SM_198a: Calcium and Phosphate Regulation Flashcards
Describe normal Ca2+ homeostasis
Normal Ca2+ homeostasis
- Some reabsorbed from GI tract
- Mainly stored in bone
- Excreted by kidney
Describe the distribution of calcium in the blood
Distribution of calcium in the blood
- Ionized Ca2+ (biologically active): 50%
- Protein-bound non-diffusible Ca: 40%
- Ca2+ complexed w/ citrate, phosphate, and bicarbonate: 10%
______ Ca2+ is biologically active
Ionized Ca2+ is biologically active
Alkalemia will ______ protein binding of Ca2+, ______ the ionized Ca2+ fraction, but total serum calcium may stay the same
Alkalemia will increase protein binding of Ca2+, decreasing the ionized Ca2+ fraction, but total serum calcium may stay the same
Change in [albumin] changes the _____ and the _____ Ca2+, but not the _____ Ca2+
Change in [albumin] changes the bound fraction and the total serum Ca2+, but not the ionized Ca2+
Describe mechanism of Ca2+ absorption in the intestine
Ca2+ absorption in the intestine
- Ca2+ enters cell through TRPV6
- Ca2+ exits cell into serum through Na+/C2+ exchanger and Ca2+ ATPase
- CaSR prevents too much Ca2+ from being in the body - decreases reabsorption of Ca2+ in the intestine
Describe Ca2+ reabsorption in the intestine
Ca2+ reabsorption in the intestine
- Absorbed mainly in duodenum and jejunum
- Gastric acid enhances Ca2+ absorption: take supplements with food; antacids, PPI, and H2 blockers decrease absorption
- Biliary and pancreatic insufficiency: Ca2+ remains bound to unabsorbed fat
Describe bone formation and bone resorption
Bone formation and bone resorption
- Bone formation (movement of Ca2+ into bone): upregulated by intermitant PTH and androgens, downregulated by immobilization
- Bone resorption (movement of Ca2+ out of bone): upregulated by low Ca2+ (PTH) and downregulated by calcitonin and vitamin D
Most Ca2+ is reabsorbed in the ______
Most Ca2+ is reabsorbed in the PCT
(also the TAL and DCT)
Describe how Ca2+ is reabsorbed in the thick ascending loop
Ca2+ reabsorption in the thick ascending loop
- Na+/K+/2Cl- channel takes these ions into cell
- Cl- leaves to interstitium via Cl- transporters and Na+ leaves via Na+/K+ ATPase
- K+ returns to lumen through ROMK
- Excess + charge in lumen
- Ca2+ and Mg2+ travel paracellularly into interstitium via Claudin 16
(CaSR decreases production of Claudin 16 and ROMK as negative feedback)
Describe Ca2+ reabsorption in the DCT
Ca2+ reabsorption in the DCT
- Ca2+ enters cell via TRPV5 and leaves to interstitium via Na+/Ca2+ exchanger and Ca2+ ATPase
In the DCT, PTH leads to _____ of _____ and _____
In the DCT, PTH leads to upregulation of TRPV5 (Ca2+ transporter in apical membrane) and Ca2+ ATPase in basolateral membrane
In the DCT, CaSR _____, so that _____
In the DCT, CaSR upregulates phosphate transport through Np2a so that Ca2+ is alone and does not form stones
Describe normal phosphorus homeostasis
Normal phosphorus homeostasis
- Less than 1% in blood (this is biologically active)
- Excreted mostly by kidney but also GI tract
Describe intestinal absorption of phosphorus
Intestinal absorption of phosphorus
- NAPI absorbs phosphorus in conjunction w/ Na+
- Phosphorus cross basolateral membrane into interstitium with the help of a particular Na+ channel
- Vitamin D helps reabsorption of Ca2+ and phosphorus
Most phosphorus is reabsorbed in the _____
Most phosphorus is reabsorbed in the PCT
Describe renal tubular handling of phosphorus
Renal tubular handling of phosphorus
- NAPI reabsorbs phosphorus in kidneys and intestines
- Kidneys have FGF23 which stimulates excretion of phosphorus
- PTH promotes excretion of phosphorus
Describe the production of Vitamin D
Production of Vitamin D
- 7-dehydrocholesterol via UV light to
- Cholecalciferol and dietary sources via 25 alpha hydroxylase to
- 25-OH Vitamin D3 via megalin mediated endocytosis involving glomerulus and D-binding protein to
- 25-OH Vitamin D3 via 1 alpha hydroxylase to
- 1,25-OH2 VItamin D3
____ increases production of 1,25-OH2 Vitamin D3
PTH increases production of 1,25-OH2 Vitamin D3
____ decreases production of 1,25-OH2 Vitamin D3
FGF23 decreases production of 1,25-OH2 Vitamin D3
Describe regulation of PTH
Regulation of PTH
- CaSR senses too much Ca2+ in serum
- Downregulates production of PTH
- Reduces PTH activity and subsequently Ca2+ levels
____ is the single most important factor regulating PTH
Ca2+ is the single most important factor regulating PTH
FGF23-Klotho system is _____
FGF23-Klotho system is principal phosphate-regulating endocrine axes
(FGF23 is secreted from bone)
FGF23 is secreted from _____
FGF23 is secreted from bone
Describe the effects of FGF23 and PTH on Vitamin D
Effects of FGF23 and PTH on Vitamin D
- FGF23 acts on kidney to decrease Vitamin D synthesis
- Vitamin D increases FGF23 expression in bone
- FGF23 acts on parathyroid to decrease PTH
- PTH increases FGF23
Describe the FGF23-phosphate axis
FGF23-phosphate axis
- FGF23
- Decreased NAPI-2a and NAPI 2c / decreased 1 alpha hydroxylase and calcitriol
- Increased phosphate excretion and decreased phosphate absorption
- Decreased serum phosphate level
Describe causes of hypercalcemia
Hypercalcemia causes
- Production or intake: increased GI absorption
- Utilization or excretion: increased bone resorption, decreased bone mineralization, increased renal excretion
- Cellular shift
- Pseudo-states: acidosis (decreased total Ca2+ but normal ionized Ca2+)
Describe diagnostic approach to hypercalcemia
Diagnostic approach to hypercalcemia
- PTH related peptide (PTHrP) means malignancy is likely
- Tumor reduces active Vitamin D levels so high Ca2+ levels
Describe the clinical presentation of hypercalcemia
Clinical presentation of hypercalcemia
- Renal: polyuria, nephrolithiasis, AKI
- Cardiac: bradycardia, short QT
- Neuro: confusion, fatigue
- MSK: weakness, bone pain, osteopenia
- GI: nausea, vomiting, constipation, pancreatitis
(painful bones, renal stones, abdominal groans, and psychic moans)
Describe management of hypercalcemia
Management of hypercalcemia
- Improve excretion: sodium containing IV fluids, loop diuretics, dialysis
- Decreased production: calcitonin (increase renal excretion and decrease bone resorption), bisphosphonates (inhibit osteoclast-mediated bone resorption)
- Treat underlying cause
Describe causes of hypocalcemia
Hypocalcemia
- Low PTH in post-surgical
- High PTH when Vitamin D deficiency or loss of Ca2+ from circulation
- Drugs
- Disorders of Mg2+ metabolism
(if give Vitamin D -> PTH normalizes -> Ca2+ normalizes, Mg2+ comes before Ca2+ so need to fix Mg2+ level and then Ca2+ will normalize)
Describe clinical manifestations of hypocalcemia
Clinical manifestations of hypocalcemia
- Neuro: anxiety, irritability, tetany, twitching, carpopedal spasm, and seizures
- Bone: fractures
- GI: cramps
- Cardiac: prolonged QT, dysrhythmia
- Blood: hypocoagulable state
Describe management of hypocalcemia
Management of hypocalcemia
- Ca2+ supplementation: oral vs IV
- Thiazide diuretics (hypocalciuric)
- Treat underlying cause: replete Mg2+ or Vitamin D, withdraw offending drugs
Look at level of phosphorus in the _____
Look at level of phosphorus in the blood
Describe causes of hyperphosphatemia
Causes of hyperphosphatemia
- Too much protein -> protein fraction increases -> serum phosphate fraction decreases -> phosphate more concentrated
- Decreased kidney function decreases phosphate excretion
- Rhabdomyolysis increases production and decreases phosphate excretion
Describe the connection between chronic kidney disease and secondary hyperparathyroidism
Describe clinical manifestations of hyperphosphatemia
Clinical manifestations of hyperphosphatemia
- Symptoms of hypocalcemia
- Itching
- Metastatic calcifications
Describe management of hyperphosphatemia
Management of hyperphosphatemia
- Low phosphorus diet
- Phosphorus binders to bind dietary phosphorus
- Hemodialysis
- Treat underlying cause
Describe the approach to hypophosphatemia
Approach to hypophosphatemia
- Serum P low but total P may not be low
- If hyperparathyroidism, defect in PTH: when treat PTH, Ca2+ goes up so P decreases
Describe clinical manifestations of hypophosphatemia
Clinical manifestations of hypophosphatemia
- Neuro: lethargy, parasthesias, seizures
- Cardiac: arrhythmia, hypotension
- Hematologic: hemolysis
- Skeletal: bone demineralization
Describe management of hypophosphatemia
Management of hypophosphatemia
- Replete: IV vs oral
- Treat underlying cause
- Dietary phosphorus (beware of refeeding syndrome if person was in starvation conditions)
