Volume regulation and fluid replacement

1

Describe the functionally distinct compartments of body water

Total body water comprises approximately 60% of body weight. About two-thirds of body water (40% of body weight) is in the intracellular fluid compartment and one-third (20% of body weight) is in the extracellular compartment. Of the fluid in the extracellular compartment, three-quarters (15% of body weight) is comprised of interstitial fluid and one-quarter (5% of body weight) is plasma volume. An easy way to remember this is to think of body water following the “20-40-60” rule: 20% extracellular, 40% intracellular, 60% total body water. Fig. 8.1 estimates body water compartments in a patient with an ideal body weight of 70 kg. Note, accurate estimations can sometimes be difficult in obese patients.

2

Describe the dynamics of fluid distribution between plasma and the endothelial glycocalyx

Sterling’s principle is the traditional model that describes filtration between the intravascular and interstitial space. Recent evidence suggests this may not capture the entire story of fluid transfer, and a new entity known as the endothelial glycocalyx has been proposed. The revised Sterling’s principle:

accounts for the endothelial glycocalyx and supports the theory that filtration continues throughout the length of the capillary bed and that reabsorption from the interstitial space does not occur. Net filtration therefore is governed by endothelial glycocalyx, endothelial basement membrane, and the extracellular matrix.

Note: J _v /A is volume filtered per area; L _p is hydraulic conductance; P _c is capillary hydrostatic pressure; P _i is interstitial hydrostatic pressure, σ is osmotic reflection; π _p is oncotic pressure on the plasma side of the endothelial layer; π _sg is the oncotic pressure in the subglycocalyx space.

3

What is the normal range for serum osmolarity and how is it calculated?

Different sources quote different ranges, but in general, normal serum osmolarity ranges between 285 and 305 mOsm/L. A quick rough estimate is to double the sodium concentration. A more accurate estimate of osmolarity can be obtained using the following equation:

United States Customary System (imperial system)

International Systems of Units (metric system)

Note that the units for the United States Customary System (imperial system) for solutes are sodium (mEq/L), glucose (mg/dL), and BUN (mg/dL), whereas the SI system are all in mmol/L. Some textbooks may use the term osmolality with units mOsm/kg, which is essentially equivalent to osmolarity, because 1 L of water = 1 kg of water. Finally, appreciate the fact that for nation states who have embraced the metric system, the equation is much simpler.

4

How are body water and tonicity regulated?

The response of the kidney to antidiuretic hormone (ADH), also called vasopressin , is the primary mechanism by which body water and tonicity are regulated. It is released by the posterior pituitary and circulates unbound in plasma. It has a half-life of approximately 20 minutes and increases the expression of aquaporin channels in the distal convoluted tubule and collecting duct of the nephron. This increases tubular permeability to water, resulting in increased resorption of free water and increased urine concentration. Stimuli for the release of ADH include the following:

• Hypothalamic osmoreceptors facilitate the release of ADH in response to hyperosmolarity

• Hypothalamic thirst center neurons regulate conscious desire for water in response to hyperosmolarity

• Aortic baroreceptors and left atrial stretch receptors respond to hypotension and hypovolemia, respectively, facilitating the release of ADH

• Increased sympathetic tone from stress, such as in surgery or critical illness

Note that hypovolemia and hypotension take precedence over osmolarity; therefore ADH may be secreted to maintain volume at the expense of osmolarity.

5

Discuss the synthesis of ADH

ADH, or vasopressin, is synthesized in the supraoptic and paraventricular nuclei of the hypothalamus. It is transported by carrier proteins down the pituitary stalk in secretory granules to the posterior pituitary gland. There, it is stored and subsequently released into the capillaries of the posterior pituitary in response to stimuli from the hypothalamus. ADH-producing neurons receive efferent innervation from osmoreceptors and baroreceptors.

6

List the conditions that stimulate and inhibit the release of ADH

See Table 8.1 .

7

What is diabetes insipidus (DI)?

DI can be caused by impaired release of ADH from the posterior pituitary (neurogenic DI), or renal resistance to ADH (nephrogenic DI). The end result is the excretion of large volumes of dilute urine, which, if untreated, leads to dehydration, hypernatremia, and serum hyperosmolarity. The usual test for DI is cautious fluid restriction. Inability to decrease urine output and concentrate urine suggests the diagnosis, which may be confirmed by plasma ADH measurements. If the osmolarity of plasma exceeds that of urine after mild fluid restriction, the diagnosis of DI is suggested. Administration of intravenous desmopressin (DDAVP) can help differentiate nephrogenic versus neurogenic DI.

8

List the causes of DI

See Table 8.2 .

9

How is central DI managed?

Available preparations of ADH include DDAVP, 2 to 4 mcg intravenously every 2 to 4 hours to maintain urine output less than 300 mL/h. Alternatively, intravenous vasopressin titrated to urine output up to 2.4 units/h may be given. Hypotonic maintenance fluids, such as dextrose 5% may be given to replace the free water deficit. Avoid giving isotonic fluids, such as normal saline (NS) as this can increase serum osmolarity. Incomplete DI may respond to thiazide diuretics or chlorpropamide (which potentiates endogenous ADH). Frequent measurements of plasma and urine osmolarity, in addition to strict urine output measurements, is often indicated.

10

Define the syndrome of inappropriate ADH. How do you diagnose it?

Syndrome of inappropriate antidiuretic hormone (SIADH) is characterized by serum hypotonicity caused by the nonosmotic release of ADH, which inhibits renal excretion of water. Three criteria must be met to establish the diagnosis of SIADH:

• 1.

  The patient must be euvolemic or hypervolemic

• 2.

  The urine must be inappropriately concentrated (plasma osmolarity < 280 mOsm/kg, urine osmolarity > 100 mOsm/kg)

• 3.

  Renal, cardiac, hepatic, adrenal, and thyroid function must be normal