Medical School · Year 2 · Renal · includes a quiz and discussion video

Lecture 5: Regulation of Sodium and Water Balance

Unit 2.1: Renal System

Learning Objectives

By the end of this lecture, students will be able to:

1. Describe the regulation of extracellular fluid volume and sodium balance
2. Explain the renin-angiotensin-aldosterone system (RAAS)
3. Describe the role of natriuretic peptides in sodium regulation
4. Explain the mechanisms of edema formation
5. Describe the pathophysiology of hyponatremia and hypernatremia
6. Apply sodium and water balance concepts to clinical management

Body Fluid Compartments

Understanding sodium and water balance requires appreciating how body water is distributed among physiological compartments. Total body water comprises approximately 60 percent of body weight in a typical adult, though this percentage is lower in elderly individuals and those with higher body fat content. This water distributes between two major compartments: intracellular fluid contains approximately two-thirds (40 percent of body weight), while extracellular fluid contains the remaining one-third (20 percent of body weight). The extracellular compartment subdivides further into interstitial fluid (approximately 15 percent of body weight) and plasma (approximately 5 percent of body weight).

Osmolality must remain equal between the intracellular and extracellular compartments at steady state because water moves freely across most cell membranes. Normal plasma osmolality ranges from 275 to 295 mOsm/kg. Sodium and its accompanying anions constitute the primary osmoles in extracellular fluid, while potassium and its anions predominate intracellularly. Changes in total body sodium alter extracellular fluid volume because water follows sodium osmotically. Changes in total body water relative to sodium alter osmolality and serum sodium concentration.

The concept of effective circulating volume (ECV) is essential for understanding volume regulation. ECV refers specifically to that portion of extracellular fluid within the arterial system that is effectively perfusing tissues. Unlike total extracellular fluid volume, ECV cannot be directly measured but is sensed by baroreceptors in the cardiovascular system. Importantly, ECV may differ dramatically from total extracellular volume in certain disease states. In heart failure, for example, total extracellular fluid is expanded (manifesting as edema), yet ECV is reduced because cardiac output is insufficient to perfuse tissues adequately. The body's regulatory systems respond to perceived decreases in ECV rather than to total body sodium or extracellular volume per se.

<image>Panel A: Whole-body outline showing intracellular fluid (40% body weight, 67% of TBW) and extracellular fluid subdivided into interstitial (15%, 25% of TBW) and plasma (5%, 8% of TBW) with proportional sizing. Panel B: Horizontal bar showing osmolality equal across all compartments (~285-295 mOsm/kg). Panel C: Normal state with ECV matching total ECF illustrated with blue shading. Panel D: Heart failure scenario with ECV decreased despite elevated total ECF, showing edema in interstitial space and congested but under-perfused tissues.</image>

Sodium Balance Overview

The body maintains sodium balance by matching urinary excretion to dietary intake, a task accomplished primarily by the kidney. Total body sodium approximates 4200 mEq in a typical adult, distributed between the exchangeable pool in extracellular fluid (approximately 40 percent) and a more slowly exchangeable pool in bone (approximately 60 percent). Plasma sodium concentration normally ranges from 135 to 145 mEq/L, representing the concentration rather than total amount.

Dietary sodium intake varies considerably depending on food choices, typically ranging from 100 to 250 mEq per day in Western diets. Under steady-state conditions, urinary sodium excretion matches intake. Gastrointestinal losses are minimal under normal circumstances, and sweat losses vary with activity and environmental conditions. The kidney demonstrates remarkable flexibility in adjusting sodium excretion from nearly zero to hundreds of milliequivalents daily, ensuring that sodium balance is maintained across a wide range of intakes.

A critical principle underpins clinical reasoning about sodium disorders: total body sodium determines extracellular fluid volume, while serum sodium concentration reflects water balance relative to sodium. When total body sodium increases, extracellular volume expands because water follows sodium osmotically, potentially manifesting as edema. Conversely, sodium depletion leads to extracellular volume contraction. The serum sodium concentration tells us about the ratio of sodium to water, not the absolute amounts of either. A patient with profound edema (sodium excess) can have low, normal, or high serum sodium concentration depending on concurrent water balance.

<image>Panel A: Balance scale with sodium intake (dietary sources: processed foods, salt) equilibrating with sodium output (primarily urine, small amounts in stool and sweat). Panel B: Conceptual illustration showing total body sodium determining ECF volume (expanding/contracting vessel) while serum sodium concentration reflects Na:water ratio. Panel C: Clinical scenario showing sodium excess with proportional water (normal serum Na, edema) and sodium excess with greater water excess (low serum Na, edema). Panel D: Sodium depletion scenario with high or low serum Na depending on water loss, with directional arrows.</image>

Sensors of Volume Status

The body monitors effective circulating volume through multiple sensor systems that detect changes in vascular stretch and pressure, triggering coordinated responses to restore homeostasis.

High-pressure baroreceptors located in the carotid sinus and aortic arch respond to changes in arterial blood pressure. When pressure decreases, afferent nerve firing decreases, leading to increased sympathetic nervous system activity and reduced tonic inhibition of ADH release. These responses promote sodium and water retention while supporting blood pressure through vasoconstriction.

Low-pressure baroreceptors in the cardiac atria and pulmonary vessels sense changes in venous return and cardiac filling. Reduced atrial stretch decreases atrial natriuretic peptide release and increases sympathetic outflow. These sensors are particularly sensitive to changes in effective circulating volume and contribute importantly to the neurohumoral response to heart failure.

Intrarenal sensors provide direct assessment of kidney perfusion. The juxtaglomerular cells of the afferent arteriole function as baroreceptors, responding to decreased stretch with increased renin release. The macula densa senses sodium chloride delivery to the distal nephron through the NKCC2 transporter; reduced delivery signals decreased filtration and triggers renin release through paracrine mechanisms. Together, these intrarenal sensors initiate the renin-angiotensin-aldosterone system response to perceived volume depletion.

<image>Panel A: High-pressure baroreceptors in carotid sinus and aortic arch with nerve pathways to brainstem and output to sympathetic nervous system and ADH release. Panel B: Low-pressure baroreceptors in cardiac atria and pulmonary vessels with pathways showing ANP release and sympathetic modulation. Panel C: Intrarenal sensors showing juxtaglomerular apparatus with JG cells sensing afferent arteriolar pressure and macula densa sensing tubular NaCl delivery with arrows to renin release. Panel D: Response arrows showing decreased pressure/volume activating RAAS, SNS, ADH while suppressing ANP.</image>

The Renin-Angiotensin-Aldosterone System

The renin-angiotensin-aldosterone system represents the body's primary hormonal mechanism for defending effective circulating volume. This cascade of enzymatic reactions and hormonal effects coordinates sodium retention, water conservation, and blood pressure support.

Three primary stimuli trigger renin release from juxtaglomerular cells. Decreased renal perfusion pressure reduces stretch on the afferent arteriole, directly stimulating renin secretion from JG cells. Decreased sodium chloride delivery to the macula densa signals reduced glomerular filtration, triggering paracrine signals that promote renin release. Increased sympathetic nervous system activity acts through beta-1 adrenergic receptors on JG cells to directly stimulate renin secretion. These mechanisms often operate simultaneously during volume depletion.

The enzymatic cascade proceeds through several steps. Renin, an aspartyl protease, cleaves angiotensinogen produced by the liver to generate the decapeptide angiotensin I. Angiotensin-converting enzyme, located predominantly on pulmonary vascular endothelium, removes two amino acids to produce the octapeptide angiotensin II. This active hormone exerts its effects through AT1 and AT2 receptors distributed throughout the cardiovascular and renal systems.

Angiotensin II produces multiple physiological effects that restore effective circulating volume. Direct vasoconstriction, more pronounced in the efferent arteriole than afferent, supports blood pressure while maintaining glomerular filtration pressure. In the proximal tubule, angiotensin II stimulates the NHE3 sodium-hydrogen exchanger, increasing sodium reabsorption. Angiotensin II triggers aldosterone release from the adrenal cortex, stimulates ADH release from the posterior pituitary, and activates thirst centers in the hypothalamus. It also potentiates sympathetic neurotransmission.

Aldosterone, a mineralocorticoid hormone, produces its effects in the collecting duct over a timescale of hours through genomic mechanisms. After crossing the cell membrane and binding to intracellular mineralocorticoid receptors, aldosterone alters gene transcription to increase expression of the epithelial sodium channel ENaC, the sodium-potassium ATPase, and the potassium channel ROMK. The net effect is enhanced sodium reabsorption from the collecting duct lumen coupled with potassium secretion. In intercalated cells, aldosterone stimulates H+-ATPase activity, contributing to acid excretion.

<image>Panel A: Three stimuli for renin release (decreased renal perfusion, decreased NaCl at macula densa, sympathetic activation via beta-1 receptors) converging on JG cells with cascade showing angiotensinogen from liver to angiotensin I via renin. Panel B: Angiotensin I to angiotensin II via ACE in pulmonary circulation, with AII effects in hub-and-spoke pattern: efferent constriction, proximal tubule NHE3 stimulation, aldosterone release, ADH release, thirst stimulation, sympathetic potentiation. Panel C: Aldosterone mechanism in principal cells showing MR binding, nuclear translocation, increased ENaC/Na+K+ATPase/ROMK expression. Panel D: Net effect showing Na+ reabsorption and K+ secretion with warm colors for stimulatory pathways.</image>

Natriuretic Peptides

Natriuretic peptides provide a counterregulatory system that opposes the sodium-retaining effects of RAAS and promotes sodium and water excretion when volume expansion is sensed.

Three related peptides constitute this system. Atrial natriuretic peptide is synthesized and stored in atrial myocytes, released in response to atrial wall stretch signaling volume expansion. Brain natriuretic peptide, despite its name, originates primarily from ventricular myocytes, released when ventricular wall stress increases as occurs in heart failure. C-type natriuretic peptide is produced by vascular endothelium and has predominantly local paracrine effects.

ANP and BNP signal through membrane-bound guanylyl cyclase receptors (NPR-A and NPR-B), generating cyclic GMP as a second messenger. Protein kinase G activation leads to target effects including relaxation of vascular smooth muscle and alterations in renal tubular transport.

The physiological effects of natriuretic peptides promote sodium and water excretion through multiple mechanisms. In the kidney, natriuretic peptides dilate the afferent arteriole while having less effect on the efferent, thereby increasing glomerular filtration rate and filtered sodium load. Direct inhibition of sodium reabsorption in the collecting duct reduces ENaC activity. Natriuretic peptides suppress renin release from juxtaglomerular cells and aldosterone release from the adrenal cortex, interrupting the RAAS cascade. They also oppose ADH release and effects, promoting water excretion. Systemically, natriuretic peptides cause vasodilation that reduces venous return and afterload.

The clinical utility of BNP and its amino-terminal fragment NT-proBNP derives from their elevation in heart failure. These biomarkers help distinguish cardiac from non-cardiac causes of dyspnea, and their levels correlate with disease severity and prognosis. Serial measurements can track treatment response.

<image>Panel A: Heart with atria releasing ANP (triggered by atrial stretch) and ventricles releasing BNP (triggered by ventricular wall stress/failure). Panel B: Receptor mechanism showing NPR-A/B guanylyl cyclase receptor generating cGMP and PKG activation with effects including afferent arteriolar dilation, collecting duct ENaC inhibition, suppression of renin and aldosterone. Panel C: Additional effects showing inhibition of ADH and systemic vasodilation, contrasting with RAAS effects at each level. Panel D: Clinical box showing BNP/NT-proBNP use in heart failure diagnosis and monitoring with cool colors contrasting RAAS warm colors.</image>

Integrated Volume Regulation

The body coordinates multiple regulatory systems to maintain effective circulating volume within narrow limits, with opposing responses to volume depletion versus expansion.

When volume depletion occurs, whether from hemorrhage, gastrointestinal losses, or inadequate intake, the integrated response promotes sodium and water retention while supporting blood pressure. The RAAS activates strongly, with increased renin, angiotensin II, and aldosterone levels promoting sodium reabsorption and vasoconstriction. Sympathetic nervous system activation causes vasoconstriction, increases heart rate, and directly stimulates renal sodium retention. ADH levels increase, both from decreased inhibition by baroreceptors and from angiotensin II stimulation, promoting water retention. Natriuretic peptide levels decrease as atrial stretch diminishes. The net effect is maximal sodium and water conservation combined with hemodynamic support.

Volume expansion triggers the opposite pattern. RAAS activity suppresses as volume repletion removes the stimuli for renin release. Sympathetic tone decreases. ADH secretion falls. Natriuretic peptide release increases as atrial and ventricular stretch increase. The net effect is enhanced sodium and water excretion with reduced vascular resistance.

Pressure natriuresis provides an additional mechanism linking blood pressure directly to sodium excretion. Increased renal perfusion pressure directly enhances sodium excretion through mechanisms including decreased sodium reabsorption in the proximal tubule and medullary washout of the concentrating gradient. This relationship ensures that long-term blood pressure regulation is ultimately tied to renal sodium handling. Chronic hypertension represents a resetting of this curve such that higher pressures are required to maintain sodium balance.

<image>Panel A: Volume depletion flowchart showing decreased ECV sensed by baroreceptors leading to increased RAAS, SNS, ADH and decreased ANP/BNP. Panel B: Volume depletion net effect showing Na+ and H2O retention, vasoconstriction, increased BP; volume expansion showing increased ECV leading to decreased RAAS, SNS, ADH and increased ANP/BNP. Panel C: Volume expansion net effect showing Na+ and H2O excretion, vasodilation, decreased BP with color gradients showing transition between states. Panel D: Pressure-natriuresis curve with Na+ excretion versus arterial pressure showing normal curve and shifted curves for hypertension.</image>

Disorders of Sodium Balance: Edema

Edema represents the clinical manifestation of extracellular fluid expansion, specifically the accumulation of excess interstitial fluid. Understanding edema formation requires applying Starling forces to capillary fluid dynamics.

Four forces determine net fluid movement across capillary walls. Capillary hydrostatic pressure drives fluid out of the capillary into the interstitium. Interstitial hydrostatic pressure (normally slightly negative) has minimal opposing effect. Capillary oncotic pressure, generated primarily by plasma proteins especially albumin, draws fluid back into the capillary. Interstitial oncotic pressure draws fluid into the interstitium, though its contribution is normally small. The net filtration is described by the equation: Net filtration = Kf × [(Pc - Pi) - (πc - πi)], where Kf represents capillary permeability and surface area.

Several mechanisms can tip this balance toward interstitial fluid accumulation. Elevated capillary hydrostatic pressure occurs in heart failure (from increased venous pressure) and with venous obstruction. Decreased plasma oncotic pressure results from hypoalbuminemia, as seen in nephrotic syndrome, cirrhosis, and severe malnutrition. Increased capillary permeability occurs with inflammation, burns, and sepsis, allowing protein to leak into the interstitium and raise interstitial oncotic pressure. Lymphatic obstruction impairs the normal drainage that clears interstitial fluid and protein.

Different edematous states reflect different pathophysiological mechanisms and relationships between total extracellular volume and effective circulating volume. In heart failure, poor cardiac output reduces effective circulating volume despite expanded total extracellular fluid; the body responds as if volume-depleted, activating RAAS and perpetuating sodium retention. Cirrhosis produces portal hypertension and splanchnic vasodilation, reducing effective circulating volume and triggering similar sodium retention while fluid accumulates as ascites and peripheral edema. Nephrotic syndrome causes hypoalbuminemia that reduces plasma oncotic pressure; whether ECV is reduced (underfill theory) or expanded (overfill from primary renal retention) varies among patients. Primary renal sodium retention from kidney disease directly expands extracellular volume.

<image>Panel A: Capillary cross-section with Starling forces shown as arrows (Pc outward, oncotic pressure inward, Pi inward, interstitial oncotic outward) with equilibrium equation labeled. Panel B: Four causes of edema illustrated: elevated Pc in heart failure with congested veins, decreased oncotic pressure in hypoalbuminemia, increased permeability in inflammation with protein leaking out, blocked lymphatics. Panel C: Table showing edema states (heart failure, cirrhosis, nephrotic syndrome) with ECV status decreased despite increased total ECF. Panel D: Explanation of why RAAS remains activated despite total body sodium excess in these conditions.</image>

Hyponatremia

Hyponatremia, defined as serum sodium below 135 mEq/L, represents the most common electrolyte abnormality encountered in clinical practice. Because sodium is the primary extracellular osmole, hyponatremia usually reflects hypoosmolality, though exceptions exist.

Classification by serum osmolality distinguishes true from apparent hyponatremia. Hypotonic hyponatremia, the most common form, reflects excess water relative to sodium and represents true hypoosmolality. Isotonic hyponatremia (pseudohyponatremia) occurs as a laboratory artifact when severe hyperlipidemia or hyperproteinemia displaces plasma water, reducing measured sodium concentration without affecting true osmolality; modern ion-selective electrode methods largely eliminate this artifact. Hypertonic hyponatremia occurs when other effective osmoles, particularly glucose, draw water from cells into the extracellular space, diluting sodium; each 100 mg/dL increase in glucose decreases measured sodium by approximately 1.6 to 2.4 mEq/L.

True hypotonic hyponatremia is further classified by volume status. Hypovolemic hyponatremia occurs when both sodium and water are lost, but water is replaced (via intake or hypotonic fluids) without adequate sodium replacement; causes include gastrointestinal losses, diuretic use, and adrenal insufficiency. Euvolemic hyponatremia occurs when water is retained without significant sodium disturbance, most classically in SIADH but also with hypothyroidism and glucocorticoid deficiency. Hypervolemic hyponatremia occurs in edematous states (heart failure, cirrhosis, advanced kidney disease) where total body sodium is increased but total body water is increased even more, reflecting the body's response to decreased effective circulating volume.

The syndrome of inappropriate ADH secretion deserves special attention as the most common cause of euvolemic hyponatremia. Diagnostic criteria include serum osmolality below 275 mOsm/kg with inappropriately concentrated urine (osmolality greater than 100 mOsm/kg when it should be maximally dilute), urine sodium greater than 40 mEq/L, clinical euvolemia, and exclusion of hypothyroidism and adrenal insufficiency. Causes include malignancies (especially small cell lung cancer), CNS disorders, pulmonary diseases, and numerous medications including SSRIs, carbamazepine, and oxcarbazepine.

Clinical manifestations depend on both severity and rapidity of development. Mild hyponatremia (130-135 mEq/L) is often asymptomatic. Moderate hyponatremia (120-129 mEq/L) may cause nausea, headache, and confusion. Severe hyponatremia below 120 mEq/L risks seizures, coma, and brain herniation from cerebral edema. Acute hyponatremia (developing over hours) produces more symptoms than chronic hyponatremia (developing over days), as brain adaptation involving organic osmolyte extrusion protects against severe swelling.

Treatment depends on the underlying cause and must balance the risk of ongoing hyponatremia against the risk of overcorrection. For hypovolemic hyponatremia, isotonic saline restores volume and removes the stimulus for ADH release, allowing water excretion. For euvolemic hyponatremia (SIADH), water restriction is first-line; salt tablets increase solute load; vasopressin receptor antagonists (vaptans) block ADH action. For hypervolemic hyponatremia, fluid and salt restriction combined with diuretics and treatment of the underlying condition is appropriate.

The rate of correction is critical in chronic hyponatremia. Overly rapid correction risks osmotic demyelination syndrome (previously called central pontine myelinolysis), a devastating neurological complication. Generally, correction should not exceed 8 to 10 mEq/L in any 24-hour period for chronic hyponatremia. Acute severe symptomatic hyponatremia may warrant more aggressive initial correction to relieve acute symptoms, but still requires careful monitoring.

<image>Panel A: Flowchart starting with serum Na+ less than 135 mEq/L leading to serum osmolality measurement, branching to hypertonic (hyperglycemia correction), isotonic (pseudohyponatremia), and hypotonic (continue workup). Panel B: Hypotonic hypovolemic branch showing GI losses, diuretics, adrenal insufficiency with saline treatment; euvolemic showing SIADH criteria, hypothyroidism, glucocorticoid deficiency with water restriction and vaptans. Panel C: Hypervolemic branch showing heart failure, cirrhosis, kidney disease with restriction, diuretics, and underlying cause treatment. Panel D: Warning box about correction rate of 8-10 mEq/L/24 hours for chronic cases with osmotic demyelination risk and color coding for each branch.</image>

Hypernatremia

Hypernatremia, defined as serum sodium above 145 mEq/L, always indicates hyperosmolality because sodium is the dominant extracellular osmole. This condition reflects a deficit of water relative to sodium and triggers cellular dehydration, particularly affecting the brain.

Hypernatremia develops through three general mechanisms. Most commonly, water loss exceeds sodium loss, as occurs with insensible losses (fever, respiratory, cutaneous), diabetes insipidus (central or nephrogenic), or osmotic diuresis. Pure water loss occurs in diabetes insipidus where dilute urine is excreted despite hyperosmolality. Less commonly, sodium gain from hypertonic saline administration, sodium bicarbonate, or excessive salt ingestion can cause hypernatremia, though functioning kidneys and intact thirst usually prevent this.

The urine osmolality helps differentiate renal from extrarenal causes. In the presence of hypernatremia, the kidneys should maximally concentrate urine. If urine osmolality is inappropriately low (below 300 mOsm/kg), the kidney is failing to conserve water appropriately, suggesting diabetes insipidus. If urine is appropriately concentrated (above 600 mOsm/kg), the cause is extrarenal water loss or sodium gain, and the kidneys are responding normally.

Clinical manifestations reflect brain cell shrinkage as water moves osmotically from cells to the hypertonic extracellular fluid. Thirst is the primary defense and, if the thirst mechanism is intact and water is accessible, prevents significant hypernatremia in ambulatory individuals. Hypernatremia therefore occurs most commonly in those unable to sense or respond to thirst: infants, elderly with dementia, critically ill or sedated patients. Neurological symptoms progress from lethargy and weakness through irritability to seizures and coma. Severe acute hypernatremia can cause intracranial hemorrhage as brain shrinkage tears bridging vessels.

Treatment involves calculating the water deficit and replacing it gradually. The water deficit can be estimated as: Total body water × [(measured Na/140) - 1], where total body water is approximately 0.5 times body weight in women and 0.6 times body weight in men. The deficit is replaced using hypotonic fluids (D5W, half-normal saline, or water via feeding tube). The correction rate should not exceed 10 to 12 mEq/L per 24 hours in chronic hypernatremia to avoid cerebral edema, as brain cells adapt to hypertonicity by accumulating organic osmolytes; rapid reduction in extracellular tonicity causes water to enter adapted cells, causing swelling. Concurrent treatment addresses the underlying cause.

<image>Panel A: Hypernatremia defined as Na+ greater than 145 mEq/L (always hyperosmolar) with flowchart based on urine osmolality branching to low/inappropriately dilute for renal water loss (diabetes insipidus types). Panel B: Central DI responds to DDAVP versus nephrogenic DI does not; high/appropriately concentrated urine indicating extrarenal losses or sodium gain with box showing at-risk populations (infants, elderly, ICU patients). Panel C: Clinical manifestations from mild to severe with water deficit formula and calculation example. Panel D: Treatment principles showing D5W or hypotonic saline with correction rate of 10-12 mEq/L/24 hours and cerebral edema risk warning.</image>

Clinical Assessment Tools

Several clinical and laboratory tools aid in assessing sodium and water balance and guiding diagnosis.

The fractional excretion of sodium (FENa) quantifies what fraction of filtered sodium is ultimately excreted. Calculated as (UNa × PCr) / (PNa × UCr) × 100%, FENa helps distinguish prerenal azotemia (where sodium is avidly retained, FENa typically less than 1%) from intrinsic renal disease such as acute tubular necrosis (where tubular function is impaired, FENa typically greater than 2%). A low FENa indicates intact tubular function responding appropriately to perceived volume depletion.

Urine sodium concentration provides related information. Values below 20 mEq/L suggest sodium avidity from volume depletion or effective circulating volume depletion (as in heart failure or cirrhosis). Values above 40 mEq/L suggest sodium wasting from diuretics, intrinsic renal disease, or SIADH.

Physical examination provides clinical assessment of volume status. Signs of volume depletion include dry mucous membranes, reduced skin turgor (tested over the clavicle in elderly patients), flat jugular veins, orthostatic hypotension with tachycardia, and prolonged capillary refill. Signs of volume expansion include peripheral edema, elevated jugular venous pressure, and pulmonary crackles. However, physical examination is notoriously unreliable, particularly at the extremes of age and in critically ill patients.

The osmolar gap, calculated as measured osmolality minus calculated osmolality (where calculated = 2[Na+] + glucose/18 + BUN/2.8), identifies unmeasured osmoles. A gap exceeding 10 mOsm/kg suggests the presence of additional osmotically active substances such as ethanol, methanol, ethylene glycol, or mannitol.

<image>Panel A: FENa calculation with formula, interpretation table showing less than 1% for prerenal and greater than 2% for ATN, with limitations noting diuretics interfere and FEurea as alternative. Panel B: Urine sodium interpretation showing less than 20 mEq/L indicating sodium avidity, volume depletion, low ECV states; greater than 40 mEq/L indicating sodium wasting, ATN, diuretics, SIADH. Panel C: Physical examination showing volume depletion signs (dry mucous membranes, poor skin turgor, flat JVP, orthostatic changes) versus volume expansion signs (edema, elevated JVP, pulmonary crackles). Panel D: Osmolar gap calculation and interpretation with gap greater than 10 indicating unmeasured osmoles and causes listed.</image>

Summary

• Extracellular fluid volume is determined by total body sodium; water follows osmotically
• Serum sodium concentration reflects water balance relative to sodium, not total body sodium
• RAAS activation by decreased effective circulating volume promotes sodium retention, vasoconstriction, and water conservation
• Aldosterone increases ENaC-mediated sodium reabsorption and potassium secretion in the collecting duct
• Natriuretic peptides oppose RAAS effects, promoting sodium excretion and vasodilation
• Edema results from imbalanced Starling forces and often occurs with decreased ECV despite increased total extracellular fluid
• Hyponatremia classification proceeds by osmolality then volume status
• SIADH causes euvolemic hypotonic hyponatremia with inappropriately concentrated urine
• Hypernatremia always indicates hyperosmolality and represents a water deficit
• Correction rates must be limited: 8 to 10 mEq/L per 24 hours for chronic hyponatremia, 10 to 12 mEq/L for hypernatremia

Key Terms

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