Calcium Flashcards
Explain what happens to serum Ca2+ levels during acidosis and alkalosis [2]
Acidosis: causes Ca2+ to increase
Alkolosis: causes Ca2+ to decrease
Ca2+ and H+ bind to same place on albumin: acidosis the H= competes with Ca2+ and causes more ionised Ca2+ in the blood
What is the difference in extracellular and intracellular Ca2+ levels? [1]
What does low Ca2+ mean with regards to membrane excitatbility? [1]
What is the difference in extracellular and intracellular Ca2+ levels? [1]
Ca2+ greater extracellularly [1]
(Intracellular calcium: 99% is in complexes within the mitochondrial compartment)
What does low Ca2+ mean with regards to membrane excitatbility? [1]
Low Ca -> high membrane excitability.
Explain which is worse out of hyper or hypocalcemia
Very low Ca2+ is more dangerous immediately:
As serum calcium falls, there is less blockage of Na+ channels by Ca2+ in cardiac cells causing cardiac AP
Fall in Ca2+ makes AP easier to fire / lowers threshold which causes: arrhythmias and tetany
= SUDDEN CARDIAC DEATH
Explain the importance of Ca2+ in cardiac AP [1]
How does low
Calcium is involved in maintaining the plateau phase:
- Na in
- Ca out.
Extracellular Ca2+: blocks the voltage gated Na channels in the cardiac cell membrane.
Low Ca2+ levels: less blockade of VGNaCs = tachyarrhythmias
Parathyroid hormone (PTH) is secreted from which hormone? [1]
Effect of PTH secretion? [3]
PTH from parathyroid
PTH causes: overall increase in Ca2+ serum levels by:
- Increased renal Ca2+ reabsorption.
- Increased bone Ca2+ release.
- Increased gut absorption via release of vitamin D (1,25vitD).
What inhibits the release of PTH? [1]
Ca2+ levels being too high (-ve feedback)
What are the two cells of the parathyroid and what are their functions? [2]
Parathyroid gland:
- Chief cell: produces PTH
- Oxyphil cells: unknown
What is the precursor to PTH ? [2]
Prepro PTH –> ProPTH –> PTH
What type of molecule is Ca2+ sensing receptor in parathyroid gland?
Enzyme linked
Tyrosine Kinase
GPCR
Nucleus binding
What type of molecule is Ca2+ sensing receptor in parathyroid gland?
Enzyme linked
Tyrosine Kinase
GPCR
Nucleus binding
What is the effect of Ca2+ binding to Ca2+ sensing receptor on parathyroid? [3]
Ca2+ binds to Ca2+ sensing receptor on parathyroid. Causes:
* Reduces PTH secretion
* Increases breakdown of stored PTH in vesicles
* Suppresses transcription of PTH gene.
What is the activated form of vitamin D? [1]
1α,25-dihydroxyvitamin D
Name 3 determinants of PTH secretion and how the effect PTH [6]
1,25-dihydroxycholecalciferol: aka Calcitriol Suppresses PTH secretion (which lowers Ca2+ levels)
Phosphate: stimulates PTH gene transcription
Cincalcet: activaates CaSR: reduces Ca2+
What effect does the inactivaton of CaSR have? [1]
What effect does the overactivation of CaSR have? [1]
What effect does the inactivaton of CaSR on parathyroid gland have? [1]
Hypercalcemia: no -ve feedback
What effect does the overactivation of CaSR on parathyroid gland have? [1]
Hypocalcaemia: too much -ve feedback
Why does PTH cause an increase in phosphate excretion?
Bone is broken down to release Ca2+, but also P is released
Therefore the kidney needs to excrete P to compensate
Effect of PTH on
a) Kidney [2]
b) Bone [2]
c) Intestine [2]
Effect of PTH on
a) Kidney: decreases Ca2+ excretion AND increases P excretion (one is broken down to release Ca2+, but also P is released. Therefore the kidney needs to excrete P to compensate)
b) Bone: Increases Ca2+ and phosphate reabsorbtion
c) Intestine: Increases Ca2+ and phosphate
Which areas of nephron cause reabsorbtion of Ca2+ dependently / independently of PTH? [3]
PCT: independent
LoH: independent
DCT: PTH dependent
Explain how Ca2+ is reabsorbed at PCT [2]
At PCT:
- independent of PTH
- Driven by NaKCl2 channel causing a voltage gradient paracellularly which Ca2+ flows (coupled with Na+ reabsorbtion)
Explain how Ca2+ is reabsorbed at LoH [2]
Driven by voltage gradient: Para/transcellular
Coupled with Na+ reabsorbtion: NKCC2 channel
Why do thiazide diuretics raise serum calcium?
Increase Ca2+ reabsorbtion into the blood / raises Ca2+ serum levels:
- Blocks Na/Cl symporter on luminal side
- This drops the Na conc. In tubular cell
- This creates Na diffusion gradient
- Na diffusion increases from capillary into tubular
cell - across Na/Ca exchanger -> takes Na into cell and transports Ca2+ into blood. -> increase in blood Ca levels.
inhibition of Na/Cl symporter: causes what to serum Ca2+ levels? [1]
Increases serum Ca2+ levels
Effect of PTH on:
- NaPi transporters (and therefore P reabsorbtion)? [1]
- Vit. D activation? [1]
- PCT GNG? [1]
- Na/H20/HCO3- reabsorbtion? [1]
- Down-regulation of NaPi transporters: Reduced phosphate reabsorption
- Vitamin D Activation Stimulation of 25(OH) D3 –> 1,25(OH)2 D3 (inactivates 1,25-dihydroxyvitamin D)
- Proximal tubule gluconeogenesis
- Inhibits sodium/water/bicarbonate reabsorption via effects on Na/H exchanger and Na/K ATPase
What effect does PTH have on bone tissue? [2]
COME BACK
What effect does PTH have on bone tissue? [2]
COME BACK
Where do you find vit. D receptors? [2]
Role of vit D? [2]
Receptors: nucleus and cytoplams
Role: Upregulates Ca2+ transporters
Effect of PTH on bone remodelling xx
The conversion of vit. D to WHAT is regulated? [1]
The conversion of vit. D to WHAT is unregulated? [1]
What are the enzymes used for each? [2]
Conversion of vit D to 25(OH)D in the liver is an unregulated process, under the action of p450 enzymes. The half life of 25(OH)D is 2-3 weeks.
The conversion of vit D to 1,25(OH)D is highly regulated, via 1αhydroxylase
How does negative feedback of activation of vitamin D receptor work?
In most cells there is a negative feedback inhibition: activation of the VDR inhibits the action of 1α hydroxylase (which converts vit D to active form), therefore reducing the amount of activated vitamin D able to bind to the VDR.
Why would chronic infection (e.g from sarcoidosis / TB granuloma) cause hypercalcemia?
- Macrophages produce vitamin D
- Release of vitamin D is converted to 1 25 dihydroxyvitamin dby 1α hydroxylase
- Causes increase in serum calcium
The major role of calcitriol is [2]?
The major role of calcitriol is in increasing gut calcium and phosphate absorption.
other vit d effects
What does the hormone FGF23 do? [1]
Which cells are they secreted from? [1]
What does FGF23 do to 1-a-hydroxylase? [1]
What does the hormone FGF23 do? [1]
Reduces serum P levels USED FOR WHEN GET P EXCRETED FROM FROM BONE BUT NEED TO EXCRETE VIA RENAL SYSTEM
Which cells are they secreted from? [1]
Secreted by osteocytes
What does FGF23 do to 1-a-hydroxylase? [1]
**reduces 1-a-hydroxylase: less activated vit. D **
FYI
Activating mutation in FGF23 - Autosomal dominant hypophosphataemic rickets
Tumour induced osteomalacia - paraneoplastic FGF23
Familial tumoral calcinosis - low levels FGF23
Explain 3 classes of symptoms seen in hypercalcemia
Hypercalcemia
Symptoms
Neuropsychiatric disorders: due to reduced membrane excitibility causing reduced nerve transmisison in the brain
GI abnormalities:
* Constipation / pancreatitis: reduced membrane excitibility causes less muscle contraction
Renal dysfunction:
* Nephrogenic Diabetes Insipidus: Ca2+ binds to CaSR in nephrone, which down regulates NaKCL2 symporter
Renal stones & Renal failure due to XS Ca2+ in urine
What is primary cause of hypercalcemia? [1]
Malignancy in parathyroid gland is main cause, usually from bone metastasis
How do you treat hypercalcemia?
Expand plasma volume - reduce voltage gradient in tubular cells -> less Ca ++ reabsorbed
Reduce Ca release from bone
Treat underlying cause
What are primary, secondary and tertiary causes of hyperparathyroidism?
Primary: Parathyroid adenoma/carcinoma/hyperplasia
Secondary: Physiological compensation for hypocalcemia or Vitamin D deficiency. Can create tertiary
Tertiary: Autonomous PTH production following chronic secondary.
What is the effect of primary hyperparathyroidism? [1] and why? [2]
hypercalcaemia + excess PTH -> osteoporosis.
How can you ID if have primary Hyperparathyroidism? [4]
Neck USS
MIBI scan
CT scan
Parathyroid Venous Sampling
How do you treat hypoparathyroidism acutely and chronically? [2]
Acutely: give Ca2+
Chronically: Give activated vit D: increased gut absorb
How would hypoT present? [4]
Neuromuscular Excitability:
Cardiac tachyarrhythmia
Tetany
Seizures
Psychiatric manifestations
What would be overall causes of Hypocalcemia? [3]
PTH problems
Vit D problems (e.g. nutritional deficiency)
Compartment shifts
kidney, [] converts 25-hydroxyvitamin-D into 1,25-dihydroxyvitamin-D
kidney, 1-α-hydroxylase converts 25-hydroxyvitamin-D into 1,25-dihydroxyvitamin-D
