WEEK 1: CALCIUM METABOLISM AND BONE Flashcards
How is the acid secreted by osteoclasts produced?
The acid secreted by osteoclasts is produced by carbonic anhydrase II in the reaction shown:
CO2 + H2O = H2CO3 = H+ + HCO3-
State the enzymes produced at the brush border.
*The enzymes released into the resorption bay are essentially the acid hydrolases normally found in lysosomes, but a few less usual enzymes are also secreted.
*Cathepsin K is a collagenase enzyme with an acidic pH optimum which has important activity in bone reabsorption.
*Some Matrix metalloproteases (MMPs) are also important.
About how many % of Ca2+ in the body is stored in the form of hydroxyapatite?
How much is found intracellularly?
How much is present in the ECF?
About 99% of Ca2+ in the body in the form of hydroxyapatite
0.9% is found intracellularly
Less than 0.1% present in the ECF
What is blood calcium volume and concentration?
*The blood plasma level of Ca2+ is very closely regulated between 9 and 11mg/100ml.
*The calcium concentration of the blood is 2.2 -2.55 mmol/L
Outline activities that are controlled by calcium ions.
This is because Ca++ ions are required for control of processes such as muscle contraction, secretion, particularly of neurotransmitters, blood clotting, and intercellular adhesion.
Outline signs of hypocalcemia.
*Tingling in fingers and toes.
*Tetany – the continuous unregulated contraction of muscles
*Epileptic seizures caused by abnormal activity of neurons
Within the blood, how much Ca++ is bound to plasma albumin?
About how much is complexed, for example to citrate?
How much is free in solution – and fraction in signaling?
Within the blood about 0.7 mmol/L of Ca++ is bound to plasma albumin, and is not diffusible.
About 0.25 mmol/L is complexed, for example to citrate.
The remainder – around 1.3 mmol/L is free in solution – and this is the important fraction in signaling.
*Parathyroid hormone (PTH) regulates Ca2+ exchange between blood and bone tissue.
*PTH acts on the kidneys to decrease loss of Ca2+ in the urine.
In adults there is usually a balance between uptake and excretion of calcium, though in growing children considerably more calcium is taken in than is lost – about 10mmol/day is estimated.
Describe the control of osteoblasts and osteocytes by PTH.
Higher concentrations of PTH cause more production of RANKL, stimulating osteoclast activity, so at high PTH concentrations more Ca++ is released from bone by osteoclasts than is deposited by osteoblasts.
Describe the role of calcitonin in calcium ion regulation.
inhibiting Ca++ absorption by the GIT
inhibiting osteoclast activity
When are calcitonin levels usually high?
-pregnancy & lactation
-growing children
Describe the synthesis process of vitamin D to calcitriol from cholestrol.
1.Conversion of cholesterol to 7 –dehydrocholesterol in the skin
2.A non-enzymic photolysis requiring uv light opens one of the cholesterol rings to form the molecule normally called vitamin D (or cholecalciferol)
3.The vitamin D molecule is then hydroxylated at position 25 by a liver cytochrome P450 enzyme to form the weakly active 25-hydroxy D.
4.At the kidney, an enzyme system in the proximal convoluted tubule carries out a second hydroxylation at position 1, forming the fully active 1,25 dihydroxy D, often known as calcitriol.
What are the other names for Vitamin D and Calcitriol?
Vitamin D: Cholecalciferol
Calcitriol: 1,25-Hydroxy D
What is the role of Vitamin D in calcium regulation?
*It increases the amount of calcium absorbed from the gut *Prevents calcium loss from the kidneys
State the 4 diseases of calcium metabolism.
-Osteomalacia: rickets in adults
-Rickets: vitamin D deficiency
-Osteoporosis
-Paget’s disease
