What is cellular adaptation?
Mechanisms which allow tissues and organs to cope with changes in demand. They may be part of an entirely normal (physiological) process or occur as part of a disease (pathological) process
Are cellular adaptations usually reversible?
yes
Give the 5 things that can alter in cellular adaptation, why do these alterations occur?
1) Size
2) Number
3) Phenotype
4) Metabolic activity
5) Function
Occur due to changes in environment or demand
What is the role of cellular adaptation? 3
1) Aquire a new and steady state of metabolism and structure
2) Better equips cells to survive in a new environment
3) Failure of adaptation may lead to lethal or sub-lethal injury
Give an example of cell which is very susceptible to damage?
Cerebral neurons
Give an example of cell which is very resistant to damage?
Fibroblast
Name a type of cell which does not need to adapt in the face of environmental change and why?
Fibroblasts - can survive severe metabolic stress without harm eg. absence of O2
Name a type of cell which adapts easily to environmental change and why?
Epithelial cells
Labile cell population, have an active stem cell compartment
Highly adaptive in number and function
Name a type of cell which cannot adapt and why?
Cerebral neurons Terminally differentiated Permanent cell population Highly specialised function Easily damaged by environment change
What is meant by physiological cellular adaptation?
A cell responding to normal changes in physiology or demand
What is meant by pathological cellular adaptation?
A cell responding to disease related changes
What cellular adaptation occurs in response to increased cellular activity?
Increased size or number of cells
What cellular adaptation occurs in response to decreased cellular activity?
Decreased size or number of cells
What is the scientific term for increase in size of cells?
Hypertrophy
What is the scientific term for increase in number of cells?
Hyperplasia
Can hypertrophy and hyperplasia co-exist?
Yes
The net result of hypertrophy/hyperplasia is what?
Increased cell mass and thus increase in functional capacity
What kind of cell populations is hypertrophy commonly seen in, give an example?
Permanent cell populations
Especially cardiac and skeletal muscle
Give a physiological example of smooth muscle hypertrophy?
Hypertrophy of the smooth muscle cells of the uterus during pregnancy
Give a pathological example of muscle hypertrophy?
Hypertrophy of bladder muscle cells in benign prostatic hyperplasia - this leads to bladder outlet obstruction, bladder has to contract harder, so muscle becomes hypertrophied
Give an example of pathological hyperplasia?
Adenomyomatous hyperplasia of the prostate
Give a physiological example of skeletal muscle hypertrophy?
Skeletal muscle of a marathon runner
Give an example of pathological cardiac muscle hypertrophy?
Hypertrophy of cardiac muscle cells of left ventricle due to calcific aortic stenosis
This can also occur in systemic hypertension
Why can left ventricular hypertrophy lead to death?
Patients with LVH have increased ectopic beats, some of which can pre-dispose to sudden degeneration of rhythm to ventricular tachychardia or VF and sudden cardiac death
What is subcellular hypertrophy and hyperplasia, give an example?
Increase in size and number of subcellular organelles
For example, smooth ER hypertrophy in hepatocytes with barbiturates
What consequence can SER hypertrophy in hepatocytes with barbiturates lead to?
Increase in P450 mixed function oxidases which causes increased metabolism of other drugs - thus inactivating them
What 2 type of cell populations is hyperplasia possible in?
Labile and stable cell populations
For which 2 broad reasons may cell populations undergo physiological hyperplasia?
In response to hormones
As a compensatory mechanism
For which 2 broad reasons may cell populations undergo pathological hyperplasia?
Due to excess hormones or growth factors
Gynaecomastia is an example of what kind of cellular adaptation?
Pathological hyperplasia of the glandular and stromal tissue of the breast
Can be related to drugs and pathology elsewhere such as cirrhosis of the liver
An enlarged kidney in the absence of the other kidney is an example of what kind of adaptation?
Hyperplasia of the kidney as a compensatory mechanism
Graves disease is an example of what kind of pathological cellular adaptation?
Uncontrolled hyperplasia of the thyroid gland due to auto-Ab
What is thyrotoxicosis?
Hyperthyroidism
What is exophthalmos and why does it occur in graves disease?
Protruding eyeballs
Due to abnormal deposition of ground substance in the orbital tissues
What kind of cellular adaptation occurs in liver cirrhosis leading to a ‘nobly’ liver?
The abnormal healing process in liver cirrhosis leads to the formation of hyperplastic nodules of hepatocytes
What is atrophy?
Reduction in size of organ or tissue by decrease in cell size and number
Give 2 examples of physiological atrophy?
1) Embryogenesis
2) Uterus after pregnancy or menopause
What are the 2 types of pathological atrophy?
1) Localised
2) Generalised
Decreased workload leads to what kind of pathological atrophy?
Disuse atrophy
Loss of innervation leads to what kind of pathological atrophy?
Denervation atrophy
Cachexia involves what kind of atrophy?
Atrophy of skeletal muscles due to inadequate nutrition
Give 6 causes of pathological atrophy?
1) Decreased workload
2) Loss of innervation
3) Diminished blood supply
4) Inadequate nutrition
5) Loss of endocrine stimulation
6) Pressure
Give 2 example of physiological global atrophy?
Shrinking of the brain with age
Physiological atrophy of the thymus with age
Renal artery stenosis can lead to what kind of atrophy and why?
Atrophy of the kidneys due to diminished blood supply
How does hydronephrosis lead to kidney atrophy?
Through back pressure from ureteric obstruction
Steroid therapy can lead to what kind of atrophy?
Pathological atrophy of adrenal glands due to a dcrease in hormonal stimulation due to suppressed ACTH by exogenous steroids
What is meant by involution?
Physiological atrophy by apoptosis
What is the basic mechanism of atrophy?
1) Reduction in volume of individual cells
2) Death of individual cells - apoptosis/involution
What embryonic failures lead to agenesis?
Have formation of an embryonic cell mass but that fails to differentiate into an organ specific tissue
What embryonic failures lead to aplasia?
Have formation of an embryonic cell mass which differentiates into organ specific tissue but fails to structurally organize that tissue into an organ
What embryonic failure leads to dysgenesis?
Have formation of an embryonic cell mass which differentiates into organ specific tissue and becomes structurally organized into an organ but don’t get growth of that organ to full size
What embryonic failure leads to hypoplasia?
Have an organ which is smaller than normal
What are the 4 developmental causes of reduced cell mass?
1) Agenesis
2) Aplasia
3) Dysgenesis
4) Hypoplasia
What is metaplasia?
Transformation of one differentiated cell type into another through transdifferentiation of stem cells, can be physiological or pathological
Why does metaplasia occur?
To make a cell mass better adapted to a new environment
What 2 type of tissues can metaplasia affect?
1) Epithelium
2) Mesenchymal tissues
Give an example of physiological metaplasia?
Movement of the squamocolumnar junction near the external os of the cervix during puberty and then again during menopause
ie. a change of epithelium beyond the external os of the cervix from squamous to columnar and back again
Cigarette smoke can cause pathological metaplasia of pseudostratified ciliated bronchial epithelium to what kind of epithelium?
Squamous epithelium
Pathological metaplasia of transitional epithelium of the bladder to become squamous epithelium can occur in response to which 3 stimuli?
1) Bladder calculus
2) Schistomosiasis
3) Long standing catheter
Chronic trauma can cause pathological metaplasia of fibrocollagenous tissue to become what type of tissue?
Bone
Acid reflux can cause pathological metaplasia of oesophageal squamous epithelium to become what kind of tissue?
Columnar (glandular) epithelium (like that of the stomach)
This is Barrett’s oesophagus
How can metaplasia link to neoplasia?
Pathological metaplasia may form the basis on which neoplasia develops
Squamous metaplasia in cervix may lead to what kind of neoplasia?
CIN and squamous cell carcinoma
Endometrial hyperplasia due to increased oestrogens may lead to what kind of neoplasia?
Adenocarcinoma
Parathyroid hyperplasia due to chronic renal failure may lead to what kind of neoplasia?
Adenoma
Squamous metaplasia in bronchus may lead to what kind of neoplasia?
Dysplasia and squamous cell carcinoma
Squamous metaplasia in the bladder may lead to what kind of neoplasia?
squamous cell carcinoma
Glandular metaplasia in the oesophagus may lead to what kind of neoplasia?
Adenocarcinoma
Why can endometrial hyperplasia be more common in obese populations?
Adipose tissue generates oestrogens which can lead to endometrial hyperplasia
Disturbances in which 2 substances cause parathyroid hyperplasia in chronic renal failure?
Calcium and phosphate
What is dysplasia?
The earliest morphological manifestation of the multistage process of neoplasia - it is irreversible
It is in-situ disease - ie. non invasive
It shows cytological features of malignancy but no invasion
Why is recognition of dysplasia useful in treatment?
It gives us a chance to treat a potentially fatal tumour before it arises, the abnormal cells have not yet acquired the capacity of invasion so they cannot yet spread - eg. this is the whole basis of the cervical screening programme
What is severe dysplasia sometimes also referred to as?
Carcinoma in situ
What is the main difference between cellular adaptations and dysplasia/neoplasia?
Cellular adaptations reversible
Neoplasia and dysplasia are irreversible
