Calcium Dysregulation Flashcards
-> Function of endocrine glands: Summarise the function of the key endocrine glands, including the synthesis, regulation and physiological effects of their hormones. -> Endocrine disorders: Describe the clinical features and treatment options of endocrine disorders.
What is the surrogate marker to measure inactive Vitamin-D?
- 25-Hydroxy vitamin D
Which cells detect serum calcium in parathyroid gland?
- G-coupled calcium sensing receptors on the parathyroid cells
What increases serum calcium & phosphate (2)?
- Increase in Vitamin D (synthesised in skin or intake via diet)
- Increase in parathyroid hormone (PTH) (secreted by parathyroid glands)
- Main regulators of calcium & phosphate homeostasis via actions on kidney, bone & gut
What is the precursor molecule of pre-vitamin D3?
7-dehydrocholesterol
What is the precursor molecule of Vitamin D3?
Pre-Vitamin D3
Which enzyme catalyses the conversion of vitamin D3 to 25-hydroxycholecalciferol?
- Hepatic 25-hydroxylase
Which enzyme catalyses the conversion of 25-hydroxycholecaliciferol to 1,25 dihydroxycholecaliciferol?
- Renal 1-alpha hydroxylase
What are the effects of calcitriol (1,25 dihydroxycholecaliciferol / active form of vitamin D) (4)?
- Increased osteoblast activity
- Increased enterocyte calcium absorption (Calbindin-D expression)
- Increased serum phosphate absorption
- Increased renal calcium and phosphate reabsorption
What are the effects of PTH (6)?
- Increased calcium resorption from bone
- Increased dietary calcium absorption
- Increased dietary phosphate absorption
- Increased renal renal calcium reabsorption
- Increased renal phosphate excretion
- Increased 1-alpha-hydroxylase activity -> Increased renal vitamin D synthesis
Therefore increase in plasma [calcium].
What is the relationship between PTH and calcium ions?
- There is an inverse relationship between calcium concentration and PTH production
Increased calcium concentration inhibits PTH release.
What is the normal physiological response to hypercalcaemia for PTH?
- PTH decreases (suppressed)
Which transporter is responsible for phosphate renal reabsorption?
- NPT2
What effects does PTH have on renal phosphate reabsorption?
- Inhibits NPT2 transporter → Increase urine phosphate excretion
What effect does FGF-23 have on calcitriol?
-
Inhibits the synthesis of calcitriol
- Less phosphate reabsorption from gut
What decreases serum calcium & phosphate (1)?
-
Increase in calcitonin (secreted by thyroid parafollicullar cells)
- Can reduce calcium acutely, but no negative effect if parafollicular cells are removed
What are the clinical features of hypocalcaemia (4)?
Mnemonic - [CATs go numb]
- Paraesthesia (hands, mouth, feet, lips, Chvostek’s sign - facial paraesthisia)
- Convulsions
- Arrhythmias
- Tetany
What are the causes of hypocalcaemia (4 PTH / 1 Vit D)?
- Low PTH levels (Hypoparathyroidism):
- Surgical - neck surgery
- Autoimmune
- Magnesium deficiency
- Congenital
-
Low vitamin D levels (Deficiency):
- Diet
- UV light
- Malabsorption
- Impaired production (renal failure)
What are the signs of hypercalcaemia (Stones (1), Moans (5) and Groans (5))?
- Stones - renal effects:
- Nephrocalcinosis (kidney stones and renal colic)
- Abdominal moans - GI effects:
- Anorexia
- Nausea
- Dyspepsia
- Constipation
- Pancreatitis
- Psychic groans:
- Fatigue
- Depression
- Impaired concentration
- Altered mentation
- Coma
What are the causes of hypercalcaemia (3)?
-
Primary hyperparathyroidism
- Excess production of PTH (parathyroid gland adenoma)
- There is no negative feeadback (elevated production of PTH)
-
Malignancy
- Bony metastases, produce local factors to activate osteoclast)
- Certain cancer (squamous cell carcinoma), secrete PTH related peptide that acts at PTH receptors
- Excess vitamin D
What is the treatment for hypocalcaemia (2)?
- Oral calcium
- Vitamin D supplements
What is the main cause of primary hyperparathyroidism?
-
Parathyroid adenoma
- Elevated production of PTH
- Calcium increases, however there is no negative feedback to PTH
What is the biochemistry of primary hyperparathyroidism (3)?
- High PTH
- High calcium
- Low phosphate - increased renal phosphate excretion (inhibition of NPT2)
- Normal Vitamin D
Because the blood serum doesn’t require any additional calcium the production and conversion of vitamin D is down-regulated as a protective mechanism for the body. This is why over 60% of patients with primary hyperparathyroidism have a lower than normal vitamin D level.
What is the main treatment of primary hyperparathyroidism?
- Parathyroidectomy
What are the associated risks of untreated primary hyperparathyroidism (3)?
- Osteoporosis
- Renal caliculi
- Mental function & mood is impaired
