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Human Histology > Unit 5: Cartilage and Bone > Flashcards

Unit 5: Cartilage and Bone Flashcards

1
Q

What are the cells that make up cartilage?

A

chondroblasts, chondrocytes

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2
Q

What is the origin, location, and function of chondroblasts?

A

Paraxial mesoderm origin
Peripheral location
Matrix producing during chondrogenesis and appositional tissue growth
• Active or inactive metabolic states

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3
Q

What is the origin, location, and function of chondrocytes?

A

Chrondroblast origin
Central/deep location
Primary matrix producing/maintaining cells within mature cartilage resulting in interstitial tissue growth
• Active or inactive metabolic states

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4
Q

What are the components of extracellular matrix that make up cartilage? What does it not consist of?

A

mostly ECM and a semi-solid portion

avascular and aneural

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5
Q

What is the semi-solid part of ECM of cartilage?

A

firm yet pliable via the “mesh like” interaction of GAGs & PGs
crucial for diffusion and chondrocyte survival

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6
Q

What is the semi-solid part of ECM of cartilage composed of?

A

Aggrecan-hyaluronan aggregates
Cartilage-specific collagen molecules

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7
Q

What are the aggrecan-hyaluronan aggregates?

A

Highly hydrated for resilience and diffusion
Binding of signaling molecules and growth factors

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8
Q

What are the cartilage-specific collagen molecules composed of?

A

Type II collagen and VI, IX, X, and XI

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9
Q

What is the function of the avascular and aneural part of ECM for cartilage?

A

tolerates intense stress but has limited ability to heal

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10
Q

Are the components of cartilage uniformly distributed?

A

no
fibrocartilage can be somewhat uniformly distributed

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11
Q

What are lacunae?

A

(void spaces)
in the ECM that accommodate chondrocytes within the semi-solid matrix

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12
Q

How do chondrocytes appear in tissue?

A

seen singularly or in isogenic groups (IGGs), representing cells that have recently divided

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13
Q

What is the capsular (pericellular) matrix? How does it stain?

A

high concentration of PGs, GAGs, MAPs surrounding cell
directly surrounds lacunae

dense micromolecues stain this darkest

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14
Q

Where is the territorial matrix? How does this stain?

A

surrounds isogenic groups

stains to a medium opacity (less than capsular but more than interterritorial)

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15
Q

Where is the interterritorial matrix? How does it stain?

A

occupies space between IGGs

stains very opaque (light)

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16
Q

What are the types of cartilage?

A

hyaline cartilage, fibrocartilage, elastic cartilage

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17
Q

Where is hyaline cartilage?

A

Articular surfaces of synovial joints, costal cartilages, cartilages of nasal cavity, larynx (thyroid, cricoid, arytenoid), trachea, bronchi, fetal skeletal tissue, epiphyseal plates

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18
Q

Where is fibrocartilage?

A

Intervertebral discs, pubic symphysis, articular discs, menisci of knee joints, triangular fibrocartilage complex (wrist joint), insertions of tendons

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19
Q

Where is elastic cartilage?

A

Pinna of external ear, external acoustic meatus, auditory tube, larynx (epiglottis, corniculate, cuneiform)

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20
Q

What are the differentiating factors of hyaline cartilage?

A

Most common type of cartilage
Weakest
Surrounded by perichondrium
Type II collagen (pressure), GAG, PGs, GPs
Staining appears homogenous
Can undergo calcification (endochondral ossification at epiphyseal plate)

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21
Q

What are the differentiating factors of fibrocartilage?

A

Less cellular than other cartilage types
NOT surrounded by perichondrium
Type II collagen, GAGs, PGs, GPs
Type I collagen (tension)
Some uniformity to tissue distribution

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22
Q

What are the differentiating factors of elastic cartilage?

A

Surrounded by perichondrium
Type II collagen, GAGs, PGs, and GPs
Elastic fibers & lamellae

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23
Q

What are the cells that compose bone?

A

osteoblasts, osteocytes, osteoclasts

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24
Q

What is the origin, location, and function of osteoblasts?

A

Mesoderm (most) or Ectoderm (specialized)
• Paraxial or Neural Crest
Located on bone surface
Bone Formation
• Osteoid secretion & mineralization

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25
Q

What is the origin, location, and function of osteocytes?

A

Osteoblast origin (fuses with osteoid)
Located in lacunar spaces
Mechanosensation
• Lacunar-canalicular network

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26
Q

What is the origin, location, and function of osteoclasts?

A

Lateral mesoderm (hematopoietic) origin - fusion of multiple preosteoclasts (multinucleated)
Located on bone surface
Bone resorption

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27
Q

What is the extracellular matrix composition of bone?

A

organic (1/3)
inorganic (2/3)
vascular and neural
-via branching of nutrient arteries into central and perforating canals

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28
Q

What is the composition and function of the organic part of the ECM of bone?

A

Type I collagen (90% on bone protein)
BMPs, CBPs, MAPs, ALP
Stretch resistant

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29
Q

What is the composition and function of the inorganic part of the ECM of bone?

A

Calcium phosphate
• Hydroxyapatite crystals [Ca10(PO4)6(OH)2]
Compression resistant

30
Q

How do osteoblasts mineralize?

A

Calcium binding proteins (CBPs) like osteocalcin bind extracellular Ca2+ which stimulates OBs to secrete alkaline phosphatases (ALPs)
ALP increases local concentration of PO4 ions which further increases the local Ca2+ concentration
OB ectosomes (matrix vesicles) accumulate Ca2+ & PO4 and assemble hydroxyapatite crystals
Bone matrix proteins (BMPs) contribute to the formation of a ECM collagen scaffold for mineral deposition
Hydroxyapatite crystals exit the matrix vesicles and develop as mineralized nodules within the ECM collagen scaffold

31
Q

What are the regions of osteoclast resorption?

A

ruffled border, clear/sealing zone, basolateral region

32
Q

What is the function of the ruffled border during osteoclast resorption?

A

increase surface area
- increases proton secretion (decalcification)
- increases hydrolytic enzyme exocytosis (Casthepsin K: collagen degredation)

33
Q

What is the function of the clear/sealing zone during osteoclast resorption?

A

tight seal “sealing zone” between OC plasma membrane and bone matrix

34
Q

What is the function of the basolateral region during osteoclast resorption?

A

exocytosis of bone debris

35
Q

What is the etiology and presentation of osteoporosis?

A

bone resorption > bone formation
Occurs due to an imbalance in the bone producing osteoblasts and bone resorbing osteoclasts
Results in decreased bone strength and a significant increase risk of fracture

36
Q

What are the types of bone ossification?

A

endochondral, intramembranous

37
Q

How does endochondral ossification occur?

A

Mesoderm → Paraxial mesoderm → Somites → Cartilage → Bone
1. Cartilage model
2. Periosteal bony collar
3. Cartilage matrix mineralized
4. Blood vessel formation & Periosteal migration
5. Cartilage matrix resorbed and replaced with bone matrix

38
Q

What bones does endochondral ossification form?

A

Most axial and appendicular skeleton (gestational 12 weeks)

39
Q

How does intramembranous ossification occur?

A

Ectoderm → Neural Crest → Mesenchyme → Bone
Unlike most axial and appendicular skeleton, much of the bone, cartilage, and CT of the head (skull, jaw, hyoid) have a unique embryonic origin from Neural Crest Cells (an ectoderm population derived during neurulation)

40
Q

What bones does intramembranous ossification form?

A

flat bones of skull and face (8th week gestation)

41
Q

What are the types of bone growth?

A

interstitial, appostitional

42
Q

What is interstitial growth?

A

Cartilage resorption & bone deposition
aka lengthening via growth plate

43
Q

What is appositional growth?

A

Uncoupled bone resorption & formation
“Bone modeling”
osteoblasts + osteoclasts work independently
changes shape (diameter) of bone

44
Q

What can bone remodeling be described as?

A

stochastic, targeted
it is a coupled process in which osteoclasts and osteoblasts work together

45
Q

What are the staining zones for bone tissue?

A

articular cartilage[
[superficial (tangential) zone
[intermediate (transitional) zone
[deep (radial) zone
[calcified zone

bone{
{subchondral bone
{cancellous bone

46
Q

What happens in osteoarthritis to the cells?

A

↓PGs = ↓H2O (no hyaluron)
↑ IL-1 & TNFα = ↓ Collagen II
↑ IL-17 = ↑ OC (osteoclastogenesis = absorb cartilage)

47
Q

What are bone-lining cells?

A

quiescent osteoclasts

48
Q

What is the periosteal layer of bone?

A

(similar to perichondrium)
fibrous + cellular outer layer of bone
innervated
attachment of muscles and tendons

49
Q

What is the intracortical layer of bone?

A

the majority of compact bone with osteons
circular with central canals and perforating channels to perfuse tissues

50
Q

What is the endocortical layer of bone?

A

(endosteum)
has osteoblasts and osteoclasts lining the surface

51
Q

What is the cancellous layer of bone?

A

extension of the endocortical layer
“spongy” layer filled with marrow

52
Q

What is stochastic bone remodeling?

A

random
along endosteal surface for Ca++ regulation

53
Q

What is targeted bone remodeling?

A

microdamage/cracks in mineralized matrix
osteoclasts bore hold to let osteoblasts fix damage and fill back in

54
Q

What are the steps of bone remodeling?

A

osteoblast (A-activation)
->RANKL
osteoclast (R-resorption)
->coupling
osteoblast (F-formation)

55
Q

What does bone maintenance require?

A

mechanical stimulation

disuse = osteoclast bone loss = fracture
overuse = osteoblast bone formation -> too quickly = woven bone formation = bone fracture

56
Q

What does bone fracture repair require?

A

inflammatory response (unlike microfractures)
results in haematoma around site of fracture

57
Q

What are the epiphyseal growth plate (interstitial growth via endochondral ossification) zones?

A

zone of reserved cartilage, zone of proliferation, zone of hypertrophy, zone of calcified cartilage, zone of resorption

58
Q

What does TRAP stain for?

A

osteoclasts

59
Q

Where does the PTHR1 bind?

A

osteoblasts to activate RANKL (activation)

60
Q

Where does RANK bind?

A

pre osteoclasts (resorption)

61
Q

What kind of ossification happens in the calvaria?

A

intramembranous

62
Q

What is the differential diagnosis for polyarticular joint pain and what is the next diagnostic step?

A

infectious arthritis, osteoarthritis (OA), RA, crystal-induced arthritis, Lyme disease, hemochromatosis, and systemic lupus erythematosus (SLE). Most likely OA or RA (given family history)

order conventional radiographs of the lumbar spine, bilateral hands, wrists, and right knee. OA and RA have distinct findings on conventional radiographs. Ultrasound is a used in cases of gout, OA, and RA. screening rheumatoid factor (RF) antibody, anti-citrullinated protein antibody (ACPA), and routine lab work is indicated, including complete blood cell counts (CBC), comprehensive metabolic panel (CMP), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP).

63
Q

What is the epidemiology and pathogenesis of the differential diagnosis?

A

OA is the leading cause of joint disease worldwide. affects 10% of men and 18% of women over 60. leading risk factor is age; increases exponentially after 50. degenerative joint disease primarily affecting the articular cartilage of weight-bearing joints such as the hips, knees, spine, and fingers. pathogenesis of OA involves the entire joint: cartilage, subchondral bone, and soft tissues, including the synovium. cartilage integrity lost by biomechanical stress; but genetics can contribute.

64
Q

Describe the images and the notable findings of osteoarthritis pre-mortem

A

radiograph of right hand: osteophyte formation, joint space narrowing, supchondral sclerosis
radiograph of right knee: advanced tricompartmental OA with joint space narrowing and osteophyte formation
radiograph of lumbar spine: multilevel degenerative changes characterized by disc space narrowing

65
Q

What are bisphosphonates?

A

group of drugs used to treat bone problems, called osteopenia or osteoporosis, conditions associated with thin or fragile bones at increased risk for fracture.
medications for low bone density or with a history of fragility bone fractures in the hip, arm, wrist or spine.
Oral: Alendronate (Fosamax), risedronate (Actonel), and ibandronate (Boniva)
IV: Pamidronate, ibandronate and zoledronic acid (Reclast/Zometa)

66
Q

Define osteoporosis.

A

bone disease that develops when bone mineral density and bone mass decreases, or when the structure and strength of bone changes. Typically, due to an imbalance of bone forming osteoblasts and bone resorbing osteoclasts

67
Q

How do bisphosphates function in order to treat osteoporosis?

A

inhibit osteoclastic bone resorption. attach to hydroxyapatite binding sites on bony surfaces, especially surfaces undergoing active resorption. When osteoclasts begin to resorb bone that is impregnated with bisphosphonate, the bisphosphonate released
during resorption impairs the ability of the osteoclasts to form the ruffled border, to adhere to the bony surface, and to produce the protons necessary for continued bone resorption. Bisphosphonates also reduce osteoclast activity by decreasing osteoclast progenitor development and recruitment and by promoting osteoclast apoptosis.

68
Q

Describe Bone Remodeling.

A
69
Q

How does one explain an increase in atypical bone fractures as a result of long-term bisphosphonate treatment?

A

Microfractures repaired by targeted bone remodeling are not able to be repaired efficiently by osteoclasts so they accumulate

70
Q

Describe the images and the notable findings of osteoarthritis post-mortem

A

intervertebral disc: narrowing of joint space, osteophytes
histology: loss of proteoglycans from hyaline cartilage = decreased metachromatic staining, chondrocytes die leaving empty lacunae

Human Histology (6 decks)

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