SM 198: Ca/P Balance Flashcards
How is calcium stored in the blood? What are the effects of hypoalbuminemia and alkalemia on calcium in the blood?
50% Ca Ionized (active); 40% Protein-bound; 10% complexed with citrate, phosphate, bicarb
Low Albumin = less protein-bound Ca = normal physiological active Ca but detected as low in blood
Alkalemia = more bicarb = less active Ca = low Ca but detected as normal :(
What sensors are found basally along gut epithelium? How do they work?
- CaSR: if high Ca in blood, Ca binds = inhibits vitamin D = lowers Ca absorption (prevents more Ca)
- VDR: high vitamin D binds = more production of TRPV6, Calbindin, Ca ATPase = more Ca2+ absorption
Low serum Ca activates vitamin D!
What factors enhance bone resorption of Ca?
What factors impair bone resorption of Ca?
Enhance: Low Ca in blood, PTH
Inhibit: Calcitonin/Vitamin D
How is Ca Reabsorption regulated in the TAL?
PTH: activates Claudin-16 = more paracellular Ca Reabsorption (active when low blood Ca)
CaSR: active when blood Ca is high; inhibits Claudin 16 = less Ca paracellular reabsorption AND inhibits ROMK = less Na reabsorption = less driving force for Ca reabsorption (less LUMENAL POSITIVITY)
How is Ca Reabsorption regulated in the DCT?
CaSR (APICAL): active when urine Ca is high (kidney stone risk) - increases phosphate reabsorption
Vitamin D: binds VDR to increase TRPV5, Calbindin, Ca ATPase to INCREASE Ca Reabsorption
PTH: binding increases vitamin D - more Ca Reabsorption (unique to kidney, not intestine)
How is P regulated in the gut?
Vitamin D = increases production of NaPi-IIb = more P absorption
How is P regulated in the kidney?
FGF23 = binds FGFR1 + Klotho = inhibits NaPi = less P reabsorption
PTH = binds PTH-R = inhibits NaPi = less P reabsorption
How is the activation of vitamin D regulated?
Vitamin D produced in liver, activated in nephron by 1alpha hydroxylase
PTH: stimulates 1alpha hydroxylase to increase vit D in Low serum Ca states
FGF23: inhibits 1alpha hydroxylase to decrease vit D in high serum P states (goal to lower P, more urine Ca binds P)
How is PTH regulated? Where?
Parathyroid Chief Cell
CaSR: high blood Ca = inhibits PTH synthesis
Vitamin D: binds VDR = inhibits PTH synthesis
FGF23: binds FGFR1 = inhibits PTH synthesis
What does FGF23 do? Where?
Bone: Source
function: lower blood P when it gets too high
Effects
Kidney: lowers NaPi-IIa/c = less P reabsorption
Gut: less 1-alpha hydroxylase = less vitamin D = less P absorption
Decreases PTH and vitamin D activity
What are the 4 etiologies of Hypercalcemia?
- High Production/Intake - more GI absroption
- Low utilization/intake - more bone resorption, less renal excretion
- Cellular Shift
- Pseudo-states (Acidosis - normal Ca, decreased total serum Ca)
Diagnostic approach to hypercalcemia
- High PTH - primary hyperparathyroidism
- Low PTH:
Measure PTH-related particle - produced by malignancy
Measure vitamin D (look for intoxication, chronic granulomatous disease - high vitamin D) - Consider medications - thiazides, lithium (more Ca reabsorption)
Diagnostic approach to hypocalcemia
- Low PTH - post-surgical removal of parathyroid
- High PTH - secondary hyperparathyroidism due to low Ca - caused by:
Vitamin D deficiency/resistance
Loss of Ca from circulation, drugs, disorders of Mg Metabolism (high Mg reabsorption competes for claudin 16)
What diuretic treats hypercalcemia?
What diuretic treats hypocalcemia?
Hypercalcemia: treat with LOOP diuretic = blocking NKCC decreases lumenal positivity = less Ca reabsorption
Hypocalcemia: treat with THIAZIDE diuretic = blocking NCCT increases Na/Ca exchanger activity = more Ca reabsorption
Diagnostic approach to hyperphosphatemia
- Poor Kidney Fx/P Excretion = due to CKD + excess diet P, or cell breakdown (hemolysis/rhabdomyolysis)
- Normal Kidney: Spurious cause - paraproteinemia (more blood protein makes P look more conc.)
True Hyper-P:
-hypoparathyroidism = low PTH = more renal P reabsorption
-Mg Deficiency, FGF-23 deficiency
