Tissue Injury and Response Flashcards
agents of stress
hypoxia physical agents (heat,cold,radiation,trauma) chemical agents and drugs infectious agents genetic derangements nutritional imbalances immunological reactions
direct cellular responses to stressors: cellular adaptations (chronic exposures)
hypertrophy, atrophy, hyperplasia, metaplasia, neoplasia
direct cellular responses to stressors: cell injury (acute exposures)
reversible injury, cell death (necrosis, apoptosis)
direct cellular responses to stressors: degeneration (chronic exposures)
subcellular alterations and cell inclusions
intracellular accumulations
pathologic calcification
hypertrophy
increase of cells in a tissue
little or no increase in size of nucleus just the cytoplasm
factors inducding hypertrophy are
- ischemia
- increased functional demand and or endocrine stimulation
- increased cardiac demand due to: increased peripheral resistance will cause hypertrophy of the cardiomyocyte
- loss of part of an organ
hyperplasia
an increase in the number of cells in a tissue
this is a non-neoplastic increase in cell number
some cells lack significant replicative ability to handle increased load, others are able to divide rapidly
EX: prostatic hyperplasia
metaplasia
reversible replacement of one cell type for another
the new cell type may be better adapted/protected against the injurious agent
this is generally consider an undesirable change
metaplastic responses
most common example of adaptive metaplasia is: the replacement of respiratory epithelium with squamous epithelium due to chronic irritation (chronic smokers will show this response)
vitamin A deficiency will also induce this change
Neoplasia
the abnormal proliferation of cells, resulting in a structure known as neoplasm
an abnormal mass of issue, the growth which exceeds and is uncoordinated with that of normal tissues and persists in the same excessive manner after cessation of the stimulus which evoke the change
- they might be benign, pre-malignant or malignant
generally the result of genetic alterations although epigenetic changes may also be involved
atrophy
an acquired decrease in the size of an organ that was once of normal proportions
atrophy is in contrast to
aplasia-defective development or congenital absence of an organ/tissue
hypoplasia: incomplete development of a tissue
agenesis: the complete absence of a tissue or organ
features of atrophy: decrease in number of cells
many times results in replacement of lost cells with fat or CT
atrophy of parenchymal cells will result in the accumulation of lipofuscin (a granular yellowish/brown pigment)
features of atrophy: decrease in cell
volume
cause of atrophy
- decreased workload (skeletal muscle following inactivation)
- loss of innervation (loss of n input lead to reduction in muscle size)
- diminished blood supply
- inadequate nutrition
- loss of endocrine stimulation (reduction of breast/uterine tissue during menopause)
- aging
testicular atrophy
can come from injury (focal atrophy)
or steroid use (gross appearance)
Reversible cell injury (degeneration)
-depending on dose and chronicity of toxicant exposure, cell possess defensive mechanisms to protect against direct toxic injury
sometimes results in cell swelling or fatty changes
Irreversible cell injury: necrosis
represents a process of events leading to destruction of the cell
- necrotic cells have characteristics of condensation of nucleus and enhance basophilic staining
- this type of cell death invokes an inflammatory response, fibrotic outcome
coagulative necrosis
commonly produced by cutting off blood supply (infarction)
characterized by loss of cellular detail while maintaining overall tissue architectural features
liquefactive necrosis
the dead tissue softens and eventually liquefies
seen in the CNS
can also be applied to the pus seen in abcesses
caseous necrosis
gets its name from the “cheesy” macroscopic appearance of the tissue, particularly striking example is necrotic tissue due to tuberculosis infection
architectural appearance of the tissue is totally lost
mechanism of necrosis: loss of cell viability
dysregulation of calcium metabolism
alteration in actin/focal adhesionite proteins
cell shape changes (blebbing)
activation of calcium-dependent proteases
disruption of cell membranes
Response to necrotic tissue damage
if a tissue undergoes necrotic damage the host repair or regeneration system will be activated
regeneration
the replacement of damaged tissue with an exact replicate of the original structure
repair
the process used to replace damaged tissue with scar, following an injury that compromises the vascular tree
component process of the repair or scarring process: acute inflammation
inflammation is the norma and beneficial response to all cellular injury
it only becomes a problem when the magnitude of the injury response exceeds that required to deal with the initial cellular or tissue insult
without some inflammation the healing response is blunted: coagulation, neutrophil influx, monocyte/macrophage activation
component process of the repair or scarring process: chronic inflammation
inflammation of prolonged duration (weeks or months) in which active inflammation tissue destruction and attempts at healing are proceeding simultaneously
sometimes chronic inflammation may follow acute inflammation when acute inflammation cannot be resolved
other component process of the repair or scarring process
- neovascularization
- CT deposition
- contraction
- remolding
Irreversible cell injury: apoptosis
an ordered physiologic process that allows for the selective elimination of a cell population
Intrinsic apoptotic pathway
results from cellular damage due to radiation, redox injury and drugs that produce direct DNA change
mitochondria central to the pathway, with cell injury resulting in leakage of cytochrome C from the mitochondria: this results in activation of the caspases, activated caspases degrade cytoskeletal and nuclear proteins
Extrinsic apoptosis pathway
involves binding of ligand to cell surface death receptors
central to physiological cell death regulation in the immune system and to prevent cancer
the receptors (dimerize/trimerize) upon ligand binding, with adaptor proteins binding to the cytoplasmic tails - leading got the activation of caspases, activated caspases degrade cytoskeletal and nuclear proteins
apoptosis results in
degenerative effects
cell death
direct action of apoptosis
direct binding to critical molecule or cellular organelles
conversion to reactive metaoblite apoptosis
formation of reactive free radical ssubsequent lipid peroxidation
