Lecture 2&3: Cell injury and death & Mechanisms/Causes of cell injury

Necrosis

INFLAMMATORY

Cell Size - Swelling

Nucleus - Pyknosis → Karyorrhexis → Karyolysis

Plasma membrane - disrupted

Cellular contents - Enzymatic digestion

Physiologic or pathologic - Pathologic (lots of irreversible cell injury)

Apoptosis

NON-INFLAMMATORY

Cell Size - Shrinkage

Nucleus - Fragmented

Plasma membrane - Intact

Cellular contents - Intact

Physiologic or pathologic - Often physiologic

Cell Injury - Reversible Cellular Swelling

Plasma membrane alterations (loss of microvilli, blunting, blebbing)

Mitochondrial changes (swelling, amorphous densities)

Cell Injury - Irreversible Necrosis

Dilation of ER (detachment of polysomes, myelin figures)

Nuclear alterations (disaggregation of granular and fibrillar elements)

• Karyolysis - dissolving of chromatin

• Pyknosis - nuclear shrinkage

• Karyorrhexis - pyknotic nucleus undergoes fragmentation

Karyolysis

Nuclear fading

• Chromatin dissolution

Pyknosis

Nuclear shrinkage

• DNA condenses into shruken mass

Karyorrhexis

Nuclear fragmentation

Intrinsic factors of cellular injury

Genetic influences

Metabolic

Nervous system

Extrinsic factors of cellular injury

Viruses

Temperature

Radiation

Chemicals

Bacteria

Intrinsic Pathway

Mitochondrial pathway

Extrinsic Pathway

Death receptor pathway

• receptor-ligand relations

Principal Mechanisms of Cell Injury

1. Oxygen Deprivation and Chemical Agents

• Hypoxia, ischemia, multiple injurious stimuli

2. Infectious Agents

• Mutations, cell stress, infections

3. Physical Agents

• Radiation

4. Immunologic Reactions

• Infections, immunologic disorders

ROS 3 Main Pathological Effects

1. Lipid Peroxidation

2. Protein modification

3. DNA damage

These lead to necrosis

5 general causes of cellular injuries

1. Oxygen deprivation

2. Chemical agents

3. Immunologic reactions

4. Physical agents

5. Aging

Oxygen deprivation

Hypoxia - oxygen deficiency

• Cyanide

• Carbon monoxide

Ischemia - loss of blood supply and/or nutrients

Chemical Agents

Membrane permeability, cell metabolism

• Air pollutants (ozone)

• Insecticides

• Asbestos (ROS)

• Therapeutic drugs

• Ethanol (-OH)

• Sterilization of implantable devices

Ethylene Oxide

One of the most commonly used sterilization methods

• For products that can’t tolerate heat, moisture, chemicals, etc.

Toxic Effects:

• MUTAGENIC from chronic exposure

• Alkylating agent (irritating, sensitizing, narcotic effects)

Sterilization of implantable devices methods

• Autoclave vs Gas

• Ethylene Oxide

• Microwaves

• Formaldehyde gas

• Hydrogen peroxide plasma

• Ozone gas

• Chemical solutions

• Ionizing radiation

Immunologic Reactions

Defends against pathogens but can turn on self

Ex: hypersensitivity

Physical Agents

• Trauma (blasts, bullets, etc.)

• Extremes of temperature

• Radiation

• Electric shock

• Sudden changes in atmospheric pressure

  • Caisson’s Disease/The Bends