disorders of calcium balance Flashcards
what glands are the main control of calcium release and storage in the bone?
parathyroid glands
outline the development of the superior and inferior parathyroid glands as well as the thymus
- thymus and inferior parathyroid gland are formed from the third pharyngeal pouch/ arch
- the arch forms they thymus as it gets dragged down
- superior parathyroid comes from the fourth pharyngeal arch
what pulls the inferior parathyroids into its position
the descending of the thymus pulls them into their position
what cells secrete parathyroid hormone
chief cells
outline the sequence by which the skin and body use sunlight to produce active vitamin D
- 7-dehydrocholesterol in the skin under the influence of sunlike is converted into cholecalciferol
- cholecalciferol is transported to the liver and it converted into the inactive 25 OH Vit D
- 25 OH Vit d is turned into its active form 1,25 di OH Vit D in the kidney via hydroxylation
- using the enzyme 1-alpha hydroxylase
outline the 3 main action of PTH (parathyroid hormone)
- inc Vit D, which acts on the gut inc Ca absorption
- act on the bone, stimulating osteoblasts to express RANK ligand to cause osteoclasts to resorb bone and inc plasma Ca
- inc Ca resorption and inc phosphate excretion, causing more free calcium in the plasma
What are the biological processes that occur when calcium levels are too high?
- 1-alpha hydroxylation of vitamin D in the kidney is inhibited
- inhibition of PTH production to compensate for high Ca
- calcitonin is produced from the c-cells of the thyroid gland
What is the action of calcitonin on bone?
- inhibit action of PTH, stopping the activation of osteoblasts with RANK ligand and stopping osteoclast resorption of bone
outline causes of hypercalcaemia
- divide causes by PTH level
high PTH causes
- hyperparathyroidism (most common)
- rare = cancers
low PTH causes
- excessive Vit D levels bc of- exogenous release, granulomatous disease, William’s syndrome
inc bone turnover
- such as in acromegaly or thyrotoxicosis
what is the rhyme for the symptoms and then outline them regarding :
- neuro
- cardio
- GI
- renal
- bones
- bones, stones and psychic moans
- neuro: confusion, fatigue
- cardio: shortening of QT interval, dec. refractory period
- GI: release of gastrin, inc acid output, peptic ulcer disease
renal: kidney stones, distal renal acidosis
bones: muscle weakness, osteoporosis
outline primary hyperparathyroidism
- serum calcium is high
- there is a tumour on the parathyroid gland which produces too much PTH
- so PTH levels are high
outline secondary hyperparathyroidism
- serum calcium is low
- PTH levels are high but this is a normal physiological response to low calcium
- can be resistance to PTH
what conditions and why would result in secondary hyperparathyroidism?
- renal disease because there is no activation of Vit D
- liver disease
- calcium malabsorption
outline tertiary hyperparathyroidism
- PTH is high
- Ca levels start to rise too high
- this is because the gland has become autonomous and can’t turn itself off, even though it isn’t required because Ca levels have normalised
what is required for tertiary hyperparathyroidism is occur
- secondary hyperparathyroidism
- where the patient must have a past reason for having low calcium levels such as renal disease and have now had a kidney transplant or where Vit D deficient but are now taking supplements
outline some epidemiology facts regarding primary hyperthyroidism
- most common cause of elevation PTH and calcium levels
- patients usually older than 40
- much more common in females
- high PTH levels may be related to multiple endocrine neoplasia (MEN)
what cancers can produce PTH?
small cell lung cancers
what cancers produce PTH-RP?
lung cancers, myeloma, lymphoma
what solid tumours go to bone and cause hypercalcaemia and how do they cause this?
- lung, kidney, breast
- go to the bone, destroying it (osteolytic), releasing calcium
why do multiple myeloma cells not show up on bone scans? what scanning technique must therefore be used?
- as myeloma cells produce osteoclast-activating factor
- these only stimulate osteoclasts who’s activity cannot be picked up by bone scans
- so X-rays of every bone of the body must be taken instead
what can be used to measure osteoblast activity?
what do osteosclerotic conditions do?
- bone scans
- make bones more solid
what does bone resorption signalling rely on?
what do cancer cells do then they invade bone?
- inflammatory cytokines from the osteoblast to activate the osteoclast
- they set up an inflammatory response which produces cutlines and immune mediators
- these activate osteoclasts to resorb bone and calcium is released
what are granulomatous disease?
- characterised by immune response
- granulomas are to deal with big parasites that macrophages cannot be consumed by macrophages
- so granulomas surround the invader and wall it off
- granulomas contain macrophages and the enzyme 1-alpha hydroxylase which activates Vit D
name 3 examples of granulomatous disease
- sarcodiosis
- tuberculosis
- berylliosis (heavy metal poisoning)
outline 5 other miscellaneous reasons for hypercalcaemia
- immobilisation of bone
- recovery from renal transplant (tertiary hyperparathyroidism)
- familial hypocaciuric hypercalcemia
- milk-alkali syndrome (large intake of milk to soothe acid and osteoporotic problems)
- thiazide diuretics (inc resorption of calcium)
why does bone immobilisation cause hypercalcaemia?
- there is no electrical signal to tell osteoblasts to work
- so osteoclast work more than osteoblasts
- so more bone resorption
- so inc in calcium
outline familial hypocalcuiric hypercalcaemia
- PTH and calcium high
- little calcium in the urine which is a normal renal response to inc calcium
- this is as theres is defect in the calcium- sensing gene (CaSR gene) which encodes the a calcium sensing receptor - is present in the bone
- so even though calcium in the blood is raised it doesn’t affect their physiology
- condition is asymptomatic despite them having hypercalcaemia and hypocalciuria
what are the investigations carried out for suspected hypercalcaemia?
look at levels of:
- calcium
- phosphate
- vit D
- PTH
- urinary calcium excretion
what investigations would be carried out to look at the causes of hypercalcaemia?
- chest xray
- measure ACE levels
- myeloma screen
what investigations would be carries out in hypercalcaemia with high PTH levels
- assume this is someone with primary hypercalcaemia
- localise the tumour in order to remove it
- look at kidneys to look for stones
- DEXA scan to measure calcium in bone (as high PTH can cause osteoporosis
what are the issues with scanning the parathyroids? how is this overcome?
- when scanning the parathyroids the markers go to both the parathyroids and they thyroid
- making them indistinguashable
- so use SetsaMIBI scanning where marker will go to both but will be retained in the parathyroids longer
outline the treatment for hypercalcaemia
- rehydrate the patient with saline, which allows the Na/Ca exchanger to work
- furosemide (loop diuretic) to flush calcium out of the body
- steroid (prednisolone) to suppress the immune response/ activity
- calcitonin
- biphospates to inhibit osteoclast activity to maintain existing bone mineralisation if patient has gotten osteoporosis
- calcimimetics that active the calcium sensing receptors, so induce the processes to reduce calcium levels
what happens when there is low calcium in regards to Vit D?
when calcium is low:
- PTH release is stimulated
- inc activation of 1-alpha hydroxylase to activate Vit D
what are the causes of hypocalcaemia when PTH is low?
hypoparathyroidism
what are the causes of hypocalcaemia when PTH is high?
- psudohypoparathyroidism
- Vit D deficiency (renal/ liver disease)
- poor dietary calcium
- malabsorption of calcium
- chelation
outline primary hypoparathyroidism
- can be congenital eg. Digeorges syndrome
- autoimmune conditions where antibiodies attack the parathyroid and stop them working
outline secondary hypoparathyroidism
usually to do with things in the neck:
- after surgery/ trauma damaging the parathyroidism
- radioiodine
what is the cause of neonatal hypoparathyroidism?
- if child is born too early
- parathyroids have not adequately developed
- PTH-RP stops being produced after birth
- so PTH deficiency
what condition to do with magnesium can cause hypoparathyroidism and why?
- hypomagnesemia or hypermagnesmia
- as magnesium is an important co-factor in PTH production
how is calcium chelation used?
- Stop blood clotting by placing citrate which takes out calcium
- this stops the clotting cascade
- this is put into blood that will be used for transfusion to stop it clotting
- When put into person it will work again because citrate will not be present in recipients blood
- when high levels of blood are transfused it can cause calcium level drops
signs and symptoms of hypocalcaemia
- pins and needs (paresthesias)
- chvostek’s sign
- trousseau’s sign
- prolonged QT interval on ECG
what is chvostek’s sign?
when tap on the facial nerve and there is a facial spasm in patients with hypocalcaemia
what is trousseau’s sign?
- when BP cuff is put on the arm and inflated to a level above systolic BP
- held for 3 mins
- patients hand will go into titanic spasm
investigations for hypocalcaemia
- ECG
- same as hypercalcaemia
treatment of hypocalcaemia
- give calcium and and Vit D supplementation
- if patient is fitting or unconscious give an IV
- if person has kidney disease you cant give Vit D bc kidney wont be able to activate it so calcidol is given
- calcidol is artificial 1-alpha hydroxylase
what will you see in the biochemistry of a patient with pseudoparathyroidism?
- high PTH
- low calcium
- high phosphate
- low active Vit D
what are the classic physical features of a person with pseudoparathyroidism?
- short stature
- obese
- moon/ round face
- ectopic calcification (calcium deposits in the wrong places)
- reduced intelligence
- short 4th and 5th fingers
outline testing for psuedoparathyroidism
- infuse patient with PTH and look at the action of the PTh receptor
- in the kidney measure cAMP in the urine
outline type 2 psuedoparathyroidism
characterized by:
- resistance to parathyroid hormone (PTH) which manifests with hypocalcemia, hyperphosphatemia
- elevated PTH levels
outline type 1a psuedoparathyroidism
- body unable to respond to PTH
- group of symptoms called Albert’s hereditary osteodystrophy which include short stature, round face and obesity
