Integrity - Cancer Flashcards
Excessive Immune response stages
Pro-inflammatory cytokines and chemokines are released.
This increases vascular permeability, bacterial killing, increased peripheral resistance, tachypnea, fever, tachycardia.
This leads to oedema, tissue damage, organ failure.
Scar formation
- hemostasis phase - clots the bleeding
- defensive/inflammatory phase - destroys bacteria
- proliferative phase - replace the tissue
- maturation phase - collagen fibers reorganise
Tissue targeted autoimmunity (Type 1 diabetes)
T cells target pancreatic beta cells, leading to insulin deficiency
Tissue targeted autoimmunity (MS)
T cells target neuron myelin sheath leading to demyelination and neurodegeneration
Tissue targeted autoimmunity (graves’ disease)
Ab stimulants target TSH receptor leading to hyperthyroidism
Tissue targeted autoimmunity (myasthenia gravis)
Ab blocks Ach receptor leading to neuromuscular transmission blockade
Tissue targeted autoimmunity (primary biliary cholangitis)
T cells target small bile duct epithelium leading to cholestasis and liver fibrosis
Atrophy
shrunken tissue from reduced cell size or number
hypertrophy
enlargement of cells in a tissue
hyperplasia
increased number of normal cells in a tissue
transdifferentiation
A switch of differentiation direct from one mature phenotype to another which is normally present in that tissue
metaplasia
a switch of differentiation from one mature phenotype to another which is not normally present in that tissue, in response to an environmental change
dysplasia
disordered microscopic appearance and maturation of cells implying neoplasia
tumour
abnormal lump of no specific cause
cyst
abnormal fluid filled lesion lined with epithelium
hamartoma
disorganised mature normal tissue elements lacking autonomous growth
neoplasm
growth of genetically abnormal cells derived from a mutated ancestor seed cell
cancer
malignant neoplasm which invades (crosses tissue boundaries) and metastasises ( discontinous spread to survive and grow at remote sites)
Craniospinal venous system
2-way venous flow (no valves), links cranial and vertebral circulation with intercostal abdominal and pelvic venous plexuses, results in a direct route for metastisis to spine and brain
TNM system
cancer staging
T: local tumour extent, diameter, invasion
N; lymph node metastasis, regional, distant, number affected
M: metastais elsewhere
Worrying ulcer
best biopsied at the edge
polyp
epithelium covers a raised core of connective tissue
papilloma/papillary neoplasm
epithelium covers long thin branches of connective tissue - much greater surface area than polyp of similar size
problems resulting from benign neoplasms
compression, obtruction, haemorrhage, infarction, secreted proucts, progression to malignancy
cancer forming
over time mutations occur, clonal expansion can lead to a large number of mutated cells. This increases with chronic inflammation and carcinogens
inside a cancer
cancer cells, non-cancer cells , nerves, blood vessels and lymphatics, high interstitial fluid pressure produces a core environment of ischaemia. Interstitial fluid flows from core into nearest lymphatics
Large uncontrolled angiogenesis with varied pO2. This surrounds a matrix structure.
Cancer hallmarks
replicative immortality, resist cell death, matrix degradation, angiogenisis, rtissue invasion, insensitivity to antigrowth
cancer stemness
cancer cells can move in and out of stemness if needed to replenish cell envrionment
cancer metabolism
anabolic (aerobic glycolysis) and chaotic vasculature that produces metabolic stress and depletes o2 and nutrients to healthy cells . This leads to immune dysfunction and CD8+ cell exhaustion and T cell senescence
Cancer cells and varying demands
cancers rebalance essential tasks via plasticity
cancer pre-cursor lesions
changes in the architecture of the epithelium, cytological morphology of the cells that precede invasion and metastasis. These have not invaded and stay on the epithelial side of basements membrane
cancer gene mutation targets
genes that control proliferation, cell death, genomic stability. regulate movement and adhesion. The transition from normal cell to malignant cancer requires several mutations
carcinogens
agents that induce cancer (mutagens): chemical, physical (UV or ionising radiation), biological (bacteria, viruses, parasites)
carcinogenisi
process of cancer induction.
- initiation: the alteration of a normal cell to a potentially cancerous cell.
- Promotion: a process which permits the clonal amplification of the initiated cell, promoters are not mutagens they induce proliferation ‘fix = make permanent’
- Progression: acquisition of further mutations within the neoplastic clone drive progression to a malignant neoplasm
dose response
a linear relationship between the amount of carcinogen delivered in a single dose and the number of tumours which develop
latent period
time lag between the administration of carcinogen and appearence of macroscopic tumours.
threshold dose
there is a thershold dose of carcinogen below which no tumours form. (in the absence of secondary non carcinogenic stimulus e.g wounding)
Replicative senescense
primary cells can only undergo a limited number of cell divisions (hayflick number) as the chromosome telomere ends shorten with each division until the cell is held in arrest (G0) and apoptosed
telomerase
inhibits telomere shortening, present in germ and stem cells as well as cancer `
Autosomal dominnant (heterozygous) cancer predispositions
retinoblastoma (Rb/Rb 1)
hereditary non polyposis colon cancer (MLH1,MSH2)
familial breast and ovarian cancer (BRAC-1/
brac-2)
autosomal recessve (homozygous) cancer predispositions
xeroderma pigmentosum (XP) fanconi's anemia (FA)
What type of disease is cancer?
Genetic, and more than one mutation is necessary for progression
Chemical carcinogens
synthetic - polycyclic hydrocarbons coal etc
aromatic amines & azo dyes hair dyes etc
naturally occurring - nitrosamines processed foods and beer. aflatoxin - peanut
carcinogenic parasites
schistosoma haematobium
carcinogenic bacteria
helicobacter pylori
carcinogenic viruses
HPV, HBV,HCV, EBV, HTLV 1, HHV 8
What gene classes are altered in cancer ?
Oncogenes (Onc) - normal version = proto-oncogenes, activated version = oncogenes . Cancer promoting genes that must be activated.
Tumour suppressor genes (TSG) - must be inactivated, suppress inappropriate proliferation
p53
protector against aberrant oncogenes, mutation in p53 makes the cell genetically unstable and allows telomerase to overcome replicative senescense
What is MMR
it corrects mismatched DNA bases
what causes the disregard of apoptotic signals?
p53 inactivation, telomerase activation, BCL2 overexpression
Cancer invasion
cancer cells move by destruction of nearby tissue using oedema. invasion requires change and or loss in cell-cell and cell-matrix adhesion, proteolysis of matrix, movement, break of cadherins that are central to adhesion
How cancer metastises
detachment and invasion of surrounding tissues, neo-vascularisation, penetration in lymph and blood, release of tumor cells, evasion of host defences, adherence at the site of arrest
lymphatic spread of 3 main cancers
breast - axillary lymph nodes
testicular - lower lumbar lymph nodes
colorectal - local mesenteric nodes and liver
common metastatic sites
liver,lung,bone,brain
cancer grading vs staging
grading - degree of differention
staging - invasion and metastasis
Diagnosis of cancer
ultimately histoligical h and g stain
causes of lung cancer
smoking, occupation (uranium, asbestos ), environmental exposures (radon gas), genetic (Li-Fraumeni Syndrome - mutated p53 genes)
sarcoma
cancer that begins in the bone and in the soft tissue
lymphoma
cancer beginning in the lymph
melanoma
cancer of the skin
hematoma
bruise
Carcinoid lung tumour
relatively rare, slow progeression, present with haemoptysis or symptoms of airway obstruciton, younger adults and children
lung cancer entity
it is not a single entity but a group of malignant epithelial tumours with different pathophysiologies
Symptoms and signs of lung cancer
cough, dyspnoea, haemoptysis, weigh loss, chest/shoulder pain, hoarseness, fatigue, slow to clear pneumonia, finger clubbing, cervical lymphadenopathy, liver-bone-brain metastases, pleural effusion.
Initial investigation of lung cancer
radiology - CXR, CT (lump)
Blood tests - high calcium, abnormal liver function tests
low serum sodium
main cells of the epidermis
keratinocytes, melanocytes (neural crest derived), langerhan cells (bone derived)
main cells of dermis
fibroblasts, ecm - collagen, mast cells
keratinisation
differentiation in skin that leads to a dead anucleated cell called the stratum corneum
cell compartments in epidermis
basal, spindle,granular,stratum corneum
melanin
synthesised melanocytes
appendageal structures
collective name for hair follicles, sebaceous glands, eccrine sweat glands. developed ONLY during first trimester of pregnancy
erythema
red colour associated with increased blood flow to skin
indomethacin
drug that inhibits some inflammatory pathways involved in sunburn
phototherapy
treatment modality in dermatology, exposure to uv radiation
fibroblasts
mesenchymal derived cells, that remodel extracellular collagen protein. found in the dermal papilla of the hair follicle
mast cells
tissue basophil, contain and discharge (Degranulate) vasoactive chemicals including histamine
inflammatory cells
lymphocytes, polymorphs, dermal macrophages
vessels
there are no vascular elements in the EPIdermis
epidermal differentiaton
as keratinocytes move from the basal layer to their terminally differentiated dead state in the stratum corneum they produce a proteins (keratins and filaggrin), and lipids
keratins and filaggrin
keratins are alpha helical proteins bound in pairs one acidic one basic, they are aggregated by filaggrin
classes of melanin
eumelanin - brown/black
pheomelanin - red or yellow
skin colour differences
everyone has same number of melanocytes, differences arise due to amount and type of melanin produced by the same number of melanocytes
Where is melanin produced
melanosomes that are passed down the dendrites into the surrounding keratinocytes
albinism
same number of melanocytes, less melanin. mutation of tyrosinase key enzyme for melanin biosynthesis
langerhan cells
antigen presenting cells, antigens are gathered and metabolised by langerhan cells before being presented to T-cells in the regional lymph node
collagen
procollagen is synthesised, secreted and remodelled by fibroblasts, collagen is a triple alpha helix.
marfan’s syndrome
mutation of fibrilin (skin elastic fibre)
sebaceous cells
produce lipids that make up sebum, oestrogen decreases sebum excretion
hair follicles
are formed in utero, once they are destroyed they cannot be regenerated
