Memoirs : Usmle Step 1 Day 2
Day 2: 10 :15 pm Beijing Time
Yes Day 1 sucked .. I just did male and female reproductive system in physiology ...
Try as I might, I couldn't focus myself to study .. on Day 2
Starting from where I left off...
1. HORMONAL CONTROL OF CALCIUM AND PHOSPHORUS
* A few words about calcium, ladies and gentlemen. It is an important ion in the human body performing multiple functions.
* 99 percent is found in bone.
* Just 1 percent is in the plasma
* Of this 1 percent about 40 percent is bound to plasma proteins , 15 percent is associated with anions such as phosphate and citrate.
* The remaining 45 percent is the physiologically active form of Calcium
--------> What does it mean ? That I don't care if your total body calcium is 20 mmol /L or 40 mmol/L . I only care about the physiologically active form.
If the free ionized calcium is within normal range NO hormone will be secreted
Let me repeat that .. IF THE FREE IONIZED CALCIUM IS WITHIN NORMAL RANGE NO HORMONE WILL BE SECRETED even if the total calcium levels are reaching Houdini levels....
A few words about solubility product..
Very simple idea
If [Ca} and [Po4] product is equal to solubility product = no change in bone
If [Ca] x [PO4] > solubility product --> Bone laid down ( Mineralization)
If [Ca} x [PO4] < solubility product --> Bone resorbed ( Demineralization)
* A simple thought. Let the serum Ca be 5 and Phosphorus be 3 ..
Assume solubility product is 15 ..  x  =15 no change
If phosphorus is increased in plasma to 4  x  = 20
Now what ? Mineralization. It's that simple. The rise in plasma phosphorus increases the solubility product to above 15 and this results in bone deposition .
What happens to interstitial serum calcium when bone is deposited ?
Exactly it decreases... to lets say 4. now  x  =16
Bone mineralization stops.
All ions tend to move towards solubility product to stop bone mineralization or demineralization.
Simple concept. Simple idea.
* Now for the control
* We have already established that it is the FREE IONIZED CALCIUM that is regulated so precisely.
What are the two major hormones regulating the Ca levels?
1. Parathyroid Hormone
2. Vitamin D
2. PARATHYROID HORMONE
*So what exactly is this hormone ?
It is a peptide secreted in response to LOW FREE INTERSTITIAL Ca++
Let me repeat it again.
The only stimulus for the release of the PARATHYROID HORMONE IS LOW FREE PLASMA Calcium
For that there is a calcium sensing receptor which we don't have to worry about now.
* What we should worry about is the interesting tidbit... For most cells the rise of calcium intracellularly allows them to carry out their intricate functions...
Parathyroid hormone ? Nope. Not so at all.
This role in parathyroid hormone is carried by Magnesium.
Let me make it very clear. Low levels of magnesium can induce a state of REVERSIBLE HYPOPARATHYROIDISM.
* Any other thing we should know? Oh yes. One more thing before we move on to Actions of PTH
The relation between PTH and Calcium is sigmoidal. And the steepest part of the curve is within normal ionized calcium range.
What the hell does that mean ? Even tiny changes in ECF Ca++ will cause an immediate release of PTH within seconds.
I guess that about covers it.
a. Regulated by free Ca++
b. Magnesium important for functioning
c. Sigmoidal curve statistics.
|The above post was thanked by:|
Dodi Jacob (06-20-2012)
A few words about action of PTH
In reponse to low plasma calcium PTH is relased.
* What is its job ?
To bring the Calcum levels back to normal. It does this by 2 mechanisms.
It increases the re-absorption of calcium from the distal convoluted tubule.
It decreases the re-absorption of phosphorus in proximal convoluted tubule.
It increases the excretion of phosphorus in urine.
* As the phosphorus decreases, the product of Ca x PO4 becomes less than solubility product.
What happens now ? You got it.
Yes, it is simple. And what does bone resorption do ? Causes rise in Free Calcium levels.
Slower actions of PTH
PTH slowly increases the formation of Osteoclasts ( bone breaking cells)
PTH increases the formation of di-hydroxy Vitamin D3 in the proximal tubules of the kidney which causes increased absorption of phosphorus and Ca++ from the intestine.
PTH related peptide
A few words about this peptide.
It is a paracrine factor secreted by many tissues
It causes majority of humoral hypercalcemias of malignancy, since it has the same strucure and affinity for the PTH receptor.
ALKALOSIS and ACIDOSIS and CALCIUM
Very critical to know.
What does alkalosis do ?
As the pH rises, the plasma proteins become more protonated, that is they get more sites available for calcium binding...
This will cause ? Yep.
Decrease in free Ca++ levels.
What does acidosis do ?
As the pH falls, the plasma proteins will become less protonated, that is they get less sites availble for binding calcium.
Increase in free Ca++ levels.
Simple enough, I hope. : )
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