Principles of Disease Flashcards
1
Q
killed whole organism vaccine
A
organism is heat killed.
effective and easy to manufacture.
booster shots likely required.
2
Q
Attenuated whole organism vaccine
A
a strain of the organism is made avirulent.
simulates natural infection.
refrigeration required.
3
Q
subunit vaccine
A
viral nucleic acid is removed (only antigens injected).
very safe.
not very immunogenic
4
Q
Toxoid vaccine
A
a modified toxin (has antigens but no toxic activity)
only produces immunity against the toxin
5
Q
active natural immunity
A
infection/ exposure
6
Q
active artificial immunity
A
vaccination
7
Q
passive natural immunity
A
placental transfer of IgG
8
Q
Passive artificial immunity
A
immunoglobulin (antibody) therapy
9
Q
Computed tomography (CT)
A
x-ray tube rotates around patient with detector opposite.
Iodinated contrast often given.
produces cross-sections/ 3D images
10
Q
Positron Emission Tomography (PET)
A
isotope bound to ligand is injected.
ligand binds to structure of interest.
isotope produces positrons which collide with surrounding electrons, emitting 2 photons in opposite directions which are detected.
used to distinguish between benign/malignant tumours
prolonged exposure to radiation is bad
11
Q
Magnetic Resonance Imaging (MRI)
A
a strong magnetic field aligns protons in the same direction.
time taken for them to “relax” to original alignment is recorded - lighter molecules take longer.
no radiation but difficult for patients
12
Q
X-rays
A
A -ve metal cathode is heated releasing inner-shell electrons by thermionic emmision.
electrons collide with a +ve anode and emit energy (1% as x-rays)
x-rays produce sparks of light on a luminescent screen
silver halide forms clumps after exposure to light
13
Q
Attenuation
A
stopping (of x-rays) power.
increases with atomic number, density and thickness.
Air
14
Q
Central self-tolerance
A
deletion of autoreactive T and B cells during maturation
15
Q
Peripheral self-tolerance
A
inhibits the activity of autoreactive cells that escaped central self-tolerance
16
Q
telomeres
A
regions of repeated nucleotide sequences at the ends of chromosomes.
some is lost during each DNA replication but then replenished by telomerase reverse transcriptase
17
Q
Euchromatin
A
region of chromosome with an open structure and active genes
18
Q
Heterochromatin
A
region of chromosome with a condensed structure and silenced genes.
contains extragenic sequences that don’t code for proteins.
19
Q
condensed chromosome exists…
A
only during cell replication. the rest of the time chromatin exists jumbled in the nucleus
20
Q
chromatin
A
non-condensed DNA wrapped around histone proteins in nucleosomes
21
Q
nucleosome
A
DNA wrapped around a histone protein
22
Q
factors of pathogenicity
A
infectivity and virulence
23
Q
factors of virulence
A
invasiveness.
Toxin production.
Evasion of immune system.
24
Q
Exotoxins
A
toxins released extracellularly by the microorganism
25
Enterotoxins
Act on the GI tract
26
Endotoxins
part of the gram negative cell wall (the bacteria itself is a toxin)
27
Type I hypersensitivity
allergens are engulfed, activate T cells which activate B cells.
B cells produce IgE which binds to mast cells
mast cells release inflammatory mediators.
allergen - T cells - B cells - IgE - mast cells - inflammatory mediators
28
Type II hypersensitivity
IgG/ IgM antibodies bind to surface antigens (exogenous or self) which leads to ...
complement activation, Fc mediated damage, ADCC, inhibition/stimulation of target cell function
29
outcomes of complement activation
opsonisation.
ADCC.
byproducts attract neutrophils.
30
Fc mediated damage
Fc receptors on immune cells bind to the Fc region of antibodies (that are bound to a pathogenic/infected cell) which stimulates the immune cell to destroy the pathogen
31
Antibody dependent cellular cytotoxicity
cytotoxic immune cell bound to Fc region of antibody releases cytotoxic factors causing lysis of cell
32
Type III
Pathological immune complexes of an antigen and antibody are formed.
These precipitate out of the blood and into tissues where they cause inflammation.
33
physiological immune complexes
travel dissolved in the blood to the liver/spleen and are destroyed.
34
Type IV hypersensitivity
A hapten/ microorganism binds to a protein carrier.
this compound is phagocytosed.
this activates Th1 cells which produce cytokines.
the cytokines cause inflammation.
35
action of chemical carcinogens
chemical carcinogens react with DNA to form DNA adducts.
| Adduct formation at particular chromosome sites can cause cancer.
36
Cancer initiation
a mutation caused by a chemical, physical or viral carcinogen
37
Cancer promotion caused by...
mutated oncogenes, growth factors or tumour suppressor genes (e.g. P53)
38
cancer progression
Metastasis
39
types of metastasis
local.
lymphatic.
by blood.
trans-coelomic (to body cavities)
40
factors which allow for cancer metastasis
degradation of the ECM by enzymes
altered cell-cell and cell-ECM adhesion
(cells must detach to move to other sites)
41
Effects of benign tumours
all are local:
| pressure, obstruction
42
Local effects of malignant tumours
```
pressure,
obstruction,
tissue destruction,
bleeding (from damage to blood vessels),
pain (pressure on/invasion of nerves),
effects of treatment
```
43
systemic effects of malignant tumours
Weight loss (cachexia)
secretion of hormones (normal or abnormal/inappropriate)
paraneoplastic syndromes
effects of treatment
44
paraneoplastic syndromes
neuropathy (loss of nerve function) and/or
myopathy (loss of muscle function)
caused by humoral immune response
45
Stages of acute inflammation
1. transient (temporary) arteriolar constriction
2. local arteriolar dilation (vasodilation)
3. relaxation of vessel smooth muscle (increases permeability)
46
results of relaxation of vessel smooth muscle in acute inflammation
1. exudation (causes oedema/swelling)
2. this increases viscosity in the capillary so the rate of flow slows causing a change in flow characteristics
3. causes the emigration of neutrophils
47
exudation
a net movement of plasma from capillaries into the extravascular space
(happens in acute inflammation as a result of increased vascular permeability)
48
emigration of neutrophils
1. Margination - neutrophils move towards the endothelial cells of the capillary wall
2. Pavementing - neutrophils adhere to the endothelium
3. Emigration - neutrophils squeeze between endothelial cells to extravascular space
49
abnormalities on chromosome number (aneuploidy)
Trisomy - an extra copy of a chromosome, e.g. triploidy 21 = down syndrome
Monosomy - only one copy of a chromosome
Sex chromosome aneuploidy syndromes
50
Types of structural chromosomal abnormalities
Translocation (balanced or unbalanced)
Deletions
Insertions
Inversions
51
Reciprocal chromosome translocation
2 chromosomes mix and form 2 new chromosomes
balanced = no missing genetic info
unbalanced = some info missing, some doubled
52
Acrocentric chromosomes
All functional DNA is on the q arm or the chromosome
53
Robertsonial chromosome translocation
fusion of 2 acrocentric chromosomes
| unbalanced translocation leads to whole chromosomes being missing or doubled
54
mutational transitions
purine-purine / pyrimidine-pyrimidine
55
mutational transversions
purine-pyrimidine
56
silent mutations
e.g. CGC(arg) - CGA(arg) amino acid is unchanged = no effect
57
missense mutations
amino acid changes. has varying effects
58
nonsense mutations
mutation codes for a stop codon. has varying effects
59
frameshift mutations
caused by insertions/ deletions. very serious effects
60
functions of fibroblasts
1. synthesise collagen (forms granulation tissue)
| 2. secrete growth factors that induce angiogenesis
61
Fibrosis
1. synthesis of stronger better arranged collagen
2. capillaries thin out
results in scar tissue
62
Statistical power
the probability that a test will reject a null hypothesis
63
purpose of statistical tests
to show if differences are due to chance
| p<0.05 is statistically significant
64
a small p value means...
strong evidence against the null hypothesis
| high statistical power
65
clinical significance
the practical importance of a treatment effect
| small statistical differences may not be meaningful to patients
66
Glomerular filtration
(metabolised or unmetabolised) unbound, uncharged, small drug particles are filtered out of the blood at the glomerulus
67
Passive tubular reabsorbtion
lipid soluble drugs are reabsorbed
| metabolism makes drugs more polar to prevent this
68
Active tubular secretion
charged drugs (that could not be filtered out at the glomerulus) are actively secreted into the proximal tubule from the blood
69
radiotherapy
Treats inoperable lesions.
Maintains function and appearance.
Given in stages to maximise tumour damage but minimise healthy tumour damage
P53 mutants are more sensitive to radiation.
Cells are more sensitive at specific cell cycle phases
70
Programmed cell death pathway
| an immune cancer therapy
PDL1 on cancer cell surface deactivates T cells by binding to PD1 on T cell surface.
blocking this interaction allows T cells to recognise cancer cells
71
Monoclonal antibodies
| an immune cancer therapy
antibodies (e.g. herceptin) bind to antigens on cancer cells. Immune cells can then recognise the cancer cells
72
CAR (Chimeric Antigen Receptor) T cell Therapy
| an immune cancer therapy
T cells from a healthy person are mixed with an attenuated virus
This makes the T cells produce CARs which can recognise cancer cells
The T cells are then injected into the patient.
This is non-patient specific
73
causes of type A adverse drug reactions
pharmacodynamic abnormalities (e.g. an excess effect such as insulin induced hypoglycaemia)
pharmacokinetic abnormalities (abnormalities in ADME) caused by disease or pharmacogenetics
74
pharmacodynamics
a drug's effects
75
types of drug-drug interactions
pharmaceutical interactions
pharmacokinetic interactions
pharmacodynamic interactions
76
pharmaceutical interactions
mixing 2 drugs in the same solution
77
Absorbtion
The rate at which a drug enters the blood
78
Factors affecting absorption
```
Gut motility
other drugs
food/drink
illness
gastric emptying time
site of absorption
lipid solubility/ionisation
```
79
Bioavailability
The amount of drug which is absorbed and is available for action
80
factors affecting bioavailability
Ability of drug to pass physiological bariers
first pass metabolism
drug interactions
81
Distribution
The rate at which a drug moves from the blood to the site of action
82
factors affecting distribution
```
capillary permeability
blood flow : tissue mass ratio
plasma protein binding
transport mechanisms available
characteristics of tissue membranes (e.g. blood-brain and blood-testes/ovaries barrier
```
83
Glandular tumours
```
Benign = adenoma
Malignant = edeno-carcinoma
```
84
Squamous tumours
```
Benign = squamous papilloma
Malignant = squamous carcinoma
```
85
Bone tumours
```
Benign = Osteoma
Malignant = Osteo-sarcoma
```
86
Fat tumours
```
Benign = Lipoma
Malignant = Lipo-sarcoma
```
87
Fibrous tissue Tumours
```
Benign = Fibroma
Malignant = Fibro-sarcoma
```
88
White Blood Cell Tumour
Malignant = Leukaemia
89
Lymphoid Tissue Tumour
Malignant = Lymphoma
90
Melanocyte tumour
```
Benign = Naevus
Malignant = melanoma
```
91
Central nervous system tumours
Astrocytoma
92
Peripheral nervous system tumours
Schwannoma
93
Germ cell tumours
Teratomas
ovarian-usually benenign
testicular-usually malignant
94
Diseases that affect how drugs work
Hepatic impairment - drugs are often metabolised in the liver so impairment can lead to toxic levels building up
Renal impairment - drugs are often excreted by the kidneys so impairment can lead to toxic levels building up
Oedema - reduces drug absorption from the gut
95
Anti-metabolites
e.g. fluorouracil
| bind to and inhibit essential enzymes, inhibiting DNA synthesis
96
Alkylating agents
e.g. cisplatin
| bind anti-parallel DNA strands together so they can't be unzipped
97
mechanisms of resistance of cancer cells (to alkylating agents)
1. decreased entry/increased exit of agent from cell
2. inactivation of agent in cell
3. enhanced DNA repair
98
intercalating agents
interfere with transcription and DNA replication
99
Antimitotic antibiotics
e.g. Doxobubicin
| inhibit DNA/RNA synthesis during mitosis
100
Spindle Poisons
e.g. Vinca Alkaloids
| blocks microtubule formation during mitosis
101
mitotic inhibitors
e.g. Etoposide
| breaks down DNA strands during mitosis
102
Examples of anti-cancer hormone therapy
Tamoxifen - blocks oestrogen receptors to decrease risk of breast cancer
Anti-androgens - block testosterone production for prostate cancer
103
Parallel clinical trial design - pros and cons
prevents confounding results from carry over effects
good for disorders with likely progression
groups may be unbalanced
104
Cross-over clinical trial design
reduces confounding variables
requires fewer subjects
carryover between treatments confounds results
bad for curative treatments or rapidly changing conditions
105
Type A ADRs
Augmented
e.g. hypoglycaemia with insulin
bradycardia (slow heart rate) with beta blockers
106
Type B ADRs
Bizarre
e.g. drug allergy hypersensitivity reactions
107
Type C ADRs
Chronic
e.g. steroid induced osteoporosis
opiate dependence
108
Type D ADRs
Delayed
e.g. Teratogenesis (damage to embryo/ foetus)
carcinogenesis
109
Type E ADRs
End of Treatment
e.g. withdrawal seizures from anti-epileptics
MI when beta blockers are stopped
110
Type F ADRs
Failure of treatment
e.g. failure of OCP (oral contraceptive pill) when administered with antibiotics
111
Hypostasis
The settling of blood after death due to gravity with areas of pallor in areas under pressure
112
Putrefaction
degradation of the body by microorganisms
113
Autolysis
Degradation of the body by endogenous enzymes
114
saponification
Fatty acids and ionic solutions form soaps in the body months after death.
115
diagnosis of bacterial infection by microscopy
quick but insensitive detection but not identification
116
diagnosis of bacterial infection by culture
strains can be identified by colonial appearance and growth patterns
117
sterile sites
blood
CSF
bladder
Lungs
118
non-sterile sites
skin
nasopharynx
urethra
gut
119
detection of viruses
a cell line must be inoculated.
electron (not light) microscopy
serology
most common: antigen detection and nucleic acid amplification
120
fimbrae
features of bacterial cells, used for adherance
121
causes of acute inflammation
```
microorganisms
mechanical trauma to tissue
chemical changes
dead tissue
hypersensitivity
```
122
systemic effects of acute inflammation
pyrexia
malaise
neutrophilia
septic shock
123
causes of chronic inflammation
failure of acute inflammation to resolve
autoimmune disorder
exogenous substances
endogenous substances
124
localised type III hypersensitivity reaction
causes localised inflammation that can be resolved by macrophages
125
systemic type III hypersensitivity reaction
complexes deposited in many organs
126
IV administration
100% bioavailability
| avoids first pass metabolism
127
Topical administration
can achieve local or systemic effects
doses can be controlled and sustained
avoids first pass metabolism
128
inhaled administration
```
drug delivered directly to site of action
rapid effect
little systemic absorption
small doses can be used
reduced adverse effects
```
129
Meiosis
Meiosis I - same as mitosis except that non, sister chromatids cross over forming chiasmata where they exchange DNA sequences, resilting in variation
Meiosis II - same as mitosis except chromosomes are not copies so 4 haploid cells are produced
130
Prophase
chromosomes condense
nuclear membrane disappears
spindle fibres form from centrioles
131
Metaphase
chromosomes align at equator
microfilaments attach to centrioles
maximum condensation of chromosomes
132
Anaphase
sister chromatids separate and move to opposite ends of the cell
133
Telophase
new nuclear membranes form
134
proto-oncogenes
code for cell growth and regulation.
mutations can turn them into oncogenes which can accelerate growth, causing a tumour.
One mutation is enough to cause cancer
135
Tumour-suppressor genes
inhibit the cell cycle/promote apoptosis.
cancer only arises when both copies of the gene are mutated.
If a mutation is in a germline cell, the child will only need one mutation as they already have one.
136
common sites of metastasis
```
liver
lung
brain
bone
adrenal glands
```
137
Dysplasia
a pre-malignant change that can indicate a tumour is becoming malignant.
Features include...
increased nuclear size
increased mitotic activity
abnormal mitosises
138
P53 pathway
P53 normally stops the cell cycle to allow DNA repair or trigger apoptosis after damage.
mutations in P53 prevent the cell cycle from stopping so mutations are replicated leading to cancer.
139
Commensal
Normal members of the microbial flora
140
ELISA
measures antibody / antigen
141
epigenetic factors
affect the phenotype without changing the genotype
142
examples of non-mendelian Inheritance
Incomplete penetrance
Genomic imprinting - gene expressed from only one chromosome (the other is switched off)
Extracellular inheritance - e.g. mitochondrial DNA
Anticipation - disease presents at an earlier age/ is more severe with each succeeding generation
143
PCR
1. DNA is denatured
2. primers anneal
3. replication by heat resistant DNA polymerase
*repeated 20-30 times
followed by analysis by gel electrophoresis
144
ARMS - amplification refractory mutation system
| allele specific PCR
like PCR, used to detect single base pair mutations
run first with normal primers, then with mutant primers
amplification will only occur if the primer matches.
145
Restriction fragment length polymorphism
restriction endonucleases cut DNA at a specific site
this creates restriction fragments
fragments are analysed by gel electrophoresis
146
DNA sequencing
PCR using chemically altered terminator bases (dideoxynucleotides) that stop replication at different points - this creates many fragments of different lengths
fragments are analysed by gel electrophoresis
the fluorescent tags on the dideoxynucleotides are "read" by a computer as they pass a point on the gel.
the shortest fragments reach the point first so the order read by the computer gives the base sequence. (each base has a different tag)
147
Causes of acute inflammation
```
Infection
Trauma (even sterile injuries)
chemical upset
Physical factors (heat, cold, ionising radiation)
dead tissue
hypersensitivity
```
148
breast tumours commonly metastasise to...
bone
149
prostate tumours commonly metastasise to...
bone
150
colorectal tumours commonly metastasise to...
liver
151
ovary tumours commonly metastasise to...
omentum
152
Cys64Arg
64th amino acid changed from Cys to Arg
153
662-42C>T
42 nucleotides before 662, C changed to T
154
M252X
252nd amino acid changed from an M to a STOP codon
155
IVS2+12insG
in the second intron, after 12 nucleotides, insertion of a G
156
1294del40
at position 1294, 40 nucleotides deleted
157
1298A>G
at position 1298, single base mutation of A to G
