**2. Fluids and physiology**

Water is the most important and abundant element of the human body, and the physiology that surrounds it is extensive. The following principles are at best, the foundations toward an informed fluid practice.

#### **2.1. The body fluid compartments**

Water, on average, makes up 60% of the total body weight. The percentage will vary depending on the gender and the fat content in the body. There is an inverse correlation between the water content of the body and the fat content as adipose tissue contains less water than lean tissue. This explains why women have lower percentages of water than men as they have a higher percentage of adipose tissue.

Water in the body is functionally distributed among the two main body fluid compartments, the intracellular fluid (ICF) and the extracellular fluid (ECF) (**Figure 1**). The ICF constitutes approximately two-thirds of the total body water or 40% of the body weight and the ECF the remaining one-third or 20% of the body weight [4]. Water crosses between the ICF and the ECF through aquaporin channels in the cell membrane to attain osmotic equilibrium. The cell

**Figure 1.** The distribution of total body water.

membrane also contains active pumps and transporters that distribute individual solutes, including electrolytes. These electrolytes account for the effective osmolality (tonicity) that governs the water movement. The mechanisms of these electrolyte movements are further defined by the Gibbs-Donnan effect of the nondiffusible large anions like protein. The end results are an ICF compartment with potassium (K<sup>+</sup> ) as the predominant ion and an ECF compartment with sodium (Na<sup>+</sup> ) and chloride (Cl− ) as the predominant ions [5].

The ECF is further divided into the interstitial fluid and the plasma compartments, the two separated by the capillary wall. Except for plasma proteins and blood cells, the pores on the capillary wall permit the flux of water and small solutes. This contributes to the two compartments having almost similar electrolyte composition with only small differences contributed by the Gibbs-Donnan effect of the plasma proteins. By volume, these plasma proteins constitute 7% of the plasma volume with the remaining 93% plasma water. As a side note, these proteins are solids in the plasma, and the changes in their plasma load will affect the waterbased measurements of plasma electrolyte concentrations [6].

#### **2.2. The body fluid regulation**

Intravenous fluids are drugs, and like other drugs, there are potential complications. In the acute setting where these fluids are commonplace, it is imperative that the practice aims at administering the right patient the right fluids, at the right volume and rate, with the right

Water is the most important and abundant element of the human body, and the physiology that surrounds it is extensive. The following principles are at best, the foundations toward an

Water, on average, makes up 60% of the total body weight. The percentage will vary depending on the gender and the fat content in the body. There is an inverse correlation between the water content of the body and the fat content as adipose tissue contains less water than lean tissue. This explains why women have lower percentages of water than men as they have a

Water in the body is functionally distributed among the two main body fluid compartments, the intracellular fluid (ICF) and the extracellular fluid (ECF) (**Figure 1**). The ICF constitutes approximately two-thirds of the total body water or 40% of the body weight and the ECF the remaining one-third or 20% of the body weight [4]. Water crosses between the ICF and the ECF through aquaporin channels in the cell membrane to attain osmotic equilibrium. The cell

overall fluid balance.

informed fluid practice.

**2. Fluids and physiology**

40 Essentials of Accident and Emergency Medicine

**2.1. The body fluid compartments**

higher percentage of adipose tissue.

**Figure 1.** The distribution of total body water.

A complex interaction of regulatory mechanisms from different organs helps the body to maintain an effective fluid volume in different circumstances. The key pathway that underpins this volume regulation is the hormonally mediated renin-angiotensin II-aldosterone-system (RAAS), with the faster neutrally mediated baroreceptor reflex contributing an indirect role through its interplay of the pressure regulation. In the context of the fluid therapy scope of the chapter, the RAAS will be elaborated below.

The RAAS pathway is activated by a decrease in the renal perfusion pressure, detected by the juxtaglomerular apparatus (JGA) (**Figure 2**). In the JGA, the reduced renal perfusion stimulates the granular cells of the afferent arteriole to secrete the proteolytic enzyme renin through a direct intrarenal baroreceptor activity and detection of reduced sodium chloride concentrations by the macula densa in the wall of the ascending limb of the loop

**Figure 2.** The juxtaglomerular apparatus.

of Henle. Besides these mechanisms, the renin release is also controlled by renal sympathetic nerves and angiotensin II.

Renin as an enzyme will then catalyze the conversion of angiotensinogen, a large protein produced in the liver, to angiotensin I, a decapeptide. This is the rate-limiting step of the RAAS pathway (**Figure 3**). Angiotensin I has little biologic activity apart from being the precursor to angiotensin II. Its conversion to angiotensin II involves the removal of two amino acid moieties by the angiotensin-converting enzyme (ACE). ACE is primarily located in the pulmonary capillaries, but it is also found in the kidney epithelial cells.

The ultimate objective of the RAAS, through the activities of angiotensin II and aldosterone as summarized in **Figure 3**, is the preservation of effective fluid volume and pressure. The RAAS demonstrates the strong interconnection between the body fluid and electrolytes in maintaining the fluid homeostasis. In the acute setting, this interconnection is very relevant given the frequent alterations of the electrolyte contents of the body in the acute phase of illness. The assessment of electrolytes in the acute patients should, therefore, be comprehensive and extend beyond the laboratory results. For example, the assessment should also consider the potential electrolyte losses from the gastrointestinal tract, a common organ affected in acute illnesses [7].

in various organs of the body (**Figure 4**). Appreciation of the dynamics of glycocalyx in the microcirculation of the acute cohort of patients will be integral in their fluid resuscitation and

**Figure 4.** The endothelial glycocalyx layer in healthy, equilibrium state (A) and damaged, leaky state (B) that leads to

Approach to Fluid Therapy in the Acute Setting http://dx.doi.org/10.5772/intechopen.74458 43

The history of intravenous fluids began during the cholera pandemic in Europe in the 1830s. The success of Thomas Latta in using a saline solution to resuscitate dying cholera patients paved the way for the widespread use of intravenous fluids and the research to refine their contents [15]. The early milestones in intravenous fluid therapy included the first experiment with albumin in 1834 [16] and the attempt by Sydney Ringer to develop a physiological solution for cardiac contractility with his Ringer's solution in 1876 [17]. Ringer's solution was modified by Alexis Hartmann in 1932 by including lactate to help overcome the acidosis in dehydrated pediatric patients [18]. The gelatins and other solutions with larger molecules only broke into the scene during the Second World War [19], although the first study in humans was performed in 1915 [20]. It is interesting that the history behind the most common type of fluids used, the 0.9% saline, is unclear. The present-day 0.9% saline, often called the "normal saline," has far higher sodium and chloride concentrations than Latta's 1832 saline solution. The only possible connection to 0.9% saline in the history was the in vitro studies of Hamburger in the 1890s that described 0.9%

NaCl as an "indifferent solution" in which erythrocytes were least likely to lyse [21, 22].

From the above breakthroughs, the science of intravenous fluids has grown progressively, especially in the last couple of decades. Whether medicine will find an answer to the ideal intravenous fluid will be debatable, but more evidence has emerged in the comparison

Crystalloids are solutions containing salts in the form of electrolytes and small molecules. The

in future fluid research in such population [13, 14].

between the different types of fluids available.

composition of commonly available crystalloids is given in **Table 1**.

**3.1. Crystalloids**

**3. The types of fluids**

interstitial edema.

#### **2.3. The microcirculation model**

The classic microcirculation model, based on the semipermeability of the capillary and postcapillary venule walls, and the presence of hydrostatic and oncotic pressure gradients across these walls had for long described the flux of fluids and electrolytes between the plasma and the interstitial fluid [8, 9]. The identification of the endothelial glycocalyx layer, a web of membrane-bound glycoproteins and proteoglycans on the luminal side of endothelial cells, has now challenged the classic model [10, 11]. The colloid oncotic pressure from the sub-glycocalyx space is a key determinant of the trans-capillary flow. The disruption to the integrity of the glycocalyx layer, or the "leakiness," in a number of acute situations like sepsis [12], trauma, and postsurgery, has been attributed to the development of interstitial edema

**Figure 3.** The renin-angiotensin II-aldosterone-system (RAAS).

**Figure 4.** The endothelial glycocalyx layer in healthy, equilibrium state (A) and damaged, leaky state (B) that leads to interstitial edema.

in various organs of the body (**Figure 4**). Appreciation of the dynamics of glycocalyx in the microcirculation of the acute cohort of patients will be integral in their fluid resuscitation and in future fluid research in such population [13, 14].
