Cell Injury And Its Mechanism

Reversible Cell Injury

 Introduction
• A normal cell has a narrow range of function and structure.
• This range is determined by
Its genetic programme of metabolism, differentiation
and specialization.
Availability of metabolic substrates.
Vascular supply
Excretory facilities
Constraints of neighboring cells
• If the cell is subjected to excessive physiological
demands, at first, it tries to adapt to these excessive
demands.

• These adaptations are brought about by alteration in

physiological and structural components of the cells
and are called cellular adaptations.

• Cellular adaptation allows a cell to cope with

excessive demands up to a certain extent.

• When the demands exceed a certain threshold, the

cell undergoes damage and is said to have suffered
cell injury
• Cell injury is said to be reversible if the cell is
able to regain its normal function when the
injurious agent is removed.

• If the cell is unable to recover its normal

function and structure, even after removal of the
injurious agent, it is said to have suffered
irreversible cell injury.

• An irreversibly damaged cell usually dies. Cell

death ultimately results in disease states within
the body.
 Normal cell Reversible
Injury

Stress Injurious
stimuli

Adaptation Cell injury

Inability to
adapt

Irreversible
injury

Necrosis Apoptosis
Causes of Cell Injury
Physical agents
Chemical agents and drugs
Infectious agents
Immune reactions
Genetic disorders
Nutritional disorders
Vascular deprivation
 Factors influencing Cell Injury
1. Response of cell to injury depends on type of injury, its
duration and its severity
2. Effect of injury is also determined by the type, state and
adaptability of the cell undergoing injury.
3. When a cell is injured, four systems are mainly affected. They
are:
Cell membrane
Aerobic respiration
Protein synthesis
Genetic apparatus
4. A time lag exists between injury and appearance of
morphological alterations.
Biochemical Alterations seen during Cell Injury
• Depletion of ATP.
• Reduced activity of sodium pump
• Anaerobic glycolysis
• Failure of calcium pump
• Reduced synthesis of proteins.
• Protein misfolding

• Generation of oxygen derived free radicals.

• Increased intracellular calcium
• Altered membrane permeability
• Irreversible mitochondrial damage
Reversible cell injury
 Reversible cell injury can be studied
best in tissues subjected to hypoxia.

 It can manifest in two forms:

Cloudy swelling, also known as hydropic

degeneration.

Fatty change, also known as steatosis.

Cloudy Swelling
 Cloudy swelling is the first change to appear during
cell injury.

 It is due to compromised function of the cell

membrane, which is unable to maintain normal fluid
and ion homeostasis.

 The affected organ becomes larger, more turgid and

pale in appearance

 Microscopically, the cell cytoplasm appears pale and

vacuolated due to accumulation of fluid.
Cloudy Swelling
 Fatty Change (Steatosis)
• Abnormal accumulation of triglycerides is called
fatty change.

• Fatty change is seen more commonly in organs like

liver, heart, kidney and skeletal muscle.

• In initial stages, fatty change is reversible; when

prolonged, it may cause cell death.

• Fatty change is commonly encountered in

conditions like exposure to toxins (chronic alcoholism
and certain drugs), PCM, starvation, obesity, prolonged
anoxia and DM.
 Gross & Microscopic Alterations
• Initially, fatty change is detectable only at microscopic level.
Later, the infiltrated organ becomes enlarged, pale and yellow.

• Liver : In late stages, the organ appears yellow and greasy. It

may weigh 2 – 4 times the normal.

• In heart:

 With moderate hypoxia – tigered pattern

 With profound hypoxia or when due to toxins (e.g.

diphtheria) - more uniform effect is seen.

• On M/E, involved organ shows parenchymal cells with

vacuolated cytoplasm (D/D – polysaccharide or water vacuoles)
Fatty Change Liver
 Fatty
Change
Liver
 Normal Fat Metabolism
Free fatty acids Diet
Increased mobilization from
adipose tissue

Fatty acids Oxidized to Ketone bodies

Phospholipids
Esterified Cholesterol esters

Triglycerides
Apoproteins

Lipoproteins Exit from liver

 Pathogenesis of Fatty change
• Alcoholism: Increased mobilization of FFA from peripheral
tissues and decreased oxidation of fatty acids. Acetaldehyde (a
product of alcohol metabolism) depresses tubulin function
thereby diminishing lipoprotein exit.

• Starvation: Increased mobilization of FFA from peripheral tissues.

• PCM: Decreased synthesis of apoprotein, thereby diminished

lipoprotein formation

• Anoxia: Decreased oxidation of fatty acids

• Diabetes Mellitus: Various abnormalities of lipid metabolism are

seen.
 Steps Affected by Alcohol
Free fatty acids
Increased mobilization from
adipose tissue

Fatty acids Decreased Oxidation to

ketone bodies

Triglycerides

Lipoproteins Decreased exit from liver

 Steps affected by Starvation
Free fatty acids
Increases mobilization of
FFA from adipose tissue

Fatty acids

Triglycerides

Lipoproteins
Steps affected in protein calorie malnutrition
Free fatty acids

Fatty acids

Triglycerides Decreased synthesis

of lipoproteins
interferes with exit

Lipoproteins Exit from liver

 Steps affected in anoxia
Free fatty acids
In presence of
anoxia, oxidation is
compromised

Fatty acids Oxidized to Ketone bodies

Triglycerides

Lipoproteins