Lecture # 20
CELL INJURY & RESPONSE-3
Dr. Iram Sohail
Assistant Professor
Pathology
OBJECTIVES
• Discuss mechanisms of injury under following headings
– Depletion of ATP
– Damage to mitochondria
– Influx of calcium
– Accumulation of Oxygen derived free radicals
– Defects in membrane permeability
– Damage to DNA & protein
1. DEPLETION OF ATP
• ATPs are main energy store of cell.
• They are required for all the functions of cell.
• In cell injury the ATPs will decrease.
• The main causes of ATP depletion are
– Reduced supply of oxygen & nutrients
– Mitochondrial damage
– Toxins like Cyanide
Because of decreased ATP ----- the activity of
ATP dependent sodium pump is reduced -----resulting in accumulation of sodium and efflux
of potassium ------- this influx of sodium also
carries water with it ------ causes cell swelling
Also
• Compensatory increase in anaerobic glycolysis
------ lactic acid accumulation ------ intracellular
PH will decrease
Also
• Because of failure of Ca pump ----Increased
intracellular Ca will increase ----- and damage
to cellular components
• Detachment of ribosomes from rough
endoplasmic reticulum ------ decreased protein
synthesis ----- irreversible injury ----- cell death
2. DAMAGE TO MITOCHONDRIA
• ATPs are formed in mitochondria.
• Mitochondria can be damaged by decrease
oxygen supply, increased Ca and reactive
oxygen species.
• When mitochondria is damaged -----decreased ATPs------ and cell will go towards
injury
3. INFLUX OF CALCIUM
• Normally the intracellular calcium is lower than
extracellular calcium.
• Because of decreased oxygen (ischemia) and
toxins ----- influx of calcium occurs -----intracellular calcium will increase ------- this
calcium activates certain enzymes ----- these
enzymes will cause cell injury.
• These enzymes are
– Phospholipases ------ cause membrane damage
– Endonucleases ------ cause DNA damage
4. ACCUMULATION OF OXYGEN DERIVED
FREE RADICALS
• Oxygen derived free radicals are chemical
species with unpaired electron in their outer
orbit.
They cause injury by
5. DEFECT IN MEMBRANE PERMEABILITY
• The cell membrane is damage by ischemia,
microbes, physical and chemical agents
• The mechanism is
6. DAMAGE TO DNA & PROTEINS
• Mainly radiation injury and free radical
oxidative injury cause damage to DNA.
• Inherited mutations & free radical injury cause
folding of proteins and ultimately damaging of
proteins.