Histopathology

Question 1

What are the three main functions of bones?

Answer 1

Mechanical – support and site for muscle attachment, Protective(contains vital organs and bone marrow), Metabolic – reserve of calcium

Question 2

What are the two main components of bone and what are their relative proportions?

Answer 2

Inorganic (65%) – calcium hydroxyapatite (store of 99% of the body’s calcium, 85% of the phosphorous and 65% of Na and Mg) Organic (35%) – bone cells and protein matrix

Question 3

Describe the classification of bone as cortical and cancellous(Differennt macroscopic bone structure)

Answer 3

Cortical bulk of Long bones  80% of skeleton  Appendicular skeleton 80-90% calcified  Mainly mechanical and protective role

Cancellous bulk of complex bones like Vertebrae and pelvis  20% of skeleton  Axial 15-25% calcified  Mainly metabolic  Large surface

Question 4

What are the indications for bone biopsy?

Answer 4

Evaluate bone pain or tenderness. Investigate abnormality seen on X-ray .For bone tumour diagnosis. To determine the cause of unexplained infection To evaluate therapy.

Question 5

What are the two types of bone biopsy?

Answer 5

Closed – needle – core biopsy with Jamshidi needle . Open – for sclerotic or inaccessible lesions

Question 6

What are the three types of bone cell?

Answer 6

Osteoblast – build bone by laying down osteoid Osteoclast – multinucleate cells of the macrophage family that resorb bone Osteocyte- mechanosensory network,embedded in mature bone

Question 7

Where are osteocytes found?

Answer 7

Lacunae

Question 8

What cytokine is important for stimulating the differentiation of osteoclast precursors into pre-osteoclasts?

Answer 8

M-CSF (this is produced by osteoblasts)

Question 9

Which cells produce RANKL and what is its effect?

Answer 9

Pre-osteoblasts It stimulates the maturation of osteoclasts

Question 10

What do mature osteoblasts produce that blocks the RANK/RANKL binding?

Answer 10

Osteoprotegrin

Question 11

How are bones classified anatomically?

Answer 11

Flat Long Cuboid/sohrt, irregular and ssamoid

Question 12

What type of ossification leads to the formation of: a. Long Bones b. Flat Bones

Answer 12

a. Long bones Endochondral ossification b. Flat bones Intramembranous ossification

Question 13

Other than the anatomical classificaton , according to shape, ho else can bones be classified

Answer 13

Trabecular (cancellous) or compact (cortical)[Different macroscopic bone structures] ,Woven (immature) or lamellar (mature)[Different microscopic bone structures]

Question 14

What is metabolic bone disease?

Answer 14

it’s a group of diseases that in general cause reduced bone mass and strength due to an imbalance of various chemicals in the body be they vitamins, hormones, minerals, or whatever.•Cause altered bone cell activity, rate of mineralisation, or changes in bone structure

Question 15

Recall Common metabolic bone diseases

Answer 15

.•Osteoporosis

• Osteomalacia/Rickets
• Primary hyperparathyroidism
• Renal osteodystrophy
• Paget’s disease

Question 16

Describe the staining of calcified and uncalcified bone in Masson-Trichrome stain.

Answer 16

Calcified – green Uncalcified – orange

Question 17

What are the primary causes of osteoporosis?

Answer 17

Age Post-menopause

Question 18

What are the secondary causes of osteoporosis?

Answer 18

Drugs Systemic disease

Question 19

Describe the histology and parthophysiology of osteoporotic bone.

Answer 19

Trabecular bone :Weak trabecular bridging ,Holes and cysts and thinning of bone(affects trabecular bone to most because it is the most metabolically active)

Cortical bone: thining, and there will be low impact fragility fractures in the long bones.

there is an imbalance in bone remodelling meaning there is more resorbtion than formation

Question 20

What is osteomalacia and what can it be caused by?

Answer 20

Condition of defective bone mineralisation that can be caused by: Vitamin D deficiency, Phosphate deficiency (usually related to chronic renal disease).

In osteomalacia there is no sufficient available calcium (or as I mentioned in some cases Phosphate) to form the hydroxyapatite crystals necessary to mineralise bone.

Question 21

What are the metabolic and endocrine consequences of vitamin D deficiency?

Answer 21

Secondary hyperparathyroidism –> increased bone resorption Hypocalcaemia – neuronal excitability causing muscle twitching, spasms, tingling and numbness

Question 22

Describe the histology of osteomalacia.

Answer 22

No calcification of bone More uncalcified osteoid Bones are very bendy and cannot carry musculature very easily

Question 23

What are the clinical consequences of osteomalacia?

Answer 23

Bone pain/tenderness, Fracture (horizontal fractures at Looser’s zone at the neck of the femur are commonly seen) ,Proximal weakness ,Bone deformity

Question 24

What is used to investigate mineralisation?

Answer 24

Fluorescent tetracycline labelling

Question 25

What are the consequences of hyperparathyroidism to the blood and to the bone

Answer 25

Hypercalcaemia (increased Ca2+ reabsorption) Hypophosphataemia (increased phosphate excretion in the urine) Osteitis fibrosa cystica (due to increased osteoclast activity-Resorption of bone and replacement with fibrous tissue and the formation of cysts like ‘brown tumours.)

Question 26

List the four organs that are directly or indirectly affected by parathyroid hormone to control calcium metabolism.

Answer 26

Parathyroid glands Bones Kidneys Proximal small intestine

Question 27

State some causes of primary hyperparathyroidism.

Answer 27

Parathyroid adenoma Chief cell hyperplasia

Question 28

State some causes of secondary hyperparathyroidism.

Answer 28

Chronic renal insufficiency Vitamin D deficiency

Question 29

What are the symptoms of hyperparathyroidism?

Answer 29

Stones, Bones, Abdominal Groans and Psychic Moans. Stones – calcium oxalate renal stones .Bones – osteitis fibrosa cystica .Abdominal Groans – acute pancreatitis. Psychic Moans – psychosis and depression.

Question 30

What is the most important investigation for hyperparathyroidism and what will it show in someone with hyperparathyroidism?

Answer 30

X-ray of the hand .Subperiosteal bone erosions. Brown cell tumours – small areas of resorption in the long bones of the fingers that are filled with osteoclasts

Question 31

What is renal osteodystrophy to the bone?

Answer 31

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

Question 32

What are the consequences of renal osteodystrophy to the blood and endocrine system.

Answer 32

Hyperphosphataemia ,Hypocalcaemia as a result of a decrease in vitamin D metabolism ,Secondary hyperparathyroidism ,Metabolic acidosis ,Aluminium deposition

Question 33

What is Paget’s disease?

Answer 33

Disorder of bone turnover (there is a lack of proper communication between the cells)

Question 34

What are the three stages of Paget’s disease?

Answer 34

Osteolytic Osteolytic-osteosclerotic Quiescent osteosclerotic

Question 35

Describe the histology of Paget’s disease.

Answer 35

Prominent reversal lines Masses of osteoclasts in the same site as osteoblasts

Question 36

In which ethnicities is Paget’s disease rare?

Answer 36

Asian African

Question 37

Which sites does Paget’s disease most commonly affect?

Answer 37

Skull ,Sternum, Spine, Humerus, Pelvis, Femur, Tibia

Question 38

List some clinical features of Paget’s disease.

Answer 38

Pain Microfractures, Nerve compression ,Skull changes, Deafness ,Haemodynamic changes, Cardiac failure, Hypercalcaemias, Development of sarcoma in the area of involvement

Question 39

What is a Haversian canal?

Answer 39

Channel that blood vessels run in within bone

Question 40

What are Howship’s Lacunae?

Answer 40

Pits in the bone surface where osteoclasts are found (also called resorption bays)

Question 42

Describe structures you would find at articular surfaces

Answer 42

end of a long bone has an articular surface at a synovial joint. Smaller articular surfaces may be called facet joints or fovea. If they are knuckle shaped they are Condyles, and a trochlea is grooved like a pully

Fovea refers to a small depression or dip in the surface, such as on the femoral head where the fovea serves as a ligament attachment point.

Question 43

Describe the bone organisation and compositoin (leave out articular surfaces) add image

Answer 43

In diaphysis, there will be the main marrow cavity or medulla(contains bone marrow), surrounded on both sides by cortical bone in the cortex with the periosteum on the outside. Metapyhsis during growth will contain the cartilage structure known as the growth plate and is the region in long bones that contains the bulk of the trabecular or cancellous bone.

Question 44

Microsopic stucture of cortical bone

Answer 44

This is lamellar bone.. Cortical bone is made up of parallel osteons. Each circular structure shown here is an individual osteon of about 0.2mm diameter,surrounding a central canal called the haversian canal which contains the blood vessels.

At the periosteum there are circumfrential lamellae that go around the whole bone, there are interstillial lamellae between the osteons, and there is trabecular lamellae which do not surround a central channel but are organized into layers. You can see these dendritic structures found in lacunae in the lamellae. Those are bone cells called osteocytes and the processes from them are the osteocyte canalicular network that spans throughout the bone and is thought to form a mechanosensory network allowing the repair of damaged bone or remodeling of structure to respond to new stresses being place on a bone.

Question 45

Structure and features of woven bone

Answer 45

Features : Weak < Find in high turnover states

Structure : Disorganised and not in organised lamellar structure

Found in : developing sekeleton

Question 46

Explain how we look at histological samples

Answer 46

Well in the majority of cases it will be simply by using H & E staining on decalcified samples. But there may be reasons to use more complex stains on calcified samples requiring histology labs that are specifically set up to perform them. These include Masson-Golder Trichrome staining to look at the amount of mineralised vs unmineralised bone. And tetracycline labelling to allow dynamic histomorphometry to measure the rates of bone formation and turnover

Question 47

Deifne osteoporosis

Answer 47

•Defined as a bone mineral density T-score of -2.5 or lower

–Standard deviations different from mean peak bone mass BMD

Question 48

What does vitamin Ddo innormal physiology

Answer 48

Well Vitamin D plays an integral role in calcium metabolism. We get vitamin D from sunlight exposure and in our diets. Activated Vitamin D acts to increase Calcium absorbtion in the intestine and re-absorbtion in the kidneys so increasing serum calcium levels.

Question 49

What are the two common outcomes of osteomalacia

Answer 49

In children the inability to properly mineralise bone results in rickets with the characteristic widening of the growth plate and bowing of the long bones shown in this x-ray.

Another common outcome is Looser’s zone fractrues. These are pseudo-fractures at locations of high tensile stress, normally at right angles to the cortex and extending only part way through the bone.

Question 50

What does this image show, what specific group of people is this for

Answer 50

Osteomalacia (rickets)

In children the inability to properly mineralise bone results in rickets with the characteristic widening of the growth plate and bowing of the long bones shown in this x-ray.

Question 51

Explain Renal Osteodystrophy

Answer 51

This is because of a failure to excrete phosphate and produce vitamin D. Secondary hyperparathyroidism may result to attempt to compensate leading to the signs of osteitis fibrosa cystica. Osteomalacia may be observed due to hypocalcemia, and there may also be osteoscelerosis, growth retardation or osteopososis apparent.