2 Injuries to Cells Flashcards
Injuries to Cells
Aims:
cellular response to stress
causes of cellular injury
morphology of cell and tissue injury
mechanisms of cellular injury
Results
Reversible
reversible – cellular repair and recovery
cells adapt by:
hyperplasia
hypertrophy
metaplasia
atrophy
Results
Irreversible
irreversible – damage too severe for cellular repair and recovery
cells are lost or changed by
apoptosis – cell “suicide”
apoptosis also has adaptive functions
necrosis – cell death
neoplasia – cancer and so on
Cellular adaptations to stress
hypertrophy
hyperplasia
atrophy
metaplasia
Hypertrophy
increase in the size of cells, resulting in increase in size of the organ
physiological
or
pathological
Hyperplasia
increase in cell number resulting in a larger (hypertrophied) organ can occur alongside hypertrophy physiological or pathological
Atrophy
shrinkage of the size of the cell by loss of cell substance decreased workload reduced blood supply inadequate nutrition loss of hormonal stimulation ageing
Metaplasia
one adult cell type is replaced by another adult cell type
reversible
new type of cell may be more able to withstand stress
eg chronic gastro-oesophageal reflux
Causes of cell injury
hypoxia
low oxygen supply
ischaemia
loss of blood supply, therefore oxygen and nutrients
chemical exposure
eg cigarette smoke, alcohol, paracetamol
infection
radiation
lack of nutrients
immunologic reactions
ageing
Morphology of reversible cellular injury
cellular swelling
fatty change
Cell death
necrosis
damage to membranes allows enzymes to digest the cell
local inflammation
always pathological
apoptosis
programmed cell death
irreparable damage to cell’s protein/DNA or deprived of growth factors
can be pathological or physiological
Apoptosis
cells activate enzymes that degrade the cells’ own DNA and proteins, resulting in death
fragments of the apototic cell break off
dead cell rapidly removed by phagocytosis
Physiological apoptosis
embryogenesis
involution of hormone dependent tissues upon hormone deprivation
elimination of cells which have served their purpose
elimination of potentially harmful self-reactive lymphocytes
Apoptosis in pathological conditions
DNA damage accumulation of misfolded proteins certain infections pathological atrophy in parenchymal organs after duct obstruction cell death induced by cytotoxic T cells
Mechanisms of apoptosis
result from the activation of enzymes called caspases mitochondrial pathway intrinsic pathway Fas (death) receptor pathway extrinsic pathway
Types of necrosis
coagulative necrosis
liquefactive necrosis
caseous necrosis
fat necrosis
Mechanisms of cell injury
depletion of ATP
mitochondrial damage
influx of calcium
oxidative stress
damage to the cell membrane
DNA damage
Depletion of ATP
energy store of cells oxidative phosphorylation of ADP within mitochondria reduced supply of oxygen and nutrients, mitochodrial damage, poisons effects: ATP dependent sodium pumps increased intracellular lactic acid failure of calcium pumps damage to protein structures
Mitochondrial damage
‘mini-factories’ for making ATP sensitive to many types of stress eg hypoxia, chemical poisons, radiation effects: failure of production of energy failure of free radical production
Influx of calcium
ischaemia, certain poisons effects increased intracellular calcium → leads to activation of enzymes → damage cellular components may trigger apoptosis
Oxidative stress
accumulation of reactive oxygen species (free radicals)
produced by normal cellular function
some insults increase their production
paracetamol overdose
removed by antioxidants
react with and damage proteins, fat, DNA, and create more of themselves in the process
Defects in membrane permeability
result in necrosis various sites of damage mitochondrial membrane damage plasma membrane damage injury to lysosomal membranes mechanisms of damage ↓ phospholipid synthesis ↓ATP oxygen free radicals lipid breakdown
Damage to DNA and proteins
may occur after radiation injury/oxidative stress
can result in apoptosis
Intracellular accumulation of abnormal material
fat in hepatocytes (liver cells) due to alcohol misuse.
cholesterol in smooth muscle cells in atherosclerosis
protein in Alzheimer’s and Parkinson’s disease
