Chemical Pathology - Calcium Flashcards
Where is 99% of calcium found?
Stored in the skeleton (calcium reservoir)
What is the breakdown of free calcium in the body?
- 45% = ionised (free, biologically active form)
- 50% bound to albumin (affected by albumin level, therefore need to use corrected calcium)
- 5% bound to globulins + other ions
What are the two hormones involved in calcium metabolism?
- Parathyroid hormone (PTH)
- Calcitriol
What does Parathyroid do in relation to calcium?
Increases calcium in the blood
- Increases tubular 1α hydoxylation of Vitamin D (25(OH)D)
- Mobilises calcium from bone through osteoclast activation
- Increases renal calcium reabsorption
- Increases renal phosphate excretion
What does calcitriol (1,25(OH)2D) do in relation to calcium?
Increases calcium in the blood
- Increases calcium and phosphate absorption from the gut
- Bone remodelling
What hormone decreases calcium levels in the blood?
Calcitonin
What is the metabolism of Vitamin D?
- 7-dehydrocholesterol converts to cholecalciferol via sunlight
- Cholecalciferol is found in Vitamin D3 tablets + Fish oils
- Cholecalciferol is converted to calciferol (25-OH D3) by 25-hydroxylase in the liver
- Calciferol gets converted to Calcitriol (1,25(OH)2D) via 1α hydroxylase
What is the process of calcium control in the body?
- Decreased calcium causes PTH release from PTH gland
- Bone resorption occurs in osteoclsts from calcium stored in bone (Increases Ca in blood - PO4 increases)
- Ca reuptake in the kidney is increased (PO4 decreased) - Ca also excreted in urine
- PTH triggers 1α dehydroxylase activity, converting calciferol to calcitriol
- Calcitriol worse in the gut to increase Ca + PO4 uptake
Which conditions have the highest to lowest calcium concentrations?
(Primary Hyperparathyroidism, Secondary Hyperparathyroidism, Parathyroud Carcinoma, Osteomalacia, Osteoporosis)
- Parathyroid Carcinoma
- Primary Hyperparathyroidism
- Osteoporosis
- Secondary Hyperparathyroidism
- Osteomalacia
What is the defect in primary hyperparathyroidism?
Intrinsic problem with parathyroid gland, causing increased PTH
What are the blood results of primary hyperparathyroidism?
(Ca, PO4, PTH, ALP, Vit D)
- Ca: Increased
- PO4: Decreased
- PTH: Increased/Normal
- ALP: Increased/Normal
- Vit D: Normal
What is the defect in secondary hyperparathyroidism?
Pathology outside parathyroid gland: stimulation of parathyroid gland to produce more PTH
What are the blood results of secondary hyperparathyroidism?
(Ca, PO4, PTH, ALP, Vit D)
- Ca: Decreased
- PO4: Increased
- PTH: Increased
- ALP: Increased
- Vit D: Decreased/Normal
What is the defect in tertiary hyperparathyroidism?
Autonomous PTH secretion
What are the blood results of tertiary hyperparathyroidism?
(Ca, PO4, PTH, ALP, Vit D)
- Ca: Increased/Normal
- PO4: Decreased/Increased
- PTH: Increased
- ALP: Increased/Normal
- Vit D: Decreased/Normal
What is the defect in hypoparathyroidism?
Low levels of PTH
What are the blood results of hypoparathyroidism?
(Ca, PO4, PTH, ALP, Vit D)
- Ca: Decreased
- PO4: Increased
- PTH: Decreased
- ALP: Decreased/Normal
- Vit D: Normal
What is the defect in Rickets/osteomalacia?
Vitamin D deficiency
What are the blood results of rickets/osteomalacia?
(Ca, PO4, PTH, ALP, Vit D)
- Ca: Decreased
- PO4: Decreased
- PTH: Increased
- ALP: Increased
- Vit D: Decreased
What is the defect in Paget’s disease?
Re-modelling of bone
What are the blood results of Paget’s disease?
(Ca, PO4, PTH, ALP, Vit D)
- Ca: Normal
- PO4: Normal
- PTH: Normal
- ALP: Increased
- Vit D: Normal
What is the defect in osteoporosis?
Bone loss
What are the blood results of osteoporosis?
(Ca, PO4, PTH, ALP, Vit D)
- Ca: Normal
- PO4: Normal
- PTH: Normal
- ALP: Normal
- Vit D: Normal
What are some causes (and their prevalence) of primary hyperparathyroidism?
- Single parathyroid adenoma (80%)
- Hyperplasia + multple adenomas (15%)
- Carcinomas (mostly non-functional) (0.5%)
- MEN1 (adenoma) + MEN2 (hyperplasia)
What are some causes of secondary hyperparathyroidism?
- CKD
- Vitamin D deficiency
- Malabsorption syndromes
- PTH resistance (pseudohypoparathyroidism)
What are some causes of tertiary hyperparathyroidism?
- Prlonged secondary hyperparathyroidism causing unregulated secretion of PTH
- Kidney transplant
What are some causes of hypoparathyroidism?
- Postsurgical (most common)
- Postradiation
- Autoimmune
- Iron deposition in people with thalassaemia
- Hypo/hypermagnasaemia
- pseudohypoparathyroidism
- DiGeorge syndrome
What is DiGeorge Syndrome and some symptoms?
Absence of PTH glands
Sx:
- Heart defects
- Cleft palate
- Thymus aplasia
If PTH is low and calcium is high what is this indicative of?
PTH attempting to correct hypercalcaemia
- MALIGNANCY
- Sarcoidosis
- Thyrotoxicosis
- Milk Alkali Syndrome
What is sarcoidosis?
Ectopic 1α hydroxylase enzyme production from macrophages
What is the commonest cause of hypercalcaemia?
- Primary hyperparathyroidism (in community)
- Malignancy (in hospital)
What are some symptoms of hypercalcaemia?
- Moans (abdo pain, constipation, N+V, decreased appetite, peptic ulcer disease)
- Groans (Confusion, dementia, depression)
- Stones (renal)
- Bones (pain)
- Thrones (polyuria)
- Muscle weakness
What are three hypercalcaemic malignancies?
- PTH-like peptide releasing tumours (PTHrp) = small cell lung cancer
- Bone metastases
- Haematological malignancy (cytokine release destroys bone)
What is the treatment of hypercalcaemia?
Treat cause
- Fluids (IV 0.9% NaCl)
- Bisphosphonates (if malignancy)
What are some complications of hypercalcaemia?
- Renal stones
- Pancreatitis
- Peptic ulcer disease
- Band keratopathy
- Bone changes: pepperpot skull (lytic lesions), osteitis fibrosa cystica
What are causes of hypercalcaemia with hyperalbuminaemia?
Increased Urea:
- Dehydration
Normal Urea:
- Cuffed specimen
What are causes of hypercalcaemia with normal albumin/hypoalbuminaemia?
Hypophosphataemia:
- Primary/tertiary hyperparathyroidism
Hyperphosphataemia:
High ALP:
- Bone metastasis
- Thyrotoxicosis
- Sarcoidosis
Normal ALP:
- Myeloma
- Excess Vit D
- Sarcoid
- Milk Alkali Syndrome
What are some symptoms of hypocalcaemia?
CATs go numb:
- C: Convulsions
- A: Arrhythmias (e.g. prolonged QT)
- T: Tetany
- Parasthesias (hand, mouth, feet, lips)
- Neuromuscular excitability: Trousseau’s + Chvostek’s signs (hyperreflexia, laryngeal spasm convulsions)
What is the treatment of hypocalcaemia?
IF symptomatic OR Ca<1.875:
- Parenteral calcium (IV 10% calcium gluconate)
Asymptomatic/mild:
- Oral calcium supplementation
- IF low PTH/Vit D: Vit D supplements (active form)
What are some causes of hypocalcaemia?
- Artefact
Hyperphosphataemia:
- CKD
- Hypoparathyroidism
- Pseudohypoparathyroidism
- Hypomagnesaemia
Normal/Hypophosphataemia:
- Osteomalacia
- Acute pancreatitis
- Overhydration
- Respiratory alkalosis
What are some RFs for Renal Stones (nephrolithiasis)?
- Dehydration
- Abnormal Urine pH (meat intake, renal tubular acidosis)
- Increased excretion of stone constituents
- Urine infection
- Anatomical abnormalities
What is the preventative management of renal stones?
- Avoid dehydration
- Reduce oxalate intake
- Maintain normal Ca intake
- Thiazides = hypocalciuric
- Cirtate (alkalinise urine)
What is struvite comprised of?
Magnesium + Ammonium phosphate
What are the different types of renal stones and their XR appearance?
- Calcium = radio-opaque
- Calcium oxalate = radio-opaque
- Calcium phosphate = radio-opaque
- Triple phosphate (Struvite) = radio-opaque (stag-horn)
- Uric acid = radiolucent
- Cysteine = Radio-opaque (light)
- Xanthines = Lucent
What is the first-line investigation for renal stones?
CTKUB without contrast (<24hrs of presentation)
- USS: pregnant women, children, young people
What is the management for renal stones?
IM diclofenac (analgesia)
- <=5mm diameter = conservative
- 6-20mm: Lithotripsy/uteroscopy
- > 20mm: Percutaneous nephrolithotomy
What are some investigations for recurrent renal stones?
- Bloods
- Stone analysis
- Spot urine
- 24hr urine
