Receptor Activator for Nuclear factor Kappa B found on osteoclast precursors in response to stimulation via. M-CSF deals with osteoclast activation & differentiation

MBD - Histopathology Flashcards by Rama Jha

Function of bone?

STRUCTURE
• gives structure & shape to body

MECHANICAL
• support & muscles attachment

PROTECTIVE
• vital organs & marrow

METABOLIC
• Ca2+ reserve (and other minerals)

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Composition of bone?

INORGANIC - 75%
• calcium hydroxyapatite
• storehouse of 99% of body Ca2+
• 85% phosphorous, 65% Na, Mg

ORGANIC - 35%
• bone cells & protein matrix

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Bone geography?

Epiphysis
• articular cartilage
• subchondral bone
• epiphyseal line

Metaphysis

Diaphysis (shaft)
• medulla
• cortex
• periosteum

ONENOTE FOR IMAGE!!

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How are the different bone types classified?

ANATOMICAL BONES
• flat, long, short/cuboid, irregular, sesamoid

MACROSCOPIC STRUCTURE
• trabecular/cancellous/spongy
• cortical/compact

MICROSCOPIC STRUCTURE
• woven bone (immature)
• lamellar bone (mature)

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Bone type classification - Macroscopic structure?

CORTICAL
 • long bones
 • 80% of skeleton
 • appendicular
 • 80-90% calcified
 • mainly structural/mechanical/protective

CANCELLOUS
 • vertebrae/pelvis
 • 20% of skeleton
 • axial
 • 15-25% calcified
 • mainly metabolic
 • large SA
 • TRABECULAR bone is avascular

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Cortical bone microanatomy?

Haversian canals = vertical in diagram

Volkmann’s canals = horizontal in diagram

Lacunae left by osteoclasts are called ‘Howship’s lacunae’

ONENOTE for diagram

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What are the indications to carry out a bone biopsy?

Evaluate bone pain
Investigate x-ray abnormalities e.g. brown lesions
Bone tumour diagnosis
Cause of unexplained infection
Evaluate medical therapy

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Type of bone biopsies?

CLOSED
• Jamshidi needle, core biopsies - taken from ASIC (anterior superior iliac crest)

OPEN
• for sclerotic or inaccessible lesions

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3 types of bone cells?

OSTEOBLASTS
• build bone & lay down osteoid
• surface osteoblasts go on to form osteoclasts

OSTEOCLASTS
• multinucleate
• resorb/remove bone

OSTEOCYTES
• mechansensory network embedded in mature bone
• osteoblast-like cells which sit in lacunae

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What is RANK?

Receptor Activator for Nuclear factor Kappa B

found on osteoclast precursors in response to stimulation via. M-CSF
deals with osteoclast activation & differentiation

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What is OPG?

Osteoprotegerin
• inhibits RANK/RANKL binding
SO
• inhibits osteoclastogenesis

It is a competitive inhibitor of RANK

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Anatomical classification for bone types?

Long, flat, cuboid

Intramembranous ossification for flat bones
Endochondral ossification for long bones (NOT clavicle)

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Functional classification for bone types?

TRABECULAR bone
• cancellous bone

COMPACT bone
• cortical bone

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Architectural classification for bone types?

WOVEN bone
• immature
• only physiological in fracture healing & at bast of teeth

LAMELLAR bone
• mature
• Trabecular lamellar bone can show ‘reversal lines
which indicate previous formation lines

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Define MBD

Disorder of bone turnover due to imbalances of chemicals in the body

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What is MBD?

Group of diseases that cause REDUCED bone mass & bone strength
• due to imbalance of various chemicals in the body (vits, hormones, minerals etc.)

Causes
 • altered bone cell activity
 • rate of mineralisation
OR
 • changes in bone structure

What is reduced bone mass called?

Osteopenia

Common MBDs?

Osteoporosis
Osteromalacia/rickets
1o hyperparathyrpidism
Renal osteodystrohpy
Paget's disease

3 main categories of MBD?

Endocrine abnormalities
e.g. VitD, PTH

Non-endocrine
• e.g. age-related osteoporosis

Disuse osteopenia
• e.g. astronauts in space

Osteoporosis definition?

Defined as a BMD T-score of

Osteomalacia definition?

Defective bone mineralisation of normally synthesised bone matrix
• rickets in children

Effectively 2 types:
• Deficiency of VitD
OR
• Deficiency of PO4

Role of Vit D in osteomalacia?

VitD plays an imp. role in PTH secretion

• VitD deficiency stimulates release of PTH
AND
• subsequent bone resorption

Most common cause of hypocalcaemia?

VitD deficiency

How can low blood Ca2+ manifest?

Muscle spasms
Twitches
Tingling
Numbness

Features of osteomalacia?

• Sequelae (condition which is the consequence of a previous disease or injury) * bone pain/tenderness * fractures e.g. horizontal fractures in Looser's zone * Proximal myopathy * Bone deformity e.g. bowing in rickets

Define hyperparathyroidism?

Excess PTH

Features of hyperparathyroidism?

* Increased Ca2+ & PO4 excretion in urine * Hypercalcaemia * Hypophosphatemia • OSTEITIS FIBROSA CYSTICA (skeletal changes including brown tumours & kidney stones)

Organs involved in hyperparathyroidism?

``` Directly/indirectly affected by PTH & between them control Ca2+ metabolism • parathyroid glands • bones • kidneys • proximal SI ```

1o & 2o hyperparathyroidism?

1o = parathyroid adenoma • 85-90% • results in chief cell hyperplasia 2o = chronic renal deficiency • resulting in vitD deficiency

Mnemonic to remember features of hyperparathyroidism?

SBAP Stones • Ca oxalate renal stones Bones • osteitis fibrosa cystica • bone resorption Abdominal groans • acute pancreatitis Psychic moans • psychosis & depression

Define renal osteodystrophy?

Comprises ALL the skeletal changes resulting from CHRONIC RENAL DISEASE

What are the skeletal changes resulting from CRD as shown by renal osteodystrophy?

* Increased bone resorption (osteitis fibrosa cystica) * Osteomalacia * Osteosclerosis * Growth retardation * Osteoporosis

Features of renal osteodystrophy?

• PO4 retention/hyperpohsphataemia • Hypocalcaemia - because of low VitD • 2o hyperparathyroidism - low Ca2+ due to low VitD so reflex hyperparathyroidism * Metabolic acidosis * Aluminium deposition

Define Paget's disease?

Disorder of bone turnover The formation breakdown leads to a mosaic effect in the bone

How is Paget's disease divided?

Divided into 3 stages: 1. Osteolytic 2. Osteolytic - osteosclerotic (bone formation) 3. Quiescent osteosclerotic (quiescent stage)

Who does Paget's disease normally effect?

* Onset >40year * Affects more males than females * Rare in asians & africans * Only affects one bone in 15% - mono-ostotic (most are poly-ostotic)

Aetiology of Paget's Disease?

Mainly unknown Familial cases - autosomal mutation in SQSTM1 or RANK Parvomyxovirus found in Pagetic bone Overuse of previous bone injury

Clinical symptoms of Paget's Disease?

o Pain o Micro fractures and bowing of tibia o Nerve compression o Skull changes may put the medulla at risk o Deafness o Haemodynamic changes and possible cardiac failure o Hypercalcaemia o Development of sarcoma (in area of involvement)