‫بسم هللا الرحمن الرحيم‬

• The common denominator in almost all

diseases.

• Alteration in cell structure or functioning

resulting from some stress that exceeds the
ability of the cell to compensate through

normal physiologic adaptive mechanisms.

 Ways of cell injury
Adaptation Injury
• cell can alter their structure • If stressed cells cannot
and/or biochemical adequately adapt,
processes in order to
critical cell functions
achieve a new "steady state"
may be impaired, and
and maintain near-normal
the cell is said to be
physiologic functions
injured.
(homeostasis).
:cell responds to stress depends on

• The severity and duration of exposure to a

stressor (dose intensity).

• The inherent vulnerability of particular types of

cells to a given stress. Some cells are more
sensitive to stress than other cells
Molecular Targets of Cellular Injury

(1) The cell membrane

(2) Energy metabolism.

(3) Protein synthesis.

(4) Genes.
Cell Membrane Integrity
Selectively permeable lipid membranes are essential
for maintaining the internal environment of cells
keeps the cell in osmotic equilibrium with
.extracellular fluid

The function of intracellular organelles such as

mitochondria, lysosomes, and the endoplasmic
reticulum also depend on the integrity of their lipid
.membranes
• Increases sodium and water:lead to cell swelling,
and may even lead to disruption of the cell (lysis).

• Potassium: may leak out of the cell affecting its

ability to maintain resting membrane potential.

• Mitochondria injury: impairs energy metabolism.

• Lysosomal injury: releases hydrolytic enzymes into
the cytoplasm leading to auto-digestion of cellular
proteins.

• Endoplasmic reticulum dammage: interferes with

protein synthesis and the intracellular transport of
biologically important compounds.
 Energy metabolism

• The Role of Calcium

• The Role of Oxygen-derived Free Radicals
(Reactive Oxygen Species)

• Aerobic Respiration and ATP Production

The Role of Calcium

Cells also use energy-dependent membrane "pumps" to

keep the intracellular concentration of calcium ions
very low.

Aerobic Respiration and ATP Production - Cells require a

constant energy supply, mainly in the form of ATP, to
drive metabolism and biosynthetic reactions.
Aerobic Respiration and ATP Production

Cells require a constant energy supply, mainly in the form

of ATP, to drive metabolism and biosynthetic reactions.

Depriving the cell of oxygen (hypoxia), or disturbing

mitochondrial function, interferes with the cell’s ability to
utilize oxygen to generate adequate amounts of ATP.
The Role of Oxygen-derived Free Radicals (Reactive
Oxygen Species)

When mitochondria generate energy by reducing

molecular oxygen to water, small amounts of
partially reduced forms of oxygen (superoxide,
hydrogen peroxide, and hydroxyl radicals) are
.produced in the process
 Functional and Structural Proteins

Denaturation of cellular enzymes or structural

proteins can severely impair cellular functions.

Damage to structural proteins can impair the

intracellular transport system of cells and disrupt
the supportive protein cytoskeleton of cells.
 Genetic Apparatus

Damage to the cell’s DNA interferes with cell

replication, and impairs the synthesis of
important structural and functional proteins.
 :Note*

ATP depletion and membrane damage are

particularly lethal events. They are probably the
central factor in the pathogenesis of irreversible
cell injury.
 Pathogenises

• Hypoxia
Depletes cellular ATP and generates oxygen-derived
free radicals.

Ex: ischemia, pulmonary disease or hypoventilation,

heart failure, anemia, carbon monoxide poisoning,
etc.
• Chemical injury
A very large number of drugs and environmental
chemical agents.

Ex: inorganic compounds, ions, and organic

molecules - including byproducts of normal
metabolism and toxins synthesized by
microorganisms.
Mechanisms of chemical injury :

(1) A compound can react directly with some critical

molecular component of the cell interfering with its
function.

(2) A compound that is itself harmless to cells can be

rendered toxic when it is metabolized and converted to a
toxic substance (such as a free radical).
• Physical agents :
(1) Mechanical injury (crush injury, fractures, lacerations, hemorrhage).

(2) Extremes of heat or cold (burns, heat stroke, heat exhaustion, frostbite,
hypothermia).

(3) Ionizing or non-ionizing radiation - (x-rays, radioactive elements, ultraviolet

radiation).

(4) Sudden changes in atmospheric pressure (blast injury, decompression injury in

divers).

(5) Electric shock. (6) Noise trauma.

• Infection :
Viruses, bacteria, fungi, protozoa, or helminths produce disease by either:

(1) Replicating inside host cells and disrupting the structural integrity of the
cell (herpes virus).

(2) Producing a toxin that is harmful to host cells (e.g., clostridia and
diphtheria).

(3) Triggering an inflammatory or immune response (e.g., rheumatic fever,

tuberculosis).
• Immune reactions :
Exaggerated immune reactions (anaphylaxis, allergy), or
the inappropriate targeting of the body's own cells by the
immune system (autoimmunity) can result in acute or
chronic inflammation and cell injury.

Abnormal suppression of the immune system can increase

vulnerability to microbial invasion.
• Nutritional imbalance :
Deficiencies or excesses in normal cellular
substrates (e.g., calories, proteins,
carbohydrates, minerals, vitamins) can produce
problems such as obesity, malnutrition, scurvy,
iron deficiency anemia, etc.
• Genetic derangements :
Inherited or acquired mutations in important genes can alter the
synthesis of crucial cellular proteins leading to developmental
defects, or abnormal metabolic functioning.

Acquired mutations to somatic cells during life can affect cell

differentiation and replication leading to diseases such as cancer.
 Manifestations of Disease at the
Cellular Level

• Adaptive Structural • Cell swelling

Changes • Intracellular
• Atrophy accumulations
• Hypertrophy • Calcification
• Hyperplasia • Enzyme leakage
• Metaplasia • Cell Death: Necrosis and
• Dysplasia Apoptosis