L17 - Abnormalities of growth, differentiation and morphogenesis Flashcards
What is a cellular adaptation?
Reversible changes in cells due to environment or demand
During cellular adaptation, the cell may make changes in what?
- size
- number
- phenotype
- metabolic activity
- function
How is cellular adaptation different to cell injury and neoplasia?
Cell injury and neoplasia are irreversible whereas cellular adaptation is most often reversible
Why do cells adapt?
- acquire new, steady state of metabolism and structure
- better equips cell to survive in new environment
What may failure of adaptation lead to?
Sub-lethal or lethal cell injury
- marked susceptibility to injury
- stimulus is too severe
Tissues differ in their susceptibility to stress.
How do cerebral neurones compare to fibroblasts?
Cerebral neurones = very sensitive to hypoxia (stress), rapidly die when subject to hypoxic stress
Fibroblasts = very resistant to damage (especially oxygen), can survive for long periods in challenging environments
Give an example of a tissue type that does not need to adapt
Fibroblasts
Survive severe metabolic stress without harm eg. absence of O2
Give an example of a tissue type that can adapt easily
Epithelial cells
Labile cell population, active stem cell population, highly adaptive in number and function
Give an example of a tissue type that cannot adapt
Cerebral neurons
Terminally differentiated, permanent cell population, highly specialised function, easily damaged by environmental change
What is PHYSIOLOGICAL cellular adaptation?
Responding to normal changes in physiology or demand
e.g muscles grow during work outs
What is PATHOLOGICAL cellular adaptation?
Responding to disease related changes
e.g Broken arm and immobility causing muscles to die off
What are 3 types of adaptive responses?
- increased cellular activity
- decreased cellular activity
- changes in cell function and/or morphology
In what ways can a cell adapt to increase cellular activity?
Increase size and/or number of cells
In what ways can a cell adapt to decrease cellular activity?
Decreased size and/or number of cells
What is hypertrophy?
increase in size of cells
what is hyperplasia?
increase in number of cells → increased cell mass
Hypertrophy and hyperplasia may co-exist. What do they both lead to?
Hypertrophy/hyperplasia = increased cell mass = increased capacity
What 2 things does hypertrophy lead to?
- increased synthesis of structural components
- increased metabolism
In which tissues is hypertrophy particularly seen in?
Permanent cell populations, especially cardiac and skeletal muscle
NB: they tend to get bigger in terms of size rather than number
Under what circumstances might a uterus be pathologically hypertrophied?
post-partum haemorrhage
Causes uterus to be significantly larger after delivery
Permanent cell populations can only respond to increased demand by doing what?
Increasing cell size
hypertrophy
What causes left ventricular hypertrophy?
- atheroma plaque
- calcification of valve cusps leading to inflexibility and narrowing of orifice (hard to push blood through)
How might you diagnose left ventricular hypertrophy?
- clinical examination
- ECG
- imaging
Which valve abnormality would lead to left ventricular hypertrophy (LVH)?
Aortic stenosis
What can LVH predispose to?
- sudden degeneration of rhythm
- ventricular tachycardia
- ventricular fibrillation and sudden cardiac death
What is subcellular hypertrophy and hyperplasia?
Increase in size and number of subcellular organelles (demand for more metabolism)
Smooth endoplasmic reticulum hypertrophy ultimately leads to what?
Increased metabolism of drugs
due to increase in P450 mixed function oxidases
Smooth endoplasmic reticulum hypertrophy is caused by which drug?
Barbiturates
What is hyperplasia?
Increase in number of cells caused by cell division
Which cell population types is hyperplasia possible in?
Labile and stable cell populations
Give 2 types of physiological hyperplasia
- hormonal
- compensatory
Give 2 types of pathological hyperplasia
- excess hormones
- growth factors
What is gynaecomastia?
Enlargement of the male breast due to hyperplasia of the glandular and stromal tissue in the breast
What may gynaecomastia be caused by?
- physioloigcal at puberty
- drugs (anabolic steroids, excess oestrogen)
- pathology eg. cirrhosis of liver
Why might you get hyperplasia of one kidney?
Due to hypoplasia of the other
What are the characteristic eye signs called in Grave’s disease and what is this caused by?
Exophthalmos
Caused by abnormal deposition of ground substance in orbital tissues
What feature do you get in adenomyomatous hyperplasia of the prostate?
Hyperplastic nodules
normal age-related change
The abnormal healing process in a cirrhotic liver leads to the formation of what?
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?
- embryogenesis
- uterus after pregnancy or menopause
Pathological atrophy can be classified into which 2 categories?
- localised
- generalised
Which factors cause pathological atrophy?
- decreased workload
- loss of innervation
- diminished blood supply
- inadequate nutrition
- loss of endocrine stimulation
- pressure
What is disuse atrophy?
atrophy caused by decreased workload
What is denervation atrophy?
atrophy caused by loss of innervation
Give an example of atrophy caused by inadequate nutrition
Cachexia
Give an example of a situation which may cause disuse atrophy
Leg in cast/broken limb
Give an example of an organ which may atrophy due to loss of endocrine stimulation
Uterus
Ageing and cerebrovascular disease has what effect on the brain?
Global atrophy
Give 2 examples of how atrophy of the kidneys may be caused
- renal artery stenosis (decreased blood supply)
- hydronephrosis (back pressure, from ureteric obstruction)
What is hydronephrosis?
A condition where the kidney becomes stretched or swollen as a result of a build up of urine inside them (eg. due to ureteric obstruction)
Which organ atrophies with age and is barely recognisable microscopically in the adult?
Thymus
physiological atrophy
What can pathologically cause atrophy of the adrenal cortex?
Steroid therapy - reduce the ACTH drive causing decrease in hormonal stimulation
What may patients be at risk of if long term steroids are stopped suddenly?
Addisonian crisis due to hypoadrenalism
Addisionian crisis = extremely low levels of cortisol (cortisol = important hormone produced by adrenal glands)
What are 2 mechanisms of atrophy?
- reduction in volume of individual cells
- death of individual cells (apoptosis)
What is involution?
Physiological atrophy caused by apoptosis
Reduction in volume of individual cells leads to formation of residual bodies. What can accumulation of residual bodies in cells be seen as?
Lipofuscin pigment
What does reduction in volume of individual cells lead to the formation of?
Residual bodies
Not all reduced cell mass is due to atrophy. What else can it be related to?
Developmental abnormalities
Give some conditions in the steps of development from embryonic cell mass to normal organ, which may cause reduced cell mass
- agenesis
- aplasia
- dysgenesis
- hypoplasia
What is metaplasia?
Transformation of one differentiated cell type into another
better adaption to new environment
Which tissues can metaplasia affect?
Epithelium and mesenchymal tissues
What pathological metaplasia does cigarette smoke cause?
Pseudostratified ciliated bronchial epithelium CHANGES TO squamous epithelium
What pathological metaplasia does bladder calculus/schistomosiasis/longstanding catheter cause?
Transitional epithelium of bladder CHANGES TO squamous epithelium
What pathological metaplasia does chronic trauma cause?
Fibrocollagenous tissue CHANGES TO bone
What pathological metaplasia does acid reflux cause?
Oesophageal squamous epithelium CHANGES TO columnar (glandular) epithelium
Why does smoking cause squamous metaplasia?
Squamous epithelium is better able to cope with noxious environment - squamous cell carcinomas
How are all these different types of adaptations linked to neoplasia?
Metaplasia/hyperplasia etc may form the basis on which neoplasia develops
Squamous metaplasia in cervix may lead to which neoplasia?
CIN and squamous cell carcinoma
Endometrial hyperplasia due to increased oestrogen may lead to which neoplasia?
Adenocarcinoma
Parathyroid hyperplasia due to chronic renal failure may lead to which neoplasia?
Adenoma
Squamous metaplasia in bronchus may lead to which neoplasia?
Dysplasia and squamous cell carcinoma
Squamous metaplasia in bladder may lead to which neoplasia?
Squamous cell carcinoma
Glandular metaplasia in oesophagus may lead to which neoplasia?
Adenocarcinoma
Which is dysplasia?
Earliest morphological manifestation of multistage process of neoplasia (hence irreversible)
Is dysplasia reversible or irreversible?
Irreversible
Dysplasia in an in-situ disease. What does this mean?
It is non-invasive. The abnormal cells have not yet acquired the capacity for invasion so they cannot spread
Carcinoma in-situ is another term for what?
Severe dysplasia
Dysplasia shows no invasion but does show what?
Cytological features of malignancy
The prostate enlarges with age with what process?
Adenomyomatous hyperplasia
how can enlargement of the prostate lead to the bladder having a trabeculated appearance?
- a degree of bladder outlet obstruction
- detrusor muscle of bladder has to work harder = hyperplasia = trabeculated appearance.
What might be the adverse consequences of having a bladder diverticulum?
- urinary tract infections
- bladder stones
- urine flowing backwards - into the kidneys (“reflux”)
- bladder tumors
- trouble urinating (the bladder doesn’t contract or empty well)
what are the 2 mechanisms of atrophy?
- reduction in volume of individual cells
- death of individual cells
what is aplasia?
failure of differentiation to organ-specific tissues
what is dysgenesis?
failure of structural organization of tissues into organ
what is hypoplasia?
failure of growth of organ to full size
