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
Discuss the organisation of trabecular bone
Trabecular bone is less organised than cortical bone.
Trabecular bone comprises of lamellae struts with continuous spaces occupied by marrow and blood vessels.
Osteocytes within the trabecular bone have processes that extend out of the bone and communicate with the marrow cavity to obtain nutrients.
Characterise the medullary cavity of bone
The medullary cavity is a feature of predominatly long bones of the human body; it contains **bone marrow **
Bone marrow can be **red bone marrow (haemopoietic cells) **or yellow bone marrow (fat cells)
Red marrow is prevalent early in life and is replaced by yellow marrow with age
- Yellow marrow preserves some haemopoietic cells capable of becoming active haemopoietic tissue if needed.
The blood vessels inside the medullary cavity are sinusoids rather than capillaries. Sinusoids have a larger diameter and can form pores that give newly produced haemopoietic cells a pathway to the blood circulation.
Characterise cortical bone
Cortical bone consists of two layers:
**Periosteum **
- Outer fibrous layer containing fibroblasts, blood vessels and collagen
- Inner cellular layer of osteoprogenitor cells which give rise to osteoblasts
**Endosteum **
- Layer lining the inner marrow cavity
- Thinner that periosteum and still has osteoprogenitor cells
What are Sharpey’s fibres?
Sharpey’s fibres is a histological term describing the penetration of tendon or ligament collagen fibres through the bone surface to anchor into the underlying bony ECM.
This means that bone collagen is contninuous with tendon collagen at sites of ligament or tendon insertion
Where would you not expect endosteum or periosteum to be present in bone?
- Insertions and origins of tendons or ligaments
- Sites of bone articulation
Describe the general blood and nerve supply of bones
Arteries supply bone at discrete points:
- Arteries supply the diaphysis (shaft) and epiphysis (ends) independently
- Penetrating arteries branch within the marrow cavity
- The periosteum is seperately supplied by non-penetrating arteries on the bone’s surface
Nerves follow the blood vessels; their function is still unknown
What type and function does the cartilage overlying articular surfaces (articular cartilage) have?
Articular cartilage is hyaline cartilage.
It si slippery, smooth and resistant to compression
IMPORTANT = there is no perichondrium within joints -> makes repair of articular cartilage difficult.
Characterise the synovial membrane and synovial space
The synovial space is full of **synovial fluid **that lubricates and provides nutrients to avascular structures within the joint such as articular cartilage. The fluid is an ultrafiltrate of synovial blood vessels and proteoglycans
The **synovial space is lined by synovial membrane **
The synovial membrane is not an epithelium making it one of the few spaces in the body where there is no epithlium lining a fluid cavity or lumen. Because of this, it lacks a BM, tight junction or desmosomes and is very leaky and unable to regulate the flux of fluid effectively
Two layers of synovial membrane:
- Intima (surface layer)
- two-to-three cells thick
- mix of fibroblast-like cells (Type A) and macrophage-like cells (Type B)
- Sub-initma
* fibrous connective tissue layer
Characterise osteoprogenitor cells
Osteoprogenitor cells are localised to the **periosteum and endosteum **
They are flattened cells that are difficult to see microscopically
Osteoprogenitor cells are usually quiescent but capable of activating to give rise to osteoblasts for bone growth and repair
Are derived and renewed from mesenchymal stem cells in bone marrow
Characterise osteoblast cells
Osteoblasts deposit new bone over the top of existing external bone layers.
They are located lining the surfaces of bone at the periosteum and endosteum
Osteoblasts produces osteoid - the ECM of bone - which contains type I collagen and bone matrix proteins.
These bone matrix proteins include:
- Osteocalcin/Osteonectin (Ca2+binding proteins)
- Adhesive proteins
- Proteoglycans
- Alkaline phosphatase
Note: Osteocalcin and alkaline phosphatase are used as markers of osteoblast activity in the blood
Inactive osteoblasts become quiescent
Characterise osteocytes
Osteocytes are derived from entombed osteoblasts as a result of bone deposition.
Maintain bone in response to loading forces sensed by their mechanotransduction properties
Osteocytes form small canal systems, known as canaliculae, between one another and to blood vessels to form a chain of nutrient supply.
Loss of osteocytes leads to bone resorption
Alternatively, osteocytes are also capable of destroying local surrounding bone to free calcium
Characterise osteoclasts
Osteoclasts sit on the surface of bone to destroy and resorb it as part of growth, repair and normal turnover
They are activated by the increased expression of RANK-L or M-CSF or the reduced expression of osteoprotegrin
The giant multinuclear cells seal themselves to the bone around their cell edge and secrete a range of factors from their ruffled border including:
- H+
- Cl-
- H2CO3
- Proteases
Note: tartrate resistant acid phosphatase is a marker of osteoclast activity
Osteoclast activity is elevated in response to parathyroid hormone and reduces as a result of calcitonin release.
Osteoclasts are derived from bone marrow granulocyte/macrophage cell lineage - a completely seperate cell lineage from osteoblasts.
Osteoclasts apoptose when not required
Describe endochondral bone formation
**Endochrondral ossification **formation is the process of producing an initial cartilagenous skeleton which is later replaced by bone.
This occurs in weight bearing bones and bone of the extremities.
- A bone collar forms around the diaphysis
- The cartilage beneath the collar degenerates due to bone restricting its blood supply
- Blood vessels invade the collar and bring in bone cell progenitors forming a nucleus of ossification that spreads throughout the diaphysis
- Secondary nucleuses of ossification occur in each of the epiphysises
- The zones of ossification grow at the same rate but remain seperated by the cartilaginous epiphyseal growth plate
Discuss the organisation of the epiphyseal growth plate
The **epiphyseal growth plates **enable long bones to grow and are present until the age of 21-22 years old before fusion. No more growth can occur after this time.
There are five layers of the growth plate, from epiphyseal to diaphyseal:
- **Resting zone: **Normal hyaline cartilage
- Proliferation zone: Dividing chondrocytes
- Maturation zone: Area of mature chondrocytes
- Hypertrophy zone: Zone of hypertrophic/dying chondrocytes
- Ossification zone: Degenerating cartilage is replaced by bone deposition
What is woven bone?
Woven bone is a special type of new bone initially during development or repair
It is more cellular, more cartilagenous and without Haversian systems compared to mature bone.
It is remodelled by osteoclasts and osteoblasts into mature bone.
Describe the process of remodelling via Haversian systems
Remodelling of bone via Haversian systems involves:
- Osteoclasts tunnel and resorb bone along stress axis
- Blood vessels invade behind osteoclasts
- Endosteum invades and lines the inside of the tunnel
- Endosteum gives rise to osteoblasts
- Osteoblasts lay down sequential layers of bone with the collagen alternating in direction
- The final layer leaves a small narrow space around the artery supplying the haversian system known as the Haversian Canal.
- During this process, some osteoblasts are entombed within deposited bone and become osteocytes
What structures are contained within the Haversian Canal?
Blood vessels
Lymphatics
Nerves
Connective Tisssue
What is the difference between woven and lamellar bone?
The bone matrix is synthesized in one of two histologic forms, woven or lamellar
Woven bone is produced rapidly, such as during fetal development or fracture repair, but the haphazard arrangement of collagen fibers imparts less structural integrity than the parallel collagen fibers in slowly produced lamellar bone.
In an adult, the presence of woven bone is always abnormal, but it is not specific for any particular bone disease since it can be found in a variety of pathologic settings.
What is intramembranous ossification?
What bones are formed by this process?
Intramembranous ossification is the production of osteoid by mesenchymal cells that have differentiate into osteoprogenitor cells.
It is a process that does not involve cartilage - as opposed to endochondral ossification
This process gives rise to the flat bones of the human body - particularly the skull
