week 5 Flashcards
Outline the major functions of the lymphatic system in (a) fluid balance, (b) host defence, and (c) nutrition
removes and extracts excess fluid and takes back to the large veins. prevents build up and undue pressure
houses white blood cells- lymph nodes.
can release cytokines which attract CC7 receptors to lymph nodes which can present cells and activate WBC
absorbs fat and fat soluble vitamins.
Understand how lymphatic dysfunction impacts on human disease
less ability to react to infection and poor transport of white blood cells
decreased ability to clear fluids resulting in swelling- possible pressure conditions.
decreased absorption of fats and minerals and resultant undernourishment
Define the following disorders of growth, giving physiological and pathological examples: hyperplasia, hypertrophy, atrophy, aplasia, hypoplasia, metaplasia.
hyperplasia: increase in number of cells- action of growth factors. compensatory- in the liver after donation. prostatic hyperplasia- excess androgens.
hypertrophy: increase in cell size- skeletal muscle hypertrophy- cardiac myocites in heart failure.
atrophy: decrease in size and number. uterus after delivery. decreased use/ blood flow.
aplasia: absence of an organ and its primordium.
hypoplasia: incomplete development of an organ due to a decreased number of cells. pulm hypoplasia due to oligohydramnios
metaplasia: replacement of one tissue type with another, to withstand a diverse environment. Barrets oesophagus- (squamous to columnar)
Define and distinguish between hamartoma and heterotopia.
hamartoma- a mass of mature but disorganised tissue at the correct site
heterotopia: well developed nest of normal tissue at the wrong site.
Define dysplasia, giving examples, and explain the link between dysplasia and invasive malignancy, understanding how this can be used as a screening tool.
dysplasia: disorganisation of cells.
e.g multicycstic renal dysplasia.
disorganised epithelial growth- can spread to full thickness of eipthelium- and can spread if reached basement membrane.
can be pre-malignenet e.g Barrets - monitor and take biopsies regularly to catch cancers early.
Understand the difference between “premalignant” conditions and conditions predisposing to the development of malignancy.
predisposing conditions- something that increases the likelihood of cancer- e.g smoking and lung cancer. TP53 mutation
premalignant- identifiable morphological alterations which increase the likelihood of cancer at that site.
Define the terms “cancer”, “carcinogenesis” and “carcinogen”.
Cancer diseases in which abnormal cells divide without
control and can invade nearby tissues.
carcinogenesis- the transformation of a normal cell to a cancer cell through passenger and driver mutations.
carcinogen-substances that can lead to cancer
Explain the Multistage Theory of Carcinogenesis.
2-8 driver mutations are required
Describe the four main types of carcinogens.
Viral- HEP B, HPV
chemical (benzene, alkylating agents)
physical- X-rays, UV, alpha radiation.
hereditary genetic predisposition- braca genes, down syndrome
Give examples of carcinogens and describe their mechanisms of action.
chemical platinum agents- bind irreversibly at guanines- bind two strands together.
UV radiation- causes thymine dimers ‘kinking’ dna
Understand the molecular mechanisms involved in tumour progression, invasion and metastasis.
progression- acquisition of specific mutations. clonal expansion (by tumour promoters). loss of heterozygosity- genomic instability. epigenetic changes.
invasion- inc mechanical pressure, hypoxia/ blood supply, increased motility and production of degradation enzymes.
metastasis- frequent extravasation (80%) but poor ‘seeding’ in other tissues (0.02%) requires EMT –> MET to properly grow. need specific adhesion between tumour cells and endothelial cells in target organ to create a favourable environment.
Describe the mechanisms of tumour cell invasion and indicate the key molecules that participate in this process.
key molecules- Vascular endothelial growth factor (VEGF)
fibroblast growth factor (FGF2) TGFB.
metalloprotinases facilitate their release.
Mechanisms: increased mechanical pressure, hypoxia, increased motility, inc prod of digestive enzymes
Summarize the steps involved in the metastatic process.
extravasation
micrometastasis + colonization (0.02% sucess)
‘seed and soil hypothesis’- need signals and factors to allow adhesion
also need to undergo msenchymal to endothelial transformation (reverse of earlier)
Explain the “Seed and Soil Hypothesis”.
Discuss the application of liquid biopsies in the detection of circulating tumour cells (CTCs).
sampling of non solid biological tissue.
facilitates detection of circulating tumor cells- markers for tumor growth and treatment effectiveness.
can detect earlier, faster. more sensitive for people to relapse (breast)
can detect treatment resistant changes in cell DNA
Give examples of oncogenes and explain their mechanisms of action.
HER-2 human epidermal growth factor 2. needs to dimerise to function. normally stimmed by growth factors. when activated RAS, MEK, RAF pathway stim growth. This can be genetically amplified - more activation- more growth. can target this with monocolnal antibodies.
KRAS- cellular signal transducers. - activation of receptor TKinase activates RAS. (On with GTP bound) RAS products activate pathways that control transcription of genes. mutation leads to permanent ON- permanent growth.
C-myc family of genes that encode transcription factors. alterations in C-myc by virus, translocation(often between 8-14 burkitts lymphoma) , amplifications.
Identify the red flag signs and symptoms for suspected malignant melanoma
type 1-2 skin
multiple melanocitic naevi (50+)
ugly duckling sign.
Outline the pathogenesis of malignant melanoma with specific reference to the role of sun exposure
sun exposure as child most significant factor.
Outline what is meant by the Breslow thickness and how it can be used in staging
Demonstrate an awareness of the epidemiology of common cancers and precipitating factors
causes of preventable cancer
smoking
obesity
alcohol
UV radiation
physical inactivity
poor diet.
Recognise the macro- and microscopic characteristics malignant neoplasms
Show familiarity with tumour classification by histological subtype and nomenclature
type of tissue –> behaviour of neoplasm –> relevant suffix
Recognise the macro- and microscopic characteristics of benign neoplasms
Explain the difference between tumour grade and stage
grade- histological assessment
stage- clinico- radiologico-pathalogico assessment.
Describe cellular and architectural features which influence the grade of a tumour
organisation vs unorganised
less wide infiltration vs wide infiltration
lower vs higher mitotic activity
less vs more necrosis.
Recognise why alternative staging classifications are needed for malignant lymphomas
need different staging due to the frequent travelling of white blood cells.
classified as 1-4.
above or below the diaphragm is important.
Explain how antibiotics inhibit protein synthesis in bacteria
Explain why some drugs selectively inhibit fungal growth
Explain how drugs exert an anti-viral action
zidovudine - prodrug
metablosed to ZDVTP
