Disorders of Ca and P metabolism Flashcards
1
Q
What is the Parathyroid anatomy?
A
- very small glands, sit in the neck - come in pairs
- behind the thyroid - can be ectopic
- ductless glands - chief cells put their output into the blood stream that perfuses the PT glands
- develop from pharyngeal poyches - superior from 4th arch and inferior from third
- thymus also develops from third, and when it descends, it drags the inferior pair with it
2
Q
What is the process of Vitamin D formation?
A
- UV hits the skin, converting 7-dehydrocholesterol into Vit D
- goes to the liver where it gets a hydroxyl group added on C25 and then to the kidney where another hydroxyl group is added to C1 (via 1alpha-hydroxylase)
- makes active VitD (1,25 dihydroxy vit d)
3
Q
What does Vitamin D do?
A
- acts in the gut to absorb more calcium
- acts on the bone to potentiate PTH, allowing more calcium resorption from the bone
- acts on bone - decreases calcium excretion by increasing calcium reabsorption in PCT
- also has negative feedback system where it inactivates 1alpha-hydroxylase and PTH.
4
Q
What does PTH do?
A
- acts mainly in the kidney - increases calcium reabsorption in DCT and decreases phosphate reabsorption
- On bone it causes calcium release
- minor effect on gut
5
Q
What happens in high calcium levels?
A
- inhibition of PTH release through Calcium sensor on the cell
- decrease in alpha-hydroxylation of VitD
- Stimulation of production of calcitonin - produced in C cells of the thyroid
- inhibits the action of PTH on the bone - only hormone that decreases calcium levels
6
Q
What are the causes of hypercalcaemia?
A
- causes divided into ones where PTH levels are high/low
- Most common is Hyperparathyroidism (PTH high)
- Very rarely a cancer can produce PTH too
- When PTH is low, it can be bony infiltration of a cancer
- High Vit D levels - exogenous, granulomatous disease or William’s syndrome
- Increased bone turnover - 9easier to break down bone than build it up again
7
Q
What are the causes of Hyperparathyroidism?
A
- Primary - tumour becomes autonomous - loses ability to switch off PTH production when Ca is high (PTH high, Ca high)
- Secondary - low calcium (due to Kidney failure, malabsorption, VitD deficiency), have to increase PTH levels (PTH high, Ca low)
- Tertiary - had secondary hyperparathyroidism then treat it (VitD replacement or renal transplant). PT gland used to giving lots of PTH for so long, it cannot regulate its output . (PTH high, Ca high)
8
Q
How do cancers cause Hypercalcaemia?
A
- PTH production (small cell lung cancer, or neuroendocrine tumour)
- PTH-rp production (lung, lumphoma, multiple myeloma)
- Osteoclast activating factor (lymphoma and multiple myeloma)
- Metastatic solid tumours (lung, breast, kidney, prostate)
9
Q
How can we miss multiple myeloma in radiotracer scans?
A
- Radiotracer put into bones, shows up where bony deposits are
= with myeloma, scan can be completely negative, but patient has lots of cancers
10
Q
What is a granulomatous disease?
A
- E.g. Sarcoidosis, TB, Berylliosis, Fungal infections
- have big pathogens in the body
- macrophages invade, coat it and encapsulate it in a granuloma
- TB is a chronic infection and you cannot clear it
- Berillyum is a large atom so cannot get rid of it, put a granuloma round it
- Macrophages also express 1a-hydroxylase and so can activate VitD
- cannot be regulated - only regulated by kidney
11
Q
What are some other causes of Hypercalcaemia?
A
- immobilisation (turn over becomes fast)
- recovery from renal transplant (calcium sensing receptor doesnt work - High Ca, High PTH)
- Familial hypocalcuric hypercalcaemia - Chr3q21 - autosomal dominant
- Milk-alkali syndrome (chalk deposits from taking antacids and drinking milk)
- Thiazide diuretics - work in DCT - block calcium excretion
12
Q
What are some symptoms of Hypercalcaemia?
A
- STONES, BONES and PSYCHIC MOANS
- band of calcium on cornea - band keratopathy
- Shortened QT interval
- Subarticular erosions
- neural depression
- slow GI motility
- thirst
13
Q
What investigations would you carry out to identify Hypercalcaemia?
A
- Mg, VitD, PTH, Urine, X-ray (lung cancer/sarcoidosis (net pattern of shadowing)), ACE levels (high in sarcoidosis)
- Myeloma - suppression of B cells (band in blood), produces bence jones proteins, bony lesions
14
Q
How do we decide if someone should have PT surgery?
A
- young patient - less than 50
- Ca lower than 3
- Dexa scan - if there is osteoperosis
15
Q
How do we localise the PT glands for surgery?
A
- SestaMIBI scan - tracer taken up lasts longer in PT than thyroid. Scan after 4/6 hours and whatever lights up is the PT glands
- Technesium thalium uptake scan - Thalium only taken up by thyroid, technesium taken up by both. Use both tracers, then you subtract one picture from the other.
- Ultrasound
16
Q
What treatments are there for Hypercalcaemia?
A
- very narrow window
- saline rehydration - rehydrates kidney allowing more Ca excretion
- Frusemide promotes glomerular filtration and Ca excretion
- Pamidronate - Phosphonic acid drugs coat the crystals in the bone and stop macrophages from binding
- Calcitonin
- Steroids - stop osteoclasts
- Dialysis
17
Q
What treatments are there for Hyperparathyroidism?
A
- Surgery
- Bisphosphonates - coat teh bone
- Calcimimetics - bind to CaSR, bring Ca down to normal range - doesnt protect bones and very expensive
18
Q
What causes Hypocalcaemia?
A
- Low PTH - Hypoparathyroidism, lack of PTH action (pseudo-/pseudo-pseudo-hypoparathyroidism), (High PTH, Low calcium, High Phosphate)
- High PTH - usually due to Vit D deficiency, poor dietary Ca, malabsorption or chelation after massive blood transfusion.
19
Q
What causes hypoparathyroidism?
A
- priamry Hypoparathyroidism is congenital - associated with branchial arch defects. DeGeorge’s syndrome is when a branchial arch defects causes no thymus to be made - have no immune system or PT glands and double aortic arch
- Secondary - after neck surgery, trauma or radioiodine treatment
- neonatal - premature PT glands
- Hypo/hypermagnesemia
20
Q
Why might someone have impaired Vit D synthesis or action?
A
- poor dietary vit D intake
- malabsorption - fat malabsorption means you dont absorb vitD
- liver/renal disease - wont make active vit D (commonest)
- Hypomagnesemia
21
Q
Why might you have Calcium chelation or precipitation?
A
- blood transfusions - citrate given to chelate the calcium out of blood so it cannot clot. when you give the blood to someone, it dilutes the citrate - calcium can then go back to normal and blood can clot again. too much citrate from a huge transfusion can cause blood thinning
- Ethylene glycol - metabolic acidosis, calcium bound out
- Pancreatitis - fat filled organ, turns into bar of soap, calcium ends up here
- Rhabdomyolysis - breakdown of striated muscle. Myoglobin ends up in circulation, binds calcium
- Chemo
22
Q
What are some symptoms of hypocalcaemia?
A
- Muscle spasms - laryngo and broncho
- Chvostek’s sign - tap on facial nerve causesing it to spasm
- Trousseau’s sign - inflate blood pressure cuff to above arterial pressure, then the acidosis causes tetanic spasm
- Prolonged QT interval
- Rickets - reduced mineralisation
- Osteomalacia - in adults
23
Q
What investigations can we do for hypocalcaemia?
A
- calcium, phosphatem UandE, Mg, VitD, PTH, active vit D, malabsorption (B12, folate, iron), amylase (pancreatitis)
24
Q
What treatments are there for Hypocalcaemia?
A
- treat underlying cause - stop taking offending drugs, correct other electrolyte disorders)
- oral supplement
- vitD supplement
25
Q
What is pseudohypoparathyroidism?
A
- post receptor defect of PTh receptor
- Short stature, obesity, round face
- reduced IQ
- brachydactyly (shortened 4th and 5th metacarpals)
- ectopic calcification
