Unit 4 Flashcards
Taste receptor for umami
T1R1 T1R3
l-glutamate
Taste receptor for sweet
T1R2 T1R3
sugars, glycine + d amino acids
Taste receptor for bitter
30 T2R
Cycloheximide
Taste receptor for sodium
ENaC
NaCl
Taste receptor for sour
PKd2L1 acids
CA IV
carbonated drinks
Routes malignancy
Blood
lymphatics
local
transcoelomic - peritoneal cavity
HER 2
ONCA-GENE
BRACA 1/2
TSG
Innervation tongue paillae
Circumvallate – IX
Foliate – VII + IX
Filiform – VII
Fungiform – VII
Describe how viruses cause cancer?
Virus can directly encode viral oncogene= viral oncogenesis. Or active proto-oncogenes inside cell. Tumour viruses (both DNA + RNA) interact with OG + TSG + transition from infection to cancer depends on the “genetic background” of the infected cell.
RSV carries viral oncogenes + inserts them directly into host genome.
ALV activates existing proto-oncogenes in host cells via insertional mutagenesis.
Others inactivate TSG -> HPV. Viral promoters which drive protein expression within the host cell.
What is the Rous Sarcoma Virus and how does it work?
Retrovirus with ssRNA genome. RSV has transforming potential via a single gene v-src (viral sarcoma) which incorporates into host cell genome. Transforming potential passes between generations.
V-src encodes a constitutively (always active) active tyrosine kinase + infected cells unable regulate v-src activity as its always active * has ability to stimulate host of cellular pathways. V-src DNA sequence similar to gene in non-cancerous cells = cellular-src.
How ALV became viral oncagene
ALV infected a cell its ds DNA was integrated into host cell genome-this is completely random in one infection the ALV virus sat next to c-src – as virus transcribed viral DNA it took with portion of c-SRC and packed into virus and ALV become a different virus which carriers a copy of this viral oncogene.
why not all cells infected ALV become tumours
In the first three examples the virus has integrated upstream of non-critical genes * effect host cell may see overexpression of these genes but not cancerous as no proliferative advantage. In cells that go onto form leukaemia the cell integrates directly upstream of myc * lots of TF * cell proliferates uncontrollable. This explains slow tumour formation as need millions and millions of insertion events after being infected with the virus for viral DNA to insert directly upstream of myc.
How lesion V3 affects ear
v3 innervates tensor tympani * lesion get hyperacusis cant dampen loud sounds
joints name ossicles
synovial
Joint name stapies
ball + socket
Innervation stapedius
facial nerve
Innervation tensor tympnai
V3 division trigeminal
Visual pathway
Inner hair cells connected type 1 spiral ganglion - cochlear nerve to cochlear nucleus
moss cross collaterally and synapse superior olivary nucleus.
Travel down lateral lemiscus to inferior colliculus - medial geniculate nucleus
Why not all cells infected ALV form tumours
If virus integrats upstream of non-critical genes * effect host cell may see overexpression but not cancerous as no proliferative advantage.
Leukaemia the cell integrates directly upstream of myc * lots of TF * cell proliferates uncontrollable. This explains slow tumour formation as need millions and millions of insertion events after being infected with the virus for viral DNA to insert directly upstream of myc.
How HPV 16 /18 creates tumour
HPV16/18 produces viral proteins e6 and e7 which inhibit actions of important TSG in infected cells. E7 inactivates Rb proteins * disrupts cell cycle progression control. E6 marks P53 for degradation * reduced p53 levels in infected cells.
how cells get immortality
express telomerase reverse transcriptase (hTERT)
6 step metastasis
Local invasion - EMT Intravasation - lymph/ BV transport Extravsation Micro mets -MET Colonisation + macromets
Neoplasm: .
mass of cells with uncoordinated growth and complete or partial loss of the normal growth control mechanisms
Dev invasive carcinoma
- Dysplasia: some abnormal cell growth/ some but not all cytological features of carcinoma in situ + confined by BM
- Carcinoma in situ: all hallmarks invasive carcinoma (neoplasia) but confined BM at this point IT DOENT HAVE METASTATIC POTENTIAL
• Invasive carcinoma: breaches BM. Carcinoma In-Situ will progress to invasive then metastatic if left untreated. Carcinoma in situ is common in epithelial – cervix, breast, colon + skin.
SIRS to sepsis
PBMC -> TNF alpha - feedback loop TF expression, neutrophil activation + NO production.
TNF aplha activates endo cells - endo cells - TF (coagulation)/NO (capillary leakage).
TNF alpha activates blood neutrophils -> TNF alpha -> NETS
Severe non localised oedema, poor perfusion tissues, hyper coagulation
-> organ dysfunction
CARS
Compensatory anti inflam response syndrome
Increase TGFB + Il-10
Downreg TNF alpha, CXCL8 + NO.
Run out cells + cnat make more as bone marrow hypoperfused - as dont have many inflam cells body assumes infection over - no longer presenting pathogen getting type 1 reposnce. Get sudden improvemnt followed by drop off
Sepsis organisms
Eschericia coli
Staph aureus
Sepsis 6
Complete 1 hour - double patients chance survival
Administer high flow oxygen Take blood cultures Broad spec AB IV fluid Serum lactate + heamoglobin Accurate hourly urine output
Sepsis from SIRS
Increase TF - hypercogulation - depletion clotting factors - increased anticogulation. Hypoperfusion, coagulation + ROS cause direct organ damage
Septic shock
Increase TF - hypercogulation - depletion clotting factors - increased anticogulation -> low BP/ MAP.
SIRS - Increase TNF alpha, Oedema + hypoperfusion - low BP/MAP
Pathogens meningitis
Group B streptococci Escherichia coli Staphylococcus aureus Streptococcus pneumoniae Neisseria meningitidis
SIRS criteria
Temperature >38oC or <36oC Heart rate >90/min Respiratory >20/min PaCO2 <32mmHg (<4.3kPa) WBC >12 or <4 x109/L
SIRS 2+ same patient
SOFA
Sequential organ failure assessment. Sepsis when documented/suspected infection with SOFA 2+ above current baseline
Fi02 Platlets Billirubin GCS Creatine Urine output
QSOFA
Respiratory >20/min CNS Altered mentation SBP <100mmHg
Septic shock definition
Septic shock
Sepsis presenting with MAP <65mmHg (quick identification and primary/community)
Sepsis requiring vasopressors to maintain MAP above 65mmHg plus serum lactate >2mmol/L (inpatient
CARS definition
Compensatory anti-inflammatory response syndrome (CARS)
A body-wide suppression of immune responses following overwhelming pathogen exposure
Sepsis summary
Virulent pathogens, compromised defenses - poorly controlled + spreading infections - organ damage + sepsis
