principles Flashcards
what can be said about the affinity of a low Km?
higher affinity - only need small amount for reaction to successfully occur
what are collaterals?
alternative vascular routes, small branches that form to bypass area of narrowing in the main artery to maintain blood flow
where are lipids produced?
SER
describe the histological features of skeletal muscle, epithelium, cardiac muscle and dense irregular connective tissue
epithelium - avascular, form cohesive sheets, lines abdominal cavity
skeletal muscle - long elongated cells, multiple nuclei
cardiac muscle - striated and branched, single cell nucleus
dense irregular connective tissue - bundles of collagen fibres arranged in random directions
which cells produce myelin for the CNS?
oligodendrocytes
which cells produces myelin for the PNS?
schwann cells
what are chondrocytes?
resistant cells within cartilage
what happens when a stop codon is reached by a ribosome (in site A)?
a termination protein binds to the codon and is used to release the growing peptide from the P site tRNA
the ribosome is likely to dissociate
is the Km for a competitive inhibitor high or low?
higher
what effect does heat exposure have on muscle tone?
decreases muscle tone
heritable mutation in mitochondrial DNA can only be transmitted from affected mother to her children
True or false?
true
x-linked conditions only transmit male to male
true or false?
FALSE !!!
NO male to male transmission
what letter represents the long arm of the chromosome?
long arm = q
short arm = p
what antibiotics target the cell wall?
penicillin’s
glycopeptides - vancomycin
cephalosporins
what antibiotics target nucleic acid synthesis?
metronidazole
ciprofloxacin
what antibiotics target protein synthesis?
aminoglycosides - gentamicin
tetracyclines - deoxycycline
macrolides - erythromycin
what can happen if c-myc is persistently expressed?
rapid proliferation of tumour cells
how can intracellular calcium contribute to cell death?
increases mitochondrial permeability
what 2 cell types are predominantly found in granulation tissue?
endothelial cells and myofibroblasts
what is pinocytosis?
internalisation of fluids (and particles within) into cells through invagination of the cell membrane
what are papillomas?
benign epithelial tumours growing exophytically (outwardly)
what do you put in a yellow sharps bin with a blue lid?
medicine vials with residual medicines
what do you put in a red bag?
soiled laundry
what does ABCDE stand for?
A - airway B - breathing C - circulation D - disability (glucose monitoring is integral) E - evidence, environment, exposure
what are isozymes?
isoforms of enzymes - catalyse the same reaction but have different properties and structure (diff. amino acid sequence)
useful for diagnoses from blood
whats an apoenzyme? holoenzyme?
apoenzyme = enzyme without a cofactor
holoenzyme = apoenzyme + apoenzyme (enzyme with cofactor)
what are foam cells?
macrophages stuffed with lipids
pol I + III synthesise all mRNA
True or false
FALSE
pol II synthesises all mRNA
which transcription factor is required for all pol II transcribed genes?
TFIID
TFIID remains at promotor during transcription initiation - allows transcription at low basal rates
which enzyme catalyses peptide bond formation between amino acids in P + A sites?
peptidyl transferase
how do free ribosomes in the cytosol make proteins and where are they for?
post-translational
- cytosol
- nucleus
- mitochondria
how do bound ribosomes on the RER make proteins and where are they for?
co-translationally - moved while still being made
plasma membrane
ER
golgi
secretion
what happens in missense mutations?
change of amino acid
what happens in nonsense mutations?
creates new termination codons
where does supplied energy come from during activity of: 4 secs 15 secs 4 mins 77 mins 4 + days
4 secs = ATP 15 secs = phosphocreatinine 4 mins = free circulating glucose 77 mins = glycogen stores 4 + days = fat stores
what are the 3 control points in glycolysis and what do they control?
control points = enzymes catalysing irreversible reactions
helokinase = substrate entry
phosphofructokinase = rate of flow
pyruvate kinase = product exit
what products and how much does each turn of the TCA cycle make?
1 GTP
1 FADH2
3 NADH
energy released by electrons in oxidative phosphorylation is used to efflux protons (H+) into matrix from innermembrane space
true or false
FALSE
… into innermembrane space from matrix
this sets up H+ electrochemical gradient which ATP synthase (integral) uses to drive ATP formation
what is a baby called between 2-8 weeks?
embryo
8 weeks + = foetus
0 - 3 weeks = conceptus
when does oogenesis start?
in DEVELOPMENT
begin meiosis but arrest in prophase until puberty
what happens during cleavage?
period of rapid cell division - no increase in size
formation of morula then blastocyst (days 1-4)
whats a teratogen?
agent that causes abnormality following foetal exposure
eg alcohol
what is the fate of the trophoblast?
cells eventually become foetal/embryonic part of placenta
splits into:
- cytotrophoblast - inner part of trophoblast
- syncytiotrophoblast - invasive layer (into endothelium)
what is the fate of the ectoderm?
skin and nervous system
what is the fate of the mesoderm?
paraxial mesoderm= axial skeleton, skeletal muscle, back dermis
intermediate mesoderm = urogenital systems
lateral plate mesoderm:
- somatic layer - most of dermis, lining of body wall
- visceral layer - Cardio, smooth muscle
what is the fate of the endoderm?
lining of:
- gut tube
- respiratory tract
- bladder + urethra
what are the first cells to move through primitive streak in gastrulation?
cardiac progenitors - derived from mesoderm
what is a normal respiratory rate?
12-20 breaths per min
why does arterial pressure not fall to zero during diastole?
elastic recoil
what are the4 types of shock?
hypovolaemic - loss of blood volume
cardiogenic - sudden severe impairment of cardiac function (heart attack)
obstructive - obstruction to circulation (PE, tension pneumothorax)
distributive - excessive vasodilation + abnormal distribution of blood flow
- neurogenic - spinal cord injury
- vasoactive - septic shock
what is secondary active transport and what are the 2 mechanisms?
transfer of solute across membrane always coupled with transfer of ion that supplies driving force
- symport (co-transport) - solute and ion move in same direction
- antiport (exchange/counter transport) - move in opposite directions
what is the threshold potential for an action potential?
-60mV
list strategies to increase passive current speed in axons
increase axon diameter
decrease leak of current across axon = myelin
myelinated axons = saltatory conduction
hepatic portal system
returns blood from the digestive tract and the spleen to the liver
subclavian vein
paired, large vein, responsible for draining blood from the upper extremities to RA
Morulla
spherical shape ball of cells, without a cavity, 3-4 days after fertilisation
acrosome
cap-like saccular organelle in the anterior half of the sperm head that contains enzymes
vascular, typically polarised forming cohesive sheets, lines body surfaces
epithelium
long elongated cells, each having multiple nuclei
skeletal muscle
Packed, extracellular bundles of collagen fibres which are arranged in random directions
dense irregular connective tissue
cardiac muscle
striated cells that are branched and have single nucleus
CNS glial cells
astrocytes, microglia and oligodendrocytes
astrocytes
number of functions including sipporting and maintaining homeostasis in extracellular environment
difference between microglial cells and oligodendrocytes
oligodrendrocytes produce myelin
phosphorylating ADP to ATP in animal cells
oxidative phosphorylation and substrate level phosphorylation
Oxidative phosphorylation
oxidation of NADH and FADH2 to NAD+ and FADH is coupled with pumping protons out of mitochondrial matrix, which in turn is coupled with phosphorylation of ADP to ATP via ATP synthase
substrate level phosphorylation
phosphate group is directly transferred to ADP forming ATP usually derived from intermediate metabolite
Quaternary structure
relative orientation of one polypeptide to another polypeptide in a multisubunit protein
rate of reduction of pyruvate to lactate
matched by NADH regeneration by glyceraldhyde 3-phosphate dehydrogenase
TATA box
type of promoter sequence (30 base pairs) upstream of the transcription start site which specifies where transcription begins
RNA polymerase
enzyme that is responsible for copying a DNA sequence into an RNA sequence during transcription
GPCRs
integral membrane protein, single polypeptide
extraceullular NH2, intracellular COOH
7 transmembrane
binds to intracellular receptor that then activates gene expression in the nucleus
steroid hormone
which substance within the cell directly stimulates protein kinase A?
cyclic AMP
which conducts ions quicker, ligand-gated ion channels or carrier molecules?
ligand gated ion channels
how is signalling terminated in the G-protein cycle?
the hydrolysis of GTP to GDP at the alpha subunit
which foetal cells is the placenta derived from?
trophoblast
what type of molecules target ligand gated ion channels and how fast are they transferred?
example = nicotinic acetylcholine receptor
‘fast’ neurotransmitters (milisecond)
targeted by hydrophilic signalling molecules –> acetylcholine, amino acids
GPCR = slow neurotransmitters (seconds)
what type of receptor is mainly targeted by hydrophilic protein mediators such as insulin and growth factors?
kinase-linked receptors
work on timescale of hours
how do steroid hormones enter the cell?
diffusion
what is the apparent volume of distribution (Vd) and what is indicated by a high/low Vd?
theoretical volume that the total amount of administrated drug would have to occupy to provide the same conc as it currently is in the blood plasma - allows determine optimal dose to get target plasma conc
small Vd = drug in just plasma
large Vd = drug in plasma + tissue
** drug with high Vd will require higher dose **
what factors can increase Vd?
liver failure
renal failure
pregnancy
what factors decrease Vd?
dehydration large molecule - confined to plasma high plasma protein hydrophilic high charge
mechanism of action of macrolides?
inhibits protein synthesis by acting on 50s subunit of ribosomes
what is the main source and function of tumour necrosis factor alpha?
source = macrophages
function = inducing fever + neutrophil chemotaxis
give examples of tumour suppressor genes?
BRCA2 BRCA1 p53 NF1 APC VHL PTEN
is c-MYC an oncogene or tumour suppressor gene?
oncogene
what is the function of the RER?
translation + folding of new proteins
manufacture of lysosomal enzymes
examples of gram positive rods
clostridium
listeria monocytogenes
list the steps of phagocytosis
macrophages express PRRs
receptor binding to PAMPs signals formation of phagocytic cup
cup extends around target + pinches off - forming phagosome
fusion with lysosomes to form phagolysosome - kills
debris released
pathogen derived peptide expressed on cell surface receptors (MHC-II molecules)
pro-inflammatory mediators released - TNF alpha
what does degranulation involve?
release of preformed proinflammatory substances eg histamine nitric oxide prostaglandins proinflammatory cytokines - TNF alpha
what type of cytokines do virally infected cells produce?
interferons- IFNalpha
what is the fate of inactive C3 post cleavage via C3 convertase?
-> C3a + C3b = fully active
C3b - unstable protein, will degrade unless bound, opsonin, can bind to ligands on pathogen surface - stabilises it
-> involved in generating enzyme complex to cleave C5
C3a - amplify acute inflammation via positive feedback loop (with C5a also)
how does MAC kill pathogens and how is it formed?
extracellular salts/water enters pore via osmosis - causing pathogen to swell + burst
formed via interactions between C5b + other complement cascade proteins
what type of cell links the innate and adaptive immune response? what is it’s main function?
dendritic cells
innate - activated in response to acute inflammation signals
adaptive - activates T cells
main function = process / present antigens on their surface for T cells
what cell is responsible for immune responses in the extracellular body fluids?
B cells
what are B cell receptors composed of?
b cell receptors = antibodies (Ig…)
4 polypeptide chains - 2 light, 2 heavy chains
how are protein antigens broken down into peptide antigens?
via proteases
what type of cells to MHC-I present peptide antigens to?
CD8+
where do B + T cells wait in the lymph node while waiting to be activated?
B cells - in stromal cells (edge of lymph node)
T cells - in middle
what is a germinal centre reaction?
b cells clonally proliferate + differentiate into long lived plasma cells that secrete high affinity antibodies - also long-lived memory b cells
B cells need help from T cells in the germinal centre in order to respond to protein antigens
true or false ????? :o
true dat
they then differentiate into plasma cells which produce + secrete antigen-specific antibodies
which part of the antibody is responsible for the effector function?
mediated by heavy chain constant region - Fc region
define agglutination
clumping together of particles caused by antibody molecules binding to antigens on the surface of 2 adjacent particles, cells, pathogens, antigens
–> increases efficacy f pathogen elimination by enhancing phagocytosis
what cells secrete growth factor IL-2?
CD4+ TH0
stimulates own + antigen activated CD8+ proliferation + differentiation
CD8+ aren’t good at making IL-2 (need it to become cytotoxic T cells) -> rely on it coming from CD4+
what do TH1 cells do?
provide proinflammatory signals that activate macrophages
what are macrophages role in the resolution of the immune system?
switch to anti-inflammatory - secrete anti-inflammatory mediators that initiate repair + wound healing
phagocytose any apoptotic cells killed by cytotoxic T cells
right shift of oxyhaemoglobin dissociation
decrease pH - acidic increased [H+] increased CO2 increased [2, 3 - DPG] increased temp
what do you call a high grade dysplasia?
carcinoma in situ (CIS)
affects whole of epithelium
last stage before becoming invasive
name some benign tumours of the mesenchymal (connective tissue)
fat = lipoma bone = osteoma cartilage = enchondroma smooth muscle = leiomyoma blood vessels = haemongioma
how do WBCs move along the endothelium in acute inflammation?
weak bonds between
selectins + glycoproteins
ICAM + integrins
chemokines activate strong bonds - stops + flattens against vessel wall
what are the 3 types of necrosis?
coagulative - ghost outline, no nucleus
liquefactive - post stroke leaves hole in brain
caseous (cheesy) - granuloma formation, associated with TB
what is the main protein responsible for apoptosis?
caspases
which cell most commonly initiates apoptosis via extrinsic pathway?
T - lymphocytes
–> have surface molecule called FAS ligand (FASL)
pathway begins when FASL binds to FAS receptors on target cell
what are anti-apoptotic proteins
BCL-2 + BCL-x
in healthy cell - anti-apoptotic bind to pro-apoptotic blocking their action
name pro-apoptotic proteins
BAX + BAK
how is the caspase cascade activated in damaged cells?
BCL-2 + BCL-x are blocked so BAX + BAK free to punch channels in mitochondria
–> allows mitochondrial substances (eg cytochrome C) to leak into cytoplasm
leaked cytochrome C binds to APAF-1 proteins to create a compound that activates the caspase cascade
which cyclin dependant kinase is responsible for activating the retinoblastoma protein? what does this activation cause?
CDK4 phosphorylates (activates) Rb --> CDK4 is activated by cyclin D
Rb inhibits E2F - E2F starts cell division
when Rb is phosphorylated by CDK4, Rb can’t bind to E2F so carries on green lighting cell division
in what stage of the cell cycle is p53 involved?
G2
–> checks for mistakes, repair attempted or destroyed
what is virchows triad?
where thrombosis is favoured
sites of endothelial injury
turbulent blood flow
hypercoagulable blood
what vitamins are fat soluble?
vitamin A, D, E, K
name the enzyme that attacks cell walls
lysozyme
define specificity
how well test detects NOT having the disease
–> ‘true’ negatives
speciFicity - Fuck no
define sensitivity
how well the test detects having the disease when it is present
–> ‘true’ positives - proportion with false neg
what part of the antigen binds to the antibody?
epitope
what is the positive predictive value (PPV)?
how reliable the test result is when it shows the disease is present
no. positive test + have disease / no. with positive test
what can a vitamin C deficiency cause?
scurvy
gingivitis
what can a vitamin A deficiency cause?
night blindness (nyctalopia)
vitamin A = retinol
- converted into retinal - important visual pigment
- important in epithelial differentiation
- antioxidant
what can a vitamin D deficiency cause?
rickets, osteomalacia
what is the difference between foetal + adult haemoglobin?
foetal haemoglobin has gamma subunits instead of beta subunits causing it to have a high affinity for oxygen that adult Hb
which cranial nerves carry parasympathetic fibres only?
oculomotor nerve (II) facial nerve (VII) glossopharyngeal nerve (IX) vagus nerve (X)
define neoplasia
new growth which is not in response to a stimulus
define proto-oncogenes
normal genes which stimulate cell division
Hallmarks of cancer
Evading growth suppressors Resisting cell death Sustaining proliferative signalling Enabling replicative immortality Avoiding immune destruction
Boyle’s law
At any constant temperature the pressure exerted by a gas varies inversely with the volume of the gas
La Place’s Law
The smaller the alveoli the higher the tendency to collapse
Dalton’s law
the total pressure exerted by a gaseous mixture= the sum of the partial pressures of each individual component of the mixture
Henry’s law
The O2 dissolved in blood is proportional to partial pressure
Bohr effect
Increased release of O2 by conditions at the tissues (a shift of the curve to the right)
Haldane effect
Removing O2 from Hb increases the ability of Hb to ick-up CO2 and CO2 generate H+
Ductus venosus
Allows oxygenated blood from the placenta to bypass the hepatic circulation
