Components Of Cell Injury

By Dr.A.Sridhar MPT(Neurology)

 What is Cell injury?

Cell injury
When the cell is exposed to an injurious agent or stress, a sequence of events follows that is loosely termed as CI

 What are adaptive response? What are the consequences due to cell injury?

Hypertrophy Hyperplasia Atrophy Metaplasia

Cellular Changes and its types

Myocyte Changes

Hypertrophy
An increase in the size of cells resulting in increase in the size of the organ. Examples of P & P

Hyperplasia
Characterized by an increase in cell number Types
hormonal hyperplasia
proliferation of the glandular epithelium of the female breast at puberty and during pregnancy

compensatory hyperplasia
hyperplasia that occurs when a portion of the tissue is removed or diseased

Guess ?

Atrophy
Shrinkage in the size of the cell by the loss of cell substance Causes
decreased workload loss of innervation diminished blood supply inadequate nutrition loss of endocrine stimulation aging

Guess ?

Metaplasia
Reversible change in which one adult cell type (epithelial or mesenchymal) is replaced by another adult cell type cells sensitive to a particular stress are replaced by other cell types better able to withstand the adverse environment Smokers

Guess ?

Autophagy
is the process in which the starved cell eats its own components in an attempt to find nutrients and survive.

Autophagy

Cell injury and cell death

Patterns Of Cell Death

There are two principal patterns of cell death: 1- Necrosis and 2- Apoptosis

Mechanism of cell injury

ATP production

MECHANISM OF CELL INJURY

1. DEPLETION OF ATP: . ATP depletion and decreased ATP synthesis are associated with both hypoxic and chemical (toxic) injury. . ATP is required for many synthetic and degradative processes within the cell.

MECHANISM OF CELL INJURY cont.

ATP is produced in two ways. A- The major pathway is oxidative phosphorylation of adenosine diphosphate. B-The second is the glycolytic pathway, which generate ATP in absence of oxygen using glucose derived from body fluids or from glycogen

MECHANISM OF CELL INJURY cont.

Effects of depleted ATP a) The activity of the plasma membrane energy-dependent sodium pump is reduced. It causes sodium to accumulate intracellularly and potassium to diffuse out of the cell causing cell swelling, and dilation of the endoplasmic reticulum.

MECHANISM OF CELL INJURY cont.

b) If oxygen supply to cells is reduced, as in ischemia, oxidative phosphorylation ceases and cells rely on glycolysis for energy production (anaerobic metabolism) resulting in depletion of glycogen stores. Glycolysis results in the accumulation of lactic acid which reduces the intracellular pH, resulting in decreased activity of many cellular enzymes.

MECHANISM OF CELL INJURY cont.

c) Failure of the Ca2+ pump leads to influx of Ca2+, with damaging effects on numerous cellular components d) Ribosomes detach from the RER and polysomes breakdown into monosomes, leading to reduction in protein synthesis. Ultimately, irreversible damage to mitochondrial and lysosomal membranes occurs, and cell undergoes necrosis

MECHANISM OF CELL INJURY cont.

e) In cells deprived of oxygen or glucose, proteins may become misfolded, and trigger the unfolded protein response leading to cell injury and even death.

MECHANISM OF CELL INJURY cont.

2- Mitochondrial Damage: . Mitochondria are important targets for all types of injury, including hypoxia and toxins.

MECHANISM OF CELL INJURY cont.

- Cells have defense systems to prevent injury caused by these products. - An imbalance between free radicalgenerating and radical-scavenging systems results in oxidative stress causing cell injury.

MECHANISM OF CELL INJURY cont.

Free radical-mediated damage are seen in - chemical and radiation injury - ischemia-reperfusion injury - cellular aging, and - microbial killing by phagocytes.

MECHANISM OF CELL INJURY cont.

- Free radicals are chemical species that have single unpaired electron in an outer orbit. - They are initiated within cells in several ways: a) Absorption of radiant energy (e.g., ultraviolet light, x-rays). b) Enzymatic metabolism of exogenous chemicals or drugs .

MECHANISM OF CELL INJURY cont.

c) The reduction-oxidation reactions that occur during normal metabolic processes. During normal respiration, small amounts of toxic intermediates are produced; these include superoxide anion radical (O2-), hydrogen peroxide (H2O2), and hydroxyl ions (OH). d) Transition metals such as iron and copper e) Nitric Oxide (NO), an important chemical mediator generated by various cells, can act as a free radical.

Necrosis

Necrosis is the type of cell death that occurs after ischemia and chemical injury Necrosis is always pathologic

Apoptosis
Apoptosis occurs when a cell dies through activation of an internally controlled suicide program. Apoptosis is designed to eliminate unwanted cells during embryogenesis and in various physiologic processes and certain pathologic conditions

APOPTOSIS
Apoptosis is programmed cell death. It is a pathway of cell death that is induced by a tightly regulated intracellular program in which cells destined to die activate their own enzymes to degrade their own nuclear DNA, nuclear proteins and cytoplasmic proteins. The cell's plasma membrane remains intact, but its structure is altered in such a way that the apoptotic cell sends signal to macrophages to phagocytose it.

Features of Necrosis and Apoptosis

Feature
Cell size Nucleus

Necrosis
Enlarged (swelling) Pyknosis karyorrhexis karyolysis Disrupted

Apoptosis
Reduced (shrinkage) Fragmentation into nucleosome-size fragments Intact; altered structure, especially orientation of lipids Intact; may be released in apoptotic bodies No

Plasma membrane

Cellular contents Adjacent inflammation

Enzymatic digestion; may leak out of cell Frequent

Physiologic or pathologic Invariably pathologic Often physiologic, means role (culmination of irreversible of eliminating unwanted cell injury)

Causes of Cell Injury

Hypoxia Physical Agents
Mechanical trauma, Burns, Deep cold Sudden changes in atmospheric pressure, radiation, and electric shock

Chemical Agents and Drugs Infectious Agents e.g. bacteria, fungi, viruses and parasites. Immunologic Reactions. Genetic Derangements. Nutritional Imbalances

Cellular and biochemical sites of damage in cell injury

Functional and morphologic consequences of decreased intracellular ATP during cell injury.

THE MORPHOLOGY OF CELL AND TISSUE INJURY

A normal cell and the changes in reversible and irreversible cell injury (necrosis).

Cellular Aging