Week 9 Flashcards
(107 cards)
1
Q
Give 3 characteristics used to recognise a chromosome.
A
- banding pattern with specific stains
- length
- position of centromere
2
Q
Name all acrocentric chromosome pairs. What does the short arm contain?
A
chromosome pairs: 13, 14, 15, 21 and 22
on the short arm: satellite ribosomal genes, tRNAs…
3
Q
Differentiate between balanced and unbalanced chromosome rearrangement.
A
BALANCED CHROMOSOME REARRANGEMENT
all chromosomal material present
UNBALANCED CHROMOSOME REARRANGEMENT
extra or missing chromosomal material
4
Q
Define aneuploidy and translocation.
A
ANEUPLOIDY
whole extra or missing chromosome caused by non-disjunction in meiosis
TRANSLOCATION
rearrangement of chromosomes
5
Q
Name two techniques for rapid prenatal diagnosis of chromosomal abnormalities.
A
- Fluorescence In Situ Hybridization (FISH)
- Array CGH
6
Q
Name these different syndrome: trisomy 21, trisomy 18, trisomy 13, 45X, 47XXX, 47 XXY.
A
Trisomy 21 = Down syndrome
Trisomy 18 = Edward syndrome
Trisomy 13 = Patau syndrome
45X = Turner syndrome
47 XXX = Triple X
47XXY = Klinefelter syndrome
7
Q
What are the two major chromosome mutation types?
A
- chromosomal insertion
- chromosomal translocation
8
Q
Explain Robertsonian location.
A
Two acrocentric chromosomes stuck end to end
9
Q
Explain the following karyotypes:
- 45, XY, t(14;21)
- 45, XX, t(21;21)
- 46, XY, der(14;21), +21
A
45, XY, t(14;21)
- male
- Robertsonian translocation of chromosome 21 to chromosome 14
- the Robertsonian chromosome counts as one: so the chromosome number is 45 instead of 46, but the translocation is most probably balanced (all genetic material present)
- very likely to be phenotypically normal
45, XX, t(21;21)
- female
- Robertsonian translocation of chromosome 21 to chromosome 21
- the Robertsonian chromosome counts as one: so the chromosome number is 45 instead of 46, but the translocation is most probably balanced (all genetic material present)
- very likely to be phenotypically normal
46, XY, der(14;21), +21
- male
- Robertsonian translocation of chromosome 21 to chromosome 14, inherited from parent (called derived chromosome), counts as one chromosome
- total number of chromosomes = 46 but because of derived chromosome: abnormal (+21)
- +21: two chromosomes 21 + chromosomal material from a third chromosome 21 on chromosome 14 –> Down syndrome
10
Q
Give the possible outcomes (genotype and phenotype) for a child whose father has a Robertsonian translocation t(14;21) and whose mother is normal.
A
1) normal genotype and phenotype
2) balanced translocation (one normal 14, one normal 21, one t(14;21) –> normal phenotype
3) unbalanced translocation for chromosome 14 –> trisomy 14 (miscarried)
4) unbalanced translocation for chromosome 21 –> trisomy 21 –> Down syndrome
11
Q
What are the 2 possible outcomes of a reciprocal translocation?
A
EXCHANGE OF ACENTRIC AND CENTRIC FRAGMENTS
one dicentric and one acentric chromosome –> no stable in mitosis
EXCHANGE OF 2 ACENTRIC FRAGMENTS
stable monocentric chromosome
12
Q
Give the possible outcomes (genotype ) for a child whose mother has a stable reciprocal translocation t(1;9) and whose father is normal.
A
1) normal genotype
2) balanced t(1;9) –> phenotypically normal
3) partial trisomy 9 and monosomy 1
4) partial trisomy 1 and monosomy 9
3 and 4 either result in miscarriage or dysmorphic delayed child
13
Q
Explain the following karyotype: 46, XY, der(17) t(12;17)(p13;p13)mat
A
- Male
- 46 chromosomes: normal total number of chromosomes
- inherited a reciprocal translocation of material from p13 from chromosome 12 on chromosome 17 –> partial trisomy 17
- missing material from p13 from chromosome 12 –> partial monosomy 12
14
Q
What is the most well-known reciprocal translocation? Which two chromosomes are involved? What would be the phenotype for a male? What disease is this change associated with?
A
Philadelphia chromosome
chromosomes 9 and 22
46, XY, t(9;22)(q34;q11.2)
chronic myeloid leukaemia
15
Q
Give one example of disease caused by chromosomal deletion, and one caused by chromosomal duplication.
A
DELETION
X-linked ichtyosis
DUPLICATION
Charcot Marie Tooth disease
16
Q
What is commonest chromosomal inversion?
A
inv(9)(p11q12)
17
Q
What is the double standard of sex steroids regarding bone growth?
A
stimulate growth spurt BUT promote closure of epiphyseal plates
18
Q
How do epiphyseal plates close?
A
plate invaded by blood vessels as epiphyseal and diaphyseal vessels unite
19
Q
Give 3 examples of bones that have only one ossification center.
A
- tarsals
- carpals
- ear ossicles
20
Q
Give one forensic significance of bones having multiple ossification centers developing at different ages.
A
allows estimation of skeletal age
21
Q
What are the 5 zones of the epiphyseal plate?
A
- resting zone
- growth (proliferating) zone
- hypertrophic zone
- calcification zone
- ossification (osteogenic) zone
22
Q
Give one disease associated with defect in the resting zone of the epiphyseal plate. Give two diseases associated with defect in each of growth, hypertrophic and metaphysic zones.
A
RESTING ZONE
diastrophic dwarfism
GROWTH ZONE
- achondroplasia
- malnutrition
- irradiation injury
- gigantism
HYPERTROPHIC
- rickets
- osteomalacia
METAPHYSIC
- osteomyelitis
- osteogenesis imperfecta (brittle bones)
- scurvy
23
Q
What are the 5 nutrients required for normal growth and development of bone? What else is required?
A
NUTRIENTS
- calcium
- phosphorus
- vitamin A
- vitamin C
- vitamin D
balance between:
- growth hormones
- thyroid and parathyroid hormones
- oestrogen and androgens
24
Q
What percentage of a long bone is typically made of trabecular bone?
A
20%
25
What two components make up the mechanism of injury of a broken bone?
- direction of force
| - energy transfer
26
Define "fracture". Give 8 points of description.
= a complete or incomplete break in a bone
- site
- open (compound) or closed
- contaminated
- associated soft tissue injury
- joint involvement
- number of pieces
- alignment
- degree of separation
27
Give the names of 12 fracture patterns. Which one is mostly associated with paediatric bone?
- traverse
- linear
- oblique non-displaced
- oblique displaced
- spiral
- greenstick (paediatric bone)
- comminuted
- avulsion
- buckled
- compression/wedge
- pathologic
- stress/hairline
28
What 7 factors are associated with a limb-threatening or a non-union risk?
- dislocation
- comminuted
- compound
- compartment syndrome
- vascular/nerve injury
- significant soft tissue injury
- pathological bone
29
What are bone-remodelling units? What is their normal function?
Osteoclasts + osteoblasts
keep adult bone mass relatively constant in the face of developmental, physiological and physical demands
30
Give 3 influencing factors on the healing time for bone.
- severity of fracture
- position of fracture
- age of patient
31
What are the three major phases of fracture healing?
1. reactive phase
2. reparative phase
3. remodelling phase
32
How would treatment vary between a simple fracture with a low non-union risk, and a fracture with limb threat or high risk of non-union?
SIMPLE FRACTURE, LOW RISK OF NON-UNION
conservative treatment, dependent in natural healing process
- immobilisation
- rehabilitation
FRACTURE WITH LIMB THREAT/ HIGH RISK OF NON-UNION
intervention:
- plates and screws or pins to augment natural healing with replacement/strengthening
- immobilisation
- rehabilitation
33
Define quantitative inheritance.
complex disorders and continuous traits are influenced by multiple genes and multiple environmental factors (probabilistic)
34
Define liability.
all the factors that influence the development of a multifactorial trait/disorder, considered as a single entity
35
Define susceptibility.
the outcome of interaction of many genetic and environmental risk variants in utero
36
Define heritability.
proportion of the total variance in a population that is genetic
37
Define overall variance of phenotype.
the sum of environmental and genetic variance
38
Differentiate between mutation and polymorphism.
MUTATION
a gene change that causes a genetic disorder
POLYMORPHISM
any variation in the human genome that has a population frequency greater than 1%, that does not cuase disease in its own right, but may predispose
39
what are the two ways to evaluate genetic contribution to a disease?
- twin stiudies
| - family studies
40
How will the liability curve shift for relatives of a person with a disease?
shifted to the right
41
Complete: "a group of people with lower incidence than the population but who still have affected members has a ... genetic susceptibility."
higher
42
Give the three characteristics of multifactorial inheritance.
- polygenic threshold characters tend to run in families because affected individuals have relatives who share their genes with them
- parents with several affected children will have more high risk alleles than parents with only one affected child
- recurrence risk increases with increasing number of previously affected children
43
What means can we use to explore the link between a polymorphism and a disease? Give one example of link.
association study
5A promotor polymorphism in MMP3 gives a small increased risk of aortic aneurysm
44
What are the three outcomes regarding the conclusion of an association study?
- significant association may be true
- significant association may be false and due to chance
- significant association may be false and due to population stratification
45
Where does the popliteal vein become the femoral vein?
at the adductor hiatus
46
Which two arteries does the popliteal artery divide into?
anterior and posterior tibial arteries
47
Which landmarks would you use to find the prepatellar and infrapatellar bursae?
PREPATELLAR BURSA
between lower pole of patella and upper part of patellar ligament
INFRAPATELLAR BURSA
between the tibial tuberosity and the lower end of the patellar ligament
48
To which two structures does the tendon of popliteus lie deep?
- biceps femoris
| - fibular collateral ligament
49
What is the unhappy triad? Give four other names for this condition.
complete or partial tear of three soft tissue: anterior cruciate ligament, medial collateral ligament, and the meniscus, that results from valgus stress with rotation of the knee
O'Donoghue's triad, terrible triad, blown knee, horrible triangle
50
To what structure does the iliofemoral attaches distally?
the intertrochanteric line
51
Describe the process of chemical carcinogenesis.
INITIATION
normal tissue --> altered genotype of an initiated cell
= mutagenic event that involves cellular genome mutations in tumour suppressor genes and oncogenes
PROMOTION
altered genotype of an initiated cell --> new phenotype with clonal expansion
= reversible stimulation of prolferation that causes both mutated and normal cells to proliferate
PROGRESSION
new phenotype with clonal expansion --> malignant metastases
= irreversible enhancement/repression of gene expression + selection of neoplastic cells for optimal growth genotype/phenotype in response to cellular environment
52
Give three examples of carcinogenesis from occupational exposure.
- scrotal cancer in chimney sweeps
- bladder cancer in dye industrial workers
- mesothelioma from asbestos exposure
53
What are the two genes most commonly mutated in smoking-induced lung cancer?
K-Ras and p53
54
What percentage of the population is null for glutathione S transferase? How does that relate with risk of smoking-induced lung and bladder cancer?
30-50% of individuals null
GSTM1 detoxifies carcinogen --> homozygous null individuals have increased risk of smoking-induced cancer
55
What is the increased risk of passive smoking?
15-24%
56
To which carcinogen are nitrites and nitrates converted to in the GI tract?
nitrosamines
57
What cancer risks are associated with aflatoxins?
- heavy or prolonged exposure: liver carcinoma
| - aflatoxins + hep B predisposes to liver cancer
58
What makes the difference between rates of GI tumours in the small intestine and in the colon?
small intestine: no Bcl2 expression, damaged cells die
| large intestine: Bcl2 expressed, protects damaged cells from dying
59
How is the increasing incidence of malignant melanoma in the UK since the 1970s explained?
behavioral change of the population
60
Which 2 types of skin cancer are caucasians most susceptible to?
- melanoma
| - basal cell carcinoma
61
Give two examples of radiation-induced cancers.
- necroses and skin cancer in early radiologist
- leukaemia in A-bomb survivors
- bone cancer in radium-dial paiter
62
What are the three main actions of NSAIDs?
- anti-pyretic
- anti-inflammatory
- analgesic
63
Describe the two main mechanisms of action of NSAIDS.
IRREVERSIBLE TIME-DEPENDENT INHIBITION
terminal serine of COX enzyme acetylated by drug --> irreversible inhibition --> further COX synthesis required for production of prostaglandins
REVERSIBLE COMPETITIVE INHIBITION
drug binds reversibly to COX and compete with arachidonic acid
64
What are the 3 products of arachidonic acid metabolism?
- prostaglandins
- leukotrienes
- thromboxanes
65
Differentiate between COX1 and COX2 enzymes.
COX-1
- constitutive
- important in maintenance of GI tract integrity
- example of inhibitor: flurbiprofen
COX-2
- inducible
- involved in inflammatory response and cancer development
- example of inhibitor: celecoxib
66
What are the three main prostaglandins that accompany inflammation? What are their 3 functions?
PGE2, PGI2, PGD2
- potent vasodilators
- synergise with histamine and bradykinin
- potentiate histamine and bradykinin
67
What type of mechanism of action does aspirin uses?
both irreversible (pro-drug: acetylsalicylic acid) and reversible competitive (active compound: salicylic acid) inhibition
68
What are the 6 categories of unwanted effects of salicylates?
- stomach
- systemic
- metabolic changes
- haemostasis
- CNS effects
- renal
69
Give 2 examples of propionic acids, one of coxibs and one of fenamates.
PROPIONIC ACID
ibuprofen, naproxen
COXIBS
celecoxib
FENAMATES
mefenamic acid
70
Which role of NSAIDs does paracetamol not fulfill?
anti-inflammatory
71
What is the main risk in case of overdose?
hepatotoxicity
72
What are the clinical uses of NSAIDS?
- analgesia (headache, dysmennorrhea, backache, bony metastases of cancer, post-operative pain)
- chronic or acute inflammatory conditions
- lower temperature
73
In a basic examination of the hip, what do you look for during the inspection of the hips?
- mal-alignment/deformity of legs
- wasting of gluteal muscle bulk
- swelling, redness, scars over and around the hip
74
What does Thomas test investigate for?
Hip flexion contracture, see in arthritis and neuromuscular disorders
75
What other examinations would you offer for completeness after a basic examination of the hip?
- examination of contralateral hip
- examination of knee and lumbar spine
- neurological examination of lower limb
- assessment of gait
76
How do you perform a patellar tap?
1) knee extended, use left hand to empty any fluid out of the suprapatellar bursa into the knee
2) keep your hand over the bursa to maintain pressure and prevent it refilling
3) attempt to tap the patella against the femoral condyles with right hand
77
Which 4 structures do you inspect for stability in a knee examination?
- medial collateral ligament
- lateral collateral ligament
- anterior cruciate ligament
- posterior cruciate ligament
78
What 3 main characteristics of tumour cells are not exhibited by normal cells?
- uncontrolled proliferation
- invasiveness
- metastases
79
What are the three main approaches to treating cancer?
- surgical excision
- radiotherapy
- chemotherapy
80
What are the 4 types of traditional agents for chemotherapy? Which one is the most commonly used?
- alkylating agents (most commonly used)
- antimetabolites
- cytotoxic antibiotics
- plant derivatives
81
What is the general mechanism of action of alkylating agents?
covalent bonds with DNA --> intrastrand crosslinking, opening of rings and depurination --> DNA damage triggers cell death by apoptosis
82
Name the 6 major groups of alkylating agents, and one drug for each of these groups.
- nitrogen mustards (cyclophosphamide)
- ethylenimines (Thiopeta)
- alkylsulphonates (Busulphan)
- hydrazines and triazines (Temozolomide)
- nitrosoureas (lomustine)
- platinum based compound (cisplatin)
83
Which condition would you treat using Busulphan?
chronic granulocytic leukaemia
84
Which group of alkylating agents is used to target tumours of the brain and meninges, thanks to their ability to cross the blood-brain barrier?
Nitrosoureas
85
What are the 3 major groups of antimetabolites? Give one example of drug for each.
- antifolates (methotrexate)
- antipyrimidines (5-FU, gemcitabine)
- antipurines (mercaptopurine, thioguanine)
86
What are the four possible routes of administration of methotrexate?
oral, IV, intramuscular, intrathecal
87
Explain the mechanisms of action of 5-FU and cytarabine.
5-FU:
fraudulent nucleotide
CYTARABINE:
analogue of cytosine, that undergoes phosphorylation and becomes a DNA polymerase inhibitor
88
What is 'lethal synthesis' of mercaptopurine?
conversion to fraudulent nucleotide that inhibits a number of enzymes in the de novo synthesis of purines
89
Which type of chemotherapy agent do anthracyclines belong to?
cytotoxic antibiotics
90
Which enzymes are respectively targeted by doxorubicin and dactinomycin?
DOXORUBICIN
inhibits topoisomerase II
DACTINOMYCIN
inhibits RNA polymerase
91
Which stages of the cell cycle are targeted by bleomycins?
G2, mitosis and G0
92
Give the 4 types of plant derivatives used as chemotherapeutic agents.
- vinca alkaloids
- taxanes
- camptothecins
- etoposide
93
Give the name and type of cancer targeted by 3 novel targeted anticancer agents.
RITUXIMAB
B cell lymphoma
TRASTUZUMAB (HERCEPTIN)
breast cancer
IMATINIB
chronic myeloid leukaemia
94
Give the 5 main drawbacks of cancer chemotherapy.
- target cell proliferation and not more lethal invasiveness and metastases
- non-specific cell killers
- development of resistance
- remaining stem cells after treatment
- patient complience due to side-effects
95
What two sorts of genes are altered in carcinogenic processes?
- oncogenes
| - tumour suppressor genes
96
How are oncogenes activated?
single dominant mutation event in proto-oncogene --> excessive cell survival and proliferation
97
What are the 3 ways a proto-oncogene can become an oncogene?
- mutation in coding sequence
- gene amplification
- chromosomal rearrangement
98
What types of genes can become oncogenes?
genes coding for:
- growth factors
- growth factor receptors
- signal transducers
- transcription factors
99
Describe the 4 possible mechanisms of action of oncogenes.
- direct stimulation of cell cycle dependent transcription
- increased/activation of growth factor receptors
- increased growth factor production
- interference with intracellular signalling
100
How are tumour suppressor genes inactivated?
Knudson's two hit hypothesis:
| 2 recessive mutation events that each inactivate one gene copy --> excessive cell survival and proliferation
101
What are the two types of tumour suppressor genes? Describe their respective roles.
GATEKEEPERS
send negative signals to cells to inhibit proliferation of promote death of cells, especially those with DNA damage
CARETAKER
maintain integrity of the genome by promoting DNA repair
102
Give 3 different systems for DNA repair.
- mismatch repair
- nucleotide excision repair
- DNA double strand break repair
103
What 6 stimuli do p53 respond to? What are the 4 possible responses?
STIMULI
- lack of nucleotides
- UV radiation
- ionizing radiation
- oncogene signalling
- hypoxia
- blockage of transcription
RESPONSES
- cell cycle arrest
- DNA repair
- block of angiogenesis
- apoptosis
104
Give on example of an oncogene. Give one example of a gene that is both a caretaker and a gatekeeper.
ONCOGENE
Bcl2
CARETAKER + GATEKEEPER
p53
105
Which enzyme can give tumour cells the limitless ability to proliferate?
telomerase
106
Describe the angiogenesis cascade started by a tumour cell.
tumour cell lacks oxygen --> secretes VEGF (vascular endothelial growth factor) --> VEGF binds to receptor on endothelial cell --> endothelial cell activated --> endothelial cell secretes MMPs (matrix metalloproteinases) that digest surrounding matrix --> activated endothelial cell migrates and divides
107
What are the main characteristics of toumour-driven angiogenesis?
- unstable
- abnormal structure
- abnormal function, inappropriate to location
- much more permeable
