Describe the compensatory mechanisms to maintain calcium homeostasis in patients with CKD.
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Rania Mahmoud
The compensatory mechanisms to maintain calcium homeostasis in patients with CKD is a reduction in klotho, an increase in FGF23, a reduction of renal mass , a reduction in alpha hydroxylation, a reduction in Vitamin D activation, and hypocalcaemia
The main impact of CKD is low calcium excessive PTH.Reduced intestinal calcium absorption, resulting in a drop in serum calcium. Hypocalcemia stimulates the synthesis and release of PTH. PTH elevation promotes the synthesis of 1–hydroxylase.High PTH contributes to cardiovascular mortality
Compensatory Mechanism to maintain calcium in haemostasis in CKD
With worsening kidney function there is decrease in klotho, increased in FGF23 , decrease in alpha hydroxylation reduction in Vitamin D activation and hypocalcaemia
CASR and VDR in parathyoid respond to decrease in calcium by promoting increasing PTH. This leads to increase bone resorption and attempt to correct calcium
PTH increases phosphate excretion but also promotes 1& hydroxylase in contrast to FGF23
However with progressive ckd main effect is low calcium and hight PTH
High PTH promotes parathroid hyperplasia to eventually nodularity and down regulating CaSR and Vit D receptor. This leads to PTH unresponsiveness and a vicious cycle.
high pth contributes to cardiovascular mortality and low as well so important to get range associated with least mortality
Calcium sensing receptors (CaSR) detect any small reduction in serum calcium.
a. It starts at first by releasing stored PTH.
b. increases PTH synthesis at posttranscriptional level
c. decreases PTH degradation and increases its stability and half life
PTH increases alpha-hydroxylase activity and increases calcitriol synthesis and increase phosphorus excretion
this compensatory mechanisms do their best in the early stages, but they fail in the advanced stages.
continuous stimulation of PTH leads to increase nodularity of the parathyroid gland and lead to severe forms of secondary hyperparathyroidism and bone turnover
increase in FGF23
the decrease of Klotho
reduction of renal mass
are possibly the earliest events in the pathogenesis of CKD-MBD.
These changes favor the reduction of 1-α-hydroxylase in the kidney, which results in low levels of calcitriol, the most active natural activator of VDR, a fact that reduces the absorption of calcium in the intestine and favors the decrease in serum calcium, which in turn acts as a stimulus for the synthesis and release of PTH. The increase in PTH favors bone turnover and resorption and stimulates the production of 1-α-hydroxylase.
All of these mechanisms translate into compensatory increases to normalize serum calcium. Furthermore, the increase in FGF23 and PTH favor urinary phosphate excretion, maintaining normal serum phosphate levels until stages 3–4 of CKD .Despite the compensatory increases in PTH, it is well known that in CKD there is currently a hyporesponsiveness to PTH which limits its action .
Initial drop in Ca is due to decreased absorption from intestine, which in turn result from deficient 1-hydroxylation in the kidney
the response to this hypocalcemia is an increase in PTH secretion which promote 1-hydroxylation and absorption of Ca from intestine,
Thanks Dr. Hassan. Here is a simplified answer: Increase in FGF23, Decrease of Klotho, Reduction of renal mass. These changes favor the low levels of calcitriol due to reduction of 1-α-hydroxylase in the kidney. This results in reduction of intestinal calcium absorption and so the decrease in serum calcium. Hypocalcemia leads to stimulation of the synthesis and release of PTH. The increase in PTH stimulates the production of 1-α-hydroxylase. All of these mechanisms translate into compensatory increases to normalize serum calcium.
What we know is that with the compensation against hyperphosphatemia, there is an increase in FGF23 and PTH which have a phosphaturic effect. they have opposite directions on 1 alpha-hydroxylase. PTH mainly continue to increase to compensate for hypocalcemia and stimulate calcitriol synthesis as well. Another important point is CaSR, which increases and exerts a sustained effect on PTH release to maintain normocalsemia
The companstory mechanisms when decrease level of serum ca due to decrease it’s absorption from intestine secondary to vit d deficiency that lead to increase secrearion of pth to increase activation of 1~hydroxylase and increase if bone resorption to over come hypocalcemia
Calcium is the body’s most abundant cation, 99% of it is found in bone and the remaining 1% in blood, extracellular fluid and soft tissues. It participates in vital processes such as cardiac contractility, neuromuscular function, membrane permeability, blood coagulation, bone mineralization and in different mechanisms of activation and secretion of hormones and enzymes
PTH release is triggered by hypocalcemia and modulated by prostaglandin E2, dopamine, and adrenergic agonists. In the parathyroid gland Ca2+ is sensed by the CaSR which controls PTH secretion Calcium and calcitriol exert their actions on the parathyroid cells through their specific receptors, the calcium sensing receptor (CaSR), and the vitamin D receptor (VDR), respectively. The CaSR detects small decreases in extracellular calcium concentrations, rapidly increases the release of stored PTH, if the stimulus is the opposite, it reduces the hormone release. If calcium decrease persists for longer periods, the synthesis of PTH increases, reduces the degradation of PTH increasing its stability and half-life; the increase in calcium has the opposite effect .
With progression in CKD There is associated decreased renal calcium excretion and decreased intestinal calcium absorption.
compensatory mechanisms to maintain calcium homeostasis in patients with CKD.# in early stage of CKD associated with bone and mineral metabolism disorder
especially ca and pi and vit d regulation and PTH
initially hyperphosphatemia , increase FGF23 >>>phosphaturia action
–with loos of kidney mass decrease production of 1-alfa hydroxylase
lead to low level of calcitriol
so decrease of absorption of calcium in intestine consequences hypocalcemia
— stimulus and release of PTH
–increase PTH increase bone turn over and production of 1-alfa hydroxylase
for compensation of hypocalcemia
Describe the compensatory mechanisms to maintain calcium homeostasis in patients with CKD.
due to low levels of calcitriol and hyperphosphatemia >>low calcium level
low calcium level >>stimulus for the synthesis and release of PTH
the increase in PTH favors bone turnover and resorption and stimulate 1- hydroxylase
the increase FGF23 and PTH >>increase urinary phosphate excretion
-patients with CKD are more liable to hypocalcemia due to many factors including decreased active vit D which decrease calcium absorption from the intestine and hyperphosphatemia which lead to decreased calcium to maintain ca*po4 product within normal values to prevent calcium deposition in soft tissues and blood vessels.
-compensatory mechansims in parathyroid gland to overcome hypocalcemia include histological changes as diffuse hyperplasia followed by polyclonal and then monoclonal nodularity which may end in formation of autonomous nodule that represent the stage of tertiary hyperparathyroidism if prolonged hypocalcemia persists.
-these changes can be observed in bone as increased bone resorption by inhibition of osteoblasts rather than stimulating osteoclasts as thought before and by activating vit D to increase vit D absorption from the GIT to compensate for hypocalcemia and increased calcium reabsorption from the kidneys as the calcium hemostasis depend on parathyroid gland , bone , GIT and kidneys.
Here is a simplified answer: Increase in FGF23, Decrease of Klotho, Reduction of renal mass. These changes favor the low levels of calcitriol due to reduction of 1-α-hydroxylase in the kidney. This results in reduction of intestinal calcium absorption and so the decrease in serum calcium. Hypocalcemia leads to stimulation of the synthesis and release of PTH. The increase in PTH stimulates the production of 1-α-hydroxylase. All of these mechanisms translate into compensatory increases to normalize serum calcium.
Stimulation of ca sensing receptors , Increase PTH effect , Increase ca reabsorption and decrease po4 reabsorption , Increase bone turnover so increase serum calcium . Increase 1 alpha hydroxylase activity leading to increase calcitriol so increase intestinal Calcium absorption .
Serum calcium level decreases during the course of CKD due to:
Phosphate retention.
Decreased calcitriol concentration (reduction of 1-alpha-hydroxylase).
Resistance to the calcemic actions of PTH on bone.
*Hypocalcemia contributes to increased PTH secretion.
Minute changes in the serum ionized calcium are sensed by a specific membrane CaSR, which is highly expressed in the parathyroid glands. The CaSR tightly regulates changes in PTH secretion in response to serum calcium. The fall in serum calcium concentration in CKD, as sensed by the CaSR, is a potent stimulus for the release of PTH.
*PTH stimulates the production of one-alpha-hydroxylase.
In CKD stage 2-3, s.ca levels are maintained in the normal range at the cost of secondary elevation of PTH level.
stimulation of ca sensing receptors
Increase PTH effect
increase ca reabsorption .and decrease po4 reabsorption .
increase bone turnover so increase s.ca.
increase 1 alpha hydroxylase activity leading to increase calcitriol so increase intestinal ca absorption .
Thanks Dr. Ibrahim. In addition to your answer: Increase in FGF23, Decrease of Klotho, Reduction of renal mass. These changes favor the low levels of calcitriol due to reduction of 1-α-hydroxylase in the kidney. This results in reduction of intestinal calcium absorption and so the decrease in serum calcium. Hypocalcemia leads to stimulation of the synthesis and release of PTH. The increase in PTH stimulates the production of 1-α-hydroxylase. All of these mechanisms translate into compensatory increases to normalize serum calcium.
Plasma calcium homeostasis correlated of PTH 1,25(OH)2D3, calcitonin, and ionized calcium. This process kidneys plays a key role by regulating the renal excretion. around 50% of ionized calcium is reabsorbed along with the renal tubules.
due to low level of calcitriol the intestinal absorption is impaired.
the elevation of PTH maintains the serum calcium in CKD patients.
in CKD the calcium absorbtion and excretion are not equal.
Increase in FGF23, Decrease of Klotho, Reduction of renal mass. These changes favor the low levels of calcitriol due to reduction of 1-α-hydroxylase in the kidney. This results in reduction of intestinal calcium absorption and so the decrease in serum calcium. Hypocalcemia leads to stimulation of the synthesis and release of PTH. The increase in PTH stimulates the production of 1-α-hydroxylase. All of these mechanisms translate into compensatory increases to normalize serum calcium.
Describe the compensatory mechanisms to maintain calcium homeostasis in patients with CKD.The major role in Ca homeostasis is through PTH, as the Ca will be low due to low 1alph hydrolase in the kidney, and this will lead to a low level of calcitriol,a fact that reduces Ca absorption from the intestine and hypocalcemia will be developed and then will trigger the release of PTH which with time will be out of control of the Ca itself.
The earliest event in ckd are increase in FGF23, decrease in klotho and decrease in renal mass, these events lead to decrease activity and secretion of 1 alfa hydrxylase, this lead to decrease calcitriol which is the active form of vitamin D and lead to decrease in the intestinal absorption of calcium so decrease in S. Calcium level which will cause stimulation of PTH and PTH increase bone turnover and resorption and increase secretion of 1 alfa hydrxylase which increase calcitriol formation and the later increase calcium absorption from the intestine.
All these are compensatory mechanism to maintain s. Calcium homeostasis
hyperparathyroidism play the major role in maintain calcium homestasis.PTH stimulate bone resorption,and production of calcitrol which in turn stimulate intesinal calcium absorption. PTH can detect small changes in extracellular calcium, and responded rapidly by releasing the stored PTH. Prolonged hypocalcemia causes degradation of PTHm-RNA, SO increasing PTH synthesis
IN CKD, increasing level go FGF23 and reduction of klotho expression due to inflammation and reduced renal mass lead to reduction in alpha 1 hydroxyls enzyme, decrease calcitriol, decrease intestinal calcium absorption, hypocalcemia.
Hypocalcemia stimulates PTH immediate release through calcium sensing receptors and persistent hypocalcemia increases calcium level at post transcriptional level (modify the stability of mRNA).
PTH tries to maintain calcium homeostasisby increasing bone turn over and resorption and stimulating production of alpha 1 hydroxyls enzyme.
PTH is released from storage in a matter of seconds or minutes when the CaSR detects a slight fall in extracellular calcium concentrations. If the stimulus is the reverse, however, the CaSR inhibits the release of the hormone. This happens at the post-transcriptional level, which modifies the stability of the mRNA.
If the calcium drop continues for prolonged periods of time (hours, days), the synthesis of PTH rises. In contrast, a rise in blood calcium has the opposite effect, causing a breakdown of PTH mRNA at a slower rate and lengthening its half-life. This occurs when the serum calcium level is lowered. Phosphate has a similar effect, but in the opposite direction; this means that an increase in phosphate will have the opposite effect on the stability and half-life of PTH mRNA, and vice versa.
Recent research has shown that the impact of phosphate may also be brought about by the CaSR, which the phosphate acts upon.
Increase in FGF23, Decrease of Klotho, Reduction of renal mass. These changes favor the low levels of calcitriol due to reduction of 1-α-hydroxylase in the kidney. This results in reduction of intestinal calcium absorption and so the decrease in serum calcium. Hypocalcemia leads to stimulation of the synthesis and release of PTH. The increase in PTH stimulates the production of 1-α-hydroxylase. All of these mechanisms translate into compensatory increases to normalize serum calcium.
When calcium level are low(or phosphorus levels are high) the CaSR will sense the low calcium and stimlate the excretion of PTH ( if acute through exocytosis and decreased cleavage of PTH and if chronic through increase translation of pth gene ).
The same interaction between Vit D3 and VDR will cause the same action on gene transcripion. Together will have synergetic effect on pth secretion.
The later on rise on pth will increase calcium level by stimulating the 1 alpha hydroxylase ( opposite to what fgf23 do to the enzyme), and increasing bone resorption and calcium release from bone, and via VDR increases calcium absorption in gut.
The phosphat level will normalize through phosphaturic action of PTH( decrease the Napi2a and NaPi2c in prox tubules) .
The compensatory mechanism of calcium homeostasis in CKD: Thekidneys as a complex organ and their endocrine function play a major role because it is the final effector of several aspects of bone metabolism, where important adjustments are done to maintain calcium and phosphorus homeostasis, and also play an important role in regulating hormonal axes and mineral metabolism, so with decline kidney function an imbalanced metabolic homeostasis occur, and the manifestation of BMD appear clinically and laboratory results. The compensatory mechanism involved in calcium homeostasis (calcitropic hormones);
PTH.
Calcitriol or 1,25 (OH)2D3.
Calcidiol or 25 (OH)2D3.
Calcitonin.
FGF23/Klotho.
The homeostatic mechanism depends on the modulation, elimination, absorption, and deposition of calcium and phosphate to maintain the serum level within the normal range. The organs and glands involved in homeostasis:
Parathyroid gland.
The bone.
The kidneys.
the intestine.
Calcium in the body:
99% found in the bone.
1% is found in the blood, ECF, and soft tissues.
The function of calcium:
Cardiac contractility.
Neuromuscular function.
membrane permeability.
Blood coagulation.
Bone mineralization.
Different mechanisms of activation and secretion of hormones and enzymes.
Phosphate in the body:
85% is found in the bone.
15% are located in the blood, ECF, and soft tissues.
The function of the phosphate:
The central part of phospholipids is in membranes, nucleotides, and nucleic acid.
Major role in enzymatic activation.
With phosphorus retention in the early stage of CKD, FGF23 increase, leading to phosphaturia, and in contrast, inhibit 1-alpha-hydroxylase which leads to decreased calcitriol level and subsequent hypocalcemia. Calcium and calcitriol exert their effect on the parathyroid gland via CaSR and VDR respectively. CaSR detects a small decrease in extracellular calcium, leading to the rapid release in stored PTH, while the phosphorous serum level does the opposite. In advance CKD with a subsequent decrease in calcium and calcitriol level with increasing phosphorus level lead to a proliferative phase of the parathyroid gland (secondary hyperparathyroidism) with hyperplasia of the gland, the pathology of the gland involves the following steps;
Proliferative phase.
Diffuse phase.
Nodular phase.
with the significant reduction in CaSR, VDR, and FGF23/Klotho expression which ends in a poor response of parathyroid glands to calcium, VDR activators (VDRA), and FGF23. The imbalance of CKD-MBD in advanced stages of CKD lead to the following complication:
Renal osteodystrophy (bone turnover, mineralization, and bone volume).
Increase in FGF23, Decrease of Klotho, Reduction of renal mass. These changes favor the low levels of calcitriol due to reduction of 1-α-hydroxylase in the kidney. This results in reduction of intestinal calcium absorption and so the decrease in serum calcium. Hypocalcemia leads to stimulation of the synthesis and release of PTH. The increase in PTH stimulates the production of 1-α-hydroxylase. All of these mechanisms translate into compensatory increases to normalize serum calcium.
The compensatory mechanisms to maintain calcium homeostasis in patients with CKD is a reduction in klotho, an increase in FGF23, a reduction of renal mass , a reduction in alpha hydroxylation, a reduction in Vitamin D activation, and hypocalcaemia
The main impact of CKD is low calcium excessive PTH.Reduced intestinal calcium absorption, resulting in a drop in serum calcium. Hypocalcemia stimulates the synthesis and release of PTH. PTH elevation promotes the synthesis of 1–hydroxylase.High PTH contributes to cardiovascular mortality
Compensatory Mechanism to maintain calcium in haemostasis in CKD
With worsening kidney function there is decrease in klotho, increased in FGF23 , decrease in alpha hydroxylation reduction in Vitamin D activation and hypocalcaemia
CASR and VDR in parathyoid respond to decrease in calcium by promoting increasing PTH. This leads to increase bone resorption and attempt to correct calcium
PTH increases phosphate excretion but also promotes 1& hydroxylase in contrast to FGF23
However with progressive ckd main effect is low calcium and hight PTH
High PTH promotes parathroid hyperplasia to eventually nodularity and down regulating CaSR and Vit D receptor. This leads to PTH unresponsiveness and a vicious cycle.
high pth contributes to cardiovascular mortality and low as well so important to get range associated with least mortality
compensatory mechanism that mentain calcium homeostasis:
* increased FGF23-> reduced vitamin D activation-> hypocalcemia & increased PTH (early increased secretion, then hyperplasia, late monoclonal nodularity).
* parathyroid gland has CaSR, VDR, FGF23R that regulate PTH secretion
* PTH stimulates vitamin D activation, increases calcium absorbtion and reabsortion, stimulates osteomyelitis to secrete RANK that stimulates osteoclact rendering bone resorption and calcium release
Great answer Dr. Marwa
Calcium sensing receptors (CaSR) detect any small reduction in serum calcium.
a. It starts at first by releasing stored PTH.
b. increases PTH synthesis at posttranscriptional level
c. decreases PTH degradation and increases its stability and half life
PTH increases alpha-hydroxylase activity and increases calcitriol synthesis and increase phosphorus excretion
this compensatory mechanisms do their best in the early stages, but they fail in the advanced stages.
continuous stimulation of PTH leads to increase nodularity of the parathyroid gland and lead to severe forms of secondary hyperparathyroidism and bone turnover
Great Dr. Radwa
increase in FGF23
the decrease of Klotho
reduction of renal mass
are possibly the earliest events in the pathogenesis of CKD-MBD.
These changes favor the reduction of 1-α-hydroxylase in the kidney, which results in low levels of calcitriol, the most active natural activator of VDR, a fact that reduces the absorption of calcium in the intestine and favors the decrease in serum calcium, which in turn acts as a stimulus for the synthesis and release of PTH. The increase in PTH favors bone turnover and resorption and stimulates the production of 1-α-hydroxylase.
All of these mechanisms translate into compensatory increases to normalize serum calcium. Furthermore, the increase in FGF23 and PTH favor urinary phosphate excretion, maintaining normal serum phosphate levels until stages 3–4 of CKD .Despite the compensatory increases in PTH, it is well known that in CKD there is currently a hyporesponsiveness to PTH which limits its action .
Great Dr. Asmaa
Compensation to hypocalcemia
Initial drop in Ca is due to decreased absorption from intestine, which in turn result from deficient 1-hydroxylation in the kidney
the response to this hypocalcemia is an increase in PTH secretion which promote 1-hydroxylation and absorption of Ca from intestine,
Thanks Dr. Hassan. Here is a simplified answer: Increase in FGF23, Decrease of Klotho, Reduction of renal mass. These changes favor the low levels of calcitriol due to reduction of 1-α-hydroxylase in the kidney. This results in reduction of intestinal calcium absorption and so the decrease in serum calcium. Hypocalcemia leads to stimulation of the synthesis and release of PTH. The increase in PTH stimulates the production of 1-α-hydroxylase. All of these mechanisms translate into compensatory increases to normalize serum calcium.
What we know is that with the compensation against hyperphosphatemia, there is an increase in FGF23 and PTH which have a phosphaturic effect. they have opposite directions on 1 alpha-hydroxylase. PTH mainly continue to increase to compensate for hypocalcemia and stimulate calcitriol synthesis as well. Another important point is CaSR, which increases and exerts a sustained effect on PTH release to maintain normocalsemia
Nice explanation. Thanks Dr. Mahmud
The companstory mechanisms when decrease level of serum ca due to decrease it’s absorption from intestine secondary to vit d deficiency that lead to increase secrearion of pth to increase activation of 1~hydroxylase and increase if bone resorption to over come hypocalcemia
Good answer. Thanks Dr. Rabab
Calcium is the body’s most abundant cation, 99% of it is found in bone and the remaining 1% in blood, extracellular fluid and soft tissues. It participates in vital processes such as cardiac contractility, neuromuscular function, membrane permeability, blood coagulation, bone mineralization and in different mechanisms of activation and secretion of hormones and enzymes
PTH release is triggered by hypocalcemia and modulated by prostaglandin E2, dopamine, and adrenergic agonists. In the parathyroid gland Ca2+ is sensed by the CaSR which controls PTH secretion
Calcium and calcitriol exert their actions on the parathyroid cells through their specific receptors, the calcium sensing receptor (CaSR), and the vitamin D receptor (VDR),
respectively.
The CaSR detects small decreases in extracellular calcium concentrations, rapidly increases the release of stored PTH, if the stimulus is the opposite, it reduces the hormone release.
If calcium decrease persists for longer periods, the synthesis of PTH increases, reduces the degradation of PTH increasing its stability and half-life; the increase in calcium has the opposite effect .
With progression in CKD There is associated decreased renal calcium excretion and decreased intestinal calcium absorption.
.
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compensatory mechanisms to maintain calcium homeostasis in patients with CKD.# in early stage of CKD associated with bone and mineral metabolism disorder
especially ca and pi and vit d regulation and PTH
initially hyperphosphatemia , increase FGF23 >>>phosphaturia action
–with loos of kidney mass decrease production of 1-alfa hydroxylase
lead to low level of calcitriol
so decrease of absorption of calcium in intestine consequences hypocalcemia
— stimulus and release of PTH
–increase PTH increase bone turn over and production of 1-alfa hydroxylase
for compensation of hypocalcemia
Great job. Thanks Dr. Elsayed
Describe the compensatory mechanisms to maintain calcium homeostasis in patients with CKD.
due to low levels of calcitriol and hyperphosphatemia >>low calcium level
low calcium level >>stimulus for the synthesis and release of PTH
the increase in PTH favors bone turnover and resorption and stimulate 1- hydroxylase
the increase FGF23 and PTH >>increase urinary phosphate excretion
Great answer. Thanks Dr. Emad
-patients with CKD are more liable to hypocalcemia due to many factors including decreased active vit D which decrease calcium absorption from the intestine and hyperphosphatemia which lead to decreased calcium to maintain ca*po4 product within normal values to prevent calcium deposition in soft tissues and blood vessels.
-compensatory mechansims in parathyroid gland to overcome hypocalcemia include histological changes as diffuse hyperplasia followed by polyclonal and then monoclonal nodularity which may end in formation of autonomous nodule that represent the stage of tertiary hyperparathyroidism if prolonged hypocalcemia persists.
-these changes can be observed in bone as increased bone resorption by inhibition of osteoblasts rather than stimulating osteoclasts as thought before and by activating vit D to increase vit D absorption from the GIT to compensate for hypocalcemia and increased calcium reabsorption from the kidneys as the calcium hemostasis depend on parathyroid gland , bone , GIT and kidneys.
Thanks Dr. Mark.
Here is a simplified answer: Increase in FGF23, Decrease of Klotho, Reduction of renal mass. These changes favor the low levels of calcitriol due to reduction of 1-α-hydroxylase in the kidney. This results in reduction of intestinal calcium absorption and so the decrease in serum calcium. Hypocalcemia leads to stimulation of the synthesis and release of PTH. The increase in PTH stimulates the production of 1-α-hydroxylase. All of these mechanisms translate into compensatory increases to normalize serum calcium.
Stimulation of ca sensing receptors ,
Increase PTH effect ,
Increase ca reabsorption and decrease po4 reabsorption ,
Increase bone turnover so increase serum calcium .
Increase 1 alpha hydroxylase activity leading to increase calcitriol so increase intestinal Calcium absorption .
Thanks Dr. Ahmed
Serum calcium level decreases during the course of CKD due to:
*Hypocalcemia contributes to increased PTH secretion.
Minute changes in the serum ionized calcium are sensed by a specific membrane CaSR, which is highly expressed in the parathyroid glands. The CaSR tightly regulates changes in PTH secretion in response to serum calcium.
The fall in serum calcium concentration in CKD, as sensed by the CaSR, is a potent stimulus for the release of PTH.
*PTH stimulates the production of one-alpha-hydroxylase.
In CKD stage 2-3, s.ca levels are maintained in the normal range at the cost of secondary elevation of PTH level.
Good answer. Thanks Dr. Amna
stimulation of ca sensing receptors
Increase PTH effect
increase ca reabsorption .and decrease po4 reabsorption .
increase bone turnover so increase s.ca.
increase 1 alpha hydroxylase activity leading to increase calcitriol so increase intestinal ca absorption .
Good job Dr. Mahmoud.
Describe the compensatory mechanisms to maintain calcium homeostasis in patients with CKD.
Thanks Dr. Ibrahim. In addition to your answer: Increase in FGF23, Decrease of Klotho, Reduction of renal mass. These changes favor the low levels of calcitriol due to reduction of 1-α-hydroxylase in the kidney. This results in reduction of intestinal calcium absorption and so the decrease in serum calcium. Hypocalcemia leads to stimulation of the synthesis and release of PTH. The increase in PTH stimulates the production of 1-α-hydroxylase. All of these mechanisms translate into compensatory increases to normalize serum calcium.
ok. thank you
Plasma calcium homeostasis correlated of PTH 1,25(OH)2D3, calcitonin, and ionized calcium. This process kidneys plays a key role by regulating the renal excretion. around 50% of ionized calcium is reabsorbed along with the renal tubules.
due to low level of calcitriol the intestinal absorption is impaired.
the elevation of PTH maintains the serum calcium in CKD patients.
in CKD the calcium absorbtion and excretion are not equal.
Thanks Dr. MOhamed.
Increase in FGF23, Decrease of Klotho, Reduction of renal mass. These changes favor the low levels of calcitriol due to reduction of 1-α-hydroxylase in the kidney. This results in reduction of intestinal calcium absorption and so the decrease in serum calcium. Hypocalcemia leads to stimulation of the synthesis and release of PTH. The increase in PTH stimulates the production of 1-α-hydroxylase. All of these mechanisms translate into compensatory increases to normalize serum calcium.
thanks Dr Nagy
Describe the compensatory mechanisms to maintain calcium homeostasis in patients with CKD.The major role in Ca homeostasis is through PTH, as the Ca will be low due to low 1alph hydrolase in the kidney, and this will lead to a low level of calcitriol,a fact that reduces Ca absorption from the intestine and hypocalcemia will be developed and then will trigger the release of PTH which with time will be out of control of the Ca itself.
Great. Thanks Dr. Rihab
Nice clarification. Thanks Dr. Ashraf
The earliest event in ckd are increase in FGF23, decrease in klotho and decrease in renal mass, these events lead to decrease activity and secretion of 1 alfa hydrxylase, this lead to decrease calcitriol which is the active form of vitamin D and lead to decrease in the intestinal absorption of calcium so decrease in S. Calcium level which will cause stimulation of PTH and PTH increase bone turnover and resorption and increase secretion of 1 alfa hydrxylase which increase calcitriol formation and the later increase calcium absorption from the intestine.
All these are compensatory mechanism to maintain s. Calcium homeostasis
Great. Thanks Dr. Israa
-Describe the compensatory mechanisms to maintain calcium homeostasis in patients with CKD ?
Great answer. Thanks Dr. Ben
wlcm prof
hyperparathyroidism play the major role in maintain calcium homestasis.PTH stimulate bone resorption,and production of calcitrol which in turn stimulate intesinal calcium absorption. PTH can detect small changes in extracellular calcium, and responded rapidly by releasing the stored PTH. Prolonged hypocalcemia causes degradation of PTHm-RNA, SO increasing PTH synthesis
Good job Dr. Ahmed.
IN CKD, increasing level go FGF23 and reduction of klotho expression due to inflammation and reduced renal mass lead to reduction in alpha 1 hydroxyls enzyme, decrease calcitriol, decrease intestinal calcium absorption, hypocalcemia.
Hypocalcemia stimulates PTH immediate release through calcium sensing receptors and persistent hypocalcemia increases calcium level at post transcriptional level (modify the stability of mRNA).
PTH tries to maintain calcium homeostasisby increasing bone turn over and resorption and stimulating production of alpha 1 hydroxyls enzyme.
Excellent answer. Thanks Dr. Alaa
PTH is released from storage in a matter of seconds or minutes when the CaSR detects a slight fall in extracellular calcium concentrations. If the stimulus is the reverse, however, the CaSR inhibits the release of the hormone. This happens at the post-transcriptional level, which modifies the stability of the mRNA.
If the calcium drop continues for prolonged periods of time (hours, days), the synthesis of PTH rises. In contrast, a rise in blood calcium has the opposite effect, causing a breakdown of PTH mRNA at a slower rate and lengthening its half-life. This occurs when the serum calcium level is lowered. Phosphate has a similar effect, but in the opposite direction; this means that an increase in phosphate will have the opposite effect on the stability and half-life of PTH mRNA, and vice versa.
Recent research has shown that the impact of phosphate may also be brought about by the CaSR, which the phosphate acts upon.
Thanks Dr. Weam.
Increase in FGF23, Decrease of Klotho, Reduction of renal mass. These changes favor the low levels of calcitriol due to reduction of 1-α-hydroxylase in the kidney. This results in reduction of intestinal calcium absorption and so the decrease in serum calcium. Hypocalcemia leads to stimulation of the synthesis and release of PTH. The increase in PTH stimulates the production of 1-α-hydroxylase. All of these mechanisms translate into compensatory increases to normalize serum calcium.
When calcium level are low(or phosphorus levels are high) the CaSR will sense the low calcium and stimlate the excretion of PTH ( if acute through exocytosis and decreased cleavage of PTH and if chronic through increase translation of pth gene ).
The same interaction between Vit D3 and VDR will cause the same action on gene transcripion. Together will have synergetic effect on pth secretion.
The later on rise on pth will increase calcium level by stimulating the 1 alpha hydroxylase ( opposite to what fgf23 do to the enzyme), and increasing bone resorption and calcium release from bone, and via VDR increases calcium absorption in gut.
The phosphat level will normalize through phosphaturic action of PTH( decrease the Napi2a and NaPi2c in prox tubules) .
Good job Dr. Nour
The compensatory mechanism of calcium homeostasis in CKD:
The kidneys as a complex organ and their endocrine function play a major role because it is the final effector of several aspects of bone metabolism, where important adjustments are done to maintain calcium and phosphorus homeostasis, and also play an important role in regulating hormonal axes and mineral metabolism, so with decline kidney function an imbalanced metabolic homeostasis occur, and the manifestation of BMD appear clinically and laboratory results.
The compensatory mechanism involved in calcium homeostasis (calcitropic hormones);
The homeostatic mechanism depends on the modulation, elimination, absorption, and deposition of calcium and phosphate to maintain the serum level within the normal range.
The organs and glands involved in homeostasis:
Calcium in the body:
The function of calcium:
Phosphate in the body:
The function of the phosphate:
With phosphorus retention in the early stage of CKD, FGF23 increase, leading to phosphaturia, and in contrast, inhibit 1-alpha-hydroxylase which leads to decreased calcitriol level and subsequent hypocalcemia.
Calcium and calcitriol exert their effect on the parathyroid gland via CaSR and VDR respectively.
CaSR detects a small decrease in extracellular calcium, leading to the rapid release in stored PTH, while the phosphorous serum level does the opposite.
In advance CKD with a subsequent decrease in calcium and calcitriol level with increasing phosphorus level lead to a proliferative phase of the parathyroid gland (secondary hyperparathyroidism) with hyperplasia of the gland, the pathology of the gland involves the following steps;
with the significant reduction in CaSR, VDR, and FGF23/Klotho expression which ends in a poor response of parathyroid glands to calcium, VDR activators (VDRA), and FGF23.
The imbalance of CKD-MBD in advanced stages of CKD lead to the following complication:
Thanks Dr. Kamal
Increase in FGF23, Decrease of Klotho, Reduction of renal mass. These changes favor the low levels of calcitriol due to reduction of 1-α-hydroxylase in the kidney. This results in reduction of intestinal calcium absorption and so the decrease in serum calcium. Hypocalcemia leads to stimulation of the synthesis and release of PTH. The increase in PTH stimulates the production of 1-α-hydroxylase. All of these mechanisms translate into compensatory increases to normalize serum calcium.