Regulation of Calcium and Phosphate

Question 1

How is calcium distributed in the body?

What is biologically active calcium?

Answer 1

Skeleton and teeth - calcium hydroxyapatite crystals

-Extracellular calcium:
in plasma as ions or
bound to proteins and anions.

The ionised unbound calcium = active

Question 2

What hormone controls the increase of calcium? ( and phosphate )

Answer 2

• Parathyroid hormone PTH
• Vitamin D made in skin or diet

Regulation of calcium and phosphate via actions on kidney, bone and gut

Question 3

What hormone works to decrease calcium?

Answer 3

Calcitonin secreted by thyroid parafollicular

Question 4

What are the sources of vitamin D?

Answer 4

Ergocalciferol from diet ( vitamin D2 )

Cholecalciferol from sun ( vitamin D3 )

Question 5

Outline Vitamin D metabolism?

Answer 5

UVB light affects skin cells –> 7-dehydrocholesterol –> pre-vitamin D3 –> Vitamin D3 –> hydroxylase in Liver –> 25(OH)cholecalciferol –>in Kidney 1 alpha hydroxylase ( regulatory enzyme to make active vitamin D)

= 1,25 (OH)2 Cholescaliferol / Calitriol

Question 6

What is a good indicator of body vitamin D status?

Answer 6

Serum 25 -OH vitamin D ( inactive pre-cursor )

Question 7

What is the active form of vitamins D?

Answer 7

Calcitrol ( 1,25 (OH)2 Vitamin D )

Question 8

How is Calcitrol regulated?

Answer 8

Negative feedback to 1-alpha hydroxylase

Question 9

What are the effects of Calcitriol?

Answer 9

Increases calcium absorption of bones Ca2+

Increases absorption from gut of Ca2+ and Po43-

Increases absorption from kidney of Ca2+ and PO4,3-

Question 10

How is Parathyroid hormone secreted from Parathryoid gland?

Answer 10

Chief cells in parathyroid glands

• Secreted as a large precursor ( pre-pro-PTH ) and cleaved to PTH
• G protein coupled calcium sensing receptor on chief cells detects change in circulating calcium concentration

Question 11

PTH secretion ( a ) to serum calcium?

Answer 11

Inversely proportional

• when high Ca2+ recepted by cheif cells imhibits PCH release

Question 12

What are the actions of the parathyroid hormone?

Answer 12

Increases calcoim reabsorption from kidney
Increases Phosphate ion exretion from kidneys
Increases 1-alpha hydroxylase activity

Increases bone reabsorption

Increases Calcium absorption from gut
Increases phosphate absorption from gut

• Opposing phosphate effects = equal net effect
• net effect of increases sereum calcium

Question 13

What do Osteoblasts do?

Answer 13

Build bone

Have PTH receptors, when bound it stimulates osteoblasts to release osteoclast activating factors

Question 14

What do Osteoclasts do?

Answer 14

Consume bone to release calcium

Question 15

What is the effect of Calcitriol on bone?

Answer 15

Low sereum calcium = calcitrol increases calcium reabsorptipon from bone = Osteoclasts > Osteoblasts

Normal serum calcium = Calcitrol works to increase bone formation = Osteoblasts > Osteoclasts

Question 16

How is PTH regulated?

Answer 16

Negative feedback from Increases Plasma Ca2+ affecting parathyroid gland

Negative feedback from serum calcium on hormone

Question 17

What is Cacitonin?

Answer 17

• Secreted from parafollicular cells of thyroid gland
• Reduces serum calcium ( decreasing osteoclast activity and Increasing Calcium excretion )
• Physiological role in calcium homeostasis in humans is unclear
  Removal of thryoid gland does not affect serum calcium

Question 18

What is FGF23?

Answer 18

Made by osteocytes

Fibroblast Growth Factor 23 reduces phosphate

Normally phosphate reabsorbed by Na+/PO43- co transporter
FGF23 inhibits this transporter

and

Inhibits Calcitriol production = less reabsorption of phosphate from the gut

Question 19

How does Hypercalcaemia affect action potentials?

How does Hypocalcaemia affects action potentials?

Answer 19

• Ca2+ blocks Na+ influx so LESS membrane excitability

- MORE membrane excitability

Question 20

What are the characteristics of Hypocalcaemia? 4

Answer 20

Paraesthesia
Convulsions
Arrhythmias
Tetany

Question 21

What are the characteristics of Chvostek’s sign?

Answer 21

Hypocalcaemia test

Tap below zygomatic arch = taps facial nerve

Positive response of hypocalcaemia - twitching of facial msucles

Question 22

What are the characteristics of Trousseau’s sign?

Answer 22

Hypocalcaemia test

Inflation of BP cuff for several minutes induces carpopedal spasm = neuromuscular irritability due to hypocalcaemia

Question 23

Causes of hypocalcaemia?

Answer 23

Low PTH levels : hypoparathyroidism

• surgical
• auto-immune
• magnesium deficiency
• congenital ( Agenesis, is rare )

Vitamin D deficiency

Question 24

Causes of vitamin D deficiency?

Answer 24

• Malabsorption or dietary insufficiency
• Inadequate sun exposure
• Liver disease
• Renal disease
• Vit D receptor defects ( rare )

Question 25

What are the consequences of Vitamin D deficiency on bones?

Answer 25

Lack of bone mineralisation = soft bones
Children - Rickets

Adults - Osteomalacia - fractures, proximal myopathy

Question 26

Hypercalcaemia signs and symptoms?

Answer 26

Stones = renal effects : nephrocalcinosis- kidney stones, renal colic

Abdominal Moans = Gi effects: Anorexia, nauseam dyspepsia, constipation, pancreatitis

Psychci groans = CNA effects: Fsatigue, depression, impared concentration, coma

Question 27

Causes of hypercalcaemia?

Answer 27

Primary hyperparathyroidism = too much PTH, due to adenoma
No negative feedback

Malignancy = Bony metastases produced local factors to activate osteoclasts, increasing calcium reabsorption from bone

Vitamin D Excess - rare