basic pathology and toxicology€¦ · reversible cell injury changes in reversible cell injury by...
TRANSCRIPT
Basic Pathology and Toxicology
PHR 225 / Lecture 02
Factors influencing effects of Cell Injury
Duration of injury
Severity of injury
Cell Susceptibility to Injury
Type of injury
Factors influencing effects of Cell Injury
Type of injury Ischemia mitochondrial dysfunction
UV-radiation DNA damage
Duration of injury Ischemia
Reversible injury Irreversible injurycell death
Short time Prolong and slow
Factors influencing effects of Cell Injury
Factors influencing effects of Cell Injury
Severity of injury Surgery
Fibrosis / repair Regeneration /
healing
scar formation
Factors influencing effects of Cell Injury
Cell Susceptibility to Injury
Type of the cell
state and adaptability of the cell
Skin rash in children
Tuberculosis / asthma in lungs
Reversible Cell Injury
Denotes pathologic changes that can be reversed when the stimulus isremoved and the cellular injury has been mild.
Cell injury is reversible only up to a certain point otherwise it will beirreversible.
Reversible Irreversible Cell Death
Time / severity factors
Reversible Cell Injury
Changes in reversible cell injury by hypoxia –
1. Cellular Swelling: Due to accumulation of intracellular water2. Loss of microvilli3. Blebs formation4. Swelling of endoplasmic reticulum, & mitochondria5. Clumping of chromatin
All the above mentioned changes are only reversible if oxygenation isrestored.
microvilli
Irreversible Cell Injury
Denotes pathologic changes that are permanent and cause cell death
They cannot be reversed to normal state.
Irreversible Cell Injury
For example,
• if the blood supply to the heart muscles is cut off for 10-15 minutes,the myocardial cells experience injury but it can recover to normalfunction.
• if the blood flow is cut off for longer period the myocardial fibre diesand necrosis occur.
Irreversible changes in cell injury
Events in Irreversible Cell Injury
1. ATP Depletion
• mitochondrial dysfunction (lack of oxidative phosphorylation) leads toATP is depletion and production of energy is reduced
2. Cell Membrane Damage• functional and structural defects in cell membranes• cell membrane damage is a central factor in the pathogenesis of
irreversible injury
3. Ischemia-Reperfusion
• After the recovery of ichemic condition
• new damage may be initiated during re-oxygenation which increasesgeneration of ROS
• cellular antioxidant defence mechanisms may not work properly
• inflammation may increase with ischemic reperfusion
Events in Irreversible Cell Injury
4. Sub-cellular Alteration in Irreversible Cell Injury
a. Autophagy :1. Due to nutritional deprivation2. cellular organelles are enclosed in dead vacuoles3. dead vacuoles fuse with lysosomes (autophagolysosome)4. organelles are digested
autophagy is a survival mechanism in times of nutrient deprivation,such that the starved cell lives by eating its own contents
Events in Irreversible Cell Injury
b. Hypertrophy of Smooth Endoplasmic Reticulum
• When the cells exposed to toxins
• Toxins are metabolised in the smooth endoplasmic reticulum (SER)
c. Mitochondrial Alterations
• mitochondrion changes in number, size, and shape
d. Cytoskeletal Alterations
• Some drugs and toxins
a. interfere with the assembly and functions of cytoskeletal filaments
b. result in abnormal accumulations of filaments
Events in Irreversible Cell Injury
Events in Irreversible Cell Injury
e. Intracellular Accumulation of Substances
Accumulation of Protein, Fat, Glycogen and Pigments
Thank you
Mohammad Ahad A Khan, PhDAssistant Professor, Department of Pharmaceutical SciencesNorth South University, Bangladesh Room: SAC 1013email: [email protected]: +880 17 0386 4707