Pathology of Calcium Homeostasis Flashcards
Understand the different pathologies causing aberrations in calcium homeostasis
How prevalent is Hypercalcaemia in cancer patients
10-30% of cancer patients
What are the most common cancers for hypercalcaemia
Breast, Lung and Myeloma cancers
What are the 3 main mechanisms of pathogenesis of hypercalcaemia in cancer
Production of PTHrP; osteolytic metastases and ectopic 1-alpha hydroxyls increases Vitamin D
Where does PTHrP normally act?
Acts on the same receptors as PTH in osteoblasts and proximal renal tubules
What is the effect of PTHrP in the 2 given sites
Osteoblasts: increases RANKL -> bone resorption increases
Prox renal tubule: increases renal calcium reabsorption
What are the 5 major causes of increased PTHrP
Squamous cell carcinoma Breast cancer Renal carcinoma Ovarian Adult T-cell leukaemia
Why is PTHrp SO SIMILAR TO pth
It has the same N terminus (site that binds to the GPCR)
What 2 cell types usually secrete PTHrP
EC matrix cells (keratinocytes, osteoblasts)
Breast and ovarian (for gestation to promote milk production)
How do bone metastases lead to hypercalcaemia?
Osteolytic metastases increase bone resorption via TGF-beta
what tumours lead to increases 1-alpha-hydroxylase
lymphoma and ovarian tumours
What is the mechanism of action of 1-alpha-hydroxylase in causes hypercaclaemia
Increase 1-alpha-hydroxylase –> increases synthesis of 1,25-Dihydroxyvitamin D (Active form) –> increases serum calcium by acting on intestines, bone remodelling and renal tubule reabsorption
What is he most common paraneoplastic syndrome
Hypercalcaemia
How does multiple myeloma lead to hypercalcaemia
Plasma cell neoplasm that causes bone breakdown
Major affects of multiple myeloma
Bone breakdown, renal dysfunction and increases infections
Prognostic indication for multiple myeloma
Bence-jones proteinuria
Investigation for multiple myeloma?
Blood/electrophoresis showing increased Ig and bence-onne proteins
What is the significance of pence-jones proteins
These are light chains that are toxic to the renal tubular epithelial cells
Define multiple endocrine neoplasms
Neoplastic syndrome affecting multiple endocrine gands
Major sites of MEN
Pituitary, parathyroid and pancreas
Presentation of pituitary multiple endocrine neoplasm
Headache, visual disturbances, often NON-SECRETING –> but can secrete GH and PRL (leading to galactorrhoea, erecile dysfunction and decreased libido
Presentation of parathyroid MEN
Nephrolithiasis
Bone abnormalities
MSK complaints
sxs of hypercalcaemia
What is the presentation of pancreas MEN
Epigastric pain, hypoglycaemia and secretory diarrhoea
How is hypercaclaemia diagnose and that are ththreshods
Mild: >2.5mmol/L
Moderate: >3mmol/L
Crisis: >3.5mmol/L
What is the number one cause of hypercaclaemia
primary hyperparathyroidism
What is the number one cause of hypercaclaemia in hospitals
Malignancy
When does hypercalcaemia become symptomatic
Is greater than 3mmol/L (moderate)
What are the majority of hypercacaleami aetiologies?
Primary Hyperparathyroidism and Malignancy
Name 4 causes of hyperparathyroidism
PHPT, Adenoma, carcinoma, tertiary hyperparathyroidism
Name 3 major aetiologies of malignant hypercalcaemia
Myelmoma, secondary deposits in bone, PTHrP
How migh excessive vit D arise?
Iatrogenic or granulomatous diseae
Why does granulomatous disease cause hypercalcaemia?
Macrophages produce Vit D
What are 2 the endocrine causes of hypercalcaemia?
Thyrotoxicosis and Addison’s Disease
What Drugs may cause hyeprcalcaemia?
Thiazide diuretico, Vit D analogues and Lithium
Define Primary Hyperparathyroidism?
Adenoma of he parathyroid or hyperplasia of the parathyroid gland
How does secondary hyperparathyroidism arise?
Hypocalcaemia induces parathyroid gland hyperplasia
What conditions can cause secondary hyperparathryrosim?
Renal failure or Vit D deficiency
Wha tis tertiary hyperparathyroidism?
When autonomous parathyroid hyperplasia arises fro chronic secondary hyperparathyrodism
What is the mnemonic for hypercalcaemia presentation?
Stones, bones, ab moans and psychic groans
What r the neuromuscular features of hypercalcaemia
Impaire concentration, confusion, fatigue and muscle weakness
What are the abdominal signs of hypercalcaemia
Nausea, ab pain, anorexia and constipation
What are the renal features of hypercalcaeamia
Polydipsia, polyuria and neophrolithiasis
What are the CVS complications of hypercalcaemia
HTN, vasc calcification and shortened QT interval
What are the skeletal signs of hypercalcaemia
Bone pain, osteoporosis and NOF fracture
How does PHPT present on serum biochemistry?
High PTH and High Ca
High does malignancy present on blood tests
High Ca, normal PTH
How does secondary hypercalcaemia present on good tests?
High ca, low PTH
How does secondary hyerpparathyroisim present on blood tests
High PTH, low ca
What blood test is critical if suspect Hypercalcaemia of malignancy?
ALP (it will be elevated in bone lysis)
How might calcitirol be elevated in malignancy
From Hodgkin’s Lymphoma (lymphatic tissues produce calcitriol)
How would you interpret rapidly rising levels of Ca?
Likely to be malignancy
How migh antacids lead to hypercalcaemia?
These contain lots of calcium cabonate
How does Lithium lead to hypercalcaemia
Increases the set point of PTH
Does PHPT mainly affect mortality or morbidity?
Morbidity -it is mild and pronlonged
What is the prognosis for hypercalcaemia secondary to neoplasms?
Not great, high likelihood of mortality
What is nephrocalcinosis and why is it important?
Is the deposition of calcium in the nephron, leading to tubulointerstitial disease and renal insufficiency
How might renal cell carcinoma present?
Hypercalcaemia (increased Vit D production)
HTN
Hepatic dysfunction (reduced toxin excretion)
Cushing syndrome (if affect adrenal glands)
