Summarize the renal handling of calcium illustrating the role of main regulators of renal calcium excretion.
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Muhammad Soobadar
10 g of calcium filtered by kidney
100mg excreted in urine meaning 98/99% reabsorbed by kidney
total serum calcium in profile includes ( ionised, complex – bound or protein bound) and filterable is only ionised and complex bound
PCT 70% Reabsorbed ( mainly passive mirrors and sodium and water( 80%) and 20% is active and mediated by PTH and Calcitonin.
Loop of Henle-20% Reabsorpbed by transcellular and paracellular . Mainly paracellular driven by transttubular electrochemical driving force. this is set up by Na/K/Cl transported and ROMK channel. There has been studies that demonstrated that inhibition of CASR but increased calcium permeability to paracellular pathway.
DCT 10% Reabsorbed by actively by transcellular route.
Main regulators of renal Ca : A.Increase Ca absorption
Ionized ca is filtered across glomerulus and tea sorbet in PCT and loop of Henle paracellulary along concentration gradient . TRPV5 regulate 10 % .
urinary Na influence urinary ca excretion strongly : in thick ascending loop of henle increases Na delivery forces na uptake at expense of ca resorption lead to hypercalciuria ( stone formation)
hypocalcemia activate parathyroid caSR lead to release of parathyroid hormone released with increase ca reabsorpotion and hydroxylation of vitamin D3 to active metabolite increasing intestinal uptake
The filtered 10 grams of calcium is mainly reabsorbed in the PCT (60-70%), followed by 20,10 and 5 % in TAL, DCT, and SD, respectively. This reabsorption in DCT is usually passive, following sodium and water and mainly (about (80%) by passive diffusion. PTH and calcitonin regulate the other 10-20 %. PTH augments renal calcium absorption. Calcium sensing receptors play a role in this regulation and sensing. The hydroxylation of vitamin D takes place in the kidneys. Importantly the kidneys regulate calcium by suppressing of 1 alpha-hydroxylase and activating 24-hydroxylase when needed to suppress the calcium reabsorption
99% of filtered Ca is reabsorbed by the kidneys, 80% mainly through passive para-cellular route (70% in PCT following Na+H2O & 10% in CTALH- following ROMK and NKCC2 activation), small but significant remaining 20% reabsorbed through secondary active trans-cellular transport under PTH control (5-10% in DCT via Na/Ca exchanger & 5-10% in CD which is the major site of regulation)
decreased by stimulation of CaSR by hypercalcemia & calcitonin & ECF expansion & metabolic acidosis & loop diuretics.
PTH: is secreted after hypocalcemia and vitamin Deficiency, it controls active trans-cellular pathway in all nephron parts (PCT, CTALH, DCT and CD), with resultant bone resorption (indirect stimulation of osteoclast) & increases renal calcium reabsorption & indirect increase intestinal calcium absorption- through vitamin D activation)
1,25 OH Vitamin D3: stimulate both intestinal calcium absorption and renal calcium reabsorption
loop diuretics: inhibit NKCC2 interfering with Na reabsorption and electric gradient resulting in decreased paracellular Ca and Mg transport
Thiazide: causes volume depletion which increases PCT Ca reabsorption, another mechanism: thiazide inhibits NCC (DCT thiazide sensitive Na/Cl cotransporter), thereby Na/K pump, blockage of the Na/Cl channel increases the flow of ions through the Na/Ca channel, resulting in increased calcium reabsorption into the interstitium in exchange for Na.
Acute/ chronic Metabolic acidosis: causes bone resorption (increased H ions are buffered in the skeleton, mobilizing calcium from the bone into circulation, increasing filtered calcium and calciuria.
Hypercalcemia causes increased filtered load of Ca hence decreases tubular reabsorption , but opposed by hypercalcemia induced renal vasoconstriction
ECF volume expansion is associated with Na & Cl & Ca excretion, where as reciprocal changes are seen with volume contraction
the renal handling of calcium illustrating the role of main regulators of renal calcium excretion:the kidneys reabsorb 97-99% of daily filtered calcium.
of this reabsorbed ,60-65%is reabsorbed by proximal tubule via the paracellular route and 25-30 is reabsorbed in the TAL,also paracelularly.
the remaining 8-10%is reabsorbed in the distal convulated
60%–70% of the filtered calcium is reabsorbed in the proximal convoluted tubule, 20% in the loop of Henle, 10% by the distal convoluted tubule, and 5% by the collecting duct.
Proximal tubular calcium reabsorption is thought to occur mainly by passive diffusion and solvent drag.
The passive paracellular pathways account for approximately 80% of calcium reabsorption in this segment of the nephron. A small but significant component of active calcium transport is observed in the proximal tubules.
No reabsorption of calcium occurs within the thin segment of the loop of Henle.
In the thick ascending limb, the bulk of calcium reabsorption proceeds through the paracellular pathway and is proportional to the transtubular electrochemical driving force.
the distal tubule reabsorbs calcium exclusively via the transcellular route.
Regulators of renal Ca excretion:
A. ↑↑↑Ca absorption
Hyperparathyroidism
vit D
Metabolic alkalosis
Thiazides diuretics
volume depletion.
B.↓↓↓ Ca absorption
Hypoparathyroidism
vit- D deficiency
Hypercalcaemia
Metabolic acidosis
Loop diuretics
volume expansion
10 g of Ca is filtered /day and 98% is reabsorbed by the renal tubules, the proximal tubules reabsorbs 65% to 70%, by solvent drag following reabsorption of water and urea
20% is reabsorbed in the thick ascending loop of Henle driven by lumen positivity, which in turn is created by NKCC channel and exiting of K via ROMK to the lumen.
Summarize the renal handling of calcium illustrating the role of main regulators of renal calcium excretion.The renal handling of calcium:
98%–99% of the filtered load of calcium is reabsorbed by the renal tubules. Approximately 60%–70% of the filtered calcium is reabsorbed in the proximal convoluted tubule, 20% in the loop of Henle, 10% by the distal convoluted tubule, and 5% by the collecting duct. The terminal nephron, although responsible for the reabsorption of only 5%–10% of the filtered calcium load, is the major site for regulation of calcium excretion
There are two routes for the absorption of calcium across the intestinal epithelium: the paracellular pathway (i.e., between the cells) and the transcellular route (i.e., through the cell)
PTH : which stimulates calcium absorption.response to a decrease in the plasmaconcentration of ionized calcium. Therefore, the major physiologic role of the parathyroid gland is to regulate calcium homeostasisPTH acts to increase the plasma concentration of calcium in three ways: (1) it stimulates bone resorption, (2) it enhances intestinal calcium and phosphate absorption by promoting the formation within the kidney of 1,25(OH)2D, and (3) it augments active renal calcium absorption. These effects are reversed by small changes in the serum calcium concentration that lower PTH secretion.
Vitamin D , 1,25(OH)2D, which acts upon the target organ receptors to maintain calcium homeostasis and bone health, it enhances intestinal calcium absorption
Metabolic Acidosis, Acute and chronic metabolic acidosis can be associated with an increase in calcium excretion, independent of PTH changes.directeffects of acidosis on tubular calcium resorption also play a role
Diuretics. Loop diuretics decrease calcium absorption as a result of inhibition of the transport of sodium chloride at the NKCC2 transporter in the ascending loop of Henle. Thiazide diuretics, which act in the distal tubule, are associated with hypocalciuria . Two main mechanisms have been proposed to explain the effect of thiazides on calcium excretion: (1) increased proximal sodium and water reabsorption due to volume depletion, and (2) increased distal calcium reabsorption at the thiazide-sensitive site in the distal convoluted tubule.
The role of main regulators of renal calcium excretion.
60 to 70% is reabsorbed by PCT (paracellular pathway)
20% in the loop of Henle
10% in DCT (Active process)
5% in CD
Main regulators of renal Ca : Increase Ca absorption: Hyperparathyroidism, vit D, Metabolic alkalosis, Thiazides diuretics, volume depletion. Decrease Ca absorption: Hypoparathyroidism, vit- D deficiency, Hypercalcaemia, Extracellular fluid expansion, Metabolic acidosis, Loop diuretics
In humans who have a GFR of 170 liters per 24 hours, roughly 10 g of calcium is filtered per day. The amount of calcium excreted in the urine usually ranges from 100 to 200 mg per 24 hours; hence, 98%–99% of the filtered load of calcium is reabsorbed by the renal tubules. Approximately 60%–70% of the filtered calcium is reabsorbed in the proximal convoluted tubule, 20% in the loop of Henle, 10% by the distal convoluted tubule, and 5% by the collecting duct. The terminal nephron, although responsible for the reabsorption of only 5%–10% of the filtered calcium load, is the major site for regulation of calcium excretion.
The reabsorption of calcium in the proximal convoluted tubule parallels that of sodium and water. Proximal tubular calcium reabsorption is thought to occur mainly by passive diffusion and solvent drag.
A small but significant component of active calcium transport is observed in the proximal tubules.
No reabsorption of calcium occurs within the thin segment of the loop of Henle .In the thick ascending limb of the loop of Henle, 20% of the filtered calcium is reabsorbed largely by the cortical thick ascending limb, through both transcellular and paracellular routes.
The apical Na1 -K1 -2Cl2 cotransporter NKCC2 and the renal outer medullary potassium K1 (ROMK) channel generate the “driving force” for paracellular cation transport.
Calcium transport in the thick ascending limb of the loop of Henle is also influenced by the calcium-sensing receptor (CaSR) ,which is localized in the basolateral membrane.
Calciotropic hormones, such as PTH and calcitonin, stimulate active cellular calcium absorption in the cortical thick ascending limb.
the distal tubule reabsorbs calcium exclusively via the transcellular route. The distal convoluted tubule absorbs 5%–10% of the filtered calcium.
Calcium absorption in this segment is active because it proceeds against a chemical and an electrical gradient.
10 g of Ca is filtered /day and 98% is reabsorbed by the renal tubules
100 to 200 mg of Ca is excreted in urine/day
Main site for reabsorbtion 60 to 70% is PCT (paracellular pathway) -ve process
20% in the thick ascending loop of Henle
10% in DCT (Active process)
5% in CD
Main regulators of renal Ca :
Renal handling
In human GFR of 170liters /24hrs filtered about 1g of calcium filtered, the amount of calcium excreted 100-200mg per day in urine, 98-99%reabsorped.
60-70%in Proximal tubule 20%in loop of henle, 5-10%in distal CT and 5% in collecting duct.
Factors increase Ca absorption include
*PTH it stimulate bone resorption, increase intestinal absorption and increase renal reabsorption
*active vitamin D :increase intestinal absorption of Ca
*hypocalcimia : it increase renal tubular absorption
*volume contraction this cause increase tubular absorption of Ca
*metabolic alkalosis :
*thiazide diuretics
Factos decrease Calcium absorption
*hypoparathyroidism
*low calcitriol
*hypercalcimia
*Volume expansion
*metabolic acidosis
*loop diuretics
Complex fraction, 7%, bound to molecules such as phosphate and citrate.
Ultrafiltered calcium contains ionized and complex calcium.
Normal serum calcium is approximately 8.9-10.1 mg/dl, (2.2-2.5 mmol/L).
For each 1.0 g /dL decrease in albumin, total serum calcium decrease by 0.8 mg/dL.
For each 1.0 g/dL decrease in serum globulin, serum calcium decrease by 0.12 mg/dL.
Acute alkalosis decreases the ionized calcium, so with every 0.1 change in pH, ionized calcium changes by 0.12 mg/dL.
In a GFR of 170 liter/24hrs, approximately 10 g of calcium is filtered per day.
The calcium excreted in the urine usually from 100-200 mg/24hrs, hence 98-99% of the filtered load is reabsorbed by the renal tubules, (60-70% in the proximal tubules,20% in the loop of Henle influenced by CaSR, 10% by the DCT, and 5% by the CD).
In the proximal tubule; reabsorption occurs mainly by passive diffusion and solvent drag, with 80% through the paracellular pathway.
Active but significant calcium reabsorption (10-15%) in the proximal tubules is processed in 2 steps; (entered via the apical membrane and exiting via the basolateral membrane) and is mainly regulated by PTH and calcitonin.
Proximal convoluted tubule – the main place Where calcium get reabsorbed . He main way of reabsorption of calcium is through paracellular way in 80 percent of cases..
The transcellular way occur in 20 percent of cases and regulated through PTH and calcitonin.
In the Ascending thick Loop of Henle – the NKCC2 channel with help of ROMK produce a intraluminal positive electrochemical charge and negative intracellular. This help calcium to diffuse theough paracellular pathway. So the main transport still paracellular.
CaSR play here. It control calcium reabsorption through Claudin expression.
The tight junctions are guarded by proteins like claudin-16 and claudin-19, which act like bouncers themselves and only let certain ions through.
Distal convoluted tubule-exclusively Transcellular and is very controlled through PTH.. The epithelial cells here had some special proteins called TRPV5 and TRPV6 that were like little calcium vacuum cleaners. These proteins actively transported calcium ions from the tubular fluid into the epithelial cells. PTH increase will increase the expression of TRPV 5&6
What alter the renal regulations of calcium?
Factors increasing calcium absorption are:
Hyperparathyroidism, calcitriol, hypocalcemia, volume contraction, met alkalosis and thiazide.
Factors that decrease calcium absorption :
Hypoparathyroidism
Low vit vitamin D
hypercalcemia extracellular fluid expansion, metabolic acidosis and loop diuretics.
The proximal convoluted tubule reabsorbs calcium like sodium and water. Passive diffusion and solvent drag cause proximal tubular calcium reabsorption. Based on the discovery that proximal tubule fluid and glomerular filtrate calcium ratios are 1:1.2.
In this nephron segment, passive paracellular routes absorb 80% of calcium. Proximal tubules have a modest but significant active calcium transport component. Calcium enters the tubular fluid via the apical membrane and exits through the basolateral membrane during active transport. PTH and calcitonin control this active transport, which accounts for 10%–15% of proximal tubule calcium reabsorption.
The thin loop of Henle does not reabsorb calcium. 20% of the filtered calcium is reabsorbed by the cortical thick ascending limb of the loop of Henle through transcellular and paracellular pathways. Calcium reabsorption via the paracellular route is proportional to the transtubular electrochemical driving force in the thick ascending limb. NKCC2 and ROMK are apical Na1-K1-2Cl2 cotransporters.
The basolateral membrane-localized calcium-sensing receptor (CaSR) affects calcium transport in the thick ascending limb of the loop of Henle.
Now we know how CaSR governs thick ascending limb calcium reabsorption. In microdissected, in vitro micro-perfused rat cortical thick ascending limb, The thick ascending limb tight junction expresses claudin-14, -16, and 19.
Divalent cation absorption in this tubular segment requires proper claudin-16 and -19 expression. Toka et al. found that CaSR disruption lowers claudin-14 mRNA and increases claudin-16.
Cinacalcet increases claudin-14 mRNA, which lowers paracellular calcium permeability in cell culture models. PTH and calcitonin activate cellular calcium absorption in the cortical, thick ascending limb.
Renal handling calcium and main regulation
Many hormones and factors regulate the ca handling
1-) PTH Secreted by parathyroid gland .The changes in serum calcium are sensed by Ca SR which is localized in the cell membrane of the para thyroid cell In hypocalcemia PTH secreted and acts to increase plasma concentration of calcium in three ways 1- stimulate bone resorption 2- enhance intestinal ca and pi absorption by promotion formation of calctriol by the kidney 3- it augment active renal ca absorption 2-) vit D 25 hydroxy vit- D ( calcidiol ) produced by the liver and then activated in the kidney tubular cell contain hydroxylase enzymes which produced active vit D 1,25 dihydroxy vit D
Enhance intestinal calcium absorption
And induce bone osteoclastic activity
10 g of calcium filtered by kidney
100mg excreted in urine meaning 98/99% reabsorbed by kidney
total serum calcium in profile includes ( ionised, complex – bound or protein bound) and filterable is only ionised and complex bound
PCT 70% Reabsorbed ( mainly passive mirrors and sodium and water( 80%) and 20% is active and mediated by PTH and Calcitonin.
Loop of Henle-20% Reabsorpbed by transcellular and paracellular . Mainly paracellular driven by transttubular electrochemical driving force. this is set up by Na/K/Cl transported and ROMK channel. There has been studies that demonstrated that inhibition of CASR but increased calcium permeability to paracellular pathway.
DCT 10% Reabsorbed by actively by transcellular route.
Main regulators of renal Ca :
A.Increase Ca absorption
B.Decrease Ca absorption
Ionized ca is filtered across glomerulus and tea sorbet in PCT and loop of Henle paracellulary along concentration gradient . TRPV5 regulate 10 % .
urinary Na influence urinary ca excretion strongly : in thick ascending loop of henle increases Na delivery forces na uptake at expense of ca resorption lead to hypercalciuria ( stone formation)
hypocalcemia activate parathyroid caSR lead to release of parathyroid hormone released with increase ca reabsorpotion and hydroxylation of vitamin D3 to active metabolite increasing intestinal uptake
The filtered 10 grams of calcium is mainly reabsorbed in the PCT (60-70%), followed by 20,10 and 5 % in TAL, DCT, and SD, respectively. This reabsorption in DCT is usually passive, following sodium and water and mainly (about (80%) by passive diffusion. PTH and calcitonin regulate the other 10-20 %. PTH augments renal calcium absorption. Calcium sensing receptors play a role in this regulation and sensing. The hydroxylation of vitamin D takes place in the kidneys. Importantly the kidneys regulate calcium by suppressing of 1 alpha-hydroxylase and activating 24-hydroxylase when needed to suppress the calcium reabsorption
99% of filtered Ca is reabsorbed by the kidneys, 80% mainly through passive para-cellular route (70% in PCT following Na+H2O & 10% in CTALH- following ROMK and NKCC2 activation), small but significant remaining 20% reabsorbed through secondary active trans-cellular transport under PTH control (5-10% in DCT via Na/Ca exchanger & 5-10% in CD which is the major site of regulation)
Ca reabsorption is
PTH: is secreted after hypocalcemia and vitamin Deficiency, it controls active trans-cellular pathway in all nephron parts (PCT, CTALH, DCT and CD), with resultant bone resorption (indirect stimulation of osteoclast) & increases renal calcium reabsorption & indirect increase intestinal calcium absorption- through vitamin D activation)
1,25 OH Vitamin D3: stimulate both intestinal calcium absorption and renal calcium reabsorption
loop diuretics: inhibit NKCC2 interfering with Na reabsorption and electric gradient resulting in decreased paracellular Ca and Mg transport
Thiazide: causes volume depletion which increases PCT Ca reabsorption, another mechanism: thiazide inhibits NCC (DCT thiazide sensitive Na/Cl cotransporter), thereby Na/K pump, blockage of the Na/Cl channel increases the flow of ions through the Na/Ca channel, resulting in increased calcium reabsorption into the interstitium in exchange for Na.
Acute/ chronic Metabolic acidosis: causes bone resorption (increased H ions are buffered in the skeleton, mobilizing calcium from the bone into circulation, increasing filtered calcium and calciuria.
Hypercalcemia causes increased filtered load of Ca hence decreases tubular reabsorption , but opposed by hypercalcemia induced renal vasoconstriction
ECF volume expansion is associated with Na & Cl & Ca excretion, where as reciprocal changes are seen with volume contraction
the renal handling of calcium illustrating the role of main regulators of renal calcium excretion:the kidneys reabsorb 97-99% of daily filtered calcium.
of this reabsorbed ,60-65%is reabsorbed by proximal tubule via the paracellular route and 25-30 is reabsorbed in the TAL,also paracelularly.
the remaining 8-10%is reabsorbed in the distal convulated
60%–70% of the filtered calcium is reabsorbed in the proximal convoluted tubule, 20% in the loop of Henle, 10% by the distal convoluted tubule, and 5% by the collecting duct.
Proximal tubular calcium reabsorption is thought to occur mainly by passive diffusion and solvent drag.
The passive paracellular pathways account for approximately 80% of calcium reabsorption in this segment of the nephron. A small but significant component of active calcium transport is observed in the proximal tubules.
No reabsorption of calcium occurs within the thin segment of the loop of Henle.
In the thick ascending limb, the bulk of calcium reabsorption proceeds through the paracellular pathway and is proportional to the transtubular electrochemical driving force.
the distal tubule reabsorbs calcium exclusively via the transcellular route.
Regulators of renal Ca excretion:
A. ↑↑↑Ca absorption
Hyperparathyroidism
vit D
Metabolic alkalosis
Thiazides diuretics
volume depletion.
B.↓↓↓ Ca absorption
Hypoparathyroidism
vit- D deficiency
Hypercalcaemia
Metabolic acidosis
Loop diuretics
volume expansion
Renal handling:
Ca Regulation :
Increase Ca absorption
Decrease Ca absorption
Summarize the renal handling of calcium illustrating the role of main regulators of renal calcium excretion.The renal handling of calcium:
The role of main regulators of renal calcium excretion.
Renal handling:
Main regulators of renal Ca :
Increase Ca absorption: Hyperparathyroidism, vit D, Metabolic alkalosis, Thiazides diuretics, volume depletion.
Decrease Ca absorption: Hypoparathyroidism, vit- D deficiency, Hypercalcaemia, Extracellular fluid expansion, Metabolic acidosis, Loop diuretics
In humans who have a GFR of 170 liters per 24 hours, roughly 10 g of calcium is filtered per day. The amount of calcium excreted in the urine usually ranges from 100 to 200 mg per 24 hours; hence, 98%–99% of the filtered load of calcium is reabsorbed by the renal tubules. Approximately 60%–70% of the filtered calcium is reabsorbed in the proximal convoluted tubule, 20% in the loop of Henle, 10% by the distal convoluted tubule, and 5% by the collecting duct. The terminal nephron, although responsible for the reabsorption of only 5%–10% of the filtered calcium load, is the major site for regulation of calcium excretion.
The reabsorption of calcium in the proximal convoluted tubule parallels that of sodium and water. Proximal tubular calcium reabsorption is thought to occur mainly by passive diffusion and solvent drag.
A small but significant component of active calcium transport is observed in the proximal tubules.
No reabsorption of calcium occurs within the thin segment of the loop of Henle .In the thick ascending limb of the loop of Henle, 20% of the filtered calcium is reabsorbed largely by the cortical thick ascending limb, through both transcellular and paracellular routes.
The apical Na1 -K1 -2Cl2 cotransporter NKCC2 and the renal outer medullary potassium K1 (ROMK) channel generate the “driving force” for paracellular cation transport.
Calcium transport in the thick ascending limb of the loop of Henle is also influenced by the calcium-sensing receptor (CaSR) ,which is localized in the basolateral membrane.
Calciotropic hormones, such as PTH and calcitonin, stimulate active cellular calcium absorption in the cortical thick ascending limb.
the distal tubule reabsorbs calcium exclusively via the transcellular route. The distal convoluted tubule absorbs 5%–10% of the filtered calcium.
Calcium absorption in this segment is active because it proceeds against a chemical and an electrical gradient.
Factors that alter renal regulation of calcium :
Increase Calcium Absorption
Hyperparathyroidism
Calcitriol
Hypocalcemia
Volume contraction
Metabolic alkalosis
Thiazides diuretics
Decrease Calcium Absorption
Hypoparathyroidism
Low calcitriol levels
Hypercalcemia
Extracellular fluidexpansion
Metabolic acidosis
Loop diuretics
Summarize the renal handling of calcium
10 g of Ca is filtered /day and 98% is reabsorbed by the renal tubules
100 to 200 mg of Ca is excreted in urine/day
Main site for reabsorbtion 60 to 70% is PCT (paracellular pathway) -ve process
20% in the thick ascending loop of Henle
10% in DCT (Active process)
5% in CD
Main regulators of renal Ca :
Increase Ca absorption, Hyperparathyroidism, vit D,Metabolic alkalosis, Thiazides diuretics,volume depletion.
Decrease Calcium Absorption:
Hypoparathyroidism, Low calcitriol levels ,Hypercalcemia,l Extracellular fluid expansion, Metabolic acidosis, Loop diuretics.
Renal handling
In human GFR of 170liters /24hrs filtered about 1g of calcium filtered, the amount of calcium excreted 100-200mg per day in urine, 98-99%reabsorped.
60-70%in Proximal tubule 20%in loop of henle, 5-10%in distal CT and 5% in collecting duct.
Factors increase Ca absorption include
*PTH it stimulate bone resorption, increase intestinal absorption and increase renal reabsorption
*active vitamin D :increase intestinal absorption of Ca
*hypocalcimia : it increase renal tubular absorption
*volume contraction this cause increase tubular absorption of Ca
*metabolic alkalosis :
*thiazide diuretics
Factos decrease Calcium absorption
*hypoparathyroidism
*low calcitriol
*hypercalcimia
*Volume expansion
*metabolic acidosis
*loop diuretics
Summarize the renal handling of calcium illustrating the role of main regulators of renal calcium excretion.
Renal handling:
Main regulators of renal Ca :
A.Increase Ca absorption
B.Decrease Ca absorption
Renal regulation of the calcium balance
Proximal convoluted tubule – the main place Where calcium get reabsorbed . He main way of reabsorption of calcium is through paracellular way in 80 percent of cases..
The transcellular way occur in 20 percent of cases and regulated through PTH and calcitonin.
In the Ascending thick Loop of Henle – the NKCC2 channel with help of ROMK produce a intraluminal positive electrochemical charge and negative intracellular. This help calcium to diffuse theough paracellular pathway. So the main transport still paracellular.
CaSR play here. It control calcium reabsorption through Claudin expression.
The tight junctions are guarded by proteins like claudin-16 and claudin-19, which act like bouncers themselves and only let certain ions through.
Distal convoluted tubule-exclusively Transcellular and is very controlled through PTH.. The epithelial cells here had some special proteins called TRPV5 and TRPV6 that were like little calcium vacuum cleaners. These proteins actively transported calcium ions from the tubular fluid into the epithelial cells. PTH increase will increase the expression of TRPV 5&6
What alter the renal regulations of calcium?
Factors increasing calcium absorption are:
Hyperparathyroidism, calcitriol, hypocalcemia, volume contraction, met alkalosis and thiazide.
Factors that decrease calcium absorption :
Hypoparathyroidism
Low vit vitamin D
hypercalcemia extracellular fluid expansion, metabolic acidosis and loop diuretics.
The proximal convoluted tubule reabsorbs calcium like sodium and water. Passive diffusion and solvent drag cause proximal tubular calcium reabsorption. Based on the discovery that proximal tubule fluid and glomerular filtrate calcium ratios are 1:1.2.
In this nephron segment, passive paracellular routes absorb 80% of calcium. Proximal tubules have a modest but significant active calcium transport component. Calcium enters the tubular fluid via the apical membrane and exits through the basolateral membrane during active transport. PTH and calcitonin control this active transport, which accounts for 10%–15% of proximal tubule calcium reabsorption.
The thin loop of Henle does not reabsorb calcium. 20% of the filtered calcium is reabsorbed by the cortical thick ascending limb of the loop of Henle through transcellular and paracellular pathways. Calcium reabsorption via the paracellular route is proportional to the transtubular electrochemical driving force in the thick ascending limb. NKCC2 and ROMK are apical Na1-K1-2Cl2 cotransporters.
The basolateral membrane-localized calcium-sensing receptor (CaSR) affects calcium transport in the thick ascending limb of the loop of Henle.
Now we know how CaSR governs thick ascending limb calcium reabsorption. In microdissected, in vitro micro-perfused rat cortical thick ascending limb, The thick ascending limb tight junction expresses claudin-14, -16, and 19.
Divalent cation absorption in this tubular segment requires proper claudin-16 and -19 expression. Toka et al. found that CaSR disruption lowers claudin-14 mRNA and increases claudin-16.
Cinacalcet increases claudin-14 mRNA, which lowers paracellular calcium permeability in cell culture models. PTH and calcitonin activate cellular calcium absorption in the cortical, thick ascending limb.
Increase Calcium Absorption :
Hyperparathyroidism, Calcitriol, Hypocalcemia Volume contraction
Metabolic alkalosis, Thiazides diuretics
Decrease Calcium Absorption:
Hypoparathyroidism Low calcitriol levels Hypercalcemia Extracellular fluid expansion Metabolic acidosis Loop diuretics
Renal handling calcium and main regulation
Many hormones and factors regulate the ca handling
1-) PTH Secreted by parathyroid gland .The changes in serum calcium are sensed by Ca SR which is localized in the cell membrane of the para thyroid cell
In hypocalcemia PTH secreted and acts to increase plasma concentration of calcium in three ways 1- stimulate bone resorption 2- enhance intestinal ca and pi absorption by promotion formation of calctriol by the kidney 3- it augment active renal ca absorption
2-) vit D 25 hydroxy vit- D ( calcidiol ) produced by the liver and then activated in the kidney tubular cell contain hydroxylase enzymes which produced active vit D 1,25 dihydroxy vit D
Enhance intestinal calcium absorption
And induce bone osteoclastic activity
Factor that change renal regulation of calcium
1-) Factor increase calcium absorption
a-Hyperparathyroidism
b-Calcitriol
c-hypocalcemia
d-Volume contraction
e-Metabolic alkalosis
f-thiazide diuretic
2-) Factor decease calcium absorption
a- Hypoparathyroidism
b-Low calcitriol level
c-hypercalcemic
d-Extracellular fluid expansion
d-Metabolic acidosis
e-Loop diuretic
Summarize the renal handling of calcium illustrating the role of main regulators of renal calcium excretion.
Renal handling:
Main regulators of renal Ca :
A.Decrease Ca absorption
B.Increase Ca absorption