GCA/mesothelioma and gangrene

Question 1

What is giant cell arteritis?

Answer 1

Inflammatory disorder of large and medium sized vessels of the head, mainly branches of ECA

Question 2

Which part of the vessel is most affectedin GCA?

Answer 2

Tunica media

Question 3

Describe microscopic changesof GCA

Answer 3

-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

Question 4

What blood test is used in diagnosis of GCA?

Answer 4

ESR

Question 5

What confirmatory test can be used for GCA?

Answer 5

Temporal artery biopsy

Question 6

Why can blindness occur in GCA?

Answer 6

If ophthalmic artery is affected

Question 7

What is the treatment for GCA?

Answer 7

-Corticosteroids
-Prednisolone 60mg/d or IV methylpred if evolving visual loss or hx amaurosis fugax. Typically 2 year course.

Question 8

One year later pt with GCA develops # NOF, why?

Answer 8

-Osteoporosis
-AVN

Question 9

Why osteoporosis in this patient? (60 yr old female, GCA)

Answer 9

-postmenopausal
-Steroid use

Question 10

What are the pathological changes in osteoporosis, and specifically in menopause?

Answer 10

-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

Question 11

What is osteoporosis and what is its pathogenesis?

Answer 11

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

Question 12

What is the mechanism by which corticosteroids cause osteoporosis?

Answer 12

-Direct inhibition of osteoblast formation
-Direct stimulation of bone resorption
-Jnhibition of GIT calcium resorption
-Stimulation of renal calcium losses
-Inhibition of sex steroids

Question 13

Causes of osteoporosis

Answer 13

Primary
-Idiopathic
-Postmenopausal
-Senile

Secondary

Endocrine
-Diabetes (type 1)
-Hypo/hyperthyroid
-Addison’s
-Neoplasia

GI
-Malabsorption
-Hepatic insufficiency

Drugs
-Alcohol
-Corticosteroids
-Chemotherapy

Question 14

What are other causes of pathological fracture?

Answer 14

-Skeletal metastasis
-Myeloma
-Rickett’s
-Hyperparathyroid
-Paget’s disease
-Osteogenesis imperfecta
-Osteomalacia

Question 15

What is multiple myeloma?

Answer 15

-Plasma cell neoplasm. Most common primary bone tumour in the elderly. See CRAB mnemonic below for features

Question 16

How is multiple myeloma diagnosed?

Answer 16

-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)

Question 17

What is bence Jones protein?

Answer 17

-Monoclonal globulin proteins or immunoglobulin light chain found in urine
-Produced by malignant plasma cells
-Present in 2/3 cases myeloma

Question 18

What concerns would you have regarding a myeloma patient on long term steroids going to surgery?

Answer 18

Addisonian crisis

Question 19

What is the definition of an addisonian crisis?What are its causes?

Answer 19

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

Question 20

What are the features of addisonian crisis?

Answer 20

-Abdo pain
-Nausea/vomiting
-Unexplained shock
-Hyponatraemia, hyperkalaemia

Question 21

What is the management of an addisonian crisis?

Answer 21

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

Question 22

How to prevent addison’s

Answer 22

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

Question 23

Cause of sudden death after THR?

Answer 23

Fat embolism

Question 24

What are the causes of fat embolism?

Answer 24

-Closed long bone fracture
-Orthopaedic surgery (IM nailing, joint reconstruction)
-major burns
-Pancreatitis
-DM
-CABG

Question 25

How is fat embolism managed?

Answer 25

Supportive -ABCDE

Question 26

Define gangrene

Answer 26

Gangrene is a type of necrosis caused by critically insufficient blood supply

Question 27

What is necrosis?

Answer 27

-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.

Question 28

What are the different types of cell death?

Answer 28

-Necrosis -Apoptosis

Question 29

Describe apoptosis vs necrosis

Answer 29

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.

Question 30

What is the pathogenesis of necrosis? Compare with apoptosis

Answer 30

Necrosis 1. Reversible cell injury 2. Swelling of endoplasmic reticulum and mitochondria 3. Progressive injury: breakdown of plasma membrane, organelles and nucleus--> leakage of cell contents --> INFLAMMATION Apoptosis 1. Fragmentation of cells into apoptotic bodies 2. Phagocytosis--> no release of contents/inflammation

Question 31

Describe wet vs dry gangrene

Answer 31

Question 32

Scenario: worker, smoker, gangrenous toe What do you think is the cause of the ischaemia?

Answer 32

Atherosclerosis

Question 33

Define atherosclerosis.What is its pathogenesis?

Answer 33

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.

Question 34

What are the risk factors for atherosclerosis?

Answer 34

-Smoking -HTN -Diabetes -Family history -Increased LDL

Question 35

Scenario worker, smoker, toe gangrene Pt develops cough, what bedside test could you do?

Answer 35

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

Question 36

What is the significance of pleural plaques?

Answer 36

-Increased risk of malignancy: mesothelioma, lung adenocarcinoma

Question 37

How could you classify lung cancers?

Answer 37

Small cell and non small cell

Question 38

Describe non small cell lung cancers

Answer 38

-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)

Question 39

Describe small cell carcinoma

Answer 39

-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

Question 40

Now the patient presents with metastases, poorly differentiated, how could you assess its epithelial origin?

Answer 40

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.

Question 41

If the tumour was epidermal growth factor positive, what would be the treatment?

Answer 41

Tyrosine kinase inhibitor (imatinib)

Question 42

What are the types of necrosis?

Answer 42

Caseous Liquefactive Gangrenous coagulative fat Fibrinoid