imms Flashcards
(140 cards)
1
Q
describe interphase
A
interphase
-G1 - rapid growth, new organelles produced. proteins involved in spindle formation produced.
-S1 - dna replication occurs. Histone proteins synthesised. centrosome replication
-G2 - chromosomes condense and become visible
energy stores accumulate and mitochondria numbers increases
2
Q
describe mitosis
A
-prophase - chromatin cndenses to give chromosomes
centrosomes nucleate microtubules which migrate to the poles of the nuclues.
-prometaphase
nuclear membrane breaks down
microtubules invade nuclear space
chromatids attach to microtubules
-metaphase
chromosomes line up on equatorial plate
-anaphase
sister chromatids pulled to opposite sides of the nucleus by spindle fibre contraction
-Telophase
nuclear membrane reforms around poles
chromosomes decondense to reform chromatin
cytokinesis
3
Q
how is genetic variation brought about?
A
recombination between non sister chromatids in meisos as homologous chromosomes pair up. pieces of dna break off and recombine on non sister chromatids.
random assortment. random way in which homologous chromosomes line up on equatorial plane.
4
Q
what is non disjunction
A
failure of chromosome pairs to separate during meiosis 1 and sister chromatids in meiosis 2
can result in downs syndrome or monosomy ie turners where only one X chromosome
5
Q
what is gonadal mosaicism? Give an example of a disease caused by this.
A
occurs when the precursor germline cells to ova/spermatazoon are a mixture of two or more genetically different cell lines due to mitotic error.
more than one set of genetic information is found in the sex cell.
example: duchenne muscular dystrophy
6
Q
what are the classification of genetic disease?
A
mendelian
- autosomal recessive
- autosomal dominant
- X linked
chromosomal
-abnormalities
non traditional
- mitochondrial (from mother) abnormal
- imprinting
- gonadal mosaicism
multifactorial
-genetic and environmental interaction
7
Q
what is imprinting?
A
when only one out of the 2 genes is active.
8
Q
what is lyonisation?
A
in the female only one X chromosome is active. The other is inactive and forms a BARR body. This is to prevent having 2 sets of proteins derived from the X chromosomes, would be double that of the males.
9
Q
what is the negative dominant effect?
A
mutation causing a protein which has a loss of a particular function however can somehow outcompete the endogenous protein.
10
Q
how can a child have a disease but parents are unaffected?
A
gonadal mosacism
mother may have reduced penetrance / variable expression
11
Q
define autosomal
A
chromosomes 1-22
excludes sex chromosomes
12
Q
define locus
A
position of a gene/DNA on geentic map
13
Q
define genotype
A
genetic constitiution of an individual
14
Q
define phenotype
A
physical characteristics due to genotype and environment
15
Q
define allele
A
one of the several alternative forms of a gene at a specific locus
16
Q
define consanguinity
A
reproductive union between 2 relatives
17
Q
define autozygosity
A
homozygous by descent. a result of consanguinity.
18
Q
define homozygous
A
both alleles same at a locus
19
Q
define heterozygous
A
alleles at same locus different
20
Q
define hemizygous
A
describes a gene carried on an unpaired chromosome. ie X for men
21
Q
define penetrance
A
proportion of people with gene or genotype who show expected phenotype.
may be complete (all) or incomplete (not all show it)
22
Q
define variable expression
A
variation in clinical features of a genetic disorder between individuals with same gene alteration
23
Q
define sex limitation
A
expression of a particular characteristic limited to one of the sexes
24
Q
define multifactorial condition
A
diseases due to a combo of genetic and environmental factors
25
define late onset
condition not manifested at birth
26
define congenital
condition is manifested at birth
27
what are the types of tissue?
```
epithelium
supportive tissue (cartilage, bone, tendons,blood)
muscle
nerves
germ cells
```
28
describe the haemotoxylin and eosin stain
haemotoxylin stains acidic things blue, such as DNA, RNA, cell nuclei.
eosin stains alkaline things red. such as cytoplasm, colloidal proteins.
29
describe alcian blue
stains structures rich in glycosaminoglycans blue
| ie mucous goblet cell, mast cell granules and cartilage matrix
30
describe iron haematoxylin
stains nuclei and elastic fibres black
31
describe periodic acid shift stain
stains hexose sugars magenta
| stains goblet cell matrix, glycogens, basement membrane, glycocalyx
32
describe toludine blue
stains nuclei, ribosomes, cytoplasm dark blue
stains cartilage matrix, mast cell granules pale blue
stains GAG rich bright purple
33
describe the components of the cytoskeleton
made up of microtubules, intermediate filaments and microfilaments.
microtubules are 25 nm diameter
made from alpha and bets tubulin arranged in groups of 13 to form a hollow tube. all cells have except erythrocytes
intermediate filaments
10 nm diameter
6 types of protein. they are anchored to the transmembrane protein and spread tensile forces though tissues. many different types. ie cytokeratins for epithelial cells.
microfilaments are made from actin.
5 nm diameter
forms a mesh around inner surface of cell membrane
34
describe the components of the cytoskeleton
made up of microtubules, intermediate filaments and microfilaments.
microfilaments 5nm
made of actin filaments
used in muscle contraction
+ and - end. negative end anchored, positive end is able to grow and meet some other some cell structure, gives tensile strength and stability.
intermediate filaments 10nm
made from 6 different protein types. similar role to microfilaments. found in the nuclear lamina and outside the cytoplasm.
microtubules 23nm
made from alpha and beta TUBULIN globular protein filaments arranged in a tube. negative end of tubule attaches to the centrosome.
synthesise the spindle important in DNA replication
involved in transport
35
which 2 proteins interact to cause cilia bending?
tubulin and dynein
| form the microtubules of the cilia. 9 peripheral doublets and a pair of central .
36
what is the general formula for carbohydrates?
Cn(H2O)n
37
what isomers can a monosaccaride form? which is the most common?
D & L isomers
D is the most common in sugars.
will rotate plane polarised light right
38
what is an Unsaturated fatty acid?
means it has one or more double carbon bonds. double bond commonly CIS (functional groups on same side of double bond)
39
what are the purines and pyrimines?
Adenine and thymine are purines
have 2 carbon nitrogenous ring
guanine and Cytosine are pyrimines
have only one carbon nitrogenous ring
40
what is the structure of a nucleotide?
ribose sugar in RNA, deoxyribose in DNA
phosphate
nitrogenous base
41
what bonds are found between the phosphate and sugar?
phosphodiester
42
what form are most amino acids found in?
the L enantiomer form
43
what is the difference between a protein and a peptide?
protein
greater than 50 aa
functional
synthesised by the cell
peptide - fragment of a protein
less than 50 aa
44
describe the structure of a protein
primary structure is the sequence of amino acids determined by the base sequence
secondary structure is the folding of the polypeptide chain into either alpha helix or beta pleated sheets.
in the alpha helix, every NH group donates the H to a CO group located 3/4 residues earlier on the protein sequence.
super secondary structure, the combination of secondary structures together
tertiary structure
complex shape formation as a result of bonds. ie disulfide, hydrogen, ionic, VDW, electrostatic, covalent
Quaternary structure is a 3D protein composed of several sub-units. 2 or more tertiary structures.
45
why can DNA polymerase only synthesis daughter DNA from 3' to 5' end?
DNA polymerase reads template DNA from 3' end to 5' end. Daughter DNA synthesised from 5' end to 3' end.
However 3' end of template does not have a phosphate group, this is needed to provide energy for synthesis. Therefore daughter DNA synthesised starting from the 5' end, phosphate group able to provide energy.
46
describe the process of DNA replication
1. tropoisomerase unwinds DNA helix
2. DNA helicase breaks hydrogen bonds exposing dna nucleotides behind the replication fork
3. SSB (single strand binding proteins) coat the single strands preventing annealing.
4. Primase enzyme makes a short DNA single strand primer complementary to each end of the 2 DNA strands.
5. DNA polymerase can now begin adding free nucleotides to the exposed nucleotides. read strand in the 3' to 5' direction so synthesis of new DNA daughter strand from 5' to 3'.
6. one leading strang and one lagging strand. leading strand is the one where DNA polymerase is about to synthesis DNA continously and is moving towards replication fork following action of DNA helicase. lagging
47
describe the process of DNA replication
1. tropoisomerase unwinds DNA helix
2. DNA helicase breaks hydrogen bonds exposing dna nucleotides behind the replication fork
3. SSB (single strand binding proteins) coat the single strands preventing annealing.
4. Primase enzyme makes a short DNA single strand primer complementary to each end of the 2 DNA strands.
5. DNA polymerase can now begin adding free nucleotides to the exposed nucleotides. read strand in the 3' to 5' direction so synthesis of new DNA daughter strand from 5' to 3'.
6. one leading strang and one lagging strand. leading strand is the one where DNA polymerase is about to synthesis DNA continously and is moving towards replication fork following action of DNA helicase. lagging strand is the one where DNA polymerase is moving away from DNA helicase, therefore must keep restarting to synthesise DNA on newly exposed template DNA.
7. RNAseH removes primers. produced Okazaki fragments on the lagging strand
8. DNA ligase connects fragements together.
48
what are the start and stop codons?
start AUG
| stop UGA UAG UAA
49
How can one gene code for a variety of proteins
exon shuffling after introns are removed
50
what form are genes that are actively used in a cell in?
euchromatin
| if not active, in heterochromatin form
51
describe a deletion mutation
deletion - in frame (whole codon is lost/1AA removed) or out of frame (whole sequence after mutation altered)
52
what is a splice site mutation
point mutation which affects the accurate removal of introns. introns may be translated
53
what is a non sense mutation
point mutation forming a stop codon. incomplete non functional protein.
54
what is a mis sense mutation
mis sense mutation - a point mutation, results in codon coding for a diff amino acid.
55
how many grams/kg is the triglyceride storage?
15 kg
56
how many grams/kg is the glycogen storage?
200 g in liver 150 g in muscle
57
how many grams/kg is the protein storage?
6kg
58
at rest, what accounts for ATP production?
70% by lipid 30% by carbohydrates
59
describe how fatty acids are brought into the mitochondrial inside the hepatocyte.
fatty acids must be activated before they can be used for beta oxidation.
fatty acid + ATP + CoA --> acyl CoA + PPi + AMP
Acyl CoA forms acyl carnitine using enzyme carnitine acyl transferase 1.
acyl carnitine transported into the matric
converted back to acyl CoA via enzyme carnitine acyl transferase 2. carnitine can diffuse back to outer membrane and re used. 'Shuttle.'
60
describe the beta oxidation of fatty acids
1. double bond formation between alpha and beta carbon of fatty acyl CoA. Enzyme acyl CoA dehydrogenase. FADH2 formed.
2. H20 added. OH added to beta carbon, H added to the alpha carbon. enzyme enoyl hydratase
3. oxidation of beta carbon to a ketone. NADH+ H+ formation. enzyme: beta hydroxy acyl CoA dehydrogenase
4. cleavage of alpha and beta bond. coA addition. acetyl coA formed and a shorter acyl coA which is recycled to start. enzyme beta keto thiolase.
61
why is it debatable that 38 ATP are formed from respiration?
assumes all NADH+H+ and FADH2 used in oxidative phosphorylation
assumes all H+ ions are used for chemiosmosis.
62
name 3 ketones
acetone
acetoacetate
b-hydroxybutyrate
63
name the process of ketogenesis
acetyl coA + acetyl Coa
enzyme thiolase
form acetoacetyl CoA
acetoacetyl CoA forms 3-hydroxy-3-methylglutaryl CoA
enzyme HMG CoA synthase
HMG forms acetoacetate
enzyme HMG CoA lyase
acetoacetate can spontaneously be removed as acetate (people with high ketone count pear smelling breath) volatile so removed quickly.
or can be converted to Beta hydroxybutyrate. by enzyme d-b-hydroxybuyrate dehydrogenase
64
why are liver cells unable to use ketone bodies as an energy source?
liver does not have enough of the enzyme succinyl CoA acetoacetate CoA.
this enables extrahepatic tissues to have access to ketone bodies in times of starvation.
65
what happens when fat/carb levels are sparse?
muscle and cardiac tissues will use ketone bodies for energy production. this conserves any remaining glucose for the brain.
66
how do extra hepatic tissues utilise ketones?
Can use ketones in the form of d-B-hydroxybutyrate or as acetoacetate.
d B hydroxybutyrate is converted to acetoacetate by enzyme d B hydroxybutyrate dehydrogenase.
acetoacetate is converted to acetoacetyl CoA by enzyme succinyl CoA acetoacetate CoA transferase.
acetoacetyl can be converted to 2 x acetyl CoA. This can be then used in Krebs.
67
what happens in diabetes mellitus?
inability to take in glucose
liver synthesises more ketone bodies to supply tissues
production exceeds tissue ability to oxidise
ketones acidic
ph of blood drops
Hb binding ability decreases
68
describe tight junctions
form a water tight connection between 2 adjacent cells. composed of protein CLAUDIN
prevents lateral movement of integral proteins on cell surface. ensures endocytosis and exocytosis occurs on appropriate side.
ensures selective transport as molecules must undergo transport.
found at lungs, bladder, intestine, kidney
69
describe the adhering junctions
zonula adherens
lie underneath the tight/occluding junctions. Made of actin filaments. Gap between zona adherens and occluding junction is a protein called E cadherin which helps to join the adjacent cells.
macula adherens (desmosomes)
made up of intermediate filaments and KERATIN protein
usually found in combination with tight junctions
hold 2 cells together tightly, important for regions which undergo constant stretch such as the intestine or skin.
hemidesmosomes connect basal epithelial surface to basal lamina.
70
describe gap junctions
connective tunnels, cylindrical. made of proteins called CONNEXINS. 2-4nm between 2 cells connected by a gap junction
found in cardiac cells where it allows Ca2+ to be able to diffuse rapidly between cells and propagate an action potential.
71
name the common reactive oxygen species?
superoxide O2•-
hydrogen peroxide H2O2
hydroxl OH•
72
how is superoxide radical formed?
from coenzyme Q action
| or from metal containing enzyme action ie CP450
73
how is the hydroxl radical formed?
Haber weiss
| Fenton reaction
74
why can ROS be dangerous?
Reactive free radical extract electrons (usually as hydrogen atoms) from other compounds to complete their own orbitals, thereby initiating free radical chain
reactions.
cause oxidative damage to proteins and DNA
damage to cell membranes
tissue damage
directly cause of emphysema, alcoholic liver disease, ageing, acute renal failure...
75
what are the exogenous sources of ROS?
```
UV
tobacco
drugs
pollutants
radiation
```
76
what are the endogenous sources of ROS?
```
mitochondria
peroxisomes
neutrophils
NADPH
electron transport chain
```
77
what are the RNOS?
reactive nitrogen oxygen species
| hypocholrous acid HOCl and nitric oxide NO
78
how do cells protect themselves against ROS?
cell compartmentalization of free radicals
repair processes
defense enzymes
antioxidants which can terminate free radical chain rxn
79
which enzyme can remove superoxide free radical?
superoxide dismutase
80
which enzymes can remove H202?
| which enzymes can remove hydroxyl radical?
catalase
| glutathione peroxidase
81
which antioxidants can protect against ROS?
C, E vitamins
| flavanoids
82
which ROS is most potent?
hydroxl OH•
lipid soluble
does lipid peroxidation
83
what is oxidative stress
when rate of ROS formation exceeds tissue capability to remove
84
how do you go from O2 to H20
O2 + e- → O2•-
O2•- + e- + 2H+ → H2O2
H202 +e- + H+ → OH• + H2O
OH• + e- + H+ → H20
85
what is the fenton reaction
H2O2 + Fe2+ → Fe3+ + OH• + OH-
86
what is the haber weiss reaction
H2O2 + O2•- → OH- + OH• + O2
87
what is the respiratory burst
immune system defence against bacteria
rapid release of ROS superoxide
damages bacterial cell membrane
88
describe the respiratory burst
1. O2 → O2•-
enzyme NADPH oxidase
NADPH forms NADP+
2. O2•- → H202
sponatenous or via superoxide dismutase
3. H202 forms HOCl via addition of Cl-
enzyme myloperoxidase. HOCl kills bacteria
4. or H2O2 forms OH• via fenton reaction
(H202 + Fe2+ → Fe3+ + OH• + OH-)
used to kill bacterium
89
what is the haber weiss fenton cycle
Fe2+ + H2O2 → Fe3+ + OH- + OH• [Fenton reaction]
OH• + H2O2 → H2O + O2•– + H+
O2•– + H2O2 → O2 + OH• + OH-[Haber-weiss reaction]
Fe2+ + OH• + H+ → Fe3+ + H2O
90
define karyotype
the number and appearance of chromosomes in a cell. spreads are arranged in order. biggest chromosome pair is number 1, smallest is number 22. sex chromosomes are 23.
91
what percentage of body weight is water?
60% (42L)
92
what is the main ion of ECF and ICF
ecf - Na+ (Cl-, HCO3-, Ca2+)
| icf K+
93
how is body water compartmentalised?
total body water 60% 42L
extracellular fluid 14L 20% Intracellular fluid 40%28L
plasma 3L - interstitial 10L - transcellular 1L
94
what is transcellular fluid?
includes CSF and giestive juices
95
what are the 3 types of hormones? describe each
peptide - short chain AA. large hydrophilic. bind to receptors. pre made and stored. rapid response. second messenger model. insulin , GH, TSH, ADH
steroid - synthesised from cholesterol. need to be bound to plasma protein to travel. made when needed, not stored. bind to receptor inside cell. slow response. testosterone, oestrogen, cortisol
amino acid derivative
synthesised from tyrosine
T3,T4, adrenaline
96
define osmosis
the net movement of solvent molecules through a semi permeable membrane to an area of higher solute concentration
97
define osmolality
measure of the number of dissolved particles in 1kg of liquid
98
define osmolarity
measure of the number of dissolved particles in 1L of liquid
99
define oncotic pressure
a form of osmotic pressure exerted by proteins, notably
| albumin, in a blood vessel's plasma (blood/liquid) that usually tends to pull water into the circulatory system.
100
define osmotic pressure
the pressure that would have to be applied to a pure
solvent to prevent it from passing into a given solution by osmosis, often used to express the concentration of the solution.
101
define hydrostatic pressure
the pressure difference between capillary blood plasma and interstitial fluid.
102
define oedema
excess water in the intracellular space.
103
how much kcal in carbohydrates, proteins,alcohol and lipids?
carbohydrate 4kcal/g
protein 4kcal/g
alcohol 7kcal/gram
lipid 9kcal/g
104
what is BMR
basal metabolic rate
energy expenditure needed to stay alive at rest state
1kcal/kg body mass/hr
105
what is the daily energy expenditure
energy needed to support BMR, physical activity and energy required to process food we eat
106
what is exocytosis?
vesicle formed from the golgi apparatus
vesicle fuses with the cell surface membrane
for waste removal or secretion
107
what is endocytosis?
energetic process to absorb molecules into a cell.
forms a vesicle (endosome).
ie phagocytes form a phagosome
ie pinocytosis engulfing liquid into a cell
108
define acid and base
acid proton acceptor
| base proton acceptor
109
define buffer
weak acid or base along with its conjugate base or acid.
able to resist changes in pH on addition of a small amount of strong acid / base.
110
what is the henderson hasselbach equation
ph = pka + log (HCO3- conc / CO2 conc)
111
what is the optimum pH
7.4
| range 7.35 - 7.45
112
how is pH kept normal?
co2 excretion by lungs
renal function control H+/HCO3-
blood and tissue buffering. HCO3- and proteins act as buffers. ie Haemoglobin
113
how is carbon dioxide transported in the blood
carbon dioxide from tissues enters the erythrocyte. Now has 3 options.
- carboxyhaemoglobin formation with deoxy Hb
- CO2 dissolves within RBC
- CO2 combines with H20 to form carbonic acid (via carbonic anhydrase). H2CO3 dissociates to give H+ and HCO3-. HCO3- is transported out of the RBC in exchange for Cl-. This is the chloride shift, important as it maintains electroneutrality.
At tissues, Hb has high affinity for oxygen. Carbon dioxide is released. carbon dioxide diffuses into alveoli along its concentration gradient. removal of carbon dioxide shifts the equation to the left. HCO3- enters the RBC (and Cl- out). combines with H+ to form H2CO3 and co2 and water can be released.
114
how is hydrogen transported in the blood?
at the cell, Hb02 releases the oxygen.
at the same time, co2 and h20 diffuse into RBC from cell.
formation of H2CO3. HCO3- taken out of cell in exchange for Cl- to maintain electroneutrality.
H+ combines with deoxy Hb to form HbH.
115
what are the causes of respiratory acidosis?
hypoventilation - co2 retention
very high metabolic rate and carbon dioxide production - high fever
paCO2 >6kPA
116
what are the causes of respiratory alkalosis?
hyperventilation due to anxiety/ pulmonary embolism or asthma
PaCO2 <4.5 kpa
117
what are the causes of metabolic acidosis?
renal dysfunction - inability to reabsorb all HCO3- or inability to secrete H+
hypoaldosteroism - aldosterone increases Na+ absorption which is coupled to H+ secretion which ties into HCO3- reabsorption
excess acid production for example due to increased anaerobic acid caused by hypoxia. ie lactic acid.
diabetic acidosis - no insulin/no glucose/fatty acid used/converted to ketone/ketones are acidic/ H+ produced/acidosis
118
what are the causes of metabolic alkalosis?
alkali ingestion
vomiting - loss of acid from gastric secretion
excessive HCO3- absorption - linked to Cl-. If Cl- levels fall (vomiting) there will be increased HCO3- reabsorption to maintain electroneutrality.
119
what is the anion gap?
the difference in serum concentration between anions and cations.
excludes some ions such as K+ PO4- SO4-
normal: 3-11 mEq/mol
120
how can we use the anion gap?
can diagnose cause of metabolic acidosis
121
name the 3 types of cartilage
hyaline -trachea, synovial joints, larync
elastic - pinna, epiglottis
fibrous - intervetebral cartilage
122
what are the 3 cell types of bone?
osteoblasts - synthesis
osteocytes - maintain and regulate Ca2+
osteoclasts - remodel break down
123
what are the 2 bone types?
primary / woven - new bone
| secondary - remodeled bone
124
what are the 3 types of epithelium?
simple
stratified
pseudostratified
125
name the 3 muscle types
cardiac
smooth/visceral
skeletal
126
name 3 contractile cells
pericyte
myoepithelial
myofibroblast
127
what is the basement membrane made from
collagen type 4
| fibronectin
128
what are the 3 types of connective tissue
fibrous loose /dense (tendon)
fatty (white adipose brown in babies)
hard (cartilage or bone)
129
how many types of collagen are there?
12
130
give an example where type I, II, III, IV, V collagen is found
```
1 - skin/tendon/organ/bone
2 - cartilage
3- liver
4 basement membrane
5 placenta
```
131
what is tropocollagen
triple helix of peptides
132
what is the cause and consequence of hypernatraemia?
Osmotic Diuresis
dehydration
renal failure
diabetes insipidus (little response to ADH, lots of water lost. dehydration)
133
what is the cause and consequence of hyponatraemia?
diuresis
134
what is the cause and consequence of hypernatraemia?
Osmotic Diuresis (lots of water lost, Na high conc)
dehydration
renal failure
diabetes insipidus (little response to ADH, lots of water lost. dehydration)
cerebellar intracellular dehydration
135
what is the cause and consequence of hyponatraemia?
diuresis
addisons disease
IV fluids
oedema
intracellular overhydration
headache
hypertension
136
what is the cause and consequence of hypercalcaemia?
hyperparathyroidism
skeletal metastases
Tb
metastatic calcification
kidney stones
137
what is the cause and consequence of hypocalcaemia?
vit D deficiency
Mg deficiency
renal disease
tetany (spasms)
138
what is the cause and consequence of hyperkalaemia?
diuresis
addisons disease
acidosis
risk of MI, high K+ affects RMP of the myocytes
139
what is the cause and consequence of hypokalaemia?
diarrhoea
vomiting
alkalosis
hypomagnesaemia
weakness and cardiac dysarrhythmia
140
name the 4 types of cell surface glycoproteins
anchors
receptors
enzymes
transporters
