PBL Block 9 Week 5 Flashcards
HPV virus
Naked double-stranded DNA virus which replicates in the nucleus of the host cell and has an icosahedral shape
How does HPV affect the cervix?
It infects the basal squamous cells of the cervix and replicates by hijacking the replication process of keratinocytes and as it ascends the epidermal junctions synthesises capsid proteins.
Cervical cancer complications
Metasases to the inguinal lymph nodes and result in leg oedema. The tumour may compress onto the bladder or bowel and cause urinary problems. Fluid build up can occur around the kidney due to issue with urinary outflow and cause hydronephorosis.
Cellular features of cancer
Scarce cytoplasm which reduces cell adhesion, prominent nucleoli due to fast rate of replication, large nucleus, poorly differentiated and irregular morphology. Increase in ribosomes and mRNA and mitochondria and poorly developed Golgi apparatus. More mitochondria but these are abnormal and results in abnormal glycolysis. Increase of smooth ER but this decreases along with rough ER
How does cancer progress?
Hyperplasia: increase in size due to tissue growth
atypia: abnormal cell characteristics
metaplasia: change in one cell type to another
dysplasia: excessive non-neoplastic proliferation
Benign tumour
Malignant tumour
What is cancer stage?
Extent of spread of tumour in the body
What is cancer grade?
Level of differentiation.
Cervical cancer symptoms
-> Abnormal heavy vaginal bleeding after sex that becomes more frequent and spontaneous
-> Red/brown vaginal discharge due to inflammatory response
-> Vaginal discomfort like irritation and pain
-> Dysuria: pain while urinating
-> Urinary retention
Early cancer features
Night sweats, unexplained weight loss, unexplained bleeding, hyperplasia, appetite loss, breathlessness, prolonged healing, persistent pain.
What are the UK cancer screening programmes?
Bowel cancer
Cervical cancer
Breast cancer
What are the cancer cellular changes?
Scarce cytoplasm, prominent nucleoli due to fast rate of replication, large nucleus, poorly differentiated and irregular morphology.
Increase in ribosomes and mRNA and abnormal; mitochondria and poorly developed Golgi apparatus. Abnormal glycolysis. Increase of smooth ER but this decreases along with rough ER
In situ melanoma
Hasn’t reached basement membrane
Ex situ melanoma
Reached the basement membrane and can be invasive
Eczema
Type 1 hypersensitivity reaction caused by deficiency in filaggrin protein present in the epidermis and junction abnormalities. This allows allergens to infiltrate the skin and induce Th1 immune response where Th2 are recruited. The dermis becomes damaged over time thickenings which causes lichenifications when there is excessive itching that leads to damage.
Superficial spread melanoma
Present on the limbs of younger people due to intermittent high UV exposure.
Lentigo melanoma
Melanoma restricted to the epidermis.
What are the subtypes of cervical cancer?
Squamous carcinoma which is most common
Adenocarcinoma which has glandular characteristics
What form of cervical cancer is inherited?
Squamous cell carcinoma which occurs in the ectocervix, which contains squamous epithelia
What is an adenocarcinoma?
Malignant tumour in the mucous producing cells. In cervical cancer, this occurs in the endocervix, which contains glandular epithelia
What is the epidemiology of cervical cancer?
Affects younger women aged 30-34, deprived areas, White women, low income countries, later stage diagnosis in Ethnic minorities
Early cancer features
Night sweats due to inflammation as immune defence builds against tumour
Weight loss unexplained: this is a paraneoplastic syndrome called cachexia where the immune system is depleted of resources fighting the tumour, utilising protein stores in muscle tissue and fat oxidation. This can lead to fatigue
* Unexplained bleeding and bruising due to tumour angiogenesis or systemic effects of the tumour because of tissue damage eg, blood in urine, stools to metasases
* Lump or mass due to tumour hyperplasia
* A new mole or changes to existing moles
* Appetite loss
* Breathlessness and persistent cough
* Prolonged healing of injuries
* Persistent pain
* Change in bowel habits
* Difficulty swallowing
* Persistent bloating
Melanoma risk factors
Type 1 skin that easily burns and freckles
High intermitted/long term UV exposure
Family history
Previous history of moles
Tanning beds
Genetics
Immunosuppression
Airline workers
Obesity
Epidemiology of melanoma
Older white people, specifically men with fair skin, red hair and blue eyes. Australia has the highest incidence
Types of tumour spread
Haematogenous spread, more prominent in veins than arteries due to thinner walls so metasases follows venous flow.
Lymphatic system is the most common route for carcinomas to spread throughout the body.
Transcolemic via the body cavities such as pleural, arachnoid, pericardial space which leads to organ compression and organ failure.
What happens in metasasis?
It separates from the main tumour and infiltrates the basement membrane to enter the bloodstream, typically the veins and enter the lymphatic system to gain entry into the distant organs and result in the formation of new lesions and induce angiogenesis.
Types of malignant tumours?
Carcinoma: due to altered epithelial cells, found on skin surface and internal organs
Sarcoma: change in muscle, bone, fat or connective tissue
Leukemia: malignant WBCS
Lymphoma: cancer of lymphatic system cells from bone marrow
Myeloma: Cancer of WBCS which produce antibodies
Bacterial causes of skin infection
Staphylcoccal and streptococcal. and corynebacterium
Corynebacterium causes erythema
How does squamous cell carcinoma present?
Scaly red patches, open red sores
Lower limb malignant melanoma
Superficial spread
Face malignant melanoma
Lentigo maligna melanoma
Trunk malignant melanoma
Nodular
What is CDK4?
Cell cycle and apoptosis mediator
K-ras
Oncogene which causes adenoma formation in bowel cancer
DCC
Colorectal cancer suppressor receptor when mutated leads to carcinoma
What is the suicide enzyme?
DNA repair enzyme used in direct reversal, coded for by the human MGMT gene. Reduced expression of MGMT by cancer cells increases response to alkylating agents
What is the most common category of mutation in cancer?
Somatic mutation due to compounds or spontaneous mutation
Cause of FAP
Mutation of gatekeeper APC
Cause of HNPCC
Mutation of caretaker MSH2 and MSL1
Cell count for cancer death
10^12
Cancer count for clinical detection
10^9 -> 10^12
How does cancer drug resistance occur?
Subclones of the least resistance tumours are killed
What is a subclone?
Clone from a founding clone which has an acquired mutation
