Calcium Homeostasis Flashcards
Plasma Ca2+ falls. What processes are involved in acting to correct this fall?
PTH is released from parathyroid cells and has 3 actions to increase Ca2+ levels:
1. Stimulate 1-alpha hydroxylase in kidney to increase conversion of 25(OH)D3 to 1,25(OH)2D3. Active VD3 increased GIT absorption and renal reabsorption
- PTH acts directly on kidney to increase Ca2+ reabsorption via upregulation of channels in DCT
- PTH binds to osteoclasts and upregulaes RANKL to increase the production of osteoclasts from precusors to increase bone resorption
What other electrolyte is linked with calcium homeostasis?
PO4
- absorbed in gut
- can be lost when Ca2+ reabsorbed in renal tubules
- release when bones resorbed by osteoclasts
What are the most common causes of hypercalcaemia? What medications can cause hypercalcaemia?
Hyperparathyroidism
-can be primary or secondary (primary more commonly)
Primary malignancy
- lung, breast, kidney and bladder commonly cause increase in calcium levels
- PTHrP releasing cancers= peptide which mimics action of PTH to stimulate action of PTH
Bone mets
-increase osteolysis= release increased skeletal calcium
Drugs
- thiazides diuretics
- excessive vitamin D supplementation
What signs/symptoms might someone with hypercalcaemia present with?
BONES
- osteoporosis= increased osteoclasts activity leads to decreased bone mineralisation= increased risk for fragility/osteoporotic fractures
- bone pain
STONES
-renal calculi= hypercalcaemic stones
GROANS
- Abdo pain
- N+V
- Pancreatitis
- muscle weakness
PSYCHIC MOANS
- depression
- confusion
- hallucinations
- coma or fall in GCS
THRONES
- polyuria= due to hypercalcaemia causing nephrogenic diabetes insipidus
- constipation= significant symptoms
How would you investigate someone who was presenting with signs of hypercalcaemia?
FBC +ESR= can indicate signs of malignancy which might be causing the hypercalcaemia
Serum calcium + phosphate + albumin
Urea and creatinine
PTH levels
24hr urinary calcium + creatinine to measure the function calcium output of kidney
Why does serum calcium not give you the actual calcium concentration? What else do you need to measure in order to calculate actual calcium concentration?
Half of serum calcium is bound to albumin meaning that changes in albumin levels can affect the interpretation of serum calcium level
Need to measure albumin concentration so can use formula to correct calcium for albumin
What is the treatment for severe hypercalcaemia?
IV saline (NS 0.9%)= dilute calcium IV frusemide= Loop diuretic which can increase Ca2+ clearance SC salmon calcitonin= inhibits bone resorption IV bisphosphonates= inhibit osteoclasts activity SC denosumab= monoclonal Ab which inhibits osteoclasts maturation and processes involved in bone turnover to try and decrease bone resorption
What causes hypocalcaemia?
Malabsorption syndrome
Vitamin D deficiency= most common cause
Acute pancreatitis
Chronic renal failure
Altered PTH homeostasis= need to check magnesium levels
-hypomagnesia can lead to PTH resistance
No PTH production
-Agenesis of parathyroid gland in DiGeorge’s
-Destruction in surgery or radiotherapy
-AI disorders
Hypocalcaemia presents differently in adults and children. What features would you expect to see for each?
Child= triad
- carpopedal spasm i.e. involuntary contraction of hands and feet
- stridor
- convulsions
Adult
- paraesthesia in hands, feet and round mouth (peri-oral parathesia)
- carpopedal spasm= flexing of wrists and fingers with fingers drawing together
- seizures
- prolonged QT interval
- spams and seizures less common
Which 2 signs can you elicit to indicate hypocalcaemia?
Trousseau’s sign:
-inflammation of BP cuff above SBP leads to carpopedal spasms
Chvostek’s sign:
-tapping branches of facial nerve as they emerge from parotid leads to twitching of facial muscles
How do you treat hypocalcaemia acutely vs in the community?
ACUTE IV calcium gluconate= 10mL 10% Replace magnesium to prevent PTH resistance Treat underlying cause Vitamin D replacement
COMMUNITY
-PO calcium supplements
-vitamin D replacement
NOTE= calcichew can be used-> contains vitamin D and calcium supplementation
What is the normal range for serum calcium? Where is the major of the bodies calcium stored?
- 2-2.6 mmol/L
99. 9% of calcium stored in bones are skeletal calcium
What 3 forms can calcium be found in in the body? How do they differ in terms of biological activity and diffusibility?
Free ionised calcium= Ca2+
- biologically active
- diffusible
Anion-bound
- not biologically active
- diffusible
Protein-bound i.e. albumin
- not biologically active
- not diffusible
Why is albumin levels important to consider when interpreting calcium levels? Which conditions does this apply to and what can be done to mitigate the influence of albumin?
Albumin levels affect the total calcium available
Low albumin can lead to apparently low calcium levels despite there being a normal ionised calcium concentration
Conditions= malnourished or CLD (decreased albumin production)
Albumin-adjusted calcium done
Which 3 hormones are involved in calcium homeostasis and where are they secreted from/formed?
Calcitriol = 1,25(OH)2D3 (metabolically active form of vitamin D
-liver and kidneys involved in vitamin D metabolism (kidneys produce the metabolically activity form of vitamin D)
PTH
- chief cells of parathyroid gland produce PTH
- released in response to fall in serum calcium
Calcitonin
- released from parafollicular cells in parathyroid gland
- released in response to raised calcium levels
