GCA/mesothelioma and gangrene Flashcards
What is giant cell arteritis?
Inflammatory disorder of large and medium sized vessels of the head, mainly branches of ECA
Which part of the vessel is most affectedin GCA?
Tunica media
Describe microscopic changesof GCA
-Intimal thickening–> reduces internal diameter
-Granulomatous inflammation to internal elastic lamina–> elastic lamina fragmentation
–> infiltrate of T cells and macrophages, giant cells in 95%
–> skip lesions
-Involved arterial segments develop intimal thickening (with occasional thromboses) that reduces internal diameter
-Classic lesions develop granulomatous inflammation centred on the internal elastic lamina that produce elastic lamina fragmentation
-There is infiltrate of T cells and macrophages
-Multinucleated giant cells are seen in ~95% of specimens, but can be absent
-inflammatory lesions are focally distributed along the vessel and normal segments may be interposed
What blood test is used in diagnosis of GCA?
ESR
What confirmatory test can be used for GCA?
Temporal artery biopsy
Why can blindness occur in GCA?
If ophthalmic artery is affected
What is the treatment for GCA?
-Corticosteroids
-Prednisolone 60mg/d or IV methylpred if evolving visual loss or hx amaurosis fugax. Typically 2 year course.
One year later pt with GCA develops # NOF, why?
-Osteoporosis
-AVN
Why osteoporosis in this patient? (60 yr old female, GCA)
-postmenopausal
-Steroid use
What are the pathological changes in osteoporosis, and specifically in menopause?
-Osteoporosis is histologically normal bone that is reduced in quantity
-In post menopausal osteoporosis the increase in osteoclast activity affects mainly bones or portions of bones with large surface area, e.g. cancellous portion of vertebral bodies
-Trabecular plates become perforated, thinned and lose their interconnections. Leads to microfractures and eventually vertebral collapse
What is osteoporosis and what is its pathogenesis?
Metabolic bone disease characterised by:
-Low bone mass
-Increased bone fragility
-Loss of bone matrix
Three main mechanisms
-Inadequate peak bone mass
-Abnormal bone resorption
-Inadequate formation of new bone during bone turnover
What is the mechanism by which corticosteroids cause osteoporosis?
-Direct inhibition of osteoblast formation
-Direct stimulation of bone resorption
-Jnhibition of GIT calcium resorption
-Stimulation of renal calcium losses
-Inhibition of sex steroids
Causes of osteoporosis
Primary
-Idiopathic
-Postmenopausal
-Senile
Secondary
Endocrine
-Diabetes (type 1)
-Hypo/hyperthyroid
-Addison’s
-Neoplasia
GI
-Malabsorption
-Hepatic insufficiency
Drugs
-Alcohol
-Corticosteroids
-Chemotherapy
What are other causes of pathological fracture?
-Skeletal metastasis
-Myeloma
-Rickett’s
-Hyperparathyroid
-Paget’s disease
-Osteogenesis imperfecta
-Osteomalacia
What is multiple myeloma?
-Plasma cell neoplasm. Most common primary bone tumour in the elderly. See CRAB mnemonic below for features
How is multiple myeloma diagnosed?
-Punched out lytic skull lesions on XR
-IgM spike on protein electrophoresis
-Igg light chains in urine (bence jones protein)
corrected Calcium >2.75mmol/L
Renal dysfunction associated with myeloma
Anaemia (Hb <10g/dl)
Bone lesions (lytic lesions or osteoporosis with compression fractures)
(formal diagnosis on bone marrow biopsy)
What is bence Jones protein?
-Monoclonal globulin proteins or immunoglobulin light chain found in urine
-Produced by malignant plasma cells
-Present in 2/3 cases myeloma
What concerns would you have regarding a myeloma patient on long term steroids going to surgery?
Addisonian crisis
What is the definition of an addisonian crisis?What are its causes?
It is the acute reduction of circulating steroids
Primary
-Addison’s disease: adrenal supply of cortisol cannot meet body’s requirements
Secondary to:
-trauma
-Surgery
-Infection
-Exogenous steroids stopped abruptly rather than tapered off
What are the features of addisonian crisis?
-Abdo pain
-Nausea/vomiting
-Unexplained shock
-Hyponatraemia, hyperkalaemia
What is the management of an addisonian crisis?
CCRISP protocol
Following ABCDE approach
IV steroids: immediate bolus of 100mg iV/IM, followed by continuous infusion 200mg over 24 hrs
IV fluids
Adjust metabolic ddisturbances
How to prevent addison’s
Increase steroid dose prior to surgery
Convert to IV steroids
< 10mg/day: assume normal HPA, additional steroid not required
> 10mg/day
-Minor surgery: 25mg hydrocortisone at induction
-Moderate: usual pre-operative steroids + 25mg at induction + 100mg/day for 24 hrs
-Major surgery: usual pre-op steroids + 25mg hydrocortisone at induction + 100mg/day for 48-72 hrs
Cause of sudden death after THR?
Fat embolism
What are the causes of fat embolism?
-Closed long bone fracture
-Orthopaedic surgery (IM nailing, joint reconstruction)
-major burns
-Pancreatitis
-DM
-CABG
How is fat embolism managed?
Supportive
-ABCDE
Define gangrene
Gangrene is a type of necrosis caused by critically insufficient blood supply
What is necrosis?
-Necrosis is defined as abnormal tissue death during life. -Necrosis is ALWAYS pathological and is accompanied by inflammation.
-Groups of cells are involved and they undergo swelling and lysis.
-Necrotic cells are phagocytosed by inflammatory cells.
What are the different types of cell death?
-Necrosis
-Apoptosis
Describe apoptosis vs necrosis
Pyknosis, or karyopyknosis, is the irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or apoptosis. It is followed by karyorrhexis, or fragmentation of the nucleus.
Karyolysis (from Greek κάρυον karyon—kernel, seed, or nucleus), and λύσις lysis from λύειν lyein, “to separate”) is the complete dissolution of the chromatin of a dying cell due to the enzymatic degradation by endonucleases. The whole cell will eventually stain uniformly with eosin after karyolysis.
What is the pathogenesis of necrosis? Compare with apoptosis
Necrosis
- Reversible cell injury
- Swelling of endoplasmic reticulum and mitochondria
- Progressive injury: breakdown of plasma membrane, organelles and nucleus–> leakage of cell contents –> INFLAMMATION
Apoptosis
- Fragmentation of cells into apoptotic bodies
- Phagocytosis–> no release of contents/inflammation
Describe wet vs dry gangrene
Scenario: worker, smoker, gangrenous toe
What do you think is the cause of the ischaemia?
Atherosclerosis
Define atherosclerosis.What is its pathogenesis?
Pathological process in which artery wall thickens as a result of the accumulation of fatty materials such as cholesterol
Endothelial injury–> accumulation of LDL –> platelet adherence + platelet derived growth factor –> attracts monocytes–> engulf LDLs + form foam cells –> proliferation of smooth muscle –> fibroblasts lay down collagen and elastin, forming plaque
Remember: treated with antiplatelet and statin.
What are the risk factors for atherosclerosis?
-Smoking
-HTN
-Diabetes
-Family history
-Increased LDL
Scenario worker, smoker, toe gangrene
Pt develops cough, what bedside test could you do?
Pt develops cough, what bedside test could you do?
-Sputum analysis
-CXR: –> pleural plaques
-Pleural plaques are the most common manifestation of asbestos exposure. Well circumscribed plaques of dense collagen that are often calcified
What is the significance of pleural plaques?
-Increased risk of malignancy: mesothelioma, lung adenocarcinoma
How could you classify lung cancers?
Small cell and non small cell
Describe non small cell lung cancers
-Share common features of prognosis and management
-Paraneoplastic syndromes are less likely than with small call cancers
Examples include:
-Adenocarcinoma (40%), most common cancer in never smokers
-Squamous cell carcinoma: more slow growing and typically centrally located
-Large cell carcinoma (10% of cases)
Describe small cell carcinoma
-Comprised of cells with neuro-endocrine differentiation
-Neuroendocrine hormones may be released from these cells with wide range of paraneoplastic associations
-Strongly associated with smoking, and typically arise in larger airways
-Disseminate early
-Are chemosensitive, but this rarely results in long lasting remission
Now the patient presents with metastases, poorly differentiated, how could you assess its epithelial origin?
Immunohistochemistry
Immunohistochemistry is the most common application of immunostaining. It involves the process of selectively identifying antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues.
If the tumour was epidermal growth factor positive, what would be the treatment?
Tyrosine kinase inhibitor (imatinib)
What are the types of necrosis?
Caseous
Liquefactive
Gangrenous
coagulative
fat
Fibrinoid