Osmolality – total solute concentration in a fluid compartment.

• Effective osmole: solute unable to cross from the extracellular fluid (ECF) compartment into the intracellular fluid (ICF) compartment, thereby Ý oncotic pressure and capable of causing water to move across membranes from ECF to ICF.
• Main players:
• Na⁺ (can travel freely between ICF and ECF but is contained to the ECF by the Na/K ATPase and so can cause water diffusion)
• Glucose
• Mannitol
• intracellular K⁺
• Ineffective osmole: solute that does Not cause water movement across membranes so can contribute to osmolality but does NOT contribute to tonicity.
• Main players:
• Urea (able to cross cell membranes so unable to translocate water)
• ethanol
• methanol
• Osmolatity calculation: (mOsm/kg) = 2 ([Na] + [K]) + [glucose]/18 + BUN/2.8
• Note: An increased osmolarity does not necessarily mean that there will be a shift from ECF to ICF (tonicity). If osmolarity Ý because of Ý BUN someone may be hyperosmolar but because urea is an INEFFECTIVE osmole there is no influence on tonicity.

• Tonicity: Ability of the combined effect of all of the solutes to generate an osmotic driving force that causes water movement from one compartment to another so tonicity is a function of the # of effective osmoles divided by the TBW.
• Control of tonicity determines the normal state of cellular hydration and therefore cell size
• Tonicity does NOT equal osmolality because the osmolality is partially defined by ineffective osmoles (urea)
• Extracellular [Na⁺] is the main determinant of plasma tonicity
• Hypertonicity is the main stimulant for Anti-Diuretic Hormone release and Thirst
• Effective osmolality (Tonicity) = 2 ([Na] + [K]) + [glucose]/18 + mannitol/18 + glycerol/9
• Notice the absence of Urea (ineffective osmole) and addition of mannitol and glycerol (effective osmoles)

• [Na⁺]< 135meq/L
• Disorder of Water metabolism NOT Na metabolism
• Sodium concentration: amount of sodium relative to the plasma water. Normal: 135-145mEq/L
• Sodium content: total amount of sodium in extracellular space. Not used clinically
• Clinical presentation:
• Brain swelling
• neurologic deficits
• death
• 3 Flavors: Isotonic, hypertonic, hypotonic (hypotonic is most often presentation because blood is typically hypoosmolal)
• (1) Isotonic hyponatremia: Pseudohyonatremia
• Definition: ß serum [Na+] but NORMAL ECF osmolality and tonicity. Essentially an error in lab analysis, ß serum [Na] is an artifact due to an Ý in plasma volume by Ý of non Na+ solids (proteins or lipids)
• Clinical Presentation: Asymptomatic
• Treatment: requires no treatment
• (2) Hypertonic hyponatremia
• Definition: Condition in which an additional "effective" osmole creates an osmotic gradient for water to move out of the ICF and into the ECF. This dilutes [Na] and contracts the ICF. Tonicity and plasma osmolality will be high.
• Etiology: Most often cause is severe hyperglycemia in uncontrolled DM. Also, hypertonic mannitol
• because glucose is an effective osmole Ý [glucose] Þ water to move from ICF to ECF Þ ß [Na]
• Rule: [Na] ß by 1.6mEq/L for ever 100mg/dl Ý in [glucose] over 100mg/dl
• (3) Hypotonic hyponatremia – most common and most clinically dangerous
• Requires: impaired renal water excretion in the presence of continued water intake so MUST INGEST WATER to get this condition
• Clinical Presentation:
• headache
• nausea
• abdominal cramps
• vomiting
• confusion
• muscle twitching
• comas and seizures
• Normal response to water load: ß effective Posm (tonicity) and Ý in ICF and ECF Þ Ý distal nephron deliver of water Þ suppression of ADH Þ ß in distal nephron water resorbtion Þ excretion of dilute urine Þ return to normal Posm and ECFV
• Requirements for kidney to excrete water: impairment in any of these can result in hypotonic hyponatremia
• (1) adequate GFR
• (2) delivery of water to distal nephron
• (3) adequate separation of the solute and the water in the loop of Henle and diluting segment
• (4) suppression of ADH

Diagnosis – Check plasma osmolality

• Rule out pseudohyponatremia with normal plasma osmolality die to hyperlipdemia or Ý serum proteins: check for normal plasma osmolality
• Rule out hypertoinc hyponatremia due to excessive glucose (insulin deficiency), mannitol, glycerol or sorbitol or an acute contrast load that can’t be excreted: check plasma osmolality
• Hypotonic hyponatremia: Why is renal water excretion impaired or what is the problem in water metabolism (total Na content)? Is patient hypovolemic, hypervolemic or euvolemic?

• (1) Pseudohyponatremia:
• Hypertriglyceridemia
• Hyperproteinemia
• (2) Hyponatremia with hypertonicity:
• Severe hyperglycemia
• Hypertonic mannitol
• (3) Hyponatremia with hypotonicity (requires water intake):
• (a) Hypovolemia (with orthostasis): ß total body Na content
• Etiology: renal disease, or one of several extrarenal mechanisms:
• diarrhea
• vomiting
• burns
• ileus
• post obstruction
• Mechanism: Ý Na and water reabsorption in the proximal nephron (volume homeostasis takes precedence over Osmolarity homeostasis) Þ ß delivery of water distally Þ inability to excrete water
• Treatment: replete volume with NORMAL saline (NEVER use hypotonic saline)
• (b) Hypervolemia: Ý total body Na content
• Etiology:
• CHF
• cirrhosis
• nephrotic syndrome
• acute/chronic renal failure
• Mech: ß in effective arterial blood volume Þ Ý water and Na resorption in the proximal nephron
• for ARF or CRF – inability to excrete water because lack of GFR
• Treatment: water restriction; treat underlying disease
• (c) Euvolemia:
• Etiology:
• Psychogenic polydipsia: massive water drinking that exceeds renal excretory capacity
• Endocrine abnormalities: hypothyroidism: hypothyroidism (inability to suppress ADH)
• Thiazide diuretics: loss of K may cause Na+ to shift into cells
• (d) SIADH (syndrome of inappropriate ADH release)
• Etiology:
• CNS disease: tumor, infection , trauma
• Pulmonary disease: Tb, asthma, infection
• Drugs: narcotic, barbituates, nicotine, etc.
• Postoperative state
• pain, anxiety
• neoplasia
• Mech: ADH levels are elevated in conditions where they should not be
• Treatment:
• Water restriction
• Treat or remove underlying causes
• Consider demeclocycline (tetracycline antibiotic)

• Basics: Correct at rate proportional to rate at which it developed. The rapidity of development of the hyponatremia is more important than the actual value of the serum sodium concentration.
• Central Pontine Myelinolysis: overly rapid correction of hyponatremia. Recall that hyponatremia initially induces swelling of brain cells. Over time cells extrude intracellular osmoles (Na, K, etc.) as a compensation for Ý volume thus normalizing cell volume. Rapid correction of ECF osmolality will lead to rapid shifts of water out of the cells.
• Principles: No faster than 1-2 mEq/L/hr
• amount to administer Na (mEq) = (125- [Na+]) (0.6 x body wt (kg))