Dysnatremia in Gastrointestinal Disorders

Abstract

The primary solute of the milieu intérieur is sodium and accompanying anions. The solvent is water. The kidneys acutely regulate homeostasis in filtration, secretion, and resorption of electrolytes, non-electrolytes, and minerals while balancing water retention and clearance. The gastrointestinal absorptive and secretory functions enable food digestion and water absorption needed to sustain life. Gastrointestinal perturbations including vomiting and diarrhea can lead to significant volume and electrolyte losses, overwhelming the renal homeostatic compensatory mechanisms. Dysnatremia, potassium and acid-base disturbances can result from gastrointestinal pathophysiologic processes. Understanding the renal and gastrointestinal contributions to homeostatis are important for the clinical evaluation of perturbed volume disturbances.

Keywords: chloride; diarrhea; emesis; homeostasis; hypernatremia; hyponatremia; sodium.

Figure 1

Sodium reabsorption throughout the nephron. The nephron has multiple sodium chloride transporters to reabsorb filtered sodium so that <1% of filtered sodium is excreted from the body. The proximal tubule (PT) reabsorbs the majority of the filtered load (60%) followed by the thick ascending Loop of Henle (TALH) and the distal convoluted tubule (DCT). Very little sodium remains for reabsorption by the time the tubular fluid reaches the cortical collecting duct (CCD). Sodium is conserved through these redundant reabsorption mechanisms.

Figure 2

Water reabsorption in the nephron. (A) Water is absorbed throughout the nephron via aquaporins (water channels) starting in the proximal tubule and descending loop of Henle. Water reabsorption in the cortical collecting duct reflects the main site of action of ADH. (B) ADH binds to vasopressin V2 receptors, activating an adenyl cyclase to produce cAMP which then activates protein kinase A (PKA). Phosphorylation of PKA leads then to the translocation of the water channel protein aquaporin 2 (AQP2) from their cytosolic location to the apical plasma membrane resulting in the movement of water from tubular lumen to blood.

Figure 3

Daily gastrointestinal fluid volume. Up to 10 liters of fluid traverses the gastrointestinal tract daily from both oral take and pancreatic and luminal secretions. The majority of the volume is reabsorbed in the jejunum and ileum with another 1.4 liters reabsorbed from the colon to reduce the stool volume to 0.1 liter per day.

Figure 4

Key apical membrane ion transporters and channels in the gastrointestinal tract. Stomach: Luminal Cl⁻ channel and H⁺/K+-ATPase play prominent roles in HCl secretion in the gastric parietal cell. Sodium and water enter the gastric lumen through paracellular mechanisms. Pancreas: the Cl⁻/${\text{HCO}}_3^{-}$ exchanger and cystic fibrosis transmembrane conductance regulator (CFTR) are essential in bicarbonate secretion to neutralize HCl secreted in the stomach. Small intestine: Sodium (Na⁺) absorption occurs via the Na⁺/H⁺ exchanger (NHE). Glucose absorption is coupled to Na⁺ absorption through the sodium-glucose cotransporter 1 (SGLT1) and exits the absorptive cell through glucose transporter 2 (GLUT2). Na⁺/K⁺-ATPase serves as efflux mechanism for absorbed Na⁺. Cl⁻ absorption is coupled with ${\text{HCO}}_3^{-}$ excretion through the regulator down-regulated in adenoma (DRA) in the jejunum and ileum. Cl⁻ secretion into the lumen occurs through CFTR. Colon: similar transporters for Na⁺ and Cl⁻ absorption as in the small intestine with the addition of epithelial Na⁺ channel (eNaC). K⁺ absorption is coupled to H⁺ secretion via H⁺/K⁺-ATPase. K⁺ secretion occurs under the influence of aldosterone in the colon, a characteristic unique to this segment. Bicarbonate (${\text{HCO}}_3^{-}$) is secreted in the colon with the absorption of small chain fatty acids (SCFA).

Figure 5

Mechanism of cholera enterotoxicity. Vibrio cholera produces 3 toxins that lead to the copious “rice water” cholera diarrhea: cholera toxin (CT), zona occludens toxin (ZOT) and a neuraminidase. CT binding followed by endocytosis leads to increase in cAMP production and ultimately activation of CFTR leading to increased intestinal Cl⁻ secretion and diarrhea. ZOT increases paracellular fluid permeability, contributing to increased stool volume. Neuraminidase increases the number of CT binding sites in adjacent intestinal cells, amplifying the enterotoxicity of CT.