Cellular Adaptations Flashcards
What does the size of cell populations in adults depend?
The rate of cell proliferation, cell differentiation and cell death by apoptosis
What are increased cell numbers seen with?
Increased cell proliferation or decreased cell death
What may cell proliferation occur as the result of?
Physiological or pathological conditions
Give an example of where excessive physiological stimulation can become pathological
Prostatic hyperplasia
What do proto-oncogenes do?
Regulate normal cell proliferation
How do cells in a multicellular organisms communicate?
Through chemical signals
How is cell proliferation largely controlled?
Largely by signals (soluble or contact dependant) from the microenvironment which either stimulate or inhibit cell proliferation
What are the potential final outcomes of signalling biochemistry?
Divide
Differentiate
Survive
Die
How do cells divide?
They enter the cell cycle
What happens when cells differentiate?
They take on a specialised form and function
How do cells die when signalled?
They undergo apoptosis
What are the types of cell signalling?
Autocrine
Paracrine
Endocrine
What is autocrine signalling?
Cells respond to the signalling molecules that they themselves produce
What is intracrine signalling?
A type of autocrine signalling whereby the cell synthesises a factor which has an effect by binding to intracellular receptors within the cell.
The factor is therefore not secreted by the cell
What is paracrine signalling?
A cell produced the signalling molecule, which acts of adjacent cells
Where are the effector cells in paracrine signalling?
Close to the secreting cell
Are the cells affecting by paracrine signalling the same as the one secreting?
No, they are often of a different type
What is endocrine signalling?
Hormones are synthesised by cells in an endocrine organ, and then conveyed in the blood stream to target cells to effect physiological activity
What happens when a signalling molecule binds to a receptor?
It causes a series of events, which results in modulation of gene expression
Where are the receptors to signalling molecules located?
Usually in the cell membrane, but can also be in the cytoplasm or nucleus
Give an example of a type of receptor located in the nucleus?
Steroid hormone receptors
What can cell to cell signalling be via?
Local mediators
Direct cell-cell or cell-stroma contract
Hormones
What is particularly important amongst local mediators for cell proliferations?
Growth factors
What are growth factors?
Polypeptides that act on specific cell surface receptors
What codes for growth factors?
Proto-oncogenes
How do growth factors differ from hormones?
Hormones from endocrine organs travel via the blood stream to reach their target cells, whereas growth factors act only over a short distance, or on the secreting cell itself
Do growth factors act on many cell types, or restricted targets?
There are many different types of growth factors, some which act on many cell types and some on restricted targets
What do growth factors do?
Stimulate cell proliferation or inhibition
May also affect cell locomotion, contractility, differentiation viability, activation and angiogenesis
How do growth factors exert their effects?
They bind to specific receptors and stimulate transcription of genes that regulate the entry of the cell into the cell cycle and the cell’s passage through it
Give 4 examples of growth factors
Epidermal growth factor
Vascular endothelial growth factor
Platelet-derived growth factor
Granulocyte colony-stimulating factor
What does epidermal growth factor (EGF) do?
Mitogenic for epithelial cells, hepatocytes and fibroblasts.
What produces EGF?
Keratinocytes, macrophages and inflammatory cells
What does EGF bind to?
Epidermal growth factor receptor (EGFR)
What does vascular endothelial growth factor (VEGF) do?
It is a potent inducer of blood vessel development (vasculogenesis), and has a role in growth of new blood vessels (angiogenesis) in tumours, chronic inflammation and wound healing
Where is platelet-derived growth factor (PDGF) stored?
In platelet α granules
When is PDGF released?
On platelet activation
Other than platelets, what produced PDGF?
Macrophages, endothelial cells, smooth muscle cells and tumour cells
What doe PDGF do?
Causes migration and proliferation of fibroblasts, smooth muscle cells and monocytes
What does granulocyte colony-stimualting factor (G-CSF) do?
Stimulates the bone marrow to produce granulocytes, particularly neutrophils, and release them into the blood
What is G-CSF used as?
A treatment to stimulate poorly functioning bone marrow, e.g. during chemotherapy
What happens when a cell receives instruction to divide?
The cell enters the cell cycle
What is the sequence of the cell cycle?
G1 → S → G2 → M
What happens after cell cycle completion?
The cell either re-starts to process from G1, or exists (G0) until further growth signals occur
What can happen to cells in G0?
They can undergo terminal differentiation
What is the result if cells undergo terminal differentiation?
There is a permanent exit from the cell cycle
How does increased growth of tissue occur?
Either by shortening the cell cycle, or by conversion of quiescent cells to proliferating cells by making them enter the cell cycle
What can be seen of the cell cycle under the light microscope?
Only M (mitosis) phase is distinctive
What does the M phase of the cell cycle consist of?
Mitosis and cytokinesis
What is mitosis?
Cellular division
What is cytokinesis?
Cell division to yield two daughter cells
What is the part of cell cycle that isn’t M called?
Interphase
What does interphase encompasses?
G1, S, and G2
What is G1?
Gap 1- pre synthetic, where the cell grows
What is S?
DNA synthesis
What is G2?
Gap 2, premitotic where the cell prepares to divide
Cumulatively, what does interphase include?
DNA replication and protein synthesis for growth in cell size
What is cell cycle progression controlled by?
Key ‘checkpoints’ which sense damage to DNA and ensure cells with damaged DNA do not replicate
What is the most critical cell cycle checkpoint?
Restriction (R) point
When is R?
Towards the end of G1
What happens to cells that pass the R checkpoint?
The majority of them will complete the full cell cycle
What happens if R checkpoint activation occurs?
The p53 protein suspends the cell cycle and triggers DNA repair mechanisms, or, if the DNA cannot be repaired, apoptosis.
Where are the other cell cycle checkpoints?
At the G1/S transition, and G2/M transition
What is checked for at the G1/S checkpoint?
DNA damage before DNA replication
What is checked for at the G2/M checkpoint?
DNA damage after DNA replication
What are defective cell cycle checkpoints a major cause for?
Genetic instability in cancer cells
What is progression through the cell cycle tightly regulated by?
Proteins called cyclins and associated enzymes called cyclin-dependent kinases (CDKs)
Which stage of the cell cycle is particularly tightly regulated?
The G1/S transition
How do CDKs become active?
By binding to and complexing with cyclins
How do activated CDKs drive the cell cycle?
By phosphorylating proteins that are critical for progression of the cell to the next stage of the cell cycle
What is the activity of cyclin-CDK complexes tightly regulated by?
CDK inhibitors
How do growth factors work, with regard to CDKs?
Some by stimulating the production of cyclins
Some by shutting off production of CDK inhibitors
How are cells classified based on their ability to multiply?
Labile
Stable
Permanet
What are labile cells?
Cells that continue to multiply through their life
What are stable cells?
Cells that can multiply in a regenerative burst, but are usually quiescent
What are permanent cells?
Cells that cannot proliferate
How has the classification of cells depending on how they divide been modified?
Following our understanding that many terminally differentiated cells can’t divide, and following the discovery that cells in a tissue are very often replaced by cells derived from stem cels and not mature differentiated cells
Are stem cells present in adult tissues?
Yes, many of them
What are stem cells?
Cells with prolonged proliferative activity which show asymmetric replication
What happens in asymmetric replication?
One of the daughter cells remains as a stem cell while the other differentiated into a mature, non-dividing cell
How are embryonic stem cells different to normal adult stem cells?
In that they are pluripotent and can give rise to any of the tissues in the human body. Adult stem cells can usually only give rise to one type of adult cell- their lineage is specific
How has the classification of cells by their ability to divide developed?
We now consider the classification in relation to tissues (a group of similar specialised cells with a specific function)
What can cell populations be classified as?
Permanent cell populations
Labile cell populations
Stable cell populations
What has happened in permanent cell populations?
The terminally differentiated cells within some tissues have left the cell cycle and cannot replicate
Give 3 examples of permanent cell populations?
Cardiac muscle
Skeletal muscle
Neural tissue
Can stem cells be present within permanent cell populations?
Yes, but they cannot mount an effective proliferative response against significant cell loss
What happens if neurones are destroyed?
The tissue space is filled by glial cells
How does skeletal muscle have a very limited regenerative capacity?
Through stem cells attached to the endomysial sheath
How does damage to the heart heal?
With a scar
Why does damage to the heart heal with a scar?
Because no stem cells are present in the heart
Give two examples of labile cell populations
Bone marrow
Epithelium
What do labile cell populations such as in bone marrow and epithelium consist of?
Mature differentiated cells that cannot replicate
Why is tissue such as bone marrow and epithelium considered proliferative?
As the cells in them are short lived, and are continually being replaced by cells derived from stem cells
What can stable cell populations be said to be?
An intermediate between permanent and labile tissues
Give two examples of stable cell populations
Liver
Kidney
What cells are involved in proliferation in stable cell populations?
Mature cells as well as stem cells
Give 5 examples of cells that are usually non-replicating, but can be induced to enter to cell cycle and replicate if necessary
Liver hepatocytes Bone osteoblasts Fibroblasts Smooth muscle cells Vascular endothelial cells
What is required to induce a usually non-replicating cell to enter the cell cycle?
A large number of genes
What genes arerequired to induce a usually non-replicating cell to enter the cell cycle?
Proto-oncognes
Genes required for ribosome synthesis and protein translation
Are stem cells present in stable cell populations?
Yes
What state are the stem cells in stable cell populations in?
Usually quiescent, or proliferate very slowly, however they can proliferate persistently when required
What is the regenerative capacity of bone?
Very good
What is the regenerative capacity of tendons?
Poor
Why do tendons heal very slowly?
As they have few cells and few blood vessels
What is the result of tendons healing very slowly?
Secondary rupture at a site of previous injury is not uncommon
What is the regenerative capacity of articular cartilage?
Poor
What is the regenerative capacity of adipocytes?
Nil
How are new fat cells formed?
By undifferentiated but committed cells that lie among the adipocytes
What is the regenerative capacity of epithelia?
Very good
What exceptions are there to epithelia having a very good regenerative capacity?
Lens of the eye
Renal podocytes
Where will surface epithelia regenerate?
Over denuded areas
What is the regenerative capacity of the liver?
Very good
How is the regeneration capacity of the liver shown in transplant patient?
Transplanted livers adjust their size to the size of the recipient
What is the regenerative capacity of mesothelia?
Good
What is the regenerative capacity of melanocytes?
They tend to regenerate too little or too much
What colour are scars in pigmented skin?
Usually pale
What is the regenerative capacity of smooth muscle?
Very good
What is the regenerative capacity of striated muscle?
Limited
What is the regenerative capacity of peripheral nerves?
Regenerate in a predictable way
How quickly do sprouting axons grow?
1-3mm/day
What happens if the gap regenerating axons have to cross is too wide?
They form a disordered tangle, which can result in a painful amputation neuroma
What is the regenerative capacity of neurone?
None (in humans)
When do neurones cease to multiply?
Before birth
How can lost neurones be replaced?
They can’t
How do people with hemiplegia secondary to strokes recover?
Because of the ability of the CNS to establish alternative pathways
What is the ability of the CNS to establish alternative pathways called?
Plasticity
How can cells respond to challenges that are not severe enough to cause injury?
By adaptations that are not truly pathologic, although they may open the door to disease
What is cell adaptation?
The state between a normal unstressed cell, and an overstressed cell
Is cell adaptation reversible?
Normally
What are the important types of cell adaptation?
Regeneration Hyperplasia Hypertrophy Atrophy Metaplasia
What is regeneration?
The replacement of cell losses by identical cells in order to maintain the size of a tissue or organ
Give an example of when is regeneration a normal process
Replacement of red and white blood cells by the bone marrow
When can regeneration occur after injury by a harmful agent?
If the harmful agent is removed, and there is limited tissue damage
When is resolution of injury not possible?
If the harmful agent persists
If there is extensive tissue damage
If the damage occurs to a permanent tissue
What happens when regeneration is not possible?
The tissue will heal with a scar
Give two examples of where regeneration is seen?
In the liver after a partial hepatectomy
In the replacement of the epidermis by keratinocytes following a skin burn
Are regenerated cells as good as the original cells?
Usually, but not always and not immediately
How long does it take regenerated cells to reach morphological and functional maturity?
Weeks, months or years
Give an example of when can the time that regenerated cells take to be the same as normal cells be an advantage
In the influenza virus- the virus kills the epithelial cells of the upper respiratory tract, but spares the regenerating cells that follow as they do not yet have receptors for the influenza virus
How many times can cells regenerate?
Many- how many times has been found to be species dependant, and depend on the maximum life-span of the species
What does a longer species life span mean for regeneration?
The more cell divisions can occur
What is the number of cell divisions possible called?
The Hayflick number
What is the mean Hayflick number in humans?
61.3
What is the Hayflick number in humans related to?
The shortening of telomeres
What factors induce cells to regenerate?
Growth factors in the microenvironment
Cell-to-cell communication
How is reconstitution different to regeneration?
It is the replacement of a lost part of the body
What does reconstitution require?
Coordinated regeneration of several types of cell
Can mammals reconstitute a body part?
No, their ability to do so is minimal, with a few exceptions
What are the exceptions to mammals inability to undergo reconstitution?
Small blood vessels (capillaries, small arteries and veins) are able to reconstitute
Children less than 4.5 years old have been reported to reconstitute the tip of a finger, if it is cleanly severed and the amputation is beyond the distal phalangeal joint
Rabbits and cats can repair holes punched in their ears up to a point
What is hyperplasia?
When there is an increase in tissue or organ size due to increased cell numbers
What is hyperplasia a response to?
Increased functional demand and/or external stimulation
Where can hyperplasia occur?
Only in labile or stabile cell populations
What does hyperplasia remain under?
Physiological control
Is hyperplasia reversible?
Yes
How does hyperplasia differ from regeneration?
They are biologically similar, but differs in that it leads to an increase in the size of the tissue or organ
What are the types of physiological hyperplasia?
Hormonal or compensatory
What is the result of hormonal hyperplasia?
An increase in functional capacity
What is the result of compensatory hyperplasia?
There is an increase in tissue mass after damage
What can hyperplasia occur secondary to?
A pathological cause
What is the cellular proliferation a normal response to when hyperplasia is secondary to a pathology cause?
Another abnormal condition
How does pathological hyperplasia usually occur?
Secondary to excessive hormonal stimulation or growth factor production
What is a risk in hyperplastic tissue?
Neoplasia
Why is neoplasia a risk in hyperplastic tissue?
As the repeated cell divisions that occur in hyperplasia expose the cell to the risk of mutations (which commonly occur during DNA replication)
Give 2 examples of physiological hyperplasia?
Increased bone marrow production of erythrocytes in response to low oxygen
Proliferation of the endometrium under the influence of oestrogen
Give 2 examples of pathological hyperplasia
Epidermal thickening in chronic eczema or psoriasis
Enlargement of thyroid gland in response to iodine deficiency
What is hypertrophy?
An increase in tissue or organ size due to an increase in cell size, without an increase in cell numbers
How do cells become bigger in hypertrophy?
Because they contain more structural components
NOT due to swelling
Where can hypertrophy occur?
In many tissues, but seen especially in permanent cell populations
Why is hypertrophy seen particularly in permanent cell populations?
As these populations have little or no replicative potential, and so any increase in organ size must occur via hypertrophy
What does knowing the regenerating capacity of each cell type enable you to do?
Predict the type of response to increased functional demand
What is hypertrophy a response to?
Increased functional demand and/or hormonal stimulation
What are cells undergoing hypertrophy and hyperplasia doing?
Synthesising more cytoplasm (i.e. protein)
What do hypertrophic cells contain?
More structural components
What is the result of hypertrophic cells containing more structural components?
The cellular workload is shared by a greater mass of cellular components
Can hypertrophy occur in cells where division is possible?
It can, but often occurs alongside hyperplasia
What is true of cases where hyperplasia and hypertrophy occur simultaneously?
They are triggered by the same stimulus
What does endocrine stimulation usually result in?
A combination of hypertrophy and hyperplasia
Give 2 examples of physiological hypertrophy
Skeletal muscle hypertrophy of a body builder
Smooth muscle hypertrophy of a pregnant uterus
How much does the uterus enlarge in pregnancy?
~70%
What is the enlargement of the uterus in pregnancy under the influence of?
Oestrogen
Give two examples of pathological hypertrophy
Ventricular cardiac muscle hypertrophy
Smooth muscle hypertrophy above an intestinal stenosis
Bladder smooth muscle hypertrophy with bladder obstruction due to an enlarged prostate gland
What causes ventricular muscle hypertrophy?
Response to systemic hypertension or valvular disease
What causes smooth muscle hypertrophy above an intestinal stenosis?
The extra work of pushing the intestinal contents through the narrowing
Where does hypertrophy of the cardiac muscle occur physiologically?
In athletes
Why is hypertrophy in the heart in athletes not pathological?
Because with exercise, unlike with hypertension or valvular heart disease, the heart is under strain for only a few hours/day, and has the rest of the day to recover
What is the problem with a pathologically hypertrophic heart?
There is relative anoxia
Why is there relative anoxia in a pathologically hypertrophic heart?
Because although the number of capillaries in the heart increases, is it not sufficient to satisfy the increased muscle mass
What is the result of the cell damage due to anoxia?
Fibrosis is often seen in pathologically hypertrophic hearts
What is the result of fibrosis in the heart?
It decreases the compliance of the cardiac muscle, and therefore its effectiveness
What does progressive pathological cardiac hypertrophy eventually lead to?
Myocardial exhaustion
What is a simple way to study the effect of functional overstrain?
To remove one of the two paired organs, e.g. if one kidney is removed, the other enlarges, leading to compensatory hypertrophy
What happens when the stimulus for hypertrophy and hyperplasia disappears?
The cells and organs become normal size again
What happens when there is excessive nutrition?
There is an increase in fat and an increase in protein synthesis
Why is obesity in children especially problematic?
Because once fat cells are made, they are with us for life- fat cells acquired at an early age will be there for life
What is atrophy?
Shrinkage of a tissue or organ due to an acquired decrease in size and/or number of cells
What results in atrophy?
A reduced supply of growth factors and/or nutrients
How can atrophy be considered?
From two perspectives- at the level of the cell, and at the level of the organ/tissue
What is cellular atrophy?
A decrease in cell size
What is organ/tissue atrophy due to?
Typically, a combination of cellular atrophy and apoptosis
When does organ/tissue atrophy occur?
When many cells in the tissue undergo atrophy and apoptosis
What does cellular atrophy involve?
Shrinkage in the size of the cell to a size at which survival is still possible
How does an atrophic cell differ from a normal one?
It contains a reduced number of structural components, and has reduced function
What is atrophy a form of?
Adaptive response which may result in cell death
How can atrophy occur?
Cell deletion or cell shrinkage
What does wether atrophy occurs by cell deletion or cell shrinkage depend on?
The type of tissue involved
What happens when cell deletion occurs?
Certain cells are picked out and induced to perform apoptosis
What happens to cell remnants left after apoptosis?
If they are situated on an external surface, they will be lost into the lumen, or from the surface of the body
Otherwise, they will be removed by phagocytosis, either by macrophages or by neighbouring cells
What happens in organs undergoing atrophy by cell deletion?
Parenchymal cells will disappear before stromal cells
What is the result of parenchymal cells disappearing before stromal cells in organs undergoing atrophy?
These organs often contain a large amount of connective tissue
Why does cell shrinkage have limits?
Because most cellular organelles are essential for survival
What can be pared down in cell shrinkage?
Some non-essential organelles, e.g. fibrillar material can be lost by skeletal muscle
How does cell shrinkage occur?
By self digestion
What happens when cell shrinkage occurs by self-digestion?
Residual bodies are seen within cells
What are the residual bodies found in cells that have shrunk?
Autophagosomes, which contain lipofuscin and the remains of organelles that can’t be further digested
How is ubiquitin involved in cell shrinkage?
It is involved in the process by binding with proteins that are to be removed and therefore targeting them for destruction
Can extracellular matrix be lost in atrophy?
Yes
What is bone atrophy, or osteoporosis?
Loss of bone mass (not bone calcium)
What is the major stimulus to bone formation?
Mechanical stress
Who can bone atrophy be a problem for?
Bed-ridden patients Astronauts
What is atrophy often linked with?
Disease
Senescence
Is atrophy reversible?
Up to a point, but after years or months it is less so, particularly when parachymal cells are replaced by connective tissue
How is atrophy best treated?
Removal of the cause
Give two examples of physiological atrophy
Ovarian atrophy in post-menopausal women
The decrease in size of the uterus after parturiton
What can cause pathological atrophy?
Reduced functional demand/workload Loss of innervation Inadequate blood supply Inadequate nutrition Loss of endocrine stimulation Persistant injury Ageing Pressure Occlusion of a secretory duct Toxic agents and drugs X-rays Immunological mechanisms
What is atrophy due to reduced functional demand/workload known as?
Atrophy of disuse
When may atrophy of disuse occur?
Due to immobilisation in a plaster cast
Is atrophy due to immobilisation reversible?
Yes, with activity
How can protein loss be reduced with immobilisation in a plaster cast?
By passive mechanical stretching and electrical stimulation
Where are the principals preventing protein loss in immobilisation used?
Physiotherapy
What is atrophy due to loss of innervation called?
Denervation atrophy
Give an example of denervation atrophy
Wasted striated muscle within the hand after median (motor) nerve damage
What can sensory nerve denervation cause?
Some degree of atrophy within the hands and feet
What happens with sensory nerve denervation?
The skin becomes thinner (atrophic) and scaly, and the nails become course and brittle
Give an example of atrophy caused by inadequate blood supply?
Thinning of ski on legs with peripheral vascular disease
When does inadequate blood supply result in tissue atrophy?
When there is partial but prolonged inadequacy of blood flow
Give an example of atrophy caused by inadequate nutrition
Wasting of muscles with malnutrition
What happens in inadequate nutrition?
Adipocytes shrink dramatically
Which tissue is least susceptible to starvation induced atrophy in adults?
The brain
Give two examples of atrophy caused by loss of endocrine stimulation?
Occurs in the breast and reproductive organs with withdrawal of hormonal stimulation
Wasting of the adrenal gland with loss of pituitary ACTH following hypophysectomy
What is the best way to shut down and atrophy an endocrine gland?
Give doses of the glands own hormone
Give an example of where persistent injury can cause atrophy?
Polymyositis
What is polymyositis?
Inflammation of the muscle
What is atrophy due to ageing called?
Senile atrophy
Where does senile atrophy usually occur?
In permanent tissues
Give 6 things affected by senile atrophy
Brain Heart Liver Kidneys Spleen Immune system
What happens to the liver, kidneys and spleen with senile atrophy?
Their weight is reduced
What happens to the immune system with senile atrophy?
It becomes less responsive
What is the reason for senile atrophy?
Seems more complex than the Hayflick number
Could involve the progressive accumulation of somatic mutations, so as the system can no longer function
What could the progressive accumulation of somatic mutations occur secondary to?
Free radical damage
Give two examples of where pressure can cause atrophy
Tissues around an enlarging benign tumour, such as the cerebral hemisphere adjacent to a meningioma
Thoracic aortic aneurysms can press against the sternum and erode through it
What can be seen when a thoracic aortic aneurysm can eroded through the sternum?
A pulsatile mass beneath the skin
Why does occlusion of a secretory duct cause atrophy?
It causes the parenchymal cells of the gland to undergo apoptosis
Give an example of atrophy due to occlusion of a secretory duct
In the pancreas ligation of the main duct, or blockage of the main duct by a stone, results in the disappearance of the exocrine glands of the pancreas alone.
What is the result of the disappearance of the exocrine glands of the pancreas?
The pancreas then appears as a mass of connective tissue contain larger ducts and intact islets of Langerhans
What is an exception to occlusion of a secretory duct causing atrophy?
The testis after ligation of the vas deferens
What is the result of the ligation of the vas deferns not causing atrophy?
Vasectomies can be successfully reversed
Where can become atrophic due to toxic agents and drugs?
Bone marrow
Testes
How do x-rays cause atrophy?
By direct cellular damage and microcirculatory damage
Give an example of where an immunological mechanism causes atrophy?
Atrophic gastic mucosa in pernicious anaemia
How does atrophic gastric mucosa in pernicious anaemia arise?
The body produces autoantibodies against parietal cells. The parietal cells produce intrinsic factor, which is required for absorption of vitamin B12. Lack of vitamin B12 results in anaemia
What is metaplasia?
Reversible replacement of one adult differentiated cell type by another of a different type
What happens in metaplasia?
Cells of one phenotype are eliminated, and replaced by cells of a different phenotype
How is the phenotype of cells changed in metaplasia?
The stem cells within the tissue are reprogrammed and switch to producing a different type of progeny
What can metaplasia be considered as?
Abnormal regeneration
Where does metaplasia occur in adult mammals?
Only within varieties of epithelia, and within varieties of connective tissue
Why could it be seen as surprising that metaplasia only occurs within epithelia and connective tissue?
Because all cells have the same full complement of genetic material, and therefore the potential to form any cell type
Is there metaplasia across germ layers?
None proven
Is there metaplasia from a connective tissue to epithelium?
Not proven
What cell populations does metaplasia occur in?
Only those can replicate- it is not known to occur in adult striated muscle or in neurones
What does metaplasia involve?
Expression of a new genetic programme- turning on certain genes, and turning certain genes off
What does expression of a new genetic programme result in?
Cells assuming a different structure and different function
What does metaplasia occur secondary to?
Signals from molecules such as cytokines and growth factors
What is metaplasia often induced by?
Stimuli that cause cell proliferation, e.g. chemical or mechanical irritants
What is the end result of metaplasia?
To change one cell type to another more suited to the altered environment
Where is metaplasia most commonly seen?
In epithelial tissue
In columnar epithelium
Why do columnar epithelium undergo metaplasia?
They are fragile, so they turn into more resilient squamous epithelium
Where is epithelial metaplasia common?
On surface linings
Why is epithelial metaplasia common on surface linings?
Because they are exposed to insults
What may happen to metaplastic epithelium?
It may loose functions that the original epithelium performed
Give an example of where metaplastic epithelium has lost function?
Mucus secretion is lost when columnar epithelium becomes squamous epithelium
How does metaplastic epithelium differ from dysplastic epithelium?
Metaplastic epithelium is fully differentiated
Dysplastic epithelium has disorganised and abnormal differentiated
How is cancerous epithelium different from metaplastic epithelium?
It is disorganised, abnormal and irreversible
Is metaplasia a good thing?
It can sometimes be adaptive and useful
However, can be of no apparent use, and may be detrimental
Give two examples of where metaplasia can be adaptive and useful
If the bone marrow is destroyed by disease, splenic tissue undergoes metaplasia to bone marrow
The conversion of columnar epithelium lining ducts to stratified squamous epithelium
What is it called when splenic tissue undergoes metaplasia to bone marrow?
Myeloid metaplasia
Which ducts may have columnar epithelium thats converted to stratified squamous epithelium?
Salivary glands
Pancreas
Bile ducts
Renal pelvis
Why may the lining of ducts change to squamous epithelium?
Secondary to chronic irritation to stones
What is the advantage of the conversion of columnar epithelial lining to stratified squamous?
As stratified squamous is more resistant to mechanical abrasion
Give three examples of when metaplasia can be detrimental
Transformation of bronchial pseudostratified ciliated columnar epithelium to stratified squamous epithelium
Flat, non- secreting epithelium can be replaced by secretory epithelium or glands such as in the lower oesophagus when the oesophageal stratified squamous epithelium changes to gastric or intestinal type epithelium
When connective tissue changes to bone
What does bronchial pseudostratified ciliated columnar epithelium change to stratified squamous epithelium in response to?
The effect of cigarette smoke
What is the problem with the transformation of bronchial pseudostratified ciliated columnar epithelium to stratified squamous epithelium?
The squamous epithelium doesn’t produce cleansing mucus, and lacks cilia to move the mucus along
When may oesophageal stratified squamous epithelium change to gastric or intestinal type epithelium?
With persistent acid reflux
What is persistent acid reflux called?
Barrett’s oesophagus
When can metaplastic develop?
In skeletal muscle following trauma, when fibroblasts within the muscle tissue undergo metaplastic change to osteoblasts
What is the development of metaplastic bone called?
Traumatic myositis ossificans
Where is traumatic myositis ossificans often seem?
In young people, usually after premature return to activity before proper healing has occured
What often happens to traumatic myositis ossificans?
It disappears by metaplasia in the opposite direction
What can metaplasia sometimes be a prelude to?
Dysplasia and cancer
Give two types of epithelial metaplasia that predispose to epithelial cancers
Barrett’s epithelium
Intestinal metaplasia of the stomach
When odes intestinal metaplasia of the stomach occur?
With chronic infection by Helicobacter pylori
What is aplasia?
The complete failure of a specific tissue or organ develop
What kind of disorder is aplasia?
Embryonic developmental
Give two examples of aplasia
Thymic aplasia
Aplasia of a kidney
What does thymic aplasia result in?
Infections and auto-immune problems
Other than an embryonic developmental disorder, what is aplasia also used to describe?
An organ whose cells have ceased to proliferate
Give an example of aplasia when cells have ceased to proliferate
Aplasia of the bone marrow in aplastic anaemia
What is involution?
The normal programmed shrinkage of an organ
What does the term involution overlap with?
Atrophy
Give 3 examples of involution
Uterus after childbirth
Thymus in early life
Temporary foetal organs, usch as the pro- and mesonephros
What is hypoplasia?
The congenital underdevelopment or incomplete development of a tissue or organ
What has happened in hypoplasia?
There is an inadequate number of cells within the tissue which is present
What kind of disorder is hypoplasia?
Embryonic developmental
Give 4 examples of hypoplasia
Renal hypoplasia
Breast hypolasia
Testicular hypoplasia
Hypoplasia of the chambers of heart
Where does testicular hypoplasia occur?
Klinefelter’s syndrome
Why is hypoplasia not the opposite of hyperplasia?
Because it is a congenital condition
What is atresia?
The congenital imperforation of an opening
Give two examples of atresia?
Atresia of anus or vagina
What is dysplasia?
The abnormal mutation of cells within a tissue
Is dysplasia reversible?
Potentially
What is the problem with dysplasia?
it is often a precancerous condition
