Calcium Flashcards by patrick ellis

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

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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.

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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

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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

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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).

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What inhibits the release of PTH? [1]

Ca2+ levels being too high (-ve feedback)

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What are the two cells of the parathyroid and what are their functions? [2]

Parathyroid gland:
- Chief cell: produces PTH
- Oxyphil cells: unknown

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What is the precursor to PTH ? [2]

Prepro PTH –> ProPTH –> PTH

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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

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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.

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What is the activated form of vitamin D? [1]

1α,25-dihydroxyvitamin D

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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+

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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

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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

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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

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Which areas of nephron cause reabsorbtion of Ca2+ dependently / independently of PTH? [3]

PCT: independent
LoH: independent
DCT: PTH dependent

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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