Clinical Calcium Homeostasis Flashcards
What are the dietary sources of calcium?
Milk/dairy
Broccoli, cabbage
Bony fish
Nuts
What is the function of calcium?
Neurotransmitter release
Bone formation
Cell division/growth
Muscle contraction
Where is calcium stored and in what proportions?
BONE - 99%
Cells - 1%
Extracellular fluid - 0.1%
What proportion of plasma calcium is bound?
45% bound to protein
10% Bound to other things
45% ionised - free
What is normal calcium?
2.2-2.6mmol/L
What is the effect of increased albumin on calcium?
Decreased free calcium
How do we adjust calcium for albumin levels?
0.1mmol calcium change for each 5g reduction in albumin from 40g
What is the effect of decreased albumin on calcium?
Increased free calcium
What is the effect of acidosis on calcium?
Increased ionised calcium - predisposes to hypercalcemia
What are the dietary sources of vitamin D?
Oily fish
Eggs
Fortified spreads/cereals
What do chief cells respond to in the parathyroid?
Changes in calcium concentrations
Changes in calcium ECF are sensed by what?
Calcium-sensing receptor
Increased calcium has what effect on the parathyroid?
Decreased PTH secretion
Decreased calcium has what effect on the parathyroid?
Increased PTH secretion
Lengthy exposure to increased PTH can lead to what?
Osteoporosis
What is the role of PTH?
Increased Ca2+ resorption from gut, renal tubules, bones
Mediates conversion of vitamin D to Calcitriol
What is vitamin D converted into in the liver?
25(OH) Vitamin D (inactive)
Which enzyme in the liver converts vitamin D, and what does it convert it to?
Vitamin D 25-hydroxylase
25(OH) Vitamin D (inactive)
Which enzyme in the kidney converts inactive vitamin D, and what does it convert it to?
25(OH) Vitamin D1a-hydroxylase
1,25(OH)2 Vitamin D (Active)
Which patients need activated vitamin D?
Low vitamin D in renal failure
What are the clinical features of acute hypocalcaemia?
TETANY PAPILLOEDEMA Trousseaus sign Chovstek's sign Seizures Parasethesia/twitching Carpopedal spasm Prolonged QT Hypotension Arrhythmia
When do symptoms of hypocalcaemia tend to develop?
Below 1.9mmol/L
What are the clinical features of chronic hypocalcaemia?
Ectopic calcification Extrapyramidal signs Parkinsonism Dementia Subcapsular cataracts Abnormal dentition Dry skin
What is Trosseau’s sign?
Sign of hypocalcaemia
Clawed wrist flexion when BP cuff inflated
What is Chovstek’s sign?
Sign of hypocalcaemia
Relax face, trap facial nerve
Corner of lip twitches towards finger
What is the most likely cause of hypocalcaemia in a recent thyroid surgery patient?
PTH gland damage/selective parathyroidectomy
What are the causes of hypocalcaemia with low PTH?
(Hypoparathyroidism) Post-surgery (thyroidectomy, parathyroidectomy) Autoimmune Infiltration Radiation damage Hungry bone syndrome HIV
Which drug can cause magnesium deficiency?
Proton pump inhibitors
Cytotoxic drugs
What are the causes of hypocalcaemia with low PTH?
Genetic disorders Post-surgery Autoimmune Infiltration Radiation-induced damage to PT gland Hungry bone syndrome HIV infection
What is hypoparathyroiditis?
hypocalcaemia with low PTH
What is High PTH with hypocalcaemia?
Secondary hyperparathyroidism in response to hypocalcaemia
Which drugs can cause hypocalcaemia?
Bisphosphonates Calcitonin Calcium chelators Phenytoin Fluoride poisoning
What are the causes of High PTH with hypocalcaemia?
Vitamin D deficiency Pseudohypoparathyroidism Low Mg2+ Renal disease Acute pancreatitis Alkalosis
Which investigations would you perform on a patient with suspected hypocalcaemia?
ECG Ca2+, Mg2+ Albumin Phosphate Vitamin D PTH U+E (Neck scars)
What would you check first in a hypocalcaemic patient?
PTH
How does pseudohypoparathyroidism present?
Childhood Short 4th 5th metacarpal Hypocalcaemia Hyperphosphatemia ELEVATED PTH
How does pseudohypoparathyroidism differ from hypoparathyroidism?
Hypoparathyroidism has DEPRESSED PTH with the same symptoms
What is Albright’s Heriditary Osteodystrophy?
Obesity
Short stature
Shortened metacarpals
May or may not have abnormal PTH/Ca2+
What is pseudohypoparathyroidism?
Hypoparathyroidism characterised by target organ unresponsiveness to PTH
What is the treatment for mild (asymptomatic) hypocalcaemia?
Oral Ca2+
Post-thyroidectomy - repeat Calcium 24hrs later
Fix deficiencies
What is the treatment for severe hypocalcaemia?
IV calcium gluconate
ECG monitoring
Treat underlying cause
When should vitamin D supplements be taken?
Winter months
October - March
How much vitamin D should be supplemented?
10mcg
400 units
When does acute hypercalcaemia require urgent correction? Why?
> 3.5
Risk of dysrhythmia
What are the parathyroid mediated causes of hypercalcaemia?
Primary hyperparathyroidism
MEN
Familial hypocalciuric hypercalcaemia
Tertiary hyperparathyroidism (renal failure)
What are the non-parathyroid mediated causes of hypercalcaemia?
HYPERCALCAEMIA OF MALIGNANCY
Vitamin D intoxication
Chronic granulomatous disorders
What are the causes of chronic granulomatous disorders?
Sarcoid
TB
Berylliosis
Histioplasmosis
Which drugs increase the risk of hypercalcaemia?
Thiazide diuretics
Lithium
Excess Vitamin A
Theophylline
Which conditions can cause hypercalcaemia?
Hyperthyroidism
Acromegaly
Pheochromocytoma
Adrenal insufficiency
What are the clinical features of hypercalcaemia?
Bones, Stones, Groans and psychic moans Polyuria/dipsia Anorexia N+V Muscle weakness Shortened QT interval
Which investigations would you use for suspected hypercalcaemia?
PARATHYROID HORMONE Albumin U+E, Ca2+ PO4 Alk phos Serum ACE Myeloma screen ECG
What must you ALWAYS check when checking Calcium?
Albumin - then correct for differences
What is the most likely cause of Normal/raised PTH with hypercalcaemia?
Primary hyperparathyroidism
Tertiary hyperparathyroidism
What is the most likely cause of low PTH and hypercalcaemia?
Malignancy
Drugs
Primary hyperparathyroidism is most common in which patients?
Female (3:1)
50-60y
What are the biggest causes of primary hyperparathyroidism?
85% Parathyroid adenoma
15% four gland hyperplasia
How should you investigate primary hyperparathyroidism?
Ca, PTH U+E AXR - renal calciuli DEXA - osteoporosis Parathyroid ultrasound Sestamibi scan Vitamin D 24hr urine Ca2+
What are the indications for surgery in primary hyperparathyroidism?
Symptoms Serum calcium >0.25 over upper limit (2.85) Osteoporosis Kidney stones/GFT<60 >50 years
What is the medical management of primary hyperparathyroidism?
Fluids
Cinacalcet
How does Familial Hypocalciuric Hypercalcaemia present?
Hypercalcaemia
PTH normal/raised
Positive family history
Benign
What is Familial Hypocalciuric Hypercalcaemia?
Autosomal dominant disorder of the calcium sensing receptor
What is the most common causal agent of Hypercalcaemia of malignancy?
Cytokines
PTHrP
What are the most common types of hypercalcaemia of malignancy?
Humoural - 80%
Local osteolytic - 20%
Which tumours typically cause Humoral Hypercalcaemia of malignancy?
Squamous cell cancer
Renal
Ovarian/Endometrial
Breast
Which tumours typically cause local osteolytic Hypercalcaemia of malignancy?
Breast
Multiple myeloma
Lymphoma
How does Multiple Endocrine Neoplasia type 1 present?
Primary hyperparathyroidism (95%)
Pancreatic
Pituitary
MENIN mutation
What part of the investigation is especially important in patients with primary hyperparathyroidism?
Family history
How does Multiple Endocrine Neoplasia type 2 present?
Medullary thyroid cancer
Phaeochromocytoma
Primary hyperparathyroidism (20-30%)
RET mutation
How is hypercalcaemia managed?
Rehydration - monitor for fluid overload
?Dialysis
IV BISPHOSPHONATES
What must be taken into consideration if giving a patient bisphosphonates?
Do it after rehydration (Zolendronic acid) Give slowly in renal failure Calcium takes 2-4 days to stabilise (calcitonin if these fail)
When is parathyroidectomy indicated in hypercalcaemia?
Acute presentation of primary severe hypercalcaemia and poor response to other measures
What are the causes of hypocalcaemia with high PTH?
Vitamin D deficiency Pseudohypoparathyroidism Hypomagnesemia Renal disease Acute pancreatitis Acute respiratory alkalosis
Which drugs are associated with hypocalcaemia?
Bisphosphonates
Calcitonin
Cinacalcet
Phenytoin