PATH3500
SEPT 18
CELL INJURY, ADAPTATION & CELL DEATH (CONT’D)
- Homeostasis is an active process that requires a lot of energy; what a normal cell would be in
o Adaptation can be good (part of physiological function) but can also lead to disease; if it
gets overcome or if it’s too much for cell, then leads to cell injury (reversible +
irreversible)
Reversible vs. irreversible injury
- Point where cell stops functioning, homeostasis stops – why cell function plummets
o Where function meets cell death is where injury becomes irreversible; hard to pinpoint
bc can’t see changes easily, first see ultra changes w/ microscope to naked eye w/ gross
changes
Cell injury
- Response to injury depends on type, duration + severity
- Consequences on cell injury depend on type, state + adaptability of injured cell
o Each cell responds differently + adapts differently
Reversible cell injury
- Response to an acute or mild stress/stimulus
- Reversible if stimulus removed
- Hallmarks
o Reduced oxidative phosphorylation
o ATP depletion
o Cellular swelling (all progressive)
- Morphology
o Phydrophic swelling = an increase in cell volume characterized by a large, pale cytoplasm
+ a normally located nucleus
▪ Everything gets diluted, pale bc of fluid intake
o Fatty change (specifically in liver)
o May follow hypoxia or chemical poisoning; common for many sources of injury
- Cellular/hydropic swelling
o Results from impairment of cellular volume regulation
▪ Plasma membrane Na pump
• Na/K pumps get energy from mitochondria but w/o it bc mitochondria’s
not working due to not enough oxygen or toxins, get influx of Na, outflux
of K
• Na sucks in water through osmosis + get cell swelling through pressure
• Get blebs (weak spots in membrane) + organelle membranes also swell
bc surrounded by pressure – early stages of cell function depletion
Hydropic swelling in renal tubules
, - Kidney’s susceptible to systemic change
o In renal tubules, can see early morphological changes w/ reversible changes
- Ultra-structurally, see same thing of swelling
Intracellular accumulations
- Can see them w/ injury, some w/o
- What accumulates
o Normal cellular products
▪ Water, lipids, proteins
o Abnormal substances
▪ Exogenous (outside of body) or endogenous (made within body)
o Pigment
- Why? (can think of example of factory producing bikes)
o Inadequate rate of metabolism
▪ Not using cells, so they accumulate
o Genetic or acquired defects in metabolism, packing, or transport
o Abnormal exogenous substances
- Lipid accumulation
o Aka steatosis (fatty change)
▪ Occurs due to toxins, protein malnutrition, diabetes, obesity, toxins
o Often in liver, but also heart, muscle + kidney (to much lesser extent)
▪ Fatty liver looks yellow & to touch, feels greasy – gross/macroscopic scale
▪ Happens in liver bc it produces our fatty acids; if any point through fatty acid
transfer, some place isn’t working or poisoned, free fatty acids will go in but
won’t know how to get out
o Fat accumulates in tiny vesicles that eventually fuse into big vesicle that pushes nucleus
to side
▪ E.g. of intercellular accumulation due to cell injury that can cause further injury
- Not always bad nor indiciative about injury, but often are + can be
o Many different reasons that they can happen
- E.g. that does cause injury – genetic or acquired defects in metabolism, i.e. specifically in alpha-
1-antitrypsin deficiency
o Usually have trypsin that breaks down protease but bc it’s antitrypsin, result in too much
protease that doesn’t get broken down; autosomal recessive disease
o Get increased partially folded protein + decreased protease inhibitor activity
o Get problems in liver + lungs bc trypsin’s released but not broken down so people are
more susceptible to emphysema of lungs or cirrhosis of liver
- Pigments can be exogenous/endogenous
o Endogenous pigments (usually appear brown)
▪ E.g. lipofuscin “wear + tear” (doesn’t cause problems, just something that you
can recognize)
▪ E.g. hemosiderin (break down of hemoglobin from blood w/ iron) from things
like a bruise – also doesn’t cause problems w/ tissue, just sits there
▪ E.g. melanin (produced by melanocytes which is helpful bc absorbs UV radiation)
SEPT 18
CELL INJURY, ADAPTATION & CELL DEATH (CONT’D)
- Homeostasis is an active process that requires a lot of energy; what a normal cell would be in
o Adaptation can be good (part of physiological function) but can also lead to disease; if it
gets overcome or if it’s too much for cell, then leads to cell injury (reversible +
irreversible)
Reversible vs. irreversible injury
- Point where cell stops functioning, homeostasis stops – why cell function plummets
o Where function meets cell death is where injury becomes irreversible; hard to pinpoint
bc can’t see changes easily, first see ultra changes w/ microscope to naked eye w/ gross
changes
Cell injury
- Response to injury depends on type, duration + severity
- Consequences on cell injury depend on type, state + adaptability of injured cell
o Each cell responds differently + adapts differently
Reversible cell injury
- Response to an acute or mild stress/stimulus
- Reversible if stimulus removed
- Hallmarks
o Reduced oxidative phosphorylation
o ATP depletion
o Cellular swelling (all progressive)
- Morphology
o Phydrophic swelling = an increase in cell volume characterized by a large, pale cytoplasm
+ a normally located nucleus
▪ Everything gets diluted, pale bc of fluid intake
o Fatty change (specifically in liver)
o May follow hypoxia or chemical poisoning; common for many sources of injury
- Cellular/hydropic swelling
o Results from impairment of cellular volume regulation
▪ Plasma membrane Na pump
• Na/K pumps get energy from mitochondria but w/o it bc mitochondria’s
not working due to not enough oxygen or toxins, get influx of Na, outflux
of K
• Na sucks in water through osmosis + get cell swelling through pressure
• Get blebs (weak spots in membrane) + organelle membranes also swell
bc surrounded by pressure – early stages of cell function depletion
Hydropic swelling in renal tubules
, - Kidney’s susceptible to systemic change
o In renal tubules, can see early morphological changes w/ reversible changes
- Ultra-structurally, see same thing of swelling
Intracellular accumulations
- Can see them w/ injury, some w/o
- What accumulates
o Normal cellular products
▪ Water, lipids, proteins
o Abnormal substances
▪ Exogenous (outside of body) or endogenous (made within body)
o Pigment
- Why? (can think of example of factory producing bikes)
o Inadequate rate of metabolism
▪ Not using cells, so they accumulate
o Genetic or acquired defects in metabolism, packing, or transport
o Abnormal exogenous substances
- Lipid accumulation
o Aka steatosis (fatty change)
▪ Occurs due to toxins, protein malnutrition, diabetes, obesity, toxins
o Often in liver, but also heart, muscle + kidney (to much lesser extent)
▪ Fatty liver looks yellow & to touch, feels greasy – gross/macroscopic scale
▪ Happens in liver bc it produces our fatty acids; if any point through fatty acid
transfer, some place isn’t working or poisoned, free fatty acids will go in but
won’t know how to get out
o Fat accumulates in tiny vesicles that eventually fuse into big vesicle that pushes nucleus
to side
▪ E.g. of intercellular accumulation due to cell injury that can cause further injury
- Not always bad nor indiciative about injury, but often are + can be
o Many different reasons that they can happen
- E.g. that does cause injury – genetic or acquired defects in metabolism, i.e. specifically in alpha-
1-antitrypsin deficiency
o Usually have trypsin that breaks down protease but bc it’s antitrypsin, result in too much
protease that doesn’t get broken down; autosomal recessive disease
o Get increased partially folded protein + decreased protease inhibitor activity
o Get problems in liver + lungs bc trypsin’s released but not broken down so people are
more susceptible to emphysema of lungs or cirrhosis of liver
- Pigments can be exogenous/endogenous
o Endogenous pigments (usually appear brown)
▪ E.g. lipofuscin “wear + tear” (doesn’t cause problems, just something that you
can recognize)
▪ E.g. hemosiderin (break down of hemoglobin from blood w/ iron) from things
like a bruise – also doesn’t cause problems w/ tissue, just sits there
▪ E.g. melanin (produced by melanocytes which is helpful bc absorbs UV radiation)
