Bone Disorders Flashcards
Regulation of calcium is by?
Vitamin d 25 and PTH
Leak of calcium by?
EcaC1 TRPV5 in kidney and EcaC2, TRPV6 in intestine
And pump basolateral calcium ATPase PMCA1b
EcaC expression is activated by?
1,25 VitD
Through gene transcription and phosphorylation of channels
And insertion of EcaC rich vesicles
Activation of vit D 1 alpha hydroxylation done by?
In kidney by PTH
As Phosphate increases, PTH
INCREASES
PTh half life
4 mins
Low magnesium causes?
Inhibits PTH release
Humeral hypercalcaemia malignancy caused by?
PTHrP
Enzymes for activation of cholecaciferol?
Renal 1 alpha hydroxylase and 25 hydroxylase
Calcitonin effect?
Reduce bone resorption
FGF23?
Reduced phosphate reabsorption in the renal proximal tubule and inhibits 1 alpha hydroxyase
Phosphate is secreted by?
Osteocytes, osteoblasts and osteoclasts
FGF23 can cause?
Reduction is phosphate reabsorption in renal proximal tubule, and inhibits 1 alpha hydroxylase
How much of calcium is ionised?
50%
What can total calcium be changed by?
Changes in albumin
Range for calcium is?
2.20 and 2.60 mmol/L
Hypercalcaemia with suppressed PTH is caused by?
Malignancy of blood, lung and breast, vit D excess and sarcoidosis
Hypercalcaemia with raised PTH caused by?
1 or 3 hyperparathyroidism or defects in calcium receptors FHH
Hypocalcaemia and increased PTH?
Vitamin D deficiency, malabsorption, renal failure, PTH receptor defect and vit D receptor defect
Hypocalcaemia and low or normal PTH?
Hypoparathyroidism, congenital Digeorge
Post surgery radiotherapy
Mg deficiency
What can cause Polyuria?
Diabetes insipidus and mellitus
Renal failure, high calcium and low potassium
How does calcium cause polyuria?
Inhibits Gs preventing ADH on V2 receptor to absorb water via luminal AQP2 insertion
Familial hypocalciuria hypercalcaemia is genetically?
Autosomal dominant, loss of function of calcium receptor
To exclude FHH you would
Ca:cr ratio over 0.01
MEN1 is for 3Ps?
Pituitary adenoma,
Parathyroid hyperplasia
Pancreatic tumours
Cause primary hyperparathyroidism is uncommon in younger people
MEN2 is for 3cs?
Calcitonin:
Medullary thyroid carcinoma
Calcium:
Parathyroid hyperplasia
Catecholamines:
Pheochromocytoma
Calcitonin is used to distinguish between?
C cell hyperplasia from medullary c cell carcinoma,
Pentagastrin stimulated values should be used
Problems with CKD mineral bone disease 3 hyperparathyroidism?
Reduced glomerular filtration of phosphate and impaired renal tubular response leads to phosphate retention
Reduced renal mass causing less activity of 1a hydroxylase so failure to increase calcitrol
Pseudohypoprathyroidism?
PTH resistance GNAS heterozygous mutation , G protein that couples the PTH receptor to adenylate cyclase
Pseudohypoparathyroidism- Albright hereditary osteodystrophy phenotype?
Short stature, short 4/5 metacarpals and or metatarsals, round facies obesity and mild mental retardation
Weird aspect of pseudohypoparathyroidism?
If mutant gene from mum then biochemical and physical features- genetic imprinting
If from father only physical features- PTH receptor not in kidney
Genetic imprinting?
Only a maternal or paternal gene is imprinted and not both
Pagets disease?
Dysregulated bone growth, immobilisation
Hypercalcaemia
High ALP
Calcium alkali syndrome?
Triad of hypercalcaemia, metabolic alkalosis and AKI renal insufficiency due to ingestion of large amounts of calcium and absorbable alkali
How do sarcoidosis cause hypercalcaemia?
Granulomas produce ACE, and a1 hydroxylase activates vit D
EDTA contamination causes what?
Chelation of ions such as calcium, magnesium and zinc
ALP needs zinc as cofactor so low activity
Difference between diabetes insipidus and mellitus?
In mellitus blood glucose levels are high
ECaC2 can be found in?
Intestine
ECaC1 can be found in?
Kidney
What does active vitamin D do?
Gene transcription, phosphorylation of channels and insertion of ECaC rich vesicles
Low magnesium does what?
Inhibits release of PTH
What does PTHrP do?
Stimulated transport of calcium across placenta
Contributes to the bone loss during lactation
What is calcitonin a marker for?
Tumour marker for medullary carcinoma of thyroid
Adjusted calcium equation?
Calcium + 0.02* (40-albumin)
Normocalcaemia hyperparathyroidism causes?
Primary hyperparathyroidism, vit D deficiency, CKD, acute illness, malabsorption dietary and drugs
High ALP can be suggestive of?
Hyperparathyroidism
FHH equation
Urine calcium x plasma creatnine/1000
Over
Calcium plasma x urine creatnine
Sarcoid is?
Inflamed cells clump otgether to make small lumps called granulomas
PTH responds to?
fall in plasma ionised calcium (acute)
- rise in plasma phosphate (chronic)
What is the main tumour marker for medullary carcinoma of the thyroid?
Calcitonin
Normocalcaemic hyperparathyroidism causes?
Primary hyperparathyroidism Vit d deficiency CKD- low 1,25 D, high PTH due to hyper phosphataemia Acute illness Malabsorption Drugs
What is the Ca:Cr ratio?
Urine calcium x plasma creatinine
/
Plasma calcium x urine creatnine