Week 8 Sem 1 2014 Flashcards
Hypertrophy
Increase in cell size
Hyperlasia
Increase in cell NO.
Atrophy
Decrease in cell NO./SIZE
Metaplasia
Change in cell TYPE
To better suit the requirement
Neoplasia
Abnormal New growth of tissue
Cellular proliferation faster than normal
Partial or complete lack of structural organization + functional coordination wit normal tissue
Can b benign or malignant
Carcinoma
Malignant neoplasm of epithelial origin
Be in epithelial regions / r epithelial cells
Benign
Non invasive
Abnormal growth that is stable
Encapsulated
Tumour
Abnormal growth of tissue
Synonym for neoplasm eg benign tumour, malignant tumour
Ability to regenerate:
Liable tissue
Constant turnover (turnover=replacement of old cells with new cells)
Eg skin
Ability to regenerate:
Stable tissue
Not ongoing turnover, but can do so (ie regenerate) if need be
Eg kidney
Ability to regenerate:
Permanent tissue
Doesnt regenerate
Eg brain & heart
Nerves that release acetylcholine (ACh)
= cholinergic nerves
Nerves that release noradrenaline (NA)/ adrenaline
Dopamine
= adrenergic nerves
Adrenergic
Primarily SNS ( sympathetic nervous system)
Cholinergic
(Both SNS + PNS
Sympathetic
Parasympathetic nervous system
Nicotinic receptors
Found in muscles n ganglia/brain
Respond to Acetylcholine
Muscarinic receptors
Found in all other parts of body xept muscles n ganglia/brain
Respond to acetylcholine
Non-depolarising blockers
Competitive( competes/ trying to get to same receptor as neurotransmitters) antagonist (just turn off receptor, no efficacy) at nicotinic (N) receptors
Can overcome this by increasing conc of ACh (clinically, we add anticholinesterase - enzyme that stops ACh from being chopped up)
Tubocurarine
Eg of non-depolarising drug
Just simple antagonist-stops ACh from gettin to receptor
Causes paralysis
Depolarising blockers
Agonists
Overstimulate Nicotinic receptors so that receptors stays in depolarised state and cant get bak to repolarised state
Initially, get initial contraction cos it acts like ACh but
It stays on receptor much longer than ACh
So get depolarisation blockade - ends up ‘turnin off’ receptor
Suxamethonium
Depolarising drug
Made of 2 ACh’s
Once gets into blood, can get chopped off by plasma cholinesterase (problem is, some ppl dont hav this enzyme- so we prefer other drugs to this one)
Botulinum toxin
Eg botox!
Bacterial exotoxin
Most toxic subs to man
Normally, vesicles release ACh by dockin at SNAP-25. If we cut up SNAP-25 (which is wat toxin does), cant dock-> no response
Acetyl cholinesterase (AChE)
Break down acetyl choline
We need to get rid of ACh (after binding to receptor) asap or else depolarization block would occur
Hence, need AChE!!
Non specific ‘pseudo’cholinesterase
Break down other stuff that is similar to ACh
Eg suxamethonium
Anticholinesterase
Blocks acetyl cholinesterase from choppin up ACh
Can b reversible/short acting
Or irreversible/long lasting
Myasthenia gravis
Autoimmune disease affectin neuromuscular (NM) transmission- stops ability of ACh from binding to receptor cos antibodies r binding to N receptors
Myasthenia gravis treatment
- Anticholinesterase (increase [ACh]
- Add atropine (cos ACh goes everywhere, not just skeletal muscles. Use atropine to stop unwanted M(muscarinic) effects)
- Immunosuppressants (suppress anitbody formation)
Ptosis
Droopin of eyelids
One of first signs of envenomin
LD50
Dose of venom that kills 50% of mice over a 24/48 h period
Venomous
Toxin + animal must hav some venom apparatus ( eg fang sting etc
Poisonous
Toxin
We hav to eg ingest it to get poisoned
No special delivery mechanism
Eg frog
How it delivers determinew whether animal is venomous or poisonous
Signs symptoms of snake bites
Paralysis Ptosis Loss of facial expression Dysarthria (difficulty speaking) Etc
Early sign of envenomin of snake:
Uncoagulatable boold
Snake neurotoxins
Beta neurotoxins Presynaptic Stop recylcin of vesicles Rapid onset Reversible Respnd to anticholinesterase n antivenom
Alpha neurotoxins Postsynaptic Stop binding of ACh to receptors Slow onset Irreversible Only respnd to antivenom of given early
Treatin snake bites
First aid.n pressure immobilisation (to stop lymph flow not blodd flow)
N stoppin movement of patient
Antivenom
= antibodies produced wen animal (eg horse) injected wit snake venom. Giv horse antibody to patient
Monovalent antivenom- get one type of antibody cos venom given to horse was from 1 species
Polyvalent antivenom- get many types of antibody cos venom given to horse was from 2+ species
Irukandji syndrome
Envenomin by carybdeid jellyfish
Get severe hypertension, nausea vomittin etc
Treatent for jelly fish envenoming- add VINEGAR (not alcohol), antivenom
Dont do pressure/immobilisation
Myotoxins
Cause skeletal muscle necrosis
Redback envenomin
Only female dangerous
Venom act presynaptically: stimulate increased telease of ACh n NA- lead to depolarisin block
Sympoms: tachycardia, hypertension,pain
Funnel web envenoming
Neurotoxins act presynaptically
Causing ‘autonomic storm’ then cardio respiratory arrest
Carcinogen
Any agent that directly causes cancer
Eg UV light, tobacco smoke, meat preservatives, ionizing radiation
Penetrance
% of ppl wit a genetic predisposition who will develop cancer
Eg colon= 100% penetrance ie if u inherited this gene- irrespective of any other factor- u WILL get colon cancer
Breast cancer= 40-70% penetrance
% of all cancers that were due to INHERITeD genes
10%
Viruses can cause up to…
15% of cancer cases
Breast cancer
Hereditary genes causin it:
BRCA 17q
BRCA 13q
Up to 10% breast cancer is due to genetic predisposition
Life time risk of breast cancer- BRCA1 and BRCA2 83- 88% by age of 70
Proto-oncogenes
Normal genes that regulate cell growth n division
Oncogenes
Promote cancer
Wen proto-oncogenes get damage they become Oncogenes. This may be bc:
1) gain of f(x) mutation eg pnt mutation
2) gene amplification (leadin 2 over expressed proteins)
3) chromosomal translocation
STI-571
Aka Gleevec/imatinib (trade name of drug)
Blocks binding of ATP to BCR-ABL tyrosine kinase
So that receptor cant phosphorylate its substrates
Hence slowing growth of cancer cells
Used to treat CML and GISTs (gastrointestinal stromal tumours)
CML
Chronic myelogenous leukemia
Increased n unregulated growth of myeloid cells in bone marrow n accumulation of these cells in blood
Only leukemic cells of this cancer has 9:22 translocation
Abl tyrosine kinase
Type of tyrosine kinase playin major role in CML
Tyrosine kinase
Genes coding for this= Largest group of oncogenes
Gp of protein receptors
Activate by binding to growth factors/cytokines
Wen stimulated results in cell proliferation/survival etc
Drugs that inhibit tyrosine kinase
ATP-competitve inhibitors eg imatinib
Antibodies against tyrosine kinase receptor or their ligands (block binding of ligand to tyrosine kinase receptor) eg in breast cancer
Anti-angiogenics
p53
A protein expressed by TP53 gene that induces cell cycle arrest, differentiation, DNA repair, APOPTOSIS basically it is a tumour suppressor. (TP53 is a tumour suppressor gene)
Cancer cells wit defective p53:
Escape apoptosis, has damaged DNA cos dont halt proliferation to repair DNA
50% of tumours show mutation/loss of p53
Just lost of one good copy can still contribute to cancer (ie ‘growth advantage’ due to reduced apoptosis)
Eg in skin cancer (squamous cell carcinoma)
Mismatch repair genes (MMR genes)
Repair DNA if error occurs during DNA replication
Follows 2 hit hypothesis
8 types
2 hit hypothesis
Both genes must b knocked out/mutated to confer loss of function- n hence get cancer
Tumour suppressor genes (TSGS)
Eg P53 gene n RB gene
Genes that act to prevent cancer
Control check pnts in cell cycle,
Induce transcription of regulatory inhibitory genes,
Prevent cells from goin through cell cycle= rapid cell cyclin/division:allow for DNA repair
Follows 2 hit hypothesis
Normal genes present in all cells
Rb gene
Retinoblastoma gene
Prevents transcriptional activation of other genes needed for onset of S phase
Plays a role in differentiation, dNA replication n apoptosis
2 copies must be lost to get cancer (retinoblastoma etc
Retinoblastoma
Childhood tumour or retina
Key concept of cancer
MULTIPLE GENES R AFFECTED (activation of oncogenes
Loss of tumour suppressor genes
Loss of mismatch repair genes)
Cancer is due to GENETIC MUTATIONS + ENVIRONMENTAL FACTORS
Stress: 3 approaches
- stress as an external stimulus (how outside affects us)
- Stress as a transaction bw external envrio n individuals reaction (nature of outside stuff + how we react to outside stuff)
- Stress as a internal physiological reaction (bio stuff)
Primary appraisal (stress approach 2)
How the person initially views the stressful event
Secondary appraisal (stress approach 2)
How the person sees their own resources n their ability to cope
Later, also how the person’s emotional repsonse influeneces how they see everythin
Autonomic nervous system (ANS)
Part or peripheral nervous system
Control many unconscious bodily f(x)s eg heart rate, digestion, respiration rate, sexual arousal
Divided into 2 subsystems:
SNS:sympathetic nervous system (‘accelerator’ fight or flight)
PNS: parasympathetic nervous system
(‘Brake’ rest and digest)
Stress as an Internal Physiological Reaction (stress approach 3)
involves ANS:
SNS- acute response to stress via fight or flight response
PNS- gets body bak to normal
Neuro-endocrine system:
Triggers hypothalamic-pituitary-adrenal axis. Results in release of hormones that prepare body for the stressful situation
Chronic stress
Leads to burnout
