Bone Physiology and Pathology Flashcards
What dietary and regulatory factors are required for bone growth?
Bone growth requires adequate dietary calcium and protein - they are the building blocksk of bone tissue.
Bone growth is highly regulated by hormonal systems:
- GH and IGF required for protein and cell division
- Thyroid hormones have a permissive role in bone growth
- Insulin supports growth and provides glucose-derived energy
- Sex steroids
Discuss bone structure
Bone is a dynamic living tissue with substantial **ECM **
Calcium phosphate crystals precipitate and attach to the ECM collagen lattice - giving bone density and strength. The most common calcium phosphate is hydroxyapatite (Ca10(PO4)6(OH)2).
A significant vascular supply of bone exists to supply blood to bone cells.
There are three different types of bone tissue:
-
Compact/Cortical Bone
* Outer layer of bone providing strength and structure -
Trabecular/Cancellous Bone
* Inner spongy layer that gives substance to the bone. It contains open, cell-filled spaces between the struts of calcified lattice -
Central Bone Marrow
* Is present in only some bones (typically long bones) and is responsible for haemopiesis
What three factors are central to the regulation of calcium within the body?
Parathyroid Hormone (PTH)
Vitamin D3 (Calcitriol)
Calcitonin
What are the key roles of calcium in human body?
- Intracellular Signalling
- Calcified matrix of bone
- Active at tight junctions between cells
- Cofactor in blood coagulation
- Excitability of neurons and muscle
Where in the body is calcium found?
There are three pools of calcium within the body:
- Bone Matrix (99%)
- Extracellular Fluid (0.1%)
- ionised calcium
- cement for tight junctions
- NT release in excitable cells
- myocardial and smooth muscle contraction
- cofactor in coagulation
- Intracellular (0.9%)
- Free Ca2+
- Signal in 2nd messenger pathways
- Muscle contraction
Illustrate the regulation of calcium
Discuss the actions of Parathyroid Hormone (PTH)
PTH produced and secreted from the parathyroid glands located on the posterior surface of the thyroid gland.
PTH is secreted in response to low plasma calcium levels.
PTH has several effects:
- Actions on bone
- Increases bone resorption
- Elevates the expression of RANKL and reduces expression of OPG on osteoblasts
- Increases the calcium and phosphate release from bone into plasma
- Bone effects within 2-3 hours of stimulation
- Actions on kidney distal nephron
- Increases calcium reabsorption
- Decreases phosphate reabsorption
- Kidney effects are immediate
- Actions on Intestine
- PTH indirectly enhances both calcium and phosphate absorption from the intestines by increasing the formation in the kidneys of 1,25-dihydroxycholecalciferol from vitamin D
- Intestinal effects occur after 1-2 days
Discuss the effects of calcitonin
Calcitonin is released only in response to extremely high levels of calcium in plasma
Calcitonin:
- reduces bone resporption
- increases calcium excretion
Has no physiological role normally - only functions in extreme hypercalcemia
Illustrate the relationship between PTH and Vitamin D3 in calcium metabolism
Compare and contrast the conditions of hyper- and hypoparathyroidism
Hyperparathyroidism
- Most commonly the result of a tumour
- Hypercalcemia and hypophosphatemia
- Variable effects on health
Hypoparathyroidism
- Rare
- Tended to result from inadvertent parathyroidectomy during thyroid surgery or autoimmune destruction of parathyroid glands
- Hypocalcemia and hyperphosphatemia
- Leads to neurovascular excitability
What are the effects of Vitamin D3 deficiency?
Vitamin D3 deficiency results in impaired intestinal calcium absorption.
As a result in sufficient Ca2+aquisition from the diet, PTH maintains Ca2+at the expense of bone - > leading to conditions of bone demineralisation:
Rickets in children and osteomalacia in adults
Describe the condition of osteoporosis
Osteoporosis develops from a **long term imbalance between bone resorption > bone formation **
Unknown cause
It is particularly prevalent in post-menopausal women -> thought to be a result of estrogen withdrawl.
Osteoporosis poses a significant fracture risk
Preventable risk factors include low dietary calcium, smoking and lack of exercise.
Characterise hyaline cartilage
Hyaline cartilage is associated with the articular surfaces of joints, ribs and trachea
It consists of:
- collagen type II
- aggrecans (large GAGs)
- hyaluronic acid
- chondronectin
Water comprises 70% of articular cartilage by weight
Hyaline / articular cartilage is avascular but is perfused by synovial fluid during compression/decompression of the cartilage - i.e exercise
What is the difference between elastic and hyaline cartilage?
Elastic cartilage is hyaline cartilage with addition of elastin
Elastic cartilage is found in ears, ear canals, epiglottis and larynx
It is very flexible and springs back to maintain normal shapes
Characterise fibrocartilage
Binds solid joints, forms minisci and invertebral discs
Composed of a mixture of dense connective tissue, type I collagen, and isolated islands of cartilage
No perichondrium is present
Chondrocytes which produce cartilage differentiate from fibroblast cell lineages