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Hyponatremia
[Na] is a measure of Na relative to water.
Low [Na] reflects abnormality of water metabolism rather than sodium metabolism Kidney is the main culprit. Brain is ultimate victim
ECF and ICF Compartments under Normal Conditions and during States of Hyponatremia.
Osmolality
Plasma Osmolality: Posm = 2 (Na) + glucose + urea Normal = 2 (140) + 5 + 5 = 290 (275-290 mM) Urine Osmolality:
Normal: 400-500 mM
Maximal dilution 50-100 mM (USG 1.002-1.003) Maximal concentration 900-1200 mM (USG 1.030-1.040)
Concentrated Urine: > 500 mM (at least!), USG > 1.017 i.e. UOSM > POSM is not enough to R/O Diabetes Insipidus
electrodes Hyperglycemia : decrease of 1.6 mmol/L in the serum sodium level per increase of 100 mg (5.6 mmol/L) in the glucose level) "standard" correction factor of 1.6 may be too low, especially when glucose levels 22.2 mmol/L. correction factor of 2.4 mmol/L may be a better overall estimate
Am J Med 1999;106:399-403
URINE OSMOLALITY
The kidney has a tremendous capacity to generate free water, about 18 liters a day In true hypoosmolar state, urine osmolality assesses ability of kidneys to excrete water.
Each in UOSM 30-35 mM USG by 0.1% (0.001) Therefore, USG of 1.010 ~ UOSM 300-350 mM Larger MW urinary OSM (glucose, radiocontrast, carbenicillin) if
segment) There has to be absence of ADH We can explain all hyponatremia by failure to fulfill one or both conditions.
Urine osmolality
Rare
Extremely reduced solute intake : ability to excrete water reduced by a poor dietary intake
Beer potomania syndrome Anorexics
Hypothyroidism:
ADH-mediated and intrarenal mechanisms implicated inability to maximally suppress AVP Decreased GFR lowers water delivery to TAL
Hyponatremia in Pregnancy
Downward resetting of serum osmolality Mediated by HCG-induced release of relaxin
WHAT NEXT?
Cirrhosis, Nephrotic Syndrome) urine sodium concentration in euvolemic hyponatremia may be less than 20 mmol/L when dietary sodium intake is low
SIADH
Diagnosis
Normal ECFv (or slightly increased) Hypothyroidism & AI ruled out serum Na/OSM UOSM > 100 mM, UNa > 40 mEq/L Low plasma uric acid (< 238 umol/L)
Treatment
Fluid Restriction Oral Salt, Hi-protein diet or Urea(30 g/d): promote solute diuresis Lasix 20 mg po od-bid: Loop direct diminishes medullary gradient Demeclocycline 300-600 mg bid (can be nephrotoxic) Lithium (induces NDI) IV salt solution:
Rarely if ever needed (i.e. only if symptomatic with SZ/coma) Solution given must be of greater OSM than UOSM or in long run will just make hyponatremia worse (often IV NS not sufficient)
SIADH Ddx
Intracranial disease Pulmonary disease Chest wall disorder (surgery, VZV) Severe pain or emotional distress Severe N/V Ectopic ADH: Small cell lung cancer Drugs: opiods, carbamazepine, chlorpropamide, cyclophosphamide, cisplatin, vincristine, vinblastine, amitriptylline, SSRI, neuroleptics, bromocriptine, ecstasy (MDMA)
SIADH: Example
UOSM fixed 600 mM due to ADH action 1L NS given: 300 mM (154 mM each of Na and Cl) All sodium will be excreted as renal sodium handling is intact in SIADH. 300 mmoles of osmols given excreted in 500cc urine (300mmoles/500mL = 600 mM) Therefore net gain of 500 cc free water! 1L 3% saline given: 1026 mmoles Excreted in 1.7L to keep UOSM 600 mM Therefore net loss of 700 cc free water! NOT advocating use of any IV NS (0.9% or 3%) in SIADH unless absolutely neccesary (i.e. SZ, coma). Most SIADH hyponatremia is chronic and should be corrected slowly with fluid restriction ONLY.
capacity. When GFR 5 mL/min, only about 1.5 L/24 h can be excreted as water
Metabolic alkalosis
Rare cause of volume depletion associated with urine
sodium > 40 mmol/l filtered load of NaHCO3 exceeds the reabsorptive capacity of the proximal tubule urinary chloride excretion is low (less than 10 to 20 mmol/L)
Reset Osmostat
25-30% of circumstances which cause SIADH Downward resetting of the threshold for both ADH
release and thirst. Mild asymptomatic hyponatremia (Na 125-135 mEq/L) Distinguish from SIADH by observing response to water load (10-15 mL/kg po or IV) Normal subjects and those with reset osmostat will secrete the entire water load over 4h without any worsening of the hyponatremia Attempts to correct hyponatremia in reset osmostat are not needed and will cause severe thirst
defect is salt wasting not water retention. Circulating factor which impairs renal tubular fn.
ECFv
UNa
Normal
UOSM
Urine volume Serum urate Urine urate
N or
N or N or