CLINICAL METABOLISM HYPONATREMIA AND HYPERNATREMIA BASIC PRINCIPLES Body

CLINICAL METABOLISM

HYPONATREMIA AND HYPERNATREMIA

BASIC PRINCIPLES

• Body Fluids : • Distribution of body fluids : • Fluid compartments : • • ~ 50% to 60% of total body weight consists of water (approximately 50% in women, 60% in men, and 70% in infants). TBW: ~50% (women) to 60% (men) of body weight

• Two thirds of total body water (TBW) is located within cells (intracellular fluid, ICF), with the remainder located in the extracellular fluid (ECF) compartment. • The ECF is composed of interstitial fluid (IF; ~75%) and plasma (~25%), with a minute fraction consisting of transcellular fluids. • Transcellular fluids include many small fluid compartments such as the peritoneal, pleural, synovial, pericardial, and cerebrospinal fluids and the aqueous humor of the intraocular compartment. • Although transcellular fluids normally comprise a minute fraction of the ECF, in disease states such as ascites from liver disease, this fraction can increase substantially.

• Composition of fluid compartments • Intracellular fluid : • Relative to ECF, the ICF has large amounts of protein, potassium, calcium, and phosphate and low levels of sodium and chloride. • Approximately 98% of total body potassium is located within cells; this potassium can play an important role in buffering of a metabolic acidosis. K+ : MAJOR ICF cation

• Extracellular fluid : • Interstitial fluid is separated from the plasma compartment by a barrier that is freely permeable to water and many electrolytes but not to red blood cells (RBCs) and most proteins. • Interstitial fluid has high amounts of sodium and chloride and low amounts of potassium and phosphate • Relatively protein poor because of the selectively permeable capillary plasma membrane.

• Proteins that do leak into the interstitial compartment from the blood are typically returned to the vascular compartment through the lymphatics. • Thus : Dysfunction or obstruction of lymphatic drainage may result in interstitial edema. • Plasma : • Plasma is the fluid component of blood that remains after blood cells (primarily RBCs) are removed. • It normally comprises about 60% of blood volume

• In conditions associated with increased vascular permeability (e. g. , infections, inflammatory states), proteins leave the intravascular space and enter the interstitium. • If the lymphatics are unable to keep up with this transudation of fluid, interstitial edema results. In the lungs, this process can result in acute respiratory distress syndrome (ARDS)

Regulation of Sodium and Water Balance

• Sodium and water are regulated differently. • In the normal state : • Volume is regulated through sodium balance whereas • Osmolarity and sodium concentration are regulated through water balance.

• The kidneys regulate ECF volume by adjusting the rate of sodium excretion. • Under normal circumstances, ECF osmolarity and sodium concentration are regulated through water balance via ADH secretion. • A low Na+ concentration (hyponatremia) results in swelling of the cells (by osmosis) and inhibition (ADH) secretion. • A high Na+ concentration (hypernatremia) results in shrinking of osmoreceptors cells and stimulates ADH secretion.

Effective circulatory volume

• The effective circulatory volume is that portion of the ECF contained within the vascular space that is effectively perfusing tissues. • Extracellular sodium content is the primary determinant of ECF volume. • ECF volume is directly proportional to total body sodium content because sodium, as the primary extracellular solute, acts to retain fluid within the extracellular space.

The body has no way to directly monitor ECF volume • Various pressure and volume detectors located throughout the circulatory system (in the atria, aortic arch, carotid sinuses, and afferent arterioles of the kidney) monitor plasma “volume” and, through various mechanisms, stimulate or inhibit renal Na+ excretion. • The renin-aldosterone-angiotensin system is the most important of these mechanisms.

• The ECV is not directly proportional to extracellular volume in certain conditions such as congestive heart failure and cirrhosis with ascites. • In CCF, the impaired cardiac output is unable to stretch the baroreceptors; this leads to the perception of inadequate circulating volume, which triggers further fluid retention. • In cirrhosis, fluid sequestration in ascitic fluid and in the dilated splanchnic bed results in a markedly expanded extracellular volume. • However, this expanded volume is effectively invisible to the detectors of effective circulating volume, which trigger further fluid retention and consequent exacerbation of the ECF excess.

• Hyponatremia is common in both conditions due to pathologically increased secretion of ADH, and its presence is a poor prognostic factor.

• Response to decrease in effective circulating volume : • The body perceives the ECV in relation to the pressure that is perfusing the arterial stretch receptors in the carotid sinus, the aortic arch, and the glomerular afferent artery. • When stretch receptors are activated by reduced blood flow, they send signals to the brainstem to increase sympathetic outflow.

• The increase in sympathetic outflow alters the circulatory system in several ways : • It increases cardiac contractility and heart rate, thereby increasing cardiac output. • It promotes venoconstriction, which moves blood into the arterial circulation increasing the effective circulating volume. • It stimulates arteriolar constriction, which raises systemic blood pressure and increases arterial perfusion pressure. • It stimulates sodium retention by the kidneys, which increases intravascular volume

• A reduced ECV can occur in conditions such as : • Diarrhea • Adrenal insufficiency • Volume depletion (dehydration).

• Response to increased effective circulating volume : • The increased cardiac output causes stretching of baroreceptors, which triggers cessation of sympathetic outflow from the brainstem. • Reduced sympathetic outflow has multiple effects, including : • Vasodilation • Reduced cardiac contractility • Decreased renal fluid retention • All of which lower cardiac output and blood pressure, thereby reducing baroreceptor stretch.

• Multiple conditions can cause a volume-expanded state : • Isotonic Na. Cl infusion • High Na. Cl intake • SIADH

• Hyponatremia : • Hyponatremia is defined as serum [Na+]<136 meq/l. • Hyponatremia can be associated with low, normal or high tonicity. • What would be a common cause?

• It can result from a particular laboratory technique or from improper blood collection, excessively high water intake, or, most commonly, an inability of the kidneys to excrete free water. • The drugs most commonly associated with the development of hyponatremia are thiazide diuretics and NSAIDs

• Most symptoms of hyponatremia are caused by cerebral edema from transcellular shifts of plasma water into cells of the central nervous system (CNS). • Symptoms and signs usually do not manifest until the sodium concentration is lower than 125 mmol/L. • These can include nausea, emesis, headache, seizures, lethargy, development of focal neurologic deficits, respiratory depression, and coma. • Serious neurologic changes such as seizure and coma are usually not seen until the sodium concentration is lower than 110 to 115 mmol/L. • Patients with rapidly developing severe hyponatremia (<120 mmol/L over 24 -48 hours) are at highest risk for developing serious, life-threatening CNS disturbances.

• Patients are classified as hypovolemic, euvolemic, or hypervolemic according to features of the : • History (e. g. , emesis, diarrhea) • Physical examination findings (e. g. , flat or distended neck veins, dry or moist skin or mucosa, heart rate, blood pressure, orthostatic vital signs, presence of edema or ascites).

Causes of Acute Hyponatremia • Iatrogenic Postoperative: premenopausal women Hypotonic fluids Glycine irrigation: TURP, uterine surgery Colonoscopy preparation Recent institution of thiazides • Polydipsia • Exercise-induced

APPROACH

• Correction of Sodium : • Calculate sodium deficit: • 0. 6 x (weight in kg) x (desired sodium - Actual sodium) • 0. 6 x (weight in kg) = ? ? ? • 0. 6 x (weight in kg) = TBW

• Fluid restriction if patient is not hypovolemic • Rate of correction? ?

• Generally, half the deficit is given over 12 hours • Patients presenting with seizures or other severe neurological symptoms suggestive of cerebral edema need a fast rate of correction 8 -12 meq/day. In general, the plasma sodium should not be corrected to >125– 130 m. Eq/l. . • Rapid correction of hyponatremia increases the risk for osmotic demyelination (central pontine myelinolysis) due to movement of water out of the edematous neurons, causing shrinkage and disruption of interaction with their myelin sheaths

• Patients that are more prone for osmotic demyelination include women, patients with chronic alcohol abuse, hepatic failure and malnutrition • Central pontine myelinolysis (CPM) presents with fatal outcomes - quadriplegia, pseudobulbar palsy, seizures, coma and death.

• A widely used formula is the • Adrogue-Madias formula: • Change in serum Na+ with infusing solution= [infusate. Na+ + infusate K+] - Serum Na+ (total body water +1)

• Assuming that total body water comprises 50% of total body weight, 1 ml/kg of 3% sodium chloride will raise the plasma sodium by 1 m. Eq/l. • IV SOLUTION?

Fluid (infusate) Na Content m. Eq/L Sodium Concentration per m. L Lactated Ringers 130 0. 13 m. Eq/ml 0. 9% Na. Cl 154 0. 154 m. Eq/ml 1. 8% 30* 0. 38 m. Eq/L 3% Na. Cl 513 0. 513 m. Eq/ml 5% Na. Cl 855 0. 855 m. Eq/ml

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