IMMS Flashcards
1
Q
Where is DNA found? What is the structure of DNA?
A
Nucleus and mitochondria. Double helix with strands in opposite directions. Complementary base pairs between strands. A-T = 2 bonds, C-G = 3 bonds
2
Q
How is DNA packaged into a chromosome?
A
DNA coils around histones to form nucleosomes, coils again into supercoils + again into chromosomes
3
Q
How many chromosomes are there to each cell? What are the two chromosome arms?
A
46 chromosomes (23 pairs). Long arm (q) + short arm (p(etite)) separated by centromere
4
Q
Which two dyes are used to stain chromosomes?
A
- Giemsa = G banding - Quinacrine = Q banding, each band = 6-8 million base pairs
5
Q
What is the purpose of mitosis?
A
- To produce 2 genetically identical daughter cells - For growth + to replace dead cells
6
Q
What stage must a cell be in for mitosis to start? What happens in the synthesis stage for the cell cycle?
A
Cell must be in interphase. S phase = DNA and centrosome replication
7
Q
What happens in the first stage of mitosis? Remember IPPMAT
A
Prophase: - Chromatin condenses into chromosomes - Centrosomes nucleate microtubules + move to opposite poles of nucleus
8
Q
What happens in the second stage of mitosis?
A
Prometaphase. - Nuclear membrane breaks down - Spindle fibres begin to form
9
Q
What are cells called that are permanently in the cell cycle? How about cells that never enter the cell cycle?
A
Permanently in = labiles. Never in = myocytes
10
Q
What is the third stage of mitosis?
A
Metaphase. - Chromosomes line up along equatorial plane
11
Q
What is the fourth stage of mitosis?
A
Anaphase. - Sister chromatids separate + pushed to opposite poles of cell
12
Q
What is the last stage of mitosis?
A
Telophase. - Nuclear membranes reform - Chromosomes unfold into chromatin - Cytokinesis begins
13
Q
What is the clinical relevance of studying cells undergoing mitosis?
A
- Can detect chromosomal abnormalities - Can categorise tumours as benign or malignant - Can grade malignant tumours - lots of mitosis = high grade
14
Q
Which drugs can be used to disrupt mitosis?
A
To break mitotic spindle: - Taxol -Vinca alkaloids, e.g. vinblastine To break spindle poles: - Ispinesib To stop anaphase: - Colchicine-like drugs
15
Q
What is meiosis? How is different to mitosis?
A
Only occurs in gametes, has 2 cell divisions to create 4 genetically varied haploid daughter cells. It is also not a cycle
16
Q
What is crossing over? Where in meiosis does it take place?
A
Crossing over = sorting genes independently. Takes place in Prophase 1. - 1: Interphase G1, Interphase S, Prophase 1, Metaphase 1, Anaphase 1, Telophase 1 - 2: Prophase 2, Metaphase 2, Anaphase 2, Telophase 2, Cytokinesis
17
Q
What is the difference between sperm and egg production?
A
Sperm: cytoplasm divides evenly, 4 equal gametes after meiosis 2 Egg: cytoplasm divided unequally to give 1 egg and 3 polar bodies (that apoptose). Meiosis completed at ovulation, meiosis 2 only completed if fertilisation occurs
18
Q
What is non-disjunction?
A
The failure of chromosome pairs to separate in meiosis 1 or sister chromatids to separate properly in meiosis 2, e.g. Down syndrome = extra chromosome on 21
19
Q
What is gonadal mosaicism?
A
All or part of parental germline is affected by disease mutation, but the parental somatic cells are not affected. Parent = healthy, foetus may have genetic disease. Risk increases with parent age
20
Q
What are the 3 categories of disease causation?
A
- Genetic, e.g. Down’s syndrome - Multifactorial, e.g. Spina bifida - Environmental, e.g. scurvy from poor diet
21
Q
What do phenotype and genotype mean?
A
- Genotype = genetic constitution of an individual - Phenotype = appearance of an individual = result of genotype + environment
22
Q
What do the terms allele and polymorphism mean?
A
- Allele = one of several forms of a gene - Polymorphism = frequent hereditary variations at a locus
23
Q
What do homozygous, heterozygous and hemizygous mean?
A
- Homozygous = both alleles the same at a locus - Heterozygous = alleles different at a locus - Hemizygous = only one allele refers to a locus on an X chromosome in a male
24
Q
What are the 3 categories of genetic disease?
A
- Chromosomal - Mendelian, e.g. autosomal dominant/recessive, X-linked - Non-traditional, e.g. mitochondrial, imprinting (one allele active, other inactive) + mosaicism (error in cell division, same cells have different genetic makeup)
25
What are acrocentric chromosomes?
Chromosomes with a short arm
26
What is autosomal dominant inheritance? How does this compare to autosomal recessive inheritance?
- Autosomal dominant inheritance = disease which is manifest in the heterozygous state. Only one defected gene needed. Affects multiple generations. Both parents can sometimes be unaffected, e.g. gonadal mosaicism, mother has reduced penetrance, mother has variable expression. IF THE TRAIT IS DOMINANT, ONE OF THE PARENTS MUST HAVE THE DISEASE. Example = Huntington’s disease - Autosomal recessive inheritance = disease manifest in homozygous state. Requires 2 defected genes. Affected individuals are in single generation. Chance of having disease = 25%, chance of being carrier = 50%. If a child has an affected sibling, their chance of being a carrier increased to 2/3 (66%), as one possibility removed. Example = Cystic fibrosis
27
What is X-Linked inheritance?
Caused by mutation in a gene on X chromosome. Never male to male - sons always get X chromosome from mother. Transmitted usually through unaffected female. All daughters from affected males are carriers. Can be recessive (Duchenne’s muscular dystrophy) or dominant (Alpert’s syndrome)
28
Why can’t males pass on mitochondrial diseases?
Mitochondria = bulky, so can’t fit into sperm
29
What are amino acids?
- Building blocks of proteins - Side chain often determines polarity (hydrophilicity) or non-polarity (hydrophobicity) - Charge determined by all 3 components (NH2, COOH and R) - 20 different R groups
30
What are the bonds between amino acids called? How strong are they?
Peptide bonds. Very stable. Cleaved by proteolytic enzymes.
31
What are proteins?
Large polypeptides, function dependent on structure
32
What is the primary structure of proteins?
Sequence of amino acids
33
What is the secondary structure of proteins? What are the 2 secondary structures?
Folding of primary structure. - Alpha helix = H-bonding across folded chain - Beta sheet = bonding between parallel chains. The bonding is due to the sugar-phosphate backbone
34
What are super secondary structures?
Helix turn helix, beta alpha beta, zinc fingers, leucine
35
What is the tertiary structure of a protein?
Folding of secondary structure into 3D shape of protein. Forces involved include electrostatic, hydrophobicity, H-bonds and covalent bonds. Bonding due to R group
36
What is the quaternary structure of a protein?
Multiple protein chains, e.g. haemoglobin has alpha and beta chains
37
Which forces and bonds are involved from the primary to quaternary structure?
- Van der Waals = weak interactive forces caused by temporary dipole - Hydrogen = dipole between H and O, N or F - Hydrophobic = uncharged and non-polar side chains poorly soluble in water, so are ‘repelled’ = hydrophobic side chains tend to form tightly packed cores in interior of proteins - Ionic = between fully or partially charged groups - Disulphide = between side chains of cisteine (amino acid) residues
38
How can we determine protein structure?
X-ray diffraction of protein crystals
39
What is an antibody? What is the portion of an antigen bound to the antibody called?
Antibody binds to antigen. Portion of antigen bound is called epitope
40
What are the functions of DNA?
- Storing and transferring genetic information - Template and regulator for transcription + protein synthesis - Structural basis of hereditary + genetic diseases
41
What is DNA like in prokaryotes?
DNA arranged in single chromosomes, no nuclear membrane
42
What is DNA like in eukaryotes?
DNA in a nucleus, bound to histones (chromatin). During mitosis, chromatin condenses into chromosomes (2 chromatids joined by centromere)
43
What happens in DNA replication?
- Topoisomerase unwinds DNA + DNA helicase separates H-bonds to expose 2 DNA strands. Replication takes place at both strands - Single stranded binding proteins (SSB’s) coat single DNA strands to prevent reannealing or snapping back together - Primase enzyme then uses original DNA sequence to synthesise short RNA primer. Primers = necessary since DNA polymerase can’t start a nucleotide chain, only extend - DNA polymerase begins to synthesise a new DNA strand (via complementary base pairing using free nucleotides) by extending an RNA primer in 5’ and 3’ direction. Each parental strand copied by one DNA polymerase (lead and lagging strand as chains antiparallel) - As replication proceeds, RNase H recognises RNA primers bound to DNA + removes them by hydrolysing the RNA - DNA polymerase can then fill the gap left by RNase H - DNA replication completed when ligament enzyme joins short DNA pieces (Okazaki fragments) from lagging strand into a continuous strand
44
What happens in the first stage of transcription?
- Topoisomerase unwinds double helix by relieving the supercoils - DNA helicase then separates the DNA strands, exposing nucleotides - SSBP’s coat single DNA strands to prevent DNA re-annealing
45
What happens in the second stage of transcription?
- AUG = start codon - Free mRNA nucleotides line up next to their complementary bases on template strand = U-T + C-G - Template runs 3’ to 5’, coding strand runs 5’ to 3’
46
What happens in the third stage of transcription?
- RNA polymerase joins mRNA nucleotides, forming phosphodiester bonds between them - Forms antiparallel mRNA strand (5’ to 3’) starting at promoter - Stops at stop codon - UAA/UAG/UGA
47
What is the final stage of transcription?
- Splicing = introns (non-coding) removed to leave exons (coding) - mRNA leaves nucleus through nuclear pores
48
How does translation work?
- mRNA attaches to 80S ribosome - mRNA strand read 5’ to 3’ - At ribosome, the mRNA sequence (bases read in codons) is used as a template to bind to complementary anticodons on tRNA molecule - tRNA molecules are attached to specific amino acids - Enzymes remove amino acid from tRNA + amino acids are linked together by peptide bond, creating polypeptide chain
49
What are the features of DNA code?
- Degenerate = many amino acids coded for by more than one codon - Almost universal = all organisms use same code (except a few) - Non-overlapping = each nucleotide read once
50
What are nucleotides?
- Building blocks of DNA, made from nitrogenous base, sugar + phosphate - Hydrogen bonds between bases - Phosphodiester bonds between sugar and phosphate - Phosphate bonds = source of energy
51
What are polysaccharides made up of? How do monosaccharides appear?
Monosaccharides. Have one hydroxyl group + generally exist as ring structures. Aldose has an aldehyde, ketose has a ketone
52
What are the bonds between carbohydrates?
Glycosidic bonds. Hydroxyl group reacts with either -OH or -NH group
53
What are the 2 glycosidic bonds?
- O-glycosidic bonds form di-,oligo- + polysaccharides - N-glycosidic bonds found in nucleotides in DNA
54
What are di-, oligo- and polysaccharides?
- Disaccharides = 2 monosaccharides - Oligosaccharides = 3-12 monosaccharides - Polysaccharides = 1000s of monosaccharides joined by glycosidic bonds, e.g. glycogen
55
Name and explain some common structural anomalies in chromosomes.
- Translocation = portion of chromosome breaks and re-attaches to another chromosome - Inversion = a segment of chromosome is reversed end to end - Deletion = portion of chromosome removed (either out of frame, where sequence shifts so that reading frame of gene is changed, or in frame, where one codon removed so reading frame unchanged) - Duplication = portion of chromosome duplicated
56
What do consanguinity and autozygosity mean?
- Consanguinity = reproductive union between 2 relatives, increases risk of AR conditions - Autozygosity = homozygosity by descent, i.e. inheritance of same altered allele through two branches of same family
57
What do penetrance and variability mean? How about sex limitation?
- Penetrance = % of individuals with specific genotype showing expected phenotype - Variability = range of phenotypes expressed by specific genotype - Sex limitation = genes present in both sexes but only expressed in one + remains turned off in the other one
58
What is the difference between somatic and gonadal mosaicism?
- Somatic mosaicism = genetic fault present at only some tissues in body - Gonadal mosaicism = genetic fault present in gonadal tissue (de novo mutation = genetic alteration present for first time in a family member as a result of a mutation in a germ cell (egg or sperm) of one of the parents
59
What do these terms mean: - Late-onset - Sex-limited - Predictive testing
- Condition not manifest at birth - Condition inherited one AD pattern that affects one sex more - Testing for a condition in a pre-symptomatic individual to predict chance of developing condition
60
What does lyonization mean?
Inactivation of an X chromosome, happens in females to prevent twice as many gene products from the X chromosome as males
61
When referring to mitochondrial inheritance, what do the terms homoplasmy and heteroplasmy mean?
- Homoplasmy = eukaryotic cell whose copies of mitochondrial DNA are identical - Heteroplasmy = denotes mutations which affect only a proportion of the molecules in the cell
62
Examining a histological section, a pathologist sees a cell undergoing mitosis. The chromosomes are moving towards opposite poles of the cell and there are no nuclear membranes. Which phase of mitosis is this? - A. Anaphase - B. Cytokinesis - C. Metaphase - D. Prophase - E. Telophase
A
63
Which is the last phase of mitosis? - A. Anaphase - B. Cytokinesis - C. Metaphase - D. Prophase - E. Telophase
B
64
During mitosis, chromosomes attach themselves to microtubules that propagate from centrosomes. What are these microtubules made of? - A. Actin - B. Cytokeratin - C. Desmin - D. Tubulin - E. Vimentin
D
65
A 33-year-old woman presents with an unusual rash which the dermatologist biopsies. A dashing pathologist examines a section of skin under the microscope. He observes some cells which he believed are mast cells. Which stain, which turns the granules in mast cells purple, can he use to confirm his hypothesis? - A. Alcian blue - B. Giemsa - C. Haemotoxylin - D. Perls stain - E. Toluidine blue
E
66
A student examines a section of liver tissue and notices some brown pigment within the liver cells. She wonders if the patient could have haemochromatosis (a form of iron overload). What stain, which turns iron-containing pigment blue, would confirm her hypothesis? - A. Alcian blue - B. Haemotoxylin - C. Iron haemotoxylin - D. Perls stain - E. Van Gieson’s trichrome
D
67
This pedigree is consistent with which pattern of inheritance? - A. Autosomal dominant - B. Autosomal recessive - C. X-linked dominant - D. X-linked recessive - E. Y-linked
A
68
A tumour cell in the synthesis phase of the cell cycle begins the process of DNA replication. Which of the substances below splits the two DNA strands apart? - A. Cytosine - B. DNA Polymerase - C. Helicase - D. Topoisomerase - E. Uracil
C
69
While analysing human genetic material, a geneticist observed that sample A contains single-stranded nucleic acids, and sample B contains double-stranded nucleic acids. Which one of the substances below will be found only in sample A and not in sample B? - A. Adenine - B. Cytosine - C. Guanine - D. Thymine - E. Uracil
E
70
A forensic scientist is presented with a minute quantity of cellular material from a crime scene. The sample contains only a few cells. In order to produce a sample that is large enough for analysis, he adds the component of DNA to the sample. Assuming that the DNA strands have been split apart, which other substance must be added to catalyse the amplification of the sample? - A. Adenosine - B. DNA polymerase - C. Helicase - D. Topoisomerase - E. Uracil
B
71
What are the different types of situations where genetic testing is offered?
- Testing for genetic conditions, e.g. diagnostic, predictive - Testing to clarify familial relationships, e.g. paternity testing - Testing to determine identity, e.g. genetic finger printing
72
What are the different types of genetic tests for genetic conditions? What are they each for?
- Chromosome analysis = tests for abnormalities of chromosome number + structure - Chromosomal microarray analysis = abnormalities of chromosome number + chromosome microdeletions/duplications - Fluorescence in situ hybridization (FISH) = abnormalities of chomosome number + chromosome microdeletions/duplications - Single gene sequencing = single nucleotide changes - Deletion/duplication analysis = whole or partial gene deletions + duplications - Targeted mutation analysis = single nucleotide changes - Multi-gene panels = tests for single nucleotide changes but all others may be picked up by this technique - Whole exome/genome sequencing = tests for single nucleotide changes but all others may be picked up by this technique
73
What is Sanger sequencing?
- Useful for single gene testing, uses PCR to amplify regions of interest. Very accurate and simple to analyse but time consuming.
74
What is next generation sequencing (NGS)?
- Multi-gene panels, whole exome/genome. Can sequence whole genome in one day. Fast + moderately accurate but huge amounts of data to interpret
75
How is the NGS data analysed?
- NGS generates millions of short DNA fragments (reads). Reads are aligned to a reference sequence + can be identified
76
What are the different types of variants?
- Pathogenic variants = these cause the disease, e.g. mutation in exon 12 causes hypertrophic cardiomyopathy - Variant of unknown significance = require more research, e.g. AAA on exon 12, we know GGG is normal but we don’t know enough about this - Normal variation = genetic info. present into 95% of the population, e.g. 95% have GGG on exon 12 - Benign = coding found in 5% or less of the population (rare), but upon research it’s found that it doesn’t cause disease (not pathogenic)
77
What are secondary findings?
Additonal findings concerning a patient that are discovered during investigation, but are beyond aims of original investigation
78
What are targeted panels?
Where we select specific genes to sequence, it means there are fewer variants of uncertain significance
79
What do these types of variant mean? - Duplications - Deletions (out of frame and in frame) - Variants within regulatory sequence - Non-sense - Mis-sense - Splice site - Tri-nucleotide repeat (and anticipation)
- sections repeating, incorrect protein generated - out of frame = bases removed, causes reading frame of gene to change (frame shift) - in frame = one codon removed (one a.a. lost), reading frame unchanged - coding sequence still intact, but gene itself is switched on or off - non-sense = mutation that produced stop codon, usually results in non-functional protein, e.g. Duchenne’s muscular dystrophy - mis-sense = single nucleotide change results in codon that codes for different a.a. - may or may not be pathogenic, e.g. Sickle cell disease (CAG replaced with CTG) - splice site variants = affects accurate removal of intron - codon repeated. Pathogenic if past certain threshold, e.g. Huntington’s disease = \>36 CAG - anticipation = repeats bigger when transmitted to next generation, so earlier symptoms of greater severity
80
What do allelic and locus heterogeneity mean?
- Allelic heterogeneity = lots of different variants in one gene, e.g. cystic fibrosis - Locus heterogeneity = variants in different genes give the same condition, e.g. hypertrophic cardiomyopathy
81
What are the three mechanisms of dominance?
- Loss-of-function variants = only one allele functioning - Gain of function variants = increased gene dosage + increased protein activity - Dominant-negative variants = where protein from variant allele interferes with protein from normal allele
82
The genetic test given depends on the clinical context. Who would be tested in: - diagnostic tests - predictive tests - carrier tests - pre-natal tests - genetic screening?
- patient who has symptoms suggesting particular diagnosis - an at-risk family member = usually for dominant condition - for autosomal recessive + X-linked disorders, couples are tested - performed in pregnancies where there is an increased risk of specific condition affecting fetus - target population, not high risk families
83
How do we get from a sample to something we can analyse cytogenetically?
- sample - add to culture medium - incubate at 37 C - add colcemid to stop mitosis in metaphase (max. no. of cells) - add hypotonic solution - fix cells + spread onto slide by dropping - staining - banding - karyotyping (putting chromosomes into pairs)
84
What are the numerical chromosomal abnormalities?
- trisomy, e.g. 47, XX, +21 (trisomy 21 causes Down syndrome) - monosomy, e.g. 45, X - polyploidy = whole set of chromosomes increased, e.g. 69, XXY
85
How does non-disjunction cause trisomy and monosomy?
Non-disjunction occurs in meiosis. Can occur in M1 (both of chromosomal pair go into one cell, other blank) or in M2 (both chromosomes go into 1 cell, 2 normal and one blank). Therefore, trisomy = 2 + 1 and monosomy = 0 + 1
86
What are the structural chromosomal abnormalities?
- Translocation - Inversion - Duplication - Deletion
87
What is reciprocal translocation?
Portions from different chromosomes are swapped. After drawing a cross, it’s clear to see that 1 child will be normal, one will have balanced portions, and 2 children will have unbalanced portions.
88
What is roberstonian translocation?
This only happens with acrocentric chromosomes (centromere located near end), so p arm = extra small + q arm = extra long. Acrocentric chromosomes are 13, 14, 15, 21 + 22. Example: person will have one 13 and 14 chromsome, and these become stuck together, so they have 45 chromosomes - they are a carrier. If this person reproduces with someone, and they pass on the mixed chromosome along with either 13 or 14, the child would have either two 13’s and three 14’s or three 13’s and two 14’s (an extra chromosome 13 or 14), so will have 47 chromosomes
89
What is unbalanced arrangement?
This is a deletion of part of a chromosome. Deletion on 5p = Cri du chat, deletion on 15q = Prader Willi
90
What is F.I.S.H?
- Fluorescence in situ hybridisation. DNA probes labelled with fluorophores are hybridised to the target DNA (has been split into single strands) - Allows us to ‘count’ chromosomes in interphase nuclei. We can look for submicroscopic deletions. - Also helps us identify the origins of marker chromosomes. Assign colours. Can’t do this with G banding
91
What are microarrays?
Technology that improves the resolution for detection of cytogenetic abnormalities. Assess colour ratios (more patient DNA = red, more control DNA = green).
92
What is the difference between acquired and constitutional abnormalities?
- Acquired = changes occur during lifetime, restricted to malignant tissue, not heritable - Constitutional = affects all cells of body, heritable
93
What are the two main mechanisms by which chromosome abnormalities can cause cancer? What is Knutson's 2-hit hypothesis?
- Fusion genes = breakpoints occur within 2 genes involved, their fusion creates hybrid which gives rise to chimaeric protein - Deregulation = juxtaposition of gene to a regulating gene, altered regulation can result in increased transcription
94
What is metabolism?
Metabolism refers to the sum of the chemical reactions that take place within each cell of a living organism
95
What are the two main metabolic processes?
- Anabolic = synthesise larger molecules from smaller components
- Catabolic = break down larger into smaller
96
What are the 4 main pathways that dietary components are metabolised?
- Biosynthetic (anabolic)
- Fuel storage (anabolic)
- Oxidative processes (catabolic)
- Waste disposal (either)
97
What is the Cori cycle?
It is a form of gluconeogenesis. It is a metabolic pathway where lactate produced by anaerobic glycolysis in the muscles moves to the liver and is converted to glucose, which then returns to the muscles and is metabolised back to lactate
98
How are glucose levels controlled?
Insulin from pancreas. Increase in glucose = increase in insulin. Adipocytes = converted to triglycerides, skeletal muscle = converted to glycogen, liver = converted to glycogen
99
What are the 3 main dietary fuels? Where are they stored?
- Carbohydrates (as glycogen in liver + muscle)
- Protein (muscle)
- Lipids (adipose tissue, fat = most efficient energy store)
100
What is the Basal Metabolic Rate (BMR)? What increases and decreases BMR?
Estimate of energy needed to stay alive at rest, e.g. respiration. Falls with age, male to female, starvation, hypothyroidism + decreased muscle mass (muscle cells require lots of energy to maintain). Increases with body weight, hyperthyroidism, cold environment + fever
101
What happens in starvation?
- Insulin switched off, glycogen stores used up.
- Gluconeogenisis from non-carbohydrate stores, e.g. amino acids and lactate
102
What are the dangers of re-feeding syndrome?
Re-feeding syndrome happens after a period of starvation. Insulin re-distributes phosphate, potassium, magnesium etc. Carbohydrate is used as main fuel again, requires phosphate + thiamine for TPP in Krebs cycle, can become thiamine deficient
103
What are micronutrients? What role do they play within the body?
Micronutrients = trace elements + vitamins. Used as co-factors in metabolism, e.g. TPP (Vitamin E1) required for acetyl co-enzyme A to function in Krebs cycle, gene expression + structural components
104
In multifactorial inheritance, what are the 3 ways of identifying a condition that has a genetic component?
- Family studies
- Twin studies
- Adoption studies
105
What are family studies? What would be true if it was a multifactorial condition?
Compare incidence of disease amongst relatives of an affected individual with general population. In multifactorial condition:
- Risk of condition in relatives greater than risk in general population
- Risk varies directly with degree of genetic relationship
- Risk varies with severity of affected individual's illness
- Risk varies with number of relatives affected
106
What are twin studies? What is the concordance rate?
- Compare genetically identical (monozygotic) twins with non-genetically identical (dizygotic) twins
- Concordance rate = % of twin pairs studies that both have condition. Gives rough figure for hereditability of multifactorial disorder
- If condition has genetic component, expect concordance rate of MZ twins to be higher than DZ twins. There will still be a high risk for separated MZ twins if genetic, as environmental factors redundant
107
What are adoption studies?
Adopted children of parent with multifactorial disease have high risk of developing disease. Normal biological parents or adopting parent with multifactorial disease = low risk
108
What is hereditability?
Proportion of aetiology (factors leading to development of disease) that can be ascribed to genetic factors as opposed to environmental
109
What are the characteristics of multifactorial inheritance?
- Incidence of condition greatest among relatives of most severely affected individuals
- Risk greatest for first degree relatives
- More than one 1 relative affected = increased risk for other relatives
- If condition more common in particular sex, relatives of affected individual of less frequently affected sex = higher risk than relatives of affected individual of more frequently affected sex, e.g. women in high-risk family more at risk than men in general population, even if men affected more generally
110
What is the Liability/Threshold model?
Shows increasing incidence of disease in relatives compared to general population. Closer the relationship = greater shift to right
111
Once you have established that a condition has a genetic component to it, how do you work out what that genetic component is? How does this technique work?
- GWAS (Genome Wide Association Studies)
- Utilises fact that gene can have several variants (alleles) - some variants = pathogenic, some result in functioning gene = polymorphisms, e.g. an SNP (single nucleotide polymorphism) is a substitution of a single nucleotide at a locus
- Compare frequency of markers in sample vs. control - look for markers, e.g. SNP seem more frequently in disease population. Then sequence that area to try to identify gene + particular allele
112
If multifactorial disease is due to the interaction of genes with environmental factors, what are the environmental factors (natal and post-natal)?
Natal: - Drugs, e.g. thalidomide
- Physical agents, e.g. radiation
- Maternal illnesses, e.g. diabetes
- Maternal infections, e.g. rubella
Post-natal: - Obesity
- Hormonal factors, e.g. the pill
- Smoking
- Recreational drug use
113
What is ATP? What is it made of? What happens in ATP hydrolysis?
Major source of energy for cell. Made of adenine, 5-carbon ribose + 3 phosphate groups.
ATP + H20 = ADP + phosphate + H+
Glucose is used by ALL cells to generate ATP during respiration
114
What are the overall products of glycolysis?
1 molecule of glucose produces 2x ATP, 2x NADH + 2x pyruvate.
Especially learn the steps which use and release ATP
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115
What happens in the first step of glycolysis?
Glucose goes to glucose-6-phosphate. Enzyme is hexokinase or glucokinase in liver. ATP to ADP + Pi
116
What happens in the second step of glycolysis?
Isomerise glucose-6-phosphate to fructose-6-phosphate via phosphoglucose isomerase.
117
What happens in the third step of glycolysis? Why is this step important?
Fructose-6-phosphate to fructose-1,6-bisphosphate via phosphofructokinase and ATP to ADP + Pi.
Phosphofructokinase is the rate-determining step
118
How does the concentration of ATP determine the function of phosphofructokinase-1?
- Low ATP conc. Increase in ATP = increase in reaction speed. ATP acts as a substrate, PFK-1 = more reactive
- High ATP conc. Increase in ATP = decrease in reaction speed. Catalytic site saturated. ATP causes allosteric inhibition, PFK-1 = less reactive. AMP opposes allosteric inhibition of ATP, makes PFK-1 more reactive. Citrase is also an allosteric inhibitor of ATP (allosteric binding site = not active site, changes shape of enzyme)
119
What is the fourth step of glycolysis?
Fructose-1,6-bisphosphate converted to dihydroxyacetonephosphate and glyceraldehyde-3-phosphate (type of triose phosphate) via aldolase. Dihydroxyacetonephosphate then converted to glyceraldehyde-3-phosphate via triose phosphate isomerase. We have 2x glyceraldehyde-3-phosphate
120
What is the fifth step of glycolysis?
Oxidation of 2x glyceraldehyde-3-phosphate to 2x 1,3-bisphosphoglycerate via glyceraldehyde-3-phosphate dehydrogenase (2 Pi in and 2 NADH produced). 2x 1,3-bisphosphoglycerate to 2x 3-phosphoglycerate via phosphoglycerate kinase 2 ADP to 2 ATP (x2 so 4 ATP produced)
121
What is the final step of glycolysis?
2x 3-phosphoglycerate to 2x 2-phosphoglycerate via phosphoglyceromutase. 2x 2-phosphoglycerate to 2x phosphoenolpyruvate via enolase and removal of water molecule. 2x phosphoenolpyruvate to 2x pyruvate via pyruvate kinase and 2x ADP to ATP.
122
What is the summary of products and reactants in glycolysis?
123
Draw out glycolysis (remember about enzymes).
124
What happens to pyruvate?
- Aerobic = Krebs cycle
- Anaerobic = lactate
125
What happens in the 'link' reaction?
Pyruvate + CoA + NAD to acetyl CoA + CO2 + NADH + H+ via pyruvate dehydrogenase
126
Draw out the Krebs cycle.
Occurs in mitochondrial matrix. Acronym for reactants: can I keep selling socks for money officer?
127
What are the 3 rate determining steps in the Krebs cycle?
- Ones highlighted in blue.
- Rate limiting step is controlled by isocitrate hydrogenase. Rate can also be determined by levels of ATP, NADH + FADH
- ATP + NADH allosterically inhibit citrate synthase, succinyl CoA competitively inhibits citrate synthase. More citrase = inhibition citrate synthase = slows cycle
- alpha-ketoglutarate inhibited by its products NADH and succinyl Co-A. Also inhibited by GTP + ATP. Activated by Ca2+
128
What is oxidative phosphorylation?
- Electron transport chain, takes place in the inner mitochondrial membrane
- NADH + FADH oxidise to deliver electrons to power proton pumps. Complex I removes electrons from NADH, Complex II removes electrons from FADH. Complexes III, IV and cytochrome C donate these electrons to cytochromes containing iron
- Work via electrochemical gradient, H+ pumped into intermembrane space, build up this gradient. H+ ions then flow down gradient, through ATP synthase to form ATP
- Electrons then transferred to O2 (acts as final electron acceptor) to split to form water
- Total ATP from one molecule of glucose is 34 ATP, one molecule of NADH = 3 ATP, one molecule of FADH = 2 ATP
129
What are fatty acids made up of? Where are they mainly derived from?
- Made up of carboxylic head group with aliphatic tail
- Most are derived from triglycerides and phospholipids, e.g. triglyceride = 3 fatty acids + glycerol
130
How are ingested lipids absorbed into cells?
- Lipids emulsified by bile salts in small intestine, forming micelles
- Lipases degrade triacylglycerols
- Fatty acids + other products taken up by intestinal mucosa + converted into triacylglycerols
- Triacylglyerols converted, with cholesterol + apoproteins, into chylomicrons
- Chylomicrons move through lymphatic system + bloodstream to tissues
- Lipoprotein lipase releases fatty acids + glycerol
- Fatty acids enter cells + oxidised as fuel or reessterifed for storage
131
Before fatty acids are used as energy store, they must be activated in the cytoplasm. How is this done?
132
What happens to the acyl Co-A if it has less than 12 carbons or more than 14 carbons?
- \<12 carbons = can diffuse through membrane to mitochondria
- \>14 carbons = takes through mitochondrial membrane using carnitine shuffle
133
Draw out fatty acid oxidation.
Fatty acid oxidation is the production of ATP from fat consumption + occurs in the mitochondria
134
What happens to the product, acetyl Co-A?
- Krebs cycle
- If there are high rates of fatty acid oxidation, no need for all acetyl Co-A, so converted to ketones
135
Which factors affect ketogenesis (forming ketones)?
- Release of free fatty acids
- Demand of ATP, e.g. more ATP required = more Krebs = less ketones
- Fat oxidation dependent on amount of glucagon (activation) or insulin (inhibition)
- Low conc. of glycerol-3-phosphate in liver = increased ketone production
136
What is ketoacidosis?
- Occurs in insulin-dependent diabetics when dose is inadequate - less insulin = more ketones. This is a problem as ketones = strong acids, so make blood acidic, so impairs ability of haemoglobin to bind to oxygen
137
What are membranes permeable for and against?
- Selectively permeable for gases and small, uncharged polar molecules, e.g. urea and water
- Impermeable to charged particles - need proteins and energy
138
What are channel proteins? What is their role?
- Narrow aqueous pore
- Selective
- Passive
- May be gated
- Usually ions (Na+, K+) or water
139
What are carrier proteins? What are the different types?
- Have specific site that changes shape to release molecule
- Different types:
- Uniport = one substance, one direction
- Symport = two substances, one direction
- Antiport = two substances, two directions
140
What are the 3 main forces that drive substances in/out of cells?
- Chemical (based on concentration differences across membranes, chemical force directly proportional to concentration gradient)
- Electrical (based on distribution of charges across membrane, force depends on size of membrane potential + charge of ion, only charged substances)
- Electrochemical (net direction = sum of electrical + chemical forces, only charged substances)
141
What is passive transport? What are the two types?
- Passive transport doesn't require energy + high to low:
- Simple diffusion
- Facilitated diffusion = uses channel or carrier protein, e.g. GLUT1 to transport glucose
142
What is active transport? What are the two types?
- Active transport requires input of energy, low to high:
- Primary = directly uses source of energy, usually ATP
- Secondary = transport of substance against gradient coupled to transport ion which moves down its gradient (co-transport), uses energy from generation of ions
143
What is cellular signalling?
- Communication between cells takes place via molecules, e.g. hormones
- Signalling molecules bind to receptors = intracellular or cell-surface
- Affect gene expression in nucleus either directly or through signalling cascades
144
How are large molecules transported?
- Endocytosis = into cell
- Exocytosis = out of cell
145
Name a couple of drugs that target membrane receptors.
- Proton pump inhibitors
- Loop diuretics
146
What is homeostasis?
Maintenance of a constant internal environment, e.g. temperature
147
What are the 5 types of cell junction?
- Tight junction = seals neighbouring cells together in an epithelial sheet to prevent leakage of molecules between them
- Adherens junction = joins an actin bundle in one cell to a similar bundle in a neighbouring cell
- Desmosome = joins the intermediate filaments in one cell to those in a neighbour
- Gap junction = allows the passage of small water-soluble ions + molecules
- Hemidesmosome = anchors intermediate filaments in a cell to the basal lamina
148
What are the 4 types of communication?
- Autocrine
- Paracrine
- Endocrine
- Exocrine
149
What is autocrine communication?
- Messenger molecules bind with receptors in the cell where they are produced. Cells 'talk' to themselves, e.g. chemical messengers
150
What is paracrine communication?
- Cells communicating to neighbouring cells a short distance away. Signal diffuses across gap between cells, doesn't enter bloodstream
151
What is endocrine communication?
- Cells communicating to other cells in the body, via secretions in the blood, e.g. thyroid, pancreas
152
What are hormones? What are the 3 types?
Hormones are molecules that act as chemical messengers. There are 3 types:
- Amino-acid derivatives
- Peptide
- Steroid
153
What are amino acid derivatives?
- Synthesised from tyrosine, act in same way as peptide (produce quick reaction), e.g. adrenaline
154
What are peptide hormones?
- Made from short chain amino acids
- Stored in cell and released when needed
- Binds to receptor on membrane
- Produces quick response via a secondary messenger cascade
- Examples: insulin, growth hormone, TSH and ADH
155
What are steroid hormones?
- Synthesised from cholesterol
- Water insoluble + lipid soluble - can cross membranes but requires transport
- Requires transport proteins in blood
- Intracellular receptor target
- Not stored, released once made
- Produce slow response as directly affects DNA + alters transcription/translation, so proteins have to be made
- Examples = testosterone, oestrogen + cortisol
156
What is positive feedback?
Amplification of signal
157
What is negative feedback?
End product in turn reduces stimulus of process, basis for homeostasis
158
What are phospholipids made of?
Glycerol, 2 fatty acids + phosphate group (+ either serine, choline or inositol). Fatty acid tails = hydrophobic, phosphate head = hydrophilic
159
What is the diffusion potential?
Diffusion potential is the potential difference generated across a membrane when an ion diffuses down its concentration gradient. Increase in ion conc. on one side of membrane = increase in tendency for ion to diffuse in one direction, so a larger diffusion potential is required to prevent further net diffusion. Example: Na+ conc. intracellular = 14mmol/l, Na+ conc. extracellular = 142mmol/l. Na+ diffuses to intracellular, so diffusion potential = +61.87mV (intracellular becomes depolarised). Number generated from an equation.
160
What is a G-Protein Coupled Receptor (GPCR)? What are the 5 parts?
- Large family of cell surface receptors that respond to variety of signals. Binding of a signalling molecule results in G protein activation, which in turn triggers the production of any numbers of second messengers
- 50 % of all drugs inhibit or mimic various GPCRs
- 5 parts:
- Receptor - gives primary specificity
- Three G-proteins - alpha, beta and gamma
- Enzyme to modulate second messenger
161
What are the prominant electrolytes in intracellular and extracellular fluid? Can all fluid losses be measured?
- ICF = potassium
- ECF = sodium, chloride, bicarbonate + Ca2+ especially in heart and muscles
Fluid losses either sensible (measured, e.g. urine) or insensible (cannot be measured, e.g. evaporation)
162
What is extracellular fluid comprised of?
Extravascular fluid and intravascular fluid (plasma = circulates as extracellular component of blood). Extravascular fluid comprised of interstitial fluid (surrounds cells but doesn't circulate) and transcellular (makes up CSF, digestive juices, mucus etc.)
163
60% of the body's weight is water. How is this water spread?
Total body water = 42L (60% of 70kg). ICF = 28L, ECF = 14L. Intravascular fluid = 3L, interstitial = 11L
164
What happens if there is change in solute content of a compartment?
There is a shift in water across a cell membrane. Fluid compartments in body are in osmotic equilibrium, with the solutes in the ECF and ICF creating an osmotic gradient across cell membranes
165
What do these terms mean?
- Osmosis
- Osmolality
- Osmolarity
- Osmotic pressure
- Oncotic pressure
- Hydrostatic pressure?
- Net movement of solvent molecules through semipermeable to higher solute conc. (lower water conc.)
- Measure number of dissolved particles per L of fluid, higher osmolality = greater amount of substance dissolved
- Measure number of dissolved particles per kg of fluid
- Pressure applied for a solution, by a pure solvent, required to prevent inward osmosis, through a semipermeable membrane
- Form of osmotic pressure exerted by protein that tends to pull fluid into its solution = water moves from interstitial fluid into plasma
- Pressure difference between capillary blood (plasma) + interstitial fluid = water and solutes move from plasma into interstitial fluid
166
What are the sources of water gain and loss? What are the regulating hormones?
- Water gain = drink, diet and IV fluid
- Water loss = kidneys + insensible losses: sweat, breath, vomiting and faeces
- Regulating hormones = ADH, aldosterone + atrial natriuretic peptide (ANP)
167
What happens when water is lost from the ECF?
Increase in osmolarity of ECF.
- Change detected by osmoreceptors in hypothalamus
- Release of ADH from posterior pituitary
- ADH increases water reabsorption in collecting ducts of kidneys, dilutes solute, ECF water back to normal
168
What are the causes and effects of dehydration?
- Causes: water deprivation, vomiting, diarrhoea, burns, heavy sweating, diabetes insipidus (too little ADH, loads of urine), diabetes mellitus + drugs
- Consequences: thirst, inelastic skin (won't go back down after pinching), sunken eyes, raised haemocrit (viscosity of blood), weight loss, confusion + hypertension
169
What are the causes and consequences of water excess?
- Causes: High intake/decreased loss of water, excess ADH
- Consequences: Hyponatraemia (low sodium levels), cerebral over-perfusion (due to high blood volume and thus pressure, causes headaches, confusion + convulsions)
170
What happens when there is excess water in the ECF?
Decreases ECF osmolarity. Osmoreceptors in hypothalamus detect this and inhibit the release of ADH from the posterior pituitary. Increased urine volume
171
What is serous effusion? What is an oedema? What are the different types of oedema?
- Serous effusion = excess water in body cavity (fluid-filled space that holds and protects internal organs). Example = pleural effusion, results from disruption of balance between hydrostatic and oncotic forces in visceral and parietal pleural vessels
- Oedema = excess water in intracellular tissue space. Types:
- Inflammatory
- Venous
- Lymphatic
- Hypoalbuminaemia
172
What is an inflammatory oedema?
Proteins leak out due to increased vascular permeability. They bring water, so dilutes toxins.
173
What is a venous oedema?
Due to increased venous pressure or venous obstruction from a thrombus
174
What is a lymphatic oedema?
Blockage in lymphatic system, prevents fluid from draining
175
What is a hypoalbuminaemic oedema?
Lower oncotic pressure. Lower albumin levels
176
What do these terms mean:
- Hypernaetraemia
- Hyponaetraemia
- Hyperkalaemia
- Hypokalaemia
- Hypercalcemia
- Hypocalcemia?
- High sodium
- Low sodium
- High potassium
- Low potassium
- High calcium
- Low calcium
177
This enzyme causes the double helix to unzip:
DNA polymerase
Helicase
Topoisomerase
Amylase
Glycosylase
Helicase
178
This enzyme unwinds supercoiled DNA:
Glycosylase
Topoisomerase
DNA polymerase
Helicase
Amylase
Topoisomerase
179
Specific amino acids bind to:
Transfer RNA
Double strand DNA
Double stranded RNA
Single strand DNA
Messenger RNA
Transfer RNA
180
The process in which mRNA is used to specify the amino acids required for protein formation is known as:
Telophase
Transference
Translocation
Transcription
Translation
Translation
181
Concerning ribosomes, which of the following is false?
They have a large and a small subunit
They are assembled outside the nucleus
They consist of rRNA and proteins
They are assembled inside the nucleus
They can attach to the rough endoplasmic reticulum
They are assembled outside the nucleus
182
A protein with a number of sub units held together by cross links has this type of structure:
Quaternary structure
None of the above
Secondary structure
Primary structure
Tertiary structure
Quaternary structure
183
Which of the following is defined as ‘A weak attractive interaction between two atoms due fluctuating electrical charges:
Hydrophobic force
Disulphide bond
None of the above
Hydrogen bond
Van der Waals force
Van der Waals force
184
Alpha helixes and beta sheets are examples of protein…
Secondary structure
Primary structure
Tertiary structure
None of the above
Quaternary structure
Secondary structure
185
Sickle cell anaemia (HbS) is caused by
An autosomal dominant inherited condition substituting an amino acid in the beta globin chain
A random genetic mutation in the beta globin chain
An autosomal recessive inherited condition substituting an amino acid in the beta globin chain
An autosomal dominant inherited condition substituting an amino acid in the alpha globin chain
An autosomal recessive inherited condition substituting an amino acid in the alpha globin chain
An autosomal recessive inherited condition substituting an amino acid in the beta globin chain
186
In hypoxia, the abnormal HbS…
dimerises
Stays the same
deforms
Flips from levo- to dextro-isomer
Polymerises
Polymerises
187
The HbS structural change causes sickling by…
Binding to the cytoskeleton
Altering nuclear transcription of cytoskeletal proteins
Pulling on the cell membrane
Dehydrating the cell by osmotic action
Changing the charge across the cell membrane
Binding to the cytoskeleton
188
Capillary occlusion is now thought to occur by….
Sickle cells binding with platelets
The sickle cells causing capillary spasm
Endothelial damage causing multicellular (platelets, white cells) aggregates which occlude the capillary
Sickle cells binding together to form a ‘plug’
Endothelial damage causing multicellular (platelets, white cells) aggregates which occlude the capillary
189
An acute pain crisis is typically caused by capillary occlusion in the …
Bone
Brain
Spleen
Cardiac muscle
Skin
Bone
190
Sickle cell disease can be treated with hydroxyurea because it…
Increases the synthesis of HbF (foetal Hb)
Prevents the transcription of mutated DNA
Increases the synthesis of normal HbA
Interferes with the translation of mutant RNA
Reverses the hydrophobic site caused by the point mutation
Increases the synthesis of HbF (foetal Hb)
191
What is a high energy bond?
- A. A chemical bond that releases as much or more energy when broken than that released by ATP hydrolysis
- B. A chemical bond that requires as much or more energy to make as the phosphorylation of ADP to ATP
- C. A chemical bond that requires high amounts of energy to break
- D. A chemical bond that requires high amounts of energy to make
- E. A phosphate bond
A
192
Which enzyme catalysts the rate-limiting step of the Krebs' cycle?
- A. Alpha-ketoglutarate dehydrogenase
- B. Citrate synthase
- C. Fumarase
- D. Isocitrate dehydrogenase
- E. Succinate dehydrogenase
D
193
What is the product of fatty acid beta-oxidation?
Acyl-CoA
194
Which of the following blood measurements would not be associated with ketoacidosis?
- A. High glucose concentration
- B. High H+ concentration
- C. High HCO3- concentration
- D. Low pCO2
- E. Low pH
C. Glucose high due to lack of insulin, ketones are acidic therefore H+ ions are high and pH is low. pCO2 = low as body responds to acidosis by increasing breathing to get rid of carbon dioxide
195
Which of these is not an endocrine organ?
- A. Adrenal gland
- B. Hypothalamus
- C. Pancreas
- D. Spleen
- E. Thyroid
D
196
Which of these is a feature of steroid hormones?
- A. Has a quick onset of action
- B. Hormone is pre-made and stored in cell ready to be released
- C. It is made from amino acids
- D. It is made from cholesterol
D
197
Which of the following is an anabolic (not catabolic) reaction?
- A. Beta-oxidation
- B. Glycogenolysis
- C. Glycogen synthesis
- D. Glycolysis
- E. Vesico-graphic reflex
C. Anabolic = synthesise larger molecules from smaller components
198
The average amount of protein we require each day is:
- A. Proportional to magnesium intake
- B. 0.1g/kg body mass
- C. 0.8g/kg body mass
- D. 4g
- E. 400g
C
199
What is the body's normal response to an increase in ECF osmolality?
- A. Diuresis
- B. Inhibition of the thirst centre
- C. Movement of water from the ECF to ICF
- D. Release of ADH from the hypothalamus
- E. Release of ADH from the posterior pituitary
E
200
Which of the following is true?
- A. ACE is produced in the liver
- B. Aldosterone causes sodium excretion and potassium reabsorption in the renal tubules
- C. Aldosterone is released from the renal medulla
- D. Angiotensin II causes arteriolar vasodilation
- E. Renin is released secondary to a decrease in renal perfusion
E
201
Which of these is not a feature of active transport?
- A. An example of primary transport is Na+/K+ ATPase
- B. An example of secondary transport is the Na+/glucose co-transport for proteins
- C. In secondary transport energy is generated by the active transport of an ion
- D. Requires direct energy input
- E. Substances move along a concentration gradient
E
202
What is eugenics? What are the two types?
Eugenics is essentially selective breeding. Positive = group you want to breed extensively, negative = group you want to stop breeding
203
What is genetic counselling?
Process by which patients or relatives at risk of a disorder that may be hereditary are advised of consequences.
204
What is the difference between directive and non-directive genetic counselling?
- Directive genetic counselling = family may not understand consequences, family may expect to be directed, doctors know best, duty to reduce disease frequency
- Non-directive genetic counselling = family may have extensive personal experience, decisions on reproduction may be personal, directive advice may be counterprodcutive
205
What is the difference between a screening and a diagnostic test?
- Screening test = process of identifying people with increased chance of a condition. Someone who is screened positive may not have the condition
- Diagnostic test = confirms whether condition is present or not
206
What is non-invasive prenatal testing?
Fragments of cell free foetal DNA are taken from the placenta and analysed for genetic abnormalities, e.g. trisomy-21
207
What are some invasive forms of prenatal testing?
- Chorionic villus sampling = uses needle or catheter to biopsy placental cells
- Amniocentesis = sample of amniotic fluid is removed
208
What are some concerns about eugenics?
- Routinisation of testing, i.e. not fully informed consent
- Society not valuing disabled children + adults
- Disapproval by society of continuing a pregnancy after screening
209
What is pre-implantation genetic diagnosis (PGD)? How is it regulated?
Can be used by people who have a serious inherited disease in their family. Involves checking genes of embryos, so IVF is needed. If fine, embryos placed back in womb.
- Done in licensed centre for IVF + PGD
- Has to be risk of serious condition \>10%
- Female partners under 40 years
- Non-smokers
- No living unaffected child
210
What is mitochondrial replacement therapy?
Form of germline (sex cell) modification. It is the replacement of mitochondria in one or more cells to prevent disease. Mitochondria have their own DNA + mitochondrial disease can only be passed on by the mother.
211
What are enzymes? What are the two types of enzyme?
- Catalysts = provide alternative reaction pathway with lower Ea
- Enable reactions to occur that otherwise would not be able occur at body temperature + conditions
- Bind to reactants + convert them to products, release products + return to original form
- Speed up reactions + provide a way to regulate rate of reaction
- Can alter concentration of substrates, products, inhibitors or activators
- Rate of reaction affected by temperature, surface area, pressure/concentration, presence of enzymes
Two types:
- Isoenzymes: enzymes that have different strcuture + sequence but catalyse same reaction
- Coenzymes: cannot catalyse a reaction but help enzymes to do so - bind with enzyme protein molecules to form active enzymes
212
Autosomal recessive
213
Autosomal dominant
214
Sex-linked
215
What are the stages 1-6?
1) Anaphase
2) Telophase
3) Prophase
4) Metaphase
5) Cytokinesis
6) Interphase
216
In which cell are you most likely to find a perinuclear hoff?
a) basophil
b) eosinophil
c) plasma cell
d) T helper cell
e) megakaryocyte
C
217
What is the Na+/K+ ATPase pump an example of?
a) primary active transport
b) secondary active transport
c) tertiary active transport
d) facilitated diffusion
e) simple diffusion
A
218
Which enzyme unwinds the DNA double helix in replication, relieving supercoils?
a) DNA helicase
b) DNA topoisomerase
c) DNA ligase
d) Okazaki fragments
e) DNA primase
B
219
What type of protein structure would zinc fingers, helix-turn-helix and beta-alpha-beta be classed as?
a) primary
b) secondary
c) tertiary
d) quaternary
e) super-secondary
E
220
In a 70kg male, how many litres of total body water distribution are accounted for by interstitial fluid?
a) 11L
b) 3L
c) 28L
d) 14L
e) 42L
A
221
What is an example of type 4 collagen?
a) placenta
b) cartilage
c) bone, skin, teeth
d) basement membranes
e) arteries, liver, kidneys, spleen, uterus
D
222
How much energy does alcohol provide?
a) 9kcal/g
b) 4kcal/g
c) 7kcal/g
d) 3kcal/g
e) 5kcal/g
C
223
Which of these is not a way ATP is produced?
a) Krebs cycle
b) Glycolysis
c) Link reaction
d) Oxidative phosphorylation
e) Substrate level phosphorylation
C
224
What is a cause of hyponatraemia?
a) hyperparathyroidism
b) water deficit
c) acidosis
d) renal failure
e) excess water due to IV fluids, diuretics
E
225
What is the function of gap junctions?
a) binds cells together to prevent leakage of molecules
b) conduct electrical signals
c) attaches cells via intermediate filaments
d) regulates what goes into and out of the cell
e) joins an actin bundle in one cell to a similar bundle on a neighbouring cell
B
226
The image is a sample obtained from a patient who died after an episode of chest pain. Which of the following statements is true?
- A. This is cardiac muscle
- B. This is smooth muscle
- C. The nuclei are in register
- D. The myofibrils are in register
- E. It is from the myometrium
D
227
Which of the following is not a component of cell membranes or the receptors associated with them?
- A. Cholesterol
- B. Dihydrogen oxide
- C. Glycolipids
- D. Lipoproteins
- E. Phospholipids
E
228
Which enzymes catalyses this part of the aerobic glycolysis pathway?
- A. Aldolase
- B. Phosphfructokinase
- C. Phosphglucose isomerase
- D. Phosphoglycerate kinase
- E. Triose phosphate isomerase
D
229
Which of the following statements about this epithelium is true?
- A. It can stretch
- B. It is keratinized
- C. It lacks a basement membrane
- D. It lines the trachea
- E. It secretes mucus
A
230
Which of the following enzymes is not involved in either aerobic or anaerobic glycolysis?
- A. Aldolase
- B. ATPase
- C. Hexokinase
- D. Phosphoglucose isomerase
- E. Triose phosphate isomerase
B
231
A 45-year-old man is trying to lose weight. How many kcal are there in one unit of of alcohol?
- A. 28kcal
- B. 40kcal
- C. 56kcal
- D. 72kcal
- E. 90kcal
C
232
Which of the following factors will lower the basal metabolic rate of an individual?
- A. Caffeine
- B. Dieting
- C. Fever
- D. Obesity
- E. Hyperthyroidism
B
233
Which of the following statements concerning oxidative phosphorylation is true?
- A. ATP synthase transports protons out of the mitochondrial matrix
- B. Cytochrome C oxidase complex transports protons into the mitochondrial matrix
- C. It occurs in the mitochondrial matrix
- D. The energy needed to phosphorylate ADP comes from the transport of electrons across a mitochondrial membrane
- E. The mitochondrial membrane is ion-permeable
None
234
A 60-year-old woman has a lack of cortisol. Which of the following statements concerning steroid hormones is true?
- A. They act on plasma membrane receptors
- B. They are formed from tyrosine
- C. They are stored in secretory granules
- D. They are transported in plasma bound to proteins
- E. They are water soluble
D
235
Which of the following statements concerning early embryonic life is true?
- A. During implantation the morula penetrates the endometrial stroma
- B. Epiblasts in a three-week embryo will become ectoderm
- C. Implantation occurs 3-4 days following fertilization
- D. Paraxial plate mesodermal cells will give rise to the circulatory system
- E. The midgut is in continuity with the amniotic cavity
B
236
What proportion of body water is found within plasma?
- A. 7%
- B. 26%
- C. 33%
- D. 66%
- E. 100%
A
237
Which of the following substances is transported into the cells by facilitated diffusion?
- A. Cholesterol
- B. Ethanol
- C. Glucose
- D. Oxygen
- E. Potassium ions
C
238
In a slim adult male standing in the anatomical position, which of the following structures lies most distal from the umbilicus?
- A. Apex of the heart
- B. Glans penis
- C. Left patella
- D. Right acetabulum
- E. Urinary bladder
C
239
A genetic disease is present within multiple generations of a family. With each generation, the disease presents earlier and is more severe. What is this an example of?
- A. Anticipation
- B. Gonadal mosaicism
- C. Haploinsufficiency
- D. Penetrance
- E. Variable expression
A
240
In Evidence Based Medicine, the PICO principle is used to frame and answer clinical questions. What does the C in PICO stand for?
- A. Cochrane
- B. Computer
- C. Consent
- D. Control
- E. Critical
D
241
Which of these phases of glycolysis generates ATP from ADP?
- A. Glucose - Glucose-6-phosphate
- B. 2-phopshoglycerate - phosphoenolpyruvate
- C. Glyceraldehyde-3-phopshate - 1,3-bisphosphoglycerate
- D. Fructose-6-phosphate - Fructose-1,6-bisphosphate
- E. Phosphoenolpyruvate - Pyruvate
E (D uses it, phospho also lost which indicates that the phosphate group has gone somewhere)
242
Where in the cell does the Krebs cycle occur?
- A. Cytoplasm
- B. Mitochondrial matrix
- C. Mitochondrial intramembranous space
- D. Mitochondrial inner membrane
- E. Mitochondrial outer membrane
B
243
Which cell junction best describes desmosomes?
- A. Allows for the flow of ions between cells
- B. Attaches cells to the extracellular matrix
- C. Connects intermediate filaments of adjacent cells
- D. Form a complete barrier, preventing movement of substances between cells
- E. Connects microtubules of adjacent cells
C
244
In what week does the embryo undergo gastrulation?
- A. Week 1
- B. Week 2
- C. Week 3
- D. Week 4
- E. Week 5
C (week 3, embryo becomes trilaminar disc)
245
Which of the following molecules is not a ketone?
- A. Acyl-CoA
- B. Acetoacetate
- C. Beta-hydroxybutyrate
- D. Acetone
A
246
During cell division, which phase best describes anaphase?
- A. Nuclear membranes break down
- B. Chromatids separate and are pulled to opposite poles of the cell
- C. Chromosomes align on the metaphase plate
- D. Nuclear membrane reforms
- E. Chromatids attach to microtubules
B
247
Edwards Syndrome is best described as:
- A. Nondisjunction
- B. Nonsense mutation
- C. Multifactorial
- D. Mosaicism
- E. Autosomal dominant
A (trisomy-18)
248
Which of the following might contain type 2 collagen?
- A. Bone
- B. Cartilage
- C. Spleen
- D. Basement membranes
- E. Placenta
B (answers in order 1-5)
249
A patient's blood pH is 7.49, they appear to be breathing normally but have been vomiting excessively, which statement best describes this condition?
- A. Respiratory acidosis
- B. Respiratory alkalosis
- C. Metabolic acidosis
- D. Metabolic alkalosis
- E. Mixed respiratory and metabolic acidosis
D. Blood is alkalotic, so what has caused it? Breathing normally, so cannot be respiratory
250
Total body water (TBW) is distributed into three compartments (Intracellular/interstitial/intravascular). How is the TBW distributed byvolume? (Assume healthy 70 Kg man)
A. 24L/14L/3L
B. 42L/11L/3L
C. 28L/11L/3L
D. 24L/11L/3L
E. 28L/14L/3L
C
251
Osmolarity can be calculated from blood results. Which of the following IS a factor in calculated osmolarity?
A. Magnesium
B. Chloride
C. Urea
D. Phosphate
E. Bicarbonate
C. 2(Na+) + 2(K+) + Glucose + Urea
252
Which of the following is an example of insensible fluid loss?
A. Diarrhoea
B. Fluid in abdominal surgical drain
C. Vomiting
D. Urine
E. Water from respiration
E
253
You examine a patient and note he has lower leg pitting oedema. You also note that his blood albumin level is low. Which statement correctly describes the relationship between albumin and oedema?
A. A low albumin causes an increase in oncotic pressure and water diffuses out of the blood into interstitial fluid
B. A low albumin causes a decrease in oncotic pressure and water diffuses from the blood into the interstitial fluid
C. A low albumin causes a decrease in oncotic pressure and water diffuses from the interstitial fluid into the blood
D. A low albumin causes an increase in oncotic pressure and water diffuses from the interstitial fluid into the blood
E. Low albumin is not related to oedema
B
254
What is the site of synthesis of ADH (antidiuretic hormone)?
A. Juxtaglomerular cells
B. Distal tubules and collecting ducts of nephron
C. Adrenal cortex
D. Hypothalamus
E. Posterior pituitary
F. Anterior pituitary
D
255
What is the site of synthesis of aldosterone?
A. Adrenal cortex
B. Juxtaglomerular cells
C. Distal tubules and collecting ducts of nephron
D. Hypothalamus
E. Anterior pituitary
F. Posterior pituitary
A
256
What is the principal site of renin production?
A. Adrenal cortex
B. Distal tubules and collecting ducts of nephron
C. Posterior pituitary
D. Anterior pituitary
E. Juxtaglomerular cells
F. Hypothalamus
E
257
Which of the following CORRECTLY describes the action of renin?
A. Angiotensinogen to angiotensin 2
B. Angiotensinogen to angiotensin 1
C. None of the above
D. Angiotensin 1 to angiotensin 2
E. Angiotensin 2 to angiotensin 1
B
258
A healthy student drinks 2 litres of water in 5 mins. Which of the following correctly describes the physiological response?
A. Osmolality falls \> ADH secretion stops \> increased urine volume
B. None of the above
C. Osmolality rises \> ADH secretion increase \> increased urine volume
D. Osmolality falls \> ADH secretion increase \> increased urine volume
E. Osmolality rises \> ADH secretion stops \> increased urine volume
A
259
A GP suspects that his young patient has cranial diabetes insipidus. This is a disorder in which the pituitary gland fails to release ADH when stimulated to do so. She is referred for a water deprivation test during which she is nil by mouth ?
Normal serum osmolality275-295mOsm/Kg; urine osmolality varies from very dilute (50) to very concentrated (1400mOsm/Kg)
If the patient does have diabetes insipidus and is not producing any ADH which of the following is MOST LIKELY to show her blood and urine osmolality after 3 hours of water deprivation?
A. Blood 300/urine 100
B. Blood 220/urine 100
C. Blood 300/urine 1200
D. She won’t produce urine
E. Blood 220/urine 1200
A. During the water deprivation test the body should detect an increased serum osmolality (300) and produce ADH in order to promote water retention. As she is unable to produce ADH she will produce dilute urine (low osmolality, 100) instead of concentrated urine.
260
Explain how the renin-angiotensin-aldosterone system works.
- When renal blood flow is reduced, juxtaglomerular cells convert prorenin to renin
- Plasma renin then converts angiotensin to angiotensin I
- This is converted to angiotensin II by ACE (angiotensin-converting enzyme)
- Angiotensin II increases blood pressure via vasoconstriction + stimulates secretion of aldosterone from the adrenal cortex
- Aldosterone causes renal tubules to increase the reabsorption of sodium and water into the blood (and excretion of potassium)
- This increases the volume of ECF + increases blood pressure
261
What is most likely represented by the x axis on the graph?
- A. Renin
- B. Sodium concentration
- C. Plasma osmolality
- D. Blood pressure
- E. Potassium concentration
C
262
A diagramatic representation of the relative amounts of intracellular actions and anions is shown. Which of the following are most likely represented by the letters Y and Z?
- A. Na and K
- B. K and lactate
- C. Na and lactate
- D. Na and HCO3
- E. K and HCO3
E
263
Picture of pedigree charts.
264
Picture of cell.
265
What are the different parts of mitochondria? What are their functions?
266
Table of cell structures and their function.
267
What is lipofuscin, lipid and glycogen?
268
What does the phospholipid bilayer contain? What is its function?
269
What are the three modes of secretion?
270
Diagram of RAAS.
271
What is the karytoype?
Number + visual appearance of the chromosomes in the nuclei of an organism or species
272
What is Mendel's second law (law of independent assortment)?
273
What are some genetic, multifactorial and environmental diseases?
274
What is an acid? What is a base? How about strong and weak acids/bases? What is a buffer?
275
What is the Henderson-Hasselbach equation? What are some body buffer systems?
276
What is a reactive oxygen species? What is the Fenton reaction? What is the Haber-Weiss reaction?
277
What you need to know from IMMS histology.
