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Calcium metabolism and disorders Flashcards

1
Q

How is vitamin D converted in the liver?

A

25-hydoxylase

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2
Q

What is vitamin D converted to in the kidneys?

A

1-hydoxyase

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3
Q

What are the effects of PTH on the kidneys?

A

Stimulates the activation of vitamin D
Promotes phosphate excretion
Reduces calcium resorption

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4
Q

What stimulates the production of PTH?

A

Low calcium
Inhibited by 1,25 (OH)2 vit D
Mg required

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5
Q

What is calcitonins effects on bone?

A

Inhibits osteoclast resorption
Lowers calcium and phosphate
No effect on magnesium

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6
Q

What is the effects of 1,24(OH)2-D on the gut?

A

Increases calcium and phosphate absorption

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7
Q

What are the effect os 1,25(OH)2-d on the kidneys?

A

Increases Ca resorption

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8
Q

What type of receptor is the calcium sensing receptor?

A

G-protein coupled receptor that plays an essential role in regulation of extracellular calcium homostasis

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9
Q

What are the actions of PTH?

A

Calcium resorption from bone
Calcium reabsorption from kidneys
Increase in 1,25(OH)2 vitamin D in kidneys

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10
Q

What are the symptoms of acute hypercalcaemia?

A 
Thirst
Dehydration 
Cofusion 
Polyuria
Coma
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11
Q

What are the symptoms of chronic hypercalcaemia?

A 
Myopathy
Fractures
Osteopaenia
Depression 
Hypertension 
Pancreatitis
Duodenal ulcers
Renal calculi
Shortened QT
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12
Q

Diagnose:
Hypercalcaemia
High PTH
Increased urinary excretion of calcium

A

Primary/tertiary hyperparathyryoidism

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13
Q

Diagnose:
Hypercalcaemia
High PTH
Decreased urinary excretion

A

Familial Hypocalciuric Hypercalcaemia

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14
Q 
Diagnose: 
Hypercalcaemia
Low PTH
High phosphate
Increased ALP
A

Bone pathology:
Bone mets
Sarcoidosis
Thyrotoxicosis

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15
Q 
Diagnose: 
Hypercalcaemia
Low PTH
High phosphate
Decreased ALP
A

Myeloma
Vit D toxicity
Milk-alkali

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16
Q

What does a high PTH with hypercalcaemia indicate?

A

Thyroid issue

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17
Q

What does a low PTH with hypercalcaemia indicate?

A

Bone pathology

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18
Q

What drugs can cause hypercalcaemia?

A

Vit D

Thiazide duiretics - reduce the ability to excrete calcium

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19
Q

How can malignancy cause hypercalcaemia?

A

Metastatic bone destruction
PTHrp from solid tumours
Osteoclast activation factor

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20
Q

How is hypercalcaemia of malignancy diagnosed?

A 
Raised calcium and alk phos
X-ray 
CT
MRI 
Isotope bone scan
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21
Q

Why will hypercalcaemia lead to dehydration?

A

Induces renal resistance to vasopressin, leading to nephrogenic DI
Dehydration in turn lead to a corresponding further increase in calcium conc

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22
Q

How is vitamin D3 synthesized in the skin?

A

Reaction of its cholesterol with UVB

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23
Q

How is vitamin D metabolised within the body?

A

D3 is converted to 25-hydroxy metabolite by hepatic pathways and a second hydroxylation to calcitrol (1,25-dihydroxyvitamin D3) occurs in the renal parenchyma

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24
Q

Where is the majority of calcium found?

A

In bone and intracellular compartments

25
How is acute hypercalcaemia managed?
0.9% saline 4-6L within 24hrs Consider loop diuretics once rehydrated to bring calcium down Bisphosphonate - single dose with lower calcium over 2/4 days Steroids (pred 40-60mg) for sarcoid
26
How is primary hyperparathyroidism manged?
Surgery - not always | Cinacalet
27
What is the mechanism of action of cinacalcet?
Calcium mimic on the calcium receptor and causes reduced PTH output
28
What are the indications of a parathyriodectomy?
``` Very high calcium (>2.85) Under age of 50 eGFR <60 mL/min End organ damage: bone disease (osteolitis fibrosa cystica; brown tumors/ pepper pot skull) Gastric ulcers Renal stones Osteoporosis ```
29
What is primary hyperparathyroidism and what is the biochem?
Primary overactivity of the parathyroid gland i.e. adenoma High calcium High PTH High urinary calcium excretion
30
What is secondary hyperparathyroidism and what is the biochem?
Physiological response to low calcium or vit D Low calcium/lower half of normal High PTH
31
What is tertiary hyperparathyroidism and what is the biochem?
Parathyroid becomes autonomous after many years of overactivity e.g. renal failure High calcium High PTH
32
What genetic syndromes are associated with hyperparathyroidism?
MEN1/2 | Familial isolated hyperparathyroidism
33
``` Clinical Case: 80 year old man presents to ARU with 1 stone weight loss, cough, back pain - cCa2+ level= 3.4 (ref 2.2.-2.6mmol/L), Phosp= 1.4 (0.8-1.5 mmol/L) , Alk Phos= 272 (30-130 U/L) CXR – LLL (left lower lobe) collapse What investigations would you want? ```
Spine x-ray Isotope bone scan Myeloma screen Dx: malignant hypercalcaemia
34
Clinical case: 33 year old woman presents to bone clinic with incidental hypercalcaemia - cCa2+ level= 2.72 (ref 2.2.-2.6mmol/L), Phosp= 1.0 (0.8-1.5 mmol/L) , Alk Phos= 120 (30-130 U/L) PTH = 7.9 – 6.5/7 is normal What investigations would you want?
Urinary calcium excretion which was 0.02 mmol/L FR | Dx: Familial hypocalciuric hypercalcaemia
35
What is familial hypocalciuric hypercalcaemia?
Issue with calcium receptor and therefore increased PTH - increased serum calcium but low calcium excretion in urine
36
What is the mode of inheritance of familial hypocalciuric hypercalcaemia?
Autosomal dominant | Usually benign
37
What are the symptoms of signs of hypocalcemia?
``` Paraesthesia - fingers, toes and perioral Muscle cramps, tetany Muscle weakness Fatigue Bronchospasm or laryngospasm Fits Chvostek's sign Trousseau sign ECG: QT prolongation - risk of VF ```
38
What is trousseau sign?
Carpopedal spasm
39
What is chvostek's sign?
Tapping over facial nerve due to hyperexcitable nerve root endings (motor units)
40
What is the treatment for acute hypocalcaemia?
IV calcium gluconate 10ml, 10% over 10 mins (in 50 ml saline or dextrose) Infusion after bolus (10ml, 10% in 100 ml infuse at 50ml/h)
41
What can cause hypoparathyroidism?
Congenital absence (DiGeorge - deletion in 22) Destruction (surgery, radiotherapy, malignancy) Autoimmune Hypomagnesaemia Idiopathic
42
What is the long term management of hypoparathyroidism?
Calcium supplement: 1-2g per day | Vitamin D tablets (alphacalcidol 0.5-1mcg)
43
Why is magnesium important?
Calcium release from cells is dependent on magnesium In magnesium deficiency intracellular calcium is high and PTH release is inhibited Skeletal and muscle receptors less sensitive to PTH
44
What is the treatment for hypomagnesemia?
Replace with calcium and magnesium
45
What can cause hypomagnesaemia?
``` Alcohol Drugs: thiazide, PPI GI illness Pancreatitis Malabsorption ```
46
What is pseudohypoparathyroidism?
Genetic defect - dysfunction of Gs alpha subunit on GNAS 1
47
What is the biochem presentation of pseudohypoparathyroidism?
Low calcium | PTH elevated due to PTH resistance
48
What are the clinical symptoms of pseudohypoparathyroidism?
``` Bone abnormalities (mccune albright = areas of abnormal scar like fibrosis tissue in bones) Obesity Subcutaneous calcification Learning difficulty Brachydactyly ```
49
What is pseudopseudohypoparathyroidism?
Albright's hereditary osteodystrophy but no alteration in PTH action and thus normal calcium
50
What can cause rickets/osteomalacia?
``` Gastric surgery Coeliac disease Liver disease Pancreatic failure Chronic renal failure Lack of sunlight Drugs: anticonvulsants ```
51
How will osteomalacia present clinically?
``` Low calcium Muscle wasting - proximal myopathy Dental defects - caries, enamel Bone - tenderness, fractures, rib deformity, limb deformity Pseudofractures ```
52
What is the classic sign of osteomalacia?
Loosers sign
53
What effects can chronic renal disease have?
Vitamin D deficiency | Secondary hyperparathyroidism
54
What are the long term consequences of vitamin D deficiency?
Bone disease: Demineralisation/ fractures Osteomalacia/ rickets Malignancy - esp colon
55
What is vitamin D resistant rickets?
X -linked hypophosphatemia PHEX or FGF23 gene mutation
56
What is the FGF 23 gene responsible for?
Phosphate levels in plasma and is secreted by osteocytes in response to calcitriol
57
How will vitamin D resistant rickets present?
Low phosphate | Vitamin D high
58
How is vitamin D resistance rickets treated?
Phosphate and vitamin D supplements +/- surgery

Endocrine (35 decks)

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