Week 7 Flashcards
(102 cards)
1
Q
What are the two essential features of cell division?
A
- faithful replication of genetic material
- accurate segregation into daughter cells
2
Q
Which phases of the cell cycle make up the interphase?
A
G1, S and G2 phases
3
Q
Describe the activity of cyclin and Cdk during the cell cycle.
A
CYCLIN
- increases linearly from the lowest point during interphase to reach maximum concentration halfway through mitosis
- from there to the end of mitosis: steep fall
CDK
- towards the end of the interphase, cyclin contraction raises from minimum concentration (initiated as the cyclin concentration reaches a threshold)
- beginning of mitosis: steep increase to plateau at maximum concentration
- about 2/3 through mitosis, fall symmetrical to increase
4
Q
Describe the activation process of Cdk.
A
Cdk on its own = inactive
binds to cyclin –> still inactive
Wee1 and Cak each phosphorylates a different site of Cdk –> P from Wee1 is inhibitory, P from Cak is activating
inhibitory P removed by cdc25 –> active cyclin-cdk
5
Q
At what size compared to normal would the cell divide if there was a mutation in the gene coding for cdc25? and in the gene coding for Wee1?
A
CDC25
divides at a bigger size
WEE1
divides at a smaller size
6
Q
What does the R point of the cell cycle represent?
A
at the R point (end of G1): G1/S transition
- production of cyclins E and A
- destruction of nuclear cyclin D1
7
Q
What are the 6 steps of destruction by a proteasome?
A
1- recognition of ubiquitine in series by proteasome
2- release of ubiquitine
3- unfolding of protein (energy-dependent)
4- opening of the proteasome to let in the unfolded protein
5- cleavage
6- discharge of amino acids
8
Q
How many checkpoints are there in each phase of the cell cycle?
A
G1 - 2
S - 1
G2 - 1
M - 1 (metaphase)
9
Q
Name 1 proteins, and its substrate, involved in the inhibition of cell division.
Name 3 proteins, and their substrates, involved in keeping the cell from replicating DNA (G0 phase)
A
p21 –> G1/S-cdk and S-cdk
p16 –> Cdk4 (keeps it from binding to cyclin D)
Rb (retinoblastoma) –> E2F (transcription factor for S-phase genes)
Cdc6 –> origin recognition complex (at origin of replication)
10
Q
What are the two main mechanisms responding to DNA damage?
A
activation of p53 –> direct transcription of cdk-inhibitors
activation of CHK2 –> inhibits cdc25 (–> no activation of cdk)
11
Q
How is the nuclear envelope broken down in mitosis? When does it happen?
A
phosphorylation of nuclear pore proteins and lamins in prometaphase
12
Q
To what part of the chromosomes do microtubules from spindles attach? What proteinsare involved?
A
centromere, through kinetochore and kinetochore microtubules
13
Q
what is checked at the spindle checkpoint in metaphase?
A
chromosomes are properly attached and under tension
14
Q
What disease is caused by defects in cohesion of sister chromatids?
A
Roberts syndrome
15
Q
Which enzyme cleaves and dissociates cohesin rings?
A
separase
16
Q
What can defects at spindle checkpoint cause?
A
aneuploidy
17
Q
What is the cleavage furrow of cytokinesis made of?
A
contractile ring of actin and myosin
18
Q
Give 6 signs of a reversible cell injury.
A
- plasma membrane bleb
- increased intracellular volume
- disaggregated ribosomes
- dilated, vesicular endoplasmic reticulum
- aggregated cytoplasmic elements
- mitochondrial swelling and calcification
19
Q
Define necrosis. Name 6 different types.
A
death of tissues following bioenergetic failure and loss of plasma integrity
- coagulative necrosis
- caseous necrosis
- gangrenous necrosis
- colliquative necrosis
- fibrinoid necrosis
- fat necrosis
20
Q
Name two enzymes that must be inactivated early in apoptosis to allow DNA fragmentation.
A
- PARP (poly ADP-ribose polymerase)
- ICAD (inhibitor of caspase-activated DNase
21
Q
How are apoptotic cells recognized? What is the aim?
A
reorganisation of phosphatidylserine from inner to outer leaflet
if not recognised –> inflammation, risk of necrosis
22
Q
Name two extrinsic triggers of apoptosis and give their key features.
A
DEATH RECEPTORS
- receptor interaction
- cytoplasmic signals (death domains…)
- caspase cascade
T/NK CELL MEDIATED
- perforin and granzymes
- cytoplasmic activation
23
Q
What is the key step involved in apoptosis?
A
release of cytochrome c from mitochondrion –> allows formation of apoptosomes
24
Q
What are apoptosomes made of? How do they work?
A
- adaptor protein
- cytochrome c
- procaspase 9
concentrate activity to push equilibrium towards cell death
25
Which family of proteins acts as a control mechanism of caspases? What is the exception to this family? Why?
Bcl2 family
BAX - does not work as a dimer
26
What are the consequences of Bcl2 overexpression? For what type of cancer is this the main pathology?
a cell that should undergo apoptosis doesn't --> very difficult to kill
B-cell malignancy
27
How can the cell keep IAPs from inactivating caspases after they have cleaved from their prodomains?
The mitochondria also release anti-IAPs from the intermembrane space, through activated BH123 proteins
28
The cleavage of which protein is respectively responsible for the fragmentation of DNA; preventing DNA repair; fragmentation of nuclear architecture; fragmentation of cytoplasmic architecture?
fragmentation of DNA --> cleaves ICAD
preventing DNA repair --> cleaves PARP
fragmentation of nuclear architecture --> cleaves lamin
fragmentation of cytoplasmic architecture --> cleaves keratin
29
Give 4 survival factors.
- increased production of anti-apoptotic Bcl2 proteins
- inactivation of pro-apoptotic BH3-only Bcl2 proteins
- inactivations of anti-IAPs
- caloric restriction
30
Define pyroptosis and anoikis.
PYROPTOSIS
microbes trigger NOD and Toll-like receptors, activating a process with characteristics similar to both necrosis and apoptosis
ANOIKIS
death after losing contact with basement membrane or extracellular matrix
31
Define a bivalent.
A bivalent is made of two replicated chromosomes (one paternal, one maternal) that have been aligned
32
What is the name of the junction of a chiasma in recombination?
Holliday junction
33
Which regions of sex chromosomes in males recombine?
pseudoautosomal regions
34
Which 2 processes in meiosis ensure genetic diversity?
- recombination
| - independent assortment
35
What are the consequences of fertilisation following meiotic errors?
trisomic zygote, not always compatible for life
36
Differentiate between uniparental heterodisomy and uniparental isodisomy.
UNIPARENTAL HETERODISOMY
3 different chromatids after fertilisation
UNIPARENTAL ISODISOMY
3 chromatids after fertilisation, 2 of which are identical
37
Which of first and second meiotic division errors happen more frequently?
first meiotic division errors
38
Describe the processes of spermatogenesis and oogenesis.
spermatogonium --> primary spermatocyte ---(meiosis 1) ---> secondary spermatocyte ----(meiosis 2)----> spermatids ---> sperm
oogonium --> primary oocyte ---(meiosis 1)---> secondary oocyte + first polar body ----(meiosis 2 and fertilisation)---> ovum + second polar body
39
Give two other names for medical abortion, and define.
therapeutic abortion or termination of pregnancy (TOP)
= cessation of pregnancy
40
What are the three domains to consider in regards of abortion?
- ethical issues
- legal framework
- professional responsibility
41
What are the three components of ethical issues in abortion?
- foetal autonomy
- maternal choice
- gestational age
42
What are the 6 medical stage points of abortion? Which one is used in legal texts?
- conception: either fertilisation or implantation
- differentiation
- brain and heart activity
- quickening
- viability
legally: implantation
43
What are the legal issues regarding the mother, father and foetus?
MOTHER
capacity, consent, confidentiality
FATHER
no right to consent
FOETUS
status is imprecise
44
Describe the decision given for S v St George's NHS trust.
the right to refuse treatment (withhold consent when competent) is absolutely irrespective of pregnancy --> the Mental Health Act does not apply to physical conditions
45
What do the GMC and laws say about the right to refuse to provide an abortion on ethical grounds?
LAW
conscientious objection allowed --> right not to participate
in emergency, duty to help
burden of proof
```
GMC
conscientious objection allowed but:
- not allowed to influence patient
- duty to find another doctor
- ...
```
46
What are the conditions to abortion?
- performed by a registered medical practitioner
- opinion of 2 registered medical practitioners
less than 24wks + risk of injury to physical or mental health of woman or existing children
OR
to prevent grave permanent injury to physical or mental health of the woman
OR
risk to life of pregnant woman
OR
risk the child would suffer from such physical or mental abnormalities as to be seriously handicapped
47
What is the occurence of miscarriage in recognised pregnancies? Why is the expected number much higher?
12-24%
a late, heavy period might be overlooked
48
What 4 types of clinical scenarios might a clinician be presented with regarding abortions?
- unplanned pregnancy
- to prevent the birth of a child with severe medical problems
- pregnancy resulting from rape or incest
- medical conditions that endanger the woman's health
49
Give 7 features of each of medical and surgical abortion.
MEDICAL ABORTION
- up to 10wks
- usually avoids invasive procedure/anesthesia
- days to weeks to complete
- high success rate
- bleeding not light
- requires follow-up
- patient participation required through a multiple-step process
SURGICAL ABORTION
- invasive procedure (physical evacuation of foetus)
- use of sedation or general anesthesia
- completable in a predictable period of time
- high success rate
- light bleeding
- does not require follow-up
- patient participation through a single-step process
50
Define unsafe abortion.
a procedure for terminating a pregnancy that is performed by an individual lacking the necessary skills, or in an environment that does not conform to minimal medical standards, or both
51
Give 5 post-abortion risks.
- uterine infection
- residual products of conception
- excessive bleeding
- damage to cervix
- damage to uterus
52
Distinguish between active, passive, voluntary, non-voluntary and involutary euthanasia.
ACTIVE EUTHANASIA
X performs an action which itself results in Y's death
PASSIVE EUTHANASIA
X allows Y to die by witholding or withdrawing life-prolonging treatment
VOLUNTARY EUTHANASIA
euthanasia when Y competently requests death himself
NON-VOLUNTARY EUTHANASIA
euthanasia when Y is not competent to express a preference
INVOLUNTARY EUTHANASIA
death is against Y's competent wishes, although X permits or imposes death for Y's benefit
53
Give the 5 reasons stated for allowing active euthanasia.
- consistency (suicide is legal)
- from passive to active (passive can lead to a slow death)
- from painkillers to lethal injections
- appeal to principles: autonomy and beneficence
- benefits of regulation (policing, doctors more secure)
54
Give the 5 reasons stated against allowing euthanasia.
- respect for sanctity of life
- palliative care
- risk of exploitation/manipulation
- contrary to aims of medicine
- slippery slope
55
Give the 6 reasons why potential organ donors do not become actual organ donors.
- tests for brainstem death not carried out
- refusal by relatives
- medical contraindication to donation
- relatives not asked about donations
- heart stopped beating before brainstem death complete
- organs offered but not retrieved
56
Give the 5 focuses of hospices, that are based on a holistic view of the person.
- physical
- emotional
- psychological
- spiritual
- social
57
What is an autacoid?
a locally produced hormone
58
True or false:
| Acetylcholine and histamine act on the same receptors.
FALSE
59
Between which two structures does the inguinal ligament extend?
- the pubic tubercle
| - the anterior superior iliac spine
60
What is the saphenous opening covered by medially?
cribriform fascia
61
Name the three tributaries of the great saphenous vein.
- superficial epigastric
- superficial circumflex iliac
- external pudendal
62
What is meralgia paresthetica commonly caused by?
compression of the lateral cutaneous nerve of the thigh due to
- tight clothing
- obesity/weight gain
- pregnancy
- trauma
- diabetes
63
What are the borders of the femoral triangle?
- base: inguinal ligament
- medial border: adductor longus
- lateral border: sartorius
- roof: fascia lata
- floor: iliopsoas and pectineus
64
How many compartments are there in the femoral sheath and what do they each contain?
```
3
lateral to medial:
- one for the artery
- one for the vein
- the femoral canal
```
65
What is the lymph node of Cloquet?
single deep inguinal lymph node found in the femoral canal
66
What structure is the mid-inguinal point a landmark of?
the femoral artery
67
Name two branches of profunda femoris.
lateral and medial circumflex femoral arteries
68
What are the borders of the adductor canal?
- floor: adductor longus and adductor magnus
- anteromedial: sartorius
- anterolateral: vastus medialis
69
What are the 4 parts of the quadriceps muscle?
- rectus femoris
- vastus medialis
- vastus intermedius
- vastus lateralis
70
Which two muscles lie in the same anterior plane as gracilis?
- adductor longus
| - pectineus
71
Describe the general organisation of a lipoprotein.
```
CENTRAL CORE
hydrophobic lipids (triglycerides or cholesterol esters)
```
COAT
hydrophilic - polar substances
phospholipids + free cholesterol + associated proteins (apoproteins or apolipoproteins)
72
What are the 5 main classes of lipoproteins? What 4 features vary?
LIPOPROTEINS
- high density lipoprotein
- intermediate density lipoproteins
- low density lipoproteins
- very low density lipoproteins
- chylomicrons
VARIABLES
- core lipids
- apoproteins
- size
- density
73
Explain the roles of chylomicrons, VLDL, HDL and LDL.
CHYLOMICRONS
- transports triclycerides and cholesterol esters from the GI to the tissues
- split by lipoprotein lipase embedded into vascular endothelium to release free fatty acids
- free fatty acids taken up by muscle and adipose tissue
- chylomicron remnants taken up by liver: cholesterol stored, oxidized to bile acids or released to VLDL
VLDL
- transports cholesterol and newly synthesized triglycerides from liver to tissues
- lipoprotein lipase embedded into vascular endothelium remove triglycerides from VLDL
- VLDL becomes LDL with a high cholesterol content
HDL
- absorbs cholesterol from cell breakdown
- transfers it to LDL or VLDL
LDL
- endocytosis by liver cells
74
What two diseases are associated with a high plasma concentration of total and LDL cholesterol?
- atherosclerosis
| - coronary heart disease
75
Give the ideal level, mildly high level, moderately high level and very high level of cholesterol.
ideal level: < 5 mmol/L
mildly high: 5 - 6.4 mmol/L
moderately high: 6.5 - 7.8 mmol/L
very high: > 7.8 mmol/L
76
What are the three sources of cholesterol?
- de novo synthesis in liver
- uptake from circulating LDL
- uptake from chylomicron remnants
77
Describe the mechanism of action of colestyramine, fibrates, nicotinic acid, ezetimibe and statins.
COLESTYRAMINE
- basic anion exchange resin
- sequesters bile acids to prevent enterohepatic recirculation --> increase in metabolism of endogenous cholesterol into bile acids --> increase in LDL receptor numbers in the liver --> more removal of LDLs from blood
FIBRATES
- activator of lipoprotein lipase --> lower triglyceride content of VLDL --> decreased elevated concentrations of VLDL ---> decreased plasma triglycerides and cholesterol
- also stimulates clearance of LDL by liver, increases HDL procution and reverse cholesterol transport
NICOTINIC ACID
- decreased VLDL production --> decreased LDL
- activates lipoprotein lipase
EZETIMIBE
- inhibits a sterol carrier protein in brush border of enterocytes --> reduces intestinal cholesterol absorption
STATINS
- long-lasting inhibitor of HMG-CoA reductase (major rate-limiting step in cholesterol synthesis)
78
Describe the clinical uses of statins and fibrates.
STATINS
- secondary prevention of MI and stroke in those with atherosclerotic diseases
- primary prevention of arterial disease in patients with high serum cholesterol
(atorvastatin only: lowers serum cholesterol in familial hypercholesterolaemia)
FIBRATES
- mixed dyslipidaemia
- patients with low HDL and high risk of atheromatous disease
- combined in patients with severe treatment-resistant dyslipidaemia
79
Give 1 side effect on each of statins, fibrates, colestyramine, ezetimibe and nicotinic acid.
STATINS
- myositis
- angio-oedema
- GI disturbances
- insomnia
- rash
FIBRATES
- myositis
- GI disturbances
COLESTYRAMINE & EZETIMIBE
- GI symptoms (nausea, abdominal bloating, constipation, diarrhea)
NICOTINIC ACID
- flushing
- palpitations
- GI disturbances
80
Give 2 reasons why safe provision of blood is important?
- preventing and managing transfusion reactions
| - prevention of haemolytic disease of the newborn
81
Which 4 genes are involved in the ABO phenotype? Which chromosomes are they on?
FUT1 and FUT2 (chromosome 19) -- > H substance
| A and B genes (chromosome 9) --> glucosyl transferases which add further sugar group
82
Which sugar groups are added to the O antigen to make an A or a B antigen?
B antigen: galactose
| A antigen: N-acetylgalactosamine
83
Give the structure of the O antigen.
fucose
|
galactose-N.acetylglucosamine-galactose-glucose-lipid
84
What are the two most frequent blood groups in the UK? What is the least frequent?
most frequent: O and A
| least frequent: AB
85
Which antibodies would make blood group A, group B, group O and group AB coagulate?
A: anti-A and anti-AB
B: anti B and anti anti-AB
AB: anti-A, anti-B and anti-AB (universal receiver)
O: none (universal donor)
86
On which chromosome is the rhesus system coded for? What are the alleles? What does rhesus negative mean?
chromosome 1
c C D e E
rhesus negative = D negative = no D in inherited triplet
87
When can antibodies for the rhesus system occur?
in response to pregnancy or transfusion
88
Explain the mechanism of disease of haemolytic disease of the newborn. How can it be prevented?
foetal red cells carrying paternal antigens transfer to the maternal circulation --> mother produces IgG antibodies to antigens --> maternal antibodies cross the placenta --> anaemia, jaundice, enlarged liver and spleen, brain damage, foetal death...
prevention: anti-D prophylaxis given to D-negative mothers at 28wks and delivery
89
How is blood cross-matched in transfusion?
- donor blood checked fro ABO, rhesus D and other antigens
- recipient's blood checked for ABO and rhesus D + plasma screened for antibodies against RBC antigens
- recipient's plasma and donor's plasma mixed to check for agglutination
90
What are the 4 types of transfusion reactions? What are they caused by?
ACUTE HAEMOLYTIC REACTIONS
pre-existing antibodies
DELAYED HAEMOLYTIC REACTIONS
new antibodies formed following transfusion
URTICARIA/ANAPHYLAXIS
reaction to drugs/plasma proteins
FEBRILE REACTIONS
HLA antibodies
91
What is the main cause of deaths associated with transfusion?
circulatory overload
92
Give 3 sources of errors in transfusion.
- failure to establish patient's ID when taking blood
- tube labelled incorrectly
- lab errors
- failure to perform bedside check of patient ID when administering blood
93
Describe the process of formation of RBCs.
IN BONE MARROW (7 days)
stem cells
- -> CFU-GEMM cells (colony-forming unit-granulocyte, erythroid, megakaryocyte, macrophage)
- -> CFU - erythroid commited cellls
CFU-Es clustered around macrophages
stimulated by eythropoietin (from kidneys) to make Hb
nucleus extruded from cell into venous sinusoid
IN BLOOD
released as reticulocytes
94
When does thalassaemia appear?
Early childhood
95
What do RBCs look like in spherocytosis. What does it mean in term of lifetime?
convex instead of concave
shorter lifetime
96
Describe the process of auto-immune haemolysis.
auto-antibodies produced directed against RBC membrane antigens
spleen recognises Fc fragment of immunoglobulin
loss of membrane and shortened RBC survival
97
Give 3 causes of aplastic anaemia. What does bone marrow look like in aplastic anaemia?
- predictable dose-related side-effect pf chemotherapy/radiation
- idiosyncratic side-effect of certain medication (chloramphenicol)
- idiopathic
bone marrow with largely over 50% of fat cells
98
Give 4 causes of marrow infiltration.
- myeloma
- leukaemia
- lymphoma
- metastatic tumour
99
How can renal failure affect RBC production?
lack of erythropoietin production --> decreased RBC production as they get stuck at one stage
100
What are the symptoms and signs of chronic myeloid leukaemia?
- symptoms of anaemia
- large spleen
- bone pain
- anaemia
- high WBC and platelet counts
101
Give 4 reasons why chronic myeloid leukaemia is a good target for designer drugs? Give one example and explain its mechanism of action.
- >95% have same genetic and molecular change (Philadelphia chromosome --> BCR-ABL enzyme)
- drug resistance is unusual
- effect can be monitored
- treatment is well tolerated
IMATINIB
competitively binds to BCR-ABL kinase domain active site --> inhibits protein --> tumor cell cannot proliferate
102
What are the signs and symptoms of acute myeloid leukaemia? Why is it not a good target for designer drugs? What problems would you likely encounter during chemotherapy?
- symptoms of marrow failure
- anaemia
- increased risk of bleeding
- frequent infections
- cells are 3 times bigger than RBCs and have crystalline structures
diverse cytogenetic changes --> no single target
- infections (shingles, fungal infections, ...)
- bleeding (distended retinal vessels and haemorrhage)
- psychological issues
- difficult venous access
