Page 1371 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

944 PART 8: Renal and Metabolic Disorders

2. The collecting duct must be permeable to water, allowing water
• Total body phosphate stores may be significantly reduced and pro- to osmotically flow out of the collecting ducts into the medullary
duce organ dysfunction even in the face of normal or minimally interstitium, concentrating the urine. This is affected by ADH. Thus
decreased serum levels; if suspicion for a depleted state exists, treat- ADH is required for production of concentrated urine.
ment should be given.
• Severe hypomagnesemia may have significant consequences itself, Antidiuretic Hormone: ADH plays a crucial role in the concentrating and
including cardiac arrhythmias and muscle weakness; lesser degrees diluting process. ADH, or vasopressin, is a six-peptide amino acid pro-
duced in the hypothalamus and stored in the posterior pituitary gland.
of hypomagnesemia often accompany hypokalemia and hypocal-
cemia and correction of the magnesium deficit facilitates correc- Release of ADH follows increases in osmolality or dramatic drops in blood
tion of the other electrolyte abnormalities. pressure or EABV. An increase in serum osmolality of 1% (2 mOsm/kg)
will stimulate ADH, while a similar decrease inhibits release. ADH
is less sensitive to changes in blood volume; a loss of 7% to 10% of
blood volume is required to release ADH. When osmolality sup-
1
SODIUM presses and volume depletion stimulates ADH release, volume effects
■ METABOLISM predominate and ADH is released. Osmolality is a more sensitive ADH
stimulus, while volume is a more potent ADH stimulus. ADH is also
Sodium is the chief extracellular cation and is critical to regulating released in response to a collection of nonosmotic, nonvolemic stimuli
extracellular and intravascular volume. Total body sodium determines (Table 99-1).
clinical volume status, but sodium concentration does not correlate Free Water Clearance and Electrolyte-Free Water Clearance: As outlined,
with volume status. Both hypernatremia and hyponatremia occur in the renal excretion or retention of water is central to the regulation
the presence of hypo-, eu-, and hypervolemia. The sodium concen- of osmolality, so specialized concepts have been developed to model
tration itself is the single ion that best represents serum osmolality; renal water handling. Clearance is a generic term used to quantify
essentially all of the clinically relevant symptoms of dysnatremia solute removal (x) by the kidney. Clearance is an artificial construct
are secondary to alterations in osmolality. Hypernatremia is largely that represents the volume of blood that is completely cleared of a
synonymous with hyperosmolality, while hyponatremia is generally substance in a set amount of time (Eq. 99-1). The clearance formula
indicative of hypoosmolality. can be manipulated to calculate the clearance of free water, called
Osmolality and tonicity are related but separate concepts. Osmolality the free water clearance. Conceptually, urine can be divided into two
measures all of the solutes in solution, while tonicity only includes par- components: an isotonic and a free water component. The isosmotic
ticles that are unable to cross from the intracellular to the extracellular component contains all of the excreted solute at the same concentra-
compartment. It is these particles which are osmotically active, and by tion as that found in plasma; since the solute and water loss occur in
drawing water across compartments they may alter cell volume. Sodium the same proportion as found in the body, excretion of this isotonic
and potassium are the primary determinants of tonicity. urine does not affect osmolality. The other component is free water;
Balancing water intake and excretion is the principal means by which this is solute-free water and excretion of this compartment raises
the body regulates sodium concentration. This balance is maintained plasma osmolality. For example: A person makes 1200 mL of urine
by the effects of thirst and antidiuretic hormone (ADH). Following a with an osmolality of 142 mOsm/kg. This urine can be divided into
water load, osmolality falls and osmoreceptors in the hypothalamus 600 mL of isotonic urine (284 mOsm/kg) and 600 mL of free water.
suppress thirst and ADH release. The latter signals the kidney to pro- In terms of osmolality, only the 600 mL of free water needs to be
duce dilute urine to clear the water load. In states of water deprivation considered. The loss of this 600 mL will tend to increase serum osmo-
(or a solute load), osmoreceptors detect the rise in osmolality and lality. The case is reversed with concentrated urine. A patient produces
increase thirst and ADH. 1000 mL of urine with an osmolality of 568 mOsm/kg. This urine can
The kidney regulates osmolality and sodium concentration by dilut- be divided into 2000 mL of isotonic urine (284 mOsm/kg) and a neg-
ing or concentrating urine. Producing dilute urine allows the kidney to ative 1000 mL of free water. In regard to changes in osmolality only
clear a water load, raising plasma osmolality. the −1000 mL needs to be considered. The −1000 mL repre-
In order to make dilute urine, multiple criteria must be met: sents water that is added to the body and will decrease serum

1. Tubular fluid must be delivered to the diluting segment of the osmolality. Despite the patient excreting 1000 mL of urine, 1000 mL
nephron. This can be ensured in any patient with adequate effec- of fluid have been effectively added to the body by the production of
tive arterial blood volume (EABV) and a normal or near normal concentrated urine. Equation 99-2 is used to calculate the free water
glomerular filtration rate (GFR). clearance.
2. There must be intact sodium resorption in the diluting segments of
the kidney (ie, the thick ascending limb of the loop of Henle [TALH]
and the distal convoluted tubule. Loop and thiazide diuretics are the
primary causes of inoperative diluting segments.) TABLE 99-1 Causes of Antidiuretic Hormone (ADH) Release
3. The collecting tubule must be impermeable to water. ADH increases Inappropriate Stimuli of ADH Release Appropriate Stimuli of ADH Release
water permeability, so the production of dilute urine requires a lack Pain Hyperosmolality
of ADH.
Nausea Hypovolemia
Concentrating urine allows the kidneys to minimize water loss and Narcotics
compensate for an increase in serum osmolality.
In order to produce concentrated urine, the following conditions Nicotine
must be met: Clofibrate
1. A hypertonic medullary interstitium draws water from the medul- Vincristine
lary collecting ducts. The TALH creates and maintains the high con- Carbamazepine
centration of the interstitium. Any factor that antagonizes the TALH Ifosfamide
(eg, loop diuretics, hypercalcemia, or hypokalemia) will disrupt the
production of concentrated urine. Chlorpropamide

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