Cell Injury

Prepared by:
AINA KHAN
BSN,RN, MPhil in Public Health
OBJECTIVES
At the completion of this unit learners will be able:
1. Discuss trauma
2. Explain the process of cell injury
3. Discuss reversible & irreversible cell injury
4. Describe the mechanisms of cell injury that is;
o Hypoxic
o Free radical
o Chemical
5. Discuss cell death in terms of:
o Mechanisms & types of necrosis
o Mechanism & Significance of apoptosis
 Trauma / Cell injury

When the limits of adaptive capacity are

11/11/2021 1
Trauma / Cell injury

The cell injury may be reversible or irreversible.

11/11/2021 2
11/11/2021 3
 Causes of cell injury
Nutritional
Hypoxia imbalance

Physical Agent Cell Injury Genetic defects

Chemical Agent Immunologic reaction

Microbiologic Agent
11/11/2021 4
 Causes of cell injury

• Hypoxia
It means lack of oxygen, which may be due to:
1. Ischemia (loss of blood supply) due to arterial occlusion
2. Inadequate oxygenation of blood secondary to pulmonary
disease
3. Loss of oxygen carrying capacity of blood as in anemia or
carbon monoxide poisoning
4. Decreased tissue perfusion as occurs is hypotension, shock and
cardiac failure

11/11/2021 5
 Causes of cell injury
• Physical agents
– Trauma, radiation, electric shock
– Extremes of temperatures
– Sudden change in atmospheric pressure
• Chemical agents
– Glucose or salt in hypertonic concentration
– Oxygen in high concentration
– Poisons e.g. arsenic, cyanide
– Insecticides, carbon monoxide, alcohol
– Drugs

11/11/2021 6
 Causes of cell injury
• Microbiologic agents
– Bacteria, viruses, fungi, parasites
• Immunologic reactions
– Anaphylatic reaction, autoimmune disease
• Genetic defects
– Congenital malformation, sickle cell anemia
• Nutritional Imbalance
– Hypovitaminosis, Protein caloric malformation

11/11/2021 7
 Mechanism of cell injury
1. Impaired cell membrane function by
• Production of free radicals
• Loss of calcium homeostasis
• Activation of complements
• Lysis of enzymes
• Direct membrane lysis by viruses, heat,
cold and chemicals

11/11/2021 8
 Mechanism of cell injury
1. Impaired cell membrane function by
• Production of free radicals
• Oxygen derived free radicals are chemical
species with a single unpaired electron in an
outer orbit. When generated in cells, they
rapidly attack and degrade nucleic acids and
membrane molecules.
• In addition, free radicals initiate autocatalytic
reactions.
• Examples of free radicals are superoxide and
hydrogen peroxide

9
11/11/2021
 Mechanism of cell injury
1. Impaired cell membrane function by
• Mechanism of cell injury by free radicals
• Lipid peroxidation of membrane resulting in
cellular and mitochondrial membrane damage
• DNA damage
• Loss of enzymatic activity by promoting cross
-linking of proteins

11/11/2021 10
 Mechanism of cell injury
1. Impaired cell membrane function by
• Loss of calcium homeostasis
• Ischemia and certain toxins cause influx of
calcium across the plasma membrane and
release calcium from mitochondria and
endoplasmic reticulum.
• This increased intracellular calcium activates
phospholipases that degrade membrane
phospholipids thus causing cell membrane
damage.

11/11/2021 11
 Mechanism of cell injury
1. Impaired cell membrane function by
• Activation complement system
• Activation of complements C5b, C6, C7, C8
and C9 membrane e.g. clostridium per fringes
bacteria that damage the cell membrane.
•Lysis by viruses, heat, cold, certain chemicals
Effects of cell membrane damage.
a. Loss of structural integrity
b. Loss of cellular function

11/11/2021 12
 Mechanism of cell injury
2. Decrease ATP production due to
• Hypoxia and hypoglycemia result in deficient ATP
production.
• ATP is required for such important processes as
membrane transport, protein synthesis, and
phospholipid turnover.

11/11/2021 13
 Mechanism of cell injury
3. Genetic alteration
• DNA in the chromosomes represents the genetic basis
of control of cellular functions such as synthesis of
structural proteins, growth regulating proteins and
enzymes.
• DNA abnormalities may be inherited from generation
to generation or acquired by any of several agents
• e.g. ionizing radiation, viruses, drugs and chemicals.

11/11/2021 14
 Mechanism of cell injury
3. Genetic alteration
• Effects
• Failure of synthesis of vital intracellular structural
proteins
• Failure of mitosis in actively dividing cells e.g. in bone
marrow leads to anemia
• Failure of growth-regulating proteins leads to cancer
formation
• Failure of enzyme synthesis affects vital biochemical
reactions

11/11/2021 15
 Mechanism of cell injury
4. Metabolic derangement
• Exposure to many exogenous injurious agents such as
alcohol, drugs, heavy metals, infectious agents and
accumulation of some endogenous substances can
damage the cell.

11/11/2021 16
 ISCHEMIC AND HYPOXIC
INJURY
• Causes of hypoxic injury
1. Ischemia-lack of blood supply due to obstruction of arterial
blood flow
2. Decreased oxygen carrying capacity of blood as in
anemia and carbon monoxide poisoning
3. Decreased oxygenation of blood due to respiratory
diseases
4. Decreased tissue perfusion hypotension and shock

11/11/2021 17
 ISCHEMIC AND HYPOXIC
INJURY
• Features of reversible injury
– Hypoxia affects mitochondria that results in decreased synthesis
of ATP.
– As a consequence of reduced ATP availability, following changes
develop in cellular structure which are reversible if oxygen
supply is restored.
1. Cellular swelling
2. Desegregation of ribosomes and failure of protein synthesis
3. Reduced intracellular pH resulting in clumping of nuclear
chromatin
4. Appearance of myelin figures and cell blebs due to membrane
damage

11/11/2021 18
 ISCHEMIC AND HYPOXIC
INJURY
• Features of irreversible injury
– Nuclear changes
– Nucleus may changes. show one of the three patterns of
• Karyorrhexis: The pyknotic nucleus may break into
numerous small particles. This process is called
karyorrhexis.
• Karyolysis: When the nucleus undergoes lysis without
pyknosis, the process is called karyolysis.

11/11/2021 19
 ISCHEMIC AND HYPOXIC
INJURY
• Features of irreversible injury
– Cytoplasmic changes
– irreversible damage to mitochondria manifested by severe
vacuolization
– Extensive damage to the plasma membrane
– Massive calcium influx acting as a poison for mitochondria
– Loss of enzymes and proteins due to increased membrane
permeability

11/11/2021 20
 ISCHEMIC AND HYPOXIC INJURY
• Features of irreversible injury
– Cytoplasmic changes
– Lysosomal swelling and leakage of enzymes
– Injury to the lysosomal membranes results in leakage of
their enzymes into the cytoplasm resulting in enzymatic
digestion of cell components (autolysis).
– Leakage of these enzymes into circulation after cell death
provides an important means of detecting tissue-specific
cellular injury and death in blood serum samples.
– For example, cardiac muscles contain specific enzyme
creatinine kinase. In myocardial infarction, serum level of
this enzyme is raised, providing a good indicator of
myocardial infarction
11/11/2021 21
 CHEMICAL INJURY
• Chemical induced cell injury occurs by one of the two general
mechanisms.
– Some chemicals act directly by combining with a critical
molecular component or cellular organelle.
– Mostly, chemicals cause injury by aiding in the formation
of free radicals.

11/11/2021 22
 NECROSIS
• Necrosis refers to a sequence of morphologic changes that
follow cell death in living tissue.
• The morphologic changes caused by the progressive
degradative action of on dead cells is called necrosis.
• Necrosis = Cell death + Morphological changes

11/11/2021 23
 Mechanism of necrosis
• Two processes cause the basic morphologic changes of
necrosis.
– Enzymatic degradation of cell
– Denaturation of proteins

11/11/2021 24
 Mechanism of necrosis
• Enzymatic degradation of cell
– In this process, hydrolytic enzymes are derived from
lysosomes of invading inflammatory cells(WBC).
– The enzymatic degradation by this method is called
heterolysis. This mechanism leads to liquefactive pattern of
necrosis.
• Denaturation of proteins
– This mechanism leads to coagulative pattern of necrosis

11/11/2021 25
 Types of necrosis
• Basic types
– Coagulative necrosis
– Liquefactive necrosis
– Caseous necrosis
• In special sites
– Fat necrosis
– Fibrinoid necrosis
– Gangrenous necrosis

11/11/2021 26
 Types of necrosis
• Basic types
1. Coagulative necrosis
– Coagulative necrosis typically occurs in solid organs, such
as kidney, heart and adrenal gland usually as a result of
deficient blood supply and anoxia.
– Examples
– Myocardial infarction
– Necrosis due to hypoxia in all tissues except in brain

11/11/2021 27
 Types of necrosis
• Basic types
2. Liquefactive necrosis
– It is that type of necrosis that occurs due to autolytic and
heterolysis actions of enzymes that convert the proteins of
cells into liquid. Therefore, it is characterized by softening
and liquefaction of tissue.
– Examples
– Ischemic necrosis of brain
– Suppurative inflammation (pus formation due to pyogenic
bacterial and fungal infection)

11/11/2021 28
 Types of necrosis
• Basic types
3. Caseous necrosis
• This type of necrosis is a combination of coagulative and
liquefactive necrosis and is characterized by the presence of
soft, dry, cheesy homogenous necrotic material.
• Example
• Principally in the center of tuberculous granuloma

11/11/2021 29
 Types of necrosis
• In special sites
1. Fat necrosis
– Fat necrosis occurs in two forms:
– Traumatic fat necrosis
– It occurs following severe injury the tissues with high fat
content such as the breast, subcutaneous tissue and
abdomen.
– Enzymatic fat necrosis
– This refers to the necrosis in adipose tissue, induced by the
action of pancreatic enzymes which are liberated due to
trauma to the pancreas or acute pancreatitis.

11/11/2021 30
 Types of necrosis
• In special sites
2. Fibrinoid necrosis
• Fibrinoid necrosis is a type of connective tissue necrosis
especially affecting arterial walls.
This type of necrosis is seen particularly in two conditions.
1. Auto immune diseases e.g. Rheumatic fever
◆ SLE.
2. Malignant hypertension

11/11/2021 31
 Types of necrosis
• In special sites
3. Gangrenous necrosis
• Gangrene is the necrosis of tissue with superadded
putrefaction (enzymatic decomposition).
• In other words, gangrene is a clinical condition in which
extensive tissue necrosis is complicated to a variable degree by
secondary bacterial infection.
• Gangrene = Necrosis+Infection+Putrefaction

11/11/2021 32
 Apoptosis
• Apoptosis is the process of programmed cell death. It is
used during early development to eliminate unwanted cells
• for example, those between the fingers of a developing hand.
• In adults, apoptosis is used to rid the body of cells that have
been damaged beyond repair.
• Apoptosis also plays a role in preventing cancer.

11/11/2021 33
11/11/2021 34
11/11/2021 35