Cell Death & Adaptation Flashcards
Cell death: effects on tissue
Regenerative capacity and intact ECM
- recovery to normal
Regenerative capacity but ECM damaged
- permanent damage and reduced function
Non-replacing tissue (CNS, cardiac)
- permeant damage and reduced function
Common causes of cellular injury and death
Lack of factors essential for normal cell function
- blood (ischaemia)
- oxygen
- nutrients
- hormones/ GF
- neural stimulation
Physical
- trauma
Chemical
- drug injury
- toxins
Inflammation
- appropriate inflammatory responses
- inappropriate inflammatory response eg auto immune
Metabolic and genetic disorders
- diabetes
- obesity
etc.
Cellular effects of injurious agents
- mitochondrial dysfunction and damage
- damage to membranes
- damage to cytoskeleton and cellular proteins
- DNA damage
Clinical recognition of cell injury and death
Deranged tissue / organ function
detection of leaked intracellular contents in blood (severe membrane damage)
Pathological recognition of cell injury and death
Morphological changes in the tissue
light microscopic changes
gross changes in surgical specimens
Common morphological manifestations of sublethal cell injury
Cell swelling:
- all cell types can show this
Fatty changes :
- intracellular accumulation of lipid due to deranged metabolism
- liver most common
Ultrastructural changes of cell swelling
Plasma membrane damage
- blebbing, loss of villi
Mitochondrial swelling due to membrane damage
ER damage
- dilated, detached polysomes
Nuclear damage
- disaggregation of granular and fibrillar elements
Reversible fatty changes in liver cells
- intracellular accumulation of lipid due to metabolic derangement
- disruption of aerobic glycolysis and B-oxidation of fat
Clinical effects of fatty change
- typically little effect on clinically measured LFTs of fatty change alone
- altered metabolism can stimulate inflammation in liver and lead to cell injury = death
6 biochemical and morphological features of Apoptosis
- physiological process
- specific enzymes break down cells
- neat and tidy
- typically single cells
- cell suicide programme
- activated by some types of injury
Cellular changes of Apoptosis
- cell shrinks, cytoplasm stains darker
- chromatin condenses under nuclear membrane an nucleus fragments
- cell membrane blebs and cell fragments into membrane bound bodies
- cells express macrophage attractants and are phagocytosed
mechanism of Apoptosis
INTRINSIC PATHWAY
1) loss of GF/ survival factors, hypoxia, DNA damage, ER stress
2) Bcl2 / BAX
3) inc mitochondrial permeability and release pro-apoptotic proteins
4) caspase activation
EXTINSIC PATHWAY
1) death receptor on cell surface
2) FAS or TNF receptor
3) caspase activation
EXECUTION PHASE OF APOPTOSIS
endonuclease activation-> DNA fragmentation
cytoskeleton breakdown -> cell shrinks
6 biochemical and morphological features of Necrosis
- not physiological
- uncontrolled cell breakdown- non specific enzyme activation
- messy process
- typically large group of cells
- mass murder
- common pattern following injury
Coagulative pattern of Necrosis
- most common
- less rapid distinegration of cells
- tissue structure transiently preserved but tissue weak and non-functional
Liquefactive pattern of Necrosis
rapid degradation of cells to liquid mass
nuclear changes of Coagulative necrosis
- non-specific breakdown by degrative enzymes
- karyolysis = pale nucleus due to endonuclease action
- pyknosis = shrinkage of nucleus, becomes darker
- karyorrhexis = nuclear fragmentation
cytoplasmic changes in Coagulative necrosis
- cytoplasm steams more darkly than usual
- cell and tissue architecture preserved
- severe membrane damage is present but not seen
evolution of Coagulative Necrosis
1) leakage of cell contents due to membrane breakdown
2) inflammatory cell response
3) leucocyte lysosomal enzymes are major factor in cell digestion
4) attracts macrophages to phagocytose and initiates granulation tissue
gross appearances of Coagulative Necrosis
Necrotic tissue:
- pale with yellow colour from acute inflammatory cells
- if blood is flowing to tissue- haemorrhage in tissue
Haemorrhaging situations:
- acute inflammation
- infarction due to venous obstruction
- arterial blockage by second blood supply to tissue
- tumour necrosis (due to angiogenesis and leaky vessels)
What causes Liquefactive Necrosis?
focal material and fungal infections
- inflammatory cell enzymes present from early stage and rapidly digest tissue
Gangrenous Necrosis
- term used when coagulative necrosis involves multiple tissue layers
- typically used for intestine and limbs
- massive inflammatory response with circulatory failure
Caseous Necrosis
pink amorphous granular material with no tissue architecture apparent
- typcial of TB infection
Fat Necrosis
- focal areas of fat destruction
caused by
- physcial damage
- chemical damage
- inflammatory injury
Fibrinoid Necrosis
seen in immune reactions involving vessels
- bright pink material seen in vessel wall typically associated with inflammatory cells
- immune complexes in vessel wall together with fibrin
Dystrophic Calcification
necrotic cells if not promptly absorbed form a nidus for calcification
definition of cell adaptation
changes in size, number or pheotype of cells in a tissue in rpesonse to altered physiological demands and environmental stresses
hypertrophy
increase in cell size due to synthesis of more structural components with also an increase in size of tissue/organ
-does not require cell division
-only response in mature tissues
hyperplasia
increase in number of cells in organ or tissue with also increase in size of that organ/tissue
-only occurs in tissues capable of division
-labile tissues (hight steady state turnover
-stable tissues
pathological hypertrophy
chronic pressure or volume load on heart
unwanted effects
-inc metabolic demand
-reduced compliance
-fibrous tissues inc aswell as muscle
pathological hyperplasia
excess endogenous or exogenous steroid hormone stimulation
viral infections- alter regulation of proliferation cells
> HPV->warts
growth factor mimetic
atrophy
reduced size of an orison or tissue due to decrease in cell size and number
-dec protein synthesis
-inc protein degradation
-cell death by apoptosis and autophagy
-dec rate of proliferation in renewing tissues
what causes atrophy
-dec workload
-prolonged physical pressure
-denervation
-dec blood supply
-inadequate nutrition
-loss of endocrine stimulation
-aging
Metaplasia
one mature cell type is replaced by a different mature cell type
-stimulus is chronic irritation
-mediators: cytokines GF
>act on stem cells in epithelia to tigger a changed differentiation pathway
-predisposed to malignant transformation
example of Metaplasia
- normal respiratory pseudo stratified ciliated epithelium
> chronic irritation due to cigarette smoke - squamous epithelium
- squamous cell carcinoma
- loss of ciliated cells- mucous plugging and cough
