Give an account of the role of the kidney in maintaining body fluid homeostasis.

Outline:

·        Importance of maintaining constant body fluid volume

·        Volume sensor signals

·        Role of sympathetic nervous system

·        Renin-angiotensin-aldosterone system

·        Role of ANP in negative feedback

Essay:

            The major solutes of the extracellular fluid (ECF) are the salts of Na⁺ and of these, NaCI is the most abundant. The kidneys are the major route of NaCI excretion from the body. As such, they play an important role in regulating the volume of ECF. Under normal conditions, the kidneys keep the volume of ECF constant by adjusting the excretion of NaCI to match the amount ingested in the diet. The typical diet contains approximately 140 mEq/day of Na⁺. However, the kidneys can vary the excretion of Na⁺ over a wide range.

            The effective circulating volume refers to the portion of the ECF volume that is contained within the vascular system and is “effectively” perfusing the tissues. ECF volume, vascular volume, arterial blood pressure, and cardiac output all depend on the effective circulating volume, which in turn is related to Na⁺ balance. Consequently, the kidneys alter NaCI excretion in response to changes in the effective circulating volume. It is important to maintain the effective circulating volume. Excessive loss of body fluid can lead to circulatory shock and tissue ischemia.

            There are various sensors involved in monitoring the effective circulating volume. Baroreceptors are located within the walls of the cardiac atria and pulmonary vessels and respond to distention of these structures. The activity of these sensors modulates both sympathetic nerve outflow and ADH secretion. Baroreceptors are also present in the arterial side of the circulatory system, located in the wall of the aortic arch, the carotid sinus and the afferent arteriole of the kidneys. These baroreceptors respond primarily to blood pressure. The aortic arch and carotid baroreceptors also send input to the brainstem via afferent fibers in the vagus and glossopharyngeal nerves. The juxtaglomerular apparatus of the kidneys responds directly to changes in pressure. If perfusion pressure of the afferent arterioles is reduced, renin is released from the myocytes. Renin secretion is suppressed when perfusion pressure is increased.

            The sympathetic nerve fibers innervate the afferent and efferent arterioles of the glomerulus, as well as nephron cells. With negative sodium balance (i.e. volume depletion), the sodium sensors stimulate renal sympathetic nerve activity. The afferent and efferent arterioles are constricted by activation of a-adrenergic receptors. This vasoconstriction decreases the hydrostatic pressure within the glomerular capillary lumen, and thereby reduces the glomerular filtration rate (GFR). With this decrease in GFR, the filtered load of sodium to the nephrons is reduced. Renin secretion by juxtaglomerular complex is stimulated via activation of b-adrenergic receptors. NaCI reabsorption along the nephrone is directly stimulated via activation of a-adrenergic receptors.

            The smooth muscle cells in the afferent and efferent arterioles are the site of synthesis, storage and release of renin. A decrease in effective circulating blood volume and perfusion pressure activates the sympathetic nerve fibers innervating the afferent and efferent arterioles as well as the afferent arteriole itself, which acts as a high-pressure baroreceptor, detecting any changes in the perfusion pressure to the kidneys. The end result is an increase in renin secretion. Renin functions solely as a proteolytic enzyme, cleaving angiotensinogen, which is produced by the liver, to yield a 10-amino acid peptide, angiotensin I. Angiotensin I is further cleaved to an 8-amino acid peptide, angiotensin II, by a converting enzyme found on the surface of vascular endothelial cells. Angiotensin II stimulates aldosterone secretion by the adrenal cortex, and arteriolar vasoconstriction, which increases blood pressure. It enhances NaCI reabsorption by the proximal tubule and stimulates ADH secretion and thirst. All these results in the conservation of sodium, and replenishment of water to raise the ECF volume back to normal.

            Aldosterone is a steroid hormone produced by the glomerulosa cells of the adrenal cortex. Aldosterone reduces NaCI excretion by stimulating its reabsorption by the thick ascending limb of Henle’s loop, the distal tubule, and the collecting duct. Aldosterone enters the cell and binds to a cytoplasmic receptor. The hormone-receptor complex enters the nucleus and regulates transcription of mRNA that encodes for proteins important for Na⁺ reabsorption by the cell, such as Na⁺-K⁺-ATPase in the basolateral membrane and Na⁺-channels in the apical membrane.

            The above mechanisms continue to conserve sodium and water till the blood pressure and volume returns to normal. This is detected by the atrial myocytes, which produce and secrete atrial natriuretic peptide (ANP) in response to increase blood volume (stretch of atrial wall). ANP antagonizes the actions of the renin-angiotensin-aldosterone system by vasodilating the afferent arterioles, inhibiting aldosterone secretion, ADH secretion and NaCI reabsorption. Together, these effects of ANP serve as a form of negative feedback to prevent excessive conservation of body fluid.