Lecture 6: Calcium and phosphate

Question 1

How much calcium is found in the body and where?

Answer 1

2.1-2.6 mmol/L (ionised-Ca2+: 1.1-1.4 mmol/L)
99% in bones as calcium phosphate
0.99% extracellular
0.01% intracellular

Question 2

Why is calcium regulation important?

Answer 2

Uses lots of ATP to ensure a very low level on intracellular calcium as high levels of calcium cause cells to die

Question 3

What groups can extracellular calcium be split into?

Answer 3

Diffusible (across the glomerular membrane)
-free ionized Ca2+ (involved in many cellular processes)
-complexed calcium (bound to negatively charged molecules like oxalate- not involved in cellular processes)
Not diffusible
-Ca2+ bound to negatively charged proteins e.g. albumin

Question 4

What are the uses of Ca2+ in cellular processes?

Answer 4

• neuronal action potentials
• contraction of muscles
• hormone secretion
• blood coagulation

Question 5

How is calcium reabsorbed?

Answer 5

65% in PCT (80% solvent drag: as water is reabsorbed it drags Ca2+ with it/ 20% transcellular: actively pump calcium out to blood so that Ca2+ can diffuse in from tubule)

25% in TAL (50% paracellular:all the pumps in tubular cell make the inside of the tubule positively charged, repelling the Ca2+ and Mg2+ through the cell gaps/50% transcellular stimulated by PTH)

8% DCT

1.5% collecting duct

Overall only excrete 0.5% of Ca2+

Question 6

Where and how is phosphate found in the body?

Answer 6

Phosphate salts (PO43-): essential for structure of bones and teeth
80% is found in bone 
20% in interstitial fluid

Question 7

How much phosphate is excreted/reabsorbed?

Answer 7

20% excreted
80% reabsorbed
Reabsorption occur with Na+: for every phosphate we have two sodium ions we reabsorb on apical membrane of tubular cells

Question 8

What does an increase in phophate in the plasma do to the urine?

Answer 8

Increase in the amount filtered and excreted

Question 9

What is a common cause of itching in CKD?

Answer 9

Fall in GFR will results in increased plasma PO43- concentration

Question 10

What do Ca2+ and PO43- form?

Answer 10

Insoluable precipitate of calcium phosphate

• adding more of one of the ions results in the precipitation of calcium phosphate, thus the other ion is removed from solution
• Ca2+ and PO43- concentrations are INVERSELY PROPORTIONAL

Question 11

What is secreted when there is a fall in plasma Ca2+?

Answer 11

PTH from parathyroid gland. This also affects the phophate concentration due to their concentrations being inversely proportional

Question 12

What is the function of PTH?

Answer 12

Bone: increases bone resorption (phosphate also released as bound together in bone)

Kidney:

• increase Ca2+ resorption in distal tubules and decrease urinary excretion of calcium
• reduction of phosphate reabsorption in proximal tubule and increase urinary excretion of phosphate
• active vit D enhances absorption of Ca2+ from intestine and increases bone resorption

Question 13

What is hypocalcaemia?

Answer 13

Decreased Ca2+ resulting in neuromuscular excitability leading to tetany with convulsions, hand/feet muscle cramps and cardiac arrythmias

Question 14

What is hypocalcaemia caused by?

Answer 14

• CKD (due to hyperphosphatasemia)
• hypoparathyroidism
• rickets/osteomalacia (lack of vit D)
• tissue injury (cells die and release intracellular phosphate
• alkalosis: reduces the amount of H+ available to bind to protein, so more Ca2+ binds to protein, resulting in decreased ionised Ca2+, but total Ca2+ remains the same

Question 15

How do you treat hypocalcaemia?

Answer 15

Oral/intravenous calcium

-in CKD patients they benefit from alfacalcidol (vit D analogue)

Question 16

What is hypercalcemia?

Answer 16

Too much calcium causing cells to be less excitable, resulting in slow reflexes, muscle weakness and constipation

Question 17

What are the signs and symptoms of hypercalcemia?

Answer 17

-polyuria
-polydipsia
Bones: bone pain/fractures
Stones
Groans: abdominal pain, vomiting, constipation
Moans: depression/confusion

Question 18

What are the causes of hypercalcaemia?

Answer 18

• primary hyperparathyroidism
• sudden acidosis, resulting in the release of bound calcium, which becomes ionized calcium
• increased intestinal absorption due to excess vit D/ ingestion of calcium
• bone destruction (usually by malignancy/myeloma)
• granulomatous disease
• drugs (thiazides)
• tertiary hyperparathyroidism in CKD

Question 19

What is the treatment for hypercalcaemia?

Answer 19

Treat underlying cause with fluids for rehydration and bisphosphonates (increase phosphate levels to decrease calcium levels)

Question 20

What is hypophosphatemia and causes?

Answer 20

Low levels of phosphate, due to excessive loss of phosphate
Causes
-hyperparathyroidism
-reduced absorption from gut (alcohol/antacids)
-malnourished/anorexia nervosa
-refeeding syndrome (phosphate into cells)
-diabetic ketoacidosis (insulin stimulates phosphate to move into cells)
-respiratory alkalosis (decrease in CO2, so pH of cell increases, stimulating glycoslysis, which requires phosphate

Question 21

What are the signs of hypophosphataemia?

Answer 21

Stones: kidney and gallbladder
Thrones: polyuria
Bones: pain
Groans: constipation and muscle weakness
Psychiatric overtones- depressed and confused

Question 22

What is the treatment of hypophosphatemia?

Answer 22

Oral/IV phosphate and close monitoring of bloods

Question 23

What causes hyperphosphatemia?

Answer 23

• CKD (lowers GFR so can’t excrete as much phosphate)
• secondary hyperparathyroidism (kidneys unable to reabsorb Ca2+)
• pseudohypoparathyroidism (kidneys do not repsond to PTH)
• hypoparathryoidism
• excessive intake
• cell death
• respiratory acidosis (inhibits glycolysis in cells soless phosphate is needed by them)
• diabetic ketoacidosis

Question 24

What are the signs and symptoms of hyperphosphatemia?

Answer 24

No symptoms with mild hyperphosphatemia
Severe:
-spontaneous firing of neurones
-tetany
-involuntary contraction of muscles
-calcium phosphate crystal formation (kidney stones/found not just in kidneys)

Question 25

What is the treatment of hyperphosphatemia?

Answer 25

Phosphate binders (reduces dietary intake)
Forced diuresis (increase excretion of phosphate)