Chemical Pathology 10 - Calcium metabolism Flashcards
Around what percentage of the body’s calcium is in the skeleton?
99%
Recall the 3 forms of serum calcium?
Free/ionised (50%)
Bound to albumin (40%)
Complexed with citrate/phosphate (10%)
What is “corrected calcium”?
What is the equation for calculating it?
Calcium corrected for albumin level
Serum calcium + 0.02(40 - serum albumin)
How can ionised calcium be measured?
Blood gas
What is the key role of circulating calcium?
Nerve and muscle function
What are the actions of PTH?
- Increase bone Ca and phosphate resorption
- Increase renal Ca reabsorption and phosphate wasting
- Increase 1-alpha hydroxylase action in kidneys - this increases vit D activation, and vit D increases gut absorption of vit D
What type of hormone is PTH?
Peptide hormone
What type of hormone is vitamin D?
Steroid hormone (derived from cholesterol)
Recall the pathway of vit D synthesis
- Cholecalciferol obtained from diet or converted by sunlight exposure from 7-dehydrocholesterol
- 100% of absorbed cholecalciferol is converted to storage form (vit D3) in liver conversion by 25 hydroxylase
- Activated by renal 1-alpha-hydroxylase - an enzyme under control of PTH - to the active form (1,25-(OH)2 D3)
In which disease can 1 alpha hydroxylase be produced outside the kidney, and where?
Sarcoidosis - in sarcoid lung tissue. This is why sarcoidosis causes hypercalcaemia.
Where is 25 hydroxylase found?
Liver
What effect does 1,25(OH)2 vit D (active form) have on calcium and phosphate?
Increases calcium and phosphate absorption from intestines
Why is bone-specific ALP high when there is increased bone turnover?
Alkaline phosphatase pushes calcium and phosphate into bone
When it does this, some ALP is leaked into blood
Therefore, when you have increased bone turnover, you can measure the bone-specific ALP in the blood and it will be high
Which electrolyte is necessary for PTH synthesis?
Magnesium
What is the difference between osteoporosis and osteomalacia in terms of bone structure and mass?
Osteoporosis = less bone of normal structure Ostemalacia = normal amount of bone of wacky structure
What type of bone disease is caused by renal failure?
Renal osteodystrophy
- Can’t make 1 alpha hydroxylase –> lack of calcium absorption into bone
- Can’t excrete phosphate in kidney failure
Which conditions are caused by vit D deficiency in children and adults?
Children: Rickets
Adults: osteomalacia
Recall 5 risk factors for vit D deficiency
Lack of sunlight exposure + dark skin Renal disease or failure Anti-convulsants -> cause Vit D breakdown Dietary (chapatis) Malabsorption (eg coeliac)
Recall 4 clinical features of osteomalacia, including the biochemistry
Bone and muscle pain
Increased fracture risk
Looser’s zone fractures
Biochem: low Ca and Pi, raised ALP
Recall 4 clinical features of Rickets
Bowed legs
Costochondral swelling
Widened epiphyses at the wrists
Myopathy
Why does chappati consumption increase vit D deficiency?
Phytic acid (This chelates vit D in gut, adding to the vit D deficiency)
What is the biochemsistry of low calcium, low phosphate and high Alk Phos indicative of?
Vit D deficiency
What is the expected calcium and phosphate level in osteoporosis?
Normal
Recall 3 endocrine causes of osteoporosis
Cushings’s
Hyperthyroidism
Acidosis (less common)
What are the 3 typical fragility fractures seen in osteoporosis
NOF
Colle’s (wrist)
Vertebral
Recall the symptoms of Paget’s disease
PAIN, warmth, deformity, fracture, increased risk of cardiac failure
Which bones are most commonly affected by Paget’s?
Pelvis, femur, skull and tibia
What is the gold standard investigation for diagnosing Paget’s disease?
IV radiolabelled bisphosphonates
How is pain treated in Paget’s disease?
Bisphosphonates
What is the expected ALP level in Paget’s disease?
High
What are the symptoms of hypercalcaemia?
Bones, stones, abdominal moans, psychic groans
Polyuria and polydipsia (increased solute –> increased urine volume)
Constipation (calcium causes muscle movement to slow down)
Neurological - seizures, confusion, coma (but only if Ca >3.0)
Recall how hypercalcaemia should be investigated to determine a cause - and some differentials for your diagnostic approach
- Question whether it is a genuine result - send back to lab
- What is the PTH?
3a. If PTH is LOW this is an appropriate response so could be due to malignancy, or more rarely - sarcoid/ thyrotoxicosis
3b. If PTH is HIGH = inappropriate response to hypercalcaemia therefore = a problem with PTH regulation (mostly primary hyperparathyroidism, rarely, familial hypocalcuric hypercalcaemia)
Which 3 types of malignancy might cause hypercalcaemia?
- Lung Cancer (squamous cell can produce PTHrP)
- Bony metastases - causes local osteolysis
- Haematological malignancy (eg myeloma and CRAB)
Recall some causes of primary hyperparathyroidism, and which of these is most common
Parathyroid adenoma (most common) Parathyroid hyperplasia (rare) Parathyroid carcinoma (eg in Men-1)
What is the pathophysiology of familial hypocalcuric hypercalcaemia?
Calcium Sensing Receptor (CaSR) is mutated
PTH glands can’t detect Ca so well
Causes a MILD hypercalcaemia which is asymptomatic
There will be low urinary calcium (in name)
How does thyrotoxicosis affect calcium?
Causes hypercalcaemia via increased bone resorption
How do thiazide diuretics affect calcium?
Cause hypercalcaemia - due to reduced calcium transport in the renal tubules
How should hypercalcaemia be treated?
FLUIDS, fluids, fluids!
0.9% saline - 1L over 1 hour
Treat underlying cause
When can bisphosphonates be used to treat hypercalcaemia?
Only if the cause is known to be malignant
Recall 2 signs of hypocalcaemia
Chovstek’s (C = cheek)
Trousseau’s (T = Tighten BP cuff)
Which calcium imbalance may cause stridor, and why?
Hypocalcaemia - due to laryngeal spasm
How should hypocalcaemia be treated?
Calcium + activated vit D
Nb: If cause is vit D deficiency (rare in UK) then give regular (not activated) vit D
Recall some differentials for hypocalcaemia when the PTH is low
This is an inappropriate response (low calcium should cause high PTH)
Could be due to:
- Surgical mishap during thyroidectomy
- Autoimmune hypoparathyroidism (rare)
- Di George syndrome (even rarer! Agenesis of parathyroids)
- Magnesium deficiency - can be caused by OMEPRAZOLE
Recall some differentials for hypocalcaemia when the PTH is high
This is an appropriate response to low calcium - SECONDARY HYPERPARATHYROIDISM
Could be due to:
- Vit D deficiency (most common cause)
- CKD (as low renal alpha-1-hydroxylase)
- Pseudohypoparathyroidism (gene deficit –> PTH resistance)
What is the difference between the Z score and the T score in osteoporosis?
Z score = compared to someone of same age and gender
T score = compared to healthy, young adult
Recall 3 lifestyle modifications that can treat osteoporosis
Weight-bearing exercise
Stop smoking
Reduce EtOH
How do SERM drugs work in osteoporosis treatment?
Antagonist of oestrogen at the breast but an agonist in the bone - so it reduces risk of breast Ca but increases bone density
How does hypoadrenalism (Addisson’s) affect calcium?
Hypercalcaemia
Renal calcium transport decreased
Is neuromuscular excitability a sign of hypocalcaemia or hypercalcaemia?
Hypocalcaemia
What is the calcium level in Paget’s disease?
Normal because even though turnover is high the balance of calcium is normal
How does Paget’s disease affect the heart?
Causes high output cardiac failure
