17. Parathyroid Gland Calcium And Phosphate Regulation Flashcards
What are the 3 interconvertible fractions that calcium is distributed between?
Ionised calcium (47%)
Protein bound calcium (47%)
Complexed calcium - Pi, citrate etc (6%)
What is the normal serum calcium?
2.2-2.6mM
Where is most of the calcium in the body stored?
Skeleton
Why is calcium important in blood clotting?
It is factor IV in clotting cascade
EDTA stops calcium clotting the blood
What affect can massive blood transfusions have?
Contains citrate which chelates calcium ions so need to give IV calcium to prevent hypocalcaemia
What are the 3 hormones involved in regulation of calcium and phosphate?
Parathyroid hormone (PTH)
Calcitriol
Calcitonin
What are some other names for calcitriol?
1,25-dihydroxycholecalciferol
1,25(OH)2D
What is the general role of PTH in regulation of calcium?
Elevates serum calcium levels
Which cells produce PTH?
Chief cells
What are the 2 types of cells in the parathyroid gland?
Oxyphil cells
How is PTH synthesis regulated?
Both at transcriptional at post transcriptional levels
Low serum calcium up-regulates gene transcription
High serum calcium down-regulate
Low serum calcium prolongs survival of mRNA
What are the target organs of PTH and what are the physiological effects?
Bone - increase resorption
Intestine - activates vitamin D and hence increases transcellular uptake from GI tract
Kidney - decrease loss to urine
What is PTH action in the gut?
Dietary intake of calcium is typically 1000mg/d
Only 30% o which is absorbed by a paracellular uptake effective when [Ca2+] is not limited
Bastion is significantly increased by vit D via a transcellular uptake
PTH stimulates conversion of vit D to its active form which increases uptake of Ca2+ from gut
How is bone deposited?
Osteoblasts produce collagen matrix which is mineralised by hydroxyapatite
How is bone reabsorbed?
Osteoclasts produce acid micro-environment hydroxyapatite dissolves
What are the actions of PTH on bone?
1-2 hours PTH stimulates osteolysis
PTH induces osteoblastic cells to synthesise and secrete cytokines on cell surface
Cytokines stimulate differentiation and activity in osteoclasts and protect them from apoptosis
PTH decreases osteoblasts activity exposing bony surface to osteoclasts
Reabsorption of mineralised bone and release of Pi and calcium into extracellular fluid
Describe the synthesis of calcitriol
Vitamin D3 is hormone precursor molecules required for synthesis
Provided mostly by UVB light on skin
25(OH)D is pre-hormone substrate, produced in liver from D3
1,25(OH)2D (calcitriol) is active hormone, produced in kidney and elsewhere from 25(OH)D
Where is calcitonin released from?
C cells in thyroid gland
Describe the feedback regulation of serum calcium when there is increase in plasma calcium
Decreased PTH secretion
Descreased calcitriol so less calcium taken from gut
Decrease calcium reabsorption in kidney
Decreased breakdown of bone, increased bone building
Decreased plasma calcium
Describe the feedback regulation of serum calcium with decrease in plasma calcium
Increased PTH secretion
Increase calcitriol so more calcium taken from gut
Increased calcium reabsorption in kidney
Increased breakdown of bone, decreased bone building
Increased plasma calcium
What happens in chronic hypercalcaemia?
Kidney damage Dehydration Renal calculi (STONES) Tiredness, depression (MOANS) Constipation (GROANS) Muscle aches (BONES)
What can hypocalcaemia cause?
Hyper-excitability of NMJ Lower serum calcium causes increase odium entry into neurones, leading to depolarisation and increase likelihood of AP Pins and needles Tetany (muscle spasms) Paralysis Convulsions
What is the serum calcium in severe hypercalcaemia?
> 3.0mmol/L
What are the symptoms of severe hypercalcaemia?
Polyuria can lead to dehydration which then exacerbates the hypercalcaemis
Can lead to lethargy, weakness, confusion, coma, renal failure
What is the main treatment for severe hypercalcaemia?
Rehydration
What are the causes of hypercalcaemia?
Malignant osteolytic bone metastasis - all calcium released from cells into blood
Multiple myeloma
Common cancers that metastasise to bone causing lytic lesions and hypercalcaemia: breast, lung, renal, thyroid
Why does prostate cancer not cause hypercalcaemia?
Common cause of bone metastasis
However causes osteoblastic metastasis instead of osteoclastic
Where are the common sites for bone metastasis?
Vertebrae Pelvis Proximal parts of the femur Ribs Proximal part of humerus Skull
What is the difference between the types of hyperparathyroidism?
Primary - one of 4 parathyroid glands develop an adenoma and secretes excessive parathyroid hormone
Secondary - all 4 parathyroid glands become hyperplastic, seen in all patients with vit D deficiency
Why does secondary hyperparathyroidism occur in patients with vit D deficiency?
Vit D deficiency means that their calcium absorption is low resulting in low serum calcium levels, that the causes PTH levels to rise
What are the symptoms of primary hyperparathyroidism?
Stones - kidney stones
Moans - tired, exhausted, depressed
Groans - constipation, peptic ulcers, pancreatitis
Bones - bone and muscle aches
How does calcium affect neuronal activity?
Calcium raises the threshold for nerve membrane depolarisation and therefore the development of an AP
What impact does hypercalcaemia have on neuronal activity?
Leads to suppression of neuronal activity - lethargy, confusion, coma
What impact does hypocalcaemia have on neuronal activity?
Leads to excitable nerves - tingling, muscle tetany, epilepsy
When is symptomatic hypocalcaemia most often seen?
Post total-thyroid to my patients because of inadvertent removal/ischaemia of parathyroid glands
Symptoms can start within 6 hrs of surgery
<2.1mmol/L
