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Phase 2A Medicine > General Pathology > Flashcards

General Pathology Flashcards

1
Q

Define inflammation.

A

It is the local physiological response to tissue injury and is usually a manifestation of disease.

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2
Q

What are the causes of inflammation?

A
  1. Microbial infection
  2. Physical agents (trauma, ionising radiation, heat, cold)
  3. Chemicals (acids, alkalis, bacterial toxins, organic compounds)
  4. Immunological (Ag-Ab, cell mediated)
  5. Tissue necrosis
  6. Hypersensitivity reactions
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3
Q

What are the classical signs of acute inflammation?

A 
Redness (rubor)
Heat (calor)
Swelling (tumor)
Pain (dolor)
Loss of function (functio laesa)
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4
Q

What are the three essential features of AI?

A
  1. Hyperaemia
  2. Exudation of fluid
  3. Emigration of leucocytes
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5
Q

Describe the role of histamine in AI.

A

Causes vascular dilatation and increased vessel permeability.
Stored in preformed granules for immediate effect.
Stored in mast cells, basophils, eosinophils and platelets.
Its release is stimulated by complement components C3a and C5a and lysosomal proteins from neutrophils.

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6
Q

Describe the role of tissue macrophages.

A

Stimulated by local infection or injury.
Secrete chemical mediators like IL-1 and TNF-alpha.
Their stimulatory effects on endothelial cells occurs after histamine and thrombin.

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7
Q

Based on macroscopic appearance, what are the different types of inflammation?

A
  1. Serous
  2. Suppurative
  3. Membranous
  4. Pseudomembranous
  5. Necrotising
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8
Q

What are the sequels of AI?

A

Resolution
Suppuration (if excessive exudate)
Repair & organisation (if excessive necrosis)
Chronic inflammation (if persistent causal agent)
last two lead to fibrosis

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9
Q

What are the systemic effects of inflammation?

A

Pyrexia
Constitutional symptoms such as malaise, anorexia, nausea
Weight loss
Reactive hyperplasia of reticuloendothelial system (enlarged lymph nodes)
Raised ESR, leucocytosis, anaemia
Amyloidosis

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10
Q

What are the essential features of chronic inflammation?

A
  1. Absence of polymorphs
  2. Appearance of lymphocytes, plasma cells & macrophages.
  3. Angiogenesis
  4. Proliferation of fibroblasts and collagen synthesis leading to fibrosis.
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11
Q

What are the causes of CI?

A
  1. Resistance of infective agent to phagocytosis
  2. Endogenous materials like bone, uric acid crystals and necrotic adipose tissue
  3. Exogenous materials like silica, asbestos, sutures, prostheses
  4. Autoimmune diseases like rheumatoid arthritis
  5. Conditions of unknown aetiology like ulcerative colitis
  6. Primary granulomatous diseases like sarcoidosis
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12
Q

Describe the macroscopic appearances of CI.

A
  1. chronic ulcer
  2. chronic abscess cavity
  3. Thickening of the wall of a hollow viscous by fibrous tissue
  4. Granulomatous inflammation with caseous necrosis
  5. Fibrosis
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13
Q

What is a granuloma?

A

A granuloma is an aggregate of epithelioid histiocytes (modified macrophages). They accumulate in small clusters surrounded by lymphocytes and giant cells.

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14
Q

What are giant cells?

A

They are derivatives of macrophages by cell fusion or nuclear division without cytoplasmic separation.

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15
Q

How is a granuloma formed?

A

Indigestible material in a macrophage leads to an immune response activated by T-lymphocytes. The causes the release of cytokines (IFN-gamma, TNF-alpha and IL-1). These lead to proliferation and activation of macrophages forming granulomas.

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16
Q

What are the causes of granulomatous disease?

A
  1. Specific infections (mycobacteria, fungi, parasites, syphilis)
  2. Materials that resist digestion
  3. Specific chemicals like beryllium
  4. Drugs like phenylbutazone and sulphonamides
  5. Unknown causes like sarcoidosis
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17
Q

Describe the production of prostaglandins.

A

Prostaglandins are arachidonic acid metabolites which are cell-derived inflammatory mediators. When a cell is injured and ruptures, the phospholipids in its cell membrane are released into the tissue fluid where phospholipase-A converts them to arachidonic acids which are further converted to prostaglandins by the action of cyclo-oxygenase.
Steroids inhibit phospholipase-A.
NSAIDs inhibit COX.

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18
Q

What are the features of SIRS?

A
  1. pyrexia
  2. increased heart rate
  3. tachypnoea
  4. leucocytosis
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19
Q

Describe the role of autopsies.

A
  1. Determines cause of death.
  2. Audit of accuracy of clinical diagnosis.
  3. Education of undergrads and postgrads.
  4. Research into causes and mechanisms of disease.
  5. Gathering accurate statistics about disease incidence.
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20
Q

What is atheroma?

A

Atheroma is a condition characterised by the focal accumulation of lipid in the intima of arteries causing their lumen to be narrowed, their wall to be weakened and predisposing them to thrombosis.

Deposition of lipid + surrounding fibrosis + chronic inflammation

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21
Q

What types of arteries are affected by atherosclerosis?

A

Large and medium sized arteries

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22
Q

What are the risk factors for atherosclerosis?

A
  1. Hypercholesterolaemia
  2. Increasing age
  3. Male gender
  4. hypertension
  5. Smoking
  6. Diabetes
  7. Raised serum lipid
  8. Obesity
  9. Sedentary lifestyle
  10. Low socio-economic status
  11. Low birth weight
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23
Q

Describe the pathogenesis of atheroma.

A

Starts off as fatty streak i.e. yellow linear elevation of intimal lining composed of lipid-laden macrophages.
Develops into central lipid core with fibrous tissue cap covered by arterial endothelium.
Surrounded by foam cells which are macrophages that have phagocytosed oxidised lipoproteins.
The plaque later undergoes dystrophic calcification.

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24
Q

What functional alterations occur in injured epithelial cells?

A
  1. Increased cell adhesion molecules for monocytes
  2. Increased permeability for macromolecules
  3. Increased thrombogenicity
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25
Q

What are the important sites of atheroma?

A
  1. Cerebral and Carotid
  2. Coronaries
  3. Abdominal aorta
  4. Renal arteries
  5. Visceral arteries (bowel ischaemia)
  6. Lower limb arteries
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26
Q

What is Virchow’s triad?

A

It describes the three problems that cause thrombosis:

  1. blood vessel wall
  2. blood flow
  3. blood cells/ coagulation proteins
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27
Q

What is the common cause of venous thrombosis?

A

Stasis

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28
Q

What are the clinical consequences of thrombosis?

A
  1. arterial - tissue infarction distally
  2. venous - oedema due to impaired drainage
  3. embolism
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29
Q

Define thrombus.

A

A thrombus is a solidification of blood constituents formed within the vascular system in life.

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30
Q

What types of granules do platelets comprise of?

A

Alpha granules for platelet adhesion to damaged vessel walls.
Dense granules for platelet aggregation.

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31
Q

What is the fate of thrombi?

A
  1. Resolution by degradative processes in the body
  2. Organisation into scar tissue by invasion of macrophages and fibroblasts
  3. Recanalisation (by angiogenesis)
  4. Death
  5. Embolism
  6. Calcification
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32
Q

Which factors inhibit and promote thrombosis?

A

Promote: endothelin & von Willebrand factor

Inhibit: nitric oxide, prostacyclin & antithrombin

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33
Q

Define embolus.

A

An embolus is any abnormal mass of matter carried in the blood stream large enough to occlude some vessel.

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34
Q

What are the different types of embolism?

A
  1. Embolic atheroma
  2. Platelet emboli
  3. Infective emboli
  4. Fat emboli
  5. Gas emboli
  6. Amniotic emboli
  7. Tumour
  8. Foreign matter like talc
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35
Q

What is infarction?

A

It is the ischaemic necrosis of tissue that elicits an inflammatory reaction.

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36
Q

Which tissues are susceptible to infarction?

A
  1. impaired vascular flow short of total cessation in watershed areas
  2. tissue perfused by portal vasculature
  3. tissues distal to arterial stenoses
  4. metabolic active tissues
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37
Q

What is reperfusion injury?

A

It is the adaptive process of clearing up of dead and damaged cells that produces deleterious effects like scarring due to the inflammatory response that is initiated when the blood supply returns to a area.

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38
Q

What are the two types of gangrene?

A
  1. Dry: sterile process where tissue dies and drops off

2. Wet: bacterial infection supervenes as secondary complication and gangrene spreads proximally.

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39
Q

What is gas gangrene?

A

It results from infection of ischaemic tissue by gas-producing anaerobic bacteria Clostridium perfringens.

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40
Q

What are the causes of capillary ischaemia?

A

frostbite
parasites
sickle cell disease
abnormal proteins that precipitate in the cold (cryoglobinaemia)

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41
Q

What is necrosis?

A

Necrosis is unintended cell death in response to cell injury (pathological).

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42
Q

What is apoptosis?

A

It is a physiological cellular process in which a defined and programmed sequence of intracellular events leads to the removal of cell without the release of products harmful to surrounding cells.

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43
Q

What does increased apoptosis lead to?

A

excessive cell loss (atrophy)

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44
Q

What does decreased apoptosis lead to?

A

cell accumulation (neoplasia)

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45
Q

What are the inhibitors of apoptosis?

A

growth factors
extracellular cell matrix
sex steroids
some viral proteins

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46
Q

What are the inducers of apoptosis?

A 
growth factor withdrawal
loss of matrix attachment
glucocorticoids
some viruses
free radicals
ionising radiation
DNA damage 
ligand-binding at 'death receptors'
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47
Q

Briefly describe the intrinsic pathway leading to apoptosis.

A

Internal and external stimuli alter ratio of Bcl-2 to Bax (inhibit:enhance) which affects the cell’s susceptibility to stress so it responds to growth factors and biochemical stress. If there is DNA damage, p53 gene usually induces cell cycle arrest and initiates DNA damage repair. If unsuccessful, it activates Bcl-2 which in turn activates caspases that lead to the formation of apoptotic bodies.

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48
Q

Briefly describe the extrinsic pathway leading to apoptosis.

A

Starts with ligand-binding at death receptors on cell surface such as TNFR1 and Fas CD95 of the TNFR gene family. Clustering of receptor molecules initiates signal transduction cascade which activates caspase 8 and then caspase 3 which activates DNAses that cause pyknosis (nuclear shrinkage) and karyorrhexis (nuclear fragmentation) leading to the formation of apoptotic bodies.

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49
Q

What is atrophy?

A

Atrophy is the decrease in the size of an organ or cell by reduction in cell size and/or reduction in cell numbers, often by a mechanism involving apoptosis.

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50
Q

Give an example of atrophy in physiological conditions.

A

post-menopausal atrophy of uterus

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51
Q

What are the various causes of pathological atrophy?

A
  1. decreased function (disuse atrophy)
  2. loss of innervation
  3. gradual diminution of blood supply
  4. pressure
  5. lack of nutrition
  6. endocrine deficiency
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52
Q

What is hypertrophy?

A

It is an increase in cell size without cell division.

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53
Q

What is hyperplasia?

A

It is an increase in cell number by mitosis and reduced cell loss by apoptosis.

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54
Q

Give physiological examples of hyperplasia and hypertrophy.

A

muscle hypertrophy (skeletal and left ventricle) in athletes
hyperplasia of bone marrow cells producing RBCs in people living at high altitudes
hyperplasia of breast tissue at puberty, pregnancy, lactation
HT & HP of uterine smooth muscle at puberty and pregnancy
thyroid hyperplasia due to increased metabolic demands at puberty & pregnancy

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55
Q

Give pathological examples of hyperplasia and hypertrophy.

A
  1. right ventricle myocardium HT in response to pulmonary valve stenosis/ pulmonary hypertension/ventricular septal defect
  2. left ventricle myocardium HT in response to aortic valve stenosis/ systemic hypertension
  3. HT of arterial wall smooth muscle in hypertension
  4. proliferative retinopathy of capillary vessels as a complication of diabetes mellitus
  5. erythrocyte precursor HP in bone marrow by increased EPO production due to hypoxia
  6. HP expansion of cytotoxic T lymphocytes in cell-mediated immune response
  7. Juvenile HT in females causing exaggerated pubertal enlargement
  8. gynaecomastia in males due to increased oestrogen levels
  9. Epithelial and connective tissue HP of prostate due to excess oestrogen
  10. follicular epithelial HP of thyroid due to thyroid-stimulating antibody (Graves’ disease)
  11. Cortical HP of adrenal cortex in response to increased ACTH production
    12 HP of myointimal cells in atheromatous plaques in response to platelet-derived factor
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56
Q

What is metaplasia?

A

Metaplasia is the transformation of one type of differentiated cell into another fully differentiated cell type in response to altered cellular environment.

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57
Q

What type of tissue does metaplasia affect?

A

epithelial and mesenchymal cells

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58
Q

Give examples of squamous metaplasia.

A
  1. smokers: ciliated resp epithelium of trachea
  2. stones: ducts of salivary gland, pancreas, bile
  3. transitional bladder epithelium to squamous due to stones or ova pf trematode Schistosoma haematobium.
    4 transitional and columnar nasal epithelium in vit A deficiency
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59
Q

What is Barrett’s oesophagus?

A

It is glandular metaplasia caused by chronic acid reflux in which the squamous epithelium of the oesophagus in transformed to columnar glandular epithelium with intestinal differentiation.

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60
Q

Give examples of osseous metaplasia.

A
  1. following calcium deposition in atheromatous arterial walls
  2. in bronchial cartilage
  3. chronic disease of uveal tract of the eye
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61
Q

What is a tumour?

A

A tumour is any abnormal swelling such as a neoplasm, inflammation, hypertrophy or hyperplasia.

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62
Q

What is a neoplasm?

A

A neoplasm is a lesion resulting from the autonomous or relatively autonomous abnormal growth of cells that persists in the absence of the initiating stimulus.
Abnormal, autonomous, persistent, new growth.

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63
Q

What does neoplasmic transformation involve?

A
  1. multiple genetic alterations (mutations, deletions, rearrangements, translocations, amplifications)
  2. epigenetic changes (promoter methylation silencing transcription)
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64
Q

When is a neoplasm deemed malignant?

A

If it is invasive and metastatic.

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65
Q

What is a tumour comprised of?

A

neoplastic cells + stroma

66
Q

What is stroma in a tumour?

A

Stroma is a connective tissue framework that provides mechanical support, intercellular signalling & nutrition. It contains blood vessels which perfuse the tumour by angiogenesis. It is initiated by vascular endothelial growth factor and opposed by angiostatin and endostatin.

67
Q

What are the histological differences between neoplasms and corresponding normal tissue?

A
  1. reduction in differentiation
  2. loss of cellular cohesion
  3. nuclear enlargement, hyperchromasia, pleomorphism
  4. Increased mitotic activity
68
Q

What is the behavioural classification of tumours?

A

Classed as benign or malignant

69
Q

What are the features of benign tumours?

A 
slow growth rate
infrequent mitosis
good histological resemblance to normal tissue
near normal nuclear morphology 
no invasion
no metastasis
encapsulated border
necrosis is rare
ulceration is rare
exophytic direction of growth
70
Q

What are the features of malignant tumours?

A 
rapid growth rate
frequent and atypical mitosis
variable and poor resemblance to normal tissue
nucleus is enlarged, hyperchromatic, irregular outline, multiple nucleoli and pleomorphic
invasive
frequently metastatic
poorly defined border
necrosis is common
ulceration is common
endophytic direction of growth
71
Q

What clinical problems can benign tumours cause?

A
  1. pressure on adjacent tissues (benign meningeal tumour causing epilepsy)
  2. obstruction to flow of fluid
  3. production of a hormone
  4. transformation into a malignant neoplasm (adenomatous polyp to adenocarcinoma)
  5. anxiety
72
Q

How do malignant tumours lead to the morbidity and mortality associated with them?

A
  1. pressure on and destruction of adjacent tissues
  2. formation of secondary tumour
  3. blood loss from ulcerated surfaces
  4. obstruction of flow
  5. hormone production
  6. other paraneoplastic effects like weight loss and debility
  7. anxiety and pain
73
Q

What is the histiogenetic classification of tumours?

A

It is classification based on cell or tissue of origin and is histologically determined. The degree of histological resemblance to parent tissue allows tumours to be graded (aka degree of differentiation). This histological grade correlated with clinical behaviour.

74
Q

What are the features of carcinomas?

A 
Originate from epithelium.
malignant.
common.
metastasize through lymph
have an in situ phase
usually in people aged over 50
75
Q

What are the features of sarcomas?

A 
Originate in connective tissue.
malignant
rare
metastasize through blood
no in situ phase
usually in people aged under 50
76
Q

What is a papilloma?

A

A papilloma is a benign tumour of non-glandular or non-secretory epithelium such as transitional or stratified squamous epithelium.

77
Q

What is an adenoma?

A

It is a benign tumour of glandular or secretory epithelium.

78
Q

What is carcinoma in situ?

A

The term refers to an epithelial neoplasm exhibiting all the cellular features associated with malignancy, but which has not yet invaded through the epithelial basement separating it from potential routes of metastasis.

79
Q

What is carcinogenesis?

A

Carcinogenesis is the transformation of normal cells to neoplastic cells through permanent genetic alterations or mutations.

80
Q

What is a carcinogen?

A

A carcinogen is an environmental agent participating in the causation of tumours.

81
Q

How are carcinogens identified?

A
  1. epidemiological studies
  2. direct accidental exposure
  3. transforming effects on cell cultures
  4. assessment of occupational risks
  5. carcinogenic effects in lab animals
  6. mutagenicity testing in bacteria
82
Q

What are the main classes of carcinogens?

A
  1. chemicals
  2. viruses
  3. ionising and non-ionising radiation
  4. exogenous hormones
  5. bacteria, fungi, parasites
  6. miscellaneous (asbestos)
83
Q

What are the host factors that play a role in carcinogenesis?

A
  1. race
  2. diet
  3. constitutional factors (sex, inherited risk)
  4. premalignant lesions and conditions
  5. transplacental exposure
84
Q

What is the latency period in carcinogenesis?

A

It is the interval between exposure to a carcinogen and clinical recognition of the tumour.

85
Q

What are the three stages of carcinogenesis?

A
  1. Initiation (when a carcinogen induces the genetic alteration that gives the transformed cell its neoplastic potential)
  2. Promotion (stimulation of clonal proliferation)
  3. Progression ( the process culminating in malignant behaviour characterised by invasion and its consequences)
86
Q

What are the genetic mechanisms involved in carcinogenesis?

A
  1. expression of telomerase
  2. loss of both copies of tumour suppressor gene
  3. activation or abnormal expression of oncogenes
87
Q

What is genomic instability?

A

It is the loss of mechanisms that preserve genomic integrity which is the maintenance of genes and their products that sense and repair DNA damage.

88
Q

What are the two types of TSGs?

A
  1. Caretaker genes maintain genomic integrity by repairing DNA damage.
  2. Gatekeeper genes inhibit the proliferation or promote the death of cells which damaged DNA.
89
Q

What is the gene p53 responsible for?

A

TSG found on short arm of chromosome 17.
Normal func:
1. repair of damaged DNA before S phase by arresting cell cycle in G1 until damage repaired.
2. apoptotic cell death if extensive DNA damage

90
Q

What causes abnormal p53 functioning?

A
  1. non-sense mutations
  2. missense mutations
  3. complexes of normal and mutant p53 in heterozygous individuals
  4. binding of normal p53 protein to protein encoded by oncogenic DNA viruses
91
Q

What are the classes of oncogenes based on the function of their oncoprotein?

A
  1. growth factors
  2. receptors for growth factors
  3. signalling mediator with tyrosine kinase activity
  4. signalling mediator with nucleotide binding activity (disrupting intracellular signalling)
  5. nuclear-binding transcription factor oncoproteins involved in regulation of cellular proliferation
92
Q

What are oncogenes in tumours activated by?

A
  1. mutations

2. excessive production of normal oncoprotein due to gene amplification or enhanced transcription or reduced degradation

93
Q

What are the various epigenetic mechanisms that contribute to tumour growth?

A
  1. gene silencing by hypermethylation of promoter DNA sequences
  2. gene up- or down-regulation due to histone modifications
  3. interference with transcription by microRNA
  4. copy number changes to enhancer and silencer DNA sequences
94
Q

What factors lead to tumour invasion?

A
  1. decreased cellular cohesion
  2. production of proteolytic enzymes
  3. abnormal cell motility
95
Q

What is the epithelial-mesenchymal transition?

A

It is the change in behaviour when epithelial neoplasms acquire motile and migratory properties which are usually observed in cells with mesenchymal lineage.

96
Q

Which adhesion molecules contribute to invasion?

A

Cadherins: altered expression leads to reduced cell-cell adhesion in carcinomas.

Integrin: receptors disperse within the cell leading to altered tumour cell-matrix adhesion.

97
Q

How does abnormal cell motility contribute to invasion?

A

These cells have greater motility than their normal counterparts. There is a loss of normal mechanism that arrests/reverses normal cell migration (loss of contact inhibition) which causes cells to accumulate and form another tumour.

98
Q

What are matrix metalloproteinases?

A

They are enzymes secreted by malignant neoplastic cells that enable them to digest surrounding connective tissue. They are counteracted by tissue inhibitors of metalloproteinases.

99
Q

What are the three major families of metalloproteinases?

A
  1. interstitial collagenases: degrade types I, II, III collagen
  2. gelatinases: degrade type IV and gelatin
  3. stromelysins: type IV and proteoglycans
100
Q

Where does invasion tend to occur?

A

Invasion occurs along tissue planes with reduced resistance to tumour growth such as perineural spaces and vascular lumina.
Not in tissues of cartilage or fibrocartilage like in spinal cord discs.

101
Q

What is pagetoid infiltration?

A

invasion within epithelium

102
Q

What is metastasis?

A

It is the process where by malignant tumours spread from their site of origin to form secondary implants that are discontinuous with the primary tumour and located in remote tissues.

103
Q

What is extensive metastatic disease called?

A

carcinomatosis

104
Q

What is the metastatic sequence?

A
  1. detachment of tumour cells from their neighbours
  2. invasion of the surrounding connective tissue to reach conduits for metastasis
  3. Intravasation into the lumen of blood or lymphatic vessels
  4. Evasion of host defence mechanisms such as natural killer cells in blood
  5. Adherence to endothelium at a remote location
  6. Extravasation of the cells from the vessel lumen into surrounding tissue
105
Q

What are the routes of metastasis?

A
  1. haematogenous: by blood stream to form secondary tumours in organs perfused by blood drained from a tumour
  2. lymphatic: to form secondary tumours in regional lymph nodes
  3. transcoelomic: in pleural, pericardial and peritoneal cavities, results in neoplastic effusion and nodules on mesothelial surface of the cavity
  4. implantation: by accidental spillage of tumour cells during surgery
106
Q

Which organs are usually targeted in haematogenous metastasis?

A

liver, lung, bone, brain

107
Q

Which 5 tumours commonly metastasize to bone?

A

lung, breast kidney, thyroid, prostate

108
Q

What are the local effects of a tumour?

A

Compression, displacement, invasion, ulceration, destruction of adjacent structures

109
Q

What are the metabolic effects of a tumour? Give examples.

A

Due to appropriate or unexpected neoplastic cell products.
thyroid adenoma- thyrotoxicosis
adrenocortical adenoma- Cushing’s syndrome
parathyroid adenoma- hyperparathyroidism

110
Q

What is cachexia?

A

It is the catabolic clinical state of a cancer patient with severe weight loss and debility. It is mediated by tumour-derived humoral factors that interfere with protein metabolism.

111
Q

What is the Warburg Effect shown by most cancers?

A

It is the production of energy by a high rate of glycolysis with fermentation of lactic acid. Normal cells have a low rate of glycolysis with oxidation of pyruvate in mitochondria. Used to image tumours by PET using FDG (increased uptake by tumours).

112
Q

What does cancer prognosis depend on?

A
  1. tumour type
  2. degree of differentiation (grade)
  3. extent of spread (stage)
113
Q

What features contribute to the assessment of tumour grade?

A
  1. mitotic activity
  2. nuclear size, hyperchromasia, pleomorphism
  3. degree of differentiation
114
Q

Describe the Dukes’ staging system for colorectal cancers.

A

Dukes’ A: invasion into, but not through, bowel muscular wall
Dukes’ B: invasion through the bowel muscular wall but without lymph node metastases
Dukes’ C: involvement of local lymph nodes
Dukes’ D: hepatic metastases present

115
Q

Describe the TNM staging system.

A

T: primary tumour. Number suffix denotes tumour size/local anatomical extent.
N: Degree of lymph node involvement. Number suffix denotes number of lymph nodes with metastases.
M: Anatomical extent of distant metastases.

116
Q

Define a coronial autopsy.

A

A coronial autopsy is a systematic scientific examination that helps the coroner determine who the deceased was, when and where they died and how they came about their death.

117
Q

Give an example of a malignant neoplasm that does not metastasize.

A

Basal cell carcinoma of the skin, can be cured by complete excision.

118
Q

What is the common site of metastases from breast carcinoma in women?

A

Spine

119
Q

What is adjuvant therapy?

A

It is extra treatment given after surgical excision.

120
Q

What are the problems with identifying environmental carcinogens?

A
  1. Latency interval may be decades
  2. Complexity of environment
  3. Ethical constraints
121
Q

What is hepatocellular carcinoma epidemiologically associated with?

A

A higher incidence of hep B/C and mycotoxins

122
Q

What is lung cancer associated with?

A

Smoking

123
Q

What is bladder cancer associated with?

A

Higher incidence in rubber and aniline dye industries.

Beta-naphthylamine

124
Q

What is the occupational risk associated with scrotal cancer?

A

Higher incidence in chimney sweeps due to exposure to polycyclic aromatic hydrocarbons on the cloth they kept in their pockets.

125
Q

What are the known common chemical carcinogens?

A
  1. polycyclic aromatic hydrocarbons- lung cancer (smoking) and skin cancer (mineral oils)
  2. Aromatic amines- bladder cancer (rubber/dye works)
  3. Nitrosamines- gut cancer
  4. Alkylating agents- leukaemia
126
Q

What diseases does asbestos exposure lead to?

A

malignant mesothelioma, lung cancer and asbestosis.

127
Q

What are the different cancers caused by exposure to radiant energy?

A

lung cancer in uranium miners
skin cancers in radiographers
thyroid cancer in Ukrainian children

128
Q

Gives examples of hormone overproduction leading to cancer.

A

Oestrogen- endometrial/mammary cancer

Anabolic steroids- hepatocellular carcinoma

129
Q

What cancer does exposure to the mycotoxin Aflatoxin B1 lead to?

A

Hepatocellular carcinoma

130
Q

What cancers are commonly caused by parasites?

A

cholangiocarcinoma by chlonorchis sinensis

bladder cancer by Shistosoma

131
Q

Give an example of transplacental carcinogenesis.

A

Increased risk of vaginal cancer (rhabdomyosarcoma) in the female foetus due to diethylstilbestrol use by the mother.

132
Q

Give examples of identifiable local abnormalities that increase the risk of malignancy at the site.

A

Colonic polyps
Cervical dysplasia/ cervical intraepithelial neoplasia
Ulcerative colitis
Undescended testis

133
Q

Define carcinoma.

A

malignant epithelial neoplasm.

134
Q

Why do benign neoplasms not exhibit central necrosis?

A

The rate of angiogenesis is equivalent to its growth rate.

135
Q

What do you mean by anaplastic?

A

Where the cell type of origin is unknown (due to poor resemblance) the tumour is said to be anaplastic.

136
Q

What is a teratoma?

A

A neoplasm that contains cells from several different tissue types.

137
Q

What is a carcinosarcoma?

A

A malignant tumour surrounded by malignant stroma.

138
Q

What is Burkitt’s lymphoma?

A

Cancer of the lymphatic system, particularly B lymphocytes found in the germinal center.

139
Q

What is Ewing’s sarcoma?

A

Type of rare cancer that affects bones or tissue around bones. Usually found in teenagers as they undergo growth spurts.

140
Q

What is Grawitz tumour?

A

Tumour found in renal cell carcinoma - malignant epithelial neoplasm resulting from proliferation of tubule cells.

141
Q

What is Kaposi’s sarcoma?

A

Cancer that affects the cells lining blood and lymphatic vessels and results in lesions in the skin, lymph nodes and other organs. Caused by the human herpesvirus 8.

142
Q

What are the various proteases that help cancer cells invade and metastasize?

A 
matrix metalloproteinases (collagenases)
cathepsin D
urokinase-type plasminogen activator
143
Q

What 2 factors are involved in intravasation?

A

collagenases and cell motility

144
Q

What 3 factors are involved in evasion of host defences?

A

aggregation with platelets
shedding of surface antigens
adhesion to other tumour cells

145
Q

What 3 factors are involved in extravasation?

A

adhesion receptors
collagenases
cell motility

146
Q

What are the promoters of angiogenesis?

A

vascular endothelial growth factor

basic fibroblast growth factor

147
Q

What are the inhibitors of angiogenesis?

A

angiostatin
endostatin
vasculostatin

148
Q

Name tumours that commonly metastasize to the lungs.

A

sarcomas

common cancers except colorectal which drains into the portal venous system and hence metastasizes to the liver.

149
Q

Name tumours that commonly metastasize to the liver.

A 
colorectal
colon
stomach
pancreas
carcinoid tumours of intestine (slow-growing neuroendocrine)
150
Q

Give examples of conventional chemotherapy treatments.

A
  1. Vinblastine- antimicrotubule agent
  2. Etoposide- inhibits topoisomerase II
  3. Ifosamide and Cisplatin- bind directly to DNA and inhibit DNA synthesis by cross-linking
151
Q

What are the disadvantages of conventional chemotherapy?

A

Not selective for tumour cells so affects all fast-dividing cells.
Does not target slow-dividing tumours.
Hits normal cells that are dividing leading to hair loss, myelosuppression and diarrhoea.

152
Q

Which tumours are well targeted by conventional chemotherapy?

A 
Good for fast-dividing tumours:
germ cell tumours of testis
acute leukaemias
lymphomas
embryonal paediatric tumours
choriocarcinoma
153
Q

Give examples of targeted chemotherapy.

A
  1. Cetuximab (Erbitux)- binds competitively to extracellular domain of EGFR (epidermal) and blocks the production of VEGF (vascular endothelial), interleukin 8, bFGF (basic fibroblastic).
  2. Herceptin- blocks Her-2 receptor and prevents its overexpression in breast cancer (trastuzumab)
  3. Gleevec- small molecular inhibitor of c-kit tyrosine kinase. originally developed as inhibitor of BCR-ABL protein to treat CML (chronic myelogenous leukaemia).
154
Q

Give an example of conventional chemotherapy.

A

Tamoxifen - oestrogen agonist/antagonist.

155
Q

What occurs in the early stages of AI?

A

Oedema fluid, fibrin and neutrophil polymorphs accumulate in the extracellular spaces of the damaged tissue.

156
Q

Name and explain the chemical mediators of acute inflammation.

A

Histamine and thrombin - up-regulation of adhesion molecules on the surface of endothelial cells (neutrophil adhesion to endothelial surface).

157
Q

Name the four enzymatic cascade systems found in plasma.

A

Complement
Kinins
Coagulation
Fibrinolytic

158
Q

What is acute inflammation?

A

The initial and transient series of tissue reactions to injury.

159
Q

Name the endogenous chemical mediators of inflammation and what they cause.

A
  • Vascular dilatation – histamine, prostaglandins, PGE2/I2, VIP, nitric oxide, PAF
  • Increased vascular permeability – transient phase (histamine), prolonged phase (bradykinin, nitric oxide, C5a, leukotriene B4 and PAF, potentiated by prostaglandins)
  • Adhesion of leucocytes – upregulation of adhesion molecules on endothelium, principally by IL-8, C5a, leukotriene B4, PAF, IL-1 and TNF-alpha
  • Neutrophil polymorph chemotaxis – Leukotriene B4, IL-8
160
Q

Name four known carcinogens of hepatocellular carcinoma.

A

Hep B virus
Hep C virus
Aflatoxin
Alcohol

Phase 2A Medicine (16 decks)

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