Hypotonic hyponatremia

Sodium is the dominant extracellular cation in blood and ECF, playing a major role in osmotic pressure regulation alongside its roles in a plethora of biochemical processes including solute transport and neural signaling. Since these are charged ions, they do not easily cross the lipophilic (nonpolar) cell membrane, unlike water which passes through the membrane freely through protein channels known as aquaporins. Under normal conditions, the osmotic gradient across the cell membrane is effectively zero, as any other value would be quickly corrected through the unimpeded flow of water towards the more concentrated side. In patients with hyponatremia, the osmotic pressure outside of the cell becomes decreased (less negative - osmotic pressure is effectively an attractive force) relative to the inside the cell. The net result is that water will flow into the cells until the equilibrium is reestablished. This causes cells to swell. Tissue swelling is particularly problematic in parts of the body that lack room for expansion - namely, the brain. Unlike most of the body, the brain is fully encased in a rigid skull that has a fixed volume. As the brain increases in volume, it will begin to fully occupy the skull, at which point it can no longer freely expand. If, by this point, the osmotic pressure of the brain tissue has not fully equalized, the osmotic pressure driving water inwards will start being countered by physical pressure applied by the surrounding skull. The increased pressure on the brain results in many adverse effects on neural function as blood and its contents become inhibited from entering the cells. This induces a local state of hypoxia as oxygen-rich blood cannot adequately reach the brain, resulting in neural disfunction. In the most extreme cases, the intracranial pressure becomes so severe that the brain is physically squeezed out of the skull through the foramen magnum, an typically fatal condition known as cerebral herniation. ==Cause==

Hypotonic hyponatremia can have many causes that can be further classified by the overall fluid status of the body - hypovolemic (low), euvolemic (normal), and hypervolemic (high). The etiology and management of hyponatremia is dependent on the fluid status of the patient. Hypovolemic Hypovolemic hyponatremia causes mainly involve loss of fluid and salt. This loss can be caused by factors both internal and external to the kidney, the organ chiefly responsible for fluid balance. Differentiation between renal and extrarenal causes can be conducted through analysis of urine sodium content - in renal cases, the kidney fails to retain sodium, resulting in inappropriately elevated urine sodium. In extrarenal cases, the kidney appropriately reabsorbs sodium, resulting in a low urine sodium concentration. • Extrarenal (urine sodium 20) • Diuretic drugs (especially thiazides) • Addison's disease • Cerebral salt-wasting syndrome • Other salt-wasting kidney diseases Euvolemic Euvolemic hyponatremias are mostly caused by conditions resulting in sodium being excreted from the body but when a patient consumes enough water to maintain their overall fluid status. These include: • Polydipsia • Syndrome of inappropriate antidiuretic hormone secretion • Hypothyroidism • Poor oral intake Hypervolemic Hypervolemic hyponatremia can be described as a dilutional condition in which excess water is retained in the body. Causes of this include: • Congestive heart failure • Hypothyroidism • Adrenal Insufficiency • Liver cirrhosis • Nephrotic syndrome • Psychogenic polydipsia • Acute kidney injury • Chronic kidney disease == Signs and Symptoms ==

Symptoms of hyponatremia are often nonspecific, and depend on both severity and chronicity. In acute cases, patients may present with a range of neurological deficits including headache, fatigue, lethargy, confusion, memory impairment, seizures, and somnolence - the latter two indicated severe hyponatremia. == Diagnosis and Treatment ==

Diagnosis Diagnosis of hypotonic hyponatremia is principally one of bloodwork and treatment involved restoration of sodium levels. Routine tests like the basic metabolic profile (BMP) will demonstrate low sodium concentration. Once low sodium is detected, the next step in diagnosis is to check overall blood osmolality. If this is also low, a diagnosis of hypotonic hyponatremia is made. Cases that occurred for longer than 48 hours are classified as chronic and require much more delicate correction to prevent a condition called Osmotic Demyelination Syndrome (ODS). Cases whose chronicity is unknown, as is usually the case since it is unlikely that a patient presenting from outside of a hospital setting to have had bloodwork done within the prior 48 hours, are considered chronic in regards to treatment. Treatment Overview of treatment Treatment of hyponatremia is simple in principle but often quite complex in practice. The goal of treatment is to return to eunatremia, accomplished by administration of sodium and/or vasopressin receptor antagonists (vaptans) a US expert panel recommending only 8 mEq/day in high risk cases, Reactive approaches are centered on halting further sodium increase after the desired level is achieved, usually through administration of D5W to replace any urinary water losses after the sodium has risen to the desired level. As its name suggests, this manifestation occurs when demyelination occurs within the central pons of the brain, a region of the brainstem that is responsible for communication between the cerebral cortex and spinal cord. This can result in various movement disorders including dysarthria, dysphagia, pupillary control, reflexes, and even Locked-In Syndrome or coma. When lesions occur outside of the pons, the condition can be described as Extrapontine Myelinolysis (EPM). In cases of EPM, the symptoms have much greater variance and will be driven by where the lesions develop. These symptoms can be expected to mirror those of any other type of brain injury in their respective region. For example, lesions developing in the Prefrontal cortex would be expected to cause disinhibition and behavioral issues much like a prefrontal cortex injury whereas a lesion in Broca's area would likely cause Broca's aphasia similar to a stroke affecting the same region. == Prognosis ==

The overall prognosis of patients presenting with hyponatremia is not easily described as there are many factors to consider. Short-term prognosis is naturally going to depend on why the hyponatremia has occurred, how severe it is, and how effectively it was corrected. Longer-term prognosis will depend on both the underlying cause of the hyponatremia and whether the patient develops ODS. While numerous studies have been published on the topic of long-term hyponatremia prognosis, most are single-center studies that focus on specific population subsets making it difficult to draw more generalized conclusions. == References ==