Metabolic Bone Disease: Histopathology Flashcards
4 functions of bone?
STRUCTURE: Gives the body structure and shape
MECHANICAL: it provides attachments for muscle sites.
PROTECTIVE: It is protective, protects vital organs and bone marrow.
METABOLIC: Metabolically it acts as a reserve of calcium (the largest reserve in the body) and other minerals.
What % of bone is inorganic vs organisation?
INORGANIC - 65%
ORGANIC - 35%
What is the organic part of bone? (2)
bone cells and protein matrix
What is stored in the inorganic part of bone? (4)
calcium hydroxyapatite (Ca10(PO4)6(OH)2)
is storehouse for 99% of Calcium in the body
85% of the Phosphorus, 65% Sodium, Magnesium
condyles are …
the knuckle shaped regions on the articular cartilage surface.
the end region of the bone is called?
Epiphysis
All the main shaft is separated from the epiphysis by the….
epiphyseal line/metaphysis
What is the main shaft of the bone known as
Diaphysis
small depression or dip in the surface in the bone is known as the…
Fovea
. The main portion of the bone is the ….
diaphysis
main marrow cavity is known as the …
medulla
outside surface of the bone in the diaphysis is the….
periosteum
the cartilage structure known as the growth plate during growth is found at the ….
metaphysis
the region in long bones that contains the bulk of the trabecular or cancellous bone is the ….
metaphysis
Ends of a long bone are known as …
epiphysis
medulla which is filled with bone marrow is surrounded by X which is surrounded by Y
Cortical bone
Periosteum
Bone has to be X% mineralised to be seen on X-ray
50%
5 types of bone
Flat bones Long bones short/cuboid bones Irregular bones Sesamoid bones
Example of flat bones? Function of these bones?
cranial bones, or the ribs, generally protect internal organs
Example of Irregular bones? Function of these bones?
complex shape like the vertebrae or the pelvis. That allows them to protect a specific organ or set of organs.
Example of short/cuboid bones? Function of these bones?
like the carpals and tarsals, stabalise and facilitate movement
Example of Long bones? Function of these bones?
femur and tibia
support weight and facilitate movement
Example of Sesamoid bones? Function of these bones?
patella, protective
2 bone formations at the microscopic level?
immature woven bone or mature lamellar bone.
Structure of immature woven bone? (4)
When do you see this type of bone?
lamellae are absent. Collagen fibres are laid down in a disorganized fashion: such as states of high bone turnover(Pagets disease of bone, certain stages of fluoride treatment, tumours) not so tightly packed, random bundles
Structure of mature woven bone? (collagen laid down how?)
Cortical and cancellous bone are lamellar and this is particularly evident when viewed under polarised light
Collagen fibres are arranged in alternating orientations allowing for the highest density of collagen per unit of tissue
Macroscopic formation of bone? (2)
trabecular/cancellous/spongy
cortical/compact
What bones are cortical?
Long bones
What bones are cancellous?
vertebrae & pelvis
Majority of bones are cancellous or cortical?
Cortical
Cortical bones are [appendicular/axial]?
appendicular
Cancellous bones are [appendicular/axial]?
axial
% calcification of cancellous bones ?
15-25%
% calcification of cortical bones?
80-90%
Main function of cortical bone?
mainly structural, mechanical, and protective
Main function of cortical bone?
mainly metabolic
Which has higher surface area, cancellous or cortical bone?
Cancellous
4 types of lamellae of bone?
circumferential
interstitial
trabecular
Concentric
Where is circumferential lamellae
layered around the bone
Describe location of interstitial lamellae
Between osteons
Describe location of trabecular lamellae
do not surround a central channel but are organized into layers
what are the dendritic structures inside lamellae?
Osteocytes
Osteocytes are…
the dendritic structures inside lamellae
The circular regions in bone are known as?
Osteons
Osteons are centred around…
haversion canal
hversion canals are found…
in the centre of an osteon
How are the mechosensory functions of osteocytes possible?
eocytes are all connected through small channels
Why can you mature bone under polarised light but not immature
You can see mature lamellar bone by imaging it under polarised light but not immature woven bone as it is much more disorganised and the collagen is disorganised and therefore it is a lot weaker.
Purpose of the osteocytes?
determine where bone needs to be repaired and replaced and do it
Inside a aversion canal is?
Blood vessels
Woven bone can be found under what conditions? (3)
Woven bone is most often found in the developing skeleton as the cartilage scaffold is first converted to bone, but can also be found in states of rapid grow, or high bone turnover.
3 types of specialised bone cells?
Osteoclasts
Osteoblasts
Osteocytes
What do osteoclasts do?
multinuclear cells formed from haematopoietic stem cell lineage that remove and resorb bone.
What do osteoblasts do?
produce osteoids, which is mineralised to form new bone.
What do osteocytes do?
mechanosensory network embedded in mature bone to find where bone needs to be repaired and replaced.
Majority of bone cells are of which type?
Osteocytes
What signals an osteoclast to resorb bone and how
Osteocyte apoptosis as it releases RANKL
What molecule activates an osteoclast
RANKL and M-CSF
Describe bone remodelling (signalling to activate, resorption, and then new bone)
Osteocyte apoptosis signals the osteoclast to come over and resorb as it releases RANKL(igand) stimulating the osteoclast to come over and resorb the old and damaged bone. They then die and are replaced by reversal cells. Osteoblasts are signalled to come in by the reversal cells and they form new bone to the same level osteoclasts resorbed.
What do osteoblasts produce?
RANKL and M-CSF
Osteoblasts produce … (3)
RANKL M-CSF and OPG
what is OPG
decoy receptor for RANKL
Differentiate between osteocyte and osteoblast/osteoclast? in histology
Osteoblasts/clasts are more purply is histology
Differentiate between osteoblast/osteoclast?
Osteoclast are have many segments of nucleus
Osteoblasts once they’ve formed new bone can become ….
embedded in the bone and go on to become osteoclasts.
Why perform bone biopsies? (6)
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
2 types of bone biopsy?
Open - needle is inserted into bone, and pulled out with the core still in it allowing for histological examination (Jamshidi).
closed - less common, in cases of really hard osteosclerotic bone or inaccessible region or you just need a large sample of bone for some reason. This is under general anaesthesia and surgical.
Most location for a bone biopsy?
transiliac bone biopsy
Usual stain for bones?
H&E
Stain for mineralised and non-mineralised bone?
Masson Goldner trichrome stain
Stain for for bone turnover?
Tetracycline/calcein labelling - inject once, then wait, then inject again, biopsy, see distance between two layers of stain which is incorporated into the bone to see the turnover
Common metabolic bone diseases? (5)
Osteoporosis Osteomalacia/Rickets Primary hyperparathyroidism Renal osteodystrophy Paget’s disease
Causes of primary osteoporosis?
age, post-menopause
Causes of secondary osteoporosis?
drugs, systemic diseases
What is high turnover osteoporosis
high resorption and formation but resorption is higher
What is low turnover osteoporosis
low level of both but resorption is lower, or same level formation but resorption is lower
unmineralized osteoid suggests ….
high turnover
2 causes of osteomalacia
Deficiency of vitamin D
Deficiency of PO4
Osteomalacia is caused by?
Defective mineralisation of normally synthesised bone matrix, no sufficient available calcium (or in some cases Phosphate) to form the hydroxyapatite crystals necessary to mineralise bone
Looser’s zone fractures are common in X disease and Y area and due to….
Osteomalacia/in the hip
due to lack of mineralisation
What mineral is in bone mainly
Calcium hydroapatite
Osteomalacia symptoms?
bone pain/tenderness
fracture
proximal weakness
bone deformity
pathogenesis of hyperparathyroidism? (7 stages)
Excess PTH. Results in increased Ca absorption and phosphate excretion. Leads to hypercalcaemia and hypophosphataemia which leads to skeletal changes of osteitis fibrosa cystica – replacement of bone with fibrous cystlike tissues.
2 types of hyperparathyroidism? and examples of each?
Primary hyperparathyroidism: parathyroid adenoma (85-90%), or chief cell hyperplasia.
Secondary: chronic renal deficiency (kidney disease), or vitamin D production deficiency (due to kidney probs).
Symptoms for hyperparathyroidism and the pneumonic?
STONES (Ca oxalate renal stones)
BONES (osteitis fibrosa cystica, bone resorption)
ABDOMINAL GROANS (acute pancreatitis)
PSYCHIC MOANS (psychosis and depression)
4 organs in/directly affected by PTH?
Parathyroid glands
Bones
Kidneys
Proximal small intestine
In the late stages of hyperparathyroidism, extensive resorption causes XXX with reparative tissue called YYYY
lytic bone lesions
giant cell reparative granuloma
Brown tumours are found in what disease?
Hyperparathyroidism
Renal osteodystrophy comprises of…. (5)
all the skeletal changes resulting from chronic renal disease:
Increased bone resorption (osteitis fibrosa cystica) Osteomalacia Osteosclerosis Growth retardation Osteoporosis
3 stages of Paget’s disease:
- Osteolytic
- Osteolytic-osteosclerotic
- Quiescent osteosclerotic
Paget’s disease:
Age and ethnicity and gender - who is it more common in?
Onset > 40y (affects 3-8% Caucasians > 55y)
M>F
Rare in Asians and Africans
Cause of Paget’s?
Unknown, genetic link, previous bone injuries and some virus particles have been seen
Symptoms of Paget’s? (11)
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
