Hyponatremia
Headache, weakness, and this symptom are among the the earliest nonspecific symptoms of hyponatremia (serum Na+ falls below 125-130 mEq/L)
What are nausea/vomiting?
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Hypertonicity-induced water entry into brain cells --> brain swells within the skull --> intracranial hypertension --> nausea and vomiting pathways activated by CNS dysfunction
Interestingly, nausea also activates vasopressin independently (possibly a compensatory mechanism for volume depletion from vomiting).
Patients with SIADH usually have this volume status on physical exam.
Euvolemia (sometimes hypervolemia)
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ADH secretion occurs in the absence of reduced ECF --> TBW increases --> RAAS inhibition and ANP activation --> urinary sodium loss --> no edema/volume overload
Distinguishing serum states with [this] deficiency from states with [this] excess is important for proper management of hypernatremic patients
What are water deficiency and sodium excess?
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Water deficiency ---> renal (diabetes) and extrarenal (diarrhea, vomiting, dehydration, etc.)
Sodium excess ---> rapid saline infusion, salt toxicity, excessive protein catabolism (urea-driven diuresis)
This is a lung malignancy classically associated with paraneoplastic SIADH.
What is small cell lung cancer?
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SCLC arises from neuroendocrine cells --> tumor cells synthesize AVP using pathway similar to that of the hypothalamus
Hyponatremia is defined by a serum Na+ below this value.
What is 135 mEq/L?
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Hyponatremia can be classified as follows:
Mild is 130–135 mEq/L.
Moderate is 125–130 mEq/L.
Severe is <125 mEq/L.
In SIADH, patients present with hyponatremia with this type of tonicity.
What is hypotonicity?
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Tonicity is dictated by serum osmolality: SIADH lowers concentration of osmotically active solutes (Na+, HCO3-) ---> hypotonic serum --> water moves into brain cells --> cerebral edema
In infants, hypernatremia most commonly results from this cause of free water loss.
What is diarrhea
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Water deficiency ---> renal (diabetes) and extrarenal (diarrhea, vomiting, dehydration, etc.)
Sodium excess ---> rapid saline infusion, salt toxicity, excessive protein catabolism (urea-driven diuresis)
In hyponatremia due to heart failure, water retention is driven by this physiologic stimulus that is absent in SIAD.
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Reduced cardiac output ---> low effective arterial blood volume ---> ADH release --> water retention and dilutional hyponatremia
Absent in SIADH as patients are typically euvolemic (ADH release independent of volume status).
In severe chronic hyponatremia, patients can present with nausea, vomiting, headache, confusion, delirium, and rarely this life-threatening neurological complication.
What are seizures?
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When sodium falls to ~115–120 mEq/L, severe cerebral edema can develop. This increases intracranial pressure and may lead to seizures, coma, and even respiratory arrest, which is why severe symptomatic hyponatremia is a medical emergency.
Before diagnosing SIADH, these two endocrine disorders must be ruled out, as they can also cause euvolemic hyponatremia with similar laboratory findings.
What are adrenal insufficiency and hypothyroidism?
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1. Adrenal insufficiency: Low cortisol/glucocorticoids --> increased ADH release --> hyponatremia with low serum osmolality and concentrated urine
2. Hypothyroidism (severe) --> low cardiac output and renal perfusion --> ADH release --> impaired excretion
This mechanism would explain why a 62-year old intubated ICU patient on day 5 post-[invasive surgery] receiving a high-protein enteral feed would develop hypernatremia with low urine sodium, high urine osmolality, and a markedly high urea-to-creatinine ratio.
What is catabolism-driven urea diuresis?
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Kidneys are excreting "electrolyte-free water" that contains urea but not electrolytes
High protein feed = increased urea generation
Post-surgical/ICU setting = catabolic stress state
Low urine sodium/high urine osmolality = kidneys retaining electrolytes while losing water
High urea-to-creatinine ratio = increased protein catabolism
This neurologic complication can occur if sodium is corrected too quickly (> ~8 mEq/L per day)
What is osmotic demyelination syndrome?
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If sodium is corrected too rapidly, brain cells cannot readjust their osmolytes fast enough --> osmotic demyelination syndrome --> quadriplegia, “locked-in” syndrome, or death.