MSK: Week 1 Flashcards
What are 7 purposes of the skeleton
- Raises us from the ground AGAINST GRAVITY
- Determines basic body SHAPE
- Transmits body WEIGHT
- Forms jointed lever system for MOVEMENT
- Protects vital structures from DAMAGE
- Houses bone marrow
- Mineral storage (ca2+ and phosphates)
Remember:
Gary Saw Will Moving Donkey Meek Mills
G - Gravity S - Shape W - Weight M - Movement D - Damage M - Marrow M - Mineral storage
How many bones are there in the body
206
What are long bones
Tubular shapes with hollow shaft and expanded ends for articulation with other bones
What are short bones
Cuboidal shaped
What are flat bones
Plates of bones that are needed for protection
What are seasmoid bones
Round, oval nodules in a tendon
What is a cortical structure of a bone
Cortical = Compact
Cortical parts of a bone from the outer shell (cortex) of the bone
What are four roles of the cortical layer of a bone
Protect organs
Support whole body weight
Provide levels for movement
Storage of calcium
What is the trabecular part of the bone
Trabecular = SPONGY
Trabecular parts of the bone form the medulla of the bone at the ends, proximal to the joints
What are Two characteristics of the trabeculated part of bones
Trabeculated
Many Holes
Where are osteoclasts located
In spaces called Lacunae
What are the two microstructures of the bone
Woven and Lamellar bone
Woven Bone vs Lamellar Bones
Woven vs Lamella:
Made Quickly vs Made Slowly Disorganised vs Organised No clear feature vs Layered More flexible vs Less flexible Weaker vs Stronger More osteocytes vs Less Osteocytes
What is the role of the wide end of the bone
Spreads load over weak, low frictioned surface
What is the role of the hollow long bone
Keeps mass away from neutral axis - minimises deformation
Role of the trabecula part of the bone
Gives structural support while minimising mass
What is the role of the flat bone
Protective
Bone composition
50-70% minerals
20-40% organic matrix
5-10% water
What is the mineral part of the bone made of
Hydroxyapatite - crystalline form of calcium phosphate
What is the organic matrix made of
Type I collagen - 90% of all proteins present
Non-collagenous protein - 10% of all proteins
Describe the arrangement of collagen fibres in the extracellular matrix
The collagen molecules are arranged in ‘staggered’ form with mineral crystals situated in gaps between them
Why do we need minerals in our bones
Provides Stiffness
Why do we need collagen in our bones
Provides elasticity
Describe the origin of osteoblasts
Mesenchymal stem cells -> Progenitors -> Adipocytes Osteoblasts Chondrocytes Myoblasts Fibroblasts
What cells are inter-differentiating
Adipocytes -> Osteoblasts (vice versa)
Osteoblasts -> Chondrocytes (Vice Versa)
What are osteoids
Unmineralised parts of the bone matrix
What cell produces osteoids
Osteoblasts
Why are osteoids needed
to form bone tissue
What happens to osteoids when they are mineralised
It and adjacent bone cells will develop into new bone tissue
How do osteoblasts mineralise the matrix
Depositing crystals with collagen fibrils into the matrix
What collagen do osteoblasts produce
Type I
What factor affects the level of activity of the enzyme alkaline phosphatase
When bones are growing or bone cells are active
What two other substances do osteoblasts secrete
- Non collagenous proteins
- Factors that regulate osteoclasts (RANKL)
Describe the origin of osteoclasts
Haematopoietic stem cells -> Determination -> Proliferation -> Differentiation -> Attachment
What enzyme causes proliferation
M-CSF
What is the role of OCG
Inhibits osteoclast production
What cell produces OCG
Osteoblasts
Define resorption
Absorption into the circulatory system of cells
What are four roles of osteoclasts
Resorb bone
Dissolve mineralised matrix
Breakdown collagen in bone
HIgh expression of TRAP + Cathepsin K
Role of TRAP
Degrades phosphoproteins in skeletal muscles
Role of Cathepsin K
A protein that breaks down bone and cartilage
Define modelling
Gross shape is altered, bone is added or take away
Define remodelling
All bone is altered, new bone replaces old bone
How does the bone enlarge during remodelling
Enlarges as cartilage grows
Cartilage is then replaced by bones
What are 7 reasons for bone-remodelling
- Form bone shape
- Replace woven bone with lamellar bone
- Reorientate fibrils + Trabecullae to increase mechanical strength
- Repair
- Response to load
- Obtain calcium
- Disease
What is the most abundant type of collagen
Type I
Describe the structure of type I collagen
Look in book
How many alpha chains are present in collagen’s helix
Three
So it is called tropocollagen
What are collagen strands arranged into
fibrils
What are the collagen fibrils arranged into
Collagen Fibres
What is the tropocollagen made of (AA wise)
Gly-X-Y tripeptide continuously repeating
What is the Y of Gly-X-Y
Usually proline or hydroxyproline
What is the X of Gly-X-Y
Any AA
What is the purpose of Y in Gly-X-Y
Allows for formation of alpha helix chain
What holds the fibril molecules together
By covalent cross-links from lysine/hydroxylysine side-chains
What cell guides the formation of fibrils
Fibroblasts
Where do covalent cross-links take place in collagen
Between tropocollagen helices and within the triple helices themselves
How do cross-links form within the triple helix
Due to 2 hydroxyglycine molecules
What enzyme is needed to form cross-links
Lysyl Oxidase
What element is required by lysyl oxidase
Copper
How do cross-links form between tropocollagen molecules
Between three hydroxylysine molecules
Forms a structure called pyrodinoline
What other force is acting in collagen
Hydrogen Bonding
How do hydrogen bonds form in collagen
Between two hydroxyproline molecules within tropocollagen
What compound is needed to produce hydroxyproline
Vitamin C
What needs to happen to type I collagen before it is moved into the extracellular matrix to produce bone
Needs to be processed
What happens during processing of tropocollagen
N-terminal peptide (P1NP) and C-terminal peptide (P1CP) need to be removed
How can we measure bone formation rate
Checking P1NP + P1CP levels in the blood (usually P1NP) shows us collagen formation rate
Why is P1NP the main way we check for bone formation rate
It is more stable than P1CP
How do we break down tropocollagen
Cleave N and C telopeptides
What two enzymes will go on to break down the rest of the tropocollagen molecule
Colaginase
Cathepsin K
Where can NTx (N-terminal telopeptides) be measured
Urine
Where can CTx be measured (C-terminal telopeptides)
In the blood
Which is a better marker and why (NTx or CTx)
CTx because it is found in the blood
When should CTx be measured
During fasting as it increases after a meal
What two reasons are there for collagen breakdown
Pathological
Normal repair and replacement
What are FACIT collagens
IX, XII, XIV
What are Microfibrillar collagens
VI
What are short-chain collagen
X + VIII
What are basement membrane collagen
IV
How can we measure bone formation
P1CP/P1NP
How can we measure bone destruction
NTx/CTx
What is the action of the iliopsoas muscle
Flexes lower limb at hip joint and assists in lateral rotation of the hip joint
What is the iliopsoas innervated by
Psoas major: L1-L3 anterior rami
Iliacus: Femoral Nerve
What muscles are the quadriceps femoris made of
Three vastus muscles
A rectus muscle
What two structures pass through the adductor canal
Superficial femoral artery
Popliteal vein
What does the popliteal vein form as it passes through the adductor canal
Superficial femoral vein
What part of the body is the main reservoir for Ca2+
Skeleton = 1200g
What are three roles of Ca2+
- Normal Blood Clotting
- Muscle Contractility
- Nerve Function
- Cell signalling
What are active metabolites of calcium
Free-floating Ca2+
What are inactive metabolites of calcium
Protein-bound calcium in the blood
What protein do calcium ions bind to and circulate in the blood with
Albumin
How does pH affect albumin binding to calcium
Increased pH = strong binding to calcium
Decreased pH = Weak binding to calcium
How does high pH affect ionised calcium and inactive ion conc.
Decreased ionised calcium ions
Increased inactive ion conc.
How is calcium re-absorbed at the intestines
Absorped by intestinal epithelial cells + bound to calbindin
Ca2+ is transferred to the opposite side of the cell without entering the cytosol
How is calcium re-absorption controlled at the kidneys
PTH controls the amount of Ca2+ absorped in the intestines
Reduces amount of PO43- reabsorped
Why do we need to decrease phosphate ions in the body to increase ionised calcium ion levels
Because phosphate will combine with calcium to form an insoluble salt
An increase phosphate ions conc. reduces amount of calcium ions in the ECF
What is the major source of calcium in diet
Dairy Products
What are three minor sources of calcium in the diet
Vegetables
Cereals
Oily Fish
How much of calcium taken in by our diet is absorbed into the GI tract
30%
Where does active absorption of calcium ion take place
Jejunum
Duodenum
Where does passive absorption of calcium ion take place
Ileum + Colon
What compound mediates absorption of calcium ions in the gut
Calcitriol
How does decreased intake of calcium in our diet affect calcitriol levels
Increases them
Why does calcitriol increase when calcium intake decreases
To increase the fraction of calcium re-absorped
Where can we get ‘rapid release’ of calcium
From exchangeable calcium on bony surface + decreased excretion at kidneys
Where can we get ‘slow release’ of calcium
From osteoclasts during bone resorption and increased reabsorption at intestines
What two factors affect how much calcium is filtered at the glomerulus
GFR
The ultrafiltrable calcium (ionised or in protein complex)
Describe calcium/phosphate ion re-absorption along the kidney nephron
Look in book
Describe vit D synthesis pathway
7-dehydrocholsterol -> Vit D -> 25(-OH)D
- > 1,25(OH)2D
- > 24,25(OH)2D
1,25(OH)2D -> Intestines or bone
24,25(OH)2D -> Calcitroic Acid
What is calcitriol
Active form of vit D
Name three roles of phosphates
Intracellular signalling
Activation of protein kinase
Cell membrane component
Post-translational protein modification (Kinases and phosphatases)
Role of kinases and phosphatases
Kinases - Add phosphate
Phosphatases - Remove phosphate
What are normal levels of phosphates in the body
500 to 800 g
What are normal serum levels of the phosphates in the body
0.8 to 1.5 mmol/L
What would be the result of excess hydroxyapatite
Deposition in tissues other than bone
What would be the result of a lack of hydroxyapatite
Poor bone mineralisation
Four dietary sources of phosphates
- Animal
- Dairy
- Soy
- Seeds + Nuts
Where does gut absorption of phosphates take place
Small intestines via passive diffusion
When conc. of phosphates decreases this becomes active via NA co-transporters
Where is more unbound phosphates re-absorbed
80% at the PCT via Na-cotransporters
10% at the DCT
What cell produces FGF-23
Osteocytes
What does the osteocyte produce FGF-23 in response to
Increased phosphate levels
PTH
1,25(OH)2D
Dietary PO43- loading
Describe FGF-23 action
Decreases expression of NA transporter in the renal tubules
Decreases 1-alpha hydroxylation of vitamin D (so less phosphate is reabsorbed at the gut)
What is Klotha
Transmembrane protein
What is Klotha needed for
Necessary for the function of FGF-23 as it acts as a receptor.
What are the borders that make up the popliteal fossa
Superomedial Border (semimembranous)
Superolateral border (Biceps Femoris)
Inferomedial Border (Medial head of the gastrocnemius)
Inferolateral Border (Lateral head of the gastrocnemius and plantaris)
What structures can I find in the popliteal fossa
Tibial nerve
Common fibular nerve
Popliteal nerve
Popliteal artery
