The document provides a comprehensive overview of cellular responses to stress, focusing on cell injury and necrosis. It discusses definitions, types of injury (reversible and irreversible), causes, timelines, and mechanisms of cell injury, including detailed descriptions of necrosis and apoptosis. Various patterns of tissue necrosis and their morphological characteristics are also outlined, alongside the pathological effects of reactive oxygen species.

1. 1
General Pathology Notes (Robbins)
By Dr. Ashish Jawarkar
Chapter 1 : CELLULAR RESPONES TO STRESS AND TOXIC INSULTS:
ADAPTATION, INJURY AND CELL DEATH
TOPIC 2. CELL INJURY AND NECROSIS
Overview
1. definition
2. types – reversible, irreversible (necrosis,apoptosis)
3. causes
4. timeline
5. Mechanisms of cell injury (necrosis)
6. morphology
7. necrosis vs apoptosis
8. patterns of necrosis
9. molecular basis
*definition and types
Cells exposed to stress
Adaptation (hypertrophy/hyperplasia/atrophy/metaplasia)
Continued stress, no more adaptation possible
Cell injury
Reversible cell injury
Irreversible cell injury
(necrosis & apoptosis)
Notes on General Pathology – Apoptosis….By Dr. Ashish V. Jawarkar
Contact: pathologybasics@gmail.com Website: pathologybasics.wix.com/notes

2. 2
*Causes of cell injury
1. O2 deprivation, nutritional imbalances
2. Physical agents – trauma, heat, cold, UV light, shock
3. Chemical agents – cyanide, arsenic, pollutants
4. Infectious agents
5. Deranged immunity
*Timeline
Reversible
Injury
Biochemical
alterations
effect
cell
function
irreversible cell injury
Minutes
Ultrastructural
changes
Days
Light
Microscopic
Changes
Gross
Morphologic
Changes
*Mechanisms of Cell injury (Necrosis)
1. Damage to membranes (plasma, lysosomal,mitochondrial)
2. Failure of calcium pump
3. Accumulation of free radicals
4. Mitochondrial membrane damage and depletion of ATP
5. Protein misfolding and DNA damage
1. Damage to membranes
Plasma membrane damage
Lysosomal membrane damage
Osmotic imbalance
Leakage of metabolites
leakage of
(DNAases, RNAases, Proteases etc.)
Notes on General Pathology – Apoptosis….By Dr. Ashish V. Jawarkar
Contact: pathologybasics@gmail.com Website: pathologybasics.wix.com/notes

3. 3
2. Failure of Ca2+ pump
Calcium influx
Activation of leaked enzymes (DNAases, RNAases)
Alteration of mitochrondrial
Membrane permeability
3. Accumulation of free radicals
Generation of free radicals
ROS
1. Redox rns in
Normal metabol
2. Radiation
3. Inflammn
4. CCl4
5. Transition metals
(Fenton rn#)
6. NO
FENTON RN
H202 + Fe2+
O2Super
Oxide
Fe3+ + OH + OH-
SOD
H2O2
fenton rn
+Fe2+
Hydrogen
Peroxide
OH
Hydroxyl
Radical
MITOCHONDRIA
Removal of free radicals done by
1. SOD (superoxide dismutase) – mitochondria
2. Glutathione peroxidase – mitochondria
3. Catalase – peroxisome
Pathologic effects of ROS
1. Fatty acid oxidation and disruption of membranes, organelles
2. Protein oxidation and loss of enzyme activity, protein misfolding
3. DNA oxidation and mutations and breaks
Notes on General Pathology – Apoptosis….By Dr. Ashish V. Jawarkar
Contact: pathologybasics@gmail.com Website: pathologybasics.wix.com/notes

4. 4
4. Mitochondrial membrane damage and depletion of ATP
Mitochondrial membrane damaged by
1. increased cytosolic calcium
2. ROS
3. hypoxia
4. mutations in mito genes
Activation of caspases
(apoptosis)
Due to leakage of cyto c
Alteration of mitochondrial membrane permeability
Due to leakage of H+
H+ leakage and Loss of membrane potential
Decreased Oxidative Phosphorylation
Decreased ATP generation
Detachment of Ribosomes
Failure of Na+ pump
Increased anaerobic
Glycolysis
Decreased protein synthesis
Influx of Na +, Ca2+
H2O
Lactic acidosis
Increased lipid deposition
Cellular swelling
ER swelling
Clumping of nuclear
chromatin
Notes on General Pathology – Apoptosis….By Dr. Ashish V. Jawarkar
Contact: pathologybasics@gmail.com Website: pathologybasics.wix.com/notes

5. 5
*Morphology
GROSS
Light
Microscopy
REVERSIBLE INJURY
1. Pallor
2. Turgor
3. Increased weight
1. Cellular swelling
2. vacuolar
degeneration/hydropic
change – clear vacuoles in
cytoplasm that represent
pinched off segments of ER
NECROSIS
1. Cytoplasm –
a. eosinophilia – due to loss of
cytoplasmic RNA
b. Glassy appearance – due to loss
of glycogen particles
c. Moth eaten app – due to
vacuolation
2. Cell membrane –
a. Myelin figures – membrane
fragments collect in cytoplasm
b. Calicification – of myelin figures
3.
a.
b.
c.
Ultra
structure
Plasma membrane – blebs, loss of
microvilli
Nucleus –
Karyoloysis – lysis of chromatin
Pyknosis – nuclear shrinkage
Karyorrhexis – chromatin
condenses into solid shrunken
basophilic mass
Plasma membrane – discontinuities
Cytoplasm – Myelin figures
Nucleus – disaggregation of
granular and fibrillar elements
Mitochondria - Large amorphous
densities
ER – dilatation and detachment of
ribosomes
Mitochondria – amorphous
densities
*Patterns of tissue necrosis
1. COAGULATIVE NECROSIS
Gross: The tissue is firm. Eg of localized coagulative necrosis is infarct.
Microscopy: preserved cell outlines, loss of nuclei, inflammatory infiltrate
2. CASEOUS NECROSIS (cheese like, in TB)
Gross: friable white app of necrotic area
Notes on General Pathology – Apoptosis….By Dr. Ashish V. Jawarkar
Contact: pathologybasics@gmail.com Website: pathologybasics.wix.com/notes

6. 6
Microscopy: Granuloma – central necrosis with lysed cells forming amorphous
debris, surrounded by inflammatory cells and epithelioid cells
3. LIQUEFACTIVE NECROSIS (necrosis in CNS)
Characterized by digestion of dead tissue – transformation into liquid viscous
mass
Gross: Abscess cavity formation with ragged margins
Microscopy: Necrotic material is creamy yellow containing dead leucocytes
4. GANGRENOUS NECROSIS
1. coagulative necrosis occurring in a limb that has lost its blood supply
2. occurs in multiple tissue planes
3. superimposed bacterial infection causes liquifactive necrosis – wet
gangrene
5. FAT NECROSIS
Refers to focal areas of fat destruction occurring due to release of pancreatic
enzymes into substance of pancreas and peritoneal cavity
Seen in acute pancreatitis
Gross: Pancreatic enzymes liquefy membranes of fat cells in peritoneum, split
triglycerides, produce saponification and deposition of calcium, chalky white
areas
Microscopy: shadowy outlines of fat cells, basophilic calcium deposits,
inflammatory reaction
6. FIBRINOID NECROSIS
Seen in immune reactions like SLE and other vasculitic syndromes
Seen in the wall of blood vessels
Microscopy: The wall of the vessels show circumferential bright pink areas of
necrosis and inflammation. Its basically immune complex deposition with
extravasated fibrin.
Notes on General Pathology – Apoptosis….By Dr. Ashish V. Jawarkar
Contact: pathologybasics@gmail.com Website: pathologybasics.wix.com/notes