Pathophysiology of disorders of mineral metabolism (chem path)

Question 1

What are the key hormones regulating mineral homeostasis (4)

Answer 1

Parathyroid hormone (PTH)
Calcitriol
Calcitonin
Fibroblast growth factor 23 (FGF23)

Question 2

How does PTH regulate minerals?

Answer 2

It acts upon the bones and stimulate osteoclast resorption activity which increases concentration of calcium and phosphate.
Acts upon kidney and promote reabsorption of calcium and excretion of phosphate.
Also activates vitD which stimulates the intestines to absorb more calciuma and phosphate.

Question 3

How does calcitriol regulate minerals?

Answer 3

It stimulates the intestines to absorb more calcium and phosphate. At high concentrations it also promotes bone resorption by osteoclast to produce more calcium and phosphate into circulation.

Question 4

How does FGF23 regulate minerals?

Answer 4

It is secreted by osteocytes when calcitriol and phospate levels in circulation are high.
-It increases renal excretion of phosphates by inhibiting the sodium phosphate cotransporter.
- Also inhibits renal 1-alpha hydroxylase.

Net effect- decreases serum phosphate, phosphaturia and decreased serum calcitriol.

Question 5

How does calcitonin regulate minerals?

Answer 5

It is secreted by the c cells in the thyroid when there are elevated calcium levels.
It inhibits bone resorption by inhibiting osteoclast activity.

Question 6

Calcitonin is used as a marker for what condition?

Answer 6

Medullary thyroid carcinoma (MTC)

Question 7

Confounding factors in calcium measurement(2)

Answer 7

Protein
pH

Question 8

What occurs during alkalosis( high pH) leading to decreased free calcium ions?(4)

Answer 8

Hydrogen ions dissociate from albumin, calcium then binds to albumin.
Also causes an increase in complex calcium formation.
If more calcium binds to albumin, free ionized calcium falls, symptoms and signs of hypocalcaemia.
Note that the total calcium concentration does not change.

Question 9

What happens during low pH?

Answer 9

In acidosis the concentration of free, ionized calcium increases, symptoms and signs of hypercalcaemia.

Question 10

Two common causes of hypercalcaemia?

Answer 10

Malignant tumours
Primary hyperparathyroidism

Question 11

Symptoms of hypercalcaemia(6)

Answer 11

-Hallucinations
-Confusion
-Constipation
-Muscle weakness
-Polyuria, polydipsia
-Arrhythmias

Question 12

What are other causes of hypercalcaemia? (4)

Answer 12

Thyrotoxicosis- causes high calcium levels by stimulating osteoclastic activity.
Immobilisation-stimulates resorption
Thiazide diuretics- decreases renal excretion of calcium.
Chronic lithium therapy- increased PTH secretion.
VitD toxicity- increases calcium concentration in circulation, stimulate more absorption of calcium from gut.

Question 13

What is familial hypocalciuric hypercalcaemia

Answer 13

An inherited autosomal dominant trait.
There is a defect in the Calcium Sensing Receptor (CaSR) gene.
Receptor cannot sense high levels of calcium, this may lead to hypercalcaemia.

Question 14

What is hypocalcaemia?

Answer 14

Low levels of circulating calcium due to hypoparathyroidism, hypomagnesaemia, or vitD deficiency.

Question 15

What does Vitamin D deficiency cause? (2)

Answer 15

Osteomalacia in adults and rickets in children.

Question 16

What is the complex metabolic bone disease that hypocalcaemia is often associated with?

Answer 16

Chronic Kidney Disease- Mineral and Bone Disorder (CKD-MBD)

Question 17

What is renal osteodystrophy? (3)

Answer 17

• Inability to excrete phosphates, leading to the stimulation of FGF23.
  -Inhibition of alpha-1 hydroxylase.
  -No activation of VitD.
  -Low levels of calcium.
• Low calcium levels stimulates high PTH secretion.

Question 18

What causes acquired hypoparathyroidism?(4)

Answer 18

-Infiltrative conditions
-Autoimmune
-Surgery
-Idiopathic

Question 19

What causes hyperphosphataemia in children?

Answer 19

Undiluted cow’s milk

Question 20

True or false
Hypophosphataemia is common during alcohol withdrawal.

Answer 20

True

Question 21

Homeostatic response in Hypophosphataemia

Answer 21

Suppression of FGF23.

Question 22

What is the NB function of magnesium?

Answer 22

It is important for the maintenance of structures of nucleic acids, proteins and ribosomes.

Question 23

What is caused by extracellular magnesium depletion?

Answer 23

Hyperexcitability

Question 24

What increases urinary excretion of magnesium?

Answer 24

ECF volume expansion, hypercalcaemia, hypermagnesaemia.

Question 25

What do very high magnesium concentration cause

Answer 25

Cardiac arrest and respiratory paralysis

Question 26

In which instances is hypermagnesaemia induced?

Answer 26

In ICU to:
-reduce bronchospasm in severe asthma.
-reduce fitting in pre-eclampsia.

Question 27

What causes hypomagnesaemia, physiologically?

Answer 27

Circulating magnesium binding to albumin

Question 28

What are the causes if hypomagnesaemia? (5)

Answer 28

-Cirrhosis
-Malabsorption, malnutrition
-Diuretic therapy
-Alcoholism
-Drug toxicity

Question 29

What are the clinical features of hypomagnesaemia? (5)

Answer 29

Tetany, agitation, ataxia, tremor, cardiac arrhythmias.

Question 30

What do we call the disease where there is an increase in both the osteoblastic and osteclastic activities.

Answer 30

Pagets disease of bone