Phase 2 - Week 1 (Bones, Osteoporosis, Fractures) Flashcards
Diaphysis
Central shaft of a long bone
Epiphysis
Regions at either end of a long bone
Epiphyseal Plate
Between diaphysis + epiphysis (also called growth plate)
Metaphysis
Area adjacent to epiphyseal plate, part of bone where growth occurs
Describe how bones grow
- During growth, the metaphysis is made of cartilage - more cartilage is produced to increase length of bone
- After puberty (by age 21) - epiphyseal plate becomes fully mineralised, becomes the epiphyseal line
- Growth in length = deposition of new cartilage at metaphysis and subsequent mineralisation/calcification of cartilage into new bone material
Periosteum
Covers surface of bones, consists of an outer layer of tough fibrous tissue and an inner layer of osteogenic tissue (bone-forming tissue consisting of osteoblast cells)
List the types of bone marrow and describe their functions
- Yellow Marrow - stores adipose tissue
2. Red Marrow - contains Haematopoietic tissue which produces red blood cells
Where is yellow bone marrow found?
In the medullary cavity - space running through centre of bone. Lined by osteogenic tissue - endosteum.
Where is red bone marrow found?
In the epiphysis of long bones and in small, flat + irregular bones
Describe the components of the bone matrix
Organic and inorganic components
Describe the organic components of bone
Organic = osteoid - produced by osteoblasts, maintained by osteocytes (type 1 collagen + ground substance)
Describe the inorganic components of bone
Inorganic = 50% of bone, hydroxyapatite (inorganic mineral - mineral salts e.g. calcium phosphate, calcium carbonate)
Describe the major blood supply of bones
- Main supply is through the nutrient artery (in long bones enters into shaft)
- Enters bone at nutrient foramen, spreads through bone, supplies trabecular, compact bone etc.
- Periosteal BV (on outside of bone) supplies outside of bone
How are Osteons supplied with blood?
Via their central canals.
Describe the function of Volkmann’s canals
Transfer blood from the periosteum to central canals
Describe the function of canaliculi
Canals which link lacunae, provide routes for nutrients to reach osteocytes/waste products to leave them
List the types of bone tissue
- Compact (dense/cortical)
2. Spongey (trabecular/cancellous)
Describe the structure of Compact bone
- Outer part of all bones
- All of flat bones
- Dense, few spaces - protection + support (reduces stress of weight bearing in long bones)
- Functional units = Haversian systems/Osteons
Osteons
- Contain a central canal with blood vessels, lymphatics + nerves
- Surrounded by concentric rings of lamellae (compact bone tissue) w/ lacunae (spaces) between containing osteocytes
- Canaliculi radiate from lacunae forming branching network
Describe the structure of Spongey bone
- In epiphysis of long bones + pelvis, ribs, vertebrae, skull
- Thin bony plates of spicules of bone called trabeculae, between which are large spaces filled w/ bone marrow
- Compressive + tensile trabeculae
- Trabeculae contain lacunae containing osteocytes - nourished by blood in marrow cavities from BV penetrating spongey bone from periosteum
Compressive Trabeculae
Arranged along line of force (vertically) to carry weight
Tensile Trabeculae
Arranged horizontally for support
List the types of bone cells
- Osteoprogenitor cells
- Osteoblasts
- Osteocytes
- Osteoclasts
Explain maturation of bone cells
Osteoprogenitor cells –> Osteoblasts –> Osteocytes
Mononuclear phagocytic cells –> Osteoclasts
Osteoprogenitor cells
- On surface of bone
- Become activated if there is injury
- Differentiate into osteoblasts
Osteoblasts
- On surface of bone + line internal marrow cavities
- Have many mitochondria + Golgi apparatus for protein synthesis
- Secrete constituents of osteoid (organic matrix of bone) - type 1 collagen, proteoglycans + glycoproteins - important in mineralisation (calcification) of matrix
- Have receptors for parathyroid hormone + calcitriol
Osteocytes
- Mature bone cells derived from osteoblasts
- In lacunae
- Adjacent osteocytes linked by cytoplasmic processes through canaliculi
Osteoclasts
- Large multinucleated cells derived from fusion of several precursor cells - contain many mitochondria/lysosomes - Very mobile
- Responsible for resorption of bone - skeletal remodelling
- Abundant at surfaces undergoing erosion
- At site of contact with bone, microvilli that infiltrate disintegrating bone surface
- Calcium, phosphate + bone matrix constituents released into extracellular fluid
- Activity controlled by hormones - parathyroid hormone, calcitonin, thyroxine, oestrogens + metabolites of Vit. D
Describe the main functions of bone
- Protection/structural support
- Attachment for muscles, tendons, ligaments allowing movement through articulation
- Homeostasis of minerals (calcium + phosphate)
- Haematopoiesis - red bone marrow
- Storage of triglycerides
Describe the functions of calcium in bone
- Calcification of bones gives strength, structural support and rigidity to bones
- Bone acts as a metabolic reservoir of calcium for extracellular homostasis
- Makes up most of inorganic ECM of bone as calcium hydroxyapatite, which gives bone rigidity
Describe why calcium is needed throughout the body
- Muscle contraction
- Nerve excitability
- Intracellular messenger
- Blood coagulation
Describe calcium in serum
- Either free (unbound/unionised), bound to albumin or complexed
- Free calcium is what regulates feedback mechanisms
- 50% of total serum calcium is bound to albumin
How is serum calcium level measured
- Total = bound + free calcium
- Adjusted calcium = total adjusted to normal albumin level
Hypercalcaemia
Serum calcium is too high
Hypocalcaemia
Serum calcium is too low
Normal serum calcium level
2.2-2.6mmol/l
List the organs involved in calcium homeostasis
- Gut - absorption of dietary calcium
- Kidney - filtration + reabsorption of calcium
- Bone - storage of calcium
- Parathyroid glands - secrete PTH
- Liver - helps production of calcitriol
Where does the calcium in the body come from?
All calcium comes from diet (25 mmol/day)
Describe how dietary calcium is absorbed
Absorbed by the gut - mainly duodenum + jejunum
- cell-mediated active transport pathway - controlled by calcitriol
- passive diffusion dependent on luminal calcium concentration
Explain how calcium absorption in the gut is mediated
Proportion of calcium absorbed by active transport depends on calcitriol - can range from 20-60%. Calcitriol increases fractional absorption if dietary intake falls, during growth, pregnancy and lactation.
Where will calcium absorbed from the gut be transported?
It is absorbed into the bloodstream - into plasma.
Describe the role of the kidneys in calcium homeostasis
- Plasma is filtered by the kidneys
- 65% of calcium reabsorbed in PCT (coupled to bulk transport of solutes e.g. Na + water)
- 20% reabsorbed in thick ascending Loop of Henle
- 15% reabsorbed in DCT
- Reabsorption in Loop + DCT increased by effect of PTH
- Remainder excreted in urine
Describe the mechanism of action of Parathyroid Hormone
Acts to vary the amount of calcium reabsorbed in kidneys and absorbed into bones + stimulates formation of calcitriol in kidneys to increase calcium absorption from gut.
Where and why is PTH produced?
Produced in the parathyroid glands in response to low levels of free calcium
How do the Parathyroid glands detect a change in free calcium levels?
Have calcium sensing receptors (G-protein coupled receptors) which sense levels of free calcium - main physiological ligand is calcium.
Describe what happens to the level of PTH when calcium levels:
a) Increase
b) Decrease
a) PTH decreases
b) PTH increases
Small change in calcium produces large change in PTH
Describe the series of events which occur when ionised calcium decreases
PTH -
- stimulates calcium reabsorption in renal tubules
- stimulates formation of calcitriol in kidney, which enhances calcium absorption from gut
- Promotes bone resorption - increase in number + activity of osteoclasts in bones, releasing calcium into blood
- Rise in iCa back to normal
Explain how bone resorption affects calcium homeostasis
Bone resorption by osteoclasts releases calcium into the bloodstream, so if bone resorption is increased (by PTH) calcium level will be increased and if bone resorption is decreased (by calcitonin) calcium level will be decreased.
Describe the series of events which occur when ionised calcium increases
- The parafolicular cells of the Thyroid gland secrete increased levels of Calcitonin
- Calcitonin stimulates an increase in number and activity of osteoblast cells in bone, preventing calcium release into blood
- Calcitonin also decreases the level of calcium reabsorption in the kidneys
- Decrease in ionised calcium levels back to normal
Define Osteoporosis
Clinical condition characterised by compromised bone strength meaning there is an increased risk of fracture