TANSIAN UNIVERSITY UMUNYA [OBA CAMPUS]

PATHOLOGY PRESENTATION

OKONKWO CHIAMAKA MILLICENT HS/NSC/20/6321

BODJOR JOYCE OGHENERIOBORUE HS/NSC/20/6331

OYERIOR EMMANUELLA OBEHIOYE HS/NSC/20/6347

IGBOKWE PRECIOUS AMARACHI HS/NSC/20/6304

OKECHUKWU PRECIOUS .U. HS/NSC/20/6373

OKAFOR IFUNANYA FAVOUR HS/NSC/20/6375

AUDU VICTORIA DANJUMA HS/NSC/20/6381

NEZIANYA IZUCHUKWU FRANKLIN HS/NSC/20/6382

IKWUNNE PRINCESS CHISOM HS/NSC/20/6383

AKINDUNNI CHARLES AKINSANMI HS/NSC/20/6385

SUBMITTED TO; DR NNAMA TOCHUKWU

Table of content
Abstract

Introduction

Definition

Types of cell injury and cell death

Mechanism of cell injury and cell death

Factors affecting

Complications

Clinical manifestations

Clinical significance

Conclusion

Reference
Abstract

When cells are injured, one of two patterns will generally result: reversible cell injury leading to
adaptation of the cells and tissue, or irreversible cell injury leading to cell death and tissue
damage. When cells adapt to injury, their adaptive changes can be atrophy, hypertrophy,
hyperplasia, or metaplasia. Injured cells may also accumulate materials including fat, cholesterol,
protein, glycogen, or pigment.

When cells are irreversibly injured and dying, specific nuclear changes may be visible, including
pyknosis, karyorrhexis, and karyolysis. If large numbers of cells die, tissue necrosis may occur.
Observable patterns of necrosis include coagulative, liquefactive, caseous, gummatous, fat
necrosis, and fibrinous necrosis; these may hint at the underlying mechanism of injury.
Understanding the cellular and tissue level aspects of necrosis is foundational to the
understanding of disease processes and conditions.
Introduction

Cell death is the state in which cell ceases to carry out functions. Part of embryogenesis, organ
development, and maintenance of homeostasis where damaged and unneeded cells are removed.
It occurs as a result of the effect of irreversible injury, when the cell cannot overcome the
damages cell undergoes a variety of changes in response to injury, which may or may not lead to
cell death. Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to
withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to
cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury
becomes irreversible. The principal targets of cell injury are the cell membranes, mitochondria,
protein synthesis machinery, and DNA. Multiple cellular abnormalities resulting from the
damage result in cell death. The 2 main types of cell death are necrosis and apoptosis. Necrosis is
an uncontrolled cell death characterized by inflammatory changes in a pathologic condition.
Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects.

DEFINITION;
Cell injury is when cells cannot adapt, or the maximum adaptive response to physiologic or
pathologic stimuli is exceeded. It occurs with damaging stimuli, loss of critical nutrients, or
mutations

Cell death: Cell death is the state in which cell ceases to carry out functions.Part of
embryogenesis, organ development, and maintenance of homeostasis where damaged and
unneeded cells are removed.It occurs as a result of the effect of irreversible injury, when the cell
cannot overcome the damages

TYPE OF CELL DEATH

1, Apoptosis

2, Neorosis

3, Autophagy

4, Entosis

1, Apoptosis: is classified as type I cell death and is the fastest type of cell death. Apoptosis is
programmed cell death and is moderated by proteolytic enzymes known as caspases. The
proteolytic caspase cascade initiates cell death through cleaving proteins in the cytoplasm and
nucleus.

2, Autophagy is classified as type II cell death, and is the degradation process to eliminate
dysfunctional organelles, damaged proteins, and begins with the creation of an autophagosome.

3, Necrosis is classified as type III cell death and has a wide variety of cell death processes such
as pyroptosis and necroptosis. Necrosis occurs when there is not enough blood or oxygen flow to
a tissue and as a result, kills cells and tissues prematurely.

4, Entosis is classified as type IV cell death and refers to the invasion of a living cell into another
cell’s cytoplasm (cell-in-cell mechanism). It requires engulfing cells to carry out cell death.

TYPES OF CELL INJURY

Some cell damage can be reversed once the stress is removed or if compensatory cellular
changes occur. Full function may return to cells but in some cases, a degree of injury will remain

1, Cellular swelling

Cellular swelling (or cloudy swelling) may occur due to cellular hypoxia, which damages the
sodium-potassium membrane pump; it is reversible when the cause is eliminated.

2, Fatty change
In fatty change, the cell has been damaged and is unable to adequately metabolize fat. Small
vacuoles of fat accumulate and become dispersed within cytoplasm. Mild fatty change may have
no effect on cell function; however, more severe fatty change can impair cellular function. In the
liver, the enlargement of hepatocytes due to fatty change may compress adjacent bile canaliculi,
leading to cholestasis.

3,Necrosis

Necrosis is characterised by cytoplasmic swelling, irreversible damage to the plasma membrane,

and organelle breakdown leading to cell death. The stages of cellular necrosis include pyknosis;
clumping of chromosomes and shrinking of the nucleus of the cell, karyorrhexis; fragmentation
of the nucleus and break up of the chromatin into unstructured granules, and karyolysis;
dissolution of the cell nucleus.

There are six types of necrosis:

•Coagulative necrosis

•Liquefactive necrosis

•Fat necrosis

•Fibroid necrosis

•Gangrenous necrosis

4,Apoptosis

Apoptosis is the programmed cell death of superfluous or potentially harmful cells in the body. It
is an energy-dependent process mediated by proteolytic enzymes called caspases, which trigger
cell death through the cleaving of specific proteins in the cytoplasm and nucleus.The dying cells
shrink and condense into apoptotic bodies. There is some evidence that certain symptoms of
"apoptosis" such as endonuclease activation can be spuriously induced without engaging a
genetic cascade.

Mechanism of cell injury and cell death

1. Oxidative stress- Oxidative stress emerges when an imbalance exists between free radical
formation and the capability of cells to clear them. For instance, an excess of hydroxyl radical
and peroxynitrite can cause lipid peroxidation, thus damaging cell membranes and lipoproteins.
2. Endoplasmic Reticulum-Disturbances in the normal functions of the ER lead to an
evolutionarily conserved cell stress response, the unfolded protein response, which is aimed
initially at compensating for damage but can eventually trigger cell death if ER dysfunction is
severe or prolonged

3. Membrane damage-Disturbances in the normal functions of the ER lead to an evolutionarily

conserved cell stress response, the unfolded protein response, which is aimed initially at
compensating for damage but can eventually trigger cell death if ER dysfunction is severe or
prolonged

4. DNA Damage- DNA damages may block replication or gene transcription. These blockages
can lead to cell death. In multicellular organisms, cell death in response to DNA damage may
occur by a programmed process, apoptosis.

5. Abnormal calcium homeostasis- Loss of Ca(2+) homeostasis, often in the form of cytoplasmic
increases, leads to cell injury. Depending upon cell type and the intensity of Ca(2+) toxicity, the
ensuing pathology can be reversible or irreversible.

Factors affecting cell injury:

Nature, duration, and severity of injury.

Oxygen deprivation

A hypoxic state results in reduced aerobic oxidative respiration, which results in cell injury. An
extremely common and important cause of cell death and injury is hypoxia. Anemia in particular
causes hypoxia, as do carbon monoxide poisoning and diminished oxygen-carrying capacity of
the blood. Hypoxia is also caused when there is reduced blood flow (celled ischemia), inadequate
oxygenation due to cardiac or respiratory failure, and severe blood loss. Cells may become
injured, die, or adapt to a hypoxic state, depending on its severity.

Physical agents

Among the physical agents capable of causing cell injury are mechanical trauma,radiation,

extreme temperature, sudden fluctuations in atmospheric pressure,and electric shock.

Chemical agents and drugs

There is no comprehensive list of chemicals that can cause cell damage. Hypertonic
concentrations of glucose or salt can cause cellular damage directly or by derangement of
electrolytes. High concentrations of oxygen are toxic as well. Arsenic, mercury salts, and
cyanide, in addition to recreational drugs, we are exposed every day to environmental and air
pollution, insecticides and herbicides; industrial and occupational hazards and ever-growing
quantities of therapeutic drugs.
Immunologic reactions

Immune responses play an essential role in countering infectious pathogens, but they can also
cause cell damage. Several autoimmune diseases are triggered by the immune system's reaction
to endogenous self-antigens. A number of external agents, including bacteria and environmental
materials, can also cause injury to cells and tissues.

Infectious agents

Submicroscopic viruses and large tapeworms are all part of these agents. The rickettsia, bacteria,
fungi, and higher forms of parasites fall between these two categories. These agents produce
injuries in a variety of ways.

Nutritional imbalances

Cell injury is still mainly caused by nutritional imbalances. A staggering number of deaths are
caused by protein-calorie deficiencies, primarily among underprivileged populations. Around the
world, many people suffer from vitamin deficiencies. Nutritional problems can occur as a result
of self-induced starvation (anorexia nervosa).

Genetic derangement

In the order described, genetic abnormalities can result in defects ranging from the severity of
congenital malformations associated with Down syndrome, which are caused by chromosomal
defects, to the subtlety of sickle cell anemia, which occurs when a single amino acid is
substituted in hemoglobin.

Pathogenesis

Numerous factors can lead to cellular damage. Here, oxygen plays an important role in the injury
process. The mechanisms by which cells are injured are:

Cell membrane damage

Cells can be damaged by destructive physical agents like heat or radiation, which cook or
coagulate their contents.

When nutrients are inadequate, such as oxygen or glucose, or ATP isn't produced properly, the
cells may lack essential materials to survive.

Mitochondrial damage

Calcium and inorganic phosphate levels increase with an increase in cytosolic calcium.
Inorganic phosphates and fatty acids by themselves do not cause mitochondrial damage, but
when combined with high Ca2+ they are extremely detrimental. Calcium alone can still cause
mitochondrial damage.

Nuclear damage

Furthermore, decreased cellular ATP levels and an increase in adenosine monophosphate (AMP)
cause phosphofructokinase glycolysis to be activated in order to maintain cellular energy by
converting glycogen into ATP. If oxygen is restored, this stage can be reversed.

COMPLICATIONS OF CELL INJURY AND CELL DEATH

Cell damage (also known as cell injury)is a variety of changes of stress that a cell suffers due to
external as well as internal environmental changes .

-It is due to physical factors we have temperature and electric shock.

-It is due to chemical factors we have mercury salt,insecticides and herbicides e.t.c

-It is due to nutritional imbalances we have atherosclerosis and diabetes.

-It is due to immunological factors we have bacteria and environmental materials.

-cell death occurs when the severity of the injury exceeds the cells ability to repair itself

-cell death is relative to both the length of exposure to a harmful stimulus and the severity of the
damage caused cell death may occur by necrosis or apoptosis

CLINICAL MANIFESTATION

Cellular swelling is the first manifestation of almost all forms of injury to cells. When it affects
many cells in an organ, it causes some pallor, increased turgor, and increase in weight of the
organ.

Several other manifestations indicate that the system is responding to cellular injury and death. A
general inflammatory response is often present, with general malaise, fever, increased heart rate,
increased white blood cell (WBC) count, and loss of appetite.

CLINICAL SIGNIFICANCE OF CELL DEATH OR CELL INJURY

The study of cell death during development has led to important and new information on the
molecular genetics involved, especially through the study of development in invertebrate
animals.

1 It helps to maintain homeostasis in the multicellular organisms

2 Cell death maintains the constancy of cell number in an organism.

3 The unwanted cells are eliminated from the body

4 The dangerous T-lymphocytes are eliminated from the body through cell death.

5 Cell death is an important process involved in the early phases of wound healing , because In
normal wound healing, programmed cell death is necessary for removing inflammatory cells and
afterwards for scar formation.

6 Cell death plays an important role in the pathogenesis of several inflammatory diseases,
including immune mediated nephritides.

7 Cell death also plays a role in preventing cancer. If cell death is for some reason prevented, it
can lead to uncontrolled cell division and the subsequent development of a tumor.

CONCLUSION;

Cell injury and cell death are, therefore, important both in physiology and in pathophysiology.
Physiological cell death is extremely important during embryogenesis and embryonic
development.Cell death also plays a role in preventing cancer. Cell injury is when cells cannot
adapt, or the maximum adaptive response to physiologic or pathologic stimuli is exceeded. It
occurs with damaging stimuli, loss of critical nutrients, or mutations.
REFERENCES;

https://www.lecturio.com/concepts/cell-injury-and-death/

https://onlinelibrary.wiley.com/doi/10.1002/9781119432463.ch5

://medicine.nus.edu.sg/pathweb/pathology-demystified/cell-damage-and-death/ii-cell-injury-and-
death/es, and tissue damage.