Calcium Disorders: Dr. Rob

Question 1

Calcium

Answer 1

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

Question 2

Phosphorus

Answer 2

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

Question 3

Hydroxyapatite formula

Answer 3

(Ca₁₀(PO₄)₆(OH)₂

Question 4

Bone is composed of

Answer 4

Hydroxyapatite

collagen

Question 5

enamel is composed of

Answer 5

hydroxyapatite

amelogenin

enamelin

Question 6

Body content and Distribution of calcium

Answer 6

Question 7

Calcium in Body fluid

Answer 7

• 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

Question 8

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

Answer 8

• 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

Question 9

Calcium Homeostasis Diagram

Answer 9

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

Question 10

How do you increase extracellular calcium pool?

Answer 10

• Increase Absorption
• Increase Bone Resorption
• Decrease Urine excretion

Question 11

Calcium absorption by the GUT/intestines

Answer 11

• 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

Question 12

Kidneys: How to increase the amount of Calcium Filtered

Answer 12

• 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

Question 13

Kidneys: After calcium has been filtered into lumen what happens

Answer 13

• 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

Question 14

Homeostatic mechanism to maintain extracellular calcium concentrations

Draw Chart

Answer 14

• 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)

Question 15

Calcitonin

Answer 15

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

Question 16

PTH

Answer 16

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

Question 17

PTH Actions on bones

Answer 17

• 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

Question 18

PTH and PTHrP MOA on Distal Convoluted tubules

Answer 18

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-D_28k*, and sodium calcium exchanger 1 (NCX1)*
   
   1. Calcitrol and estrogen increase expression of the same 3 proteins

Question 19

Calcium-sensing receptor (CaSR)

Answer 19

• sense changes in calcium concentrations