Calcium Dysregulation Flashcards
How can your body get vitamin D?
Synthesised in skin or intake via diet (Cholecalciferol - D3)
What hormone is the main regulator of calcium and phosphate homeostasis via actions on the kidney bone and gut?
PTH secreted by the parathyroid glands.
What do parafollicular cells secrete?
Calcitonin
Is there any negative effect if parafollicular cells are removed in a thyroidectomy?
No
Explain vitamin-D metabolism.
7-dehydrocholesterol is converted into pre-vitamin D3; UV radiation stimulates the action of pre-vitamin D3 conversion into vitamin D3 within the epidermis by keratinocytes.
7-dehydrocholesterol > Pre-vitamind D3 (UVB) > Vitamin D3
Stage I: Vitamin D2 and D3 are relatively inactive therefore undergo hydroxylation. Hepatic 25-hydroxylase hydroxylates vitamin D3 into 25-cholecalciferol.
Stage II: 1-alpha-hydroxylase catalyses the hydroxylation of 25-cholecalcifcerol into 1,25-dihydroxycholecalciferol (calcitriol).
Process occurs within the PCT of the kidney.
What is the active form of vitamin D?
Calcitriol
What is substance is a good indicator of body vitamin-D status?
serum 25-hydroxycholecalciferol
How are calcitriol levels regulated?
Calcitriol auto-regulates vitamin-D synthesis by decreasing transcription of 1-alpha- hydroxylase, exhibiting a negative feedback system.
List the effects of calcitriol.
Increases osteoblast activity
Increases calcium absorption (Increased transcription of Calbindin-D proteins > Calcium uptake within enterocyte).
Increased phosphate and calcium reabsorption within the PCT
Increased gut phosphate absorption
What cells secrete PTH? Explain how these cells are stimulated to release PTH.
Chief cells within the parathyroid gland.
G-protein coupled calcium sensing receptor on chief cells detect changes in serum calcium concentrations. PTH synthesis is increased in hypocalcaemic conditions.
List the effects of PTH
Osteoclast activity > Bone resorption. PTH binds onto PTH receptors on osteoblasts initiating the release of osteoclast activating factor and RANKL.
Osteoclast causes demineralisation of calcium hydroxyapatite, liberating calcium from bone.
Increases renal 1-alpha-hydroxylase activity > increased calcitriol synthesis > increased calcium and phosphate gut absorption.
Increased calcium reabsorption
Increased phosphate excretion from the kidney
What secretes FGF-23?
Osteocytes
Outline the regulation of serum phosphate by FGF-23.
FGF23 inhibits phosphate reabsorption in the kidneys by inhibiting Na+-PO43- co-transporters and also inhibits synthesis of calcitriol, causing less phosphate absorption from the gut.
List the symptoms a person with hypocalcaemia would present with.
Sensitises excitable tissues; muscle cramps, tetany, tingling
Signs & symptoms: Paraesthesia (hands, mouth, feet , lips) Arrhythmias Tetany Convulsions
Name and define the 2 signs that a hypocalcaemia patient would have.
Chvostek’s sign (Facial paraesthesia) - A manifestation of hypocalcaemia in which tapping the zygomatic arch results in involuntary contraction of facial muscles.
Trousseau’s sign - Inflation of BP cuff for several minutes induces carpopedal spasm. Neuromuscular irritability due to hypocalcaemia.
What are the causes of hypocalcaemia?
Hypoparathyroidism:
- Surgical-neck surgery
- Auto-immune (Degeneration of parathyroid hormone by immunoglobulins > decreases PTH secretion)
- Magnesium deficiency (Ion is required for PTH synthesis)
- Congenital (Agenesis, rare, complete absence of parathyroid gland).
Vitamin-D deficiency
- Diet, UV light, malabsorption
- Renal failure (Reduced calcitriol synthesis). Therefore stimulatory effects of calcium absorption and reabsorption are unavailable.
- Liver disease - 25- hydroxylase enzyme deficiency or dysfunctional.
List the signs and symptoms of hypercalcaemia.
Reduced neuronal excitability – atonal muscles
Stones – renal effects:
- Nephrocalcinosis – kidney stones, renal colic
Abdominal moans - GI effects: anorexia, nausea, dyspepsia, constipation, pancreatitis
Psychic groans - CNS effects > Fatigue, depression, impaired concentration, altered mentation, coma (usually >3mmol/L)
Explain the relationship between PTH and serum calcium.
There is an inverse relationship between PTH and calcium (Low PTH due to high serum calcium).
Function of PTH is to increase the available circulating amount of calcium to an appropriate homeostatic level. G-coupled calcium sensing receptors on chief cells detect calcium concentrations.
What are the causes of hypercalcaemia?
Primary hyperparathyroidism:
- Too much PTH, ussually due to a parathyroid gland adenoma
No negative feedback - high PTH, but high calcium
Malignancy: Bony metastases produce local factors to activate osteoclasts. Certain cancers (e.g. squamous cell carcinomas) secrete PTH-related peptide that acts at PTH receptors
Vitamin D excess intake (rare)
Explain the pathophysiology of primary hyperparathyroidism.
Parathyroid adenoma producing too much PTH.
An adenoma is unresponsive to negative feedback exerted by calcium, therefore there is autonomous PTH secretion. Hypercalcaemia due to increased calcium absorption, reabsorption and bone resorption.
Calcium = High | PTH = High | Low phosphate (Increased phosphate excretion due to inhibition of NPT2)
What is the main treatment option of primary hyperparathyroidism?
Parathyroidectomy for primary hyperparathyroidism.
Explain the biochemistry of primary hyperparathyroidism.
High calcium
Low phosphate – increased renal phosphate excretion (inhibition of Na+/PO43- transporter in kidney)
High PTH (not suppressed by hypercalcaemia)
List the risks of untreated hyperparathyroidism.
Osteoporosis (Reduced BMD due to abnormal rates of bone resorption and osteoclastogenesis)
Renal canaliculi (stones)
Psychological impact of hypercalcaemia – mental function, mood
Explain the pathophysiology of secondary hyperparathyroidism.
Secondary hyperparathyroidism is a normal physiological response to hypocalcaemia, G-coupled calcium sensing receptors on chief cells detect low serum calcium, and thus respond by increasing PTH secretion from the parathyroid glands.
Calcium = Low
PTH = High secondary to low calcium
