Calcium Metabolism and Disorders Flashcards

1
Q

Describe vitamin D metabolism

A

Taken in via skin and diet
25 hydroxylated in the liver
Activated in the kidney by PTH as it stimulates further hydroxylation

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2
Q

Which element is needed for PTH production

A

Magnesium

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3
Q

How does PTH impact osteoblast activity

A

It inhibits sclerostin which is an inhibitor of osteoblasts

Overall it allows an increase in osteoblast activity

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4
Q

Describe bone metabolism

A

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

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5
Q

List the acute symptoms hypercalcaemia

A

Thirst and dehydration
Confusion
Polyuria

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6
Q

List the chronic symptoms of hypercalcaemia

A
Myopathy
Fractures
Osteopenia
Depression
Hypertension
Pancreatitis
Duodenal ulcers 
Renal calculi
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7
Q

Which tests do you do to diagnose hypercalcaemia

A

PTH levels - may be raised if primary hyperparathyroidism
Serum calcium - will be raised
Urine calcium excretion- will be increased

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8
Q

If PTH levels are high and urinary calcium excretion is raised what is the pathology

A

Parathyroid issue

Primary or tertiary hyperparathyroidism

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9
Q

If PTH levels are high and urinary calcium excretion is low what is the pathology

A

Parathyroid issue

Familial hypocalciuric hypercalcemia

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10
Q

If PTH levels are low and ALP is low what is the pathology

A

Bone pathology
Myeloma
Vit D Toxicity
Milk-Alkali

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11
Q

If PTH levels are low and ALP is high what is the pathology

A

Bone pathology
Metastases
Sarcoidosis
Thyrotoxicosis

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12
Q

List the causes of hypercalcaemia

A

Primary hyperparathyroidism
Malignancy

Drugs: vit D and thiazides
Granulomatous disease
Familial Hypocalciuric Hypercalcaemia
High bone turnover - bedridden, thyrotoxic, Paget’s

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13
Q

how can malignancy lead to hypercalcaemia

A

Metastatic Bone destruction - calcium released from bone

PTHrp from solid tumours - peptide that mimics effect of PTH
Osteoclast activating factors

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14
Q

Describe the acute treatment for hypercalcaemia

A

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

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15
Q

What is a sestamibi scan

A

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

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16
Q

How do you manage primary hyperparathyroidism

A

Surgery - definitive treatment
Diet and drugs - less effective
Cinacalcet - mimics calcium effect on PTH receptor to decrease PTH and overall calcium

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17
Q

List the indications for a parathyroidectomy

A

End organ damage - bone disease, gastric ulcers, renal stones and osteoporosis
Under 50 y/o
very high calcium

18
Q

What is primary hyperparathyroidism

A

Primary overactivity of Parathyroid gland i.e. adenoma

Will have high calcium and PTH

19
Q

What is secondary hyperparathyroidism

A

Physiological response to low calcium or Vit D

Will have low calcium but high PTH

20
Q

What is tertiary hyperparathyroidism

A

Parathyroid becomes autonomous after many years of overactivity e.g. renal failure
High calcium and PTH

21
Q

Which genetic conditions can lead to hyperparathyroidism

A

MEN 1/2 - almost always develop a parathyroid adenoma with hypercalcaemia at a young age
Familial isolated hyperparathyroidism - adenoma

22
Q

Describe familial hypocalciuric hypercalcaemia

A

Inherited condition - autosomal dominant
Often asymptomatic as only gives mild hypercalcaemia
Low calcium excretion from urine leading to high serum calcium

23
Q

What are the symptoms of hypocalcaemia

A
Paranesthesia - fingers, toes and perioral 
Muscle cramps and tetany 
Muscle weakness 
Fatigue 
Bronchospasm or laryngospasm
Fits
24
Q

What are the signs of hypocalcaemia

A

Chvostek’s sign - tapping over facial nerve
Trosseau’s sign - spasm in wrist when blood pressure cuff put on
QT prolongation

25
How do you treat acute hypocalcaemia
IV calcium gluconate - 10ml 10% over 10 mins | Given in 50ml saline or dextrose
26
What can cause hypoparathyroidism
``` Congenital absence (Di George syndrome) Destruction (surgery, radiotherapy, malign) Autoimmune Hypomagnesaemia Idiopathic ```
27
Describe the long term management of hypocalcaemia
Calcium supplement - 1-2g per day | Vitamin D supplement
28
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
29
How do you treat hypomagnesaemia
Replace with calcium and magnesium
30
List causes of hypomagnesaemia
``` Alcohol Drugs: thiazide and PPI GI illness Pancreatitis Malabsorption ```
31
What is pseudohypoparathyroidism
genetic defect - dysfunction of G protein (Gs alpha subunit) Gene = GNAS 1 Low calcium but high PTH due to PTH resistance
32
What are the symptoms of pseudohypoparathyroidism
``` Bone abnormalities Obesity Subcutaneous calcification Learning disability Brachydactyly - shortened 4th metacarpal ```
33
What is pseudo-pseudohypoparathyroidism
Albright’s Herditary Osteodystrophy | However no altered PTH level so normal calcium
34
What causes Rickets and Osteomalacia
Vitamin D deficiency | Can be caused by dietary deficiency, malabsorption, renal failure or lack of sunlight
35
What are the long term consequences of vitamin D deficiency
Bone Disease: Demineralisation/ Fractures Osteomalacia/ Rickets Malignancy - colon Heart disease
36
How do you treat vitamin D deficiency
Vitamin D supplements - tablets | Combined calcium and vitamin D supplement
37
Which cancers are associated with hypercalcaemia
``` Those with bony mets Breast Lung Bone Multiple myeloma ```
38
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)
39
How do granulomatous diseases cause hypercalcaemima
Granulomas can hydroxylate vit D increasing the levels of its active form Examples: sarcoidosis and TB
40
What is the most common cause of hypercalcaemia in the general population
Parathyroid adenoma