Musculoskeletal 1 - MBD Histopathology Flashcards
List the functions of bone
- Give structure to the body
- Sites for muscle attachment
- Protects vital organs and bone marrow
- Acts as a reserve of calcium and other minerals
Describe the composition of bone
65% inorganic
- Calcium hydroxyapatite
- Stores 99% calcium in the body
- 85% of the phosphorous, 65% sodium and magnesium
Organic 35%
- Bone cells and protein matrix
How can bone be classified?
- Anatomically (flat, long , short/cuboid, irregular, sesamoid)
- Macroscopic structure (trabecular, cancellous, spongy, cortical or contract)
- Microscopic structure (woven/lamellar)
Which bones are cortical?
- Long bones
- 80% skeleton
- Appendicular
- 80-90% calcified
- Mainly structural, mechanical and protective
Which bones are cancellous?
- Vertebrae and pelvis
- 20% of the skeleton
- Axial
- 15-25% calcified
- Mainly metabolic
- Large SA
List the bone cells and their function
- Osteoclasts (multinuclear cells that resorb/remove bone)
- Osteoblasts (produce osteoid to form new bone)
- Osteocytes (mechanosensory network embedded in mature bone)
Why are bone biosies performed?
- Confirm the diagnosis of a bone disorder
- Find the cause of or evaluate ongoing bone pain or
tenderness - Investigate an abnormality seen on X-ray
- For bone tumour diagnosis (benign vs malignant)
- To determine the cause of an unexplained infection
- To evaluate therapy performance
List the types of biopsy
- Closed (needle - core biopsy using Jamshidi needle)
- Open (for sclerotic/inaccessible lesions - open surgery)
List the types of histological stains
- H & E (used on decalcified bone)
- Masson - Goldner trichrome (mineralised bone is stained green, unmineralised bone orange, useful in patients with osteomalacia)
- Tetracycline/calcein labelling (measure rate of bone formation/ turnover)
What is metabolic bone disease?
- A group of diseases that cause reduced bone mass and reduced bone strength
- Due to imbalance of chemicals in the body (vitamins, hormones, minerals.ect)
- Causes altered bone cell activity, rate of mineralisation, or changes in bone structure
List the common metabolic bone diseases
- Osteoporosis
- Osteomalacia/rickets
- Primary hyperparathyroidism
- Renal osteodystrophy
- Pagets disease
How is osteoporosis defined?
- Bone density T-score of -2.5 or lower
- Standard deviations different from peak bone mass BMD
List the types of osteoporosis
- Primary (age/post-menopause only)
- Secondary (drugs/systemic disease)
- High turnover (both formation and resorption are increased, but resorption is higher than formation) vs low turnover (both formation and resorption are decreased, but formation is decreased more than resorption)
What is osteomalacia?
- Defective mineralisation of normally synthesised bone matrix
- Rickets in children
What are the two types of osteomalacia?
- Deficiency in vitamin D (vit D increases calcium renal reabsorption and intentinal absorption, and increases bone formation)
- Deficiency in PO4
List the sequelae of osteomalacia
- Bone pain/tenderness
- Fracture
- Proximal weakness
- Bone deformity (rickets in children - widening of growth plates and bowing of the legs)
List the characteristics of hyperparathyroidism
- Excess PTH
- Increased calcium and phosphate excretion in urine
- Hypercalcaemia
- Hypophosphataemia
- Skeletal changes of osteitis fibrosa cystica (brown tumour like cysts)
Which organs are afffected by PTH?
- Parathyroid glands
- Bones
- Kidneys
- Proximal small intestine
List the types of hyperparathroidism
- Primary (80% due to parathyroid adenoma, can be chief cell hyperplasia)
- Secondary (chronic renal or vit D deficiency)
List the consequences of hyperparathyroidism
- Stones (calcium oxalate renal stones)
- Bones (osteitis fibrosa cystica, bone resorption - occurs at a late stage of the disease)
- Abdominal groans (acute pancreatitis)
- Psychic moans (psychosis & depression)
What is renal osteodystrophy?
Comprises all the skeletal changes resulting from
chronic renal disease:-
- Increased bone resorption (osteitis fibrosa cystica)
- Osteomalacia
- Osteosclerosis (increase in bone mass)
- Growth retardation
- Osteoporosis
What is paget’s disease? List the three stages.
- Disorder of bone turnover
- Stage 1: osteolytic (breakdown)
- Stage 2: osteolytic-osteosclerotic (mixed)
- Stage 3: quiescent osteosclerotic
Describe the epidemiology of Paget’s disease
- Onset over 40 years (3-8% caucasians over 55)
- Males > females
- Rare in Asians and Africans
- Mono-ostotic 15%
- The remainder are polyostotic
List the causes of Pagets disease
- Aetiology unknown
- Overuse/ previous bone injury
- Familial causes show autosomal pattern of inheritence (pattern of inheritance with incomplete penetrance, mutations in RANK and SQSTM1)
- Parvomyxovirus type particles have been seen on EM
List the clinical symptoms of Pagets disease
- Pain
- Microfractures
- Nerve compression (incl. Spinal N and cord)
- Skull changes may put medulla at risk
- Deafness
- +/- Haemodynamic changes, cardiac failure
- Hypercalcaemia
- Development of sarcoma in area of involvement 1%
What is the metaphysis?
- Contains the growth plate, which allows linear growth of bone. This is where most trabecular bone is found.
- Connects the epiphysis to the diaphysis (shaft)
What is contained in the diaphysis?
- Medullary cavity
- Cortical bone around the outside
Which bones are flat? What is their function?
- Skull
- Protection
Which bones are long? What is their function?
- Fibia
- Strength, structure and mobility
Which bones are short/cuboid? What is their function?
- Carpals/tarsals
- Support and stability, little movement
Which bones are irregular? What is their function?
- Vertebrae/sacrum
- Protection
Which bones are sesamoid? What is their function?
- Patellar
- Modify pressure, diminish tension
Describe the cortical bone microanatomy.
- Parellel osteons
- Structured in circular layers surrounding the haversian canal
- Haversian canal contains blood vessels
- Periosteum contains circumferential lamellae, with interstital lamellae in between osteons
- In trabeculae, there are no oseons, it is instead in layers
- Osteocyte cannalicular network is throughout the bone
Where are bone biopsies typically taken?
- Transilliac bone biopsy
- Allows viewing of the cortical and trabecular bone easily
How does tetracycline labelling work?
- Injections produce fluorescent lines where bone mineralisation is taking place (incorporated into any osteoid currently being mineralised)
- Wait a few days and inject again
- Work out bone formation rate (overall bone formed between those two formations) and mineral apposition rate (distance between the two fluorescent lines)
Which type of bone is mainly affected by osteoporosis?
Trabecular bone - thinning of cortical bone as the disease progresses
Where do looser zone fractures occur?
- High tensile stress areas
- Occur in osteomalacia
What are the main histological signs of hyperparathyroidism?
- Centre of trabeculae are resorbed (tunneling resorption)
- Osteoclasts penetrate into the middle of the trabeculae and resorb the central channel
- Brown cell tumours (formed by giant cell reparative granulomas, fibrous tissue replaces bone)
Describe the histopathology in Pagets
- Resorption of trabeculae (active phase)
- Mosaic pattern of quiescent-sclerotic phase, as the osteoblasts produce lines throughout the lamellar bone while attempting to repair resorption
Describe the histology of woven bone
- No clear structure
- Irregular, no layers
- Most often found in the developing skeleton (initial bone laid down)
Describe histopathology of osteomalacia
- Decreased mineralised bone
- Masson Goldner trichrome stain
Describe the histopathology of osteoporosis
- Loss of trabeculae
- Thinner trabeculae
- Free floating trabeculae
