Week 4 - J - Calcium metabolism and disorders

Question 1

How does the human body get calcium? What is required for absorption?

Answer 1

Calcium from diet and absorption from gut

need vitD from sun and diet to aid with B12 formation for calcium absorption

Question 2

What is the receptor (also what type of what receptor is it?) that senses low calcium levels on the parathyoird glands? How does this work to maintain calcium levels in blood?

Answer 2

When there is a hypocalcaemia this is detected by the calcium sensing receptor (CaSR) on the parathyroid gland

This is a G-protein coupled receptor

The low calcium levels will cause PTH to be secreted which causes increased bone resorption and absorpts calcium in the gut increasing blood calcium levels

Question 3

When vitamin D is absorbed from the sun or via diet, what is it converted to in the liver and the kidney? What hormone causes the conversion in the kidney?

Answer 3

Liver converts vitamin D to 25-hydroxy Vitamin D which is then converted in the kidney to 1,25- dihydroxy vitD3

It is the parathyroid hormone which increases the action of 1alpha hydroylase (1a-OHase) - which converts 25hydroxyvitD to 1,25hydorxyvitD3

Question 4

What is 25 hydroxy vit D also known as? What is 1,25 hydorxy vit D3 also known as? What is vitamin D also known as?

Answer 4

25 hydroxy vit D - also known as calcifediol (25(OH)D) (25-hydroxycholecaliferol = calcifdiol)

1,25 hydorxy vitamin D3 -calcitriol (1,25 dihyroxycholecalciferol = calcitriol)

Vitamin D also known as cholecalciferol

Question 5

What is absorbed alongside calcium in the gut and the bone due to the actions of parathyroid hormone on converting calcifediol to calcitriol?

Answer 5

PTH does this conversion which increases calcium absorption from the gut & calcium due to resoprtion of the bone - both of these help with the absorption of phosphate (therefore a low vitD will result in a low phosphate and calcium and high PTH level)

PTH also directly absorbs calcium from the gut

Question 6

What are the symptoms of hypercalcaemia?

Answer 6

thirst, dehydration, confusion, polyuria

Question 7

What are the chronic symptoms of hypercalcaemia? (stones, bones, abdo groans, psychic moans)

Answer 7

Stones - renal stones

Bones - osteopenia

Abdo Groans - ulcers and pancreatitis

Psychic moans - depression

Question 8

When there is hypercalcaemia, what tets should you think to do?

Answer 8

Parathyroid hormone test

Question 9

In testing for hypercalcaemia, what do you suspect if albumin is raised and urea is raised?

Answer 9

Dehydration

Question 10

If in hypercalcaemia, albumin is normal/low and PTH is normal/high with a normal or low phosphate - test the urine If urine is high in calcium what do you think? If urine is low in calcium what do you think?

Answer 10

Primary/tertiary hyperparathyroidism

Familial hypocalciuric hypercalcaemia

Question 11

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Answer 11

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Question 12

What are the two main causes of hypercalcaemia and what are the other causes? (eg drugs, diseases, bone turnover)

Answer 12

Main - primary hyperparathyroidism and malignancy

Drugs - vit D and thiazdies

Turnover - Paget’s and thyrotoxicosis

Disease - Sacroidosis, TB

Question 13

What are the biochemical measurements of primary hyperparathyroidism?

Answer 13

Raised serum calcium

Raised PTH

Raised urine calcium

Question 14

What are the three causes of primary hyperparathyroidism?

Answer 14

1. Adenomas
2. Hyperplasia
3. Carcinomas (rare)

Question 15

What two biochemcial feautres make you think bone mets when there is high calcium?

Answer 15

High serum calcium and alkaline phosphate

Question 16

Parathyorid adenomas account for 80% of primary hyperparathyroidism What scan is carried out for primary hyperparathyroidism?

Answer 16

Sestamibi scan

Question 17

Management of Primary Hyperparathyroidism?

Answer 17

SURGERY OR NOTHING

Question 18

What is the characteristic xray feature of primary hyperparathyroidism? What other condition can cause this feature on xrays?

Answer 18

Pepperpot skull is the characteristic feature of primary hyperparathyroidism and of multiple myeloma seen on xray (due to increased osteoclast activtiy)

Question 19

What are the indications for parathyroidectomy? (end organ damage)

Answer 19

End organ damage

• Osteitis fibrosa cystica – resorption of bone leading to fibrosis and cystic spaces

Gastric ulcers - abdo groans

Renal stones - stone

Osteoporosis - bones

Question 20

WHat is the major cause of secondary hyperparathyroidism? Secondary hyperparathyroidism is a physiological response to low calcium

Answer 20

 Most common cause is chronic renal failure

The kidneys cannot make active vitamin D (1,25 dihydroxy vitamin D3) (needed to absorb calcium) therefore hypocalcaemia which causes negative feedback increasing PTH secretion

Question 21

What causes tertiary hyperparathyroidism? What are levels of PTH and Ca?

Answer 21

o Tertiary hyperparathyroidism–parathyroid becomes autonomous after years of secondary

PTH raised

Calcium raised

Question 22

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 collapse

What is this suspected to be?

Answer 22

Malignant hypercalcaemia

Check for bone metastases

Question 23

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 - raised Ix: Urinary calcium excretion 0.02 mmol/L

GFR - low

What is this?

Answer 23

Familial hypocalciuric hypercalcaemia

Question 24

Where is the mutation in FHH?

Answer 24

Deactivating mutation in the calcium sensing receptor

* Mild Hypercalaemia

* Reduced urine calcium excretion

* PTH may be (marginally) elevated

* Genetic Screening

Question 25

What is the inheritance of familial hypocacliuric hypercalcaemia? What is the urine calcium : creatinine ratio that distinguishes this from primary hyperparathyroidism?

Answer 25

FHH is autosomal dominant

* Diagnosis is usually made by genetic testing and concordant biochemistry (urine calcium : creatinine clearance ratio <0.01)

Question 26

WHat are signs and symptoms of hypocalcaemia?

Answer 26

Paraesthesia - fingers, toes, perioral

Muscle cramps, tetany

Fatigue

Chovstek’s sign - facial twitching when touching facial nerve and

troussea sign - swan hand

QT prolongation on ECG

Question 27

What are the main causes of hypocalcaemia?

Answer 27

Hypoparathyroidsim

Vit D deficiecny - osteomalacia and rickets

Chronic kidney failure

Question 28

What is the acute hypocalcaemia treatment?(2 options)

Answer 28

IV calcium gluconate 10mls, 10%, for 10minutes in 50ml saline or dextrose or

IV calcium gluconate 10mls, 10% in 100mls infusate at 50ml per hour

Question 29

What is a congenital cause of hypoparathyoridism leading to hypocalcaemia?

Answer 29

Di George’s syndrome

Chromosome deletion on 22q11

Question 30

What is calcium release from cells dependent on?

Answer 30

Dependent on magnesium therefore hypomagnesaemia is a cause of hypocalcaemia

Question 31

What is long term management of hypoparathyroidism? Management of hypomagnesaemia?

Answer 31

Hypoparthyroidism - give calcium and vit D supplements

Hypomagnesaemia - give calcium and magnesium

Question 32

What genetic condition can cause pseudo-hypoparathyroidism? What is the gene that is mutated?

Answer 32

McCune Albright syndrome associated with GNAS1 mutation

Question 33

What are the calcium and PTH levels and what are the clinical findings in pseudo-hypoparahyroidism?

Answer 33

Low calcium and elevated PTH - in psuedohypoparathyroidism, there is failure of target cell response to PTH short stature and short 4th and 5th digits

Question 34

What is the difference from pseudo-hypoparathyroidism and pseudo-pseudo hypoparathyroidism?

Answer 34

Pseudo-pseudohypoparathyroidism has a normal biochemistry with the same everything else

Question 35

Low calcium, low phosphate, high alk phosp, low vit D (25-(OH), PTH-high What is this?

Answer 35

Osteomalacia

Osteomalacia refers to a marked softening of your bones, most often caused by severe vitamin D deficiency.

Question 36

X-linked hypophosphataemia also known as what? What two genes can have the mutation? Low phosphate High Vitamin D

Answer 36

Vitamin D resistant rickets

Mutation in the PHEX gene which regulates the fibroblast growth factor 23 (produced from the FGF23 gene) regulates phosphate levels in plasma - mutation causes increased activity of FGF 23 reducing phsophate absorption in the kidneys leading to rickets

Question 37

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Answer 37

Primary hyperparathyroidism is a high calcium and high PTH with high urine calcium

Malignancy will cause a high calcium and high AlkPhos

FHH will cause a mildly elevated calcium, potential elevated PTH and a low urine calcium

Hypoparathyroidism will have a low calcium and low PTH

Osteomalacia has low calcium, low vit D with raised alk phos and mildly elevated PTH

Paget’s has increased Alk Phos with other LFTs normal and potential for mildly elevated calcium