BASIC FUNCTIONS AND HOMEOSTASIS
Blood enters the kidneys in a series of branching vessels that give rise to afferent arterioles. Each afferent arteriole leads to a tuft of glomerular capillaries. Plasma and small, non–protein bound solutes are ﬁltered across the walls of the glomerular capillaries into Bowman’s space, the initial portion of the nephron. From there, the ﬁltrate is conveyed through the remaining segments of the nephron which include the proximal tubule, thin limb, distal tubule, and collecting duct before being excreted in the ﬁnal urine.
In the various segments of the renal tubules, there is extensive exchange of material with the surrounding capillaries. Such exchange is known as “reabsorption” if materials are transferred from the tubular lumen to the capillaries and/or interstitium, and as “secretion” if they are transferred in the opposite direction.
By continuously adjusting the contents of blood, the kidneys make critical contributions to the maintenance of ﬂuid and salt homeostasis, as well as to the excretion of unwanted chemicals and waste products. In addition, the kidneys contribute to the regulation of arterial pressure, acid-base status, erythropoiesis, and vitamin D synthesis.
Mechanisms Of Homeostasis
To maintain homeostasis, the kidneys must adjust their retention or excretion of ﬂuid and ﬁltered solutes so that, in cooperation with other excretory organs (lungs, skin, bowel), overall output equals intake.
Water, for example, accounts for approximately 60% of total body weight. Approximately two thirds of this volume is intracellular, whereas the remaining third is extracellular. Each day, the average individual consumes approximately 2000 to 2500 mL of water, while carbohydrate oxidation produces another 200 to 300 mL of water. At baseline, these input volumes must be offset by an equal amount of output. On an average day, the kidneys excrete approximately 1500 mL of water, while sweat and feces each contain approximately 100 mL of water. The remaining water is insensibly lost through the skin and lungs.
During signiﬁcant physical exertion, a greater amount of water is lost as sweat and insensible losses. As a result, the relative amount of ﬂuid excreted as urine decreases. Likewise, a person who is severely dehydrated needs to produce far less urine than a person who consumes a large volume of water. A reduction in urine volume could be effected by reducing the rate of plasma ﬁltration from the glomerular capillaries into nephrons; however, this would be an impractical response because the kidneys would consequently be unable to excrete other unwanted substances. Instead, the kidneys continue to ﬁlter a large amount of plasma, but they increase the rate of ﬂuid reabsorption from the tubules so that the ﬁnal urine volume remains low.
The same basic mechanism applies to solutes, such as potassium, calcium, and other salts, the concentrations of which are maintained in very narrow ranges in the extracellular and intracellular spaces. The kidneys ﬁlter these solutes at a largely constant rate, but they alter their rate of excretion based on input from homeostatic sensor mechanisms. Solute excretion can be adjusted by altering the rate of either reabsorption or secretion. Many substances are reabsorbed or secreted using active, transcellular mechanisms that can be very ﬁnely tuned.
The signals that modulate these processes differ depending on the substance in question. For example, aldosterone is released in response to elevated extracellular potassium levels and promotes increased potassium secretion (see Plate 3-10). In contrast, parathyroid hormone (PTH) is released in response to decreased calcium levels and promotes a net increase in calcium reabsorption (see Plate 3-11). The details of these homeostatic mechanisms, as well as some of the complications that occur when they are are discussed in detail later in this section.