Mineral Homeostasis

Question 1

describe the renal handling of calcium

Answer 1

proximal tubule: reabsorbs 60-70% of filtered calcium

thick ascending limb: reabsorbs 20% paracellularly due to the K+ backleak creating a positive charge in the lumen

distal convoluted tubule: reabsorbs 10%; transcellular reabsorption of calcium exchanged with Na+ on basolateral membrane
collecting duct: reabsorbs 5%

Question 2

describe the renal handling of phosphorous

Answer 2

proximal convoluted tubule: reabsorbs 85%!!; via co-transport with Na+; the amount reabsorbed depends on the abundance of sodium-phosphate cotransporters in the apical membrane; a Tm-limited system where parathyroid hormone and fibroblast growth factor-23 reduce reabsorption by decreasing abundance of sodium-phosphate co-transporters

thick ascending limb: reabsorbs 10%

distal convoluted tubule: reabsorbs 3%

collecting ducts: reabsorb 2%

Question 3

describe the renal handling of magnesium

Answer 3

proximal convoluted tubule: only reabsorbs 10-20%!

thick ascending limb: reabsorbs 70%!!; paracellular reabsorption of magnesium due to the K+ backleak (like calcium)

distal convoluted tubule: rebsorbs 10%; transcellular reabsorption as magnesium is exchanged with Na+ on the basolateral membrane

none left to be reabsorbed in collecting ducts

Question 4

explain the regulation of vitamin D and how its effects on bone, kidney, and GI tract alter plasma concentration of calcium and phosphorous

Answer 4

in order to be active, vitamin D has to be converted from cholecalciferol (D3) to calcidiol (25-hydroxyvitamin D3) by the liver, and then to calcitriol (1,25-hydroxyvitamin D) by the enzyme 1alpha-hydroxylase in the kidney

a decrease in plasma phosphate concentrations activates/enhances the activity of 1alpha-hydroxylase, which activates vitamin D to calcitriol

an increase in plasma phosphate concentrations inhibits/decreases the activity of 1alpha-hydroxylase, resulting in less calcitriol

parathyroid hormone also stimulates activity of 1alpha-hydroxylase, and then the calcitriol produced negatively feeds back to decrease parathyroid hormone levels

once activated, calcitriol:
1. increases intestinal absorption of calcium and phosphate
2. increases renal calcium reabsorption
3. enhances calcium and phosphate resorption from bone

Question 5

explain the regulation of parathyroid hormone and how its effects on bone, kidney, and vitamin D alter plasma concentrations of calcium and phosphorous

Answer 5

parathyroid hormone is a peptide hormone secreted by chief cells of the parathyroid gland

a decrease in plasma calcium concentration stimulates the parathyroid gland to secrete parathyroid hormone

once secreted, PTH:
1. stimulates 1alpha-hydroxylase to activate vitamin D to calcitriol, which will negatively feedback and decrease PTH secretion
2. enhances calcium and phosphate resorption from bone
3. decreases renal phosphate reabsorption and increases renal calcium reabsorption, increasing calcium in ECF

Question 6

explain the regulation of fibroblast growth factor-23 and how its effects on kidney and vitamin D alter plasma phosphorous concentration

Answer 6

fibroblast growth factor-23 is a phosphatonin hormone regulating phosphate balance

FGF-23 is released from osteocytes in response to increased phosphorous, calcitriol, and PTH concentrations whose result is decreasing phosphorus and calcitriol concentrations

Question 7

explain the regulation and effects of caclcitonin

Answer 7

calcitonin is a peptide hormone secreted by parafollicular cells of the thyroid gland that acts to decrease plasma calcium levels by decreasing bone resorption and increasing renal excretion of calcium, opposing the effects of PTH and vitamin D

Question 8

predict changes in parathyroid hormone, vitamin D, and calcitonin in response to alterations in plasma concentration of ionized calcium

Answer 8

ionized calcium decrease:
1. increased PTH which leads to
2. increased calcitriol (vitamin D) via 1alpha-hydroxylase (negative feedback on PTH)
3. decreased calcitonin

all this results in increased calcium and phosphate intestinal absorption, efflux from bone, and increased renal calcium reabsorption; the increased renal calcium reabsorption decreases renal phosphate reabsorption, as well as decreased calcium and increase phosphate excretion in urine, leading to a net result of restoring calcium levels to normal while leaving phosphate levels unchanged

ionized calcium increase:
1. decrease in PTH secretion which leads to
2. decreased vitamin D (calcitriol)
3. increased calcitonin