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An expert introduction for pharmacists to the elements of fluid physiology and the basis of fluid therapy
Adequate hydration is essential for the human body to maintain both cell metabolism and perfusion of vital organs. It is therefore important for pharmacists to understand basic fluid physiology to be able to advise in safe prescribing and administration of parenteral fluid therapy.
Water is the largest single component of the body. It is the solvent in which solutes in the body are either suspended or dissolved. Total body water (TBW) is consistently 70% of the lean body weight across age and sex ranges. Because fat is essentially water-free while muscle has a high water content, TBW as a percentage of actual body weight varies between groups and individuals, as illustrated in Table 1.
In adults about two-thirds of TBW is contained within cells, the intracellular fluid (ICF) compartment (Figure 1). The remaining one-third of TBW is found outside of cells, the extracellular fluid (ECF) compartment. The ECF compartment is further divided into: the intravascular fluid or plasma compartment and the interstitial fluid compartment, which is outside the vascular system. Interstitial fluid is mostly found in tissues adjacent to the microvascular circulation; more distant connective tissues remain relatively dry. The solutes found in body fluids include non-electrolytes (eg, protein, urea, glucose, oxygen, carbon dioxide and organic acids) and electrolytes (eg, sodium, potassium, calcium, magnesium, chloride, bicarbonate, phosphate and sulphate). The electrolyte concentration varies from one compartment to another, as illustrated in Table 2.
The volume of ECF is determined mainly by the total amount of osmotically active solutes (sodium and chloride). Because the changes in chloride are largely secondary to changes in sodium, the amount of sodium in the ECF is the most important determinant of ECF volume.
Cell membranes separating ICF and ECF compartments are selective to solutes but allow water to diffuse freely between the two compartments to ensure iso-osmolarity. Variation in ECF tonicity is the main determinant of the relative distribution of total body water between the ICF and ECF compartments. An increase in ECF tonicity results in the movement of water out of cells into the extracellular space. If ECF tonicity is decreased, the reverse applies.
In contrast, the capillary endothelium is freely permeable to both water and ions, but is relatively impermeable to larger molecules such as proteins. As a result, proteins are the major determinant of water movement between the interstitial and the intravascular compartments (see Table 3).
Physiological regulation of fluid balance
The two main factors in the human body that result in changes in water intake or excretion are the sensation of thirst and levels of antidiuretic hormone (ADH/ vasopressin).
Osmoreceptors in the hypothalamus react to minute changes in ECF tonicity. A rise above 295 mosmol/l will result in activation of the “Thirst Centre” located in the anterior hypothalamic structures and cause increased release of ADH. Thirst is defined as the “urge to drink water” and will prompt enteral intake of fluids. ADH increases the water permeability of the collecting tubules in the kidney via expression of aquaporin2 and thereby improves water reabsorption. The resulting dilution of the ECF acts as negative feedback on the hypothalamic osmoreceptors.
Baroreceptors located in the walls of the aorta, the great veins, right atrium and carotid artery are less sensitive than osmoreceptors but will respond to a 10% fall in intravascular volume or to hypotension with a more pronounced rise in ADH and stimulation of thirst. If there is a concomitant fall in tonicity and pressure, baroreceptors will in effect “override” osmoreceptors, as maintenance of circulating volume is more
important than preserving plasma tonicity.
A rise in circulating angiotensin II following activation of the renin–angiotensin system in response to significant extracellular volume depletion can also stimulate sensation of thirst.
Normal fluid intake and loss
The average daily requirement for an adult is 2.5 l of water to replace sensible and insensible losses (Table 4). The kidneys need to produce a minimum of 500 ml urine per day to excrete metabolites and maintain electrolyte balance, but urine volume can be much higher depending on plasma electrolyte and water load. Insensible losses can only be estimated and will be increased under pathological conditions (eg, fever) or with increased physical activity.
In the healthy person with unrestricted access to drinking water, fluid requirements are generally met by oral intake of fluids and by water derived from metabolism of food and waste products.
Causes of blood volume depletion
An imbalance between fluid intake and requirements can occur if either excessive losses are not met by a corresponding increase in intake or if regular intake is not maintained. Common causes of dehydration in the hospitalised patient are:
In some disease states total body water may be unchanged (or even increased) but circulating intravascular volume is depleted following fluid redistribution, resulting in functional hypovolaemia. There are several possible aetiologies: inflammatory response to sepsis, general anaesthetics or other disease states can cause increased capillary membrane permeability, resulting in a breakdown of fluid compartments. Accumulation of fluids in normally “dry” compartments (eg, the pleural cavity) following major surgery is often referred to as “third spacing” and may take several days to resolve while the fluid is slowly reabsorbed into the main compartments. Ascites and other large effusions can also cause functional hypovolaemia.
Signs and symptoms of hypovolaemia
Scrutinising a patient’s recent medical history should alert to risk factors for fluid depletion, such as admission following a period of self-neglect or major surgical procedures. Some populations can be at particular risk of dehydration and hypovolaemia – for example, older people, who have a weaker response to thirst.
A range of physical signs and symptoms indicate hypovolaemia but need to be interpreted in context as their specificity in isolation is limited. Typical signs are:
Tachycardia occurs during hypovolaemia as the body attempts to maintain cardiac output (cardiac output = heart rate x stroke volume). Hypotension may not develop until a 20% loss of circulating volume has occurred, and urine output will drop once renal compensation mechanisms are unable to maintain filtration pressure. Hypernatraemia, a rising haematocrit and progressive metabolic acidosis can also occur in response to dehydration.
Indication for volume replacement therapy
Whenever it is possible, fluid requirements should be met by enteral intake. Parenteral fluid supplementation exposes patients to risks associated with any injectable medicine (infection, administration errors, cost) and to adverse effects associated with the different types of intravenous fluids (as will be discussed in the second article of this series). Oral fluid intake stimulates mechanical receptors in the mouth and pharynx, providing feedback to the hypothalamus prior even to any changes in plasma tonicity and thereby preventing water overload. Parenteral administration of fluids overrides these physiological safeguards.
If enteral intake is not sufficient to maintain homoeostasis, intravenous (or in some cases subcutaneous) fluid therapy will be needed to both provide basic requirements and replace any additional losses.
In this article we have given an introduction to basic fluid physiology and the principles of fluid therapy. The next article will describe the properties of different types of fluids and how those may affect their application in therapy.
1. Rassam SS, Counsell DJ. Perioperative electrolyte and fluid balance. Continuing Education in Anaesthesia, Critical Care & Pain 2005;5(5):157-60.
2. Guyton AC, Hall JE. The body fluid compartments. In:Textbook of Medical Physiology. 11th ed. Elsevier; 2006.
3. Fluid and electrolyte balance and assessment. In: Price S, Wilson L, editors. Pathophysiology, clinical concepts of disease processes. 5th ed. Mosby; 1997.
4. Baylis PH. Water and sodium homoeostasis and their disorders. In: Warrell DA, Cox TM, Firth JD, editors. Oxford Textbook of Medicine. 4th ed. Oxford University Press; 2003.
5. Al-Khafafi A, Webb AR. Fluid resuscitation. Continuing Education in Anaesthesia, Critical Care & Pain 2004;4(4):127-131.
6. Farrell MJ, Zamarippa F, Shade R, et al (2008). Effect of aging on regional cerebral blood flow responses associated with osmotic thirst and its satiation by water drinking: a PET study. Proc Natl Acad Sci USA 2008;105(1):382-7.
7. Grocott MP, Mythen MG, Gan TJ. Perioperative fluid management and clinical outcomes in adults. Anaesthesia Analgesia 2005;100:1093-106.