1
Q
Haemotoxylin and Eosin summary
A
-most commonly used dye combination
-stains acids blue (eg. nuclei)
-stains alkali pink (eg. cytoplasm)
2
Q
PAS
A
-Stains sugars bright purple, like magenta
3
Q
Van Gieson
A
-Stains elastin brown
4
Q
Why do metabolically active cells tend to be larger?
A
-They have more nucleoli
-there is a higher demand for protein synthesis
-Nucelolus is site of DNA transcription
5
Q
what happens at the nucleolus?
A
-site of ribosomal RNA formation
6
Q
RER
A
-site of protein synthesis, converting mRNA to protein
7
Q
SER
A
-Site of lipid synthesis
8
Q
Golgi apparatus
A
-processes macromolecules that have been synthesised in the endoplasmic reticulum
9
Q
Can you see the golgi apparatus under a light microscope?
A
-not typically, but very present in plasma cells
10
Q
Cis golgi network
A
-faces the nucleus
-receives transport vesicles from SER and phosphorylates some proteins
11
Q
medial golgi
A
-central part
-forms complex oligosaccharides by adding sugars to lipids and peptides
12
Q
trans golgi
A
-outer part
-sorts macromolecules into vesicles
-proteolysis (breakdown of proteins into amino acids)
13
Q
what are the several types of vesicles
A
-cell surface derived vesicles
-golgi derived transport vesicles
-ER derived transport vesicles
-lysosomes
-peroxisomes
14
Q
Lysosomes
A
-contain acid hydrolases that degrade proteins, that work best in low ph conditions
-has a proton pump on membrane which creates low ph for optimum function
15
Q
peroxisomes
A
-they contain enzymes which oxidise long-chain fatty acids
16
Q
What is the cytoskeleton composed of
A
-microfilaments, microtubules and intermediate filaments
17
Q
microfilaments
A
-made of actin, roughly 5nm
-forms a bracing mesh on the inner surface of the cell membrane
-does this by globular actin polymerising to form filamentous actin
18
Q
microtubules
A
-made of tubulin, roughly 25 nm
-made of alpha and beta tubulin which arrange in groups of 13 to form hollow tubes
19
Q
in what cells do we find microtubules
A
all cells apart from erythrocytes
20
Q
intermediate filaments
A
-10nm
-anchor to transmembrane proteins and spread tensile forces through tissues
21
Q
how do lipids appear on a microscope
A
-as empty space, as they dissolve during processing
22
Q
what does interstitial fluid in tissues contain
A
-water, salts in solution, peptides and proteins
23
Q
what does extracellular material in tissues contain
A
fibrillar proteins, inorganic salts as solids, glycosaminoglycogen jelly (
24
Q
chromosome structure
A
-p arm (short, petite)
-q arm (long)
-centromere
25
robertsonian chromosomes
-lack a short arm
-chromosomes 13,14,15,21,22
-likely to be involved in translocation
26
what can we describe genes as?
-dosage sensitive
-an imbalance caused by deletion or duplication can result in disease
27
what is translocation
where sections move between chromosomes
28
what are the different genomes in the human body?
-germline, somatic, mitochondrial
29
germline genome
-genome present in the sperm/egg, is heritable
30
somatic genome
-the genome present in every other tissue, not heritable
31
mitochondrial genome
-found only within the mitochondria
-is heritable, but only maternal mitochondria is, as sperm are too small to contain mitochondria
32
what is mutagenesis?
-mutagen
-alteration to genomic code by exposure to a substance
-can be in womb/post natal
33
what is teratogenesis?
-teratogen
-a damaging effect on an embryonic/fetal development by an exposure to a substance
34
monogenic/mendelian
when a mutation in a single gene is sufficient to cause disease
35
malformation in genetic disease
-intrinsic issue with development of an organ/tissue, is typically genetic
36
deformation in genetic disease
-extrinsic factors impact development of an organ, not typically genetic
37
Summary of autosomal dominant inheritance
-parents with disease can produce healthy children
-males and females affected in equal proportions and there is transmission between sexes
-disease occurs in heterozygous state
38
what is penetrance
-the percentage of individuals who have a variant in a certain gene that will develop a medical condition because of it
39
recurrence risk in autosomal dominant inheritance
-an affected person has a 1 in 2 chance of having an affected child
40
what is variable expressibility
-people who have the same gene variant can have a wide range of symptoms
41
what is a de novo mutation
the disease causing the variant occurs in either the sperm or the egg
42
Summary of autosomal recessive inheritance
-healthy siblings have a 2/3 chance of being carriers themselves
-more common in consanguineous unions
-occurs in homozygous state
43
x-linked recessive
-females are unaffected carriers, typically only males are affected
44
x-linked dominant
-both males and females are affected
45
What does it mean if there is male to male transmission in a family?
the condition is not x-linked
46
What is lyonisation?
-females randomly inactivate one of their x-chromosomes to prevent their being twice as many x linked products as males
-this can cause problems, if the healthy x chromosome is inactivated, then the mutated x chromosome in a tissue can cause disease
47
what is non mendelian?
- a disease cannot be explained by a dominant, recessive or x linked mode of inheritance
48
What is multifactorial inheritance?
-a treat/disease formed by many genes working together, often being impacted by environmental factors also
-recurrence risk is higher when relatives also have this condition
49
what is an exmaple of a disease inherited by multifactorial inheritance?
-spina bifida, cleft lip/palate
50
what is meant by liability?
-every person has liability related to the genetic and environmental combined risk of them developing a disease
-after a certain threshold, the disease will occur
51
somatic mosaicism summary
-certain tissues have a genetic variant and others don't
-is for autosomal dominant genes
-occurs when one of the cells from the zygote mutates during early development, causing all cells and tissues derived from this cell to have the disease
52
why does somatic mosaicism happen?
-happens by chance
-likelyhood of occurence increases with certain risk factors, such as smoking or exposure to the sun
53
what is homoplasmy and heteroplasmy
homoplasmy - all mitochondria in cell have same genetic code
heteroplasmy - certain proportion of mitochondria in a cell has a genetic variant (causes disease at certain thresholds)
54
mitochondrial disease summary
-all offspring of an affected/carrier female are at risk
-males cannot have an affected child
-all daughters of affected/carrier female at risk of transmitting the condition
55
imprinting disorders summary
-for an autosomal gene, one copy is switched off (either maternal/paternal)
-genes are imprinted when carbohydrates attach to DNA
-If one gene is imprinted, then another gets deleted, there is no functioning gene, leading to disease
-disease can be caused when imprinting is altered
56
What are single nucleotide variants?
-change of one nucleotide to another
-are either synonymous or non synonymous
57
non-synonymous
-protein is altered
-either missense (one amino acid is altered)
-or loss of function (frameshift, nonsense, or splice site variant)
58
what can happen when an amino acid is altered?
-may change size or solubility or amino acid
-which can affect folding, which affects protein function
59
out of frame shift
-caused by insertion/deletion of nucleotides in a non-multiple of 3
-leads to formation of premature STOP codon and nonsense mediated decay
60
Splice site variant
-alters splice acceptor site
-this can lead to an intron being present in mature mRNA and translated into a protein or introduces a premature stop codon, leading to nonsense mediated decay
61
trinucleotide repeat expansion
-when a sequence of 3 nucleotides is abnormally repeated
-forms an elongated toxic mRNA which resists degradation
-eg huntingtons disease
62
copy number variants
-deletion/duplication of segment of chromosome, which can potentially affect hundreds of genes
-deletions are more harmful than duplications
63
comparative genomic hybridisation
-can detect copy number variants involving single exons
-compares DNA from patients to a control to see if there is any excess/losses in DNA
64
exome sequencing
-can miss non coding variants and trinucleotide repeates
-tests exons plus some splice sites
65
genome sequencing
-tests entire genome
-can detect CNVs
66
What suggests a variant is pathogenic?
-variation if found in several people in the family who have the disease
-the single nucleotide variant is absent from healthy populations
-computational tools can predict damaging effect
67
what suggests a variant is benign?
-the variant is found in an unaffected parent
-variant is commonly found in healthy populations
-computational tools predict variant has no effect on gene function
68
what is the importance of trio testing?
-testing mother, father and affected offspring
-can identify de novo variants
69
what are the types of chromosome abnormality?
numerical and structural
70
what is eugenics?
The selection of traits using selective breeding or other genetic means to result in more sought after offspring
71
What is genetic counselling?
Where patients or relatives at risk of genetic disorders are advised of the outcomes of reproduction and the consequences of the disorder
72
What is directive genetic counselling?
Patients being told what to do as 'the doctor knows best', family may not know all the consequences
73
What is non-directive genetic counselling?
Let the family make the choice, give them all the consequences and come to an informed outcome
74
When do we screen for down syndrome in the UK?
When the maternal age is greater than 35
75
What is the risk of miscarriage from invasive tests?
roughly 1 %
76
What is NIPT?
A prenatal screening test to identify genetic disorders
77
Why is NIPT preferable?
More accurate and less invasive, so fewer late termination occur
78
What is PGD?
Pre-implantation Genetic Diagnosis
79
What do you need to be eligible with PGD?
Risk of a serious condition is needed, with the risk of conceiving a pregnancy with this condition greater than 10%
No living unaffected child
Non smokers
Couple seen for genetic counselling
Maternal age <40
80
What does the ACMG criteria determine?
Formal scoring system to decide if a gene variant is pathogenic
81
What is anticipation in genetics and why does it occur?
When the genetic disorder affects successive generations earlier or more severely, usually due to expansion of unstable triplet repeat sequences
82
What is gonadal mosaicism?
Where more than one set of genetic information is found specifically within gamete cells
83
What are the 3 domains of public health?
health protection, health improvement/promotion, improving health services
84
health protection examples
infectious disease, chemicals, radiation, emergency response
85
health improvement examples
lifestyles, inequalities, education, housing, employment
86
improving health services examples
clinical effectiveness, service planning, efficiency
87
what is epithelia?
Epithelia is comprised of a cohesive sheet of cells, with one or more layers, resting on a basement membrane.
88
What do epithelia form barriers for?
protection, absorption, secretion
89
what is simple and stratified epithelia?
simple: single layer of cells on a basement membrane
stratified: two or more layers of cells on a basement membrane
90
simple squamous epithelium
-single layer of flattened plate-like cells on a basement membrane
-lines inside of blood vessels (endothelium), outside of lungs(mesothelium) and abdominal organs (peritoneum)
-have a oval shaped nuclei
91
simple cuboidal epithelium
-single layer of cube shaped cells
-have a central spherical nuclei
-line the kidney tubules and small ducts
92
simple columnar epithelium
-single layer of cells that are taller than they are wide on a basement membrane
-single nuclei close to basement membrane
-line stomach intestines and uterus (may also have cilli/microvilli)
93
microvilli
-small projections on luminal surface of absorptive cells
-found on intestinal brush border
94
cilia
-small projections on luminal surface of cells
-found in respiratory and reproductive tracks
95
stratified epithelia features and locations
Features: form a protective layer, that is continuously worn down and replaced by cells below
Location: found at sites subject to abrasive forces
96
stratified squamous non-keratinising
-consists of multiple layers of cells on a basement membrane
-lines the mouth, oropharynx, oesophagus and vagina
-in places where doesnt need to be waterproof
97
stratified squamous keratinising
-waterproof layer of keratin
-found in skin
98
pseudostratified epithelium
-single layer of cells of variable height (makes it appear like there are multiple layers)
-all the cells are in contact with the basement membrane
-it lines the conducting airways, such as the trachea
99
urothelium
-specialised stratified
-lines collecting part of urinary tract
100
basement membrane
-seen when stained with PAS, not normally seen
-essential for the functioning and survival of the epithelium
-consists of several extracellular proteins including collagen IV and fibronectin
101
tight/occluding junctions
-prevent diffusion between cells
-band like fusions between cells (which are impervious to most molecules)
102
desmosomes
-spread forces across several cells
-plaques tha tform physical joins between cells and connect cells to cytoskeleton
103
gap junctions
-permit transfer of small molecules
104
What is metabolism?
The sum of all the chemical reactions that take place within each cell of a living organism
105
What are the 4 main pathways for metabolism?
Biosynthetic
Fuel storage
Oxidative processes
Waste disposal
106
What are anabolic and catabolic processes?
Anabolic processes synthesise larger molecules from smaller components
Catabolic processes break down larger molecules into smaller ones
107
What is the purpose of catabolic processes?
They produce energy for cell processes that use anabolic processes
108
What are the electron accepting coenzymes?
NAD+
NADP+
FAD+
109
How much energy per gram?
carb: 4kcal/g
lipid: 9kcal/g
protein: 4kcal/g
alcohol: 7kcal/g
110
What conditions must be met to measure a persons basal metabolic rate (BMR)?
12 hour fast
Lying still at physical and mental rest
Thermoneutral environment (27-29℃)
No tea/coffee/nicotine/alcohol in previous 12 hours
No heavy physical activity previous day
111
What factors affect BMR?
Age
Gender
Dieting/starvation
Hypo/hyperthyroidism
Decreased muscle mass
Infection
112
How much glucose does the brain require each day?
150g
113
What is malnutrition?
A state of nutrition with a deficiency, excess, or imbalance of energy, protein, or other nutrients, causing measurable adverse affects
114
Why does refeeding syndrome occur?
Due to a lack of electrolytes needed to process carbs into energy, as a result of a period of fasting or chronic illness
115
What is vitamin B1 called and what is it used for?
Thiamine
Helps with energy production in the body
116
What is vitamin B2 called and what is it used for in the body?
Riboflavin
Helps with energy production in the body and enables the use of other B vitamins
117
What is vitamin B3 called and what is it used for?
Niacin = Helps your body to use protein, fat, and carbs to make energy and helps enzymes to work properly in the body
118
What is biotin used for in the body?
Allows your body to use protein, fats, and carbs from food
119
What is vitamin B6 and what is it used for?
Pyridoxin = Helps your body to make and use protein and glycogen and helps form haemoglobin
120
What are the different types of vitamin B?
B1 (Thiamine)
B2 (Riboflavin)
B3 (Niacin)
Biotin
B6 (Pyridoxin)
B12 (Cobalamin)
Folate
121
What is vitamin B12 called and what is it used for?
Cobalamin
Works with folate to make DNA, helps make healthy blood cells, and keeps nerves working properly
122
What is folate used for?
Helps to produce and maintain DNA in cells
Helps to make erythrocytes and prevent anaemia
Having sufficient folate in pregnancy reduces the risk of birth defects
123
What are the 2 stages of glycolysis?
The preparative phase and the ATP generating phase
124
Where does glycolysis occur and under what conditons + why?
Glycolysis occurs in the cytosol of the cell under aerobic and anaerobic conditions
In anaerobic conditions, only glycolysis occurs
In aerobic conditions, glycolysis occurs alongside the Kreb's cycle
To produce ATP
125
What are the net products of glyolysis?
2 NADH
2 ATP
2 Pyruvate
126
Mnemonic and names for glycolysis substrates
"Gross Guys Feed Fat Dorky Girls Bananas and 4 Pears"
Glucose
Glucose-6-phosphate
Fructose-6-phosphate
Fructose-1,6-biphosphate
Dehydroxyacetone phosphate
G-3-P
1,3-Bisphosphoglycerate
3-Phosphoglycerate
2-Phosphoglycerate
Phosphoenolpyruvate
Pyruvate
127
Mnemonic and names for glycolyis enzymes
"High Profile People Act Too Glamorous Picture Posing Every Position"
Hexokinase
Phosphoglucoisomerase
Phosphofructokinase
Aldolase
Triose phosphate isomerase
Glyceraldehyde phosphate dehydrogenase
Phosphoglycerokinase
Phosphoglyceromutase
Enolase
Pyruvate kinase
128
What is the rate limiting step of glycolysis?
Phosphofructose kinase
129
What can also control glycolysis?
Insulin and glucagon
ATP and AMP
130
how is glycolysis controlled?
By inhibitors and activators, which can be allosteric or hormonal
131
what is phosphofuctokinase inhibited by?
-ATP, citrate and fructose 2,6 biphosphate
- Citrate allosterically inhibits PFK-1
-fructose-2,6-biphosphate is another allosteric inhibitor of PFK-1
132
what is PFK-1 activated by?
AMP
When ATP is used up, ADP accumulates and is converted to AMP to generate ATP ( 2 ADP = 1 ATP + AMP
Increased level of AMP relives inhibition of PFK-1 by ATP
133
Allosteric regulation of glycolysis
-binds to a non catalytic site
-results in conformational change
-which increases/decreases affinity for the substrate
133
Glycogen and insulin role in controlling glycolysis
Glycogen and insulin oppose each other, so while one inhibits a molecule, the other stimulates it, which keeps energy production at an effective level
134
Hormonal regulation of glucose
-Increases/decreases gene expression of the enzyme
-which inc/dec enzyme activity
135
Where does the Krebs cycle occur?
The mitochondrial matrix, under aerobic conditions
136
What are the enzymes responsbile for the regulation of the Krebs' cycle?
Pyruvate dehydrogenase, citrate synthase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase
137
What is citrate synthase activated and inhibited by?
Activate: ADP
Inhibit: ATP, NADH, Citrate, Succinyl-CoA
138
What is isocitrate dehyrogenase activated and inhibited by?
Activate: ADP
Inhibit: ATP, NADH
139
What is α-ketoglutarate dehydrogenase activated and inhibited by?
Activate: Ca2+
Inhibit: ATP, NADH, Succinyl CoA, GTP
140
What is the mnemonic for the reagents in Kreb's cycle?
Only Crazy Individuals Act So Surprised For Me
Oxaloacetate
Citrate
Isocitrate
α-Ketoglutarate
Succinyl-CoA
Succinate
Fumarate
Malate
141
Mnemonic and names for Kreb's enzymes
"Corrupt Anti-Intelligence Agents Sell Secrets For Money"
Citrate synthatase
Aconitase
Isocitrate dehydrogenase
α-ketoglutarate dehydrogenase
Succinyl CoA thiokinase
Succinate
Fumarase
Malate dehydrogenase
142
What is the net energy gain for the Kreb's cycle?
6 NADH
2 FADH
2 ATP
Because the cycle goes around twice
143
What is the rate limiting step for Kreb's?
Isocitrate dehydrogenase
144
What can Kreb's also be controlled by?
High levels of ATP, NADH, and FADH2
145
What is the Kreb's activated by?
High ADP
146
What happens in the electron transport chain?
Oxidative phosphorylation
Complex I - removes electron from NADH
Complex II - removes electrons from FADH2 in presence of coenzyme Q
Complexes III, IV, and cytochrome C donate these electrons to cytochromes containing iron
Oxygen is released as a result and converted to H2O
147
How many molecules of ATP does the Kreb's cycle produce following further breakdown?
With 2 cycles:
24 molecules (in sheff exams)
20 molecules (otherwise)
(Sheff refers to them as NADH=3ATP and FADH2=2ATP)
(These are actually NADH=2.5ATP and FADH2=1.5ATP)
148
where does oxidative phosphorylation occur?
in the inner mitochondrial membranes, under aerobic conditions
149
overview of oxidative phosphorylation
1. electrons from coenzymes are passed to components of ETC
2. electrons are accepted by carries with pass them on in redox reactions
3. as electrons pass down the chain, energy is released, powering the movement of protons across the inner membrane space creating a proton gradient
4. protons in the intermembrane space flow back into the mitochondrial matrix down their conc gradient via protein channel atp synthase, where ADP is phosphorylated intp ATP
5. electrons are transferred to their final electron acceptor (oxygen)
Phase 1 medicine UoS
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