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MBBS III Sem II > Pathology of Calcium Homeostasis > Flashcards

Pathology of Calcium Homeostasis Flashcards

Understand the different pathologies causing aberrations in calcium homeostasis

1
Q

How prevalent is Hypercalcaemia in cancer patients

A

10-30% of cancer patients

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2
Q

What are the most common cancers for hypercalcaemia

A

Breast, Lung and Myeloma cancers

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3
Q

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

A

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

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4
Q

Where does PTHrP normally act?

A

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

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5
Q

What is the effect of PTHrP in the 2 given sites

A

Osteoblasts: increases RANKL -> bone resorption increases

Prox renal tubule: increases renal calcium reabsorption

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6
Q

What are the 5 major causes of increased PTHrP

A 
Squamous cell carcinoma
Breast cancer
Renal carcinoma
Ovarian
Adult T-cell leukaemia
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7
Q

Why is PTHrp SO SIMILAR TO pth

A

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

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8
Q

What 2 cell types usually secrete PTHrP

A

EC matrix cells (keratinocytes, osteoblasts)

Breast and ovarian (for gestation to promote milk production)

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9
Q

How do bone metastases lead to hypercalcaemia?

A

Osteolytic metastases increase bone resorption via TGF-beta

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10
Q

what tumours lead to increases 1-alpha-hydroxylase

A

lymphoma and ovarian tumours

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11
Q

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

A

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

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12
Q

What is he most common paraneoplastic syndrome

A

Hypercalcaemia

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13
Q

How does multiple myeloma lead to hypercalcaemia

A

Plasma cell neoplasm that causes bone breakdown

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14
Q

Major affects of multiple myeloma

A

Bone breakdown, renal dysfunction and increases infections

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15
Q

Prognostic indication for multiple myeloma

A

Bence-jones proteinuria

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16
Q

Investigation for multiple myeloma?

A

Blood/electrophoresis showing increased Ig and bence-onne proteins

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17
Q

What is the significance of pence-jones proteins

A

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

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18
Q

Define multiple endocrine neoplasms

A

Neoplastic syndrome affecting multiple endocrine gands

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19
Q

Major sites of MEN

A

Pituitary, parathyroid and pancreas

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20
Q

Presentation of pituitary multiple endocrine neoplasm

A

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

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21
Q

Presentation of parathyroid MEN

A

Nephrolithiasis
Bone abnormalities
MSK complaints
sxs of hypercalcaemia

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22
Q

What is the presentation of pancreas MEN

A

Epigastric pain, hypoglycaemia and secretory diarrhoea

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23
Q

How is hypercaclaemia diagnose and that are ththreshods

A

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

24
Q

What is the number one cause of hypercaclaemia

A

primary hyperparathyroidism

25
Q

What is the number one cause of hypercaclaemia in hospitals

A

Malignancy

26
Q

When does hypercalcaemia become symptomatic

A

Is greater than 3mmol/L (moderate)

27
Q

What are the majority of hypercacaleami aetiologies?

A

Primary Hyperparathyroidism and Malignancy

28
Q

Name 4 causes of hyperparathyroidism

A

PHPT, Adenoma, carcinoma, tertiary hyperparathyroidism

29
Q

Name 3 major aetiologies of malignant hypercalcaemia

A

Myelmoma, secondary deposits in bone, PTHrP

30
Q

How migh excessive vit D arise?

A

Iatrogenic or granulomatous diseae

31
Q

Why does granulomatous disease cause hypercalcaemia?

A

Macrophages produce Vit D

32
Q

What are 2 the endocrine causes of hypercalcaemia?

A

Thyrotoxicosis and Addison’s Disease

33
Q

What Drugs may cause hyeprcalcaemia?

A

Thiazide diuretico, Vit D analogues and Lithium

34
Q

Define Primary Hyperparathyroidism?

A

Adenoma of he parathyroid or hyperplasia of the parathyroid gland

35
Q

How does secondary hyperparathyroidism arise?

A

Hypocalcaemia induces parathyroid gland hyperplasia

36
Q

What conditions can cause secondary hyperparathryrosim?

A

Renal failure or Vit D deficiency

37
Q

Wha tis tertiary hyperparathyroidism?

A

When autonomous parathyroid hyperplasia arises fro chronic secondary hyperparathyrodism

38
Q

What is the mnemonic for hypercalcaemia presentation?

A

Stones, bones, ab moans and psychic groans

39
Q

What r the neuromuscular features of hypercalcaemia

A

Impaire concentration, confusion, fatigue and muscle weakness

40
Q

What are the abdominal signs of hypercalcaemia

A

Nausea, ab pain, anorexia and constipation

41
Q

What are the renal features of hypercalcaeamia

A

Polydipsia, polyuria and neophrolithiasis

42
Q

What are the CVS complications of hypercalcaemia

A

HTN, vasc calcification and shortened QT interval

43
Q

What are the skeletal signs of hypercalcaemia

A

Bone pain, osteoporosis and NOF fracture

44
Q

How does PHPT present on serum biochemistry?

A

High PTH and High Ca

45
Q

High does malignancy present on blood tests

A

High Ca, normal PTH

46
Q

How does secondary hypercalcaemia present on good tests?

A

High ca, low PTH

47
Q

How does secondary hyerpparathyroisim present on blood tests

A

High PTH, low ca

48
Q

What blood test is critical if suspect Hypercalcaemia of malignancy?

A

ALP (it will be elevated in bone lysis)

49
Q

How might calcitirol be elevated in malignancy

A

From Hodgkin’s Lymphoma (lymphatic tissues produce calcitriol)

50
Q

How would you interpret rapidly rising levels of Ca?

A

Likely to be malignancy

51
Q

How migh antacids lead to hypercalcaemia?

A

These contain lots of calcium cabonate

52
Q

How does Lithium lead to hypercalcaemia

A

Increases the set point of PTH

53
Q

Does PHPT mainly affect mortality or morbidity?

A

Morbidity -it is mild and pronlonged

54
Q

What is the prognosis for hypercalcaemia secondary to neoplasms?

A

Not great, high likelihood of mortality

55
Q

What is nephrocalcinosis and why is it important?

A

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

56
Q

How might renal cell carcinoma present?

A

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

MBBS III Sem II (16 decks)

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