The Endocrine Control of Salt and Water Balance Introduction The extracellular fluid ECF has an approximate molarity of 150 mMol L cid 127 Our bodies are protected by an impermeable skin allowing us to retain water which we normally imbibe in a controlled manner cid 127 Our cells have developed mechanisms which maintain an intracellular environment suitable to allow vital enzyme catalyzed reactions to take place in order to sustain life cid 127 Water moves across cell membranes up an osmotic gradient The regulation of osmotically active particles is essential to the maintenance of the internal environment Sodium and chloride ions make up almost all the osmotically active particles in the ECF cid 127 Water is essential for life and represents approximately 2 3 of our body weight Approximately 2 3 of this volume is intracellular with the remainder being extracellular Na K ATPase pumps ensure that Na ions are continually pumped out of cells as fast as they enter down their own electrochemical gradient in exchange for K ions Ensure that the tonicity of the intracellular fluid is closely regulated A sizable part of the BMR is associated with the continuous functioning of these membrane pumps Any increase in extracellular fluid volume ECFV within a restricted space will be associated with an increase in pressure Consequence of sodium retention This can result in chronic increase in mean arterial blood pressure MABP Salt and water regulation and the human body cid 127 Gastrointestinal GI tract The control of salt and water balance involves the GI tract the kidneys and to a lesser extent the skin and lungs Large volumes of NaCl and fluid are secreted into and absorbed from the gut lumen daily Absorptive and secretory processes determining Na and Cl ion movement across the intestinal epithelium are regulated in parallel in order to maintain balance between the systemic fluid volume and the hydration of gut contents Salt and water are absorbed through mechanisms involving channels and pumps within the cell membranes Provides the necessary gradient at the apical membrane down which these ions can enter cells through carrier mechanisms Provides the osmotic gradient up which water flows via aquaporins The kidneys In the general circulation salt and water are mainly regulated by the kidneys There are approximately 1 000 000 renal nephrons per kidney cid 127 Water Na and Cl ions pass through each glomerulus to enter a proximal convoluted tubule along which approximately 2 3 are reabsorbed Driven by Na K ATPase pumps cid 127 More of the remaining water and ions are then reabsorbed along the descending limb of the loop of Henle Near the top of the ascending limn as it becomes the distal convoluted tubule are the specialized sodium sensing cells of the macula densa Adjacent to the juxtaglomerular JG cells of the afferent arterioles from which blood enters the glomerulus JG cells are the source of the enzyme renin which is secreted into the blood where it splits off angiotensin I from the angiotensinogen precursor The distal convoluted tubule is impermeable to water so the final concentration of the tubular fluid takes place along the collecting duct Sweat is produced by two types of sweat gland the eccrine glands which are found on the surface of most of the skin and the apocrine glands which are The skin and lungs found exclusively in the armpit and groin The eccrine glands produce the sweat which promotes cooling Innervated by cholinergic sympathetic nerves cid 127 Water is lost from the lungs on expiration water vapor Insensible water loss unregulated Regulatory mechanisms Salt regulation cid 127 Gastrointestinal absorption Hormones regulate the amount of NaCl absorbed along the intestinal tract The driving force is provided by the low intracellular Na concentration and maintained by the activity of Na K ATPase pumps Angiotensin II and aldosterone receptors are present along different sections of the GI tract Angiotensin type 1 receptors ATR1 are found in smooth muscle angiotensin II stimulated contraction through this receptor Angiotensin type 2 receptors ATR2 are associated with epithelial cells cid 127 Mineralocorticoid receptors MRs are present along the intestinal tract especially the colon but are absent from the gastric mucosa Aldosterone stimulates sodium absorption and potassium secretion Progesterone has an anti mineralocorticoid effect on sodium resorption Iodothyronines stimulate sodium absorption cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 Renal reabsorption The kidneys are central to the overall regulation of NaCl in the body All sections of the renal nephron are involved in NaCl handling The sympathetic nervous system also has an important indirect controlling influence The renin angiotensin aldosterone system RAAS Principal mechanism regulating the production and release of mineralocorticoids Renin is released from juxtaglomerular cells along the afferent arteriole when Renal perfusion pressure is reduced Direct sympathetic stimulation is increased There is a decreased presentation of tubular Na reaching the macula densa cells Renin cleaves the circulating protein angiotensinogen to produce angiotensin I This is then cleaved by ACE angiotensin converting enzyme to produce the active angiotensin II Essentially protected from overwhelming glucocorticoid stimulation because cortisol is converted to inactive form cortisone in the kidneys cid 127 Mineralocorticoids can cause hypertension when produced in excessive quantities chronically ex Conn s syndrome cid 127 When glucocorticoids are produced in excessive amounts ex Cushing s syndrome they can cause hypertension as well Excessive production of angiotensin II as a consequence of a renin producing tumor ex Bartter s syndrome can also cause hypertension directly Stimulates proximal tubular sodium reabsorption directly Accompanied by osmotically driven water reabsorption cid 127 Main controlling influence for aldosterone production cid 127 MRs have an equal affinity for cortisol Converted by beta hydroxysteroid dehydrogenase 2 beta HSD2 beta HSD1 converts cortisone back to cortisol and indirectly Natriuretic peptides NPs Initiate the loss of sodium in the urine natriuresis