Histopathology and biochemistry Flashcards
(72 cards)
1
Q
What are the functions of bone?
A
mechanical - support an d site of muscle attachment
protective - of vital organs and bone marrow
metabolic - calcium reserve
2
Q
Describe the composition of bone
A
INORGANIC – 65%
- Calcium hydroxyapatite - A store house for 99% of Ca in the body
- 85% of the phosphorous, 65% Na & Mg
ORGANIC – 35%
- Bone cells and protein matrix (collagen, osteoid)
3
Q
Where does bone grow from?
A
epiphyseal line - growth plate
4
Q
What is the area beneath the growth plate called?
A
metaphysis
5
Q
What are the different parts of bone?
A
epiphysis, metaphysis and diaphysis
6
Q
What is the connective tissue lining the cavity of bone?
A
endosteum
7
Q
What happens when the periosteal surface is damaged and why?
A
The blood supply is cut off and bone becomes necrotic as blood supply comes through the periosteum.
8
Q
What are the two types of bone?
A
cortical and cancellous (spongy, trabecular)
9
Q
Where is cortical bone found, what % of the skeleton is cortical, appendicular or axial, what % is calcified and what is its role?
A
- Long bones
- 80% of skeleton
- Appendicular
- 80-90% calcified
- Mainly mechanical and protective
10
Q
Where is cancellous bone found, what % of the skeleton is cancellous, appendicular or axial, what % is calcified and what is its role?
A
- Vertebrae & pelvis
- 20% of skeleton
- Axial
- 15-25% calcified
- Mainly metabolic function
- Large surface
IN BONE MARROW
11
Q
How is bone arranged?
A
in concentric lamellae
12
Q
Where do blood vessel travel through the bone in?
A
Blood vessels travel through and across the bone in Haversian canals. Vessels come into the periosteum and travel up, down and across the bone.
13
Q
What are the indications for bone biospy?
A
- Evaluate 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
14
Q
What are the two types of bone biopsy?
A
CLOSED – needle, core biopsy (Jamshidi needle)
OPEN – for sclerotic or inaccessible lesions (requires general anaesthetic)
15
Q
What are the types of anatomical bones?
A
flat, long, short/cuboid, irregular and sesamoid
16
Q
What are the names for mature and immature bone?
A
mature - lamellar
immature - woven
17
Q
What is the histology of the femoral head?
A
Bone is organised with cartilage on the surface between the two articular surfaces. Trabecular bone is on the inside, with cortical bone on the outside (thick, dense bone).
18
Q
Describe the histology of the shaft of a long bone
A
You can see the periosteum where the blood vessel is delivered. The thick cortical bone can be seen, as well as the marrow (where trabecular bone will be).
19
Q
Describe the histology of the articular surface
A
This is the cartilage, the subchondral bone and trabecular bone on the inside of the marrow.
20
Q
What is RANKL?
A
Receptor Activator for nuclear factor kappa b
21
Q
What is OPG?
A
Osteoprotegerin - inhibits RANK/RANKL binding inhibits RANK/RANKL binding and therefore inhibits osteoclastogenesis.
22
Q
What upregulates RANKL?
A
In response to many stimuli (e.g. infection, trauma etc.)
23
Q
What cane compete with RANKL and what does this do?
A
OPG competes with RANK for RANK-L and switches off osteoclastogenesis
24
Q
What happens after menopause to OPG?
A
Oestrogen levels fall, OPG levels fall -> more resorption. Oestrogen is one of the main instigators for the formation of OPG.
25
What is the significance of reversal lines in lamellar bone?
Lamellae are the lines that form in response to gravity. When bone is remodelled (when it is built on or resorbed), it leaves a tidemark called a reversal line.
This allows pathologists to see changes and processes that have gone on in the bone
26
Describe the skeletal role of bone
- Lightweight frame that protects vital organs
- It is very mobile
- It can grow and remodel
- It is very strong for its size
27
Explain the bone remodelling cycle
- Osteoclasts are involved in bone resorption: they ‘eat up’ bone -> calcium release into the bloodstream
- Osteoblasts build up bone -> increases calcium storage in bones
- Osteoclasts and osteoblasts are constantly working together and there is a homeostatic balance
- Bones will atrophy if they are not used
- There hormones to communicate with osteoclasts and osteoblasts
28
What is the normal calcium range?
2.20mM to 2.6mM
29
What happens if you are calcium deficient?
- If you are calcium deficient, the brain won’t function and you are essentially paralysed
- If calcium falls, nerve-muscle transmission will fail (Chvostek and Trousseau signs)
30
What happens if calcium levels fall?
Stimulates the parathyroid glands to release PTH:
- Acts in the kidney to activate the renal enzyme 1-alpha hydroxylase
- Causes bone resorption (osteoclast activation) to increase serum calcium
- PTH inhibits reabsorption of phosphate in the nephron, and stimulates resorption of calcium
31
What is the RANKL system?
- Receptor Activator of a Nuclear Factor Kappa
- PTH causes bone resorption through the RANK system
- The ligand on osteoblasts is RANK-L (RANK on the osteoclast)
- Binding causes activation and differentiation of osteoclasts
32
What is metabolic bone disease and what causes it?
- Disordered bone turnover
- It occurs due to imbalance of various chemicals in the body (vitamins, hormones, minerals etc.)
- The overall effect is reduced bone mass (osteopenia) often resulting in fractures with little or no trauma
- Patients present with bone pain and difficulty performing normal tasks
33
What are the three main categories of metabolic bone disease?
1. Related to endocrine abnormality (Vitamin D, Parathyroid hormone)
2. Non-endocrine (e.g. age-related osteoporosis)
3. Disuse osteopenia (results from the reduced use of bones e.g. in injury)
34
What causes secondary hyperparathyroidism and what does it lead to?
Vitamin D deficiency - rickets and malacia
35
What is osteoporosis?
Development of spaces -> decreased bone mass). Mineralisation is still normal in osteoporosis, there is just decreased bone mass.
36
What usually causes osteoporosis?
old age, post-menopausal changes, not using your bones will make you develop osteoporosis faster
37
What will a bone biopsy show in osteoporosis?
- 2/3 of bone is calcified and 1/3 is osteoid
| - ratio of calcium, phosphate and protein etc is the same
38
What causes osteomalacia?
Vit D deficiency, and lack of Vit D activation in renal failure, also liver failure, lack of sunlight, phytic acid
39
What is seen in osteomalacia?
Bone is demineralised
40
Which drugs or conditions can cause osteoporosis or osteomalacia?
Cushing's or taking steroid - osteoporosis
Drugs that stimulate vit D breakdown e.g. anticonvulsants
41
What can cause osteoporosis?
lack of exercise, disuse, lack of oestrogen, age, menopause
42
What does osteoporosis lead to? How is this different in men and women?
As time goes on and you age, the risk of having hip, spine or wrist fractures increases. There is a big jump upwards in women, because they lose a lot of bone at menopausal age (45-55). If they live long enough, they are more likely to fracture after menopause. This is the same for men, but they are older when it happens (they are protected, because they still have testosterone).
43
What is BMD?
Bone density used to predict fracture risk
- measured using DEXA scan
- definition of osteoporosis is based on this
44
What is a T score?
measured BMD - young adult mean BMD/young adult standard deviation (compares you to 25 year old), z score compares to person your age
45
What do the different T scores mean?
- Anything above -1 is normal (a score of 0 is the average 25 year old in the UK)
- Anything below -2.5 is osteoporosis
- Anywhere between -1 and -2.5 is osteopenia
46
What is osteomalacia and what can cause it?
- Defective bone mineralisation
- The bone is bendy and is mostly osteoid
- Can result from deficiency of vitamin D
- Can result from deficiency of phosphate (usually due to CKD)
47
What are the symptoms for osteomalacia?
- Bone pain/tenderness
- Fracture and microfracture
- Proximal weakness
- Bone deformity (e.g. tibia bowing in rickets)
48
What is the difference between osteomalacia and rickets?
- Rickets occurs in children, osteomalacia in adults
- Rickets occurs because in children, the epiphyses have not fused – so they start to bend
- This is why we see tibial bowing and wide wrists and ankles – these shapes stay with the patient for life
- Bones are still growing so there is permanent damage to the growth plates
49
Where is vitamin D obtained from? Does it have to be converted?
Which conditions put people at risk of vit D deficiency and why?
- You can get vitamin D from sunlight (skin) and the diet
- It is hydroxylated in kidney and liver.
- These processes are influenced by PTH
- You get vitamin D from oily fish and meat, but you can take it as supplement
- If you are malnourished, you are at risk of vitamin D deficiency
- If you have liver or kidney diseases, vitamin D cannot be converted into its biochemically active form
50
What is seen in children with rickets?
Expanded growth plates, bowing of legs (can detect calcium and vit D hence not seen much in UK)
51
What is vit D deficiency in osteomalacia associated with in an X ray?
horizontal fractures in Looser’s zones
52
What is tetracycline labelling used for?
We can detect and examine bone mineralisation in the living patient, by giving them tetracycline antibiotic, related to a fluorescent stain. You give a dose, then another 2 weeks later. You then take a bone biopsy from the iliac crest.
53
Why is tetracycline labelling not used in children?
This technique is contraindicated in children (they are bone-seeking and they turn the teeth black in children).
54
What causes hyperparathyroidism?
* Primarily due to a parathyroid adenoma (85-90%), chief cell hyperplasia
* Secondarily due to chronic renal deficiency, vitamin D deficiency
55
What happens in hyperparathyroidism?
- Increased Ca and PO4 excretion in urine (calcium hydroxyapatite is broken down into its constituents)
- Hypercalcaemia
- Hypophosphatemia
- Skeletal changes of osteitis fibrosa cystica if disease is allowed to progress
- 4 organs are directly or indirectly affected by PTH and between them control Ca metabolism: Parathyroid glands, bones, kidneys and proximal small intestine
56
What are the symptoms of hyperparathyroidism?
stones (renal calcium stones), bones (osteitis fibrosa cystica, bone resorption), abdominal groans (acute pancreatitis) and psychic moans (psychosis and depression)
57
What used to be the test for hyperparathyroidism?
| What caused this?
The test for suspected hyperparathyroidism used to be an x-ray of the hand. The hand would show small, brown cell tumours (lytic lesions) usually on the radial side of the digits and thumb.
Composed of osteoclast cells. Osteoclasts have become out of control (they are being induced to resorb bone -> form small brown tumours composed of groups of osteoclast cells on a background of fibrous tissue and blood).
58
What is renal osteodystrophy?
bone diseases related to CKD
1. Increased bone resorption (osteitis fibrosa cystica)
2. Osteomalacia
3. Osteosclerosis (osteoblasts aren’t working properly)
4. Growth retardation
5. Osteoporosis
59
What happens to phosphate and calcium levels in renal osteodystrophy?
What else happens?
* PO4 retention – hypophosphatemia
* Hypocalcaemia as a result of ↓ vitamin D
* Secondary hyperparathyroidism
* Metabolic acidosis
* Aluminium deposition
60
What happens in renal failure that causes renal osteodystrophy?
Renal failure -> less of the enzyme 1-alpha hydroxylase -> calcium levels fall
- This causes secondary hyperparathyroidism to try to increase Ca and reduce phosphate
- But the kidneys fail to excrete phosphate (they can’t) -> low calcium, high phosphate and high PTH
- The the PTH secretion becomes autonomous
- This is now tertiary hyperparathyroidism
- As the CKD progresses, renal osteodystrophy occurs, slow bone turnover due to lack of phosphate excretion which causes reduced calitriol and you become slightly acidotic -> this contributes to bone loss
61
How can renal osteodystrophy and osteomalacia be distinguished?
Low phosphate levels in RO
62
What is metastatic calcification in CKD?
Due to high levels of phosphate, the calcium-phosphate product can be found all over the body. This is found in odd places.
63
What is paget's disease?
A disorder of bone turnover
64
What are the three stages of paget's disease?
1. Osteolytic (osteoclast predominant stage)
2. Osteolytic-osteosclerotic (osteoblasts will try to build bone)
3. Quiescent osteosclerotic (there is disorganised, mineralised bone)
65
Describe the histology of paget's disease?
- Histologically, in the initial (osteolytic phase), you see the bone being remodelled in a disorganised way
- We see lots of osteoclast giant cells, and multinucleated osteoclasts
- Then the osteoblasts fight back and build bone
- We are left with a paving pattern – there are reversal lines where the bone is being remodelled
66
Who does paget's disease affect?
- Normally when patients are over the age of 40 (affects 3% of Caucasians > 55 year olds)
- Equal in males and females
- Rare in Asian and African populations
- Mono-ostotic cases (affects just one bone) only make up 15% (the remainder is polyostotic)
67
What causes paget's disease?
- Aetiology is unknown
- Familial cases show autosomal pattern of inheritance with incomplete penetrance – runs in families
- Mutation 5q35-qter – sequestosome 1 gene
- Parvomyxovirus type particles have been seen on EM in Pagetic bone
68
What areas are affected by paget's disease?
* Paget’s affects the skull quite often
* It also affects the vertebrae (particularly lower vertebrae)
* It also affects the long bones in the leg
69
What are the symptoms of paget's?
- Pain
- Microfractures
- Nerve compression (incl. Spinal N and cord)
- Skull changes may put medulla at risk
- Deafness – if affects region of temporal bone
- Haemodynamic changes (sometimes)
- Cardiac failure haemodynamic changes
- Hypercalcaemia
- Development of sarcoma in area of involvement
70
Why may paget's cause haemodynamic changes?
If paget's is extensive throughout the skeleton, and there is massive bone breakdown, then a lot of the CO can go into bones instead of around the body
71
What happens in paget's disease?
When may the condition be left alone and when is intervention needed?
Which enzyme is elevated?
- Bone has increased turnover
- Increased osteoblast and osteoclast activity in one bone – building up and breaking down, rapidly
- The problem is that bones get bigger and weaker as a consequence
- This seems to spread around the body and affect more and more bone
- High alkaline phosphatase (because they are making lots of osteoblast activity)
- Normal calcium handling
- If only a small number of bones are affected, you may not intervene
- If the tibia is affected, it will fracture, so drugs must be prescribed to slow down bone turnover
72
What happens to the tibia in paget's?
Bowing- this is because the bone becomes osteomalacic – it is not mineralising properly. Bone cannot respond to the gravitational forces appropriately. You can get Looser’s zone fractures. Most likely seen in older patients.
