Osmoregulation: Control and abnormalities of body water (Physiology)

The osmolarity of the ECF is adjusted by:

❀ Adding or removing water, rather than adding or removing solute.

❀ Regulated water loss primarily occurs in the renal tubule.

❀ The amount of solute-free water excreted by the kidney can be varied.

Water excess leads to:

❀ Large volume of dilute urine.

Water deficit leads to:

❀ Small volume of concentrated urine.

Renal tubule mechanisms of osmoregulation include the ability to vary the amount of solute-free water in the urine.

This involves:

❀ Concentration of interstitial fluid in the medulla.

❀ Dilution of urine in the ascending limb and distal tubule.

❀ Urine concentration (and hence water excretion) can be varied between certain limits by adjusting the concentration of interstitial fluid in the medulla and by dilution of urine in the ascending limb and distal tubule.

❀ ADH is the osmoregulatory hormone.

❀ In its absence, the collecting duct is impermeable to water.

❀ Urine entering the collecting duct in the absence of ADH is maximally dilute.

❀ In the presence of ADH, the osmotic gradient for water reabsorption is large.

❀ Maximally dilute urine is excreted with an osmolarity of approximately 50 mOsm/kg.

❀ ADH is required to unlock water permeability of the collecting duct.

❀ With low levels of ADH, some water will still be reabsorbed in the collecting duct.

❀ Urine osmolality greater than 100 mOsmol/kg is considered to signify the presence of ADH, albeit at a low level.

❀ ADH is the osmoregulatory hormone.

❀ The limit of water reabsorption is set by the osmolality of the medullary interstitial fluid.

❀ The osmolality of the medullary interstitial fluid determines the maximum urine concentration (and hence minimum water excretion) that can be achieved.

ADH exerts its action through:

❀ Binding to vasopressin V2 receptors on principal cells of the collecting duct (CD).

❀ Insertion of aquaporin 2 water channels into the membrane of these cells.

❀ ADH can also bind to vasopressin V1 receptors on vascular smooth muscle, causing vasoconstriction. However, this effect is only significant with very high levels of ADH.

❀ Net water loss increases extracellular fluid (ECF) osmolarity, which is normally maintained within the range of 285-295 mOsm/kg.

❀ Changes in osmolality are detected by osmoreceptors in the anterior hypothalamus.

❀ Osmoreceptors project to the magnocellular neurons of the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus.

❀ PVN and SON neurons release ADH from their axon terminals in the posterior pituitary.

❀ The threshold for ADH release is 280-285 mOsm/kg.

❀ Above the threshold range, small changes in osmolality produce large changes in ADH secretion.

❀ ADH secretion can also be stimulated by large (10-15%) decreases in blood volume or pressure.

❀ Net water loss increases extracellular fluid (ECF) osmolarity, which is normally maintained within the range of 285-295 mOsm/kg.

❀ Changes in osmolality are detected by osmoreceptors in the anterior hypothalamus.

❀ When plasma osmolality is ≥295 mOsm/kg, a strong desire to drink is experienced.

❀ Osmoreceptors project to centers mediating thirst and drinking.

❀ Thirst is reduced by oropharyngeal and upper gastrointestinal receptors after drinking.

❀ Thirst is also stimulated by large (10-15%) drops in blood volume or pressure, as well as by angiotensin 2 acting on the hypothalamus.

❀ Hyponatremia and hypernatremia are examples of abnormalities related to body water control.

❀ Plasma sodium concentration ([Na+]) is the main determinant of ECF osmolality.

❀ The normal range of plasma sodium concentration is 135-145 mmol/L.

❀ The principle of electro neutrality dictates that a molar equivalent number of anions must be present in the ECF, mainly chloride ions (Cl-) with significant amounts of bicarbonate ions (HCO3-) and small contributions from other inorganic and organic anions.

❀ The contribution of sodium to ECF osmolality is estimated as twice the plasma sodium concentration ([Na+]).

❀ Plasma osmolarity in milliosmoles per liter (mOsm/L) can be estimated from the sum of two times the plasma sodium concentration ([Na+]), two times the plasma potassium concentration ([K+]), the concentration of glucose, and the concentration of urea.

❀ Disturbances of water balance are reflected as disturbances of plasma sodium concentration ([Na+]).

❀ Water deficit leads to an increase in extracellular fluid (ECF) osmolality (hyperosmolality) and hypernatremia (plasma sodium concentration > 145 mmol/L).

❀ Water excess leads to a decrease in ECF osmolality (hypoosmolality) and hyponatremia (plasma sodium concentration < 135 mmol/L).

❀ Hypernatremia does not necessarily mean too much sodium; it indicates too little water in relation to sodium.

❀ The total amount of sodium in the body may remain the same, decrease, or increase. The increase in sodium concentration indicates a relative water deficit.

❀ Hypernatremia, with a plasma sodium concentration greater than 145 mmol/L, always indicates hyperosmolality of the extracellular fluid (ECF).

Logically, there are just two possibilities:

❀ Gain of sodium (rare)

❀ Loss of water (common)

Causes of hypernatremia due to gain of sodium include:

❀ Iatrogenic factors.

❀ Excess ingestion of sodium (rare).

❀ Excess mineralocorticoid activity, such as in primary hyperaldosteronism (Conn's syndrome).

❀ In cases of excess mineralocorticoid activity, such as in primary hyperaldosteronism (Conn's syndrome), hypernatremia, if present, is usually mild.

Causes of hypernatremia due to loss of water include:

Extra-renal losses:

❀ Dehydration.

❀ Infection (increased losses via skin and lungs).

Renal losses:

❀ Osmotic diuresis.

❀ Diabetes insipidus.

Diabetes insipidus is characterized by:

❀ Renal water loss due to the inability to concentrate urine.

Diabetes insipidus can result from:

Central causes:

❀ Failure of secretion of antidiuretic hormone (ADH) in the hypothalamus or posterior pituitary.

❀ Nephrogenic causes: lack of response to ADH in the kidneys.

Diabetes insipidus typically presents with:

❀ Polydipsia (excessive thirst) and polyuria (excessive urination).

❀ The thirst mechanism alone is normally enough to prevent significant hypernatremia in diabetes insipidus.

❀ Hypernatremia can rapidly develop in diabetes insipidus if access to water is restricted.

❀ Hyponatremia is more complicated than hypernatremia because the presence of hyponatremia does not always indicate hypoosmolality.

❀ Checking plasma osmolality is unnecessary in cases of hypernatremia because hypernatremia always indicates hyperosmolality.

❀ Checking plasma osmolality is necessary in cases of hyponatremia to determine whether the patient is hypoosmolar or whether another osmotically active solute is present.

❀ Hypoosmotic hyponatremia, sometimes considered "true" hyponatremia, occurs when the proportional contribution of sodium to plasma osmolality is reduced due to the presence of another solute in sufficient quantity.

❀ True hyponatremia is associated with hypoosmolality, indicating water excess, while pseudo-hyponatremia occurs when the proportional contribution of sodium to plasma osmolality is reduced due to the presence of another solute.

❀ Continued ingestion of water without reducing ADH secretion will always lead to hyponatremia.

SIADH is characterized by:

❀ Hyponatremia.

❀ High urine osmolarity.

Many causes of SIADH include:

❀ CNS damage or disease.

❀ Ectopic ADH production by tumors.

❀ Under normal conditions, the function of ADH is osmoregulation.

❀ A large drop in arterial pressure is also a powerful stimulus for the release of ADH.

❀ In the hypovolemic state, maximal renal water retention occurs, leading to the dilution of the extracellular fluid (ECF).

❀ In the hypovolemic state, the low volume/pressure signal overrules osmotic signals, leading to increased ADH release and water retention.

❀ Hyponatremia can occur when total sodium is increased, but total water is increased more, leading to dilution of sodium concentration relative to water.

❀ Congestive heart failure is an example where hyponatremia and hypervolemia can occur concurrently.

❀ In congestive heart failure, the renin-angiotensin-aldosterone system (RAAS) is activated, leading to sodium and water retention (volume expansion).

❀ Volume expansion in congestive heart failure is ineffective due to perturbed Starling forces, resulting in excess capillary filtration and edema formation.

❀ If low volume signals activate ADH, hyponatremia can ensue due to increased water retention despite volume expansion.