CHEMPATH: Calcium Handling Flashcards
What are the 3 forms of calcium in serum?
What is the total serum calcium?
What is corrected calcium?
- Corrected - correcting for albumin.
- Equation is (serum Ca + 0.02 * [40 - serum albumin]).
- If Ca falls then epilepsy can result.
How do you know if low albumin state is the cause of abnormal calcium?
Use corrected Ca and compare to total Ca
What is the function of Ca in the body?
- Nerve and muscle function
- Bone maintenance
What is the response to low Ca?
- Osteoclast activation
- Increased gut absorption
- Kidney retains calcium - 1 -alpha hydroxylase is activated in the kidney
What 2 hormones invovled in calcium homeostasis?
- PTH
- Vitamin D (steroid hormone)
What is the function of PTH?
84 aa protein, only released from parathyroids
Roles
- Bone & renal Ca2+ resorption
- Stimulates 1,25 (OH)2 vit D synthesis (1α hydroxylation)
- Also stimulates renal Pi wasting
“phosphate trashing hormone”
Cholecalciferol or ergocalciferol is a plant product?
Ergocalciferol - D2 - plant product
Cholecalciferol - D3 - comes from mammals; this is an inactive form, made in the skin under the influense of sunlight
No differences in activity but slightly different molecular shape
What is the influence of sunlight on vitamin D?
How is Vitamin D activated? What happens in sarcoid?
- In the kidney by 1-alpha-hydroxylase
- 1-alpha hydroxylase is overactivated in the lung in sarcoid so you get dysregulation of calcium. They should not take vit D.
What is the activated form of vitamin D called?
Calcitriol = activated vit D with OH in position 1 and 25.
Where is 25 hydroxylase found?
Liver
What is the role of 1,25 dihydroxy vitamin D?
- Intestinal Ca absorption
- Intestinal P absorption
- Critical for bone formation
(opposite of PTH)
Other:
- Controls many genes e.g. for cell proliferation, immune system
- Vit D deficiency is associated with cancer, AI and metabolic syndrome (does not mean causation)
Where is phosphate excreted?
In the kidney - activated by PTH
What is phoshate absorbed alongside and how?
In the intestine alongside Ca with the help of vitamin D
What is the role of the skeleton?
- Metabolic role in calcium homeostasis
- Reservoir of Ca, P and Mg
- Structural framework
Name 3 metabolic bone diseases.
- Osteoporosis
- Osteomalacia
- Paget’s disease
- Parathyroid bone disease
- Renal osteodystrophy
What is the difference between osteomalacia vs osteoporosis?
Osteoporosis - normal ageing process with normal ratios, normal Ca with bone loss e.g. in Cushing’s, hyperthyroidism, menopause. The bone is just weak so the ALP is normal.
Osteomalacia - bone disease caused by vitamin D deficiency
What are the effects of vit D deficiency in children vs adults?
Rickets vs osteomalacia
What are the features of vit D deficiency clinically?
Pseudofractures
Low Ca, low P, raised ALP
Name 3 risk factors for osteomalacia.
What is the calcium in 2o hyperparathyroidism?
In secondary hyperparathyroidism the calcium is always low
What is PTHrP important for?
- Made in placenta and goes into mother’s blood to make your own skeleton and steal her calcium
- Found in breast milk
Also found in many cancers and usually kills people within 6 months. Bisphosphonates are therefore used a lot in oncology. If Ca is high and PTH is low it is usually the result of PTHrP.
What happens to Ca if you have high dietary phosphate intake?
High diet phosphate causes low calcium because it binds calcium in the kidneys and they are both lost
What are the presenting symptoms of osteoporosis? What is the biochemistry in osteoporosis?
What is the diagnostic test for osteoporosis?
DEXA scan - much less than CXR radiation so relatively safe
How is the DEXA scan done? What does DEXA stand for? What results does DEXA produce?
T score is low in all old people because you are comparing to a population of age ~ 20years
What is the difference between the T score and Z score?
How does anorexia affect bone health?
Failure to attain peak bone mass so risk of fracture earlier will be higher. Furthermore early menopasue (before age 45) can make this even earlier.
Name some lifestyle/endocrine/drug causes of osteoporosis.
How is osteoporosis managed conservatively/medically?
What is the effect of tamoxifen on bone? What is the risk of using it?
Increases the bone density and reduces risk of breast cancer (but increases risk of endometrial cancer). Raloxifene does not cause endometrial cancer.
What is the range for normal Ca levels in plasma?
2.2-2.6mmol/L
What are the effects of hypercalcaemia? How high must Ca be for these symptoms to occur?
- Polyuria/polydipsia
- Constipation
- Neuro - confusion/seizures/coma
Unlikely unless Ca is >3.0mmol/L.
What is one of the most common causes of hypercalcaemia?
primary hyperparathyroidism
What is the first question to ask if you find Ca on a blood test?
- Is it real?
- What is the PTH?
- Is the PTH suppressed?
- If suppressed then probably malignancy because they have PTHrP
- If not then probably (1) primary hyperparathyroidism as there is a clear problem with PTH regulation (or (2) familial hypocalcuric hypercalcaemia)
Which blood tube is used for PTH measurement in blood?
Purple top
What is a genetic cause of hypercalcaemia?
Familial hypocalcuric hypercalcaemia (rare)
What are the most common causes of primary hyperparathyroidism?
- Parathyroid adenoma
- Hyperplasia
- Carcinoma
- Hyperplasia associated with MEN1 (dominant inheritance)
What sex is 1o hyperparathyroid more common in ?
Females > males
What is the biochemistry in 1o hyperparathyroidism?
- High serum Ca or
- high inappropriately normal PTH
- Hypercalcuria
- Low serum phosphate
What is the sensor for calcium and where is it found? What is its effect on the kidneys? Which genetic condition affects this receptor?
CaSR - calcium sensing receptor in the parathyroid glands which regulate PTH release.
Its effect in the kidneys is PTH dependent
What are the types of hypercalcaemia in malignancy?
Name 5 causes of non-PTH/non-malignancy driven hypercalcaemia.
- Thiazides - block the release of calcium into the urine so they can decrease stone risks but increase serum Ca
- Vitamin D would have to be very high for it to cause hypercalcaemia
What is the acute management of hypercalcaemia?
- FLUIDS - 1L over 1 hour
- If that fails, give bisphosphonates (especially if the cause is known to be calcium, otherwise avoid).
- Treat underlying cause - to know the diagnosis measure the PTH before you give bisphosphonates.
What is the clinical effect of hypocalcaemia (on examination)?
- Neuromuscular excitability
- Trousseau’s sign - when you take BP then you have more albumin. This binds the already low Ca and causes carpal spasm (flexion of the fingers).
- Chvostek’s sign
- Convulsions
NB: these signs will only be seen if Ca falls rapidly; not if chronically low Ca
What are the non-PTH driven causes of hypocalcaemia?
Wha are the PTH related causes of hypocalcaemia?
Which type of hyperparathyroidism is related to hypocalcaemia in CKD?
secondary hyperparathyroidism - Ca is always low
This can PROGRESS to tertiary hyperparathyroidism (large parathyroid glands)
What happens in CKD patients with long term hypocalcaemia followed by kidney transplant?
Secondary hyperparathyroidism - low Ca eventually leads to..
Tertiary hyperparathyroidism - after transplant this acts like primary hyperparathyroidism due to overactive parathyroids in relation to kidney function
What bone scan is used for Paget’s disease?
Technetium radionucleotide bone scan - also used in cancer
What is the biochemistry of Paget’s disease?
normal Ca, normal P, with very high ALP
What is the cause of renal osteodystrophy?
Due to secondary hyperparathyroidism and aluminium retention from dialysis fluid
What is osteitis fibrosa?
Long standing hyperparathyroidism causes cortical bone loss
