How does the brain sense osmolality?
Before answering this question, it is necessary to understand the meaning of the term osmolality as well as its implications for human physiology.
In chemistry, the osmolality of a solution is defined as the number of moles of solute (e.g. salt or sugar) per kilogram of solvent. When the solvent in question is water, osmolality is practically the same as the more familiar unit osmolarity, which is defined as moles of solute per liter of solvent. Since 1 liter of water has a mass of approximately 1 kilogram, the two values are virtually the same.
In the case of the human circulatory system, approximately 55% of blood volume is composed of straw colored plasma while the remainder is occupied by the so called formed elements of blood: red blood cells, white blood cells, and platelets. Plasma itself is 90% water and contains many dissolved components: glucose, electrolytes (sodium, chloride, and bicarbonate ions); as well as a variety of proteins including albumin, clotting factors, and soluble antibodies.
All of these plasma components contribute to the osmolality of blood, the most important ones being sodium and glucose. Physiologists have assigned a unit to blood osmolality called the milliosmole, abbreviated mOsm. As with all other metabolic parameters, the body must maintain serum osmolality within a safe range, from 280 to 303 mOsm per kilogram of body weight. In other words, the body cannot allow the blood to become either too dilute or too syrupy.
Three brain sensors regulate osmolality
Certain regions of the brain, known as the circumventricular organs, lack a blood brain barrier. In a sense, they act as the brain’s eyes and ears allowing it to quickly assess metabolic parameters and make necessary adjustments. In humans, two of these sensors are the subfornical organ (SFO) and the vascular organ of the lateral terminalis (OVLT), both located near the hypothalamus. These clusters of neurons contain specialized surface proteins called osmoreceptors capable of sensing changes in the concentration of sodium and chloride ions. If the blood becomes too concentrated (hyperosmolality), the SFO and OVLT activate hypothalamic neurons, ultimately culminating in the sensation of thirst.
The third brain sensor is located in the hypothalamus and posterior pituitary gland. It consists of neurons whose cell bodies are located in the suproptic (SON) and paraventricular nuclei (PVN) of the hypothalamus but whose axon terminals extend into the posterior pituitary. These cells also contain osmoreceptors, but to some extent, they rely on hormonal signals from the kidney and adrenal glands to gauge osmolality.
Because the kidneys interpret low blood pressure to mean low blood volume, their default response is to retain sodium. This is accomplished by an elaborate system known as the renin-angiotensin-aldosterone axis. In addition to its renal effects, angiotensin II stimulates SON and PVN cells to release vasopressin, also called antidiuretic hormone (ADH), directly into the bloodstream.
ADH travels to the kidneys, where it acts on cells in the distal convoluted tubules and collecting ducts, causing them to insert special proteins called aquaporins in their membranes. Aquaporins are protein channels that selectively transport water out of the kidney tubules where it finds its way back into the bloodstream, as opposed to being lost in the urine.
Diabetes Insipidus (DI) and SIADH
As you may have guessed, negative consequences ensue if the brain’s osmolality sensors are damaged or become overactive.
Head trauma, tumors, or increased intracranial pressure can compress the posterior pituitary or destroy this structure altogether. Any of these situations lead to a disorder known as central diabetes insipidus, ADH is not released into bloodstream. The kidneys are unable to concentrate urine, and the person may lose over a gallon of fluid a day in the form of dilute urine. Central DI usually responds to desmopressin, a synthetic form of ADH which may be administered intranasally or taken orally. In contrast, in nephrogenic DI, the kidneys themselves are unresponsive to ADH. Nephrogenic DI may respond to thiazide diuretics, although sometimes the only effective treatment is to increase fluid intake to match urine output.
Excessive release of ADH is termed SIADH or Syndrome of Inappropriate ADH release. This condition seldom occurs as an isolated event. For poorly understood reasons, it may occur in the context of pneumonia as well as a paraneoplastic effect of certain malignancies, especially small cell lung cancer. Most cases of SIADH respond to diuretics or to lithium, which induces urination as a side effect.