Midterm 2- Bone Flashcards
(24 cards)
WHat is the hormonal regulation of calcium balance?
- parathyroid hormone regualtes the levels of calcium in extracellular fluid volume (plasma levels of calcium)
- Calcitrol (Vitamin D) affects absorption of calcium in the gastrointestinal tract
Calcium and bone relationship
- 99% of body calcium is stored in bones
- stored as hydroxyapatite crystals (calcium and phosphate salts) in bone to prevent large changes in plasma calcium levels
- these crystals also provide bone strength
- bone serve more functions than just locomotions and protection of vital organs
- bone is primarily composed of Type 1 collagen
- skeleton is an endocrine organ to maintain conc of calcium
What does your body do if you need to increase plasma levels of calcium?
- calcium from bone is released in blood via PTH and the degradation of bone is not too quick, thus there is no reduction in strength
What are the two types of bone formation?
- Endochondra ossification- most bones form this way
- Intramembranous ossificatin
- bones are categorized by type of developmental process that forms them
What is the overview of endochondral ossification
- cartilage template replaced by bone tissue
- forms most of our bones
- developed from cartilage template
What is the overview of intramembranous ossification
- mes cells in utero became bone forming tissue-> osteoblast
- formed without a cartilage template- skull
When calcium diet in our body changes, the kidney does not change the calcium levels to the same magnitude why?
- poor absorption levels of calcium in GI tract
2 calcium is not secreted in the kidney and GFR is tubed to meet Na levels
Describe calcium
- stored in bone as crystal hydroxyapatite to prevent large changes in plasam calcium levels
- formation and dissolution of hydroxyapatite in bone does not require hormonal change, but plasma calcium levels are regualted by hormone
What are the steps to endochondral bone formation?
- Early development:Mesenchymal cells condense together and start to differentiate into chondrocytes, cell type of cartilage
- Chondrocytes- spherical in shapeand express and secrete cartilage matrix proteins such as type 2 collagen and proteoglycan, aggrecan
- forms the cartilage temp- chondrocyte + matrix - As chondrocyte begin to expand, it runs out of resources such as oxygen and nutrients
- until now, the template recieves nutrients via diffusion - Hyposiz can cause the chondrocytes in center to further differntiate into chondrocytel which is much larger in volume, alled hypertrophic chondrocyte
- express Type 10 collagen, and less proteoglycans
- secrete minerals to strengthen the matrix, Calcium and PO2 to form a pre-bone mineral form called hydroxyapatite
- angiogenic factor called vascular endothelial grwoth factor is secreted by hypertrophic chondrocytes and thereby recruit blood vessel near to infiltrate the cartilage templaate - With vasculation, nutrients can be delivered to help fuel the metabolically active chondrocytes
- Blood vessel that supply the inner most part can bring in two clell type that function to replace the cartilage template by bone
a. osteoclasts- degrade and remove the matrix that was modified by hypertrophic chondrocytes
b. osteoblasts- replace the extracellualr matrix with a matrix thaat is much stronger, containing mostly of type 1 collagen - matrix is mineralized by osteoblasts by secretion of ca and PO4 to form the mineral component of hydroxyapatite
* together, organic and inorganic portiosn of bone matrix form a very strong matrix, hard and compressive
What is the difference between hypertrophic chon and chon?
Chondrocyte are metabolically active and able to differentiate
- Hypertrophic chon are metabolically active since they secrete a specialized matrix, but they are unable to proliferating
- once the chon has differentiated into hyper chon, it is at the terminal stage and will shortly die via apoptosis
- Nearby chon can continue to secrete the matrix component to contribute to expansion of cartilage template but can also expand pop of cells via proliferation
What is primary ossification
-process of chondrocyte, hypertrophy, recruitment of blood vessel and then replacement to a bone matrix
What is secondary ossification
- same process of ossification is initaited on eithre side of the primary ossification center
- chondrocytes in the most
centre of these template regions differentiate into hypertrophic chondrocytes,
modifying the extracellular matrix with type X collagen and minerals, recruitment
of blood vessels, recruitment of osteoclasts and osteoblasts, apoptosis of
hypertrophic chondrocytes and replacement of the cartilage template with bone
matrix.
What is growth plate and what contributes to max longitudinal grwoth of long bones?
- cartilage region that remains between the primary and secondary ossification, also known as epiphyseal plate
- chon in this region activatly proliferate and differentiate into hypertrophic chon
- contribute to max longitudinal grwoth of long bones
Describe how growth plate activity leads to increased bone growth
- chon in the grwoth plate are highly organized and contain differing zones; zones of chon that are in rest phase, highly proliferative phase, and a zone of hypertrophic chond
What determines how much a bone grows?
- during childhood and early adolescence is highly depended on genetics- but can be affected by the environment of the bones
Example:
-chon of each individual have a set number of proliferation cycles that it can undergo - if chon can proliferate more, it will result in larger pop of these chon, which can then proliferate followed by differentiation to hypertrophy
- results in larger bone as there is more matrix being produced, expanding the region for replacement by bone matrix
- if the chon can increase by a larger volume when differentiating to hypertrophy, this will contribute to long grwoth of the bone
however, despite having the potential to proliferate, and hypertrophy, hormonal imbalancces, lack of nutrients, pharmacological compounds and stress can thwart grwoth, thereby impeding potential bone growth
- mechanical stress, drugs for asthma
Describe the growth mechanistically
- Resting chon clcoser to the secondary ossification- ready to proliferate but they havent yet
- Center part of the grwoth- acivatly prolifering, quick cell cycle producing more cells, prolierating in vertical direction-> one reason how you can increase longitudional growth
- Chon closer to primary ossification will undergo hyperthropy- increase in cell volume and size which will contribute to longitudinal growth
- at end of puberty, mostly hormonal signals stmualte all chon remaining in the grwoth plate to hypertrophy and undergo apoptosis
- remaining cartilage template is then replaced by bone tissue and halts further growth
What are the cell types in bones?
- osteoblasts- secretion of bone matrix and stimulate osteoclasts activity
- immature bone cell that secretes the bone matrix
Osteocytes - when osteoblasts become trapped in bone, they differentiate and become osteocytes - these cells do not secrete the bone matrix, but act to transduce signals throughout the bone to osteoblasts and osteoclasts
- mature bone cell that maintains the bone matrix
- long extension of their memebraen that are connected chemically through gap junction to spread the singal
Osteoclasts: - multinucleated cell that secretes acids and enzymes to dissolve bone matrix
- macrophage that break down the
- produce HCL to dissolve the inorganic phase and protease thaat will degrade the oganic collagen and proteoglycans
Describe bone degradation/regeneration
osteoclasts are the cells of the bone that are responsible for
degrading (resorbing) bone. This is a normal and essential process that occurs
throughout our lifetime. After sealing to a region of bone, osteoclasts secrete
hydrochloric acid and proteases to break down the underlying bone matrix. The
process of bone resorption and formation must be tightly regulated together or else
pathologies can occur. Osteoclasts degradation of a bone region is fast, two to
three weeks in length, but osteoblasts process of bone formation is much slower,
around three months. Interestingly, osteoclasts release chemo-attractants to
stimulate osteoblasts to follow and lay down new bone. Osteoblasts also act to
stimulate osteoclasts thereby coupling the two processes.
- bones have the ability to adjust strength depended on use
- bone shape can be rearranged if mechanical forces are altered
- bone matrix becomes more brittle with age so a new organic matrix needs to be deposited
What is the process of intramembranous ossification
- selected centrally located mesenchymal cells cluster and differentiate into osteoblasts
- starts at 8th week of embryonic development - osteoblasts secrete type 1 collage nadn mineralize the matrix
- trapped osteoblasts become osteocytes - bone matrix is laid down between blood vessel of spongy bone
- Compact bone replaces regions of spongy bone near the outer surface
What is osteoporosis
- caused by imbalance of osteoblasts and osteoclasts activity
- more resorption, less bone formation
What is the treatment of osteoporosis?
- biphosphatanse
- drugs that bind to calcium and stick to it
- osteoclasts will degrade the bone and ingest the bisphosphatase and die
Why do menopausal women are at a greater risk
- estrogen is protected for your bone
- reduction in estrogen, do not get stimulating factor for osteoblast and clast
Persistent cartilage of articular cartilage
- articualr cartilage in our joints is essential to provide cushion in weight bearing joints
- chon within this cartilage matrix should continue to secrete cartilage specific collagen and proteoglycans
- pathology occur if the chon do not secrete sufficient matrix, undergo early cell death or differentiate into hypertrophic chondrocytes
What is osteoarthritis
-Articular cartilage (persistent cartilage) is composed mostly of ECM and some chondrocytes that secrete and maintain that matrix
ECM composed mostly of type II collagen and proteoglycans
-If matrix maintenance and production is inhibited, osteoarthritis can occur
-Also issues if chondrocytes become hypertrophic and mineralize the matrix
- insufficient cartilage matrix is produced leading to cartilage degradatio nand osteoarthritis
- stimulus that causes tehse chondrocytes to hypertrophy pathologically
- current treatment: pain management and total joint replacement
-Chon in their persistent state that should remain as resting undergo hypertropic developmental process – large and hypertropicc and they undergo apoptosis –secrete rigid collagen, secrete minimalize, and apoptosis
Form bone in cartilage surface, more degradation
