Cell Death and Adaption:

Homeostasis operate in a narrow range of function

If environmental stresses exceed the response cell becomes
injured
Adaptive responses:
Changes in size or number of cells
Not all cells have the same compacity for these types of change
When these cells have made these adaptations, they are normal
(if you remove the stilulus, cells can go back to their normal
state)
Perment tissues non-dividing permenant cells (Skeletal muscles,
CNS neurons
Labile high turn onver and division
Hypertrophy:
Increase in size of the cell due to synthesis of more structural
components
No cell division is required so all types of tissue can show this response
Tissue gets bigger
Hyperplasia:
Increase in number
The tissue gets bigger
Permenant types of tissue cant go through this response
Hyperplasia and Hypertrophy are adaptive responses seen in areas
were there are increased growth factors and cytokines
Can be physiological stimulus is appropriate, adaptive for organism,
and non sustained
Can be pathological inappropriate, and sustained (organ doesnt
return to normal)
Muscle Hypertrophy:
Response to increased work demand on the heart muscle left
ventrical because of obstruction or pressure overload and hypertension
As a result the muscel cells get larger and the nucleus that also gets
bigger
Adaptive response increase contractility but that muscle has an
increased oxygen demand thats not always met by the blood supply
Also, if you have large hypertrophy, you may have impairment of
dyostolic filling because you have increased ragidity

Benign Prostatic Hypertrophy:

Abnormal growth factor signaling to the cells of the prostate
Hyperplasia obstructs outflow of urine
Graves disease of Thyroid:
Stimulus is autoantibodies
Hyperplasia less colloid because overactive cells are producing
more hormone
Goitre
Management of hyperplasia is mainly removal or if problem is
excess hormone production, use drugs to antagonize them
Atrophy:
Reduced size and number
This occurs due to loss of stimulation for the cells
Reduced work load, prolonged physical pressure, denervation,
reduced blood supply (chronic), loss of endocrine stimulation
Mechanism:
Due to autophagy lysosomal activity
Decrease protein synthesis and increased protein degredation
Reduced rate of proliferation
Atrophic are adaptiving to survive in their new environment
reduced function, particularly when it affects the epithelial or
skin surface (bruising, bleeding)
Reversible change (if you give back estrogen to a post
metapausal lady, everything will go back to normal)
Phenotypic change one mature cell type is replaced by
another fully functioning cell type
Again, this means the cells are able to surivie in hteir altered
environment but your losing function (stimulus through to be
cytokines and growth factors thought to affect stem cells to
change the cells being produced)
These changes are predisposed to malignant transformation
(more genetically unstable continuation of same stimuli to
different cells is subjected to malignancy)
Metaplasia in Resp. Tree
normal resp. pseudostratified ciliated epithelium
CHronisce irritation due to smoking
Stimulate change to squamous epithelium epithelim is better
adaptive but lose glands and and cilia (removal of debris)
Also, with continued smoking, you may get carcinoma
Cell Injury and Cell Death:

Causes of cell injury: Overlap to some extent to causes of cell atrophy,

exceeding the atrophic response it can make
Oxygen deprivation
Infection
Immunologic reaction bystander cell damage or autoimmune
Chemical agent and drugs
Key Mechanism:
Depletion of ATP affect membrane pumps (organelle or cell
membrane)
DNA damage
Accumulato f oxygen derived free radicals chemical or
ischemic injury
Mitochondrial damage as a result of energy depletion, results
in the release in preapoptotic damage and release of calcium and
activation of degradative enzymes
Cell response to injurious stimuli depends on duration and severity of
stimulus:
Determined by the normal metabolic status
Loss of function will occur before morphological changes occur
Following ischemic injury loss of contratability 40 min, perminant
damage gross changes will take 10-24 hours to show (after the
ischemic events)
Morpholofical manifestations:
Acute Reversible Inflammation: 2 key
Cell swelling (vacuolar degeneration) in almost all types of cell
injury, typically a reversible stage (mitochondria) usually look
more pale: vacuoles within the cells
Intracellular accumulation intracellular accumulation of lipid
due to metabolic derangement (aerobic glycolysis and B
oxidation of fat) fatty liver (reversible change)
Persistant or excessive injury:
Key events:
unable to reverse mitochondrial function and profound
membrane distrubances
No morphological correlates
Can die via apoptosis and necrosis
Necrosis:
Cougulative necrosis internal proteins become denatured
Can be ischemia induced death
First change is cell swelling but once it becomes irreversible, the
proteins become denatured, stain dark pink, and cant see nuclei

In this type of necrosis, its a slower process

As proteins leak out of cell, this stimulates an inflammatory
response
Mediators from the inflammatory response will then start to
break down the cell and cells are also phagocytosied and fibrosis
replaced the empty spots
Outcome of necrosis:
Will usually be replaced with fibrous scar perminant loss of
function (in the heart because heart muscles cant regenerate)
May be regeneration of normal cells if cell division is possible ( in
the liver
Liquefactive necrosis:
Rapid tissue breakdown
See in the brain (Acute cerebral infarction)
Gangrenous necrosis:
Coagulative necrosis involves multiple tissue layers clinical
term very serious inflammatory condition
Caseous necrosis:
Typical of TB cheese like
Fat Necrosis:
Form of coagulative necrosis of fat cells
Apoptosis:
Regulated controlled mechanism of cell death
Usual part of normal cell life
But can also pathological
Key caspase activation within the cell wich results in the
breakdown of cell cytoskeleton
Cells shrinks, nucleus fragments see little dark staining
membrane bound bodies (within them you might see a few dark
framgents of nuceus material)
Express surface molecules that attract macrophages to
phagocytose
No leakage of cell content so no inflammatory response