Calcium Metabolism and Disorders Flashcards
Describe vitamin D metabolism
Taken in via skin and diet
25 hydroxylated in the liver
Activated in the kidney by PTH as it stimulates further hydroxylation
Which element is needed for PTH production
Magnesium
How does PTH impact osteoblast activity
It inhibits sclerostin which is an inhibitor of osteoblasts
Overall it allows an increase in osteoblast activity
Describe bone metabolism
Inorganic pyrophosphate – under stimulation of TNAP it is converted to inorganic phosphate
The inorganic phosphate joins with calcium to form hydroxyapatite – mineralisation building block of bone
List the acute symptoms hypercalcaemia
Thirst and dehydration
Confusion
Polyuria
List the chronic symptoms of hypercalcaemia
Myopathy Fractures Osteopenia Depression Hypertension Pancreatitis Duodenal ulcers Renal calculi
Which tests do you do to diagnose hypercalcaemia
PTH levels - may be raised if primary hyperparathyroidism
Serum calcium - will be raised
Urine calcium excretion- will be increased
If PTH levels are high and urinary calcium excretion is raised what is the pathology
Parathyroid issue
Primary or tertiary hyperparathyroidism
If PTH levels are high and urinary calcium excretion is low what is the pathology
Parathyroid issue
Familial hypocalciuric hypercalcemia
If PTH levels are low and ALP is low what is the pathology
Bone pathology
Myeloma
Vit D Toxicity
Milk-Alkali
If PTH levels are low and ALP is high what is the pathology
Bone pathology
Metastases
Sarcoidosis
Thyrotoxicosis
List the causes of hypercalcaemia
Primary hyperparathyroidism
Malignancy
Drugs: vit D and thiazides
Granulomatous disease
Familial Hypocalciuric Hypercalcaemia
High bone turnover - bedridden, thyrotoxic, Paget’s
how can malignancy lead to hypercalcaemia
Metastatic Bone destruction - calcium released from bone
PTHrp from solid tumours - peptide that mimics effect of PTH
Osteoclast activating factors
Describe the acute treatment for hypercalcaemia
Fluids - rehydrate with 0.9% saline, 4-6L in 24 hours
Once rehydrated you can give loop diuretics to increase Ca excretion
Bisphosphonates- single dose will lower Ca over 2-3d
High dose steroids for sarcoid patients for at least a year
What is a sestamibi scan
Use scan taken up only by thyroid and another taken up by both thyroid and para – subtract one from the other to look at parathyroid only
How do you manage primary hyperparathyroidism
Surgery - definitive treatment
Diet and drugs - less effective
Cinacalcet - mimics calcium effect on PTH receptor to decrease PTH and overall calcium
List the indications for a parathyroidectomy
End organ damage - bone disease, gastric ulcers, renal stones and osteoporosis
Under 50 y/o
very high calcium
What is primary hyperparathyroidism
Primary overactivity of Parathyroid gland i.e. adenoma
Will have high calcium and PTH
What is secondary hyperparathyroidism
Physiological response to low calcium or Vit D
Will have low calcium but high PTH
What is tertiary hyperparathyroidism
Parathyroid becomes autonomous after many years of overactivity e.g. renal failure
High calcium and PTH
Which genetic conditions can lead to hyperparathyroidism
MEN 1/2 - almost always develop a parathyroid adenoma with hypercalcaemia at a young age
Familial isolated hyperparathyroidism - adenoma
Describe familial hypocalciuric hypercalcaemia
Inherited condition - autosomal dominant
Often asymptomatic as only gives mild hypercalcaemia
Low calcium excretion from urine leading to high serum calcium
What are the symptoms of hypocalcaemia
Paranesthesia - fingers, toes and perioral Muscle cramps and tetany Muscle weakness Fatigue Bronchospasm or laryngospasm Fits
What are the signs of hypocalcaemia
Chvostek’s sign - tapping over facial nerve
Trosseau’s sign - spasm in wrist when blood pressure cuff put on
QT prolongation
How do you treat acute hypocalcaemia
IV calcium gluconate - 10ml 10% over 10 mins
Given in 50ml saline or dextrose
What can cause hypoparathyroidism
Congenital absence (Di George syndrome) Destruction (surgery, radiotherapy, malign) Autoimmune Hypomagnesaemia Idiopathic
Describe the long term management of hypocalcaemia
Calcium supplement - 1-2g per day
Vitamin D supplement
Describe hypomagnesaemia
Calcium release is dependent on Mg
If Mg low then intracellular Ca becomes high and PTH release is inhibited
Skeletal and muscle receptors less sensitive to PTH
How do you treat hypomagnesaemia
Replace with calcium and magnesium
List causes of hypomagnesaemia
Alcohol Drugs: thiazide and PPI GI illness Pancreatitis Malabsorption
What is pseudohypoparathyroidism
genetic defect - dysfunction of G protein (Gs alpha subunit)
Gene = GNAS 1
Low calcium but high PTH due to PTH resistance
What are the symptoms of pseudohypoparathyroidism
Bone abnormalities Obesity Subcutaneous calcification Learning disability Brachydactyly - shortened 4th metacarpal
What is pseudo-pseudohypoparathyroidism
Albright’s Herditary Osteodystrophy
However no altered PTH level so normal calcium
What causes Rickets and Osteomalacia
Vitamin D deficiency
Can be caused by dietary deficiency, malabsorption, renal failure or lack of sunlight
What are the long term consequences of vitamin D deficiency
Bone Disease:
Demineralisation/ Fractures
Osteomalacia/ Rickets
Malignancy - colon
Heart disease
How do you treat vitamin D deficiency
Vitamin D supplements - tablets
Combined calcium and vitamin D supplement
Which cancers are associated with hypercalcaemia
Those with bony mets Breast Lung Bone Multiple myeloma
If PTH is low but calcium is high what does this suggest
That the excess calcium is coming from somewhere else and is not due to excess PTH (hyperparathyroidism)
How do granulomatous diseases cause hypercalcaemima
Granulomas can hydroxylate vit D increasing the levels of its active form
Examples: sarcoidosis and TB
What is the most common cause of hypercalcaemia in the general population
Parathyroid adenoma
