disorders of calcium homeostasis part 1 W2 Flashcards
clinical manifestations of hypercalcaemia - phrase to remember?
‘stones, bones, abdominal moans and psychic groans’
hypercalcaemia clinical manifestations - general?
muscle weakness
central effects
renal effects
bone involvement
abdominal pain
ECG changes
features of muscle weakness in hypercalcaemia?
striated and smooth muscle weakness
possible competition between calcium and sodium ions into cells
central effects in hypercalcaemia?
anorexia
nausea
mood change
depression
renal effects of hypercalcaemia?
impaired water concentration
renal stone formation
features of bone involvement in hypercalcaemia?
depends on underlying cause and severity of hypercalcaemia
what feature of the ECG changes in hypercalcaemia?
shortened QT interval
what can factitious hypercalcaemia (non-pathological) be due to?
raised calcium due to high plasma (albumin) due to eg:
-venous stasis
-dehydration
-IV albumin
primary hyperparathyroidism epidemiology
affects women:men in 3:2 ratio
age 50
primary hyperparathyroidism - what is this caused by? what types?
caused by growth in parathyroid gland
90% solitary adenoma
also due to hyperplasia or rarely a carcinoma
primary hyperparathyroidism?
autonomous and inappropriate overproduction of PTH leading to hypercalcaemia
secondary hyperparathyroidism?
appropriate increase of PTH in response to hypocalcaemia
tertiary hyperparathyroidism?
rare. when secondary overactive gland becomes so overactive it is completely autonomous even in absence of hypocalcaemia
histology of primary hyperparathyroidism?
cell types more similar and homogenous
radiology of hyperparathyroidism?
osteopenia - PTH activates osteoclasts, leading to increased bone resorption. loss of normal bone structure, weakness.
white dots in abdomen - renal stones
diagnosis of primary hyperparathyroidism?
raised calcium with inappropriately increased PTH
phosphate and bicarbonate tend to be low in serum (increased renal excretion)
alkaline phosphatase normal or moderately increased in more severe disease
further investigations - parathyroid imaging scan
treatment of primary hyperparathyroidism?
acutely - rehydration, drugs
surgical removal of pituitary adenoma
mild cases - repeat follow-up of serum calcium/PTH
if surgery is difficult - drugs to lower calcium levels
drugs to treat hypercalcaemia?
bisphosphonates - inhibit osteoclasts (after rehydration)
furosemide - inhibits Ca reabsorption (after rehydration)
calcitonin - inhibits osteoclasts (short term management)
glucocorticoids - inhibit vit D -> calcitriol (can prolong calcitonin action)
why does cancer often cause hypercalcaemia?
endocrine factors secreted by malignant cells acting on bone
metastatic tumour deposits in bone locally stimulating bone resorption via osteoclast activation
which malignancies more likely to cause hypercalcaemia?
lung 35%
breast 25%
endocrine factors in malignant hypercalcaemia?
PTHrP (PTH-related peptide)
secreted from solid tumours
similar structure to PTH and shares similar actions
name for when PTHrP is responsible for hypercalcaemia?
humoral hypercalcaemia of malignancy
features of malignant hypercalcaemia associated with bony metastases?
secretion of osteoclast activating cytokines or other factors into the bone micro-environment
multiple myeloma and hypercalcaemia of malignancy?
cancer of plasma cells (normally produce antibodies). excess production of plasma cells which produce single clone of an antibody or immunoglobulin called a monoclonal protein. also produce cytokines that lead to hypercalcaemia of malignancy. diagnosis involves bone marrow biopsy.
pepperpot skull?
well defined lesions due to local bone absorption due to presence of cancer.
diagnosis of malignancy? biochemistry
raised Ca with suppressed PTH
phosphate tends to be high
alkaline phosphatase may be very high (liver/bone metastases)
often clear from previous history of malignant disease
principals of treatment of malignant hypercalcaemia?
rehydrate the patient
if required, use drugs which lower serum calcium (bisphosphonate)
treat underlying malignancy (surgery/chemo)
‘other’ causes of hypercalcaemia?
granulomatous disease
exogenous vit D excess
familial hypocalciuric hypercalcaemia
drugs
some endocrine diseases
immobilization
drugs which cause hypercalcaemia?
Li, thiazide diuretics
what is sarcoidosis? how does it cause hypercalcaemia?
granulomatous disease - causes granulomas (full of macrophages - also found in eg TB)
raised calcium, normal PTH
granulomas hydroxylase vit D (which drives high calcium)
familial hypocalciuric hypercalcaemia (FHH)?
rare
reduced sensitivity of calcium sensing receptors in parathyroid glands. altered set point for PTH/Ca interaction.
PTH normal/slightly raised
plasma ionised calcium increased
urine calcium excretion low
