28.4 - 28.9 Flashcards

1
Q

___ are cells of cartilage. ___ cartilage is the most common type of cartilage. It consists of connective tissue cells in ECM. ECM is mainly composed of type ___ collagen, aggrecans, ___ acid, and chondronectin. It is incompressible and smooth.

A

Chondrocytes
Hyaline
Type 2 collagen
Hyaluronic acid

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2
Q

Elastic cartilage is ___ cartilage with the addition of ___. It is very flexible and maintains shapes e.g. in ears, ear canals, epiglottis, larynx.

A

Hyaline cartilage with elastin

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3
Q

___ is a mixture of fibrous/dense connective tissue and some cartilage. It binds solid joints and forms menisci and IVDs. There is no ___ (surface connective tissue layer) and is composed of type ___ collagen.

A

Fibrocartilage
No perichondrium (surface connective tissue layer found in hyaline and elastic cartilage)
Type 1 collagen

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4
Q

The IVD is composed of an external ring of ___ called the annulus fibrosus. The internal core is called the ___ ___ and is derived from the notochord. The gelatinous core is composed of collagen type ___. By the age of 20, all collagen type ___ is converted to ___.

A
Fibrocartilage
Nucleus pulposus
Collagen type 2
Collagen type 2
Fibrocartilage
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5
Q

Bone is hollow and composed of 2 types: ___ bone that forms a dense, outer layer, and ___ or ___ bone that forms a spongy interior.

A

Compact bone

Cancellous or trabecular bone

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6
Q

Blood vessels in the medullary cavities of bone are called ___ - large diameter, open vessels with pores in walls for cells from bone marrow to enter circulation.

A

Sinusoids

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7
Q

The thin layer of fibrous connective tissue on the inside of bone is called ___, and on the outside is called ___.

A

Inside - endosteum

Outside - periosteum

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8
Q

Type ___ collagen fibres of tendons penetrate into the surface of bone for strong attachment. The collagen fibres that penetrate the bone surface are called ___ ___. These are the basis for avulsion fractures.

A

Type 1 collagen fibres of tendons

Sharpey’s fibres

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9
Q

Long bones receive blood supply at 2 major points: in the ___ and in both ___. Nerves are associated with the blood vessels.

A

Diaphysis

Both epiphyses

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10
Q

Cartilage is avascular. Therefore, nutrients usually diffuse from the ___ (layer of connective tissue) to the cartilage. There are also ___ precursors in this layer. Repair of articular cartilage (in joints) is slow because there is no ___ (layer of connective tissue).

A

Nutrients diffuse from perichondrium to cartilage
Chondrocyte precursors
No perichondrium in joints

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11
Q

Synovial ___ lines the synovial space - this is NOT an ___, so there is no ___ ___, ___ junctions or desmosomes.

A

Synovial membrane
Not an epithelium
No basement membrane, tight junctions or desmosomes

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12
Q

Synovial fluid is an ___filtrate of synovial blood vessels and proteoglycans.

A

Ultrafiltrate

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13
Q

___ systems (i.e. ___) are oriented in lines of stress.

A

Haversian systems

Osteons

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14
Q

Osteoid (produced by ___) is composed of collagen type ___ and bone matrix proteins e.g. osteocalcin and osteonectin, proteoglycans and ___ phosphatase.

A

Osteoblasts
Collagen type 1 (c.f. type 2 in hyaline cartilage)
Alkaline phosphatase

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15
Q

In any long bone there is usually ___ centers of ossification.

A

3

One in diaphysis, one for each epiphysis

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16
Q

New bone (during development or repair) is called ___ bone - it is more cellular with more collagen and NO ___ systems. It is rapidly remodelled by osteoblasts and osteoclasts to ___ systems, called ___ bone.

A

Woven bone
No Haversian systems
Remodelled to Haversian systems
Lamellar bone

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17
Q

Remodelling of woven bone occurs when ___ form tunnels in bone and ___ ___ invade tunnels. ___ cells move down the walls of the tunnel to form ___ and produce new Haversian systems. They produce layers of bone in different orientations (approx. ___ degrees) from the outside in to form a smaller tunnel for the blood vessel in the tunnel.

A
Osteoclasts
Blood vessels
Osteoprogenitor
Osteoblasts
90
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18
Q

Mechanotransduction occurs in ___, allowing direct remodelling to stresses.

A

Osteocytes

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19
Q

___ cells and resting ___ are found in the periosteum and endosteum.

A

Osteoprogenitor cells

Resting osteoblasts

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20
Q

Osteoid is composed of collagen type ___, whereas hyaline cartilage is composed of collagen type ___. In osteoid there are other proteins/proteoglycans and some GAGs, but there are ___ compared to cartilage.

A

Collagen type 1
Collagen type 2
Less in osteoid c.f. cartilage

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21
Q

There are some growth factors and cytokines in osteoid. Therefore, in resorption of bone by ___ there is release of growth factors for growth of bone by ___.

A

Osteoclasts

Osteoblasts

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22
Q

In histology of endochondral ossification, cartilage appears ___ due to GAGs and osteoid from osteoblasts, on the outside of the cartilage model appears ___.

A

Cartilage - basophilic due to GAGs

Osteoid - eosinophilic, on the surface/outside of cartilage model

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23
Q

Osteoblasts secrete collagen and secretory vesicles to increase the concentrations of ___ and ___ (note - osteoblasts do NOT directly secrete these, but secrete enzymes for precipitation of them) which precipitate into ___.

A

Calcium and phosphate

Hydroxyapatite

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24
Q

Normal bone turnover is ___-___% per year, but up to 200x faster in children.

A

5-10%/year

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25
Q

The functional unit of bone remodelling is called a ___ ___ ___, with osteoclasts in the front and osteoblasts in the back. The osteoclast resorbs a tunnel of bone and produces a new ___ ___ (or osteon). A capillary enters the tunnel and osteoblasts produce new bone. This new bone is “remodelled” bone, therefore it is ___ bone and NOT ___ bone.

A

Bone multicellular unit - osteoclast and osteoblast
Haversian system
Lamellar bone
NOT woven bone

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26
Q

Mineralisation of new osteoid depends on ___ and ___ in serum.

A

Calcium and phosphate

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27
Q

What are some factors that slow healing of fractures?

A
Age
Comorbidities
Medications
Social factors
Nutrition
Fracture type
Trauma
Local factors e.g. infection
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28
Q

What is the expected healing time for fractures of the upper limb (in weeks)?

A

6-8

29
Q

Bone is a reservoir of ___ (98-99% of total body) and ___ (95% of total body). 80% of the skeleton is composed of ___ bone, and 20% is composed of ___ bone.

A

Calcium and phosphate
Cortical bone
Trabecular bone

30
Q

Use of ___ during development of teeth can result in accumulation and binding of the compound to calcium ions in dentin resulting in ___ discolouration.

A

Tetracycline

Yellow

31
Q

Osteoid is composed of collagen type 1, proteoglycans, osteocalcin and osteonectin. ___ joins organic collagen type 1 with inorganic ___ crystals.

A

Osteonectin

Joins organic collagen type 1 with inorganic hydroxyapatite crystals

32
Q

Processes that affect bone remodelling preferentially affect ___ bone due to the larger surface area and higher metabolic activity compared to ___ bone.

A

Trabecular bone

Cortical bone

33
Q

Members of the ___ family are the principal mediators of bone resorption. These include receptor activator of ___ (RANK/RANKL) and ___ (OPG). ___ is the principal transcription factor in osteoclastic differentiation.

A

TNF family
Receptor activator of NFkB (RANK/RANKL)
Osteoprotegrin (OPG)
NFkB is the principal transcription factor in osteoclast differentiation

34
Q

Glucocorticoids are required for normal bone differentiation, but at high concentrations results in ___ of osteoblasts and ___ of osteoclasts. For example, as concentration of dexamethasone increases, secretion of OPG ___, and RANKL ___. Therefore, in patients with ___ syndrome, there is risk of osteoporosis.

A
Inhibition of osteoblasts
Stimulation of osteoclasts
Secretion of OPG decreases
Secretion of RANKL increases (mRNA)
Cushing's syndrome (hypercortisolism)
35
Q

Parathyroid hormone is produced by the parathyroid gland. If there is low serum calcium, there is secretion of precursor and activation by a ___ sensitive protease.

A

Calcium

36
Q

PTH acts on parathyroid hormone receptors in ___, ___ and the ___ tract. It ___ plasma Ca2+: by increasing ___ synthesis which indirectly increases Ca2+ absorption via vitamin D; by increasing ___ activity and releasing calcium from bone; and reducing ___ calcium excretion. Therefore, hyperparathyroidism increases risk of ___.
Osteoporosis

A
Bone, kidney and GI tract
Increases plasma Ca2+
Increases calcitriol synthesis
Increases osteoclast activity
Reduces renal calcium excretion
37
Q

Calcitonin comes from ___ cells of the ___ gland. Calcitonin binds to receptors on ___ to inhibit them and decrease resorption of bone, and therefore, decrease calcium release. It also inhibits calcium ___ in the kidney.

A

C cells of the thyroid gland
Binds to receptors on osteoclasts
Inhibits calcium reabsorption in kidney

38
Q

Precursors of vitamin ___ come from diet or metabolism of cholesterol in the skin by ___. Precursors are converted to calcifediol in the ___. Calcifediol is metabolised in the kidney to ___ (active vitamin D3).

A

D
UVB
Conversion to calcifediol in the liver
Conversion to calcitriol in the kidney

39
Q

___ (active vitamin D3) increases plasma calcium by ___ intestinal absorption, ___ renal excretion and ___ osteoclast activity.

A

Calcitriol increases plasma calcium
Increases intestinal absorption
Decreases renal excretion
Increases osteoclast activity

40
Q

Vitamin D deficiency can result in low serum ___ and therefore is a cause of ___ in children and ___ in adults.

A

Low serum Ca2+/calcium
Rickets in children
Osteomalacia in adults

41
Q

Osteoporosis is defined as a reduction in bone mass > ___ SDs under the normal for healthy 30 y.o. females. Osteopaenia is defined as a reduction in bone mass ___-___ SDs under the normal for healthy 30 y.o. females.

A

Osteoporosis >2.5 SD under the normal

Osteopaenia 1-2.5 SDs under the normal

42
Q

Peak bone mass occurs in ___s. From ___s, bone density decreases. In females, there is a rapid decrease in bone density after ___, esp. due to increased ___ activity that affects trabecular bone.

A

Peak bone mass in 20s
From 30s, bone density decreases
After menopause
Increased osteoclast activity

43
Q

In osteoporosis, there is loss and thinning of ___ bone. This reduces cross-sectional area so that loads on bone are relatively higher, leading to an increased risk of ___.

A

Trabecular bone

Increased risk of fractures

44
Q

Bisphosphonates are administered ___, but they are poorly ___ and most is ___ so there is low bioavailability. So they may also be administered by IV. There are some adverse GI effects e.g. ___ reflux and ___.

A

Orally
Poorly absorbed
Most is secreted
Acid reflux and oesophagitis

45
Q

Osteomyelitis may be classified as ___ and non-___. In non-___, it may be classified as direct inoculation (e.g. trauma or surgery), or as local invasion (e.g. periodontal disease, sinus disease).

A

Haematogenous

Non-haematogenous

46
Q

Septic arthritis due to osteomyelitis does NOT occur in ___, but occurs in ___ because the growth plate is poorly developed and blood vessels cross bone and joint.

A

Does not occur in adults

Occurs in children

47
Q

50% of bone and joint infections occur under ___ years of age (and 25% under ___ year of age). They are more common in ___ than ___ (2:1 ratio).

A

50% under 5 years
25% under 1 year
More common in boys than girls (2:1)

48
Q

Osteomyelitis is ___ common in the fastest growing bones, and tubular long bones compared to flat bones.

A

More

Note - it can also present in vertebra (delayed presentation), pelvis (delayed diagnosis) and neonates

49
Q

Differentials for osteomyelitis include ___ arthritis, malignancy or ___ (infection of skin and soft tissue only).

A

Septic arthritis
Malignancy (Ewings, osteosarcoma, leukaemia, etc.)
Cellulitis

50
Q

In osteomyelitis, ___ increases and decreases rapidly over 1-2 weeks with a high peak, and ___ increases and decreases slowly over 3-4 weeks with a lower peak.

A

CRP

ESR

51
Q

In early osteomyelitis, there are no changes seen on ___. The main modality for early diagnosis of osteomyelitis is a ___ ___ - use of radioactive labelled dyes which are taken up more with blood flow, inflammation and osteoblast activity. ___ is the gold standard technique.

A

X-ray
So X-ray does not exclude the possibility of bone infection
Only after 1-2 weeks is there new periosteum formation at bone infection
Bone scan
MRI

52
Q

Bone and joint infections are most commonly due to ___ ___ or ___ ___. They are treated by using ___. If they are resistant, then use ___. BUT if the infection is NEONATAL (G-ves) or if the patient is UNIMMUNISED (H. influenzae), use ___ AND ___.

A
Staphylococcus aureus
Streptococcus pyogenes
Flucloxacillin
If resistant (i.e. MRSA), use vancomycin
If neonatal or unimmunised, use flucoxacillin AND cefotaxime - targets other bacteria that are not targeted by flucloxacillin
53
Q

Chronic ___ is often associated with poor initial treatment for bone infections.

A

Chronic osteomyelitis

54
Q

___ (distributive) refers to fairness in the distribution of resources.

A

Justice
Note - sometimes inequalities in the way resources are shared between moral equals are unavoidable e.g. donor kidney matches only one transplant patient
Sometimes inequalities are avoidable BUT justifiable
Sometimes inequalities are avoidable AND unjustified - this is unfair!

55
Q

What is the harm principle?

A

The only justification to restrict the freedom of anyone is to prevent harm to others
(But what is harm e.g. emotional, physical or social, etc.?)

56
Q

COX1 is ___ active and found in most cells. COX2 is ___ and found in inflammatory cells e.g. macrophages, and also fibroblasts, smooth muscle and endothelium. While COX enzymes are almost ubiquitous, the 5-lipoxygenase pathway is more restricted to ___ cells.

A

COX1 - constitutive
COX2 - inducible
Inflammatory

57
Q

COX enzymes convert ___ ___ into cyclic ___. Isomerases convert cyclic ___ into stable ___, ___ (PGI2) and ___ (TXA2).

A
Arachidonic acid
Cyclic endoperoxides
Cyclic endoperoxides
Stable prostaglandins
Prostacyclin
Thromboxane
58
Q

Endogenous cannabinoids are endogenous metabolites of phospholipids that are agonists of ___ receptors. There are ___ and ___ receptors. Of these two, ___ receptors are esp. expressed in inflammatory cell compartments.

A

Cannabinoid receptors
CB1 and CB2 receptors
CB2 receptors are esp. expressed in inflammatory cell compartments

59
Q

Epoprostenol is a PGI2 analogue used for pulmonary ___. Misoprostol is a PGE1 analogue used as an adjuvant to abortifacients.

A

Hypertension

60
Q

___ should NOT be used in gout because it blocks the transporters for uric acid.

A

Aspirin

61
Q

___ sensitises pain fibres. Therefore, ___ are used to reduce ___ for an analgesic effect.

A

PGE2
NSAIDs
Reduce PGE2

62
Q

NSAIDs are antipyretics, but ___ is preferred due to less adverse effects and relative safety in children compared to ___.

A

Paracetamol is preferred

Compared to aspirin

63
Q

Many hospitalisations in the 60+ age group are associated with complications of chronic use of ___.

A

NSAIDs

64
Q

NSAIDs inhibit mucosal synthesis of ___ and ___.

A

PGI2

PGE2

65
Q

By inhibiting COX, NSAIDs can result in bronchoconstriction because there is more ligand (___ ___) that can enter the ___-___ pathway to produce more ___.

A

Arachidonic acid
5-lipoxygenase pathway
More leukotrienes
(Causes bronchoconstriction)

66
Q

Acetylation of ___ does not inactivate the enzyme, but results in the production of different metabolites called aspirin ___ ___ (ATLs). These are ligands for ___.

A

COX2
Aspirin triggered lipoxins
FPR2

67
Q

Specific effects of aspirin include ___ syndrome, ___ and ___ ___ retention (so contraindicated in gout).

A

Reye’s syndrome
Tinnitus
Uric acid retention

68
Q

Neutralisation of ___ (cytokine) is beneficial in RA. Neutralisation can be by ___ receptors or ___. But it may result in reactivation of latent ___, or the need for aggressive antibiotic treatment for new infections.

A

TNFalpha
Decoy receptors e.g. etanercept
Antibodies e.g. infliximab, etc.
TB