Pathology Flashcards
what are the types of skeletal muscle fibres
Red fibres i.e. Type 1, slow twitch.
- large mitochondria and increase myoglobin
White fibres i.e. Type 2, fast twitch
- small mitochondria and large motor end plates
Intermediate fibres
what are indications for muscle biopsy
evidence of muscle disease (elevated CK, weakness)
Presence of neuropathy
Presence of vascular disorder (vasculitis)
when are CK levels 20-30 times of normal
inflammatory myopathy
intermediate levels of CK
what are changes seen in muscles with dystrophic diseases
variability in muscle fibre size endomysial fibrosis fatty infiltration and replacement myocyte hypertrophy Increased central nuclei Segmental necrosis Regeneration Ring fibres- condensation
what are common muscular dystrophies and what do they affect
Duchenne - pelvic girdle
Becker - pelvic girdle
Limb girdle - pelvic girdle
Myotonic dystrophy - face, respiratory, limbs
typical case of DMD
present in boys 2-4 years of age
proximal weakness
pseudo hypertrophy of calves
very raised levels of CK
where is the mutation in DMD and what does it cause
in dystrophin gene on long arm chromosome X
causes alterations in anchorage of actin cytoskeleton basement membrane
fibres liable to tearing
uncontrolled calcium entry into cells
what are the characteristics of BMD
later onset and milder symptoms that DMD
mutations in the dystrophin gene
slower progress, not as severe as DMD
more calf enlargement
what are the features of Myotonic dystrophy
Muscle weakness, myotonia, non-muscle features
Most common dystrophy to affect adults
Adolescence – face predominantly affected, distal limbs
Later – respiratory muscles most affected
what are examples of inflammatory myopathies
infective agents
polymyositis
dermatomyositis
what is polymyositis
chronic inflammatory disease
progressive muscular weakness, pain and tenderness
pathology of polymyositis
Cell-mediated immune response to muscle antigens
Endomysial lymphocytic infiltrate, invasion of muscle by CD8 + T lymphocytes
Segmental fibre necrosis
what is dermatomyositis
skin changes plus polymyositis
upper body erythema
swelling of eyelids with purple discolouration
pathology of dermatomyositis
Immune complex and complement deposition within and around capillaries within muscle
Perifascicular muscle fibre injury
B-lymphocytes and CD4 + T cells > cf polymyositis
what is Motor Neuron Disease
progressive degeneration of anterior horn cells
Denervation atrophy, fasciculation and weakness
what is spinal muscular atrophy
inherited; autosomal recessive
Degeneration of anterior horn cells in spinal cord
Denervation of muscle
Types 1 - 4
features of myasthenia graves
Autoimmune
Weakness, proptosis, fatigue, and dysphagia
Women between 20 - 40
what is rhabdomyolysis
breakdown of skeletal muscle
what antibodies are associated with SLE
Antinuclear antibodies (ANAs)
symptoms/signs of SLE
Skin –“butterfly” rash (sun exposed areas), discoid lupus erythematosus (DLE)
Joints – arthralgia
Kidneys – glomerulonephritis
CNS – psychiatric symptoms, focal neurological symptoms
CVS – pericarditis, myocarditis, necrotising vasculitis
Lymphoreticular – lymphadenopathy & splenomegaly
Lungs – pleuritis, pleural effusions
Haematological – anaemia, leucopenia, thrombophilia
what hypersensitivity is responsible for SLE symptoms
Visceral lesions – mediated by Type III hypersensitivity
Haematological effects – mediated by Type II hypersensitivity
what is Polyarteritis nodosa
Inflammation and fibrinoid necrosis of small/medium arteries
symptoms and signs of PAN
Non-specific +/- organ specific features such as hypertension, haematuria, abdominal pain, melaena, diarrhoea, mononeuritis multiplex, rash, cough, dyspnoea
investigation/diagnosis of PAN
Biopsy; fibrinoid necrosis of vessels
Serum contains pANCA (perinuclear antineutrophil cytoplasmic autoantibody)
features of PMR
elderly
pain, stiffness in shoulder and pelvic girdles
no muscle weakness
responds to corticosteroids
features of Temporal arteritis
a.k.a GCA
inflammation affecting cranial vessels
Risk of blindness of terminal branches of opthalmic artery affected
Headache & scalp tenderness
diagnosis of temporal arteritis
raised ESR
temporal artery biopsy; inflammation +/- giant cells
what is scleroderma
Excessive fibrosis of organs and tissues (excessive collagen production)
symptoms/signs of scleroderma
Skin – tight, tethered, ↓ joint movement
GI tract – fibrous replacement of muscularis
Heart – pericarditis and myocardial fibrosis
Lungs – interstitial fibrosis
Kidneys – affects arteries, leads to hypertension
Musculoskeletal system – polyarteritis and myositis
what is scleroderma associated with
CREST syndrome Calcinosis Raynaud’s Esophageal dysfunction Sclerodactyly Telangiectasia
what can kill in scleroderma
Renal failure secondary to malignant hypertension
Sever respiratory compomise
Cor pulmonale
Cardiac failure or arrhythmias secondary to myocardial fibrosis
what are the benign tumours of MSK
Osteochondroma
Chondroma
Osteoid osteoma
Chondroblastoma
what is osteochondroma
Cartilage capped bony projection arising on external surface of bone containing a marrow cavity that is continuous with that of the underlying bone.
features of osteochondroma
affects the young
M = F
tend to develop near epiphyses of long bones
cell of origin - chondrocytes
what is a chondroma
Benign hyaline cartilage tumour arising in medullary cavity of bones of hands and feet
what are the two types of chondroma
Single or multiple (Ollier’s disease and Mafucci’s syndrome)
what is Ollier’s disease
Rare developmental disorder
Enchondromas (metaphyses and diaphyses)
Typically unilateral and involving one extremity
what is Maffucci’s syndrome
Multiple enchondromatosis with soft tissue and visceral haemangiomas
greater malignant risk than Ollier’s
what is an osteoid osteoma
benign osteoblastic tumour composed of a central core of vascular osteoid tissue and a peripheral zone of sclerotic bone
features of osteoid osteoma
Benign - usually found in children and young adults
Found in femur, tibia, hands/feet, and axial skeleton (spine)
resolve w/out tx in average of 33 months
symptoms of osteoid osteoma
joint tenderness swelling synovitis dull pain worse at night pain relieved by aspirin and NSAIDs
what are chondroblastoma
Benign cartilage tumour arising in bone
what are features of chondroblastoma
found at epiphysis of long bones
20-30 y/o
histology of chondroblastoma
Closely packed polygonal cells plus areas of immature chondroid.
Mitotic activity is low.
Distinct cytoplasmic borders with foci of “chicken-wire” calcification.
tumours that are benign but locally aggressive
Giant cell tumour
Osteoblastoma
Chordoma
features of giant cell tumour
cell of origin - osteoclast
site - long bones, often around knee
radiology of giant cell tumour
Radiolucent with increasing density towards periphery.
Destruction of medullary cavity and adjacent cortex.
May expand into soft tissue - locally aggressive
what are Osteoblastoma
Solitary, benign and self-limited tumour that produces osteoid and bone but can damage surrounding structures
where are osteoblastomas found and what are the symptoms
metaphysis or diaphysis of long bones
pain of long duration, swelling, tenderness
treatment of osteoblastomas
surgical resection by-
- curettage
- intralesional excision
features of chordoma
Very rare tumour arising from notocord remnants (midline tumour, often in sacral region)
40+ years
Benign but locally destructive and invasive - due to areas affected can cause spinal problems and symptoms
where do macroscopic tumours grow
often tracks along nerve roots in the sacral plexus or out the sciatic notch in planes of least resistance
malignant MSK tumours
Osteosarcoma
Chondrosarcoma
Ewing’s sarcoma
what is the commonest primary malignant tumour
osteosarcoma
features of osteosarcoma
Malignant osteoblasts forming osteoid
Young adults; 60%
sites of osteosarcoma
Ends of long bones particularly distal femur, proximal tibia, and proximal humerus
osteosarcomas grow slowly - true or false
false
Rapid growth; mitotically active - patients may well already have metastasise when they present
what is Codman’s triangle
raised triangle seen in aggressive bone lesions e.g. osteosarcoma, Ewing sarcoma
osteosarcoma treatment
Biopsy, CT, bone scan
Pre-operative chemotherapy
Surgical resection
Post-operative chemotherapy
what is a chondrosarcoma
The second commonest primary malignant tumour of bone
Exhibits pure hyaline cartilage differentiation
Composed of malignant chondrocytes
can extend into soft tissue
treatment of chondrosarcoma
Wide surgical excision - best option, but often impossible due to location of tumour
Limited use of chemotherapy and radiotherapy
features of Ewing’s sarcoma
highly malignant
Mainly occurs in the metaphysis and diaphysis of femur, tibia, then humerus.
Most common in second decade of life.
how does Ewing’s sarcoma appear histologically
small round blue cell
treatment of Ewing’s sarcoma
surgery
radiation therapy
chemotherapy
what cancers commonly cause bony mets
thyroid, breast, lung, kidney, prostate
what is multiple myeloma
Malignant proliferation of plasma cells in bone marrow
what does multiple myeloma often cause
renal failure
destruction of axial skeleton
