Transcript Cellular Injury-Adaptations-Necrosis-Apoptosis

CELLULAR
INJURY,ADAPTATIONS,
NECROSIS, APOPTOSIS,
AGING
Cells
Tissues
Organs
Systems
Organism
ADAPTATIONS
Change in size
Change in number of cells
Change into another type of
cell
ATROPHY
• Decreased size & function
• Metabolic processes shut
down to conserve energy
• Due to
• decreased demand
• ischemia
• lack of nerve or hormonal
stimulation
• chronic inflammation
HYPERTROPHY
• Increased size &
functional capacity
• Due to
• hormonal stimulation
• increased functional
demand
HYPERPLASIA
• Increase in number
of cells
• Due to
• hormonal
stimulation
• increased
functional demand
• chronic stress or
injury
DYSPLASIA
• Disorderly overgrowth of
cells
• Premalignant
• Reversible
METAPLASIA
• One cell type to another
• Reversible
REVERSIBLE OR IRREVERSIBLE
• Adaptations may be normal physiological responses to stimuli, or
pathological conditions
Reversible Injury
• Functional or morphological changes reverse when stimulus is
removed, even if cellular injury has begun:
 Moderately reduced oxidative phosphorylation of ATP slows active transport
 Aqueous vacuoles may bud from ER—hydropic change
 Fatty vacuoles may appear in cytoplasm—fatty change
• Severe disruption of compartmentalization triggers either
necrosis or apoptosis—cells die
 Necrosis: swelling, protein denaturation and digestion, membrane
breakdown and blebbing
 Apoptosis: shrinkage, fragmentation, phagocytosis
REVERSIBLE DAMAGE – CELLULAR SWELLING
Cellular swelling (synonyms: hydropic change, vacuolar degeneration, cellular edema) is an acute reversible
change resulting as a response to nonlethal injuries. It is an intracytoplasmic accumulation of water due to
incapacity of the cells to maintain the ionic and fluid homeostasis. It is easy to be observed in parenchymal
organs : liver (hepatitis, hypoxia), kidney (shock), myocardium (hypoxia, phosphate intoxication). It may be
local or diffuse, affecting the whole organ.
REVERSIBLE DAMAGE – FATTY CHANGE
Intracellular accumulations of a variety of materials can occur in response to
cellular injury. Here is fatty metamorphosis (fatty change) of the liver in which
deranged lipoprotein transport from injury (most often alcoholism) leads to
accumulation of lipid in the cytoplasm of hepatocytes.
NECROSIS
• Pathologic cell death
• Usually in a collection of cells fed by a single artery
APOPTOSIS
• Programmed cell death
• Especially during fetal development
• In response to hormonal cycles (e.g. endometrium)
• Normal turnover in proliferating tissues (e.g. intestinal epithelium)
• Cells shrink, not swell
• Nuclei condense and DNA fragments
• Cells fragment into membrane-bound bits
• Bits are phagocytosed by macrophages
The main factors acting in aging process and the functional relationship between them
• Cell cycle is regulated by different specific proteins,
cancer supressors, cyclins, and MAP kinases. When
these proteins are damaged by mutations cell cycle
regulation can be disturbed.
• We know genes concerned with pathological aging. When they
are damaged organism ages much faster. These genes are
named gerontogenes - aging genes. Genetic polymorphisms
(determining individual's longevity) are found. The existence of
longevity gene is still very real. Some age linked diseases are
known in medical practice (Werner's, Bloom's, Cocaine's
syndromes, progery and other). Patents had damaged various
gerontogenes. It was observed that these genes encoded
replication, transcription and repair machinery components of
the cell.
• Telomeres are the terminal parts of eukaryotic
chromosomes. The influence to aging of telomeres is
highly discussed. They are called "molecular clock" of
the cell.
• Cell division times are correlated with telomere length.
After each cell division telomeres get shorter. When
telomere shortens to the critical stage, the intensity of
cell division significantly decreases, and then cell
differentiates and ages.
CHROMOSOME
TELOMERE
TTAGGGTTAGGGTTAGGGTTAGGGTTAGGG
AATCCCAATCCC
5’
3’
WHAT ARE TELOMERES?
•
Telomeres are…
• Repetitive DNA sequences at the ends of all human chromosomes
• They contain thousands of repeats of the six-nucleotide sequence,
TTAGGG
• In humans there are 46 chromosomes and thus 92 telomeres (one at
each end)
• senescent cells have shorter telomeres
• length differs between species
• in humans 8-14kb long
• telomere replication occurs late in the cell cycle
HOW DOES TELOMERASE WORK?
•
Telomerase works by adding back telomeric DNA to the ends of chromosomes, thus
compensating for the loss of telomeres that normally occurs as cells divide.
•
Most normal cells do not have this enzyme and thus they lose telomeres with each
division.