Endocrine control of calcium metabolism

Question 1

Roles of calcium

Answer 1

Neuromuscular excitability
Muscle contraction
Strength in bones
Intracellular second messenger
Intracellular co-enzyme
Hormone/ neurotransmitter stimulus-secretion coupling
Blood coagulation (factor IV)

Question 2

Where is calcium found?

Answer 2

Mainly in bone (99%= 1kg) as hydroxyapatite crystals
In blood (1%= 2.5mM) as ionised calcium (Ca2+), 45% bound to plasma proteins, 50% free, 5% as diffusable salts
Only free part= bioactive

Question 3

Calcium handling in body- diagram
(slide 8, lecture 12)
Trends?

Answer 3

Most of Ca isn’t absorbed

Blood:bone ratios usually same unless severe osteoclast/ osteoblast activity (exercise)

Question 4

Ca2+ increased by

Location of production of substance?

Answer 4

Parathyroid hormone (PTH- Parathormone) released from parathyroid glands
1,25 (OH)2 Vitamin D3 (Dihydroxy-cholecalciferol), also named Calcitrol

Question 5

Ca2+ decreased by

Location of production of the substance?

Answer 5

Calcitonin (released by thyroid NOT parathyroid glands) from parafollicular cells

Question 6

Calcium sensing receptor mechanism?
When is PTH released?
How are Ca levels detected?

Answer 6

G-protein coupled receptor mechanism
Ca= normal= not a lot of PTH release
More PTH released when Ca levels= low
Parathyroid glands have calcium-sensing receptors which control PTH levels

Question 7

PTH production
Initially synthesised as?
How many aas is PTH?
Action of PTH?

Answer 7

Pre-proPTH
84 aas
Binds to transmembrane G-protein linked receptors= activation of adenyl cyclase+ PLC (Phospholipase C) as second messanger systems

Question 8

PTH actions
Learn diagram (slide 14, lecture 12)
To increase phosphate levels?

Answer 8

Calcium+ phosphate reabsorption= inversly linked

Need vitamin D to increase phosphate

Question 9

PTH effect on blood
Learn diagram (slide 15, lecture 12)

Answer 9

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Question 10

PTH action on bone
Learn diagram (slide 16, lecture 12)

Answer 10

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Question 11

Difference between osteoclasts+ osteoblasts

Answer 11

PTH receptors only on osteoblasts

Question 12

PTH regulation
Learn diagram (slide 17, lecture 12)

Answer 12

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Question 13

Dihydroxy-cholecalciferol (Calcitrol) synthesis
Learn diagram (slide 18, lecture 12)

Which organs are necessary for this process?

Answer 13

From cholecalciferol, add OH group in liver then another in kidney
Therefore need liver and kidney to be working properly to get active form

Question 14

Calcitrol actions
Learn diagram (slide 19, lecture 12)

Aims of actions?

Actions compared to PTH?

Answer 14

Works on trying to BUILD bone, requires phosphate+ calcium
Works on osteoblasts instead of osteoclasts
Works slower than PTH, more chronic effect
Tries to reabsorb Phosphate unlike PTH

Question 15

Phosphate metabolism
Learn diagram (slide 20, lecture 12)
What is required to regulate phosphate metabolism?

Answer 15

Most of phosphate= static in body

Fibroblast growth factor 23, if phosphate= too high+ not actively building bone, FGF23= released

Question 16

Calcitonin
Precursor?
How many amino acids?
Action

Answer 16

Pre-procalcitonin
32 aas
Binds to transmembrane G-protein linked receptor
Activation of adenyl cyclase/ PLC as second messenger systems

Question 17

Calcitonin Actions+ Regulation
Learn diagram (slide 24, lecture 12)
Leads to?
Gastrin relation?

Answer 17

Inhibits bone breakdown+ increases Ca excretion

Gastrin= signal of high circulating calcium
Can also be detected by stomach ulcers because of high gastrin levels

Question 18

Endocrine causes of hypocalcaemia

Answer 18

Hypoparathyroidism (too little parathyroid hormones)
Pseudoparathyroidism
Vitamin D definciency

Question 19

Endocrine causes of hypocalcaemia
Causes?
Features?
Relation of cause to Plasma Ca, Plasma PO4, PTH

Answer 19

Hypoparathyroidism (too little parathyroid hormones)
Causes:
1. Idiopathic (low circulating levels of PTH)
2. Hypomagnesaemia (low magnesium because of nutrition/ GI problem) (need Mg for parathyroid gland function+ downstream PTH effects on target cells)
3. Supression by raised plasma Ca concentration
Decrease plasma Ca, Increase plasma PO4, Decrease PTH

Pseudoparathyroidism (target organ resistance to PTH as well (similar to T2 diabetes))
Cause= defective G proteins
Features= Short stature, round face, low IQ, subcutaneous calcification+ bone abnormalities, other endocrine disorders
Decrease plasma Ca, Increase plasma PO4, Increase PTH

Vitamin D definciency
Rickets in children
Osteomalacia in adults
Features= Decreased calcification of bone matrix= softening of bone= bowing of bones in children+ fractures in adults
Decrease plasma Ca, Decrease plasma PO4, Increase PTH

Question 20

Clinical signs of hypocalcaemia

Reasoning?

Answer 20

Tetany:
Trousseau’s sign (padmakosha)
Chvostek’s sign (abnormal reaction in stimulation of facial nerve)

Low Ca in nerves= easier for Na to enter axon= depolarises nerve more easily= easier for muscle contraction

Question 21

Endocrine causes of hypercalcaemia

Answer 21

Primary hyperparathyroidism
Tertiary hyperparathyroidism
Vitamin D Toxicosis (very high levels)

Question 22

Hyperparathyroidism types

Clinical features?

Answer 22

Type 1:
Adenoma that releases a lot of PTH, isn’t correctly regulated by feedback cycle
Clubbing of fingers (Bone erosion in terminal phalanges)

Type 2:
Parathyroid hormone can’t fix low Ca levels e.g. because one of the organs isn’t functioning properly= parathyroids become hyperplasic

Type 3:
Patient= cured from Type 2 by organ transplant (kidney= normal now) but parathyroid gland= autonomous, don’t respond well to negative feedback (like the adenoma)+ they’ve grown a lot

Question 23

Effect of PTH excess on
Kidneys
GI tract
Bone

Answer 23

Kidney:
Increased Ca reabsorption
Increased PO4 excretion
Polyuria- large urine volume
Renal stones
Nephrocalcinosis- calcium in nephrons
Increased 1,25 (OH)2D2 synthesis

GI tract:
Gastric acid
Duodenal ulcers

Bone:
Bone lesions
Bone rarefraction
Fractures

Question 24

Summary diagram (if you want)
(slide 37, lecture 12)

Answer 24

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