What is the pathophysiology of cerebral salt wasting (CSW)?

Pathophysiology of Cerebral Salt Wasting

Cerebral salt wasting (CSW) is a syndrome of hypovolemic hyponatremia caused by excessive renal sodium excretion (natriuresis) and diuresis in the setting of intracranial pathology, with the underlying mechanism strongly implicating abnormal elevations in circulating natriuretic peptides. 1

Primary Mechanism: Natriuretic Peptide Dysregulation

• The central pathophysiologic mechanism involves abnormally elevated circulating natriuretic peptides that drive inappropriate renal sodium wasting despite volume depletion 1
• These natriuretic peptides override normal compensatory mechanisms that would typically conserve sodium in hypovolemic states 2
• The exact mechanisms have not been precisely delineated, but existing evidence strongly implicates this natriuretic peptide pathway as the primary driver 1

Renal Sodium Wasting and Volume Depletion

• CSW is characterized by inappropriately high renal sodium loss (typically urinary sodium >20 mmol/L) despite clinical evidence of extracellular volume depletion 3, 4
• The hallmark is substantial renal sodium wasting that leads to progressive intravascular volume depletion 4
• Unlike SIADH where AVP secretion is inappropriate, in CSW the secretion of arginine vasopressin (AVP) is actually appropriate—it represents a normal physiologic response to the volume depletion caused by the primary renal sodium wasting 2

Volume Status: The Critical Distinguishing Feature

• CSW presents with hypovolemia and clinical signs of volume depletion including hypotension, tachycardia, dry mucous membranes, and central venous pressure (CVP) <6 cm H₂O 5, 3
• This hypovolemic state is the direct result of ongoing natriuresis and diuresis 1
• The volume depletion distinguishes CSW from SIADH, which is euvolemic with CVP 6-10 cm H₂O 5, 3

Laboratory Characteristics Reflecting the Pathophysiology

• High urine osmolality relative to serum osmolality reflects the appropriate AVP response to volume depletion 3
• Inappropriately elevated urinary sodium concentration (>20 mmol/L) despite hypovolemia demonstrates the primary renal defect 3, 4
• Serum hyponatremia develops as a consequence of both sodium loss and the compensatory AVP-mediated water retention 2

Clinical Context and Risk Factors

• CSW occurs in the setting of cerebral pathology, most commonly subarachnoid hemorrhage, traumatic brain injury, and other intracranial lesions 4, 2
• CSW is more common in patients with poor clinical grade, ruptured anterior communicating artery aneurysms, and hydrocephalus 3
• Increased urinary sodium excretion in the early phase (within 3 days) of subarachnoid hemorrhage serves as a predictive factor for subsequent development of CSW 6

Temporal Pattern

• In subarachnoid hemorrhage patients, urinary sodium excretion tends to increase around 3 days after the event and significantly increases by 7 days 6
• Serum sodium levels typically begin to decline significantly around 7 days after the initial cerebral insult 6

Critical Pathophysiologic Distinction from SIADH

• The fundamental difference is that SIADH represents a primary water retention problem (volume expanded state) due to inappropriate AVP secretion, while CSW represents a primary sodium wasting problem (volume depleted state) with appropriate compensatory AVP secretion 2
• This distinction is clinically crucial because the treatments are diametrically opposed: SIADH requires fluid restriction while CSW requires aggressive volume and sodium replacement 7, 3
• Fluid restriction in CSW worsens the underlying pathophysiology and can precipitate cerebral ischemia 7, 3