Isotonic fluids

In the gut, many pathogens adhere to the gut wall and produce their toxic effect via toxins which pervade the surrounding gut wall or enter the systemic circulation. Vibrio cholerae and some enteropathic E. coli strains localize on the gut wall and produce toxins which increase vascular permeability. The end result is a hypersecretion of isotonic fluids into the gut lumen, acute diarrhoea and consequent dehydration which may be fatal in juveniles and the elderly. In all these instances, binding to epithelial cells is not essential but increases permeation ofthe toxin and prolongs the presence of the pathogen. 

ECF depletion tends to occur acutely. In this setting, rapid and aggressive fluid replacement is required to maintain adequate organ perfusion. Because ECF depletion is generally due to the loss of isotonic fluid (proportional losses of sodium and water), major disturbances of plasma osmolality... 

Normal saline is an isotonic fluid composed of water, sodium, and chloride. It provides primarily ECF replacement and can be used for virtually any cause of TBW depletion. Common uses of normal saline include perioperative fluid administration volume resuscitation of shock, hemorrhage, or burn patients fluid challenges in hypotensive or oliguric patients and hyponatremia. 

V. cholerae is a gram-negative bacillus. Vibrios pass through the stomach to colonize the upper small intestine. Vibrios have filamentous protein extensions that attach to receptors on the intestinal mucosa, and their motility assists with penetration of the mucus layer.2 The cholera enterotoxin consists of two subunits, one of which (subunit A) is transported into the cells and causes an increase in cyclic AMP, which leads to a deluge of fluid into the small intestine.20 This large volume of fluid results in the watery diarrhea that is characteristic of cholera. The stools are an electrolyte-rich isotonic fluid, the loss of which results in blood volume depletion followed by low blood pressure and shock.2 Of note, the diarrheal fluid is highly infectious. 

Cholera is characterized by a spectrum from the asymptomatic state to the most severe typical cholera syndrome. Patients may lose up to 1 L of isotonic fluid every hour. The onset of diarrhea is abrupt and is followed rapidly or sometimes preceded by vomiting. Fever occurs in less than 5% of patients. In the most severe state, this disease can progress to death in a matter of 2 to 4 hours if not treated. 

Patients who present with heat exhaustion require fluid resuscitation. An attempt should be made to assess the amount of salt depletion and dehydration. This may be difficult clinically although the presence of symptoms such as muscle cramps in sodium depletion, and signs such as loss of tissue turgor may help. Laboratory measurement of sodium, urea, creatinine and haematocrit are the best guide. Pre-renal renal impairment is common. Treatment usually requires 5-10 1 of oral or intravenous isotonic fluids in the first 24 hours. In severe hyponatraemia the rapid correction of sodium should be carefully monitored with frequent sodium measurements and a reduction in fluid infusion rate if necessary to reduce the risk of osmotic demyelination (central pontine myelinol-ysis). 

Fig. 5 Aquaporin-4 deletion increases brain swelling in vasogenic edema, a Increased ICP in AQP4-null mice in response to intraparenchymal fluid infusion. Left representative ICP traces from two wildtype and AQP4 null mice. Right, increased ICP at 60 min in response to isotonic fluid infusion (0.5 p.l/min). Data shown for individual mice and mean SE. b Increased ICP and in AQP4 null mice with melanoma brain tumor. Top, site of injection of melanoma cells. Bottom., tumor size at 4 and 7 days after implantation showing similar-sized tumors in wildtype and AQP4 null mice, c ICP measured 7 days after tumor implantation. From Papadopoulos et al. (2004)...

Human blood is a complex mixture with a variety of functions provided by four major components red and white blood cells, platelets, and plasma. When a person begins to lose blood rapidly, the body can survive for at least a short time without the white blood cells (which are needed only to stave off infection), the platelets (of which there are large excesses in the body), and plasma (which can he replaced by an isotonic fluid, such as saline or Ringer s solution). But life cannot continue long with a replacement for the red blood cells. These are the cells that carry oxygen from the lungs to other cells, where it is used to carry out the metabolic processes that keep the body alive. 

Crystalloid fluids rapidly pass from the circulation to the interstitial fluid. This means that their resuscitation effect may be short lived and they can cause edema. Only 30% of isotonic fluids and 10% of hypotonic fluids remain in the circulation after 30 min (Spalding Goodwin 1999). The increase in interstitial fluid may actually decrease tissue oxygen uptake in normal animals by increasing the diffusion distance between... 

NE at the JGA of the kidney and this stimulates the release of renin (/ ]), ultimately resulting in aldosterone-mediated sodium retention at the nephron. The overall result is preservation and promotion of vascular volume due to isotonic fluid retention, decreased urine flow, and decreased glomerular filtration rate, all of which are attributable to neurotransmitted NE. 

The pancreas possesses both endocrine and exocrine fnnctions. The islets of Langerhans, which contain the cells of the endocrine pancreas, secrete insnlin, glncagon, somatostatin, and other polypeptide hormones. The exocrine pancreas is composed of acini that secrete about 1 to 2 L/day of isotonic fluid that contains water, electrolytes, and pancreatic enzymes necessary for digestion. Bicarbonate is secreted primarily by the centroacinar (ductular) cells, and is the principal ion of physiologic importance. Pancreatic juice is delivered to the duodenum via the pancreatic ducts (Fig. 39-1) where the alkaline secretion (pH about 8.3) neutralizes gastric acid and provides an appropriate pH for maintaining the activity of pancreatic enzymes."... 

V. cholerae is a gram-negative baciUus sharing similar characteristics with the family Enterobacteriaceae. Most pathology of cholera results from an enterotoxin (cholera toxin) produced by the bacteria. Conditions that reduce gastric acidity, such as the use of antacids, histamine-receptor blockers, or proton pump inhibitors or infections with Helicobacter pylori, increase the risk for clinical disease. Cholera toxin stimulates adenylate cyclase, which increases intracellular cAMP and results in inhibition of sodium and chloride absorption by microvillli and promotes the secretion of chloride and water by crypt cells. The toxin likely acts along the entire intestinal tract, but most fluid loss occurs in the duodenum. The net effect of the cholera toxin is isotonic fluid secretion (primarily in the small intestine) that exceeds the absorptive capacity of the intestinal tract (primarily the colon). This results in the production of watery diarrhea with electrolyte concentrations similar to that of plasma. 

Bacterial infections are the other common neglected diseases. They comprise leprosy and trachoma, which are controlled by antibiotic treatments, Buruli ulcer, managed by surgery and antibiotics, cholera, caused by Vibrio cholerae living in contaminated drinking water, and for which antibacterials and isotonic fluid replacement therapy are recommended. 

Epithelia like those of the small intestine, proximal renal tubule, and gall bladder are characterised by low or negligible transepithelial potential, low trans-epithelial resistance, and high hydraulic conductivity, and the shunt conductance is a large fraction of the total transepithelial conductance. These epithelia are able to transport large volumes of isotonic fluid. 

A popular model since 1967 has been that of Diamond and Bossert [145]. According to this model, sodium enters the cell and is pumped into the interspace at its apical end by sodium pumps particularly concentrated at the apical ends of the baso-lateral membranes. A local hypertonicity is then created at the blind end of the interspace so that water moving through the cell osmotically increases the volume and pushes the fluid out of the interspace as isotonic fluid. In this way, a standing gradient is set up causing isotonic fluid flow. However, it is now known that in leaky epithelia the tight junctions are permeable to ions and probably to water molecules too. Also, there is no histochemical evidence for a concentration of pump sites at the apical end of the interspaces. 

Altered isotonic fluid reabsorption in the proximal nephron mediates variations of fractional urate excretion during circadian rhythm, diuretic treatment, renal insufficiency. 

Isotonic Fluid containing the same concentration of dissolved materials as is in a cell causes no change in cell volume. 

Isotonic fluids have the same concentration of solutes as cells, and thus no fluid is drawn out or moves into the cell. 

Other tests include the Ames test in which a strain of bacteria, such as Salmonella typhimurium, is mixed with rat liver and the test substance then incubated for two days. The carcinogenicity is indicated by the number of mutants induced. This test is sensitive, quick and cheap. Also tissue cultures tests in which cells from a test animal are cultured in an isotonic fluid medium and the effects of adding the test substance are observed. 

A 26-year-old woman in the second stage of labor received an infusion of oxytocin 10 U/l in 5% dextrose at a variable rate of 10-150 ml/ hour. In the 5 hours after delivery, which was complicated by a retained placenta requiring general anesthesia for removal, she received isotonic fluid 5500 ml, 5% dextrose 3500 ml with oxytocin 50 U/l, hydroxyethyl starch 1000 ml, and 4 units of blood. She then received 5% dextrose 7500 ml with oxytocin 100 U/l over 15 hours 24 hours later her serum sodium concentration was 113 mmol/l. She became unconscious and had a generalized convulsion. She subsequently made a full recovery. 

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