or potassium chloride is commonly used to achieve isotonicity in a parenteral formula. 

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