:)))) Flashcards
which channels let water through membranes?
aquaporins
what are similar or differences between them?
difference between ECF and ICF?
-Plasma and interstitial fluid: same electrolyte components BUT plasma has proteins - e.g. albumin and anions c.f. interstitial fluid
Intracellular fluid c.f. extracellular fluid: ICF has very little Na+. Lots of K+ and PO43- - (buffers acid / base situation), protein anions (think - sea with Na+ is ECF, banana tree: ICF). ECF has high Na+ and Cl-
what characteristics do osmoreceptors have?
(in the Subfornical organ: in the hypothalumus. (Organum Vasculosum of the lamina terminalis (OVLT) - dont need to know)
- characterised by: a) extensive vasculature b) lack of normal blood brain barrier
- where are the osmoreceptors found in brain?
- what is another stimuli that triggers sensation to drink?
- osmoreceptors: in hypothalamus
- baroreceptors: detect when there is decreased blood volume (in great veins, right atrium of heart -> relied to vasomoto center) -> relayed to hypothalamus
Q
what is the main stimulus for the thirst sensation?
increase in plasma osmolality
describe mechanism of aldosterone working
(where made? released from? what does it cause to do? result?)
aldosterone:
released from: adrenal cortex
released when: reduced Na+ or increased K+
function: increases reabsorbtion of Na or increased K secretion
result: homeostatic plasma levels of Na+ and K+.
aldosterone binds to kidney cells:
a) ENAC (Na channel) - can reabsorb more Na
b) Na/K pump ( pumps Na in / K out)
how does atrial natruiretic peptide work? released from? releaed when?
Atrial natriuretic peptide (ANP)
released from: cardiac Atria
released when: increased blood volume (stretches atria)
function: promotes excretion of Na+ and Cl-, in turn decreases water reabsorbtion (brings blood volume back towards normal)(acts on hypothalamus and adrenal cortex up the mechanism.)
what horomone does same role as aldoesterone (i think)
angiotension II
which channels in the kindey, controlled by ADH and aldosterone, controls the variable reabsorbtion of water?
- *-aquaporins
- ENAC
- Na/K pumps**
what are ways you can test blood glucose? (3)
fasting glucose test - (not eating / drinking anything other than water for 8hrs)
glucose tolerance test - after fasting and again after 2 hours after being given a glucose drink
glycated haemoglobin test (HbA1C) - measure of average blood sugar level over past 3 months.
state and say use of each type of blood test pls
- complete blood count:
- arterial blood gas: CO2 and O2 levels
- blood smear: represents a snapshot of cells in blood at the time. size, shape and colour of RBC and WBC can be measured - can determine diagnosis
- blood cultures: suspect a pathogen
what is hematocrit a measure of ?
Hematocrit, the proportion of red blood cells to the fluid component, or plasma, in your blood
the concentation of hydrogen ions is regualted by which systems?
how long does it take for each system to regulate?
1. chemical buffer system in blood and ICF: immediate action
2. Respiratory centre in brain stem:acts within 1-3 minutes
3. kidneys : hours to days
what are the three major chemical buffer systems in the body?
Bicarbonate (HCO3-) buffer system: H20 + CO2 ⇌ H2CO3 + HCO3- + H+
Proteins (Hb and albumin) buffer system
Phosphate buffer system
what is anion gap?
what happens if have high anion gap?
- measure the conc of Na, Cl and HCO3- in blood. - cations should be greater by anions by 8 to 12 mEq/L.
[Na+] - ([Cl-] + [HCO3-]) = 8 to 12 mEq/L
If your results show a high anion gap, you may have acidosis, which means higher than normal levels of acid in the blood
which part of brain controls for difference in breathing rate due to acid / alkaline blood lvels?
- change incurred by Pons and medulla
- expelling more co2 lowers the acid levels
how does the kidney produce bicarbonate?
- Glutamine -> glucose, HCO3-, NH4+ (excreted out and used to combine with H+ ions to make sure excreted into urine)
when the body is in acidosis, how do we ensure H+ stay out of renal tubule cells?
when the body is acidosis:
@ distal proximal tubule:
H+ get secreted out of renal tubule cell into lumen. BUT want to stay here. SO, use NH4+ and H2PO4 buffes to keep the H+ in the filtrate
what do you look for when get results from arterial blood gas? what does each one mean
- pH low (acidosis) or high (alkalosis)?
- what is PaCO2 value? (resp. indicator)
- what is HCO3- value? (metabolic indicator)
what test do you if have a metabolic acidosis?
check anion gap
Therefore, values greater than 12 define an anion gap metabolic acidosis.
describe briefly synthesis of phosphocreatine
what is it used for?
location?
phosphocreatine synthesis:
- transfer of phosphate group from ATP
- enzyme used: creatine kinase
- anaerobic conditions
function: ATP buffer (can restore ATP when needed)
Location: in tissues that have high, fluctuating energy demands - muscle and brain
-
explain proton motive force
- making a gradient to keep out of equilibrium.
- get an electrochemical gradient (gradient of BOTH electrical potential and chemical concentration across a membrane)
- transfer of H+ via proton pumps across membrane creates a source of energy (PMF): get a proton electrochemical gradient of proteins: proton motive force
can use thise electrochemical conc. gradient of protons across a membrane to power the synthase of ATP
which are the energy conversion pathways that occur in cellular resp?
- glycolysis
- krebs cycle
- electron transport chain
why / how is cyanide a poison?
- binds to cyctochrome c oxidase (4th complex in ECT)
- cyanide attaches to iorn within protein complex and inhibits activity of the complex system
- ECT can’t pump H+ into intermembrane space = pH of intermembrane space increases -> pH gradient decreases.
- ATP synthesis stops
describe the structure of two motors in ATP synthase
what are they used for?
function: converting ion gradients to ATP
in ATP synthase:
- 2 motors - one electrical, one chemical
- one motor location: membrane - powered by flow of protons
- one motor location: intermembrane space: powered by ATP
WHEN ONE TURNS, CAUSES THE OTHER TO TURN
how does muscle contraction work with ATP?
- myosin has two heads: one binds to ATP, one binds to actin.
- when ATP binds to myosin. ATP is hydrolysed as a result.
- change in 3D shape of myosin.
- changes the position between actin and myosin filaments
- = muscle contracts
how is energy used in heat?
how does this process work with ATP synthase?
- thermogenin (uncoupling protein): found in the mitochondria of Brown adipose tissue
- allows passage of protons back into mt matrix
- generates HEAT
- do not have enzyme activity to catalyse production of ATP - so H+ move down energy gradient without using this energy for synthesis of ATP
= NON SHIVERING HEAT PRODUCTION
with ATP synthase:
- ATP synthase and thermogenin / uncoupling protein work in parrallel
- both in mitochondria membrane
- uncoupling protein generates HEAT
- ATP synthase generates ATP
- last step in ox. phosphorylation
what are three stores of biological energy?
What are 4 general uses of biological energy?
- *stores:**
- ATP
- Phosphate
- PMF
- *uses:**
- anabolism (synthesis of x)
- transport (primary / secondary AT)
- motility
- heat
why are biofilm associated infections really problematic? (2)
- extreme resistance to antiobiotics and other anti-microbrial agents
- high resistance to host immune defences
how do microbes undergo local spread and invasion through degredative enzymes / spreading factors ?
explain 2 pls
bacterial patogens often produce degradative enzymes - aka spreading factors: facilitate growth and spread of pathogen (dont kill host cells)
- *1. hyaluronidase:**
- breaks down hyaluronic acid (intracellular cement of CT). e.g. Strept. spp, Staph aureas. allows invasion further into tissues
- *2. collagenase:**
- breaks down collagen network - gives access to deeper tissues. E.g. Clostridium spp.
how does invasion of host cell oocur by bacterial invasion of host cells?
- *1. triggered invasion:**
- bacteria inject virulence factors into host cell cytoplasms to activate uptake by cell
- bacteria force the cell to extend local protrusion that engulf the bacterium
- = type 3 secretion system-dependent
- Salmnoella spp, Shigella flexneri
- *2. Zippered invasion:**
- bacteria produce outer membrane protein, with extracellular part exposed
- recognises receptor on target cell
- taken up by the cell
- specifc high affinity interaction between bacteria molecule and host cell receptor.
whats hypersensetivity? give example of type II, III and IV?
Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity.
Type II: IgG/IgM to patients own RBCs due to M. pneumonia
Type III: complement activation causing inflammation e.g. S. pyogenes causing glomerulonephritis
Type IV: T cell mediated e.g. TB granulomas
what are the specific (3) and non-specific ways that biofilm adherence occurs
non specific: Force of attraction e.g. Van der Waals forces
- *specific:**
- Proteins on microbe cell surface binds to host cells e.g. Hemagglutinin
- Fimbriae interact with cell surface receptors
- Pili transfers DNA between Bacteria
all creates a dense biofilm that protects pathogen
natural host defences are type of which immunity?
innate immune response
which specific proteins from complement system cause: opsonisation, membrane attack complex (MAC) and inflammation
opsonisation: (C3b and IGG):
membrane attack complex (MAC): (C5b)
inflammation: (C5a & C3a)
what are ways that microbibes can evade host defences when INSIDE the host? (4)
microbiocidal effects
- escape from endosome-phagosome and grow in cytoplasm: Listeria / Shigella
- inhibition of phagosome-lysosome fusion: Leigonella pneumophilia
- survive within phagolysosome
- replicate within phagolysosome: Salmonella
how can some microbes survive detoxifcation of oxygen derived harmful substances?
detoxifcation of oxygen derived harmful substances from the host:
e.g. some microbes have:
- superoxide dismutase (SOD): neutralises free radicals such as O2
- catalase (breaks down H2O2): e.g. Staph. aureas
how do some microbes destory antibodies?
- create IgA proteases
- these destroy IgA (IgA coat foreign microbes with mucous)
- toxins that damage membranes: cytolysines and pore forming toxins. help spread of bacteria
- toxins that act as enzymes: A/B toxins, more diverse group of toxins
- 2 subunits: A&B
- A = enzymatic activity
- B = binds to cell membrane (allows A to go into cell( - toxins that activate immune response: superantigens
which bacteria produce lipooploysaccharide (LPS)?
where located in bacteria?
made of? which part is toxic?
what happens?
gram negative bacteria
location: outer membrane of bacteria cell wall
structure: lipid A, core polysaccharide, O antigen
lipid A = toxic
activates complement and stimualtes producion of cytokines: results in septic shock, ferver, intravascular coagulation = haemorrage and endotoxin shock.
how can some microbes survive detoxifcation of oxygen derived harmful substances?
detoxifcation of oxygen derived harmful substances from the host:
e.g. some microbes have:
- superoxide dismutase (SOD): neutralises free radicals such as O2
- catalase (breaks down H2O2): e.g. Staph. aureas
what do superantigens caused to be released? compared to normal antigens?
- *superantigens:**
- induces _non-specific class II MHC and T cell receptor binding: w_idespread binding stimulation of T cells.
- Excessive cytokine release: fever, vomiting, diarrhea, organ failure
- *- 20 / 30% T cells activated**
How can microbes cause cancers?
- some microbes can cause development of chronic inflam processes: H. pylori (stomach cancer)
- some viruses incorp. nucleic acids into host genome: cause development of cancers
- Hep B: hepatocellular carcinoma
- HIV: lymphoma
- HPV: cervical carcinoma
- Epstein Bar - Burkitt’s lymphoma
which cytokines causes the differentation of ThO into:
a) Th1
b) Th2?
a) Th1: IL-12
b) Th2: IL-4
people with non-functional IFNy receptor are highly suscepitble to ?
mycobacterial infections
which B-lactam antibiotics are used on gram postive / negative bacteria?
glycopeptide antibiotics: gram postive
polymyxins: gram negative
which are the current exploited antibiotic targets?
what are the most successful?
- inhibition of bacterial cell wall synthesis
- inhibition of bacterial protein synthesis
- inhibition of DNA transcription and replication
- inhibition of RNA synthesis and replication
most successful hit:
- rb
- cell wall synthesis
- DNA gyrase or DNA toposiomerase
which drugs act on pathogen nucelic acid synthesis?
quinolones / fluoroquinolones:
- broad spectrum
- bind to topoisomerase II (DNA gyrase) and topoisomerase IV and inhibit DNA synthesis.
Rifampicin:
- acts on RNA transcription: inhibits RNA polymerase on gram postive
- treats TB
what does susceptibility, intermediate and resistant mean?
what is a breakpoint??
susceptibility: bacterial strain inhibited in-vitro by a conc of an antimicrobial agent that is associated with a high likelihood of therapeutic success
intermediate: bacterial strain inhibited in-vitro by a conc of an antimicrobial agent that is associated with a uncertain therapeutic success
resistant: bacterial strain inhibited in-vitro by a conc of an antimicrobial agent that is associated with a high likelihood of therapeutic failure
breakpoint concentration: A breakpoint is a chosen concentration (mg/L) of an antibiotic which defines whether a species of bacteria is susceptible or resistant to the antibiotic. changes all the time
how do antibacterial targeting protein synthesis work?
what do aminglycosides, tetracylines, macrolides and chloramphenicol do?
- aminglycosides: change shape of 30S portion & disrupt the structure (Gentamicin, tobramycin and amikacin). Gram-negative bacteria. can cause hearing loss and renal impairment. IV drugs
- tetracyclines: bind to 30S. interfere with attachment of tRNA to rb. oral drugs
- macrolides: bind to 50s subunit. prevents translocation
- chloramphenicol: bind to 50S, inhibit formation of peptide bond
what are PD indecies for antimicrobial activity and MIC?
effect of drug regarding its antimicrobial activity can differ regarding PD indices:
- *- Cmax / MIC ratio** - concentration depending killing: most importnat is getting high conc above MIC.
- T>MIC - time dependent killing - most important is time above MIC. with minimal prolonged antibiotic effect
- *- AUC24 / MIC ratio** - combo of above time dependent killing with prolonged antibiotic effect
how does activation of efflux pumps work in bacteria to cause antibiotic resistance?
normally used to pump out metabolic waste:
- undergo mutations - pump out drug instead
- high level of resistance provided
- genes for multidrug resistance efflux pumps integrate into plasmids can transfer between bacteria: can be acquired or intrinsic
what are 4 acquired antiobiotic resitance mechanisms
- drug inactivation
- activation of drug pumps (pump out)
- modification of target: e.g. acquire new gene that methylates Rb, so is resistant to drugs that target Rb.
- alternative metabolic pathways: e.g. with FA production, get mutations which mean that enzymes change structure so cant be targeted
give an example of drug inactivation by B-lactamases
how get over this?
B-lactamases (aka penicillinase): Beta-lactamases are enzymes (EC 3.5. 2.6) produced by bacteria that provide multi- resistance to β-lactam antibiotics such as penicillins
- beta-lactamase hydrolyse the b-lactam antibiotics and make it ineffective
beat this by: use inhibitors of b-lactamases.
which bacteria have high priority antibacterial resistance?
the highly cirtical ones are all gram negative: have multi drug resistance. BUT THERE ARE NO NEW DRUGS IN THE PIPELNE :(
what are two intrinsic mechanisms of antibiotic resistance?
- gram-negative bacteria: outer membrane forms a permability barrier - drugs cannot cross
- efflux pumps: active transporter. Efflux systems function via an energy-dependent mechanism (active transport) to pump out unwanted toxic substances through specific efflux pumps.
what do the following do with rna ?
Reverse transcriptase
Integrase
Protease
RNA polymerase
Reverse transcriptase – turns +ssRNA into DNA
Integrase – integrates viral DNA with host genome
Protease – help create viral building blocks
RNA polymerase – forms mRNA before going to ribosome
how does viral evasion of host defence occur?
- *Latency**: Dormancy that reactivates when host is immunocompromised e.g. HIV, Herpes
- *Phagocyte** evasion: Prevention of phagosome and lysosome fusion e.g. HIV
- *Antigenic shift and drift:** Genetic shuffling and random mutation makes immune system naïve again
- *Hiding**: Within cells: HSV, VZV, malaria
what is herd immunity threshold?
Ro = ?
1/ Ro = ?
Ro < 1 ?
Ro > 1 ?
1-1/Ro ?
- *Ro =** av. number of new transmissions per case over infectious period in sus or non vaccinated pop
- *1/ Ro** = proportion of the population sus. to virus (aka epidemic threshold)
- *Ro < 1** infection dies out
- *Ro > 1** infection will spread
- *Ro = 1** infection stable
proportion of pop. that needs to be vaccinated to eliminate virus: 1-1/Ro
how can antivirals target viruses?
Targets viral replication process:
• Reverse transcriptase: RNA to DNA
- Integrase: integration of viral genetic material into host genome
- Protease: cleave precursor proteins
why are there so few antivirals?
- the virus life cycle is tied to host cell: difficult to target virus alone
- viruses are difficult to grow
- most virus infections are short lived
- compound must block virus replication compelely otherwise the virus will mutate and become resistant
what is herpesvirus?
how work?
- dsDNA viruses
- stays latent in body after infection:
- chickenpox infection: virus goes into dorsal root ganglia and stays latent and can reemrge later in life as shingles
how does Aciclovir treat herpesvirus?
acyclovir:
- reduces symptoms but doesnt cure
- mimics one of the 4 bases for DNA (but misses OH group): terminates DNA sythesis
- prodrug mechanism:
- has to be activated by HSV enzyme thymdine kinase to add P
- cellular kinases add 2nd and 3rd P
- chain termiantes
- can get resistance
- need to treat IC patients
what are the different types of viral mutations that occur?
Antigenic shift: combination of different viral RNA in the host cell to produce a new variant
Antigenic drift: accumulation of random mutations during viral replication
how do HIV ARV works?
drugs: HAART (Highly Active ART)
Uses a variety of inhibitors in from different classes of anti-viral drugs to reduce the viral load.
- Entry inhibitors
- Reverse transcriptase inhibitors (NRTI, NNRTI)
- Integrase inhibitors
- Protease inhibitors
- Fusion inhibitors
