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Mineral Homeostasis
Mineral Homeostasis
Mineral Homeostasis
(Section Editor: Ego Seeman)
dren; during grow spurts in adolescence; and during pregnancy Renal C a Handling. The kidney plays a central role in ensur-
and lactation. The efficiency of Ca absorption increases during ing Ca balance, and PTH has a major role in fine-tuning this
prolonged dietary Ca restriction to absorb the greatest portion renal function("'-l2) by stimulating both renal Ca reabsorption
of that ingested. Net absorption declines with age in men and (proximal tubule) and excretion (distal nephron). Multiple in-
women, and so increased Ca intake is required to compensate fluences of Ca handling are listed in Table 2. Descriptions of
for the lower absorption rate. Fecal Ca losses vary between 100 the molecular actions of PTH on the kidney are found else-
and 200 mg/d (2.5-5.0 mmol). Fecal Ca is composed of unab- where in the Primer. PTH has little effect on modulating Ca
sorbed dietary Ca and Ca contained in intestinal, pancreatic, fluxes in the proximal tubule where 65% of the filtered Ca is
and biliary secretions. Secreted Ca is not regulated by hor- reabsorbed, coupled to the bulk transport of solutes such as
mones or serum Ca. sodium and water.'") In this nephron region, PTH can also
Because of the large surface area of the duodenum and
jejunum, 90% of absorbed Ca occurs in these regions. In- I
stimulate the 25(OH)D,-la hydroxylase la(OH)ase], leading
to increased synthesis of 1,25(OH),D,.(13 A reduction in ECF
creased Ca requirements stimulate expression of the epithelial Ca can itself stimulate 1,25(OH),D, production but whether
cellular Ca active transport system in duodenum, ileum, and this occurs through the CaSR is presently unknown. Finally
throughout the colon sufficient to increase fractional Ca ab- PTH can also inhibit Na and HC0,- reabsorption in the proxi-
sorption from 2 0 4 5 % in older men and women to 55-70% in mal tubule by inhibiting the apical type 3 Na'lH' e ~ c h a n g e r " ~ )
children and young adults.l,25(OH),D3 increases the effi- and the basolateral Na'/K'-ATPase'lS' by inhibiting apical
ciency of the small intestine and colon to absorb dietary Ca. Na'/Pi cotransport.
~
Active Ca absorption accounts for absorption of 1Ok15% of a About 20% of filtered Ca is reabsorbed in the cortical thick
dietary load.(') Active transcellular intestinal absorption in- ascending limb of the loop of Henle (CTAL) and 15% is re-
volves three sequential cellular steps: a rate-limiting step in- absorbed in the distal convoluted tubule (DCT). At both sites,
volving transfer of luminal Ca into the intestinal cell through PTH binds to the PTH receptor (PTHR)'".") and enhances
the epithelial Ca channel, expression of TRPV6, a channel- Ca reabsorption. In the CTAL, at least, this seems to occur by
associated protein, annexin2, and calbindin-D9K, and to a
lesser extent, the basolateral extrusion system PMCAl
Reductions in dietary Ca intake can increase PTH secretion TAI3L.E 1. CONDITIONS THATINCREASE O K DEC-RFASE
INTESTINAL
and 1,25(OH),D, production, which can enhance fractional Ca CA ABSOKPTION
absorption and compensates for the dietary reduction.
Intestinal epithelial Ca transport includes both an energy- Iiicreami Cu UhWr[JtlOn Decreused Cu absorption
dependent, cell-mediated saturable active process that is Increased renal 1,2S(OH),D, Decreased renal 1,2S(OH),D,
largely regulated by 1,25(OH),D,, and a passive, diffusional production production
paracellular path of absorption that is driven by transepithelial Growth Vitamin D deficiency
electrochemical gradients. The cell-mediated pathway involv- Pregnancy Chronic renal insufficiency
ing the TRPV6 Ca channel is saturable with a Kt (1/2 maximal Lactation Hypoparathyroidism
transport) of 1.0 mM. Passive diffusion increases linearly with Primary hyper1,arathyroidism Vitamin D-dependent rickets
luminal Ca concentration and is not regulated by 1,25(OH),D,. Idiopathic hypercalciuria type 1
In adults fed a diet low in Ca, enhanced 1,25(OH),D, produc- Increased extrarenal 1,2S(OH)2D3 Aging
tion increases the efficiency of absorption through an increase production Normal 1,2S(OH),D,
in saturable Ca transport. During high dietary Ca intake ab- Sarcoid and other granulomatous production
sorption, 1,25(OH),D, is suppressed and passive paracellular diseases Glucocorticoid excess
transport accounts for most all absorption. Causes of increased B-cell lymphoma Hyperthyroidism
and decreased intestinal Ca absorption are listed in Table 1.
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