Regulation of Calcium Excretion
- The regulation of ECF calcium levels is complex and involves the interaction of multiple endocrine hormones acting on multiple organ systems (See: Calcium and Phosphate Endocrinology). The unique aspect of calcium is that bone represents a large store of the ion that can be mobilized to maintain ECF calcium levels. However, the bone calcium reservoir is not inexhaustible and over the long-term calcium intake must be balanced with calcium excretion. Regulated calcium excretion occurs both in the intestines and kidneys. Here we focus on renal calcium excretion which is largely regulated by its rate of tubular resorption.
- It should be noted that protein-bound calcium cannot be filtered through the glomerular barrier and thus is not subject to renal regulation (See: Calcium and Phosphate Physiologic Forms). Consequently, only the unbound ionic ECF calcium, representing 60% of the total, is subject to renal regulation. Calcium resorption occurs in multiple segments of the nephron via distinct resorptive mechanisms.
- Proximal Tubule and Thick Ascending Loop of Henle
- Roughly 67% of calcium is resorbed in the proximal tubule while 25% is resorbed in the thick ascending Henle. Calcium resorption in these early segments occurs largely via a paracellular route and is dependent on the large amounts of sodium resorption performed. When sodium resorption is inhibited, either by the action of diuretics or ECF volume expansion, calcium resorption also declines and its urinary loss increases.
- The driving force for calcium resorption in the proximal tubule is likely the fact that the ion becomes concentrated as large volumes of water are resorbed in this segment. This is also the case in the thick Henle but in addition the thick Henle carries a large positive luminal potential that adds to the driving force for paracellular calcium resorption.
- Early Distal Tubule
- The early distal tubule is responsible for resorbing the remaining 8% of filtered calcium; however, as discussed below this segment represents the most important locus for regulation of calcium excretion. Unlike the proximal tubule and thick Henle, resorption of calcium in the early distal tubule is independent of sodium. Here, luminal calcium resorption appears to occur through a calcium channel. The resorptive electrochemical gradient for calcium is generated by a basolateral calcium-ATPase.
- Renal calcium resorption is enhanced by all three calcium-modulating hormones, Parathyroid Hormone (PTH), Vitamin D, and Calcitonin; however, the most important hormone is PTH. As discussed in parathyroid hormone physiology, PTH levels are modulated by both blood calcium and phosphate levels. All things being equal, PTH levels rise when blood calcium levels fall whereas PTH levels fall when blood calcium levels rise. The capacity of PTH to enhance renal calcium resorption appears to be by stimulating the basolateral calcium-ATPase in the early distal tubule. Taken together then, the relationship between blood calcium levels, PTH, and renal sodium excretion represent a negative feedback control circuit that maintains relatively stable levels of ECF calcium concentration over the long term.