Pathology of Calcium Homeostasis

Question 1

How prevalent is Hypercalcaemia in cancer patients

Answer 1

10-30% of cancer patients

Question 2

What are the most common cancers for hypercalcaemia

Answer 2

Breast, Lung and Myeloma cancers

Question 3

What are the 3 main mechanisms of pathogenesis of hypercalcaemia in cancer

Answer 3

Production of PTHrP; osteolytic metastases and ectopic 1-alpha hydroxyls increases Vitamin D

Question 4

Where does PTHrP normally act?

Answer 4

Acts on the same receptors as PTH in osteoblasts and proximal renal tubules

Question 5

What is the effect of PTHrP in the 2 given sites

Answer 5

Osteoblasts: increases RANKL -> bone resorption increases

Prox renal tubule: increases renal calcium reabsorption

Question 6

What are the 5 major causes of increased PTHrP

Answer 6

Squamous cell carcinoma
Breast cancer
Renal carcinoma
Ovarian
Adult T-cell leukaemia

Question 7

Why is PTHrp SO SIMILAR TO pth

Answer 7

It has the same N terminus (site that binds to the GPCR)

Question 8

What 2 cell types usually secrete PTHrP

Answer 8

EC matrix cells (keratinocytes, osteoblasts)

Breast and ovarian (for gestation to promote milk production)

Question 9

How do bone metastases lead to hypercalcaemia?

Answer 9

Osteolytic metastases increase bone resorption via TGF-beta

Question 10

what tumours lead to increases 1-alpha-hydroxylase

Answer 10

lymphoma and ovarian tumours

Question 11

What is the mechanism of action of 1-alpha-hydroxylase in causes hypercaclaemia

Answer 11

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

Question 12

What is he most common paraneoplastic syndrome

Answer 12

Hypercalcaemia

Question 13

How does multiple myeloma lead to hypercalcaemia

Answer 13

Plasma cell neoplasm that causes bone breakdown

Question 14

Major affects of multiple myeloma

Answer 14

Bone breakdown, renal dysfunction and increases infections

Question 15

Prognostic indication for multiple myeloma

Answer 15

Bence-jones proteinuria

Question 16

Investigation for multiple myeloma?

Answer 16

Blood/electrophoresis showing increased Ig and bence-onne proteins

Question 17

What is the significance of pence-jones proteins

Answer 17

These are light chains that are toxic to the renal tubular epithelial cells

Question 18

Define multiple endocrine neoplasms

Answer 18

Neoplastic syndrome affecting multiple endocrine gands

Question 19

Major sites of MEN

Answer 19

Pituitary, parathyroid and pancreas

Question 20

Presentation of pituitary multiple endocrine neoplasm

Answer 20

Headache, visual disturbances, often NON-SECRETING –> but can secrete GH and PRL (leading to galactorrhoea, erecile dysfunction and decreased libido

Question 21

Presentation of parathyroid MEN

Answer 21

Nephrolithiasis
Bone abnormalities
MSK complaints
sxs of hypercalcaemia

Question 22

What is the presentation of pancreas MEN

Answer 22

Epigastric pain, hypoglycaemia and secretory diarrhoea

Question 23

How is hypercaclaemia diagnose and that are ththreshods

Answer 23

Mild: >2.5mmol/L
Moderate: >3mmol/L
Crisis: >3.5mmol/L

Question 24

What is the number one cause of hypercaclaemia

Answer 24

primary hyperparathyroidism

Question 25

What is the number one cause of hypercaclaemia in hospitals

Answer 25

Malignancy

Question 26

When does hypercalcaemia become symptomatic

Answer 26

Is greater than 3mmol/L (moderate)

Question 27

What are the majority of hypercacaleami aetiologies?

Answer 27

Primary Hyperparathyroidism and Malignancy

Question 28

Name 4 causes of hyperparathyroidism

Answer 28

PHPT, Adenoma, carcinoma, tertiary hyperparathyroidism

Question 29

Name 3 major aetiologies of malignant hypercalcaemia

Answer 29

Myelmoma, secondary deposits in bone, PTHrP

Question 30

How migh excessive vit D arise?

Answer 30

Iatrogenic or granulomatous diseae

Question 31

Why does granulomatous disease cause hypercalcaemia?

Answer 31

Macrophages produce Vit D

Question 32

What are 2 the endocrine causes of hypercalcaemia?

Answer 32

Thyrotoxicosis and Addison's Disease

Question 33

What Drugs may cause hyeprcalcaemia?

Answer 33

Thiazide diuretico, Vit D analogues and Lithium

Question 34

Define Primary Hyperparathyroidism?

Answer 34

Adenoma of he parathyroid or hyperplasia of the parathyroid gland

Question 35

How does secondary hyperparathyroidism arise?

Answer 35

Hypocalcaemia induces parathyroid gland hyperplasia

Question 36

What conditions can cause secondary hyperparathryrosim?

Answer 36

Renal failure or Vit D deficiency

Question 37

Wha tis tertiary hyperparathyroidism?

Answer 37

When autonomous parathyroid hyperplasia arises fro chronic secondary hyperparathyrodism

Question 38

What is the mnemonic for hypercalcaemia presentation?

Answer 38

Stones, bones, ab moans and psychic groans

Question 39

What r the neuromuscular features of hypercalcaemia

Answer 39

Impaire concentration, confusion, fatigue and muscle weakness

Question 40

What are the abdominal signs of hypercalcaemia

Answer 40

Nausea, ab pain, anorexia and constipation

Question 41

What are the renal features of hypercalcaeamia

Answer 41

Polydipsia, polyuria and neophrolithiasis

Question 42

What are the CVS complications of hypercalcaemia

Answer 42

HTN, vasc calcification and shortened QT interval

Question 43

What are the skeletal signs of hypercalcaemia

Answer 43

Bone pain, osteoporosis and NOF fracture

Question 44

How does PHPT present on serum biochemistry?

Answer 44

High PTH and High Ca

Question 45

High does malignancy present on blood tests

Answer 45

High Ca, normal PTH

Question 46

How does secondary hypercalcaemia present on good tests?

Answer 46

High ca, low PTH

Question 47

How does secondary hyerpparathyroisim present on blood tests

Answer 47

High PTH, low ca

Question 48

What blood test is critical if suspect Hypercalcaemia of malignancy?

Answer 48

ALP (it will be elevated in bone lysis)

Question 49

How might calcitirol be elevated in malignancy

Answer 49

From Hodgkin's Lymphoma (lymphatic tissues produce calcitriol)

Question 50

How would you interpret rapidly rising levels of Ca?

Answer 50

Likely to be malignancy

Question 51

How migh antacids lead to hypercalcaemia?

Answer 51

These contain lots of calcium cabonate

Question 52

How does Lithium lead to hypercalcaemia

Answer 52

Increases the set point of PTH

Question 53

Does PHPT mainly affect mortality or morbidity?

Answer 53

Morbidity -it is mild and pronlonged

Question 54

What is the prognosis for hypercalcaemia secondary to neoplasms?

Answer 54

Not great, high likelihood of mortality

Question 55

What is nephrocalcinosis and why is it important?

Answer 55

Is the deposition of calcium in the nephron, leading to tubulointerstitial disease and renal insufficiency

Question 56

How might renal cell carcinoma present?

Answer 56

Hypercalcaemia (increased Vit D production) HTN Hepatic dysfunction (reduced toxin excretion) Cushing syndrome (if affect adrenal glands)