Ca & Phos Homeostasis Flashcards
Normal Calcium-Phosphorous Homeostasis
Parathyroid gland: calcium-sensing receptor
PTH is released during low serum Ca & stimulates bones: osteoclasts (breakdown of bone cells –> Ca release in the blood)
Kidney: absorbs more ca in proximal tubule & excrete more phosphate in prox tubule & regulates production of Vitamin D
Gut: tells intestine to absorb more Ca and Phosphorous from food
Cutaneous Vitamin D3 Synthesis
P7-Dehydrocholesterol (a preVit D) –> UVB radiation from sun –> Previtamin D –> temperature sensitive isomerization –> binds Vitamin D binding hormone in the blood & can travel to the liver where it’s further metabolized
Calictriol synthesis in liver and kidney
In the liver: Vitamin D3 –> 25-Hydroxyvitamin D
This goes to the kidney
In the kidney: 1-alpha hydroxylase –> Calcitriol = active vitamin D3
This last step is the final step and is highly regulated!
Regulation of last step of calcitriol synthesis?
Activates its conversion: high PTH, low serum levels of Ca/Phos
Inhibits its conversion: high Ca/Phos, high calcitriol
What are the 2 mechanisms of gut absorption of Ca?
Cell mediated: modulated by Calcitriol; saturable, active process
Passive diffusion: dominates at high levels of Ca intake
Renal Calcium handling: how much is filtered/excreted?
10g/day filtered, 100-300 mg/day excreted
70% passively reabsorbed in prox tubule
TALH reabsorbs 20%:
- paracellular via Na-K-2Cl (establishes electrochemical gradient that encourages Ca reabsorption)
- Ca sensing receptor on basolateral membrane of TALH cells reduces lumen charge with hypercalcemia
DCT: 8% is reabsorbed: physiologic regulatoin of Ca excretion, induced by Calcitriol to enhance excretion
-Na-Ca exchanger, Ca-ATPase
Collecting duct: <5% filtered Ca load
What regulates Ca handling in kidney?
PTH is the main regulator: it reduces urine calcium in the proximal tubule, increases Ca reabsorption in the TALH, opens the epithelial Ca channel in the DCT
Calcitriol: decreases Ca absorption in kidney
Phosphorous: reduces urine Ca, stimulates PTH expression
How is phosphate absorbed in the gut?
Passive transport, driven by how much one eats: usually 60-80%
Vitamin D doesn’t play much of a role in net phos absorption except with administration of active D, as in CKD
How is phosphate handled in the kidney?
85% of serum phosphate is ultrafiltered
Na-Phos co-transporter moves phos against an electrochemical gradient, hence it’s actively removed from the urine
85% of reabsorption occures in the prox tubule
12.5% is excreted into the urine
FGF-23
Synthesized in the bone
Has overlapping function with PTH to reduce renal Pi absorption, keeps phosphate levels in blood within a narrow range
Suppresses NP2a and NPT2 (Na/Phosphate channel)
Suppresses production of Vitamin D
CKD Stages 1-5
Stage 1: GFR >90, evidence of kidney damage
Stage 2: GFR 60-89, evidence of kidney damage
Stage 3: GFR 30-59
Stage 4: GFR 15-29
Stage 5: GFR <15
What’s the pathophysiology of CKD-MBD (bone mineral disorders)?
Increased plasma HPO4
Decreased GFR
Decreased Vitamin D metabolism
–> decreased Ca absorption –> decreased plasma Ca
–> increased PTH
–> increased osteoclasts
–> Ca and HPO4= reabsorbed from bones
–> osteodystrophies
OR
–> increased CaHPO4 product –> metastatic calcifications (skin, blood vessels, kidney stones)
Which organ abnormalities can you get in CKD-MBD?
Multi-organ sydrome: kidney, skeleton, parathyroid glands, cardiovascular system, soft tissues
Disorders include: hyperparathyroidism, increased risk of heart attack and stroke, fractures, ectopic calcifications
How do you get impaired Vitamin D synthesis in CKD-MBD?
The kidney can’t convert it to calcitriol (active vitamin D)
How do you get impaired phosphate clearance in CKD-MBD?
High phosphate levels –> more PTH, more FGF-23 –> tell kidney to secrete phosphate but it’s damaged so it can’t –> phosphate levels continue to go up
