Calcium and Phosphate Metabolism: Disorders Flashcards
What is primary hyperparathyroidism?
Primary: Commonest cause of elevated PTH and Ca levels. Affects women >40 usually
If it is cancer → Extremely high PTH ; pain in neck; palpable mass in neck (normally, PT gland is tiny so you rly shouldnt feel it)
What is secondary hyperparathyroidism?
Secondary: High PTH, low Ca ;; All four glands are hyperplastic. This is a compensatory hyperfunctioning of the parathyroid glands caused by hypocalcaemia or peripheral resistance to PTH
- Chronic renal insufficiency
- Ca malabsorption
- Vitamin D deficiency
- Deranged vitamin D metabolism
What is tertiary hyperparathyroidism?
Teritiary → a condition that caused secondary and was cured [must have had hypocalcaemic reason before in order to classify this as teritirary ]
Renal failure with a renal transplant; low Vitamin D even with supplements
Forget how to control themselves - become autonomous - high PTH and high CA, but 4 gland hyperplasia
Treatment of hyperparathyroidism?
Treatment: Surgery, medical observation, calcimimetics → Cinacalcet
Describe primary and secondary HYPOparathyroidism
Primary: congenital or autoimmune eg
Di George’s syndrome → born without thymus (have no immune cells!) - part of congenital in primary
Autoimmune → can be cause of multiple endocrine deficienies eg addisons, T1DM, premature ovarian failure
Secondary: After neck surgery or trauma, radioiodine
neonatal, hypomagnesemia, hypermegnesemia
What is Pseudohypoparathyroidism?
THIS IS A POST RECEPTOR DEFECT OF PTH RECEPTOR
High PTH (due to PTH resistance), Low Ca, High phosphate, Low vitamin D hydroxylation
Basically, it seems that it is not producing enough PTH, but when measured it is very high - there is therefore PTH resistance; not used by cells
Symptoms: Short stature, obesity, round face, reduced IQ, Brachydactyly, ectopic calcification. 4th and 5th metacarpals are short
Describe the inheritance and genetic pattern of pseudohypoparathyroidism
pseudopseudohypothyroidism → you have normal biochemistry, but have the phenotype
Inheritance depends on father or mother
Mother → parathyroidism type 1
Father → you get pseudo pseudp
this is due to different methylation in development
What are the symptoms of hypocalcaemia?
Trousseau’s sign→ inflate cuff to above systolic BP for 3 mins, arm becomes acidotic, displacement of Ca in cells and then you have tetanic spasm
Chovstek’s sign
Muscle cramps, SOB, tetany, condusion, seizures, syncope, congestive HF, dry skin, coarse hair, pruitus;; prolonged QT interval
What are the causes of hypocalcaemia?
Blood transfusion: citrate preservative in blood transfusion binds to the pt’s endogenous calcium, rendering calcium inactive.
Ethylene glycol consumption and Pt chemo drugs
Pancreatitis → Ca is taken out of circulation into pancreas)
Rhabdomyolosis → skeletal muscle crush injury, releases myoglobin from inside the muslce. Myoglobin goes into circulation and drops the levels of Ca as well
ALSO causes of vit D deficiency cause hypocalcaemia
Causes of Vitamin D deficiency?
Signs and symptoms of Vit D deficiency?
Aches and pains in bones
Proximal myopathy
Mild hypocalcaemia → secondary hyperparathyroidism
Hypophosphatemia and hyperchloremic acidosis
Bone deformities → osteomalacia, which can lead to psedofractures called loosers zone
Vit D deficiency in childood - rickets
Investigations of hypocalcaemia?
Treatement of hypocalacaemia?
TREATMENT OF HYPOCALCAEMIA
Treat underlying cause
- discontinue the offending drugs
- correct other electrolyte disorder
Oral (enteral) → up to 2 g per day
Vit D supplementation (even if normal vit D levels)
TREATMENT OF SEVERE HYPOCALCAEMIA
IV 10ml; 10% Ca gluconate diluted in 200ml N saline over 10 minutes
Treatment of vit D deficiency?
TREATMENT OF VITAMIN D DEFICIENCY
- Ca and Vitamin D tablets: 800-1000 IU daily
- Vitamin D injections: 300,000U im every 6 months
- Alpha-calcidol (1-⍺ hydroxy vitamin D): 0.25-1mg daily
Note that this also indirectly treats hypocalcaemia as vit D deficiency causes HypoC
Discuss the pathophysiology of hypercalcaemia as well as the signs and symptoms
note- this is in the other lecture too (card 34 i think)
PTH + 1⍺ hydroxylase production is inhibited
Signs and symptoms:
kidney Stones
Lack of Ca in Bones, leading to bone erosion
Psychic Moans (super high Ca can lead to coma)
Band keritinopathy- Ca deposition in cornea
Shortened QT interval on ECG, bradycardia Hypertension, vomiting, nausea, pancreatitis etc etc
Explain the hormonal causes of hypercalcaemia of malignancy
PTH: Small cell lung cancer releases PTH
PTH-rP
- Lung, Lympohoma, Multiple Myeloma
Osteoclast-activating Factor
- Lymphoma, Multiple Myeloma
Metastatic solid tumours
(these are the ones that metastasise to the bone from onc lecture)
- Lung, Breast, Kidney, Prostate
Commonest cause is metastatic solid tumours
Cancers also sends these inflammatory signals such as IL1,6,11, TNF, TGFB and causes OC activity too
What kind of disease can lead to hypercalcaemia?
Granulomatous diseases lead to hypercalcaemia
Sarcoidosis → giant cells made in body in repsonse to intrinisc Ag
These next three are controlled by giant cells- too big to be digested by 1 macrophage ; so the body recruits several other cells to swallow these big cells in an isolated area
TB → chronic infection
Berrylliosis → infection from berrylium metal
Mycoses → fungal infection
Macrophages express 1-⍺ hydroxylase, which activates vitamin D ⇒ this can lead to overactive Vit D
What are the other causes of hypercalcaemia?
immobilisation: If bones get no stress on them, there is no electrical signal to OCs. OC>OB activity, bones get weaker
Renal transplant rcovery
Familial hypercalcaemia hypocalciuria: loss of function mutations in the CaSR gene
Milk-alkali syndrome: milk given for stomach ulcers given in excess (lol)
Thiazide diruretics, work on Na/Ca exchanger in PCT → stops Ca excretion, as puts Ca back in blood
BUT loop diuretics causes calciuria and subsequently, hypocalcaemia
hyperparathyroidism (high PTH), acromegaly (low PTH) ;; thyrotoxicosis (low PTH), hypervitaminosis D (low PTH)
Investigations for hypercalcaemia?
Increased PTH
SestaMIBI Scan
US of neck and/or Renal tract
DEXA ⇒ under 60 or kidney stones or already thin bones or Ca level is around 2.8, consider surgery. Ca above 3 is fatal!!
Decreased PTH
Bone Scan, esp if we suspect cancer. Localisation of primary
Why do we use a SestaMIBI Scan?
Need to find a method of just seeing the parathyroid
- Technetium is taken up by the parathyroid and the thyroid.
- Thallium is only taken up by thyroid
- Take those two images - take one from the other - then you would just be left with the parathyroid.
Not done anymore as this is a double dose of radiation⚠️
Now, we use sestaMIBI - taken up by both, but stays in PT gland longer - take image after 1 hour and then delayed image 6 hours
How would you diagnose hypercalcaemia?
Measure PTH → if high, measure urine Ca/creatinine ; → if low, measure PTHrP and vitamin D levels
PTHrP takes 6 weeks to come back - so usually measure Vitamin D
Treatment for hypercalcaemia?
Saline rehydration: ~3-6L, allowing the kidney to function again
Frusemide
Pamidronate infusion:15-90mg
Calcitonin: 400iU im qds
Prednisolone 40mg. These are immune inhibitors that stop OCs from working
Dialysis: if Ca is 4 or above to get rid of it quickly- Ca2+ more than 3mg can kill you - needs to be treated aggresively
