34- Regulation of Phosphate, Calcium, and Magnesium Balance

phosphate plays a critical role in

bone and urinary buffer for H

kidneys regulate blood phosphate and are influenced by what hormone

parathyroid hormone PTH

location of phosphate

bone matrix (hydroxyapatite) 85%

ICF 15% (organic form)

ECF <.5% (inorganic form)

list some of the ICF organic forms of phosphate

• dna

• rna

• atp

• metabolic intermediates

• cell membranes 

describe the <.5% ECF inorganic phosphate

buffer for H

some protein bound in plasma

describe the mechanisms that maintain serum phosphate in physio range 

pathways associated with…

• intestines - absorption

• bone - blood

• kidneys - regulation 

what can phosphorus deficiency lead to

1. impaired bone mineralization

2. abnormal erythrocyte, leukocyte, platelet function

3. impaired cell membrane integrity (rhabdomyolysis)

4. impaired cardiac output

impaired bone mineralization for old people vs kids

osteomalacia vs rickets

% of plasma phosphate filtered

90%

% of filtered phosphate reabsorbed in PCT

70%

% of filtered phosphate reabsorbed in proximal straight tubule

15%

later phosphate reabsorption is debatable and depends on what

dietary phosphate and hormones

what % of filtered phosphate is excreted and whats it important for

15%

important for acid buffering

serum phosphorus increases above reference when how much % of nephron mass is lost 

> 85%, late CKD 

why do serum phosphate levels increase only so late into CKD

PTH and FGF23 regulate serum phosphate fairly well until late CKD

describe the role proximal tubule cells play in phosphate reabsorption

Na/Phosphate co transporter in luminal membrane

• transport here is saturable - above T max Phosphate is excreted

what role does PTH play in phosphate regulation

regulates reabsorption of phosphate in PT by inhibiting Na/Phosphate co transport- causes phosphaturia

describe the process of PTH when regulating phosphate

1. PTH binds receptor on basolateral membrane

2. coupled to adenylyl cyclase and G protein and cAMP is produced

3. protein kinases activated

4. phosphorylation of luminal membrane components

5. Na/phosphate transport inhibited

PTH ____ blood Ca and ___ blood phosphate

inc, dec 

what are phosphatonins

macromolecules in ECF, usually proteins or peptides

what do phosphatonins do

• induce neg phosphate balance by inhibiting renal phosphate reabsorption in PT

• indirectly reducing intestinal absorption of phosphate and inhibiting synthesis of active vitamin D3

what will vitamin D3 normally do?

increase phosphate retention 

name 4 phosphate regulating substances

1. fibroblast growth factor 23 (FGF 23)

2. fibroblast growth factor 7 (FGF 7)

3. secreted frizzled related protein 4 (sFRP-4)

4. matrix extracellular phosphoglycoprotein (MEPE)

what is the overall result of FGF 23 and phosphate regulation

phosphaturia

describe FGF 23 and phosphate regulation

• secreted by osteocytes in response to elevated calcitriol (vit d)

• acts on kidneys to decrease na/phosphate cotransporter in PT

• suppresses 1-a-hydroxylase inactivating vit a which impairs ca absorption

location of calcium

bone 99%

ECF and ICF 1%

describe plasma Ca

• 40% bound to plasma proteins

• 10% bound to anions like phosphate

• 50% ionized (free Ca available)

hows Ca regulated

by PTH and involves bone, GIT, and kidneys

calcium homeostasis involves the interaction of what

• bone, kidney, intestine, PTH, calcitonin, and vit D

PTH ____ blood Ca and calcitonin ___ blood Ca

inc, dec 

describe the process of calcium homeostasis

1. bone is constantly remodeled so Ca can be released into or absorbed from blood

2. intestine will absorb Ca, amt regulated by vit D

3. PTH stimulates Ca reabsorption in DCT of kidneys

describe the % of renal handling of calcium

• 40% of plasma bound Ca to protein cant filter

• 60% is unfilterable

• 99% Ca reabsorbed and <1% excreted

% of Ca reabsorbed in proximal tubule

67%

what is Ca reabsorption tightly coupled to 

Na reabsorption in proximal tubule and thick ascending limb 

• changes in Ca reabsorption mirror changes in Na reabsorption

describe what occurs in the thick ascending limb for renal handling of calcium

• 25% filtered Ca reabsorbed here

• paracellular route coupled to Na reabsorption and K leaking back into lumen

what occurs if K leaks back to lumen

creates a lumen net charge and drives reabsorption of additional cations via paracellular route (Ca)

what do loop diuretics do with calcium

inhibit Ca reabsorption as a result of inhibiting Na reabsorption. can use this relationship to treat hypercalcemia

• lumen pos charge is lost w lack of k so driving force to reabsorb Ca is lost

the early distal tubule reabsorbs what % of filtered Ca

8%

is early distal tubule a site of regulation of ca absorption?

yes but NOT coupled to Na reabsorption here

how does PTH regulate Ca reabsorption in DT

• increases reabsorption - hypocalciuric action

• mostly transcellular reabsorption via TRPV-5 luminal Ca channel

• carried across the cell, bound to calbindin

  • Na-Ca antiporter or Ca ATPase

how to thiazide diuretics increase Ca absorption

• inhibit Na/Cl symporter on luminal membrane

• inhibit Na reabsorption

• Dec Na inside cells, inc Na excretion

what does less Na entering from lumen do

increases activity of Na/Ca antiporter on basolateral membrane

• brings Na in from blood and reabsorbs more Ca from lumen

what can thiazide diuretics treat

idiopathic hypercalciuria or animals prone to forming calcium stones

how much % of plasma Mg is bound to proteins and filterable

20% bound to proteins

80% filterable

% of Mg reabsorbed and excreted 

95% reabsorbed, 5% excreted

% of filtered Mg reabsorbed in PT

30%

____% filtered Mg is reabsorbed in TAL which is driven by lumen pos charge

60%

what % of Mg is reabsorbed in DT

5%