Endocrine control of calcium metabolism Flashcards
Roles of calcium
Neuromuscular excitability Muscle contraction Strength in bones Intracellular second messenger Intracellular co-enzyme Hormone/ neurotransmitter stimulus-secretion coupling Blood coagulation (factor IV)
Where is calcium found?
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
Calcium handling in body- diagram
(slide 8, lecture 12)
Trends?
Most of Ca isn’t absorbed
Blood:bone ratios usually same unless severe osteoclast/ osteoblast activity (exercise)
Ca2+ increased by
Location of production of substance?
Parathyroid hormone (PTH- Parathormone) released from parathyroid glands 1,25 (OH)2 Vitamin D3 (Dihydroxy-cholecalciferol), also named Calcitrol
Ca2+ decreased by
Location of production of the substance?
Calcitonin (released by thyroid NOT parathyroid glands) from parafollicular cells
Calcium sensing receptor mechanism?
When is PTH released?
How are Ca levels detected?
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
PTH production
Initially synthesised as?
How many aas is PTH?
Action of PTH?
Pre-proPTH
84 aas
Binds to transmembrane G-protein linked receptors= activation of adenyl cyclase+ PLC (Phospholipase C) as second messanger systems
PTH actions
Learn diagram (slide 14, lecture 12)
To increase phosphate levels?
Calcium+ phosphate reabsorption= inversly linked
Need vitamin D to increase phosphate
PTH effect on blood Learn diagram (slide 15, lecture 12)
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PTH action on bone Learn diagram (slide 16, lecture 12)
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Difference between osteoclasts+ osteoblasts
PTH receptors only on osteoblasts
PTH regulation Learn diagram (slide 17, lecture 12)
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Dihydroxy-cholecalciferol (Calcitrol) synthesis Learn diagram (slide 18, lecture 12)
Which organs are necessary for this process?
From cholecalciferol, add OH group in liver then another in kidney
Therefore need liver and kidney to be working properly to get active form
Calcitrol actions Learn diagram (slide 19, lecture 12)
Aims of actions?
Actions compared to PTH?
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
Phosphate metabolism
Learn diagram (slide 20, lecture 12)
What is required to regulate phosphate metabolism?
Most of phosphate= static in body
Fibroblast growth factor 23, if phosphate= too high+ not actively building bone, FGF23= released
Calcitonin
Precursor?
How many amino acids?
Action
Pre-procalcitonin
32 aas
Binds to transmembrane G-protein linked receptor
Activation of adenyl cyclase/ PLC as second messenger systems
Calcitonin Actions+ Regulation
Learn diagram (slide 24, lecture 12)
Leads to?
Gastrin relation?
Inhibits bone breakdown+ increases Ca excretion
Gastrin= signal of high circulating calcium
Can also be detected by stomach ulcers because of high gastrin levels
Endocrine causes of hypocalcaemia
Hypoparathyroidism (too little parathyroid hormones)
Pseudoparathyroidism
Vitamin D definciency
Endocrine causes of hypocalcaemia
Causes?
Features?
Relation of cause to Plasma Ca, Plasma PO4, PTH
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
Clinical signs of hypocalcaemia
Reasoning?
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
Endocrine causes of hypercalcaemia
Primary hyperparathyroidism
Tertiary hyperparathyroidism
Vitamin D Toxicosis (very high levels)
Hyperparathyroidism types
Clinical features?
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
Effect of PTH excess on
Kidneys
GI tract
Bone
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
Summary diagram (if you want) (slide 37, lecture 12)
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