Reversible Cell Injury I

Cell injury

A change in cell structure, metabolism, physio-chemical properties and function which leads to impairment of its vital activity

Reversible

A cell injury is considered ________ when environmental changes exceed the capacity of the cell to maintain normal homeostasis

irreversible

a cell injury is considered ________ if the injury persist or is severe that could lead to cell death

• Depletion of ATP

• Influx of Calcium

• Oxidative Stress (Oxygen-Derived Free Radicals)

• Damage to DNA and Proteins

What are the mechanisms of Cell injury?

• Reduced supply of oxygen and nutrients

• mitochondrial damage

• toxins (like cyanide)

Major causes of ATP depletion

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Study the Diagram as it Explains the Consequences of Depletion of ATP

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study the mechanism of Calcium Influx

Oxidative Stress

A condition called in increased production or decrease degradation of ROS (Reactive Oxygen Species/Free Radicals)

• Absorption f radiant energy

• Oxidation of Endogenous and Exogenous compounds

Oxidative Stress is generated by:

Molecular species with at least one oxygen atom and one or more unpaired electron available in an outer orbital.

What is an ROS?

• oxygen (O2)

• Superoxide anion

• peroxide

• hydrogen peroxide (non-radical)

• hydroxyl radical

• hydroxyl ion

Examples of ROS

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Study this Diagram about Respiratory Burst and ROS

• site-specific amino acid modification

• fragmentation of the peptide chain

• aggregation of cross-linked reaction products

• altered electric charge

• enzyme inactivation

• increased susceptibility of proteins to proteolysis

What does oxidative stress (high con. of ROS) do to protein?

• Chain breakage

• Increased in membrane fluidity and permeability

What does oxidative stress (high con. of ROS) do to lipds?

• Deoxyribose oxidation

• strand breakage

• removal of nucleotides

• modification of bases

• DNA-protein crosslinks

What does oxidative stress (high con. of ROS) do to DNA?

1. Radiation injury

2. oxidative stress

3. inherited mutations

What are the 3 major cause of DNA and protein damage?

The cell initiates its suicide program ad dies by apoptosis

Cells have mechanisms that repair damage to DNA. What will happen if the damage is too severe?

ROS

Endogenous cause of DNA damage

errors in DNA repair

spontaneous cause of DNA damage

• ionizing radiation such as gamma rays and x-rays

• Ultraviolet, especially UV-C rays (260nm) that are absorbed strongly by DNA, and UV-B that penetrates the ozone shield

What kind of radiation exposure can cause DNA damage?

1. food additives

2. aflatoxin

3. nicotine

Examples of Mutagenic substances

sublethal, sustained

When cellular injury is _____ and _____, cells and tissues tend to accumulate substances in abnormal quantities.

exogenous or endogenous

Cellular degeneration can be _____ or ______

1. Intra and extra accumulation

2. intra and extra pigmentation

3. pathological mineralization

3 Patterns od morphological changes in Cellular Degeneration:

1. cloudy swelling

2. hydrophic change or vacuolar degeneration

3. ballooning degeneration

What physical change on the cell indicates acute cellular swelling?

acute cellular swelling

This type of cellular accumulation appear whenever cells are incapab;e of maintaining ionic and fluid homeostasis.

This is also the first manifestation of almost all forms of cell injury.

wet tissue; blisters

Gross lesion of Acute cellular swelling

clear vacuoles in the cytoplasm and progressive dilatation of the swollen cell

Histological appearance of Acute cellular accumulation in light microscopy

watery fluid in the dilated mitochondria and endoplasmic reticulum

Appearance of Acute cellular accumulation in electron microscopy

1. chemical or biologic toxins

2. viral or bacterial infections

3. ischemia

4. thermal injuries

Possible causes of Acute cellular Swelling