Hormonal regulation of Calcium and Phosphate Balance- 26 Flashcards
What are processes that calcium is essential for.
Excitation- contration coupling
Stimulus-secretion coupling
Blood Coagulation
Structural component of bone
What cellular structures and chemicals is phosphate essential for.
Phospholipid
DNA
ATP
What are hormones that regulate Ca2+ and PO43- levels
Parathyroid Hormone
1,25-dihydroxyvitamin D
Calcitonin
What type of hormone is parathyroid hormone
Peptide hormone
Where and why is parathyroid hormone secreted.
Secreted by the chief cells of the parathyroid gland in response to low plasma Ca2+ levels.
What is the process of parathyroid regulation by Ca2+ levels
Ca2+ binds to the CasR (Calcium sensing receptor)
This leads to activation of a signalling pathway and generation of Arachondic Acid
AA inhibits secretion of PTH
Reduced Ca2+ levels switches off this signalling pathway and allows PTH secretion
What type of receptor is the PTHR1 receptor
GPCR
What are the two main targets of Parathyroid hormone
Bone and Kidney Cells
What effect does PTH have on bones
Stimulates Calcium and Phosphate resorption by stimulating osteoclast activity.
What effect does PTH have on kidneys
Enhances resorption of Calcium but increases excretion of Phosphate.
What effect does PTH have on 1,25-dihydroxyvitamin D
Increased synthesis
Where is the majority of calcium and phosphate stored
In the Bones
What is the name of the protein matrix found in bones and what does it contain
Osteoids made mostly of collagen
What is the organic matrix of bone mineralised by
hydroxyapatite a calcium-phosphate-hydroxide salt
What regulates bone resorption and formation
Osteoclasts and Osteoblasts
What do osteoblasts do during bone formation
They secrete collagen and other proteins such as osteocalcin and osteopontin
When do osteoblasts become osteocytes?
When they are embedded into the bone matrix.
How do osteoclasts mediate bone formation
They attach tightly to the surface of the bone.
They then secrete proteases and H+ ions.
H+ ions dissolve the hydroxyapatite crystals and expose the organic matrix, allowing the degradation of collagen by proteases.
Resulting in release of Calcium and Potassium from the bone.
What happens when parathyroid hormone binds to osteoblasts and how is this process achieved
It leads to osteoclastogenesis from osteoclast precursor cells.
It enhances expression of the RANK ligand and inhibiting expression of osteoprotegerin which is a decoy receptor for RANKL
What is the process of the production of new osteoclasts.
PTH binds to osteoblast cells which increases RANKL and decreases Osteoprotegerin
This enhances the interaction of osteoblasts with osteoclast precursor cells.
Leading to the activation of signalling pathways that promote differentiation of the precursor cells into mature osteoclasts which mediate bone resorption.
In what ways does PTH effect the reabsorption of Calcium and Phosphate in the kidneys
Ca2+ reabsorption increases due to PTH stimulation of calcium transporter expression and activity.
Phosphate reabsorption decreases due to PTH-stimulated internalisation and lysosomal degradation of a Phosphate transporter.
Why is the enhanced secretion of phosphate important
To prevent plasma levels of the ion rising as a result of the increased resoprtion from bone and increased absorption from the intestines.
How is Vitamin D synthesized
It is synthesized in the body which requires sun exposure (UV light)
How does PTH increase 1,25-dihydroxyvitamin D synthesis
By up-regulating the expression of 25-hydroxyvitamin D 1-alphahydroxylase in the kidney
What type of hormone is 1,25-dihydroxyvitamin D
A steroid hormone so receptor is inside the cells
What effect does 1,25-dihydroxyvitamin D have on intestines
Increases calcium and phosphate absorption
What effect does 1,25-dihydroxyvitamin D have on kidneys
Increases calcium reabsorption by increasing expression of transporter proteins
how does 1,25-dihydroxyvitamin D protect bones from PTH
It increases calcium uptake from the GI tract therefore reducing PTH secretiion.
What is the mechanism of 1,25-dihydroxyvitamin D regulation of Calcium absoprtion.
Enter cells
Activates receptor in the nucleus
Increased transcription/expression of Ca2+ transporter proteins
Leads to increased absorption of Ca2+
By a similar mechanism increases expression of Ca2+ transporters in kidneys to enhance reabsorption
What are good sources of vitamin D
From april to end of september we get required vitamin D from sunlight
Between october and March eat food high in vit D like oily fish, red meat, egg yolks or dietary supplements.
What is the reccomended vitamin D consumption
It is recommended to take a supplement of 10micrograms vitamin D during October-march.
What groups of people are at risk for vitamin D deficiency
Those who dont go outdoors
Those with dark skin
Women who are pregnant or breastfeeding.
What can taking too much vitamin D do over time
Over time it can cause hypercalcaemia which can weaken bones and damage kidneys and heart.
What type of hormone is calcitonin
Peptide Hormone
Where is calcitonin secreted and why
Secreted by the C-cells (parafollicular cells) of the thyroid gland in response to an elevation in plasma Ca2+ levels.
What does calcitonin do to bones.
It inhibits the activity and differentiation of osteoclasts, thus inhibits resorption (bone failure) and promotes deposition
What negatively feedbacks Calcitonin
Plasma Calcium levels
What negatively feedbacks PTH
Plasma Calcium and 1,25-dihydroxyvitamin D
