11.1 - Parathyroid And Ca And P Regulation Flashcards
What does the skeleton provide?
- structural support
- major reserves of calcium (stored as calcium phosphate)
- help buffer serum levels
- releasing calcium phosphate into interstitium
- up taking calcium phosphate
Nb: only free calcium ca2+ is biologically active
What does ca2+ do?
- assists in clotting
- maintain nerve and muscle function
- essential for kidney function
- Reduced blood cholesterol levels
- needed for enzymes and hormone receptor binding
- intracellular signalling pathways
- builds and maintains bones and teeth
- regulates heart rhythm
What happens in chronic hypercalcaemia?
- renal calculi
- kidney damage
- constipation
- dehydration
- tiredness
- depression
What happens in hypocalcaemia?
Low serum calcium Get hyper excitability of neuromuscular junction - pins and needles - tetany (muscle spasms) - paralysis - convulsions
Where is the parathyroid gland located?
Lobes attached to the back of the thyroid
What cells make up the parathyroid gland?
Chief cells (produce parathyroid hormone), oxyphil cells and adipose tissue.
What hormones regulate calcium and phosphate levels?
- parathyroid hormone
- calcitriol (active vitamin D metabolite)
- calcitonin (lowers serum calcium levels)
How is PTH synthesised?
- Straight chained polypeptide hormone
- low serum calcium up regulates gene transcription
- high serum calcium down regulate
- low serum calcium prolongs survival of mRNA
- chief cells degrade hormone as well as synthesis it
- cleavage of PTH is accelerated by high serum calcium levels
How does dietary calcium get to the bone?
In GI tract, is absorbed with help of calcitriol
Then deposition by osteoblasts in bone with help of calcitonin
How is calcium from bones lost in urine?
Resorption into blood stream by osteoclasts done with hep of calcitriol and PTH
Then filtered by kidneys = lost as urine
NB: may go from kidneys back to blood stream = uses PTH and calcitriol
What are the target organs for PTH and what are its physiological effects?
Kidney
- decreases calcium loss to urine, particularly in the ascending loop of Henley
Gut
- activates vitamin D and hence increases transcellular uptake of Ca from GI tract
Bone
- increases reabsorption of Ca from bone by activating osteoclasts.
Where is the majority of calcium reabsorbed in the kidney??
Proximal convoluted tubule
How do osteoblasts produce bone?
Make a collagen matrix which is mineralised by hydroxyapatite
How do osteoclasts facilitate bone reabsorption?
Produce acid microenvironment hydroxyapatite dissolve.
What are the actions of PTH on bone?
- induces osteoblastic cells to synthesise and secrete cytokines on cell surface
- cytokines activate osteoclasts and protect them from apoptosis
- PTH decreases osteoblasts activity = exposes bony surfaces to osteoclasts
- reabsorption of mineralised bone and release of Pi and Ca2+ into extracellular fluid
Sources of vitamin D?
The body makes vitamin D itself when exposed to sunlight
Cheese, butter, margarine, fish and fortified cereals are food sourced of vit D.
How is calcitriol made?
7- dehydrocholesterol
Becomes
Vit D3
Goes to liver
Vit d3 is hydroxylate on C25
Goes to kidney
With PTH and hydroxylation to make di hydroxy vit D3 = calcitriol
What happens when plasma calcium is increased (negative feedback)?
PTH secretion decreases
- decreases Ca reabsorption in kidney
- less calcitriol so less ca taken from gut
- more bone building than breaking down
As a result plasma Ca decreases
What role does calcium play in the clotting cascade?
It’s factor IV in the clotting cascade
How can you get hypercalcemia?
- malignant osteolytic bone metastasis
- multiple myeloma
Common sites of metastasis
- Vertebrae, pelvis, femur (proximal) , ribs, humerus (proximal), skull (raindrop)
What’s primary hyperparathyroidism?
Primary
One of 4 parathyroid glands develops an adenoma and secretes excessive parathyroid hormone = ultimately serum calcium falls
What’s second hyperparathyroidism?
Secondary
All four glands become hyper plastic. Seen in patients with vit D deficiency. Can be seen in renal failure as cant hydroxylate vit d3 in kidney. Get low serum calcium levels which then causes PTH levels to rise.
Main problem = bone pain due to osteomalacia in vit D deficiency and in chronic renal failure due to renal osteodystrophy.
What are the symptoms of primary hyperparathyroidism?
Moans - tired, exhausted, depressed
Groans - constipation, peptic ulcers, pancreatitis
Stones - kidney stones. Also, polyuria due to impaired sodium and water reabsorption
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 action potential.
So,
Hypercalcemia = suppression of neuronal activity (lethargy, confusion, coma)
Hypocalcemia = excitable nerves (tingling, muscle tetany and epilepsy)
