Week 4 Flashcards
How are X-rays produced?
They are produced when beam of X-rays are passed through the human body and detected by photographic film
How can tissues be differentiated amongst on an X-ray?
The tissues absorb different amounts of radiation
What colours will tissues appear on X-rays?
Gas-black
Fat-dark grey
soft tissues (except fat) - grey
Bone - white
Metal objects - bright white
What are X-rays good for?
-Bone fractures breaks
-Tooth/dental problems
-Scoliosis
-Tumours
What are ultrasounds?
They produce pictures of the inside of the body using high frequency sound waves
How do ultrasounds work?
High frequency sound waves travel through the body and bounce off structures back to a transducer which uses these to form a picture
What are the benefits of ultrasounds?
-They don’t use ionizing radiation
- Images are in real time so can show movement of organs and blood in vessels
What is a colour doppler?
Uses a computer to convert the scan into an array of colours to show the speed and direction of blood flow
What is a power doppler?
Provides greater detail of blood flow but not direction
What is a spectral doppler?
Shows blood flow in graphs with distance and time
What are the functions of ultrasounds?
-Viewing organs
-evaluating pain causes
-viewing babies in pregnant women
How are MRIs produced?
A strong magnetic field forces the protons in the body to align with that field. A radiofrequent current is the then pulsed through the body causing the protons to push against the field. This current is then turned off and the protons realign with the field and the energy released is detected by sensors in the machine
What is contrast dye used for?
To produce a clearer/brighter image
What are MRIs used for?
Soft-tissue/non-bony parts of the body.They are particularly useful for muscles, ligaments and tendons
How do MRIs differ from CTs?
They don’t use ionizing radiation
How are CTs taken?
Using X-rays that move around the body taking cross sections
When would CTs most commonly be used?
CTs are one of the fastest and most accurate tools for examining the chest,abdomen and pelvis. For this reason they are likely to be used in trauma situations like MVCs
What are PET scans?
They use radioactive tracers to show how well organs and tissues are functioning
How do PET scans work?
The build up of the radiotracer (and where it doesn’t build up) is analysed to work out if there are any abnormalities
What are the functions of PET scans?
-detect cancer
-determine if cancer has spread
-Determine blood flow to organs and tissues
-determine effects of heart attacks
-map normal brain and heart function
What are the two major stages of the cell cycle?
Interphase and m phase (mitosis)
What is the cell cycle?
The interval between two mitotic divisions?
What happens during S phase?
When the DNA is replicated in the nucleus.
What is the purpose of G1 and G2 on each side of the s phase?
Time to allow for cell growth before and after DNA synthesis
What can happen at G1?
The cell either enters the S phase or G0
What is G0?
A resting state where it can remain for days, months or years before re-entering the cell cycle
What happens during m phase?
chromosomes and cytoplasm are separated into two daughter cells
What are the distinct phases of M phase?
Prophase, metaphase, anaphase, telophase and then cytokinesis
What happens in prophase?
Beginning at the emd of G2, the chromosomes begin to condense and form an array of loops. The duplicated centrosomes separate and form the poles of the mitotic spindle
What is prometaphase?
Before metaphase the nuclear envelope breaks down and chromosomes begin to attach randomly to microtubules that come from the two sides of the forming mitotic spindle
When is the cell considered to be in metaphase?
When all chromosomes are properly attached and lined up in their pairs across the equator of the cell
What happens in anaphase?
This is where the exit from metaphase begins. The chromosomes separate abruptly
What happens in telophase?
A contractile ring of actin and myosin assembles as a circumferential belt and constricts the equator of the cell
What is cytokinesis?
The separation of the two daughter cells
How is progression of the cell cycle regulated?
Control networks and checkpoints
What is the restriction point?
a control network that determines if conditions are favourable from the cell cycle to proceed
What happens at the restriction point?
The cell irreversibly commits to the cell division process
What is checked for at the G1 checkpoint?
Appropriate energy reserves and size. If it doesn’t have these things it will enter G0
What is checked for at the G2 checkpoint?
That all chromosomes have been accurately replicated without mistakes or damage
What happens at G2 if problems are detected?
The cell cycle is halted and the cell will either fix the problem or destroy this cell
When does the M checkpoint occur?
near the end of the metaphase stage of mitosis
What is checked for at the m checkpoint?
If the chromatids are correctly attached to the spindle microtubules.
What happens if a cell fails the m checkpoint?
The cell cycle will not proceed until this check point is completed because the separation of sister chromatids is an irreversible step
When do tumours occur?
When cell proliferation goes ahead unregulated/uncontrolled
What (except CdK-cyclin complexes) control the progression and completion of the cell cycle?
Limiting mitogenic growth factors
regulatory genes
How does limiting mitogenic growth factors control the cell cycle?
growth factors such as platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) are limited
How do regulatory genes control the cell cycle?
Regulatory genes actively supress proliferation. These genes, called suppressor genes, control normal cell proliferation.
How does Rb show activity of suppressor genes?
Each cell has duplicate copies of the retinoblastoma gene as a safety back up. When both copies are mutated, an abnormal Rb protein induces cancerous growth of the retinal cells
How do teratomas arise?
When germ cells lodge in extragonadal sites
What are germ cells?
a cell containing half the number of chromosomes of a somatic cell and able to unite with one from the opposite sex to form a new individual; a gamete.
what are teratomas?
Bizarre growths that contain many different types of tissue such as skin, hair, cartilage and even teeth.
Are teratomas malignant or benign?
they can be either
What stages must cells go through in order to metastasize?
-They have to be able to break away from the original tumour and enter either the blood or lymph
-They need to be able to attach to the wall of a blood/lymph vessel and move through it to a new organ
-they must be able to grow and thrive in their new location
-they need to be able to avoid attacks from the body’s immune system
What are proto-oncogenes?
Genes that normally help cells to grow
What happens when a proto-oncogene mutates?
It becomes a bad gene that can become permanently turned on or activated when it’s not supposed to be
What can happen when proto-oncogenes go ‘bad’?
Cells grow out of control and can lead to cancer
What is an oncogene?
The ‘bad’, permanently activated proto-oncogene.
What is the ‘bad’, permanently activated proto-oncogene now known as?
An Oncogene
How do most cancer causing oncogenes occur?
They are mainly acquired rather than inherited
What are oncogenes usually activated by?
-Chromosome rearrangements
-Gene duplication
How do chromosome rearrangements cause the activation of oncogenes?
Changes in chromosomes that put one gene next to another which allows one gene to activate the other
How does gene duplication cause the activation of oncogenes?
Having extra copies of a gene can lead to it making too many copies of a certain protein
What gene abnormality us found in more that half of human cancers?
The TP53 gene - codes for the protein p53
What is Intraepithelial neoplasia?
New growth within the epilelium
What is meant by a benign tumour?
The tumour does not invade nearby tissues but can be serious if it is pressing on vital structures like blood vessels, nerves or organs
What is meant by a malignant tumour?
They are cancerous and can metastasize. The hae a fast growth rate.
What is metastasis?
When a tumour spreads to nearby tissues
Why do malignant tumours stop differentiating?
because they proliferate so fast, they also dont receive the signal to switch from proliferation to differentiation
Which type of tumour has the bigger chance of relapse?
malignant
What is a tumour?
A tumour is formed by an excessive, uncontrolled proliferation of cells as a result of irreversible genetic change which is passed from one tumour cell to its progeny
What is cancer?
A neoplastic disease of which the natural course of which is (often) fatal
For epithelial tumours what is the normal way in which cells change to become cancerous?
normal > dysplasia > benign > pre-malignant > malignant
What is dysplasia?
“Bad growth” - loss of architectural orientation and development of cellular atypic. Cannot yet invade neighbouring tissue so is not cancer
What is metaplasia?
cells change from one differentiated tissue to another. Unstable environment so high chance of mutations in DNA - precursor to dysplasia and cancer
What are some modes of cancer spread?
local invasion
lymphatic spread
blood spread
transcolaemic spread
What do proto-oncogenes do?
Code for proteins that are needed for normal cell proliferation
What is a oncogene?
a mutated proto-ongogene
what are activating mutations?
only certain mutations in a proto-oncogene will convert it to the oncogenic form
What does the activation of proto-oncogenes do?
allows cells to bypass the need for extracellular growth signals
Why are porto-oncogenes described as dominant acting?
only one allele of a photo-oncogene needs to be acquire an activating mutation
What do oncogenes code for?
a hyperactive version of a protein product
or
normal protein BUT
in abnormal quantities
at the wrong time
in the wrong cell type
What mutations can lead do hyperactive proteins being formed?
point mutation - e.g ras Ki-ras in colon cancer
deletion
chromosomal rearrangement e.g. ber-able in CML
What mutations can cause proteins to be formed in the wrong place, time or amount?
gene amplification (HER2) breast cancer
Chromosomal rearrangement - places gene downstream of a promoter e.g lg-myc
What external signals for growth be mutated to lead to cancer?
hormones
peptide growth factors
Give examples of cell surface receptors that can be mutated
HER2
EGFR
Give examples of intracellular molecules that can be mutated?
signal transducers (ras)
cyclins (cyclin D)
transcription factors (myc)
What can constitutive telomerase expression do?
hay flick limit not reached so the cell is immortalised
What is a benign tumour?
stay localised at their site of origin
What is a malignant tumour?
able to invade and spread to different sites
What are the b and m endings for epithelial tumours?
oma and carcinoma
what are the b and m names for covering epithelium tissues?
papilloma and carconoma
what are the b and m names for glandular epithelial tumours?
adenoma, adenocarcinoma
What are the b and m names for tumours in the epithelium forming organs (e.g. liver)
adenoma
carcinoma e.g. hepatocarcinoma
What are the b and m endings for connective tissue tumours?
oma
sarcoma
what are the b and m names for smooth muscle tumours?
leiomyoma
leiomyosarcoma
what are the b and m names for skeletal muscle tumours?
rhabdomyoma
rhabdomyosarcoma
what are the b and m names for bone forming tumours?
osteoma
osteosarcoma
what are the b and m names for cartilage tumours
chondroma
chondrosarcoma
what are the b and m names for fibrous tumours?
fibroma
fibrosarcoma
what are the b and m names for tumours of blood vessels
angioma
angiosarcoma
what are the b and m names for adipose tissue tumours?
lipoma
liposarcoma
what are the b and m names for lymphoid tumours?
n/a
lymphoma
what are the b and m names for haematopoetic tumours?
n/a
leukaemia
what are the b and m names fir primitive nerve cell tumours?
n/a
neuroblastoma e.g. retinoblastoma
what are the b and m names fir glial cell tumours?
n/a
glioma e.g. astrocytoma
what are the b and m names for tumours in melanocytes?
pigmented naevi
malignant melanoma
what are the b and m names for tumours in the mesothelium?
n/a
malignant mesothelioma
what are the b and m names for tumours in germ cells
teratoma
teratoma, seminoma
How do tumours get an adequate nutrient supply once they are larger than 1-2mm?
secrete VEGF (vascular endothelial growth factor)
promotes production of new vascular tubules
what are MMPs?
matrix metalloproteinases (chew up basement membrane)
what is uPA?
urokinase plasminogen activator
What are some risk factors for cancer?
age
alcohol
cancer-causing substances
chronic inflammation
diet
hormones
immunosuppression
infectious agents
obesity
radiation
sunlight
tobacco
what happens during G1?
growth in mass, centrosome duplication
what happens during s phase?
chromosome duplication - synthesis of DNA
what happens during G2?
cell grows in size, duplicating organelles and preparing for division
what happens during cytokinesis?
cleavage of daughter cells
what are the 5 stages of mitosis?
prophase
pro-metaphase
metaphase
anaphase
telophase
what happens during prophase?
chromatin condensation
nucleolus disappears
centrioles move to the poles of the cell
what happens during pro-metaphase?
nuclear membrane dissolves
chromosomes attach to microtubules and begin moving
What happens during metaphase?
spindle fibres align the chromosomes along the middle of the cell nucleus (metaphase plate)
What happens during anaphase?
paired chromosomes separate and move to opposite sides of the cell
What happens during telophase?
chromatids arrive at opposite poles of the cell
new membranes form around the daughter nuclei
chromosomes decondense
spindle fibres disperse
What are cyclin-dependent kinases?
serine / threonine kinases that require the binding of cyclin for full activity
regulate progression through the cell cycle
activity must be tightly regulated
waves of expression of specific cyclins
phosphorylation / dephosphorylation
What are cyclins?
activator proteins that are up - or down - regulated depending on the phase of the cell cycle
What are cyclin-dependent kinase inhibitors?
small proteins that block cdk/cyclin activity either by forming an inactive complex or acting as a competitive CDK ligand
What is the cyclin / cdk complex needed at the end of G1?
CDK4/6 - cyclin D
What is the cyclin / cdk complex needed for progression through mitosis?
CDK1 - cyclin B
What is CDK1 - cyclin B also known as?
maturation promoting factor (MPF)
What are the four well established check points in the cell cycle?
restriction point (G1)
DNA damage check points (end of G1 and G2)
Metaphase check point
What is cell cycle progression dependent on?
growth factors
the accumulation of which cyclin means that no growth factors are required for the rest of the cell cycle and that cell is committed to cell division?
cyclin D
What acts as the gate keeper at the restriction point?
retinoblastoma (RB)
What is the function of p53?
cellular stress e.g. DNA damage leads to transcription of p53
at low levels this results in p21 expression which arrests the cell cycle and allows time for the DNA to be repaired
at high levels it promotes apoptosis of the cell
What are the benefits and limitations of X-rays?
good for bones
chest X-ray
abdomen limited
What are the benefits and limitations of CT scans?
excellent for bones
chest and abdomen
25 seconds
limited for soft tissues of spine, limbs and brain
What are the benefits and limitations of MRI?
great for brain, spine soft tissues, limbs
less good for abdomen / pelvis
no good for heart or lungs
25 minutes
What is CT?
A modern imaging tool that combines X-rays with computer technology to produce a more detailed, cross-sectional view of the body
How does an MRI work?
Magnetic field around the patient
pulses radio waves
radio waves cause tissues to resonate
a computer measures the rate at which various tissues give of vibrations and converts it into a 2D picture
What are the 3 main stages of life before birth?
pre-implantation
embryonic stage
foetal stage
When is the pre-implantation stage?
week 1
When is the embryonic stage and what does it involve?
weeks 2-8
organogenesis
When is the foetal stage and what does it involve?
weeks 9-38
growth and development
Describe cleavage
mitotic divisions of fertilised oocyte
overall size remains the same
allows passage down narrowest part of the uterine tube (isthmus)
surrounded by a glycoprotein coat - zona pellucida - to prevent premature implantation
Describe morula formation
around day 4, cells maximise contact with each other
a cluster of cells forms held together by tight junctions
enters the uterus
Describe blastocyst formation
first sign of cellular differentiation
inner cell mass - goes on to form embryo and extra-embryonic tissues
outer cells form trophoblast - contributes to placenta
fluid enters via the zona pellucida into the spaces of the inner cell mass
A fluid-filled blastocyst cavity forms
What causes the blastocyst to “hatch”
ICM cells undergo proliferation and fluid builds up in cavity
eventually blastocyst “hatches” from the zona pellucida to facilitate implantation
What happens in week 2?
implantation
what days does implantation occur?
7-12
Which cells implant first?
trophoblast
What does the trophoblast differentiate into?
cytotrophoblast
syncytotrophoblast
what makes up the bilaminal disk?
the epiblast and the hypoblast
Describe the amnion
continuous with the epiblast
persists until birth
cavity fills with amniotic fluid
protection for developing embryo
Describe the yolk sac
continuous with the hypoblast
important for nutrient transfer in weeks 2-3
disappears around week 20
Describe the chorion
trophoblast and extra embryonic mesoderm
forms foetal component of placenta
chorionic cavity seen early in pregnancy disappears when amnion expands
What is gastrulation?
a process of cell division and migration resulting in the formation of three germ layers
What are the three germ layers?
ectoderm
mesoderm
endoderm
Describe the formation of the three germ alters
once the cells have invaginated, some displace the hypoblast creating the endoderm and others between the epiblast and the newly created endoderm form the mesoderm
the remaining cells in the epiblast form the ectoderm
the cells in these layers give rise to all tissues and organs in the embryo
Describe gap junction communication
sieve like structure at plasma membranes of opposing cells
hemi-channels composed of connexin molecules
Hemi-Channels of one cell align with those of another
physical sharing of ions and small cytoplasmic molecules
cells behave as a syncytium
What is endocrine signalling?
long range (blood)
e.g. oestrogen
What is paracrine signalling?
local - neighbouring cells (via diffusion)
e.g. epidermal growth factor
What is autocrine signalling?
same cell
insulin-like growth factor 1
what is juxtracrine signalling?
signal adjacent to receptor
e.g. laminin
What is intracrine signalling?
signal produced in cell acts on nuclear or internalised receptor
e.g. fibroblast growth factor 11
How do steroids work?
diffuse across plasma membrane
bind directly to intracellular receptors
hormone-receptor complex acts as a transcription factor
Affects gene expression directly
