Lecture 22 - Renal handling of calcium Flashcards
What can rickets be caused by?
a deficiency or impaired metabolism of vitamin D, calcium or phosphorus.
The predominant cause is vitamin D deficiency
What is Ca2+ homeostasis a balance between?
Kidneys, intestine and bone
What is the concentration % of Ca2+ in the Body?
(Bone/Teeth, ICF and the ECF)
Bone and Teeth (99%)
ICF = generally < 0.1 µM (1%)
ECF = 2-3 mM (0.1%)
What happens when ECF Ca2+ > 3 mM?
Hypercalcemia (High Ca2+ blood)
What happens when ECF Ca2+ < 2 mM?
Hypocalcaemia (Low Ca2+ blood)
Why is it important to maintain appropriate ICF and ECF concentrations of Ca2+?
- proper bone formation
- neurotransmission
- mitosis, cell division and growth
- muscle contraction
- blood clotting
- growth
- enzymatic reactions
- 2nd messenger function
What are the problems of low ECF Ca2+ (hypocalcaemia)? (6)
- increase excitability of:
– nerve cells
– muscle cells - ʻpins and needlesʼ
- airway obstruction
- epileptic seizures
- cardiac arrhythmias
- hypocalcemia tetany
– muscle spasms
What are the problems of high ECF Ca2+ (hypercalcemia)? (5)
- decrease excitability of:
– nerve cells
– muscle cells - disorientation
- lethargy
- cardiac arrhythmias
- death
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.
C. The ECF Ca2+ concentration is between 2-3 mM.
What % of Ca2+ in the plasma can be filtered?
60%
How is Ca2+ stored in plasma?
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=)
What is the average Daily filtered load of Ca2+?
GFR x [Ca2+]plasma = Daily filtered load
180 L/day x 2.5 mmol/L = 450 mmoles/day (filtered)
What is the reabsorption of Ca2+ in the PT?
The PT Reabsorbs 50-60% of Filtered load of Ca2+ through solvent drag/bulk flow. This Ca2+ transport is via the paracellular (100%) pathway
What is the reabsorption of Ca2+ in the TAL?
The TAL Reabsorbs 15% of Filtered load the of Ca2+. This reabsorption however is regulated by Ca2+sensing receptor
monitors.
What does Claudin-16 do?
Claudin-16 plays a role in maintaining the permeability of the tight junctions that favours transport and Ca2+, Mg2+ and Na+
What % of Ca2+ reabsorption does the DCT do?
10-15%
How is Ca2+ reabsorbed in the DCT?
Ca2+ channel entry - TRPV5 and TRPV6
Exit via Ca2+-ATPase and Na+/Ca2+-exchanger
What does Claudin 8 (CLND8) do?
Claudin 8 (CLND8) is a tight junctional protein which prevents the movement of Ca2+
What claudin is found in the TAL?
Claudin-16
What claudin is found in the DCT?
Claudin 8
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.
D. Ca2+-sensing receptors monitor the intracellular Ca2+ concentration. - Senses ECF
What is the role of calbindin (CB) in Ca2+ reabsorption?
Calbindin binds to calcium - neutralises Ca2+ so can’t be used in other reaction, carries it to the Ca2+-ATPase
What hormones are involved in Ca2+ homeostasis?
Parathyroid hormone (parathyroid gland)
Calcitriol
When is Parathyroid Hormone (PTH) stimulated?
PTH is stimulated by low plasma Ca2+ levels (hypocalcemia)
What does PTH do?
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
What stimulates the release of calcitriol?
Calcitriol is released by the influence of PTH due to low calcium
What does calcitriol do?
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
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.
B. The parathyroid hormone is released by high plasma Ca2+.
