S4C4 Flashcards
What is the biopsychosocial approach to healthcare?
Mind-body relationship dynamic system
Cause of disease has multiple factors at different levels
Causality is circular
Psychosocial factors are essential
Holistic approach to illness and treatment
Individuals and society are responsible for health
Physical, psychological and social factors are responsible for treatment
Reduction of physical, psychological and social risk factors are the main focus
What is the COM-B framework?
Capability and Opportunity lead to motivation.
Behaviour links to them all
What is the PRIME theory?
Plans, evaluations, motives, and Impulses lead to response impacted by the internal and external environment
What is the health belief model?
Demographic variable lead to susceptibility, severity, costs, benefits, cues to action, health motivation, and perceived control. These all affect the likelihood of behaviour.
What is the self-regulation model?
Illness representation links to the emotional reaction. It also links to their coping behaviour for control of illness and emotion.
Describe multi-step tumorgenesis
The initiating mutation goes under first clonal expansion, representing ~10^6 cells.
A second mutation then occurs and through an increased mutation rate, many multiple independent mutations occur causing multiple parallel clonal expansion
What are viral oncogenes?
Viral genes that when introduced into cells have dominant transformative effects
What are cellular oncogenes?
Cancer DNA transfected into normal cells caused transformation, again in a dominant manner
What is the two-hit theory?
That you need 2 random sporadic hits on a tumour suppressor gene. (unilateral)
Describe a signalling pathway
Ligand Receptor Signaling cascade Transcription factors Delta gene expression
How does RAS become active?
GEF (Guanine nucleotide exchange factors) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP) which activates RAS
How does RAS become inactive?
GAP (GTPase activating proteins) removes an inorganic phosphate making ADP bind to RAS
What happens when Wnt isn’t active?
GSK-3β is active, meaning Apc is active with an inorganic phosphate and β-catenin gets degraded
What happens when Wnt is active?
GSK-3β is inactive, meaning Apc is inactive and β-catenin doesn’t get degraded. This can now interact with the DNA in the nucleus.
How does Cyclin D1 become activated
Growth factors activates Ras which activates Fos/jun. In addition, Ras and Wnt signalling activates β-catenin which activates Tcf/lef. This activates cyclin D1
What 2 things consistently change the genome?
Continuous damage
Continuous repairs
List examples on continuous damage to the genome.
oxidation replication errors UV x-rays chemicals mitosis
List examples on continuous repair to the genome
BER NER proofreading NHEJ DSBR/HR the SAC
What is senescence?
The condition or process of deterioration with age
In what type of cell is telomerase active?
Tumour cells
What is the end replication problem
When the replication fork reaches the end of the chromosome, however, there is a short stretch of DNA that does not get covered by an Okazaki fragment.
Also, the primer of the last Okazaki fragment that does get made can’t be replaced with DNA like other primers.
Meaning part of the DNA at the end of a eukaryotic chromosome goes uncopied in each round of replication, leaving a single-stranded overhang.
Over multiple rounds of cell division, the chromosome will get shorter and shorter as this process repeats.
Why are liquid biopsies done?
Tumours shed cells and DNA into the blood
Minimally invasive and inexpensive
Advanced detection technology
What does CRP indicate?
produced in the liver
rises in response to inflammation
Why are Chemotherapeutic agents used? How are the classified?
directly or indirectly inhibit theproliferationof rapidly growing cells, typically in the context of malignancy. They are classified according to their mechanism of action and includealkylating agents,antimetabolites,topoisomerase inhibitors, andmitotic inhibitors.
What side effects are associated with chemotherapy?
It’s associated with arangeof adverse effects (e.g., nausea, vomiting, increased risk of infection, and impaired growth of healthy cells), and with some agents, an increased risk of secondary neoplasms. Symptomatic management of associated side effects is recommended to improve tolerance.
what are the general side effects of chemotherapy?
Gastrointestinal mucosa:mucositis→ stomatitis,esophagitis, enteritis associated withdiarrhoea
Hematopoiesis(myelosuppression)
Granulocytopeniaandlymphocytopenia(increased risk of infection)
Thrombocytopenia(increased bleeding risk)
Anemia(fatigue)
Hair follicles:hairloss
Chemotherapy-induced peripheral neuropathy
Pain, burning, tingling, and loss of sensation in the distal extremitiesthat spread from the hands and feet.
Typically spreads in a“stocking-glovepattern”
Causative agents includeplatinum-basedmedications (e.g.,cisplatin),taxanes(e.g.,paclitaxel), andvinca alkaloids(e.g.,vincristine).
Centrally inducedvomiting
Gonadal damage
What is neoadjuvant cytostatic therapy?
Administeredpreoperatively to reducetumormass
What is adjuvant cytostatic therapy?
Administeredpostoperatively to reduce risk of recurrence and/or to improve prognosis
What is Palliative cytostatic therapy?
Administered if curative therapy is not possible; indications vary
What is cytoreductive conditioning?
high-dosecytostatic therapy(sometimes in combination with whole body radiation)to suppress bone marrowbeforebone marroworstem cell transplantation.
What are the benefits of oral chemotherapy?
Oral administration of cytostatic drugsallows for outpatient treatment and avoids the need for inpatient hospitalization(e.g., for patients in need of palliative chemotherapy).
What cytostatic drugs can be administered orally? (classification : name)
Anthracyclines:idarubicin
Pyrimidine analogs:capecitabine
Alkylating agents:temozolomide
Topoisomerase inhibitors:etoposide
What is the effect of immunotherapy with APC?
An anti CTLA-4 antibody can block the binding between CD80/86 on the APC and CTLA-4. This activates the T-cell allowing elimination of tumour cells
What is the effect of immunotherapy with Tumour cells?
Anti-PD-L1 binds to PD-L1 on a tumour cell.
Anti-PD-1 binds to PD-1 on a T-cell.
This stops binding between PD-L1 and PD-1 meaning the T-cell can be activated leading to the elimination of tumour cells
What is ALT involved in? What does an increase show?
Involved in gluconeogenesis - specific to hepatic cells
Shows hepatocyte damage
What is ALP involved in? What does an increase show?
Responsible for cleaving phosphate groups off various substances under alkaline conditions
Increased during pregnancy, cholestasis and increased osteoblast activity
What causes increased serum bilirubin?
Cholestasis
What is C reactive protein?
An acute phase reactant involved in the opsonization of pathogens with a half-life of 24 hours. It is a highly sensitive marker for inflammation but is not specific to any disease or organ. Increases about 6–12 hours after the inflammatory process begins
What does ESR measure?
Measures the distance that erythrocytes have fallen after one hour in a vertical tube of anticoagulated blood
Elevated in infection
What causes increased urea levels?
Increased in severe renal failure, catabolic states and dehydration
What is GFR?
volume of primary urine that is filtrated by the kidneys over a certain amount of time per standardized body surface area
What is eGFR based on?
creatinine levels
What causes decreased ferritin?
iron deficiency and nephrotic syndrome
What causes increased ferritin?
acute phase reaction and iron overload
How do you collect a stool sample?
make sure the sample doesn’t touch the inside of the toilet
use the spoon or spatula that comes with the container to place the sample in a clean screw-top container and screw the lid shut
if you’ve been given a container, aim to fill around a third of it – that’s about the size of a walnut if you’re using your own container
What is a carcinoma in situ?
abnormal cells have not spread beyond where they first formed
Define a malignant tumour.
Cancerous cells which have invaded and destroyed nearby tissue, possibly spread to other parts of the body
What happens in the S-phase of the cell cycle?
Genome duplication
What happens in the G2-phase of the cell cycle?
Genome segregation
How do you get from genes to tissues?
Genome undergoes transcription to form transcriptome.
Transcriptome undergoes translation to form proteome
Proteome undergoes biogenesis to form functioning cells
Cells undergo metabolism and proliferation to form the tissue architecture
What is another name for Cdc2?
Cdk1
What is the R point in the cell cycle?
The point at G1 at which commitment occurs and the cell no longer requires growth factors to complete the cell cycle has been termed the restriction (R) point. The R point has been temporally mapped at 2–3 hours prior to the onset of DNA synthesis.
Describe the Cyclin-CDK involvement in the cell cycle.
From the start of G1 to the R point: D-CDK4/6
From R point to just into S phase: E-CDK2
From start of S to midway: A-CDK2
Just before midpoint of S to end of G2: A-CDC2
M: B-CDC2
What inhibits cyclin-Cdks?
Cyclin-dependent kinase inhibitor (CKI)
