IMMS Flashcards
cholesterol in cell membrane role
supports fluidity
proteins in cell membrane role
as transporters
glycolipids and glycoproteins in cell membrane role
involved in cell signalling
tight junction role
seals neighbouring cells together in epithelial sheet to prevent leakage of molecules between them
adherens junction role
joins an actin bundle in one cell to a similar bundle in neighbouring cell
desmosome role
joins intermediate filaments in one cell to those in a neighbour
gap junction role
allows passage of small water-soluble ions and molecules
hemidesmasome role
anchors intermediate filaments in a cell to basal lamina
steroid hormone response is
slow
peptide hormone response is
fast
example of steroid hormone
sex hormones - oestrogen, testosterone
example of peptide hormone
insulin
homeostasis definition
maintenance of a constant internal environment
autocrine signalling
chemical is released from cell into ECF then acts upon same cell that secreted it
paracrine signalling
chemical messengers involved in communication between cells, released into ECF
example of paracrine signalling
ACh at neuromuscular junction
endocrine signalling
secretion into blood, longer distance, systemic communication
exocrine signalling
secretion into ducts then into organs
proportions of water in body
1/3rd extracellular
2/3rd intracellular
how much water in intracellular vs extracellular
28L intracellular
14L extracellular
breakdown of extracellular fluid
1L transcellular
3L plasma
10L interstitial
ECF contains
glucose urea Cl- HCO3- Na+
main cation in ICF
K+
main cation in ECF
Na+
osmolality definition
concentration of solutes in plasma per kilogram of solvent
osmolarity definition
concentration of solutes in plasma per litre of solution
osmotic pressure definition
measure of how easily a solution can take in water
oncotic pressure
form of osmotic pressure exerted by proteins pulling fluid into a solution (albumin)
oedema
increased movement of fluid from plasma to interstitial space
monosaccharide
sugar that cannot be hydrolysed
oligosaccharide
3-10 monosaccharides
glycosidic bonds formed by
condensation reaction of 2 monosaccharides water produced as byproduct
triglyceride made up of
3 fatty acids 1 glycerol
ATP
adenosine triphosphate
basal metabolic rate (BMR)
measure of energy required to maintain non-exercise bodily functions
1st step of glycolysis
glucose to glucose 6 phosphate by hexose kinase
1 atp to adp
2nd step glycolysis
glucose 6 phosphate to fructose 6 phosphate by phosphohexose isomerase
3rd step glycolysis
fructose 6 phosphate to fructose 1,6 bisphosphate by phosphofructokinase
1 atp to adp
4th step glycolysis (1)
fructose 1,6 bisphophate to dihydroxyacetone phosphate by triose phosphate isomerase
4th step glycolysis (2)
fructose 1, 6 bisphosphate to 3 phosphoglyceraldehyde x2 by fructose bisphosphate aldolase
5th step glycolysis
3 phosphoglyceraldehyde x2 to 1,3 bisphosphoglyceraldehyde x2 by glyceraldehyde-3-phosphate dehydrogenase
2NAD+ and 2Pi to 2NADH
6th step glycolysis
1,3 bisphosphoglyceraldehyde x2 to 3 phosphoglycerate x2 by phosphoglycerate kinase
2adp to 2atp
7th step glycolysis
3 phosphoglycerate x2 to 2 phosphoglycerate x2 by phosphoglycerate mutase
8th step glycolysis
2 phosphoglycerate x2 to phosphoenolpyruvate x2 by enolase
9th step glycolysis
phosphoenolpyruvate x2 to pyruvate x2 by pyruvate kinase
2adp tp 2atp
mneumonic for krebs cycle
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intermediated of krebs cycle
citrate isotrate alphaKetoglutarate succinyl coA succinate fumerate malate oxoalacetate
enzymes of krebs cycle
aconitase isocitrate dehydrogenase alphaKetoglutarate dehydrogenase succinyl coA synthetase succinase dehydrogenase fumarase malate dehydrogenase citrate synthetase
enzyme of krebs cycle mneumonic
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oxidative phosphorylation takes place in
inner mitochondrial membrane
explain oxidative phosphorylation
H+ pumped into intermembrane space via proton pumps
form electrochemical gradient
electrons transferred to O2 (final electron acceptor)
O2 split to form water
1 NADH is equal to
3ATP
1 FADH is equal to
2ATP
total atp from 1 molecule of glucose is
34 - 38 ATP
examples of fatty acids
linoleic acid
oleic acid
palmitic acid
arachidonic acid
fatty acid (beta) oxidation definition
catabolic process by which fatty acids are broken down in mitochondria to produce acetyl coA which enters krebs
where does beta oxidation take place
mitochondrial matrix
carnitine shuttle
acyl coA too big to transport into mitochondria
carnitine acyltransferase 1 on outer mitochondrial membrane removes CoA and ads carnitine
becomes acyl carnitine - transported into matrix
in matric carnitine acyltransferase 2 removes carnitine adds coA
acyl coA is oxidised to form acetyl coA
each round of fatty acid beta oxidation produces
1NADH
1FADH2
1 Acetyl CoA
can fatty acids act as nervous system fuel source
no FA cannot get through BBB
where does the krebs cycle take place
mitochondrial matrix
beta oxidation is dependent on
oxygen
good blood supply
adequate mitochondria number
ketogenesis is caused by
during high rates of fatty acid oxidation too much acetyl CoA is produced
this overwhelms the Krebs cycle and so you get ketone body formation
3 ketone bodies
acetone
acetoacetate
B-hydroxybutyrate
where does ketogenesis occur
in hepatocytes in the liver
3 causes of disease
genetic
multifactorial
environmental
ketone bodies used as fuels
- b-hydroxybutyrate oxidised to acetoacetate
- acetoacetate activated to acetoacetyl coA
- cleaved by thiolase enzyme to form acetyl coA
- can enter krebs
karyotype definition
number and appearance of chromosomes in a cell
G1 phase
not visible
rapid growth
protein synthesis of spindle proteins
cell cycle phases
G1 S G2 M
S phase
DNA doubles
histone proteins double
centrosome replication
double the DNA by the end of phase
G2 phase
energy stores accumulate
mitochondria and centrioles double
what happens in prophase
chromatin condenses into chromosomes
centrosomes nucleate microtubules and move to opposite poles
what happens in prometaphase
nuclear membrane breaks down
chromatids attach to microtubules
cell no longer has nucleus
what happens in metaphase
chromosomes line up along equator
what happens in anaphase
sister chromatids separate and pushed to opposite poles as spindle fibres contract
what happens in telophase
nuclear membrane reform
chromosomes unfold into chromatin
cytokinesis begin
what happens in cytokinesis
cell organelle evenly distributed
cell divides into 2 daughter cells with nucleus and 46 chroms each
clinical significance of cytokinesis
downs syndrome occurs here
how is genetic diversity introduced in meiosis
metaphase 1 = random assortment
prophase 1 = crossing over
what is non-disjunction
failure of chromosome pairs to separate in meiosis 1 or sister chromatids to separate in meiosis 2
example of non disjunction disorders
downs syndrome = 1 extra
turners syndrome = only 1 X
what is gonadal mosaicism
when there are 2 different populations of cells in the gonads
one normal population one mutated
all gametes from the mutated line are effected
allele definition
one of several alternative forms of a gene at a specific locus
polymorphism
frequent hereditary variations at locus
not mutation = doesnt cause problems
autozygosity
homozygous by descent
= inheritance of same mutation from 2 branches of same family
penetrance definition
proportion of people with gene/genotype who show expected phenotype
what is lyonisation
process of X chromosome inactivation
what is knudson’s 2 hit hypothesis
genes can be inherited or acquired
sporadic cancer requires 2 acquired mutations
inherited cancer requires 1 acquired mutation
higher chance of inherited cancer
what are peroxisomes
small membrane bound organelles containing enzymes which oxidase long-chain fatty acids
lactose made up of
glucose and galactose
sucrose made up of
glucose and fructose
maltose made up of
glucose and glucose
chiral centre is
carbon surrounded by 4 different groups
purine bases
adenine
thymine
pyrimidine bases
cytosine
guanine
glutamic acid charge
negative
primary structure of protein held together by
covalent bonds
bonds in secondary protein structure
hydrogen bonds between amino acids
bonds in tertiary protein structure
ionic bonds
disulphide bridges
van der Waal forces
what is an isoenzyme
enzymes have different structure and sequence but catalyse same reactions
what is sickle cell anaemia
genetic disorder characterised by hard sticky sickle-shaped RBC created by a mutation in Hb
role of antibodies
bind to antigens on toxins or proteins
label for destruction by immune system
what is the specificity of antibodies determined by
the variable region
features of prokaryote
no nuclear membrane
dna arranged in single chromosome
DNA in the mitochondria is
purely maternal
DNA polymerase role
reads template strand from 3’ to 5’
thus DNA is synthesised on daughter strand from 5’ to 3’
why is DNA synthesised from 5’ to 3’
because phosphate at 5’ is used for energy for reaction to occur
topoisimerase role
unwinds double helix by relieving the supercoils
DNA helicase role
separates DNA apart
breaks H bonds between bases
exposes nucleotides
DNA polymerase role
reads 3’ to 5’ and synthesises DNA on daughter strand
starts at a primer
single strand binding protein role
keeps 2 strands apart during synthesis to prevent annealing
primase enzyme role
RNA polymerase that synthesises short RNA primers needed to start the strand replication process
RNAse H role
removes RNA primers that began DNA strand synthesis
how is DNA replication completed
ligase enzymes join together short DNA pieces = Okazaki fragments
what are transcription factors
proteins which bind to promotor regions
what is a promotor
specific sequence of nucleotides that act as binding sites at the 5’ end
where does a transcription complex form
around the TATA box
start codon
AUG
stop codons
UGA, UAG, UAA
where is mRNA made
the nucleus
what is an exon
contain the coding sequence
what is splicing
the removal of introns from pre-mRNA
what is exon shuffling
exons can be joined together in different order following splicing
allows new proteins to be made
degenerate but unambiguous definition
amino acids specified by more than one codon but each codon only specifies one amino acid
factors that turn off gene expression
activation of repressors (inhibitors of RNA polymerase binding)
enzymes no longer activated
transcription and processing proteins no longer produced
what is an out of frame deletion
base is lost within a codon so whole sequence shifts over and reading frame of gene is changed
catastrophic effects
what is an in frame deletion
complete codon is removed
milder effects - late onset
what is a mis-sense mutation
point mutation in which single nucleotide change results in a codon that codes for a different amino acid (substitution)
can result in silent mutation/non-functional protein
what is a non-sense mutation
point mutation that produces a stop codon
results in an incomplete/non-functional protein
example of a non-sense mutation disorder
duchennes muscular dystrophy
what is a splice site mutation
affects the removal of an intron
what is anticipation
when a disease will affect the future generation earlier and with greater severity than the past generation
e.g. huntingtons
role of a positive feedback loop
amplification of a signal
role of a negative feedback loop
inhibits a signal
what is a hormone
molecule that acts as a chemical messenger
peptide hormone properties
large
hydrophilic
bind to receptors on membranes
dissolved in blood when needed
steroid hormone properties
hydrophobic, lipid soluble
require transport proteins in blood
binds to receptors in cell - directly affects DNA
what is transcellular fluid composed of
CSF digestive juices mucus
3 ways to intake fluid
drinking
diet
IV
what are insensible losses
losses unaware of cannot be measured e.g. sweat, breath, vomiting, faeces
hydrostatic pressure definition
pressure difference between plasma and interstitial fluid
what happens when water is lost from ECF
ECF increase in osmolality
detected by osmoreceptors in hypothalamus
ADH released from post pituitary
increase water reabsorption from collecting duct
what happens when decreased renal bloodflow
renin released from jgc in kidney
renin = angiotensinogen to angiotensin 1
angiotensin 1 to angiotensin 2 by ACE
release of aldosterone from adrenal cortex
what does aldosterone do
increase Na+ reabsorption in kidneys in exchange for K+/H+ excretion
brings water into ECF
what is hyponatraemia
low sodium levels
consequences = intracellular overhydration
what is serous effusion
excess water in a body cavity
what is oedema
excess water in intercellular tissue space
types of oedema (4)
inflammatory
venous
lymphatic
hypoalbuminaemic
what is hypernatraemia
high sodium
consequences = intracellular dehydration
what is hyperkalaemia
high postassium
consequences = risk of myocardial infarction
what is hypokalaemia
low potassium = weakness and cardiac dysrhythmia
what is hypercalcaemia
high calcium
consequences = metastatic calcification
what is hypocalcaemia
low calcium
consequences = spasms
3 types of endocytosis
phagocytosis
pinocytosis
receptor mediated
3 types of cell receptors
ion channel
g protein coupled
enzyme linked
how much energy per g of carbs
4kcal
how much energy per g of protein
4kcal
how much energy per g of alcohol
7kcal
how much energy per g of lipid
9kcal
BMR calculation
1kcal/kg body mass /hr
factors increase BMR (5)
high BMI hyperthyroidism exercise low ambient temp fever/infection
factors decrease BMR
age
female
starvation
hypothyroidism
what is daily energy expenditure DEE
energy needed to support BMR, physical activity, digestive energy
atp production at rest
30% carbs
70% lipids
where does glycolysis take place
cytosol
pyruvate to lactate in what conditions
in anaerobic conditions
pyruvate to lactate equation
2 pyruvate + 2APD + 2Pi = 2 lactate + 2ATP + 2H2O
why is glycolysis inhibited by acidosis?
phosphofructokinase-1 is pH dependent and is inhibited by acidic actions
AMP affect on glycolysis
AMP is an allosteric activator
increases affinity of PFK-1 for fructose-6-phosphate
ATP affect on glycolysis
ATP is an allosteric inhibitor
decreases affinity of PFK-1 to fructose-6-phosphate
high ATP levels = slow reaction
before being oxidised, fatty acids must
be activated in the cytoplasm
activation of fatty acid equation
fatty acid + ATP + CoA = Acyl-CoA + pyrophosphate + AMP
when are fatty acids used as fuel
when hormones signal fasting or increased demand
electron transport chain is formed from
cytochromes and other proteins
role of ATP synthestase
forms a channel in the membrane to allow H to flow back into matrix via chemiosmosis
where are ketone bodies synthesised
mitochondrial matrix
what enzyme does the liver not have enough of and what are the consequences of this
succinyl CoA/acetoacetate CoA
cannot utilise ketone bodies as fuel
extrahepatic tissues have access to ketone bodies during prolonged starvation
what is diabetic ketoacidosis
reduced glucose supply so more fatty acid oxidation
increased ketone body production exceeds ability of peripheral tissues to oxidise
ketone bodies strong acids so lower ph of blood
what are the consequences of low blood pH
impairs ability of Hb to bind to O2
what is a reactive oxygen species (ROS)
reactive molecules and free radicals derived from O2
endogenous sources of ROS
NADPH and electron transport chain
exogenous sources of ROS
UV radiation
tobacco
drugs
fenton reaction
H2O2 + Fe2+ = Fe3+ + OH- + OH+
harber-weiss reaction
O2radical- + H2O2 + H+ = O2 + H2O + OHradical
what is respiratory burst
rapid release of oxygen species (superoxide radical/hydroxyl radical) from different types of cells during phagocytosis
name 3 enzymes that protect against oxygen toxicity
superoxide dismutase
catalase
glutathione peroxidase
name 3 antioxidant vitamins
vitamin E
vitamin C
carotenoids
name 3 diseases associated with free radical injury
parkinsons
emphysema
diabetes
2 other ways to protect against oxygen toxicity
cellular compartmentalisation
repair
henderson hasselbalch equation
pH = pKa + log( [HCO3-] / [CO2] )
buffer definition
solution which resists changes in pH when small quantities of strong acids or base are added
normal pH range
7.35-7.45
the most important buffer system in the body is
carbonic acid and bicarbonate
3 systems for H+ concentration
blood/tissue buffering
excretion of CO2 by lungs
renal excretion of H+/regeneration of HCO3-
bicarbonate buffer equation
CO2 + H2O = H2CO3 = HCO3- + H+
3 biological buffers
protein
bicarbonate
haemoglobin
how do protein buffers work
If pH falls H+ binds to the amino group of the protein
If the pH rises H+ can be released from the carboxyl group of the protein
what occurs in the buffering of CO2
co2 from tissues diffuses into RBC
binds with Hb to form carbaminohaemoglobin
released at lungs and diffuses into alveoli
expired
what happens to the PaCO2 in respiratory acidosis
PaCO2 increases leading to an increase in H+ ions and so pH decreases
CO2 production is greater than CO2 elimination
causes of respiratory acidosis
inadequate ventilation due to airway obstruction - COPD/asthma
causes of respiratory alkalosis
CO2 elimination is more than O2 reabsorption
hyperventilation in response to hypoxia
3 causes of metabolic acidosis
renal failure
loss of HCO3- ions
excess H+ production
2 causes of metabolic alkalosis
vomiting (excess H+ loss)
increased HCO3- reabsorption
response in respiratory acid/alkalosis
rapid response limited effect
response in metabolic acid/alkalosis
delayed response greater effect
what is the anion gap
difference in serum concentration of cation and anions
type 1 collagen example
bone skin and teeth
type 2 collagen example
cartilage
type 3 collagen example
arteries liver kidneys spleen unterus
type 4 collagen example
basement membranes
type 5 collagen example
placenta
when does the trilaminar embryonic disc form
3rd week
what layer of trilaminar disc form epiblast
ectoderm
what cells does the epiblast give rise to
amnioblasts that line the amniotic cavity
what cells does the hypoblast give rise to
cells that line the blastocyst cavity - become endodermal cells
what is the chorion composed of
extra-embryonic mesoderm and 2 layers of trophoblast
what are the 2 differentiated layers of trophoblast
cytotrophoblast
synctiotrophoblast
ectoderm becomes
structures outside the body:
CNS, PNS
epidermis of skin/hair/nails
pituitary/mammary/sweat glands
mesoderm becomes
3 parts: paraxial plate intermediate plate lateral plate = bones/muscles/heart and circulatory system/int sex organs
endoderm becomes
epithelial lining of GI/resp/urinary tracts
parencyma of thyroid/parathryoid/liver/pancreas
