Lecture 6 Flashcards
What are the different roles of calcium in the body?
- Structural
In bones and teeth - Signalling
Constriction and relaxation of blood vessels, nerve impulse transmission, muscle contraction, secretion of hormones (e.g. insulin), mechanism of vision, taste and smell - Co-factor in proteins and enzymes
Clotting/coagulation of blood in association with vitamin K dependent proteins
What are the factors affecting calcium absorption in the body?
Absorption enhanced by:
Vitamin D, which promotes the production of a calcium binding protein in intestinal cells. Vitamin D deficiency can lead to rickets.
Lactose, other sugars and proteins keep calcium in a soluble form
Absorption inhibited by:
Oxalic acid binds to calcium and makes it insoluble
High fat diet results in unabsorbed fats, which will form soaps with calcium preventing absorption
Where does calcium absorption primarily occur, and why?
In the duodenum, since it has a low pH
What is the source of calcium for the human body?
- Plants
What are the two ways that calcium can be absorbed?
- Active transport
- Passive diffusion
When does calcium’s solubility increase?
- When the pH decreases
Calcium enters the body as a salt, which is not soluble in water, but it becomes more soluble with a decrease in the pH
Two types of bone?
Cortical bone (Compact bone) and Trabecular bone (Cancellous bone)
Cortical bone (Compact bone)?
Dense, low porosity, found in the shaft and forms outer shell around cancellous bone
Trabecular bone (Cancellous bone)?
Low density, high porosity, forms insides of the bones. The spaces between the bone are filled with fluid bone marrow cells
What are the two type of chemical components of bone?
Two types:
Organic (protein) matrix and Inorganic minerals
-Bone is composed of collagen stiffened by crystals of calcium hydroxyapatite
Organic (protein) matrix?
- Comprises mainly type 1 collagen (highly cross-linked triple helical protein structure)
- Also found in cartilage
- Osteocalcin
Inorganic minerals?
- Major minerals are calcium and phosphate
- Found as calcium hydroxyapatite which has a molecular formula: Ca5(PO4)3(OH)
How much of human bone is mineralised?
About 60%
What is the mineral component of human bones?
Calcium hydroxyapatite
Ca5(PO4)3(OH)
What happens if you increase the mineral component of bones (calcium hydroxyapatite)?
- Increases stiffness
- Reduces flexibility
Ex: Auditory ossicles
What happens if you increase the mineral component of bones (calcium hydroxyapatite)?
- Decrease stiffness
- Increase flexibility
(Can absorb energy without breaking)
What are the 3 types of cells only found in the bone?
- Osteoclasts: responsible for degrading bone (resorption), and come from bone marrow
- Osteoblasts: cells that form new bone, and come from bone marrow
- Osteocytes: sense bone deformation and signal then the need for adaptive remodelling of bone size/shape, and they come from osteoblasts, once they become trapped in the matrix they secrete
Osteoid?
- New bone produced by the osteoblasts, which is made of collagen and other protein
- They control calcium and mineral deposition
Bone modeling?
Produces a change in the size and shape of bone, when new bone is deposited without previous bone resorption
Bone remodeling?
- Resorption by osteoclasts precedes bone formation by osteoblasts
- Coupling of osteoblast and osteoclast activities
- Need to remove bone to build it up again
Remodeling of bone (more in depth)?
- Osteocytes release local factors that attract cells from blood and marrow into the remodeling compartment
- Osteoclasts resorb matrix and microcrack, then successive teams of osteoblasts deposit new bone
Production of extracellular organic matrix?
The first step in bone formation (osteogenesis):
Consists of type 1 collagen and osteocalcin (non-collagenous protein)
- In bone, collagen formed of tropocollagen subunits
Tropocollagen molecule?
- Each molecule contains three helices
of protein chains wound around each other to form a helical rod 3000 Å long and 15 Å in diameter - The three protein chains are linked together by hydrogen bonds, which can be formed bc some amino acids in tropocollagen are oxidised
What is the purpose of the 400 Å gaps between the tropocollagen subunits?
Serve as nucleation sites for the deposition of long, hard, fine crystals of the mineral component (hydroxyapatite)
What does a collagen fibre consist of?
A staggered array of tropocollagen molecules
What causes scurvy?
- A lack of vitamin C
Bc since some amino acids in tropocollagen are oxidised, and that oxidation requires vitamin C, if there is a lack of that vitamin then the body will be unable to make collagen
Mineralisation?
- Calcium and phosphate are derived from blood plasma
- Mineralisation occurs soon after deposition of extracellular organic matrix
- Mineral crystals form along the collagen fibrils and osteocalcin chains
Osteocalcin?
It contains carboxyl groups (COO-) for binding calcium Ca2+
What contributes to bone strength?
- Renewal of bone
- Remodeling causes increase in bone density up to 25 yrs
- Bone mass and density are stable until 45 yrs
- > 45 yrs bone mass starts to decrease
- In women bone loss starts a few years before menopause
Postmenopausal Osteoporosis?
Low estrogen levels in menopausal women can lead to increased bone resorption and accelerated bone loss
Osteoporosis?
- Bone disease in which the amount of bone reduces significantly, causing them to become weaker
- Structural integrity of trabecular bone is impaired and the cortical bone becomes more porous and thinner
What do strong and dense bones result from?
A balance between bone resorption and bone formation
What happens if the balance between bone resorption and bone formation is disturbed?
- Activity of bone-degrading osteoclast cells becomes greater than activity of bone-building osteoblast cells
- Bone resorption become more important than bone formation and results in weak bones that are prone to fracture
What are the most important risk factors for osteoporosis?
- Female gender
- Increased age
- Estrogen deficiency
- Smoking
How to treat osteoporosis?
- Use a type of drug called antiresorptive agents
- Prevent further bone loss but also inhibit new bone formation, as the activities of osteoblast and osteoclast are coupled
Classes of antiresorptive agents?
- Estrogens and selective estrogen-receptor modulators
- Peptide hormone (calcitonin)
- Bisphosphonates
Estrogen-Replacement Therapy?
- To treat osteoporosis by slowing bone resorption by blocking signaling to the osteoclasts
Pros:
- Relief of menopausal symptoms
- Prevention of bone loss and fractures
Cons:
- Risk of endometrial carcinoma (cancer)
- Risk of breast carcinoma (cancer)
Selective estrogen-receptor modulator?
- To treat osteoporosis by slowing bone resorption by blocking signaling to the osteoclasts
Pros:
- Reduce the rate of bone turnover
- Prevention of bone loss and fractures
Calcitonin?
- To treat osteoporosis by rapidly inhibiting the action of osteoclasts
Pros:
- Therapy results in an increase in bone mineral density
Cons:
- Expensive, must be given by injection or nasal spray
- Some patients become resistant to its action during long-term use
Bisphosphonates?
- Most widely prescribed antiresorptive agents
- first-line therapy for the treatment of post-menopausal osteoporosis
- Block bone resorption with immediate effect
- Bisphosphonates reside in the bones for long period: resorption still inhibited after discontinuation of the therapy
Mode of action of non N-containing bisphosphonates?
- Bind to bone mineral when they are administered and are then slowly released as bone is resorbed by osteoclasts
- Suppress resorption by inhibiting the attachment of osteoclasts to bone matrix
- Enhance osteoclast apoptosis (cell death)
Mode of action of N-containing bisphosphonates?
- Inhibit modification of proteins required for signaling
- Block signals important for osteoclast activity
What percentage of calcium in your food is going to be absorbed?
10-40%
What causes rickets?
A lack of vitamin D, which causes the skeleton to be weak
