Calcium metabolism and Disorders Flashcards
where do you get vitamin D from
skin and diet
where is vitamin D converted
the liver
what does PTH do to vit D and calcium
stimulates the phosphorylation of vit D and reduces calcium (in bone, increases it in serum)
what is the main stimulus of PTH
low serum calcium
what senses serum calcium
calcium sensing receptor (C ASR) (GPCR)
describe how the mineralised aspects of bone are formed
inorganic pyrophosphate turns into inorganic phosphate- by alkaline phosphatase- which joins to calcium to make hydroxyapatite
what promotes bone mineralisation
PTH (elevated serum calcium promotes bone mineralisation) and sclerostin
what can make you loose the ability to metabolise vit D
renal failure, nephrectomy, hypoparathyroidism, anticonvulsants
what are the general symptoms of hypercalcaemia
Bones (ache)
Stones (kidney stones)
Abdominal Groans
Psychic Moans
what are the acute symptoms of hypercalcaemia
Thirst
Dehydration
Confusion
Polyuria
what are the chronic effects and symptoms of hypercalcaemia
Myopathy Fractures Osteopaenia Depression Hypertension Pancreatitis Duodenal ulcer Renal calculi
how do you investigate hypercalcaemia
PTH
what can cause hypercalcaemia with a low PTH
bone pathology
what do you check in hypercalcaemia with a low PTH
ALP
what can cause hypercalcaemia with a low PTH and a high ALP
Metastases
Sarcoidosis
Thyrotoxicosis
what can cause hypercalcaemia with a low PTH and a low ALP
Myeloma
Vit D Toxicity
Milk-Alkali (take too many rennie make gut alkaline
Thyrotoxicosis, sarcoid, HCO3
what do you check in hypercalcaemia with high/normal PTH
urine calcium excretion
what can cause hypercalcaemia with a high/normal PTH and a low urine calcium excretion
FHH- Familial Hypercalcemic Hypocalciuria
what can cause hypercalcaemia with a high/normal PTH and a high urine calcium excretion
primary/ tertiary hyperparathyroidism
what drugs can cause hypercalcaemia
Vit D, thiazides
what are the most common causes of hypercalcaemia
Primary Hyperparathyroidism
Malignancy
what diseases can cause hypercalcaemia
Primary Hyperparathyroidism
Malignancy
Granulomatous Disease eg Sarcoid, TB
Familial Hypocalciuric Hypercalcaemia
High turnover: bedridden, thyrotoxic, Pagets
Tertiary hyperparathyroidism (usually renal disease)
how do thiazides cause hypercalcaemia
reduce ability to secrete calcium
how do you diagnose primary hyperparathyroidism
Raised serum calcium
Raised serum PTH (or inappropriately normal)
Increased urine calcium excretion
Ensure Vitamin D replete
how does malignancy cause hypercalcaemia
Metastatic Bone destruction
PTHrp (PTH related peptide) from solid tumours
Osteoclast activating factors
how do you diagnose hypercalcaemia due to malignancy
Raised calcium and alkaline phosphatase (and a low PTH)
X-ray, CT, MRI
Isotope Bone Scan
what is the acute treatment for hypercalcaemia
fluids- saline
Consider loop diuretics once rehydrated- avoid thiazides
Bisphosphonates- single dose will lower Ca over 2-3d, maximum effect at 1 week
Steroids occasionally used e.g Pred 40-60mg/day for sarcoidosis
what can reduce calcium in metastatic disease
chemotherapy
what is the management for primary hyperparathyroidism
surgery
Cinacalcet- Cacium Mimetic (mimic calcium on PTH receptor, reduced PTH secretion)
Can be useful if need treatment, but unfit for surgery
what are the indications for a parathyroidectomy
End Organ Damage: Bone disease (Osteitis Fibosa et cystica; brown tumours/ pepper pot skull) Gastric ulcers Renal stones Osteoporosis
very high calcium (>2.85)
under age 50
eGFR<60
why is the treatment for osteoporosis PTH when hyperparathyroid causes osteoporosis
PTH in non continuous injection (non pulsuatile as normal) will get rid of receptors and have paradoxical effect to normal affect of PTH on bone
what is secondary hyperparathyroidism
Physiological response to low calcium or vit D
what is tertiary hyperparathyroidism
Parathyroid becomes autonomous after many years of overactivity e.g renal failure
what is primary hyperparathyroidism
Primary overactivity of Parathyroid gland i.e adenoma or carcinoma
what genetic syndromes are linked to hypercalcaemia
MEN1/ 2
-Will almost always have developed a parathyroid adenoma with hypercalcaemia at a young age
Familial isolated hyperparathyroidism
-Adenoma as in primary hyperparathyroidism
what is familial hypocalciuric hypercalcaemia
condition where a deactivating mutation in the calcium sensing receptor (CaSR) causes increased PTH production + low calcium in urine = increased serum calcium
what inheritance pattern does FHH follow
autosomal dominant
what is the severity of FHH
usually benign/ asymptomatic
what are the tests for FHH
Mild Hypercalaemia
Reduced urine calcium excretion
PTH may be (marginally) elevated
Genetic Screening
what are the signs and symptoms of hypocalcaemia
Paraesthesia - fingers, toes, perioral Muscle cramps, tetany Muscle weakness Fatigue Bronchospasm or laryngospasm Fits Chovsteks sign (tapping over facial nerve) Trousseau sign (carpopedal spasm) ECG: QT prolongation (risk of R on T, VF)
what is the treatment for acute hypocalcaemia
IV calcium gluconate (in saline or dextrose)
what are the possible causes of hypocalcaemia
congenital - DiGeorge (babies have no PTH)
destruction (surgery, radiotherapy, malignancy)
autoimmune
hypomagnesaemia (functional hypoparathyroidism)
idiopathic
what is the long term management for hypocalcaemia
calcium supplement
vit D tablets
how is hypomagnesaemia related to hypocalcaemia
calcium release from cells is dependent on magnesium
in magnesium deficiency intracellular calcium is high
PTH release in inhibited
skeletal and muscle receptors less sensitive to PTH
what can cause hypomangesaemia
Alcohol Drugs -Thiazide -PPI GI illness Pancreatitis Malabsorption
what is pseudohypoparathyroidism
genetic defect (GNAS 1) that causes low calcium but PTH concentrations are high
caused by PTH resistance
what are the features of pseudohypoparathyroidism
Bone abnormalities (McCune Albright) Obesity Subcutanous calcification Learning Disability Brachdactyly (4th metacarpal- short)
what is pseudo-pseudohypoparathyroidism
Albright’s Herditary Osteodystrophy with no alteration in PTH action so normal calcium
what can cause malabsorption of vit D
gastric surgery, coeliac disease, liver disease, pancreatic failure
what can cause rickets/ osteomalacia (vit D deficiency)
dietary deficiency malabsorption chronic renal failure lack of sunlight drugs (anticonvulsants)
what are the clinical signs of osteomalacia
low calcium muscle wasting (proximal myopathy) dental defects (caries, enamel) bone- tenderness, fractures, rib deformity, limb deformity waddling gate
what are common features of chronic renal disease
vit D deficiency
secondary hyperparathyroidism
what are the long term consequences of vitamin D deficiency
bone disease- demineralisation/ fractures
osteomalacia/ rickets
malignancy (esp colon), heart disease, diabetes
what is the chronic treatment for vit d deficiency
vit D tablets, combined calcium + vit D
what causes vitamin D resistant rickets
PHEX or FGF23 gene mutation
FGF 23 regulates phosphate levels in plasma and is secreted by osteocytes in response to calcitriol
what are the features of vitamin D resistant rickets
Low phosphate
High Vitamin D
what is the treatment for vitamin D resistant rickets
phosphate and Vit D supplements +/- surgery
name the disease: Ca ++ PTH ++ AP N(+) Phos -
primary parathyroidism
name the disease: Ca ++ PTH --- AP +++ Phos N
malignancy
name the disease: Ca + PTH N/+ AP N Phos N
FHH
name the disease: Ca -- PTH -- AP N Phos +/N
hypoparathyroidism
name the disease: Ca -- PTH + AP ++ Phos -
osteomalacia
name the disease: Ca N(+) PTH N AP ++ Phos N
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