Lecture 22: Ca metabolism Flashcards

1
Q

What regualtes Ca concentrations:

A

Ca, Vit D and PTH are responsible for Ca homeostasis

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2
Q

What are the main organs involved in Ca homeostasis:

A

Intestine
Kidneys
Bones (stores)

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3
Q

How is Ca found?

A

iCa - 50%
Protein bound - 40%
Ion-complexed - 10%

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4
Q

Write an overview on PTH:

A
  • Chief cells of parathyroid gland
  • Released within minutes of decreased Ca
  • Main defender of the serum Ca
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5
Q

How does PTH act?

A
  • Stimulates osteoclastic bone resorption
  • Stimulates renal tubular reabsorption of Ca2+
  • Stimulates renal 1-hydroxylation of 25(OH)D

Restores serum Ca by acting on all effector organs. Bone and kidney directly; Intestine indirectly

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6
Q

Insert the diagram

A

Slides 2-3

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7
Q

insert slide five

A

thanks

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8
Q

What regulates PTH?

A
  • Serum ionized Ca (most imp) (decreases PTH)
  • Serum phosphate (increases PTH)
  • Serum 1,25 dihydroxyvitamin D (decreases PTH)
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9
Q

Describe how ECF Ca is found:

A

45-50% ionized, bioactive
5-10% complexed with anions i.e HCO3
45-50% protein-bound, albumin and globulins

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10
Q

Describe how Ca can induce PTH release:

A

Ca binds the receptor with Mg as a cofactor to decreased PTH released from cheif cells

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11
Q

How does CaR regulate renal tubular Ca handling:

A

Ca binds CaR and decreases the absorption via:

  • Paracellularly
  • Na,Cl,K pumps and K efflux pumps (i.e the gradients that create the gradient for Ca paracellular transport)
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12
Q

Describe Vit D metabolism:

A

slide 10

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13
Q

Does calcitonin regulate serum Ca?

A

no

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14
Q

What is PTHrP?

A

PTH related peptide

  • Important paracrine regulator of breast, skin and bone development.
  • Not a physiological regulator of serum Ca BUT in excess acts same was as PTH and can cause hypercalcemia
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15
Q

What are the PTH-dependent causes of hypercalcemia?

A

Primary hyperparathyroidism

FHH/Inactivating CaSR mutations

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16
Q

What are the PTH-independent causes of hypercalcemia?

A

[High Ca and low PTH]

  1. Cancer
    - > PTHrP
    - > Lytic bone disease
    - > Vit D issues
  2. Vit D - dependent
    - Sarcoidosis
    - Vit D intoxication
17
Q

What are the causes of hypocalcemia:

A
Hypoparathyroidism
- Post surgical, post neck irradiation
Parathyroid hormone resistance
Abnormal Vit D metabolism
-> Vit D deficiency, resistance
-> Renal failure
18
Q

Insert slide 15 ishq

A

thanks

19
Q

What are the important hormones in phosphate metabolism?

A

Vit D
PTH
Phosphotonins

20
Q

What do phosphotonins do?

A

Regulate renal handling of phosphate

21
Q

What hormone determine flux of phosphate between ICF and ECF?

A

High pH (Drives from ECF to ICF)

22
Q

What are the important organs of phosphate metabolilsim?

A

Intestines (dietary)
Bone (storage)
Kidneys (Filtration and reabsorption)

23
Q

What are the causes of hyperphosphatemia?

A

Increased input: IV phosphate, cell death

Decreased excretion: Renal failure, PTH deficiency or resistance

24
Q

What are the causes of hypophosphataemia?

A
  • Inadequate GI absorption i.e b/c Vit D deficient
  • Intracellular shift
  • Resp. alkalosis (Illness, pain), usually self limiting
  • Prolonged intense exercise
  • Refeeding malnourished patients
  • renal loss
  • Inc. PTH
  • Inc. phosphatonins
  • Alcoholism
    (Sufficient impairment can alter bone metabolism)
25
Q

Whats the action of phosphotonins?

A

Phosphatonins i.e FGF23 (derived from bone)

  • > Inhibits kidney phosphate reabsoprtion
  • > Inhibits Vit D and thus gut phosphate absorption

= Hypophosphatemia

26
Q

What is FGF23 essential in? where does it act?

A

Phosphate conditions

Acts in kidneys to increase phosphate excretion and decrease renal production of 1,25 OH D…

= Phosphate loss

27
Q

In the FGF23 pathway (insert slide) where can mutations occur?

A
  • Defective luminal GI Pi transports i.e Fanconi syndrome can increase phosphate excretion in kidneys
  • Ectopic FGF23 can enhance its effects i.e oncogenic osteomalacia
  • Abnormal FGF23 can mean its inactivated.
  • Abnormal PHEX in bones can lead to inactive FGF23

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