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Flashcards in Calcium Disorders: Dr. Rob Deck (19)
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1

Calcium

  • 1-2% of adult lean body mass
  • 99% of calcium is in bones and teeth

2

Phosphorus

  • 1-1.5% of adult lean body mass
  • 85% of Phosphorus is in bones

3

Hydroxyapatite formula

(Ca10(PO4)6(OH)2

4

Bone is composed of

Hydroxyapatite

collagen

5

enamel is composed of

hydroxyapatite

amelogenin

enamelin

6

Body content and Distribution of calcium

7

Calcium in Body fluid

  • 45% bound to proteins (mostly albumin (80%) and globulins)
    • cannot:
      • cross membranes 
      • used by tissue
    • Highly pH Dependent
  • 5-10% complexed with anions
    • mostly phosphate and carbonate
    • sulfate
    • citrate
  • 45-50% of calcium is ionized
    • Ionized calcium=bioactive
    • increases in acidosis, decreases in alkalosis
    • decreases as anion concentrations increase
      • especially phosphate

8

Why is the 0.025% calcium in the plasma clinically important?

  • BECAUSE most disorders of calcium homeostasis correlate with the calcium in the extracellular fluid
  • Extracellular [Ca2+] of 10.5 or more=hypercalcemic
    • 10.5-12
      • mild
      • asymptomatic
    • 12-14
      • moderate
    • 14+
      • severe
      • life threatening
  • Hypocalcemia= Below 8.5
    • Ionized Calcium below 4.4 =Hypocalcemic

9

Calcium Homeostasis Diagram

  • Main source of alcium is ingested from:
    • milk
    • fish
    • beans
    • greens

10

How do you increase extracellular calcium pool?

  • Increase Absorption
  • Increase Bone Resorption
  • Decrease Urine excretion

11

Calcium absorption by the GUT/intestines

  • Passive Transport=Diffusion
    • entire small intestine
    • driving force=difference in calcium conc between the lumen and the blood
    • [Ca2+]>5
  • Active transport
    • duodenum and early jejunum
    • driving force=Plasma membrane ATPase (PMCA)
    • [Ca2+]<5

12

Kidneys: How to increase the amount of Calcium Filtered

  • Increase Filtered load to increase amount of calcium filtered
    • Filtered Load=GFR
      • Increase Hydrostatic Pressure=Increased GFR (=Increase Filtered load=Increase Calcium filtered)
  • Increasing Afferent arteriole pressure
    • directly increases hydrostatic pressure, GFR, and filtrated load

13

Kidneys: After calcium has been filtered into lumen what happens

  • Proximal tubule and Thick Ascending Limb (TAL)
    • Passive transport
      • Solvent drag (Ca2+) as water diffuses
        • initial driver
      • Water reabsorption creates concentration gradient
        • main driver
      • Transepithelial electrical potential
  • Distal Convoluted Tubule
    • Active Transport
      • Plasma membrane calcium ATPase=driver

14

Homeostatic mechanism to maintain extracellular calcium concentrations

Draw Chart

  • PTH is secreted with circadian rhythm and pulsatile fashion
    • peaks overnight when calcium is minimum
  • Calcitonin follows circadian rhythm
    • minimum at night
    • peak when calcium is absorbed by the intestine (after meal)

15

Calcitonin

  • corrects hypercalcemia
  • effects are mainly by its action on bone
    • maximized in children 
      • bc growing bones=high calcium deposition
    • marginal in adults

16

PTH

  • corrects hypocalcemia
  • effects mainy due to action on kidneys and bones

17

PTH Actions on bones

  • PTH
    • acutely (mins to hours) increases bone deposition
      • binds to osteoblasts (not osteoclasts
    • increases the expression of RANKL
      • stimulates the:
        • proliferation and fusion of osteoclast precursors
        • differentiation into mature osteoclasts
      • Progressively enhances bone resorption
  • Prolonged PTH exposure:
    • decreases the expression of OPG
      • decoy for activator for the RANK B ligand
  • Prolonged PTH exposure or prolonged PTHrP leads to bone resorption

18

PTH and PTHrP MOA on Distal Convoluted tubules

Increases calcium reabsorption in the distal convoluted tubule by 2 mechanisms:

  1. PTH acutely increases Phosphorylation of transcient potential receptor vanilloid 5
  2. PTH chronically increases the expression of TRPV5*, Calbindin-D28k*, and sodium calcium exchanger 1 (NCX1)*
    1. Calcitrol and estrogen increase expression of the same 3 proteins

19

Calcium-sensing receptor (CaSR)

  • sense changes in calcium concentrations