Limbs and Back: Week One Flashcards
What is the effect of CBFA1?
Mesenchymal differentiation into osteoblast precursor
What is OPG?
A decoy receptor preventing RANKL binding and osteoclast activity
Name five things that osteoblast secret
- Type I collagen
- Type V collagen
- Osteonectin
- Osteopontin
- Osteoprotegerin
Name the forms of vitamin D
- Vitamin D2 (ergocalciferol) from plants
- Vitamin D3 (cholecalciferol) from animals
Name the two ways in which vitamin D3 can be obtained
- UV radiation converts 7-dehydrocholoesterol into vitamin D3 (endogenous)
- Obtained from the diet (exogenous)
Describe the process of active Vitamin D formation in the body
- Vitamin D3 is transported in chylomicrons and it will bind to DBP protein
- This complex will travel to the liver and meets the enzyme 25-hydroxylase. This forms 25-hydroxy vitamin D.
- This travels to the kidney to meet the enzyme 1-alpha-hydroxylase and this forms 1.25-dihydroxyvitamin D.
Name three ways in which 1-alpha-hydroxylase activity is stimulated.
- induced by PTH
- hypocalcaemia
- hypophosphatemia
Give three functions of vitamin D
- Forms calcium channels in the intestine resulting in increased calcium absorption in the intestine
- Forms calcium channels in the kidney and this will increase calcium absorption
- Increase expression of RANKL on osteoblasts and causes increased differentiation of pre-osteoclasts
Name two things that mature osteoclasts secret
- Hydrochloric acid
- Cathepsin K
What does RANKL stand for?
Receptor activator of nuclear factor kappa B ligand
What is the difference between Rickets and Osteomalacia?
Rickets occurs in children. Symptoms include occipital bone flattening, frontal bossing, square head, rachitic rosary, pigeon breast and lumbar lordosis.
Osteomalacia occur in adults and increases the risk of getting fractures.
What is Osteoporosis?
A condition that weakens the bones, making them fragile and likely to break.
Bone density will fall 2.5 standard deviations below the mean for young adults of same sex.
Give some risk factors of Osteoporosis
- over 70 years
- menopause under 40
- anorexia
- glucocosteroids
- smoking
- alcohol
- obesity
- oestrogen deficiency
- low calcium
What are the serum results from Osteoporosis?
Calcium, Phosphate, ALK Phosphate and PTH are normal.
Bisphosphonates are drugs used to treat osteoporosis. There are three generations. Give examples and the mechanism of action for the first generation.
Examples include Etidronate. These drugs are non-nitrogen containing and incorporated into ATP and interfere with ATP-dependent pathways, causing apoptosis.
Bisphosphonates are drugs used to treat osteoporosis. There are three generations. Give examples and the mechanism of action for the second generation.
Examples include alendronate. These drugs are nitrogen containing. They inhibit osteoclast farnesyl pyrophosphate synthase and prevent protien prenylation required for GTPase formation and therefore inducing apoptosis.
Bisphosphonates are drugs used to treat osteoporosis. There are three generations. Give examples and the mechanism of action for the third generation.
Examples include risedronate and zoledronic acid. These drugs are nitrogen containing. They inhibit osteoclast farnesyl pyrophosphate synthase and prevent protien prenylation required for GTPase formation and therefore inducing apoptosis.
Give the mechanism of action of Raloxifene.
Binds to oestrogen recepotrs and produces oestrogen -like effects and hence slows bone loss.
Give the mechanism of action of Teriparatide.
Portion of PTH that activates osteoblasts.
Give the mechanism of action of Strontium ranelate
Enhances osteoblasts to express for OPG and less RANKL
Give the mechanism of action of Denosumab
Inhibits RANKL expression
Describe Type One osteoporosis
This is due to oestrogen deficiency. There is increased sensitivity to PTH hormones and this leads to increased resorption. There is also a decrease in transforming GF by osteoblasts, increased IL-6 mediated osteoclast differentiation and an increase in lysosomal production.
Describe Type Two osteoporosis
This is known as Senile Osteoporosis and is a result of increasing age (usually over 70). There is decreased ability of the kidneys to produce 1.25-dhyrdroxyvitamin D and hence decreased calcium absorption. There will therefore be an increase in PTH.
Describe the distribution of calcium in the body
99% of calcium is found in bone in the form of hydroxyapatite. The 1% in the serum is split into three:
- 50% ionized (only one physiologically active)
- 40% bound to albumin
- 10% complexed to anions
How is phosphate stored in the body?
Most is in the form of hydroxyapatite.
Other forms include the intracellular component of DNA, RNA and cell membranes. There is a small amount existing as inorganic phosphate and phospholipids.
What is PTH
- 84 amino-acid polypeptide
- Produced by chief cells of parathyroid gland
Net effect is to increase calcium and decrease phosphate.
What is calcitriol?
1.23-dihydroxyvitamin D
When is PTH secreted?
It is secreted when there is a lowered calcium.
A significant magnesium depletion can caused decreased PTH secretion.
Describe the negative feedback response of calcitriol.
When calcitriol is synthesized, one molecule will inhibit one molecule on 1-alpha-hydroxylase to prevent over-production.
What effect on 1-alpha-hydroxylase does FGF23 have?
It inhibits the action. It is released by osteoblasts and osteoclasts in response to PTH.
What is calcitonin and where is it secreted?
- polypeptide secreted by parafollicular cells (C cells) in thyroid gland
What is a communuted fracture?
Bone has broken into many pieces
What is a green-stick fracture?
One side bends and the other side breaks
Describe the first stage of Bone Remodelling
Activation: activation of bone lining cells. The mechanical stress causes them to secret IGF-1.
Describe the second stage of Bone Remodelling
Bone Resorption: osteoclast migrate and become activated. There is MMP activity. Osteoclasts maintain contact though riffled border and integrin. Osteoclasts secrete lysosomes form ecm digestion and HCL for mineral digestion. They release contents into blood.
Describe the Third stage of Bone Remodelling
Reversal: Osteoclasts detach. Osteoprogenitor cells are recruited and they differentiate. There is the formation of the cement line.
Describe the fourth stage of Bone Remodelling
Formation: Osteoblasts form osteoid. This is hydroxyapatite.
Describe the five stage of Bone Remodelling
Osteoblasts become trapped and form osteocytes
What is the function of carbonic anhydrase?
This is found in bone and it catalyses the formation of carbon acid which is a supply of Hydrogen ions.
What is function of RANKL?
This is secreted by osteoblasts and binds to the receptor on osteoclasts precursors.
Give three factors that inhibit osteoclasts activation
- OPG
- Calcitonin
- Oestrogen
- Transforming Beta-GF
- IL-10
Where is GH secreted and what is its function?
It is secreted from somatropic cells in the pituitary gland. Its secretion is enhanced by oestrogen. IGFs are synthesized by GH direct response and this stimulates bone formation.
Give the composition of Bone
Bone is 65% organic which consists on hydroxyapatite.
35% is inorganic and this is 25-30% collagen (mainly type one) and 5-7% non-collagenous proteins (osteocaclin, Osteonectin, Osteopontin)
Give the function of the bone protein Osteocaclin
Bonds hydroxyapatite to collagen
Give the function of the bone protein Osteonectin
Hydroxyapatite crystallization
Give the function of the bone protein Osteopontin
Anchors osteoclasts
Describe the pathway of the nutrient artery
The nutrient artery pieces the diaphysis at the nutrient foramen into the medullary canal. It branches into ascending and descending branches. They will anastomoses with metaphyseal and epiphyseal arteries.
What is the functional unit of Compact Bone?
The functional unit are osteons. This forms the Haversain system. Osteons have a central canal and are surrounded by lamellae. There are spaces called lacunae and they are connected by canaliculi.
What are the properties of principle tensile trabeculae?
Horizontal and for strength
What are the properties of principle compressive trabeculae?
Vertical and for force
What do mesenchymal cells gives rise to?
Osteoblasts
Describe primary hyperparathyroidism.
There is a problem with the parathyroid gland and too much PTH is produced. The gland will become enlarged. There will be an increase in calcium, decrease in phosphate and increase in phosphorus.
Describe secondary hyperparathyroidism
The parathyroid glands produce too much PTH due to a low calcium level. There is therefore decreased calcium, and high phosphorus.
What are the serum results for Osteomalacia?
There is low calcium, low phosphate and low vitamin D. There is high serum ALK phosphate and PTH.
describe the two categories of vitamin D deficiency causes
Primary: Asian , lack of sunlight, elderly housebound and unhealthy diet
Secondary: chronic renal failure, partial gastrectomy, small bowel malabsorption, pancreatic disease
What is the cause of type one Rickets?
25 hydroxylase deficiency
What is the cause of type two Rickets?
Lack of the vitamin D receptor gene
What is the difference between lordosis and kyphosis?
Lordosis is lumbar and cervical and is secondary.
Kyphosis is thoracic and sacral and is primary.
When do lordosis segments form?
Cervical: around 3-4 months when the infant holds their head up
Lumbar: around 6 months when the infant starts to crawl
What vertebral forms the prominent process?
C7
What is the surface landmark for T3?
The spine of the scapula
What is the surface landmark for T7?
The inferior angle of the scapula
When does the spinal cord end?
L1
During tendon reflex damage, what is the difference between afferent and efferent damage?
- Afferent: no tendon reflex with associated sensory loss
- Efferent: no tendon reflex with associated muslce paralysis
What are the signs of an upper MN injury?
Increased tone, muscle spasticity and hypereflexia
What are the signs of a lower MN injury?
Reduced tone, Reduced power and hyporeflexia
What are the three types of Rickets?
- Nutritional
- Renal
- Hypophosphatemia (low phosphate)
What is Fanconi syndrome
This is a disorder of the kidney that causes too much phosphate, glucose and bicarbonate to be excreted. There is a normal vitamin D level.
What will be the phosphate level in X-linked hypophosphatemia?
Reduced
What is the myotome for C5?
Elbow flexors
What is the myotome for C6?
Wrist extensors
What is the myotome for C7?
Elbow extensors and Wrist flexors
What is the myotome for C8?
Finger extension and flexion. Thumb extension
What is the myotome for T1?
Finger abduction and adduction.
What is the myotome for L2?
Hip flexors
What is the myotome for L3?
Knee extensors
What is the myotome for L4?
Ankle dorsiflexion
What is the myotome for L5?
Long toe extensors
What is the myotome for S1?
Ankle plantar flexion
What is the function of the trapezius?
elevates, depress and retract scapula
What is the function of the Latissimus Dorsi?
Adducts arm, Extends arm, Internally rotates arm
What is the innervation of the Latissimus Dorsi?
The Thoracodorsal nerve
What is the function of the Rhomboids?
Retraction of Scapula. These are Hands away from pockets!
What is the difference in insertion of the rhomboid major and minor?
Minor: C7-T1
Major: T2-T5
What is the innervation of the Rhomboid muscles?
Dorsal scapular nerve
What is the blood supply of the Rhomboids and the Latissimus Dorsi?
The dorsal scapular artery supplies the Rhomboids ad the thoracodorsal artery supplies the Latissimus Dorsi
What is the function of the Levator scapula and what is its innervation?
It elevates the scapula and is innervated by the Dorsal scapula nerve.
Which vertebral does the Levator scapula originate from?
C1
What is the difference between the serratus posterior superior and inferior?
The superior originates are ribs 2-5 and elevates the ribs. The inferior originate at ribs 9-12 and depresses the ribs.
The pectoralis major inserts in the intertubercular grove of the humerus. What is its innervation and function?
The functions include adduction and medial rotation of humerus. It also draws the scapula anteroinferoroly.
It is innervated by the lateral and medial pectoral nerves.
What is the origin, insertion, and innervation of the Pectoralis Minor?
Origin: 3-5 ribs
Insertion: Coracoid process
Innervation: Medial pectoral nerve
What is the function, innervation and blood supply of the Teres Major?
Function: adducts and internally rotates arm
Innervation: lower subscapular nerve
Blood Supply: circumflex scapula artery
What are the functions of PTH?
- increase activity of 1-alpha-hydroxylase activity
- increase calcium reabsorption in distal tubule
- decrease phosphate reabsorption in proximal tubule
- increase osteoclast activity
- increase osteoclast maturation
- decrease osteoblast collagen matrix
- increase in calcium and phosphate in GI tract
What are the functions of Calcitonin?
- decrease in kidney reabsorption of calcium and phosphate
- decrease in osteoclasts activity
- no effect on GI tract
What are the functions of Vitamin D?
- increases the production of calcium channels in the intestine to increase absorption
- increases the production of RANKL and causes differentiation of pro-osteoclasts into osteoclasts
- increases the calcium channels in the kidney to increase calcium absorption
What vertebrae has no body?
C1
What is unique about C2?
C2 is known as the axis and it has the Odontoid Peg.
What section of the spine have bifid spinous processes?
Cervical. This means they are split.
How many openings do the cervical vertebrae have?
Three:
One vertebral foramina
two transverse foramina (vertebral artery)
What is the direction of the zygapophyseal joints in the in the cervical region?
Backwards, upwards, medially
What is the direction of the zygapophyseal joints in the Thoracic region?
Backwards, upwards, laterally
What is the direction of the zygapophyseal joints in the Lumbar region?
Backwards and Medially
What is the shape of the body in the thoracic region?
Heart
Which region of the spine has the costal and demi facets for articulation with the ribs?
Thoracic
Which way do the spinous processes of the thoracic spine slant?
Inferiorly
What shape is the lumbar vertebrae?
Kidney shaped
The vertebral foramen of the Lumbar region is larger than the thoracic but small than the cervical. True or False?
True
What is the name of the ligament that attaches the laminae of adjacent vertebra?
Ligamenta Flava
What is the principle eccentric role of the erector spinae muscles?
Limit/Control flexion of the back
What does the nutrient artery supply?
Inner 2/3 of the cortex and the medullary cavity
What does the periosteal artery supply?
Outer 1/3 of the cortex. They enter through the Volkmann’s canal.
Where is FGF23 secreted from?
Osteocytes secrete FGF23 in response in an increase in calcitriol. This inhibits phosphate absorption in the kidney.
Where does the nuchal ligament extend from?
The occipital prominence and C7
Describe the two parts of the intervertebral disc
This is between the vertebrae bodies. They are described as secondary cartilaginous joints as they are made up of fibrocartilage.
They have a central nucleus pulposes, which is made up of a gel-like mass of water and proteoglycans surrounded by randomly arranged collagen fibres.
There is a peripheral annulus fibrosis and this is made up of concentrically arranged collagen fibres.
They is the end plates which is the barrier between the body and the intervertebral disc.
What does the thoracolumbar fascia cover?
The thoracic and lumbar vertebrae.
What are the border of the triangular space and what are the contents?
Superior: teres minor
Inferior: teres major
Lateral: long head of the triceps
This space is medial to the quadrangular space and it contains the circumflex scapular artery.
What are the border of the quadrangular space and what are the contents?
Superior: teres minor
Inferior: teres major
Medial: long head of the triceps
This space is lateral to the triangular space. This contains the axillary nerve and the posterior humeral circumflex artery.
What is the surface landmark of L4/5?
This is a line drawn between the iliac crests.
Which area of the spine is responsible for flexion and extension?
Cervical and lumbar
Which area of the spine is responsible for rotation?
Thoracic
Which area of the spine is responsible for head nodding and rotation?
Atlantoaxial joint: pivot joint
Atlanto-occipital joint: Condyliod joint
What is reduction of a fracture?
This is the process of setting a fracture.
Closed: this is done manually
Open: this is done surgically
What is osteomyelitis?
Severe bone infection caused due to open fracture
