Abnormal Growth, Differentiation & Morphogenesis Flashcards
What is meant by cellular adaptations?
Why do they need to occur?
cellular changes in response to changes in environment or demand
they need to occur as a normal cell in its resting state is confined to limited function and structure
What is meant by cellular adaptations being reversible?
when there is a change in demand, the cell adapts and reaches a new steady state of normal
the cell can recover and return to its original state without any harmful consequences
What are the 5 ways in which cells tend to adapt?
- size
- number
- phenotype
- metabolic activity
- function
Why do cells adapt?
they need to acquire a new, steady state of metabolism and structure
this better equips cells to survive in a new environment
What happens if cells fail to adapt?
failure of adaptation may lead to sub-lethal or lethal cell injury
What determines a cell’s susceptibility to environmental change?
whether or not it is able to adapt
some cells don’t need to adapt
some adapt easily
some cannot adapt at all
What is an example of a cell that doesn’t need to adapt?
Why?
fibroblasts
they can survive metabolic stress without harm
e.g. absence of oxygen
What is an example of a group of cells that can adapt easily?
How do they tend to adapt and how are they able to do this?
epithelial cells
they are a labile cell population with an active stem cell compartment
they are highly adaptive in number and function
What is meant by labile cells?
labile cells are cells that multiply constantly throughout life
they have a high turnover
What is an example of a cell that cannot adapt?
Why can it not adapt and what does this mean for the cell?
cerebral neurones
they are terminally differentiated and a permanent cell population
they have a highly specialised function and are easily damaged
What are the 2 types of stimuli that lead to cellular adaptation?
- physiological stimuli
- pathological stimuli
they are not always mutually exclusive - a physiological stimulus can become pathological if it persists for too long
What is an adaptation to a physiological stimulus?
responding to normal changes in physiology or demand
What is an adaptation to a pathological stimulus?
responding to disease related changes
What are the 3 types of adaptive response?
- increased cellular activity
- decreased cellular activity
- change of cell function and/or morphology (type of cells that are there in the first place)
How is an increase or decrease in cellular activity acheived?
through an increased or decreased size or number of cells
What is the difference between hypertrophy and hyperplasia?
hypertrophy:
increase in SIZE of cells
hyperplasia:
increase in NUMBER if cells due to excessive cell division
they both lead to an increased cell mass
How does hypertrophy affect cells, their functional capacity and their metabolism?
there is an increase in size of existing cells and an increase in functional capacity
there is increased metabolism and increased synthesis of structural components
What type of cell populations does hypertrophy tend to be seen in?
permanent cell populations
particularly cardiac and skeletal muscle
these are cells that don’t divide very well
What is the stimulus that leads to hypertrophy in the heart?
chronic haemodynamic overload e.g. due to high blood pressure
this increases the demand of the heart, leading to an increase in size of the muscles
What is an example of physiological hypertrophy?
during pregnancy, the uterus becomes hypertrophied to meet the demands of the growing foetus
What is shown by the different coloured arrows?
green - uterus in an elderly woman
yellow - normal healthy uterus
red - uterus in pregnancy
What changes are seen in the uterus in pregnancy (bottom picture)?
there are fewer cells which are larger
there are spaces between the cells due to oedema (fluid) between the cells
you can clearly see individual cells
What can benign hyperplasia of the prostate gland lead to?
trabeculated hypertrophied urinary bladder
this is because the bladder has to work harder to push urine through the urethra, so it becomes hypertrophied
What is the difference in the skeletal muscle shown?
left - normal 50 year old man
right - veteran marathon runner with hypertrophied skeletal muscle due to increased demands of the cells
What defect/condition is seen in this aortic valve?
it has 2 cusps instead of 3
a congenitally bicuspid aortic valve is more prone to calcification, which makes the valve stiff
this is aortic stenosis
How can aortic stenosis affect the ventricles of the heart?
a stiff calcified valve means the myocardium has to work harder to open the valve
this leads to left ventricular hypertrophy
What condition is shown in this image?
the bottom image shows left ventricular hypertrophy
the cardiac myocytes cannot increase in number by dividing so have increased in size
Other than aortic stenosis, what are other causes of LVH?
1, hypertension increases peripheral resistance so the heart has to work harder to pass blood around the body
- mitral and aortic regurgitation
- hypertrophic cardiomyopathy
What are the symptoms of LVH?
there are no symptoms for a long time and then:
- breathlessness
- decrease in exertion levels
- tired when walking up stairs
- palpitations
- dizziness and fainting
How is LVH diagnosed?
- clinical examination
- ECG or echocardiogram
- other imaging of the heart
What are the problems associated with LVH, relating to blood supply?
hypertrophied muscle needs an increased blood supply, but the blood supply has not changed
this leads to problems with ischaemia, risk of MI
How can LVH lead to an increased risk of stroke?
the myocardium becomes dilated
aneurysm formation can lead to clots and thrombuses forming in the dilated myocardium
What is meant by subcellular hypertrophy and hyperplasia?
an increase in size and number of subcellular organelles
How can barbiturates lead to subcellular hypertrophy and hyperplasia?
What is the main problem with this?
barbiturates cause hypertrophy of smooth endoplasmic reticulum in hepatocytes
this increases the amount of P450 mixed function oxidases
increasing ER leads to an increased metabolism of other drugs
What is hyperplasia?
In which cell populations can it occur?
an increase in number of cells caused by cell division
this is possible in labile and stable cell populations
What are the 2 types of physiological hyperplasia?
hormonal:
increase in the capacity of an organ to perform its function
compensatory:
an increase in cell number needed due to injury
What are the outcomes of pathological hyperplasia?
It can be hormonal or growth factor driven
it leads to either:
- proliferation of mature cells
- increased output of new cells
What is shown in this image?
hyperplasia of breast tissue
this can occur physiologically or pathologically in response to certain drugs
How is Graves disease an example of hyperplasia?
- autoantibody to TSH receptor leads to constant stimulation of the thyroid gland
- thyroid gland becomes hyperplastic to meet demand
- there is constant production of T3 and T4 leading to patient becoming hot, sweaty, lose weight and have palpitations
How can the liver undergo both physiological and pathological hyperplasia?
physiological:
when parts of the liver are removed from a living donor, the liver can divide and regenerate
pathological:
when the liver regenerates after damage, it leads to nodules of regenerating tissue surrounded by areas of fibrosis
What is meant by atrophy?
reduction in size of organ or tissue by decrease in cell size and normal
What are examples of physiological atrophy?
- the uterus atrophies after pregnancy or menopause
- during embryogenesis many structures will atrophy and disappear
What are the 2 types of pathological atrophy?
- localised
- generalised
What are the 6 types of pathological atrophy?
- disuse atrophy - due to decreased workload
- denervation atrophy - due to loss of innervation
- diminished blood supply
- inadequate nutrition
- loss of endocrine stimulation
- pressure
What is an example of pressure atrophy?
if a tumour is compressing another organ, this may lead the other organ to become atrophic
What are the 2 types of atrophy which may occur in the thyroid gland?
physiological:
there is natural atrophy in the thymus from childhood to adulthood
pathological:
steroid use reduces the release of ACTH causing the adrenal gland to shrink as it is not being used
What are the 2 ways in which atrophy occurs?
How is this acheived?
- reduction in volume of individual cells
- death of individual cells
this is acheived through:
- decrease in normal protein synthesis of the cell
- increase in protein degradation
What is meant by agenesis?
complete failure of an organ to develop at all
What is meant by aplasia?
failure of an organ to attain size or function but there is some recognisable tissue present
What is meant by dysgenesis?
abnormal organ development during embryonic growth
What is meant by hypoplasia?
under-development or incomplete development of a tissue or organ
What occurs if organ development fails at each of the following stages
What is meant by metaplasia?
the transformation of one differentiated cell type into another
this is acheived by trans-differentiation of stem cells
it is REVERSIBLE
Why does metaplasia occur?
Which tissues tend to be affected?
it occurs to allow cells to become better adapted to a new environment
it can affect epithelium and mesenchymal tissues
What are the 2 types of cell in the cervix?
What cellular changes occur in the cervix during puberty?
Ectocervix is made from stratified squamous epithelium to withstand outside environment
Endocervix is made from columnar cells
During puberty, the endocervix moves down and becomes exposed
There is a change in cell type from columnar to stratified squamout
Which part of the cervix is more vulnerable to cancer and why?
transition zone
this is where the epithelium changes from columnar and stratfied squamous
this area of metaplasia is turning over more quickly and is more vulnerable to HPV infection
Fill out the table
What types of carcinomas can develop from the following metaplasias?
What is dysplasia?
Why is it important to detect?
dysplasia is disordered growth that is IRREVERSIBLE
it is the earliest morphological manifestation of multistage process of neoplasia
it shows cytological features of malignancy, but no invasion
What is meant by dysplasia being ‘in-situ’?
it is non-invasive
the cancer has not yet invaded through the basement membrane and spread
Why is dyplasia important to detect?
it gives a chance to treat a potentially fatal tumour before it arises
the abnormal cells have not yet acquired the capacity for invasion so they cannot spread
What are the stages in dysplasia leading to carcinoma?
