What are the two types of bone growth and how are they measured?
- Soft tissue: measured by weight
- Bone: measured by height
Tissue and bone growth requires multiple hormones & paracrines have direct or permissive effects on growth
What are some examples of the hormone interactions involved?
- GH and IGFs required for protein and cell division
- Thyroid hormone plays permissive role in growth: Directly contributes to nervous system development
- Insulin supports growth, provides glucose energy
- Sex steroids
What are the two absolute essential requirements for bone and tissue growth?
- Adequate dietary calcium and protein
- Regulated hormonal control of calcium homeostasis
What is the most substantial component of bone?
What does it contain?
Extracellular matrix
- Calcium phosphate crystals precipitate & attach to collagen fiber lattice
- Most common calcium phosphate: Hydroxyapatite (Ca10(PO4)6(OH)2)
Describe the structure of bone
- Compact or cortical bone (Outer)
- Provides strength
- Trabecular bone (Inner spongy layer)
- Open, cell‐filled spaces
- between struts of calcified lattice
- Central bone marrow (only in some bones)
- Hematopoiesis = blood formation
Describe the relationship between bone resorption and deposition required for bone growth
Matrix is deposited (osteoblast activity) faster than it is bone resorption (osteoclast activity)
What is the role of the osteoblast?
- Lineage
- What does it produce
- Specialised proteins it produces
- Specialised bone‐forming cells
- Modified fibroblasts
- Produce enzymes & osteoid (collagen & protein mix) to
- which hydroxyapatite binds
- Osteocalcin & osteonectin, proteins aid in deposition
In what direction does bone lengthening occur and how?
Bone diameter increases as the matrix deposits on outer surface
- Epiphyseal plate is the site of linear growth of long bone growth
- At the end of the bone shaft (diaphysis)
Describe the role of chondrocytes in bone growth
Form the growth plate of elongating bones
- Located near the epiphysis
- Cartilage cells that are collagen‐producing
- Continuously dividing in columns; to lengthen
- Collagen layer thickens & old chondrocytes disintegrate leaving spaces
- These spaces are then filled in with bone matrix by osteoclasts
Describe the role in more detail of the osteoblasts in bone elongation (growth)
- Lay down bone ontop of cartilage bases where the old chondrocytes degenerated
- They enable the shaft to lengthens, when the epiphyseal plate is active
- Osteoblasts revert to less active form of osteocytes when complete work
Describe the difference in the role of osteoblasts vs. Osteoclasts in terms of calcium regulation
Osteoblasts
- Deposit calcium as they create bone matrix thereby reducing caclium levels in the plasma
Osteoclasts
- Are large, mobile, multinucleate cells derived hematopoietic stem cells
- Secretes acid & protease enzymes dissolves calcified matrix & collagen support
- To release Ca2+ into the plasma increasing levels
What three organs regulate calcium homeostasis in the body?
- Bone
- Kidneys
- Intestine
Each of which has its own mechanism of regulation
What are the three hormones involved in calcium regulation?
- Parathyroid hormone (PTH)
- Vitamin D3 (calcitriol)
- Calcitonin
What are the key roles of calcium in the body? [4]
- important intracellular signalling molecule
- Structural functions
- contribute physical strength to bone matrix
- help hold cells together at tight junctions
- cofactor in blood coagulation
- required for normal excitability of neurons and muscle
Complete the equation:
Total body calcium = _________ - ___________
Total body calcium = Calcium dietary intake - Calcium output
What are the three pools of calcium in the body?
- Which of these is the most substantial?
- What are the roles of calcium in each of these pools?
- Bone matrix (Most substantial 99%)
- Extracellular (0.1%) = ionized Ca2+
- Intracellular (0.9%) = Free Ca2+
What is important about ECF concentrations of calcium (plasma concentrations)
This is the component that is very carefully regulated
- ECF Ca2+ ions move freely in and out of plasma
What is the general concentration of extracellular (plasma) Calcium?
2.5 mM
What is the main mechanism by which cells are able to regulate calcium plasma concentration
(ie balance intracellular [Ca] with extracellular [Ca])
- Maintenence of the electrochemical gradient through active transport mechanisms
Describe how Ca2+ Ions in the plasma exchange with Calcium in Bones
Via the action of osteoblasts and osteoclasts
(which are themselves regulated by PTH, Calcitonin, Calitriol and Cortisol)
What proportion of dietary intake of calcium is absorbed in the gut?
How is this regulated?
About 1/3rd is absorbed and this is regulated through hormone levels
- Calcitriol
- Also slightly via the action of PTH and prolactin
How is calcium excreted from the body (another important factor in regulating calcium levels)
- Most calcium lost via urine; some feces
- The kidneys passively filter calcium into the urine while the distal nephron contains transporters to reabsorb calcium (these are all regulated by PTH and calcitonin)
- ECaC
- Na+‐Ca2+ antiporter
- Ca2+ ‐ATPase
Where are the parathyroid glands located?
- What do they secrete?
- Are the essential for life?
There are 4 small parathyroid glands located on the back of the thyroid gland
- They secrete PTH
- They are absolutely essential for life (death without it)
What (and how) triggers release of PTH from the parathyroid gland?
- What are the two basic actions of it once it is secreted?
Secreted in response to low serum [calcium] which is sensed by calcium sensitive receptors
Acts to
- Increase plasma calcium
- Decrease plasma phosphate
