Lecture 22 - Renal handling of calcium

Question 1

What can rickets be caused by?

Answer 1

a deficiency or impaired metabolism of vitamin D, calcium or phosphorus.
The predominant cause is vitamin D deficiency

Question 2

What is Ca2+ homeostasis a balance between?

Answer 2

Kidneys, intestine and bone

Question 3

What is the concentration % of Ca2+ in the Body?
(Bone/Teeth, ICF and the ECF)

Answer 3

Bone and Teeth (99%)
ICF = generally < 0.1 µM (1%)
ECF = 2-3 mM (0.1%)

Question 4

What happens when ECF Ca2+ > 3 mM?

Answer 4

Hypercalcemia (High Ca2+ blood)

Question 5

What happens when ECF Ca2+ < 2 mM?

Answer 5

Hypocalcaemia (Low Ca2+ blood)

Question 6

Why is it important to maintain appropriate ICF and ECF concentrations of Ca2+?

Answer 6

• proper bone formation
• neurotransmission
• mitosis, cell division and growth
• muscle contraction
• blood clotting
• growth
• enzymatic reactions
• 2nd messenger function

Question 7

What are the problems of low ECF Ca2+ (hypocalcaemia)? (6)

Answer 7

• increase excitability of:
  – nerve cells
  – muscle cells
• ʻpins and needlesʼ
• airway obstruction
• epileptic seizures
• cardiac arrhythmias
• hypocalcemia tetany
  – muscle spasms

Question 8

What are the problems of high ECF Ca2+ (hypercalcemia)? (5)

Answer 8

• decrease excitability of:
  – nerve cells
  – muscle cells
• disorientation
• lethargy
• cardiac arrhythmias
• death

Question 9

Which of the following statements is TRUE?
A. The bulk of Ca 2+ in the body is located within the ICF.
B. Low ECF Ca2+ causes decreased excitability of nerve cells.
C. The ECF Ca2+ concentration is between 2-3 mM.
D. Osteoporosis causes and increase in bone mass.

Answer 9

C. The ECF Ca2+ concentration is between 2-3 mM.

Question 10

What % of Ca2+ in the plasma can be filtered?

Answer 10

60%

Question 11

How is Ca2+ stored in plasma?

Answer 11

50% of the Ca2+ is ionized
40% of the Ca2+ is bound to protein (normally albumin), thus not filtered
10% of the Ca2+ is complexed with anions (HCO3, citrate, phosphate, SO4=)

Question 12

What is the average Daily filtered load of Ca2+?

Answer 12

GFR x [Ca2+]plasma = Daily filtered load
180 L/day x 2.5 mmol/L = 450 mmoles/day (filtered)

Question 13

What is the reabsorption of Ca2+ in the PT?

Answer 13

The PT Reabsorbs 50-60% of Filtered load of Ca2+ through solvent drag/bulk flow. This Ca2+ transport is via the paracellular (100%) pathway

Question 14

What is the reabsorption of Ca2+ in the TAL?

Answer 14

The TAL Reabsorbs 15% of Filtered load the of Ca2+. This reabsorption however is regulated by Ca2+sensing receptor
monitors.

Question 15

What does Claudin-16 do?

Answer 15

Claudin-16 plays a role in maintaining the permeability of the tight junctions that favours transport and Ca2+, Mg2+ and Na+

Question 16

What % of Ca2+ reabsorption does the DCT do?

Answer 16

10-15%

Question 17

How is Ca2+ reabsorbed in the DCT?

Answer 17

Ca2+ channel entry - TRPV5 and TRPV6
Exit via Ca2+-ATPase and Na+/Ca2+-exchanger

Question 18

What does Claudin 8 (CLND8) do?

Answer 18

Claudin 8 (CLND8) is a tight junctional protein which prevents the movement of Ca2+

Question 19

What claudin is found in the TAL?

Answer 19

Claudin-16

Question 20

What claudin is found in the DCT?

Answer 20

Claudin 8

Question 21

Which of the following statements is FALSE?
A. 50% of the Ca2+ in plasma is ionized.
B. 60% of the blood Ca2+ can be filtered at the glomerulus.
C. The proximal tubule reabsorbs 50-60% of the filtered Ca2+.
D. Ca2+-sensing receptors monitor the intracellular Ca2+ concentration.

Answer 21

D. Ca2+-sensing receptors monitor the intracellular Ca2+ concentration. - Senses ECF

Question 22

What is the role of calbindin (CB) in Ca2+ reabsorption?

Answer 22

Calbindin binds to calcium - neutralises Ca2+ so can’t be used in other reaction, carries it to the Ca2+-ATPase

Question 23

What hormones are involved in Ca2+ homeostasis?

Answer 23

Parathyroid hormone (parathyroid gland)
Calcitriol

Question 24

When is Parathyroid Hormone (PTH) stimulated?

Answer 24

PTH is stimulated by low plasma Ca2+ levels (hypocalcemia)

Question 25

What does PTH do?

Answer 25

Stimulates bone resorption (break down) which releases Ca2+ into the plasma
Stimulates reabsorption of Ca2+ by the TAL and DT
Increases the release of calcitriol from the kidney

Question 26

What stimulates the release of calcitriol?

Answer 26

Calcitriol is released by the influence of PTH due to low calcium

Question 27

What does calcitriol do?

Answer 27

Stimulates resorption (breakdown) of bone and releases Ca2+ into the plasma
Stimulates reabsorption of Ca2+ by the DT
Stimulates Ca2+ absorption by the intestine
Negative feedback on the parathyroid gland to regulate the release of PTH

Question 28

Which of the following statements is FALSE?
A. The kidneys, bone and intestine all play roles in Ca2+ homeostasis.
B. The parathyroid hormone is released by high plasma Ca2+.
C. Calcitriol is activated vitamin D3.
D. Parathyroid hormone stimulates resorption of bone.

Answer 28

B. The parathyroid hormone is released by high plasma Ca2+.