Pathology Flashcards
What does bone act as a reservoir for?
Calcium
Hypocalcaemia stimulates the parathyroid glands to produce ____1_____ which promotes _______2_______ As the serum calcium rises PTH production is ____3______
1) parathyroid hormone
2) bone resorption, calcium absorption from the gut and reabsorption of calcium from the kidney
3) switched off
Define arthritis
wide range of disorders causing pain and inflammation in joint
What is the most common disorder of joints?
Osteoarthritis
Describe the two groups of osteoarthritis
Secondary- clear association with some predisposing condition which may be virtually any abnormality of a joint e.g. injury or abnormal stresses. This type often affects a single joint.
Primary- no obvious predisposing cause but often runs in family. More generalised.
Describe early pathological changes in osteoarthritis
Chondrocytes are injured and proliferate replacing the specialised matrix resulting in the matrix becoming softer .
Then get flaking and fibrillation of the surface.
Describe later pathological changes in osteoarthritis
Cartilage is completely worn away – bone on bone
Subchondral cysts
Surface becomes “polished” – eburnation
Remodeling to cope with stress
Formation of osteophytes- outgrowth of irregular bone
Explain radiological appearance of osteoarthritis
Loss of joint space = Cartilage loss
Subchondral sclerosis = Eburnation
Subchondral cysts = Synovial fluid accumulation
Osteophytes = Disorganised bone remodelling
What is rheumatoid arthritis?
A common systemic chronic inflammatory disease that is auto-immune.
Early pathological changes of rheumatoid arthritis?
signs of inflammation and swelling over joints
swollen inflamed synovium
will see fibrinous exudate, villiform hyperplasia and intense infiltration with lymphocytes and plasma cells
Intermediate pathological changes of rheumatoid arthritis?
joints are swollen and marked muscle wasting
laxity (loose) of capsule and soft tissue inflammation in periarticular tissues.
Destructino of cartilage by enzymatic action and granulation tissue spreading over the articular surface (pannus- abnormal layer of granulation tissue)
What is pannus?
Abnormal layer of granulation tissue
Late pathological changes of rheumatoid arthritis?
Severely distorted joint and permanent deformity due to contracture and often subluxation
Inflammation is usually less marked- fibrous adhesions across the joint may be irregular bony union
Describe extra-articular manifestations of rheumatoid arthritis?
Loads- rheumatoid nodules big one
What are the seronegative spondyloarthritides
Group of rheumatological disorders with some common features:
ankylosing spondylitis
psoriatic arthritis
IBD arthritis
Ankylosing spondylitis is an arthritis affecting particularly the _____1______ but peripheral arthritis is also seen. `The disorder is like Rheumatoid arthritis but differs in that it causes ____2_____
1) sacroiliac, costovertebral and vertebral joints
2) osseous ankylosis (bony union) so that no movement of the affected joints is possible
Describe enteritis associated arthritis
Auto-immune associated reaction to infection or organisms with high LPS trigger an immune response causing the arthritis
Describe psoriatic arthritis
10% patients with psoriasis Predominantly affects joints of hands and feet 20% cases involve sacro-iliac joints Joint involvement may be asymmetrical DIP joints characteristically affected Similar histology to RA
Why is history and examination important when diagnosing an arthritis?
Histologically they all look almost the same
Describe infectious arthritis
Potentially destructive process
Suppurative
Haematogenous spread of organisms
S aureus in adults (H influenza in young children)
Gonococcal infection in young adults
Sickle cell predisposes to Salmonella arthritis
Typically involves single joint (knee most common)
Systemic features of infection
Acutely painful & swollen joint ; Aspirate purulent fluid
Mycobacterial, Lyme disease, Viral
What are the crystal arthropathies?
Crystal arthropathy is a class of joint disorder (called arthropathy) that is characterized by accumulation of tiny crystals in one or more joints.
Gout – urate metabolism
Pseudo-gout – calcium pyrophosphate
What two things do you need for gout?
Increased production of uric acid and decreased excretion
Causes of gout?
INCREASED PRODUCTION Usually idiopathic Unkown enzyme defect (90%) Known enzyme defect - HGPRT deficiency Lesch Nyhan syndrome – rare Impairs purine nucleotide salvage pathway Degraded to urate Increased cell turnover Psoriasis, Cancer and tumour lysis following chemotherapy
REDUCED EXCRETION Under- excretion A common cause of gout Chronic renal disease Drug side effect thiazide diuretics reduce urate excretion
Pathological findings of gout?
Cytology
Joint fluid examined under cross-polarized light to detect needle shaped crystals.
Histology (tophus)
Amorphous eosinophilic debris and inflammation (giant cells)
Crystals lost during tissue processing
NB – pyrophosphate arthropathy
Causes of pseudo gout?
Usually idiopathic
May be known cause – hypercalcaemia (inc. hyperparathyroidism), haemachromatosis, hypomagnesaemia, ochronsis, hypothyroidism
What will you see on X-ray in pseudo gout?
dense deposits
Pseudogout is often ______ and found incidentally on ______
asymptomatic
x-ray
What is osteoporosis characterised by?
Low bone mass
Microarchitectural deterioration of bone with an increase in bone fragility and susceptibility to fracture
Define osteoporosis and osteopenia?
Osteopenia 1-2.5 SD below mean peak bone mass
Osteoporosis >2.5 SD below mean peak bone mass
When does osteoporosis become more common?
It becomes more common with increasing age and is more common in women especially after menopause
When is peak bone mass?
Young adult hood (20s) thereafter bone mass decreases. A high peak bone mass makes osteoporosis less likely.
When would you get localised osteoporosis?
Commonly due to disuse and is seen as a complication of other disorders such as immobilisation following a fracture, limb paralysis adjacent to severe joint disease with limitation of movement.
What is cause of osteomalacia and rickets? What does this result in?
Disorders of bone due to failure of mineralisation of newly formed osteoid caused almost always by deficiency of vitamin D. The poorly calcified bones are soft causing deformity or fracture as calcium cannot be absorbed as well from the gut with low Vit D.
Describe what happens in osteomalacia?
Occurs in adult life and affects the osteoid (the unmineralised organic component of bone) which is continually laid down in normal remodelling of the bone.
Even when PTH raises calcium levels back to normal in osteomalacia why is bone still soft?
Reducing renal calcium lost increases renal excretion of phosphate and low phosphate also impairs bone mineralisation.
What causes avascular necrosis? Where and when does this tend to happen?
Interruption of bone blood supply causes the bone to undergo necrosis. This tends to occur with fracture sites where the vascular supply is damaged.
What places are more prone to avascular necrosis when fractured? Why?
Fracture of neck of femur
Scaphoid fracture
Humerus fracture
Due to blood supply often end arteries
What are you at increase risk of with avascular necrosis? Why?
Secondary osteoarthritis as the dead tissue often collapses and then prone to OA as ball doesn’t fit the socket.
Name some predisposing conditions to avascular necrosis
Alcohol Corticosteroids, Bisphosphonates Connective tissue disorders Decompression (the bends) Sickle cell disease Infection, Pregnancy Pancreatitis Radiation
Why may bone changes be seen in hyperparathyroidism?
There is increased bone resorption due to PTH-induced osteoclastic activity. Due to coupling osteoblastic activity is also increased but the net effect is bone loss.
Explain what a brown tumour is?
It is tumour found in hyperparathyroidism that mimics a giant cell tumour. It is due to haemorrhage initiating a macrophage reaction.
What must you do if you see lots of giant cells in a bone tumour?
Check serum calcium as it may be a brown tumour associated with hyperparathyroidism
What is Paget’s disease?
A disease that causes abnormal bone turnover with unknown aetiology.
What bones are particularly affected by Paget’s disease?
Pelvis, vertebrae, skull and lower limbs
Describe the pathological stages of Paget’s disease
Three stages Osteolytic Resorption pits with large osteoclasts Mixed Osteoclasis and osteoblastic activity Osteosclerotic. Net result is thick excess bone with abnormal reversal lines – mosaic pattern Bone matures but is soft and porous
Clinical features of Paget’s disease?
Often asymptomatic- large proportion of population may have it and not know about it. Can cause bone pain and deformity, pathological fracture, osteoarthritis, nerve compression and 30x risk of developing bone sarcoma.
Describe a ganglion cyst
These occur around synovial joints (often the wrist) or around a synovial tendon sheath.
The weakness may be developmental or as a result of underlying joint damage
Example is a Baker’s cyst (swelling in the popliteal fossa)
They are usually well defined and may be quite firm and readily transilluminate
Excision may be required for localised discomfort
Describe nodular fasciitis
Between a reactive process and a benign tumour
Self limiting benign soft tissue lesion caused by cellular proliferation of fibroblastic and myofibroblastic cells
Tends to occur in young adults and on the upper body
Rapidly growing tumour with genetic abnormalities but lacks key features for it to become cancerous
Describe fibromatoses
Between a reactive process and a benign tumour
Can be superficial or deep
Large infiltrative masses that do not metastasise
What is Dupuytrens contracture an example of?
Superficial fibromatoses
Name for benign smooth muscle tumour?
Leiomyoma e.g. uterine fibroids
Name for benign skeletal muscle tumour? How common?
Rhabdomyoma
Very rare
What is the most common benign soft tissue tumour?
Lipoma
Describe lipomas?
Common benign tumour of fat. Most often found in the subcutaneous tissues of the back, shoulder and neck
Lipomas must be superficialities to be benign. Location is very important. In superficial atypical lipomas are classed benign but if they are deep they are liposarcomas.
What is the most common benign bone tumour?
Osteochondroma
What type of tumour produces a bony outgrowth on the external surface with a cartilaginous cap?
Osteochondroma
Name 3 benign bone tumours that may be asymptomatic?
osteochondroma, endchondromas and simple bone cyst
If multiple osteochondroma patient probably has?
Autosomal dominant hereditary disorder
What is endchondroma caused by?
Intramedullarly cartilaginous tumour caused by failure of normal endochondral ossification at the growth plate.
Describe a simple bone cyst?
Single cavity benign, fluid filled cyst in bone, many are asymptomatic
Describe an aneurysmal bone cyst
Contains lots of chambers full of blood or serum. Thought to be due to arteriovenous malformation. Locally aggressive and painful so treatment is needed.
Describe giant cell tumour of bone?
Benign but locally aggressive tumour that can cause pathological fracture and pain. They are lytic lesions and a very small number can undergo malignant transformation.
Describe fibrous dysplasia?
Disease of bone in adolescence where a genetic mutation results in lesions of fibrous tissue and immature bone
Predominant clinical feature of osteoid osteoma?
Intense constant pain, worse at night due to inflammatory response, the pain is generally relieved by NSAIDs BECAUSE THE TUMOUR PRODUCES PROSTAGLANDINS
What is osteoid osteoma?
Small nidus of immature bone surrounded by an intense sclerotic halo. They most commonly occur in adolescence and common sites include the proximal femur, the diaphysis of long bones and the vertebrae
Describe treatment of osteoid osteoma?
The lesion may resolve spontaneously over time but some cases may require CT guided radiofrequency ablation or en bloc excision.
Malignant primary bone tumours are rare compared to _____1_______ but ______2____ affecting the skeleton is common
1) carcinoma
2) metastatic cancer
What is the most common primary malignant bone tumour?
Osteosarcoma
When are most cases of osteosarcoma seen? When must you investigate?
Most cases are seen in adolescence and early adulthood with 60% affecting the bones around the knee. In older adults osteosarcoma would be secondary to another cause so must investigate. For example Paget’s disease of bone.
Presentation and treatment of osteosarcoma?
Most patients complain of bone pain and when the tumour penetrates the cortex there may be soft tissue swelling. Chemo can prolong survival.
What is the name of a malignant cartilage producing bone tumour?
Chondrosarcoma
Compare osteosarcoma growth and chondrosarcoma?
Chondrosarcoma tends to have a slower growth pattern and affects older age group of 40-70 compared to osteosarcoma which is faster growing and affects young people and adolescents.
Where does chondrosarcoma tend to affect?
The limb girdles and proximal long bones
Is chondrosarcoma generally responsive to radio and chemo therapy?
No
Describe fibrosarcoma and malignant fibrous histiocytoma?
Fibrous malignant primary bone tumours that tend to occur in abnormal bone. Usually affects young people/
Describe Ewing’s Sarcoma?
Malignant tumour of primitive cells in the marrow. Very aggressive and metastasises early. Most cases occur between age 10 and 20. Associated with fever, raised inflammatory markers and a warm swelling so may mimic osteomyelitis. Tends to be radio and chemo sensitive.
What sarcoma may mimic osteomyelitis?
Ewing’s sarcoma
What sarcoma is a malignant tumour of primitive cells in the marrow?
Ewing’s sarcoma
In order of frequency list five cancers that commonly metastasise to the bone?
Breast carcinoma Prostate carcinoma Lung carcinoma Renal cell carcinoma Thyroid adenocarcinoma
What is one of the most common sarcomas? What does it affect?
Liposarcoma. This affects deep soft tissues of extremities or the retroperitoneum.
