Week 4 - J - Calcium metabolism and disorders Flashcards
How does the human body get calcium? What is required for absorption?
Calcium from diet and absorption from gut
need vitD from sun and diet to aid with B12 formation for calcium absorption
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?
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
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?
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
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?
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
What is absorbed alongside calcium in the gut and the bone due to the actions of parathyroid hormone on converting calcifediol to calcitriol?
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
What are the symptoms of hypercalcaemia?
thirst, dehydration, confusion, polyuria
What are the chronic symptoms of hypercalcaemia? (stones, bones, abdo groans, psychic moans)
Stones - renal stones
Bones - osteopenia
Abdo Groans - ulcers and pancreatitis
Psychic moans - depression
When there is hypercalcaemia, what tets should you think to do?
Parathyroid hormone test
In testing for hypercalcaemia, what do you suspect if albumin is raised and urea is raised?
Dehydration
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?
Primary/tertiary hyperparathyroidism
Familial hypocalciuric hypercalcaemia
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What are the two main causes of hypercalcaemia and what are the other causes? (eg drugs, diseases, bone turnover)
Main - primary hyperparathyroidism and malignancy
Drugs - vit D and thiazdies
Turnover - Paget’s and thyrotoxicosis
Disease - Sacroidosis, TB
What are the biochemical measurements of primary hyperparathyroidism?
Raised serum calcium
Raised PTH
Raised urine calcium
What are the three causes of primary hyperparathyroidism?
- Adenomas
- Hyperplasia
- Carcinomas (rare)
What two biochemcial feautres make you think bone mets when there is high calcium?
High serum calcium and alkaline phosphate
Parathyorid adenomas account for 80% of primary hyperparathyroidism What scan is carried out for primary hyperparathyroidism?
Sestamibi scan
Management of Primary Hyperparathyroidism?
SURGERY OR NOTHING
What is the characteristic xray feature of primary hyperparathyroidism? What other condition can cause this feature on xrays?
Pepperpot skull is the characteristic feature of primary hyperparathyroidism and of multiple myeloma seen on xray (due to increased osteoclast activtiy)
What are the indications for parathyroidectomy? (end organ damage)
End organ damage
- Osteitis fibrosa cystica – resorption of bone leading to fibrosis and cystic spaces
Gastric ulcers - abdo groans
Renal stones - stone
Osteoporosis - bones
WHat is the major cause of secondary hyperparathyroidism? Secondary hyperparathyroidism is a physiological response to low calcium
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
What causes tertiary hyperparathyroidism? What are levels of PTH and Ca?
o Tertiary hyperparathyroidism–parathyroid becomes autonomous after years of secondary
PTH raised
Calcium raised
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?
Malignant hypercalcaemia
Check for bone metastases
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?
Familial hypocalciuric hypercalcaemia
Where is the mutation in FHH?
Deactivating mutation in the calcium sensing receptor
* Mild Hypercalaemia
* Reduced urine calcium excretion
* PTH may be (marginally) elevated
* Genetic Screening
What is the inheritance of familial hypocacliuric hypercalcaemia? What is the urine calcium : creatinine ratio that distinguishes this from primary hyperparathyroidism?
FHH is autosomal dominant
* Diagnosis is usually made by genetic testing and concordant biochemistry (urine calcium : creatinine clearance ratio <0.01)
WHat are signs and symptoms of hypocalcaemia?
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
What are the main causes of hypocalcaemia?
Hypoparathyroidsim
Vit D deficiecny - osteomalacia and rickets
Chronic kidney failure
What is the acute hypocalcaemia treatment?(2 options)
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
What is a congenital cause of hypoparathyoridism leading to hypocalcaemia?
Di George’s syndrome
Chromosome deletion on 22q11
What is calcium release from cells dependent on?
Dependent on magnesium therefore hypomagnesaemia is a cause of hypocalcaemia
What is long term management of hypoparathyroidism? Management of hypomagnesaemia?
Hypoparthyroidism - give calcium and vit D supplements
Hypomagnesaemia - give calcium and magnesium
What genetic condition can cause pseudo-hypoparathyroidism? What is the gene that is mutated?
McCune Albright syndrome associated with GNAS1 mutation
What are the calcium and PTH levels and what are the clinical findings in pseudo-hypoparahyroidism?
Low calcium and elevated PTH - in psuedohypoparathyroidism, there is failure of target cell response to PTH short stature and short 4th and 5th digits
What is the difference from pseudo-hypoparathyroidism and pseudo-pseudo hypoparathyroidism?
Pseudo-pseudohypoparathyroidism has a normal biochemistry with the same everything else
Low calcium, low phosphate, high alk phosp, low vit D (25-(OH), PTH-high What is this?
Osteomalacia
Osteomalacia refers to a marked softening of your bones, most often caused by severe vitamin D deficiency.
X-linked hypophosphataemia also known as what? What two genes can have the mutation? Low phosphate High Vitamin D
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
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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
