WEEK 1: CALCIUM METABOLISM AND BONE Flashcards
(22 cards)
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
How are rickets different from Osteomalacia?
1.Rickets
Defective mineralisation of bone caused by low Ca++ levels in the blood
found in growing children
Caused by vit D deficiency
2.Osteomalacia
Found in adults
bone pain, increasing bone fragility, and fractures
What happens in osteoporosis?
Loss of bone density
Leads to increased risk of fracture.
Usually occurs in older people.
Decline greater in women than men
Describe the role of estrogen on bone formation and osteoporosis.
*Estrogen stimulates production of osteoprotegerin
*Binds ton RANK L
*Decreases effect of RANKL in activating osteoclasts
*Estrogen inhibits PTH stimulation of bone erosion by osteoclasts
Describe what happens in Paget’s disease.
Increased and disorganized bone remodeling.
Bone deformity and weakening leading to fractures.
but some bones can thicken.
Outline the effect of alcohol on bone health.
*It increases levels of PTH.
*It results into loss of balance hence likely to fall and break bone
*Inhibit absorption of calcium.
What happens in osteoarthritis?
Risk factors for osteoarthritis.
It occurs when the protective cartilage that cushions the ends of the bones wears down over time.
1.Obesity.
2.Women
3.Hyperparathyroidism
How does hip replacement surgery work?
The hip joint consists of a ball (at the top of the femur, also known as the thigh bone) and a socket (in the pelvis, also known as the hip bone). Hip replacement surgery includes replacement of one or both parts.
