Pathophysiology of Regulation of Plasma Osmolality

Definition of Osmolarity

Osmolarity refers to the concentration of osmotically active particles per liter of solution, expressed in milliosmoles per liter (mOsm/L). It determines the movement of water between compartments and is calculated as:

Mechanisms of Regulation of Plasma Osmolality (8 marks)

Plasma osmolality is tightly regulated by mechanisms involving osmoreceptors, antidiuretic hormone (ADH), and thirst.

1. Sensors: Osmoreceptors

• Located in the hypothalamus (e.g., organum vasculosum of the lamina terminalis).
• Detect changes in plasma osmolality (threshold: ~280–290 mOsm/L).

1. Effectors

• ADH Secretion:
  • Increased osmolality (>280 mOsm/L) stimulates ADH release from the posterior pituitary.
  • ADH acts on V2 receptors in renal collecting ducts, promoting water reabsorption via aquaporin-2 insertion.
• Thirst Mechanism:
  • Stimulated when plasma osmolality exceeds ~290 mOsm/L.
  • Results in increased water intake, reducing plasma osmolality.

1. Kidney’s Role

• Kidneys regulate water excretion based on ADH levels.
• Maximal urine concentration (~1200 mOsm/L) in dehydration; dilute urine (~50 mOsm/L) in overhydration.

1. Feedback Regulation

• Normalization of plasma osmolality inhibits ADH secretion and suppresses thirst.

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Calculation, Determinants, and Diagnostic Criteria of SIADH

Calculation

Plasma osmolality:
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Urine osmolality and sodium concentration are critical in assessing SIADH.

Determinants

• ADH Secretion: Inappropriate secretion despite normal or low osmolality.
• Renal Response: Persistent water retention leading to dilutional hyponatremia.
• Plasma Findings: Low plasma sodium (<135 mEq/L) and osmolality (<275 mOsm/L).
• Urine Findings: Elevated urine osmolality (>100 mOsm/L) and sodium (>40 mEq/L).

Diagnostic Criteria (3 marks)

1. Hyponatremia with low plasma osmolality.
2. Inappropriately concentrated urine.
3. Euvolemia (normal extracellular fluid status).
4. Absence of adrenal, thyroid, or renal dysfunction.

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Regulation of Plasma Osmolality (5 marks)

• Primary Determinants: Sodium and water balance.
• Mechanisms: Coordination between hypothalamus, pituitary gland, and kidneys.
• Pathophysiological States:
• Dehydration: Increased osmolality triggers ADH secretion and thirst.
• Overhydration: Suppressed ADH secretion reduces water reabsorption.
• SIADH: Disruption in ADH regulation leading to hyponatremia and low plasma osmolality.