I. BIOCHEMICAL BASIS OF FLUID THERAPY

A. Body water

1. Water content is 55–60% of body weight in mature animals, 70–75% in immature animals, and 50% in obese animals.

2. Intracellular fluid (ICF) represents 40% of the body weight.

3. Extracellular fluid (ECF) consists of:

a. Plasma water: 5% of the body weight.

b. Interstitial fluid: 14% of the body weight.

c. Transcellular fluid: 1–6% of the body weight.

4. Body water turnover

a. It is regulated by thirst and drinking control centers and vasopressin (antidiuretic hormone [ADH]), responding to osmolarity and blood volume changes: the higher the osmolarity and the lower the blood volume, the more stimulation of the drinking control centers and vasopressin secretion. As a result, large volume of water is being drunk.

b. Body water turnover is 50–130 mL/kg/day, 65 mL/kg/day in mature animals.

c. The role of skin and body surface. Skin is the largest organ of the body. The smaller the size of an animal, the larger the body surface is; thus, the higher the body water turnover rate. This is why dehydration has a much greater impact on young animals than mature animals.

B. Concept of milliequivalents (mEq)

1. Most of the electrolyte concentrations are expressed as mEq/L; mEq is calculated as mg of chemical divided by its equivalent weight. For example, the equivalent weight of NaCl is 58.5; 1 mEq of NaCl = 58.5 mg.

2. Total concentration of cations in the plasma is equal to that of anions.

3. Calcium and phosphorus in the plasma are measured as mg%, ~50% of plasma calcium is in the free ionized form and ~50% is bound by plasma proteins. Plasma phosphorus is present as

, and

C. Osmosis and osmolarity

1. Role of semipermeable membranes in osmosis. Fluid compartments are separated by semipermeable membranes, which allow free passage of water but restrict particles. Water moves to the compartment with the highest number of particles (osmotic pressure).

2. Osmolarity is to describe properties related to the number of particles in solution and is expressed as mOsm/L of body fluid.

3. Calculation of mOsm/L from mM

a. For electrolyte solutions. Since NaCl dissociates into two particles, Na⁺ and Cl⁻, 1 mmol/L (1 mmolar or 1 mM) of NaCl solution yields 2 mOsm/L. A total of 1 mmol of NaCl contains 58.5 mg since its molecular weight is 58.5.

b. For nonelectrolyte solutions. Since glucose does not dissociate, 1 mM of glucose solution yields 1 mOsm/L.

4. Osmolarity of an isotonic solution is ~300 mOsm/L. One should be able to determine if a solution in mM is isotonic depending on whether the chemical can dissociate in the solvent. For example, 150 mM NaCl and 300 mM glucose solutions are isotonic.

D. Role of the kidney in water and electrolyte regulation

1. A total of 80–90% of water, Na⁺, Cl⁻, and so forth, is reabsorbed from the proximal tubule.

2. Information on renal physiology is presented in Chapter 9, I B (Review of nephron ion and water transport).

E. Acid–base regulation

1. Definition of acid, base, and pH Acid is a proton (H⁺) donor and base is a H⁺ acceptor. Thus, HCl is an acid, and

is a base, so is NH₃; chloride (Cl⁻) is not an acid and Na⁺ is not a base. pH is −log [H⁺]. If [H⁺] = 10⁻⁷ M, pH = 7.

2. Use of Henderson–Hasselbalch equation to calculate the ratio between base and acid

When this ratio is disturbed, the result is either acidosis or alkalosis.

3. Buffer systems in the body

a. Intrinsic buffering system. Bicarbonate, hemoglobin, phosphate, and proteins (amino acids) constitute 53, 35, 5, and 7% of the intrinsic buffering system, respectively.

b. The cellular component of the buffering system takes place during the first stage of the abnormality.

(1) Na⁺–H⁺–K⁺ exchanges (Figure 18-1). Normally, H⁺ generated during cellular metabolism is removed via Na⁺–H⁺ antiport, which exports H⁺ and imports Na⁺. The increased [Na⁺]_i will then exchange for [K⁺]_o via Na⁺, K⁺-ATPase. Thus, the net result of the reaction is one molecule of

exchanges for one molecule of

. During acidosis (acidemia), this exchange process is inhibited by low pH, and thus more H⁺ stays in the cells and more K⁺ stays in the ECF. During alkalosis (alkalemia), this exchange is accelerated, and thus more H⁺ is lost to the ECF and more K⁺ enters the cells.

(2)

exchange. The plasma membranes of animal cells contain an anion exchange protein, which exports

and imports Cl⁻. The activity of this protein is stimulated to lower intracellular pH once it rises above 7.0 (normal intracellular pH is <7.0). With alkalosis, this exchange process is active and thus more

is expelled to keep the cells less alkaline. With acidosis, this exchange process is inhibited and thus less

is expelled, resulting in the cells being less acidic.

FIGURE 18-1. The compensatory mechanisms for acid–base disturbances involving intra- and extracellular H⁺, Na⁺, and K⁺ exchanges. As a result of these exchanges, acidosis and alkalosis can lead to hyperkalemia, and hypokalemia, respectively. By the same token, hyperkalemia and hypokalemia can lead to acidosis and alkalosis, respectively.

FIGURE 18-2. The compensatory mechanisms for simple acid–base disturbances as explained by the changes in the Henderson–Hasselbalch equation.

(3) Renal regulation of H⁺ and K⁺. Renal regulation of H⁺ and K⁺ occurs at the distal renal tubule level, where one molecular of Na⁺ is reabsorbed into the tubular cell at the expense of one molecule of H⁺ or K⁺. With acidosis, more H⁺ than K⁺ is expelled (secreted) into the lumen, resulting in hyperkalemia as part of the compensatory process. By the same token, alkalosis would lead to hypokalemia through this same process.

c. Respiratory and metabolic components

Since is the major buffering system in the body, respiratory and renal control of the blood CO₂ and concentrations intends to keep body pH normal. Under normal physiological condition, the ratio of blood [] and [H₂CO₃] is 20:1, where is the metabolic component and H₂CO₃ (or dissolved CO₂) is the respiratory component. This ratio will change by addition or loss of CO₂ and to the system. Figure 18-2 depicts changes in the ratio of [] and [H₂CO₃] that might occur during simple acid–base disturbances.

During hypoventilation (respiratory acidosis), retention of CO₂ will lower the ratio. In order to return the ratio to 20:1, the body must retain more through metabolic compensation.

During metabolic acidosis, loss of will decrease the ratio. In order to return the ratio to 20:1, body must expel more CO₂ to lower the ratio through respiratory compensation.

These changes in also account for the compensatory processes during respiratory alkalosis (hyperventilation) and metabolic alkalosis (Figure 18-2).

4. Acid–base parameters and terminology

b. Base deficit/excess is defined as the titratable acid or base, respectively, needed to titrate the blood to a pH of 7.4 under standard conditions of PCO₂ (40 mm Hg), temperature (38°C), and complete hemoglobin oxygenation.

c. Acidemia and alkalemia. Acidemia is defined as arterial pH of <7.35 and alkalemia is defined as arterial pH of >7.45.

d. Anion gap. The difference between the ECF concentration of Na⁺ (140 mEq/L) and the sum of the concentrations of

(25 mEq/L) and Cl⁻ (105 mEq/L). The normal anion gap varies with the species, but is 13–25 in dogs and cats. Metabolic acids contribute to the anion gap. Untreated cases of metabolic acidosis may have high anion gaps.

II. GENERAL CONCEPTS OF FLUID AND ELECTROLYTE THERAPY

A. Institution of fluid therapy. Fluid therapy should be instituted for the following conditions: dehydration, acid–base disturbances and/or electrolyte imbalances, nutritional problems, and loss of body fluids.

1. Basis for institution of fluid therapy

a. Accurate diagnosis based on clinical examination and laboratory data is important for fluid therapy.

The clinical signs for detection of dehydration include: loss of skin elasticity, dry buccal mucosa and tongue, and sunken eyeballs should be taken into account.

b. Signs of vomiting, diarrhea, abnormal respiratory pattern, and CNS depression or excitation may help with the diagnosis of acid–base disturbances.

c. Blood gas and urine analyses are useful for the precise diagnosis of acid–base and electrolyte disturbances.

2. Dehydration

a. General considerations. Dehydration may be considered in three general categories:

(1) Hypertonic dehydration, which is attributable to loss of pure water or hypotonic fluid.

(2) Isotonic dehydration, which is attributable to loss of isotonic body fluids. However, isotonic dehydration is only seen in acute cases, since with some degree of water replacement, isotonic dehydration will become hypotonic dehydration.

(3) Hypotonic dehydration. The loss of a hypertonic fluid or loss of isotonic fluid with water replacement results in hypotonic dehydration.

b. Causes

(1) Decreases in water intake usually lead to hypertonic dehydration.

(a) Lack of water source.

(b) Disorders and pain of the buccal cavity and pharynx.

(c) CNS disturbances.

(2) Increases in body fluid excretion usually lead to hypotonic dehydration.

(a) Polyuria. Diabetes, nephrosis, hypoaldosteronism, and diuretics. Diabetes insipidus will cause hypertonic dehydration.

(b) Respiratory loss of water during high temperature may lead to hypertonic dehydration.

(c) Profuse sweating in horses.

(d) Vomiting/diarrhea.

(e) Third space loss. Body fluid lost to the body cavities and hollow organs.

c. Role of electrolytes on hydration states and acid–base balance:

(1) ↑ [Na⁺] in ECF → water retention

(2) Changes in [K⁺] in ECF result in changes in acid–base balance:

(a) ↑ [K⁺] in plasma→↑[K⁺],↓[H⁺] in urine → Acidemia

(b) ↓ [K⁺] in plasma→↓[K⁺],↑[H⁺] in urine → Alkalemia.

FIGURE 18-3. Daily water, calorie, and electrolyte requirements for dogs and cats. (Reprinted with permission from Fluid, Electrolyte, and Acid–Base Disorders, 3rd ed. Edited by DiBartola S. P. Saunders/Elsevier, 2006, Figure 14-1. This figure was modified from Harrison J. B., Sussman H. H., and Pickering D. E. Fluid and electrolyte therapy in small animals. JAVMA 137:637–645, 1960, Figure 1.)

d. Role of carbohydrate metabolism on hydration states and acid–base balance:

(1) ↓ Carbohydrate utilization → Hyperglycemia → Glucosuria→ Polyuria → Dehydration

(2) ↓ Carbohydrate utilization →↑ Gluconeogenesis → Ketoacidosis

(3) ↑ Carbohydrate intake (grain overload) in herbivores →↑ Lactic acid production → Acidosis.

e. Treatment (amount of fluid to be used) must be based on the body water maintenance plus replacement of the deficit and ongoing loss

(1) Amount of body water maintenance

(a) On the basis of body water turnover

(b) A total of 50–75 mL/kg/day (average 65 mL/kg/day)

(c) For more precise estimation of water maintenance doses in dogs and cats, see Figure 18-3.

(2) Determination of water deficit (dehydration)

(a) Dehydration of 4, 6, 8, and 12% (of body weight), only loss >4% needs a replacement

(b) A total of 4% dehydration (mild)

i. Animals with 4% dehydration have a history of fluid loss, but without significant signs of dehydration.

ii. No replacement is needed.

(c) A total of 6% dehydration (moderate)

i. Animals with 6% dehydration have decreased skin turgor. In dogs and cats, when the skin over the lateral thorax is picked into a tented fold, it will return to normal slowly; in species having tight skin, pinch the dorsal eyelid to do the test.

ii. A decrease in skin elasticity is also seen in cachexia; thus, one cannot conduct this test in cachectic animals.

iii. Animals with 6% dehydration have dull haircoat and dry mucous membranes.

(d) About 8–10% dehydration (severe). The animals with 8–10% dehydration have the following signs:

i. The skin lacks pliability. In dogs and cats, when the skin is pinched into a tented fold, it will tent and stay after the pinch is released.

ii. Dry mucous membranes and tongue.

iii. Soft eyeballs that are sunken into the orbit.

iv. Cold extremities.

v. Capillary refill time >3 seconds (normal <2 seconds).

(e) About 12% dehydration (extremely severe). The animals with 12% dehydration have following signs:

i. All the signs seen with 8–10% dehydration.

ii. Circulatory collapse (shock).

(3) Estimation of water deficit. The replacement volume for the initial deficit is estimated according to the following equations:

Replacement volume (L) = %dehydration × body weight (kg)

(4) The composition of replacement fluid should be similar to the volume of fluid lost. For example, if the deficit is due to loss of the electrolyte-rich GI fluid, then a balanced salt solution containing Na⁺, K⁺, Ca²⁺, Cl⁻, and

(or indirect alkalinizing agents) should be used. See Table 18-1 for the compositions of commonly used replacement fluids of crystalloid in nature. In contrast, if the deficit is due to loss of pure water, volume can be replaced with 5% dextrose (glucose in water) over 24–72 hours. An isotonic solution of 2.5% dextrose and 0.45% NaCl can also be used.

(5) The ongoing loss must be taken into account when estimating the fluid therapy volume. The ongoing loss of fluid via vomiting, diarrhea, and polyuria must be estimated and replaced.

(6) Additional factors need to be considered

(a) Dehydration affects young animals much faster than adult animals.

(b) Old animals with chronic diseases require more water than younger adult animals.

(c) Physical and weather conditions may affect the requirement, particularly when it is hot and humid.

(d) Drugs will alter requirements, particularly diuretics and mineralocorticoids can affect water and electrolyte balances.

(7) The volume to be used for treatment of dehydration is considered an estimate, since it is based on clinical signs to estimate the body water deficit. Despite the importance of good data collection and application of principles of fluid therapy, the adjustment of volume based on the “reassess” process is needed for each individual case.

3. Therapy in acid–base disturbances

a. Metabolic acidosis

(1) Causes

(a) Gain of acid. Severe tissue breakdown, grain overload, ketosis, poor tissue perfusion, hyperkalemia, lactic acid overproduction, and drug overdose, for example, acidic NSAIDs, chemical poisonings, for example, ethylene glycol (which is metabolized into oxalic acid in the body).

(b) Loss of base. Severe diarrhea, severe salivation, renal insufficiency, and so forth.

(2) General signs. Hyperpnea, CNS depression.

TABLE 18-1. Composition of Selected Fluid Therapy Solutions

(3) Laboratory data and pathogenesis. ↑ Blood [H⁺], ↓[

] (Base deficit >4 mEq/L).

(4) Therapy. Treatment of the underlying disease and the use of alkalinizing agents.

(a) Direct alkalinizing agents: NaHCO₃ and THAM (Tris). NaHCO₃ is used commonly in animals, but THAM is not frequently used.

i. Advantage of NaHCO₃: It directly works to neutralize excess of H⁺.

ii. Disadvantages of NaHCO₃:

– It has a short shelf life of 2 years in solution. Discard the solution when it is cloudy.

– It cannot be autoclaved, since heat will cause: 2NaHCO₃ → Na₂CO₃ + H₂O + CO₂

– Oral dosing of NaHCO₃ decreases gastric acidity, which will interfere with milk clot formation, resulting in poor milk digestion.

(b) Indirect alkalinizing agents. Na lactate, lactated Ringer’s, Na gluconate, Na acetate, acetated polyionic solution, and Na citrate. The most frequently used indirect alkalinizing agents are Na acetate and Na lactate. The onset of alkalinizing action for an indirect agent is ~30 minutes.

i. How do they alkalinize? See Figure 18-4.

ii. Most of commercial lactate solutions are the mixture of D- and L-forms (racemic form). D-lactate is minimally metabolized, thus is eliminated mostly via renal excretion.

iii. Other indirect agents do not have the problem with D-form of the chemical as with Na lactate.

iv. Lactate is metabolized in the liver (Krebs cycle), whereas Na acetate is used throughout the body, especially by the muscle. Thus, acetate is metabolized to form

more efficiently than lactate.

v. Acetate can induce vasodilation, which may be detrimental when it is administered IV to patients in shock.

vi. Do not use Na lactate in patients with lactic acidosis, who already have had a problem metabolizing lactate.

vii. Do not use Na acetate in patients with ketoacidosis, since acetate can form ketone bodies.

viii. Since the acidotic animals usually have K⁺ deficit, supplement of alkalinizing agents with K⁺-containing solutions.

ix. Dose of NaHCO₃ to be administered, if base deficit (BD) is known: mEq of NaHCO₃ administered = BW (kg) × 0.3 × BD

x. The NaHCO₃ should be administered via IV infusion for over a few hours, and the blood gas reevaluated before making a decision on further therapy.

xi. Dose of NaHCO₃, if base deficit is not known: 1–2 mEq/kg in a balanced electrolyte solution can be administered.

xii. It is rather difficult to over-alkalinize the body using an indirect agent in a patient with normal renal function. Excess NaHCO₃ produced can easily be excreted in the urine.

FIGURE 18-4. The metabolism of lactate into bicarbonate by the Krebs cycle.

b. Metabolic alkalosis

(1) Causes. Gain of base, excessive gastric vomiting, GI stasis or obstruction, hypokalemia, excess of aldosterone or diuretics, urea poisoning in cattle, and so forth.

(a) How does GI stasis lead to metabolic alkalosis? NaHCO₃ and HCl are produced in the parietal cell of the stomach. Once being made, NaHCO₃ is diffused into ECF, and HCl is released into the gastric lumen.

H₂CO₃ + NaCl → NaHCO₃ + HCl

HCl will then be absorbed from the small intestine. GI stasis will prevent/delay the absorption of HCl into the circulation, thereby resulting in metabolic alkalosis.

(b) How does urea poisoning lead to metabolic alkalosis?