Lecture 8.2: Calcium Handling in the Kidney and Stone Formation Flashcards
What is the physiological role of calcium?
- Structural
- Coagulation
- Muscle contraction + regulation of
excitability - Intracellular signalling molecule
- Regulates excitability of neurones and
myocardial cells
How do we regulate our plasma calcium level? Hormones?
- Parathyroid hormone (PTH): Acts to
INCREASE plasma calcium - Vitamin D metabolites (calcitrol): Acts to
INCREASE whole body calcium - Calcitonin: Acts to DECREASE plasma
calcium
What is the physiological response to falling calcium levels? (5)
- Chief cells secrete increased PTH
release - Increased intestinal absorption
- Increased calcium reabsorption
(kidney) - Decreased phosphate reabsorption
(kidney) - Increased calcium resorption (bone)
What effect does calcitriol (1, 25 – dihydroxyvitamin D) have? (3)
- Increased intestinal absorption of
calcium and phosphate (PRIMARY) - Increased kidney reabsorption calcium
and phosphate - Facilitates resorption of calcium
What are some Hypocalcaemia Symptoms? (7)
- Neuromuscular Instability (tetany)
- Paraesthesia
- Muscle twitching
- Seizures
- Laryngospasm
- Chovtek’s Sign
- Trousseau’s Sign
Why does Hypocalcaemia cause muscle spasms?
Hypocalcaemia causes increased neuronal sodium permeability > increased excitability of neurones
What is Chovtek’s Sign?
Twitching of the muscle of facial
expression when the facial nerve is tapped
What is Trousseau’s Sign?
Spasm of the hand and forearm when a blood pressure cuff is inflated around the arm
What are causes of Hypocalcaemia?
- Hypoparathyroidism (after thyroid
surgery, autoimmune) - Vitamin D deficiency (dietary, CKD,
lack of sun)
Treatment of Hypocalcaemia?
- Vitamin D supplements
- Calcium supplements
- Treat the underlying cause
What is the physiological response to rising calcium levels? (3)
- C cells (parafollicular cells) of the
thyroid release Calcitonin - Decreased reabsorption of calcium and
phosphate in the kidneys - Inhibition of osteoclastic activity
What are some Symptoms of Hypercalcaemia? (9)
- ’Bones, stones, groans, thrones, and
psychiatric overtones’ - Bone Pain
- Renal Stones
- Abdominal Pain/Nausea/Vomiting
- Polyuria
- Confusion
- Altered Behaviour
- Fatigue
- Coma
What are causes of Hypercalcaemia? (4)
- Primary hyperparathyroidism
- Hypervitaminosis
- Malignancy
- Renal Failure
What is the Treatment for Hypercalcaemia?
- IV hydration
- Treat the underlying cause
How is calcium reabsorbed in the PCT?: Overview
Mostly via the passive, paracellular route down an (electro) chemical gradient
How is calcium reabsorbed in the PCT?: 4 Steps
1) The sodium potassium pump extrudes
sodium from the cell generating a
concentration gradient
2) Sodium is reabsorbed from the
filtrated in the lumen down the
concentration gradient (can be
coupled to glucose reabsorption,
amino acid reabsorption etc)
3) As the concentration of sodium in the
filtrate falls, water is reabsorbed
moves by osmosis thorough the
paracellular route
4) As the concentration of calcium ions
(and other ions) in the lumen starts to
increase, calcium ions follow water
through the paracellular route
How is calcium handled by different parts of the kidney? Percentages?
- PCT (65% reabsorbed)
- TAL (25% reabsorbed)
- DCT-CNT (8% reabsorbed)
What does the transcellular part (DCT-CNT) of the nephron help regulate?
Major site for regulation of calcium
excretion
How is calcium reabsorbed in the TAL?: Overview
Mostly via the passive, paracellular route down an electro(chemical) gradient
How is calcium reabsorbed in the thick ascending limb?: 5 Steps
1) NKCC pumps one Na, one K and two
Cl ions from the lumen
2) Na and Cl ions exit the cell via.
basolateral transporters
3) K re-enters the lumen of the nephron
via ROMK channels.
4) There has been a net movement of
two negative ions (Cl) and one
positive ion (Na) from the lumen,
giving the lumen a weak positive
charge
5) Calcium moves down electrochemical
gradient via the paracellular route
How is calcium reabsorbed in the DCT?: Overview
Mostly via an active, transcellular route down an (electro)chemical gradient
How is calcium reabsorbed in the DCT?: 4 Steps
1) A basolateral ATPase extrudes
calcium
2) Calcium is also exchanged for sodium
at the basolateral surface
3) This creates a concentration gradient
between the lumen and the epithelial
cell
4) Calcium moves down concentration
gradient via the TRPV channels
What are TRPV5 channels are up-regulated by? What does this mean?
- Increase in the number or density of
cell surface receptors/increase activity - PTH
- Vitamin D
How is phosphate handled by different parts of the kidney? Percentages?
- PCT (80% reabsorbed)
- DCT (5% reabsorbed)
