Clinical Calcium Homeostasis Flashcards by Peter Savage

What are the dietary sources of calcium?

Milk/dairy
Broccoli, cabbage
Bony fish
Nuts

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What is the function of calcium?

Neurotransmitter release
Bone formation
Cell division/growth
Muscle contraction

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Where is calcium stored and in what proportions?

BONE - 99%
Cells - 1%
Extracellular fluid - 0.1%

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What proportion of plasma calcium is bound?

45% bound to protein
10% Bound to other things
45% ionised - free

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What is normal calcium?

2.2-2.6mmol/L

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What is the effect of increased albumin on calcium?

Decreased free calcium

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How do we adjust calcium for albumin levels?

0.1mmol calcium change for each 5g reduction in albumin from 40g

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What is the effect of decreased albumin on calcium?

Increased free calcium

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What is the effect of acidosis on calcium?

Increased ionised calcium - predisposes to hypercalcemia

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What are the dietary sources of vitamin D?

Oily fish
Eggs
Fortified spreads/cereals

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What do chief cells respond to in the parathyroid?

Changes in calcium concentrations

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Changes in calcium ECF are sensed by what?

Calcium-sensing receptor

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Increased calcium has what effect on the parathyroid?

Decreased PTH secretion

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Decreased calcium has what effect on the parathyroid?

Increased PTH secretion

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Lengthy exposure to increased PTH can lead to what?

Osteoporosis

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What is the role of PTH?

Increased Ca2+ resorption from gut, renal tubules, bones

Mediates conversion of vitamin D to Calcitriol

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What is vitamin D converted into in the liver?

25(OH) Vitamin D (inactive)

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Which enzyme in the liver converts vitamin D, and what does it convert it to?

Vitamin D 25-hydroxylase

25(OH) Vitamin D (inactive)

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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)

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Which patients need activated vitamin D?

Low vitamin D in renal failure

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What are the clinical features of acute hypocalcaemia?

TETANY
PAPILLOEDEMA
Trousseaus sign
Chovstek's sign
Seizures
Parasethesia/twitching
Carpopedal spasm
Prolonged QT
Hypotension
Arrhythmia

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When do symptoms of hypocalcaemia tend to develop?

Below 1.9mmol/L

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What are the clinical features of chronic hypocalcaemia?

Ectopic calcification
Extrapyramidal signs
Parkinsonism
Dementia
Subcapsular cataracts
Abnormal dentition
Dry skin

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What is Trosseau’s sign?

Sign of hypocalcaemia

Clawed wrist flexion when BP cuff inflated

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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