Cell death, Cell injury and adaptations Flashcards
Homeostasis
Normal cells have a narrow steady state to perfom vital cellular functions
Adaptation
Response of the cell to stress where it undergoes changes in the steady state to preserve its function and viability
Cell injury
Cell stress exceeds adaptive capability
Reversible injury
Cell can recover from stress(non lethal)
Cell death
irreversible or severe cell stress (persistent)
Causes of cell injury - 6 (PIC GNH)
- Physical
- Chemical
- Infections
- Genetic mutations
- Nutritional deficiencies
- Hypoxia/ ischaemia
Cellular responses to stress - 4
- Adaptation
- Intracellular accumulation
- Reversible injury
- Cell death
Examples of intracellular accumulations - 3
- Chronic injury
- Metabolic alterations
- Genetic alterations
Cellular adaptation is due to
altered physiologic stimuli
Is metaplasia reversible or not
Reversible
Hypertrophy - 3
- No new cells, just increase in amount and production of structural protein/ cell organelles
- In non dividing/replicating cells
- Can occur with hyperplasia in cells that are dividing in response to the same stimuli (uterus in pregnancy due to hormonal stimuli)
Increase in functional demand - 2
- Increase in skeletal muscle secondary to exersice
- Increase in cardiac muscle in chronic HTN and stenotic valve heart lesions
Hormonal/ GF stimulation
Increase in uterine smooth muscke and myometrium in pregnancy to accomodate the growing fetus
Hyperplasia - 4
- due to GH driven proliferation of mature cells
- increased output of new cells from tissue stem cells
- in cells that are rapidly dividing
- can be pathologic or physiologic
Atrophy - 4
- Caused by loss of cell substance
- Reduced size of organ/tissue
- Caused by decreased protein synthesis or increased protein degradation
- Pathologic or physiologic
Pathologic examples of hyperplasia
- Endometrial hyperplasia - prolonged exposure to estrogen with no opposition from progesterone. Thickening of endometrium
- Prostatic - due to aging and hormonal changes. Urinary symptoms due to compression of the urethra
Physiologic examples of hyperplasia
- Breast tissue hyperplasia in respinse to estrogen and progesteron to prepare the mammary glands ffor lactation
- Liver tissue hyperplasia following hepatectomy to restore function and size
Physiologic causes of atrophy
Thymic atrophy = thymus is essential for T cell development. gradually shrinks and becomes inactive with age. Leads to decrease in immune function
- Uterine atrophy = after menopause. Uterus shrinks, ovaries produce less estrogen, cessation of cyclic changes
Pathologic causes of atrophy
- Muscle atrophy = loss of innervation and disuse
- Cerebral atrophy = alzheimers - progressive loss of neurons and brain tissue leading to brain atrophy
- Cachexia = inadequate nutrition, cancer and serious infection
Metaplasia - 4
- caused by chronic irritation
- a sensitive cell type is replaced with a cell type that can withstand adverse environment
- stem cells are programmed to differentiate using a new pathway
- influences is persistent maye predispose to malgnant change/dysplasia
dysplasia (bonus)
change in cell size, shape and rearrangement
Types of reversible injury
- cell swelling - accumulation of water due to ATP depletion
- fatty change - lipid droplet accumulation in the cytoplasm (common in liver cells)
examples of metaplasia - 5
Types of irreversible injury
- necrosis= unregulated cell death caused by severe damage
- apoptosis - programmed cell death that occurs in a controlled manner
Mechanisms of cell injury - i AM CFM
- ATP depletion = failure of ion pumps = cell swelling
- Mtd damage = failure of oxidative phosphorylation and energy production
- Calcium influx = incr intracellular calcium activates enzymes that damage the cell
- Free radical injury = unstable molecules causing damage to lipids, proteins and DNA
- Membrane damage= loss of membrane integrity leads to leakage of cellular contents
Mtd damage
release of proapoptotic proteins
entry of Ca2+
incr in mtd permeability
lysosomal membrane
enzymatic digestion of cellular components
protein misfolding/DNA damage
activtion of pro-apoptotic proteins
blebbing
formation of blisters on the cell membrane
reversible changes - DRB
- dilatation of organelles
- ribosomal diaggregration
-blebbing
point of no return
- mtd high amplitude swelling
- mtd matrix densities
- violent blebbing
morphological changes in reversible injury
- Nuclear alterations - chromatin clumping
- Cellular swelling due to plasma membrane incr permeability
- Mtd swelling
- Intracellular accumulations - failure of ebergy ion dependant pump on PM
- Dilatation of ER with loss of ribososmes
irreversible changes -BAMD
- Breakdown of lysosomes
- Activation of inflammatory responses
- Membrane rapture
- Dispersal of organelles
Cell death is characterised by- 3
- loss of mtd function even after removal of the noxious stimuli
- loss of structure and function os plasma membrane and intracellular membrane
- loss of dna and chromatin structure integrity
cytoplasmic necrotic changes
- myelin figures
- eosinophilia
-vacuoles and calcifications
4 pathways to cell death
- necrosis
- apoptosis
- necroptosis
- pyroptosis
nuclear necrotic changes
- pyknosis
- karyolysis
- karyorrhexis
pyknosis
- nucelar shrinkage
- DNA condenses into shrunken basohilic granule
karyolysis
- nuclear fading
- chromatin dissolution by DNAses and RNAses
Karyorrhexis
- nuclear fragmentation
- pyknotic nuclear membrane raptures and nuclear undergoes fragmentation
Patterns/Types of necrosis - CLC FGF
Coagulative
Liquefactive
Caseous
Fat
Gangrenous
Fibrinoid
Coagulative necrosis - 4
- due to cutting off of blood supply - ischaemia
- injutyr denatures structural proteins/enzymes limiting proteolysis of cells
- architecture of cell remains presures but the thissure has a firm texture
- dead cells removed by phagocytosis
dead cells are removed by phagocytosis
- cells form an eosinophilic opaque mass with loss of nuclei
- the basic cell shape is preserved resulting in a shadow or ghost outline
Liquefactive necrosis - TIC
- Total and rapid enzymatic dissolution of tissue, complete destruction of cells, transforming into viscious liquid (pus)
- Infections stiumlate rapid inflammatory response
- Common in brain tissue = infarcts
Caseous necrosis - MC NC
- Microscopically observed as granules surrounded by a collection of immune cells
- Cheese like apparences in necrotic tissue
- Necrotic focused of lysed cells with pink granular appearence
- Cells converted into a granular eosinophilic mass of amorphous fat and protein with total loss of cellular detail and outline
Enzymatic fat necrosis
lipases leak out of the tissue and hydrolyse fat into glycerol and fatty acids which saponify. Calcification may result
Traumatic fat necrosis
fat leaks out of the tissue (e.g breaat) and itis engulfed by macrophages leaving scarring and fibrosis following inflammationa
the fat necrosis slide ;(
Fibrinoid necrosis
- in immune reactions, complexes of antigen and antibody deposit into the walls of blood vessels
- or a deposit of eosinophilic material in the walls of the small arteries in hypertension or immune complex disease
Apoptosis features - 4
- energy dependant process
- cells activate enzymes tthat degrade the cells own nuclear DNA and nuclear/cytoplasmic DNA
- without leakage of cellular contents
- no inflammatory reactiong
Gangrenous necrosis
- dry =loss of bloos supply to a limb
- wet = superimposed bacterial infection
- gaseous = clostridial organisms in war wounds = bubbles in the tissue
Physiologic apoptosis
elimination of damaged or surplus cells (embryogenesis)
Key NB features of apoptosis
- Cell shrinkage
- Chromatin condensation
- Phagocytosis by adjacent cells
Pathologic apoptosis
Cancer, neurodegenerative disease
