General Pathology 601 for Dental Students

Cell Injury and Death, and Cellular Adaptation 

Nitya Ghatak, MD
Autopsy Pathology & Neuropathology
Sanger Hall, 5th Floor
(804) 828-9739
nrghatak@vcu.edu

I. Cell Injury and Death

Objectives
Upon completion of this lecture you will be able to:

1. Define 4 types of cellular adaptation to physiologic and pathologic conditions.
2. List 7 common causes of cell injury.
3. Explain the difference between reversible and irreversible cell injury.
4. Explain the difference between necrosis and apoptosis.
5. Describe patterns of necrosis In tissues or organs.

Important Terms
Cellular Adaptation
Cell Injury
Necrosis
Apoptosis
Atrophy
Hypertrophy
Hyperplasia
Metaplasia

Brief Introduction to Cellular Adaptation

Cells are the structural and functional units of tissues and organs. They are capable of adjusting their structure and functions in response to various physiological and pathological conditions. This capability is called cellular adaptation.

Cellular adaptations include:

1. Atrophy--shrinkage of cells
2. Hypertrophy--increase in the size of cells which results in enlargement of the organs
3. Hyperplasia--increased number of cells in an organ or tissue
4. Metaplasia--transformation or replacement of one adult cell type with another

Cellular adaptation is discussed at length in Section II of this lecture.

Cell Injury

If the cells fail to adapt under stress, they undergo certain changes called cell injury. The affected cells may recover from the injury (reversible) or may die (irreversible).

Causes of Cell Injury

1. oxygen deprivation (anoxia)
2. physical agents
3. chemical agents
4. infections agents
5. immunologic reactions
6. genetic defects
7. nutritional imbalances

Morphology of Cell Injury
Reversible:

• Cellular swelling and vacuoles formation (Hyodropic changes)
• Changes at this stage are better appreciated by the EM that may show blebbing of the plasma membrane, swelling of mitochondria and dilatation of ER
• Fatty changes

Irreversible/Necrosis:
The changes are produced by enzymatic digestion of dead cellular elements, denatunation of proteins and autolysis (by lysosomal enzymes)

• Cytoplasm - increased eosinophilia
• Nucleus - nonspecific breakdown of DNA leading to pyknosis (shrinkage), karyolysis (fading) and karyorrhexis (fragmentation).

Chronic Cell Injury
Non-lethal injury may cause subcellular changes some of which are characteristically seen in certain pathologic conditions. The following are examples of some of these changes:

• Changes in mitochondria seen in various conditions in some of which there is an increase in the number of mitochondria with various morphological abnormalities.
• Cytoskeletal changes with formation of distinctive intracellular inclusions such as Mallory body Neurofibrillary tangles, or Lewy body.

Cell Death

Death of cells occurs in two ways:

1. Necrosis--(irreversible injury) changes produced by enzymatic digestion of dead cellular elements
2. Apoptosis--vital process that helps eliminate unwanted cells--an internally programmed series of events effected by dedicated gene products

Mechanisms of Cell Death
Mechanisms of cell death caused by different agents may vary. However, certain biochemical events are seen in the process of cell necrosis:

• ATP depletion
• Loss of calcium homeostasis and free cytosolic calcium
• Free radicals: superoxide anions, Hydroxyl radicals, hydrogen peroxide
• Defective membrane permeability
• Mitochondrial damage
• Cytoskeletal damage

Patterns of Necrosis In Tissues or Organs
As a result of cell death the tissues or organs display certain macroscopic changes:

• Coagulative necrosis: the outline of the dead cells are maintained and the tissue is somewhat firm. Example: myocardial infarction 
• Liquifactive necrosis: the dead cells undergo disintegration and affected tissue is liquified. Example: cerebral infarction.
• Caseous necrosis: a form of coagulative necrosis (cheese-like). Example: tuberculosis lesions.
• Fat necrosis: enzymatic digestion of fat. Example: necrosis of fat by pancreatic enzymes.
• Gangrenous necrosis: Necrosis (secondary to ischemia) usually with superimposed infection. Example: necrosis of distal limbs, usually foot and toes in diabetes.

Apoptosis
This process helps to eliminate unwanted cells by an internally programmed series of events effected by dedicated gene products. It serves several vital functions and is seen under various settings.

• During development for removal of excess cells during embryogenesis
• To maintain cell population in tissues with high turnover of cells, such as skin, bowels.
• To eliminate immune cells after cytokine depletion, and autoreactive T-cells in developing thymus.
• To remove damaged cells by virus
• To eliminate cells with DNA damage by radiation, cytotoxic agents etc.
• Hormone-dependent involution - Endometrium, ovary, breasts etc.
• Cell death in tumors.

Morphology of Apoptosis

• Shrinkage of cells
• Condensation of nuclear chormatin peripherally under nuclear membrane
• Formation of apoptotic bodies by fragmentation of the cells and nuclei. The fragments remain membrane-bound and contain cell organelles with or without nuclear fragments.
• Phagocytosis of apoptotic  bodies by adjacent healthy cells or phagocytes.
• Unlike necrosis, apoptosis is not accompanied by inflammatory reaction

Mechanisms of Apoptosis
Apoptosis can be induced by various factors under both physiological and pathological conditions: It is an energy-dependent cascade of molecular events which include protein cleavage by a group of enzymes (caspases), protein cross-linking, DNA breakdown. Apoptosis is regulated by a large family of genes some of which are inhibitory (bcl-2) and some are stimulatory (bax).

Apoptosis goes through several complex phases. To put it simply, abnormal mitochondrial membrane permeability is a crucial event which allows escape of cytochrome-c into the cystosol which, in turn, activates proteolytic enzymes (caspases) leading to the execution of the process. The final phase is the removal of dead cell fragments by phagocytosis without inflammatory reactions.

Digital Legends for Labs
Lab 1 | Lab 2 | Lab 3 | Lab 4 | Lab 5 | Lab 6 | Lab 7 | Lab 8 | Lab 9 | Lab10 |
Lab 10b | Lab11 | Lab 12 | Lab 13 | Lab 14 | Lab 15 | Lab 16 | Lab 17 |

Lab 18

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Updated September 5, 2007