Soft Tissue Pathology Flashcards
What is the function of the perimysium?
Surrounds bundles of muscle fibres
Function of the endomysium?
Surrounds individual fibres
Function of the epimysium?
Surrounds the entire muscle
Ragged red fibres are seen in muscle when?
Mitochondrial disease, metabolic disease, normal features in small numbers at the extremes of age
Tubular aggregates are seen in muscle when?
Tubular aggregate myopathy, periodic paralysis, alcoholic myopathy, incidental finding
Types of skeletal muscle fibre? (3)
Red (Type 1, slow twitch, lots of mitochondria & myoglobin, good for marathon runners, able to regenerate ATP v quickly)
White (Fast twitch, Type 2A; fast oxidative glycolytic, type 2b; fast glycolytic)
Intermediate
Muscle Biopsy Indications
Evidence of muscle disease
-Weakness
-Muscle symptoms (atrophy, fasciculation)
-Elevate creatine kinase (CK)
Presence of neuropathy (+ nerve biopsy)
Presence of vascular disorder (vasculitis)
Creatine Kinase High, Intermediate and Low levels
High: (e.g. Dystrophies) 200-300 times of normal.
Intermediate: (e.g. Inflammatory myopathy) 20-30 times of normal.
Low: (e.g. Neurogenic disorder) 2-5 times of normal
What is electron microscopy used for?
To examine the ultra-structure of the muscle
Duchenne (DMD) method of inheritance and where found?
X-linked recessive, pelvic girdle
Becker (BMD) method of inheritance and where found?
X-linked recessive, pelvic girdle
Limb girdle (LGMD) method of inheritance and where found?
Autosomal recessive, pelvic girdle
Fascioscapulohumeral method of inheritance and where found?
Dominant, face, shoulder girdle and arm
Scapulohumeral method of inheritance and where found?
Autosomal recessive, shoulder girdle and arm
Oculopharyngeal method of inheritance and where found?
Dominant, external ocular and pharynx
Myotonic dystrophy method of inheritance and where found?
Dominant, face, respiratory and arms
Signs of Duchennes?
Proximal weakness, pseudohypertrophy of calves
RAISED CK
DMD pathogenesis
- Mutations in dystrophin gene on long arm chromosome X
- Alterations in anchorage of actin cytoskeleton to basement membrane
- Fibres liable to tearing
- Uncontrolled Ca2+ entry into cells
Variant of DMD?
BMD (Becker)
Are muscular dystrophies inherited?
Yes
Which inflammatory marker will be raised in Duchennes?
CK!!!
Most common types of Myotonic dystrophy?
DM1 and DM2
Non-muscle features of myotonic dystrophy?
Frontal baldness (in men), low intelligence, cataracts (clouding of the lens), cariomyopathies
Atrophy of which type of fibres in myotonic dystrophy?
Atrophy of type 1 fibres in myotonic dystrophy
Myotonic dystrophy histological features?
Atrophy of type 1 fibres Ring fibres Central nuclei Fibrofatty replacement Fibre necrosis
In which condition might you see ring fibres?
Myotonic dystrophy
Primary inflammation of muscle inflammatory myopathies
Infective agents
Polymyositis
Dermatopolymyositis
Most common form of muscular dystrophy?
Myotonic dystrophy
-Characterised by progressive muscle wasting and weakness
At what age do the features of myotonic dystrophy tend to develop? (bearing in mind they can actually develop at any age)
20’s-30’s
Where does DM1 affect?
Distal
Where does DM2 affect?
Proximal
Features of Polymyositis?
Progressive muscular weakness, PAIN and TENDERNESS :(
Genes involved in myotonic dystroophy?
Ch19 and Ch3
Polymyositis histological findings?
Endomysial lymphocytic infiltrate, invasion of muscle by CD8+ T lymphocytes
Segmental fibre necrosis
What is dermatositis?
Polymyositis and skin changes
What does dermatomysitis share a 10% link with?
Malignancy
Skin features of dermatmyositis?
Upper body erythema
Eyelid swelling with purple discolouration
Which condition would you find immune complex and complement deposition within & around capillaries within muscle?
Polymyositis
You would also find perifasicular muscle fibre injury
and B-lymphocytes and CD4 + T cells > cf polymyositis
Neurogenic disorders of muscle (histological findings)
- Small, angulated muscle fibres (adults)
- Small, round muscle fibres (infants)
- Target fibres
- Fibre type grouping
- Grouped atrophy
Motor Neurone Disease
Progressive degeneration of anterior horn cells
Denervation atrophy, fasciculation and weakness
Which cells progressively degenerate in motor neurone disease?
Anterior horn cells
Method of Spinal Muscular Atrophy Inheritance?
Autosomal recessive
What gene is affected in spinal muscular atrophy?
Ch5
How many types of muscular atrophy are there?
4
Age and gender usually affected by myasthenia gravis?
Women aged 20-40
Which thymus conditions are linked with myasthenia gravis?
25% have thymoma
Others have thymic hyperplasia
Myasthenia gravis symptoms?
Fatigue, muscle weakness, proptosis and DYSPHAGIA
Rhabdomyolysis histological findings
Breakdown of skeletal muscle:
- Myoglobinuria
- Hyperkalaemia
- Necrosis & shock
What might you test the urine for in rhabdomyolysis?
Myoglobin
myoglobulinuria
Outcome of rhabdomyolysis?
Acute Renal Failure
Hypovolaemia & hyperkalaemia
Metabolic acidosis
Disseminated intravascular coagulation
Which condition might present with acute kidney failure and disseminated intravascular co-agulation?
Rhabdomyolysis (acute renal failure so u would probs see hypovolaemia and hyperkalaemia aswell)
What kind of drugs do connective tissue disorders usually respond to?
Anti-inflammatory
What anti-bodies do you see in SLE?
Anti-nuclear! omgeeee
What drugs can induce SLE?
Hydralazine and pracainamide
Lol, every single SLE symptom
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
Hypersensitivity in SLE
Visceral lesions – mediated by Type III hypersensitivity
Haematological effects – mediated by Type II hypersensitivity
What does PAN stand for?
Polyarteritis nodosa
What is PAN?
Inflammation and fibrinoid necrosis of small/medium arteries
Target organs for PAN?
Major - kidneys, heart, liver, GI tract
Minor – skin, joints, muscles, nerves, lungs
Which infection is PAN often associated with?
Streptococcal infection
Diagnosis of PAN
Biopsy- FIBRINOID NECROSIS OF VESSELS
Which condition is characterised by fibrinoid necrosis of vessels (found from bioopsy?)
PAN! Polyarteritis nodosa
Which antibody would you find in PAN?
pANCA (perinuclear antineutrophil cytoplasmic autoantibody)
Clinical Features of PAN?
Non-specific +/- organ specific features such as hypertension, haematuria, abdominal pain, melaena, diarrhoea, mononeuritis multiplex, rash, cough, dyspnoea
Clinical features of polymyalgia rheumatica?
Pain, stiffness in shoulder & pelvic girdles
No muscle weakness
Responds to corticosteroids
Where is the pain in polymyalgia rheumatica?
Shoulders and pelvic girdle
Who is affected by polymyalgia rheumatica?
The elderly!
What kind of medication does polymyalgia rheumatica respond to?
Corticosteroids
Another name for Giant Cell Arteritis?
Temporal arteritis
Diagnosis of temporal arteritis?
raised ESR
Temporal artery biopsy; inflammation,+/- giant cells, fragmentation of internal elastic lamina
What is scleroderma?
Excessive fibrosis of organs and tissues (excessive collagen production)
CREST syndrome
- Calcinosis
- Raynaud’s
- Oesophageal dysfunction
- Sclerodactyly
- Telangectasia
Death due to Scleroderma
- Renal failure secondary to malignant hypertension
- Severe respiratory compromise
- Cor pulmonale
- Cardiac failure or arrhythmias secondary to myocardial fibrosis
Which condition is associated with CREST?
Scleroderma
Epstein-Barr virus could predispose to which connective tissue disease?
SLE
Silica dust (found in cleaning powders, cigarette smoke and cement) may increase risk of developing what?
Silica dust (found in cleaning powders, cigarette smoke and cement) may increase risk of developing SLE
Aetiology of SLE
Environmental factors:
Viruses eg Epstein-Barr Virus
UV light may stimulate skin cells to secrete cytokines stimulating B-cells
Silica dust (found in cleaning powders, cigarette smoke and cement) may increase risk of developing SLE
In SLE, what is the significance of nuclear material release from necrotic cells?
The nuclear material released from necrotic cells may act autoantigens
Autoimmunity possibly results by the extended exposure to nuclear and intracellular autoantigens
Possible source of autoantigens in SLE?
Nuclear material released from necrotic cells may act as autoantigens
Autoimmunity possibly results by the extended exposure to nuclear and intracellular autoantigens
Coombes test
Coombes test involves taking a blood sample and checking it for the presence of antibodies which may destroy red blood cells
-Do not count in the presence of haemolytic anemia
When would you not count coombes test?
In the presence of haemolytic anemia
Requirements for classification of lupus?
At least 4 clinical and 1 laboratory finding
Or biopsy proven lupus nephritis with positive ANA or anti-DNA
Serositis in SLE?
Pericarditis, pleuritis, peritonitis
Levels of C3, C4 and CH50 in active SLE?
Levels of C3, C4 and CH50 will decrease because SLE is highly active and body will use them up
What is lupus nephritis?
Kidney inflammation caused by lupus
Levels of IgG and anti-dsDNA in active SLE?
Levels of IgG and anti-dsDNA will increase
Jaccoud arthropathy
Jaccoud arthropahy (JA) is a deforming non erosive arthropathy characterised by ulnar deviation of the second to 5th fingers with MCP subluxation. -Can be seen in SLE
Pulmonary features of SLE?
- Pleurisy
- Infections
- Pulmonary hypertension
- Pulmonary infarct
- Diffuse lung infiltration and fibrosis
Which type of endocarditis might be seen in SLE?
Libman-sach endocarditis
SLE cardiac features
Cardiomyopathy
Libman-sach endocarditis
Pulmonary hypertension
Pericarditis
Screening tests for suspected SLE
Full blood count Renal function incl. urine ANA ENA Anti-DNA Complement levels
Which immunological thingy is specific for SLE?
Anti-DNA
-Correlates with disease activity
-may be associated with lupus nephritis
Anti-Sm also very specific
Anti-DNA is highly specific for what?
SLEEEEEE
-Correlates with activity
-may be associated with lupus nephritis
Anti-Sm is also very specific
Anti-Ro is associated with which manifestations
Cutaneous
Anti-RNP overlap features
Overlap features – sclerodermatous skin lesions, Raynaud’s phenomenon, low grade myositis
If you have SLE should you go to the desert?
No, you want to avoid excessive sun exposure
Anti-CD20
Rituximab (one of the biologics used in SLE)
Anti-Blys
Belimumab
Ciclosporin A and tacrolimus are what kind of drug?
Calcineurin inhibitors
Name 2 calcineurin inhibitor
Ciclosporin A and tacrolimus
