• Plasma osmolality (Posm): Osmolarity refers to the number of solute particles per 1 L of solvent, whereas osmolality is the number of solute particles in 1 kg of solvent. Osmolarity are temperature dependent because the volume of solvent varies with temperature. In contrast, osmolality, which is based on the mass of the solvent, is temperature independent. For this reason, osmolality is the preferred term for biologic systems. The normal Posm is 275 to 290 mosmol/kg. The ECF and ICF osmolality are the same as water moves across the membrane

• Posm  =  2  x  [Na] + [Glucose]/18 + Blood urea nitrogen/2.8

• Plasma tonicity reflects the concentration of solutes that do not easily cross cell membranes (mostly sodium salts) and therefore affect the distribution of water between the cells (ICF) and the ECF. By contrast, the plasma osmolality also includes the osmotic contribution of urea, which is considered an "ineffective" osmole since it can equilibrate across the cell membrane.

• Urea equilibration across the blood-brain barrier occurs much more slowly than water equilibration. Thus, urea can transiently act as an effective osmole with respect to the brain. A rapid fall in plasma urea occurs by hemodialysis in a uremic patient. Thus, the plasma osmolality falls much more rapidly than the intracellular osmolality, which promotes osmotic water movement into cells, the water shift can result in cerebral oedema and acute neurologic dysfunction, changes that partially explain the dialysis disequilibrium syndrome.

• Colligative properties affect the freezing point, boiling point, and vapour pressure or dew point of any solution. Osmolality is a colligative property. Measurements reported from an osmometer (lab value) measure osmolality (mosm/kg water) while calculated measurements are estimates of osmolarity (mosm/L solution).

• Hyponatremia is, in most cases, accompanied by a fall in plasma tonicity, which results in osmotic water movement from the ECF into the cells, including brain cells, and can contribute to the neurologic symptoms of hyponatremia.

• Dehydration — Dehydration is defined as a reduction in TBW below the normal level without a proportional reduction in sodium and potassium, resulting in a rise in the plasma sodium concentration. Loss of free-water (insensible loss) results in Hypernatremia

• Hyponatremia:

Hyponatremia represents a relative excess of water in relation to sodium. It can be induced by 

1. Polydipsia  

2. Impaired water excretion (for example CKD or SIADH

•  Hyponatremia treatment depends upon the acuity: the more acute the hyponatremia, the greater the risk for complications.

Acute – If the hyponatremia has developed over a period of fewer than 48 hours. Usually results from parenteral fluid administration in postoperative patients (who have ADH hypersecretion associated with the stress; surgery) and from polydipsia. 

Chronic – Hyponatremia for more than 48 hours or if the duration is unclear.

Goals of hyponatremia therapy: 

Attain the below goals in both initial (first six hours) and subsequent therapy

1. Relieve symptoms of hyponatremia

2. Avoid excess correction (Risk for ODS - Osmotic demyelination syndrome)

3. Decrease intracranial pressure (prevent risk of brain herniation)

4. Prevent further decline in sodium concentration 

1. Relieve symptoms of hyponatremia (<130); 

Though the symptoms are non-specific, they can be relieved by a 4 to 6 mEq/L increase in serum sodium during the first 24 hours (This is the goal rate of correction). Thus, if symptoms persist after an increase of this magnitude, there is no benefit from correcting at faster rate. 

2. Prevent brain herniation;

The risk groups are 1. women and children with acute post-operative hyponatremia, and 2. Patients with intracranial pathology. These patients may rapidly progress to seizures & respiratory arrest. Concurrent hypoxemia, which may result from noncardiogenic pulmonary oedema, can exacerbate hyponatremia-induced cerebral oedema

3. Avoid overcorrection;

Rapid correction can lead to ODS (osmotic demyelination syndrome), especially in chronic hyponatremia with a sodium value below 105 mEq/L and hypokalemia patients.  

4. Prevent further decline in sodium concentration;

The risk groups are 1. Polydipsia (delayed absorption of ingested water), and 2.  Post-operative patients => [ parenteral fluid administration + surgery-induced SIADH ].

Large parenteral isotonic saline administration produce volume expansion and result in sodium excretion in the urine. If ADH levels are high (SIADH), the urine becomes concentrated, and serum sodium falls further (called "desalination"). Thus, administration of additional isotonic saline should be avoided in such patients.

Goal rate of correction; 

• Goal of initial (first six hours) therapy is to raise the sodium concentration by 4 to 6 mEq/L in acute hyponatremia (The rationale is, this increase in concentration is sufficient to reverse symptoms ). In chronic hyponatremia, the same correction happens over 24 hours. The actual correction often exceeds what is intended, and, therefore, targeting an increase of 4 to 6 mEq/L in 24 hours may help avoid overly rapid correction.

• The maximum rate of correction should be 8 mEq/L in any 24-hour period

• Osmoticallay-driven water flows across the blood-brain barrier is the reason for symptoms in hyponatremia. Aggressive treatment with hypertonic saline to prevent brain herniation is the goal of the treatment. Mannitol do the same, but it is nephrotoxic and lowers the serum sodium too.

• The Initial therapy (for the patients with symptoms) is to give 100ml 3% saline followed, if symptom persist, by up to two additional 100ml doses (total 300ml); each bolus is infused over 10 minutes. The goal is to increase serum sodium by 4-6 mEq/L, to alleviate symptoms and prevent herniation. Once the daily correction goal of 4 to 6 mEq/L has been achieved, infusion of 3 percent saline should be discontinued

• If the patient is asymptomatic and sodium level is below 120 mEq/L (sever hyponatremia), then the initial therapy is to start 3% saline at a rate of 15 to 30 ml/hr. 3% saline (rather than normal saline) used in patients with or without hypovolemia.

• Desmopressin can cause hyponatremia (used to treat overt correction). Desmopressin is the hormone that plays role in the control of the body’s osmotic balance. 

• 3% saline (hypertonic) can safely infuse in a peripheral line. The NaHCO3 has the same sodium concentration as 3% saline (50ml of 8.4% is equevalent to 100ml 3% saline = Osmolarity is 2000 mOsml/L)

• Isotonic saline should be avoided in severe hyponatremia (< 120mEq/L)

• Symptomatic hypovolemic hyponatremia management is 3% saline along with normal saline

Rapidly reversible causes of hyponatremia

1. Hypovolemic hyponatremia; Correction of hypovolemia --> inhibit ADH secretion --> Water diuresis

2. Hyponatremia in adrenal insufficiency; Administraion of steroid --> inhibition of ADH secretion --> water diuresis

3. SIADH hyponatremia (post-surgical or SIADH response to pain or drug)

Risk factors of ODS

1. Hyponatremia below 105 mEq/L (The lower the serum sodium concentration, the greater the risk) 

2. Hypokalemia

3. CLD

Fluid restriction;

Fluid restriction to below the level of urine output is indicated for the treatment of symptomatic or severe hyponatremia in edematous states (such as heart failure, CLD, SIADH, and CKD. Restriction to 50 to 60 percent of daily fluid requirements may be required to achieve the goal of inducing negative water balance. The effectiveness of fluid restriction alone can be predicted by the urine-to-serum cation ratio. A ratio of less than 0.5 suggests that the serum sodium concentration will rise with fluid restriction, while a ratio greater than 1 indicates that it will not. Concurrent use of a loop diuretic may be beneficial in patients with SIADH who have a urine-to-serum cation ratio greater than 1

Other therapies for chronic hyponatremia;

• Loop diuretics: Beneficial in patients with SIADH who have a urine-to-serum cation ratio greater than 1

• Urea: It will increase the serum sodium concentration by increasing the excretion of electrolyte-free water. Useful in patients with SIADH

• Potassium: Giving potassium (usually for concurrent hypokalemia) can raise the serum sodium concentration and osmolality in hyponatremic patients. (Intracellular sodium moves into the extracellular fluid in exchange for potassium). Thus, giving potassium chloride alone will correct both the hyponatremia and the hypokalemia. By contrast, many commercially available intravenous potassium solutions are hypotonic (10 mmol in 100 mL of water producing a 100 mmol/L solution). This solution will generally not increase the serum sodium. However, a more concentrated intravenous potassium solution (eg, 20 mmol in 50 mL of water producing a 400 mmol/L solution) will have the same effect on the serum sodium as 40 mL of hypertonic saline.

• Vasopressin antagonists (Tolvaptan): The vasopressin receptor antagonists produce a selective water diuresis (also called aquaresis) without affecting sodium and potassium excretion. The ensuing loss of free water will tend to correct the hyponatremia. 

Approach points

• Use of isotonic saline; It has a limited role in the management of symptomatic or severe hyponatremia

• In true volume depletion (diarrhoea, vomiting or diuretic therapy) the isotonic saline corrects hyponatremia by correcting hypovolemia --> ADH secretion stops --> excess water secreted. Additionally, 1 Litre of NS is approximately correct 1 mEq of sodium (since NS has a higher concentration of 154 mEq/L than plasma)

• Hypertonic saline is indicated in 

  • • • • Acute hyponatremia

        • Symptomatic hyponatremia

        • Severe (<120) hyponatremia

• Do not use isotonic saline in edematous patients or in SIADH

Homeostasis:

Osmotic equilibrium, electrical equilibrium, and acid-base equilibrium are interconnected and play critical roles in maintaining overall homeostasis in the body. Homeostasis refers to the body's ability to maintain a stable internal environment despite changes in the external environment. These equilibriums are fundamental aspects of maintaining the internal balance required for optimal cellular function and overall physiological stability.

Osmotic equilibrium: Osmotic balance ensures that cells are neither excessively swollen nor dehydrated. Cells require a specific balance of water and solutes to function optimally. If there is an imbalance, such as too much water entering or leaving cells, it can lead to cell damage or dysfunction. Osmoregulation, which involves hormonal control of water reabsorption in the kidneys and thirst mechanisms, helps maintain osmotic equilibrium. This regulation ensures that the concentration of solutes in the extracellular fluid and within cells remains relatively stable, contributing to overall homeostasis.

Electrical equilibrium: Electrical balance is crucial for nerve conduction, muscle contraction, and the proper functioning of cells. Cells maintain a specific distribution of ions across their membranes, creating an electrical potential. This potential allows for the transmission of electrical signals necessary for various physiological processes. Disruptions in electrical equilibrium can lead to abnormal nerve impulses, muscle weakness, or irregular heart rhythms. The regulation of ion channels, pumps, and the movement of ions across cell membranes helps maintain electrical equilibrium, contributing to overall homeostasis.

Acid-base equilibrium: The body tightly regulates blood pH to maintain a relatively constant and optimal pH level. Acid-base balance is crucial for enzymatic activity, protein structure, and cellular processes. If blood pH deviates too much from the normal range, it can lead to metabolic acidosis or alkalosis, disrupting various physiological functions. The respiratory and renal systems work together to regulate acid-base equilibrium. The lungs control the elimination of carbon dioxide (a byproduct of metabolism), which helps regulate pH, while the kidneys control the excretion of acids and the reabsorption of bicarbonate ions to maintain acid-base balance. This regulation ensures that blood pH remains within the appropriate range, contributing to overall homeostasis.

These equilibriums are interconnected because imbalances in one can affect the others. For example, disturbances in acid-base balance can influence osmotic balance and electrical equilibrium. The body's intricate regulatory mechanisms aim to maintain these equilibriums within narrow ranges, ensuring that cells and tissues function optimally and overall homeostasis is achieved.