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Plasma Osmolality

(mOsmol/kg H20)

FIGURE 5 Effect of plasma osmolality on the plasma vasopressin (VP) concentration and thirst.

FIGURE 6 Normal physiologic response to a hyperosmotic plasma. Increased water ingestion and the excretion of a hyperosmotic urine cause a decrease in the plasma osmolality toward normal.

Plasma Osmolality Flowchart

FIGURE 7 Normal physiologic response to a hypo-osmotic plasma. Decreased water ingestion and excretion of a hypo-osmotic urine cause an increase in the plasma osmolality toward normal.

FIGURE 6 Normal physiologic response to a hyperosmotic plasma. Increased water ingestion and the excretion of a hyperosmotic urine cause a decrease in the plasma osmolality toward normal.

FIGURE 7 Normal physiologic response to a hypo-osmotic plasma. Decreased water ingestion and excretion of a hypo-osmotic urine cause an increase in the plasma osmolality toward normal.

of vasopressin release; larger fluid volume decreases can lead to extremely high plasma vasopressin levels, approaching 50 pg/mL. In clinical situations, the decrease in extracellular fluid volume can override the normal response to plasma osmolality and cause the urine to be concentrated even when the plasma osmolality becomes dangerously low. Consider the following Clinical Note.

QUANTIFYING RENAL CONCENTRATING ABILITY: FREE WATER CLEARANCE

The ability of the kidney to concentrate or dilute the urine decreases with age and may be considerably compromised in the elderly. Urinary concentrating and diluting ability is also disturbed in renal failure and, consequently, it can be a useful index of renal function.

Clinical Note

Hyponatremia Due to Gastrointestinal Fluid Losses

A patient has had a severe gastrointestinal disturbance during the past week or more, and has lost large volumes of salt and water through diarrhea and vomiting. Because of this illness, the patient has been unable to eat, but has been able to drink clear fluids. The large losses of salt and water deplete the patient's extracellular fluid volume. Under these circumstances, the dehydration is a strong volume signal to increase vasopressin release. The release of vasopressin causes urinary concentration with a resulting dilution of the plasma. Thus, the patient conserves most of the water she or he ingests, which expands the extracellular fluid compartment and all other body fluid compartments. However, because the patient cannot eat solid food, plasma osmolality will decrease as water is retained because it is not matched by an equivalent salt intake. Normally, this decrease in plasma osmolality, which is reflected by a decrease in the plasma Na+ concentration (called hyponatremia when the plasma Na+ falls below 135 mmol/L), would decrease the

Clinical Note (continued)

secretion of vasopressin. However, in this situation, the serious volume depletion overrides the normal osmotic stimulus, and vasopressin continues to be released.

Hyponatremia is the most common fluid and electrolyte disorder observed in the hospital setting. Especially when acute, hyponatremia is associated with lethargy, hyporeflexia, and mental confusion progressing to seizures and coma. Severe acute hyponatremia (plasma Na+ less than 120 mmol/L) has a 50% mortality rate. In the case of the patient just described, the hyponatremia could be treated effectively merely by infusing isotonic saline (possibly with a K+ and/ or Ca2+ supplement) to slowly replace the gastrointestinal salt and water losses. A slow return of the plasma osmolality toward normal is important to avoid brain damage from rapid shrinking of neurons that have adapted to a lower plasma osmolality.

It is important to understand that the above case is just one example of how hyponatremia can develop. Hyponatremia can also occur in patients who have a normal or even an expanded extracellular fluid volume. For example, increased vasopressin secretion and hyponatremia often occur despite severe volume expansion caused by heart or liver failure. This settings, which is often referred to as a functional hypovolemia, the body is reacting to a decrease in the ''effective'' circulating blood volume that is actually perfusing the tissues. In this setting, the hyponatremia should be treated with fluid restriction and diuretics. Thus, the differential diagnosis of hyponatremia is extremely important in deciding on a course of therapy.

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