Calcium, Phosphate And Magnesium

Question 1

What the plasma concentrations of calcium, phosphate and magnesium?

Answer 1

Ca= 1.3

Ph= 1.3

Mg= 1.1

Question 2

What is the difference in the distribution of these ions in the EC and IC compartments?

Answer 2

Ca mainly in the extracellular compartment

Ph and mg are similar distributed between the EC and IC compartment

Question 3

What regulatory roles are calcium, phosphate and magnesium involved in?

Answer 3

Calcium:
Cell signalling and 2nd messenger 
Neurotransmitter and hormone release 
Exocytosis of proteins 
Muscle contraction 
Blood clotting 
Biomineralisation 

Phosphate:
Integral component of DNA and RNA
ATP
Phosphate groups can be added or deleted from proteins

Magnesium 
DNA and protein synthesis 
Oxidative phosphorylation 
Enzyme function 
Ion channel regulation 
Neuromuscular excitability

Question 4

What hormones are involved the metabolism of these minerals?

Answer 4

PTH

Vitamin D

FGF-23

PTHrP

CT (calcitonin)

Question 5

Which organ acts as the main regulator of these minerals homeostasis? How can it adapt its function to maintain homeostasis?

Answer 5

Kidney
NOTE: Ca/Mg sensory receptor in particular

Can decrease or increase the filtered load depending on whether there is a hypo or hyper state

Question 6

What implications would impaired renal function have on levels of calcium, magnesium and phosphate in the body?

Answer 6

Would lead to impaired reabsorption and increased excretion

I.e. loss of homeostasis

Question 7

How is vitamin D related to GIT calcium absorption?

Answer 7

Calcitrol (1,25-OH VD3) acts on ileum cell nuclei to cause transcription of Calbindin which acts to form Calbindin-Ca2+ complex to aid with transportation of Ca2+ from microvilli and into vesicles

Question 8

Which parts of the nephron is associated with the absorption of the different minerals? Why is this clinically significant?

Answer 8

PCT= Ca + Phos primarily

DCT= Mg

Need to be aware that electrolyte imbalance might occur with the use of certain diuretics depending on which part of the nephron they target

Question 9

What form of calcium regulates feedback mechanisms? What factors can influence this levels of this form of calcium?

Answer 9

Free ionised calcium

Decreased ph= increased Ca2+
Increased ph= decreased Ca2+

Question 10

Why is it important to know the albumin concentration of a patient if you want to measure their calcium levels?

Answer 10

The concentration of free calcium depends on the concentration of albumin

Calcium concentrations need to be corrected to account for the fact that for 0.02mmol/L calcium binds to each gram of albumin

Question 11

What are the causes of hypocalcaemia?

Answer 11

CDK and AKI

Vit D deificiency

Hypoparathyroidism

Acute pancreatitis

Magnesium deficiency i.e. Mg is a cofactor for PTH

Artefact i.e. wrong test tube (EDTA is a chelating agent which may lead to apparent hypocalcaemia)

Question 12

Why is hypocalcaemia commonly associated with acute pancreatitis?

Answer 12

High levels of pancreatic lipase breakdown lipids to free fatty acid which accumulate in abdominal cavity and act to CHELATE calcium

Question 13

What is the homeostatic response to low Ca2+ levels?

What feedback mechanism prevents excess PTH release?

Answer 13

Parathyroid gland detects low levels and secretes PTH
PTH:
-stimulates osteoclasts to increase bone resorption= Ca2+ and PO4 released
-stimulates 1-alpha hydroxylase production in the kidney which acts to convert 25(OH)D3 to 1,25(OH)D3
-1,25(OH)D3 acts on bone to stimulate release of FGF23 to decrease PO4 reabsoprtion and feeds back to parathyroid gland to prevent excess PTH release and acts on gut to increase Ca2+ and PO4 absorption

Question 14

What is the homeostatic response to high calcium levels?

Answer 14

Calcitonin released from thyroid gland to decrease calcium reabsorption in kidney and decrease PO4 reabsorption

Question 15

What are the 2 conditions associated with vitamin D deficiency? How are they different?

Answer 15

Rickets= affects growing bone 
osteomalacia= affects adult skeleton 

Due to lack of mineralisation of osteoid

Question 16

What are the causes of vitamin D deficiency? How can it be treated?

Answer 16

Impaired availability of vit D

Impaired liver hydroxylation or renal hydroxylation

End organ insensitivity to vit D metabolites

Vit D replacement through diet or sunlight

Question 17

How can glucocorticoids cause vitamin D deficiency?

Answer 17

Inhibit intestinal vit D dependent calcium absorption

Question 18

Why might surgery or radiotherapy targeting the thyroid gland lead to hypocalcaemia?

Answer 18

Can lead to iatrogenic damage to parathyroid glands which results in decreased PTH production

Question 19

How might someone with hypocalcaemia present?

Answer 19

Asymptomatic

Neuromuscular symptoms are fairly common
I.e. pins and needles or spasm due to nerve irritations

Question 20

What tests are done to differentiate between the different causes of hypocalcaemia?

Answer 20

Biochemical test to look at PTH and PO4

Question 21

What conditions are indicate by the following test results?

1. Increased PTH + decreased PO4
2. Increased PTH + PO4
3. Decreased PTH + increased PO4

Answer 21

1.
Vitamin D deficiency due to malabsorption or liver disease
Acute pancreatitis
Drugs I.e. Bisphosphonates

2.
CKD
Tumour lysis 
Early rhabomyolysis 
Pseudohypoparathyroidism 

3.
Reduced parathyroid function
Hypomagnesemia 
Drugs 
Neonatal hypocalcaemia due to maternal hypercalcaemia 
AI
Surgery

Question 22

How can you treat hypocalcaemia?

Answer 22

IV calcium= acutely ill w/ neuromuscular symptoms
Oral calcium= mildly symptomatic/asymptomatic

Treat underlying cause:
VD replacement
1,25 D3 products for hypoparathyroidism

Question 23

What causes hypercalcaemia?

Answer 23

Primary hyperparathyroidism

Malignancy

Question 24

What are the different causes of primary and secondary hyperparathyroidism?
How can you differentiate between the 2?

Answer 24

Primary:
Increased PTH secretion due to adenoma or parathyroid hyperplasia

Secondary:
Renal failure
Vitamin D deficiency

High calcium in primary
Low calcium in secondary

Question 25

What are clinical features of hypercalcaemia?

Answer 25

Thirst 
Polyuria 
Constipation 
Aches and pain 
Anxiety + depression 
Confusion 
Coma 
Renal stones
Osteoporosis 
Pancreatitis

Question 26

Why is it important to identify malignancy-associated hypercalcaemia early?

Answer 26

Acts as poor prognostic signs and can lead to life saving therapy being put in place

Question 27

What are the mechanisms behind malignancy associated hypercalcaemia?

Answer 27

Humoral hypercalcaemia i.e. PTHrP secreting tumour

Bone invasion

Immobilisation

Parathyroid carcinoma

Question 28

How can malignancy associated hypercalcaemia be treated?

Answer 28

Aggressive IV hydration

IV bisphosphonates +/- calcitonin

Manage renal failure if associated

Question 29

What are the main causes of hypophosphataemia?

Answer 29

Increased renal excretion

GIT malabsorption

Cellular shifts

Question 30

What are the clinical consequences of hypophosphataemia?

Answer 30

Asymptomatic

Neuromuscular disturbance

Question 31

How is hypophosphataemia treated?

Answer 31

Oral phosphate tablet if low

IV phosphate polyfusor if more significant

Question 32

What are the causes of hyperphosphataemia?

Answer 32

Decreased renal excretion due to renal failure or hypoparathyroidism

Question 33

What are the symptoms of hyperphosphataemia?

Answer 33

Acute
Tetany i.e. seizures and hypotension

Chronic
Secondary hyperparathyroidism i.e. can present with soft tissue calcification

Question 34

What is the main cause of Mg deficiency?

Answer 34

GI causing malabsorption

I.e. associated with alcoholism

Question 35

How does hypomagnesemia present?

Answer 35

Non-specific lethargy
Weakness
Increase neuromuscular excitability i.e. tremors or carpopedal spasm, muscle cramps, tetany

Cardiac arrhythmias i.e. A tachycardia + VT

Question 36

What are distinct features of Gitelmen syndrome?

Answer 36

Hypomagnesium and renal magnesium wasting

Question 37

How would you treat hypomagnesemia? When is IV magnesium indicated?

Answer 37

Oral magnesium glycerophosphate tablets

<0.5mmol/L= IV magnesium sulphate 50% solution

Question 38

What are the causes and presentation of magnesium excess?

Answer 38

Acute renal failreu
Severe diabetic ketoacidosis
Addison’s disease
Supplements

Loss of deep tendon reflexes
Increased PR interval which can lead to MI (when Mg >2.0 mmol/L)

Question 39

How are patients with severe mineral imbalance monitored?

Answer 39

Fluid intake and output
Daily weight to see if fluid accumulating
ECG to look for arrhythmias
Renal function and electrolytes tested daily
(U&E, LFT, Ca, Mg, Phos, Bicarbonate, Cl)