Calcium Homeostasis and Disorders of Metabolism Flashcards
In which 3 ways can serum calcium be increased?
- Gut absorption
- Bone resorption
- Kidney reabsorption
Which receptor will serum calcium act on in order to self regulate its level?
Calcium sensing receptor (CaSR)
Stimulation of the CaSR will inhibit production of which hormone?
Parathyroid hormone (PTH)
What is the overall action of parathyroid hormone?
Increase serum calcium
In which 3 key ways does PTH increase serum calcium?
- Resorption of bone
- Reabsorption by the kidneys
- Absorption from the gut
Which vitamin is useful in calcium homeostasis?
Vitamin D3
What roles does vitamin D3 have on calcium homestasis?
- Increases calcium uptake from the gut
- Increases bone mineralisation (also increases resorption)
- Potentially reduces PTH activity
In which ways will hypercalcaemia acutely present?
- Thirst
- Dehydration
- Confusion
- Polyuria
In which ways will hypercalcaemia acutely present?
- Myopathy
- Osteopenia
- Fractures
- Depression
- Hypertension
- Abdominal pain (pancreatitis, ulcers, renal stones)
Stones, groans, bones and psychic moans
What is the most important test to do in someone with suspected hypercalcaemia?
PTH
If a patient has hypercalcaemia and high albumin, what will urea levels be like in the following circumstances?
a) Dehydration
b) Cuffed sample
a) Raised urea
b) Normal urea
If a patient has hypercalcaemia and normal/low albumin what are the 3 main things to consider?
- Familial hypocalciuric hypercalcemia (FHH)
- Primary/tertiary hyperparathyroidism
- Bone pathology
How may a bone pathology be differentiated from either FHH or primary/tertiary hyperparathyroidism in a patient with hypercalcaemia and low/normal albumin?
PTH (and phosphate) levels
(PTH is low and phosphate is high in such patients with bone pathology)
If a patient has primary/tertiary hyperparathyroidism or FHH, what levels are both phosphates and PTH expected to be?
PTH - Normal/high
Phosphates - Normal/low
How may primary/tertiary hyperparathyroidsm and FHH be differentiated biochemically?
- Primary/tertiary hyperparathyroidsm - High urine Ca2+
- Familial hypocalciuric hypercalcemia - Low urine Ca2+
(Both conditions have hypercalcaemia, normal/low albumin, normal/high PTH and normal/low phosphates)
What are the key biochemical markers which suggest a general bone pathology as the cause of hypercalcaemia?
- Hypercacaemia
- Normal/low albumin
- Low PTH
- High phosphates
When considering a bone pathology as the cause of hypercalcaemia, what 3 things would a high ALP suggest as the cause?
- Bone metastasis
- Sarcoidosis
- Thyrotoxicosis
When considering a bone pathology as the cause of hypercalcaemia, what 3 things would a low ALP suggest as the cause?
- Myeloma
- Vitamin D excess
- Milk-alkali syndrome
What causes milk-alkali syndrome?
- Excess dietary milk or alkali (e.g. dyspepsia)
- Excess calcium supplementation (e.g. in post-menopausal women)
What are the main causes for hypercalcaemia?
- Primary hyperparathyroidism
- Malignancy
- Drugs - vitamin D, thiazides
- Granulomatous disease - sarcoidosis, TB
- Familial hypocalcuric hypercalcaemia
- Tertiary hyperparathyroidism
- High calcium turnover - bedridden, thyrotoxic, Paget’s etc
- Dehydration
Primary hyperparathyroidsm has which 3 key biochemical abnormalities?
- Raised serum calcium
- Raised (or inappropriately normal) serum PTH
- Increased urine calcium excretion
(such abnormalities would also present with tertiary hyperparathyroidsm)
In which 3 main ways can malignancies induce hypercalcaemia?
- Parathyroid hormone release protein (PTHrp) release
- Metastatic bone destruction
- Osteoclast activating factors
How is acute hypercalcaemia treated?
- Fluids 0.9 saline 4-6L in 24hrs
- Loop diuretics once rehydrated
- Bisphosphonates
- Steroids (rarely used, e.g. sarcoidosis)
- Salmon calcitonin (rarely used)
How are the parathyroid glands imaged?
Sestamibi scintigraphy scan
What are the treatment menthods for primary hyperparathyroidsm?
- Surgery
- Cinacalcet
How does cinacalet work?
Acts on CaSR as a calcimemetic
Calcium levels are negatively regulated
What is secondary hyperparathyroidism?
Excess PTH secretion in response to hypocalcaemia
(this is usually as a result of chronic kidney disease leading to excessive calcium loss)
Hyperplasia of the parathyroid glands is usually implicated
Secondary hyperparathyroidism involves:
a) High/Low calcium levels
b) High/Low PTH levels
a) Low calcium levels
b) High PTH levels
Which genetic syndromes can result in hyperparathyroidism?
- MEN 1 and 2
- Familial hyperparathyroidism
What is the reference interval for serum calcium?
2.2-2.6 mmol/L
Familial hypocalciuric hypercalcaemia is usually associated with a _____ hypercalcaemia
Familial hypocalciuric hypercalcaemia is usually associated with a mild hypercalcaemia
Pseudohypercalcaemia is usually associated with people with ___________
Pseudohypercalcaemia is usually associated with people with dehydration
Why does pseudohypercalcaemia occur?
- Increased serum albumin
- Increased calcium required to bind to albumin
- Free serum levels remain roughly the same due to increased production
(this occurs in dehydration as albumin becomes more concentrated)
Why is calcium useful at normal levels in relation to nerve cells?
It helps to stabilise the resting potential preventing sodium influx
What symptoms may hypercalcaemia cause related to nerve cells and why?
- Slower or absent reflexes
- Slow muscle contraction (constipation, generalised muscle weakness)
High extracellular calcium makes sodium channels in nerve cells less likely to open so depolarisation does not occur as easily