Lecture 9: Calcium metabolism Flashcards Preview

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Flashcards in Lecture 9: Calcium metabolism Deck (17):

Major hormonal players?

Most important is PTH which provides min to min regulation of extracellular fluid Ca which in itself plays a role as it controls PTH release. 

Bioactive Vitamin 1,25(OH)2D from 25(OH)D is in part related to PTH 

Calcitonin doesn't do shit, it is not a physiological regulator of serum calcium


Bound/non-bound forms of Ca?

50% in ionised Ca2+ (bioactive and regulated PTH production)

40% protein bond (mostly albumin)

10% ion-complexed


Major organ involvement in Ca metabolism?

Bone acts as a reservoir for Ca 

The kidney regulates the excretion of Ca and contributes to the rapid response to changes


What is PTH?

Parathyroid hormone (PTH) 

Main 'defender' of serum calcium 

84aa hormone from chief cells (has receptors in membrane for ionised Ca2+ detection) of parathyroid gland (we have 4 or 5) and bind to PTH receptor 1 

Released within minutes of a drop in Ca2+ 

  1. stimulaes ostclastic bone resorption 
  2. stimulates renal tubular reabsorption of Ca (V QUICK)
  3. Stimulates renal 1-hydroxylation of 25(OH)D - forms bioactive VitD that stimulates intestinal Ca and phosphate absorption 

Restores serum Ca2+ by acting on all effector organs: Bone and kidney directly + intestine indirectly 


PTH regulation?

Mostly by serum ionised calcium (-vely)

secondarily: Serum phosphate (+vely) and serum 1,25dihydroxyvitamin D (-vely) 

(-vely) = if levels are high then PTH production is switched off


Role of ECF Ca on renal tubular secretion?

There are the same calcium sensing receptors in the basolateral membrane of the renal tubule and so high levels of ECF Ca lead to changes resulting in a decreased uptake of more Ca and other ions. 


Vitamin D metabolism explain quickly?

Firstly it's straight up a hormone not a vitamin but any who moving on

It is a hormone made due to UV B and is stored as calcidiol (25OHD) where it can be then converted to calcitriol (1,25(OH)2D) due to increased PTH or decreased Pi. This then causes increased absorption of both Ca and Pi in the intestine to increase the levels. 




Parathyroid hormone-related peptide 

Important paracrine regulator of breast, skin and bone development NOT a physiological regulator of serum calcium

Produced in excess by some cancers (esp. epithelial cell tumours) leading to humoral hypercalcemia of malignancy (HHM) 

Most common cause of cancer-associated hypercalcemia 

Acts similar to PTH, signals via PTHR1 and can lead to severe and life-threatening hypercalcaemia. 

Normally by the time the cancer is big enough to cause hypercalcaemia it is known about so isn't normally a signal for occult cancer. 


What are some causes of hypercalcaemia?

PTH-dependent - increased sCa2+ and PTH (or abnormally normal PTH for the raised PTH)

  • Primary hyperparathyroidism 
  • FHH/inactivating CaSR mutations (Ca Sensing Receptor)

PTH-independent - increased sCa2+ BUT decreased PTH

  • Cancer (PTHrP, extensive lytic bone disease such as multiple myeloma releasing large amounts of Ca) 
  • Vitamin D-dependent (sarcoidosis, VitD intoxication) 


Some important causes of hypocalcaemia?


  • postsurgical, post neck irradiation 
  • genetic - CaSR activating mutations 
  • Severe hypomagnesaemia (impairs ability to respond) - can come from PP inhibitors like omeprazole
  • autoimmune 

Parathyroid hormone resistance

  • pseudohypoparathryoidism (types Ia, Ib, Ic, II) - signalling to effector tissues are inactivated - low Ca levels but high PTH

Abnormalities of vitamin D metabolism 

  • Vitamin D deficiency from sunlight deprivation 
  • Renal failure - impried ability to make bioactive VitD 
  • deficiency of 1a-hydroxylase 


Phosphate metabolism? 

Like Calcium, both Vitamin D's role with the intestine and PTH's role with bone is involved with increasing ECF levels as well as its role with the kidneys to stimulate the excretion of Pi. 

The hormonal difference is the phosphatonins (eg. Fibroblast growth factor (FGF) 23), these are derived from osteocytes in bone and - regulate the renal handling of phosphate such that they stimulate phosphoturia. Present in high enough levels can lead to significant defecit in Pi with impact on bone mineralisation. 


Organs involved with Pi metabolsim? Important contributors to level of Pi?

The diet is somewhat important but is very hard to become deficient from lack in diet

More important is the flux between ICF and ECF. Many ilnesses that cause respiratory alkalosis stimulate movement from extracellular to intracellular. Not really a problem and better to focus on the underlying ilness. 

The kidney is important in regulation as it is the source of the tissue responsble for hypophosphotaemia. 


Causes of hyperphosphatemia?

Decreased excretion

  • Renal failure (eGFR below 30ml/min) 
  • PTH deficiency or resistance (mild hyperphosphatemia)

Incrased input 

  • IV phosphate, cell death -(burns, rapid onset tumour cell death) 


Causes of hypophosphatemia?

Intracellular shift 

  • resp alkalosis usually self-limiting 
  • prolonged intense exercise 
  • refeeding malnourished patients 

Renal Loss 

  • increased PTH 
  • Increased phoshatonins (inherited or aquired pathophysiological conditions) 
  • Alcoholism 

Inadequate GI absorption eg. Vitamin D deficiency 


Sodium phosphate transporters in the renal tubule are regulated by?

To some extent by PTH but mostly by FGF-23


Phosphate losing conditions?

FGF 23 inhibits both 1a-hydroxylase and NaPi transporters in the renal tubules. 

This leads to decreased intestinal absorption and increased renal excretion (exacerbated by an increase in PTH due to decreased Ca absorption) 

= Phosphate loss


How are high levels of FGF-23 achieved?

FGF-23 can be: 

Elaborated by tumours often from mesenchymal origin so fixed to the skeleton or cartilage components 

These tumours make and secrete FGF-23 at levels that exceed the ability to inactivate the protein 

= hypophosphatemia 

FGF-23 gene itself can be mutated making it resistant to normal catabolic processes. 

The PHEX enzyme from osteoblasts that normally inactivates/catabolises FGF can be mutated