Week 8 Flashcards
(128 cards)
1
Q
What are the two components of a tumour?
A
- neoplastic cells
- stroma (connective tissue, blood vessels, inflammatory cells)
2
Q
What is the main feature of a tumour?
A
autonomic growth
3
Q
Give the 3 most common cancers in the UK for each of males and females.
A
MALES
- prostate
- lung
- colorectal
FEMALES
- breast
- colorectal
- lung
4
Q
Give the 6 hallmarks of cancer.
A
- self-sufficiency in growth signals
- insensitivity to anti-growth signals
- tissue invasion and metastasis
- limitless replicative potential
- sustained angiogenesis
- evading apoptosis
5
Q
Compare benign and malignant macro- and microscopic features.
A
BENIGN
- intact surface
- exophytic growth
- homogeneous cut surface
- circumscribed/encapsulated edge
- resembles tissue of origin
- well-circumscribed and differentiated
- minimal nuclear pleomorphism
- normal mitotic figures
MALIGNANT
- heterogeneous cut surface
- ulcerated surface
- endophytic growth
- vascular permeation
- irregular infiltrative edge
- variable resemblance/differentiation
- variable nuclear and cytoplasmic pleomorphism
- abnormal mitotic figures
- necrotic
6
Q
Compare the clinical relevance of benign and malignant tumours.
A
BENIGN
- does not invade surrounding structures or metastasise
- not always clinically benign
MALIGNANT
- invades surrounding structures and metastasises
7
Q
Describe the clinical effects of non-clinically benign benign tumours.
A
SPACE OCCUPYING EFFECTS
- obstruction
- epilepsy
- conduction abnormalities
HAEMORRHAGE
- pulmonary
- GI
HORMONE PRODUCTION
- pituitary
- adrenal
- endocrine pancreas
8
Q
Give the 4 ways malignant tumours spread.
A
- direct local invasion
- via lymphatics
- via bloodstream (haematological)
- through body cavities (transcoelomic)
9
Q
Give the most likely distribution(s) of prostate (1), lung (2), breast (4), ovary (1).
A
PROSTATE
bone
LUNG
brain, adrenal glands
BREAST
lung, liver, bone, brain
OVARY
peritoneal cavity
10
Q
Describe the TNM staging of cancer spread, and Duke’s staging system for colorectal cancer.
A
TNM
T - Tumour size (1-4)
N - Degree of lymph node involvement (0-2)
M - extent of distant metastases (0-2)
DUKE'S A - confined to bowel wall B - through bowel but no lymph node involvement C - lymph nodes involved D - distant spread
11
Q
Name the 3 major tumours categories.
A
- epithelial origin
- connective tissue origin (mesenchymal)
- lymphoid/haematopoietic origin
12
Q
Give three types of each of benign and malignant epithelial tumours.
A
BENIGN
- squamous papilloma
- transitional papilloma
- adenoma
MALIGNANT
- squamous cell carcinoma
- transitional cell carcinoma
- adenocarcinoma
13
Q
What are two non-invasive precursors of epithelial tumours?
A
- carcinoma in situ
- intraepithelial neoplasia
14
Q
Give two types of each of benign and malignant mesenchymal tumours.
A
BENIGN
- lipoma
- haemangioma
MALIGNANT
- liposarcoma
- haemangiosarcoma
15
Q
Give 4 examples of miscellaneous tumours.
A
- melanoma
- lymphoma
- teratoma
- blastoma
- carcinoid tumours
- cysts
16
Q
What enzyme was used to prove the clonal origin of tumour cells?
A
Glucose-6-phosphate dehydrogenase
17
Q
How do you call cells in tumours that are responsible for growth/replication?
A
tumour stem cells or tumour initiating cells
18
Q
Give the respective lifespan of RBCs, neutrophils, lymphocytes and platelets.
A
RBCs
120 days half-life
NEUTROPHILS
9-10hrs in blood
few days in tissues
LYMPHOCYTES
some long-lived, some short-lived, depending on their function
PLATELETS
4-5 days in blood
19
Q
What are the two types of stem cells found in bone marrow? Differentiate between yellow and red marrow.
A
- haematopoietic
- stromal
RED MARROW
haematopoiesis
most important type of marrow at birth
YELLOW MARROW
fat cells
increases with age
can be converted back to red if severe anaemia
20
Q
Which 3 types of blood cells would you find in a bone marrow smear?
A
- RBCs
- lymphocytes
- neutrophils
21
Q
Give one possible site for bone marrow transplant.
A
posterior iliac crest
22
Q
What are the three main sources of haematopoietic cells in the foetus under 6 months?
A
- yolk sac
- liver
- spleen
23
Q
What is the size of an early proerythroblast?
A
20 microns
24
Q
What is the particularity of reticulocytes?
A
residual mRNA present for a short time
25
What hormone is involved with RBC synthesis? By which cells is it secreted?
erythropoietin
fibroblasts in kidneys
26
Some kidney tumours cause excess erythropoietin production. What consequences does this have?
polycythaemia --> thicker blood and higher risks of clots and strokes
27
What is the name of the technique used to study stem cells?
colony formation
28
How much time do T-cell precursors spend in the thymus? Name the process they undergo there and its two stages.
7-21 days
T-cell education: positive selection, then negative selection
29
What are the respective goals for positive and negative selection in T-cell education? Which cells overview each of these processes?
POSITIVE SELECTION
eliminate the T-cells that do not recognize MHC properly
overviewed by cortical epithelial cells
NEGATIVE SELECTION
eliminate the T-cells that recognize MHC too well --> prevent autoimmunity
overviewed by dendritic cells
30
To which superfamily does TcR belong? What two main feature distinguishes them from antibodies?
immunoglobulin superfamily
- membrane-bound
- not Y-shaped
31
Which mechanism is responsible for TcR diversity?
chromosomal rearrangement
32
Explain why TcR recognition of an antigen is qualified of "MHC-restricted".
the TcR only ever recognises an antigen when the latter is bound by an MHC molecule
33
Differentiate between MHC class I and MHC class II (structure, peptides, recognition, expression).
MHC CLASS I
- 2 chains: one heavy, one small beta-2 microglobulin
- elongated groove for 8-10 amino acids
- expressed on almost all cells of the body (except on RBCs) to signal infection
- recognised by CD8 T-cells
- peptides from intracellular contents in endoplasmic reticulum
MHC CLASS II
- 2 chains: one alpha and one beta, both membrane-bound
- extended groove for > 20 amino acids
- specialised antigen for immune cells only
- recognised by CD4 T-cells
- peptides from extracellular sources in endosomes
34
Which chromosome codes for MHC molecules? How many alleles does one individual possess?
chromosome 6
| 6 alleles per individual (2*3)
35
Give one positive and one negative point of the highly polymorphic features of MHC.
+: evolutionary protection against pathogen
| -: rejection risks for transfusion/grafts
36
Name 3 health issues that arise from B-cells, T-cells or MHC molecules problems.
- autoimmune reactions
- cancer
- superantigens
37
What is a superantigen? Give two examples of toxins that act as superantigens.
Protein that interferes with the interaction of TcR and MHC, stimulating large numbers of T-cells
- staphylococcal enterotoxin
- toxic shock syndrome toxin 1
38
Give the full name of MHC.
Major Histocompatibility Complex
39
Define chemokine and leucokine.
```
CHEMOKINE
a class of cytokines that has chemoattractant properties
```
LEUCOKINE
cytokine secreted by a leukocyte
40
What are the 2 main groups of cytokines?
CC and CXC
41
Describe the roles of IL-8, IL-2, IL-4, IF-gamma, TNF-alpha.
IL-8:
mobilises/recruits neutrophils and naive T-cells
IL-2:
activates T-cell growth (including self-proliferation)
IL-4:
activates B-cells to produce IgE
```
IF-gamma:
upregulates MHC class I and class II
```
TNF-alpha:
highly pro-inflammatory
42
Name the process neutrophils use to access infection sites from the vasculature.
diapedesis
43
What is the main functional difference between TH1 and TH2 CD4 T-cells?
TH1 activate macrophages for cell-mediated immunity
TH2 activate B-cells for antibody-producing
44
Define dendritic cell.
Professional antigen presenting cell that sits at the interface between the innate and adaptive immune system
45
What is the role of dendritic cells in tissues? and in lymph nodes?
IN TISSUES
sampling of external environment
upon stimulation, cease phagocytosis and migrate to lymph nodes
IN LYMPH NODES
activates T-cells and also influences B-cells to produce antibodies
46
Which family do Pattern recognition receptors belong to? Which cells present these receptors? What do they recognise?
Toll-like receptor family
dendritic cells
bacterial structures and modified genetic material
47
Define pharmacology, toxicology, pharmacodynamics, pharmacokinetics.
PHARMACOLOGY
origin, nature, chemistry, effects and uses of drugs
TOXICOLOGY
study of the adverse effects of chemical, physical or biological agents
PHARMACODYNAMICS
what the drug does to the body (effect site concentration and pharmacological effects)
PHARMACOKINETICS
what the body does to the drug (drug dose, biological fluid concentration, effect site concentration)
48
Give 5 reasons for the importance of pharmacokinetics.
- how dose recommendations in inserts are arrived at
- identify possible drug interactions
- to adjust monitoring strategies such as therapeutic dose monitoring
- to safely administer drugs when urgency is required
- predict the influence of disease on drugs
49
What are the 4 stages of pharmacokinetics?
absorption
distribution
metabolism
excretion
50
Give one advantage and one disadvantage for each of the following routes of administration: oral, sublingual, inhalation, topical, transdermal, intramuscular, IV.
ORAL
+: convenient
-: first-pass effect, many variables and barriers
SUBLINGUAL
+: no first-pass effect
-: inconvenient, limited to small doses, taste
INHALATION
+: fast, rapid to blood
-: requires specialised properties of drugs
TOPICAL
+: convenient, localised
-: only local
TRANSDERMAL
+: prolonged release
-: skin is very effective barrier
INTRAMUSCULAR
+: rapid for aqueous drugs, slow for oily drugs
-: painful, requires trained personnel
IV
+: direct, total dose, rapid
-: requires professionals, risk of infection, rapid responses
51
Define bioavailability. Which route of administration gives 100% bioavailability?
= fraction of unchanched drug that reaches the systemic circulation
IV injection
52
Give the two preferrential ways drug cross cell membranes.
- diffusing directly through the lipids
| - using a transmembrane carrier proteins
53
Give the pH ranges of gastric acid, large intestine, small intestine and plasma. Explain why this is relevant to drug absorption.
gastric acid: pH 1.0-3.0
large intestine: pH 8.0
small intestine: pH 5.0-6.0
plasma: pH 7.4
The ionized:unionized drug ratio depends on the pH. Ionised drugs have low lipid solubility, and cannot cross membranes
54
Name the 2 main drug properties that affect absorption.
- lipophilicity
| - ionisation
55
Give 6 factors that affect drug distribution.
- degree of drug ionisation
- lipid solubility
- pH of compartments
- cardiac output and blood flow
- capillary permeability
- plasma protein binding
56
What tissue acts as a peripheral compartment in the compartment model for bisphosphanates?
bone
57
Give 4 examples of plasma proteins drugs bind to.
- albumin
- alpha-1 acid glycoprotein
- lipoproteins
- globulins
58
Why might a patient be given aspirin and warfarin?
Warfarin binds to albumin in blood, only ~2% free to have effects.
Aspirin has high affinity for albumin --> competition
Increase in unbound warfarin --> increased effects
59
Give 4 factors affecting drug distribution between body fluid compartments.
- permeability across tissue barriers
- binding within compartments
- pH partition
- fat:water partition
60
Define epidemiology.
= the study of the distribution and determinants of health-related states or events in specified populations and the application of this study to control of health problems
61
What are the two data meaningful statistics need?
- a denominator population
| - a time frame
62
Define and contrast incidence and prevalence.
INCIDENCE
= number of new cases
- rate or proportion
- useful for identifying causes of diseases
- occurs only in people without the disease
```
PREVALENCE
= proportion of the population that has disease
- a proportion
- identifies disease burden
- useful for planning services
```
63
Name 4 patterns of outcome occurrence, from the most severe to the less severe.
- pandemic
- epidemic
- endemic
- sporadic
64
Give the 6 categories of outcomes, and 3 categories of exposures.
OUTCOMES
- death
- hospitalisation
- first diagnosis with a disease
- recurrence
- quality of life
- surrogates
EXPOSURES
- non-modifiable
- modifiable
- interventions
65
What are cross-sectional studies, case-control studies, cohort studies and randomised controlled trials?
CROSS-SECTIONAL STUDIES
- sample a population
- estimate the % of different exposures, signs/symptoms, outcomes
- use data to describe prevalence/burden and explore associations
CASE-CONTROL STUDIES
- select cases with an outcome and controls without the outcome
- explore exposures in cases and controls
- compare exposures in cases and controls
- identify association
COHORT STUDIES
- select people without an outcome
- classify according to exposure
- prospective or retrospective follow-up
- compare risk of disease in exposed and unexposed
RANDOMISED CONTROLLED TRIALS
- random allocation (one group intervention, one group control/comparator)
- compare risk of outcome in intervention and control groups
66
Differentiate between confounding and bias.
CONFOUNDING
= true relationship confused by a third factor
BIAS
= systematic error that leads to wrong conclusions concerning effectiveness and/or causation
67
Give the 9 criteria for causality.
- strength (effect size)
- consistency
- specificity
- temporality
- biological gradient
- plausibility
- coherence
- experiment
- analogy
68
Which muscle of the gluteal region is not supplied by the superior gluteal artery?
Gluteus maximus
69
Which nerve lays by the side of the sciatic nerve in the gluteal region?
the posterior cutaneous nerve of the thigh
70
Through which foramen does obturator internus go?
lesser sciatic foramen
71
Which regions are supplied by the pudendal nerve and the internal pudendal artery?
pelvis and peroneum
72
What is the common origin of the hamstring muscles?
ischial tuberosity
73
What is responsible in the GI tract for de-conjugation and reuptake of excreted drugs? What is the consequences of this process? Give one example of a drug type that makes use of that process, and one example of drug type that interferes with it.
bacterial exposition in the GI tract
re-uptake --> increases the half-life
used in oral contraceptives
antibiotics interfere
74
How many genes code for cytochrome P450 enzymes in the human genome? What are the functions of these enzymes?
57 genes
- biosynthesis of steroids, fatty acids and bile acids
- metabolism of endogenous and exogenous substrates
75
Which protein is involved in the normal pathway of paracetamol, and without which taking paracetamol has toxic effects?
glutathione
76
Explain the effect of phenobarbital on warfarin.
phenobarbital increases expression of CYP450
warfarin is metabolised by CYP450
in presence of phenobarbital, there is increased excretion of warfarin, so warfarin is less effective
77
What drink is contra-indicated in the use of simvastatin?
grapefruit juice
78
Give 8 possible sources of excretion.
- breath
- urine
- saliva
- perspiration
- feces
- milk
- bile
- hair
79
What is the therapeutic window? The onset of action? The duration of action?
THERAPEUTIC WINDOW
interval in plasma drug concentration between minimum toxic dose and minimum effective concentration
ONSET OF ACTION
time to reach minimum effective plasma concentration from drug administration
DURATION OF ACTION
time period where the plasma drug concentration is equal of higher to the minimum effective concentration
80
What is usually meant by half-life of a drug?
plasma clearance half-life
81
Name one drug given as an IV infusion in cardiogenic shock.
dobutamine
82
Give 9 factors that can affect pharmacokinetic parameters.
- age
- sex
- pregnancy
- body weight
- genetic variability
- diet
- disease
- ethnicity
- other medications
83
Which pulses are felt during vascular examination of the upper and lower limbs?
- brachial pulse
- radial pulse
- ulnar pulse
- femoral pulse
- popliteal pulse
- posterior tibial pulse
- dorsalis pedis pulse
84
How is Allen's test performed?
1) tight fist, raise hand above heart
2) compress both radial and ulnar arteries at wrist
3) release the ulnar artery, wait for reperfusion
4) repeat for radial artery
85
In the presence of which sign would a Trendelenburg test be performed? How is it performed?
varicose veins
1) elevate limb as far as comfortably possible and empty the superficial veins of the leg
2) occlude saphenofemoral junction (3.5 cm below and lateral pubic tubercle
3) patient stands, pressure on junction maintained
4) if varicosities refill immediately: leaking perforating vein further down leg. If not, incompetence at saphenofemoral junction
5) release pressure: if veins refill rapidly, confirms saphenofemoral incompetence
86
How is Buerger's test performed?
1) assess pain or hip restriction
2) elevate leg at towards 90 degrees
3) normally: feet will go pale at 90 degrees. severe ischaemia: 50 degrees; critical ischaemia: 25 degrees
4) after a minute, patient to stand
5) if peripheral vascualr disease, feet become engorged and purple, to deep red
87
When might a biphasic signal be heard in a doppler assessment of pulse?
early atherosclerosis, minimal stenosis
88
When might a monophasic signal be heard in a doppler assessment of pulse?
severe vascular disease
89
Give the 6 signs of an ischaemic limb.
```
pallor
pain
paraesthesia
paralysis
perishingly cold
pulselessness
```
90
What 3 mechanisms are involved in epigenetic gene silencing?
- DNA methylation
- histone modifications
- nucleosome remodelling
91
Define epigenetics.
heritable modification of DNA that do not alter the primary sequence but result in altered gene expression
92
What is DNA methylation chemically?
covalent modification of a methyl group to cytosine at position C5 to make 5-methylcytosine
93
Which area of DNA is targeted by DNA methylation?
CpG islands in promoter regions
94
What are the 2 roles of methyl CpG binding proteins?
- recognise and bind to methylated CpG
| - recruit other proteins to remove acetyl groups, favouring compact chromatin
95
Give two symptoms for each of Prader-Willi syndrome and Angelman syndrome.
PRADER-WILLI SYNDROME
- mental retardation
- obesity
ANGELMAN SYNDROME
- mental retardation
- happy puppet syndrome
- jerky movements
- inappropriate laughter
96
Give the difference between heterochromatin and euchromatin in term of S phase DNA replication.
HETEROCHROMATIN
replicates late in S phase
EUCHROMATIN
replicates early in S phase
97
Define the position effect.
cell-to-cell variability in gene expression caused by the spreading of heterochromatin into euchromatic regions
98
Explain the mechanism for X-chromosome inactivation. When does it happen?
Xist (X inactive specific transcript) marks inactive X chromosome
no protein product + RNA coded for remains in nucleus
followed by DNA methylation
happens early in embryological development
99
How many genes are imprinted in human autosomes?
~80
100
When is imprinting reset?
passage through germline
101
What are the two conditions that make DNA methylation the most likely mechanism for imprinting?
- must be somatically stable
| - must be reversible
102
Give 3 examples of evidence in humans for imprinting.
- hydatidiform mole
- ovarian teratoma
- uniparental disomy
103
Give 3 conditions linked to uniparental disomy.
- Prader-Willi syndrome
- Angelman syndrome
- Wilm's tumour
104
Give 3 examples of diseases associated with genomic imprinting.
- Prader-Willi syndrome
- Angelman syndrome
- Wilm's tumour
- Beckwith-Wiedemann syndrome
- fragile X syndrome
- myotonic dystrophy
105
How is DNA methylation used by cancer cells?
silencing of tumour suppressor genes
106
Define locus and allele.
locus = precise position of a gene arranged along the chromosome in a linear order
allele= the alternative forms of a gene
107
Give 3 categories of causes for genetic diseases.
- chromosome aneuploidies
- chromosomal abnormalities (missing or extra piece)
- change in gen sequence (mutation)
108
Which property of the DNA code results in the fact that not every base change results in an amino acid change?
redundancy
109
Which of sickle cell anaemia and diabetes is not inherited in a Mendelian fashion?
diabetes
110
Give two diseases caused by autosomal dominant defects.
Marfan's syndrome
| Hereditary Haemorrhagic Telangiectasia 1 and 2
111
Define allelic heterogeneity and locus heterogeneity.
ALLELIC HETEROGENEITY
different mutations in the same gene can cause the same disease
LOCUS HETEROGENEITY
the same disease might be caused by mutations in one of several genes
112
Give 6 features of autosomal dominant diseases.
- 1 faulty copy of gene to cause disease
- disease seen in all generations
- 50% risk for child if one parent affected
- variable disease severity
- male and females equally likely to be affected
- no carriers
113
Give 5 features of autosomal recessive diseases.
- 2 faulty copies of a gene to cause disease
- often only one generation affected
- 25% risk for child if both parents carriers
- increased likelihood in consanguineous families
- carriers
114
Give 1 example of autosomal recessive disease
sickle cell anaemia
115
Give 2 examples of X-linked recessive disorders.
- haemophilia
| - Duchenne muscular dystrophy
116
Give the 2 possible outcomes for children of each of a female carrier and an affected male with an unaffected spouse.
FEMALE CARRIER
- 50% of male children affected
- 50% of female children carriers
MALE AFFECTED
- all male children normal
- all female children carriers
117
Define non-penetrance and variable expression.
NON-PENETRANCE
failure of a genotype to manifest
VARIABLE EXPRESSION
different family members may show different features of a disease
118
What 2 kinds of diseases mostly arise from mitochondrial mutations ?
- neurodegenerative disorders
| - muscular disorders
119
Give 4 symptoms of Duchenne muscular dystrophy.
- mild developmental delay
- slow to walk
- difficulty standing
- unable to run
- hypertrophy of calf muscles
- proximal muscle weakness
120
Define life events and hassles.
LIFE EVENTS
major happenings that can occur in a person's life that require some degree of psychological readjustment
HASSLES
minor stressors that occur regularly
121
Give the three main sources of life events, and two examples for each.
INDIVIDUAL
illness, internal conflict, personal relationships, lacking control
FAMILY
divorce, marriage, illness, disability, death, addition to family
SOCIETY
job, environment
122
Explain the three different types of internal conflicts.
APPROACH-APPROACH
choice between two positive things
APPROACH-AVOIDANCE
choice between a positive and a negative thing
AVOIDANCE-AVOIDANCE
choice between two negative things
123
What three systems do life events impact on?
- physiological system
- psychological system
- social aspect
124
Describe the Social Readjustment Rating Scale. Give its strengths and limitations.
list of 43 life events rated on a scale from 0 to 100
adults indicate which have occurred within the past 12 months --> summation for total stress score
STRENGTHS
- wide range of events
- values assigned to items based on broad sample of adults
- easy, quick to complete
- useful tool for assessment of stress and illness
- positive correlations between life events and illness
LIMITATIONS
- items vague/ambiguous
- failure to consider individual impact of event
- failure to distinguish desirable/undesirable
- accuracy of memory
- causality
125
Name 3 conditions that have been associated with life events.
- breast cancer
- asthma
- burnout
- depression
- blood pressure
- heart disease
- non-ulcer dyspepsia
126
Name two scales used to assess daily hassles. Which one is the most reliable?
- Hassles scale (most reliable)
| - uplifts scale
127
Name the two types of stress.
Distress and eustress
128
Why can stress sometimes be considered to be a positive thing?
enhances performance
