Limbs and Back: Summary concepts Flashcards
1
Q
What are the five stages of bone remodelling?
A
- Bone resting
- Bone resorption
- Bone reversal
- Bone formation
- Bone mineralization
2
Q
What happens during the first stage of bone remodelling (bone resting)?
A
Bone lining cells are activated by mechanical or hormonal stimuli. Osteocytes will begin to secrete IGF-1.
3
Q
What happens during the second stage of bone remodelling (bone resorption)?
A
Osteoclast precursors will be recruited and activated by osteoblasts cells through the secretion IL-1, M-CSF, RANKL and IGF-1.
Osteoclasts will bind to bone through a ruffled integrin border. They will secrete two chemicals: lysosomal enzymes will degrade the matrix and hydrogen ions will degrade the minerals.
The dissolved substances will enter the blood through interstitial fluid.
4
Q
What is the function of carbonic anhydrase, a substance found within bone?
A
This catalyses the formation of carbonic acid which acts as a source of hydrogen ions.
5
Q
What happens during the third stage of bone remodelling (bone reversal)?
A
Monocular cells deposit proteoglycan onto the bone to form a cement line. Osteoblasts precursor cells are recruited and they begin to differentiate.
6
Q
What happens during the fourth stage of bone remodelling (bone formation)?
A
Osteoblasts secrete osteoid which is laid between the unmineralized area (osteoid seam) and the mineralized bone.
7
Q
What happens during the firth stage of bone remodelling (bone mineralization)?
A
This is where osteoblasts form osteocytes and as layers build up, they become mineralized.
8
Q
Name five drugs that are used in the treatment of osteoporosis
A
- Bisphosphonates
- Raloxifiene
- Teriparatide
- Strontium ranelate
- Denosumab
9
Q
Give example of a first generation bisphosphonate
A
Etidronate
10
Q
Give example of a second generation bisphosphonate
A
Alendronate
11
Q
Give example of a third generation bisphosphonate
A
Risedronate and zoledronic acid
12
Q
What bisphosphonate generation is Etidronate?
A
First
13
Q
What bisphosphonate generation is Alendronate?
A
Second
14
Q
What bisphosphonate generation is Risedronate?
A
Third
15
Q
What bisphosphonate generation is zoledronic acid?
A
Third
16
Q
What is the mechanism of action of first generation bisphosphonates?
A
These are non-nitrogen containing drugs. They are incorporated into ATP and interfere with ATP-dependant pathways, resulting in apoptosis. Examples include Etidronate.
17
Q
What is the mechanism of action of second and third generation bisphosphonates?
A
There are nitrogen containing drugs. They interfere with the osteoclasts Farnelysation pathway and therefore result in apoptosis. Examples of second include alendronate. Examples of third include zoledronic acid and risedronate.
18
Q
What is the mechanism of action of Raloxifene?
A
This binds to oestrogen recepotrs and mimics their affects
19
Q
What is the mechanism of action of Teriparatide?
A
This is part of PTH which stimulates osteoblasts
20
Q
What is the mechanism of action of Strontium ranelate?
A
They enhance osteoblasts by increased OPG production
21
Q
What is strontium ranelate used for?
A
Osteoporosis
22
Q
What is the mechanism of action of Denosumab?
A
Inhibits RANKL
23
Q
What are the effects of decreased oestrogen in the body?
A
There is decreased GF (this promotes proliferation of osteoblasts). There is increased IL-6 mediated osteoclasts differentiation. There is increased RANKL production and osteoclasts increase their lysosomal activity.
24
Q
What is the difference between endogenous and exogenous vitamin D supply?
A
Endogenous: there is 7-dehydrocholesterol stored in the skin and this is transformed into vitamin D3 when it is activated by sunlight.
Exogenous: this is obtained from the diet. Vitamin D3 form animals and vitamin D2 from plants.
25
What is the pathway that vitamin D3 takes to form its active form?
Vitamin D3 will travel in the blood in chylomicrons and the it will bind to the protein DBP.
This will travel to the liver where is converted into 25-hiudroxyvitamin D by the enzyme 25-hydroxylase. This will then travel to the kidney where it is transformed into 1.25-dihyroxyvitamin D by the enzyme 1-alpha-hydroxylase.
26
Name three factors that will stimulate the action of 1-alpha-hydroxylase
- PTH
- hypocalcaemia
- hypophosphatemia
27
What are the three stages of tendon healing and what is their time length?
- Inflammation: 0-7 days
- Repair: 3-60 days
- remodelling: 28-180 days
28
What happens during the first stage of tendon healing?
Erythrocytes, platelets and immune cells migrate from epitendinous and endotendon. There is inflammation, granulation tissue formation and haematoma. matrix protien are laid down for collagen synthesis. This process lasts around 0-7 days.
29
What happens during the second stage of tendon healing?
This stage is known as repair. Tenocytes/ fibroblasts begin to make collagen III which is made quickly and laid down randomly. This forms a tendon callus. There is then a switch to collagen I to increase strength. There is vascular ingrowth between collagen/fibronectin scaffolding. This process lasts around 3-60 days.
30
What happens during the third stage of tendon healing?
This is remodelling and lasts around 28-180 days. This is where the final stability is achieved, although the strength is not the same as the previous tendon. There is cross-linking of fibrils to increase the strength.
31
Explain the process of inflammation
The first response is vasoconstriction.
However, injured or infected cells will release prostaglandins, histamine and bradykinin which will cause vasodilation. This will also cause increase vascualr permeability.
Normally, blood flows in an axial line and this involves the plasma cell being on the outside and the red blood cells and leukocytes flowing in the middle. Due to the increased vascualr permeability, the plasma leaks out and hence the leukocytes migrate to the vessel wall.
When macrophages detect damaged of infected cells they secrete IL-1 and TNF-alpha and this causes expression of E-selectin on endothelial walls. P-selection is normally stored in granules and s only released when in contact with histamine and thrombin. This will also form on the endothelial surface. These recepotrs will bind to glycoprotein on the leukocyte surface (sialyl-lewis x-modified protien).
Chemokines, for example IL-1 and TNF will bind to proteoglycans on the endothelial wall and activate rolling leukocytes. There will be firm adhesion to the leukocytes through their ICAM proteins.
Leukocytes will extend their pseudopods through the wall and secrete collagenases to break the BM. This is known as Diapedesis.
The leukocytes will follow a chemotaxis gradient (IL-8, Leukotriene B4, C3b) to the damaged area. This will then result in phagocytosis.
32
Where are P-selectins found?
Weibel-Palade bodies
33
Why does blood become more viscous when there is vasodilation?
Plasma leakage
34
What do selectins bind to?
Sialyl-lewis-modified-x-proteins
35
What is the function of PECAM-1 during inflammation?
This will help the leukocyte migrate across the vessel wall.
36
There are two types of chemotaxic factors: endogenic and endogenous. Give examples of both
Exogenous: bacteria products
Endogenous: IL-8
37
Give some examples of DMARDs that are used to treatment rheumatoid arthritis
Methotrexate, hydroxychloroquine, gold, leflunomide
38
Give some examples of biologic treatments for rheumatoid arthritic
Infliximab, etanercept, golimumab
39
What is the function and structure of IgD?
This is a monomer and it is found on naïve B cells
40
What is the function and structure of IgE?
This is a monomer and it is responsible for allergic reactions.
41
What is the function and structure of IgM?
This is pentamer and is the first antibody to be made after an infection.
42
What is the function and structure of IgA?
This is a dimer and is found in mucous membranes. This prevents infections from entering the body. This is secreted in breast milk.
43
What is the function and structure of IgG?
This is a monomer and is the main antibody secreted during infection. As the concentration of this increases, the concentration of IgM decreases. This antibody is able to cross the placenta during pregnancy.
44
If there is a problem with glycosylation during the formation of collagen, what condition can develop?
Osteogenesis imperfecta
45
What is the difference between upper motor lesion and lower motor lesion?
Upper motor lesion will have increased tone, be spastic, have a positive Babinski sign, be hypereflexia, hypertonic, have disuse atrophy.
Lower motor lesion will have reduced power, reduced tone, be hypoflexic, hypotonic, have a negative Babinski and have denervation atrophy
46
What are the thenar muslces and what is their innervation?
- Abductor pollicis brevis
- Flexor pollicis brevis
- Opponens pollicis
They are supplied by the median nerve (recurrent branch).
47
What are the hypothenar muslces and what is their innervation?
- Opponens digit minimi
- Flexor digiti minimi brevis
- Abductor digiti minimi
They are supplied by the ulnar nerve.
48
What are some examples of Primary immunodeficiency diseases?
- Bruton's agammaglobulinemia
- MHC class one deficiency
- MHC calls two deficiency
- Hyper IgM syndrome
- IgA deficiency
- Wiskott Aldrich syndrome
- X-linked SCID (bubble boy disease)
- Digeorges syndrome
- Dendritic cell deficiency
- Complement deficiency
49
What are some examples of Secondary immunodeficiency?
- HIV
- Corticosteroids
- Spleen removal
- Stress/emotion
- Leukaemia
- Chemotherapy/irradiation
- protein/calories malnutrition
- cancer spread to bone marrow
- aging
50
What are some examples of organ-specific autoimmune diseases?
- Graves disease
- Type one diabetes
- MS
- Addison's disease
- Myasthenia Gravis
- Goodpastures syndrome
- Guillain-Barre syndrome
- Hashimoto thyroiditis
51
What are some examples of non-organ-specific autoimmune diseases?
- Systemic lupus
- RA
- Mixed connective tissue disorder
- Sjogren syndrome
52
What is the molecule targeted in Graves disease?
TSH receptor
53
What is the molecule targeted in Guillain-Barre syndrome?
Gangliosides
54
What is the molecule targeted in Myasthenia gravis?
Acetylcholine
55
What is the mechanism of action of Glucocorticoids?
Glucocorticoids mimic the hormones that are released from the adrenal gland. The bind to the Glucocorticoids receptor that is linked to the HSP46/90 protien and this causes detachment and this affects protein transcription. Annexin-1 is up-regulated and this blocks arachidonic acid. This down-regulates cytokines,, adhesion molecules and enzymes.
56
What are some side effects of Glucocorticoids?
- increased abdominal fat
- moon face
- benign intracranial hypertension
- skin thinning
- muscle wasting
- poor wound healing
- buffalo hump
- euphoria
- increased risk of osteoporosis, infection and hyperglycaemia
57
What is the absence of limbs called?
Amelia
58
What is the partial absence of limbs called?
Meromelia
59
What is the absence of long bones called?
Phocomelia
60
What is the fusion of limbs called?
Sirenomelia
61
What is the condition called where there is an absence of digits?
ectrodactlyly
62
What is the condition called where there is a failure of differentiation of digits?
Syndactyly
63
What is the condition called where there is duplication of digits?
Polydactyly
64
What is the condition called where there is shortened digits?
brachydactyly
65
What is the condition called where there is enlarged digits?
Macrodactyly
66
Describe what happens in the first stage of fracture healing
This phase is known as fracture haematoma and inflammation. There is a lot of damage to the blood vessels and hence there is extensive bleeding. The blood vessels form a clot, known as a fracture haematoma, and this closes of injured blood vessels and leaves a fibrous meshwork. The disruption causes the death of osteocytes in the area. Dead bone cells will extend along the shaft of either direction of the break. There is swelling and inflammation in response to the dead cells and this will produce additional cellular debris. Phagocytes and osteoclasts will remove the dead/damaged tissue.
This process occurs 6-8 hours after injury.
67
What happens during the first stage of fracture healing?
Inflammation and fracture haematoma: There is extensive damage to the blood vessels which means there is extensive blood loss. The damaged blood vessels will form a clot, known as a fracture haematoma, which will close off the broken vessels and prevent further blood loss. This will form a fibrous meshwork around the area. The disruption to the bone will cause the osteocytes on the surface to die. Dead bone cells will extend along the shaft of the break in either direction. The dead bone cells and damaged bone cause immune cell to recruit and there is swelling and inflammation. Phagocytes will remove the debris and dead cells. This process occurs 6-8 hour after injury?
68
In the first stage of fracture healing, there is the formation of a fracture haematoma. What is the result of this?
Fibrous meshwork forms
69
What happens during the second stage of fracture healing?
This is known as fibrocartilage callus. This last s around 3 weeks. New capillaries will organise the haematoma into granulation tissue. There will be recruitment of fibroblasts and oestrogenic cells. Fibroblasts will begin to make collagen which holds the ends together. Chondrocytes will begin to make fibrocartilage.
70
What is the role of the new capillaries in the second stage of fracture healing?
The organise the fracture haematoma in granulation tissue
71
What cells are recruited during the second stage of fracture healing?
Oestrogenic cells
Fibroblasts: begin to secrete collagen to help keep the ends together
Chondrocytes: produce fibrocartilage
72
What happens during the third stage of fracture healing?
When blood supply is sufficient, oestrogenic cells develop into osteoblasts and they begin to produce trabeculae and primary woven bone. Near the fracture site, where the blood supply is less adequate, oestrogenic cells will differentiate into chondroblasts. Trabeculae bone joins living and dead portions of the original bone fragments. In time, the fibrocartilage callus is converted into bone and this is referred to as the bony hard callus. This lasts around 3-4 months.
73
What is the significance of the blood supply to the bone during the third phase of fracture healing?
When there is sufficient blood supply, oestrogenic cells will divide into osteoblasts and they begin to secrete trabecula bone and primary woven bone. The trabeculae bone will join the dead and living portion of the bone.
Where there is insufficient blood supply, i.e near the fracture site, the cells will divide into chondrocytes.
74
What happens during the fourth stage of fracture healing?
This is bone remodelling and lasts around 6 months. The dead portions of bone are gradually remodelled by osteoclasts. Compact bone replaces the trabeculae bone around the periphery of the fracture. As both the external callus (made of cortical bone) and the internal callus (made of cancellous bone) harden from the cartilage stage of through ossification, the fracture site becomes firm and stable.
75
What is the innervation of the anterior leg muslces?
Deep fibular nerve. They are also all supplied by the anterior tibia artery.
76
What is the innervation of the lateral leg muslces?
Superficial fibular nerve
77
What is the innervation of the posterior leg muslces?
tibia nerve
78
What is PTH and where is it secreted?
This is an 84-amino acid peptide secreted by the chief cells of the parathyroid glands
79
What is calcitonin and where is it secreted?
Calcitonin is a 32-amino acid polypeptide that is secreted by the C cells in the thyroid gland.
80
What muscles does the axillary nerve supply?
Deltoid and teres minor
81
What structure does the axillary nerve travel posterior to?
Surgical neck of the humerus
82
Which nerve travels posterior to the surgical neck of the humerus?
The Axillary nerve
83
If there is an injury to the surgical neck of the humerus, which nerve is likely to be damaged?
The Axillary nerve
84
What is the sensory supply of the Axillary nerve?
The shoulder
85
What are the three muslces that the musculocutaneous nerve supplies?
The Biceps brachii, the Coracobrachialis and Brachialis
86
What can a patient not do when the axillary nerve becomes damaged?
Abduction of shoulder ( 15 - 90 degrees )
87
What can a patient not do when the musculocutaneous nerve becomes damaged?
Flexion of arm
88
Where is the median nerve in comparison to the arm?
Anterior
89
What is the motor supply of the median nerve?
Lateral flexors of the wrist, lateral tow lumbricals and thenar muscles (through recurrent branch).
90
What branch of the median nerve supplies the thenar muscles?
Recurrent branch
91
What is the difference between distal and proximal median claw hand?
Distal: when the patient tries to open their hand, the 2nd and 3rd fingers stay flexed
Proximal: when the patient is asked to make a fist, the thumb and 2nd and 3rd finger stay extended.
92
What is the difference between proximal median claw hand and ulna claw hand?
In proximal claw hand, the patient is unable to oppose thumb whereas in ulna claw hand, they are able to oppose their thumb.
93
What happens to the thenar muslces when there is damage to the median nerve?
They atrophy and the patient is unable to oppose thumb.
94
What muslces does the radial nerve supply?
Triceps, Brachioradialis, Extensors of the wrist
95
Where is the radial nerve located?
The posterior side of the arm. It runs in the radial groove.
96
What nerve supplies the sensory supply to the back of the arm and forearm?
Radial nerve
97
What part of the humerus would cause damage to the radial nerve if it become damaged?
The body
98
Inappropriate use of crutches and Saturday night palsy can result in wrist drop. Which nerve is damaged?
The radial nerve
99
Which side does the ulnar nerve travel in relation to the media epicondyle?
Posterior
100
What is the motor supply of the ulnar nerve?
The hypothenar eminence. The medial lumbricals and the interossei muscles.
101
Which carpal bone could cause damage to the ulnar nerve when damaged?
The Hook of Hamate
102
What are results of damage to the ulnar nerve?
Inability to abduct and adduct fingers
103
What happens to the third and fourth fingers during ulnar claw hand?
They are unable to extend.
104
What is Erbs Duchenne palsy?
This is an upper trunk lesion affecting the nerves C5-C6. This is caused by trauma or by a traumatic birth.
105
What is are the signs of Erbs Duchenne palsy?
The limb will be hanging by their side, medially rotated and there will be a pronated forearm.
106
What is Klumpes palsy?
This is a lower trunk lesions. This affects C7,8 and T1. This is caused by a traumatic birth or pancoast tumour.
107
What are the effects of Klumpes palsy?
This affects the nerves: radial, median and ulnar. There is therefore loss of all lumbricals resulting in all fingers being clawed. There is also the loss of the wrist extensors and flexors.
108
Name the six stages of endochondral ossification
1) development of cartilage model
2) growth of cartilage model
3) development of primary ossification centre
4) development of medullary cavity
5) development of secondary ossification centre
6) development of articular cartilage and epiphyseal growth plate
109
Explain what happens during the first stage of endochondral ossification (development of cartilage model)
This is where mesenchymal cells aggregate into the general shape of the bone. They differentiate into chondroblasts. The chondroblasts begin to secrete cartilage ecm. The end result is a hyaline cartilage model.
110
Explain what happens during the second stage of endochondral ossification (growth of cartilage model)
Once the chondroblasts become surrounded by cartilage ecm, they are known as chondrocytes. The chondrocytes continue to divide and secrete cartilage matrix, hence the cartilage model grows.
111
Explain what happens during the third stage of endochondral ossification (development of primary ossification centre)
A nutrient artery will penetrate the perichondrium towards the centre of the calcifying cartilage and cause oestrogenic cells to differentiate into osteoblasts. As perichondrium bone forms, it is known as periosteum (periosteal bone collar). The osteoblasts will secrete bone ecm and this will replace the cartilage in the middle, forming the primary ossification centre. The bone ecm will also replace remnant of calcified carriage, forming spongy bone. The primary ossification centre will extend through out the bone.
112
Explain what happens during the fourth stage of endochondral ossification (development of medullary cavity)
As the primary ossification centre's extend towards the end of the bone, the osteoclasts begin to break some of the spongy bone down to form the medullary cavity. The medullary cavity extends the diaphysis. The spongy bone on the wall of the diaphysis will be replaced with compact bone.
113
Explain what happens during the five stage of endochondral ossification (development of secondary ossification centres)
As developing arteries reach the epiphysis, secondary ossification centres form. This is usually around the time of birth. The spongy bone formed here will remain and there will be no formation of the medullary cavity. Unlike primary ossification centres, the secondary ossification centres will extend outwards, away from the centre of the epiphysis.
114
Explain what happens during the sixth (last) stage of endochondral ossification (development of articular cartilage and epiphyseal growth plate)
The hyaline cartilage covering the epiphyses becomes articular cartilage.
Hyaline cartilage will remain in the epiphysis and the diaphysis and this forms the epiphyseal growth plate.
115
What are the four layers of the epiphyseal growth plate?
- zone of resting cartilage
- zone of proliferating cartilage
- zone of hypertrophic cartilage
- zone of calcified cartilage
116
What happens during interstitial growth?
There is a layer of stem cell immediately below the epiphysis and they give rise to chondrocytes. The layer closest to the diaphysis is eroded by osteoclasts to allow the medullary cavity to grow. Therefore, as the top layer if dividing and growing, the bottom layer is being disintegrated.
117
What happens during appositional growth (width)?
Osteoblasts on the surface of the bone will secrete osteoid and this will make the bone stronger and thicker. There will be rapid ossification in order to keep up with growth in length.
118
What happens during the first stage of intramembranous ossification?
The mesenchymal cells in the centre of the fibrous connective tissue in the embryo condense. Some of the cells will become osteoblasts while some will become capillaries. The area of condensing mesenchyme will be known as the ossification centre.
119
What happens during the second stage of intramembranous ossification?
The osteoblasts will begin to secrete osteoid and mineralization will occur within several days. After mineralization occurs, the osteoblasts will become embedded and form osteocytes.
120
What happens during the third stage of intramembranous ossification?
Bony spicules or Trabeculae bone will radiate from the centre of the ossification centre in random patterns between blood vessels to form woven bone. This will eventually turn into lamellar bone.
The bony spicules will have mesenchymal cells around them around them and this will form the periosteum.
The osteoblasts will continue to secrete osteoid and this will become calcified.
121
What happens during the fourth stage of intramembranous ossification?
Layers of osteoid will build up and this will form compact bone. The trabeculae bone deeper will persist and this will form spongy bone
122
What is proliferation of satellite cells induced by?
MyoD
123
What are satellite cells?
They are precursors to skeletal muslce cells
124
What is the main action of the subtalar joint?
Inversion and Eversion
125
What nerve is damaged during foot drop?
The common peroneal
126
What does the tibial nerve supply?
The posterior leg compartment
127
What are the branches that form the femoral nerve?
L2-L4
128
What is the motor function of the femoral nerve?
Hip flexors and knee extensors
129
What is the sensory function of the femoral nerve?
The anteromedial thigh and medial side of leg and foot
130
What are the branches that form the obturator nerve?
L2-L4
131
What is the motor and sensory function of the obturator nerve?
Motor: thigh adductors
Sensory: skin of inner thigh
132
What branches form the sciatic nerve?
L4-S3
133
What is the motor function of the sciatic nerve?
The posterior thigh and hamstring part of the adductor magnus
134
What are the branches that form the tibial nerve?
L4-S3
135
What is the motor supply of the tibial nerve?
Posterior compartment of the leg
136
What is the sensory function of the tibial nerve?
Skin of posterolateral leg and the sole and lateral side of the foot
137
What are the braches that form the superficial peroneal nerve?
L4-S1
138
What is the motor and sensory function of the superficial peroneal nerve?
Motor: lateral leg muscles
Sensory: dorsum of the foot
139
What are the branches that form the deep fibular nerve?
L4-5
140
What is the motor and sensory function of the deep fibular nerve?
Motor: anterior leg compartment
Sensory: triangular region between toes 1 and 2
141
What nerve will become damaged with tarsal tunnel syndrome?
The tibial nerve.
142
What action is lost when the tibial nerve is damaged?
Plantarflexion
143
When doing an intramuscular injection into the gluteal region, what nerve must be considered and hence where should the needle go?
The nerve to be considered is the sciatic nerve. The gluteal region is split into six quadrants and only the top left and right can be used.
144
What will happen to skeletal muslce development when there is absence of MyoD?
NO affect
145
What sensation will occur in the foot if the superficial peroneal nerve is split?
Numbness of the dorsum of the foot.
146
What bony landmark is associated with the cords of the brachial plexus?
The coracoid process
147
What is an aneurysm?
Focal abnormal dilation
148
What is Paget's disease?
Disruption of the normal bone remodelling process
149
What is the correct order of strucutre going across the ankle, lateral to medial, out of: tibial anterior, extensor digitorum longus and extensor hallucis longus
Tibialis anterior, extensor hallucis longus, extensor digitorum longus
150
What position will the thumb be in during hallux valgus?
Adducted
151
What are the attachments of he inguinal ligaments?
Anterior superior iliac spine and pubic tubercle
152
How is the weight of the upper limb transmitted through to the axial skeleton?
Coracoclavicular ligament
153
What enzyme activity does PTH increase?
1-alpha-hydroxylase
154
What are the three main effects of PTH?
- increases 1-alpha-hydroxylase activity so there is an increase in calcitriol
- increases calcium absorption in the DCT and CD but decreases potassium absorption in the PCT
- increases the expression of RANKL in osteoblasts and decreases the production of OPG
155
What are the three main effects of Calcitriol?
- increased production of RANKL from osteoblasts
- increased calcium absorption in the intestine
- increased calcium absorption in kidney
156
What is the effect of decreased oestrogen on bone (what happens in menopause)?
Oestrogen usually stimulates the production of OPG from osteoblasts and hence a decrease in oestrogen, will decrease OPG. This will mean there is increased osteoclasts activity through RANKL.
