Osmolality and Tonicity Quiz

Osmolality and Tonicity

• Osmolality: the concentration of osmotically active particles in a solution. Measured by freezing point thermodynamics (or boiling point) and expressed as mOsm/kg.
• Plasma Osmolality: 275-295 mOsm/kg.
• Urine Osmolality: 50-1200 mOsm/kg.
• Calculated Osmolality: Determined by (2 x [Na] + [urea] + [glucose]) of plasma.
• Osmol Gap (OG): Measured osmolality - Calculated osmolality.
  • Normal OG < 10: Osmolality is primarily generated by ions like Cl-, K+, Ca2+, serum proteins, and lipids.
  • OG > 10: Indicates the presence of exogenous substances that are osmotically active, such as alcohols, sugars, lipids, and proteins.
• Tonicity: Determines water movement across compartments. Influenced by effective osmoles, which create an osmotic gradient.
  • Effective osmoles: Na+, K+, glucose (in diabetics), and urea (at extremely high levels). These solutes cannot easily cross cell membranes.
  • Ineffective osmoles: Glucose (in normal individuals), urea, and alcohol. These solutes readily cross cell membranes.
  • Implications:
    • Changes in Na+ concentration affect water movement and lead to hyper/hyponatremia manifestations.
    • Iso-osmolar solutions may not be isotonic, like D5 dextrose 5% - this can result in net water movement as the dextrose is metabolized.
    • Urea contributes to osmolality but not tonicity. A falsely high measured osmolality due to urea should not be treated with hypotonic intravenous fluids.

Water Metabolism

• Daily water requirement (~1500 mL):
  • Obligatory losses: 1500mL (Skin: 500mL, Lungs: 400mL, Gut: 100mL, Urine: 500mL).
  • Sources: 1500mL (Water from oxidative metabolism: 400mL, Diet: 1100mL).
• Minimum Urine Output: Obligatory osmoles excreted / Maximum urine osmolality = 600/1200 = 0.5L.

Response to Water Depletion

• Antidiuretic Hormone (ADH) / Vasopressin (AVP):
  • Produced in the hypothalamus and stored in the posterior pituitary.
  • Stimulus: Osmolality increase (1% change), non-osmotic stimuli (blood volume decrease (10%), stress, nausea).
    • In severe hypovolemia, ADH is secreted to preserve plasma volume at the expense of osmolality and Na+ regulation.
  • Action:
    • Water reabsorption: Through AQP-2 channels at the collecting duct and distal convoluted tubule, mediated by V2 receptors.
    • Vasoconstriction: Via V1a receptors, leading to increased peripheral vascular resistance and blood pressure (in hypovolemia).
    • Negative feedback loop: ADH levels are minimal when plasma osmolality is below 280 mOsm/kg.

Thirst

• Osmolality detected by osmoreceptors in the hypothalamus, stimulating the hypothalamic thirst center (outside of the blood-brain barrier) and activating the median preoptic nucleus.

Disorders of Water Metabolism

Diabetes Insipidus

• Causes:
  • Cranial: 50% idiopathic - dysfunction of the hypothalamus or pituitary gland.
    • Primary hypothalamic (more common): Tumors, vascular incidents, head injury, etc.
  • Nephrogenic: Kidney cannot respond to ADH (tubular injury).
    • Familial: Inherited.
    • Metabolic: Low potassium, high calcium.
    • Lithium toxicity
• Manifestations: Polyuria (dilute urine - >3L/24h), Polydipsia. The patient is often euvolemic with normal Na+ levels (or hyponatremia if insufficient water intake)
• Investigation: Fluid deprivation test.
• Treatment:
  • Treat underlying cause.
  • Cranial DI: DDAVP (desmopressin).
  • Nephrogenic DI: Thiazides (increase Na+ excretion), amiloride (decrease K+ loss), create mild hypovolemia to encourage salt and water uptake in the proximal tubule.

Syndrome of Inappropriate ADH Secretion (SIADH)

• Causes:
  • CNS: Encephalitis, stroke.
  • Lung: Pneumonia, tuberculosis.
  • Drugs: SSRIs, carbamazepine, morphine.
  • Surgery: Small cell lung cancer.
  • Ectopic: Small cell lung cancer, prostate cancer, thymoma.
• Manifestations: Concentrated urine, euvolemic, hypotonic hyponatremia (dilutional hyponatremia). If acute or extreme, cerebral edema can develop.
• Investigation: Urine Na+ and urine osmolality.
• Treatment:
  • Treat underlying cause.
  • Fluid restriction: 1200mL/day
  • Salt: PO administration, hypertonic IV (rare).

Water and Sodium Regulation

• Sensing Parameter:
  • Water: Osmolality, sensed by osmoreceptors in the hypothalamus.
  • Sodium: Intravascular volume, sensed by baroreceptors and chemoreceptors, leading to vasoconstriction.
• Endocrine Regulator:
  • Water: ADH - regulates water reabsorption in the kidneys.
  • Sodium: RAAS (Renin-Angiotensin-Aldosterone System), ANP (Atrial Natriuretic Peptide).
• Major Compartment:
  • Water: ECF and ICF.
  • Sodium: ECF.
• Manifestations:
  • Water: Dehydration (more chronic).
  • Sodium: Hypovolemia (more acute).
• Parameter Affected:
  • Water: ECF sodium content/total sodium content.
  • Sodium: ECF volume.
• Clinical Presentations:
  • Water: Hypernatremia - lethargy, coma due to brain cell dehydration.
  • Sodium:
    • Hyponatremia:
      • Mild: Nausea, lethargy.
      • Severe: Seizures, coma, cerebral edema.
    • Hypervolemia: Edema, weight gain, increased jugular venous pressure, increased right atrial pressure, shortness of breath (pulmonary edema), decreased lung compliance, decreased arterial blood volume, vasoconstriction.
    • Hypovolemia:
      • Poor skin turgor, tachycardia, orthostatic hypotension, decreased capillary refill.
• Implications in Treatment:
  • Water: Free water, e.g., water restriction or D5W (dextrose 5% in water) for hypernatremia.
  • Sodium: Sodium restriction for hypervolemia and normal saline (NS) for hypovolemia.

Test your understanding of osmolality and tonicity concepts with this quiz. Dive into the details of plasma and urine osmolality, the osmol gap, and the role of effective osmoles in regulating water movement. Perfect for students studying physiology or biochemistry.